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- Herausgeber: John Wiley & Sons
- Kategorie: Fachliteratur
- Sprache: Englisch
Principles and Practice of Particle Therapy Although radiation has been used therapeutically for over 100 years, the field of radiation oncology is currently in the midst of a renaissance, particularly with regards to the therapeutic use of particles. Over the past several years, access to particle therapy, whether it be proton therapy or other heavy ion therapy, has increased dramatically. Principles and Practice of Particle Therapy is a clinically oriented resource that can be referenced by both experienced clinicians and those who are just beginning their venture into particle therapy. Written by a team with significant experience in the field, topics covered include: * Background information related to particle therapy, including the clinically relevant physics, radiobiological, and practical aspects of developing a particle therapy program * "Niche" treatments, such as FLASH, BNCT, and GRID therapy * The simulation process, target volume delineation, and unique treatment planning considerations for each disease site * Less commonly used ions, such as fast neutrons or helium Principles and Practice of Particle Therapy is a go-to reference work for any health professional involved in the rapidly evolving field of particle therapy.
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Principles and Practice of Particle Therapy
Edited by
Timothy D. Malouff and Daniel M. Trifiletti
Mayo ClinicJacksonville, Florida, USA
This edition first published 2022© 2022 John Wiley & Sons Ltd
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Library of Congress Cataloging-in-Publication DataNames: Malouff, Timothy D., editor. | Trifiletti, Daniel M., editor.Title: Principles and practice of particle therapy / edited by Timothy D. Malouff, Daniel M. Trifiletti.Description: Hoboken, NJ : John Wiley & Sons, 2022. | Includes bibliographical references and index.Identifiers: LCCN 2021052728 (print) | LCCN 2021052729 (ebook) | ISBN 9781119707516 (hardback) | ISBN 9781119707400 (pdf) | ISBN 9781119707523 (epub) | ISBN 9781119707530 (ebook)Subjects: LCSH: Radiotherapy.Classification: LCC RM847 .P758 2022 (print) | LCC RM847 (ebook) | DDC 615.8/42--dc23/eng/20211116LC record available at https://lccn.loc.gov/2021052728LC ebook record available at https://lccn.loc.gov/2021052729
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Set in 9.5/12.5pt STIXTwoText by Integra Software Services Pvt. Ltd, Pondicherry, India
Contents
Cover
Title page
Copyright
Preface
List of Contributors
Foreword
Abbreviations
Section I: Background
1
A Brief History of Particle Radiotherapy
2
The Physics of Particle Therapy
3
The Radiobiology of Particle Therapy
4
Practical Aspects of Particle Therapy Accelerators
5
Treatment Planning for Scanning Beam Proton Therapy
6
Image-Guided Particle Therapy and Motion Management
7
Advanced Particle Therapy Delivery: A Review of Advanced Techniques for Particle Therapy Delivery
8
FLASH Radiotherapy
9
Boron Neutron Capture Therapy
10
Grid Therapy
11
Particle Therapy and the Immune System
12
The Economics of Particle Therapy
Section II: Particle Therapy by Clinical Indication
13
Intracranial Tumors: Principles and Practice of Particle Therapy
14
Ocular Malignancies
15
Brain, Skull Base, and Spinal Tumors
16
Head and Neck Cancers
17
Thoracic Malignancies: Proton Beam and Carbon-ion Therapy for Thoracic Cancers and Recurrent Disease
18
Gastrointestinal Tumors
19
Hepatobiliary Cancers
20
Breast Cancer
21
Prostate Cancer
22
Non-prostate Genitourinary Cancers
23
Gynecologic Cancers
24
Lymphoma and Leukemia
25
Sarcomas and Soft Tissue Malignancies
26
Pediatric Central Nervous System Tumors
27
Particle Therapy for Non-CNS Pediatric Malignancies
Index
End User License Agreement
List of Illustrations
Chapter 1
Figure 1.1 The early treatment room...
Figure 1.2 A vertical CT scanner...
Figure 1.3 An early patient treated...
Figure 1.4 Location of Proton Therapy...
Figure 1.5 Location of Currently Operational...
Chapter 2
Figure 2.1 Nitrogen-14 neutron capture...
Figure 2.2 Hydrogen neutron capture cross...
Figure 2.3 Visual representation of 10B...
Figure 2.4 Boron-10 neutron captures...
Figure 2.5 Major neutron capture cross...
Figure 2.6 Neutron quality factors per...
Figure 2.7 Comparison of a clinical...
Figure 2.8 The relationship of stopping...
Figure 2.9 Percent depth dose curves...
Figure 2.10 The percent depth dose...
Figure 2.11 Diagram of carbon fragmentation...
Figure 2.12 Simulated 12C depth dose...
Chapter 3
Figure 3.1 DSB are visualized with...
Figure 3.2 Survival of melanoma TS...
Figure 3.3 “Biologically optimized four...
Chapter 4
Figure 4.1 A proton moves in...
Figure 4.2 The classic cyclotron design...
Figure 4.3 Magnetic field modulation with...
Figure 4.4 A Varian ProBeam superconducting...
Figure 4.5 A 3D computer rendering...
Figure 4.6 A 3D computer rendering...
Figure 4.7 The phase space stable...
Chapter 5
Figure 5.1 Gaussian distribution as seen...
Figure 5.2a radiographic image of proton...
Figure 5.2b Proton beam generating primary...
Figure 5.3 Depth dose distribution of...
Figure 5.4 Comparing dose distribution from...
Figure 5.6 Comparing lateral profiles and...
Figure 5.6 All major contributors to...
Figure 5.7a Constructing planning margins by...
Figure 5.7b Identifying shaded region to...
Figure 5.7c Constructing an optimization target...
Figure 5.7d Constructing a scanning target...
Figure 5.8 Selective cropping of the...
Figure 5.9 Midline dose bath compared...
Figure 5.10 Rigid patient support device...
Figure 5.11 H&N CT...
Figure 5.16 (Left) Extended range shifter...
Figure 5.17 Uniform dose distribution from...
Figure 5.18 Sharp dose gradients and...
Figure 5.15 Split target-based multifield...
Figure 5.16 Various metallic hardware implants...
Figure 5.21 Dose colorwash showing an...
Figure 5.18 Robustness evaluation of a...
Figure 5.19 Heterogenous anatomy posing significant...
Figure 5.20 Dose-sparing effects of...
Figure 5.21 Four distinct anatomical locations...
Figure 5.22 Showing vaginal excursion due...
Figure 5.23 A representative slide showing...
Figure 5.24 A dose color wash...
Figure 5.25 Various OARs while treating...
Figure 5.26 Rectal filling and distensibility...
Figure 5.27 A representative slice indicating...
Figure 5.28 Prone setup with a...
Chapter 6
Figure 6.1 A typical thoracic immobilization...
Figure 6.2 CT on rails within...
Figure 6.3 Defining projection data bins...
Figure 6.4 Accelerator cycle for discrete...
Figure 6.5 Schema showing various possible...
Figure 6.6 A treatment planning workflow...
Figure 6.7 A block of reflective...
Figure 6.8 Example of an infrared...
Figure 6.9 A half gantry solution...
Chapter 7
Figure 7.1 Example of comparison between...
Figure 7.2 A. Scanning proton arc...
Figure 7.3 Single-fraction 4D dynamic...
Figure 7.4 A representative of the...
Figure 7.5 The dose (upper row...
Chapter 8
Figure 8.1 The effect of SSD...
Chapter 9
Figure 9.1 Delivery of BNCT...
Chapter 10
Figure 10.1 Key pathways affecting bystander...
Figure 10.2 Brass grid block for...
Figure 10.3 Lattice radiotherapy (LRT) utilizing...
Figure 10.4 Peak–valley dose...
Figure 10.5 Example of planned dose...
Chapter 11
Figure 11.1 Mechanism of immunogenicity of...
Figure 11.2 Dose deposition of photons...
Figure 11.3 An 85-year-old...
Chapter 12
Figure 12.1 Cumulative number of proton...
Figure 12.2 Currently active or upcoming...
Chapter 13
Figure 13.1 The absorbed dose as...
Figure 13.2 Understanding the impact of...
Figure 13.4 Demonstration on the use...
Figure 13.3 Understanding dose calculation. Panel...
Chapter 14
Figure 14.1 Uveal melanoma examples: (a...
Figure 14.2 Patient pathway: (a) surgical...
Figure 14.3 Treatment delivery (a) patient...
Figure 14.4 Examples of treatment planning...
Figure 14.5 (a) Time to first...
Chapter 16
Figure 16.1 Example PBS plan (MFO...
Figure 16.2 Example PBS plan (MFO...
Figure 16.3 Example PBS plan (MFO...
Figure 16.4 Example PBS plan (MFO...
Chapter 17
Figure 17.1 Example comparisons between proton...
Figure 17.2 Example comparisons between (A...
Figure 17.3 Example demonstration of the...
Figure 17.4 Comparison of intensity-modulated...
Chapter 18
Figure 18.1 Representative esophagus treatment plan...
Figure 18.2 Representative pancreas treatment plan...
Figure 18.3 Representative recurrent rectal treatment...
Chapter 19
Figure 19.1 Typical imaging characteristics of...
Figure 19.2 Adapted Barcelona Clinic Liver...
Figure 19.3 Photon volumetric modulated arc...
Figure 19.4 Eighty-year-old female...
Chapter 20
Figure 20.1 Images from computed tomography...
Figure 20.2 In treatment of the...
Figure 20.3 The (A) positron emission...
Figure 20.4 Target contours in colorwash...
Figure 20.5 (A, B) Isodose distribution...
Figure 20.6 (A,B) Isodose distribution...
Figure 20.7 Sagittal computed tomography simulation...
Figure 20.8 For treatment of the...
Figure 20.9 (A) Contour of the...
Chapter 21
Figure 21.1 (a) Four carbon fiducials...
Figure 21.2 A CT sagittal view...
Figure 21.3 Patient immobilization devices (left...
Figure 21.4 Example of endorectal balloon...
Figure 21.5 Example of fiducial marker...
Figure 21.6 Example of fiducial images...
Figure 21.7 Example of target contour...
Figure 21.8 Example of OTV and...
Figure 21.9 High LET (>6...
Figure 21.10 Typical DVH histogram for...
Figure 21.11 Example of an ideal...
Figure 21.12 Example of conformal dose...
Figure 21.0013 Example of 12 scenarios...
Figure 21.0014 Posterior oblique beam is...
Figure 21.0015 Planning structures and dose...
Figure 21.0016 Two examples of drifted...
Chapter 22
Figure 22.1 Figure of intensity modulated...
Figure 22.2 Figure of intensity modulated...
Figure 22.3 An example of a...
Figure 22.4 An example of a...
Chapter 23
Figure 23.1 Ovarian avoidance. A 35...
Figure 23.2 Re-irradiation for recurrent...
Figure 23.3 Re-irradiation for recurrent...
Figure 23.4 Unilateral or bilateral hip...
Figure 23.5 IMPT and VMAT comparative...
Figure 23.6 Single posterior beam for...
Figure 23.7 Two posterior obliques for...
Figure 23.8 IMPT and VMAT comparative...
Figure 23.9 Re-irradiation. A patient...
Chapter 24
Figure 24.1 Passive scatter proton therapy...
Figure 24.2 A 53-year-old...
Figure 24.3 A 57-year-old...
Figure 24.4 Proton CSI treatment using...
Chapter 25
Figure 25.1 Initial CT (a) and...
Figure 25.2 Axial (a) and coronal...
Figure 25.3 Axial (a) and coronal...
Figure 25.4 Primary cardiac high-grade...
Chapter 26
Figure 26.1 Example of our institutional...
Figure 26.2 Left temporal low-grade...
Figure 26.3 Proton plan of age...
List of Table
Chapter 2
Table 2.1 Neutron energy regions...
Table 2.2 Stopping power dependencies.
Table 2.3 Mean ionization energies for soft tissues.
Chapter 3
Table 3.1 Changes in RBE with LET and dose.
Chapter 6
Table 6.1 4D CT scan...
Chapter 9
Table 9.1 Comparison of the...
Table 9.2 Studies of select...
Chapter 10
Table 10.1 Summary of Early...
Table 10.2 NIH Registered Clinical...
Chapter 12
Table 12.1 Number of proton...
Chapter 13
Table 13.1 Prospective trials and...
Table 13.2 Selected series of...
Table 13.3 Ongoing particle therapy...
Table 13.4 Selected series of...
Table 13.5 Ongoing particle therapy...
Table 13.6 Recommended target volumes...
Chapter 14
Table 14.1 Prospective trials and...
Table 14.2 Sample dose constraint...
Table 14.3 Type of eye...
Table 14.4 Type of other...
Chapter 15
Table 15.1 Recommended target volumes...
Table 15.2 Recommended target volumes...
Table 15.3 Recommended target volumes...
Table 15.4 Recommended target volumes...
Chapter 16
Table 16.1 Sample dose constraint...
Table 16.2 Recommended target volumes...
Table 16.3 Ongoing clinical trials...
Table 16.4 Recommended target volumes...
Table 16.5 Recommended target volumes...
Table 16.6 Recommended target volumes...
Table 16.7 Recommended target volumes...
Table 16.8 Recommended target volumes...
Table 16.9 Recommended target volumes...
Table 16.10 Recommended target volumes...
Table 16.11 Recommended target volumes...
Chapter 17
Table 17.1 Selected published and...
Table 17.2 Overview of studies...
Table 17.3 Selected published and...
Table 17.4 Example target volumes...
Chapter 18
Table 18.1 Recommended target volumes...
Table 18.2 Particle therapy for...
Table 18.3 Recommended target volumes...
Table 18.4 Particle therapy for...
Table 18.5 Particle therapy for...
Table 18.6 Recommended target volumes...
Table 18.7 Particle therapy for...
Chapter 19
Table 19.1 Prognostic scores for...
Table 19.2 American Joint Committee...
Table 19.3 Select series of...
Table 19.4 Select series of...
Table 19.5 Select series of...
Table 19.6 Select series of...
Table 19.7 Recommended target volumes...
Chapter 20
Table 20.1 Clinical studies for...
Table 20.2 Clinical studies for...
Chapter 21
Table 21.1 Selected proton beam...
Table 21.2 Selected carbon ion...
Table 21.3 Published results from...
Table 21.4 Recommended target volumes...
Table 21.5 Ongoing clinical trials...
Chapter 22
Table 22.1 Comparison of doses...
Table 22.2 Recommended target volumes...
Table 22.3 Recommended target volumes...
Table 22.4 Recommended target volumes...
Table 22.5 Recommended target volumes...
Chapter 23
Table 23.1 Dosimetric comparison studies...
Table 23.2 Recommended target volumes...
Table 23.3 Recommended target volumes...
Chapter 24
Table 24.1 Summary of dose...
Table 24.2 Definition of lower...
Table 24.3 Site-specific simulation...
Chapter 25
Table 25.1 Particle therapy for...
Table 25.2 Particle therapy for...
Chapter 27
Table 27.1 Clinical experiences utilizing...
Table 27.2 Active clinical trials...
Table 27.3 Recommended target volumes...
Table 27.4 Clinical experiences utilizing...
Table 27.5 Active clinical trials...
Table 27.6 Recommended target volumes...
Table 27.7 Clinical experiences utilizing...
Table 27.8 Active clinical trials...
Table 27.9 Recommended target volumes...
Table 27.10 Clinical experiences utilizing...
Table 27.11 Active clinical trials...
Table 27.12 Recommended target volumes...
Table 27.13 COG-STS risk...
Table 27.14 Clinical experiences utilizing...
Table 27.15 Active clinical trials...
Table 27.16 Recommended target volumes...
Guide
Cover
Title page
Copyright
Table of Contents
Preface
List of Contributors
Foreword
Abbreviations
Begin Reading
Index
End User License Agreement
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Preface
Although radiation has been used therapeutically for over 100 years, we are currently in the midst of a renaissance in our field, especially with the use of particle irradiation. Over the past several years, access to particle therapy, whether it be proton therapy or heavy ion therapy, has increased dramatically. In the United States, more patients are able to benefit from proton therapy than ever before, with the number of centers and indications for proton therapy growing rapidly. Outside of the United States, many centers, including those in Japan and Germany, are gaining expertise as they push the envelope with carbon ion radiotherapy, something that was recently announced in the United States. There is also a renewed interest in using other heavy ions, and even combining radiation treatment modalities to improve oncologic outcomes while minimizing adverse effects.
With the widespread use of proton therapy worldwide, as well as growth of carbon ion therapy throughout Europe, Asia, and soon to be the United States, it became clear that a concise, yet comprehensive, resource was needed for the growing number of radiation oncologists treating with particle therapy. Our inspiration for Principles and Practice of Particle Therapy was exactly this – to provide a go-to, clinically oriented resource that can be referenced by both experienced clinicians and those who are just beginning their venture into particle therapy.
To meet this goal, our text is divided into three sections. In the first section, we discuss the most pertinent background information related to particle therapy. The clinically relevant physics, radiobiological, and practical aspects of developing a particle therapy program, including less-commonly discussed topics such as treatment planning software, are included. Our next section is one that focuses on “niche” treatments, many of which are still in their relative infancy, including FLASH, BNCT, and GRID therapy. A special focus is given to how these novel therapeutics can be implemented in the context of particle therapy. Our final section aims to be a clinical reference, organized by disease site, reviewing both the clinical data as well as providing a practical reference for practicing radiation oncologists. Each chapter includes discussions on the simulation process, target volume delineation, and unique treatment planning considerations for each disease site. When applicable, each clinical chapter also includes a discussion on less common ions, such as fast neutrons or helium, which we hope will become more pertinent as our understanding and experience of treating with heavy ions grows. The authors for each chapter were carefully chosen, and represent experts from around the world, and we hope their diversity of experiences in treating with particle therapy helps provide a framework in which to build your own practice.
We recognize that the field of particle therapy is evolving rapidly, and we hope this text will provide a guide map as to the next questions that should be asked in our understanding of the role of particle therapy in patient care. It is our sincere hope that our text will be obsolete in the near future, with well-designed trials and increased expertise in particle therapy answering many of the currently unanswered questions. Until that time, we hope this textbook provides insight and improves your ability to care for your patients, as this is the ultimate goal of our field.
List of Contributors
Armin R. Afshar, MD, MBA, MASAssistant Professor,Department of Ophthalmology,Wayne & Glady Valley Center for Vision, University ofCalifornia San Francisco, San Francisco,CA, USA
Gregory Alexander, MDResident Physician, Department of Radiation Oncology,University of Maryland School of Medicine,Baltimore, MD, USA
Aman Anand, PhDAssistant Professor, Department of Radiation Oncology,Mayo Clinic, Phoenix, AZ, USA
Justin D. Anderson, MDResident Physician, Department of Radiation Oncology,Mayo Clinic, Phoenix, AZ, USA
Jonathan B. Ashman, MD, PhD,Assistant Professor, Department of Radiation Oncology,Mayo Clinic, Phoenix, AZ, USA
Ronik S. Bhangoo, MDResident Physician, Department of Radiation Oncology,Mayo Clinic, Phoenix, AZ, USA
Julie A. Bradley, MDAssociate Professor, Department of Radiation Oncology,University of Florida College of Medicine,Jacksonville, FL, USA
Martin Bues, PhDAssociate Professor,Department of Radiation Oncology, Mayo Clinic,Phoenix, AZ, USA
Justin Cohen, MDResident Physician, Department of Radiation Oncology,University of Maryland School of Medicine,Baltimore, MD, USA
Danielle A. Cunningham, MDResident Physician, Department of Radiation Oncology,Mayo Clinic, Rochester, MN, USA
Bertil E. Damato, MD, PhD, FRCOphthProfessor, Oxford Eye Hospital,University of Oxford, Oxford, UK
Xuanfeng Ding, PhDMedical Physicist, Department of Radiation Oncology,Beaumont Health System,Oakland University William Beaumont School of Medicine,Royal Oak, MI, USA
J. Michele Dougherty, PhDMedical Physicist, Department of Radiation Oncology,Mayo Clinic, Jacksonville, FL, USA
Daniel K. Ebner, MD, MPHResident Physician, Hospital of the National Institutes ofQuantum and Radiological Science and Technology(QST Hospital), Chiba, Japan
Omar El Sherif, PhDClinical Medical Physicist, Department of Radiation Oncology,Mayo Clinic, Rochester, MN, USA
Dr. Piero FossatiRadiation Oncologist,MedAustron Ion Therapy Center,Wiener Neustadt, Austria
Keith M. Furutani, PhDAssociate Professor of Medical Physics, Department ofRadiation Oncology, Mayo Clinic,Jacksonville, FL, USA
Fantine Giap, MDResident Physician, Department of Radiation Oncology,University of Florida College of Medicine,Jacksonville, FL, USA
Michael P. Grams, PhDAssistant Professor of Medical Physics, Department ofRadiation Oncology, Mayo Clinic,Rochester, MN, USA
Christopher L. Hallemeier, MDAssociate Professor, Department of Radiation Oncology,Mayo Clinic, Jacksonville, FL, USA
Steven Herchko, DMP, MSInstructor in Medical Physics,Department of Radiation Oncology,Mayo Clinic, Jacksonville, FL, USA
Prof. Dr. Eugen B. HugMedical Director, MedAustron Ion Therapy Center,Wiener Neustadt, Austria
Daniel J. Indelicato, MDProfessor, Department of Radiation Oncology,University of Florida College of Medicine,Jacksonville, FL, USA
Elizabeth B. Jeans, MEd, MDResident Physician, Department of Radiation Oncology,Mayo Clinic, Rochester, MN, USA
Krishnan R. Jethwa, MDAssistant Professor, Department of Therapeutic Radiology,Yale University School of Medicine,New Haven, CT, USA
Peyman Kabolizadeh, MD, PhDDirector of Proton Therapy Center, Department of RadiationOncology, Beaumont Health System,Oakland University William Beaumont School of Medicine,Royal Oak, MI, USA
Andrzej Kacperek, PhDEmeritus Physics, Clatterbridge Cancer Centre,Wirral, UK
Rupesh Kotcha, MDAssistant Professor, Department of Radiation Oncology,Miami Cancer Institute, Baptist Health South Florida, Miami,FL, USA and Herbert Wertheim College of Medicine, FloridaInternational University, Miami, FL, USA
Sunil Krishnan, MBBS, MDProfessor, Department of Radiation Oncology, Mayo Clinic,Jacksonville, FL, USA
Anna Lee, MD, MPHAssistant Professor, Department of Radiation Oncology,University of Texas MD Anderson Cancer Center,Houston, TX, USA
Nancy Y. Lee, MD, FASTROVice Chair, Department of Radiation Oncology,Memorial Sloan Kettering Cancer Center,New York, NY, USA
Xiaoqiang Li, PhDMedical Physicist, Department of Radiation Oncology,Beaumont Health System, Oakland University WilliamBeaumont School of Medicine,Royal Oak, MI, USA
Xingzhe (Dillion) Li, MD, MPHResident Physician, Department of Radiation Oncology,Memorial Sloan Kettering Cancer Center,New York, NY, USA
Xiaoying Liang, PhDAssociate Professor, Department of Radiation Oncology,University of Florida College of Medicine, Jacksonville, FL, USA
Steven H. Lin, MD, PhDAssociate Professor, Department of Radiation Oncology,University of Texas MD Anderson Cancer Center,Houston, TX, USA
Daniel J. Ma, MDAssociate Professor, Department of Radiation Oncology,Mayo Clinic, Rochester,MN, USA
Anita Mahajan, MDProfessor, Department of Radiation Oncology,Mayo Clinic, Rochester, MN, USA
Raymond Mailhot Vega, MD, MPHAssistant Professor, Department of Radiation Oncology,University of Florida College of Medicine,Jacksonville, FL, USA
Timothy D. Malouff, MDResident Physician, Department of Radiation Oncology,Mayo Clinic, Jacksonville, FL, USA
Minesh P. Mehta, MDProfessor, Deputy Director, and Chief of Radiation Oncology,Department of Radiation Oncology,Miami Cancer Institute, Baptist Health South Florida,Miami, FL, USA and Herbert Wertheim College of Medicine,Florida International University,Miami, FL, USA
Robert Miller, MD, MBA, FASTRODirector, Division of Radiation Oncology,UT Medical Center at the University of Tennessee,Knoxville, TN, USA
Kavita K. Mishra, MD, MPHProfessor, Director, Ocular Tumor Radiation TherapyProgram, Department of Radiation Oncology,University of California San Francisco,San Francisco, CA, USA
Mark V. Mishra, MDAssociate Professor, Department of Radiation Oncology,University of Maryland School of Medicine,Baltimore, MD, USA
Osama Mohamad, MD, PhDAssistant Professor, Department of Radiation Oncology,University of California San Francisco,San Francisco, CA, USA
Pranshu Mohindra, MD, MBBSAssociate Professor, Department of Radiation Oncology,University of Maryland School of Medicine and MarylandProton Treatment Center, Baltimore, MD, USA
Sina Mossahebi, PhDPhysicist, Department of Radiation Oncology,University of Maryland School of Medicine,Baltimore, MD, USA
Matthew S. Ning, MD, MPHAssistant Professor, Department of Radiation Oncology,University of Texas MD Anderson Cancer Center,Houston, TX, USA
Deanna Pafundi, PhDAssistant Professor of Medical Physics,Department of Radiation Oncology, Mayo Clinic,Jacksonville, FL, USA
Chirayu G. Patel, MD, MPHInstructor, Department of Radiation Oncology,Massachusetts General Hospital, Boston, MA, USA
Ariel E. Pollock, MDResident Physician, Department of Radiation Oncology,University of Maryland School of Medicine andMaryland Proton Treatment Center,Baltimore, MD, USA
Jill S. Remick, MDAssistant Professor, Department of Radiation Oncology,Winship Cancer Institute,Emory University Hospital, Atlanta, GA, USA
Pouya Sabouri, PhDMedical Physicist, Department of Radiation Oncology,Miami Cancer Institute, Baptist Health South Florida,Miami, FL, USA
Santanu Samanta, MDResident Physician, Department of Radiation Oncology,University of Maryland Medical Center,Baltimore, MD, USA
Jessica Scholey, MAClinical Instructor, Department of Radiation Oncology,University of CaliforniaSan Francisco, San Francisco, CA, USA
Danushka Seneviratne, MD, PhDResident Physician, Department of Radiation Oncology,Mayo Clinic, Jacksonville, FL, USA
Christopher Serago, PhDAssociate Professor of Medical Physics, Department ofRadiation Oncology, Mayo Clinic,Jacksonville, FL, USA
Sherif G. Shaaban, MB ChBResident Physician, Department of Radiation Oncology,University of Minnesota,Minneapolis, MN, USA
Jiajian (Jason) Shen, PhDAssociate Professor, Department of Radiation Oncology,Mayo Clinic, Phoenix, AZ, USA
Makoto Shinoto, MD, PhDPhysician, Hospital of the NationalInstitutes of Quantum and Radiological Science andTechnology (QST Hospital), Chiba, Japan
Matthew Spraker, MD, PhDAssistant Professor, Department of Radiation Oncology,Washington University in St. Louis,St. Louis, MO, USA
Cameron S. Thorpe, MDResident Physician, Department of Radiation Oncology,Mayo Clinic, Phoenix, AZ, USA
Raees Tonse, MBBSClinical Research Fellow,Department of Radiation Oncology,Miami Cancer Institute, Baptist Health South Florida,Miami, FL, USA
Daniel M. Trifiletti, MDAssociate Professor, Department of Radiation Oncology,Mayo Clinic, Jacksonville, FL, USA
Yolanda D. Tseng, MDAssociate Professor, Department of Radiation Oncology,University of Washington, Seattle, WA, USA
Dr. Slavisa TurbinRadiation Oncologist, MedAustron Ion Therapy Center,Wiener Neustadt, Austria
Carlos E. Vargas, MDAssociate Professor, Department of Radiation Oncology,Mayo Clinic, Phoenix, AZ, USA
Vivek Verma, MDRadiation Oncologist, Department of Radiation Oncology,University of Texas MD Anderson Cancer Center,Houston, TX, USA
Mark R. Waddle, MDAssistant Professor, Department of Radiation Oncology,Mayo Clinic, Rochester, MN, USA
Eric Welch, DMPClinical Medical Physicist,Department of Radiation Oncology, Mayo Clinic, Rochester,MN, USA
Shigeru Yamada, MD, PhDDirector of Department of Charged Particle TherapyResearch, Hospital of the National Institutes of Quantum andRadiological Science and Technology (QST Hospital),Chiba, Japan
James E. Younkin, PhDAssistant Professor, Department of Radiation Oncology,Mayo Clinic, Phoenix, AZ, USA
Elaine M. Zeman, PhDAssociate Professor, Department of Radiation Oncology,University of North Carolina School of Medicine,Chapel Hill, NC, USA
Abbreviations
2D:
2-Dimensional
3D:
3-Dimensional
3DCRT:
3-Dimensional conformal radiotherapy
4D:
4-Dimensional
4D-bsPTV:
4-Dimensional Beam Specific PTV
5-FU:
5-Fluorouracil
6D:
6-Dimensional
A:
Atomic Mass
AAPM:
American Association of Physicists in Medicine
ABCS:
Active Breathing Controlled Spirometers
ABVD:
Adriamycin, Bleomycin, Vinblastine, Dacarbazine
ABVE-PC:
Adriamycin, Bleomycin, Vincristine, Etoposide, Prednisone, Cyclophosphamide
ACC:
Adenoid Cystic Carcinoma
ACNU:
Nimustine Hydrochloride
ACR:
American College of Radiology
ACROP:
Advisory Committee on Radiation Oncology Practice
ADT:
Androgen Deprivation Therapy
AE:
Adverse Event
AER:
Absolute Excess Risk
AFP:
Alpha-fetoprotein
AI:
Anterior Inferior
AJCC:
American Joint Commission on Cancer
ALARA:
As Low as Reasonably Achievable
ALBI:
Albumin-Bilirubin Grade
ALT:
Alanine Aminotransferase
AMU:
Atomic Mass Unit
AO:
Anterior Oblique
AP:
Anteroposterior
APC:
Antigen Presenting Cell
ART:
Adaptive Radiotherapy
AST:
Aspartate Transaminase
ASTRO:
American Society for Radiation Oncology
ATP:
Adenosine Triphosphate
ATRT:
Atypical Teratoid Rhabdoid Tumor
AVF:
Azimuthally Varying Field
B:
Boron
BBB:
Blood Brain Barrier
BCCA:
British Columbia Cancer Agency
BCG:
Bacillus Calmette-Guérin
BCLC:
Barcelona Clinic Liver Cancer Staging System
BCS:
Breast Conserving Surgery
BCVA:
Best Corrected Visual Accuity
Be:
Beryllium
BEACOPP:
Bleomycin, Etoposide, Adriamycin, Cyclophosphamide, Oncovin, Procarbazine, Prednisone
BED:
Biologically Effective Dose
BID:
Twice Daily
BMI:
Body Mass Index
BNCT:
Boron Neutron Capture Therapy
BOPP:
Boronated Porphyrin
bp:
Base Pair
BPA:
Boronophenylalanine
BS:
Bone Sarcoma
BSH:
Sodium borocaptate
BsPTV:
Beam-specific Planning Target Volume
C:
Carbon
CAD:
Coronary Artery Disease
CAPOX:
Capecitabine and Oxaliplatin
CAR-T:
Chimeric Antigen Receptor T-cells
CB:
Ciliary Body
CBCT:
Cone-beam Computed Tomography
CDDP:
Cisplatin
CERN:
European Council for Nuclear Research
CGE:
Cobalt-Gray Equivalent
cHL:
Classic Hodgkin Lymphoma
CI:
Confidence Interval
CIRT:
Carbon Ion Radiotherapy
CLSS :
Continuous Line Scanning System
CMMI:
Center for Medicare and Medicaid Innovation
CMS:
Center for Medicare and Medicaid Services
CNAO:
National Centre for Oncological Hadrontherapy
CNS:
Central Nervous System
Co:
Cobalt
COG:
Children’s Oncology Group
COMS:
Collaborative Ocular Melanoma Study
CONV RT:
Conventional radiotherapy
COPDAC:
Cyclophosphamide, Oncovin, Prednisone, Dacarbazine
CP:
Child-Pugh Score
CPT:
Charged Particle Therapy
CPT:
Current Procedural Terminology
CRC:
Colorectal Cancer
CSC:
Cancer Stem-like Cells
CSF:
Cerebrospinal Fluid
CSI:
Craniospinal Irradiation
CSS:
Cause-Specific Survival
CT:
Computed Tomography
CTCAE:
Common Terminology Criteria for Adverse Events
CTL:
Cytotoxic T Lymphocytes
CTLA-4:
Cytotoxic T-Lymphocyte Antigen 4
CTV:
Clinical Target Volume
CVD:
Cardiovascular Death
DAMPS:
Danger Associated Molecular Patterns
DC:
Dendritic Cell
DET:
Distal Edge Tracking
DFS:
Disease-free Survival
DIBH:
Deep Inspiration Breath Hold
DICOM:
Digital Imaging and Communications in Medicine
DKFZ:
German Center for Cancer Research
DLBCL:
Diffuse Large B-cell Lymphoma
DLCO:
Diffusing Capacity for Carbon Monoxide
DM:
Distant Metastasis
DMFS:
Distant Metastasis-Free Survival
DNA:
Deoxyribonucleic Acid
DO:
Density-Override
DSB:
Double-strand break
DSS:
Disease Specific Survival
DTC:
Differentiated Thyroid Cancer
DVH:
Dose-Volume Histogram
EBM:
Evidence-Based Medicine
EBRT:
External Beam Radiation Therapy
EBV:
Epstein-Barr Virus
ECOG:
Eastern Cooperative Oncology Group
EFS:
Event-free Survival
EGFR:
Epidermal Growth Factor Receptor
EHCC:
Extrahepatic Cholangiocarcinoma
ELST:
Energy Layer Switching Time
EOR/Gy:
Excessive Odds Ratio Per Gray
EORTC:
European Organisation for Research and Treatment of Cancer
EPIC:
Expanded Prostate Cancer Index Composite
EQD2:
Equivalent Dose in 2 Gray
ERCP:
Endoscopic Retrograde Cholangiopancreatography
ERR:
Excess Relative Risk
ERS:
Extended Range Shifter
ESCC:
Esophageal Squamous Cell Carcinoma
ESFT:
Ewing Sarcoma Family of Tumors
ESMO:
European Society for Medical Oncology
ESR:
Erythrocyte Sedimentation Rate
ESS:
Energy Selection System
ESTRO:
European Society for Radiotherapy and Oncology
EUS:
Endoscopic Ultrasound
eV:
Electronvolts
EVH:
Error Bar Volume Histogram
FACT-P:
Functional Assessment of Cancer Therapy for Prostate Cancer Patients
FDA:
Food and Drug Administration
FDG:
Fluorodeoxyglucose
FFCD:
Fédération Francophone de Cancérologie Digestive
FFDR:
Freedom from Distant Recurrence
FFLP:
Freedom from Local Progression
FFLR:
Freedom from Locoregional Recurrence
FFRR:
Freedom from Regional Recurrence
FISH:
Fluorescent
in-situ
Hybridization
FLAIR:
Fluid Attenuated Inversion Recovery
FLR:
Future Liver Remnant
FLT:
Flourothymidine
FNT:
Fast Neutron Therapy
FOLFIRINOX:
Folinic Acid, Fluorouracil, Irinotecan, Oxaliplatin
FOLFOX:
Folinic acid, Fluorouracil, Oxaliplatin
FRAX:
Fracture Risk Assessment Tool
FSRT:
Fractionated Stereotactic Radiotherapy
FU:
Follow Up
Fx:
Fraction
G:
Grade
GBCA:
Gallbladder Cancer
GBM:
Glioblastoma
GEM:
Genetically Engineered Mouse
GEP:
Gene Expression Profile
GETUG:
Genitourinary Group
gEUD:
Generalized Equivalent Uniform Dose
GI:
Gastrointestinal
GIST:
Gastrointestinal Stroma Tumor
GSI:
Gesellschaft für Schwerionenforschung
GTR:
Gross Total Resection
GTV:
Gross Tumor Volume
GU:
Genitourinary
Gy (RBE):
Gray, Relative Biological Effectiveness
Gy:
Gray
GyE:
Gray Equivalent
H&N:
Head and Neck
H:
Hydrogen
HBV:
Hepatitis B Virus
HCC:
Hepatocellular Carcinoma
HCL:
Harvard Cyclotron Laboratory
HCP:
Heavy Charged Particles
HCV:
Hepatitis C Virus
He:
Helium
HF:
Hypofractionation
HFPV:
High-frequency Percussive Ventilation
HFV:
High-frequency Ventilation
HGG:
High-grade Gliomas
HIF-1α:
Hypoxia-inducible Factor 1-alpha
HIMAC:
Heavy Ion Medical Accelerator in Chiba
HIT:
Heidelberg Ion Beam Therapy Center
HL:
Hodgkin Lymphoma
HMA:
Homovanillic Acid
HMGB1:
High Mobility Group Protein B1
HNC:
Head and Neck Cancer
HNSCC:
Head and Neck Squamous Cell Carcinoma
HPV:
Human Papillomavirus
HR:
Hazard Ratio
HR:
Homologous Recombination
HSG:
Human Salivary Gland
HT:
Helical Therapy
HU:
Hounsfield Units
ICD:
Immunogenic Cell Death
ICER:
Institute for Clinical and Economic Review
ICRU:
International Commission on Radiation Units & Measurements
iCTV:
Internal Clinical Target Volume
IDH:
Isocitrate Dehydrogenase
IFRT:
Involved Field Radiation Therapy
IFSO:
Individual Field Simultaneous Optimization
IGF:
Insulin Growth Factor
IGRT:
Image guided radiotherapy
iGTV:
Internal Gross Tumor Volume
IHCC:
Intrahepatic Cholangiocarcinoma
IL:
Interleukin
ILROG:
International Lymphoma Radiation Oncology Group
IMPT:
Intensity Modulated Proton Therapy
IMPT-PBS:
Intensity Modulated Proton Therapy Pencil Beam Scanning
IMRT:
Intensity Modulated Radiation Therapy
INRGSS:
International Neuroblastoma Risk Group Staging System
INRT:
Involved Node Radiation Therapy
INSS:
International Neuroblastoma Staging System
IOERT:
Intraoperative Electron Radiotherapy
IR:
Ionizing Radiation
IRB:
Institutional Review Board
IRSG:
Intergroup Rhabdomyosarcoma Study Group
IS:
Interstitial
ISRT:
Involved Site Radiation Therapy
ITV:
Internal Target Volume
IV:
Intravenous
J-CROS:
Japan Carbon-Ion Radiation Oncology Group
JPY:
Japanese Yen
keV:
Kiloelectronvolts
KPS:
Karnofsky Performance Status
kV:
Kilovolt
LAD:
Left Anterior Descending Artery
LAO:
Left Anterior Oblique
LAPC:
Locally Advanced Pancreatic Cancer
LAT1:
L-type amino acid transporter
LBNL:
Lawrence Berkley National Laboratory
LC:
Local Control
LCD:
Local Coverage Determination
LDH:
Lactate Dehydrogenase
LED:
Light-Emitting Diode
LEM:
Local Effect Model
LET:
Linear Energy Transfer
LETd:
Dose-Averaged Linear Energy Transfer
LGG:
Low-grade Glioma
Li:
Lithium
LI-RADS:
Liver Imaging Reporting and Data System
LMA:
Large Mediastinal Adenopathy
LN:
Lymph nodes
LOH:
Loss of Heterozygosity
LQ:
Linear Quadratic
LRC:
Locoregional Control
LRF:
Locoregional Failure
LRPFS:
Locoregional Progression Free Survival
LRR:
Locoregional Recurrence
LRRC:
Locally Recurrent Rectal Cancer
LRT:
Lattice Radiotherapy
LS-SCLC:
Limited-Stage Small Cell Lung Cancer
LVSI:
Lymphovascular Space Invasion
LYL:
Life Years Lost
MAC:
Medicare Administrative Contractors
MALT:
Mucosa-Associated Lymphoid Tissue
MAP:
Methotrexate, Adriamycin, Cisplatin
MAPKs:
Mitogen Activated Protein Kinase
MBRT:
Microbeam Radiotherapy
MC:
Monte Carlo
MDACC:
MD Anderson Cancer Center
MDASI:
MD Anderson Symptom Inventory
MDM:
Monocyte-derived Macrophages
MDSC:
Myeloid-derived Suppressor Cells
MEE:
Multiple Energy Extraction
MELD:
Model for End-Stage Liver Disease
MELE:
Multi-energy Layer Extraction
MeV:
Millielectronvolt
MFH:
Malignant Fibrous Histiocytosis
MFO:
Multi-Field Optimization
MG:
Microglia
MGH:
Massachusetts General Hospital
MHC:
Major Histocompatibility Complex
MHD:
Mean Heart Dose
MI:
Myocardial Infarction
MIBC:
Muscle Invasive Bladder Cancer
MIBG:
Metaiodobenzylguanidine
MID:
Minimally Important Difference
MIP:
Maximal Intensity Projection
MKM:
Microdosimetric Kinetic Model
MLC:
Multi-leaf Collimator
MLD:
Mean Liver Dose
MLIC:
Multi-layer Ionization Chambers
MLPA:
Multiplex Ligation-dependent Probe Amplification
MM:
Motion Management
MMP:
Matrix Metalloproteinase
Mo:
Month
MPM:
Malignant Pleural Mesothelioma
MPNST:
Malignant Peripheral Nerve Sheath Tumor
MRCP:
Magnetic Resonance Cholangiopancreatography
MRI:
Magnetic Resonance Imaging
MRT:
Microbeam Radiation Therapy
MSK:
Memorial Sloan Kettering Cancer Center
MU:
Monitor Unit
MV:
Millivolt
MVA:
Multivariate Analysis
MWA:
Microwave Ablation
N:
Nitrogen
N
A
:
Avogadro’s Number
NAFLD:
Nonalcoholic Fatty Liver Disease
NASA:
National Aeronautics and Space Administration
NASH:
Nonalcoholic Steatohepatitis
NBL:
Neuroblastoma
NCCN:
National Comprehensive Cancer Network
NCD:
National Coverage Determination
NCDB:
National Cancer Database
NCF:
Neurocognitive Function
NCI CTC:
National Cancer Institute Common Toxicity Criteria
NCI:
National Cancer Institute
NCT:
Neutron Capture Therapy
N
e
:
Electron Density
NED:
No Evidence of Disease
NF-κB:
Nuclear Factor-κB
NGGCT:
Non-Germinomatous Germ Cell Tumors
NGS:
Next-Generation Sequencing
NHEJ:
Non-homologous end joining
NIDCR:
National Institute of Dental and Cranial Research
NIH:
National Institute of Health
NIRS:
National Institute of Radiological Sciences
NK:
Natural Killer Cells
NMSC:
Non-melanomatous Skin Cancer
NO:
Nitric Oxide
NPC:
Nasopharyngeal Cancer
NPX:
Nasopharyngeal
NR:
Not Reported
NRG:
National
ns:
Not Significant
NSABP:
National Surgical Adjuvant Breast and Bowel Project
NSC:
Neural Stem Cells
NSCLC:
Non-Small Cell Lung Cancer
NSRL:
NASA Space Radiation Laboratory
NTCP:
Normal Tissue Complication Probability
NVG:
Neovascular Glaucoma
OAR:
Organ at Risk
OCT:
Optical Coherence Tomography
OEPA:
Oncovin, Etoposide, Prednisolone, Adriamycin
OER:
Oxygen Enhancement Ratio
OM:
Ocular Melanoma
ON:
Optic Nerve
ONB:
Olfactory Neuroblastoma
OPC:
Oropharyngeal Cancer
OPSCC:
Oropharyngeal Squamous Cell Carcinoma
OR:
Odds Ratio
ORN:
Osteoradionecrosis
OS:
Overall Survival
OTV:
Optimization Target Volume
PA:
Posteroanterior
PBA:
Pencil Beam Analytical
PBI:
Partial Breast Irradiation
PBRT:
Proton Beam Radiation Therapy
PBS:
Pencil Beam Scanning
PBT:
Proton Beam Therapy
PCG:
Proton Collaborative Group
PCORI:
Patient-Centered Outcomes Research Institute
pCR:
Pathologic Complete Response
pCT:
Proton Computed Tomography
PD-1:
Programmed Cell Death Protein 1
PDD:
Percent Depth Dose
PDL-1:
Programmed Death Ligand 1
PET:
Positron Emission Tomography
PFS:
Progression Free Survival
PI3K:
Phosphatidylinositide 3-kinase
PIDE:
Particle Irradiation Data Ensemble
pMBRT:
Proton Minibeam Radiation Therapy
PNET:
Primitive Neuroectodermal Tumors
PO:
Posterior Oblique
POG:
Pediatric Oncology Group
PR:
Partial Response
PR:
Pathological Response
PRAME:
Preferentially Expressed Antigen in Melanoma
pRG:
Proton Radiography
PRO:
Patient Reported Outcomes
PRV:
Planning Organ-at-risk Volume
PSA:
Prostate-specific Antigen
PSC:
Primary Sclerosing Cholangitis
PSI:
Paul Scherrer Institute
PSPT:
Passive Scatter Proton Therapy
PSQA:
Patient Specific Quality Assurance
PT:
Particle Therapy
PTCOG:
Particle Therapy Co-Operative Group
PTV:
Planning Target Volume
QA:
Quality Assurance
QACT:
Quality Assurance Computed Tomography
QALY:
Quality-Adjusted Life-Years
QD:
Once Daily
QOL:
Quality-of-life
QS:
Quad Shot
QST:
National Institutes of Quantum and Radiological Science and Technology
QUANTEC:
Quantitative Analysis of Normal Tissue Effects
r/r:
Relapsed/Refractory
RAI:
Radioactive Iodine
RAO:
Right Anterior Oblique
RB:
Retinoblastoma
RBE:
Relative Biological Effectiveness
RC:
Regional Control
RCT:
Radio(chemo)therapy
RCT:
Randomized Controlled Trials
RECIST:
Response Evaluation Criteria In Solid Tumours
RF:
Radiofrequency
RFA:
Radiofrequency Ablation
RFS:
Relapse-free Survival
RIBC:
Radiation Induced Brain Changes
RIBE:
Radiation-induced Bystander Effects
RILD:
Radiation-Induced Liver Disease
RION:
Radiation Induced Optic Neuropathy
RMS:
Rhabdomyosarcoma
RNI:
Regional Nodal Irradiation
RO-APM:
Radiation Oncology Alternative Payment Model
ROS:
Reactive Oxygen Species
RP:
Radiation Pneumonitis
RPA:
Recursive Partitioning Analysis
RPO:
Right Posterior Oblique
RPS:
Retroperitoneal Sarcoma
RR:
Radiological Response
RR:
Relative Risk
RS:
Repair Saturation
RSP:
Relative Stopping Power
RT:
Radiotherapy
RTOG:
Radiation Therapy Oncology Group
RT-PCR:
Reverse Transcription Polymerase Chain Reaction
RVH:
Root Mean Square Deviation Dose Volume Histogram
S:
Stopping Power
SABR:
Stereotactic Ablative Radiotherapy
SBRT:
Stereotactic Body Radiotherapy
SCC:
Squamous Cell Carcinoma
SCLC:
Small Cell Lung Cancer
SEER:
Surveillance, Epidemiology, and End Results Program
SFO:
Single-Field Optimization
SFRT:
Spatially Fractionated Radiotherapy
SFUD:
Single Field Uniform Dose
SGRT:
Surface-guided Radiation Therapy
SIB:
Simultaneous Integrated Boost
SIOPE:
European Society for Paediatric Oncology
SIRT:
Selective Internal Radiotherapy
SLD:
Sublethal Damage
SOBP:
Spread-out Bragg Peak
SPA
RC
:
Spot Scanning Proton Arc Therapy
sPBT:
Scanning Proton Beam Therapy
SPECT:
Single Photon Emission Computed Tomography
SPHIC:
Shanghai Proton and Heavy Ion Center
SPR:
Stopping Power Ratio
SRS:
Stereotactic Radiosurgery
SSB:
Single-strand breaks
SSD:
Source Surface Distance
SST:
Spot Scanning Time
STING:
Stimulator of Interferon Genes
STR:
Subtotal Resection
STS:
Soft-Tissue Sarcoma
STV:
Scanning Target Volume
SUV:
Standardized Uptake Value
SWOG:
Southwest Oncology Group
TA:
Tumor Antigens
TACE:
Transarterial Chemoembolization
TAE:
Transarterial embolization
TAM:
Tumor-Associated Macrophages
TARE:
Transarterial Radioembolization
TCP:
Tumor Control Probability
TGF-β:
Tumor Growth Factor- β
TIL:
Tumor Infiltrating Lymphocytes
TIVA:
Total Intravenous Anesthesia
TLN:
Temporal Lobe Necrosis
TNFα:
Tumor necrosis factor alpha
TPS:
Treatment Planning System
TRAIL:
Tumor Necrosis Factor Related Apoptosis-Inducing Ligand
Tregs:
Suppressive Regulatory T Cells
TTB:
Total Toxicity Burden
TURBT:
Transurethral Resection of Bladder Tumor
TURP:
Transurethral Resection of the Prostate
UCLBL:
University of California Lawrence Berkeley Laboratory
UCSF:
University of California San Francisco
UFPTI:
University of Florida Proton Therapy Institute
UK:
United Kingdom
UM:
Uveal Melanoma
UNOS:
United Network for Organ Sharing
UPS:
Undifferentiated Pleomorphic Sarcoma
US:
Ultrasound
US:
United States
USD:
United States Dollars
UT:
University of Texas
UTI:
Urinary Tract Infections
UV:
Ultraviolet
VA:
Visual Acuity
VAC:
Vincristine, Actinomycin-D, Cyclophosphamide
VEGF:
Vascular Endothelial Growth Factor
VMA:
Vanillylmandelic Acid
VMAT:
Volumetric Modulated Arc Therapy
WBC:
White Blood Cell
WEPL:
Water Equivalent Path Length
WET:
Water-Equivalent Thickness
WHO:
World Health Organization
Y:
Yttrium
Z:
Atomic Number
Section I Background
1 A Brief History of Particle Radiotherapy
Timothy D. Malouff, Christopher Serago, and Daniel M. Trifiletti
Department of Radiation Oncology, Mayo Clinic Florida Address: 4500 San Pablo Road South, Jacksonville, FL, USA 32224
TABLE OF CONTENTS
1.1 History of the Clinical Use of Particles
1.2 History of Proton Therapy
1.3 History of Carbon Ion Therapy
1.4 History of Other Heavy Particles
1.5 History of Boron Neutron Capture Therapy
1.6 Conclusions
1.1 History of the Clinical Use of Particles
One of the most revolutionary events in the history of medicine was the discovery of X-rays by Wilhelm Röntgen in 1895[1]. Within 2 months of their discovery, they were used experimentally for diagnostic imaging, as well as the treatment of a multitude of malignant and benign diseases, to varying degrees of success [1,2]. Since that time, the indications for radiation therapy have become better established, with an estimated 60% of cancer patients receiving radiation as part of their treatment course[3]. Corresponding to this increase in usage of radiation therapy over the past century, there have been a multitude of technological advances aimed at improving the “therapeutic window” of radiotherapy, whereby the efficacy of treatment is maximized and the toxicity is minimized, leading to the development of high-energy accelerators and techniques such as intensity-modulated radiation therapy (IMRT). At its heart, the use of particle therapy for therapeutic purposes attempts to maximize the “therapeutic window” and provide highly efficacious therapies with a greater degree of safety.
Occurring at approximately the same time as Röntgen’s experiments with X-ray irradiation, Ernest Rutherford made a discovery that would revolutionize our understanding of chemistry and physics: the proton. Hans Wilhelm Geiger and Sir Ernest Marsden, while working in Rutherford’s lab, conducted experiments with alpha particles shot into a sheet of metal foil. Based on the reflected angles of the alpha particles, Rutherford hypothesized that the alpha particles, and therefore atoms, contained a positively charged central structure of large size that was surrounded by negatively charged particles[1]. Rutherford continued his work after World War I, when he irradiated nitrogen gas with alpha particles, creating oxygen and dense hydrogen nuclei. Based on this reaction, he concluded that nitrogen must contain hydrogen nuclei, which he named “proton,” based on the Greek word for “first.” [1,4].
Though the existence of neutrons was hypothesized by Rutherford in 1923, it was not until later that the idea of the neutron was formalized. Walther Wilhelm Georg Franz Both and Herbert Becker created a radiation beam that was more penetrating than gamma rays by using alpha particles shot at boron and beryllium, and the subsequent work by Joliot-Curies and Sir James Chadwick formally identified the neutron[1].
The physical advantages of proton and heavy ion radiation for therapeutic purposes began to be understood in 1904, when Sir William Henry Bragg reported on the characteristic energy deposition for charged particles in a given medium in which a small amount of energy is deposited entering the tissue, with a large amount deposited at the distal portion of the path. This “Bragg-peak” remains one of the defining physical and dosimetric advantages when using particle therapy [1,2,5].
Clinically, charged particles have been used for over 60 years. With the discovery of a method to accelerate particles without the use of high voltage, Earnest O. Lawrence helped develop the first cyclotron in 1929. Interestingly, the first model of the cyclotron was only 4 in. in diameter and was featured on a cover of Time. Larger cyclotrons were eventually constructed at the University of California Berkeley, and, in 1938, 24 patients were treated with a single fraction of fast neutron therapy using a 37-in. cyclotron. The early successes of these treatments led to a total of 226 patients treated with fast neutrons from 1938 to 1943[2], although the toxicities were later judged to be too severe to continue treatment[6]. Although the concerns of fast neutron therapy led to the decrease in use in the US, Gerald Kruger, in 1938, hypothesized that tumors can be treated with alpha particles emitted from boron when irradiated with neutrons[2]. This technique, which is now known as “boron neutron capture therapy,” is gaining interest and is discussed extensively in subsequent sections of this text.
Fast-neutron therapy enjoyed a reemergence in the late 1960s, with the development of the cyclotron at the Hammersmith Hospital in London. Based on this, the US National Cancer Institute began funding research at the University of Washington in Seattle, Washington, in 1971. Initially, five cyclotrons were to be used in clinical trials, mostly based out of physics laboratories. In 1984, the University of Washington was brought into service, although development of clinical equipment at the other sites was hampered due to financial problems[7]. Today, the University of Washington is the only site in the US treating with fast neutron therapy, most commonly for locally advanced and unresectable salivary gland tumors.
1.2 History of Proton Therapy
In his innovative paper published in 1946, Dr. Robert R. Wilson proposed the use of accelerated protons, and heavy ions, for oncologic treatment in humans [2,8]. Given the high energy needed to accelerate heavy ions, a 184-in. synchrocyclotron was developed at Berkley in 1947, which was subsequently used by Cornelius Tobias and John Lawrence in animal models with some success [2,4,9].
This preclinical work led to the first patients treated with proton therapy in Berkley in 1954. The first patient treated with proton therapy was a patient with widely metastatic breast cancer who underwent pituitary irradiation, mirroring earlier experiments with pituitary irradiation in a dog model [2,4]. The pituitary provided an ideal location to treat, as it could be located readily using orthogonal X-ray films and rigid immobilization[4]. Although she initially responded well to therapy, she unfortunately died several months after treatment [2,10]. Furthermore, approximately 700 patients with acromegaly were treated with proton therapy[11]. In 1957, the use of proton therapy at Berkley was discontinued and the accelerator began to be used as a source of helium ions and other heavy charged particles until the particle treatment program was discontinue in 1992[12]. In total, approximately 2,000 patients were treated at Berkley with protons, helium, and other heavy charged particles[13].
