Oncothermia: Principles and Practices

ABOUT THIS BOOK

Oncothermia is the next generation medical innovation that delivers selective, controlled and deep energy for cancer treatment. The basic principles for oncothermia stem from oncological hyperthermia, the oldest approach to treating cancer. Nevertheless, hyperthermia has been wrought with significant controversy, mostly stemming from shortcomings of controlled energy delivery. Oncothermia has been able to overcome these insufficiencies and prove to be a controlled, safe and efficacious treatment option.

This book is the first attempt to elucidate the theory and practice of oncothermia, based on rigorous mathematical and biophysical analysis, not centered on the temperature increase. It is supported by numerous in-vitro and in-vivo findings and twenty years of clinical experience. This book will help scientists, researchers and medical practitioners in understanding the scientific and conceptual underpinnings of oncothermia and will add another valuable tool in the fight against cancer.

Professor Andras Szasz is the inventor of oncothermia and the Head of St Istvan University's Biotechnics Department in Hungary. He has published over 300 papers and lectured at various universities around the world. Dr. Oliver Szasz is the managing director of Oncotherm, the global manufacturer and distributor of medical devices for cancer treatment used in Europe & Asia since the late 1980s. Dr. Nora Szasz is currently a management consultant in healthcare for McKinsey & Co.

Content Level » Professional/practitioner

Keywords » bioelectromagnetism - heat-therapy - hyperthermia - oncology - radiofrequency

Related subjects » Applications - Cancer Research - Cell Biology - Education & Language - Life Sciences, Medicine & Health - Oncology & Hematology

TABLE OF CONTENTS

OBJECTIVE OF THE BOOK 1. ONCOLOGY – TREATMENTS AND THEIR LIMITS 1.1. CANCER – SHORT HISTORY AND EFFORTS TO CURE 1.1.1. Historical notes 1.1.2. The “war” against cancer 1.2. PARADIGM AND CHALLENGES OF ONCOTHERAPIES 1.3. LIMITATIONS OF ONCOTHERAPIES – QUEST FOR STEPS FORWARD 1.3.1. Medical challenge of oncotherapies 1.3.2. Ethical challenge of oncotherapies 1.3.3. Evaluation challenge of the results 2. HYPERTHERMIA RESULTS AND CHALLENGES 2.1. HYPERTHERMIA APPROACH 2.1.1. Definition of hyperthermia in oncology 2.1.2. Basic concepts of oncological hyperthermia 2.1.3. Technical variations of hyperthermia in oncology 2.2. EFFECTS OF HYPERTHERMIA 2.2.1. Higher baseline temperature 2.2.2. Vascular changes 2.2.3. Cellular membrane changes 2.2.4. Lactic acid formation 2.2.5. ATP depletion 2.2.6. Altered DNA replication 2.2.7. Enhanced immune reaction 2.2.8. Pain reduction 2.2.9. Selective gain of the heat-resistance 2.3. CLINICAL ONCOLOGICAL HYPERTHERMIA 2.3.1. Local and whole-body heating 2.3.2. Hyperthemia as a complementary method 2.4. HYPERTHERMIA SUCCESSES 2.4.1. Brain tumor treatments by hyperthermia 2.4.2. Pancreas tumor treatment by hyperthermia 2.4.3. Lung and bronchus 2.4.4. Hepatocellular carcinoma and metastatic tumors of liver 2.4.5. Colo-rectal tumors 2.4.6. Esophagus 2.4.7. Head and neck localizations 2.4.8. Gastric tumors 2.4.9. Breast tumors 2.4.10. Other localizations treated by hyperthermia 2.5. HYPERTHERMIA CHALLENGES IN ONCOLOGY 2.5.1. Challenge of selection and focus 2.5.2. Challenge of temperature 2.5.3. Medical challenges of hyperthermia in oncology 2.5.4. Challenge on quality control and dosimetry of hyperthermia 2.5.5. What we expect? 2.5.6. Possible solution: oncothermia 3. THERMO-BIO-PHYSICS 3.1. FACTORS OF PHYSIOLOGY HEATING 3.2. BIOTHERMODYNAMICS 3.2.1. Energy, heat and temperature 3.2.2. Energy of the chemical bonds and reactions 3.2.3. Energy sources and driving forces 3.2.4. Energy and structure 3.2.5. Energetics of malignant cells 3.2.6. “Non-thermal” effects – thermodynamial approach 3.3. BIOELECTRODYNAMICS 3.3.1. Basic interactions 3.3.2. The bioimpedance 3.3.3. “Nonthermal effects” – electrodynamical appraoch 3.3.4. “Non-thermal effects” – approach of electric currents 3.3.5. Membrane effects 3.3.6. Stochastic processes 3.3.7. Noises and signals 3.3.8. Resonances 3.3.9. Modulation-demodulation 3.3.10. Special field-effects of bio-systems 4. ONCOTHERMIA – NEW KIND OF ONCOLOGIC HYPERTHERMIA 4.1. ONCOTHERMIA CHARACTERISTICS 4.1.1. Electro Cancer Therapy (ECT) 4.1.2. Concept of oncothermia 4.1.3. Pennes equation revised 4.1.4. Thermal limit problem 4.1.5. Energy-transfer through the body surface 4.1.6. Penetration depth 4.1.7. Arrangement of electrodes 4.1.8. Far from equilibrium 4.1.9. Energy intake and temperature 4.1.10. Macroscopic focusing on the tumor 4.1.11. Heating the extracellular electrolyte 4.1.12. Temperature gradient and heat-flow on the membrane 4.1.13. Changes of the membrane potential 4.1.14. Membrane damage by constrained ion-currents 4.1.15. Effect on cell-cell connections 4.1.16. Oncotherm comparison 4.2. ONCOTHERMIA TREATMENT GUIDELINES 4.2.1. Treatment planning 4.2.2. Treatment consensus 4.3. COMPLEMENTARY APPLICATIONS 4.3.1. Complementary to radiotherapy 4.3.2. Complementary to chemotherapy 4.3.3. Clinical toxicity, safety 4.4. ONCOTHERMIA CASE REPORTS 4.4.1. Near eye treatments 4.4.2. Brain cases 4.4.3. Gynecology cases 4.4.4. Gastrointestinal cases 4.4.5. Pulmonary cases 4.4.6. Other cases 4.5. EVALUATION OF ONCOTHERMIA STUDIES 4.5.1. Evaluation conditions 4.5.2. Evaluation methods 4.6. GENERAL OVERVIEW ON A LARGE PATIENT’S POOL 4.7. BRAIN STUDIES 4.7.1. Brain safety study (Phase I) 4.7.2. Brain efficacy study (Phase II) 4.7.3. Hungarian brain glioma study 4.7.4. Small prospective, double arm brain glioma study 4.7.5. Study of brain gliomas with local clinical responses 4.7.6. Brain glioma study with relapses 4.7.7. Bicentral brain glioma study 4.7.8. Oncothermia for heavy pre-treated & relapsed brain gliomas 4.7.9. Study of metastatic brain tumors 4.7.10. Comparison of oncothermia brain studies 4.8. PANCREAS STUDIES 4.8.1. Pancreas efficacy study I. 4.8.2. Pancreas efficacy study II. (HTT) 4.8.3. Additional historical control to HTT pancreas study 4.8.4. Comparison of pancreas efficacy studies I. & II. 4.8.5. Pancreas efficacy study III. 4.8.6. Pancreas efficacy study IV. 4.8.7. Other oncothermia pancreas studies and their comparison 4.9. LUNG STUDIES 4.9.1. Oncothermia lung study I. 4.9.2. Oncothermia lung study II. 4.9.3. Meta-analysis of oncothermia lung studies 4.9.4. Compare to historical control 4.10. LIVER STUDIES 4.10.1. Study of liver metastases colorectal origine 4.10.2. Study of advanced liver metastases colorectal origine II. 4.10.3. Comparison study of treatment lines of colorectal liver metastases 4.10.4. Study of platinum derivatives with oncothermia for liver metastases from colorectal origine 4.10.5. Study of liver metastases rectal origine 4.10.6. Study of liver metastases various origine 4.10.7. Study of far advanced liver metastases various origines. Comparison of complementary therapies 4.11. COMPARISON OF STUDIES OF LIVER METASTASES 4.12. GYNECOLOGICAL (PELVIC) CANCER STUDY 4.12.1. Ovary study 4.12.2. Uterine corpus cancer 4.12.3. Uterine cervix 4.12.4. Comparison of oncothermia in pelvic gynecology 4.13. BREAST STUDY 4.14. ESOPHAGUS STUDY 4.14.1. Esophagus study I. 4.14.2. Esophagus study II. 4.15. STOMACH STUDY 4.16. COLO-RECTAL STUDIES 4.16.1. Preoperative oncothermia for rectum carcinoma 4.16.2. Colorectal carcinoma study 4.17. BONE STUDIES 4.17.1. Refractory bone metastases complementary to radiotherapy 4.17.2. Advanced bone metastases monotherapy 4.17.3. Osteosarcoma study 4.18. KIDNEY STUDY 4.19. HEAD AND NECK STUDY 4.20. URINARY BLADDER MALIGNANCIES 4.21. SOFT-TISSUE MALIGNANCIES 4.22. PROSTATE STUDY 4.23. ONCOTHERMIA PERSPECTIVES APPENDIX 1 ENTROPY AND TEMPERATURE APPENDIX 2 THERMODYNAMICS – ONSAGER’S RELATION APPENDIX 3 SELF-SIMILARITY AND BIOSCALING APPENDIX 4 ENERGY SUPPLY BY DEMANDS APPENDIX 5 ONCOGENIC GROWTH APPENDIX 6 BASIC BIOELECTROMAGNETICS APPENDIX 7 BIOIMPEDANCE OF CELLS & TISSUES APPENDIX 8 BOUNDARY CONDITIONS APPENDIX 9 DIRECT CURRENT APPLICATIONS APPENDIX 10 DEVELOPMENT OF EDEMA APPENDIX 11 WARBURG-IMPEDANCE APPENDIX 12 CELL-MEMBRANE PERMEABILITY APPENDIX 13 STOCHASTIC PROCESSES – PINK-NOISE APPENDIX 14 AUTOCORRELATION APPENDIX 15 DISSIPATIVE SYSTEMS APPENDIX 16 STOCHASTIC RESONANCE APPENDIX 17 RESONANCE OF ENZYMATIC REACTIONS APPENDIX 18 DEMODULATION BY STOCHASTIC RESONANCE APPENDIX 19 NON-LINEAR EFFECTS OF ENERGY-FLOW APPENDIX 20 PRINCIPLE OF MINIMAL ENERGY-DISPERSION APPENDIX 21 CHARGE-INHOMOGENETIES APPENDIX 22 PENNES’ EQUATION APPENDIX 23 PENNES’ EQUATION IS REVISED APPENDIX 24 SELF-FOCUSING APPENDIX 25 DYNAMISM OF TEMPERATURE ON THE MEMBRANE APPENDIX 26 CHANGES OF THE MEMBRANE-POTENTIAL APPENDIX 27 MEMBRANE DAMAGE BY INCREASING PRESSURE APPENDIX 28 DYNAMICS OF ADHERENT BONDS APPENDIX 29 MODULATION EFFECT APPENDIX 30 COMPONENTS OF CELL-DESTRUCTION APPENDIX 31 EXPERIMENTAL CONDITIONS IN VITRO APPENDIX 32 EXPERIMENTAL CONDITIONS IN VIVO APPENDIX 33 CONSIDERATIONS FOR EXPERIMENTAL SETUP IN VIVO APPENDIX 34 VALIDATION OF MORPHOLOGIC EVALUATION APPENDIX 35 EVALUATION OF SURVIVAL STUDY WITH SINGLE ARM 5. ACKNOWLEDGEMENT 6. REFERENCES