# Radiation Oncology/Hyperthermia

* Front Page: Radiation Oncology | RTOG Trials | Randomized Trials
Hyperthermia
* Hyperthermia uses higher temperatures than diathermy, which is the deep heating of body tissue for relaxation or physical therapy
* When combined with radiation therapy, it is called thermoradiotherapy
Hyperthermic intraperitoneal chemotherapy
* Intraperitoneal hyperthermic chemoperfusion (HIPEC or IPHC) is a type of hyperthermia therapy used in combination with surgery in the treatment of advanced abdominal cancers
* In this procedure, warmed anti-cancer medications are infused and circulated in the peritoneal cavity (abdomen) for a short period of time
* The chemotherapeutic agents generally infused during IPHC are mitomycin-C and cisplatin
* Santiago González-Moreno, et al. World J Gastrointest Oncol. 2010 Feb 15; 2(2): 68–75. Hyperthermic intraperitoneal chemotherapy: Rationale and technique (PMID: 21160924)
Whole-body hyperthermia
* Subpage: Level I evidence
* Breast cancer
* Melanoma
* Cervical cancer

## RT +/- Hyperthermia

* Duke (1994-2001)
** Randomized. 109 patients with superficial tumors (<= 3cm depth); breast 65%, H&N 13%, melanoma 10%. Tumors had to be "heatable" on initial HT. Arm 1) RT alone vs. Arm 2) RT + HT. Hyperthermia to >43C x1 hour, 2x/week. RT dose 30-60 Gy if previous RT, otherwise 60-70 Gy in 1.8-2.0 Gy/fx
** 2005 PMID 15860867 -- "Randomized trial of hyperthermia and radiation for superficial tumors." (Jones EL, J Clin Oncol. 2005 May 1;23(13):3079-85.)
*** Outcome: CR RT 42% vs. RT+HT 66% (SS). Patients with prior RT had most benefit (68% vs. 23%, SS)
*** Toxicity: Well tolerated, 1 Grade III thermal burn
*** Conclusion: Significant local control benefit for HT
* International Collaborative Hyperthermia Group (1988-1991) -- combined results from 5 PIII trials
** Randomized. 5 trials merged due to slow accrual, closed early after benefit. 306 patients. Advanced primary or recurrent BCA; 50% active disease outside treatment area. Could have had prior RT. Trials: Dutch Hyperthermia Group (DHG), Medical Research Council (MRC BrI and BrR), European Society of Hyperthermic Oncology (ESHO), and Princes Margaret (PMH). Target hyperthermia 43C. RT given in various fractions.
** 1996 PMID 8690639 -- "Radiotherapy with or without hyperthermia in the treatment of superficial localized breast cancer: results from five randomized controlled trials. International Collaborative Hyperthermia Group." (Vernon CC, Int J Radiat Oncol Biol Phys. 1996 Jul 1;35(4):731-44.)
*** Outcome: CR RT 41% vs. RT+HT 59% (SS); greatest effect in recurrent lesions in previous RT, where re-irradiation dose was low. 2-year OS ~40% (NS), 74% patients progressed outside HT area during follow-up
*** Conclusion: Combined result demonstrated efficacy of hyperthermia as adjunct to RT for treatment of recurrence
* RTOG, 1991 PMID 1903023 -- "Randomized phase III study comparing irradiation and hyperthermia with irradiation alone in superficial measurable tumors. Final report by the Radiation Therapy Oncology Group." (Perez CA, Am J Clin Oncol 1991 Apr;14(2):133-41.)
** Randomized. 307 patients with superficial tumors. Treated with RT alone or RT + HT (following, to 42.5C for 45-60 min)
** Response: CR RT 30% vs. RT+HT 32%; improved LC in tumors <3cm
** Toxicity: comparable, but 30% thermal blisters in heated tumors

## Timing of Hyperthermia

* Jefferson, 1993 (1983-1990) PMID 8515137 -- "Randomized trial of one versus two adjuvant hyperthermia treatments per week in patients with superficial tumours." (Engin K, Int J Hyperthermia. 1993 May-Jun;9(3):327-40.)
** Randomized. 41 patients with 44 superficial tumors. Treated with QW vs. BIW HT + RT (mean dose 45 Gy)
** 2-month CR: 59% QW HT vs. 55% BIW HT
** Predictive factors for CR: RT dose, tumor volume; Predictive factors for duration of response: minimum tumor temperature, tumor volume
** Toxicity: No difference.
** Conclusion: No difference in response or duration between once weekly and twice weekly hyperthermia

## Duration of Hyperthermia

* Temperature should be converted to 43 celsius-equivalent minutes
** Each 1C above 43C requires 1/2 time for equivalent thermal damage (e.g. 1 min @ 45C = 4 min @ 43C)
** Each 1C below 43C requires 4x increase in time for equivalent thermal damage (e.g. 1 min @ 42C = 0.25 min @ 43C)
** t$_2$/t$_1$ = 2^(Temp1-Temp2)

## Hyperthermic Intraperitoneal Chemotherapy (HIPEC)

* S J Valle et al. Hyperthermic Intraperitoneal Chemotherapy (HIPEC) Methodology, Drugs and Bidirectional Chemotherapy. Indian J Surg Oncol. 2016 Jun;7(2):152-9. (PMID: 27065705)
* Wim Ceelen et al. Hyperthermic Intraperitoneal Chemotherapy: A Critical Review. Cancers (Basel). 2021 Jun 22;13(13):3114. (PMID: 34206563)