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)
  • t₂/t₁ = 2^(Temp1-Temp2)