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FUNDAMENTALS OF
RADIATION ONCOLOGY
FUNDAMENTALS OF
RADIATION ONCOLOGY
PHYSICAL, BIOLOGICAL, AND
CLINICAL ASPECTS
THIRD EDITION
HASAN MURSHED, M.D., M.S

Medical Director
Hope Regional Cancer Center
Panama City, Florida, United States
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Dedication
This book is dedicated to my children Ishraq and Ishmam.

Their faces remind me every day that “may I always act so as
to preserve the finest traditions of my calling and may I long experience
the joy of healing those who seek my help.”*
d*Hippocratic Oath, Modern version, Louis Lasagna, MD, 1964
Contents
ForeworddJames A. Bonner xvii

ForeworddThomas A. Buchholz xix
Preface xxi
Contributors xxiii
Reviewers xxvii
PART I
BASIC SCIENCE OF RADIATION ONCOLOGY
1. Radiation Physics, Dosimetry, and Treatment Planning 3
IVAN BREZOVICH, ALLAN CAGGIANO AND KENT GIFFORD
Fundamental Physical Quantities 3

Atomic Structure 4
Nuclear Structure 5
Radioactive Decay 6
Modes of Radioactive Decay 6
Electromagnetic Radiation and Properties of Interaction 11
Particulate Radiation Properties and Interactions 15
The Physics of Dosimetry 17
Linac Calibration 22
The Physics of Radiation Treatment Planning and Delivery 27
Radiation Treatment Planning 29
External Beam Radiation Therapy 31
Brachytherapy 33
Other Radiation Therapy Modalities 35
References 36
2. Radiation Protection and Safety 39

IVAN BREZOVICH, ALLAN CAGGIANO AND KENT GIFFORD
Measurement of Radiation Quantities 39

Radiation Protection Principles 41
Organizations 42
Regulations 42
Occupational and General Public Dose Limits 44
vii
viii CONTENTS
ALARA and Radiation-Induced Biological Effects 46

Radiation Treatment Room Design 46
Signage and Labeling Requirements 51
Equipment and Area Monitoring 52
Personnel Monitoring 53
References 54
3. Radiation Biology 57
JIMMY CAUDELL, RICHARD C. MILLER AND BARRY ROSENSTEIN
Radiobiological Quantities 57
Radiation Effects on Chromosomes 61
Cell Survival Curves 64
Fractionation Protocols Used in Clinical Radiotherapy 70
Dose Rate Effect and Repair of Damage 71
The Oxygen Effect and Reoxygenation 72
Radiosensitizers and Radioprotectors 73
Cell and Tumor Cell Kinetics 74
Normal Tissue Kinetics and Proliferation Status 77
Early and Late Reacting Tissues: Specific Organs 79
Acute Effects of Whole-Body Irradiation 81
Deterministic and Stochastic Effects of Radiation 82
Effects of Radiation on the Embryo and Fetus 83
Radiation-Induced Heritable Changes 84
Sources of Radiation Exposure 85
References 86
4. Molecular Cancer Biology 89

JIMMY CAUDELL, RICHARD C. MILLER AND BARRY ROSENSTEIN
Cell Cycle Control 89

Carcinogenesis and Metastasis 90
Tumor Suppressor Genes 92
DNA Repair Genes 93
Proto-Oncogenes and Oncogenes 93
Apoptosis 95
Angiogenesis 98
Therapeutics 99
Targeted Therapies 100
References 103
CONTENTS ix
PART II
TECHNIQUES AND MODALITIES OF RADIATION
ONCOLOGY
5. Brachytherapy 107
SHEN SUI AND JACK YANG
Techniques of Brachytherapy 107

Physics and Biology of Brachytherapy Sources 108
Source Strength Specification 108
Source Strength Calibration 110
Brachytherapy Dose Calculation 111
High-Dose-Rate Remote Afterloader 113
Computerized Treatment Planning 114
Clinical Indication of Brachytherapy 116
References 120
6. Intensity-Modulated and Image-Guided Radiation Therapy 123

YASEMIN BOLUKBASI, NULIFER KILIC DURANKUS, RICHARD POPPLE, UGUR SELEK AND DUYGU SEZEN
Target Volumes, Margins and DoseeVolumes for Intensity-Modulated Radiation

Therapy 123
Inverse Planning Intensity-Modulated Radiation Therapy 125
Image-Guided Radiotherapy 126
Clinical Experience of Intensity-Modulated Radiation Therapy and Volumetric-Modulated
Arc Treatment 128
References 135
7. Stereotactic Radiation: Cranial Lesions 139

BERRIN PEHLIVAN, UGUR SELEK, ERKAN TOPKAN AND BERNA AKKUS YILDIRIM
Radiobiology of Stereotactic Radiation 139

Stereotactic Radiosurgery Technique 139
Patient Immobilization and Setup 140
Imaging 140
Target Volume Delineation 141
Treatment Plan 142
Treatment Plan Assessment 144
Clinical Indication of Cranial Stereotactic Radiation 145
Stereotactic Radiosurgery Toxicity 147
Clinical Trials of Stereotactic Radiosurgery for Metastatic Brain Cancer 147
References 150
x CONTENTS
8. Stereotactic Body Radiation Therapy: Lung Cancers 153

YASEMIN BOLUKBASI, UGUR SELEK AND ERKAN TOPKAN
Lung Cancer 153

Clinical Trials for Stereotactic Body Radiation Therapy 157
References 160
9. Proton Radiation Therapy 161

YASEMIN BOLUKBASI, BERRIN PEHLIVAN, RICHARD POPPEL, UGUR SELEK, ERKAN TOPKAN
AND BERNA AKKUS YILDIRIM
Proton Beam Depth Dose 161

Proton Relative Biological Effectiveness 161
Beam Production, Delivery, Treatment Planning, and Quality Assurance 162
Clinical Experience of Proton Radiotherapy 165
References 169
10. Immunotherapy 173

KAMRAN AHMAD, BARRY ROSENSTEIN AND KIM SUNJUNE
Immune System Components 173

The Immune Synapse 174
Immune Tolerance Mechanism 175
Cancer Immunotherapy 175
Radiation and Immunotherapy 178
Site-Specific Cancer Immunotherapy 180
Immunotherapy Toxicity 185
References 186
11. Radiation and Combined Modality Therapy 191

ROBERT OLDHAM AND DAVID REISMAN
Radiation Therapy 191

Surgery Combined with Radiation Therapy 193
Side Effects of Combined Modality of Radiation and Surgery 194
Chemotherapy Combined with Radiation Therapy 195
Side Effects of Combined Modality Radiation and Chemotherapy 195
Site-Specific Chemotherapeutic Agents Used in Combination with Radiotherapy:
Mechanisms of Action and Side Effects 196
References 199
CONTENTS xi
12. Statistical Considerations in Radiation Oncology 201

TIMOTHY SCHULTHEISS AND DAVID SMITH
Definition of Statistical Terms 201

Model Fitting 208
Logistic Regression and Its Pitfalls 211
Proportional Hazards and Their Pitfalls 213
Retrospective Studies and Their Pitfalls 215
Metaanalysis and Its Pitfalls 216
References 217
PART III
CLINICAL RADIATION ONCOLOGY
13. Skin Cancers 221
JEFFERSON TRUPP
Nonmelanoma 221
Melanoma 224
Merkel Cell Cancer 228
Annotated Bibliography 230
14. Primary Brain Cancers 237

JERRY JABOIN, RAKESH JALALI, BLAIR MURPHY AND DEREK TSANG
Low-Grade Glioma 238

High-Grade Glioma 241
Brainstem Glioma 243
Optic Glioma 244
Ependymoma 245
Meningioma 247
Medulloblastoma 248
Pituitary Adenoma 252
Craniopharyngioma 254
xii CONTENTS
15. Head and Neck Cancers 269

JONATHAN LEEMAN
Head and Neck Lymph Node Borders 269

Lymph Node Risk 271
Oral Cavity Cancer 272
Nasopharyngeal Cancer 277
Oropharyngeal and Hypopharyngeal Cancers 282
Laryngeal Cancer 290
Nasal Cavity and Paranasal Sinuses 296
Parotid Gland 300
Unknown Primary 304
16. Breast Cancers 317

DREXELL BOGGS, YASEMIN BOLUKBASI AND NAOMI SCHECHTER
RTOG Breast and LN Volume Guidelines 317

Risk for Axillary Nodes 319
Noninvasive Breast Cancer (DCIS) 323
Early-Stage Breast Cancer 324
Postmastectomy Radiation Therapy 325
Locally Advanced Breast Cancer 326
Recurrent Breast Cancer 327
17. Thoracic Cancers 351

ANDREW BANG AND SAUMIL GANDHI
NoneSmall-Cell Lung Cancer 351

Superior Sulcus Tumors 357
Medically Inoperable NSCLC 357
Small-Cell Lung Cancer 358
Thymoma 359
Malignant Mesothelioma 360
18. Gastrointestinal Cancers 381

ROJYMON JACOB AND GULER YAVAS
Esophageal Cancer 381

Gastric Cancer 389
Pancreatic Cancer 394
Colon and Rectal Cancer 398
Anal Cancer 404
CONTENTS xiii
19. Genitourinary Cancers 429

HILARY BAGSHAW, MARK BUYYOUNOUSKI AND NICOLAS PRIONAS
Renal Cell Cancer 429

Bladder Cancer 432
Prostate Cancer 437
Testicular Cancer 449
20. Gynecological Cancers 475

MELIS GULTEKIN AND NEIL TAUNK
Endometrial Cancer 475

Cervical Cancer 482
Ovarian Cancer 492
Vaginal Cancer 495
Vulvar Cancer 499
21. Lymphoma and Hematologic Cancers 515

JAYANT SASTRI GODA AND GOZDE YAZICI
Hodgkin Lymphoma 515

Non-Hodgkin Lymphoma 520
22. Sarcomas 545

ASTRID BILLFALK-KELLY
Soft-Tissue Sarcomas 545

Retroperitoneal/Intraabdominal Sarcoma 548
GIST 548
Kaposi Sarcoma 548
23. Pediatric Cancers 557

JERY JABOIN, BLAIR MURPHY AND DEREK TSANG
Hodgkin’s Lymphoma 557

Neuroblastoma 561
Wilms0 Tumor (Nephroblastoma) 565
Rhabdomyosarcoma 570
Ewing’s Sarcoma 574
Retinoblastome 578
xiv CONTENTS
24. Benign Diseases 599

DOROTHY GUJRAL AND MATTHEW WILLIAMS
Skin and Connective Tissue Disorders 599

Benign Neoplasms of the Brain, Head, and Neck 600
Paraganglioma/Pheochromocytoma (Glomus Tumor) 603
Eye/Orbit Diseases 603
Vascular Disorders 604
Functional Disorders 604
Diseases of the Bone 605
References 605
PART IV
PALLIATIVE CARE AND RADIATION TREATMENT
TOXICITY
25. Metastatic Cancers 609
MOLLY GABLE
Metastatic Brain Cancer 609

Spinal Cord Compression 612
Superior Vena Cava Syndrome 614
Metastatic Bone Cancers 614
26. Radiation Treatment, Toxicity, and Their Management 621

TIMOTHY W. DZIUK
Normal Tissue Tolerance to Therapeutic Irradiation 621

Skin 630
Head and Neck 633
Thorax 639
Breast 642
Gastrointestinal Tract 644
Genitourinary 655
Gynecological 659
Nervous System 660
Pain Management 662
Psychotropic Medications 666
CONTENTS xv
Radiation Fibrosis and Muscle Relaxants 669

Common Toxicity (Side Effect) Criteria 669
References 674
Acronyms and Abbreviations 675

Index 691
About the Editor 713
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Forewordd
James A. Bonner
Once again, Dr. Murshed has done an excellent job of producing an

information-packed textbook that can be used in the day-to-day practice of
radiation oncology. This new issue of Fundamentals of Radiation Oncology is an
important compilation of the new and established literature that affects
routine and complex decision-making in our clinics. Since the last edition of
Clinical Fundamentals for Radiation Oncologists, there have been many new
advances in radiation oncology. These advances have occurred in almost every
disease site. This wealth of new information is difficult to summarize in a
concise manner, but Dr. Murshed and all the contributors have artfully
accomplished this goal. This edition is filled with crucial information for the
busy practitioner.
Since the publication of the last edition, there have been breakthroughs in
stereotactic radiosurgery, proton therapy, and immunotherapy to name just a
few innovative areas. This textbook provides detailed information regarding
new applications of radiotherapy, while still maintaining a strong backbone of
basic principles of radiation oncology, radiobiology, and physics. The textbook
creatively organizes and summarizes the major clinical trials, frequently using
helpful tables, in each disease site.
It is also important to note that Dr. Murshed has substantially increased the
number of contributing authors for this edition of the text. This edition in-
cludes contributions from 48 experts in the field. These experts have been able
to encapsulate the major advances in a manner that highlights the most sig-
nificant issues that frequently arise on a daily basis. This is the beauty of this
textbook. It is also noteworthy that the contributors represent programs from
all over the world and these authors provide a comprehensive perspective to
radiation oncology care.
Therefore, Dr. Murshed has done a very thorough job of presenting the
basic and detailed issues that are associated with all oncologic disease sites. He
has made this information relevant for the daily practice of radiation oncology.
Dr. Murshed has always had a strong interest in the educational aspects of our
field. This fact was obvious during his residency at The University of Alabama
at Birmingham. He has continued this interest over the past 20 years, and this
xvii
xviii FOREWORDdJAMES A. BONNER
updated version of Fundamentals of Radiation Oncology is a great testament to

his commitment to our field. I believe that all radiation oncologists will find
this textbook a “must have” in their armamentarium.
James A. Bonner, M.D.

Merle M. Salter Professor and Chairman
Department of Radiation Oncology
University of Alabama at Birmingham
Birmingham, Alabama, United States
June, 2018
Forewordd
Thomas A. Buchholz
I would like to personally acknowledge and thank Dr. Hasan Murshed for
providing our community with an outstanding Third Edition of the Fundamentals
of Radiation Oncology. This comprehensive textbook includes 26 chapters auth-
ored by a variety of thought-leaders. It is unique in including chapter authors
from around the world in addition to notable authorities in the United States.
The field of radiation oncology is rapidly changing, and this new edition
provides a single source that captures the many conditions seen by radiation
oncologists. In addition, it provides much of the foundational science behind
the field of radiation oncology. Selected chapters are also dedicated to the
importance of technique, including describing the role of newer proton tech-
niques and the important evolving role of stereotactic treatments for intra-
cranial and extracranial disease. Finally, exciting new materials are provided
regarding the interactions of radiation oncology and immunotherapy, an area
that is likely to significantly increase in importance over the next decade.
One hallmark that has impressed me about this textbook is its compre-
hensive content and ease of use. The structure and design allow for this book
to use for an immediate reference or to address an immediate clinical question.
However, it also serves as an outstanding comprehensive study guide for the
field of radiation oncology.
I am sure that many will share my very high opinion of this impressive work.
More importantly, I am sure that this textbook will help bring forward the
many clinical and technical advances in radiation oncology to centers around
the world, and in doing so, help raise the standard of care. On behalf of the
radiation oncology community and the patients who benefit from their excellent
care, I say thank you to Dr. Murshed and the nearly 50 contributing authors.
Thomas Buchholz, M.D.

Professor Emeritus
University of Texas, MD Anderson Cancer Center
Medical Director
Scripps MD Anderson Cancer Center
La Jolla, California, United States
June, 2018
xix
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Preface
Cancer management, specifically Radiation Oncology, has undergone ground

breaking changes over the past several years. The AJCC 8th staging system has
been implemented, and new tools for cancer diagnosis, and novel radiation
modalities and techniques are now available. Most importantly, new studies
and their associated data have led to rapid changes in recommendations for
cancer treatment, requiring this third edition of Fundamentals of Radiation
Oncology.
This new edition continues to provide current, concise, and a readily
available source of clinical information for busy practicing radiation oncolo-
gists. The book consists of 26 chapters, divided into four parts.
Part I describes the basic science of radiation oncology, with discussions of
radiation physics, radiation protection, and radiation biology, as well as
molecular biology.
Part II describes techniques and modalities of radiation oncology including
brachytherapy, intensity-modulated radiation therapy (IMRT), stereotactic
radiotherapy (SRS), stereotactic body radiation therapy (SBRT), and proton
therapy. Significant recent advances made in the areas of immunotherapy and
combined modality therapy; as such, these chapters have also been added to
this new edition.
Part III describes the clinical science of radiation oncology including risk
factors, symptoms/signs, and investigations needed for the cancer diagnosis
and up-to-date treatment recommendations in accordance with the new AJCC
staging system. In addition, radiation treatment techniques, with an emphasis
on IMRT, have been expanded to all the chapters. Also included in this version
of the book is a chapter on benign diseases. Updated annotated bibliographies
of latest landmark studies providing evidence-based rationale for the recom-
mended treatments are presented at the end of each chapter.
Part IV describes palliative radiation treatments to improve the quality of
life for cancer patients and the management of side effects from radiation
treatment.
This updated edition was made possible through an international collabo-
ration of contributing authors from Australia, Canada, India, Turkey, United
Kingdom, and United States. I am immensely indebted to all of the contrib-
uting authors; without their assistance, this book would not be. I am especially
grateful to Ugur Selek, M.D., who contributed several chapters to this edition.
I am also thankful for his continuing friendship over the past 16 years.
xxi
xxii PREFACE
In addition, I sincerely thank all of the excellent reviewers of this book for their
thoughtful input in updating the clinical chapters. Finally, I wish to thank
Tracy Tufaga, Rafael Teixeira and Poulouse Joseph at Elsevier for their
commitment to excellence and expert editorial contribution to this book.
May this updated edition provide you, the reader, the best knowledge,
excellent skills, and the compassion to “cure sometimes, treat often, comfort
always.”*
Hasan Murshed, M.D.

June 2018
*
Hippocrates Asclepiades (460 BCe370 BC).
Contributors
Kamran Ahmad M.D. Assistant Member, Radiation Oncology, Moffitt Cancer

Center, Tampa, FL, USA
Hilary P. Bagshaw M.D. Assistant Professor, Radiation Oncology, Stanford Univer-
sity, Stanford, CA, USA
Andrew Bang M.D. Clinical Fellow, Radiation Oncology, University of Toronto,
Princess Margaret Cancer Centre, Toronto, ON, Canada
Astrid Billfalk-Kelly M.D. Clinical Fellow, Radiation Oncology, University of
Toronto, Princess Margaret Cancer Centre, Toronto, ON, Canada
Drexell Boggs M.D. Assistant Professor, Radiation Oncology, University of Alabama,
Birmingham, AL, USA
Yasemin Bolukbasi M.D. Associate Professor, Radiation Oncology, Koc University,
Istanbul, Turkey
Ivan Brezovich Ph.D. Professor, Radiation Oncology, University of Alabama,
Birmingham, AL, USA
Mark K. Buyyounouski M.D., M.S. Professor, Radiation Oncology, Stanford
University, Stanford, CA, USA
Allan Caggiano M.S. Chief Medical Physicist, Sr. Patricia Lynch Regional Cancer
Center, Teaneck, NJ, USA
Jimmy Caudell M.D., Ph.D. Adjunct Assistant Professor, Radiation Oncology,
University of Alabama, Birmingham, AL, USA
Nulifer Kilic Durankus M.D. Consultant, Radiation Oncology, Koc University,
Istanbul, Turkey
Timothy W. Dziuk M.D. Consultant, Radiation Oncology, Texas Oncology, San
Antonio, TX, USA
Molly Gabel M.D. Adjunct Associate Professor, Radiation Oncology, SMG MD
Anderson Cancer Center, Berkeley Heights, NJ, USA
Saumil Gandhi M.D., Ph.D. Assistant Professor, Radiation Oncology, University of
Texas, MD Anderson Cancer Center, Houston, TX, USA
Kent Gifford Ph.D. Assistant Professor, Radiation Physics, University of Texas, MD
Anderson Cancer Center, Houston, TX, USA
Jayant Sastri Goda M.D. Professor, Radiation Oncology, Tata Memorial Centre,
Mumbai, India
Melis Gultekin M.D. Associate Professor, Radiation Oncology, Hacettepe University,
Ankara, Turkey
xxiii
xxiv CONTRIBUTORS
Dorothy Guzral MBChB, Ph.D. Consultant, Clinical Oncology, Imperial College

Healthcare NHS Trust, London, UK
Jerry Jaboin M.D., Ph.D. Associate Professor, Radiation Medicine, Oregon Health
and Science University, Portland, OR, USA
Rojymon Jacob M.D. Associate Professor, Radiation Oncology, University of
Alabama, Birmingham, AL, USA
Rakesh Jalali M.D. Medical Director, Radiation Oncology, Apollo Proton Cancer
Center, Chennai, India
Jonathan Leeman M.D. Clinical Instructor, Radiation Oncology, Brigham and
Women’s Hospital/Dana Farber Cancer Institute, Boston, MA, USA
John Leung M.B.B.S. Associate Professor, Radiation Oncology, University of
Adelaide, Adelaide, Australia
Richard Miller M.D. Associate Professor, Radiation and Cellular Oncology, the
University of Chicago, Chicago, IL, USA
Blair Murphy M.D. Resident, Radiation Medicine, Oregon Health and Science Uni-
versity, Portland, OR, USA
Robert Oldham M.D. Clinical Professor, University of Missouri, Columbus, MO,
USA
Berrin Pehlivan M.D. Associate Professor, Radiation Oncology, Istanbul Kemerburgaz
University, Istanbul, Turkey
Andrew Pippas M.D. Consultant, Medical Oncology, John B Thomas Cancer Center,
Columbus, GA, USA
Richard Popple Ph.D. Professor, Radiation Oncology, University of Alabama,
Birmingham, AL, USA
Nicolas D. Prionas M.D., PhD. Resident, Radiation Oncology, Stanford University,
Stanford, CA, USA
David Reisman M.D., Ph.D. Consultant, Hematology Oncology, Baptist Medical
Group, Pensacola, FL, USA
Barry Rosenstein Ph.D. Professor, Radiation Oncology, Icahn School of Medicine at
Mount Sinai, New York, NY, USA
Naomi Schechter M.D. Associate Professor, Radiation Oncology, Keck Medical
Center of USC, Los Angeles, CA, USA
Timothy Schultheiss Ph.D. Professor, Radiation Physics, City of Hope Medical
Center, Duarte, CA, USA
Ugur Selek M.D. Professor, Radiation Oncology, Koc University, Istanbul, Turkey
Duygu Sezen M.D. Consultant, Radiation Oncology, Koc University, Istanbul,
Turkey
David Smith Ph.D. Research Professor, Radiation Physics, City of Hope Medical
Center, Duarte, CA, USA
Shen Sui Ph.D. Professor, Radiation Oncology, University of Alabama, Birmingham,
AL, USA
CONTRIBUTORS xxv
Kim Sunjune M.D., Ph.D. Assistant Member, Radiation Oncology, Moffitt Cancer
Center, Tampa, FL, USA
Neil Taunk M.D., M.S. Assistant Professor, Radiation Oncology, University of
Pennsylvania, Philadelphia, PA, USA
Erkan Topkan M.D. Professor, Radiation Oncology, Baskent University, Adana,
Turkey
Jefferson Trupp M.D. Consultant, Radiation Oncology, Hope Regional Cancer
Center, Panama City, FL, USA
Derek Tsang M.D. Assistant Professor, Radiation Oncology, University of Toronto,
Princess Margaret Cancer Centre, Toronto, ON, Canada
Matthew Williams MBChB, Ph.D. Consultant, Clinical Oncology, Imperial College
Healthcare NHS Trust, London, UK
Jack Yang Ph.D. Director, Medical Physics, Monmouth Med Ctr/RWJBarnabas
Health, Long Branch, NJ, USA
Guler Yavas M.D. Associate Professor, Radiation Oncology, Selcuk University,
Konya, Turkey
Gozde Yazici M.D. Associate Professor, Radiation Oncology, Hacettepe University,
Ankara, Turkey
Berna Akkus Yildirim M.D. Consultant, Radiation Oncology, Baskent University,
Adana, Turkey
Reviewers
Aziz Ahmad M.D. General Surgeon, Lynn Haven Surgical Center, Lynn Haven,
FL, USA
Penny Anderson M.D. Professor, Radiation Oncology, Fox Chase Cancer Center,
Philadelphia, PA, USA
Michael Asare-Sawiri B.S. Medical Dosimetrist, Hope Regional Cancer Center, Lynn
Haven, FL, USA
Kin-Sing Au M.D. Consultant, Radiation Oncology, Island Cancer Centre, Guam,
USA
Jerry Barker, Jr. M.D. Radiation Oncologist, Texas Oncology, Fort Worth, TX USA
James Beggs M.D. Otolaryngologist, Gulf Coast Facial Plastics and ENT Center,
Panama City, FL, USA
Donald Buchsbaum Ph.D. Professor, Radiation Oncology, University of Alabama,
Birmingham, AL, USA
Hans Caspary M.D. Otolaryngologist, Head & Neck Associates, Panama City,
FL, USA
Jason Cundiff M.D. General Surgeon, Bay Medical Sacred Heart, Panama City,
FL, USA
Daniel Daube M.D. Otolaryngologist, Gulf Coast Facial Plastics and ENT Center,
Cyril DeSilva M.D. Neurosurgeon, Bay Medical Center, Panama City, FL, USA
Gregory England M.D. Cardiothoracic Surgeon, Coastal Cardiovascular Surgeons,
Robert Finlaw M.D. Gastroenterologist, Digestives Diseases Center, Panama City,
FL, USA
Brian Gibson M.D. Otolaryngologist, Gulf Coast Facial Plastics and ENT Center,
Moses Hayes M.D. Medical Oncologist, Sacred Heart Medical Oncology Group, San
Destin, FL, USA
Heather Headstrom M.D. Neurosurgeon, Panama City Neurosurgery, Panama City,
FL, USA
Bret Johnson M.D. Dermatologist, Dermatology Associates, Panama City, FL, USA
N. Alex Jones M.D. General Surgeon, Emeralds Bay Surgical Associates, Panama
City, FL, USA
xxvii
xxviii REVIEWERS
Mariusz Kiln M.D. Gastroenterologist, Emerald Coast Gastroenterology, Panama

City, FL, USA
Charles Kovaleski M.D. Dermatologist, Dermatology Associates, Panama City,
Florida, USA
Glen MacAlpin M.D. General Surgeon, Sacred Heart Medical Group, Port St Joe,
FL, USA
Lawrence Margolis M.D. Professor Emeritus, Radiation Oncology, University of San
Francisco, San Francisco, California, USA
William Mckenzie M.D. Pulmonologist, Lung and the Sleep Center, Panama City,
FL, USA
Pierre Mechali M.D. Consultant, Hope Urology Center, Panama City, FL, USA
Angel Nunez M.D. Pulmonologist, Panama City Pulmonary, Panama City, FL, USA
Christopher Nutting M.D., Ph.D. Professor, Radiation Oncology, Royal Marsden
Hospital NHS Foundation, London, UK
Marwan Obid M.D. Pulmonologist, Obid Allergy and Respiratory Center, Panama
City, FL, USA
Jesus Ramirez M.D. Pulmonologist, Bay Clinic and Sleep Disorder lab, Panama City,
FL, USA
Shilpa Reddy M.D. Gastroenterologist, Digestive Diseases Center, Panama City,
FL, USA
George Reiss M.D. General Surgeon, Surgical Associates-NW Florida, Panama City,
FL USA
Albibi Riyad M.D. Gastroenterologist, Digestive Diseases Center, Panama City,
FL, USA
Sharon Spencer M.D. Professor, Radiation Oncology, University of Alabama,
Birmingham, AL, USA
Quang Tran M.D. Otolaryngologist, Head & Neck Associates, Panama City, FL, USA
Maciej Tumial M.D. Gastroenterologist, Panama City Gastroenterology, Panama
City, FL, USA
Richard Wilson M.D. General Surgeon, Surgical Associates-NW Florida, Panama
City, FL USA
Larry Wong D.O. General Surgeon, Bay Medical Sacred Heart, Panama City, FL, USA
Kristina Woodhouse M.D. Assistant Professor, Radiation Oncology, University of
Texas, MD Anderson Cancer Center, Houston, TX, USA
Ibrahim Yazji M.D. Cardiothoracic surgeon, Coastal Cardiovascular Surgeons,
Panama City. FL, USA
PART I
BASIC SCIENCE OF
RADIATION
ONCOLOGY
C H A P T E R
1
Radiation Physics, Dosimetry, and
Treatment Planning
Wilhelm Roentgen discovered X-rays in 1895 while experimenting with a gas-filled

cathode tube; Henri Becquerel discovered radioactivity in 1896 while experimenting
with uranium salts. Soon after these discoveries, radiation was used to treat cancer
and other diseases. To effectively use radiation, it is important to understand its basic
properties, which are addressed in this chapter.
FUNDAMENTAL PHYSICAL QUANTITIES

Mass, energy, charge, and force all have key roles in radiation physics.
Mass
Mass is the amount of matter within any physical object. Mass is measured as weight
and the standard international (SI) unit of mass is the kilogram (kg), represented by a
lump of platinumeiridium alloy kept in Paris, France. In the much smaller realm of
atomic physics, weights are expressed as atomic mass units (amu or u). An amu is
equivalent to 1/12th the mass of one atom of carbon (C12 isotope).
Einstein’s theory of relativity (E ¼ mc2) suggests that mass (m) can be converted
into energy (E), as a function of the speed of light squared (c2). One amu of mass is con-
verted into 931 MeV of energy. The mass of a moving object, its “relativistic mass,” is
larger than its mass at rest because the kinetic energy associated with its motion adds to
the resting mass.
Energy
Energy is the ability of a system to perform work. There are two types of energyd
potential energy and kinetic energy. One electron volt (eV) is the energy acquired by
an electron when it moves across a potential of 1 V. One million electron volts are desig-
nated by MeV.
Fundamentals of Radiation Oncology Copyright © 2019 Elsevier Inc.

https://doi.org/10.1016/B978-0-12-814128-1.00001-5 All rights reserved.
3
4 1. RADIATION PHYSICS, DOSIMETRY, AND TREATMENT PLANNING
Charge
Electric charge is the property of matter that causes it to experience a force in the pres-
ence of an electromagnetic field. Charges are positive or negative with an electron being
the smallest unit of negative charge (1) and the proton being the smallest unit of pos-
itive charge (þ1). The SI unit of charge is the Coulomb (6.25 1018 elementary charges).
Force
A force is an interaction that can change the direction or velocity of an object. Coulomb
force (electromagnetic force) is the force between two charged bodies. Protons and
electrons are held together by the Coulomb force. Gravitational force is the attraction
between two masses. It is a very weak force unless the masses are very large, like
the earth or the sun. Strong force holds particles together in the atomic nucleus (pro-
tons, neutrons, and quarks), is the strongest known fundamental physical force, but
only acts over atomic distances. Weak force is the force that is responsible for particle
decay processes (beta decay) and is approximately one-millionth of the strong force.
ATOMIC STRUCTURE
The atom consists of three fundamental particles: protons, neutrons, and electrons. The
particles are bound together by the abovementioned four fundamental forces.
Atomic Models
In the Rutherford model of the atom, protons and neutrons reside in the center
(nucleus), whereas electrons revolve around the nucleus in circular orbits. The Bohr
model of the atom introduced four refinements to the Rutherford model.
1. Electrons can only occupy certain discrete orbits while revolving around the
nucleus.
2. When electrons are in stationary orbits, they do not emit radiation as predicted by
classical physics.
3. Each stationary orbit has a discrete energy associated with it.
4. Radiation is only emitted whenever an electron moves from a higher orbit to a
lower orbit, and radiation is absorbed whenever an electron moves from a lower
orbit to a higher orbit.
Electron Binding Energy

Because negative electrons are bound to the positive nucleus by the Coulomb force, it
requires a certain amount of energy to remove an electron from the atom. This energy is
called “ionization energy.”
I. BASIC SCIENCE OF RADIATION ONCOLOGY

NUCLEAR STRUCTURE 5
Atomic Shell Filling Rules

Electron shells are labeled from the nucleus outward either by the letters K, L, M, N.
or by the numbers 1, 2, 3, 4. (principal quantum numbers, n). The maximum number
of electrons allowed in a given atomic shell is given by:
Maximum number of electrons in a given shell ¼ 2n2where n is the principal quan-
tum number.
Characteristic Radiation
When an electron acquires enough energy from an incident photon to leave an inner
orbit of the atom, a vacancy is created in that shell, which is immediately filled by
an outer shell electron, emitting the excess energy as a photon. This photon is a
“characteristic X-ray.”
Auger Electrons
The characteristic X-ray can leave the atom or it can displace an outer shell electron. The
displaced electron is called as “Auger electron,” and its kinetic energy is equal to the
energy of the characteristic X-ray that displaced it minus the energy required to remove
the electron from its shell.
Nuclear Binding Energy

The particles contained in the nucleus are bound together by the strong and the weak
nuclear forces discussed above. The mass of a nuclide is always less than the mass of
the constituent components. This deficiency of mass is called the mass defect. The en-
ergy required to separate the nucleus into its constituent particles is called the nuclear
binding energy. It can be computed using Einstein’s equation.
NUCLEAR STRUCTURE
Atoms are identified by their atomic symbols A Z X, where X is the atomic symbol, A is the
mass number (number of protons plus neutrons), and Z is the atomic number (number
of protons). The number of neutrons (N) in an atom can be determined by the equation
N ¼ A Z.
Special types of nuclei are defined as follows:
• Isotopes: Isotopes are atoms that have the same number of protons (Z), but a
different number of neutrons (A Z). Examples of two isotopes are 12 14
5 C and 6 C.
• Isobars: Isobars are atoms with nuclei that have the same number of total parti-
cles (A), but a different number of protons (Z) and neutrons (A Z). Example of
40
isobars are 40
19 K and 20 Ca.
• Isotones: Isotones are nuclides that have the same number of neutrons (A Z)
and a different number of protons (Z). Examples of isotones are 14 15
6 C and 7 N.
• Isomers: Isomers are atoms with nuclei that have the same number of total parti-
cles (A) and the same number of protons (Z), but different levels of energy in the
nucleus. Examples of isomers are 9943 Tc and 43 Tc.
99m

RADIOACTIVE DECAY
Radioactivity is the process by which an unstable nucleus is transformed by giving off
the excess energy and forming a new stable element. The transformation may involve
the emission of electromagnetic radiation or emission of particles, involving mecha-
nisms such as beta decay, alpha decay, or isomeric transitions. Examining the ratio
of neutrons to protons in all stable nuclei, the following conclusions can be made
(see Fig. 1.1):
If Z is less than or equal to 20, the ratio of neutrons to protons is 1.
If Z is greater than 20, the ratio becomes greater than 1 and increases with Z.
As more protons are added to the nucleus, the effects of the Coulomb force begin to
overwhelm the strong nuclear forces, which can make an atom unstable. This unstable
nucleus will tend to lose energy by different decay mechanisms, described in the next
section, to reach a more stable state.
MODES OF RADIOACTIVE DECAY

Alpha Decay
Radionuclides that have a Z greater than 82 are decayed most frequently by the emis-
sion of a helium nucleus, or alpha particle (a). The alpha particle is identical to the
nucleus of a helium atom, 42 He.
Beta Decay
By this process, a radioactive nucleus emits either an electron or a positron. There are
two types of beta decay: b (beta minus or negatron emission) and bþ (beta plus or
positron emission).
FIGURE 1.1 Neutron versus proton in stable nucleus.

MODES OF RADIOACTIVE DECAY 7
FIGURE 1.2 The conversion of mass into energy; the annihilation radiation is
traveling in the opposite direction.
• Negatron emission: If a radionuclide has a high number of neutrons (high n/p

ratio), it tends to reduce the n/p ratio by converting a neutron into a proton,
negatron, and antineutrino.
• Positron emission: If a radionuclide has a deficit of neutrons (low n/p ratio), it
tends to increase the n/p ratio, either by converting a proton into a neutron and a
positron (positron emission) or by capturing an orbital electron (electron capture).
In positron emission, a proton is converted into a neutron, positron, and a neu-
trino. The creation of a positron requires 1.02 MeV of energy to be available from
the nuclear decay. The positron is an unstable antiparticle of the electron, possess-
ing the same mass but opposite charge. Once the traveling positron has slowed
down enough, the positron and another electron will annihilate each other, and
their rest masses are converted into energy (1.02 MeV). This energy appears as
two 0.511 MeV annihilation photons traveling in opposite directions (see Fig. 1.2).
Electron capture: This process competes with positron emission. An orbital electron
is captured by the nucleus, which then rearranges its structure and transforms a proton
into a neutron in order to reach electronic stability. Because an orbital electron has been
removed from its orbital, an electron from a higher orbital fills this void and character-
istic X-rays and/or Auger electrons are emitted from the atom as a result.
Gamma Emission
In gamma emission, the nucleus releases the excess energy by emission of one or more
gamma rays. Gamma emission occurs with alpha or beta decay. Gamma emission is
isomeric as there is no change in atomic mass or number.
Isomeric Transitions
The most stable arrangement of the nucleus in an atom is called its ground state. In
some nuclear decays, the daughter nucleus stays in a more excited state (metastable
state) for some period of time. The only difference between the metastable state and
the final ground state is a difference in energy; hence the two states are called isomers
and the transition from the metastable state to the ground state is called an isomeric
transition. There are two competing methods by which a nucleus can lose excess energy
during an isomeric transition: gamma emission and internal conversion.

Internal Conversion
The gamma ray displaces an electron from its orbital by transferring all of its energy to
the electron (the gamma ray ceases to exist). The displaced electron is called an
“internal conversion electron.” Characteristic X-rays follow as the shell from which
the electron was displaced is filled by electrons from outer shells.
Mathematics of Radioactive Decay

The mathematics of radioactive decay depends on the observation that in a large collec-
tion of N radioactive atoms, the number of decays DN that occur in a time interval Dt is
found to be proportional to Dt and to the total number N of radioactive nuclei. The pro-
portionality constant l is called the decay (or disintegration) constant and gives the rate
at which a radionuclide is disintegrating per unit time. The units of the decay constant
are s1 (or disintegrations per second).
If we solve the difference equation:
DN ¼ lNDt
After making this difference equation into a differential equation and solving, the
final result is an equation that allows us to calculate the number of radioactive atoms
N(t) at any time t:
NðtÞ ¼ N0 elt ;
where N(t) is the number of atoms remaining at time t, N0 is the number atoms at time
t ¼ 0, e is the mathematical constant 2.718, l is the decay constant, and t is the elapsed
time (see Fig. 1.3.)
The decay constant gives the rate at which a radionuclide is disintegrating per unit
time. The units are s1 (or disintegrations per second).
Activity
Activity is the rate of decay of a radioactive material at any given point in time. The
activity (A) is related to the number of disintegrations by:
AðtÞ ¼ lNðtÞ
The equation for N(t) can be rewritten in terms of activity A(t):
AðtÞ ¼ A0 elt
where A(t) is the activity remaining at time t, A0 is the activity at time t ¼ 0, e is the
mathematical constant 2.718, l is the disintegration constant, and t is the elapsed time.
The original unit of activity was the curie (Ci). The curie is defined as the number of
disintegrations given of by 1 g of radium (226Ra) and is equal to 3.7 1010 disintegra-
tions per second (dps). The newer SI unit of activity is the becquerel (Bq), defined by:
1 Bq ¼ 1 dps

MODES OF RADIOACTIVE DECAY

FIGURE 1.3 Graphs of the equation for exponential decay on (left panel) semi logarithmic and (right panel) linear scale.
9
The relationship between the curie and the becquerel is then given by:
1 Ci ¼ 3.7 1010 Bq
Half-life: The half-life, t1/2, of a radionuclide is the time it takes for one-half of the
atoms in a given sample to decay. It is denoted by t1/2 and can be calculated from the
disintegration constant by:
0:693
t12 ¼
=
l
Mean life: The mean (average) life is the average amount of time a nucleus lives
before it decays. It is given by:
tavg ¼ 1:44t1=2
Equilibrium
In radioactive decay, a “parent” radionuclide decays gives rise to a “daughter” radio-
nuclide. If the half-life of the daughter species is considerably shorter than that of the
parent, then the activity of the daughter increases from zero until it reaches the activity
of the parent. Decay then continues with the activity of the parent. This is called secular
equilibrium and is attained after about five half-lives of the daughter species. An
example of secular equilibrium is the decay of 226Ra as shown below (Fig. 1.4):
226
Ra(t1/2 ¼ 1620 y) / 222Rn(t1/2 ¼ 4.8 d).
FIGURE 1.4 A secular equilibrium plot showing the activity of the parent and
daughter for different times t.

ELECTROMAGNETIC RADIATION AND PROPERTIES 11
FIGURE 1.5 A transient equilibrium plot showing the activity of the parent and
daughter for different times t.
If the half-life of the daughter is slightly shorter than that of the parent, then tran-
sient equilibrium is reached after some time whereby the activity of the daughter
builds till equals that of the parent and then slightly exceeds the activity of the parent.
Subsequently, the activity of the daughter follows the activity of the parent but remains
slightly higher. An example of transient equilibrium is given by the decay of 99Mo to
99m
Tc as shown below (Fig. 1.5):
99
Mo(t1/2 ¼ 66 h) / 99mTc(t1/2 ¼ 6 h).
ELECTROMAGNETIC RADIATION AND PROPERTIES

OF INTERACTION
X-ray and gamma radiation are a part of a larger set of photon radiation called the elec-
tromagnetic spectrum. Fig. 1.6 shows the types of radiation in the spectrum.
FIGURE 1.6 The electromagnetic spectrum. Reprinted from McDermott PN, Orton CG. The
physics & technology of radiation therapy. Madison, WI: Medical Physics Publishing; 2010, Fig. 2.13, p. 2e18, © 2010,
with permission from the author.

FIGURE 1.7 Illustration of an electromagnetic wave showing the wavelength and

frequency.
All photons have two fundamental parameters (Fig. 1.7):
Wavelength (l): The wavelength of a photon is the distance from one point on the
photon wave to the next identical point on the wave.
Frequency (n): The frequency of a photon is the number of times the wave oscillates
per second.
Photons are known to travel at a constant velocity in space equal to the speed of
light (c), which is 3 108 meters per second (m/s) in a vacuum.
The relationship between the frequency n of a photon and its wavelength l is given
by:
c
n ¼
l
where n is the frequency of the photon, l is the wavelength of the photon, and c is the
speed of light.
Photons are known to have zero mass and zero charge but do have energy given by:
E ¼ hn
where n is the frequency of the photon (in units of s1 or Hz [hertz]), and h is the phys-
ical constant called Planck’s constant (6.62 1034 J-s).
The energy of a photon can be rewritten in terms of wavelength by:
hc
E ¼
l
Photon Interaction Process, Kerma, Absorbed Dose

As photons travel through material, they can displace atomic orbital electrons along
their paths. These freed electrons (primary electrons) are responsible for most of the
energy deposition that occurs in therapeutic photon beams. Photon interactions with
matter are a two-step process:
1. Energy transfer and kerma

An incident photon interacts with an orbital electron in the atom of the material
through photon interaction mechanism such as photoelectric, Compton, or pair
production (described later). During these interactions, photons transfer some or
all of their energy to an atomic orbital electron. This orbital electron can gain
enough kinetic energy to leave the atomic orbital and become a primary electron.

ELECTROMAGNETIC RADIATION AND PROPERTIES 13
This process of energy transfer (uncharged photons to charged electrons) is called

kerma (kinetic energy released in matter). The SI unit for kerma is joules per
kilogram (J/kg) or gray (Gy).
2. Energy absorption and absorbed dose
Primary electrons released during the energy transfer process interact with other
orbital electrons, thereby ionizing and exciting atoms along their irregular tracks.
Also, primary electrons displace other electrons as they travel through matter,
called “delta rays.” Energy deposited per unit mass of matter is called “absorbed
dose.”
The old unit of absorbed dose is the rad (radiation absorbed dose). The rad has been
replaced in the SI system with the gray (Gy). They are related as follows:
100 rad ¼ 1 J/kg ¼ 1 Gy.
Because the gray is large compared to the rad, the centiGray (cGy) is often used:
1 rad ¼ 1 cGy.
Modes of Photon Interaction

Mechanisms of interaction for photons are described below. These interactions transfer en-
ergy from photons to the irradiated material, where it is ultimately dissipated as heat.
Coherent scattering is dominant interaction in the low-energy region (<50 keV) and in
high Z materials. Photons interact with electrons of an atom causing them to oscillate. This
oscillation energy is reradiated by another photon of the same energy as the incident
photon, but at a different angle. No net energy is transferred.
Photoelectric absorption occurs when an incident photon is totally absorbed by an elec-
tron, typically one from an inner shell. It has dominant interaction in the 10e26 KeV. If the
energy of the photon exceeds the binding energy of the electron, the electron is ejected from
the atom as a “photo electron,” which has energy equal to the incident photon minus the
binding energy. The probability for photoelectric absorption increases rapidly with the
atomic number of the atom where the interaction occurs. This is the main interaction
responsible for diagnostic imaging (Fig. 1.8A).
Compton scattering occurs when only part of the incident photons are transferred to
the electron, which is emitted at an angle 4 relative to the incoming photon. It has domi-
nant interaction in the 26 KeVe24 MeV. The remaining energy accompanies the photon
that is scattered at an angle q. The electron’s kinetic energy equals the energy of the incident
photon minus the energy of the scattered photon minus the binding energy of the electron.
Compton scattering is the dominant interaction at therapeutic photon energies (Fig. 1.8B).
Pair production occurs when incident photons interact with the nuclear field and is
completely absorbed. It has dominant interaction above 10 MeV. Part of its energy
is converted into matter by creating an electronepositron pair. The remaining energy
is kinetic energy associated with the electron and the positron. The positron is antimatter
and as it slows down while traveling in matter, it combines with an electron forming two
photons known as “annihilation photons,” each having energy of 0.51 MeV. Because the
resting energy of an electron and a positron is 0.51 MeV each, pair production cannot
occur unless the incident photon has at least 1.02 MeV energy (Fig. 1.8C).

FIGURE 1.8 (A) Photon interaction of photoelectric absorption. (B) Photon

interaction of Compton scattering. (C) Photon interaction of pair production.
Photodisintegration occurs when high-energy photons are absorbed by the nucleus.
It has interaction above 8e16 MeV. The energy can be used to eject a neutron, a proton,
or an alpha particle or to break the nucleus into several components.
Mathematics of Photon Attenuation

The mathematics of attenuation of radiation is identical to the decay of radioactive nu-
clides. The process of photon attenuation is a random event that must be treated statis-
tically and depends on the assumption that as N photons pass through a material of
thickness x, a given fraction m will be removed from the photon beam per unit path
length.
Stated in mathematical terms:
DN
¼ mN
Dx
where m is a constant and is called the linear attenuation constant.

PARTICULATE RADIATION PROPERTIES AND INTERACTIONS 15
The linear attenuation constant m gives the rate at which photons are removed from
a material per unit thickness. The units are cm1.
If we integrate this differential equation, we arrive at a formula that can be used to
calculate the number of photons that will remain after a photon beam has passed
through a thickness x of material, given by:
NðxÞ ¼ N0 emx
where N(x) is the number of photons remaining after passing through a material of
thickness x, N0 is the number photons with no material in the beam (x ¼ 0 cm), e is
the mathematical constant 2.718, and m is the linear attenuation coefficient for the
photon beam energy and material irradiated.
This algebraic equation states that if we know m, N0, and x, we can solve for N(x).
This type of attenuation is known as exponential attenuation. It is known that the
amount of attenuation for the same thickness x of material is different for different den-
sity materials; it follows that m depends on the density p of the material. If we divide m
by p, we obtain the mass attenuation coefficient (m/p). The mass attenuation coeffi-
cient has units of cm2/g and is independent of density.
PARTICULATE RADIATION PROPERTIES AND

INTERACTIONS
Particulate radiation consists of particles that possess resting mass. Its interaction with
matter is different from the interaction of photons with matter. Particulate radiation has
mass but may or may not possess electric charge. Interactions of electrons, neutrons,
and heavy particles are described below.
Interactions of Electrons
Because of their charge, electrons displace other electrons from their orbits and thereby
cause ionization as they travel through matter. Because electrons are relatively light,
their original paths are substantially altered (“scattered”), as they interact with other
electrons. Because of their strong scattering, the Bragg peak, which is associated with
heavier particles, is not observed with electrons. Occasionally an electron transfers
enough energy to another electron that the new electron can cause ionization on its
own. The new electron is called a “delta ray.” Free electrons can interact with atomic
electron or with nuclei as below:
• Interactions with atomic electrons: Free electrons interact with other atomic elec-
trons predominantly by inelastic collisions, causing excitation and ionization of
the atom along their tracks. Excitation is the promotion of an orbital electron to a
higher energy level in the atom, without the ejection of the orbital electron. On
the other hand, if the incident electron had enough energy to eject the orbital elec-
tron, then the interaction is called an ionization (see Fig. 1.9).

FIGURE 1.9 Excitation and ionization of an atom.
FIGURE 1.10 Creation of bremsstrahlung radiation.
• Interactions with nuclei (bremsstrahlung): Electrons with kinetic energy will

interact with atomic nuclei, mostly by inelastic collisions. As the electron is bent
from its original path by the Coulomb force of the atomic nucleus, it decelerates
and loses energy in the form of a photon. This photon is called a bremsstrahlung
photon (see Fig. 1.10).
Interactions of Neutrons
Because neutrons have no charge, they cannot cause ionization directly. Their main
interaction of interest in radiation therapy is their collision with protons that lead to
further ionization. Furthermore, neutron interactions typically produce a wide range
of subatomic particles, recoil nuclei, and photons. These particles deposit energy in
very different ways, producing differing biological effects. Slow (thermal) neutrons
have energy around 0.025 eV and fast neutrons have much higher energy of KeV
and MeV.
Interactions of Heavy Charged Particles

Heavy charged particles generally include any charged particles with resting masses
greater than that of electrons. These include protons, heavy ions, and pions. Heavy
charged particles do not change direction appreciably while traveling through matter.

THE PHYSICS OF DOSIMETRY 17
Heavy charged particles with large amounts of kinetic energy generally interact with
matter by undergoing inelastic collisions with atomic electrons. In this process, they
give up a portion of their energy with each interaction, finally giving up a large portion
of energy at the end of their range, causing the Bragg peak.
THE PHYSICS OF DOSIMETRY

The radiation dose prescribed by a radiation oncologist for a patient must be quantified
by a dosimetrist or medical physicist to determine monitor unit (MU) settings. It is
important to understand the basic parameters used for dosimetry calculations and
treatment planning. A brief review of the major concepts in dose calculation leading
to MU settings follows.
Inverse Square Law

The inverse square law can be derived by considering a point source that is emitting
radiation equally in all directions; two spheres are centered on this source with radii
r1 and r2 (r2 > r1). The intensity I of the photons emitted from the source is defined
as the number N of photons going through a spherical surface per unit area A per
unit time of the sphere:
The inverse square law: r1 is the distance from the point source to a sphere of area
A1, and r2 is the distance from the point source to a sphere of A2. It is assumed that no
photons are lost due to absorption as they travel away from the source, so: N1 ¼ N2.
Noting that the area of a sphere is A ¼ pr2; solving these equations yields:
2
I2 r1
¼ ;
I1 r2
As can be seen from equation, the ratio of intensities of a photon beam is inversely pro-
portional to the square of the ratio of the distances from the source. This decrease in the
number of photons at a function of increasing distance is known as the inverse square
law.
Backscatter Factor
Consider the following two experimental arrangements. In Fig. 1.11, situation
(A) illustrates an exposure calibration of a photon beam in air. Situation (B) illustrates
the irradiation conditions of the phantom. The reading on the electrometer in (B) is
increased considerably compared with (A). This increase in dose, caused by radiation
that was scattered back toward the probe from the phantom/patient, is called backscat-
tered radiation. The factor used to correct this effect is called the backscatter factor (BSF).
The BSF is defined as:
Exposure at phantom surface

BSF ¼
Exposure at same point with no phantom present
The BSF increases as the energy approaches a maximum value in the orthovoltage
range and then decreases. It also increases as the field size increases; however, it is in-
dependent of SSD (source-to-surface distance).

FIGURE 1.11 The left panel shows backscatter factor measurement: (A) dose
measurement in air; (B) dose measurement in phantom surface at the same point. The
right panel shows peak scatter measurement. The buildup cap placed around the
chamber in air measurement is to give dose in free space.
Peak Scatter Factor

The BSF only applies to low-energy photon radiation. With the use of megavoltage ra-
diation, a buildup effect occurred that shifts the depth maximum dose, dmax, from the
surface to a new depth. A quantity similar to the BSF was defined and called the peak
scatter factor (PSF) (Fig. 1.11):
Dose at depth dmax in phantom

PSF ¼
Dose in free space at same point
where dmax is the maximum dose and dose in free space is the dose to an ionization
chamber with a small amount of buildup material wrapped around it to provide elec-
tronic equilibrium.
Depth of Maximum Dose (dmax)

The radiation dose deposited within the first few millimeters of the patient’s skin is
highly variable because of the lack of electronic equilibrium, which is a function of
the PSF. The first few millimeters are also known as the buildup region. dmax is the
depth in tissue where the electronic equilibrium occurs for a radiation beam. This
depth, dmax, is a function of energy (Table 1.1). As nominal energy increases, dmax
also increases.
Percentage Depth Dose

One of the most used quantities in dosimetry is the dose at any depth along the central
axis of the radiation beam or percentage depth dose (PDD) (Figs. 1.12 and 1.13) [3,4].
The PDD is defined by:
Dose at depth d along central axis

PDD ¼
Dose at depth of maximum dose along central axis

THE PHYSICS OF DOSIMETRY 19
TABLE 1.1 Depth of dmax Variation With Nominal Beam

Energy (10 10 cm2)
Energy Nominal dmax (cm)
Co-60 0.5
4 MV 1.0
6 MV 1.5
10 MV 2.5
15 MV 3.0
20 MV 3.5
25 MV 4.0
34 MV 5.0
Data from Jani SK. Handbook of dosimetry data for radiotherapy. Boca Raton,
FL: CRC Press; 1993. p. 63, Table 1.I1.
FIGURE 1.12 Percentage depth dose measurement: (A) dose measured at depth of
central axis; (B) dose measured at dmax along central axis. SSD, source-to-surface
distance.
The PDD is a function of beam energy, depth of measurement, beam field size, and
the SSD.
The PDD depends on the following parameters:
Energy: As beam energy increases, the PDD (for a fixed depth) also increases. This
results from the greater penetrating power of the photon beam.
Depth: As depth of the measurement increases, PDD decreases (with the exception
of the buildup region). This is due to exponential attenuation of the photon beam as it
passes through the patient.
Field size: As field size increases, PDD increases. This result from increased scatter
because of the larger collimator and patient area irradiated.
SSD: As SSD increases, PDD increases due to the definition of the PDD and the
inverse square law.

70 kVp
100.0
120 kVp
3 mm Cu
Cobalt-60
80.0 6 MV
10 MV
Percent depth dose
18 MV
60.0
40.0
20.0
0.0
0.0 10.0 20.0
Depth in water (cm)
FIGURE 1.13 Central axis depth dose distribution for different-quality photon
beams. Field size, 10 10 cm; source-to-surface distance (SSD) ¼ 100 cm for all beams
except for 3.0 mm Cu half-value layer (HVL), SSD ¼ 50 cm. (Reproduced from Fig. 6.36 from
Clinical Radiation Oncology by Gunderson and Tepper, fourth edition, 2016, Elsevier).
TissueeAir Ratio
The PDD was used as the primary dosimetric variable when treatment techniques were
predominantly SSD.
When newer machines became available, which rotated around an isocenter, it
became possible to treat patients using isocentric techniques. In an isocentric technique,
the distance from the source to the center of the target volume is held constant, whereas
the distance from the source to the surface of the patient changes for each beam orien-
tation. A new quantity was then defined to address isocentric treatment calculations,
called the tissueeair ratio, or TAR. The TAR is defined as:
Dose at depth d in phantom
TAR ¼
Dose in free space at the same point.
Note that the TAR varies like the PDD with respect to the beam energy;
depth and field size. It is independent of SSD.
ScattereAir Ratio
TAR can be divided in to a two-component model. In this model, the absorbed dose to
any point in the patient is the sum of two components:
Total dose ¼ primary dose þ scatter dose.

Another random document with
no related content on Scribd:
Hodgkinson. Letters on Emigration. London, 1794.
Smith, William. Address to his Constituents. Philadelphia, 1794.
Taylor, John. An Examination of the Late Proceedings of Congress,
Respecting the Official Conduct of the Secretary of the Treasury.
Philadelphia, 1793.
Contemporary Newspapers
Boston:
The Columbian Centinel.
The Independent Chronicle.
New York:
New York Daily Advertiser.
Commercial Advertiser.
New York Journal.
American Minerva.
The Argus.
The Time Piece.
Gazette of the United States.
Louden’s Diary, or Register.
Philadelphia:
National Gazette.
Gazette of the United States.
The General Advertiser.
The Aurora.
Porcupine’s Gazette.
Pennsylvania Daily Advertiser.
Baltimore:
Maryland Gazette.
Maryland Journal.
Portsmouth:
New Hampshire Gazette.
Charleston:
City Gazette.
Windsor, Vermont:
Spooner’s Vermont Journal.
Hartford:
The Courant.
The American Minerva.
New Haven:
Connecticut Gazette.
Magazines
American Historical Review, October, 1899, January, 1900, ‘Contemporary
Opinion of the Virginia and Kentucky Resolutions,’ by Frank M.
Anderson.
American Historical Association, Annual Reports, 1912, ‘The Enforcement
of the Alien and Sedition Laws,’ by Frank M. Anderson; 1896-97, ‘Letters
of Phineas Bond.’
The Nation, July 18, 1912, ‘Extracts from Diary of Moreau de St. Mery’;
September 5, 1895, ‘The Authorship of the Giles Resolutions,’ by Paul L.
Ford.
INDEX
Adams, Abigail, New York house at Richmond Hill, 16;
on removal of capital to Philadelphia, 116;
on Philadelphia, 125;
and Mrs. Bingham, 128, 129.
Adams, Abijah, bookkeeper for editor of Independent Chronicle,

imprisoned for libel, 394, 395.
Adams, John, begins ‘reign’ as Vice-President, 3;

troubled as to proper titles for the President and Vice-President, 3;
on reception of President in Senate, 3;
what is the Vice-President when the President is in Senate?, 3;
writer of ‘Discourses of Davilla,’ published in Fenno’s Gazette, 17;
on Hamilton, 37;
Jeffersonians attempt to defeat for Vice-Presidency in 1792, 181;
elected, but by small margin, 183;
candidate for Presidency, in 1796, 310;
suspects trickery, 312;
retains Washington’s Cabinet, 314;
sketch of, at time of entering on Presidency, 316-26;
Maclay on, 317;
his vanity, 318;
jealousy of Washington, 319;
difficult in conference, 320;
not in sympathy with democracy, 322;
his love of country, 323;
moral courage, 325, 326;
war with France threatened, 339;
sends special mission to France, 345;
reports failure of envoys to France, and recommends Congress to
authorize warlike measures, 363;
is ignorant that Hamilton through McHenry is dictating policy, 363;
action on publication of X Y Z papers commended, 366;
pulls down the pillars, 412;
is troubled about French situation, 412;
offers command of army to Washington, 412, 413;
conspiracy in Cabinet in favor of Hamilton, 412, 413;
nominates Hamilton, Pinckney, and Knox as major-generals, 413;
Federalist conspirators bombard him with suggestions that Hamilton
should be second in command, 414;
war plans all in Hamilton’s hands, 418-28;
is ignorant of much going on, 426;
considers sending new mission to France, 428;
submits questions to Cabinet, for new negotiations with France or a
declaration of war, 429;
Cabinet conspirators with Hamilton write war Message, 429;
A. rewrites Message, 429, 430;
is conscious of Cabinet conspiracy, 430;
appoints Minister to France, 430;
contest with Senate over confirmation, 430, 431;
agrees to compromise, 432, 433;
confounds his Cabinet conspirators, 436-38;
depressed by Federalist defeat in New York elections in 1800, 455, 456;
suspects Hamilton, 456;
dismisses McHenry and Pickering from Cabinet, 456, 457;
defeated for Presidency, 486;
relations with Jefferson, on quitting office, 489, 490.
Adams, John Quincy, on speculation by Congressmen, 47;

on Madison, 57.
Adams, Samuel, defeated for Representative to First Congress by Fisher

Ames, 1;
looked to by Jefferson for aid in forming opposition party in
Massachusetts, 144;
chosen by Jefferson as lieutenant, 144;
presides at meeting in Boston on Jay Treaty, 278.
Adams, Thomas, editor Boston Independent Chronicle, 152;

prosecuted under Sedition Law, 393-94.
Adet, ——, Minister to United States, from French Republic, credited with
efforts to influence election in 1796, 311.
Alien Bill, aimed at Irish immigrants, 374;
French residents frightened and sail for France, 376;
passed by close vote, 379.
Allen, John, Representative from Connecticut, 379.
American Minerva, on party feeling, 232.
Ames, Fisher, Representative from Massachusetts, elected over Samuel

Adams, 1;
cynical over prospect of improvement in form of government over old
Confederation, 1;
not impressed by his fellow Congressmen, 1;
on cost of Federal Hall, 2;
on titles, 6;
Hamilton’s defender in House, 47;
on Madison, 51, 52;
disgusted with contest for site of permanent capital, 65;
on proposed amendment to Excise Bill, 73;
defends doctrine of ‘implied powers,’ 76;
elected director of Bank of United States, 90;
on Giles’s resolutions attacking Treasury management, 201, 203;
on yellow fever epidemic in Philadelphia, 237;
on Madison commerce resolutions, 240, 241;
sketch of, 302-04;
makes strong plea in House for appropriations to carry out Jay Treaty,
305, 306.
An Examination of the Late Proceedings of Congress Respecting the

Official Conduct of the Secretary of the Treasury, pamphlet published in
Philadelphia, 205;
authorship attributed to John Taylor of Caroline, 206.
Assumption, favored by North, where most of State indebtedness was

unpaid, 59;
opposed by Virginia, whose debt was largely paid, 59;
defended by Madison, 61;
lobbying for passage of bill, 61;
uneasiness of friends of, 61, 62;
Hamiltonian press comments, 63;
adopted after Hamilton’s bargain with Jefferson, 65, 68.
Aurora, The, on the Jay Treaty, 273, 274, 276, 277, 280, 286;
on Hamilton’s Reynolds pamphlet, 355, 356.
Austin, Ben, rope-maker, Jeffersonian organizer in Massachusetts, 144.
Bache, Benjamin F., editor Pennsylvania Daily Advertiser, 152.
Bank of the United States, Hamilton’s Report on, 74;

bill for establishing, 75, 76;
debate on bill in Congress, 75, 76;
constitutionality questioned, 76;
fears of veto, 77;
much speculation in stock, 87, 88;
members of Congress involved, 89;
charges of ‘corrupt squadron,’ 89;
election of directors, 90;
public indignation, 90;
bill introduced to reimburse for loan to Government, 190.
Bard, Dr. John, fashionable physician, 15.
Barnwell, Robert, Representative from South Carolina, on Giles’s

resolutions attacking Treasury management, 203.
Beckwith, ——, British Agent at Philadelphia, cultivates Madison, 80;

Jefferson on, 80;
protests Jefferson’s commendation of Paine’s Rights of Man, 83.
Biddle, Charles, resolutions of welcome to Genêt prepared at home of, 219;

leads parade in honor of Genêt, 220.
Bingham, Marie, daughter of Mrs. William Bingham, 130.
Bingham, William, elected director of Bank of United States, 90.
Bingham, Mrs. William, social leader in Philadelphia, 127, 128;

one of her fashionable gatherings described, 131-35.
Bishop, Abraham, Jeffersonian organizer in Connecticut, 145.
Black Friars, New York City club, 10.
Bloodworth, Timothy, on Excise Bill, 72;

lieutenant for Jefferson in North Carolina, 150.
Bond, Phineas, British Consul in Philadelphia, 244.
Boudinot, Elias, speculator in public securities, 62, 170;

on Giles’s resolutions attacking Treasury management, 201.
Bowen’s Wax Works, Philadelphia, 138.
Bradford, William, classmate of Madison at Princeton, 157.
Breckel, Van, Dutch Minister to United States, entertains lavishly, 13.
Breckenridge, John, of Kentucky, in conference with Jefferson on Alien and

Sedition Laws, 407;
author of the Kentucky Resolutions, 408;
sketch of, 408, 409.
Brown, John, Jeffersonian leader in Kentucky, 180.
Burk, John D., editor of New York Time Piece, arrested for sedition, 405.
Burke, Ædanus, Representative from South Carolina, makes vicious attack

on Hamilton and his financial measures, 62.
Burke, Edmund, and the French Revolution, 82.
Burr, Aaron, on wines in Philadelphia, 126, 147;

Jefferson moves to attach him to his party, 147;
fellow student of Madison at Princeton, 157;
possible candidacy of, for Vice-President in 1792, 181;
leader of Jeffersonians in New York election of 1800, 448;
sketch of, contrasted with Hamilton, 449;
combines forces with Society of Tammany, 451;
his campaign methods, 452-54;
urged for the Vice-Presidency in 1800, 455;
secures copy of Hamilton’s pamphlet attacking Adams, publishes it in
The Aurora, 478.
Butler, Pierce, Senator from South Carolina, 9;

a ‘democrat’ whose associates were aristocrats, 134;
votes against ratification of Jay Treaty, 280.
Cabot, George, sees irrevocable ruin of country, 63;

pained at attitude of Madison, 63;
candid friend and supporter of Hamilton, 63;
on meeting in Boston on Jay Treaty, 278;
on Washington’s hesitation in signing Jay Treaty, 285.
Callender, James Thomas, author of pamphlet, The Prospect Before Us,

indicted and convicted under Sedition Law, 400-02;
defended by William Wirt, 401.
Capital of the Nation, battle on permanent site for, 64, 65;

bargaining to trade votes on Assumption, 65;
bargain between Hamilton and Jefferson on location of, 65, 67;
Hamilton indifferent as to location, 65;
Virginians and Marylanders want it at Georgetown, 65;
Jefferson’s part in bargain, 66.
Carrington, Edward, letter from Hamilton to, in 1792 campaign, 180.
Carroll, Charles, of Carrollton, Senator from Maryland, on titles, 5;

mentioned for Vice-President in 1792, 181.
Certificates of indebtedness, issued to soldiers of Revolution, in lieu of

cash, bought up by speculators, 44, 45;
Hamilton’s plans for redemption by funding scheme known in advance to
members of Congress and friends, 46.
Charleston City Gazette, on the Jay Treaty, 281.
Chase, Samuel, Judge, and Mrs. William Bingham, 131;

presiding justice in Alien and Sedition trials, 398, 400-02.
Chateaubriand, Viscount de, on Philadelphia, 123, 125.
Chestnut Street Theater, Philadelphia, 137, 185.
Church, Mrs. Angelica, sister-in-law of Hamilton, 12;

letters on Hamilton, 39.
Cincinnati, Society of the, 48.
City Tavern, Philadelphia, 119.
Clinton, George, newspaper attack on Hamilton’s funding plans ascribed to,

50;
Jeffersonian leader in New York, 147;
in bitter fight with John Jay for governorship of New York in 1792, 178;
urged to become candidate for Vice-President in 1792, 181;
receives votes of four States, though not an avowed candidate, 183;
Jeffersonian candidate for Governor in New York election of 1800, 452.
Clymer, George, Representative from Pennsylvania, on Assumption, 58, 62;

dinner party at house of, described, 126, 127.
Cobbett, William, author of reply to Priestley’s addresses, 259;
proprietor of Porcupine’s Gazette, q.v.
Columbian Centinel, on Funding Bill, 57;

letters to, on Madison and the Funding Bill, 57;
‘Publicola’ (John Quincy Adams) attacks Jefferson, Paine, and
democracy, 84;
on Jeffersonians, 152;
on Freneau’s attacks on Hamilton, 164;
on speculative craze, 176, 178;
on Indian expedition of St. Clair, 175;
on Hamilton’s vindication of official conduct of Treasury, 199;
on French Revolution, 207, 211;
on relations with England, 220;
on the Jay Treaty, 278;
on prospects of war with France, 366;
war propaganda, 370, 371.
Congress, meets in New York City, 1;

Washington and Adams declared elected, 2;
ceremonial forms and titles excite much discussion, 3-6;
first tariff measure in, 19;
executive departments established, 19, 20;
jealousy of executive, 20;
Hamilton’s Report on Public Credit debated, 44 ff.;
debate on Funding Bill, 48 ff.;
scandal over speculation by members in certificates, Bank stock, and
scrip, 89;
‘corrupt squadron,’ 89;
bill to pay loan from Bank of United States hotly debated, 190-92;
Giles’s resolutions condemning Hamilton, debates on, 199-203;
resolutions defeated, 203;
Madison’s resolutions on Jefferson’s Report on Commerce, 240;
Non-Intercourse Act, as reply to England’s high-handed seizure of
American vessels, 244;
debates in Senate on Jay Treaty, 272;
debate in House over right to have papers as to treaty, 298;
Alien Bill, debates on, 374-79;
Sedition Bill, debates on, 378, 380.
Connecticut Gazette, on French Revolution, 211, 212;

on Genêt, 219.
Cooper, Dr. Thomas, scientist and physician, indicted under Sedition Act,
398;
convicted and imprisoned, 399;
refuses to ask for pardon, 399.
Coxe, Tench, Assistant Secretary of Treasury under Hamilton, and location

of capital, 65.
Croswell, Joseph, poem by, on French Revolution, 208.
Dallas, Alexander James, one of Jefferson’s leaders in Pennsylvania, 148;

aids in preparations for reception of Genêt, 219;
efforts of, in case of brig Little Sarah, 227, 228;
defends Duane in prosecution under Alien Law, 396, 397.
Davie, William R., on opposition to Jay Treaty, 281.
Dayton, Jonathan, 148;

scandal over retention of public funds, 466.
Democratic Party. See Jeffersonians.
Democratic Clubs, organized, 222, 223;

Federalists insist they must be abolished, 260;
condemned by Washington in Message, 261.
Democratic Societies. See Democratic Clubs.
De Moustier, French Minister to United States, Jefferson on, 108.

Dodd, William E., quoted on Jefferson, 96.
Duane, William, editor of The Aurora, arrested and prosecuted under the
Alien Act, 396, 397;
is acquitted, 397;
indicted for sedition, 397;
assaulted and beaten by soldiers, 420;
prosecuted under Sedition Law, 442.
Duer, William, financial failure of, in 1792 starts panic, 176, 177;
threatens damaging revelations from debtors’ prison, 187.
Dunlap, William, historian of American theater, 10.
Dwight, Timothy, on newspapers, 156.
Ellsworth, Oliver, Senator from Connecticut, on titles, 4;

and the Assumption Bill, 62;
on French Revolution, 209;
efforts of, to induce Washington to send Hamilton on special mission to
England, 247;
on Washington’s delay in signing Jay Treaty, 285.
Emmet, Thomas Addis, Irish refugee (brother of Robert Emmet), of the

New York Bar, 375.
Everleigh, Nicholas, appointed Comptroller of the Treasury, 21.
Excise Bill, warm debate on, in Congress, 71, 73;

amendment proposed to prohibit revenue officers interfering in elections,
73;
debate on duration of tax, 73.
Fairfax estate, Virginia, litigation over, 281.

Federal Gazette, Freneau in, opposes Bank Bill, 78.
Federalists, policy to capitalize politically

popularity of Washington, 41;
from beginning under domination of Hamilton, 140;
favored by commercial, intellectual, and professional classes, 140;
leaders men of strength in most of the States, 140, 141;
opposition to, inevitable, 144;
denounce Democrats as conspirators, 151;
attack Jeffersonian newspapers in Federalist organs, 203, 204;
sympathies with royalists in French Revolution, 207, 208;
enforce policy of neutrality in French Revolution wars, 216;
force recall of Genêt, 231;
avert war with England and send Jay to negotiate treaty, 247;
leaders induce attacks on ‘Democratic Societies,’ 261;
defend Jay Treaty, but with wry faces, 285-88;
refuse to confirm nomination of Rutledge as Chief Justice, 289;
pass Alien and Sedition Acts, 375-80;
efforts of leaders to force war with France, 412-28;
mean war to be a Federalist war, 412;
Hamilton is to conduct war with no interference from Adams, 412;
secure appointment of Hamilton as second in command, 415;
conspire to prevent Jeffersonians from securing commissions in army,
416;
war not popular among the people at large, 418;
raising funds for war purposes difficult, 418;
taxes for war arouse resentment, 419;
recruiting slow, 421;
public refuse to believe there is to be a war, 421, 422;
Logan’s visit to France upsets Federalist war plans, 423, 424;
the war hawks disappointed, 425, 426;
Federalists determined on war, 426, 427;
Cabinet conspirators write war Message for Adams, 429;
scheme to override Adams, 430;
caucus, 430;
friends of Adams’s policy in majority, 430;
losing ground politically in 1799, 440;
plan for changing method of counting electoral votes in Presidential
election, 441, 442;
bill passes Senate, but fails in the House, 442, 443;
spring elections of 1800 show tide running against them, 448, 451-55;
under Hamilton’s influence leaders plan to defeat Adams for Presidency,
455-58;
hints at secession from Federalist leaders in case of Jefferson’s election,
468, 470;
party split hopelessly on publication of Hamilton’s attack on Adams, 481,
482;
defeated in election, leaders conspire to have electors vote for Burr, 491;
Hamilton opposed to plan, 491-501;
plan fails, after much balloting, 506.
Fenno, John, protégé of Hamilton, establishes Gazette of the United States,

4;
his paper aspires to be the ‘court journal,’ 4;
King and Hamilton interested in financing paper, 153, 154;
patronage of government printing, 154;
death of, from yellow fever, 381.
Fenno, John Ward, son of founder of Fenno’s Gazette, continues

publication, 381.
Fitzsimons, Thomas, Representative from Pennsylvania, speculator in

certificates, 47;
Hamiltonians meet at lodgings of, 58;
and the Assumption Bill, 62;
Hamilton’s lieutenant in the House, 186;
introduces resolution asking Hamilton to report plan for redemption of
part of national debt, 186;
resolution precipitates sharp debate, 186, 187;
on Giles’s resolutions attacking Treasury management, 201.
Florida Tea Garden, New York City, 10.

Ford, Paul Leicester, quoted, on Jefferson, 199.
France, revolution in, effect of, in United States, 207;

asked to recall Genêt, 216;
Adams sends mission to, 345;
envoys unsuccessful, 363;
publication of X Y Z papers, 364, 365;
Adams recommends preparations for war with, 365.
Franchise, in 1789 limited in most of the States, 142;

property qualifications, 142;
Jefferson and, 142.
French Revolution, the, its influence in the United States, 207, 208;
Hamiltonians instinctively hostile to purposes of, 208;
denounced by leading Federalist Senators, 209;
supported by Jefferson, 210;
sympathy for, of the common people, 213;
enthusiasm for the French, 213, 214;
enthusiasm for, heightened by arrival of Genêt, 221, 222;
liberty caps and liberty poles, 222;
Democratic and Jacobin Clubs everywhere, 223;
Federalists alarmed, 223;
clubs denounced as vicious ‘nurseries of sedition,’ 223.
Freneau, Philip, ‘Poet of the Revolution,’ induced by Madison to establish

newspaper, 154;
appointed to clerkship in Department of State, 155;
establishes National Gazette, 155;
Jeffersonians aided, 155;
at once assumes leadership, 155;
paper recognized as Jefferson’s organ, 155;
arouses Federalist rage, 156;
influence of paper felt in back country, 156;
classmate of Madison, Lee, Burr, and Brockholst Livingston at Princeton,
157;
rebel by nature, 158;
his career in the Revolutionary War, 158, 159;
Gazette carefully watched by Hamilton, 163;
attacks Hamilton’s policies, 164-68;
attacked anonymously in Fenno’s Gazette, 168;
his dignified reply, 168;
denies any connection of Jefferson with his paper, 169;
renews crusade against Hamilton’s financial policies, 195, 196;
contrast of newspaper with Fenno’s, 163;
criticisms of acts of Administration, 163;
‘Brutus’ article, 164;
‘Sidney’ articles open attacks on Hamilton, 164, 165;
controversy with Fenno, 166, 167;
charges Hamilton with authorship of anonymous articles in Fenno’s
Gazette, 169, 170;
‘Patriot’ articles in National Gazette, 195-97;
analyzes votes in Congress vindicating Hamilton’s financial policies,
204;
on Genêt and French Revolution, 218, 219;
begins series of attacks on Washington, 221.
Funding of debt, Hamilton’s scheme for, well received, 44;

protests against, because of speculations in certificates, 45.
Funding Bill, acrimonious debate on, in Congress, before passage, 48 ff.
Gallatin, Albert, Representative in Pennsylvania Legislature, denounces

Hamilton’s Excise Bill, 70;
leading Jeffersonian in Pennsylvania, 149;
elected to Senate from Pennsylvania, but not allowed to take seat, on
technicality, 289;
elected as Representative, 289;
sketch of, 292-94.
Gates, Horatio, Jeffersonian candidate in New York elections of 1800, 452.
Gazette of the United States, ‘court journal,’ 4, 10;

Adams’s ‘Discourses of Davilla’ published in, 17;
Fenno defends speculation in public securities, 48;
Fenno in, on criticisms of proceedings of Congress, 57;
on Funding Bill, 57;
attacks in, on ‘demagogues,’ 63;
on Bank, 79;
Fenno’s verses on passage of Bank Bill, 79;
probably established with aid of Rufus King, 153;
Hamilton interested in raising money for, 154;
tone pro-English, 154;
received government patronage, 154;
controversy with National Gazette, 166-70;
Fenno engages in controversy with Freneau, 166, 167, 169;
on Hamilton’s defense of official conduct of Treasury, 199;
on Boston Argus, 203;
on French Revolution, 211;
on attacks on Washington, 221;
‘Pacificus’ letters in, by Hamilton, 225, 226;
attacks on Jefferson, 233;
on the Jay Treaty, 282.
Geisse’s Tavern, Philadelphia, 121.
General Advertiser, on defeat of Jay by Clinton in New York election, 178.
Genêt, Edmond Charles, Minister from the French Republic, arrives in

Charleston, 124;
enthusiastically received everywhere, 218;
his progress to Philadelphia continuous ovation, 218;
formally welcomed at Philadelphia by people, 219, 220;
cordially received by Jefferson, 220;
cold reception of, by Washington, 220;
impudent conduct of, 224.
Giles, William Branch, Representative from Virginia, in favor of Excise

Bill, 71, 72;
opposes Bank Bill, 76;
organizer for Jefferson in Virginia, 149;
opposes bill to repay loan from Bank of United States, 190, 191;
his personal characteristics, 192;
a giant in debate, 194;
selected by Jefferson to lead in attacks on Hamilton’s financial policies,
195, 197;
presents resolutions demanding information from Secretary of the
Treasury, 197;
presents resolutions condemning Hamilton’s conduct in management of
Treasury, 199-203;
in conference of Jeffersonian leaders, 205;
on Madison commerce resolutions, 241.
Golden Lion, the, Philadelphia tavern, 120.
Goodrich, Chauncey, on adoption of French Revolution titles, 222.
Gove, Christopher, prominent Massachusetts Federalist, 47;

speculates largely in certificates, 47.
Granger, Gideon, Democratic leader in Connecticut, 145.
Gray’s Gardens, on the Schuylkill, 121, 122.
Graydon, Rev. Alexander, on yellow fever epidemic in Philadelphia, 237.
Greenleaf, Thomas, editor New York Journal, 152.
Grenville, Lord William Wyndham, negotiates treaty with John Jay, 269-71.
Grout, Jonathan, opposes Bank Bill, 76.
Gunn, Georgia Senator, votes for ratification with Jay, 283;

burned in effigy along with Jay, 283.
Hamilton, Alexander, an interested spectator at Washington’s inaugural, 7;

appointed Secretary of the Treasury, 21;
a portrait, 22-42;
his personal appearance, 22;
his birth, illegitimate, 23;
his mother brilliant and high-strung, 23;
his ambition always military, 24;
comes from the West Indies to America, 25;
his genius that of writer and thinker on governmental affairs, rather than
as soldier, 25;
his Federalist writings, 26;
master of invective, 26;
a persuasive orator, 26, 27;
refused permission by Congress to present his reports personally, 27;
essentially an aristocrat, 28;
ideal of government ‘the rule of gentlemen,’ supported by a strong
military force, 29;
distrusted always a democracy, 29;
held public opinion of no value, 29;
disapproved of the Constitution as adopted, but urged its ratification as
better than nothing, 30;
his own plan presented to the Constitutional Convention radically
different from that adopted, 30, 31;
his republic to be an aristocratic republic, with the States as States
abolished, 31;
took little part in Constitutional Convention, 32;
large factor in making the Convention possible, and in securing
ratification of Constitution, 32, 33;
his sense of system, 33;
capable of long-sustained exertion, 33, 34;
a hard fighter, 34;
honesty, 34;
as a party leader, lacking in tact, 35;
never consulted, but directed, 35;
egotistical and vain, 36;
lacking in judgment in handling of men, 36;
unnecessarily offended sensibilities, 36, 37;
lacked sympathy always with the ‘common man,’ 37;

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Fundamentals of radiation oncology :

physical, biological, and clinical

HASAN MURSHED, M.D., M.S

For information on all Academic Press Publications visit our website at

Publisher: Stacy Masucci

This book is dedicated to my children Ishraq and Ishmam.

ForeworddJames A. Bonner xvii

Fundamental Physical Quantities 3

2. Radiation Protection and Safety 39

Measurement of Radiation Quantities 39

ALARA and Radiation-Induced Biological Effects 46

4. Molecular Cancer Biology 89

Cell Cycle Control 89

Techniques of Brachytherapy 107

6. Intensity-Modulated and Image-Guided Radiation Therapy 123

Target Volumes, Margins and DoseeVolumes for Intensity-Modulated Radiation

7. Stereotactic Radiation: Cranial Lesions 139

Radiobiology of Stereotactic Radiation 139

8. Stereotactic Body Radiation Therapy: Lung Cancers 153

Lung Cancer 153

9. Proton Radiation Therapy 161

Proton Beam Depth Dose 161

10. Immunotherapy 173

Immune System Components 173

11. Radiation and Combined Modality Therapy 191

Radiation Therapy 191

12. Statistical Considerations in Radiation Oncology 201

Deﬁnition of Statistical Terms 201

14. Primary Brain Cancers 237

Low-Grade Glioma 238

15. Head and Neck Cancers 269

Head and Neck Lymph Node Borders 269

16. Breast Cancers 317

RTOG Breast and LN Volume Guidelines 317

17. Thoracic Cancers 351

NoneSmall-Cell Lung Cancer 351

18. Gastrointestinal Cancers 381

Esophageal Cancer 381

19. Genitourinary Cancers 429

Renal Cell Cancer 429

20. Gynecological Cancers 475

Endometrial Cancer 475

21. Lymphoma and Hematologic Cancers 515

Hodgkin Lymphoma 515

22. Sarcomas 545

Soft-Tissue Sarcomas 545

23. Pediatric Cancers 557

Hodgkin’s Lymphoma 557

24. Benign Diseases 599

Skin and Connective Tissue Disorders 599

Metastatic Brain Cancer 609

26. Radiation Treatment, Toxicity, and Their Management 621

Normal Tissue Tolerance to Therapeutic Irradiation 621

Radiation Fibrosis and Muscle Relaxants 669

Acronyms and Abbreviations 675

Once again, Dr. Murshed has done an excellent job of producing an

updated version of Fundamentals of Radiation Oncology is a great testament to

James A. Bonner, M.D.

Thomas Buchholz, M.D.

Cancer management, speciﬁcally Radiation Oncology, has undergone ground

Hasan Murshed, M.D.

Kamran Ahmad M.D. Assistant Member, Radiation Oncology, Mofﬁtt Cancer

Dorothy Guzral MBChB, Ph.D. Consultant, Clinical Oncology, Imperial College