Basic Radiation Oncology

Murat Beyzadeoglu  •  Gokhan Ozyigit  •  Cuneyt Ebruli

Basic Radiation
Oncology
Murat Beyzadeoglu MD Cuneyt Ebruli MD
Professor and Chairman of Radiation Oncology Instructor of Radiation Oncology
Gulhane Military Medical School Gulhane Miltary Medical School
Department of Radiation Oncology Department of Radiation Oncology
Ankara Currently affiliated to:
Etlik Kocaeli State Hospital
Turkey Department of Radiation Oncology
[email protected] Kocaeli, Turkey
[email protected]
Gokhan Ozyigit MD
Associate Professor of Radiation Oncology
Hacettepe University, Faculty of Medicine
Department of Radiation Oncology
06100 Ankara
Turkey
[email protected]

ISBN: 978-3-642-11665-0 e-ISBN: 978-3-642-11666-7

DOI: 10.1007/978-3-642-11666-7

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 Dedication

Dedicated to the memory of Professor

Ibtisam Lale Atahan, MD (1945–2007)

v
 Foreword

Revolutionary advances have been taking place in radiation oncology as our world has
entered a new millennium. Developments in radiological and functional imaging tech-
niques over the last two decades have enabled us to delineate tumors more accurately in
the three spatial and the fourth (temporal) dimensions. More powerful computerized plan-
ning systems are facilitating accurate three-dimensional dose calculations as well as
inverse planning processes. We have even started to use robotic technology to track our
targets in real time for more precise delivery of radiotherapy.
All of those high-tech machines sometimes cause us to spend many hours in front of
detailed displays of serial computerized tomography (CT) slices. However, we are still
treating our patients with the same types of ionizing radiation discovered more than a cen-
tury ago. Therefore, every member of a radiation oncology team should know the interac-
tions of ionizing radiation with matter at the atomic level, and be familiar with its effects
in biological systems. In addition, every radiation oncologist should have an essential
knowledge of evidence-based clinical oncology in relation to the indications and technical
aspects of radiotherapy at major cancer sites.
Basic Radiation Oncology is an up-to-date, bedside-oriented textbook that integrates
radiation physics, radiobiology and clinical radiation oncology. The book includes the essen-
tials of all aspects of radiation oncology, with more than 300 practical illustrations and color
figures. The layout and presentation is very practical and enriched with many eye-catching
conceptual highlights. The first three chapters review crucial ideas in radiation physics and
radiobiology as well as the terminology of clinical radiation oncology. Basic descriptions of
all high-tech radiotherapy machines are also given. The remaining eleven clinical chapters
describe anatomy, pathology, general presentation, treatment algorithms and the technical
aspects of radiotherapy for major cancer sites. The 2010 (seventh) edition of the AJCC
Staging System is provided for each tumor type. Practical details about key studies, particu-
larly randomized ones, and available RTOG consensus guidelines for the determination and
delineation of targets are also included at the end of each clinical chapter.
Basic Radiation Oncology meets the need for a practical and bedside-oriented radiation
oncology textbook for residents, fellows, and clinicians of radiation, medical and surgical
oncology, as well as for medical students, physicians and medical physicists interested in
clinical radiation oncology.

 K.S. Clifford Chao, MD

vii
 Preface

The aim of writing Basic Radiation Oncology was to provide a structured overview of the
theory and practice of radiation oncology, including the principles of radiation physics,
radiation biology and clinical radiation oncology. We have encompassed the fundamental
aspects of radiation physics, radiobiology, and clinical radiation oncology. In the last two
decades, there have been many technical and conceptual advances in both treatment plan-
ning systems and radiation delivery systems. However, there are no changes in the basic
interactions of radiation with atoms or cells. Therefore, basic concepts that are crucial to
understanding radiation physics and radiobiology are reviewed in depth in the first two
sections. The third section describes radiation treatment regimens appropriate for the main
cancer sites and tumor types according to the seventh edition of the American Joint
Committee on Cancer Staging System. Many ‘pearl boxes’ are used to summarize impor-
tant information, and there are more than 350 helpful illustrations. Basic Radiation
Oncology meets the need for a practical radiation oncology book. It will be extremely use-
ful for residents, fellows, and clinicians in the fields of radiation, medical, and surgical
oncology, as well as for medical students, physicians, and medical physicists with an
­interest in clinical oncology.
Evidence-based data are also available at the end of the section on each clinical subsite.
However, every clinician should be aware of the fact that there is a very fine line between
evidence-based and probability-based medicine. Cancer is a highly complex subject, and
it is impossible to fit it into a simple mathematical formula or “p” value. Therefore, we
must not throw away experience-based data during our clinical decision-making proce-
dures. We extend our most sincere gratitude to Zeki Bayraktar, the Dean of Gulhane
Military Medical School, as well as to our families for their understanding as we worked
to meet our publication deadlines.

Ankara, Turkey Dr. M. Beyzadeoglu

Ankara, Turkey Dr. Gokhan Ozyigit
Kocaeli, Turkey Dr. Cuneyt Ebruli

ix
 Acknowledgments

The editors are indebted to Nel van der Werf, Ute Heilmann, Stefanie Schafer, Meike
Stoeck, Wilma McHugh from Springer and Dakshinamoorthy Mahalakshmi from SPi for
their assistance in preparing Basic Radiation Oncology. Special thanks are extended to
Professor K.S. Clifford Chao, who is chairman of the radiation oncology departments at
Columbia University, New York Presbyterian Hospital and Weill Cornell Medical College,
for honoring us with his foreword. We extend our most sincere gratitude to our colleagues
and friends at Gulhane Military Medical School and the Faculty of Medicine at Hacettepe
University.

xi
 Contents

  1  Radiation Physics................................................................................................ 1
1.1 Atom............................................................................................................... 1
1.2 Radiation........................................................................................................ 3
1.3 Ionizing Radiation.......................................................................................... 4
1.3.1 Ionizing Electromagnetic Radiation.................................................. 4
1.3.2 Ionizing Particulate Radiation............................................................ 10
1.4 The Interaction of Radiation with Matter...................................................... 12
1.4.1 Photoelectric Effect............................................................................ 13
1.4.2 Compton Effect.................................................................................. 14
1.4.3 Pair Production................................................................................... 15
1.4.4 Coherent Effect (= Rayleigh Scattering,
= Thomson Scattering)..................................................................... 16
1.5 Specific Features of X-Rays........................................................................... 19
1.6 Specific Features of Electron Energies.......................................................... 21
1.7 Ionizing Radiation Units................................................................................ 21
1.8 Radiotherapy Generators................................................................................ 24
1.8.1 Cobalt-60 Teletherapy Unit................................................................ 27
1.8.2 Linear Accelerator (Linac)................................................................. 30
1.9 Measurement of Ionizing Radiation............................................................... 33
1.9.1 Portable Measuring Equipment.......................................................... 34
1.9.2 Other Measuring Equipment.............................................................. 37
1.10 Radiation Dosimetry...................................................................................... 38
1.10.1 Phantom............................................................................................. 38
1.10.2 Definition of Beam Geometry............................................................ 39
1.10.3 Build-Up Region................................................................................ 41
1.10.4 Half-Value Layer (HVL).................................................................... 42
1.10.5 Percentage Depth Dose (PDD).......................................................... 43
1.10.6 Isodose Curves................................................................................... 45
1.10.7 Dose Profile........................................................................................ 47
1.10.8 Penumbra........................................................................................... 49

xiii
xiv Contents

1.10.9 Inverse Square Law.......................................................................... 51

1.10.10 Backscatter Factor (BSF).................................................................. 52
1.10.11 Tissue to Air Ratio (TAR)................................................................ 52
1.10.12 Tissue Maximum Ratio (TMR)........................................................ 53
1.10.13 Scatter Air Ratio (SAR).................................................................... 54
1.10.14 Collimator Scattering Factor (Sc )...................................................... 54
1.10.15 Phantom Scattering Factor (Sp)......................................................... 55
1.10.16 Monitor Unit (MU) Calculation in a Linear Accelerator................. 55
1.10.17 Treatment Time Calculation in a Co-60
Teletherapy Unit............................................................................... 57
1.11 Beam Modifiers.............................................................................................. 57
1.11.1 Bolus................................................................................................. 57
1.11.2 Compensating Filters........................................................................ 58
1.11.3 Wedge Filters.................................................................................... 58
1.11.4 Shielding Blocks............................................................................... 60
1.11.5 Multileaf Collimator (MLC)............................................................. 61
1.12 Pearl Boxes.................................................................................................... 64
References............................................................................................................... 68

  2  Radiobiology........................................................................................................ 71
2.1 Cell Biology and Carcinogenesis................................................................... 71
2.1.1 Cell Structure.................................................................................... 71
2.1.2 Cell Types and Organelles................................................................ 72
2.1.3 Cell Cycle......................................................................................... 75
2.1.4 Carcinogenesis and the Cell Cycle................................................... 80
2.1.5 Features of Cancer Cells................................................................... 82
2.2 Cellular Effects of Radiation.......................................................................... 83
2.2.1 The Direct Effect of Radiation at the Molecular Level.................... 85
2.2.2 The Indirect Effect of Radiation at the Molecular Level.................. 86
2.3 Factors Modifying the Biological Effects of Ionizing Radiation................... 88
2.3.1 Characteristics of the Radiation........................................................ 88
2.4 Target Tissue Characteristics......................................................................... 90
2.5 Target Theory................................................................................................. 94
2.6 Cell Survival Curves...................................................................................... 95
2.6.1 Exponential Survival Curves.............................................................. 97
2.6.2 Linear–Quadratic Model (LQ Model)................................................ 101
2.6.3 Types of Cellular Damage Due to Radiation...................................... 106
2.6.4 Factors Affecting the Cell Survival Curve......................................... 107
2.7 Tissue and Organ Response to Radiation....................................................... 111
2.8 Stochastic and Deterministic Effects............................................................. 117
2.9 Tumor Response to Radiation........................................................................ 118
2.9.1 Therapeutic Index............................................................................... 118
2.9.2 Tumor Control Probability (TCP)...................................................... 119
2.9.3 Normal Tissue Complication Probability (NTCP)............................. 122
Contents xv

2.10 The Five R’s of Radiotherapy........................................................................ 125

2.10.1 Repopulation...................................................................................... 126
2.10.2 Repair................................................................................................. 128
2.10.3 Redistribution (= Reassortment)........................................................ 129
2.10.4 Reoxygenation.................................................................................... 129
2.10.5 Radiosensitivity (Intrinsic Radiosensitivity)...................................... 131
2.11 Fractionation.................................................................................................. 132
2.12 Radiation Protection....................................................................................... 134
2.13 Pearl Boxes.................................................................................................... 136
References............................................................................................................... 141

  3  Clinical Radiation Oncology.............................................................................. 145

3.1 Introduction.................................................................................................... 145
3.2 The Radiotherapy Procedure.......................................................................... 150
3.2.1 Simulation.......................................................................................... 151
3.2.2 Treatment Planning............................................................................. 161
3.2.3 Target Volume Definitions.................................................................. 163
3.2.4 Setup and Treatment........................................................................... 169
3.2.5 Quality Assurance.............................................................................. 170
3.2.6 Treatment Fields in Radiotherapy...................................................... 173
References............................................................................................................... 173

  4  Central Nervous System Tumors....................................................................... 175

4.1 Anatomy......................................................................................................... 176
4.2 General Presentation and Pathology.............................................................. 178
4.3 Staging........................................................................................................... 185
4.4 Treatment Algorithm...................................................................................... 186
4.5 Radiotherapy.................................................................................................. 189
4.5.1 External Radiotherapy........................................................................ 189
4.5.2 Craniospinal RT.................................................................................. 192
4.5.3 Symptomatic Treatments and Special Therapies................................ 195
4.5.4 Side Effects Due to CNS Radiotherapy.............................................. 196
4.6 Selected Publications..................................................................................... 197
4.7 Pearl Boxes.................................................................................................... 201
References............................................................................................................... 202

  5  Head and Neck Cancers..................................................................................... 205

5.1 Pharyngeal Cancers........................................................................................ 212
5.1.1 Nasopharyngeal Cancer...................................................................... 213
5.1.2 Oropharyngeal Cancer........................................................................ 224
5.1.3 Hypopharyngeal Cancer..................................................................... 231
5.2 Laryngeal Cancer........................................................................................... 239
5.2.1 Pathology............................................................................................ 239
5.2.2 General Presentation........................................................................... 240
5.2.3 Staging................................................................................................ 240
xvi Contents

5.2.4 Treatment Algorithm.......................................................................... 244

5.2.5 Radiotherapy...................................................................................... 245
5.2.6 Selected Publications.......................................................................... 247
5.3 Oral Cavity Cancers....................................................................................... 249
5.3.1 Pathology............................................................................................ 251
5.3.2 General Presentation........................................................................... 252
5.3.3 Staging................................................................................................ 252
5.3.4 Treatment Algorithm.......................................................................... 254
5.3.5 Radiotherapy...................................................................................... 254
5.3.6 Selected Publications.......................................................................... 256
5.4 Sinonasal Cancers.......................................................................................... 257
5.4.1 Pathology............................................................................................ 259
5.4.2 General Presentation........................................................................... 259
5.4.3 Staging................................................................................................ 260
5.4.4 Treatment Algorithm.......................................................................... 264
5.4.5 Radiotherapy...................................................................................... 264
5.4.6 Selected Publications.......................................................................... 268
5.5 Major Salivary Gland Tumors....................................................................... 270
5.5.1 Pathology............................................................................................ 271
5.5.2 General Presentation........................................................................... 273
5.5.3 Staging................................................................................................ 273
5.5.4 Treatment Algorithm.......................................................................... 274
5.5.5 Radiotherapy...................................................................................... 275
5.5.6 Selected Publications.......................................................................... 278
5.6 Thyroid Cancer.............................................................................................. 279
5.6.1 Pathology............................................................................................ 281
5.6.2 General Presentation........................................................................... 282
5.6.3 Staging................................................................................................ 283
5.6.4 Treatment Algorithm.......................................................................... 285
5.6.5 Radiotherapy...................................................................................... 287
5.6.6 Selected Publications.......................................................................... 289
5.7 Radiotherapy in Unknown Primary Head–Neck Cancers.............................. 290
5.8 Selected Publications for Head and Neck Cancers........................................ 291
5.9 Pearl Boxes.................................................................................................... 294
References............................................................................................................... 299

  6  Lung Cancer........................................................................................................ 303

6.1 Non-Small Cell Lung Cancer (NSCLC)........................................................ 304
6.1.1 Pathology............................................................................................ 304
6.1.2 General Presentation........................................................................... 305
6.1.3 Staging................................................................................................ 306
6.1.4 Treatment Algorithm.......................................................................... 311
6.1.5 Radiotherapy...................................................................................... 313
6.1.6 Selected Publications.......................................................................... 319
Contents xvii

6.2 Small Cell Lung Cancer (SCLC)................................................................... 323

6.2.1 Pathology............................................................................................ 323
6.2.2 General Presentation........................................................................... 323
6.2.3 Staging................................................................................................ 324
6.2.4 Treatment Algorithm.......................................................................... 324
6.2.5 Radiotherapy...................................................................................... 325
6.2.6 Selected Publications.......................................................................... 325
References............................................................................................................... 327

  7  Breast Cancer...................................................................................................... 329

7.1 Pathology....................................................................................................... 330
7.2 General Presentation...................................................................................... 334
7.3 Staging........................................................................................................... 335
7.4 Treatment Algorithm...................................................................................... 340
7.5 Radiotherapy.................................................................................................. 342
7.6 Selected Publications..................................................................................... 350
References............................................................................................................... 361

  8  Genitourinary System Cancers.......................................................................... 363

8.1 Prostate Cancer.............................................................................................. 363
8.1.1 Pathology............................................................................................ 366
8.1.2 General Presentation........................................................................... 367
8.1.3 Staging................................................................................................ 370
8.1.4 Treatment Algorithm.......................................................................... 373
8.1.5 Radiotherapy...................................................................................... 375
8.1.6 Selected Publications.......................................................................... 380
8.2 Testicular Cancer............................................................................................ 385
8.2.1 Pathology............................................................................................ 386
8.2.2 Treatment Algorithm.......................................................................... 391
8.2.3 Radiotherapy...................................................................................... 393
8.3 Bladder Cancer............................................................................................... 397
8.3.1 Pathology............................................................................................ 399
8.3.2 General Presentation........................................................................... 400
8.3.3 Staging................................................................................................ 400
8.3.4 Treatment Algorithm.......................................................................... 403
8.3.5 Radiotherapy...................................................................................... 404
8.3.6 Selected Publications.......................................................................... 405
References............................................................................................................... 409

  9  Gynecological Cancers........................................................................................ 411

9.1 Cervical Cancer.............................................................................................. 411
9.1.1 Pathology............................................................................................ 412
9.1.2 General Presentation........................................................................... 413
9.1.3 Staging................................................................................................ 413
xviii Contents

9.1.4 Treatment Algorithm.......................................................................... 415

9.1.5 Radiotherapy...................................................................................... 418
9.1.6 Selected Publications.......................................................................... 428
9.2 Endometrial Cancer........................................................................................ 432
9.2.1 Pathology............................................................................................ 433
9.2.2 General Presentation........................................................................... 434
9.2.3 Staging................................................................................................ 435
9.2.4 Treatment Algorithm.......................................................................... 438
9.2.5 Radiotherapy...................................................................................... 440
9.2.6 Selected Publications.......................................................................... 443
9.3 Vaginal Cancer............................................................................................... 445
9.3.1 Pathology............................................................................................ 446
9.3.2 General Presentation........................................................................... 447
9.3.3 Staging................................................................................................ 447
9.3.4 Treatment Algorithm.......................................................................... 449
9.3.5 Radiotherapy...................................................................................... 450
9.3.6 Selected Publications.......................................................................... 452
References............................................................................................................... 453

10  Gastrointestinal System Cancers....................................................................... 455

10.1 Esophageal Cancer......................................................................................... 455
10.1.1 Pathology............................................................................................ 456
10.1.2 General Presentation........................................................................... 457
10.1.3 Staging................................................................................................ 457
10.1.4 Treatment Algorithm.......................................................................... 462
10.1.5 Radiotherapy...................................................................................... 462
10.1.6 Selected Publications.......................................................................... 464
10.2 Gastric Cancer................................................................................................ 467
10.2.1 Pathology............................................................................................ 468
10.2.2 General Presentation........................................................................... 469
10.2.3 Staging................................................................................................ 470
10.2.4 Treatment Algorithm.......................................................................... 473
10.2.5 Radiotherapy...................................................................................... 474
10.2.6 Selected Publications.......................................................................... 476
10.3 Pancreatic Cancer........................................................................................... 476
10.3.1 Pathology............................................................................................ 478
10.3.2 General Presentation........................................................................... 478
10.3.3 Staging................................................................................................ 478
10.3.4 Treatment Algorithm.......................................................................... 481
10.3.5 Radiotherapy...................................................................................... 481
10.3.6 Selected Publications.......................................................................... 483
10.4 Rectal Cancer................................................................................................. 485
10.4.1 Pathology............................................................................................ 486
10.4.2 General Presentation........................................................................... 487
10.4.3 Staging................................................................................................ 487
Contents xix

10.4.4 Treatment Algorithm.......................................................................... 490

10.4.5 Radiotherapy...................................................................................... 491
10.4.6 Selected Publications.......................................................................... 493
10.5 Anal Cancer.................................................................................................... 494
10.5.1 Pathology............................................................................................ 495
10.5.2 General Presentation........................................................................... 496
10.5.3 Staging................................................................................................ 496
10.5.4 Treatment Algorithm.......................................................................... 499
10.5.5 Radiotherapy...................................................................................... 499
10.5.6 Selected Publications.......................................................................... 501
References............................................................................................................... 503

11  Soft Tissue Sarcoma............................................................................................ 505

11.1 Pathology....................................................................................................... 505
11.2 General Presentation...................................................................................... 508
11.3 Staging........................................................................................................... 509
11.4 Treatment Algorithm...................................................................................... 511
11.5 Radiotherapy.................................................................................................. 512
11.6 Selected Publications..................................................................................... 514
References............................................................................................................... 516

12  Skin Cancer......................................................................................................... 519

12.1 Pathology/General Presentation..................................................................... 520
12.2 Staging........................................................................................................... 522
12.3 Treatment Algorithm...................................................................................... 525
12.4 Radiotherapy.................................................................................................. 526
12.5 Selected Publications..................................................................................... 527
12.5.1 Radiotherapy Alone (Retrospective).................................................. 527
12.5.2 Perineural Invasion............................................................................. 528
12.5.3 Hypofractionation............................................................................... 528
References............................................................................................................... 529

13  Lymphomas and Total Body Irradiation.......................................................... 531

13.1 Hodgkin’s Lymphoma.................................................................................... 531
13.1.1 Pathology/General Presentation......................................................... 531
13.1.2 Clinical Signs..................................................................................... 532
13.1.3 Staging................................................................................................ 533
13.1.4 Treatment Algorithm.......................................................................... 535
13.1.5 Radiotherapy...................................................................................... 537
13.2 Selected Publications..................................................................................... 546
13.3 Non-Hodgkin Lymphoma.............................................................................. 550
13.3.1 Pathology/General Presentation......................................................... 551
13.3.2 Staging................................................................................................ 552
13.3.3 Treatment Algorithm.......................................................................... 552
13.3.4 Radiotherapy...................................................................................... 554
13.3.5 Selected Publications.......................................................................... 554
xx Contents

13.4 Cutaneous Lymphoma.................................................................................... 557

13.4.1 Treatment Algorithm.......................................................................... 558
13.4.2 Total Skin Irradiation (TSI)................................................................ 558
13.4.3 Selected Publications.......................................................................... 560
13.5 Total Body Irradiation (TBI).......................................................................... 561
13.5.1 Selected Publications.......................................................................... 566
References............................................................................................................... 567

Index ............................................................................................................................ 577

 Introduction and History

Roentgen was working on Crook’s Vacuum tube on November 8th 1895. He suddenly
realized that shadows of his wife’s finger bones and ring in her finger appeared on the
palette. This was the discovery of X-rays and the beginning of radiation history (Fig. 1).

Fig. 1   The first X-ray (X-ray of the hand

of Anna Bertha Roentgen)

Henri Becquerel opened his drawer in his laboratory on March 1896. He was greatly
­surprised when he saw blackened photo glasses despite their being kept in a totally dark
medium. This was the discovery of natural radioactivity (Fig. 2).
It has been more than a century since the discovery of X-rays by Roentgen and that of
natural radioactivity by Becquerel, and in that time the field of radiation oncology has seen
enormous changes due to the now-standard use of extraordinarily complex systems and

xxi
xxii Introduction and History

Fig. 2  The blurred photo glasses of Becquerel

Fig. 3  The first radiation

oncologist, Emil Grubbe

high-technology products to treat cancers. Indeed, just two months after the discovery of
X-rays (i.e., on 1 Jan 1896), a medical student named Emil Grubbe (Fig. 3) used X-rays to
treat a 65 year old female patient named Rosa Lee with recurrent breast carcinoma at a
lamp factory in Chicago.
We can summarize the most important developmental steps in the field of radiation
oncology chronologically as follows:

1895: Discovery of X-rays by Wilhelm Conrad Roentgen (Germany)

1895: Use of X-rays in breast cancer by Emil Grubbe (Chicago, USA)
1896: Use of X-rays in nasopharyngeal cancer and in pain palliation by Voigt J. Ärztlicher
Verein (Germany)
1896: Discovery of natural radioactivity by Henri Becquerel (Paris, France)
1896: Use of X-rays in the treatment of gastric cancer by Despeignes (France)
1896: Use of X-rays in the treatment of skin cancer by Léopold Freund (Austria)
1897: Discovery of electrons (Thompson)
1898: Discovery of radium by Pierre and Marie Curie (France)
1899: Definition of the alpha particle (E. Rutherford)
Introduction and History xxiii

1901: The first use of radium in skin brachytherapy (Dr. Danlos, France)
1903: Publications showing the efficacy of radiotherapy in lymphoma (Senn & Pusey)
1905: Discovery of the sensitivity of seminoma to radiation (A. Béclère, France)
1905: Discovery of the photoelectric effect by A. Einstein (Germany)
1906: Discovery of characteristic X-rays (G. Barkla)
1922: Demonstration of the Compton effect (Arthur H. Compton)
1931: First cyclotron (Ernest O. Lawrence, USA)
1932: Discovery of neutrons (Sir James Chadwick, UK)
1934: Discovery of artificial radioelements (Irène and Frédéric Joliot-Curie, France)
1934: 23% cure rate in head and neck cancer (Henri Coutard)
1934: Death of Mrs. Marie Curie due to pernicious anemia (myelodysplasia)
1940: The first betatron (Donald W. Kerst)
1951: The first cobalt-60 teletherapy machine (Harold E. Johns, Canada)
1952: The first linear accelerator (linac) machine (Henry S. Kaplan, USA)
1968: Discovery of the gamma knife (Lars Leksell)
1971: The first computerized tomography (CT) (G.N. Hounsfield, UK)
1973: The first MRI machine (Paul C. Lauterbur, Peter Mansfield)
1990: The first use of computers and CT in radiotherapy (USA)
1994: The first clinical IMRT treatment (USA)
1996: FDA approval of the first IMRT software
2001: FDA approval of robotic radiosurgery
2002: FDA clearance of spiral (helical) tomotherapy
2003: The first use of image-guided radiation therapy (IGRT) technology
 Radiation Physics
1
Murat Beyzadeoglu, Gokhan Ozyigit, and Cuneyt Ebruli

1.1 
Atom

The word “atom” derives from the Greek word “atomos,” which means indivisible; an atom
was the smallest indivisible component of matter according to some philosophers in Ancient
Greece [1]. However, we now know that atoms are actually composed of subatomic particles:
protons and neutrons in the nucleus of the atom, and electrons orbiting that nucleus (Fig. 1.1).

Fig. 1.1  The structure of an atom

M. Beyzadeoglu et al. Basic Radiation Oncology, 1

DOI: 10.1007/978-3-642-11666-7_1, © Springer-Verlag Berlin Heidelberg 2010
2 1  Radiation Physics

Electrons are negatively charged particles.

Protons are positively charged particles. The mass of a proton is about 1,839 times
greater than that of an electron.
Neutrons are uncharged (neutral) particles. The mass of a neutron is very slightly
larger than that of a proton.
Protons and neutrons form the nucleus of an atom, and so these particles are also
called nucleons.
The diameter of an atom is about 10−8 cm, whereas the diameter of the atomic nucleus
is 10−13 cm.

The total number of protons and neutrons in a nucleus (p + n) (i.e., the total number of
“nucleons”) is termed the mass number of that atom, symbolized by A [1]. The total num-
ber of protons is called the atomic number and is symbolized by Z. The atomic number and
the mass number of an element X are usually presented in the form ZA X (Fig. 1.2).

MASS
NUMBER
14

6 8

ATOM NEUTRON
NUMBER NUMBER
Fig. 1.2  Writing a element in nuclide
format (carbon-14 is used as an example)

Nuclide → if an atom is expressed in the form A

Z X , it is called a nuclide (e.g., 42 He ).
Radionuclide → if the atom is expressed in the form ZA X and is radioactive, it is called
a radionuclide.
1.2  Radiation 3

1.2 
Radiation

The propagation of energy from a radiative source to another medium is termed radia-
tion. This transmission of energy can take the form of particulate radiation or electro-
magnetic radiation (i.e., electromagnetic waves). The various forms of radiation
originating from atoms, which include (among others) visible light, X-rays and g-rays,
are grouped together under the terms “electromagnetic radiation” [1] or “the electro-
magnetic spectrum” [1, 2]. Radio waves, which have the longest wavelengths and thus
the lowest frequencies and energies of the various types of electromagnetic radiation,
are located at tone end of the electromagnetic spectrum, whereas X-rays and g-rays,
which have the highest frequencies and energies, are situated at the other end of this
spectrum.

Photon

• If the smallest unit of an element is considered to be its atoms, the photon is the smallest
unit of electromagnetic radiation [3].
• Photons have no mass.
Common features of electromagnetic radiation [4, 5]:

• It propagates in a straight line.

• It travels at the speed of light (nearly 300,000 km/s).
• It transfers energy to the medium through which it passes, and the amount of energy
transferred correlates positively with the frequency and negatively with the wavelength
of the radiation.
• The energy of the radiation decreases as it passes through a material, due to absorption
and scattering, and this decrease in energy is negatively correlated with the square of
the distance traveled through the material.

Electromagnetic radiation can also be subdivided into ionizing and nonionizing radia-
tions. Nonionizing radiations have wavelengths of ³10−7 m. Nonionizing radiations
have energies of <12 electron volts (eV); 12 eV is considered to be the lowest energy
that an ionizing radiation can possess [4].
Types of nonionizing electromagnetic radiation [5]:

• Radio waves
• Microwaves
• Infrared light
• Visible light
• Ultraviolet light
4 1  Radiation Physics

1.3 
Ionizing Radiation

Ionizing (high-energy) radiation has the ability to remove electrons from atoms; i.e., to
ionize the atoms. Ionizing radiation can be electromagnetic or particulate radiation
(Fig.  1.3). Clinical radiation oncology uses photons (electromagnetic) and electrons or
(rarely) protons or neutrons (all three of which are particulate) as radiation in the treatment
of malignancies and some benign conditions [6].

Ionizing
radiation

Electromagnetic Particulate

Neutron Proton
Electron (β)
X-rays γ-rays α particles Π Meson
particles
Heavy ions

Fig. 1.3  Ionizing radiations

1.3.1 
Ionizing Electromagnetic Radiation

The electromagnetic spectrum comprises all types of electromagnetic radiation, ranging

from radio waves (low energy, long wavelength, low frequency) to ionizing radiations
(high energy, short wavelength, high frequency) (Fig. 1.4) [7].

Electromagnetic Spectrum

101 100 1 1/100 10 4

Micro eV (Energy)
Gamma rays infrared waves Radio waves
10−4 10−1 101 101 10−1 10 4 nm
Wavelength

100 200 300 400 500 600 700 nm

VUV UVC UVB UVA BLUE YELLOW RED
UV Visible light

Fig. 1.4  Electromagnetic spectrum

1.3  Ionizing Radiation 5

Electrons are knocked out of their atomic and molecular orbits (a process known as
ionization) when high-energy radiation interacts with matter [8]. Those electrons produce
secondary electrons during their passage through the material. A mean of energy of
33.85 eV is transferred during the ionization process, which in atomic and molecular terms
is a highly significant amount of energy. When high-energy photons are used clinically, the
resulting secondary electrons, which have an average energy of 60  eV per destructive
event, are transferred to cellular molecules.

1.3.1.1 
X-Rays

X-rays were discovered by the German physicist Wilhelm Conrad Roentgen in \95 [9].
The hot cathode Roentgen tube, which was developed by William David Coolidge in 1913,
is a pressured (to 10−3 mmHg) glass tube consisting of anode and cathode layers between
which a high-energy (106 –108 V) potential is applied (Fig. 1.5a, b). Electrons produced by
thermionic emission in the cathode are accelerated towards the anode by the potential.
They thus hit the anode, which is a metal with high melting temperature. X-rays are pro-
duced by the sudden deceleration of these electrons due to Coulomb interactions with
nuclei in the anode (this sudden deceleration of fast-moving electrons is known as
bremsstrahlung; Fig.  1.6). The energy and the wavelength of the X-rays depend on the
atomic number of the target (anode) metal, as well as the velocity and the kinetic energy of
the electrons. This process is used to produce medical radiation in diagnostic X-ray units,
linear accelerators (linacs), and betatrons.

a b
Electrons
Tungsten target Glass housing
Copper anode Heated tungsten
filament cathode
+ −

+ −
High voltage
source
X-rays

Fig. 1.5  (a) Schematic representation of an X-ray tube; (b) photograph of an X-ray tube

X-rays are produced by extranuclear procedures. Two kinds of X-rays are created by
X-ray tubes [10, 11]. The first type corresponds to the bremsstrahlung X-rays mentioned
above. The second type occurs because an electron in an inner atomic orbital is knocked
out by an incoming electron, and the resulting space in the orbital is filled by other electron
that moves from an outer atomic orbital (Fig. 1.7). This electron must shed energy to move
in this manner, and the energy released is radiated as characteristic X-rays [12]. They are
characteristic due to the fact that their energy depends on the target metal onto which the
electrons are accelerated.
6 1  Radiation Physics

Fig. 1.6  Bremsstrahlung
process

Fig. 1.7  Characteristic X-ray

generation

X-rays produced by bremsstrahlung have a broad energy spectrum (→ heterogeneous),

while characteristic X-rays are monoenergetic beams.

1.3.1.2 
Gamma (g) Rays

Gamma rays are physically identical to X-rays, but they are emitted from atomic nuclei
(intranuclearly). An unstable atomic nucleus sheds its excess energy in the form of either
an intranuclear electron (e−) (beta particle) or a helium nucleus (an “alpha particle”)
(Fig. 1.8). If it still possesses excess energy after that, gamma rays are emitted in order to
reach its steady state (Fig. 1.9).
1.3  Ionizing Radiation 7

Fig. 1.8  Alpha particle Alpha parcticle

generation Unstable Nucleus (Helium nucleus)

Spontaneous Gamma Rays

radiation

Beta particle
(Electron)

60
27Co

0.31 M
eV β

1.17 MeV γ
1.33 MeV γ
60
Fig. 1.9  Co-60 decay 28Ni

Gamma rays have well-defined energies. For instance, two monoenergetic gamma rays
with a mean energy of 1.25 MV (1.17 and 1.33 MV) are emitted after beta rays of 0.31 MV
energy have been emitted during the decay of 60Co (cobalt-60; Co-60). Through this pro-
cess, 60Co transforms into a final, stable decay product, 60Ni (nickel-60; Ni-60). There is
actually a stable naturally occurring form of cobalt: 59Co. 60Co is created through neutron
bombardment in nuclear reactors, and has a half-life of 5.26 years. One gram of 60Co has
an activity of 50 Ci (1.85 terabecquerels) [13, 14].
The half-life of a radioisotope is the time required for its activity to half [15].
The activity of a radioisotope is the number of decays per second, and is defined in
becquerels or curies.

• Becquerel (Bq): the standard unit of (radio)activity; it is defined as one disintegration

(decay) per second.
• Curie (Ci): an older unit of (radio)activity, corresponding to 3.7 × 1010 disintegrations
per second.

The decay of a radioactive nucleus is a spontaneous process. There are three forms of
radioactive decay. Alpha or beta particles are emitted during the alpha and beta decays of
an unstable nucleus in order to reach a stable nucleus. A gamma decay occurs without any
change in the form of the nucleus.
8 1  Radiation Physics

Alpha Decay [16]. An alpha particle consisting of two protons and two neutrons is
emitted if a nucleus is unstable because it has an excessive number of both protons and
neutrons (Fig. 1.10).
After alpha decay, the alpha particle possesses most of the energy, due to the conserva-
tion of momentum and the fact that the alpha particle is much less massive than the residual
nucleus. Although the 42 He nucleus is very energetic, does not travel very far compared to
most forms of radiation, due to its relatively heavy mass. Alpha decay is usually observed
in nuclei with mass numbers of more than 190. The energy spectrum of alpha decay is not
continuous, and varies between 4 and 10 MeV. Alpha particles strongly interact with the
electrons of the matter through which they pass, since they are charged particles.

Large, unstable Smaller, more stable Alpha particle

nucleus nucleus

Fig. 1.10  Alpha decay

Beta Decay [17]. There are three types of beta decay.

If a radionuclide is unstable because it has an excess number of neutrons in its nucleus,
it transforms one of the neutrons into a proton and an electron in order to reduce the
amount of energy in its nucleus (Fig. 1.11). The electron is rapidly propelled out of the
nucleus, while the proton remains. This high-speed electron called a b− particle or nega-
tron, and the process is termed b− decay. The atomic number of the radionuclide
increases by one, and thus it changes into the next element in the periodic table. Note
that the mass number does not change (it is an “isobaric” decay) [16, 17].

Carbon-14 Nitrogen-14

Antineutrino Electron
β-
−
ν −

6 protons 7 protons
8 neutrons 7 neutrons

Fig. 1.11  b− decay
1.3  Ionizing Radiation 9

If a radionuclide is unstable due to an excess amount of protons or a lack of neutrons,

one of the protons transforms into a neutron and a small positively charged particle
called a positron in a process termed b+ decay [17]. The neutron stays in the nucleus
while the positron is propelled out of it (Fig. 1.12). The atomic number of the radionu-
clide that emits the positron decreases by one, and thus it changes into the preceding
element in the periodic table. Again, note that the mass number does not change.

Carbon-10 Boron-10

Neutrino Positron
β+
ν +

6 protons 5 protons
4 neutrons 5 neutrons

Fig. 1.12  b+ decay

If the nucleus is unstable due an excess amount of protons, one of the electrons close to
the atomic nucleus, such as an electron in a K and L orbital, is captured by the nucleus
(Fig. 1.13). This electron then combines with a proton, yielding a neutron and a neu-
trino. This process is called electron capture [16]. Note that no particle is emitted from
the nucleus, but the atomic number decreases by one, as in positron decay. Yet again,
the mass number does not change. The space in the inner orbital is filled by an electron
from an outer orbital, resulting in the emission of characteristic X-rays.

Carbon-11 Boron-11

Electron Neutrino
− ν

6 protons 5 protons
5 neutrons 6 neutrons

Fig. 1.13  Electron capture phenomenon

There are also three types of beta decay. In all of them, the mass number of the nucleus
remains constant during the decay, while the numbers of protons and neutrons change by
one unit. Furthermore, the emission of some massless, uncharged particles called neutrinos
and antineutrinos is observed during each beta decay process. The existence of these par-
ticles was first suggested by Pauli in 1930, although it was Fermi that provided the name
“neutrino” [16].
10 1  Radiation Physics

Gamma Emission [13, 14, 16]. A nucleus is not always fully stable (i.e., at its basal
energy level) just after it decays; sometimes, the nucleus will be in a semi-stable state
instead (Fig. 1.14). The excess energy carried by the nucleus is then emitted as gamma
radiation. There is no change in the atomic or mass number of the nucleus after this
decay, so it is termed an “isomeric” decay.
The half-lives of gamma radiation sources are much shorter than sources of other types
of decay, and are generally less than 10−9 s. However, there are some gamma radiation
sources with half-lives of hours or even years. Gamma energy spectra are not continuous.

60 60
Co Co
Fig. 1.14  Gamma emission 27 27

Isotope [18]. Atoms with the same atomic number but different mass numbers are
called isotopes (e.g., 11 12 13
6 C, 6 C, 6 C).
Isotone. Atoms with the same number of neutrons, but different numbers of protons are
called isotones (e.g., 93 Li, 10 11 12
4 Be, 5 B, 6 C).
Isobar. Atoms with the same number of nucleons but different numbers of protons are
called isobars (e.g., 12 12 12
5 B, 6 C, 7 N).
Isomer. Atoms with the same atomic and mass numbers but which are in different
energy states are called nuclear isomers (Tc99m)

1.3.2 
Ionizing Particulate Radiation

Electrons, protons, alpha particles, neutrons, pi mesons and heavy ions are all forms of
ionizing particulate radiation [19]. Electrons are the particles that are generally used in
routine clinics. Other particles are only used in specific clinics worldwide.
Electrons, due to their negative charge and low mass, can be accelerated to high ener-
gies in linacs or betatrons.

The mass of an electron is 9.109 3826(16) × 10−31 kg.

The electrical charge of an electron is −1.602 176 53(14) × 10−19 C.

Electrons are normally bound to a (positively charged) nucleus. The number of electrons is
equal to the number of protons in a neutral atom. However, an atom can contain more or less
electrons than protons, in which case it is known as a negatively or positively charged ion,
1.3  Ionizing Radiation 11

respectively. Electrons that are not bound to an atom are called free electrons; free electrons
can be produced during nuclear decay processes, in which case they are called beta particles.

Electrons have much smaller ranges (i.e., they travel smaller distances) in matter than
gamma and X-rays, and can be absorbed by plastics, glass or metal layers (Fig. 1.15).

Paper Plastic Steel Lead

Alpha

Beta

Beta

Gamma

Fig. 1.15  Penetration ranges of various ionizing radiations

Neutrons are the neutrally charged particles that enable the formation of stable large atomic
nuclei (Fig. 1.16) by decreasing the repulsion between the protons in the nucleus. However,
neutrons, like protons, actually consist of particles called quarks; a neutron is one up quark
and two down quarks, while a proton (Fig. 1.17) is two up quarks and one down quark.

U
D

Neutron

U = “up” quark

D = “down” quark
Fig. 1.16  Neutron
12 1  Radiation Physics

Fig. 1.17  Proton

U
U

Proton

U = “up” quark

D = “down” quark

1.4 
The Interaction of Radiation with Matter

Radiation is scattered and absorbed when it passes through tissue [19, 20]. The intensities of
monoenergetic X-rays or gamma rays attenuate exponentially within tissues. In other words,
the intensity of radiation constantly decreases as it propagates within tissues. This decrease
depends on the type of tissue and its thickness. If the wavelength stays constant, the intensity
of the radiation passing through a tissue can be calculated by the following formula:

I = I 0 .e − mt  (1.1)
I = intensity of outgoing radiation beam
I0 = intensity of incoming radiation beam
m = absorption coefficient (which is positively correlated with the fourth power of the
atomic number of the penetrated tissue, and the third power of the wavelength of
the radiation)
t = tissue thickness

As seen in the above formula, the intensity of the radiation decreases exponentially with
the absorbent thickness, and the intensity of the outgoing radiation depends on the tissue
absorption coefficient and its thickness.