Hyperthermia: Safety and precautions - CancerChoices



Many types and varieties of hyperthermia (heat treatment) are used in conventional cancer care, and some additional uses are being explored for improving survival and reducing risk of recurrence.

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 uncontrolled studiesa study in which a therapy is used, but without a comparison group against which to judge outcomes; an uncontrolled trial is considered a weak study design, case series, and case reportsa descriptive and exploratory analysis of a person, group, or event regarding changes observed over time; because changes due to treatment are not compared to similar changes over time without treatment, a case study is considered a weak study design. 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.

  • Skin lesions, blisters, necrosis, thermal burns, or ulceration
  • Heel discomfort
  • Headache
  • Pain, including when swallowing (odynophagia)
  • Fatigue
  • Fever
  • Cough
  • Infections including urinary tract infection, abdominal infection, herpes infection, and pneumonia
  • Blood in urine
  • Diarrhea
  • Nausea and vomiting
  • Hiccups
  • Liver dysfunction
  • Kidney dysfunction
  • Multiple organ dysfunction
  • Neuropathy and other neurological side effects including myalgias and weakness
  • Mood disorder
  • Cardiovascular side effects including low blood pressure, arrhythmias, swollen or inflamed vein due to a blood clot (thrombophlebitis), or venous thromboembolism
  • Blood-related side effects including neutropeniaan abnormally low number of neutrophils in the blood, leading to increased susceptibility to infection, leukopeniaan abnormally low number of white cells in the blood, leading to increased susceptibility to infection, anemia, low albumin protein (hypoalbuminemia), and low platelets (thrombocytopenia), or changes in coagulation
  • Bone marrow toxicity
  • Hair loss (alopecia)
  • High blood sugar related to perfusion (intraoperative hyperglycemia) 
  • Changes in some hormone levels or markers of inflammation or immune activation

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.

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:

Keep reading about hyperthermia

Authors

Nancy Hepp, MS

Lead Researcher
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Ms. Hepp is a researcher and communicator who has been writing and editing educational content on varied health topics for more than 20 years. She serves as lead researcher and writer for CancerChoices and also served as the first program manager. Her graduate work in research and cognitive psychology, her master’s degree in instructional design, and her certificate in web design have all guided her in writing and presenting information for a wide variety of audiences and uses. Nancy’s service as faculty development coordinator in the Department of Family Medicine at Wright State University also provided experience in medical research, plus insights into medical education and medical care from the professional’s perspective.

Nancy Hepp, MS Lead Researcher

Andrew Jackson, ND

Research Associate
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Andrew Jackson, ND, serves as a CancerChoices research associate. As a naturopathic physician practicing in Kirkland, Washington, he teaches critical evaluation of the medical literture at Bastyr University in Kenmore, Washington. His great appreciation of scientific inquiry and the scientific process has led him to view research with a critical eye.

Andrew Jackson, ND Research Associate

Reviewers

Susan Yaguda, MSN, RN

Manager at Atrium Health’s Levine Cancer Institute and CancerChoices Clinical Consultant
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Susan Yaguda, MSN, RN, has been a nurse for nearly 40 years, working in a variety of healthcare settings. She currently works in Charlotte, North Carolina, at Atrium Health’s Levine Cancer Institute as the manager for Integrative Oncology and Cancer Survivorship. She works with a multidisciplinary team to deliver holistic, evidence-based support and education for patients and care partners at any point along the trajectory of cancer care. She completed the Integrative Oncology Scholars Program through the University of Michigan in 2020, is certified as an Integrative Health Coach through Duke Integrative Medicine and has a post-graduate certificate in Nursing Education from the University of North Carolina, Charlotte. Susan also was awarded the Planetree International Scholar’s Award in 2018 and was recognized by the Daisy Foundation for Nurse Leadership in 2021. Susan has a particular interest in empowering patients and care partners with knowledge to help drive informed decision making and educating nurses on the benefits of integrative care for patients and self-care. She has presented nationally and internationally on integrative oncology and nursing education.

She and her husband, Mark, have two adult children and a very spoiled foxhound. She enjoys hiking, knitting, cooking, and pickleball.

“As a frequent consumer of Beyond Conventional Cancer Therapies, and now CancerChoices, for both professional education and patient support, it is an honor to have the opportunity to engage with the dedicated team at CancerChoices to serve those impacted by this disease.”  

 

Susan Yaguda, MSN, RN Manager at Atrium Health’s Levine Cancer Institute and CancerChoices Clinical Consultant

Gurdev Parmar, ND, FABNO

Co-Founder and Medical Director of Integrated Health Clinic
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Dr. Gurdev Parmar is co-founder and medical director of the largest naturopathic health care facility in Canada, the Integrated Health Clinic (IHC). He is licensed in both British Columbia, Canada, and Washington State, USA.

Dr. Parmar has launched the IHC Research Department with researchers and statisticians now on staff, with publishing patient outcomes on the horizon. He is also the residency director and primary teaching supervisor of a naturopathic oncology residency at IHC, a CNME-approved postdoctoral training facility for Bastyr University.

Dr. Parmar established locoregional hyperthermia treatment in Canada in 2009, and in 2018, he was nominated president of the International Clinical Hyperthermia Society (ICHS). He has served on numerous boards over the years, including an appointment to the OncANP Delphi Panel which has begun building consensus statements for the naturopathic oncology field, the first of which was published in Integrative Cancer Therapies.

Dr. Parmar writes and lectures internationally on a wide variety of topics, including clinical hyperthermia, the tumour microenvironment, and integrative cancer care. He has served on the editorial board of several medical journals and is the lead author and editor-in-chief of the Textbook of Naturopathic Oncology: A Desktop Guide of Integrative Cancer Care, as well as the Pearlz Clinical eBook Series. Dr. Parmar recently published a timely book, Arming the Immune System: The Incredible Power of Natural Immunity & the Fever Response.

Gurdev Parmar, ND, FABNO Co-Founder and Medical Director of Integrated Health Clinic

Last update: April 11, 2024

Last full literature review: March 2023

We are grateful for research support from Ma Victoria Acuña.

CancerChoices provides information about integrative in cancer care, a patient-centered approach combining the best of conventional care, self care and evidence-informed complementary care in an integrated plan cancer care. We review complementaryin cancer care, complementary care involves the use of therapies intended to enhance or add to standard conventional treatments; examples include supplements, mind-body approaches such as yoga or psychosocial therapy, and acupuncture therapies and self-care lifestyle actions and behaviors that may impact cancer outcomes; examples include eating health-promoting foods, limiting alcohol, increasing physical activity, and managing stress practices to help patients and professionals explore and integrate the best combination of conventionalthe cancer care offered by conventionally trained physicians and most hospitals; examples are chemotherapy, surgery, and radiotherapy and complementary therapies and practices for each person.

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