Risk of Second Malignant Neoplasms Following Proton Arc Therapy and Volumetric Modulated Arc ...

133 Pages·2016·3.06 MB·English

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The University of Texas MD Anderson Cancer
The University of Texas MD Anderson Cancer
Center UTHealth Graduate School of
Center UTHealth Graduate School of
Biomedical Sciences Dissertations and Theses
Biomedical Sciences
(Open Access)
5-2011
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Laura A. Rechner
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Rechner, Laura A., "Risk of Second Malignant Neoplasms Following Proton Arc Therapy and Volumetric
Modulated Arc Therapy for Prostate Cancer" (2011). The University of Texas MD Anderson Cancer Center
UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access). 115.
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Risk of Second Malignant Neoplasms Following Proton Arc Therapy
and Volumetric Modulated Arc Therapy for Prostate Cancer

By

Laura Ann Rechner, B.S.

APPROVED:

___________________________________
Wayne D. Newhauser, Ph.D.
Supervisory Professor

___________________________________
Rebecca Howell, Ph.D.

___________________________________
Rajat Kudchadker, Ph.D.

___________________________________
Lei Dong, Ph.D.

___________________________________
Dragan Mirkovic, Ph.D.

___________________________________
Carol Etzel, Ph.D.
APPROVED:

___________________________________
Dean, The University of Texas
Health Science Center at Houston
Graduate School of Biomedical Sciences
Risk of Second Malignant Neoplasms Following Proton Arc Therapy and
Volumetric Modulated Arc Therapy for Prostate Cancer
A
THESIS
Presented to the Faculty of
The University of Texas
Health Science Center at Houston
and
The University of Texas
M. D. Anderson Cancer Center
Graduate School of Biomedical Sciences
In Partial Fulfillment

Of the Requirements

For the Degree of

MASTER OF SCIENCE

By

Laura A Rechner, B.S.
Houston, Texas
May, 2011
Dedication

To my parents
For encouraging me in everything I do

To my husband
For always being my buddy

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Acknowledgements

I would like to thank my advisor, Dr. Wayne Newhauser, for his guidance and support
throughout this project. Being part of this research group has provided educational
opportunities above and beyond what I could have imaged. I would also like to thank Dr.
Rebecca Howell for her mentorship on my committee and throughout my graduate studies.
Also, many thanks to my committee members for their support of this project: Dr. Lei Dong,
Dr. Rajat Kudchadker, Dr. Dragan Mirkovic, and Dr. Carol Etzel.
Many other people contributed to this project. I would like to thank the members of my
research group, whose help and input were invaluable: Rui Zhang, Annelise Giebeler, Kenny
Homann, Dr. Phil Taddei, Dr. Jonas Fontenot, Dr. Angelica Perez-Andujar, Tim Jones, and
John Eley. Other students were also an important part of my education: Kelly Kisling, Sarah
Scarboro, and Ryan Bosca. Additionally, I would like to thank Jennifer Johnson for taking me
under her wing and Scharlene Wilson for taking care of everything.
I would also like to thank my family. Their love and support has made me who I am
today. Specifically, I would like to thank my husband for the countless hours of listening to my
presentations and editing my thesis, putting up with my nerdy conversations about medical
physics, picking me up after late nights in the office, and most importantly, moving with me so
I could further my education. Thank you.

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Risk of Second Malignant Neoplasms Following Proton Arc Therapy and
Volumetric Modulated Arc Therapy for Prostate Cancer

Publication No. ________

Laura Ann Rechner, B.S.

Supervisory Professor: Wayne D. Newhauser, Ph.D.

The risk of second malignant neoplasms (SMNs) following prostate radiotherapy is a concern
due to the large population of survivors and decreasing age at diagnosis. It is known that
parallel-opposed beam proton therapy carries a lower risk than photon IMRT. However, a
comparison of SMN risk following proton and photon arc therapies has not previously been
reported. The purpose of this study was to predict the ratio of excess relative risk (RRR) of
SMN incidence following proton arc therapy to that after volumetric modulated arc therapy
(VMAT). Additionally, we investigated the impact of margin size and the effect of risk-
minimized proton beam weighting on predicted RRR. Physician-approved treatment plans were
created for both modalities for three patients. Therapeutic dose was obtained with differential
dose-volume histograms from the treatment planning system, and stray dose was estimated
from the literature or calculated with Monte Carlo simulations. Then, various risk models were
applied to the total dose. Additional treatment plans were also investigated with varying margin
size and risk-minimized proton beam weighting. The mean RRR ranged from 0.74 to 0.99,
depending on risk model. The additional treatment plans revealed that the RRR remained
approximately constant with varying margin size, and that the predicted RRR was reduced by
12% using a risk-minimized proton arc therapy planning technique. In conclusion, proton arc
therapy was found to provide an advantage over VMAT in regard to predicted risk of SMN
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following prostate radiotherapy. This advantage was independent of margin size and was
amplified with risk-optimized proton beam weighting.

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Table of Contents
Signature Page ..................................................................................................................... i
Title Page ............................................................................................................................ ii
Dedication .......................................................................................................................... iii
Acknowledgements ............................................................................................................ iv
Abstract ................................................................................................................................ v
Table of Contents .............................................................................................................. vii
List of Figures ...................................................................................................................... x
List of Tables ................................................................................................................... xiii
Chapter 1 Introduction ....................................................................................................... 1
1.1 Prostate Cancer .................................................................................................... 1
1.2 External Beam Radiation Therapy ....................................................................... 2
1.2.1 Photon Therapy ............................................................................................ 2
1.2.2 Proton Therapy ............................................................................................ 6
1.3 Risk of Second Malignant Neoplasms from Radiation Therapy ....................... 12
1.4 Statement of the Problem ................................................................................... 16
1.5 Hypothesis and Specific Aimes ......................................................................... 17
Chapter 2 Methods and Materials .................................................................................... 18
2.1 Patient Selection and Contouring ..................................................................... 18
2.2 Treatment Planning and Therapeutic Dose Determination ............................... 20
2.2.1 Volumetric Modulated Arc Therapy ......................................................... 22
2.2.2 Proton Arc Therapy ................................................................................... 23
2.3 Stray Dose Estimation ....................................................................................... 32
2.3.1 Volumetric Modulated Arc Therapy ......................................................... 32
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2.3.2 Proton Arc Therapy ................................................................................... 33
2.4 Risk Prediction ................................................................................................... 36
2.4.1 Linear-No-Threshold Model ...................................................................... 36
2.4.2 Alternate High Dose Risk Models ............................................................. 38
2.4.3 Example Risk Calculations ........................................................................ 42
2.4.4 Statistical Analysis ..................................................................................... 44
2.4.5 Uncertainty Analysis ................................................................................. 45
2.4.6 Summary of Risk Calculations .................................................................. 49
Chapter 3 Results ............................................................................................................. 50
3.1 Therapeutic Dose Distributions ......................................................................... 50
3.1.1 Volumetric Modulated Arc Therapy ......................................................... 50
3.1.2 Proton Arc Therapy ................................................................................... 54
3.1.3 Dose-Volume Histogram Comparisons ..................................................... 62
3.2 Stray Dose Determination .................................................................................. 72
3.2.1 Volumetric Modulated Arc Therapy Stray Dose ....................................... 72
3.2.2 Proton Arc Therapy Stray Dose ................................................................. 74
3.3 Risk Prediction ................................................................................................... 74
3.3.1 Statistical Analysis ..................................................................................... 82
3.3.1 Uncertainty Analysis ................................................................................. 83
Chapter 4 Discussion and Conclusion ............................................................................. 86
4.1 Outcome of the Specific Aims ........................................................................... 86
4.1.1 Outcome of Specific Aim 1 ....................................................................... 86
4.1.1 Outcome of Specific Aim 2 ....................................................................... 87
4.1.1 Outcome of Specific Aim 3 ....................................................................... 88
viii
4.2 Comparison with Existing Literature ................................................................. 88
4.3 Implications and Significance of this Study ...................................................... 91
4.4 Strengths of this Study ....................................................................................... 92
4.5 Limitations of this Study ................................................................................... 93
4.6 Future Work ....................................................................................................... 95
4.7 Conclusions........................................................................................................ 96
Biliography ........................................................................................................................ 96
Vita .................................................................................................................................. 118

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