Volumetric Modulated Arc Therapy versus Dynamic Conformal Arc

58 Pages·2013·7.59 MB·English

by  Nishele Lenards

UNIVERSITY OF WISCONSIN-LA CROSSE
Graduate Studies

VOLUMETRIC MODULATED ARC THERAPY VERSUS DYNAMIC CONFORMAL ARC
STEREOTACTIC RADIOSURGERY FOR INTRACRANIAL LESIONS

A Research Project Report Submitted in Partial Fulfillment of the Requirements for the Degree
of Master of Science in Medical Dosimetry

Angela Marie Kempen

College of Science & Health
Medical Dosimetry Program

May 2013
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VOLUMETRIC MODULATED ARC THERAPY VERSUS DYNAMIC CONFORMAL ARC
STEREOTACTIC RADIOSURGERY FOR INTRACRANIAL LESIONS

By Angela Marie Kempen

We recommend acceptance of this project report in partial fulfillment of the candidate's
requirements for the degree of Master of Science in Medical Dosimetry

The candidate has met all of the project completion requirements.

April 30 , 2013
Nishele Lenards, M.S. Date
Graduate Program Director
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The Graduate School
University of Wisconsin-La Crosse
La Crosse, WI

Author: Kempen, Angela M.
Title: Volumetric Modulated Arc Therapy versus Dynamic Conformal Arc
Stereotactic Radiosurgery for Intracranial Lesions
Graduate Degree/ Major: MS Medical Dosimetry
Research Advisor: Nishele Lenards, M.S.
Month/Year: May 2013
Number of Pages: 58
Style Manual Used: AMA, 10th edition

Abstract
The aim of this study is to dosimetrically evaluate dynamic conformal arc therapy
(DCAT) and volumetric modulated arc therapy (VMAT) via frameless, linear accelerator based
stereotactic radiosurgery (SRS) for the treatment of brain metastases. Dosimetric evaluation
parameters included the target coverage, conformity index (CI), homogeneity index (HI),
gradient index (GI), and the volume of the normal brain tissue receiving doses of 12 and 5 Gray
(Gy). Two plans were developed per each patient, with a total of ten patients, utilizing DCAT
and VMAT. Results of this research outline which planning method may provide benefits or
lack thereof depending on the brain metastases location and size, thus providing data in terms of
conformity of target coverage as well as lower dose spillage to the rest of the brain. This study
also provides dosimetric results regarding advantages and disadvantages of forward versus
inverse planning, in addition to the impact of a multi-leaf collimator (MLC) width size. The
results of this study showed the superiority of DCAT when compared to 2 coplanar arc VMAT
treatment plans.
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The Graduate School
University of Wisconsin - La Crosse
La Crosse, WI

Acknowledgments
I would like to give special thanks to the Gundersen Lutheran Medical Center physics
staff for teaching me so much about medical dosimetry, in addition to all their help and support.
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Table of Contents
.................................................................................................................................................... Page
Abstract ............................................................................................................................................3
List of Tables ...................................................................................................................................6
List of Figures ..................................................................................................................................7
Chapter I: Introduction ....................................................................................................................8
Statement of the Problem ...................................................................................................12
Purpose of the Study ..........................................................................................................13
Assumptions of the Study ..................................................................................................13
Definition of Terms ............................................................................................................13
Limitations of the Study………………………………………………………………….17
Methodology ......................................................................................................................17
Chapter II: Literature Review ........................................................................................................19
Chapter III: Methodology ..............................................................................................................32
Sample Selection and Description .....................................................................................32
Instrumentation ..................................................................................................................32
Data Collection Procedures ................................................................................................33
Data Analysis .....................................................................................................................34
Limitations .........................................................................................................................34
Summary ............................................................................................................................35
Chapter IV: Results ........................................................................................................................36
Item Analysis .....................................................................................................................36
Chapter V: Discussion ...................................................................................................................39
Limitations .........................................................................................................................39
Conclusions ........................................................................................................................39
Recommendations ..............................................................................................................40
References ......................................................................................................................................55
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List of Tables
.................................................................................................................................................... Page
Table 1: Patients, tumor and treatment parameters ........................................................................42
Table 2: Description of treatment planning techniques .................................................................42
Table 3: SRS plan evaluation data for DCAT and VMAT ............................................................43
Table 4: SRS Plan Comparison .....................................................................................................43
Table 5: Volume of normal brain tissue at V12 and V5 doses for DCAT and VMAT .................44
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List of Figures
.................................................................................................................................................... Page
Figure 1: 3D views of the planning or gross target volumes for patients #2 and #10 ...................45

Figure 2: Dose distribution of the DCAT plan on the top and the VMAT plan on the bottom for
(a) patient #2, and (b) for patient #10 taken at similar 3D views. Isodose lines are
scaled at the same levels of dose to indicate plan comparisons visually.. ....................46
Figure 3: Dose distribution for (a) patient #2 and (b) patient #10 for DCAT plans on the top and
VMAT on the bottom showing 100%, 95% and 50% isodose levels on axial slices. ...48
Figure 4: Dose-volume histograms for target "R Temporal Lobe GTV", and "Brain-GTV" which
is the only OR structure for patient #2. Data on the top (a) is for the DCAT plan while
the bottom one (b) is for the VMAT plan. ....................................................................50
Figure 5: Dose-volume histograms for target "GTV", and "Brain-GTV", "Brain Stem" and
"OpticNerveChiasm" which are the OR structures for patient #10. Data on the top (a)
is for the DCAT plan while the bottom one (b) is for the VMAT plan. ........................51
Figure 6: RTOG Conformity index as a function of target volume for DCAT and RapidArc
(VMAT) plans ...............................................................................................................52
Figure 7: Paddick Conformity index as a function of target volume for DCAT and RapidArc
(VMAT) plans ...............................................................................................................52
Figure 8: Gradient index as a function of target volume for DCAT and RapidArc plans .............53
Figure 9: Homogeneity index as a function of target volume for DCAT and RapidArc plans .....53
Figure 10: Normal brain tissue minus target volume receiving 12 Gy dose .................................54
Figure 11: Normal brain tissue minus target volume receiving 5 Gy dose ...................................54
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Chapter I: Introduction
Brain tumors account for 1.5% of all malignancies diagnosed annually in the United
States.1 Approximately, 85-90% of central nervous system (CNS) tumors involve the brain,
whereas the spinal cord is involved in 20% of cases.2 According to the National Cancer Institute,
22,910 new cases of brain and other CNS tumors were diagnosed leading to 13,700 deaths in
2010.2 Brain tumors are the second leading cause of death in children, trailing behind leukemia.1
There are different classifications of tumors of the CNS; gliomas (including astrocytoma,
glioblastoma, glioblastoma multiforme, brainstem and thalamus tumors), in addition to pituitary,
medulloblastoma, oligodendroglioma, ependymoma, meningioma, lymphoma and schwannoma.1
Primary brain tumors are moderately uncommon; however, cerebral metastases occurs in
approximately one third of those diagnosed with cancer; therefore, making them the most
common brain lesion.1 The prognosis for brain tumors is generally poor. However, the 5-year
survival rates for patients with primary tumors has risen over the past couple decades to an
overall survival of 35%.1 Treatment for primary and metastatic brain tumors includes surgery,
chemotherapy, radiation therapy, immunotherapy and vaccine therapy.2 The options for
radiation therapy and chemotherapy vary depending on histology and anatomic location of the
brain lesion.2 Radiation therapy plays a major role in the treatment of patients diagnosed with
high-grade gliomas, including glioblastoma, anaplastic astrocytoma, anaplastic
oligodendroglioma, and anaplastic oligoastrocytoma, as well as those with brain metastases.
The origin of primary CNS tumors is currently unknown.1 Occupational and
environmental exposures, lifestyle and dietary factors, medical conditions and genetic factors are
all thought to perhaps have an association with brain tumors.1 The three most important
prognostic factors include age, performance status and tumor type. The incidence rate for CNS
tumors is 5 per 100,000 people.1 While age is the dominant variable in the occurrence of these
tumors, race and gender also play a significant role. An increase in the incidence of CNS tumors
diagnosed in the elderly population has been noted.1 An increase in age expectancy, improved
availability and use of computed tomography (CT) and magnetic resonance imaging (MRI), as
well as increased knowledge and interest in improving quality of life in the elderly contribute to
the rise in incidence.1 The average age at diagnosis is 50 to 80. In 2008, approximately 21,810
CNS tumors were diagnosed, with 16,400 of them being in the cerebrum. Of those, half were
diagnosed as gliomas, and 75% were high-grade gliomas.1
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During recent years, radiation therapy has played a significant role in the treatment of
CNS tumors; therefore, increasing survival rates and improving quality of life.1 Patients
diagnosed with malignant tumors that cannot be surgically removed, are only partially excised,
or are associated with metastatic disease should undergo radiation therapy. Tumor type, tumor
grade, patterns of recurrence, and radio-responsiveness are important factors to consider in
determining the doses for radiation treatment. When determining total doses, the progression of
the tumor in addition to the potential risk of radiation necrosis of normal tissues, must be taken
into consideration. Radiation therapy used in the treatment of brain tumors can be delivered in
multiple approaches. Consideration for the type of disease, tumor location and extent are
essential. Not only is a total resection of a brain tumor challenging, but also obtaining adequate
resection margins in brain tissue is almost impossible with surgery alone. Therefore, radiation
therapy can be utilized after surgical procedures in an effort to prevent tumor recurrence.1 The
most common treatment technique is whole brain radiation therapy (WBRT), where the entire
brain is treated via opposing lateral fields. Additionally, this technique is commonly used in the
presence of brain metastases as well. Currently, standard treatment in the United States is 30 Gy
of WBRT delivered in 10 fractions.3 A rapidly growing, important treatment option for patients
with CNS tumors is stereotactic radiosurgery (SRS).4 Stereotactic radiosurgery is a technique
utilizing radiation treatments in a single, high-dose fraction of ionizing radiation that conforms to
the shape of the lesion.5 Radiobiology of such high dose fraction(s) needs to be well understood
in terms of its differences regarding toxicities and side effects, as well as the possible benefits
when compared to conventional fractionation of 1.8 to 2.0 Gy per fraction.
As previously mentioned, radiobiology is an important component in treating cancer with
radiation. Throughout history, accepted radiobiology has relied on the linear quadratic (LQ)
model which evaluates the effectiveness of radiation delivery treatments by comparing daily
doses.6 Currently, typical clinical daily doses range from 1.2-2.5 Gy. Puck and Marcus7 showed
that fractional cell surviving radiation is equal to S.F. = e- (αΔ+βΔ2). This formula takes into
account the alpha/beta (α/β) ratio, which demonstrates differentiated dose response of late and
acute responding tissues. The ratio is low for late responding tissues and high for acute
responding tissues. Conventionally, it is the tolerance of late responding tissues within the field
that limits the radiation dose.6 For tumor cells where the α/β ratio is low, such as 2 Gy for
melanoma, soft tissue sarcoma, liposarcoma, prostate and breast, shortening the treatment time
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through hypofractionation may be beneficial. In terms of radiobiology of hypofractionation,
which is a dose of 12-20 Gy per single fraction, the traditional behavior of the radiobiology
fractionation is altered.6 Radiobiology fractionation principles include repair, re-assortment, re-
oxygenation, and re-population. The new dominating role players become bystander/abscopal
factors, immune activation and tumor endothelium cell deaths.6 Bystander/abscopal effects
occur when unirradiated tumor cells behave as if irradiated due to the messages being carried out
by irradiated cells.6 High dose radiotherapy may help activate immune system response, which
does not occur with conventional fractionation. Such immune system response can help fight
against the primary tumor as well as potentially prevent distant metastases.6 At fractional doses
of 10 Gy or higher, animal studies showed endothelial cell death by activation of
acidsphingomyelinase (ASMase) and ceramide generation.6 It is important to note that
endothelium in brain, lung and stomach are radio-resistant in the absence of ASMase.6
With the radiobiology of SRS proven to be successful, various clinical studies have been
conducted to evaluate the efficacy of SRS for intracranial lesions. The most commonly treated
lesions with SRS include arteriovenous malformations (AVMs), vestibular schwannomas,
acoustic schwannomas, meningiomas, gliomas and metastatic brain tumors.5 Recently, there
have been studies showing strong evidence of the efficacy of SRS. University of Pittsburgh
Medical Center (UPMC) reported a study including 829 patients with vestibular schwannoma
who were treated with SRS to dose of 12-13 Gy.6 The results showed a 10 year control rate as
high as 97%.6 Studies performed evaluating SRS treatment of brain metastases either alone or in
addition to whole brain irradiation have shown improved local control. A trial conducted by
Radiation Therapy Oncology Group (RTOG) 09-58 randomized 333 patients with 1-3 brain
metastases (< 4 centimeter diameter) and Karnofsky Performance Status (KPS) ≥ 70 to either
WBRT alone versus WBRT followed by an SRS boost.6 The results demonstrated significant
improvement in local control for all patients, in addition to improved survival rates for patients
with a single brain metastasis with WBRT followed by an SRS boost.6 There were two studies
conducted by UPMC evaluating treatment of meningiomas. The first study included 159 patients
treated with a median margin dose of 13 Gy.6 The results showed tumor control rates at 5 and 10
years both to be 93.1%.6 The second trial included 168 patients with petroclival meningiomas.6
The 5 and 10 year survival rates were 91% and 86% respectively.6