BABEȘ-BOLYAI UNIVERSITY CLUJ-NAPOCA FACULTY OF PHYSICS SCIENCE AND ENGINEERING DOCTORAL THESIS SCIENTIFIC SUPERVISOR S: Prof. Univ.Dr. Onuc COZAR… [610998]
BABEȘ-BOLYAI UNIVERSITY CLUJ-NAPOCA
FACULTY OF PHYSICS
SCIENCE AND ENGINEERING
DOCTORAL THESIS
SCIENTIFIC SUPERVISOR S:
Prof. Univ.Dr. Onuc COZAR
DOCTORAL CANDIDATE:
Șerban MORCOVESCU
CLUJ-NAPOCA
2020
BABEȘ-BOLYAI UNIVERSITY
CLUJ-NAPOCA
FACULTY OF PHYSICS
SCIENCE AND ENGI NEER I
NG
Dosime tric and qu ality a ssurance proce dure
evaluat
ion of the strut-adjusted SAVI hybrid
device used in accelerated partial breast
irradiation
DOCTORAL THESIS
SCIENTIFIC SUPERVISOR:
Prof. Univ.Dr. Onuc COZAR
DOCTORAL CANDIDATE:
Șerban MORCOVESCU
CLUJ-NAPOCA
2020
2
ACKNOWLEDGMENTS
I enrolled into this doctoral degree program in 2006 strongly encouraged and
supported by the one who eventually had the bravery of taking on the responsibility of
being my supervisor and dissertation chair, Professor Dr. Constantin COSMA, of blessed
memory. Unfortunately he is no longer with us and unable to partake of this special
moment, of seeing me crossing the finish line. Time is never too generous. Prof. Dr.
Constantin COSMA has worked with me patiently during those years and helped me
eventually find and fine tune my area of research. He was a great mentor and invaluable
resource of wisdom and promoter of scientific debate and dialogue throughout the
program. Words are unable to express the loss of him, and the significance of his life in
my life. May the Lord grant him the peace and the rest he deserves and so much was
entitled to, after a life of hard work, done with dedication and unfailing passion.
I am therefo re that much more grateful to Professor Dr. Dumitru RISTOIU, for
be
ing generous enough to adopt me, and to accept taking me under his wing as my
supervisior for the final stage of my doctoral program. His advice and leadership was in
fact vital and invaluable, and helped me correct, adjust, improve and finalize a thesis in
much need of trimming and format adjustments.
I
am also very grateful to Professor Dr. Onuc COZAR, for his kindness, leadership,
insightful scientific supervision and invaluable feedback, without which I would have not
been able to complete my work in a robust and timely fashion.
I owe a lot of gratitude to the special people and excellent professionals I started
working with and for in USA, Dr. Marius and Rodica Alecu from AROS LLC Texas, who
g
reatly helped me during my first years of practice as a Medical Physicist in Texas.
I
am also grateful to Dr. Jeffery Morton, MD, from Texas Oncology Denton, my
pra
ctice Radiation Oncologist, and to all my colleagues and research partners, for the
construc
tive feedback, encouragement and support.
L
a s t , b u t n o t t h e l e a s t , h u g e t h a n k s t o m e w i f e A n c a a n d m y
e x t e n d e d f a m i l y for their unrelenting support, understanding and love they embraced
me with throughout the program.
3
Table of Contents
CHAPTER 1 INTRODUCTION …………………………………………………………………………… 5
CHAPTER 2 THEORETICAL ASPECTS ………………………………………………………….. 12
2.1. Ionizing Radiation. Fundamentals ………………………………………………………………… 12
2.2. Sources and ty
pes of ionizing radiation …………………………………………………………. 12
2.3 Energy transfer, absorption and attenuation ……………………………………………………. 13
2.4. Interactions of photons with matter……………………………………………………………….. 16
2.4.1. Photoelect
ric effect ………………………………………………………………………………………….. 17
2.4.2. Compton effect ……………………………………………………………………………………………….. 18
2.4.2.1. The kinematics of the Compton effect ………………………………………………………….. 18
2.4.2.2 Probability of Compton Interactions ……………………………………………………………… 20
2.4.3 The Pair Production ………………………………………………………………………………………….. 21
2.4.4 Interactions of charged particles with matter ………………………………………………………… 22
2.5. Quantities describing the interaction of ionizing radiation with matter ………………. 23
2.5.1 Kerma …………………………………………………………………………………………………………….. 24
2.5.2 Exposure …………………………………………………………………………………………………………. 25
2.5.3. Absorbed Dose ……………………………………………………………………………………………….. 26
2.6. Measurement of ioniz
ing radiation ……………………………………………………………….. 28
CHAPTER 3 BRACHYT
HERAPY …………………………………………………………………….. 31
3.1. High Dose Rate
Brachytherapy – General Aspects …………………………………………. 31
3.1.1. Dose calcu
lations in brachytherapy – TG43 formalism …………………………………………. 31
3.1.2. Novel computa
tional algorithms – ACUROS BV ………………………………………………… 35
3.1.3.1 The linear quadratic model ………………………………………………………………………….. 39
3.1.4 High D
ose Rate unit description and source calibration …………………………………………. 40
CHAPTER 4 OVERVIEW OF BREAST CANCER TREATMENT MODALITIES
…………………………………………………………………………………………………………………………… 45
4.1. Breast Canc
er and anatomy ………………………………………………………………………….. 45
4.2. Treatment modalities …………………………………………………………………………………… 46
4.3. Brachytherapy in the treatment of breast cancer. Developments. ………………………. 48
4.3.1 Partial breast irradiation. Brachytherapy devices and techniques. …………………………… 50
4.4. The Strut-Adjusted-Volume-Implant (SAVI) device. Study motivation …………….. 53
4.4.1 Study motivation ………………………………………………………………………………………………. 53
4.4.2 Material
s and Methods ……………………………………………………………………………………… 53
4.4.3 Results a
nd Discussions …………………………………………………………………………………….. 54
CHAPTER 5 DOSIMETRICAL EVALUATION OF A STRUT-ADJUSTED-
VOLUME-IMPLANT SAVI DEVICE USED FOR ACCELERATED PARTIAL
BREAST IRRADIATION …………………………………………………………………………………… 57
5.1 Device desc
ription ……………………………………………………………………………………….. 57
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5.2 Patient selection criteria ……………………………………………………………………………….. 59
5.3 Equipment ………………………………………………………………………………………………….. 60
5.4 Structure Definitions a
nd Nomenclature …………………………………………………………. 60
5.5 Treatment planning technique ……………………………………………………………………….. 61
5.6 Dose prescription and optimization ……………………………………………………………….. 66
5.7 Evaluation of dosimetric advanta
ges of the SAVI device compared to balloon-type
APBI devices ……………………………………………………………………………………………………. 67
5.7.1. Study Motivat
ion …………………………………………………………………………………………….. 67
5.7.2. Materials and Methods …………………………………………………………………………………….. 67
5.7.3. Results a
nd Discussions ……………………………………………………………………………………. 70
CHAPTER 6 COMPREHENSIVE DOSIMETRIC ANALYSIS OF THE SAVI
DEVICE …………………………………………………………………………………………………………….. 74
6.1. Study Motivation
………………………………………………………………………………………… 74
6.2. Materials and Methods ………………………………………………………………………………… 74
6.3. Results and Discussions. Original contributions. …………………………………………….. 89
6.3.1 Multi-institutional study on all SAVI type devices ……………………………………………….. 89
6.3.2 Single institution study results, on SAVI6-1mini device – TG43 ……………………………. 90
6.3.3 Single institution study results, on SAVImini device – ACUROS …………………………… 93
CHAPTER 7 COMPREHENSIVE EVALUATION OF A STRUT-ADJUSTED-
VOLUME-IMPLANT SAVI DEVICE QUALITY ASSURANCE PROGRAM …….. 96
7.1 Study motivation …………………………………………………………………………………………. 96
7.2 Pre-treatment Quality Assurance …………………………………………………………………… 97
7.2.1. Imaging
and documentation for treatment planning ……………………………………………… 97
7.2.2 Treatment Time Nomogram for Strut-Based Accelerated Partial Breast Applicators.
Original Contributions. ……………………………………………………………………………………………. 101
7.2.2.1 Study motivation ………………………………………………………………………………………. 101
7.2.2.2 Materials and Methods ………………………………………………………………………………. 101
7.2.2.3 Results and Discussion ……………………………………………………………………………… 102
7.3 During and post treatment Quality Assurance – Interfractional Variance. Original
Contributions. …………………………………………………………………………………………………. 103
7.3.1 Material
s and Methods ……………………………………………………………………………………. 103
7.3.2 Results a
nd Discussion ……………………………………………………………………………………. 105
7.4 Overall Results and Discussion ……………………………………………………………………. 106
CHAPTER 8 CLINICA
L RESULTS …………………………………………………………………. 108
CONCLUSIONS …………………………..
………………………………………………………………….. 112
BIBLIOGRAP
HY …………………………………………………………………………………………….. 114
List of scientific pap
ers presented at National and International Congresses and
Scientific Meetings ……………………………………………………………………………………………. 130
5
CHAPTER 1 INTRODUCTION
Ever since the discovery of X-rays and of radioactivity, slightly more than a
century ago, the study of the nature and of the mechanisms of interaction of charged
particles became one of the most fertile research fields in the modern history of applied
science. This is mainly due to the fact that, like in Roentgen’s personal case, there was a
very strong connection and an immediate application of these newly discovered physical
phenomena to the field of medicine. The fact that x-ray diagnostic radiography was
adopted widely in both Western Europe and America within just one year after Roentgen’s
discovery speaks very clearly about how prominently the new technology impacted the
field of medicine and how quickly it was adopted and adapted to new practical
applications.
Radiological physics and radiological medicine are the two closely related
scientific fields that were born shortly after, the former dealing with the science of
ionizing radiation and the way it interacts with matter, and the second dealing with how
the findings of the first are integrated and applied in the field of medicine.
Cancer is considered nowadays as being one of the most aggressive large groups of
diseases that ca
n affect the normal functionality of any part or organ the human body, due
to its ability to grow and spread uncontrolled. When cancer cells develop and are able to
involve nearby organs, metastasis occur, with cancer cells able to migrate in other parts of
the body, away from the original tumor site. External (exposure to alcohol, tobacco,
chemicals)
or internal (genetic background, metabolism) factors can influence the
evolution of cancer, but there are various different main methods currently available for
the treatment of cancer: systemic chemotherapy, surgery, radiotherapy, hormone therapy,
and targeted therapy. For the purpose of our research project, this thesis focuses on the
application of radiation therapy in the treatment of cancer, more specifically, of breast
cancer.
Breast cancer is among the most common cancer in women in the world, and the
most common in women in USA. Breast tumors are usually diagnosed and found during
routine examinations, either through mammography, ultrasound examination or regular
physical examination. Advanced mammographic techniques are able to identify tumors as
6
small as a few millimeters, but small tumor formations are easily identified through
regular checks performed by the educated patient.
Treatment of breast cancer can be a combination of local management and
systemic treatment. Most breast cancer patients are treated with both using local and
systemic treatment regimens. The selection of local management is made based on
diagnosis, patient and disease related characteristics, and it consists of surgery and, of
much interest for us, radiation therapy. Chemotherapy and hormonal therapy are the
systemic treatment options available.
The main purpose of the use of local therapies is the eradication of the primary
local disease. Mastectomy is many times involved, with or without reconstruction, but in
most cases, breast-conserving surgery combined with radiation therapy is used with much
success. When radiation therapy is the sole and primary treatment option, the excision of
the tumor is usually followed by a course of radiation therapy, which can be 1) external o r
2) internal (brachytherapy), meant to remove residual microscopic disease. This is a
conservative treatment modality, since it conserves the breast, decreases the chance of
recurrence and eradicates the residual tumor. Various irradiation techniques, traditional or
novel, are available and can be employed (Devlin et al., 2016; Baglan et al., 2001; Benitez
et al., 2004; Mooij et al., 2014). The normal treatment regimen for external beam therapy
consists of daily treatments delivered for 4 to 5 weeks with the use of a linear accelerator
and a combination of photon and electron beams. The electron beams are usually used as a
boost field that only targets to original tumor bed. Another radiation treatment option
currently available is the use of brachytherapy. Interstitial needles or balloon type devices
are implanted at the site of the primary tumor bed and radiation is delivered remotely,
using afterloader techniques, or using permanent implants, a more recent treatment option
developed in Canada in the last years.
The research objective of this thesis is to quantify the dosimetric performance and
to evaluate quality assurance procedures for a device specifically designed for the
treatment of early stage breast cancer patients by means of High Dose Rate brachytherapy.
There are many studies done on these particular areas of research, many focused on the
dosimetry aspect (Edmunson et al ., 2002; Dou et al ., 2011; Gurdalli et al ., 2011;
Scanderbeg et al., 2009), others on the quality assurance program implementation (Dou et
7
al., 2010; Thomadsen, 2000; Ji et al ., 2016), and several approaching both aspects
altogether (Gurdalli et al., 2007 ; Dou et al., 2012).
The numerous scientific papers published in the last two decades is an undeniable
indicator that breast brachytherapy is one of the fastest growing medical procedures today.
Over the last two
decades, breast conservation therapy (BCT) has been accepted as one of
the standard treatment regimens in patients with early-stage breast cancer. Especially since
the early 2000s, Accelerated Partial Breast Irradiation (APBI) has been embraced with
great interest by both cancer care providers and breast cancer patients as a great and
efficient treatment alternative to conventional whole-breast irradiation. There is data that
indicates that APBI is an acceptable option of treatment for properly selected patients
(Arthur et al ., 2003).
Historically, partial breast irradiation was first performed with interstitial
implantation using multi-catheter brachytherapy that typically triggered the tumor bed plus
a generous margin of 2.0-2.5 cm. Because of its procedural complexity, interstitial
brachytherapy was not widely adopted in the United States and eventually led to the
development of a number of other methods of delivering APBI, including intraoperative
radiotherapy with photons and electrons and conformal three-dimensional external-beam
approaches (Vaidya et. al , 2004) The MammoSite approach was eventually developed,
allowing for the delivery of hypofractionated high-dose rate brachytherapy to the tumor
bed in a relatively straightforward manner, which eliminated many of the technical
difficulties inherent to traditional double-plane interstitial implants.
Many techniques, all image-guided, have been designed and improved since the
beginning of breast brachytherapy era. The MammoSite® – Hologic, Bedford, MA – was
envisioned a
s an alternative to the interstitial implants, drastically reducing the number of
catheters used for insertion, from multiple to a single treatment catheter centered in a
balloon that fills and fits the lumpectomy cavity. This new technology was widely adopted
because of its decreased surgical procedural complexity, even though it equated with less
flexibility in dosimetrical control. A single source position is normally used for balloon
applicators, which, because of the anisotropic dose distribution of the source, results both
in low doses near the source axis and the escalation of the dose near the surface of the
balloon tends to about 2 times the prescription dose. That led to the general
recommendati
on of limiting the use of the balloon applicators to cases where the minimal
8
separation between the balloon and the skin is larger than 6 mm. The trapping of air
pockets on the surface of the balloon during insertion, can pose real problems, since those
are pushing the target tissue away, making it even more difficult to achieve acceptable
dosimetric coverage.
After the launch and initial use of the single-lumen MammoSite, many other
treatment multicatheter d evices such as the multilumen MammoSite (Hologic, Bedford,
MA), Contura Mul
ti-Lumen Balloon (Contura MLB, SenoRx Inc.,Irvine, CA), ClearPath
or Strut Adjusted Volume Implant (SAVI) were developed, in order to allow better
targeting of the primary tumor site and better sparing of the adjacent normal tissues and
organs. Among those, the SAVI device proves to be a unique solution for cases where
other APBI devices are not a fit (Morcovescu et al ., 2009). Because of its design, the
SAVImini version of the SAVI applicator allowed excellent dosimetric conformance and
skin sparing for cases where the location of the lumpectomy cavity site and the size of the
ipsilateral breast
hindered the use of balloon-type devices, like MammoSite or Contura.
Strut-based applicat ors have been widely adopted in United States as an alternative to
balloon-ty
pe applicators in APBI, and were increasingly used at our practice since early
2008. The Strut Adjusted Volume Implant (SAVI) applicator studied (Cianna Medical,
Aliso Viejo, CA), also focuses on the smallest of its kind (6-1mini), which has been
especially used on patients with reduced breast or/and lumpectomy cavity size.
Our research is a comprehensive dosimetric evaluation of various coverage
parameters, and doses to adjacent critical structures have been estimated in all patients
included in a retrospective study encompassing more than five years of cumulated clinical
data. Proposed
improved guidelines for daily treatment clinical QA and workflow are also
presented and discussed.
The main body of our work consists on a comprehensive dosimetric analysis of
extensive clinical data, collected for all four different size SAVI devices (SAVI6-1mini,
SAVI6-1, SAVI8-1 and SAVI10-1). Our study is structured and focused on two subsets of
data: 1) a major pool of data collected at a multi-institutional level, that presents the
dosimetric analysis of the entire range of SAVI applicators, and a 2) minor pool, a subset
of the entire data, considering patients implanted with the smallest of the SAVI devices,
the SAVI6-1mini device, in our clinic only. The total number of patients included in our
multi-institutional pool study is 817. There were 14 different participating institutions
9
involved in the multi-institutional study, each providing data for all four SAVI device
models. The subset study presented on the SAVI6-1mini device is a single-institution
study of
plans created for 121 patients, treated over the span of 5 years, from 2009 to
2014. We ha
ve also performed intercomparison studies among different APBI devices,
which allowed us to highlight the various dosimetrical advantages of the SAVI device
over the balloon type devices.
The dosimetric parameters reported in this study include: cavity volume, volume of
the defined treatment region (PTV_EVAL), V90(%), V95(%), V100(%), V150(cc),
V200(cc), skin distance (minimum distance from the lumpectomy cavity wall to the skin),
chest wall and ipsilateral lung distances (mm), and the maximum doses to critical
structures (skin and chest-wall). Conformity Indexes (CI), related to reported air/seroma
and invagination volumes, were also evaluated. Our dosimetric coverage criteria for this
study was V90>90%, V150<50 cm3, V200<20 cm3. Additional constraints are placed to
try limiting the chest wall and skin doses to 100%. All dosimetric data, both the major
pool and minor subset, was stratified using 5 mm skin-bridge intervals, therefore
differentiating among cases with major or no PTV volume reduction.
The current thesis is structured in eight chapters, a short description of each being
presented in the following paragraphs.
Chapter 2 is meant to review the fundamental theoretical concepts and quantities
used to describe the interactions of ionizing radiation, both gamma and x-ray, with matter,
and the methods used to measure those quantities. We briefly surveyed the main types of
interactions of photons with matter, with an emphasis on the kinematics and probability of
the Compton interactions, as the Compton Effect is the predominant mechanism of
interaction in the range of energies commonly used in radiotherapy.
Chapter 3 overviews general aspects of High Dose Rate Brachytherapy, with
special attention given to describing the standard TG43 dose calculation formalism
historically and widely used in USA for brachytherapy calculations, as well as to
addressing the novel computational algorithm commissioned and implemented in our
department, ACUROS BV, which allowed us to account for inhomogeneity corrections
and more realistically evaluated the extent to which these can become clinically relevant in
the setting of brachytherapy HDR planning and delivery.
10
Chapter 4 offers an overview of the treatment modalities currently available for
breast cancer, with an emphasis on the brachytherapeutical options. We surveyed the
brachytherapy devices currently used clinically in the USA, and highlight the device we
focused our research on, the SAVI device.
Chapter 5 presents the framework of our study, in which we describe the physical
characteristics of the SAVI device, the patient selection criteria, and we clarify the main
dosimetric parameters used in evaluating the performance of this device. We present our
initial results with the device, on the background of a preliminary comparison study we
performed on the dosimetric performance of balloon type devices, MammoSite versus
Contura. We are showing that the SAVI device is the device of choice when there is a
need to treat lumpectomy cavities of volumes of less than 35 cm3, which are usually
entirely
filled by properly inflated balloon devices.
Chapter 6 is the main body of our work consisting of a comprehensive dosimetric
analysis of extensive clinical data, collected for all four different size SAVI devices
(SAVI6-1mini, SAVI6-1, SAVI8-1 and SAVI10-1). Our study is structured and focused
on two subsets of data: 1) a major pool of data collected at a multi-institutional level, that
presents the dosimetric analysis of the entire range of SAVI applicators, and a 2) minor
pool, a subset of the entire data, considering patients implanted with the smallest of the
SAVI devices, the SAVI6-1mini device, in our clinic only. The total number of patients
included in our multi-institutional pool study is 817. There were 14 different participating
institutions involved in the multi-institutional study, each providing data for all four SAVI
device models. The subset study presented on the SAVI6-1mini device is a single-
institution stud
y of plans created for 121 patients, treated over the span of 5 years, from
2009 to 2014.
In ch
apter 7 we present our own contribution to designing a comprehensive quality
assurance program that deals with all stages of an APBI treatment process in a busy
radiotherapy department. We bring to light all possible un-common clinical situations, we
highlight the common practices and the extra measures we included into our customized
QA program, in an attempt to incorporate those into a comprehensive QA program
capable dealing with even the least frequent clinical situations.
The final re
sults and conclusions of this multi-layered study are in fact
corroborated with the results of a 5 year long clinical study we were part of, that confirms
11
the validity of our dosimetrical study. This report also confirmed outstanding target
coverage with
excellent skin and rib sparing over the entire cohort of clinical data. We
concluded that the SAVI applicators were designed to simplify brachytherapy APBI
compared to interstitial brachytherapy, allowing the advantages of brachytherapy over
other forms of accelerated partial breast radiation therapy accessible to more women. The
strut open architecture design and multiple catheter options allow dose sculpting to each
patient’s unique anatomy and cavity location. This flexibility helps to overcome prior
concerns with skin spacing and tumor beds positioned between the overlying skin and
chestwall that limited patient eligibility. The clinical report presented at the end of this
thesis confirms excellent tumor control comparable to other published APBI rates and
survival with low toxicity. Compared to external beam techniques for APBI,
brachytherapy seems to be as effective, with less toxicity.
12
CHAPTER 2 THEORETICAL ASPECTS
2.1. Ionizing Radiation. Fundamentals
The radiations of primary concern for us are the ones originating in atomic and
nuclear processes. Ionizing radiations are those radiations that can excite or ionize the
atoms of the material they interact with. They are usually identified with radiations that
surpass the minimal kinetic energy value of ~ 10 eV, the typical energy required by a
valence electron to escape an atom. The International Commission on Radiation Units and
Measurements (ICRU, 1971) makes a clear distinction between interactions of charged
and uncharged particles, emphasizing the fact that there are two different mechanisms by
which the process of ionization can take place: directly and indirectly ionizing radiation.
2.2. Sources and types of ionizing radiation
It is therefore proper and right to enumerate the most important sources and types
of radiations that can initiate and take part in an ionization process. An important source
consists of non-particulate radiations, 1) X-rays and 2) gamma-rays (γ-rays), which are
electromagnetic radiations of atomic or nuclear origin. They are created either due to the
interactions between energetic charged particles and atomic targets or due to nuclear
energetic instability (Betel, 1996). The practical energy ranges of X-rays are stretching
from gene
rating voltages of 0.1 KV all the way up to the megavoltage values, and are
normally grouped in voltage intervals, i.e. low-energy (0.1-20 kV, diagnostic (20-120kV),
orthovoltage (120-300kV), intermediate (300kV-1 MV) and megavoltage (above 1 MV).
A graphic depiction of the mechanisms of X-ray production is shown in Figure 1.
Particulate
radiations, 3) electrons (β-rays or δ-rays), 4) neutrons and other 5)
heavy charged particles (protons, alpha particles, etc), are either the products of
radioactivity or nuclear reactions or are obtained through the process of acceleration in
high energy generators. The range of energies of interest in clinical radiological physics is
from a few eV (for electrons) to hundreds of MeV (for protons or alpha-particles).
13
Figure 1 . Mechanisms of X-ray production
The main difference between the particulate and the non-particulate radiations has
to do with the process of energy deposition in matter, since this is a two-step process for
X-rays and γ-rays, a detail of much importance when describing and defining the basic
concepts of radiation dosimetry. We will further discuss the most important concepts
describing the mechanism of interaction of ionizing radiation with matter.
2.3 Energy transfer, absorption and attenuation
Ionizing x-ray or gamma photons indirectly deposit their energy by interacting
with the atoms of the material and producing high energy electrons. These electrons then
lose their energy by three major mechanisms: photoelectric effect, Compton effect and
pair-production, and by two other minor ones, of not much interest for radiological
physics: coherent scattering and photonuclear reactions.
The energy absorption process is a complex phenomenon, of mutual interchange
and interaction between particulate and non-particulate radiations (Cember, 1983). Highly
14
energetic x-ray or gamma-ray beams have a wide array of applications in radiotherapy and
are the principal method of producing particulate radiation beams, mainly electron
fascicules, for the same purpose. In fact, highly energetic photon beams are extremely
useful in clinical applications exactly because they are capable of transferring their energy
to the target materials or tissues by ejecting orbital electrons from their otherwise
relatively stable energetic states. These high-speed electrons have then the capability of
producing ionization and excitation of other atoms along their own paths of interaction.
This energy deposition and absorption process can be of great use when occurring inside
living tissues, since it has the potential of destroying or damaging the reproduction
capacity of tumor cells and tissues.
A photon beam consists of a very large number of photons, of various energies,
and in order to characterize the way this beam of radiation interacts with the material it
transverse, some basic quantities of statistical nature were introduced:
1. The fluence (Φ) is the ratio between the number of photons dN that enter a finite
sphere surrounding the point of measurement and the cross-sectional area da of the
imaginary sphere:
dadN
(2.1)
usually expressed in units of m-2 or cm-2.
2. The fluence rate or flux density (φ) is the fluence dΦ per unit time dt,
dtd
(1.2)
and is expressed in units of m-2 s-1.
3. Energy fluence (Ψ) is the quotient of the total energy dE carried by all dN rays
entering the imaginary sphere and the cross-section da of that sphere,
dadE
(2.3)
usually expressed in units of J m-2 or erg cm-2. For the special case of a monoenergetic
beam,
15
dE = dN· hν (3.4)
where hν is the individual kinetic energy of any photon in the beam.
4. Energy fluence rate or energy flux density (ψ) is the energy fluence per unit time:
dtd
(4.5)
The quantities listed above are of much importance and useful in many practical
applications but they are not descriptive in terms of the energy and type of the photon
beams. These factors become extremely important especially when talking about radiation
detection and measurement.
Especially when discussing about uncharged ionizing radiations we have to
introduce a very important concept, i.e., exponential attenuation . Charged ionizing
radiations interact with the matter in a much more sophisticated way, through small
interactions, and their gradual attenuation is not described by an exponential function
(Meredith, 1972). An uncharged particle can pass through matter without losing a
significant amount of energy, while a charged particle always loses some or all of its
energy.
A beam of uncharged particles has therefore no specific range and its energy
degradation mainly depends on its energetic profile. A monoenergetic beam is attenuated
exponentially, according to this equation:
dN = – μN dx or I(x) = I 0e-μx
(5.6)
where dN is the reduction in the number of incident photons, N is the initial number of
incident photons in the beam, I(x) is the intensity transmitted by a thickness x , I0 is the
incident energy on the target material and μ is the attenuation coefficient . When the beam
consists of a spectrum of photon energies, the attenuation is not exactly exponential, since
photons of different energies are attenuated differently in the medium, with the lower
energy photons being preferentially removed from the beam.
The mass attenuation coefficient , μ/ρ (cm2/g), is a more relevant indicator of the
attenuation of a photon beam in a medium, since it factors out the density of the material
16
and it brings into discussion its atomic composition. An even more relevant quantity is the
electronic attenuation coefficient μ e,
01
Ne cm2 / electron
(6.7)
since, ultimately, the attenuation of the photon beam and the inherent energy deposition in
the medium depends mainly on the electronic composition and characteristics of the target
material. Two other important processes take place when a photon interacts with the
electrons in a medium, described by two other coefficients:
i) energy transfer coefficient, μ tr:
hEavg
tr
tr (7.8)
where
avg
trE is the average energy transferred into kinetic energy of charged particles per
interaction and μ is the attenuation coefficient of the material, and
ii) energy absorption coefficient, μ en:
μen = μtr (1 – g)
(8.9)
where g is the fraction of the energy of secondary charged particles lost to bremsstrahlung
in the material. Energy transfer and energy absorption are the two processes by which the
energy of a photon beam is imparted to the surrounding electrons. A photon can have
multiple interactions in which its energy is converted into kinetic energy of the electrons it
interacts with, and then these high speed electrons impart their energy with other electrons
trough ionization or excitation. Part of their energy is lost in bremsstrahlung processes and
does not contribute to the energy absorbed in that specific volume. The energy absorption
coefficient is the quantity of special interest for radiotherapy since it is used in evaluations
of the energy absorbed in tissues, therefore prone to producing biological effects.
2.4. Interactions of photons with matter
As we mentioned earlier, there are five different mechanisms by which the photons
are interacting with matter. Each of these can be represented by its own attenuation
coefficient, characteristic for the energy of the incident photon and for the atomic number
17
of the absorbing material. The total attenuation coefficient can be expressed as the sum of
all these individual coefficients:
ph c coh (9.10)
where μcoh, τ, σc, π, and μph are the attenuation coefficients for coherent scattering,
photoelectric effect, Compton effect, pair production and photo disintegration,
respectively. The coherent scattering, or Rayleigh scattering, involves no energy
absorption but only scattering of the low energy incident photons at small angles relative
to their initial path, especially in high atomic number materials. It has no major relevance
in radiation dosimetry. The process of photo disintegration is, at the other end of the
energy interval, only occurring for photon energies above 10 MeV, and is, for that reason,
not taken into account when dealing with the dosimetry of X-rays in the range of clinically
relevant energies.
2.4.1. Photoelectric effect
The photoelectric effect is a phenomenon in which a photon interacts with and
imparts part of its energy to the orbital electrons of a target atom, ejecting them from the
atom. The ejection of the photoelectron results in the creation of a shell vacancy that can
be subsequently filled by an outer orbital electron, with the emission of characteristic x-
rays. Auger electrons can also be produced by the re-absorption of these characteristic x-
rays inside the mother atom (Figure 2).
Figure 2. The photoelectric effect.
18
The probability of the photoelectric effect depends on the energy of the incident
photon and on the atomic number of the absorbing material. This dependence is expressed
as
33
EZ (10.11)
and is at the foundation of many applications in diagnostic radiology. Low energy X-rays,
when used for therapeutical purposes, are highly absorbed in bone, due to its high Z. The
direction the photoelectrons are emitted is either close to 90o degree for low energy
photons or in a more forward direction for higher energy photons. The photoelectric effect
in water is predominant at energies around 30 keV but is almost nonexistent for photon
energies above 100 keV.
2.4.2. Compton effect
The Compton effect refers to the interaction between a photon and a stationary or
unbound electron, i.e. loosely bound electrons that can be considered “free” electrons
because of their weak and low energetic binding inside the atom, when compared with the
energy of the incident photon. The Compton effect is the dominant effect in the range of
energies regularly dealt with in brachytherapy, therefore we will summarize important
theoretical aspects of this physical phenomenon.
2.4.2.1. The kinematics of the Compton effect
In terms of kinematics, the equations that describe the Compton effect are the
following:
) cos 1 )( / ( 1'2 c m hhh
o
(11.12)
T = hν – hν’ (12.13)
)2tan( ) 1 ( cos2 c mh
o (13.14)
19
where moc2 is the rest energy of the electron and T is its kinetic energy, ω and θ are the
scatter angle of the photon and of the electron, respectively. Figure 3 represents the
collision betwe
en a photon of energy hν with an unbounded electron that has no kinetic
energy (being in a stationary state). The forward momentum of the incident photon is
transferred to the electron in the form of kinetic energy T, which then is scattered at angle
θ, with both kinetic energy and momentum conserved during the process.
Figure 3. The Compton effect.
Compton scattering is nearly elastic for low energy photons, and is able to transfer
almost its entire energy to the recoiling electron. Special cases of the Compton effect are
a) the direct hit , when the energy transferred to the electron is maximum and the scattered
photon travels backward at minimum energy, b) 90-degree photon scatter , when the
photon is scattered at right angles ( ω=90o) and the photon and, c) grazing hit , when the
photoelectron is deflected at 90o and the scattered photon continues on the forward
direction ( ω=0o). When the energy of the incident photon is high, if the radiation is
scattered at right angles it attains a maximum energy of 0.511 MeV, and if the radiation is
scattered backwards it attains the energy of 0.255 MeV. These are special situations of
much importance in calculating shield barrier and wall thicknesses against scattered
radiation.
Because the Compton interaction practically involves electrons weakly bound in
the atom, it is independent of the atomic number Z of the material. Even more, since the
number of electrons per gram decreases slowly but steadily with Z, the Compton mass
attenuation coefficient is practically the same for all materials. Therefore, σ c/μ ∞ 1/E,
20
since the Compton effect decreases with increasing the photon energy. In the range of
photon energies commonly used in radiation therapy, the Compton effect is the most
relevant mode of interaction of incident photons with the absorbing medium.
2.4.2.2 Probability of Compton Interactions
J.J. Thompson was the one who first introduced the concept of the probability of
Compton interactions, theory which assumed that the free electron oscillates under the
influence of the electric vector of an electromagnetic incident wave. The electron is not
transferred any of the kinetic energy of the process, but it releases a photon of the same
energy as of the incident one in an elastic scattering.
The differential cross section per electron for a photon scattered at angle ω, per
unit solid angle, is expressed as:
𝑑 𝜎0𝑒
𝑑𝛺𝜑= (𝑟02
2) (1+ 𝑐𝑜𝑠2𝜔) (14.15)
in units of cm2 sr-1 per electron. The quantity r o = e2/moc2 = 2.818 x 10-13 is the “classical
electron radius”.
The total Thomson scattering cross section per electron, 𝜎0𝑒, can be obtained by
integrating the last equation, over all directions of scattering. This is simplified by
assuming cylindrical symmetry and integrating over 0≤ ω ≤π, with the annular element of
solid angle given by dΩ φ = 2π sin ω dω, in terms of angle ω:
𝜎0𝑒= ∫𝑑 𝜎0𝑒𝜋
𝜑=0= 𝜋𝑟02∫(1+ 𝑐𝑜𝑠2𝜔)𝜋
𝜑=0sin𝜔𝑑𝜔 =
= 8𝜋𝑟02
3=6.65 𝑥 10−25 𝑐𝑚2/𝑒𝑙𝑒𝑐𝑡𝑟𝑜𝑛 (15.16)
Because this cross section value predicted in J.J. Thomson’s theoretical description
of the Compton process is too large for photon energies ℎ𝜈 > 0.01 MeV, further theoretical
work was done by Dirac and Nishina in 1928, by applying Dirac’s relativistic theory to
describe the Compton interaction process (Attix, 1986). They were able to better predict
and more comprehe
nsively express the differential cross section for photon scattering, as
21
𝑑 𝜎0𝑒
𝑑𝛺𝜑= (𝑟02
2) (ℎ𝜈′
ℎ𝜈)2
(ℎ𝜈′
ℎ𝜈+ ℎ𝜈
ℎ𝜈′− sin2𝜔) (16.17)
with ℎ𝜈′ given by Eq. (2.12). Since for low energies ℎ𝜈′ ≈ ℎ𝜈, Eq. (2.17) becomes
𝑑 𝜎0𝑒
𝑑𝛺𝜑= (𝑟02
2) (2− 𝑠𝑖𝑛2𝜔)= (𝑟02
2) (1+ 𝑐𝑜𝑠2𝜔) (17.18)
form identical to Eq. (2.15), proving that the Klein Nishina differential cross section is
simply the Thompson cross section for the special case of low photon energies.
If we integrate Eq (2.17) over all photons scattering angles ω, the total Klein
Nishina cross section per electron becomes:
𝜎𝑒= 2𝜋∫𝑑 𝜈𝑒
𝑑𝛺𝜑𝜋
𝜑=0 sin𝜔·𝑑𝜔 =
= 𝜋·𝑟02∫ (ℎ𝜈′
ℎ𝜈)2
(ℎ𝜈′
ℎ𝜈+ ℎ𝜈
ℎ𝜈′− sin2𝜔)𝜋
0 sin𝜔·𝑑𝜔 =
= 2𝜋·𝑟02{1+𝛼
𝛼2 [2(1+𝛼)
1+2𝛼− 𝑙𝑛(1+2𝛼)
𝛼]+ 𝑙𝑛(1+2𝛼)
2𝛼− 1+3𝛼
(1+2𝛼)2} (18.19)
where α = hν/m0c2, with m0c2 = 0.511 MeV and hν also expressed in MeV.
2.4.3 The Pair Production
This mechanism of interaction takes place when the energy of the incident photon
is greater than the threshold energy of 1.02 MeV. In this process there is a strong
interaction between the electromagnetic field of the atomic nucleus and the incident
photon in which the photon releases and imparts its entire energy to a newly created pair
of particles, a negative electron (e-) and a positron (e+) (see Figure 4).
22
Figure 4 . Pair production
Because the pair production is a process of interaction with the energetic field of
the nucleus, it greatly depends on the atomic number, its probability increasing with higher
Z. The pair production mass attenuation coefficient π/ρ is proportional to Z2. This
mechanism predominates for energies above 25 MeV.
In conclusion, the total mass attenuation coefficient is large at low energies (<
100keV) due to the predominance of the photoelectric effect, then slightly decreases with
energy up to 25 MeV, in the Compton effect predominance region (and remains relatively
independent of Z), and increases slightly above 25 MeV due to the predominance of pair
production.
2.4.4 Interactions of charged particles with matter
Charged particles interaction and exchange of energy with matter is very different
then the one specific to photon beams. This is due to the Coulombian nature of interaction
between a moving charged particle and the bound electrons or with the nucleus. Any
charged particle is losing its energy through a process of successive interactions and
energy losses with the surrounding medium. The heavier the particle is, the smaller the
number of interactions will be. In the case of electrons , a Bragg peak is not observed
because they exchange energy in multiple successive scattering interactions. Neutrons
have a very complex nature of interaction, and their dosimetry very intricate exactly
because they create a multitude of other types of radiations (heavy particles, neutrons,
gamma rays) when they interact with matter. Heavy particles lose their energy at a very
23
high rate, proportional with the square of the particle charge and inversely proportional
with its velocity. The Bragg peak indicates a high energy loss related to the slowing down
process that takes place.
Figure 5. Spread Out Bragg peak for a proton beam
It is possible
to manipulate and use weighted superposition methods in order to
obtain a much flatter and broader Bragg peak, as shown in Figure 5 above, for a proton
beam. The red the dose curve represents the Bragg peak of a monoenergetic, thin pencil
beam of protons. By grouping multiple Bragg peaks of different proton ranges and
energies together, it is possible to deposit a homogenous dose in the target region (Perez,
1992). The resulting (range-modulated) proton beam distribution is called Spread Out
Bragg Peak (SOBP, indicated in blue). The dose degradation with depth curve of an X-ray
beam is shown in green. The picture shows that protons deposit a much smaller dose than
X-rays outside plateau region, which can be of great applicability when a uniform
deposition of energy in a medium is desired.
2.5. Quantities describing the interaction of ionizing radiation with matter
The quantities describing the interaction of radiation with matter are 1) Kerma, K ,
a quantity that describes the energy transfer from indirectly ionizing radiations (photons)
to charged particles, 2) the Exposure, X , a quantity that describes gamma or X-ray beams
24
in terms of their ability to ionize a volume of air, and 3) the Absorbed Do se, D , a quantity
that describes the energy transfer from directly ionizing radiations to matter.
2.5.1 Kerma
The Kerma K (kinetic energy released in a medium) can be defined by introducing
another quantity, the energy transfer, E tr, in a volume V, and the radiant energy, R:
Etr = R i – Ro + Q (19.20)
where
Ri is the radiant energy of uncharged particles entering volume V,
Ro is the radiant energy of uncharged particles exiting volume V, except that
created through radiative losses of kinetic energy by charged particles inside
volume V, and
Q is the net energy derived from rest mass in V.
All processes, in which the kinetic energy of a charged particle is converted into
kinetic energy of a photon, either by bremsstrahlung or by in-flight annihilation of
positrons, are considered radiative losses.
The radiant energy R is defined as the energy of particles (excluding the rest
energy), emitted, received or transferred to a medium. Etr does not reflect how the energy
imparted to charged particles is spent inside the specified volume V, and does not count
for the energies by charged particles in volume V.
Kerma K is defined simply as
dmdEKtr (20.21)
the total energy transferred to charged particles by uncharged particles, per unit mass,
including the radiative loss energy but excluding the energy exchanged among charged
particles in volume V. The unit of kerma is gray (Gy), which equals 1 J/kg. The special
unit for kerma is rad. There is a strong relation between kerma and enegy fluence for
25
photons, and for monoenergetic x-ray beams of energy E, that transverse a material of
atomic number Z, this can be expressed as
gK
Z Een
Z Etr
11
, ,
(21.22)
where μ tr/ρ is the mass energy transfer coefficient, μ en/ρ is the mass energy absorption
coefficient, Ψ the energy fluence at the point A of measurement and K is the kerma at
point A in that volume. The energy gained by an electron after an interaction with an x-ray
photon can be partially lost as ionization energy in collision interactions with the atomic
electrons of the absorbent, or by radiative interactions, whit the emission of secondary x-
ray photons. We can therefore make a distinction between two components of kerma,
K = K col + K rad =
gg
Z Een
Z Een
1, ,
(22.23)
where K col is the collision kerma and K rad is the radiation kerma. The collision component
of kerma, K col, is a very important quantity used when discussing the concept of charged-
particle equilibrium (CPE) in a given volume V, and can be viewed as the net energy
transferred to the charged particles, since it does not incorporate the radiant energy losses
Rrad of the charged particles originated in V,
Enet = R i – Ro – Rrad + Q = E tr – Rrad (23.24)
2.5.2 Exposure
Exposure
is another important quantity for radiological physics, one that has
historical precedence over the concepts of kerma and absorbed dose. It is a measure of
ionization produced in air by photons and is defined as the quotient of the absolute value
of the total charge, dQ, of the ions of one sign produced in air when all the electrons
liberated by photons in air mass dm are completely stopped in air,
26
dmdQX (24.25)
its SI unit is coulomb per kilogram (C/kg), and its special unit is roentgen (1R). Exposure
can be expressed in relationship with the collision component of kerma by knowing that
the mean energy required to produce an ion pair in air is almost constant for all electron
energies, and has a value of W = 33.97 eV/ion pair. Therefore X equates to K col as follows:
WeK Xair
col =
air airen
airWe
(25.26)
where e/W is the average energy required per unit charged of ionization produced.
Exposure is a quantity that applies only to uncharged radiations below 3MeV, and is a
measure of ionization in air only.
2.5.3. Absorbed Dose
The absorbed dose is a quantity that is relevant to all types of ionizing radiation
fields, whether indirectly or directly ionizing. The absorbed dose is the ratio between the
mean energy dE imparted by ionizing radiation to a material of mass dm,
dmdED (26.27)
its SI unit is gray (Gy) and its special unit is rad ( radiation absorbed dose), like for kerma.
There is a strong relationship between absorbed dose and collision kerma and it brings into
discussion the concept of electronic equilibrium in a given absorbing volume. Kerma is
maximum at surface and decreases with depth and the dose builds up to a maximum and
then decreases with depth, proportionally with kerma. If we introduce a new quantity, β,
defined as
colKD
(27.28)
we can differentiate between two different electronic equilibrium regions: for β < 1, we
are in the electronic build-up region , when β = 1, electronic equilibrium is achieved, and
when β >1, we are referring to the region of transient electronic region. This is graphically
lustrated in Figure 6 below.
27
Figure 6. Absorbed dose and collision kerma relationship, for a megavoltage photon beam
In the t
ransient electronic equilibrium region, the absorbed dose is greater than
kerma because of the combined effect of photon attenuation and the predominantly
forward motion of electrons in the field. β is known for various photon energies in
different medium like air and water and it varies with energy.
The relationship between absorbed dose and photon energy fluence Ψ at a point
where transient electronic equilibrium exists is
D = β • (μ/ρ) • Ψ (28.29)
At the foundation of radiation dosimetry stays the relationship that can be
established between absorbed dose, kerma and exposure, in conditions of electron
equilibrium. Because for energetic photon beams, in the order of a few MeV, the photon
fluence at a certain point in the medium is related to and depends on the photon fluence
some distance upstream of the point of interest, the process of photon attenuation is taken
into account and energy-dependent corrections need to be considered. A rigorous
determination of absorbed dose form exposure is limited to energies up to ~ 1 MeV, when
charged particle equilibrium ca be achieved. In these conditions,
Dair = (K col)air = X • W/e = 0.876 (rad/R) • X(R) (29.30)
28
where 0.876 is the roentgen- to-rad conversion factor for air, under electronic equilibrium
conditions.
2.6. Measurement of ionizing radiation
The measurement of ionizing radiation effects was performed in a somehow non-
quantitative way at the beginning of the 20-th century, when the science of radiology was
born. Biological and chemical effects, like the amount of reddening of human skin, where
considered. But in late 1920’s, the ICRU introduced the unit of exposure, the roentgen, as
a unit of measuring x-ray radiation exposure.
For the first time, the concept of electronic equilibrium was introduced and applied
to the ionization produced by x-rays in free-air ion chamber , which consisted of a
coupling of ion-collection plates connected to a voltage.
The free-air ionization chamber is design for the measurement of roentgen, and it
became the primary standard used for the calibration of other exposure and dose
measuring devices. A fee-air chamber is a parallel plate camber; a voltage of ~ 100 V/cm
is applied across the plates and because of this voltage, the electrons created when any x-
ray beam crosses and ionizes the chamber’s air volume are accelerated between and
collected on the plates. The ionization is then measured for a length defined by the
limiting electrical field lines between the plates, defined by the adjacent guard electrodes
(see Figure 7 below). The collected charge is then converted in units of exposure.
Figure 7.
Free-air ionization chamber
29
It was for practical reasons that other devices where designed for the purpose of measuring
dose and exposure. Thimble chambers (Figure 8) are ionization
Figure 8.
Thimble ionization chamber
chambers
of small volumes that function on the same principle as free-air ionization
devices. Special theories were developed in order to describe the process of charge
collection and measurement for small cavities of air enclosed in a very thin solid material,
the walls of the chamber, since conditions of electronic equilibrium must be achieved. The
effective Z of the chamber walls and central electrode need to be carefully selected as
most of the electrons producing ionization inside such a cavity originate in the immediate
surroundings of the small air cavity. The exposure measured with a thimble chamber is
obtained from
AQX1 (30.31)
where Q is the ionization charge in the cavity volume of denity ρ and volume υ; A is a the
fraction of the energy fluence transmitted through the wall.
Other types of chambers are used for measuring x-rays if higher energies. In 1955,
Farmer designed a chamber that became the standard measurement device for all energies
in the therapeutical range. Its collecting volume is 0.6 cm3, its walls are made of graphite,
its central electrode of aluminum and the insulator of polytrichlorofluorethylene. The
charged collected is measured by another device, the electrometer, which holds a constant
bias voltage of ~ 300 V on the collector. The electrometer charge reading is converted in
units of exposure by applying various correction factors like pressure and temperature
correction, ion chamber calibration factor for a given energy, stem correction, etc.
30
The dosimetry of ionizing radiation is a very complex topic in the field of medical
physics, because of its high degree of applicability in radiotherapy (Knoll, 2000). Major
concepts, quantities and units are to be thoroughly understood, since they are the
foundation of all the computational systems and models that were and are still used in the
evaluation and measurement of dose deposited in tissues by ionizing radiation, the
fundamental process that contributed to the emergence of novel fields of medicine, like
radiology, radiation oncology, nuclear medicine.
The calculation of dose in both external beam therapy and brachytherapy is a very
complex process because of the complexity of factors that are to be taken into account.
Only the fundamental factors were presented in this paper but many other are included in
current dose calculation formalisms, especially because the evolvement of new
technologies that were adopted into the clinical environment nowadays. Special treatment
procedures like intensity modulated radiation therapy IMRT, stereotactic radiosurgery
SRS, tomotherapy are in use today, and specific factors are to included and accounted for
into dose computations for these new technologies.
31
CHAPTER 3 BRACHYTHERAPY
3.1. High Dose Rate Brachytherapy – General Aspects
As previously discussed, the use of remote afterloaders provides the ability to
irradiate tumors at a variety of dose rates, from high dose rate to conventional low dose
rate. Since the method of testing used in this project utilized High Dose Rate
Brachytherapy (HDR), only the characteristics related to this method of treatment are
presented in the following pages.
Since the introduction of remote afterloading technology in the 1950’s, numerous
authors published studies regarding the advantages and disadvantages of HDR
brachytherapy over the traditional Low Dose Rate (LDR) brachytherapy (Kubo et al ,
1998).
One major concern in the era of LDR brachytherapy was the staff’s exposure to the
harmful effects of ionizing radiation. This led to the development of remote afterloaders,
where the empty applicators are inserted in the patient, and then the radiation is delivered
remotely
from the control room, thus reducing the staff’s exposure to radiation.
3.1.1. Dose calculations in brachytherapy – TG43 formalism
The most
popular and almost universally used dose calculation formalism today is
TG43 (Raviner et al ., 1994), a formalism used to establish the 2-D dose distribution
around cylindrically symmetric sources. Cylindrical type sources are the most common
shape of clinically used sources and their dose distribution can be described in terms of a
polar coordinate system with its origin at the source center, where r is the distance from
the origin to the point of interest P and θ is the angle with respect to the long axis of the
source, as shown in Figure 9. Point P( r0, θ0) is the refer ence point that lies on the
transverse bisector of the source at a distance of 1 cm from the origin (i.e. at r0 = 1 cm and
θ 0 = π/2).
32
Figure 9. TG43 dose calculation formalism geometry for a linear source
The dose rate
) , (r D at point P in a medium from the center of the source of air kerma
strenght Sk is expressed as:
) ( ) , () 2 / , 1 () , () , ( r g r FGr GS r Dk (3.1)
Where:
Sk is the air kerma strength (U) of the source (Kubo et al., 1998);
G(r,θ) is the geometry function (cm-2) that describes inverse square falloff ,
and accounts for the distribution of the radioactive material (see
following paragraphs);
F(r,θ) is the anisotropy function that accounts for angular dependence of
dose due to absorption and scatter by the encapsulation and the
medium, is dimensionless, and is equal to unity on the transverse
axis;
g(r) is the radial dose function that accounts for radial dependence of
dose on the transverse axis due to photon absorption and scatter in
the medium, is dimensionless, and is equal to unity at 1 cm on the
transverse axis.
33
Λ is the dose rate constant (cGy h-1 U-1) and is described in more
detail below;
r is the radial distance (cm) of a point of interest from the source
center;
θ is the polar angle (radian) formed by the longitudinal axis of the
source and the ray from the source center to the point of interest;
G(r,θ)
As already indicated Λ is the dose rate constant, defined as the dose rate per air
kerma strength S k at 1 cm along the transverse axis of the source, and is given by:
Λ = D (1,π/2)/ Sk (3.2)
It depends on the source type, its construction and material the source is
encapsulated in. At this point we have to clarify that the quantity air kerma strength is
recommended by the AAPM as the standard indicator of a source strength; this quantity, in
turn, relates to another one, the air kerma rate constant Γ δ, which is the quantity ICRU
recommended to replace a former one, namely exposure rate constant (which is the
exposure rate in R/h at a point 1 cm from a 1 mCi point source). Its SI unit is m2Jkg-1h-1Ci-
1. The air kerma rate constant at a distance l from the source is given by
dtdk
Alair2 (3.3)
and it relates the activity A of a radionuclide emitting photons of energy greater than δ to
the exposure rate. The relationship between the air kerma strength Sk and air kerma rate is
given by
2l K Sl k (3.4)
The geometry function , G(r, θ), accounts for the variation of the relative dose with
the distance from the source, due to the spatial distribution of activity within the source.
G(r, θ) reduces to 1/ r2 for point source approximation and to β/( Lr sin θ) for a line source
approximation with β and L as defined in Figure 12. For idealized source geometry,
AAPM TG 43 recommends the use of the following equation to express G(r, θ):
34
G(r,θ) = r –2 for a point source approximation
G(r,θ)= 𝜃2 −𝜃1
𝐿𝑟 𝑠𝑖𝑛𝜃 for a line source approximation of active length L
L, r and θ are defined in Figure xxx. For points along the transverse axis, the geometry
factor for a
line source is given by:
G(r,π
2)=2 𝑡𝑎𝑛−1(𝐿/2𝑟 𝑠𝑖𝑛𝜃)
𝐿𝑟 𝑠𝑖𝑛𝜃 (3.5)
The radial dose function g(r) accounts for the effects of attenuation and scatter in
the medium on the transverse plane of the source (θ = π/2), excluding falloff, which is
included by G(r, θ). It is also influenced by filtration of photons, by the encapsulation
materials and source type and is given by:
g(r)=𝐷̇ (𝑟,𝜋 / 2) ⋅ 𝐺(1,𝜋 / 2)
𝐷̇ (1,𝜋 / 2) ⋅ 𝐺(𝑟,𝜋 / 2) (3.6)
For a point source, this reduces to:
g(r)=𝐷̇(𝑟)𝑟2
𝐷̇ 𝑟02 (3.7)
The anisotropy function , F(r, θ), accounts for the anisotropy of dose distribution
around the source, including the effects of absorption and scatter in the medium:
) , ( ) 2 / , () 2 / , ( ) , () , ( r G r Dr G r Dr F (3.8)
F(r, θ) is defined as unity on the transfer plane, for θ = π/2 ; however, its value off
the transfer plane decreases: (1) as r decreases; (2) as θ approaches 0ș or 180ș; (3) as the
source encapsulation thickness increases; and (4) as the photon energy decreases.
The distribution of the dose cloud around brachytherapy sources are generall y
computed by assuming only photon interactions, affected by the surroundings and the
emitted radiation. The dose contribution at a certain point from a single source of finite
35
dimensions is the sum of doses from multiple point sources. When free space is the
medium for a give
n source, it is considered that there are scattering or absorption effects to
be counted fo
r, but absorption and scatter effects need to be considered at any point
situated at some distance away from the source placed in a water medium.
If the source
is approximated by a point, Eq. (3.1) can be simplified to provide the
approximate value of dose rate from an actual point source:
𝐷̇ (r)≈ΛSk𝑔 (𝑟)
r2 Φ an(r) (3.9)
where Φan(r) is a distance dependent average anisotropy factor, which is defined as the
ratio of 4π averaged dose rate at a given radial distance divided by the dose rate at the
same distance along the transverse axis of the source (Rivard et al., 2004)
3.1.2. Novel computational algorithms – ACUROS BV
Acuros B
V is an algorithm that allows dose- to-medium distribution calculations,
in addition to the standard dose- to-water calculations available in modern treatment
planning systems using just the TG43 formalism. Advantages also include the possibility
of assigning CT values of different materials for structures identified and reconstructed in
a series of CT images, and accounting for heterogeneity effects introduced by these
structures, thus allowing for a more realistic and accurate rendition of the dose
distribution in inhomogeneous media.
Specific to the
Acuros BV is that it calculates dose distributions through solving
the Linear Boltzmann Transport Equation (LBTE). The LBTE is the equation that
describes the macroscopic behavior of radiation particles (neutrons, gamma-rays,
electrons, etc.) as they travel through and interact with matter. For a given volumetric
region, subject to a radiation source, the solution to the LBTE would render a more
accurate dose distribution within that particular region of interest. Though, analytic
solutions to the LBTE can only be obtained for a few simplified situations , therefore the
LBTE must be solved in a non-analytic manner.
Of the two ge
neral approaches to obtaining such solutions to the LBTE, the first is
the widely known Monte Carlo method, which stochastically predicts particle transport
36
through media by tracking a statistically significant number of particles through successive
random interactions, and the second is to explicitly solve the LBTE using mathematical
numerical methods.
Monte Carlo methods only obtain an indirect solution to this equation,
while some methods e
xplicitly solve the LBTE equation, as it is the case with Acuros BV.
Acuros BV is a strong alternative to Monte Carlo computational methods in the
field of brachytherapy, with even predecessors of this solver being validated on a broad
range of applications (Gifford et. al , 2006).
Acruos BV is a computational method that solves the time-independent form of
LBTE. For a computational volume, V, with surface, δV, the LBTE is given by:
Ω̂ ·Δ⃗⃗ Ψ+ 𝜎𝑡Ψ= qscat+ ∑qp
4πp
p=1δ(r −r p) (3.10)
Ψ=0,𝑟 ∈ 𝛿 𝑉,Ω̂· 𝑛⃗ <0 (3.11)
where
𝚿 is the angular photon fluence (or flux if not time integrated),
Ψ(r ,E,Ω̂), as a function of position, r = (x,y,z), E, and direction, Ω̂ = (μ, η, ζ);
qscat is the photon scattering source qscat(r ,E,Ω̂), as a function of
position, r = (x,y,z), energy, E and direction, Ω̂ = (μ, η, ζ);
qp is the photon point source, qp(E,Ω̂), for brachytherapy point
source p, at position r p, of which there are P point sources in total;
𝛅(𝐫 −𝐫 𝐩) is the Dirac delta function between the point source location, r p,
and position, r ;
𝝈𝒕 is the macroscopic total cross section, 𝜎𝑡(r ,E ), and
𝒏⃗⃗ is the normal vector to surface 𝛿 𝑉.
The first term on the left-hand side of the above equation is the streaming operator
and the second is the collision operator. The first term on the right-hand side of the
equation is the scattering source, and the second is the source from the prescribed
37
brachytherapy point sources. The scattering source is also a function of the angular fluence
and is defined as
qscat(r ,E,Ω̂)= ∫∫𝜎𝑠
4𝜋∞
0(𝑟 ,𝐸′ →𝐸,Ω̂ ⋅ Ω̂′)Ψ(r ,E,Ω̂′)𝑑Ω̂′ 𝑑𝐸′ (3.12)
where 𝜎𝑠(𝑟 ,𝐸′ → 𝐸,Ω ̂ ⋅ Ω̂′) is the macroscopic differential scatter cross section, whose
angular dependence is expressed in terms of Legendre polynomials in μ o = Ω̂ ⋅ Ω̂′.
The LBTE equation is a six-variable integro-differential equation which is solved
by Acuros BV by discretizing three variables in space, (x,y,z), two variables in angle, (μ,
η, ζ = √1−η2 − μ2 ), and one variable in energy, E. By solving the discretized equation,
Acuros BV calculates the angular and energy dependent photon fluence at every spatial
degree of freedom in the computational domain.
Because the radioactive sources in HDR are geometrically small compared to the
spatial region in which the dose calculation is done, they can be approximated as point
sources. In thi
s representation, the collided, scattered particles are transported and
accounted for differently than the un-collided, non-scattered particles.
Therefore, three independent processes of discretization are operated through
multiple methods: 1) energy discretization, through a multigroup method that divides the
particle energy range of interest, E max ≥ E ≥ E min, into a finite number of intervals, 2)
angular discretization of the collided component, through a discrete ordinates method
using Triangular-Tchebyshev quadrature sets of various orders, ranging from N=4 (24
discrete angles) to N=36 (1368 discrete angles), and 3) spatial discretization, namely the
linear discontinuous Galerkin finite-element method (DFEM) (Lewis et al ., 1984), in
which the computational volume domain, V, is subdivided in variable sized Cartesian
elements, and the local element size is adapted based on the anatomical and applicator
material properties and gradients in the scattered photon fluence.
In brachytherapy radioactive sources low energy ranges, specifically for a 192Ir
mean weighted energy of roughly 350 keV, electron equilibrium can be assumed to exist,
therefore the kinetic energy released per unit mass, KERMA, approximation can be
38
employed, which in turn eliminates the need to account for secondary electrons. When
KERMA approximation is used, dose calculation is done using the following formula:
𝐷(𝑟 )= 1
𝜌(𝑟 ) ∑𝜎𝐾𝐸𝑅𝑀𝐴,𝑔(𝑟 ){∑𝛷𝑝,𝑔𝑢𝑛𝑐(𝑟 )+𝑃
𝑝=1 𝛷𝑔𝑐𝑜𝑙𝑙(𝑟 )}𝐺
𝑔=1 (3.13)
where
𝐷(𝑟 ) is the dose at position 𝑟
𝜌(𝑟 ) is the density at position 𝑟
𝜎𝐾𝐸𝑅𝑀𝐴,𝑔(𝑟 ) is the macroscopic KERMA cross section
∑𝛷𝑝,𝑔𝑢𝑛𝑐(𝑟 )+𝑃
𝑝=1 𝛷𝑔𝑐𝑜𝑙𝑙(𝑟 ) is the total scalar fluence, that includes un-collided
and collided components, at position 𝑟
The fundamental data used by Acuros BV are the macroscopic atomic cross
sections accounted for all four types of photon interactions of photons with matter:
Compton and Rayleigh scatter (incoherent and coherent, respectively), photoelectric effect
and pair production. Macroscopic cross sections are obtained from two physical quantities:
the microscopic c
ross section for a given reaction, and the mass density of the material. In
order to perform a dose calculation, Acuros BV has each voxel of the grid a macroscopic
section assigned, with their correspondent densities derived from HU values.
3.1.3 Radiobiological models
Although there are several advantages of HDR over LDR (Kubo et al., 1998), the
biggest controversies over the two techniques of dose delivery, were related to the
radiobiological effects. For LDR the most significant advantage in terms of radiobiology is
the dose-rate effect, where for low doses and low dose-rates the repair of sublethal damage
takes place. It was demonstrated, that the dose-rate effect is greater for normal cells than
for tumor cells and this is the reason why the fractionation and dose-rate are playing major
roles in both external beam radiation therapy and brachytherapy [59-63]. Based on this
39
theory, in order to obtain comparable clinical results with HDR as with LDR, the dose per
fraction and fractionation needed to be increased.
3.1.3.1 The linear quadratic model
Historically, the comparison between LDR and HDR was done by the application
of the Linear Quadratic Model (L-Q model). In this model the biologically effective dose
(Fowler et al, 1992) (BED) is expressed as:
BED = – (ln S.F.) / α = NRt [ 1 + G x Rt / (α/β)] – kT (3.14)
where:
S.F. is the cell surviving fraction
N is the number of fractions
R is the dose rate expressed in Gy/h
t is the time for each fraction
T is the overall time, expressed in days, available for repopulation
α, β are tissue specific parameters, with α relating to the initial slope of the cell
survival curve, and β defining its curviness
α/β is the dose in Gy for which α and β are equal
G is a function of the irradiation time, the dose rate, the cellular repair and
40
time between fractions
The calculation of G is different for LDR vs. HDR treatments. For conventional
LDR treatments G can be expressed as:
G = 2/µt [1 – (1 – e –µt) / µt] (3.15)
where µ is the repair-rate constant.
For HDR tre
atments, where the time between fractions is long compared to the
half-time for repair, and the fraction is short, time t is approaching zero, so in this case G
equals unity.
Since each HDR treatment is delivered in a time that is short compared to the half-
time for repair, it is obvious that the difference between LDR and HDR is that significant
repair occurs during LDR exposure, while only negligible repair takes places during a
short HDR procedure.
Several publications contrasted and compared the effects of LDR and HDR with
respect to tumor control and late effects (Hall, 2000) and it was concluded that at least
from radiobiological standpoints HDR can safely replace LDR if enough fractions are
delivered and the total doses are reduced accordingly.
3.1.4 High Dose Rate unit description and source calibration
The high-dos
e rate remote afterloader used in our department (Figure 10) is a
VariSource iX HDR afterloader (VARIAN Medical Systems, Inc., Palo Alto, CA) that
uses a patented active wire of 0.59 mm in diameter, with two built-in Iridium-192 (192Ir)
sources, of 5 Ci (185 Gbq) nominal activity each. Both sources are encapsulated in a
homogeneous nickel titanium alloy wire so that there are no welds to break, that would
potentially create stiff spots in the wire itself. 192Ir is the radioisotope of preference for
HDR afterloaders, because of its small dimensions, high specific activity, and low photon
energy. Due to its short half-life, the 192Ir source requires replacement at least every 4
months, or when the control system warns about approaching the cycle limit of 1000
41
cycles for the active wire. When not in use, the active source wire is dwelling in a
shielded safe inside the HDR unit and is only remotely extended, and automatically sent
from the storage place and into the applicators during treatments or quality assurance tests
performed by the Medical Physicist. The design of the HDR unit includes 20 individual
channels, the source can be moved into sequentially via the turret of the unit. The source
wire travels from the safe, through the unit’s channels into the transferring tubes and
finally in the applicators that are placed interstitially or intracavitary into the tumor.
Before the initiation of each treatment, an inactive, dummy wire tests all connections
before an actual treatment run is permitted, to verify that they are free of obstructions. If
the path is clear the source wire is engaged, and dwells at predetermined positions for the
prescribed and planned treatment times.
Figure 10
. Depiction of a VariSource iX unit, with its main components
One of the
most important tasks a Medical Physicist is required to perform is
patient specific quality assurance (QA) (Khan, 2003). A robust quality assurance program
is mandatory for the smooth operation of an HDR department. Radiation oncology
facilities licensed for the use of HDR are following well established safety and emergency
procedures, addressing patient and facility pre- and post- treatment surveys, redundant
42
checks of the patients’ identity, dose prescription, treatment times and location of the
tumor. The HDR unit and console operation are tested prior to delivery of each treatment
for safety int
erlocks, source decay and treatment time calculation (Kutcher, 1995).
The 192Ir source has a half-life of 73.82 days with a rate of decay of roughly
1%/day. In order to ensure an optimum rate of dose delivery, the active wire is replaced
every 12 to 14 weeks, process that implicitly requires the new installed source to be
comprehensively
tested for mechanical and safety interlocks functionality, positioning
accuracy and reproducibility. One of the most important tests performed is the source
calibration, procedure summarized below.
As alread
y mentioned, the strength of a brachytherapy source can be specified in
terms of activity, apparent activity, exposure rate at a specified distance or air kerma
strength. The American Association of Physicists in Medicine recommends the use air
kerma strength (S k) to specify the source activity. S k can be determined from the
measurement of the exposure rate X measured in free air at a distance of 1m from the
source following the formalism (Beaulieu, 2012),
Sk = Kl x l2 (3.16)
where K l is the kerma rate in free space, and l is the distance at which is specified, usually
1m. The relation between kerma and exposure is:
K = X (W/e) avg x [ (µ tr/ρ )avg / (µen/ρ)avg] (3.17)
where K is kerma, X is exposure, (W/e) avg is the average energy absorbed per unit charge
of ionization in air, (µtr/ρ )avg and (µ en/ρ)avg are the average values of the mass transfer
coefficient and the mass energy absorption coefficient of air for the photons. In the energy
range of brachytherapy photons µ en/ρ ≈ µ tr/ρ, so Eq. 3.17 becomes :
K = X (W/e) avg (3.18)
We can then express the air kerma strength as:
43
Sk = Xl (W/e) avg l2 (3.19)
When the exposure rate is measured in R/h at l = 1m, and with the value of (W/e) avg =
0.876 cGy/R for dry air, air kerma strength for a brachytherapy source to be used in high
dose rate brachytherapy is expressed as:
Sk = X(R/h) (8.76 x 103 m2 µGy/R) (3.20)
The calibration of 192Ir sources is routinely performed using a well-type re-entrant
ionization chamber. One type of a well-type ionization chamber is filled with air and
communicates to the outside air through a vent hole. The chamber has an outer shell of
conductive material with walls that are forming an inner well electrically connected to and
disposed within the outer shell (Goetsch, 1991). The active volume of the chamber is
usually 245 c
m3, which give an optimum ionization current that is measured with an
electrometer. The chamber’s sensitive volume is defined between the inner well and the
outer shell.
The value of air kerma strength can be determined from the measurement of the
ionization current produced by the 192Ir source in the ionization chamber, corrected for ion
recombination, temperature and pressure at the time of source and chamber calibration
(Khan, 2003).
Sk = I x C T,P x N el x N c x A ion x P ion (3.21)
wher e:
I is the current reading, expressed in nA,
CT,P is the correction for temperature and pressure,
Nel is the electrometer calibration factor,
Nc is the chamber calibration factor,
Aion is the ion recombination correction factor at the time of chamber
calibration,
Pion is the ion recombination correction at the time of source calibration.
44
Traditionally, orthogonal films were used for the purpose of treatment planning for
HDR brachytherapy but nowadays the most frequent imaging modality employed is
Computer Tomography (CT), which allows for a full 3D anatomy reconstruction, dose
calculation and isodose distribution (Williamson, 1996). As described in detail earlier in
the chapter,
the recommended dose calculation formalism for point and linear sources is
AAP M’s TG-43 (Nath, 1995).
Dose distribution analysis in the irradiated volume is most efficiently done using
dose-volume histogram curves, since they allow individual patient plan evaluation and
provide an excellent comparison tool for subsequent plans performed on the same CT data
set (Gurdalli, 2008). DVHs allow for dose uniformity assessment, evaluation of the extent
of hot spots in the irradia
ted volume, and greatly help in the plan optimization process.
45
CHAPTER 4 OVERVIEW OF BREAST CANCER TREATMENT
MODALITIES
4.1. Breast Cancer and anatomy
Breast anatomy is very important in order to understand the methods used in
radiotherapy. The breast is made up of the mammary gland, fat, blood vessels, lymphatics
and nerves (see Figure 11). The surface of the breast has deep attachments of fibrous septa
which run betwe
en the superficial fascia attached to the skin and the deep fascia covering
the pectoralis major and the other muscles of the chest wall.
The mamma consists of glandular tissue arranged in multiple lobes composed of
lobules connected in ducts, blood vessels and areolar tissue. The smallest lobules are
arranged in clusters of alveoli that open into the small branches of the lactiferous ducts,
which in turn form larger ducts that converge into single canals in the nipple,
corresponding to each lobe of the gland. A network of lymph vessels encompasses the
entire surface of the chest, neck and abdomen and become very dense under the alveola.
Figure 11. Breast anatomy : A ducts B lobules C dilated section of duct to hold milk D
nipple E fat F pectoralis major muscle G chest wall/rib cage
46
The breast can be virtually divided into four separate quadrants (see Figure 12).
The most comm
on site of origin of breast cancer is the upper outer quadrant (UOQ)
(~38%), and the incidence decreases in the following order: central area (~30%), upper
inner quadrant (UIQ), lower outer quadrant (LOQ) and lower
Figure 12. Quadrants of a left breast
inner quadrant.
The rates of incidence correlate very well with the amount of breast tissue
in the respective quadrants. The tumors usually travel along the ducts, breaking then
through the basement membrane of the duct, invading adjacent lobules, ducts and
mammary fat, spreading through the lymphatics and eventually into the peripheral
lymphatics.
The staging of breast cancer is actually related to the amount of tumor
dissemination. Staging helps determining the best treatment available and estimates
prognosis. The most widely used staging system for breast cancer, based on tumor size,
number of lymph nodes involved and evidence of distant metastasis, is the TNM system
developed by the American Joint Committee on Cancer. The most common histological
type of breast cancer is infiltrating ductal carcinoma (~75%), followed by infiltrating
lobular carcinoma (~10%), the rest consisting of other histological types.
4.2. Treatment modalities
As it was already mentioned in the introduction, the treatment of breast cancer can
be a combination of local management and systemic treatment. When radiation therapy is
47
employed, as a breast-conservation therapy alternative to mastectomy alone, early trials
indicated that whole breast irradiation significantly improved the management of risk
recurrence after surgery, and whole breast irradiation became a standard component of
breast cancer therapy (Wazer et al ., 2006). The standard radiotherapeutical options
available for breast cancer are external beam therapy and internal radioisotope therapy, or
brachytherapy. We will briefly survey both techniques, with an emphasis on the latter.
In ex
ternal beam therapy, immobilization and positioning of the patient is of major
importance and reproducibility of the treatment set-up very important in order to warrant
the consistency of treatment delivery. Traditionally, the patients are positioned in a supine
position, with the arm on the involved side elevated above the shoulder level (see Figure
13).
Figure 13. Common set-up for external radiation for breast: A breast tissue, B radiation
beam, C radiation field LINAC collimation, D arm support system
in different directions in order to spare as much normal tissue as possible. The breast and
chest wall are normally treated with opposed tangential fields, and the supraclavicular and
axillary nodes with a combination of anterior and posterior fields adjacent to the tangential
fields. Matching the field margins is extremely difficult and requires a lot of attention, as
overlapping can result in unreasonably high doses at depth. Various treatment accessories
are used in order to achieve uniform distribution of dose in the breast tissue. Physical
wedges of different angles can tilt the dose profiles as to make up for the oblique
incidence on the breast and consequent air gaps involved. A common dose distribution in
external beam therapy is shown below, in Figure 14.
48
Figure 14. External beam therapy dose distribution
While
external beam therapy provides excellent tumor coverage and control, it also
comes with high dose deposition in underlying tissues, especially the lung, heart (for felt
breast treatments), and skin. Due to scatter form the wedges, when high energy photon
beams are used, the opposed breast can receive undesirable amounts of radiation,
sometimes linked to and promoting secondary breast cancer incidence in the opposing
breast.
Certain disadvantages of external beam radiation therapy for breast cancer, mostly
related to its relative complexity and related expenses, led to investigations done in the
direction of accelerated radiation courses that would eventually alleviate those problems.
Even though these many different strategies of delivering APBI, including low-dose-rate
interstitial brachytherapy, HDR brachytherapy, or HDR interstitial brachytherapy differ
with respect to certain variables, they all have in common the shortening of the treatment
schedule from 6 to 7 weeks to a course extended over 1 week or less. The following
subchapter is offering an historical overview of brachytherapy options for breast cancer.
4.3. Brachytherapy in the treatment of breast cancer. Developments.
The history of brachytherapy can be traced all the way back to the beginning of the
20th century, with the use of radium. The radium and radon gas where used in tumor
49
therapy in the years between the two world wars, and techniques were developed either in
Sweden or France. Low intensity radium tubes were used in the early days, and soon,
Patterson and Parker developed special techniques for radium clinical applications in
England, still in use today. Quimby studied the dose distributions of radium packs in USA
and published dosimetry tables for individual sources, establishing simple rules to follow
in clinical practice.
The years of 1950 to 1960 brought into picture a lot of new isotopes, due to the
flourishing of research in the atomic field, some of them rapidly integrated into the field of
medicine, because of their properties and features. Afterloading techniques were
developed during the same years, because of increasing concern and knowledge about the
effects of radiation exposure on the radiation workers, mostly practicing physicians.
The 1990s were the booming years of brachytherapy because of the discovery of
new isotopes, of the more refined dosimetry and because of the new treatment
brachytherapy methods, most of them employing remote afterloading techniques.
Brachytherapy (sometimes referred to as curietherapy or endocurie therapy) is
nowadays a term used for the short distance treatment of cancer with radiation from small,
encapsulated radionuclide sources. Brachytherapy is administered by placing sources
directly into or near the volume to be treated. The dose is then delivered continuously,
either over a short period of time (temporary implants) or over the lifetime of the source to
a complete decay (permanent implants). Most common brachytherapy sources emit
photons but, in certain situations, sources emitting beta or neutron radiations are used.
There are two main types of brachytherapy treatments :
● Intracavitary, in which the sources are placed in body cavities close to the
tumour volume;
● Interstitial, in which the sources are implanted within the tumor volume
Historically,
partial breast irradiation was initially performed with interstitial
implantation using multi-catheter brachytherapy that typically triggered the tumor bed plus
a generous margin of 20-25 mm. Low Dose Rate (LDR) iridium interstitial implants of the
breast were
used to boost the tumor site following external beam irradiation, but the novel
applicators
are brachytherapy devices used in a short 1 week long accelerated partial
50
breast irradiation scheme, a logistically desirable alternative to the longer 6 to 7 weeks of
whole breast e
xternal beam radiation therapy.
The simplic
ity of the single catheter insertion and the ability of the multi-catheter
implants to adapt the dose distribution to the target was eventually achieved by the
development of a new set of applicators, variation of the MammoSite balloon prototype,
that all contained several catheters bunched together for insertion into the cavity, that can
be expanded into a ovoidal or spherical shape, in order to fill the initial lumpectomy
cavity. The ConturaTM Multilumen Balloon (MLB) -SenoRx, Aliso Viejo, CA, is a hybrid
design, with several catheters enclosed in a balloon, and another novel device, the device
we investigated in this study, the SAVI APBI device (Cianna Medical, Aliso Viejo, CA,
USA) uses the same catheters to open and prop the walls of the cavity and provide several
different entries and paths for the radioactive source.
The availability of multiple catheters in the breast cavity can theoretically allow for
better dose shaping
control and sculpting of dose in the directions needed, away from the
skin or che
st wall, without compromising the dose coverage of the. It is the purpose of this
study to dosimetrically evaluate the SAVI device and to establish a sound procedural
scheme for the clinical implementation of this device.
4.3.1 Partial breast irradiation. Brachytherapy devices and techniques.
With evolving brachytherapy techniques in recent years, a lot of research was done
in the attempt to find better treatment options for patients diagnosed with early stages
breast cancer. It is for this reason why the National Surgical Adjuvant Breast Project
(NSABP) was initiated in USA, which tried to produce general and standard treatment
guidelines for novel treatment techniques emerging from the brachytherapy side mostly.
Breast conserving therapy is nowadays a widely accepted option in the treatment
of most patients with early stage breast cancer (stage I and II), that comes with both major
advantages (superior cosmetic results, reduction of emotional trauma compared to
mastectomy) a
nd disadvantages (prolonged treatment regimens of roughly 6 weeks long,
increased logistical problems).
Standard therapy regimens after tumor excision usually stretch over a period of
time of five (25 fractions) weeks of external beam radiation therapy to the whole breast
51
tissue (45-50 Gy) followed by a boost treatment to the tumor bed only with either of
external therapy or brachytherapy, via an interstitial implant, in an attempt to achieve
tumor control and eliminate or reduce the possibility of tumor spread in other areas of the
breast.
Brachytherapy alone is known now to achieve several things at once, while being a
comparatively efficient treatment method: a considerable reduction of treatment time,
health expenses, and scheduling times, reduced toxicity to adjacent normal structures (i.e.,
heart, underlying chest wall, and contralateral breast) due to significantly decreasing the
volume of irradiated ti
ssue.
Most of the published clinical data have been generated using interstitial breast
brachytherapy . This is an invasive procedure consisting of temporarily placing a series of
10-20 needles or catheters in the breast, eventually loaded with a radiation source at a later
time, in such a way as to encompass the entire lumpectomy cavity (Figure 15)
Figure 1
5. Interstitial brachytherapy for breast
The relative compl
exity associated with the interstitial implants and the lack of
significant patient interest in this rather invasive procedure were factors that can explain
the unsuccessful widespread adoption of this technique. As a consequence, partial breast
irradiation (PBI) techniques and devices gained a slow interest as a potential treatment
option, and only with those few institutions that had a previous experience with interstitial
breast brachytherapy. Several recent developments have occurred that are rapidly
increasing interest in the use of PBI as a treatment option. First, newer “user friendly”
52
novel interstitial breast brachytherapy techniques that are more easily taught and
performed are generally well tolerated and more comfortable for patients.
Figure 16. The MammoSite device
The Food and
Drug Administration (FDA) eventually approved the use of single-
entry, single- and multi-lumen intracavitary devices that are simplifying the brachytherapy
technique and providing a more reproducible method to perform breast brachytherapy,
allowing widespread access and adoption of partial breast irradiation in North America .
Proxima Therapeutics was the first to develop and achieve FDA approval for a new breast
brachytherapy catheter (MammoSite® – Figure 16) device that consists of only one central
catheter positioned in the breast positioned in the breast for the duration of the treatment
course, which considerably helped with improving patient comfort.
Figure 17. The Contura Multi-Lumen Balloon and the SAVI device
Since 2005, the y
ear the NSABP B-39/RTOG 0413 breast national protocol was
initiated and used, there have been three FDA (Federal Drug Administration – the official
53
regulatory entity of medical devices use in USA) approved single-entry multi-lumen
intracavitary devices that have been introduced to the market: the MammoSite Single and
Multi-Lumen device , the Contura Multi-Lumen (four different lumens) Balloon device,
and the SAVI (Strut-Adjusted Volume Implant), the most recent device, which, on its
largest model, can have up to 11 lumens (Figure 17). One of the greatest achievements
with this method
of PBI is its non-invasive nature. There are signs and indications of the
great interest in PBI in recent years. As long-term, randomized clinical data is piling up
and published, we have more and more proofs of the fact that partial breast irradiation is as
effective as its external counterpart option. The use of these devices ultimately increased
the number of patients embracing partial breast therapy as an option.
4.4. The Strut-Adjusted-Volu
me-Implant (SAVI) device. Study motivation
4.4.1 Study motivation
It is the purpose of our study to show that among all multi-lumen devices in
clinical use today, the SAVI device offers a more sophisticated and better optimized
radiation delivery approach as compared to the others and especially to the original single-
lumen MammoSite® balloon catheter, even though minimal dose optimization can be
obtained with the single catheter MammoSite as well (Dickler et. al , 2004. All three of
these intracavitary devices maintained and used the single-entry concept, having the
ability to improve dosimetric coverage of the target and reduce dose to critical surrounding
structures, chest wall and skin, but the entire cohort of SAVI devices proves to be the most
versatile and adaptable to extremely difficult implant situations. Our ultimate goal was to
make a significant contribution, through our published and conference presented clinical
studies, to the adoption of the SAVI solution for APBI by the breast surgeons and the
radiation oncology community of North America.
4.4.2 Materials and Methods
One of the greatest achievements with this method of PBI is its non –
invasive nature. There are signs and indications of the great interest in PBI in recent years.
As long-term, randomized clinical data is piling up and published, we have more and more
proofs of the fact that partial breast irradiation is as effective as its external counterpart
option. The use of these devices ultimately increased the number of patients embracing
54
partial breast therapy as an option. The private clinic the candidate functions in was a beta
testing site for the clinical use of the SAVI devices since 2008, and since then hundreds of
patients were treated with this accelerated partial breast irradiation technique, making our
center one of the busiest satellite clinical sites for SAVI use in North America. Because of
the scientific work presented at national and international conferences during the period
between 2009 and 2011 (Morcovescu et. al , 2009; Morcovescu et. al ., 2009; Morcovescu
et. al , 2009; Morcovescu et. al , 2011), noticed by the management team of the vendor and
manufacturing company, Cianna Medical (Aliso Viejo, CA, USA), the candidate was
invited to be part of a newly formed SAVI Collaborative Research Group (SCRG), a team
of outstanding researchers, both radiation oncologists and medical physicists, which
ultimately produced a great amount of scientific content, published in peer review
scientific journals and presented at national and international conferences around the
world during the period between 2012 and 2015.
The availability of a large patient clinical data, comprised of almost a thousand
(1000) individual cases shared among the 15 different university or private industry
radiation oncology departments participating in the SCRG group, favored comprehensive
and diversified clinical follow-up studies of the SAVI device. All these efforts
dramatically contributed to the expansion of clinical knowledge about the clinical pros and
cons of the use of the SAVI devices, and lead to the wide adoption of this hybrid strut
based APBI device by the medical community within United States of America. Actually,
the very first comprehensive multi-institutional dosimetrical study on the SAVI APBI
devices published and presented by the SCRG group had the candidate as the prime
investigator and leader of the scientific team (Morcovescu et. al , 2012).
4.4.3 Results and Discussions
Our center was one of the first stand-alone clinics in United States that published
clinical research studies pertaining to the newly adopted PBI SAVI device (Morcovescu
et. al, 2009), shortly after the initiation of its usage in our clinic. Our own experience with
planning and treating SAVI patients is unique, and it comprises of more than 400 SAVI
patients treated since the adoption of the SAVI device in our radiation department here at
Texas Oncology Denton. This translates in roughly these average numbers: 40+ SAVI
patients/year, ~ 4 SAVI patients/ month, or 1 SAVI patient every week, since the very first
case, in mid-2008.
55
The following Table 1 will be relevant about the trend of APBI devices usage in
our department in the last 11 years, since 2006.
Table 1. Number of APBI cases treated at Texas Oncology Denton between 2006 and 2017,
distributed per calendar year and per type of APBI device used ( * – 1st SAVI case done in June, so
# of cases accumulated until the end of 2008; ** – # of cases done until end of June, 2017)
Year
2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 Device type MM sl 30 28 16 5 1 0 0 0 0 0 0 0
MM ml 0 0 0 0 1 0 0 0 0 0 0 0
Contura 0 3 24 3 0 0 0 0 0 0 0 0
SAVI 0 0 20* 39 33 43 44 46 30 50 60 30**
Tabel 1 clearly shows the fact that while in 2006 only the MammoSite single
lumen (MM sl) device was used, due to unavailability of other APBI devices, the year of
2007 marked the slow and steady adoption of multi-lumen devices, i.e., the Contura
device. We started using the SAVI device in June of 2008, and only one year later the
profile of our HDR APBI program changed dramatically, significantly driven towards the
use of multi-lumen devices (with only one use of the upgraded balloon type device, the
multi-lumen MammoSite, MM ml), favored over the use of the single-lumen MammoSite
balloon.
Figur
e 18. The SAVI device was fully adopted in 2009, and is the only APBI
device used in our cli
nic from 2011 until end of June, 2017
MMslMMmlConturaSAVI
0102030405060
MMsl
MMml
Contura
SAVI
56
The year of 2011 marked the full abandonment of this original single-
lumen device and the full adoption of the use of the SAVI type devices for all our APBI
patients, a steady trend in the last seven (7) years of our practice, much better visualized in
Figure 18 above.
This trend and evolution is extremely relevant, since it reveals the fact that the use
of SAVI devices was easily embraced by the breast surgeon practice, adapted to their and
our workflow, and overwhelmingly elected as the device of choice because of the positive
cosmetic and clinical outcomes, reflective of the highly effective design of the device,
which allowed for better dosimetrical optimization and adaptability to difficult clinical
situations (reduced chest-wall and/or skin to lumpectomy cavity distances, due to small
breasts or lumpectomy localization in the breast).
57
CHAPTER 5 DOSIMETRICAL EVALUATION OF A STRUT-
ADJUSTED-VOLUME-IMPLANT SAVI DEVICE USED FOR
ACCELERATED PARTIAL BREAST IRRADIATION
5.1 Device description
The SAVI (Strut-Adjusted-Volume Implant) device is a multi-catheter, single entry
device manufactured by Cianna Medical, Aliso Viejo, CA, USA, that received 510(k)
clearance in July 2006. The device was slowly but gradually introduced and gained
popularity on the US market, after the first patient cases reportedly being performed as
early as the late 2008. The first preliminary scientific papers eventually including the
SAVI device as a treatment option on their studies concerning accelerated partial breast
irradiation were eventually first accepted and published no sooner than early of 2009
(Yashar et al., 2009), with publication of first clinical follow-up studies shortly thereafter
(Yashar et al, 2009; Yashar et. al , 2011). The Texas Cancer Center clinic (one of the over
175 practice locations of one of the largest private oncology companies in US), where the
candidate functions as a solo Physicist since late 2003, was elected to be one of the beta
testing sites for the SAVI device, and therefore our first planned and delivered patient
cases were the first ones done in Texas, and among the firsts in the US, in November of
the year 2008.
The device is shown in Figure 19 in both expanded (post-insertion) and collapsed
(pre-insertion) for
mat. The SAVI device comes in four different sizes, as displayed in
Figure 20. The device itself is built with a central straight strut surrounded by 6, 8, or 10
peripheral
struts (these struts are straight, in the collapsed neutral position, and curved, in
full expansion of the SAVI device), corresponding to the four (4) available sizes of the
device (Fig
ure 20). The configuration of the struts allows for a differential radioactive
source dwell-time loading, which translates in optimal dose modulation around the
lumpectomy cavity and sparing of adjacent normal tissues.
58
Figure 19. The SAVI device: A) collapsed and B) fully expanded
The major
advantage of the SAVI device is patient-specific dose optimization from
the multiple dwell positions in each strut to minimize dose to normal tissues, including
skin, chest wall, and lung. A fixed hub located near the base of the implant and an
expansion tool that slides over the central strut allows for the expansion of the device once
inside the lumpectomy cavity, and for the collapsing of the device upon removal. The
device is inserted through the incision site in the collapsed position and is expanded when
fully inserted in the lumpectomy cavity . The fully expanded peripheral struts anchor the
device against the cavity walls securing the struts in place and a very stable position, if the
SAVI device size elected for the implant properly fits the lumpectomy cavity size and
shape.
Figure 20. SAVI applicator sizes: 6-1Mini (top), 6-1, 8-1 and 10-1 (bottom)
A
B
59
The expansion tool of the SAVI device is used at the time of the surgical placement
in the lumpectomy cavity, and then reinserted and engaged prior to each treatment, for
quick collapse and removal of the device in case of an emergency. Radio-opaque markers
are built-in on same, for all sizes of the SAVI device, three peripheral struts (numbers 2, 4,
and 6) in order to facilitate the reconstruction process, the one on number 2 strut (M2)
being located distally, closest to the tip of the implant, the one on number 4 (M4) being
located midway along the length of the device and the number 6 marker (M6) being
located most proximally. The different components of the SAVI device are demonstrated
in Figure 21.
Of note, a
n experimental design version of the SAVI device, a double helix
prototype, having only three struts, one central to two peripheral ones, was tested in 2010,
and proved to dosimetrically feasible, but it never made it in the market, for clinical use
(White et al., 2010).
Figure 2 1. The different components of the SAVI device
5.2 Patient selection criteria
Patient eligibility criteria for a SAVI implant verify those currently and widely
accepted and employed in the industry, and in compliance with American Brachytherapy
60
Society (ABS) and American Society of Breast Surgeons (ASBS) guidelines and the
ASTRO consensus statement. As a rule, only patients with invasive breast cancer or ductal
carcinoma in situ , stage 0, I or II breast cancer resected by lumpectomy, up to 3 cm tumor
size, and excised with negative lymph nodes involvement, age ≥ 45 years, were accepted.
Device selection and appropriateness is assessed and done by the breast surgeon during
surgery, after the tumor is excised and the lumpectomy cavity is created.
5.3 Equipment
In order to evaluate the dosimetric features of the four (4) different SAVI devices
subtypes described in the previous section, the following equipment was also used in this
study designed to explore and demonstrate the SAVI device applicability to a diverse array
of clinical situation and scenarios often encountered in APBI.
The CT scanner used in this study was an 8 slice GE LightSpeed helical multislice
CT Scanner. All treatment plans were created and optimized using a Varian BrachyVision
Treatment Planning System – Brachytherapy Planning Software (Version 13.6).
5.4 Structure Definitions and Nomenclature
As emphasized in many publications on breast brachytherapy (Arthur et al., 2003;
Patel et al., 2007; Hong et al ., 2012; Mooney et al., 2015), dose volume histogram
evaluation is the standard method of dosimetric plan characterization, usually used to
determine the reliability of an implant, as eventually reflected in skin and normal tissue
toxicity. Therefore we used the following prescribing, optimizing and reporting indices in
this study:
Rx Dose – prescribed dose, expressed in cGy.
PTV – Ideal Planning Target Volume. This is the intended treatment volume (cubic
centimeters).
PTV_EVAL – Adjusted Planning Target Volume. This is the actually treatment
volume used for opti
mization and coverage evaluation (cubic centimeters).
Isodose Curve – A geometric curve graphically documenting all the points that
receive a
n equal radiation dose.
61
DVH – Dose-Volume Histogram. A plot of a cumulative dose-volume frequency
distribution that graphically summarizes the simulated radiation distribution within
a volume of interest of a patient that would result from a proposed radiation
treatment plan.
Coverage index (CI) – a measure of the fraction of the target volume receiving a
dose equal to or greater to the prescribed dose, i.e. V100 expressed as a percent.
V100 – Volume of tissue receiving at least 100% of the prescribed dose, expressed
in absolute terms (cubic centimeters).
V95 – Volume of tissue receiving at least 95% of the prescribed dose, expressed as
a percentage of the total target volume.
V90 – Volume of tissue receiving at least 90% of the prescribed dose, as a
percentage of the total target volume.
D90 – the percentage of the prescribed dose delivered to 90% of the PTV.
V150 – the volume of tissue receiving at least 150% of the prescribed dose,
expressed in absolute terms (cc’s).
V200 – the volume of tissue receiving at least 200% of the prescribed dose,
expressed in absolute terms (cc’s).
Max Skin Dose – the maximum dose as calculated by the DVH in the Max Skin
structure, expr
essed in absolute terms (cGy) or in relative terms (as a percentage of
the prescribed dose).
Max Chest-Wall/Rib Dose – the maximum dose as calculated by the DVH in the
Max Chest-
Wall or Rib structure, expressed in absolute terms (cGy) or in relative
terms (as a percentage of the prescribed dose).
DHI – dose homogeneity index, which is the equivalent to the fraction of the total
treatment volume which receives a dose between 100% and 150% of the Rx dose
5.5 Tr eatment planning technique
The CT images are sent to a BrachyVision treatment planning computer (Varian
Medical Systems, Inc., Palo Alto, California) where a full three-dimensional
reconstruction of the SAVI device is performed. Planning is performed only once, as re-
62
planning is only employed and necessary if intra-fractional in-out or rotational motion of
the device is assessed and confirmed.
Treatment planning is usually more time consuming than for a typical MammoSite
balloon applicator, but planning times are not prohibitive as standard template plans are
created for each of the SAVI device types. Standardization of created APBI SAVI cavities
was later adopted by others (Dahl et al ., 2014), since it improves consistency of SAVI
cavity reconstruction. This allows for quick digitization and reconstruction of the multiple
struts. The lumpectomy or SAVI cavity is defined by the physician, as this becomes the
reference structure from which all planning target volumes are eventually obtained.
CT images for all 4 SAVI devices subtypes were exported to the BrachyVision
Treatment Planning. A carefully designed selection procedure is employe d, in order to
select and model each device type based on published dimensional data. Each device type
was evaluated in axial and multiplanar reconstruction views for long axial and sagittal
lengths, symmetry and conformance of the applicator, in order to closely match the
manufacturer’s specifications, see Table 2 below.
Table 2. Sum
mary of criteria and recommendations for SAVI size selection based on
lumpecto
my cavity dimensions (Courtesy of Cianna Medical)
Long axis of cavity
(cm) Diameter of cavity (cm)
2-3 3-4 4-5
2-3 SAVI 6-1mini n/a n/a
3-4 SAV I6-1mini SAVI 6-1mini n/a
4-5 SAV I6-1mini SAVI 6-1mini n/a
5-6 SAVI6 -1 SAVI6 -1 SAVI6 -1
6-7 SAVI6 -1 SAVI 8-1 SAVI 8-1
7-8 SAVI 8-1 SAVI 10-1 SAVI10 -1
The Planning Target Volume (PTV) is generated by a 1 cm uniform expansion of
the lumpectomy cavity volume, and it is defined as the difference between the expanded
volume and the cavity volume. Th e Planning Target Volume for Evaluation (PTV_EVAL)
is, according to the definition given by the National Surgical Adjuvant Breast and Bowel
Project (NSABP) B-39/ (RTOG) 0413 Protocol, the same as the PTV but limited to 5 mm
63
from the skin surface and by the posterior breast tissue extent (chest wall and pectoralis
muscles not included).
Other structures are created, including but not limited to these: Air/Seroma , Heart ,
Normal Tissue , Chest Wall , Ipsilateral Lung and Skin Surface .
The library of created structures was created based and following closely on the
recommendations of the NSABP B-39/Radiation Therapy Oncology Group 0413 protocol.
The Body
structure is automatically reconstructed by the BrachyVision software upon the
import of any CT studies into the system. The device is then accurately reconstructed,
following a detailed step- by-step procedure, and all other structures associated with the
device and
with the (hypothetical) surrounding healthy tissue are created for prescription
and optimization and described below.
For eac
h device studied the SAVI cavity is reconstructed by using the metal frame of
the device, easily detectable in the CT axial, sagittal or coronal views. 2.5 mm CT slices
are always used, with no gaps between the slices, in order to provide excellent image
resolution. Patients are always scanned with arms up and with a breath hold technique that
allows contiguous and smooth data acquisition, free of any motion artifacts.
When reconstructing the cavity, we always aim for replicating the physical
dimensions of the SAVI applicator (Figures 22-25), according to the manufacturer’s
specifications indi
cated below (the length refers to the distance between the proximal hub
and the base of the distal tip), Table 3:
Table 3. SAVI devices physical reference dimensions
Type of Device Length of central shaft Width/Max Expansion
mm mm
SAVI 6-1mini 50 24
SAVI6+1 61 30
SAVI8+1 67 40
SAVI10+1 75 50
64
Figure 22. SAVI6+1 reconstructed cavity and applicators
Figure 23
. SAVI8+1 reconstructed cavity and applicators
65
Figure 24. SAVI10+1(the largest SAVI device) reconstructed cavity and
applicator
s
Figure 25. SAVI6-1mini (the smallest SAVI device) reconstructed cavity and
applicat
ors
66
Once the cavity is reconstructed, we use a reconstruction wizard tool to reconstruct
the ipsilateral lung. The CHEST_WALL structure is then created by applying a 5.0 mm
margin exterior extension to the LUNG, and the SKIN structure is created by applying a
5.0 mm margin interior extension to the BODY contour. The Planning Target Volume
(PTV) is generated as a uniform layer of 1cm around the SAVI structure. Using Boolean
tools, we created the PTV_EVAL structure by subtracting the CHEST_WALL and SKIN
volumes from the PTV volume. The SKIN structure is then reset, and its final rendition
will be obtained by applying a 3.0mm exterior margin to the BODY contour. No
subcutaneous region is included in the SKIN, so all reported Max Skin values reflect the
dose values at the very surface of the skin edge. The process is shown in Figure 26 below:
Figure 26
. Reconstruction of device and creation of PTV volume
5.6 Dose prescription and optimization
The standard fractional dose is of 340 cGy to the outer surface of PTV_EVAL. The
total dose of a full course of treatment is of 3400 cGy, delivered in 10 fractions, twice
daily, with daily pair-fractions at least six hours apart. The planning criteria used for
planning are matching the once recommended by the NSABP B-39/ RTOG 0413 protocol
guidelines for APBI irradiation with respect to D90, V100, V150, V200 and conformity
indexes, as well as to Maximum Skin Dose (MSD). V100, V150 and V200 represent the
volumes (in cm3) covered by the respective (IL) isodose line (in %).
D90 represents the percentage of the prescribed dose delivered to 90% of the PTV.
MSD is the Maximum Skin Dose, MCWD is the Maximum Chest Wall Dose, V150 and
67
V200 represent the volumes (cc) covered by the percentage (%) of the dose. In preliminary
papers on thi
s topic (Wazer et al ., 2006), it is indicated that escalated values for these
entities are linked to the increasing risk of developing fat tissue necrosis. Lately, different
authors or groups (Cuttino et al ., 2009) published early tolerances and late toxicities
related to th e dosimetric parameters indicated above.
5.7 Evaluation of dosimetric adv
antages of the SAVI device compared to
balloon -type APBI devices
5.7.1. Study Motivation
As stated before
, the main precursors of the SAVI device were two balloon-type
devices, the later being the ConturaTM MLB applicator, a five (5) lumen balloon-type
device, clinically launched in January 2008 by SenoRX, Inc, believed to be a better
solution for certain cases unfit for PBI (partial breast irradiation) using a similar device,
the MammoSite (Hologic) single-lumen balloon, due to either minimal balloon- to-skin
distance, balloon symmetry or tissue-balloon conformance. Multiple studies (Arthur et. al ,
2003; Foo et al., 2008; Brown et al., 2009; Kim et al., 2011; Sherman et al., 2011) show
that balloon type devices with multiple lumen entries, like the Contura device, allow for
better PTV_EVAL coverage, reduction of maximum doses on skin and chest-wall
compared to single lumen devices, like MammoSite, the use of which can also lead to late
chest wall or skin toxicities (Brashears et al ., 2008). Also, the SAVI applicator use is
proved to result in lower doses to the contralateral breast, compared to external beam
radiation (Robinson et al., 2015). In this section we present our dosimetrical evaluation of
both balloon-type applicators against each other and relative to the SAVI device, in a
comparative study ( Morcovescu et al., 2009) meant to highlight the relevant advantages
of one balloon type device over the other, and of the SAVI device over both balloon type
devices, in view of the RTOG 0413 protocol.
5.7.2. Materials and Methods
We considered ten (10) cases elected to be treated with the ConturaTM balloon. The
treatment plans were designed following the RTOG 0413 planning guidelines. All five (5)
68
available channels were used when creating plans with the ConturaTM balloon, as shown in
Figure 27.
Figure 2
7. ConturaTM balloon, all 5 channels fully loaded
Figure 28 . ConturaTM balloon, central lumen, single position
Surrogate plans were then designed for each of the ten cases, using only the
centered lumen of the ConturaTM balloon (see Figure 28), in order to mimic the use of a
69
MammoSite-contura (MMc) applicator. Single and multiple dwell position surrogate plans
were created. For each patient, the outcome of the three plans were then compared and
analyzed both from a dosimetrical perspective and from the treatment delivery hands-on
experience perspective as well. 3D treatment planning and DVH analysis was employed in
order to evaluate geometric and dosimetric parameters.
Figur e 29. Body contour optimization
The SAVI device was the applicator of choice in our first two cases presented in
the next study, because of the small lumpectomy cavity sizes, 9.6cc and 8.5cc
70
respectively. The SAVI6-1mini catheters were differentially loaded following a PTV
optimizati
on process, in order to allow V95>95%, V150<50cc, V200<20cc and acceptable
rib and skin maximum doses. These two cases were evaluated in a comparison with the
other two commonly used APBI treatment balloon-type devices, the MammoSite and the
Contura balloons. A single source dwell position was placed in the central lumen of the
SAVI6-1mini device in order to create a virtual MammoSite plan.
The prescriptio
n dose of 34 Gy was delivered at 3 cm radial distance from this
central single dwell position. This is the equivalent radius of the PTV spherical volume
created for a regularly filled 35.0 cc MammoSite balloon.
A Contura plan template
was also superimposed on the CT image set and fit into
the cavity volume. A plan was then created as to deliver the prescription dose to the same
PTV surface as the one considered for the MammoSite virtual plan. A Body-Deformed
Contour was created in order to mimic the shape of the skin (Figure 29) when a balloon-
type a
pplicator was virtually placed inside the cavity. More realistic maximum skin doses
were than assessed and reported.
5.7.3. Results and Discussions
When comparing the balloon type applicators, the intrinsic design of the ConturaTM
MLB applicator corroborated with an automated plan optimization process that considered
the use of all its five (5) channels, contributed to a generally better dosimetrical
characterization of the target volumes, when trying to limit the Maximum Skin Dose
(MSD) to less than 145% of the Prescription Dose (PD). Coverage Indexes for both PTV
and PTV_EVAL structures, as defined in the RTOG 0413 protocol, were evaluated. With
Contura, the PTV Coverage Index – CI1 is better by an additional 1.5–3.5% compared to
the MammoSite ( MM
) balloon. An increase of V150 and V200 values were recorded for
Contura compared with MM, in the range of 1.0-2.0 cc (V150) and 0.1-1.0 cc (V200),
while maintaining acceptable limits for both. The most common limiting factor for the use
of interstitial PBI is the MSD. While improving the coverage of both PTV and
PTV_EVAL with the Contura, the MSD was reduced by 8.0-12.0% of PD compared to the
MM. Close and thorough monitoring of the balloon positioning during the treatment
course is also essential, as rotation of the balloon may occur.
71
The symmetry of the balloon no longer plays a crucial role with the Contura
balloon, since adequate shaping of the dose cloud can be achieved by differential loading
of off-centered catheters. Better conformity can also be achieved with the Contura balloon
due to availability of a suction/vacuum channel that allows immediate action at the time of
the initial CT simulation, when air or/and seroma trapped around the balloon can be
removed. The better dosimetrical outcome that the ConturaTM MLB applicator potentially
offers comes with a price though: it involves a more time-consuming planning process and
more extensive quality assurance program, which includes prior to each fraction balloon
position monitoring and adjustments, incision site re-taping and re-bandaging.
Overall, compared to the simulated MammoSite-Contura balloon, better target
coverage was possible with the new ConturaTM MLB applicator while being able to reduce
the MSD values and to achieve better conformity.
When comparing the cases where the SAVI device was elected against the MM
and Contura balloon devices, the following results are reported. Lumpectomy cavity
volumes of less than 10 cm3 were easily accommodated by the SAVImini. Because of
possible differential loading of up to 7 catheters, even cases that would normally not meet
the criteria outlined in NSABP B-39 can were successfully treated without any clinical and
dosimetrical compromi
ses. In general though, studies show that plans done with both
balloon-type and SAVI devices conform well to guidelines specified in national protocols
(Scanderbeg et al., 2009; Sehgal et al., 2011 ).
The 95% isodose line coverage in all three situations is very similar, in the 96.5% –
99.8% range
. Though, the maximum skin dose and the maximum rib dose vary greatly,
especially for the case where the recorded SAVI- to-skin distance was 1.3 mm.
Balloon-type applicators cannot accommodate volumes of less than 15cc without
causing extreme patient discomfort, skin overstretching and prohibitive skin doses, up to
almost 600% of the prescription dose, as the study shows. Body contour modeling or
editing should be employed in order to realistically account for skin stretching and shaping
caused by the use of a balloon applicator in a lumpectomy volume less than 15cc, when
assessing the maximum dose to skin for comparative studies.
Maximum skin doses of 244.3% (MM) and 249.4 % (Contura) were estimated
when the body surface was conformed to the shape of a balloon applicator (Figure 28 ).
72
These are still unacceptable values, but realistically lower values than the ones reported
for case #2 in Table 4.
Table 4. Comparison data for Contura, MM and SAVI6-1mini cases
Because
of the size of the cavity in the case of SAVI6-1minis, V150/V100 volume
ratios tend to
exceed the 0.5 value, therefore further investigation and reevaluation of the
DHI acceptance criteria, and relevance, for APBI for small cavity volumes is necessary.
APBI has become a very efficient and attractive method of treatment for women
diagnosed with early stage breast cancers. Balloon- type applicators like MammoSite or
Contura can accommodate a large range of clinical situations but fail to address the ones
where the lumpectomy cavity volumes are below 15cc. Properly inflated balloons can fill
up cavities of at least 30cc, normally larg er than 35cc. The SAVI6-1mini applicator proves
to be the
only implant solution for small lumpectomy volumes, below 15cc. Its design
allows a proper dose optimization, with excellent PTV coverage and acceptable skin
sparing.
New devices are developed for the treatment of breast cancer and better results are
observed. An intricate and exhaustive study of the advantages of one over the others needs
to be done, in order to improve the current treatment options and allow for further # Applicator
type V100
(cc) V95
(%) V90
(%) V150
(cc) V200
(cc) DHI Max
skin
dose
(%) Max
CW
dose
(%) PTV
volum
e
(cc) Min
Skin
Distance
(mm)
1 SAVI 6-1mini 47.2 98.6 99.6 27.4 17.1 0.419 72.5 170.3 48.92
13.9 MM1dw 73.3 96.5 98.3 25.1 5.1 0.658 147.2 355.7
82.0
Contura 77.0 99.1 99.8 28.7 7.8 0.627 143.0 325.3
2 SAVI 6-1mini 24.8 97.0 98.7 16.0 10.2 0.355 105.7 163.9 26.3
1.3 MM1dw 78.4 98.4 99.0 30.0 8.2 0.617 582.7 323.1
82.0
Contura 79.4 99.3 99.6 31.6 9.5 0.602 592.8 280.1
73
developments. Our studies indicate that the SAVI device proves to be a desirable option,
with excellent coverage results and minimal skin reactions and late secondary effects.
74
CHAPTER 6 COMPREHENSIVE DOSIMETRIC ANALYSIS OF THE
SAVI DEVICE
6.1. Study Motivation
Appropriateness of the accelerated partial breast irradiation option in the case of
breast cancer patients was and still is one of the most important questions to be answered
when determining whether this should be offered to a woman candidate, and is historically
understood in view of many aspects, including pathology, anatomic patterns, etc., which
are mainly seen as clinical patient selection criteria. With the evolvement and development
of different technologies designed specifically for the treatment of breast cancer alone,
another important additional aspect that is crucial to the implementation of a
comprehensive (APBI) accelerated partial breast irradiation program is a robust quality
assurance program that confirms that the treatment target is appropriately defined and
dosimetrically covered within the intended prescription dose (Wazer et al., 2006), and that
the organs at risk are not irradiated above widely accepted and protocol imposed tolerance
values (NSABP Protocol B-39/RTOG 0413 Protocol, 2007), when also confronted and
confirmed with values obtained by the application of novel computational algorithms such
as Acuros or Monte-Carlo (Graf et al ., 2011).
Our preli
minary studies ( Morcovescu et al ., 2009; Morcovescu & Morton, 2009)
indicated that the SAVI device’s dosimetric performance is superior to that of balloon type
APBI device
s, so we further attempted to comprehensively evaluate the dosimetric
performance of SAVI type devices.
6.2. Materials and Methods
The main body of our work consists on a comprehensive dosimetric analysis of
extensive clinical data, collected for all four different size SAVI devices (SAVI6-1mini,
SAVI6-1, SAVI8-1 and SAVI10-1). Our study is structured and focused on two subsets of
data: 1) a
major pool of data collected at a multi-institutional level, that presents the
dosimetric analysis of the entire range of SAVI applicators, and a 2) minor pool, a subset
of the entire data, considering patients implanted with the smallest of the SAVI devices,
the SAVI6-1mini device, in our clinic only. The total number of patients included in our
multi-institutional pool study is 817. There were 14 different participating institutions
75
involved in the multi-institutional study, each providing data for all four SAVI device
models. The subset study presented on the SAVImini device is a single-institution study of
plans created for 121 patients, treated over the span of 5 years, from 2009 to 2014.
The dosimetric
parameters reported in this study include: cavity volume, volume of
the defined treatment region (PTV_EVAL), V90(%), V95(%), V100(%), V150(cc),
V200(cc), skin distance (minimum distance from the lumpectomy cavity wall to the skin),
chest wall and ipsilateral lung distances (mm), and the maximum doses to critical
structures (skin and chest-wall). Conformity Indexes (CI), related to reported air/seroma
and invagination volumes, were also evaluated, and shown in tables from Table 5 to Table
29. Our dosimetric coverage criteria for this study was V90>90%, V150<50 cm3,
V200<20 cm3. Additional constraints are placed to try limiting the chest wall and skin
doses to 100%. All dosimetric data, both the major pool and minor subset, was stratified
using 5 mm skin-distance (SD) intervals, therefore differentiating among cases with major
or no PTV volume
reduction.
We have also evaluated and reported the volumes of the cavity, of the PTV and of
the PTV_EVAL, and evaluated the volume reduction of the PTV. For this we proposed
and used this equation for calculating PTV-VR:
PTV -VR (%) = (PTV volume – PTV_EVAL volume) / PTV volume (6.1)
The Task Group TG43 formalism was employed on all dosimetric evaluations, and
both TG43 and ACUROS formalisms used on the SAVI6-1mini device study only.
76
TG43 V90 V95 V100 V150 V200 V cav V PTV V PTVe Max
Skin D Min
Skin Max
CW D Min
CW
% % % cc cc cc cc cc cGy mm cGy mm
n = 762.0 637.0 768.0 665.0 758.0 514.0 532.0 693.0 687.0 470.0 419.0 317.0
MEAN 96.5 93.7 89.9 28.6 14.0 28.7 90.9 66.9 2884.3 12.1 2565.0 15.8
MEDIAN 97.5 94.8 90.9 26.7 13.8 24.6 78.8 62.0 2954.0 10.0 2620.0 13.0
MINIMUM 75.2 70.9 65.7 8.2 3.7 2.8 14.6 14.2 120.0 0.5 217.6 0.0
MAXIMUM 100.0 100.0 100.0 70.1 38.7 78.4 202.8 160.1 7854.0 76.4 6730.0 93.5
STANDARD
DEV 3.2 4.5 5.7 9.1 4.1 18.0 39.5 24.7 942.8 9.5 1152.5 13.8
Table 5. Full data, for all SAVI devices (above) Table 6. Sorted Data for the SAVI10-1 device (below)
TG43 V90 V95 V100 V150 V200 V cav V PTV V PTVe Max
Skin D Min
Skin Max
CW D Min
CW
% % % cc cc cc cc cc cGy mm cGy mm
n = 115.0 80.0 123.0 82.0 109.0 96.0 89.0 101.0 103.0 84.0 81.0 68.0
MEAN 97.0 94.6 90.7 41.7 17.5 57.6 148.3 105.5 2786.3 12.9 2538.0 15.8
MEDIAN 97.8 95.2 91.1 42.4 17.6 58.6 155.0 107.6 2850.0 10.4 2689.4 13.2
MINIMUM 90.3 82.8 75.6 19.2 6.3 29.4 49.7 49.7 500.0 1.0 250.0 1.0
MAXIMUM 100.0 100.0 99.3 70.1 36.5 78.3 202.8 160.1 6543.0 50.0 4284.0 93.5
STANDARD
DEV 2.6 3.8 4.8 6.9 3.8 9.4 31.8 18.1 886.0 10.7 979.7 15.1
77
TG43 V90 V95 V100 V150 V200 V cav V PTV V PTVe Max
Skin D Min
Skin Max
CW D Min
CW
% % % cc cc cc cc cc cGy mm cGy mm
n = 193.0 148.0 189.0 158.0 185.0 152.0 146.0 172.0 169.0 123.0 119.0 84.0
MEAN 96.6 93.7 89.5 33.4 15.2 34.5 107.6 79.9 2853.3 11.5 2720.4 14.9
MEDIAN 97.4 94.9 90.9 34.1 15.4 33.2 110.9 82.4 2850.0 9.2 2740.0 12.0
MINIMUM 79.3 79.2 68.2 19.0 5.2 7.0 30.2 30.2 315.3 0.5 390.0 0.0
MAXIMUM 100.0 99.8 99.3 49.9 26.8 78.4 160.8 121.5 5694.0 76.4 6400.0 66.2
STANDARD
DEV 3.1 4.7 6.0 6.6 3.4 7.7 25.3 15.8 819.6 9.7 1104.4 12.6
Table 7. Sorted Data for the SAVI8-1 device (above) Table 8. Sorted Data for the SAVI6-1 device (below)
TG43 V90 V95 V100 V150 V200 V cav V PTV V PTVe Max
Skin D Min
Skin Max
CW D Min
CW
% % % cc cc cc cc cc cGy mm cGy mm
n = 321.0 279.0 322.0 297.0 324.0 181.0 187.0 290.0 291.0 159.0 151.0 111.0
MEAN 95.9 92.9 89.1 24.6 12.8 16.7 71.2 55.0 2951.8 12.3 2551.4 15.0
MEDIAN 97.1 94.0 90.0 23.9 12.3 15.9 70.8 55.5 2992.0 10.0 2550.0 11.0
MINIMUM 75.2 70.9 65.7 8.2 3.7 2.8 14.6 22.5 450.0 2.0 400.0 0.0
MAXIMUM 100.0 100.0 100.0 58.1 38.7 50.4 167.0 113.7 7854.0 56.3 6730.0 79.6
STANDARD
DEV 3.5 4.7 5.7 6.8 4.0 6.9 19.7 13.5 992.8 8.9 1253.0 13.0
78
TG43 V90 V95 V100 V150 V200 V cav V PTV V PTVe Max
Skin D Min
Skin Max
CW D Min
CW
% % % cc cc cc cc cc cGy mm cGy mm
n = 128.0 126.0 129.0 123.0 135.0 81.0 107.0 126.0 121.0 104.0 68.0 54.0
MEAN 97.1 94.9 91.6 23.2 12.5 10.5 53.9 45.1 2860.4 11.7 2355.6 18.9
MEDIAN 98.2 95.7 92.7 22.7 12.2 10.0 52.9 46.3 3033.0 10.0 2459.0 14.0
MINIMUM 85.3 79.6 74.0 10.5 4.5 5.0 25.4 14.2 329.8 1.0 217.6 0.0
MAXIMUM 100.0 100.0 99.8 52.6 23.0 24.1 99.1 75.1 5359. 0 53.4 5650.0 71.2
STANDARD
DEV 2.7 3.9 5.2 5.7 3.0 3.3 10.1 9.3 960.1 9.3 1178.8 15.3
Table 9. Sorted Data for the SAVI6-1mini device (above) Table 10. Sorted Data for all devices, SD < 3mm (below)
TG43 V90 V95 V100 V150 V200 V cav V PTV V PTVe Max
Skin D Min
Skin Max
CW D Min
CW
% % % cc cc cc cc cc cGy mm cGy mm
n = 38.0 33.0 40.0 26.0 37.0 28.0 40.0 36.0 43.0 44.0 31.0 32.0
MEAN 94.6 92.7 88.3 25.3 12.7 28.7 80.5 55.8 3221.4 2.3 2916.0 8.2
MEDIAN 94.2 91.5 88.1 23.9 12.0 29.3 64.7 47.4 3200.0 2.6 2856.0 7.1
MINIMUM 77.0 79.2 65.7 14.4 5.2 5.3 15.9 20.8 2274.6 0.5 1170.0 0.0
MAXIMUM 100.0 98.7 97.9 42.5 19.9 68.5 160.1 105.1 4617.2 3.0 6730.0 18.0
STANDARD
DEV 4.3 4.3 6.6 7.8 3.9 18.9 38.4 21.9 517.5 0.7 1253.6 5.5
79
TG43 V90 V95 V100 V150 V200 V cav V PTV V PTVe Max
Skin D Min
Skin Max
CW D Min
CW
% % % cc cc cc cc cc cGy mm cGy mm
n = 56.0 51.0 61.0 45.0 55.0 39.0 51.0 48.0 58.0 62.0 38.0 35.0
MEAN 96.6 93.8 90.7 28.4 14.3 28.5 86.3 65.8 3083.7 4.4 2758.9 13.5
MEDIAN 97.0 94.1 90.9 26.5 13.6 24.1 76.2 58.9 3128.0 4.1 3018.0 11.0
MINIMUM 89.8 85.2 79.0 12.4 4.5 5.8 25.4 25.4 329.8 3.3 873.0 0.0
MAXIMUM 99.9 99.3 99.3 48.5 23.0 68.9 177.2 119.5 5359.0 5.0 4570.0 58.0
STANDARD
DEV 2.2 3.1 4.6 8.5 3.8 17.0 36.8 24.9 651.5 0.5 933.6 12.1
Table 11. Sorted data, all devices, 3mm < SD < 5mm (above) Table 12. Sorted data, all devices, 5mm< SD < 7mm (below)
TG43 V90 V95 V100 V150 V200 V cav V PTV V PTVe Max
Skin D Min
Skin Max
CW D Min
CW
% % % cc cc cc cc cc cGy mm cGy mm
n = 50.0 44.0 47.0 36.0 49.0 33.0 40.0 47.0 48.0 51.0 36.0 35.0
MEAN 96.4 94.4 90.0 28.0 13.8 28.5 83.2 64.0 3058.1 6.4 2456.8 16.3
MEDIAN 97.5 95.9 90.7 26.0 13.7 18.7 68.8 57.2 3055.0 6.4 2285.0 14.5
MINIMUM 90.0 84.4 78.8 8.2 3.7 8.1 31.8 23.2 1990.0 5.2 445.3 1.9
MAXIM UM 99.9 99.4 98.2 42.8 19.9 77.9 182.9 123.7 4134.0 7.0 5000.0 53.2
STANDARD
DEV 2.9 3.8 5.4 8.7 3.4 19.6 37.4 24.4 432.9 0.5 1079.7 12.4
80
TG43 V90 V95 V100 V150 V200 V cav V PTV V PTVe Max
Skin D Min
Skin Max
CW D Min
CW
% % % cc cc cc cc cc cGy mm cGy mm
n = 295.0 245.0 303.0 237.0 293.0 216.0 218.0 265.0 260.0 313.0 200.0 212.0
MEAN 96.9 94.9 91.1 30.1 14.9 29.5 86.5 70.2 2465.2 15.9 2569.4 17.4
MEDIAN 97.9 95.8 91.6 29.2 14.9 24.3 78.6 64.7 2600.3 13.0 2616.1 14.0
MINIMUM 79.3 73.0 68.2 11.6 4.6 6.6 14.6 14.2 340.0 7.1 217.6 0.0
MAXIMUM 100.0 100.0 99.8 52.6 35.7 78.4 190.3 160.1 4180.0 76.4 6400.0 93.5
STANDARD
DEV 3.1 4.3 5.5 8.0 3.6 18.6 35.9 24.9 743.3 9.5 1199.7 14.8
Table 13. Sorted Data, all devices, SD > 7mm (above) Table 14. SAVImini full data TG43 (below)
TG43 V90 V95 V100 V150 V200 V cav V PTV V
PTVe Max
Skin D Min
Skin Max
CW D Min
CW
% % % cc cc cc cc cc cGy mm cGy mm
n = 72 72 72 72 72 72 72 72 72 72 72 71
MEAN 98.53 97.38 95.34 24.44 14.1 8.3 49.5 43.2 2595.4 11.9 3220.1 15.7
MEDIAN 99.45 98.30 96.00 25.85 14.7 8.3 49.6 47.1 2893.5 10.4 3187.0 12.0
MINIMUM 91.60 88.10 84.80 10.90 6.5 6.2 25.7 14.2 329.8 1.0 438.0 0.3
MAXIMUM 100.00 100.00 99.80 31.30 20.0 10.4 57.9 53.9 3594.0 53.4 9064.0 61.0
STANDARD
DEV 1.92 2.76 3.42 4.72 2.91 0.90 3.82 8.96 714.93 8.54 1684.5 12.04
81
ACUROS V90 V95 V100 V150 V200 V
air/seroma V
invag VR Ipsi
Lung d Max
Skin D Max
CW D
% % % cc cc cc cc cc mm cGy cGy
n = 71 71 71 71 71 71 71 72 71 71 71
MEAN 98.03 96.53 94.11 23.88 13.80 2.02 0.40 0.13 20.73 2489.2 3129.4
MEDIAN 98.90 97.10 94.60 24.80 14.20 1.10 0.00 0.07 17.00 2730.0 3080.0
MINIMUM 89.90 86.30 82.20 10.40 6.20 0.00 0.00 0.00 5.30 905.0 403.0
MAXIMUM 100.00 100.00 99.70 49.50 19.00 19.10 4.00 0.59 66.00 3371.0 9697.0
STANDARD
DEV 2.28 3.10 3.86 5.43 2.78 3.26 0.95 0.16 12.04 643.2 1745.1
Table 15. SAVImini full data Acuros (above) Table 16. SAVImini data, SD < 5mm TG43 (below)
TG43 V90 V95 V100 V150 V200 V cav V PTV V
PTVe Max
Skin D Min
Skin Max
CW D Min
CW
% % % cc cc cc cc cc cGy mm cGy mm
n = 13 13 13 13 13 13 13 13 13 13 13 12
MEAN 96.12 93.97 91.48 17.45 10.0 8.1 47.7 29.7 3262.3 2.9 3290.0 18.3
MEDIAN 97.10 95.60 93.60 18.10 10.2 8.1 48.6 28.6 3298.0 3.0 3958.0 10.1
MINIMUM 91.60 88.10 84.80 10.90 6.5 7.1 41.5 20.8 2910.0 1.0 438.0 2.0
MAXIMUM 98.70 97.20 95.70 24.80 12.3 9.6 51.0 38.5 3594.0 4.3 6200.0 61.0
STANDARD
DEV 2.39 3.05 3.63 3.82 1.81 0.72 2.66 5.67 167.92 1.13 1953.8 17.58
82
ACUROS V90 V95 V100 V150 V200 V
air/seroma V
invag VR Ipsi
Lung d Max
Skin D Max
CW D
% % % cc cc cc cc cc mm cGy cGy
n = 12 12 12 12 12 12 12 13 12 12 12
MEAN 95.27 92.86 89.96 16.60 9.90 1.46 0.08 0.37 23.31 3119.3 3216.5
MEDIAN 96.60 94.30 91.40 16.85 10.40 0.70 0.00 0.37 15.05 3173.0 3656.5
MINIMUM 89.90 86.30 82.20 10.40 6.20 0.00 0.00 0.21 7.00 2754.0 403.0
MAXIMUM 98.20 96.60 94.90 21.30 12.00 4.60 1.00 0.59 66.00 3371.0 6200.0
STANDARD
DEV 2.84 3.48 4.07 3.50 1.95 1.71 0.29 0.12 17.58 177.4 2059.2
Table 17. SAVImini data, SD < 5mm Acuros (above) Table 18. SAVImini data, 5mm<SD< 10mm TG43 (below)
TG43 V90 V95 V100 V150 V200 V cav V PTV V
PTVe Max
Skin D Min
Skin Max
CW D Min
CW
% % % cc cc cc cc cc cGy mm cGy mm
n = 20 20 20 20 20 20 20 20 20 20 20 20
MEAN 98.28 96.98 95.03 23.65 13.7 8.4 50.5 42.2 3052.0 7.0 3523.4 12.6
MEDIAN 98.40 96.90 95.10 23.40 13.4 8.2 49.7 42.8 3115.0 7.0 3723.0 11.2
MINIMUM 96.20 94.30 92.30 17.10 10.2 6.4 45.7 30.8 1816.0 5.0 1145.0 3.1
MAXIMUM 100.00 99.90 98.20 28.40 18.3 10.1 57.9 50.7 3325.0 9.5 7807.0 30.0
STANDARD
DEV 1.09 1.37 1.43 2.85 2.00 0.93 2.67 4.93 328.27 1.27 1531.7 8.22
83
ACUROS V90 V95 V100 V150 V200 V
air/seroma V
invag VR Ipsi
Lung d Max
Skin D Max
CW D
% % % cc cc cc cc cc mm cGy cGy
n = 20 20 20 20 20 20 20 20 20 20 20
MEAN 97.59 95.89 93.29 22.60 13.18 1.72 0.50 0.17 17.64 2867.7 3402.0
MEDIAN 97.40 95.70 93.45 22.15 12.90 0.80 0.00 0.16 16.20 2949.5 3492.0
MINIMUM 95.60 93.80 90.10 16.60 9.80 0.00 0.00 0.00 8.10 1726.0 1083.0
MAXIMUM 100.00 99.70 98.40 27.60 17.80 6.90 3.60 0.33 35.00 3177.0 7689.0
STAN DARD
DEV 1.18 1.43 1.93 2.71 2.01 2.07 1.13 0.08 8.22 312.5 1609.4
Table 19. SAVImini data for 5mm<SD<10mm ACUROS (above) Table 20. SAVImini data for 10mm<SD<15mm TG43 (below)
TG43 V90 V95 V100 V150 V200 V cav V PTV V
PTVe Max
Skin D Min
Skin Max
CW D Min
CW
% % % cc cc cc cc cc cGy mm cGy mm
n = 20 20 20 20 20 20 20 20 20 20 20 20
MEAN 99.28 98.47 96.70 26.98 15.9 8.1 50.1 48.0 2655.4 12.5 3161.2 16.5
MEDIAN 99.80 99.10 97.45 26.95 15.6 8.3 50.0 48.0 2694.5 12.8 3080.0 12.3
MINIMUM 94.00 91.00 87.80 16.90 9.6 6.2 45.5 35.1 1639.0 10.0 634.0 0.3
MAXIMUM 100.00 100.00 99.00 31.30 20.0 10.4 57.6 53.9 3108.0 14.3 9064.0 40.0
STANDARD
DEV 1.37 2.00 2.52 2.95 2.18 1.07 2.51 3.59 357.39 1.35 1965.3 11.27
84
ACUROS V90 V95 V100 V150 V200 V
air/seroma V
invag VR Ipsi
Lung d Max
Skin D Max
CW D
% % % cc cc cc cc cc mm cGy cGy
n = 20 20 20 20 20 20 20 20 20 20 20
MEAN 98.80 97.55 95.27 25.88 15.41 2.05 0.79 0.04 21.49 2530.7 3102.4
MEDIAN 99.40 98.10 95.85 26.10 15.10 0.45 0.00 0.02 17.25 2548.5 2947.0
MIN IMUM 91.70 88.40 84.80 16.10 9.80 0.00 0.00 0.00 5.30 1546.0 591.0
MAXIMUM 100.00 100.00 99.70 29.50 19.00 19.10 4.00 0.29 45.00 3058.0 9697.0
STANDARD
DEV 1.83 2.52 3.21 2.83 2.01 4.48 1.28 0.07 11.27 372.7 2070.2
Table 21. SAVImini data, 10mm<SD<15mm ACUROS (above) Table 22. SAVImini data, 15mm<SD<20mm TG43 (below)
TG43 V90 V95 V100 V150 V200 V cav V PTV V
PTVe Max
Skin D Min
Skin Max
CW D Min
CW
% % % cc cc cc cc cc cGy mm cGy mm
n = 8 8 8 8 8 8 8 8 8 8 8 8
MEAN 99.95 99.51 97.96 27.79 15.9 8.7 47.9 46.1 2085.4 17.3 2802.4 19.5
MEDIAN 100.00 99.60 97.55 28.10 15.9 8.7 50.3 49.8 2024.5 17.6 3176.0 12.2
MINIMUM 99.80 99.00 97.30 25.70 14.2 7.1 25.7 14.2 1724.0 15.2 499.0 4.5
MAXIMUM 100.00 99.90 99.00 29.50 18.0 10.1 53.1 52.9 2666.0 19.7 4740.0 53.3
STANDARD
DEV 0.08 0.31 0.70 1.52 1.17 0.96 9.07 12.96 277.54 1.69 1601.0 17.91
85
ACUROS V90 V95 V100 V150 V200 V
air/seroma V
invag VR Ipsi
Lung d Max
Skin D Max
CW D
% % % cc cc cc cc cc mm cGy cGy
n = 8 8 8 8 8 8 8 8 8 8 8
MEAN 99.78 98.84 96.5 6 26.88 15.45 1.44 0.18 0.06 24.46 1965.1 2686.6
MEDIAN 99.80 98.70 96.10 27.15 15.50 1.30 0.00 0.00 17.15 1884.0 3084.5
MINIMUM 99.50 98.00 94.70 24.60 13.50 0.00 0.00 0.00 9.50 1634.0 469.0
MAXIMUM 100.00 100.00 99.20 28.50 17.60 3.70 1.00 0.45 58.30 2543.0 4439.0
STANDARD
DEV 0.23 0.76 1.80 1.53 1.27 1.16 0.36 0.16 17.91 274.8 1536.0
Table 23. SAVImini data, 15mm<SD<20mm ACUROS (above) Table 24. SAVImini data, 20mm<SD<25mm TG43 (below)
TG43 V90 V95 V100 V150 V200 V cav V PTV V
PTVe Max
Skin D Min
Skin Max
CW D Min
CW
% % % cc cc cc cc cc cGy mm cGy mm
n = 7 7 7 7 7 7 7 7 7 7 7 7
MEAN 99.20 98.27 95.34 27.00 15.2 8.6 50.6 50.4 1629.3 21.8 3234.3 13.8
MEDIAN 100.00 99.90 97.30 28.90 16.8 8.3 50.9 50.9 1703.0 21.5 3980.0 10.5
MINIMUM 94.90 90.00 84.90 19.00 9.5 7.8 48.6 47.8 972.0 20.0 1408.0 7.5
MAXIMUM 100.00 100.00 99.80 30.90 17.7 9.8 52.5 52.5 1887.0 24.4 4745.0 23.1
STANDARD
DEV 1.90 3.68 5.69 4.26 2.94 0.77 1.53 1.73 298.49 1.89 1348.7 6.47
86
ACUROS V90 V95 V100 V150 V200 V
air/seroma V
invag VR Ipsi
Lung d Max
Skin D Max
CW D
% % % cc cc cc cc cc mm cGy cGy
n = 7 7 7 7 7 7 7 7 7 7 7
MEAN 98.93 97.79 95.73 29.23 14.86 1.91 0.00 0.00 18.80 1534.4 3139.6
MEDIAN 100.00 99.70 98.20 27.90 16.40 1.90 0.00 0.00 15.50 1588.0 3885.0
MINIMUM 93.30 88.40 82.70 19.30 9.50 0.00 0.00 0.00 12.50 905.0 1355.0
MAXIMUM 100.00 100.00 99.50 49.50 17.00 3.90 0.00 0.02 28.10 1800.0 4619.0
STANDARD
DEV 2.49 4.21 6.03 9.64 2.74 1.55 0.00 0.01 6.47 288.9 1337.2
Table 25. SAVImini data, 20mm<SD<25mm ACUROS (above) Table 26. SAVImini data, SD>25mm TG43 (below)
TG43 V90 V95 V100 V150 V200 V cav V PTV V
PTVe Max
Skin D Min
Skin Max
CW D Min
CW
% % % cc cc cc cc cc cGy mm cGy mm
n = 4 4 4 4 4 4 4 4 4 4 4 4
MEAN 99.83 99.30 97.35 27.33 15.6 8.4 49.5 49.3 1299 .0 35.0 2582.1 15.5
MEDIAN 99.80 99.25 98.20 27.90 16.1 8.4 48.9 48.7 1195.5 30.1 2345.5 16.3
MINIMUM 99.70 99.00 94.50 24.20 13.4 7.8 48.0 47.7 989.0 26.2 1472.2 6.4
MAXIMUM 100.00 99.70 98.50 29.30 16.8 8.8 52.1 52.1 1816.0 53.4 4165.0 23.2
STANDARD
DEV 0.15 0.36 1.91 2.43 1.58 0.42 1.83 2.01 367.25 12.47 1133.3 6.92
87
ACUROS V90 V95 V100 V150 V200 V
air/seroma V
invag VR Ipsi
Lung d Max
Skin D Max
CW D
% % % cc cc cc cc cc mm cGy cGy
n = 4 4 4 4 4 4 4 4 4 4 4
MEAN 99.68 98.93 97.18 26.70 15.33 6.40 0.00 0.00 20.53 1218.0 2508.5
MEDIAN 99.65 98.90 97.30 27.20 15.75 4.15 0.00 0.00 21.25 1117.0 2251.5
MINIMUM 99.50 98.50 96.00 23.80 13.30 1.30 0.00 0.00 11.40 918.0 1409.0
MAXIMUM 99.90 99.40 98.10 28.60 16.50 16.00 0.00 0.02 28.20 1720.0 4122.0
STANDARD
DEV 0.17 0.40 0.87 2.23 1.47 6.89 0.00 0.01 6.92 357.8 1146.8
Table 27. SAVImini data, SD>25mm ACUROS (above) Table 28. Stratified dosimetry for 5mm SD grouping interval (below)
Skin
Distance #
patients Max Skin
Dose (Gy) PTV
reduction
(%) CW Dos e (Gy)
mm TG43 Acuros TG43 Acuros
<< 55 13 35.94 33.71 37.0±12.0 32.9±19.5 32.2±20.6
55 << ss..dd..
<<1100 20 33.25 31.77 17.0±8.0 35.2±15.3 34.0±16.1
1100<<ss..dd..<<1155 20 31.1 30.6 4.0±7.0 31.6±19.7 31.0±20.7
1155<<ss..dd..<<2200 8 26.66 25.43 6.0±16.0 28.0±16.0 26.9±15.4
2200<<ss..dd<<2255 7 18.87 18 0.0±1.0 32.3±13.5 31.4±13.4
ss..dd >> 2255 4 18.16 17.2 0.0±1.0 25.1±11.5 24.4 ±8.8
88
Table 2 9. SAVImini centralized data (TG43 and ACUROS)
Skin
Distance Max Skin Dose
(Gy) PTV_EVAL Normal Tissue PTV
reduction†
(%) CW Dose (Gy)
mm #
patients TG43 Acuros V90(%) V95(%) V100(%) V150(cc) V200(cc) TG43 Acuros
<< 55 13 35.94 33.71 95.3±2.8 92.9±3.5 90.0±4.1 17.5±3.8 10.0±1.8 37.0±12.0 32.9±19.5 32.2±20.6
55 <<SSBB<<1100 20 33.25 31.77 97.6±1.2 95.9±1.4 93.3±1.9 23.6±2.9 13.7±2.0 17.0±8.0 35.2±15.3 34.0±16.1
1100<<SSBB<<1155 20 31.1 30.6 98.8±1.8 97.6±2.5 95.3±3.2 27.0±3.0 15.9±2.2 4.0±7.0 31.6±19.7 31.0±20.7
1155<<SSBB<<2200 8 26.66 25.43 99.8±0.2 98.8±0.8 96.6±1.8 27.8±1.5 15.5±1.3 6.0±16.0 28.0±16.0 26.9±15.4
2200<<SSBB<<2255 7 18.87 18 98.9±1.9 97.8±3.7 95.7±6.0 27.0±4.3 15.2±2.9 0.0±1.0 32.3±13.5 31.4±13.4
SSBB>>2255 4 18.16 17.2 99.7±0.2 98.9±0.4 97.2±0.9 27.3±2.4 15.6±1.6 0.0±1.0 25.1±11.5 24.4 ±8.8
89
6.3. Results and Discussions. Original contributions.
The tables from Table 5 to Table 29 present the data for both the mul ti-institutional
and single-institution studies. The bulk data was stratified based on the distance from the
device to the skin, in increments of 5mm. Our dosimetric coverage criteria for this study
was V90>90%, V150<50 cm3, V200<20 cm3. Additional constraints are placed to try
limiting the chest wall and skin doses to 100%. All dosimetric data was stratified using 5
mm skin-bridge intervals, therefore differentiating among cases with major or no PTV
volume reduction.
6.3.1 Multi-institutional study on all SAVI type devices
The lumpectomy cavity volumes averaged 10.5±3.3 cm3 for the 6-1SAVImini
device up to 57.6.5±9.4 cm3 for the largest 10-1 SAVI applicator.
PTV_EVAL volumes averaged 45.1±9.3 cm3 for the smallest applicator to
105.5±18.1 cm3 for
the largest. V90 values averaged 96.5±13.2% of the PTV_EVAL
volume a
cross all applicator sizes, which is well within the criteria imposed by the
NSABP B-39/RTOG 0413 protocol. V95 averaged 93.7±4.5% and V100 averaged
89.9±5.7%. V150 ave
raged 23.2±5.7 cm3 for the smallest device, and 41.7±6.9 cm3 for the
large
st. V200 averages ranged from 12.5±3.0 cm3 for the smallest device, to 17.5±3.8 cm3
for the largest.
The
Mean, Media
n, Maximum, Minimum and SD values for V90, V95, V100,
V150 and V200 of PTV_EVAL are reported in Table 30. Similar data for Cavity, PTV,
and PTV_Eval Volumes
is reported in Table 31.
Skin spacing v
aried widely with 460 reported values ranging from 0.5 mm to 76.4
mm (12.1 ± 9.5mm). Skin spacing in these patients were: ≤3 mm (9.4%), 3-5 mm
(13.2%), 5-7 mm (10.9%), >7 mm (66.6%). The minimum skin bridge for these patients
averaged 12.1 mm, although each model was used in patients with ≤3.0 mm (44, total).
The maximum
skin dose (n=687) was 85%±28% of prescription (mean ± SD).
From smallest to largest models, the values were: 82%±26%, 84%±24%, 87%±29%,
84%±28%.
90
Chestwall bridge varied widely (n=317), ranging from 0.0 mm to 93.5 mm (15.8 ±
13.8mm), and was similar regardless of model. For each applicator size, the maximum
dose to the chest wall was 75% ± 34% of the prescription dose.
Table 30. Multi-institutional, all SAVI type devices – values for V90, V95,
V100, V150 and V200 of PT
V_EVAL
Parameter V90 V95 V100 V150 V200
(units) % % % cc cc
MEAN 96.5 93.7 89.9 28.6 14.0
MEDIAN 97.5 94.8 90.9 26.7 13.8
MINIMUM 75.2 70.9 65.7 8.2 3.7
MAXIMUM 100.0 100.0 100.0 70.1 38.7
SD 3.2 4.5 5.7 9.1 4.1
Table 31. Multi-institutional, all SAVI type devices – values for Cavity, PTV,
and PTV_Eval Volu
mes
Parameter V(cavity) V(PTV) V(PTV_Eval)
(units) cc cc cc
MEAN 28.7 90.9 66.9
MEDIAN 24.6 78.8 62.0
MINIMUM 2.8 14.6 14.2
MAXIMUM 78.4 202.8 160.1
6.3.2 Single institution study results, on SAVI6-1mini device – TG43
The lumpe
ctomy cavity volumes for the SAVI6-1mini device, the device of
interest for
our initial study on this SAVI device subtype ( Morcovescu et. al , 2009),
averaged 8.3±0.9 cm3.
PTV_EVAL and PTV volumes averaged 43.2±9.0 cm3 and 49.5 ±3.8 cm3,
respectively. V90 values averaged 98.5±1.9% of the PTV_EVAL volume, which is again
91
well within the criteria imposed by the NSABP B-39/RTOG 0413 protocol. V95 averaged
97.4±2.8% and V100 averaged 95.3±3.4%. V150 averaged 24.4±4.7 cm3 while V200
avera
ged 14.1±2.9 cm3.
PTV reduction mounted up to 37.0±12.0% for the cases where the skin distance
(SD) was
< 5 mm, especially where combined with reduced Chest Wall bridges (CWB).
This can result in dramatic drops of the CI (conformity index) values for PTV_EVAL,
where air/seroma is present, down to 61.1%. Though, across the entire cohort, CI values
averaged 96.6±5.7 %.
Skin and CW
sculpting of PTV is always employed when creating PTV_EVAL
structures. The PTV volume reduction PTV VR averaged 1 3.0±16.0%, with min and max
values of
0.0% (no reduction) and 59.0% (when both SB and CWB were < 5mm)
respectively.
Thirteen (13) patients had a skin bridge (SD) of less than 5 mm. For these patients,
the V90 (n=13)
was 96.1±2.8% (mean±standard deviation). Chest wall bridge (CWB)
varied widely
, ranging from 0.3 mm to 61.0 mm (15.2±11.7 mm).The maximum dose to
the chest wall, over the entire cohort of patients, was 94.5±49.5% of the prescription dose.
Dosimetric data for
a later study of ours ( Morcovescu et al., 2014), which included 121
patients, is shown in Table 32. No major variation from the numbers previously published
is observed.
The maximum skin dose for the patients where the skin distance SD was less than
5 mm was 96.0±4.9%. Chest Wall bridge varied widely, ranging from 0.3 mm to 61.0 mm
(15.7 ± 12.0m
m). The maximum dose to the chest wall, over the entire cohort of patients,
was 94.5% ± 49.5%.
The V150 “hotspots” averaged 24.4±4.7 cm3, while V200 averaged 14.1±2.9 cm3.
The a
ver
age minimum skin distance was 13.5 mm, but the applicator was used in patients
where the skin bridge was as low as 1mm. The average maximum skin dose (MSD) was
72.8% of the prescription dose. The average minimum CWB was 15.2 mm, with the
shortest of less than 0.3mm, and the average maximum dose to the chest wall of 90.5% of
the prescription dose.
92
Table 32. Stratified dosimetry for 5mm skin-distance grouping interval
Skin Bridge
(mm) # Patients Max Skin
Dose (Gy) V90 (%) V200 (cm3) PTV VR (%)
< 5 16 35.94 96.3±2.3 10.1±1.7 36.0±12.0
5 <SB <10 34 33.25 98.4±1.2 13.4±1.7 16.0±7. 0
10 <SB <15 31 31.78 99.3±1.2 16.0±1.9 3.0±6.0
15 <SB <20 14 26.66 99.9±0.2 15.7±2.2 4.0±12.0
20 <SB <25 16 18.87 99.6±2.5 15.6±2.1 1.0±3.0
SB > 25 10 18.16 99.6±0.4 16.4±2.3 0.0±1.0
The PTV-VR values are largest for the cases with reduced skin bridges, where
there is a significant reduction of the volume of PTV_EVAL compared to PTV. Dose
coverage in those marginal cases was still excellent, with average V90 of 96.3%.
The Mean,
Median, Maximum, Minimum and SD values for V90, V95, V100, V150 and
V200 of PTV_EVAL are reported in Table 33. Similar data for Cavity, PTV, and
PTV_Eval Volumes is reporte
d in Table 34.
Table 33. Sing
le-institution, SAVI6-1mini type device – values for V90, V95, V100,
V150 and V200 of PTV_EVA
L
Parameter V90 V95 V100 V150 V200
(units) % % % cc cc
MEAN 98.0 96.5 94.1 24.4 14.1
MEDIAN 98.9 97.1 94.6 25.9 14.7
MINIMUM 89.9 86.3 82.2 10.9 6.5
MAXIMUM 100.0 100.0 99.7 31.3 20.0
SD 2.3 3.1 3.9 4.7 2.9
93
Table 34. Single-institution, SAVI6-1mini type device – values for Cavity,
PTV, and
PTV_Eval
Volumes
Parameter V(cavity) V(PTV) V(PTV_Eval)
(units) cc cc cc
MEAN 8.3 49.5 43.2
MEDIAN 8.3 49.6 47.1
MINIMUM 6.2 25.7 14.2
MAXIMUM 10.4 57.9 53.9
SD 0.9 3.8 9.0
The PTV to PTV_EVAL volume reduction may be large for SB < 5mm
(37.0±12.0), but plans still met all other dosimetric criteria. Less PTV reduction, 17.0±8.0
(5mm<s.d.<10mm), and 4.0±7.0 (10mm<s.d<15mm) results in better dose
conformity/critical structure sparing.
6.3.3 Single institution study results, on SAVI6-1mini devi ce – ACUROS
When using the ACUROS formalism, our comparison study ( Morcovescu et. al .,
2012) revealed the following results.
V90 values averaged 98.0±2.3 % of the PTV_EVAL volume, V95 averaged 96.5
±3.1% and V100
averaged 94.1±3.9%. V150 averaged 23.9±5.4 cm3 while V200 averaged
13.8±2.8 cm3. The values indicate a small but quantifiable degradation of the PTV_EVAL
coverage compared with when employing the TG43 protocol for calculations.
Dosimetric data f
or all 72 patients is also shown in Table 13.
The maximum
skin dose for the patients where the skin distance SD was less than
5 mm was 91.7±5.2%.
The maxim
um dose to the chest wall, over the entire cohort of patients, was 92.0%
±51.3% of the prescription dose.
Stratified dosimetry for all 72 patients is centralized in Table 35.
94
Table 35. Stratified dosimetry for 5mm skin-distance grouping interval
Skin Bridge
(mm) # Patients Max Skin
Dose (Gy) V90 (%) V200 (cm3) Max CW
Dose (Gy)
< 5 13 33.71 95.3±2.8 9.9±2.0 32.2±20.6
5 <SB <10 20 31.77 97.6±1.2 13.2±2.0 34.0±16.1
10 <SB <15 20 30.6 98.8±1.8 15.4±2.0 31.0±20.7
15 <SB <20 8 25.43 99.8±0.2 15.5±1.3 26.9±15.4
20 <SB <25 7 18 98.9±2.5 14.9±2.7 31.4±13.4
SB > 25 4 17.2 99.7±0.2 15.3±1.5 24.4±8.8
The SAVI6-1mini strut-based device is an excellent APBI solution for patients
with reduced skin and/or rib bridges, and it accommodated volumes unfeasible for other
types of single-entry brachytherapy devices. The Acuros data indicates a minor
degradation of the RTOG 0413 reference V90 coverage of the PTV_EVAL (0.5% on
average) while revealing that TG43 slightly overestimates the average dose values for skin
(by 4.1%) and for chest-wall (by 2.6%).
6.3.4 Overall Results and Discussion.
All data reported and pertaining to both the multi and single institution studies
clearly show that all SAVI devices allow for excellent PTV_EVAL coverage, in all
encountered clinical situations. This is achieved while concomitantly being able to keep
the skin and chest wall maximum doses below protocol imposed values (NSABP Protoco l
B-39/RTOG 0413 Protocol, 2007). Because of its versatility in dose shaping and adaptable
device desig
n, the SAVI6-1mini was successfully used in the treatment of a stenotic distal
vagina as well ( Morcovescu et al., 2016).
Our study on the smallest SAVI6-1mini device indicate that it can efficiently be
used in clinical
situations where stringent limitations are imposed by close proximity of
the lumpectomy cavity either to the skin or chest wall. Even for situations where SB < 5
mm all PTV coverage criteria are met, while avoiding skin overexposure.
Another dosimetry
study of ours on 108 all-type SAVI devices (Reiff et al., 2013)
used on patients where the distance from the applicator to both skin and ribs were less than
95
7 mm indicates that the doses on all critical structures were within tolerable limits, as
recommended by standard protocols or society accepted standards (Smith et al. 2009).
The use
of the ACUROS formalism, when dose inhomogeneity corrections are
applied in such a complex anatomical environment, where the presence of air pockets,
seroma, breast tissue of different densities, proximity of the skin surface or of the rib cag e
can change the scatter and back scatter conditions dramatically, falls in line with
theoretical predictions, showing that overall coverages and reported maximum doses to
critical organs degrade slightly, more for skin average maximum reported doses (~ 4%)
than for correspondent chest wall doses (~ 2%). These results are confirmed by more
recent studies on the impact of heterogeneity correction implications on brachytherapy
planning, all indicating minimal effects on the average values of PTV coverage and
maximum dose usually in the range of 2%, and 4% respectively (Loupot et al ., 2014 ;
Slessinger et al., 2012), but sometimes as high as 5%, and 7% or 10% respectively (Zhang
et al., 2012;
Likhacheva et al ., 2016; Thrower et al., 2016), with variations due to
placement of the device or heterogeneity information.
As other biological model based studies indicate (Bovi et al ., 2007), the clinical
significance of these differences we also observed is unclear in terms of variations of
tumor control.
96
CHAPTER 7 COMPREHENSIVE EVALUATION OF A STRUT-
ADJUSTED-VOLUME-IMPLANT SAVI DEVICE QUALITY
ASSURANCE PROGRAM
7.1 Study motivation
Considering the complexity of the entire treatment process involving APBI cases and
other brachytherapy procedures in general, there is a need of designing a comprehensive
quality assurance program, as already done for other specific brachytherapy procedures
(Brown et al.
2016) but also specifically for APBI (Cui et al., 2011; Chilukuri, 2016), that
deals with all stages of this process taking place in a radiotherapy department: 1) the QA
of the cavity and device localization and reconstruction, 2) the QA of the treatment plan,
3) the QA at the time of treatment and 4) the post treatment QA. We discuss all those in
sequence and we highlight the common practices and the extra measures we included into
our customized QA program, in an attempt to incorporate our clinical experience with the
device into a comprehensive QA program capable of preventing and addressing even the
least frequent clinical situations. A number of recent retrospective studies (Iftimia et al.,
2015; Shah et al., 2016; Pinn-Bingham et al., 2011) clearly outline a variety of clinical
factors and situations that can have a major impact on the outcome of high-dose-rate
brachytherapy treatments, encompassing all stages of a QA program, from pre-delivery to
post-delivery, and emphasizing its importance in the cases of any type of breast
brachytherapy type applicators (Kyriacou, 2016; Pinder et al., 2016 ).
The implementation of a comprehensive quality assurance of a brachytherapy
program is mandatory by state and federal regulations (Kutcher et al .,1995), and its
effectiveness and thoroughness vital for a successful delivery of brachytherapy treatments
(Wazer et al., 2006). A number of studies on partial breast irradiation applicators clearly
indicate the variety of clinical situations raising concerns and requiring special attention
that need to be accounted for in an all-inclusive QA program. This is because of the
potential harmful effect of improperly evaluated and addressed apparently infrequent
clinical situations that can properly be flagged and identified in various stages of the QA
program, before, during or after the time of treatment, such as: impact of breast
augmentation (Akhtari et al., 2015; Bloom et al., 2011), inter-fractional displacement or
motion of SAVI devices (Chandrasekara et al., 2015; Morcovescu et al., 2011; Park et al.,
2011; Hyvarinen et al., 2014), presence of air/fluid single or cluster cavities (Harmon et
97
al., 2013; Richardson et al ., 2010; Huang et al ., 2010), irregularly and asymmetrically
shaped volumes of breast tissue (Lu et al., 2012; Lu et al., 2010), geometric anatomical
uncertainties when using the SAVI device (Akino et al ., 2014), proximity of rib cage
(Brown et al., 2012) or the presence of pacemakers (Jacob et al., 2011; Kalavagunta et al.,
2015). All these studies are clearly indicative of the impact all these possible factors can
have on the fina
l outcome of these types of treatments, and emphasizes the importance of
having a carefully design ed QA program.
7.2 Pre -treatment Quality Assurance
7.2.1. Imaging and documentation for treatment planning
The imaging sequence is an important part of the planning process. In our clinic, a
patient is usually scheduled for a CT planning simulation and a CT is acquired the day
following the implant surgery, in order to allow time for adequate tissue conformance
around the SAVI device (Liu et al., 2012). The acquired images become the reference set
of images all subsequent pre-fractional images will be compared against. It is important to
have a thorough verification process of the position and placement of the SAVI device
because the patient should be treated in the same position as planned.
During the initial planning scan done using a GE Lightspeed, large-bore, 4 slice CT
scanner (GE Medical Systems, Waukesha, Wisconsin), two CT scouts, one anterior and
one lateral, are acquired. For a high quality image reconstruction, we use 2.5 mm slice
thickness for CT planning scan, extending at least 5 cm superiorly and inferiorly to the
SAVI defined cavity area, typically resulting in a number of transverse images of around
65 slices. We employ a breath-hold during the CT scan, or at least we instruct the patients
having breathing difficulties to exert a shallow breath pattern during the actual scan, in
order to minimize respiratory motion artifacts.
M2, M4 and M6 markers are identified with the built-in markers of the SAVI
devices, pertaining to their corresponding catheter number, 2, 4 or 6. We evaluate
distances between the three pairs of strut markers in the AP or Lateral CT scouts, Figure
30, and compare, record and review these values prior to each fractional treatment.
98
Figure 30. Pre-fractional comparison and review of implant placement: daily CT scout
(right image
) compared against original planning CT scout (left image)
An in-house form, Figure 31, was developed in order to document and record
relevant position parameters for the initial planning scan and for all subsequent pre-
treatment verification scans. Several items need to be recorded on this form, which we
generically refer to as the “SAVI daily CT checks and measurements” sheet. The
standardized form is printed front and verso. The information on the front page is:
F1) Patient Name;
F2) Patient unique identifier or ID;
F3) Breast Side: LEFT or RIGHT; needs to be circled.
F4) SAVI applicator type;
F5) The direction of the catheter exit: MEDIAL or LATERAL.
F6) Number of CT (transverse or axial) slices above or below the SAVI device.
F7) the LONG axis length;
F8) The M2- to-M4 marker distance (mm);
F9) The M2- to-M6 marker distance (mm);
F10) Maximum Expansion (mm)
99
F11) Min. SAVI – chest wall distance (mm) – evaluated in an axial CT image;
F12) Min. SAVI – skin distance (mm) – evaluated in an axial CT image;
F13) CT Tech initials – the initials of the CT scanner operator;
F14) PHYSICIAN: the initials of the Radiation Oncologist care provider, supervising
the treatment;
F15) the A distance – the reading, on the SAVI device shaft’s scale, from the hub to
the skin entrance;
F
16) position of the #2 catheter in reference to the incision site on the skin, viewed
along the shaft of the device;
The information on the verso page of the “SAVI daily CT checks and measurements”
sheet is: the lengths of the individual catheters of the SAVI device, a minimum of 7 (for
the SAVI6-1mini or SAVI6-1) or maximum of 11 (for the SAVI8-1 or SAVI10-1)
catheters.
This information allows for the verification of the patient’s identity (F1-F2),
implant and positioning setup (F3-F5), and for monitoring the device’s inter-fractional
position variations or deviations from the standard position, assigned to the very first set of
images recorded at the time of the planning simulation scan. All F6- to-F12 values will
help monitoring both rotational and translational variations of the particular device, for a
particular patient.
100
Figure 3 1. Front page (above) and Verso page (below) of our QA form
101
There is need for a very detailed quality assurance program for SAVI treatments,
patient specific, that is performed in addition to the routine daily and quarterly HDR
machine QA.
One important test to be performed on the day of the planning CT simulation is the
verification of the SAVI device catheter lengths. This is usually performed while
connecting the re-usable treatment catheters to the device and measuring and confirming
the treatment lengths, usually found to be approximately within ± 2mm of the
manufacturer’s expected values. In parallel with the device positioning reproducibility
test, evaluated using the anterior or lateral CT scouts, we employ a more visual
verification p
rocess of the device position, by recording the distance from the hub to the
skin and marking the position of the 2nd strut on the skin.
7.2.2 Treatment Time Nomogram for Strut-Based Accelerated Partial Breast
Applicators. Original Contributions.
7.2.2.1 Study motivation
The purpose of this work was to generate a tabular nomogram of treatment times
for strut-based APBI applicators. The nomogram is intended to provide guidance and a
pre-treatment quality assurance check for clinics establishing new treatment techniques or
transitioning from balloon-based applicators.
7.2.2.2 Materials and Methods
A retrospective analysis was conducted of 486 patients receiving APBI using the
SAVI strut-based applicators at three separate institutions. Patient data was organized
based on applicator size (a surrogate of treatment volume) and number of organs at risk.
Three organs at risk categories were determined based on the proximity of the
device to the patient’s skin and/or chest wall (0, 1, or 2 OARs). Organs at risk were
defined as being < 5 mm from cavity wall/peripheral struts. A tabular nomogram of
treatment time (based on a nominal 10 Ci source strength) was generated from descriptive
statistics of each combination of applicator size and organs at risk category.
102
Figure 32: Boxplot of treatment times of various combinations of applicator size and
Number of nearby organs at risk.
7.2.2.3 Results and Discussion
The treatment time was observed to be directly proportional to applicator size and ,
to a lesser extent, inversely proportional to the number of nearby organs at risk.
Distributions of treatment times observed for each combination of applicator size and
organs at risk category are depicted in Figure 32. The tabular nomogram featuring average
treatment tim
es with standard deviations is presented in Table 36.
Table 36: Tabular nomogram of average treatment times in seconds. Standard
deviations are presented in parentheticals.
Number of Nearby Organs at Risk
0 1 2
Applicator
Size 6-1 mini 148.0 (9.4) 137.0 (14.4) 126.6 (19.1)
6-1 175.7 (13.9) 165.7 (19.9) 152.1 (24.5)
8-1 226.4 (16.0) 229.0 (25.0) 189.5 (25.0)
10-1 287.2 (24.1) 269.4 (30.0) 252.6 (25.9)
103
Strut-based APBI treatment times were observed to depend in a consistent manne r
on applicator size and number of nearby organs at risk. Information provided in the
nomogram presented here represents several hundred treatments performed at multiple
institutions. This data can serve as guidance or quality assurance for institutions with
limited experience using strut-based APBI applicators. This work distills considerable
multi-institutional experience with strut-based APBI applicators into an accurate and
pragmatic clinical tool that promotes treatment consistency and quality.
7.3 During and post treatment Quality Assurance – Int erfractional Variance.
Original Contributions.
7.3.1 Materials and Methods
In a study we presented in 2011 at the ASTRO (Morcovescu et al ., 2011), we
e
valuated the effect on target coverage and organ of risk sparing caused by interfraction
variance of
a SAVI6-1mini APBI applicator in patients with small breast tissue volumes
and limited skin
/chest wall spacing. Daily setup combined with tissue conformance
variations are confirmed to potentially have a big impact on dosimetric parameters in
SAVI-based breast brachytherapy, as a number of recent studies indicate (Liu et al., 2012;
Chandrasekara et al ., 2015), therefore the outmost importance of a thorough QA of the
planning process (Pella, 2016). Mammographic evaluation of an breast implant is also
referred to as post treatment evaluation of an APBI treatment or plan (Ojeda-Fourier et al.,
2011), but in this study we refer to the actual on-going dosimetric evaluation of a plan on
subsequent CT data acquired during the treatment course itself.
The study c
onsidered three (3) patients treated with a SAVI6-1mini device in our
clinic. Individua
l Initial treatment plans were generated based on the original CT-SIM
scans and saved as template plans for fractional re-planning. Pertinent dosimetrical
parameters were evaluated and recorded (i.e., V200, V150, V100, V95 and V90,
maximum skin and chest wall dose). The template plan was then superimposed on the
subsequent pre-treatment fractional CT-Sim and tomography-based treatment plans were
generated for Fractions 1-10. All pertinent structures were reconstructed as to closely fit
the volumetric profiles of the initial plan structures. Relevant dosimetric comparison was
104
then performed using the maximum doses to organs at risks, %PTV_EVAL and % PTV
coverage, and target dose homogeneity index.
A Reference Line was created in the Initial CT-sim&TemplatePLAN (Figure 33).
This structure wa
s used for further rotational shifts evaluations in subsequent fractional
CT-sim&PLANS.
Figure 33. The Reference Line created in the Initial CT-sim&TemplatePLAN
A total of 11 plans were generated for each patient, a total of 33 plans for the entire
current study. Accurate reconstruction of the SAVI planning structure was an initial study
objective, thus only variations of +/- 0.2 cc from the reference SAVI device volume in the
initial CT-Sim scan were accepted. Minor PTV_EVAL volume changes of +/- 1.5 cc were
then estimated. The SAVI6-1mini applicator average rotational axial shift, over the course
of the entire
treatment, was 2.8o ± 2.1o, hardly assessable or detectable based on
prefractional CT-sim and external skin marker positional checks.
105
7.3.2 Results and Discussion
We found that due to interfraction variance in local anatomy (i.e., altered SAVI to
chest wall and skin distances, slightly changed skin surface contours, air/seroma profile
difference), skin and chest wall dose escalations of up to 30% and PTV_EVAL V90 and
V95 coverage degradation for and of up to 5% of the reported values on the initial plan
can be observed.
Figure 3 4. Absolute value inter -fractional variations of planning parameters
Variations on monitored parameters were recorded and trended, Figure 34. The
highly se
nsitive parameters to rotational variances are the Maximum Doses to Skin and
Chest Wall, which can mount to escalations of those values of up to 140% of the
prescription dose.
The treatment time reduction, due to imposed to necessary cooling off of the dose on
the skin or chest wall, and preservation of planning objectives, was up to 4.8% of the
initial treatment time, when re-planning was employed. A summary of the data analysis
for Patient 1 is shown in Table 37 below.
106
Table 3 7. Summary of the data analysis for Patient 1
Parameter Average SD MAX MIN
Max Skin DOSE (cGy) 100.2 8.34 115 89
Max CW DOSE (cGy) 123.2 8.19 144 115
PTV_EVAL Volume (cc) 31.3 0.77 32.7 30.2
PTV_EVAL V95(%) 89.8 1.35 92.3 88.3
PTV_EVAL V90(%) 92.3 1.31 94.9 91.0
PTV_EVAL V150cc) 15.7 0.24 16.2 15.2
PTV_EVAL V200(cc) 9.4 0.22 9.8 8.9
PTV V95(%) 71.5 3.32 79.4 68.6
PTV V90(%) 75.4 2.51 79.7 72.7
SAVI Volume (cc) 7.5 0.06 7.6 7.4
Individual differential source dwelling times adjustments, building up to as low as
3% of the total treatment time of the Initial plan, were sufficient for recovering the desired
standard APBI planning objectives.
Routine pre-treatment CT scan checks are unlikely to point out hard- to-quantify local
anatomy inter-fraction variances, which are identified as the main impact factor for APBI
treatments in patients with reduced chest wall and skin sparing.
Therefore, carefully conducted pre-treatment QA procedures are mandatory for th e
correct delivery of a SAVI6-1mini APBI treatment and for the achievement of a high
degree of
conformance between the initial reference TPS plan and the clinically delivered
plan (Morcovescu et al., 2016). Inter-fractional TPS plan re-evaluations should become a
routine when dealing with cases where the applicator is very proximal to organs of risk
and where highly asymmetrical PTV_EVAL volumes are employed, in order to avoid
overlooking prohibitive sensitive structure doses and unacceptable treatment volume
coverages.
7.4 Overall Results and Discussion
The SAVI6-1mini strut-based device proves to be a highly adaptable and versatile
APBI solution for patients with reduced breast and lumpectomy cavity volumes, and skin
107
and/or chest wall bridges. Inside the framework of a detailed and clear QA program, when
it is appropriately elected as the APBI device of choice, optimally implanted, and
comprehensively monitored during the course of treatment, all SAVI device types, but the
SAVI6-1mini in particular, indeed offer a very effective and highly reproducible tool for
the treatment of complex breast cancer cases.
The SAVI (the Strut Adjusted Volume Implant ) device is one of the most novel
devices used in APBI. Our analysis demonstrates the dosimetric versatility and outlines
the clinical implementation process of the SAVI brachytherapy device, especially for
APBI cases that require more flexible dose optimization, for both coverage of PTV
volumes and sparing of dose to adjacent critical structures.
108
CHAPTER 8 CLINICAL RESULTS
The accelerated partial breast irradiation (or APBI) treatment technique
has been widely embraced as an acceptable modality for delivering adjuvant radiation
therapy for a selected group of patients undergoing breast-conserving therapy. The
recently published GEC -ESTRO trial, a Phase III randomized prospective trial, and other
recent studies (Polga r et al., 2004; Bitter et al., 2016) demonstrated superior cosmesis and
noninferiority of APBI with brachytherapy when compared to whole breast irradiation
(WBI). Several recently published APBI studies demonstrat ed that local control that is
equivalent to WBI with 5 to 10 years of followup (Vicini et al., 1997). M ulticatheter
interstitial therapy was originally the method of choice, and all interstitial data reveal
outstanding results (Vicini et al ., 1999; Wazer et al ., 2006). More recently introduced
single-entry intracavitary devices, like the MammoSite balloon, improved ease of use, but
early experience proved to be challenging in cases of inadequate skin and chest wall
spacing, where there is a difficulty in dosimetrically modulating the dose, which in turn
can lead
to significantly increased toxicity (Keisch et al., 2003; Hong et al., 2010; Kuske
et al ., 2014; Kamrava et al ., 2014). The introduction of multilumen catheter devices
allowed for a more customized sculpting of the dose, better conformed to the woman’s
anatomy,
increasing the number of women eligible for PBI, which in term resulted in a
number of excellent comparative studies trying to determine the dose modulation
capacities, pros and cons of all available multilumen devices (Cross et al., 2008; Patel et
al., 2010; Raffi et al ., 2010; Yashar, 2011; Rana et al ., 2015; Zaker et al ., 2015) In
addition to multicatheter and single-entry devices, external beam APBI using photons or
protons is also described in the literature (Vaidya et al., 2004; Njeh et al., 2010). In this
chapter we indicate the results of our own 5 year retrospective study on all SAVI device
types (Yashar et al ., 2016), reporting them in terms of local control, toxicity, and
survival for the first 250 patients treated across multiple institutions.
Toxicity
Toxicity was graded according to the Common Terminology Criteria for Adverse Events
version 3.0, commonly used in prospective toxicity analysis for breast cancer studies
109
(Rehman et al ., 2016), except seroma and fat necrosis, which were modified by the
consortium to more appropriately fit APBI as shown in Table 38.
Tabel
38. Toxicity Definitions
Toxicity (CTCAE version 3.0) Grade 2
Hyperpigmentation Slight or localized
Induration Marked increase in density and firmness on palpation with or without minimal
retraction
Telangiectasias Moderate number
Breast pain Moderate, pain, or analgesics interfering with function, but not ADL
Toxicity (modified from
CTCAE version 3.0) Grade 0 Grade 1 Grade 2 Grade 3
Seroma Not mention ed or not
present Radiographic or clinical but
asymptomatic Symptomatic Aspirated or excised for
symptoms Fat necrosis
The collected data included comprehensive information such as disease status,
recurrence and whether true recurrence/marginal miss (TR/MM) or elsewhere and
histology of recurrence, contralateral and regional recurrence, DM, date of last
mammogram/ultrasound/magnetic resonance imaging, cosmesis score, and grading of late
effects including hyperpigmentation, induration, hormonal therapy, erythema, fibrosis,
breast pain, seroma, fat necrosis, telangiectasia, breast asymmetry and cause (surgical or
radiation), and othe
r toxicities. Cosmesis was graded excellent, good, fair, and poor
according to the Harvard scale (Rose et al., 1989). Of note, in some centers, ultrasound
was routinely done, and fat necrosis or seroma was routinely indicated on follow-up
mammograms, but in others, changes expected after lumpectomy with or without radiation
were simply reported as ‘‘post lumpectomy changes’’. This difference prompted the
modification of the grading of seroma and fat necrosis as per the included table to
represent those that were symptomatic.
The median age of the 250 patients in this study was 62 years (range, 40-85), out of
who 73.5%
had invasive disease and the remaining 26.5% had pure ductal carcinoma in
situ.). The
majority (57%) of these women were older than 60 years, although 36 (14.4%)
were younger than 50 years (11% were <45 year s). Most patients were postmenopausal
(84%), had estrogen receptor positive tumors (90%), received endocrine therapy (65%),
and did not receive chemotherapy (91%).
110
Tumor size was reported in 94% of subjects with 85% of patients having
pathologic tumor sizes in the range of 1 – 20 mm (2% were > 30 mm). Median follow-up
in these patie
nts was 59.5 months. Of this group, 80% had ≥ 3 years of follow-up and 70%
had ≥ 4 years of follow-up.
For the 250 pati
ents, the mean V 90 was 96.1 ± 3.7%, V 95 was 93.5 ± 6.1%, V100
was 90.4 ± 5.5 cc, V150 was 30.5 ± 11.0 cc, and V 200 was 14.7 ± 5.1 cc. These
dosimetric variables differed by device. Skin dose mean was 269 cGy (79.1% of
prescription dose)
. For those patients with a skin bridge >3 mm and ≤5 mm or ≤3 mm, the
mean values we
re 274 cGy and 281 cGy (80.7 and 82.7% of the prescription dose),
respectively. The mean rib dose was 273 cGy (80.4% of the prescription dose).
In this cohort,
all four sizes of applicator were used: 10-1 (21%), 8-1 (32%), 6-1
(38%), and 9% received the SAVI6-1mini size. More than half the patients had skin
spacing less than or equal to 10 mm (44% > 10 mm) with 12% and 17% having skin
bridges of 3-5 mm and ≤3 mm, respectively. Of the entire population, 85.9% had
excellent/good cosmesis at 60 months. Ten of the 11 reporting sites had excellent/good
cosmesis in 96.2%, and in one center, excellent/good cosmesis was reported in 57.9%.
Grade 2 or higher adverse events at any time for hyperpigmentation, induration,
erythema, telangiectasia, breast pain, symptomatic seroma, and symptomatic fat necrosis
were 0.4%, 3.0%, 3.5%, 3.0%, 3.9%, 4.8%, and 1.3%, respectively. Time course of
toxicity is shown in Table 39. Infection rate was 3.7%, with some centers giving
prophylac
tic antibiotics.
Table 39. Toxicity onset at any time
Toxicity
(≥ Grade 2) At any time,
N (%) 0-12 Months >12-18
Months >18-24
Months >24 Months
Subjects at risk 230 230 220 217 214
Hyperpigmentation 1 (0.4%) 0 (0%) 0 (0%) 0 (0%) 1 (0.5%)
Induration 7 (3.0%) 2 (0.9%) 0 (0%) 1 (0.5%) 4 (1.9%)
Erythema 8 (3.5%) 6 (2.6%) 0 (0%) 0 (0%) 2 (0.9%)
Telangiectasia 7 (3.0%) 0 (0%) 1 (0.5%) 0 (0%) 6 (2.8%)
Breast pain 9 (3.9%) 3 (1.3%) 1 (0.5%) 3 (1.4%) 2 (0.9%)
Seroma 11 (4.8%) 6 (2.6%) 0 (0%) 0 (0%) 5 (2.3%)
Fat necrosis 3 (1.3%) 1 (0.4%) 0 (0%) 0 (0%) 2 (0.9%)
111
Dosimetric targets were met in virtually all patients and are similar to other
published series with excellent target coverage and normal tissue avoidance. With the
struts adjacent to the target tissue, the allowable target for V 200 is more similar to the
interstitial target than the balloon target. But, as demonstrated in this series, this has not
led to increased toxicity. A recent single institutional series compared a large cohort of
patients (n=594) with APBI using different single-entry devices. This report also observed
outstanding target coverage with excellent skin and rib sparing (Rana et. al , 2015) .
Associations between dose and telangiectasia were made possible based on univariate
analysis. Since dose and skin spacing are related, and other publications have
demonstrated a similar correlation, this is was of no surprise. Other possible correlations
are made between V 90 and V 150 and symptomatic seroma, and V 90 and fat necrosis, but
the numbers were overall too small to trigger for a prompt alteration of guidelines.
The strengths
of this report include its multi-institutional participation and robust
numbers ( n = 250) with the longest follow-up for a single-entry multilumen breast
brachytherapy device. The selection criteria were practically unbiased, free of any
screening filters, since it basically included the first 250 subjects accrued . It is limited by
its retrospective nature, which may confound data as institutional toxicity reporting and
treatment policies may differ.
112
CONCLUSIONS
Based on the results of our studies, we can conclude that the use of multilumen
applicators clearly simplifies brachytherapy APBI compared to interstitial brachytherapy,
allowing the advantages of brachytherapy over other forms of accelerated partial breast
radiation therapy accessible to more women.
The clinical implementation of the SAVI device poses various challenges to the
potential users, but within the frame of a robustly designed and implemented quality
assurance program, all standard dosimetrical goals are achieved, including conformance to
the tumor bed coverage and dose minimization to surrounding normal tissues, as indicated
by other similar studies (Scanderbeg et al., 2009 ; Yashar et al., 2008).
We argue that the PTV_EVAL and PTV coverage goals achievable with the SAVI
device, with mean V95 over 95% and mean V90% over 97%, way above the protocol
required criteria of 90%/90%, on almost all possible clinical situations, is an assurance that
the use of thi
s APBI device can adequately compensate for random and systematic errors
inherent in these type of treatments (Stojadinovic et al., 2008).
Even though the NSABP B-39/RTOG 0413 protocol imposes VHI criteria of 0.750
across all brachytherapy type applicators, therefore promoting rather restrictive criteria
widely accepted and used for multi-catheter interstitial implant (Wu et al ., 1988), our
study indicates that the use of these same criteria is unfit for SAVI type devices. Our
recommendation is that this parameter should not be used for the evaluation of the
adequacy of plans in breast brachytherapy, when SAVI type devices are used, and if used,
to relax the threshold value from 0.750 to a more realistic value of 0.500.
The use of
the ACUROS formalism, when dose inhomogeneity corrections are
applied in such a complex anatomical environment, where the presence of air pockets,
seroma, breast tissue of different densities, proximity of the skin surface or of the rib cage
can change the scatter and back scatter conditions dramatically, falls in line with
theoretical predictions, showing that overall coverages and reported maximum doses to
critical organs degrade slightly compared with those reported for when the standard TG43
algorithm is employed, more for skin average maximum reported doses (~ 4%) than fo r
correspondent chest wall doses (~ 2%). These results are confirmed by more recent studies
113
on the impact of heterogeneity correction implications on brachytherapy planning, all
indicating minimal effects on the average values of PTV coverage and maximum dose
usually in the range of 2%, and 4% respectively (Loupot et al ., 2014; Slessinger et al .,
2012), but sometimes as high as 5%, and 7% or 10% respectively (Zhang et al., 2012;
Likhacheva et al ., 2016; Thrower et al., 2016), with variations due to placement of the
device or heterogeneity information.
The strut open architecture design and multiple catheter options allow dose
sculpting to each patient’s unique anatomy and cavity location. This flexibility helps to
overcome prior concerns with skin spacing and tumor beds positioned between the
overlying skin and chestwall that limited patient eligibility. The dosimetric parameters
considered relevant for our studies, and data reporting of those parameters, namely
especially Max Skin Dose, is accurately reflected in our clinical data outcome reports,
which indicates that the definitions in use for these parameters needed no reconsideration,
as some studies suggest (Park et. al , 2016). The clinical report we contributed to with
patient data confirms excellent tumor control comparable to other published APBI rates
and survival with low toxicity, based on median 59.5 month outcomes for patients treated
with the strut-based applicator. Compared to external beam techniques for APBI, SAVI
brachytherapy seems to be as effective, with less toxicity.
114
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ȘERBAN MORCOVESCU
6205 Saddleback Drive, Denton, Texas 76210
(940)387- 3884 ● serban.morcovescu@usoncology.com
(moescu@gmail.com )
Date of Birth: January 19th, 1974
Place of Birth: Baia Mare, Maramures County, ROMANIA
Marital Status: Married
EDUCATION
Master of Science in Medical Physics March 2003
Wright State University, Dayton, Ohio, USA GPA 4.0/4.0
Master of Science in Biophysics and Medical Physics June 1998
“Babes -Bolyai” University, Cluj -Napoca, Romania GPA 9.9/10.0
Bachelor of Science in Physics June 1996
“Babes -Bolyai” University, Cluj -Napoca, Romania GPA 8.54/10.0
EXPERIENCE
Therapeutic Medical Physicist April 2010 – present
Texas Oncology, Denton, Texas – solo practice
Same as below;
Due to my clinical research work and interest , the practice
was included in the Strut-Based Brachytherapy Research Group
a multi-institutional group created to study the dosimetry
and outcomes of APBI using strut-based applicators; co-author of 13
published/presented research studies;
Completed several benchmark RTOG cases, with patient inclusion
in national clinical trials such as RTOG0413 (PBI, WBI G1 and G2),
RTOG0617, RTOG 1005;
Therapeutic Medical Physicist July 2002 – March 2010
AROS, LLC, Colleyville, Texas
Active in more than 12 (twelve) Cancer Centers
across North and Central Texas, performing specific medical physics tasks and services
including, but not limited to:
monthly QAs and calibrations for Varian and Siemens LINACs;
annual scans – Scanditronix,Wellhofer, OmniPro;
1
QAs and TG21/TG51 calibrations for Varian LINACs;
daily and quarterly checks for Varisource HDR Treatment Unit,
HDR program coordinator: extensive BrachyVision Varian HDR planning experience :
(prostate – over 90 plans ( o90p); vaginal cylinder – o130p , T&O – o50p, lung – o30p, tongue
MAMMOSITE implants – o150p), Contura – o50p, rectum , floor of mouth , endometrium needle
implants, SAVI – o500p (one of the top SAVI users nationwide – # of cases planned)
familiar with different TPS ( ADAC Philips , CMS-Focus and XiO, VARIAN-Eclipse, Elekta Render-Plan),
commissioning of ADAC and Focus-CMS TPS;
IMRT planning on ADAC Pinnacle TPS (DMPO);
RadCalc v.5.0 – v6.2 system implementation/commissioning/maintenance;
IMRT plan validations using MapCheck /MapCheck2 SunNuclear;
Daily QA/QA2/QA3 ; IVD; MapCheck/MP2 SunNuclear device calibration and usage,
Calibration/maintenance for Sonoray Z-Med Varian ultrasound device,
familiar with IMPAC, MultiAccess, MOSAIQ and VARIS R&V systems,
participation in several I-131 seed implants (in 2003) procedures,
calibration and loading of I-131 seed implants, Zevalin Sm-153 procedures
participation in one IVBT procedure using Novoste BetaCathTM (Sr-90) IVB system and
in one using Guidant Galileo IVB System (P-32) (in 2003)
responsible of Radiation Department records keeping, State correspondence,
State Book and Radiation Program Auditing and Implementation, etc.
Therapeutic Medical Physics Training July 2001 – June 2002
Reid Hospital, Richmond, Indiana
Research Assistant January 2002 – July 2002
Coordinator: Dr. Brent Foy, Ph.D,
Wright State University, Dayton, Ohio
Nuclear magnetic resonance spectrometry
applied to toxicological studies: measurements,
data handling and interpretation
Physics Teaching Assistant June 2001 – January 2002
Wright State University, Dayton, Ohio
Grading lab reports, teaching and conducting
basic experiments on Mechanics, Electricity, Optics
and Magnetism
Physics High School Teacher September 1996 – March 2001
“Anghel Saligny” Technical College, Baia Mare, Romania
MEMBERSHIPS
AAPM – American Association of Physicists in Medicine February 2002
ΦΚΦ – Phi Kappa Phi Honor Society May 2003
ABMP – American Brachytherapy Society June 2009
ASTRO – American Society for Therapeutic Radiology and Oncology July 2005
RSNA – Radiological Society of North America June 2007
2
PROFESSIONAL ACHIEVMENTS
Radiological Physics Board Exam – Oral Exam Passed ( 1st attempt ) – August 2006
American Board of Radiology, ABR Louisville, KY
Radiological Physics Board Exam – Part 2of 3 Passed ( 1st attempt ) – August 2005
American Board of Radiology, ABR Chicago, IL
Radiological Physics Board Exam – Part 1 of 3 Passed ( 1st attempt ) – August 2003
American Board of Radiology, ABR Tucson, AZ
MammoSite®RTS Clinical Training Program Completed – September 11, 2002
Plano, TX
IMRT Treatment Planning Course, ADAC Pinnacle, Varian Completed – April, 2005
Cleveland, OH
Contura SenoRX –On-line Clinical Training Course Sept., 2007
SAVI Cianna-Varian Planning/Clinical Training Course Completed – June, 2008
Charlottesville, VA
Licensed Medical Physicist in the State of TEXAS since August 2002
MISCELLANEOUS
President and Co- Founder of the “ Asociația Alumni a Colegiului Național Gheorghe Șincai ”
Baia Mare, 2011;
Earned several prizes at national poetry contests in Romania, 1998-2001;
Published books: Despre iubire.oarecum – poeme cuminți , poetry, Ed. Napoca Star, Cluj-
Napoca, 2012;
Music Record/Album: Despre tăcere , songwriter, singer, guitar player. 21 original folk-music
songs (in Romanian)
LANGUAGE SKILLS
Romanian (native language);
English (read, write, speak – fluently);
French (read – fluently, write – some difficulty, speak – some difficulty);
Septembri
e 2017,
Drd. Șerban Morcovescu
3
ȘERBAN MORCOVESCU
6205 Saddleback Drive, Denton, Texas 76210
(940)387- 3884 ● serban.morcovescu@usoncology.com
(moescu@gmail.com )
Date of Birth: January 19th, 1974
Place of Birth: Baia Mare, Maramures County, ROMANIA
Marital Status: Married
EDUCATION
Master of Science in Medical Physics March 2003
Wright State University, Dayton, Ohio, USA GPA 4.0/4.0
Master of Science in Biophysics and Medical Physics June 1998
“Babes -Bolyai” University, Cluj -Napoca, Romania GPA 9.9/10.0
Bachelor of Science in Physics June 1996
“Babes -Bolyai” University, Cluj -Napoca, Romania GPA 8.54/10.0
EXPERIENCE
Therapeutic Medical Physicist April 2010 – present
Texas Oncology, Denton, Texas – solo practice
Same as below;
Due to my clinical research work and interest , the practice
was included in the Strut-Based Brachytherapy Research Group
a multi-institutional group created to study the dosimetry
and outcomes of APBI using strut-based applicators; co-author of 13
published/presented research studies;
Completed several benchmark RTOG cases, with patient inclusion
in national clinical trials such as RTOG0413 (PBI, WBI G1 and G2),
RTOG0617, RTOG 1005;
Therapeutic Medical Physicist July 2002 – March 2010
AROS, LLC, Colleyville, Texas
Active in more than 12 (twelve) Cancer Centers
across North and Central Texas, performing specific medical physics tasks and services
including, but not limited to:
monthly QAs and calibrations for Varian and Siemens LINACs;
annual scans – Scanditronix,Wellhofer, OmniPro;
1
QAs and TG21/TG51 calibrations for Varian LINACs;
daily and quarterly checks for Varisource HDR Treatment Unit,
HDR program coordinator: extensive BrachyVision Varian HDR planning experience :
(prostate – over 90 plans ( o90p); vaginal cylinder – o130p , T&O – o50p, lung – o30p, tongue
MAMMOSITE implants – o150p), Contura – o50p, rectum , floor of mouth , endometrium needle
implants, SAVI – o500p (one of the top SAVI users nationwide – # of cases planned)
familiar with different TPS ( ADAC Philips , CMS-Focus and XiO, VARIAN-Eclipse, Elekta Render-Plan),
commissioning of ADAC and Focus-CMS TPS;
IMRT planning on ADAC Pinnacle TPS (DMPO);
RadCalc v.5.0 – v6.2 system implementation/commissioning/maintenance;
IMRT plan validations using MapCheck /MapCheck2 SunNuclear;
Daily QA/QA2/QA3 ; IVD; MapCheck/MP2 SunNuclear device calibration and usage,
Calibration/maintenance for Sonoray Z-Med Varian ultrasound device,
familiar with IMPAC, MultiAccess, MOSAIQ and VARIS R&V systems,
participation in several I-131 seed implants (in 2003) procedures,
calibration and loading of I-131 seed implants, Zevalin Sm-153 procedures
participation in one IVBT procedure using Novoste BetaCathTM (Sr-90) IVB system and
in one using Guidant Galileo IVB System (P-32) (in 2003)
responsible of Radiation Department records keeping, State correspondence,
State Book and Radiation Program Auditing and Implementation, etc.
Therapeutic Medical Physics Training July 2001 – June 2002
Reid Hospital, Richmond, Indiana
Research Assistant January 2002 – July 2002
Coordinator: Dr. Brent Foy, Ph.D,
Wright State University, Dayton, Ohio
Nuclear magnetic resonance spectrometry
applied to toxicological studies: measurements,
data handling and interpretation
Physics Teaching Assistant June 2001 – January 2002
Wright State University, Dayton, Ohio
Grading lab reports, teaching and conducting
basic experiments on Mechanics, Electricity, Optics
and Magnetism
Physics High School Teacher September 1996 – March 2001
“Anghel Saligny” Technical College, Baia Mare, Romania
MEMBERSHIPS
AAPM – American Association of Physicists in Medicine February 2002
ΦΚΦ – Phi Kappa Phi Honor Society May 2003
ABMP – American Brachytherapy Society June 2009
ASTRO – American Society for Therapeutic Radiology and Oncology July 2005
RSNA – Radiological Society of North America June 2007
2
PROFESSIONAL ACHIEVMENTS
Radiological Physics Board Exam – Oral Exam Passed ( 1st attempt ) – August 2006
American Board of Radiology, ABR Louisville, KY
Radiological Physics Board Exam – Part 2of 3 Passed ( 1st attempt ) – August 2005
American Board of Radiology, ABR Chicago, IL
Radiological Physics Board Exam – Part 1 of 3 Passed ( 1st attempt ) – August 2003
American Board of Radiology, ABR Tucson, AZ
MammoSite®RTS Clinical Training Program Completed – September 11, 2002
Plano, TX
IMRT Treatment Planning Course, ADAC Pinnacle, Varian Completed – April, 2005
Cleveland, OH
Contura SenoRX –On-line Clinical Training Course Sept., 2007
SAVI Cianna-Varian Planning/Clinical Training Course Completed – June, 2008
Charlottesville, VA
Licensed Medical Physicist in the State of TEXAS since August 2002
MISCELLANEOUS
President and Co- Founder of the “ Asociația Alumni a Colegiului Național Gheorghe Șincai ”
Baia Mare, 2011;
Earned several prizes at national poetry contests in Romania, 1998-2001;
Published books: Despre iubire.oarecum – poeme cuminți , poetry, Ed. Napoca Star, Cluj-
Napoca, 2012;
Music Record/Album: Despre tăcere , songwriter, singer, guitar player. 21 original folk-music
songs (in Romanian)
LANGUAGE SKILLS
Romanian (native language);
English (read, write, speak – fluently);
French (read – fluently, write – some difficulty, speak – some difficulty);
Septembri
e 2017,
Drd. Șerban Morcovescu
3
129
THE LIST OF PAPERS PUBLISHED DURING THE DOCTORAL PROGRAM
Scientific Papers published in ISI impact journals
1. Yashar C., Attai D., Butler E., Einck J., Finkelstein S., Han B., Hong R., Komarnicky
L., Lyden M., Mantz C., Morcovescu S ., Nigh S., Perry K., Pollock J., Reiff J.,
Scanderbeg D., Snyder M., Kuske R., 2016 , Strut-based accelerated partial breast
irradiation: Report of treatment results for 250 consecutive patients at 5 years from
multicenter retrospective study , Brachytherapy, 15(6), 780-787 (ISI Thompson impact
factor: 2.088)
2. Brown D.B., Damato A.L., Sutlief S., Morcovescu S ., Park S-J., Reiff J., Shih A.,
Scanderbeg D.J., 2016 , A consensus-based, process commissioning template for high-
dose-rate gynecologic treatments , Brachytherapy, 15(5), 570-577 (ISI Thompson impact
factor: 2.088)
3. Morcovescu S ., Cosma C., Morton J.D., 2016 , Dosimetrical Evaluation and clincail
implementation of a strut-adjusted-volume-implant SAVI device used for accelerated
partial breast irradiation , Romanian Journal of Physics, 61(7-8), 1312-1320 (ISI
Thompson impact factor: 1.398)
130
List of scientific papers presented at National and International
Congresses and Scientific Meetings
1. Morcovescu S. , Cosma C., Ferenczi J., 1999 , Radon measurement from touristic
underground waters in Maramureș county, Radon in the Living Environment, April
19-23, Athens, Greece, Book of Proceedings, 269-279.
2. Morcovescu S. , Morton J.D., Perry K., 2009 , The SAVI 6-1 Mini APBI applicator:
A unique solution for small lumpectomy cavities and skin distances , ASTRO 51st
Annual Meeting, November 1-5, 2009, Chicago, IL, Int. Journal of Radiation Oncology
Biology Physics, 75, S718.
3. Morcovescu S. , Morton J.D., 2009 , A comparative clincal study and dosimetry
planning experience with the new Contura multi-lumen versus MammoSite single-
lumen high-dose-rate balloon breast applicators under the RTOG 0413 protocol ,
ABS Annual Meeting, May 31-June 2, 2009, Toronto, Canada, Brachytherapy,
8(2), S136-137.
4. Morcovescu S. , Morton J.D., 2009, The miniSAVI multicatheter accelerated
partial breast irradiation applicator and its use in patients with small lumpectomy
cavities and/or inadequate skin distance: early clinical experience , ABS Annual
Meeting, May 31-June 2, 2009, Toronto, Canada, Brachytherapy, 8(2), S138.
5. Morcovescu S. , Morton J.D., Perry K., 2011 , Investigation of Interfraction
Variance of a SAVI6-1 Mini APBI Applicator in Patients with Reduced Chest Wall
and Skin Sparing , ASTRO 53rd Annual Meeting, October 2-6, 2011, Miami Beach,
FL, USA, (poster
)
6. Morcovescu S. , Scanderbeg D., Reiff J., Butler E., Sadeghi A., Graves Y.,
Huaying J., Imhoff K. Webster J., Patra P., Mohideen N., Jacob D., Mantz C.,
2012 , Dosimetric Characteristics of Strut-Based APBI Devices , American College
Radiation Oncology (ACRO) Annual Meeting, February 25, 2012, Fort. Myers,
FL, (poster)
7. Hong R, Lorio V, Huaying J, Han B, Shieh E, Imhoff K, Kuske R, Quiet C,
Sadeghi A, Perry K, Morcovescu S , Yashar C, Scanderbeg D, Graves Y, Strasser
J, Dayee Jacob D, Reiff J, Komarnicky L, Mahalingam S, Webster J, Nigh S,
Mohideen N, Lobo P, Farmer M, Berry M, Patra P, Mantz C, Finkelstein S,
Pollock J, Butler E, Attai D, Patel R, 2012 , Excellent/Good Cosmetic Outcomes in
131
Patients Treated with a Strut-Based Brachytherapy Applicator (SAVI) for
Accelerated Partial Breast Irradiation , National Consortium of Breast Centers,
Inc. annual meeting, March 10-14, National Consortium of Breast Centers, Inc.
annual meeti
ng, Mar ch 10-14, 2012, Las Vegas, NV (poster)
8. Morcovescu S , Morton J, Perry K, 2012 , Comprehensive dosimetric evaluation of
a small strut -based APBI Device: a retrospective single -institution study , World
Congress of Brachytherapy, May 10 -12, 2012, Barcelona, Spain ( poster)
9. Strasser J., Jacob D., Koprowski C., Attai D., Butler E., Finkelstein S., Han B.,
Hong R., Komarnicky L., Kuske R., Lyden M., Mahalingam S., Mantz C.,
Morcovescu S. , Nigh S., Perry K., Pollock J., Reiff J., Scanderbeg D., Yashar C.,
2012 , Accelerated partial breast irradiation using a strut-based brachytherapy
device: A multi
-institutional initial report on acute and late toxicity with greater
than 24-month follow-up , Breast Cancer Symposium, September 13-15, 2012, San
Francisco, CA (poster)
10. Perry K, Attai D, Finkelstein SE, Han B, Hong R, Kuske R, Lyden M,
Mahalingam S, Mantz C, Morcovescu S , Nigh S, Pollock J, Reiff J, Scanderbeg D,
Strasser J, Yashar C., 2013 , Outcomes for Accelerated Partial Breast irradiation
with a strut-based brachytherapy applicator: 320 patients with 3-year median
follow up , American Society of Breast Surgeons 14th annual meeting, May 1-5,
2013, Chicago, IL (poster)
11. Reiff J. E., Scanderbeg D., Morcovescu S. , Butler E., Imhoff K., 2013 , Dosimetry
of 108 Strut-Based Accelerated Partial Breast Irradiation (APBI) Treatments With
Applicator Distance Less Than 7 mm from Both the Skin and Ribs , American
Association of Physicists in Medicine (AAPM) 55th annual meeting, August 4-8,
2013, Indianapolis, IN
12. Einck J.P., Scanderbeg D., Kuske R., Hong R., Han B., Perry K., Reiff J.,
Mahalingam S., Nigh S., Strasser J., Mantz C., Pollock J., Morcovescu S ,
Komarnicky L, Finkelstein S., Yashar C., 2013 , Accelerated partial breast
irradiation using strut-based brachytherapy in ductal carcinoma in situ patients: A
report on 321 patients with median 25-month follow up. Data updated for 284
patients with median 27-month follow up , Breast Cancer Symposium, September
7-9, 2013, San Francisco, CA (poster)
132
13. Reiff J. E., Scanderbeg D., Morcovescu S. , Butler E., Imhoff K., 2013 , Dosimetric
analysis of 1007 Strut-based APBI treatments , American Society of Radiation
Oncology (ASTRO) 55th annual meeting, September 22-25, 2013, Atlanta, GA
(poster)
14. Morcovescu S. , Morton J.D., Boleware Y.E., Kerri P., 2014 , Clinical experience
with a miniature accelerated partial breast irradiation device: a 5-year single
institution comprehensive study , American Brachytherapy Society (ABS) Annual
meeting, April 3-5, 2014, San Diego, CA , Brachytherapy, 13, S82.
15. Yock A.D., Reiff J.E., S. Morcovescu , D. Sca nderbeg, 2015 , Treatment time
nomogram for strut-based accelerated partial breast applicators , American
Association of Physicists in Medicine (AAPM) 57th annual meeting, July 11-16,
2015, Anaheim, CA (poster)
16. Morcovescu S. , Morton J.D., 2016 , The use of a SAVI strut-based device in the
boosting of a stenotic distal vagina , World Congress of Brachytherapy, June 27-
29, 2016, San Francisco, CA, Brachytherapy 15, S132.
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