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.

Nishele Lenards, M.S. Date Graduate Program Director

April 30, 2013

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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

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Stereotactic radiosurgery has become a routine approach over the past couple decades.

To effectively acquire the benefits of SRS, high precision is vital. The treatment requires an

overall accuracy of approximately 1 mm.4 Historically, SRS has referred to targeting intracranial

lesions. Stereotactic radiosurgery can be delivered using multiple modalities and has been

applied to a number of various benign and malignant malformations. Different specialized

approaches for radiosurgery include Elekta’s GammaKnife, which utilizes a live Cobalt-60

source inside a gamma-ray treatment device, Accuray’s CyberKnife that is a particle beam

accelerator, or a medical linear accelerator with either a frame or frameless system using

BrainLab’s Novalis system.6 GammaKnife uses 201 very small well-collimated beams of

gamma radiation that focus precisely on the tumor. The patient has a stereotactic frame attached

to his or her skull, which is then attached to the automatic positioning system. The patient is

advanced into the machine and the shielded vault is closed for treatment. CyberKnife utilizes a

linear accelerator attached to a robotic arm with 6-degrees of freedom, each of which delivers

pencil beams of radiation. A medical linear accelerator can be adapted to deliver SRS treatment.

A linear accelerator system involves a gantry, which rotates around an axis of the machine in

space, to vary the delivery angle of a photon beam used for treatment. A stereotactic frame can

be used; however, more recently with the linear accelerator coupled with improved real-time

imaging methods, frameless systems have emerged. With MLC advancements and image-

guidance capabilities, linear accelerator based SRS has dramatically improved its accuracy and

viability. There are a few systems, from various manufacturers, being used in clinical

application such as Novalis (BrainLab, Heimstetten, Germany), Varian Medical Systems, and X-

knife (Radionics, Burlington, MA, USA).

For any type of SRS treatment, a vigorous immobilization is mandated. Historically,

linear accelerator based SRS required a stereotactic head frame, or halo, with a rigid fixation to

the skull. With recent advances in imaging modalities, more centers are utilizing the non-

invasive approach for patient comfort while maintaining similar accuracy as the rigid fixation

systems. Often, an aquaplast mask is used with a bite block for a non-invasive approach to

immobilization. An optical positioning system or image guidance tools such as on-board

imaging, cone beam CT, Tomotherapy, or Novalis ExacTrac may be used for position accuracy.6

The new dose delivery technologies, in addition to improved imaging capabilities, have

increased the use of precise stereotactic treatment delivery instead of conventional fractionation.

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Image guided radiation therapy (IGRT) techniques are required in order to achieve

stereotactic localization of the tumor.4 Linear accelerator based systems use secondary

collimation close to the patient that shapes the beam while reducing penumbra.4 Penumbra is

analogous to radiation beam width; therefore, as penumbra becomes smaller, the dose falls off

quicker. Ideally, the smaller the penumbra, the more conformal the radiation field size becomes.

Multi-leaf collimators can create off-axis beams. The MLC, with narrow leaves, is used in a

tertiary device even closer to the patient to further reduce penumbra.4 Dynamic delivery is

typically used with a large number of beams to irradiate the target. Intensity modulated radiation

therapy (IMRT), VMAT and DCAT are most commonly used with single isocenter, frameless,

linear accelerator based systems.

Over time, great advances have been made in regards to treatment techniques used to

deliver SRS. Non-invasive, frameless SRS has been implemented in many clinics and allows

patients to receive the benefits of SRS treatment without the invasive component. Multiple

studies have proven the efficacy for this method of radiation treatment. With the promise of SRS

becoming such a prominent role in increasing overall survival rates, it is essential to continue to

study and evaluate the various treatment techniques in order to continually improve treatment of

brain lesions.

Statement of the Problem

Studies have been done to evaluate the dosimetric differences between treatment

techniques used to deliver SRS for intracranial tumors.(8-16) Stereotactic radiosurgery is

becoming a widely accepted treatment approach for intracranial tumors; therefore, further

research is essential to provide data on various treatment techniques for SRS. The popularity of

non-invasive brain surgery is on the rise due to significantly improved imaging technologies.

There are multiple treatment techniques that can be utilized for non-invasive linear accelerator

based SRS, namely cone-based, DCAT, IMRT, Tomotherapy and VMAT. The specific problem

is determining which method will yield superior planning, resulting in improved treatment for

the patient. One main difference between these delivery methods is the planning, consisting of

forward versus inverse. Secondly, with the advent of smaller MLC leaf widths, it is expected

that DCAT or VMAT may yield better dosimetric results.16 Knowledge gained between these

two planning techniques would enable clinics to deliver SRS for intracranial tumors utilizing

techniques with dosimetric advantages.

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Purpose of the Study

The purpose of this research is to evaluate the dosimetric differences between treatment

plans using DCAT and VMAT. The plan comparisons of 20 treatment plans include target

coverage, conformity and homogeneity index, GI and dose fall-off or spillage. Between DCAT

and VMAT, the study aims to determine which technique offers a better planning evaluation

index depending on the brain metastases location, shape and size. This will in turn provide data

in terms of conformity of target coverage, in addition to lower doses to the normal brain tissue.

Potentially the results of the study will indicate the most beneficial technique for delivery of SRS

treatments for intracranial tumors.

Assumptions of the Study

The volume of normal brain tissue receiving doses of 12 and 5 Gy was tracked per the

radiation oncologists. This is an assumption in terms of clinical patient outcome. Another

assumption is in terms of the results of this research study. It is assumed that the DCAT

technique will produce slightly better results than VMAT due to the use of non-coplanar beams,

which was concluded from multiple literature reviews.(8-19) Otherwise, this research does not

have any other assumptions.

Definitions of the Terms

Acidsphingomyelinase (ASMase). This is a type of enzyme that hydrolyse certain types

of lipids to yield ceramide.6

Alpha/beta ratio. The ratio is a term used in the LQ model. It is the dose where the

number of cells killed by the linear component α is equal to the cell kill from the quadratic

component β. Early responding tissues have a high ratio, whereas late responding tissues have a

low ratio.20

Analytical Anisotropic Algorithm (AAA). A convolution-superposition algorithm used

to calculate radiation dose distribution in a treatment planning system computer.

Aquaplast mask. A trade name for a thermoplastic that is used frequently as an

immobilization device of the head and neck region.1

Astrocytoma. Low grade or anaplastic tumors of the CNS. They originate from the

non-neuronal supporting cells.1

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Bite block. An object placed between the patient’s teeth to assist in immobilization. It

also aids in placement of the tongue. It can be made of various materials including dental wax

and Aquaplast pellets.1

Ceramide generation. The generation of ceramides is a family of lipid molecules,

which are found in high concentrations within the cell membrane of cells. They are signal-

carrying molecules, which function and regulate programmed cell death and apoptosis of cells.6

Clinical Target Volume (CTV). Per ICRU Report 62, this volume indicates the gross

palpable or visible tumor volume (GTV) and a surrounding volume of tissue that may contain

subclinical or microscopic disease.21

Computed tomography (CT) simulator. A diagnostic imaging modality, used in

radiation therapy treatment planning, that provides accurate information on tumor localization

and identifying dose-limiting structures.

Conformity index (CI). The volume enclosed by the prescription isodose surface

divided by the target volume.22 The index is a dosimetric tool that attributes a score to a

treatment plan that can compare several treatment plans.

CyberKnife. A robotic radiosurgery system designed by Accuray that delivers pencil

beams of radiation via a linear accelerator attached to a robotic arm with 6-degrees of freedom.

Dynamic conformal arc therapy (DCAT). A treatment technique in which MLC leaves

move to dynamically conform to the tumor volume during gantry rotation.

Ependymoma. Low or high grade tumors arising from the ependymal cells lining the

brain ventricles and central spinal canal.1

GammaKnife. A treatment machine utilizing Cobalt-60 gamma radiation for use in

radiosurgery of the head only. It is designed by Elekta.

Glioblastoma. A fast-growing type of CNS tumor. It arises from glial (supportive)

tissue of the brain and spinal cord and the cells have an appearance quite different from normal

cells. Also known as Glioblastoma Multiforme or grade IV astrocytoma.2

Gradient Index (GI). A treatment planning index used to measure the dose gradient or

dose fall-off, which complements the conformity index when comparing several plans.

Gray (Gy). A unit of measured radiation dose. It is the absorption of one Joule (J) of

energy, in the form of ionizing radiation, per kilogram of matter. (J/kg)

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Gross Tumor Volume (GTV). Per ICRU Report 62, this volume indicates the gross

palpable or visible tumor.21

Homogeneity index (HI). This is defined by the target dose maximum divided by the

volume of reference isodose. The index is a dosimetric tool that attributes a score to a treatment

plan that can compare several treatment plans.

Histology. The study of tissues and cells under a microscope.2

Hypofractionation. This term describes a dosage of radiation that is divided into several

large doses given every few days.6

Image Guided Radiation Therapy (IGRT). A device used to image the patient

immediately before treatment in order to compare the position of the external set-up and internal

anatomy to the treatment plan.1

Image registration. Process where the images of the patient are aligned with respect to

the isocenter of the accelerator.1

Integral dose. The total energy absorbed by an organ(s) in terms of ionizing radiation,

expressed in gram-rads, also called volume dose, e.g. integral brain dose.

Intensity Modulated Arc Therapy (IMAT). A form of radiation treatment, where the

radiation field is divided into small “beamlets” via the aid of blocks/MLCs, and the intensity of

the beamlets are determined by planning optimization in the form of arc-rotation.

Intensity Modulated Radiation Therapy (IMRT). A form of radiation treatment,

where the radiation field is divided into small “beamlets” via the aid of blocks/MLCs, and the

intensity of the beamlets are determined by planning optimization. Tomotherapy utilizes IMRT

methods and delivers radiation slice by slice in a rotating fashion.

Isocenter. The isocenter is the point of intersection of the three axes of rotation (gantry,

collimator, and couch) of the treatment machine.1

Isodose lines. Isodose lines are connecting points of equivalent relative radiation dose.1

A radiation dose of equal intensity, e.g. 80% isodose line.

Karnofsky Performance Status (KPS). A scale, ranging from 1 to 100, which

measures the neurological and functional status of a person. Karnofsky Performance Scale

allows measuring of the quantity and quality of neurological defects.1

Linear accelerator. This is a radiation therapy treatment machine that accelerates

electrons and produces x-rays or electrons for treatment.1

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Linear quadratic (LQ) model. This is a method of demonstrating cell survival

following radiation with an equation. The equation approximates clonogenic survival data with a

truncated power series (second order polynomial) expansion of natural log of S (surviving

proportion) as follows:

lnS = -α x d – β x d2, where d = dose, α and β = expansion parameters.23

Lymphoma. A cancer that originates in cells of the immune system.2

Medulloblastoma. A highly malignant cerebellar tumor with the tendency to spread via

the cerebrospinal fluid.1

Magnetic resonance imaging (MRI). A diagnostic, non-ionizing way to visualize

internal anatomy through a noninvasive technique. Imaging is based on the magnetic properties

of the hydrogen nuclei.1

Meningioma. A type of slow-growing tumor that forms in the meninges, which are the

thin layers of tissue covering the brain and spinal cord.2

Metastases. The spread of cancer beyond the primary site of origin.1

Monitor Unit (MU). A measurement of output on a linear accelerator used to deliver

radiation treatments.

Multileaf collimator (MLC). A secondary part of the linear accelerator that allows

treatment field shaping and blocking through the use of motorized leaves in the head of the

machine.1

Oligodendroglioma. A type of slow-growing tumor that forms in the oligodendrocytes,

which are the cells that cover and protect nerve cells in the brain and spinal cord.2

Penumbra. The region near the edge of the field margin where the dose falls off rapidly.

The width of the penumbra depends on the size of the radiation source, the distance from the

source to the distal part of the collimator, and the source-to-skin distance (SSD).24

Photon. A small packet of electromagnetic energy, such as x-rays or gamma rays.1

Pituitary tumor. Being mostly benign, it is a cancer that forms in the pituitary gland,

which is a pea-sized organ at the base of the brain.2

Planning target volume (PTV). Per ICRU Report 62, this volume indicates the clinical

target volume (CTV) plus margins for geometric uncertainties, such as patient motion, beam

penumbra, and treatment setup differences.21

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Radiobiology. The study of the sequence of events following the absorption of energy

from ionizing radiations, the efforts of the organism to compensate and the damage to the

organism that may be produced.1

Radiation Therapy Oncology Group (RTOG). This is a nationally recognized research

group funded by the National Cancer Institute to improve quality of care in radiation oncology.

Schwannoma. Usually benign tumors of the peripheral nervous system that originate in

the nerve sheath, which is a protective covering.2

Stereotactic radiosurgery (SRS). The use of a high-energy photon beam with multiple

ports of entry convergent on the target volume.1 Usually high doses of 10 Gy or more are

delivered in a single fraction.

Thalamus. An area of the brain that helps process information from the senses and

transmit it to other areas of the brain.2

Target volume (TV). The area of a known and presumed tumor.1 This may be a GTV

or PTV depending on the patient and immobilization methods used.

Volumetric modulated radiation therapy (VMAT). An innovative approach to

delivering IMRT via arcs where the gantry, MLC speed, and dose rate of the linear accelerator

may be modified via optimization.

Limitations

A limitation to this study includes the number of patients. A small volume of patients

was studied therefore the data collected is limited. Optimization parameters may be a limitation

if the same optimization objectives are used for each case. To date, most of the treatment

planning algorithms for SRS are still pencil-beam calculations (PBC) that do a very poor job for

heterogeneous mediums, such as brain tissue. Therefore, it is a limitation that the study utilizes

analytical anisotropic algorithm (AAA), as other algorithms will produce slightly different

results. Lastly, all plans were calculated with a 1 mm grid size. The results may significantly

change, especially for target volumes less than 5 cc if a courser grid size were used; albeit the

course grid size would not yield the correct data.

Methodology

This research compares and evaluates two separate linear accelerator based SRS

treatment techniques for intracranial lesions. The two treatment techniques that were compared

include DCAT and VMAT. The study compares a variety of dosimetric parameters. The

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parameters analyzed are target coverage of the GTV or PTV, CI, HI, GI and the integral brain

dose by determining the volume of normal brain tissue receiving doses of 12 and 5 Gy.

Ten patients were included in this retrospective study. These patients were planned

utilizing the Eclipse treatment planning system (TPS) (v10, Varian Medical Systems). Two

treatment plans were created for each patient, one plan using VMAT, or RapidArc, and another

plan using DCAT. The plans were constructed using the RTOG 95-08 guidelines for total dose,

dependent on maximum tumor diameter. The goal of the study is to determine whether or not

the treatment techniques generate comparable plans, in addition to potential dosimetric

advantages.

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Chapter II: Literature Review

Brain tumors account for 1.5% of all malignancies diagnosed annually in the United

States.1 Primary brain tumors are moderately uncommon; however, cerebral metastases occurs

in approximately 1/3 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 brain 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.

Stereotactic radiosurgery is a treatment technique growing in popularity for the treatment

of brain tumors. There have been multiple studies done on increased survival and local control

rates with SRS in addition to external beam radiation therapy.6 Since studies are showing the

efficacy of SRS, it is important to understand the multiple modalities used to deliver these

treatments, in addition to possible dosimetric advantages of certain techniques. This review of

literature will cover topics such as a variety of dosimetric parameters used to analyze multiple

treatment planning techniques, effects of radiobiology, conformity index and effects of

calculation grid sizes.

Pollack and Ahmed6 described multiple intracranial tumors treated with SRS and the

advantages of this type of treatment. Additionally, the dose selections and tumor control rates

were studied and reported. With SRS, delivering high doses and conformity is possible while

effectively sparing critical structures adjacent to a tumor volume from radiation-induced

toxicities. Pollack and Ahmed6 mentioned several specific studies and RTOG protocols specific

to meningioma, vestibular schwannoma (VS), glomus tumor, pituitary adenoma,

craniopharyngioma, chordoma, chondrosarcoma, and brain metastases. Regarding meningiomas,

studies were conducted at Mayo Clinic and UPMC, which showed increased tumor control rates

with 12-18 Gy SRS. Studies done with VS at UPMC giving 12-13 Gy SRS yielded 10-year

tumor control rates of 97%. A UCSF study treated glomus jugulare with SRS and had a tumor

control rate of 95% with a mean follow-up of 71 months. Johns Hopkins found linac-based SRS

20

to have the same control rate of 95%. Pituitary ademonas treated with SRS had excellent tumor

control rates of 92-100%; however, endocrine cure rates were reported lower. There were

inconsistencies of the endpoints used in varying studies, but an average endocrine cure rate was

approximately 20-30%. In a study from Japan, tumor control rates were reported at 79.6% for

patients with craniopharyngiomas treated with 11.5 Gy SRS. The University of Pittsburgh

Medical Center treated with 13 Gy SRS and found the 1, 3, and 5-year overall local control rates

were 91%, 81%, and 68% respectively. Mayo Clinic studies involving skull base chordomas

treated with SRS to a marginal dose of 15 Gy had 2 and 5-year survival rates of 89% and 32%

respectively, with a follow-up time of 4.8 years. A dose of 16 Gy SRS was reported at UPMC to

yield a 5-year actuarial local tumor control rate of 62.9%.6

Brain metastases have historically been treated with WBRT; however, numerous RTOG

protocols and randomized trials have utilized SRS for selected patients with brain metastasis. A

trial at the University of Pittsburg showed the median survival for WBRT + SRS increased to 11

months versus 7.5 months for WBRT alone. A phase III study from MD Anderson showed

patients with SRS + WBRT also demonstrating increased survival rates, but unfortunately found

patients were significantly more likely to show decline than patients assigned to SRS alone.6

One of the most feared complications of brain radiotherapy is optic neuropathy. Utilizing

SRS to treat skull base tumors has shown a low incidence of this occurrence. Mayo Clinic

showed that the risk of developing clinically significant radiation-induced optic neuropathy was

1.1% for patients receiving a single SRS dose of 12 Gy or less. In addition, vascular damage

from SRS is rare as well. In order to decrease vascular damage, it is recommended that the

prescribed dose cover less than 50% of the diameter of the internal carotid artery or the

maximum dose to the internal carotid artery be limited to 30 Gy or less. Damage to the

brainstem has low occurrence also. According to Quantitative Analyses of Normal Tissue

Effects in the Clinic (QUANTEC), the tolerance of the brainstem to a single dose of radiation,

based on a maximum dose, is 12.5 Gy.6

A study similar to those reviewed in the book by Pollack and Ahmed6 was conducted by

Mehta, et al.20 The researchers systematically reviewed evidence for the use of SRS in patients

diagnosed with brain metastases. Key clinical questions were addressed comparing a

radiosurgery boost with WBRT to WBRT alone. The outcomes considered overall survival,

quality of life or symptom control, brain tumor control or response, and toxicity. Multiple

21

databases were searched and reviewed from 1990-2004 to collect data regarding the role of

radiosurgery for brain metastases. The data was tabulated to create an evidence-based review,

which included an assessment of the level of evidence. The review evaluated 3 randomized trials

regarding newly diagnosed brain metastases. Level I evidence indicated that overall survival

does improve for patients with a single brain metastasis, and that local brain control was

significantly improved in those patients with 1 to 4 metastases. Six months after treatment, one

trial demonstrated decreased steroid dosage and improvement of KPS; however, a non-

significant increase in the risk of toxicity was noted. Evidence from 2 randomized trials, 2

prospective cohort studies, and 16 retrospective series indicated that radiosurgery alone as the

initial treatment did not alter overall survival in patients. It was noted that utilizing radiosurgery

at the time of progressive or recurrent brain metastases requires stronger evidence.20

Similar to the evidence-based reviews conducted by Mehta et al,20 data was collected

from 10 different institutions by Sneed et al.25 The researchers quantitatively compared survival

probabilities for 569 patients with newly diagnosed brain metastases. Initially, 268 patients

underwent radiosurgery alone, which was assessed in comparison to 301 patients who were

managed with radiosurgery plus whole brain irradiation. One of the trials completed reviewed

236 patients with 1-3 brain metastases and KPS ≥ 50. The trial demonstrated that patients with

no known extracranial disease had a median survival time of 15.4 months when managed with

radiosurgery plus whole brain irradiation versus 8.3 months survival time when treated with

radiosurgery alone. However, a similar study looking at 105 patients showed no survival

difference. Regarding salvage therapy, it was determined that more data needs to be collected

from prospective trials following patients being treated with salvage therapy.25

In addition to the previous articles, the American College of Radiology conducted a study

looking at multiple trials and clinical scenarios regarding treatment for brain metastases.26 It was

found that the median survival for a patient with brain metastases varies between 4 to 6 months

after WBRT, which is an established standard of care for most patients diagnosed with brain

metastases. Many different dose schemes and fractionations, as well as various total doses have

been studied. However, none of the regimens have proven better than another in terms of

survival or efficacy. The most commonly used prescriptions include 30 Gy in 10 fractions or

37.5 Gy in 15 fractions and have proven to be an effective palliative treatment for brain

metastases. A majority of patients who receive WBRT do not receive local control, although

22

approximately half of these patients do experience an improvement in neurologic symptoms.

The multiple studies reviewed did show the effectiveness of SRS, however, this may be related

to choosing an appropriate patient selection. It was also stated that SRS alone probably could

not replace the benefits of WBRT.26

Treating with high dose schemes requires careful consideration since the risk of damage

to normal tissues associated with this type of treatment increases with increased dose. Nedzi27

reviewed radiation treatment courses using dose per fraction schemes of 10 Gy or above. He

evaluated the efficacy and safety of such high doses, also known as ablative therapy. Many

disease sites were reviewed, including trigeminal neuralgia, epilepsy, arteriovenous

malformations, acoustic neuromas, meningiomas, pituitary adenomas, malignant tumors

including early stage lung cancer, brain metastases, and liver and spine metastases. High rates of

recurrence are noted if complete resection of meningiomas is not achieved and unfortunately a

variety of meningiomas can be challenging to completely surgically resect due the location of the

tumor. In a situation such as this, SRS can be extremely effective. Retrospective data of small

meningiomas that could not undergo surgery supported an 89% - 94% progression-free effect for

patients treated with 15 - 16 Gy radiosurgery. Prospective trials are needed to evaluate the

efficacy of SRS with pituitary adenomas. Evaluation of 2 retrospective studies identifying

patients with multiple brain metastases treated with WBRT ± SRS showed that SRS added to

WBRT has benefits. The addition of SRS improves performance status and survival; however,

because these patients do not have long-term survival, more data is required on the patient’s

quality of life. Liver and spine metastases have been studied with stereotactic radiation therapy,

a promising treatment method requiring extra precise planning due to the proximity to crucial

adjacent structures.27 Certain critical organ dose tolerances specific to ablative therapies must be

carefully followed in any radiosurgery treatment.

The decision to treat a patient diagnosed with brain metastases is often influenced by a

variety of considerations. One factor frequently considered is whether a SRS program is readily

available to the institution where a patient is treated. A multi-institutional study of factors

influencing the use of SRS for brain metastases was recently conducted by Hodgson et al.28

Because the implementation of SRS is technically complex, this study chose to look at how local

availability of SRS affected how patients diagnosed with brain metastases were treated. Logistic

regression analyses were performed on 973 randomized patients. This analysis indicated factors

23

associated with using SRS as a boost treatment in combination with WBRT. Of these patients,

SRS was given as a boost treatment to 70 Gy, which accounted for approximately 7.8% of the

randomized population. The analysis showed the factors most significantly influencing the use

of SRS treatment were fewer brain metastases, controlled extracranial disease, age, and the

availability of an onsite SRS program at the hospital or clinic where the patient was being

treated. Results showed that whether or not the institution offered SRS changed the percentage

of patient receiving SRS drastically, especially for patients with 1-3 brain metastases, good

performance status, and no evidence of extracranial disease. For facilities that did not have a

SRS program, 3.0% of patients underwent SRS treatment, versus 40.3% of patients who were

treated at a facility with an onsite SRS program.28

With multiple factors influencing treatment decisions for patients diagnosed with brain

metastases as mentioned above, Sperduto et al29 conducted a study to introduce a new prognostic

index for patients with brain metastases. They looked at 1,960 patients in the RTOG database

and compared the new prognostic index with 3 other indices. Advantages and disadvantages

were found with all 4 indices compared. However, Recursive Partitioning Analysis (RPA) and

the new Graded Prognostic Assessment (GPA) had the most statistically significant differences,

with the GPA being the least subjective and most quantitative. Graded Prognostic Assessment

along with Score Index for Radiosurgery (SIR) incorporated the number of brain metastases,

whereas RPA and Basic Score for Brain Metastases (BSBM) did not include this parameter.

Score Index for Radiosurgery requires calculation of the volume of the largest lesion, which

varies depending on the treatment system used. With varying systems, it is often only assessed

at the time of treatment planning.29 This study was important in determining which treatment

approach is most appropriate for a given patient. Determining the appropriate treatments are

crucial to a patient’s outcome, and a useful prognostic index could guide the decisions made and

presented by physicians and their colleagues.

Stereotactic radiosurgery is becoming more and more utilized in the treatment of

intracranial tumors because of its precision and high dosage. Researchers have conducted

several studies, which have compared and evaluated the dosimetric differences between linear

accelerator based stereotactic radiosurgery techniques.(8-19) The various techniques included

three dimensional conformal radiation therapy (3D-CRT), IMRT, DCAT, and VMAT

(RapidArc), in addition to CyberKnife and GammaKnife. The dosimetric comparisons included

24

target coverage of the GTV and PTV, CI, HI, and dose received by critical structures proximal to

the tumor. (8-19)

Ding et al8 looked at dosimetric comparisons of different treatment techniques, including

3D-CRT, DCAT, and IMRT for the treatment of brain tumors. In this study, 15 patients were

selected who had been treated with Novalis. For all patients, 3D-CRT, DCAT and IMRT plans

were done. A standard margin of 1 mm was used for the planning target volume (PTV) and 90%

was used as the prescription isodose line for all plans. In order to quantify comparisons made in

the study, the target coverage at the prescription dose, conformity index (CI), and heterogeneity

index (HI) were analyzed. For PTVs ranging in size from ≥ 2 cm3 to ≤100 cm3, IMRT plans

yielded a high CI. Plans utilizing IMRT had better target coverage at the prescription dose, in

addition to a better HI for medium sized tumors. For large tumors with PTV >100 cm3, the

Intensity modulated radiation therapy plans demonstrated good target coverage at the

prescription dose and HI and CI values were comparable to those values found with the 3D-CRT

and DCAT plans. Intensity modulated radiation therapy utilizes inverse planning, which is better

for overlapping of the target and critical structures. It also lends the ability to decrease the dose

to normal brain tissue. Intensity Modulated Radiation Therapy was not recommended for small

tumors; however, for large tumors IMRT was superior. Dynamic conformal arc therapy was

found suitable for most treatments of brain tumors, and showed improved coverage of the

treatment volume when used for larger tumors. The plans produced high conformity, and the

treatment could be delivered in less time than 3D-CRT treatment plans. Three-dimensional

conformal radiation therapy was useful for small tumors because it demonstrated increased

ability to conform the dose distribution to irregular target shapes.8

Solberg et al9 compared absolute dose distributions from 3 radiosurgery delivery

techniques, including conventional approach using non-coplanar circular arcs, static field

conformal treatment, and dynamic arc field shaping. A simulated target with 3 overlapping

spheres was used for straightforward planning. The tumors ranged in size and required different

numbers of isocenters. The study found that circular arc techniques required multiple isocenters

for the treatment of large tumors, which in this case was 9.79 cm3, or irregularly shaped tumors

resulting in very low homogeneity within the target volume. The single isocenter approach used

with both the static fields and dynamic conformal arcs, increased the homogeneity within the

target volume and decreased the dose to surrounding critical structures.9

25

Hazard et al10 assessed the conformity of DCAT treatments for SRS delivered on a linear

accelerator. One hundred and seventy four cases were studied and quantitatively compared to

evaluate the target volume, and prescription isodose volume, which is defined as the total volume

encompassed by the prescription isodose surface. The 3 mm MLC improved conformity by the

ability to shape the MLC pattern to the beams eye view of the target volume for each 10 degrees

of the arc. The resulting CIs were similar to that of GammaKnife treatment plans. Treatment

times with DCAT are less than with GammaKnife as well. In addition, because conformity

varies with different prescription isodose surfaces, the researchers chose a uniform method for

selection of this surface. It was required that 95% of the target volume receive 100% of the dose,

in addition to 99% of the target volume receiving 95% of the dose.10 It is crucial to achieve high

dose coverage to the target volume by the prescription isodose surface, as well as decrease

complications by minimizing the volume of normal tissue receiving minimal dose.

Wang et al11 analyzed coplanar and non-coplanar arc treatments using intensity

modulated arc therapy (IMAT). Patients included in the study were diagnosed with 2 - 5 lesions.

A Novalis TX linear accelerator with high-definition MLC was used to deliver the treatments.

The MLC leaf width was 2.5 mm at isocenter. Treatment planning was done utilizing RapidArc

and the study compared the effects of a single arc versus 5-arcs on IMAT SRS treatment plans.

The target coverage, CI and volume of tissue within the low dose isodose line of 5 Gy were

compared. It was concluded that 5-arc non-coplanar treatment plans were superior regarding CI

and volume of tissue within the 5 Gy isodose line. The 5-arc plans produced a smaller volume

within the 5 Gy isodose line in addition to higher conformality.11

Lo,12 at Stanford University Medical Center, evaluated the quality of brain SRS treatment

plans between Accuray CyberKnife and Varian RapidArc. CyberKnife is a non-isocentric, cone-

based SRS system utilizing 6 MV, which has the ability to generate isodose distributions with a

high conformity index and rapid dose fall off. RapidArc is MLC based VMAT. With 2.5 mm

high-definition (HD) MLC, the treatment planning system can design the potential isodose

distributions required for brain SRS. CyberKnife treatment plans were recreated using RapidArc

with the same target coverage and dose constraints. The results of the study yielded superior

plans created when using CyberKnife. The RapidArc treatment plans were found to have higher

CI by 10%, a 70% higher ratio of volume receiving 50% of the prescription dose to a volume

26

receiving the prescription dose, 50% of the brainstem receiving more than 8 Gy, and 45% higher

dose 2 cm from the target on average.12

A study reviewing the feasibility of single-isocenter VMAT SRS for multiple brain

metastases was reported by Clark et al.13 The study looked at the plan quality of single versus

multiple isocenter VMAT planning technique using Varian RapidArc technology. The treatment

plans were created using single-arc/single isocenter, triple-arc (non-coplanar)/single isocenter,

and triple-arc (coplanar)/triple isocenter arrangements. Each patient had 3 brain metastases. In

using Paddick and RTOG evaluation tools, plans were quantitatively evaluated with dosimetric

parameters including CI scores, GI scores and 12 Gy isodose volumes. As a result, all 3 plans

were clinically acceptable; however, non-coplanar arcs demonstrated small improvements in the

CI as well as decreased 12 Gy isodose volumes when the 3 metastases were in close proximity to

each other. When the lesions increased distance between them, only small differences were

observed. The study concluded that a single isocenter could be used to deliver plans with

equivalent conformity to the multiple isocenter plans.13

A study was conducted by Mayo et al14 evaluating intracranial SRT. This study was the

researcher’s initial experience delivering linear accelerator based, frameless SRT with RapidArc.

The treatment plans were created using 2-3 arcs per isocenter, in addition to at least one of the

arcs being non-coplanar. The study compared a few dosimetric parameters including

conformity, homogeneity within the tumor volume, dose gradient and treatment times. The

results showed comparable outcomes with other treatment techniques such as CyberKnife,

Tomotherapy and static-beam IMRT. In addition, treatment times ranged from 4-7 minutes,

which is considerably shorter than other techniques. Therefore, it was concluded that SRT using

volumetric IMRT with RapidArc is a viable alternative.14

Similar to the study conducted by Mayo et al,14 Yang et al15 investigated the feasibility of

RapidArc for SRS and SRT for the treatment of intracranial lesions. Ten patients were studied

that had previously been treated with conventional DCAT plans. The patients were replanned

with RapidArc utilizing multiple non-coplanar arcs along with a single arc. The plan quality was

evaluated by comparing conformity and homogeneity indexes as well as the volumes of normal

tissue receiving low doses (V50, V25 and V10) of radiation between the RapidArc linear

accelerator based with DCAT. The volumes of normal brain receiving 50%, 25% and 10% of

the dose increased with the single arc RapidArc treatment plans. Increased MU’s were found

27

with the RapidArc plans; however, treatment time was comparable to DCAT. The results

yielded RapidArc superior when multiple arcs were implemented.15

Lagerwaard et al17 conducted a study evaluating a single arc utilizing RapidArc treatment

for SRS. A single arc can be delivered in less than 10 minutes, which is beneficial to both

patients and the staff in radiation therapy departments. Stereotactic radiosurgery in addition to

WBRT is an established treatment option for patients who are diagnosed with a limited number

of brain metastases. Most SRS treatments are delivered in a time frame of 20 minutes up to an

hour depending on the number of lesions. The researchers evaluated whether one arc using

RapidArc could possibly lessen the treatment duration. For this study, RapidArc treatments were

created for 6 patients with between 2 and 8 brain lesions. The volumes of these lesions ranged

from 1.0 to 37.5 cm3. All the lesions were treated to 18 Gy and prescribed to the 80% isodose

line. The single arc RapidArc plans were compared to 4-5 conventional dynamic conformal arcs

using CI and dose volume histograms (DVH). The results of the study found the CI of the

RapidArc plans to be superior to the dynamic conformal arcs. RapidArc yielded a CI of 1.5 ±

0.6 versus 2.1 ± 0.7 for dynamic conformal arcs. The RapidArc plans also had a decreased

volume of normal brain tissue encompassed in the 80% isodose surface. In addition, the

RapidArc plans resulted in a drastic decrease in treatment delivery times, averaging 8 minutes to

deliver each treatment. In conclusion, RapidArc can be regarded as an effective way to deliver

SRS treatments in addition to WBRT.17

A few studies focused on specific intracranial lesions and compared different treatment

techniques using SRS. Lee et al18 conducted a study on vestibular schwannomas using DCAT

with the Novalis system and Tomotherapy. They compared the dosimetric results of these

treatment methods using CI, HI, comprehensive quality index for 9 critical structures, gradient

score index, and plan quality index. Ten to 16 Gy was prescribed to PTV volumes ranging from

0.27 – 19.99 cm3. The study found Tomotherapy conformed better to the PTV but had a

decreased gradient score index. Tomotherapy also showed an advantage over DCAT with a

better plan quality index; however, the radiation beam was on longer and more monitor units

were used to deliver the treatment. The study confirmed more research should be conducted to

determine whether the dosimetric advantage of Tomotherapy confirms a clinical benefit as

well.18

28

Grabenbauer et al19 evaluated different techniques for SRS of pituitary adenomas. Out of

152 SRS procedures, 10 patients with pituitary adenomas were compared using conformal,

DCAT with a micro multi-leaf collimator (mMLC), circular collimators, and 8-10 conformal

static mMLC beams with and without IMRT. The prescribed total dose used was 18 Gy, with

Dmax of the optic chiasm < 8 Gy, and < 10 mL of the temporal lobe receiving 10 Gy. The

dosimetric parameters the researchers chose to compare the plans were coverage, CI, HI, and the

volume of the temporal lobe receiving 10 Gy. Intensity Modulated Radiation Therapy had better

coverage in 5 out of 10 patients over DCAT. In addition, IMRT had a smaller volume of tissue

outside the PTV receiving > 18 Gy in 9 of 10 patients. One patient had better conformity with

circular collimators. Circular arcs, however, yielded the highest maximum dose of 39.8 Gy,

which produced a HI of 2.2 versus HI of 1.13-1.2 for the other treatment techniques. The study

concluded that IMRT techniques are safe and appropriate for SRS of pituitary adenomas.19

The treatment modalities mentioned previously have been compared in many of the

studies quantitatively by utilizing a variety of dosimetric parameters. Conformity Index was a

common parameter assessed; however, there are multiple formulas used to calculate CI. Feuvret

et al30 analyzed and evaluated conformity indices based on their field of application. Medical

Dosimetry treatment planning systems provide dose distribution for each CT slice and a DVH to

aid in analyzing treatment plans, but there is no indication of conformity. A CI can be helpful by

providing a quantitative score in order to compare several treatment plans for the same patient.

The CI was primarily developed for SRS treatment plans, and integrates multiple parameters.

There were several volume-based conformity indices in various clinical settings. For SRS,

RTOG based its CI on several parameters, including reference isodose values of the treatment

plan, reference isodose volume or prescription isodose, and the target volume. Ideal CI equals 1,

while an index greater than 1 indicates the irradiated volume is greater than the target volume

and extends into normal structures. A CI less than 1 indicates the target volume is only partially

irradiated. As defined by RTOG, when a CI value is between 1 and 2, the treatment complies

with guidelines, if the index falls between 2 and 2.5, or 0.9 and 1 it is a minor violation, and

values less than 0.9 or greater than 2.5 are considered major violations. The disadvantage to this

CI is it does not consider the degree of spatial intersection of two volumes or their shape. An

ideal CI is yet to be determined in order to achieve the desired objective of the CI, which is to

quantify the quality of treatment with 100% specificity and sensitivity.30

29

The conformity of linear accelerator-based SRS using DCAT was assessed by Hazard et

al31 in a research study. In addition, the researchers also evaluated and described a standardized

method of isodose surface selection. The CI at the prescription isodose surface of 174 targets

was calculated. A prescription dose was chosen using the following criteria: 95% of the target

volume encompassed by the prescription isodose volume and 99% of the target volume

encompassed by 95% of the prescription dose. It was found that median CI was 1.63 at the

prescription isodose surface and 1.47 at the “standardized” prescription isodose surface. The CI

values previously reported for GammaKnife SRS were similar to the CI found in this study

looking at linear accelerator-based SRS. A “standardized” prescription isodose surface may aid

physicians in choosing a prescription isodose surface that takes into consideration coverage and

conformity, thus helping with CI comparison.31

Wagner et al32 presented a simple way to compare SRS plans. The purpose of the index

evaluated was to gauge multiple competing SRS plans, but not necessarily to assess the

superiority of one method of treatment delivery over another. The researchers provided a

combined conformity/gradient index (CGI), which is an average of a conformity score and

gradient score. Only 3 pieces of data were required to compute this relatively simple index.

This includes the total volume irradiated to the prescription isodose level, the target volume, and

the total volume irradiated at 50% of the prescription isodose level. A limitation of the CGI

score is its inability to consider the issue of dose inhomogeneity within the tumor volume.

Another limitation is that the CGI does not assess radiation dose to radiosensitive structures

beyond normal brain tissue. Therefore, it is concluded that the CGI is a very simple tool to

calculate for homogenous lesions that are located away from radiosensitive structures. The CGI

tool was proven useful as a simple, quick calculation for “forward” planning as well as “inverse”

radiosurgery planning.32

The studies reviewed previously included multiple treatment techniques including

GammaKnife and CyberKnife, in addition to techniques utilized for non-invasive linear

accelerator based SRS, namely cone-based, DCAT, IMRT, Tomotherapy and VMAT. One main

difference between these delivery methods was the planning, which was forward versus inverse.

Another comparison that has been analyzed includes the MLC utilized in treatment delivery.

With the introduction of smaller MLC leaf widths, it is expected that DCAT or VMAT may yield

better dosimetric results.16 Chern et al16 performed a dosimetric comparison of BrainLAB

30

micro-MLC with the leaf widths being 3 mm, 4.5 mm and 5.5 mm and Varian Millennium MLC

with leaf widths of 5 mm and 10 mm. For dynamic conformal arc SRS for treatment of

intracranial lesions, it was assumed that the micro-MLC would yield further improvement in

target conformity and normal tissue sparing. Two plans were done for each of the 23 patients in

the study, one using the minimal 3 mm MLC and one using the minimal 5mm MLC, while

keeping all parameters the same except for collimator angle, which were optimized for each arc

in the separate plans. In order to evaluate the normal tissue sparing in close proximity to the

target volume, a peritumoral rind structure of 1 cm was created. The CI used was an equation

described by Paddick, as used in a few other studies. The CI and normal tissue sparing was

found to be slightly improved with the minimal 3 mm MLC. In conclusion, the 3 mm micro-

MLC provided small improvements with better target coverage and increased normal tissue

sparing with SRS utilizing DCAT.16

Similarly, a dosimetric study was completed by Jin et al33 using different leaf-width

MLCs for treatment planning with DCAT and IMRT. Three mm micro MLC, 5 mm MLC, and a

10 mm MLC were evaluated for SRS using the Brainscan treatment planning system. The

dosimetric analysis used for comparison of the treatment techniques, target volumes, and

treatment sites included CI, DVH for organs at risk (OR), and the percentage target coverage.

When using DCAT, significant differences were found between the different leaf-width MLCs.

The CI ratio depends on the size of the target volume, and targets approximately 1 cm3 showed a

large variation between CI, however, for relatively large targets over 8 cm3, the variation

decreased. For IMRT plans, the results demonstrated the CI with minimal difference between

different MLC leaf widths. For both treatment planning techniques, the 3 mm MLC showed

improved OR DVHs, more notable with the OR with smaller volumes. The study concluded that

narrower leaf-width MLC could have some advantages over wider leaf-width MLC.33

Monk et al34 conducted a study comparable to Jin et al33 regarding a comparison of

different leaf-width MLCs. Three mm MLC and 5 mm MLC were dosimetrically compared on a

linear accelerator for SRT treatment of intracranial lesions. Fourteen patients diagnosed with

brain metastases who had been treated with BrainLAB’s 3 mm micro MLC were replanned using

the 5 mm Varian Millennium MLC. The same target coverage was achieved by adjusting the

MLC shape to conform around the PTV; however, noncoplanar beam arrangements were used.

The results demonstrated that the 5 mm Varian Millennium MLC provided an increase in the CI.

31

The DVH curves showed an increase in the volume of normal tissues receiving low dose

radiation, but the maximum dose to critical structures did not significantly increase with the 5

mm MLC. It was concluded that the 3 mm micro MLC does consistently improve PTV

conformity and achieves decreased low dose spillage to surrounding normal tissues. However,

quantitatively the improvements are not significant enough to give evidence of one leaf-width

MLC to be more beneficial than the other.34

Another principal component to consider when planning and evaluating SRS is proper

calculation of the dose distribution. Ong et al35 investigated the impact of calculation resolution

using anisotropic analytical algorithms (AAA). They were looking specifically at 3D-CRT

utilizing small fields in homogeneous and heterogeneous mediums and with the use of RapidArc

plans. Dose distributions were calculated utilizing AAA version 8.6.15 and 10.0.25. These

distributions were compared with measurements performed using GafChromic film on phantoms

made of polystyrene. They evaluated the accuracy of the algorithms calculated using grid

resolution sizes of 2.5 and 1.0 mm. Both AAA versions demonstrated lower peak doses and

broader penumbra widths than the measured. However, using AAA version 10.0.25 with a 1.0

mm calculation grid improved the dose distribution. It was found that 1.0 mm was superior to

2.5 mm and was recommended. However, when using the smaller dose grid at 1.0 mm, the

calculation times were longer.35

In conclusion, several studies have indicated the use of SRS, in addition to external beam

radiation therapy, can provide increased survival and local control rates.6 There are multiple

modalities used to deliver these treatments and the possible dosimetric advantages of certain

techniques are advantageous in treatment planning of SRS. The variety of dosimetric parameters

used to analyze multiple treatment planning techniques, effects of radiobiology, and the effects

of calculation grid sizes is important when determining the most effective way to plan and

deliver SRS in the treatment of brain lesions. Dynamic conformal arc therapy and VMAT are

two commonly used methods in planning and delivery of SRS treatment. This study aimed to

quantify the dosimetric indicies utilized in evaluating SRS treatment plans and indicate a

superior planning method between DCAT and VMAT.

32

Chapter III: Methodology

Patients diagnosed with primary brain tumors or brain metastases may be candidates for

radiation therapy. Traditionally, 3D-CRT or WBRT have been used as the treatment technique

for these lesions. However, SRS has been rapidly growing in popularity and can be applied to a

number of various benign and malignant intracranial lesions. There are multiple treatment

techniques that can be utilized for non-invasive linear accelerator based SRS, namely cone-

based, DCAT, IMRT, Tomotherapy and VMAT. Prior research has proven the efficacy of SRS

in conjunction with WBRT for brain metastases.20 Stereotactic radiosurgery delivered via

DCAT or VMAT has the ability to increase local control and survival rates. The specific

problem is determining which method will yield superior planning, resulting in improved

treatment for the patient. Knowledge gained between these 2 planning techniques would enable

clinics to deliver SRS for intracranial tumors utilizing techniques with dosimetric advantages.

The purpose of this research is to evaluate a variety of dosimetric parameters between treatment

plans using DCAT and VMAT.

Subject Selection and Description

For this retrospective research study, 10 patients were selected using a purposive

sampling method; therefore, the study will involve a deliberate selection of individuals. By

using this method of sampling, it will be ensured that the patients included in the study meet

specific, pre-determined criteria. The patients selected will have intracranial tumors and meet

requirements for SRS treatment. The patients included in this research study will meet the

requirements of RTOG 95-08, which allowed a maximum tumor diameter of 4.0 cm. All

patients included have received previous radiation treatment for brain metastases. Figure 1

displays the location and size of the brain metastases for all 10 patients included in the study.

The patients included have a single lesion metastasis. The patients were all treated at Gundersen

Lutheran Medical Center in La Crosse, Wisconsin.

Instrumentation

A variety of different equipment was needed for this research study. A treatment

planning computed tomography (TPCT) scan was obtained using a GE lightspeed R16. The

precision of SRS requires the patients to have extensive immobilization. The patients included

in the study each had a custom, reinforced Orfit facemask, in addition to an “S” frame. This

frame extends over the edge of the treatment couch allowing for increased couch treatment

33

angles, as well as less attenuation, during treatment delivery. Image fusion of MRI and the

TPCT was required in order for the physician to accurately delineate the tumor volume, as well

as critical structures in proximity to the tumor volume. The treatment plans created for the

patients in this study were developed through the use of the Eclipse treatment planning system

(TPS) (v10, Varian Medical Systems). Two treatment plans were created for each patient; one

using VMAT RapidArc, in addition to another plan using DCAT. The plans were developed

following RTOG 95-08 guidelines. Per the protocol, total dose is dependent on the size of the

lesion.3 An assigned total dose of 24 Gy was prescribed for planning a maximum tumor

diameter of ≤ 2 cm, 18 Gy was prescribed for a maximum tumor diameter of 2.1-3.0 cm, and 12

Gy was prescribed for a maximum tumor diameter of 3.1-4.0 cm.3 The MLC dimensions varied

for each treatment technique. Volumetric modulated radiation therapy utilized two full

optimized, coplanar arcs around the patient with 120-leaf millennium MLC (Varian Medical

Systems), which project 5 mm width from isocenter in each direction for the inner 10 cm. In

contrast, DCAT used seven non-coplanar arcs with micro (m3) MLC (BrainLAB) that project 3

mm out to 2.1 cm on either side of isocenter, 4 mm for 3.3 cm on either side of isocenter and 5

mm out to 4.5 cm on either side of isocenter. For the above DCAT technique, a standard table

arrangement was used setting the table approximately 27 degrees apart for each non-coplanar arc

delivered (90°, 63°, 36°, 10°, 350°, 323° and 296°). The treatment planning calculations were

done using AAA due to its ability to accurately calculate heterogeneous mediums. For field

sizes of < 3x3 cm2, a recent publication indicated the significant improvement of dose

calculation accuracy using AAA v10 when the calculation grid size was reduced from 2.5 mm to

1.0 mm.35 Therefore, for this study the calculation grid size was set to 1.0 mm.

Data Collection

Data collection for this research study consisted of multiple steps. The 10 patients that

were chosen for this retrospective study had previously been treated for SRS; therefore,

MRI/TPCT fusion had already been completed. The physician previously contoured GTV and

PTV volumes, in addition to critical structures. Upon review of the previous planning, some

modifications were made in order to standardize the planning criteria of the patient population

included.

The next step in the process was to re-plan utilizing the Eclipse TPS. Each patient had

two plans developed, one using DCAT and the other using VMAT or RapidArc. Seven non-

34

coplanar arcs with various table angles were created for DCAT and two full coplanar arcs were

used for VMAT. Dynamic conformal arc therapy uses forward planning methods versus VMAT

using inverse planning optimization. Once optimal treatment plans were created, the next step

was gathering the dosimetric parameters including target coverage, CI, HI, GI, and the volume of

the normal brain tissue receiving doses of 12 Gy and 5 Gy.

Data Analysis

Data collection was analyzed utilizing descriptive statistical analysis. This type of

analysis allowed the large amount of data generated from the treatment plans to condense into a

comprehensible and interpretable form. A DVH was utilized to determine target coverage.

Additionally, the mean, range and standard deviations were calculated. To determine isodose

volumes, which are required to calculate the conformity and homogeneity indexes, the “convert

isodose level to structure” tool was used. In order to evaluate CI, the formula created by RTOG

and Paddick36 was utilized, PITV = VRI/TV and CIPaddick = TV2RI/TVxVRI, respectively. PITV is

defined as the RTOG conformity index where VRI is the reference isodose volume and TV is the

target volume. TVRI is the target volume covered by the reference isodose.37 Two conformity

indexes were calculated because the RTOG index does not penalize for the prescription isodose

line that does not cover the target. For evaluation of homogeneity index, HI = Dmax/VRI, where

Dmax is the maximum dose to the target will be used.37 The GI was evaluated using a formula

created by Paddick;38 GI = V50%RI/VRI, where V50%RI is defined as the volume of 50% of the

reference isodose. A DVH was utilized to determine the volume of normal brain tissue receiving

doses of 12 Gy and 5 Gy.

Limitations

A limitation to this study includes the number of patients. A small volume of patients

was studied therefore the data collected is limited. Optimization parameters may be a limitation

if the same optimization objectives are used for each case. To date, most of the treatment

planning algorithms for SRS are still pencil-beam calculations (PBC) that do a very poor job for

heterogeneous mediums, such as brain tissue. Therefore, it is a limitation that the study utilizes

analytical anisotropic algorithm (AAA), as other algorithms will produce slightly different

results. Lastly, all plans were calculated with a 1 mm grid size. The results may significantly

change, especially for target volumes less than 5 cc if a courser grid size were used; albeit the

course grid size would not yield the correct data.

35

Summary

Ten patients were included in this study that met specific, pre-determined criteria. Two

plans were developed per patient, with a total of ten patients, utilizing DCAT and VMAT. Data

was collected and analyzed utilizing descriptive statistical analysis. Measures of central

tendency and variability including the mean, range and standard deviation were used.

Dosimetric evaluation parameters included the target coverage, CI, HI, GI, and the volume of the

normal brain tissue receiving doses of 12 and 5 Gy.

36

Chapter IV: Results

The purpose of this research was to evaluate the dosimetric differences between treatment

plans using DCAT and VMAT. The plan comparisons included target coverage, conformity and

homogeneity index, GI and normal brain tissue doses. Between DCAT and VMAT, the study

aimed to determine which technique offers a better planning evaluation index for 10 metastatic

brain SRS patients outlined in Table 1. Treatment plans were optimized using 7 non-coplanar

DCAT and 2 coplanar VMAT fields as outlined in Table 2. Target coverage to the GTV or PTV,

according to the indices, as well as normal brain tissue doses were used to evaluate the treatment

plans. The results of this study showed the superiority of DCAT when compared to 2 coplanar

arc VMAT treatment plans.

Item Analysis

The results section is divided into 2 comparisons. Comparison 1 analyzed the treatment

planning efficacy in terms of the RTOG and Paddick36 conformity indices, Paddick38 gradient

index, and HI between DCAT and VMAT. A total of 20 plans, 10 each per planning modality,

indices were compared. Stereotactic radiotherapy plan evaluation data for DCAT and VMAT is

summarized in Table 3 for the patient pool. In addition, the mean values for each index were

calculated along with the standard deviation in order to differentiate the target coverage between

DCAT and VMAT. Table 4 provides the mean data for comparison of treatment plan indices.

Comparison 2 looked at the dose to critical structures. Since all 10 patients’ lesions were not

located near the optical or auditory apparatus, brain stem, spinal cord, or pituitary gland, normal

brain tissue doses were analyzed. Moreover, V12, which is the absolute volume of normal brain

tissue in cc’s receiving 12 Gy of dose, and V5, were cumulated demonstrating that DCAT

provided a statistical advantage over VMAT at either dose level.

Comparison 1

The first comparison between DCAT and VMAT treatment plans looked at treatment

plan indices for target coverage and dose fall-off. All 20 of the treatment plans were normalized

as 99% of the target volume receiving 100% of the prescription dose. While RTOG and

Paddick36 conformity indices, along with HI provided how well the target was covered,

Paddick38 GI provided valuable information regarding how fast the dose fall-off occurred beyond

the target. The index specifically compared the ratio of 50% of the reference isodose volume to

the prescription isodose volume. As outlined in Table 3, the target volumes ranged from 0.13 cc

37

– 10.24 cc. Radiation Therapy Oncology Group CI for the targets ranged from 0.85 – 1.33 for

DCAT, and 1.08 – 1.44 for VMAT, mostly increasing with target volume. Similar results were

seen studying the Paddick36 CI, which takes the target volume covered by the referenced isodose.

Thus Paddick36 CI ranged from 0.45 – 0.78 for DCAT and 0.45 – 0.83 for VMAT, increasing in

number with increasing target volume. In terms of homogeneity of the plans, the HI values for

DCAT ranged from 1.17 – 1.22, and VMAT values ranged from 1.05 – 1.21. In terms of mean

values, the PITV was 1.18 ± 0.13 for DCAT and 1.27 ± 0.11 for VMAT. Paddick36 CI mean

results were 0.68 ± 0.11 for DCAT and 0.69 ± 0.11 for VMAT. Lastly, HI means were 1.20 ±

0.02 for DCAT and 1.12 ± 0.06 for VMAT. Therefore, the HI was slightly better for VMAT.

However, the PITV and Paddick36 CI mean results showed DCAT as slightly superior. Plots for

RTOG and Paddick36 conformity indices can be seen on Figure 6 and 7 respectively, while

Figure 9 shows the plot of the HI as a function of tumor volume.

In terms of dose fall-off or spillage, the GI values ranged from 2.65 – 8.45 for DCAT and

4.25 – 18.21 for VMAT. The mean Paddick38 GI values were 3.99 ± 1.76 for DCAT versus 7.55

± 4.17 for VMAT. The GI as a function of target volume for each treatment plan modality was

plotted in figure 8.

Comparison 2

Along similar lines of evaluating dose spillage and its effects on OR structures, normal

brain tissue volumes receiving 12 and 5 Gy of dose were compared for DCAT and VMAT plans.

V12 for normal brain tissue is outlined in the QUANTEC report and suggests that such volume

be less than 5-10 cc for symptomatic necrosis avoidance. V5 was added as a parameter to track

based on clinical discussions with the physicians, in order to evaluate lower dose spillage

volumes. Table 5 outlines the volume of normal brain tissue receiving 12 and 5 Gy doses for

DCAT and VMAT. V12 Brain – Target values ranged from 0.9 – 13.8 cc for DCAT, and 2.4 –

22.3 cc for VMAT. V5 Brain – Target volumes for DCAT were 3.7 – 68.7 cc, and 9.9 – 124.8

cc for VMAT. This demonstrated that the volume of brain receiving 12 and 5 Gy was less with

the DCAT plans. The plots for V12 comparison between treatment plans for DCAT and VMAT

can be seen in figure 10, while V5 values are plotted in figure 11.

Results of this study can be analyzed in two parts: i) Target coverage in terms of

treatment plan evaluation indices including CI and HI, and ii) Dose fall-off in terms of gradient

index, and absolute normal brain tissue volumes receiving 12 and 5 Gy doses. In terms of target

38

coverage DCAT has a slightly better RTOG defined conformity, however Paddick CI and HI

values indicate that VMAT provides comparable coverage to the target as DCAT within

statistical error margins. Therefore, unless the tumor volumes are very small, as is the case of

0.13 cc for patient 1, both DCAT and VMAT can cover the target similarly. In the case of such

small target volumes, caution regarding the prescription isodose should be applied. A lower

prescription isodose would have increased both plans to a better index coverage. Analyzing the

dose fall-off showed that DCAT plans completed with 7 non-coplanar arcs provided a

statistically superior GI and normal brain tissue volumes receiving 12 and 5 Gy dose when

compared to the VMAT plans completed using 2 full coplanar arcs. Two coplanar arc, VMAT

plans yielded nearly twice the values seen for DCAT in terms of GI as well as normal brain

tissue volumes receiving 12 and 5 Gy.

39

Chapter V: Discussion

Stereotactic radiosurgery is a treatment technique growing in popularity for the treatment

of brain tumors. There have been multiple studies done on increased survival and local control

rates with SRS in addition to external beam radiation therapy.6 Since studies are showing the

efficacy of SRS in addition to external beam radiation therapy, it is important to understand the

possible dosimetric advantages of certain techniques. The purpose of this study was to compare

SRS treatment plans, namely DCAT and VMAT, based upon plan evaluation tools including

indices and dose to normal brain tissue. Ten patients were included in this study that met

specific, pre-determined criteria. Two plans were developed per patient, with a total of ten

patients, utilizing DCAT and VMAT. Data was collected and various dosimetric evaluation

parameters were analyzed including the target coverage, CI, HI, GI, and the volume of the

normal brain tissue receiving doses of 12 and 5 Gy. These dosimetric parameters were evaluated

to determine a superior treatment technique for SRS delivery. The results of this study showed

the superiority of DCAT when compared to 2 coplanar arc VMAT treatment plans.

Limitations

A limitation to this study includes the number of patients. A small volume of patients

was studied therefore the data collected is limited. Optimization parameters may be a limitation

if the same optimization objectives are used for each case. To date, most of the treatment

planning algorithms for SRS are still pencil-beam calculations (PBC) that do a very poor job for

heterogeneous mediums, such as brain tissue. Therefore, it is a limitation that the study utilizes

analytical anisotropic algorithm (AAA), as other algorithms will produce slightly different

results. Lastly, all plans were calculated with a 1 mm grid size. The results may significantly

change, especially for target volumes less than 5 cc if a courser grid size were used; albeit the

course grid size would not yield the correct data.

Conclusions

This study concluded that VMAT plans compared to DCAT for SRS treatment plans

produced similar results in terms of target coverage; however, produced almost twice the dose

spillage, which in turn doubles the 12 and 5 Gy dose to the healthy brain tissue. In addition, in

terms of RTOG and Paddick36 conformity indices, and HI, both treatment plan modalities

produced similar coverage to the target volume. However, in terms of Paddick38 GI, and normal

brain tissue receiving doses of 5 and 12 Gy, DCAT was superior. The plans utilizing VMAT

40

were 1.9 times the average GI to DCAT. Furthermore, VMAT plans would have irradiated twice

the amount of normal brain tissue compared to DCAT. These findings are consistent with

various studies previously conducted and outlined in the literature review. Monk et al34

concluded that RapidArc plans had an increased CI and higher dose spillage to normal brain

tissue. Additionally, Mayo et al14 and Yang et al15 yielded similar results. The researchers

conducting these studies found increased volumes of normal brain tissue when treating with

VMAT (RapidArc). However, Clark et al13 demonstrated an improved CI with VMAT using

non-coplanar arcs, as well as a decreased volume of normal brain tissue receiving 12 Gy. This

could be clinically very significant in order to avoid symptomatic necrosis to the brain, as

VMAT V12 volumes were greater than 10 cc on 4 out of the 10 patients planned, while DCAT

plans produced only a single patient that went over this QUANTEC threshold. If such a

threshold were to be reduced to 5 cc, then 6 out of 10 VMAT plans did not meet this criterion

while only 4 out of 10 DCAT plans did not. These findings strongly agree with published results

of IMRT as well as VMAT studies when a smaller number of coplanar fields or arcs were used.

Though previous research did look at normal brain tissue dose, this study expands on the

previous data by providing 12 and 5 Gy dose volumes in hopes to identify dose/volume

parameters for symptomatic necrosis of the healthy brain tissue. Laangerward et al17 had

findings slightly different from this study whereas RapidArc decreased the volume of brain

encompassed by the 80% isodose line. Finally, the current research study concluded that

treatment plan evaluation using indices is a great tool comparing SRS plans.

Recommendations

Although this study conclusively states 7 non-coplanar DCAT plans are better than 2

coplanar RapidArc (VMAT) plans in terms of target coverage as well as dose spillage, a more

extensive study is needed. A more extensive study would need to increase the number of arcs for

VMAT planning to 3, and then to 4 or 5 with a non-coplanar approach. These VMAT plans may

reduce dose spillage, thus reducing the volumes of brain tissue getting 5 and 12 Gy dose and still

maintain excellent target coverage. In addition, dose objectives for RapidArc were not modified

for each plan to maintain plan development consistency; however, a more active optimization

role may help produce statistically better results depending on the target location. Additionally,

this study involved a limited number of patients. An increased patient population could enhance

the results of this study and may certainly prove to have more comprehensive findings. Finally,

41

the VMAT plans used 5 mm width MLCs while the DCAT used 3 mm microMLCs. An

additional study could be done utilizing the 2.5 mm HD MLC set that is available with Varian

linear accelerators. Reducing the MLC width to 2.5 mm may produce comparable dose fall-off

as seen on DCAT plans due to reduction in penumbra. Utilizing conformity, homogeneity, and

gradient index is extremely important in evaluating patient plans and should be used during SRS

planning.

42

Tables

Table 1. Patients, tumor, and treatment parameters

Patient Sex Age (y)

ICD9 / Diagnosis Tumor Location Prescription

Dose (Gy)

Target Diameter

(cm)

1 F 70 198.5 Lung Met R frontal lobe 24 0.6

2 F 42 174.9 Breast Met R temporal lobe 24 0.8

3 M 59 162.9 Lung Met R sup frontal lobe 24 0.8

4 F 62 198.3 Renal Cell Met

R midline sup frontal/parietal lobe

24 1.0

5 F 76 174.9 Breast Met R parietal lobe 24 1.3

6 M 63 198.3 Parotid Met R occipital lobe 24 1.6

7 F 73 182.0 Uterine Met L parietal lobe 24 1.9

8 F 50 198.3 Breast Met L occipital lobe 18 2.1

9 F 61 198.3 Colon Met R frontal lobe 18 2.3

10 F 47 198.3 Lung Met L parietal lobe 18 2.7

Abbreviations: M = male, F = female, y = years, Gy = Gray, cm = centimeters

Table 2. Description of treatment planning techniques Radiosurgery

Technique Dynamic Conformal Arcs IMRT

Description 7 non-coplanar rotations, mMLC positions according to shape of PTV/GTV and ORs, monoisocentric

2 coplanar RapidArc (VMAT) rotations, Millenium MLC optimized, monoisocentric

Abbreviations: IMRT = intensity-modulated radiation therapy; mMLC = micromultileaf collimator; PTV = planning target volume; GTV = gross tumor volume; OR = organs-at-risk; VMAT = volumetric-modulated arc therapy

43

Table 3. SRS plan evaluation data for DCAT and VMAT

DCAT VMAT

Patient TV (cc) PITV CIPaddick GIPaddick HI PITV CIPaddick GIPaddick HI 1 0.13 0.85 0.45 8.45 1.18 1.08 0.45 18.21 1.10 2 0.27 1.26 0.58 4.68 1.20 1.44 0.55 7.85 1.19 3 0.27 1.15 0.63 5.00 1.17 1.19 0.72 9.53 1.09 4 0.58 1.22 0.68 3.68 1.20 1.33 0.68 8.83 1.09 5 1.26 1.15 0.78 3.57 1.20 1.30 0.72 6.65 1.05 6 2.21 1.19 0.71 3.26 1.19 1.32 0.66 4.79 1.21 7 3.75 1.15 0.78 2.92 1.18 1.28 0.75 5.47 1.05 8 4.15 1.33 0.71 2.99 1.21 1.37 0.71 5.29 1.13 9 6.20 1.22 0.78 2.75 1.22 1.14 0.83 4.63 1.18 10 10.24 1.29 0.75 2.65 1.21 1.23 0.79 4.25 1.13

Abbreviations: SRS = stereotactic radiosurgery; DCAT = dynamic conformal arc therapy; PITV = RTOG conformity index; CIpaddick = Paddick conformity index; GI = gradient index; HI = homogeneity index

Table 4. SRS Plan Comparison Patient PITV CIPaddick GIPaddick HI

DCAT ± SD 1.18 ± 0.13 0.68 ± 0.11 3.99 ± 1.76 1.20 ± 0.02

VMAT ± SD 1.27 ± 0.11 0.69 ± 0.11 7.55 ± 4.17 1.12 ± 0.06

Abbreviations: SRS = stereotactic radiosurgery; DCAT = dynamic conformal arc therapy; SD = standard deviation; PITV = RTOG conformity index; CIpaddick = Paddick conformity index; GI = gradient index; HI = homogeneity index

44

Table 5. Volume of normal brain tissue at V12 and V5 doses for DCAT and VMAT

DCAT VMAT

Patient TV (cc) V12 Brain - Target (cc)

V5 Brain - Target(cc)

V12 Brain - Target (cc)2

V5 Brain - Target(cc)2

1 0.13 0.9 3.7 2.4 14.1 2 0.27 1.1 4.1 2.1 9.9 3 0.27 1.3 5.6 2.8 15.6 4 0.58 1.3 5.2 4.1 18.8 5 1.26 3.9 17.4 9.6 50.0 6 2.21 3.9 14.2 5.7 30.6 7 3.75 8.9 35.3 22.3 103.3 8 4.15 6.9 30.0 12.6 60.3 9 6.20 8.1 37.4 26.1 88.9 10 10.24 13.8 68.7 21.6 124.8

Abbreviations: DCAT = dynamic conformal arc therapy; TV = Target volume; V12 = Volume (cc) of tissue that receives 12 Gy dose; V5 = Volume (cc) of tissue that receives 5 Gy dose.

45

Figures

Figure 1. 3D views of the planning or gross tumor volumes (PTV or GTV) for (a) patient #2 and (b) patient #10. (a).

(b).

46

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. (a).

47

(b).

48

Figure 3. Dose distribution for (a) patient #2 and (b) patient #10 for DCAT plans first and VMAT plans second showing 100%, 95% and 50% isodose levels on axial slices. (a).

49

(b).

50

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. (a).

(b).

51

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. (a).

(b).

52

Figure 6. RTOG Conformity index as a function of target volume for DCAT and RapidArc (VMAT) plans

  Figure 7. Paddick Conformity index as a function of target volume for DCAT and RapidArc (VMAT) plans

                     

53

Figure 8. Gradient index as a function of target volume for DCAT and RapidArc (VMAT) plans

    Figure 9. Homogeneity index as a function of target volume for DCAT and RapidArc (VMAT) plans

   

             

54

Figure 10. Normal brain tissue minus target volume receiving 12 Gy dose

 

Figure 11. Normal brain tissue minus target volume receiving 5 Gy dose

 

 

 

55

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