Timothy D. Malouff is an emerging leader in particle therapy. He has published and presented extensively on a variety of topics related to particle therapy, including proton therapy, carbon ion therapy, boron neutron capture therapy, and other heavy ion therapy. Dr. Malouff’s research goals include critically evaluating and expanding the indications for “novel” radiation modalities, including particle therapy. Outside of the clinic, Dr. Malouff enjoys spending time with his family.Daniel M. Trifiletti as an international leader in radiation oncology and stereotactic radiosurgery at the Mayo Clinic, the research of Dr. Trifiletti includes numerous clinical studies involving radiation, surgery and drug therapies in the treatment of tumors. Dr. Trifiletti’s short-term research goals focus on describing the impact of radiation on the priming of the brain tumor microenvironment. Discovering the biological underpinnings of radiation priming will allow for novel, “game-changing” cancer therapies, rapid translation to early-stage clinical trials and, ultimately, improved outcomes in patients with fatal diseases.

• Preface viiList of Contributors ixForeword xiiiAbbreviations xviiSection I: Background 11 A Brief History of Particle Radiotherapy 32 The Physics of Particle Therapy 113 The Radiobiology of Particle Therapy 274 Practical Aspects of Particle Therapy Accelerators 475 Treatment Planning for Scanning Beam Proton Therapy 556 Image-Guided Particle Therapy and Motion Management 817 Advanced Particle Therapy Delivery: A Review of Advanced Techniques for Particle Therapy Delivery 1018 FLASH Radiotherapy 1159 Boron Neutron Capture Therapy 12110 Grid Therapy 13711 Particle Therapy and the Immune System 15112 The Economics of Particle Therapy 165Section II: Particle Therapy by Clinical Indication 17713 Intracranial Tumors: Principles and Practice of Particle Therapy 17914 Ocular Malignancies 20115 Brain, Skull Base, and Spinal Tumors 22516 Head and Neck Cancers 23917 Thoracic Malignancies: Proton Beam and Carbon-ion Therapy for Thoracic Cancers and Recurrent Disease 26118 Gastrointestinal Tumors 28719 Hepatobiliary Cancers 31120 Breast Cancer 35721 Prostate Cancer 38322 Non-prostate Genitourinary Cancers 41123 Gynecologic Cancers 42524 Lymphoma and Leukemia 44525 Sarcomas and Soft Tissue Malignancies 46526 Pediatric Central Nervous System Tumors 48327 Particle Therapy for Non-CNS Pediatric Malignancies 495Index 521

Timothy D. Malouff is an emerging leader in particle therapy. He has published and presented extensively on a variety of topics related to particle therapy, including proton therapy, carbon ion therapy, boron neutron capture therapy, and other heavy ion therapy. Dr. Malouff’s research goals include critically evaluating and expanding the indications for “novel” radiation modalities, including particle therapy. Outside of the clinic, Dr. Malouff enjoys spending time with his family.Daniel M. Trifiletti as an international leader in radiation oncology and stereotactic radiosurgery at the Mayo Clinic, the research of Dr. Trifiletti includes numerous clinical studies involving radiation, surgery and drug therapies in the treatment of tumors. Dr. Trifiletti’s short-term research goals focus on describing the impact of radiation on the priming of the brain tumor microenvironment. Discovering the biological underpinnings of radiation priming will allow for novel, “game-changing” cancer therapies, rapid translation to early-stage clinical trials and, ultimately, improved outcomes in patients with fatal diseases.

• Preface viiList of Contributors ixForeword xiiiAbbreviations xviiSection I: Background 11 A Brief History of Particle Radiotherapy 32 The Physics of Particle Therapy 113 The Radiobiology of Particle Therapy 274 Practical Aspects of Particle Therapy Accelerators 475 Treatment Planning for Scanning Beam Proton Therapy 556 Image-Guided Particle Therapy and Motion Management 817 Advanced Particle Therapy Delivery: A Review of Advanced Techniques for Particle Therapy Delivery 1018 FLASH Radiotherapy 1159 Boron Neutron Capture Therapy 12110 Grid Therapy 13711 Particle Therapy and the Immune System 15112 The Economics of Particle Therapy 165Section II: Particle Therapy by Clinical Indication 17713 Intracranial Tumors: Principles and Practice of Particle Therapy 17914 Ocular Malignancies 20115 Brain, Skull Base, and Spinal Tumors 22516 Head and Neck Cancers 23917 Thoracic Malignancies: Proton Beam and Carbon-ion Therapy for Thoracic Cancers and Recurrent Disease 26118 Gastrointestinal Tumors 28719 Hepatobiliary Cancers 31120 Breast Cancer 35721 Prostate Cancer 38322 Non-prostate Genitourinary Cancers 41123 Gynecologic Cancers 42524 Lymphoma and Leukemia 44525 Sarcomas and Soft Tissue Malignancies 46526 Pediatric Central Nervous System Tumors 48327 Particle Therapy for Non-CNS Pediatric Malignancies 495Index 521

Timothy D. Malouff is an emerging leader in particle therapy. He has published and presented extensively on a variety of topics related to particle therapy, including proton therapy, carbon ion therapy, boron neutron capture therapy, and other heavy ion therapy. Dr. Malouff’s research goals include critically evaluating and expanding the indications for “novel” radiation modalities, including particle therapy. Outside of the clinic, Dr. Malouff enjoys spending time with his family.Daniel M. Trifiletti as an international leader in radiation oncology and stereotactic radiosurgery at the Mayo Clinic, the research of Dr. Trifiletti includes numerous clinical studies involving radiation, surgery and drug therapies in the treatment of tumors. Dr. Trifiletti’s short-term research goals focus on describing the impact of radiation on the priming of the brain tumor microenvironment. Discovering the biological underpinnings of radiation priming will allow for novel, “game-changing” cancer therapies, rapid translation to early-stage clinical trials and, ultimately, improved outcomes in patients with fatal diseases.

• Preface viiList of Contributors ixForeword xiiiAbbreviations xviiSection I: Background 11 A Brief History of Particle Radiotherapy 32 The Physics of Particle Therapy 113 The Radiobiology of Particle Therapy 274 Practical Aspects of Particle Therapy Accelerators 475 Treatment Planning for Scanning Beam Proton Therapy 556 Image-Guided Particle Therapy and Motion Management 817 Advanced Particle Therapy Delivery: A Review of Advanced Techniques for Particle Therapy Delivery 1018 FLASH Radiotherapy 1159 Boron Neutron Capture Therapy 12110 Grid Therapy 13711 Particle Therapy and the Immune System 15112 The Economics of Particle Therapy 165Section II: Particle Therapy by Clinical Indication 17713 Intracranial Tumors: Principles and Practice of Particle Therapy 17914 Ocular Malignancies 20115 Brain, Skull Base, and Spinal Tumors 22516 Head and Neck Cancers 23917 Thoracic Malignancies: Proton Beam and Carbon-ion Therapy for Thoracic Cancers and Recurrent Disease 26118 Gastrointestinal Tumors 28719 Hepatobiliary Cancers 31120 Breast Cancer 35721 Prostate Cancer 38322 Non-prostate Genitourinary Cancers 41123 Gynecologic Cancers 42524 Lymphoma and Leukemia 44525 Sarcomas and Soft Tissue Malignancies 46526 Pediatric Central Nervous System Tumors 48327 Particle Therapy for Non-CNS Pediatric Malignancies 495Index 521