Biomedical Physics in Radiotherapy for Cancer

By Barry Allen, Loredana Marcu, Eva Bezak
Biomedical Physics in Radiotherapy for Cancer
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The scientific and clinical foundations of Radiation Therapy are cross-disciplinary. This book endeavours to bring together the physics, the radiobiology, the main clinical aspects as well as available clinical evidence behind Radiation Therapy, presenting mutual relationships between these disciplines and their role in the advancements of radiation oncology.

  1. Page iii
    Foreword
    By Eric Yeoh, MD, FRCP (EDIN), FRCR, FRANZCR, Professor
  2. Page xiv
    Acknowledgements
  3. Page xv
    Introduction
  4. Page 1
    1. Interactions of radiation with matter
    1. Page 1
      Ionising radiation
    2. Page 2
      X-rays
      1. Page 3
        Characteristic X-rays
      2. Page 4
        Bremsstrahlung radiation
    3. Page 5
      Interaction of X-rays with matter
      1. Page 5
        Linear attenuation coefficient
      2. Page 7
        Photoelectric effect
      3. Page 8
        Compton scattering
      4. Page 12
        Pair production
      5. Page 15
        Coherent scattering
      6. Page 15
        Total interaction coefficient
    4. Page 16
      Interactions of heavy charged particles with matter
      1. Page 17
        Bragg peak
      2. Page 18
        Linear energy transfer (LET)
      3. Page 18
        Stopping power (mass stopping power)
      4. Page 19
        Range of charged particles
      5. Page 20
        Bethe-Bloch formula
      6. Page 21
        Rutherford scattering
      7. Page 22
        Interactions of electrons with matter
    5. Page 24
      Neutron interactions
      1. Page 25
        Nuclear reactions with neutrons
    6. Page 25
      Radioactivity
      1. Page 25
        Basic definitions
      2. Page 28
        Quantities and units of radioactivity
      3. Page 30
        Sources of radionuclides and ionising radiation
    7. Page 30
      Radiation quantities and units
      1. Page 31
        Radiation weighting factors and equivalent dose
      2. Page 31
        Tissue weighting factors and effective dose
    8. Page 32
      The interaction of radiation with cells
    9. Page 33
      DNA – the target
    10. Page 33
      References
  5. Page 35
    2. Elements of radiobiology
    1. Page 35
      Target theory
      1. Page 35
        Single hit single target theory
      2. Page 36
        Single hit multiple target theory
      3. Page 36
        Linear quadratic model
    2. Page 38
      Cell survival curves
    3. Page 40
      The cell cycle and cellular radiosensitivity
    4. Page 41
      Characterisation of radiation damage
      1. Page 41
        Lethal damage
      2. Page 41
        Sublethal damage (SLD)
      3. Page 43
        Potentially lethal damage (PLD)
    5. Page 44
      Loss of reproductive ability in cells
      1. Page 44
        Clonogenic assay
      2. Page 46
        Main quantifying factors in radiation biology: LET, RBE, OER
    6. Page 46
      Linear energy transfer (LET)
      1. Page 46
        Energy dependence of LET
    7. Page 47
      Relative biological effectiveness (RBE)
      1. Page 48
        RBE as a function of LET
    8. Page 49
      The oxygen effect: Oxygen enhancement ratio (OER)
      1. Page 49
        The oxygen ‘fixation’ hypothesis
      2. Page 49
        Oxygen enhancement ratio (OER)
      3. Page 50
        OER as a function of LET
    9. Page 50
      References
  6. Page 53
    3. Elements of radiotherapy physics
    1. Page 53
      X-ray and particle generators
      1. Page 53
        Production of radioisotopes
      2. Page 54
        Production of X-rays
      3. Page 54
        X-ray tube
      4. Page 54
        Accelerators
    2. Page 64
      Radiation quantities and units
      1. Page 65
        Particle fluence
      2. Page 65
        Energy fluence
      3. Page 65
        Exposure
      4. Page 65
        Exposure rate
      5. Page 65
        Kerma
      6. Page 65
        Absorbed dose
      7. Page 66
        Relationship between exposure, kerma and absorbed dose
      8. Page 66
        Electronic equilibrium
    3. Page 67
      Radiation dose measurements
      1. Page 68
        Ionisation in gases
      2. Page 68
        Ionisation potential
      3. Page 68
        Average energy per ion pair, W
      4. Page 68
        Experimental values of W for gases
      5. Page 69
        Ionisation in solids
      6. Page 69
        Bragg-Gray cavity theory
      7. Page 70
        Spencer–Attix cavity theory
    4. Page 71
      Radiation detectors and dosimeters
      1. Page 71
        Ionisation chamber
    5. Page 78
      Determination of absorbed dose
      1. Page 78
        Absorbed dose in free space
      2. Page 78
        Absorbed dose in a phantom
      3. Page 79
        Determination of absorbed dose for megavoltage X-rays
      4. Page 80
        Absorbed dose in the neighbourhood of an interface between different materials
      5. Page 80
        Dosimetry for electron beams
    6. Page 80
      Radiotherapy dosimetry protocols
      1. Page 81
        Calibration of low energy X-rays
    7. Page 82
      Quality assurance
      1. Page 83
        Secondary standard equipment and calibration
      2. Page 83
        Ionisation chamber
      3. Page 84
        Measuring assembly (electrometer)
      4. Page 84
        Portable stability check source
      5. Page 84
        Transfer of secondary standard calibration to field instruments; measuring the output of an X-ray machine with cross-calibrated field ionisation chambers
      6. Page 85
        Quality assurance tests on radiotherapy treatment machines
    8. Page 85
      References
  7. Page 89
    4. Tumour characteristics, development and response to radiation
    1. Page 89
      The induction of cancer
    2. Page 89
      Normal cells versus malignant cells
    3. Page 91
      Tumour growth characteristics
      1. Page 91
        Tumour kinetic parameters
      2. Page 92
        Tumour composition and characteristics of tumour cells
    4. Page 93
      Tumour kinetic parameters
    5. Page 93
      Tumour behaviour during radiotherapy
    6. Page 96
      Tumour cell death
    7. Page 97
      Tumour hypoxia and angiogenesis
      1. Page 97
        Tumour hypoxia
      2. Page 100
        Tumour angiogenesis
    8. Page 101
      Tumour metastasis
    9. Page 103
      References
  8. Page 107
    5. Fractionation and altered fractionation in radiotherapy
    1. Page 107
      Introduction
      1. Page 112
        Volume effects
    2. Page 107
      The 5 R’s of radiobiology
      1. Page 108
        Repair
      2. Page 110
        Repopulation
      3. Page 110
        Redistribution
      4. Page 110
        Reoxygenation
      5. Page 111
        Radiosensitivity
    3. Page 112
      Organ architecture: functional sub-units (FSU)
    4. Page 112
      Fractionation in radiotherapy
    5. Page 116
      Biologically effective doses in radiotherapy
    6. Page 116
      Incomplete repair model
    7. Page 117
      The LQ model at high dose per fraction regions
    8. Page 118
      Altered fractionation schedules
      1. Page 118
        Altered fractionation schedules for head & neck cancers
      2. Page 120
        Altered fractionation schedules for prostate cancers
      3. Page 122
        Altered fractionation schedules for breast cancer
    9. Page 124
      Summary
    10. Page 124
      References
  9. Page 129
    6. Three-dimensional conformal radiotherapy: Technical and physics aspects of treatment
    1. Page 129
      Introduction
    2. Page 130
      Three-dimensional radiation therapy
    3. Page 132
      Treatment simulation
      1. Page 133
        CT scanner
      2. Page 134
        Virtual simulator software
    4. Page 135
      Digitally reconstructed radiographs (DRR)
    5. Page 135
      Dose-volume histograms
    6. Page 136
      Dose calculation
    7. Page 140
      Dynamic wedge
    8. Page 141
      Multi leaf collimator
      1. Page 143
        Leaf travel
      2. Page 143
        MLC radiation transmission
      3. Page 144
        Tongue-and-groove effects
      4. Page 145
        Multileaf collimator dose undulation
      5. Page 146
        MLC QA
    9. Page 146
      Electronic portal imaging devices
    10. Page 151
      Record and verify system
    11. Page 152
      Implementation of 3D CRT
    12. Page 153
      References
  10. Page 155
    7. Image guided radiotherapy: Radiobiology and physics aspects of treatment
    1. Page 155
      Introduction
    2. Page 156
      Use of X-ray imaging in radiation therapy
      1. Page 156
        Development of computed tomography
      2. Page 158
        Cone beam computed tomography
      3. Page 158
        Cone beam CT imaging devices
    3. Page 163
      Adaptive radiation therapy
    4. Page 164
      Alternative approaches to IGRT
      1. Page 164
        Tomotherapy
      2. Page 166
        In-room CT
      3. Page 166
        US-guided EBRT
      4. Page 167
        US-guided brachytherapy
      5. Page 168
        Beacon guided radiation therapy
    5. Page 169
      Four-dimensional imaging and tumour tracking
    6. Page 171
      Radiobiological aspects of image-guided radiotherapy (IGRT)
      1. Page 172
        Clinical trials/studies
      2. Page 172
        IMRT-IGRT
      3. Page 173
        Image guided stereotactic body radiotherapy (IG-SBRT)
    7. Page 174
      The future of IGRT: Biologic image-guided radiotherapy
    8. Page 176
      Conclusion
    9. Page 177
      References
  11. Page 183
    8. Intensity modulated radiotherapy: Radiobiology and physics aspects of treatment
    1. Page 183
      Introduction
    2. Page 184
      Principles of IMRT – delivery methods
      1. Page 186
        Step-and-shoot or segmented IMRT
      2. Page 186
        Three-dimensional physical compensator-based IMRT
      3. Page 187
        Dynamic or ‘sliding-window’ IMRT
    3. Page 188
      IMRT treatment planning – dose calculation algorithms
      1. Page 190
        Traditional IMRT optimisation
      2. Page 191
        Direct machine parameter optimisation
      3. Page 191
        Dose calculation algorithms
    4. Page 191
      Quality assurance in IMRT
      1. Page 193
        Patient set-up verification
      2. Page 193
        Treatment planning system QA
      3. Page 193
        Multileaf collimator QA
      4. Page 194
        IMRT dose delivery QA
    5. Page 195
      Volumetric IMRT – Intensity Modulated Arc Therapy (IMAT)
    6. Page 197
      The radiobiology of IMRT
    7. Page 198
      IMRT in clinical trials
      1. Page 198
        Head & neck cancer
      2. Page 200
        Brain cancer
      3. Page 202
        Prostate cancer
    8. Page 203
      References
  12. Page 209
    Colour plates
  13. Page 225
    9. Brachytherapy: Radiobiology and physics aspects of treatment
    1. Page 225
      Short history of brachytherapy
    2. Page 226
      Physical and radiobiological aspects of brachytherapy
      1. Page 227
        Classification of brachytherapy
      2. Page 227
        Dose rate classification
      3. Page 228
        Radioisotopes used in brachytherapy: Physical and biological characteristics
    3. Page 230
      Radiobiological models in brachytherapy (the LQ model)
    4. Page 231
      Dose prescription and dose calculation in brachytherapy
      1. Page 231
        Manchester system
      2. Page 232
        Paris system
      3. Page 232
        Present reporting
      4. Page 232
        Intracavitary treatments
      5. Page 233
        Interstitial treatments
      6. Page 233
        Dose calculations
    5. Page 234
      Brachytherapy for various tumour sites
      1. Page 234
        Brachytherapy for prostate cancer
      2. Page 237
        Brachytherapy for head & neck cancers
      3. Page 238
        Brachytherapy for breast cancer – MammoSite
      4. Page 242
        Brachytherapy for gynaecological malignancies
      5. Page 242
        Ophthalmic brachytherapy (eye plaques)
    6. Page 244
      Radiation protection and quality assurance
    7. Page 245
      References
    8. Page 249
      Appendix A1
  14. Page 253
    10. Stereotactic radiosurgery: Radiobiology and physics aspects of treatment
    1. Page 253
      Introduction
    2. Page 254
      Treatment planning and dose prescription
    3. Page 255
      Treatment delivery
      1. Page 255
        Treatment delivery techniques
      2. Page 259
        Frame-based procedures
      3. Page 259
        Frameless procedures
    4. Page 261
      Stereotactic body radiotherapy (SBRT)
    5. Page 261
      Radiobiological aspects of SRS/SRT
      1. Page 262
        The radiosensitivity of the brain
    6. Page 264
      Radiosurgery of radiation-induced secondary (intracranial) tumours
    7. Page 265
      References
  15. Page 269
    11. Total body irradiation: Radiobiology and physics aspects of treatment
    1. Page 269
      Introduction
    2. Page 270
      Physics and technical aspects of TBI
    3. Page 274
      TBI dose prescription
      1. Page 275
        Inhomogeneity compensation in TBI
      2. Page 276
        Set-up procedure
      3. Page 277
        In vivo dosimetry in TBI
      4. Page 278
        Quality assurance in TBI
    4. Page 279
      Radiobiological aspects of TBI
      1. Page 279
        The hematopoietic system
      2. Page 280
        The spinal cord
      3. Page 280
        The lung
      4. Page 281
        TBI treatment
    5. Page 281
      Clinical trials
    6. Page 282
      References
  16. Page 285
    12. Electron therapy: Radiobiology and physics aspects of treatment
    1. Page 285
      Introduction
    2. Page 286
      Production of electron beams
    3. Page 288
      Electron interactions
    4. Page 290
      Electron dose distribution
      1. Page 292
        Percentage depth dose curve of an electron beam
    5. Page 294
      Electron therapy treatment planning
      1. Page 294
        Lead skin collimation
      2. Page 294
        Internal shielding
      3. Page 295
        Bolus
      4. Page 296
        Electron field abutment
      5. Page 296
        Tissue heterogeneities
    6. Page 296
      Total skin electron therapy (TSET)
    7. Page 298
      Intraoperative Electron Radiation Therapy (IOERT)
    8. Page 302
      Electron boost radiotherapy
    9. Page 302
      Modulated Electron Radiotherapy (MERT)
    10. Page 304
      References
  17. Page 309
    13. External beam hadron radiotherapy
    1. Page 309
      Radiobiology
    2. Page 314
      Medical accelerators
    3. Page 314
      Beam shaping
    4. Page 316
      Clinical studies of proton beam radiotherapy
    5. Page 319
      Protons versus Intensity Modulated Radiotherapy (IMRT)
      1. Page 319
        Dose distributions
    6. Page 320
      Heavy Ion Therapy (HIT)
    7. Page 321
      Clinical studies of carbon ion radiotherapy
    8. Page 324
      Conclusions
    9. Page 324
      References
  18. Page 327
    14. Fast neutron therapy
    1. Page 327
      Introduction
    2. Page 328
      Radiobiology
      1. Page 328
        Hypoxia
      2. Page 329
        Cell cycle effects
      3. Page 329
        Repair of Potentially Lethal Damage (PLD)
      4. Page 329
        RBE effects
    3. Page 332
      Clinical results
      1. Page 332
        Soft tissue sarcoma
      2. Page 333
        Prostate cancer
      3. Page 333
        Head & neck cancer
      4. Page 334
        Conclusions
    4. Page 334
      Neutron sources
    5. Page 335
      Neutron brachytherapy
    6. Page 340
      References
  19. Page 345
    15. Targeted radiotherapy for cancer
    1. Page 345
      Introduction
    2. Page 346
      Binary therapies
      1. Page 347
        Photodynamic therapy (PDT)
      2. Page 348
        Photoactivation therapy (PAT)
      3. Page 348
        Boron neutron capture therapy (BNCT)
      4. Page 350
        Gadolinium neutron capture therapy (GdNCT)
      5. Page 351
        The avidin-biotin effect
    3. Page 353
      Targeted alpha therapy (TAT)
      1. Page 353
        Background
      2. Page 354
        Alpha emitting radioisotopes
      3. Page 355
        Preclinical studies
      4. Page 357
        Clinical trial protocols
      5. Page 359
        Clinical trials
      6. Page 363
        Conclusions
    4. Page 364
      References
  20. Page 369
    16. Palliative radiotherapy
    1. Page 369
      Introduction
    2. Page 369
      Principles of palliative radiotherapy (PRT)
      1. Page 370
        Bone pain and bone metastasis
      2. Page 371
        Cerebral metastases
      3. Page 372
        Cerebral metastases
      4. Page 372
        Obstruction/compression symptoms
      5. Page 372
        Control of physical symptoms
    3. Page 372
      External beam radiotherapy with Cobalt-60 and 6 MV linac
    4. Page 375
      Comparative costs for C0-60 and Linacs
      1. Page 375
        Comparative radiotherapy technical costs in USA
    5. Page 376
      Palliative treatment by unsealed sources of radiopharmaceuticals for bone metastases of cancer
      1. Page 379
        Clinical practice
      2. Page 379
        Therapeutic procedure
      3. Page 380
        Conclusions
    6. Page 380
      Multidisciplinary care and telemedicine
    7. Page 381
      Consensus and recommendations
    8. Page 381
      References
  21. Page 383
    17. Predictive assays
    1. Page 383
      Introduction
    2. Page 383
      Predictive assays
      1. Page 384
        Predictive assays for tumour response
      2. Page 391
        Predictive assays for normal tissue response
    3. Page 393
      Disease staging
    4. Page 393
      Treatment assessment
      1. Page 394
        Dose volume histograms
    5. Page 395
      References
  22. Page 399
    18. Elements of health physics
    1. Page 399
      Radiation response and tolerance of normal tissue
    2. Page 400
      Low level irradiation
    3. Page 400
      Deterministic and stochastic effects of radiation
      1. Page 401
        Deterministic effects
      2. Page 401
        Stochastic effects
      3. Page 401
        Detriment
    4. Page 402
      Radiation hormesis
    5. Page 403
      Natural background radiation
    6. Page 404
      Bystander effects and adaptive responses to radiation
    7. Page 406
      Bystander effects and clinical implications
      1. Page 406
        Bystander effects and implications for head & neck cancer
      2. Page 407
        Bystander effects and implications for prostate cancer
      3. Page 408
        Bystander effects and implications for lung cancer
    8. Page 408
      Radiation incidents and radiation accidents in medical environment
    9. Page 409
      Biological dosimetry
    10. Page 410
      Radioprotectors
    11. Page 412
      Risk of second cancer development following radiation therapy
      1. Page 414
        Evaluations of the second primary cancer risk
      2. Page 414
        Estimation of second primary cancer risks using radiation dosimetric data and risk models
      3. Page 418
        Peripheral photon and neutron doses from cancer external beam irradiation and the risk of second primary cancers
    12. Page 419
      References
  23. Page 441
    Index

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