HYPERTHERMIA, 한국의학물리학회에 바란다. 영남대학교 의과대학 방사선종양학교실 김명세
회원 여러분, 환영 합니다.
감사 드립니다. • 회장님, 회원 여러분! • 귀중한 시간.
2000년 ICHO 세계온열종양학회 -의학물리학회 협조 -성공적인 학회 개최 가능.
HYPERTHERMIA • Elevation of temperature to supraphysiologic level, between 40ºC-45ºC • 45ºC : Thermal ablation
HYPERTHERMIA • BIOLOGIC RATIONALE 1. Direct cytotoxicity 2. Radiosensitizer 3. Chemosensitizer 4. Gene therapy 5. Protein denature
HYPERTHERMIA • Direct cytotoxicity - 43. 5ºC : cell die exponentially 43. 5 (breakpoint) - Rate of killing: increase with temperature (1ºC : doubles the rate of cell killing) (Gunderson & Tepper, clinical Radiation Oncology, 385 p, 2007)
HYPERTHERMIA 2. Radiosensitizer - Inhibits potentially lethal & sublethal damage repair. - DNA repair process: heat sensitive. : No repair of chromosomal aberration by radiation.
HYPERTHERMIA 2. Radiosensitizer • Reoxigenation in periphery at 40ºC - 42ºC : Improve hypoxic, radiosensitive • In tumor: vascular stasis - Arteriovenous shunting, thrombus formation. leucocyte plugging. - Vascular permeability - edema. stasis. - Anaerobic metabolism : Lactic acid , p. H : sensitive to HT,
HYPERTHERMIA 3. Chemosensitizer • Many chemotherapeutic agents: synergism with HT. • Mechanism 1) Increased cellular uptake 2) Increased oxygen radical production 3) Increased DNA damage & inhibition of repair
HYPERTHERMIA 3. Chemosensitizer • Chemotherapy agents: Loaded into liposomes (100 nm diameter) -HT augment liposome drug delivery. -Liposome: do not extravasate at normothermia, but do at 40 -42ºC - even brain is sensitive
HYPERTHERMIA 3. Chemosensitizer • Most chemotherapy: sensitive, esp. 5 -FU: supraadditive with HT between 39 -41ºC • 5 FU: continuous infusion-Lead to cell cycle block in S phase, relatively sensitive part to HT. • Reversal of drug resistance mechanisms • Topoisomerase II activity - activity of drug (>41. 8ºC )
HYPERTHERMIA 4. Gene therapy • Heat shock protein: potential role in regulating immune responses. • 42ºC, 30 min. : Several hundredfold induction of reporter protein expression under control of the HSP 70 promotor. • Improved tumor growth delay in B 16 melanoma model. • + RT: superior result
HYPERTHERMIA 4. Gene therapy *HT : effective in altering both adaptive & innate immunity. * 40ºC : could accelerate immune reactivity.
HYPERTHERMIA • Protein denaturation : ≥ 40ºC - Apoptosis & necrosis.
HYPERTHERMIA In clinics • Hyperthermia alone : No long term tumor control - Widely practiced in alternative & complementary medicine • HT + RT - Clinical response rate: almost doubled in randomized &/or non randomized.
Rectal ca.
HYPERTHERMIA In clinics • Trimodality with HT + RT + Chemo. TX. - Ongoing randomized trial - Cervical cancer, colorectal cancer, esophageal cancer, brain tumor, Head & neck tumor, bladder tumor, pelvic tumor : Not finished, but favorable results.
HYPERTHERMIA In clinics • In triple treatment(HT+RT+CT) - Almost 100% local control. • No complication, except mild burn. -- Accident due to carelessness.
HYPERTHERMIA WHY NOT POPULAR? In Clinics • Time consuming: about 1 hr. for 1 Tx. • At least one doctor/ nurse/ technician should keep the patient. • In many clinical trials: good results, but no real time confidence.
HIFU(High Intensity Focused Ultrasound)
HYPERTHERMIA WHY NOT POPULAR? In Physics In International J Hyperthermia (2007. 2) 90%: Physics field.
HYPERTHERMIA WHY NOT POPULAR? In Physics • Homogenous temperature in target volume • Define temperature range precise and reproducible manner. • Non invasive dosimetry x • Should be visible, easy application
PROBLEMS? • Non invasive thermometry+ - still not use in most clinics • Cancer Tx. : Surgery + RT + Chemo. Tx. - Overall survival: ~40% - Very expensive • Complementary & Integrative Medicine (보완통합의학회)
보완통합의학? • 대체의학 : 질병 치료에 효능이 있다고 주장하지만, 정통 서양의학의 관점에서 볼때 그 효능 을 입증할만한 객관적이고 과학적인 근 거가 부족한 치료법. (대한보완통합의학회지 4(1) S-19, 2007) • 미국, 대체의학 비용: 40 -60% 의료보험비 지급 WHY NOT HYPERTHERMIA?
HYPERTHERMIA *Even with the limitations of current technology, the promise of HT is emerging from the clinical trials. • As the technology improves, the benefits will only become more visible. (Gunderson & Tepper. Clinical Radiation Oncology. 385 p, 2007)
성공하는 사람들은 길에 눈이 쌓여도, 눈을 밟아가며 길을 나서지만, 실패하는 사람들은 눈이 녹기를 기다렸다가 길을 떠난다
내겐 당신이 있습니다! 내 부족함을 채워주는 사람, 당신의 사랑이 쓰러진 나를 일으킵니다. 내게 용기, 위로, 소망을 주는 당신, 내가 나를 버려도 나를 포기하지 않는 당신, 나를 사랑하는 이가 이 세상에 존재 한다는것, 그것이 내 삶의 가장 커다란 힘입니다. 저의 힘이 되어주신 여러분, 다시 한번 감사 드립니다!
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