Hyperthermia

Safety and precautions

In general, the toxicity of hyperthermic treatments is tolerable.¹Zivanovic O, Abramian A et al. HIPEC ROC I: a phase I study of cisplatin administered as hyperthermic intraoperative intraperitoneal chemoperfusion followed by postoperative intravenous platinum-based chemotherapy in patients with platinum-sensitive recurrent epithelial ovarian cancer. International Journal of Cancer. 2014; 136: 699–708; Choi M, Harper MM et al. A multicenter phase 1 trial evaluating nanoliposomal irinotecan for heated intraperitoneal chemotherapy combined with cytoreductive surgery for patients with peritoneal surface disease. Annals of Surgical Oncology. 2023 Feb;30(2):804-813; Reutovich MY, Krasko OV, Sukonko OG. Hyperthermic intraperitoneal chemotherapy in serosa-invasive gastric cancer patients. European Journal of Surgical Oncology. 2019 Dec;45(12):2405-2411; van der Kaaij RT, Wassenaar ECE et al. Treatment of PERItoneal disease in Stomach Cancer with cytOreductive surgery and hyperthermic intraPEritoneal chemotherapy: PERISCOPE I initial results. British Journal of Surgery. 2020 Oct;107(11):1520-1528; Yoo HJ, Lim MC et al. Phase I/II clinical trial of modulated electro-hyperthermia treatment in patients with relapsed, refractory or progressive heavily treated ovarian cancer. Japanese Journal of Clinical Oncology. 2019 Sep 1;49(9):832-838; Fosmire H, Hynynen K et al. Feasibility and toxicity of transrectal ultrasound hyperthermia in the treatment of locally advanced adenocarcinoma of the prostate. International Journal of Radiation Oncology, Biology, Physics. 1993 May 20;26(2):253-9; Lustosa RJC, Batista TP et al. Quality of life in a phase 2 trial of short-course hyperthermic intraperitoneal chemotherapy (HIPEC) at interval debulking surgery for high tumor burden ovarian cancer. Revista do Colégio Brasileiro de Cirurgiões. 2020;47:e20202534. Portuguese, English; Koole SN, Kieffer JM et al. Health-related quality of life after interval cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with stage III ovarian cancer. European Journal of Surgical Oncology 2019; S0748-7983(19): 30444–30445; Van Vulpen M, De Leeuw JR et al. A prospective quality of life study in patients with locally advanced prostate cancer, treated with radiotherapy with or without regional or interstitial hyperthermia. International Journal of Hyperthermia. 2003 Jul-Aug;19(4):402-13; Cashin PH, Mahteme H. Quality of life and cost effectiveness in a randomized trial of patients with colorectal cancer and peritoneal metastases. European Journal of Surgical Oncology. 2018 Jul;44(7):983-990; Kim JH, Lee DE et al. Quality of life outcomes from the randomized trial of hyperthermic intraperitoneal chemotherapy following cytoreductive surgery for primary ovarian cancer (KOV-HIPEC-01). Journal of Gynecological Oncology. 2022 Jul;33(4):e54; Foster JM, Sleightholm R et al. Morbidity and mortality rates following cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy compared with other high-risk surgical oncology procedures. JAMA Network Open. 2019 Jan 4;2(1):e186847; Kukiełka AM, Hetnał M et al. Interstitial hyperthermia of the prostate in combination with brachytherapy: an evaluation of feasibility and early tolerance. Strahlentherapie und Onkologie. 2013 Jun;189(6):467-75; Sheng L, Ji Y, Wu Q, Du X. Regional hyperthermia combined with radiotherapy for esophageal squamous cell carcinoma with supraclavicular lymph node metastasis. Oncotarget. 2017 Jan 17;8(3):5339-5348; Varma S, Myerson R et al. Simultaneous radiotherapy and superficial hyperthermia for high-risk breast carcinoma: a randomised comparison of treatment sequelae in heated versus non-heated sectors of the chest wall hyperthermia. International Journal of Hyperthermia. 2012;28(7):583-90’ Wismeth C, Dudel C et al. Transcranial electro-hyperthermia combined with alkylating chemotherapy in patients with relapsed high-grade gliomas: phase I clinical results. Journal of Neuro-oncology. 2010 Jul;98(3):395-405; Hua Y, Ma S et al. Intracavity hyperthermia in nasopharyngeal cancer: a phase III clinical study. International Journal of Hyperthermia. 2011;27(2):180-6; Huilgol NG, Gupta S, Sridhar CR. Hyperthermia with radiation in the treatment of locally advanced head and neck cancer: a report of randomized trial. Journal of Cancer Research and Therapeutics. 2010;6(4):592-496. HIPEC with cytoreduction was found to be safe when performed in selected patients by experienced doctors.²Hughes MS, Lo WM. A phase II trial of cytoreduction and hyperthermic intraperitoneal chemotherapy for recurrent adrenocortical carcinoma. Journal of Surgical Research. 2018 Dec;232:383-388.

Side effects

These side effects were noted in published studies. Most were mild and seen in a minority of people receiving treatment,³Liebl CM, Kutschan S, Dörfler J, Käsmann L, Hübner J. Systematic review about complementary medical hyperthermia in oncology. Clinical and Experimental Medicine. 2022 Nov;22(4):519-565; Lindholm CE, Kjellén E, Nilsson P, Weber L, Hill S. Prognostic factors for tumour response and skin damage to combined radiotherapy and hyperthermia in superficial recurrent breast carcinomas. International Journal of Hyperthermia. 1995 May-Jun;11(3):337-55; Linthorst M, Baaijens M et al. Local control rate after the combination of re-irradiation and hyperthermia for irresectable recurrent breast cancer: results in 248 patients. Radiotherapy and Oncology. 2015 Nov;117(2):217-22; Seegenschmiedt HM, Karlsson UL et al. Superficial chest wall recurrences of breast cancer: prognostic treatment factors for combined radiation therapy and hyperthermia. Radiology. 1989 Nov;173(2):551-8; Cui, Shu-zhong et al. PILGRIM: Phase III clinical trial in evaluating the role of hyperthermic intraperitoneal chemotherapy for locally advanced gastric cancer patients after radical gastrectomy with D2 lymphadenectomy(HIPEC-01). Journal of Clinical Oncology. 2020;38(15 supplement):4538-4538; Engelhardt R, Muller U, Weth-Simon R, Neumann HA, Lohr GW. Treatment of disseminated malignant melanoma with cisplatin in combination with whole-body hyperthermia and doxorubicin. International Journal of Hyperthermia. 1990;6(3):511–515; Westermann AM, Grosen EA et al. A pilot study of whole body hyperthermia and carboplatin in platinum-resistant ovarian cancer. European Journal of Cancer. 2001 Jun;37(9):1111-7; Stewart CL, Gleisner A. Implications of hyperthermic intraperitoneal chemotherapy perfusion-related hyperglycemia. Annals of Surgical Oncology. 2018 Mar;25(3):655-659; Atanackovic D, Pollok K et al. Patients with solid tumors treated with high-temperature whole body hyperthermia show a redistribution of naive/memory T-cell subtypes. American Journal of Physiology. Regulatory, Integrative and Comparative Physiology. 2006 Mar;290(3):R585-94; Qiao G, Wang X et al. Immune correlates of clinical benefit in a phase I study of hyperthermia with adoptive T cell immunotherapy in patients with solid tumors. International Journal of Hyperthermia. 2019 Nov;36(sup1):74-82; Lundbech M, Krag AE et al. Postoperative bleeding and venous thromboembolism in colorectal cancer patients undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy: a systematic review and meta-analysis. International Journal of Colorectal Diseases. 2022 Jan;37(1):17-33; Beck M, Ghadjar P et al. Salvage-radiation therapy and regional hyperthermia for biochemically recurrent prostate cancer after radical prostatectomy (results of the planned interim analysis). Cancers (Basel). 2021 Mar 6;13(5):1133; Kukiełka AM, Hetnał M et al. Interstitial hyperthermia of the prostate in combination with brachytherapy: an evaluation of feasibility and early tolerance. Strahlentherapie und Onkologie. 2013 Jun;189(6):467-75; Robins HI, Rushing D et al. Phase I clinical trial of melphalan and 41.8 degrees C whole-body hyperthermia in cancer patients. Journal of Clinical Oncology. 1997 Jan;15(1):158-64. although some showed higher grade and more widespread effects:⁴Westermann AM, Wiedemann GJ et al. A Systemic Hyperthermia Oncologic Working Group trial. Ifosfamide, carboplatin, and etoposide combined with 41.8 degrees C whole-body hyperthermia for metastatic soft tissue sarcoma. Oncology 2003;64(4):312–321; Wiedemann GJ, Robins HI et al. Ifosfamide, carboplatin and etoposide (ICE) combined with 41.8 degrees C whole body hyperthermia in patients with refractory sarcoma. European Journal of Cancer. 1996;32a(5):888–892; Blum Murphy M, Ikoma N et al. Phase I trial of hyperthermic intraperitoneal chemoperfusion (HIPEC) with cisplatin, mitomycin, and paclitaxel in patients with gastric adenocarcinoma and associated carcinomatosis or positive cytology. Annals of Surgical Oncology. 2020 Aug;27(8):2806-2811; Hebert ME, Blivin JL, Kessler J, Soper JT, Oleson JR. Anaphylactoid reactions with intraperitoneal cisplatin. Annals of Pharmacotherapy. 1995 Mar;29(3):260-3; Kim YP, Choi Y et al. Conventional cancer treatment alone or with regional hyperthermia for pain relief in lung cancer: a case-control study. Complementary Therapies in Medicine. 2015 Jun;23(3):381-7; Classe JM, Meeus P et al; UNICANCER/CHIPOR Investigators. Hyperthermic intraperitoneal chemotherapy for recurrent ovarian cancer (CHIPOR): a randomised, open-label, phase 3 trial. Lancet Oncology. 2024 Nov 13:S1470-2045(24)00531-X.

Small studies have found concerns about an increased potential for severe kidney (renal) toxicity.⁵Richel O, Zum Vörde Sive Vörding PJ et al. Phase II study of carboplatin and whole body hyperthermia (WBH) in recurrent and metastatic cervical cancer. Gynecologic Oncology. 2004;95(3):680-685; Gerke P, Filejski W, Robins HI, Wiedemann GJ, Steinhoff J. Nephrotoxicity of ifosfamide, carboplatin and etoposide (ICE) alone or combined with extracorporeal or radiant-heat-induced whole-body hyperthermia. Journal of Cancer Research and Clinical Oncology. 2000 Mar;126(3):173-7; Classe JM, Meeus P et al; UNICANCER/CHIPOR Investigators. Hyperthermic intraperitoneal chemotherapy for recurrent ovarian cancer (CHIPOR): a randomised, open-label, phase 3 trial. Lancet Oncology. 2024 Nov 13:S1470-2045(24)00531-X.

Do not use (contraindications)

One study recommended against carboplatin and whole-body hyperthermia for palliative care among people with recurrent and/or metastatic cervical cancer.⁶Richel O, Zum Vörde Sive Vörding PJ et al. Phase II study of carboplatin and whole body hyperthermia (WBH) in recurrent and metastatic cervical cancer. Gynecologic Oncology. 2004;95(3):680-685.

Reducing the side effects of hyperthermia

These factors are linked to better non-cancer outcomes from use of hyperthermia:

• Shorter length of hospital stay and fewer 60-day complications after surgery when using restrictive fluid therapy⁷Hendrix RJ, Damle A et al. Restrictive intraoperative fluid therapy is associated with decreased morbidity and length of stay following hyperthermic intraperitoneal chemoperfusion. Annals of Surgical Oncology. 2019 Feb;26(2):490-496.
• Less thermal skin damage, with scar tissue more at risk, when using lower temperature and thermal dose values⁸Bakker A, Kolff MW et al. Thermal skin damage during reirradiation and hyperthermia is time-temperature dependent. International Journal of Radiation Oncology, Biology, Physics. 2017 Jun 1;98(2):392-399.
• Less local pain and normal tissue reactions when using a coupling deionized water bag system with microwave-induced local hyperthermia⁹Lindholm CE, Kjellen E, Nilsson P, Hertzman S. Microwave-induced hyperthermia and radiotherapy in human superficial tumours: clinical results with a comparative study of combined treatment versus radiotherapy alone. International Journal of Hyperthermia. 1987 Sep-Oct;3(5):393-411. 
• Less toxicity with HIPEC perfusion with oxaliplatin compared to mitomycin,¹⁰Moaven O, Votanopoulos KI et al. Health-related quality of life after cytoreductive surgery/HIPEC for mucinous appendiceal cancer: results of a multicenter randomized trial comparing oxaliplatin and mitomycin. Annals of Surgical Oncology. 2020 Mar;27(3):772-780; Roth L, Eshmuminov D et al. Systemic inflammatory response after hyperthermic intraperitoneal chemotherapy (HIPEC): the perfusion protocol matters! European Journal of Surgical Oncology. 2019 Sep;45(9):1734-1739. although more reported complications¹¹Zhang X, Wu Q et al. Oxaliplatin versus mitomycin C in HIPEC for peritoneal metastasis from colorectal cancer: a systematic review and meta-analysis of comparative studies. International Journal of Colorectal Disease. 2020 Oct;35(10):1831-1839.
• Less venous thromboembolism when discharging patients with medication to reduce risk of thrombosis¹²Khan S, Kelly KJ et al. Incidence, risk factors, and prevention strategies for venous thromboembolism after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Annals of Surgical Oncology. 2019 Jul;26(7):2276-2284.
• Greater success of microwave ablation for benign breast tumors with more practitioner experience, as is true for most procedures¹³Li C, Li C, Ge H. Technical analysis of US imaging for precise microwave ablation for benign breast tumours. International Journal of Hyperthermia. 2018 Dec;34(8):1179-1185.