Hyperthermia

Our assessments of evidence for each medical benefit fall into one of these categories:

• Strong evidence: consistent, significant effects in several large (or at least one very large) well designed clinical studies or at least two meta-analysesa statistical analysis that combines the results of two or more research studies; the results of smaller research studies addressing the same or similar questions can be analyzed as though they are one bigger, more powerful study of clinical studies of moderate or better quality (or one large meta-analysis) finding similar results
• Good evidence: significant effects in one large or several mid-sized and well-designed clinical studies ( randomized controlled trialsa study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects with an appropriate placebo or other strong comparison control or observational studies that control for confounds)
• Modest evidence: significant effects in at least three small but well-designed randomized controlled trials (RCTs), or one or more well-designed, mid-sized clinical studies of reasonably good quality (RCTs or observationala type of study in which individuals are observed or certain outcomes are measured, but no attempt is made to affect the outcome (for example, no treatment is given); an example is a study that records people’s diets, but doesn’t try to alter their diets, and looks for patterns of disease or other outcomes related to different foods studies), or several small studies aggregated into a meta-analysis
• Preliminary evidence: significant effects in small or poorly designed clinical studies OR conflicting results in adequate studies but a preponderance of evidence of an effect
• Weak evidence: one or more case studies, supported by animal evidence OR small treatment effects of limited clinical significance OR studies with no controls OR weak trends of effects
• Insufficient evidence: preclinical evidence only OR clinical studies with such poor or unclear methodology that no conclusion can be drawn OR conflicting findings across clinical studies with no preponderance of evidence in one direction; conflicting evidence occurs when studies find conflicting effects (positive effect vs no effect or negative effect) with the same treatment and the same general study population (same cancer type, for example)

Learn more about how we research and rate therapies and practices in How We Rate Therapies ›

• Higher response rate and more complete remissions after low-dose radiotherapy among people with superficial recurrent malignant tumors, mainly adenocarcinomas, treated with microwave-induced local hyperthermia compared to radiotherapy alone in a small controlled triala study design in which people are assigned to either an experimental group or a control group to compare the outcomes from different treatment; assignment is not random, and so this is not as strong a study design as a randomized controlled trial, but still stronger than an uncontrolled trial¹⁰Lindholm 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.

Advanced cancer as a whole

Unspecified hyperthermia: preliminary evidence of higher complete response rate after external beam radiation among people with painful bony metastasis from a variety of primary tumor types treated with hyperthermia

• Higher complete response rate 3 months after external beam radiation among people with painful bony metastasis from a variety of primary tumor types treated with hyperthermia compared to radiation alone in a small RCTrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects¹¹Chi MS, Yang KL et al. Comparing the effectiveness of combined external beam radiation and hyperthermia versus external beam radiation alone in treating patients with painful bony metastases: a phase 3 prospective, randomized, controlled trial. International Journal of Radiation Oncology, Biology, Physics. 2018;100(1):78-87.

Whole-body hyperthermia: preliminary evidence of better rates of complete and partial remission and better overall response rates among people with advanced cancer as a whole treated with whole-body hyperthermia

• Better rates of complete and partial remission and better overall response rates among people with advanced cancer treated with whole-body hyperthermia in addition to cancer-appropriate chemotherapy regimens compared to chemotherapy alone in a mid-sized controlled triala study design in which people are assigned to either an experimental group or a control group to compare the outcomes from different treatment; assignment is not random, and so this is not as strong a study design as a randomized controlled trial, but still stronger than an uncontrolled trial of low quality¹²Liu XL, Ma F et al. [Therapeutic effect of whole body hyperthermia combined with chemotherapy in patients with advanced cancer]. [Article in Chinese] Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2006 Jun;31(3):350-2.

Advanced breast cancer

Preliminary evidence of higher rates of partial regression and stabilization and lower rate of progression after combined chemotherapy among people with breast cancer with multiple liver metastases treated with regional inductive moderate hyperthermia

• Higher rates of partial regression and stabilization and lower rate of progression after combined chemotherapy of paclitaxel and carboplatin among people with breast cancer with multiple liver metastases treated with regional inductive moderate hyperthermia compared to chemotherapy alone in a mid-sized controlled trial¹³Klimanov MY, Syvak LA et al. Efficacy of combined regional inductive moderate hyperthermia and chemotherapy in patients with multiple liver metastases from breast cancer. Technology in Cancer Research & Treatment. 2018;17.

Advanced cervical cancer

Higher doses of hyperthermia are linked to better survival. See “Dosing” in How do experts use hyperthermia? ›

Unspecified hyperthermia: modest evidence of better tumor response or survival among people with locally advanced cervical cancer treated with hyperthermia

• Better local-regional control after radiotherapy among people with previously untreated locally advanced cervical cancer treated with hyperthermia compared to radiotherapy alone in a network meta-analysisa statistical analysis that combines the results of two or more research studies; the results of smaller research studies addressing the same or similar questions can be analyzed as though they are one bigger, more powerful study of 59 RCTs¹⁴Datta NR, Stutz E et al. Efficacy and safety evaluation of the various therapeutic options in locally advanced cervix cancer: a systematic review and network meta-analysis of randomized clinical trials. International Journal of Radiation Oncology, Biology, Physics. 2019 Feb 1;103(2):411-437.
• Longer overall survival but no evidence of an effectoverall, one or more studies did not demonstrate that a treatment or intervention led to an expected outcome; this does not always mean that there is no effect in clinical practice, but that the studies may have been underpowered (too few participants) or poorly designed. Larger, well-designed studies provide more confidence in making assessments. on local relapse-free survival among people with locally advanced cervical cancer treated with hyperthermia and chemoradiotherapy compared to chemoradiotherapy alone in a meta-analysis of 2 clinical studies¹⁵Yea JW, Park JW et al. Chemoradiotherapy with hyperthermia versus chemoradiotherapy alone in locally advanced cervical cancer: a systematic review and meta-analysis. International Journal of Hyperthermia. 2021;38(1):1333-1340.

Regional whole-pelvis hyperthermia: weak evidence of longer overall survival but no evidence of an effect on 5-year survival after chemoradiotherapy among people with locally advanced cervical cancer treated with regional whole-pelvis hyperthermia

• A weak trendan apparent change due to a therapy, close to but not achieving full statistical significance (this is the CancerChoices definition; other researchers and studies may define this differently toward longer overall survival but no evidence of an effect on 5-year survival after chemoradiotherapy among people with locally advanced cervical cancer treated with regional whole-pelvis hyperthermia compared with chemoradiotherapy alone in a mid-sized RCT¹⁶Harima Y, Ohguri T et al. A multicentre randomised clinical trial of chemoradiotherapy plus hyperthermia versus chemoradiotherapy alone in patients with locally advanced cervical cancer. International Journal of Hyperthermia. 2016 Nov;32(7):801-8.

Laser interstitial thermal therapy: no evidence of an effect on local control among people with advanced cervical cancer treated with interstitial hyperthermia

• No evidence of an effect on local control among people with advanced cervical cancer treated with interstitial hyperthermia and interstitial brachytherapy compared to interstitial brachytherapy alone in a mid-sized RCT¹⁷Zolciak-Siwinska A, Piotrkowicz N et al. HDR brachytherapy combined with interstitial hyperthermia in locally advanced cervical cancer patients initially treated with concomitant radiochemotherapy—a phase III study. Radiotherapy and Oncology. 2013;109(2):194-199.

Modulated electro-hyperthermia (mEHT): modest evidence of better local control and greater complete metabolic response rate after chemoradiotherapy among people with locally advanced cervical cancer treated with modulated electro-hydrotherapy (mEHT)

• Better 3-year disease-free survival after treatment with radiotherapy, chemotherapy, and brachytherapy among people with stage 2B to stage 3B locally advanced cervical cancer (LACC), and better overall survival only among people with with stage III LACC, treated with modulated electro-hyperthermia (mEHT) compared to radiotherapy, chemotherapy, and brachytherapy alone in a mid-sized RCT¹⁸Minnaar CA, Maposa I, Kotzen JA, Baeyens A. Effects of modulated electro-hyperthermia (mEHT) on two and three year survival of locally advanced cervical cancer patients. Cancers (Basel). 2022 Jan 27;14(3):656.
• Better local control and greater complete metabolic response rate after chemoradiotherapy—including disease both inside and outside the radiation field—among people with locally advanced cervical cancer treated with modulated electro-hydrotherapy (mEHT) compared to chemoradiotherapy alone in a mid-sized RCT;¹⁹Minnaar CA, Kotzen JA, Ayeni OA, Vangu MD, Baeyens A. Potentiation of the abscopal effect by modulated electro-hyperthermia in locally advanced cervical cancer patients. Frontiers in Oncology. 2020 Mar 24;10:376. HIV status did not appear to affect these outcomes

Advanced colorectal cancer

Local or regional hyperthermia, including modulated electro-hyperthermia (mEHT): modest evidence of better tumor response to radiotherapy or chemoradiotherapy among people with advanced rectal cancer treated with local or regional hyperthermia

• Better tumor response and 5-year survival after radiation therapy among people with advanced carcinoma of the rectum treated with local hyperthermia compared to radiation therapy alone in a mid-sized RCT²⁰Berdov BA, Menteshashvili GZ. Thermoradiotherapy of patients with locally advanced carcinoma of the rectum. International Journal of Hyperthermia. 1990;6(5):881-890.
• A weak trend toward better 5-year survival after neoadjuvanttherapy used before a main treatment, such as chemotherapy, radiation therapy, and hormone therapy before surgery radiochemotherapy among people with locally advanced non-metastatic rectal cancer treated with deep regional hyperthermia compared to radiochemotherapy alone in a mid-sized controlled trial²¹Gani C, Schroeder C et al. Long-term local control and survival after preoperative radiochemotherapy in combination with deep regional hyperthermia in locally advanced rectal cancer. International Journal of Hyperthermia. 2016;32(2):187-92.
• Higher regression of large tumors (more than 65 cm³) with less gastrointestinal toxicity after neoadjuvant treatment of capecitabine or 5-fluorouracil with radiotherapy among people with locally advanced rectal cancer treated with modulated electro-hyperthermia (mEHT) and lower median radiation dose compared to typical neoadjuvant treatment in a mid-sized observationala type of study in which individuals are observed or certain outcomes are measured, but no attempt is made to affect the outcome (for example, no treatment is given); an example is a study that records people’s diets, but doesn’t try to alter their diets, and looks for patterns of disease or other outcomes related to different foods study²²Kim S, Lee JH, Cha J, You SH. Beneficial effects of modulated electro-hyperthermia during neoadjuvant treatment for locally advanced rectal cancer. International Journal of Hyperthermia. 2021;38(1):144-151.
• Higher rate of complete pathological response after neoadjuvant radiochemotherapy among people with locally advanced cancer of the middle or lower rectum treated with at least 4 regional hyperthermia treatments compared to radiochemotherapy alone, and with a weak trend toward a higher rate of sphincter-sparing surgery only among people with low-lying tumors located within 8 cm of the anal verge prior to treatment, in a mid-sized observational study²³Schroeder C, Gani C et al. Pathological complete response and sphincter-sparing surgery after neoadjuvant radiochemotherapy with regional hyperthermia for locally advanced rectal cancer compared with radiochemotherapy alone. International Journal of Hyperthermia. 2012;28(8):707-14.

Enhancing the effectiveness of hyperthermia

Higher hyperthermia-related cumulative temperatures are linked to more tumor regression after 5-fluorouracil based preoperative radiochemotherapy among people with locally advanced rectal cancer²⁴Gani C, Lamprecht U et al. Deep regional hyperthermia with preoperative radiochemotherapy in locally advanced rectal cancer, a prospective phase II trial. Radiotherapy & Oncology. 2021 Jun;159:155-160.

Advanced head, neck, or oral cancer

Unspecified hyperthermia: preliminary evidence of better tumor control among people with advanced carcinoma of the head and neck treated with hyperthermia

• Better tumor control among people with advanced (stage 3 or 4) carcinoma of the head and neck treated with hyperthermia and radiation therapy compared to radiation therapy alone in a small RCT²⁵Datta NR, Bose Ak, Kapoor HK, Gupta S. Head and neck cancers: results of thermoradiotherapy versus radiotherapy. International Journal of Hyperthermia. 1990;6(3):479-486.

Local or regional hyperthermia: modest evidence of better tumor response after conventional treatment (surgery, radiotherapy and/or chemotherapy) among people with advanced head, neck, or oral cancer treated with local or regional hyperthermia

• Higher clinical response rate and a weak trend toward longer overall survival after induction chemotherapy followed by radical surgery with postoperative radiotherapy among people with locally advanced resectable oral squamous cell carcinoma treated with ultrasonic thermal therapy compared to chemotherapy, surgery, and radiotherapy alone in a mid-sized RCT²⁶Ren G, Ju H et al. A multicenter randomized phase II trial of hyperthermia combined with TPF induction chemotherapy compared with TPF induction chemotherapy in locally advanced resectable oral squamous cell carcinoma. International Journal of Hyperthermia. 2021;38(1):939-947.
• Better complete response rates at 3 months and 5 years, and better survival at 3 and 5 years, but no evidence of an effect on metastases at 5 years after treatment with cisplatin chemotherapy and radiotherapy among people with nasopharyngeal carcinoma with metastatic foci in cervical lymph nodes treated with microwave hyperthermia compared to chemoradiotherapy alone in a mid-sized RCT, and better complete response rates with higher temperatures (at least 43°C) or with 4 to 10 hyperthermic treatments²⁷Kang M, Liu WQ, Qin YT, Wei ZX, Wang RS. Long-term efficacy of microwave hyperthermia combined with chemoradiotherapy in treatment of nasopharyngeal carcinoma with cervical lymph node metastases. Asian Pacific Journal of Cancer Prevention. 2013;14(12):7395-400.
• Greater complete response rate without additional toxicities after radiotherapy among people with locally advanced epithelial cancer of the head and neck treated with local radiofrequency hyperthermia compared to radiotherapy alone in a small RCT²⁸Huilgol 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.
• Better 5-year actuarial nodal control and 5-year overall survival after local radiotherapy among people with advanced locoregional stage 4 squamous cell carcinoma of the head and neck treated with local hyperthermia compared to radiotherapy alone in a small RCT²⁹Valdagni R, Amichetti M. Report of long-term follow-up in a randomized trial comparing radiation therapy and radiation therapy plus hyperthermia to metastatic lymph nodes in stage IV head and neck patients. International Journal of Radiation Oncology, Biology, Physics. 1994;28(1):163-169.

Enhancing the effectiveness of hyperthermia

Higher temperatures (at least 43°C) and 4 to 10 hyperthermic treatments are linked to better complete response rates among people with nasopharyngeal carcinoma.³⁰Kang M, Liu WQ, Qin YT, Wei ZX, Wang RS. Long-term efficacy of microwave hyperthermia combined with chemoradiotherapy in treatment of nasopharyngeal carcinoma with cervical lymph node metastases. Asian Pacific Journal of Cancer Prevention. 2013;14(12):7395-400.

Advanced lung cancer

Radiofrequency hyperthermia: no evidence of an effect on complete response, partial response, or stable disease among people with advanced non-small cell lung cancer treated with radiofrequency hyperthermia

• No evidence of an effect on complete response, partial response, or stable disease after treatment with gemcitabine and cisplatin among people with advanced non-small cell lung cancer treated with radiofrequency hyperthermia compared to gemcitabine and cisplatin alone in a small RCT³¹Shen H, Li XD et al. The regimen of gemcitabine and cisplatin combined with radio frequency hyperthermia for advanced non-small cell lung cancer: a phase II study. International Journal of Hyperthermia. 2011;27(1):27-32.

Advanced melanoma

Unspecified hyperthermia: preliminary and conflicting evidence of tumor response among people with malignant melanoma treated with hyperthermia

• Better complete tumor response and better 2-year local control after radiation among people with metastatic or recurrent malignant melanoma tumors treated with hyperthermia compared to radiation alone in a mid-sized RCT³²Overgaard J, Gonzalez Gonzalez D et al. Hyperthermia as an adjuvant to radiation therapy of recurrent or metastatic malignant melanoma. A multicentre randomized trial by the European Society for Hyperthermic Oncology. International Journal of Hyperthermia. 1996;12(1):3-20.
• No evidence of an effect on tumor response among people with disseminated malignant melanoma treated with chemotherapy and hyperthermia compared to typical results of chemotherapy alone in a small comparison triala study in which two different treatments are compared for their effects³³Engelhardt 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.

Advanced pancreatic cancer

Local or regional hyperthermia: preliminary evidence of better survival among people with locally advanced pancreatic cancer treated with local or regional hyperthermia

• Better progression-free survivalthe time during and after treatment of a disease that a patient lives without disease progression (worsening) and overall survival after chemoradiotherapy using gemcitabine among people with locally advanced pancreatic carcinoma treated with regional hyperthermia compared to chemoradiotherapy alone in a small controlled trial³⁴Ohguri T, Imada H et al. Concurrent chemoradiotherapy with gemcitabine plus regional hyperthermia for locally advanced pancreatic carcinoma: initial experience. Radiation Medicine. 2008 Dec;26(10):587-96.
• Less progressive disease and better overall survival after treatment with chemotherapy (5-FU) before surgery, bypass surgery with intraoperative bolus infusion of 5-FU and then multi-agent chemotherapy plus sandostatin and external beam irradiation after surgery among people with stage 4 pancreatic adenocarcinoma treated with a single session of intraoperative hyperthermia directly on the tumor compared to no hyperthermia in a small controlled trial³⁵Kouloulias VE, Kouvaris JR et al. Intraoperative hyperthermia in conjunction with multi-schedule chemotherapy (pre-, intra- and post-operative), by-pass surgery, and post-operative radiotherapy for the management of unresectable pancreatic adenocarcinoma. International Journal of Hyperthermia. 2002 May-Jun;18(3):233-52.
• Longer survival time by 3 months after chemoradiotherapy among people with locally advanced unresectable pancreatic cancer treated with hyperthermia compared to chemoradiotherapy alone in a small observational study³⁶Maebayashi T, Ishibashi N et al. Treatment outcomes of concurrent hyperthermia and chemoradiotherapy for pancreatic cancer: insights into the significance of hyperthermia treatment. Oncology Letters. 2017 Jun;13(6):4959-4964.
• Longer overall survival by 4 months after chemoradiotherapy among people with locally advanced unresectable pancreatic cancer (either primary or recurrent) treated with hyperthermia compared to chemoradiotherapy alone in a small observational study³⁷Maluta S, Schaffer M et al. Regional hyperthermia combined with chemoradiotherapy in primary or recurrent locally advanced pancreatic cancer: an open-label comparative cohort trial. Strahlentherapie und Onkologie. 2011 Oct;187(10):619-25.

Advanced prostate cancer

Enhancing the effectiveness of hyperthermia for advanced prostate cancer

Longer duration of hyperthermia exposure may improve outcomes after hyperthermia.³⁸Algan O, Fosmire H et al. External beam radiotherapy and hyperthermia in the treatment of patients with locally advanced prostate carcinoma. Cancer. 2000 Jul 15;89(2):399-403.

Advanced stomach (gastric) cancer

Local or regional hyperthermia: preliminary evidence of better survival among people with advanced stomach cancer treated with regional hyperthermia in addition to chemotherapy

• Longer median survival time and better 3-year survival among people with advanced gastric cancer treated with regional hyperthermia with chemotherapy (RHCT) compared to chemotherapy alone in a mid-sized RCT³⁹Fang H, Zhang Y et al. Regional hyperthermia combined with chemotherapy in advanced gastric cancer. Open Medicine (Warsaw, Poland). 2019;14:85-90.

Brain metastases

Laser interstitial thermal therapy: weak evidence of tumor response (69% local control rate at 12 months and median overall survival of 17.5 months) among people with brain metastases with in-field recurrence treated with laser interstitial thermal therapy

• 69% local control rate at 12 months and median overall survival of 17.5 months among people with brain metastases with in-field recurrence treated with laser interstitial thermal therapy (LITT) in a low-quality meta-analysis of 14 uncontrolled trialsa 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 design⁴⁰Chen C, Guo Y et al. The efficacy of laser interstitial thermal therapy for brain metastases with in-field recurrence following SRS: systemic review and meta-analysis. International Journal of Hyperthermia. 2021;38(1):273-281.

• A higher rate of 24-month progression-free survivalthe time during and after treatment of a disease that a patient lives without disease progression (worsening) after intravesical adjuvanttreatment applied after initial treatment for cancer, especially to suppress secondary tumor formation therapy with pirarubicin after transurethral resection of bladder tumors (TURBT) among people with urothelial carcinoma of the bladder treated with thermochemotherapy comprising 3 consecutive sessions in which only the second added precision intraperitoneal thermal perfusion treatment compared to chemotherapy without hyperthermia in a mid-sized controlled triala study design in which people are assigned to either an experimental group or a control group to compare the outcomes from different treatment; assignment is not random, and so this is not as strong a study design as a randomized controlled trial, but still stronger than an uncontrolled trial⁴¹Zhou J, Li L et al. Efficacy analysis of a novel thermochemotherapy scheme with pirarubicin for intermediate- and high-risk nonmuscle-invasive bladder cancer: a single-institution nonrandomized concurrent controlled trial. International Journal of Hyperthermia. 2019;36(1):868-875.
• Higher incidence of tumor downstaging and tumor degeneration and a weak trend toward greater 5-year survival after radiotherapy among people with bladder cancer treated with regional hyperthermia compared to radiotherapy alone in a small controlled trial⁴²Masunaga SI, Hiraoka M et al. Phase I/II trial of preoperative thermoradiotherapy in the treatment of urinary bladder cancer. International Journal of Hyperthermia. 1994;10(1):31-40.

Local or regional hyperthermia

Preliminary evidence of higher tumor response among people with relapsed glioblastoma multiforme and astrocytomas treated with modulated electro-hyperthermia (mEHT)

• Higher tumor response rates at 3 months among people with relapsed glioblastoma multiforme and astrocytomas treated with mEHT compared to best supportive care in a mid-sized controlled trial⁴³Fiorentini G, Sarti D et al. Modulated electrohyperthermia in integrative cancer treatment for relapsed malignant glioblastoma and astrocytoma: retrospective multicenter controlled study. Integrative Cancer Therapies. 2019 Jan-Dec;18:1534735418812691.

Weak evidence of tumor response after temozolamide-based chemotherapy and radiotherapy among people with relapsed malignant glioma treated with hyperthermia from short radiofrequency waves

• 25% response rate, 9-month median survival, and 25% survival 1 year after temozolamide-based chemotherapy and radiotherapy among people with relapsed malignant glioma treated with hyperthermia from short radiofrequency waves in a small uncontrolled triala 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 design⁴⁴Fiorentini G, Giovanis P et al. A phase II clinical study on relapsed malignant gliomas treated with electro-hyperthermia. In Vivo. 2006 Nov-Dec;20(6A):721-4.

Stronger effects are seen with higher doses. See “Dosing” in How do experts use hyperthermia? ›

Unspecified hyperthermia: modest evidence of higher response rates after radiotherapy among people with breast cancer treated with hyperthermia

• Higher complete response rate after radiotherapy among people with breast cancer treated with hyperthermia compared to radiotherapy alone in a combined analysis of 5 RCTsrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects⁴⁵Vernon CC, Hand JW et al. Radiotherapy with or without hyperthermia in the treatment of superficial localized breast cancer: results from five randomized controlled trials. International Journal of Radiation Oncology, Biology, Physics. 1996:35(4):731-744.
• Higher response rates after radiotherapy among people with chest wall recurrences of breast carcinoma treated with hyperthermia compared to radiotherapy alone in a small controlled triala study design in which people are assigned to either an experimental group or a control group to compare the outcomes from different treatment; assignment is not random, and so this is not as strong a study design as a randomized controlled trial, but still stronger than an uncontrolled trial⁴⁶Gonzalez Gonzalez D, van Dijk JD, Blank LE. Chestwall recurrences of breast cancer: results of combined treatment with radiation and hyperthermia. Radiotherapy and Oncology. 1988 Jun;12(2):95-103.

Local or regional hyperthermia: preliminary evidence of better tumor response and survival after neoadjuvant chemotherapy among people with breast cancer treated with regional inductive moderate hyperthermia

• More reduction in median tumor size, higher objective response rate, more axillary lymph node regression, and better 10-year survival after neoadjuvant chemotherapy among people with breast cancer treated with regional inductive moderate hyperthermia compared to chemotherapy alone in a mid-sized RCT⁴⁷Loboda A, Smolanka I Sr et al. Efficacy of combination neoadjuvant chemotherapy and regional inductive moderate hyperthermia in the treatment of patients with locally advanced breast cancer. Technology in Cancer Research and Treatment. 2020 Jan-Dec;19

• Better cancer-specific survival after the first recurrence and a weak trend towards higher rates of downstaging and complete tumor response after chemoradiotherapy among people with locally advanced rectal cancer positive for carbonic anhydrase 9 (CA9, associated with worse prognosis) treated with radiofrequency hyperthermia compared to chemoradiotherapy alone in a mid-sized RCTrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects⁴⁸Kim SW, Yea JW. Selecting patients for hyperthermia combined with preoperative chemoradiotherapy for locally advanced rectal cancer. International Journal of Clinical Oncology. 2018 Apr;23(2):287-297.

Anal cancer: preliminary evidence of better overall survival, local control, and colostomy-free survival after chemoradiotherapy among people with anal cancer treated with hyperthermia

• Better 5-year overall survival rates, local control, and colostomy-free survival after chemoradiotherapy among people with anal cancer treated with hyperthermia compared to chemoradiotherapy alone in a mid-sized controlled triala study design in which people are assigned to either an experimental group or a control group to compare the outcomes from different treatment; assignment is not random, and so this is not as strong a study design as a randomized controlled trial, but still stronger than an uncontrolled trial⁴⁹Ott OJ, Schmidt M et al. Chemoradiotherapy with and without deep regional hyperthermia for squamous cell carcinoma of the anus. Strahlentherapie und Onkologie. 2019 Jul;195(7):607-614.

Stomach cancer: preliminary evidence of longer overall survival after radical gastrectomy among people with stomach (gastric) cancer treated with hyperthermic chemotherapy

• Longer overall survival after radical gastrectomy among people with stage 3 gastric cancer treated with HIPEC using cisplatin and and oral S-1 compared to standard intravenous cisplatin and oral S-1 in a mid-sized RCTrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects⁵⁰Liu L, Sun L et al. A novel method of bedside hyperthermic intraperitoneal chemotherapy as adjuvant therapy for stage-III gastric cancer. International Journal of Hyperthermia. 2022;39(1):239-245.

Cervical cancer

Unspecified hyperthermia: preliminary evidence of better survival or treatment response after conventional treatment among people with cervical cancer treated with hyperthermia

• Better 5-year overall survival rate and a weak trendan apparent change due to a therapy, close to but not achieving full statistical significance (this is the CancerChoices definition; other researchers and studies may define this differently toward better 5-year relapse-free survival after radiochemotherapy among people with stage 1B–4 cervical cancer treated with hyperthermia compared to radiochemotherapy alone in an analysis of a mid-sized RCTrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects⁵¹Wang Y, Hong W et al. Outcomes for hyperthermia combined with concurrent radiochemotherapy for patients with cervical cancer. International Journal of Radiation Oncology, Biology, Physics. 2020 Jul 1;107(3):499-511.
• Better complete response rate and better 3-year locoregional control rate after radiotherapy and brachytherapy among people with stage 3B cervical carcinoma treated with hyperthermia compared to radiotherapy and brachytherapy alone in a small RCT⁵²Harima Y, Nagata K et al. A randomized clinical trial of radiation therapy versus thermoradiotherapy in stage IIIB cervical carcinoma. International Journal of Hyperthermia. 2001;17(2):97-105.

Deep hyperthermia: preliminary evidence of higher complete response rate and longer duration of local control after radiotherapy among people with cervical cancer treated with deep hyperthermia

• Higher complete response rate and longer duration of local control after radiotherapy among people with cervical cancer treated with deep hyperthermia treatment compared to radiotherapy alone in a mid-sized RCT⁵³van der Zee J, González González D et al. Comparison of radiotherapy alone with radiotherapy plus hyperthermia in locally advanced pelvic tumours: a prospective, randomised, multicentre trial. Dutch Deep Hyperthermia Group. Lancet. 2000 Apr 1;355(9210):1119-25.

Modulated electro-hyperthermia (mEHT): preliminary evidence of better 6-month local disease control after chemoradiotherapy among people with squamous cell carcinoma of the cervix treated with modulated electro-hyperthermia (mEHT)

• Better 6-month local disease control after chemoradiotherapy among people with stage 2B–3B squamous cell carcinoma of the cervix treated with mEHT compared to chemoradiotherapy alone in a mid-sized RCT⁵⁴Minnaar CA, Kotzen JA et al. The effect of modulated electro-hyperthermia on local disease control in HIV-positive and -negative cervical cancer women in South Africa: early results from a phase III randomised controlled trial. PLoS One. 2019 Jun 19;14(6):e0217894.

• Better complete response and 5-year local control rates and better progression-free survivalthe time during and after treatment of a disease that a patient lives without disease progression (worsening) at 5 years, but no evidence of an effectoverall, one or more studies did not demonstrate that a treatment or intervention led to an expected outcome; this does not always mean that there is no effect in clinical practice, but that the studies may have been underpowered (too few participants) or poorly designed. Larger, well-designed studies provide more confidence in making assessments. on overall survival at 5 years after conventional radiotherapy among people with nasopharyngeal cancer treated with intracavity hyperthermia compared to radiotherapy alone in a mid-sized RCTrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects⁵⁵Hua Y, Ma S et al. Intracavity hyperthermia in nasopharyngeal cancer: a phase III clinical study. International Journal of Hyperthermia. 2011;27(2):180-6.
• Better survival at 36 months after chemoradiotherapy among people with nasopharyngeal carcinoma treated with non-invasive extracorporeal radiofrequency (ERF) hyperthermia compared to chemoradiotherapy alone in a small RCT⁵⁶Zhao C, Chen J, Yu B, Chen X. Improvement in quality of life in patients with nasopharyngeal carcinoma treated with non-invasive extracorporeal radiofrequency in combination with chemoradiotherapy. International Journal of Radiation Biology. 2014 Oct;90(10):853-8.
• No evidence of an effect on tumor control after radiation therapy among people with early (stage 1 or 2) carcinoma of the head and neck treated with local diathermic hyperthermia compared to radiation therapy alone in a small RCT⁵⁷Datta NR, Bose Ak, Kapoor HK, Gupta S. Head and neck cancers: results of thermoradiotherapy versus radiotherapy. International Journal of Hyperthermia. 1990;6(3):479-486.
• Much higher complete response rate of the primary lesions and metastatic lymph nodes and better survival after external irradiation among people with stage 3 or 4 squamous-cell carcinoma of the oropharynx and hypopharynx (oro-hypopharyngeal cancer) treated definitively (without surgery) or before surgery with 13.56 MHz radiofrequency capacitive hyperthermia compared to irradiation alone in a small controlled triala study design in which people are assigned to either an experimental group or a control group to compare the outcomes from different treatment; assignment is not random, and so this is not as strong a study design as a randomized controlled trial, but still stronger than an uncontrolled trial⁵⁸Hiraki Y, Nakajo M et al. Effectiveness of RF capacitive hyperthermia combined with radiotherapy for stages III and IV oro-hypopharyngeal cancers: a non-randomized comparison between thermoradiotherapy and radiotherapy. International Journal of Hyperthermia. 1998 Sep-Oct;14(5):445-57.

• Higher complete response rate and longer duration of local control after radiotherapy among people with bladder cancer, cervical cancer, or rectal cancer treated with deep hyperthermia treatment compared to radiotherapy alone in a mid-sized RCTrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects⁵⁹van der Zee J, González González D et al. Comparison of radiotherapy alone with radiotherapy plus hyperthermia in locally advanced pelvic tumours: a prospective, randomised, multicentre trial. Dutch Deep Hyperthermia Group. Lancet. 2000 Apr 1;355(9210):1119-25.

• Better relapse-free survival after intensity-modulated radiotherapy (IMRT) and androgen deprivation therapy (ADT) among people with high-risk localized prostate carcinoma treated with regional hyperthermia compared to IMRT and ADT alone in a small observationala type of study in which individuals are observed or certain outcomes are measured, but no attempt is made to affect the outcome (for example, no treatment is given); an example is a study that records people’s diets, but doesn’t try to alter their diets, and looks for patterns of disease or other outcomes related to different foods study⁶⁰Nakahara S, Ohguri T et al. Intensity-modulated radiotherapy with regional hyperthermia for high-risk localized prostate carcinoma. Cancers (Basel). 2022 Jan 13;14(2):400.

Achieving target hyperthermic temperatures was challenging in treating prostate cancer in some early studies.⁶¹Anscher MS, Samulski TV, Leopold KA, Oleson JR. Phase I/II study of external radio frequency phased array hyperthermia and external beam radiotherapy in the treatment of prostate cancer: technique and results of intraprostatic temperature measurements. International Journal of Radiation Oncology, Biology, Physics. 1992;24(3):489-95; Prionas SD, Kapp DS et al. Thermometry of interstitial hyperthermia given as an adjuvant to brachytherapy for the treatment of carcinoma of the prostate. International Journal of Radiation Oncology, Biology, Physics. 1994 Jan 1;28(1):151-62. Newer technologies more effectively achieve target hyperthermic temperatures in the treatment of prostate and cervical cancers.⁶²Diederich CJ, Wootton J et al. Catheter-based ultrasound hyperthermia with HDR brachytherapy for treatment of locally advanced cancer of the prostate and cervix. Proceedings of SPIE—the International Society for Optical Engineering. 2011 Feb 22;7901:79010O; 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.

Good evidence of longer survival after chemotherapy, sometimes following surgery, among people with soft tissue sarcoma treated with regional hyperthermia

• Longer overall survival after chemotherapy among people with high-risk soft tissue sarcoma treated with regional hyperthermia compared to chemotherapy alone in a mid-sized RCTrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects⁶³Issels RD, Lindner LH et al. Neo-adjuvant chemotherapy alone or with regional hyperthermia for localised high-risk soft-tissue sarcoma: a randomised phase 3 multicentre study. Lancet Oncology. 2010;11(6):561-570.
• Longer progression-free survivalthe time during and after treatment of a disease that a patient lives without disease progression (worsening) and overall survival after neoadjuvant chemotherapy among people with localized soft tissue sarcoma treated with regional hyperthermia compared to chemotherapy alone in a mid-sized RCT⁶⁴Issels RD, Lindner LH et al. Effect of neoadjuvant chemotherapy plus regional hyperthermia on long-term outcomes among patients with localized high-risk soft tissue sarcoma: the EORTC 62961-ESHO 95 randomized clinical trial. JAMA Oncology. 2018;4(4):483-492.
• Better local progression-free survival but no evidence of an effectoverall, one or more studies did not demonstrate that a treatment or intervention led to an expected outcome; this does not always mean that there is no effect in clinical practice, but that the studies may have been underpowered (too few participants) or poorly designed. Larger, well-designed studies provide more confidence in making assessments. on overall survival after complete macroscopic resection and chemotherapy among people with abdominal and retroperitoneal soft tissue sarcomas treated with regional hyperthermia compared to resection and chemotherapy alone in a mid-sized subgroup analysis of an RCT⁶⁵Angele MK, Albertsmeier M et al. Effectiveness of regional hyperthermia with chemotherapy for high-risk retroperitoneal and abdominal soft-tissue sarcoma after complete surgical resection: a subgroup analysis of a randomized phase-III multicenter study. Annals of Surgery. 2014 Nov;260(5):749-54; discussion 754-6.

Preliminary evidence of higher tumor response after neoadjuvant chemotherapy among people with with high-risk soft-tissue sarcoma treated with regional hyperthermia

• Higher tumor response mediated by markers of immune activation (tumor-infiltrating lymphocytes) after neoadjuvant chemotherapy among people with with high-risk soft-tissue sarcoma treated with regional hyperthermia compared to chemotherapy alone in a mid-sized RCT⁶⁶Issels RD, Noessner E et al. Immune infiltrates in patients with localised high-risk soft tissue sarcoma treated with neoadjuvant chemotherapy without or with regional hyperthermia: A translational research program of the EORTC 62961-ESHO 95 randomised clinical trial. European Journal of Cancer. 2021 Oct 16;158:123-132.

• Smaller tumor volume and 93.27% volume reduction ratio at 12 months among people with papillary thyroid microcarcinoma treated with ultrasound-guided radiofrequency ablation compared to baseline in a meta-analysisa statistical analysis that combines the results of two or more research studies; the results of smaller research studies addressing the same or similar questions can be analyzed as though they are one bigger, more powerful study of 5 uncontrolled trialsa 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 design⁶⁷Xue J, Teng D, Wang H. Efficacy and safety of ultrasound-guided radiofrequency ablation for papillary thyroid microcarcinoma: a systematic review and meta-analysis. International Journal of Hyperthermia. 2022;39(1):1300-1309.

Hyperthermia with chemotherapy, including hyperthermic intraperitoneal chemotherapy (HIPEC) and hyperthermic intrathoracic chemotherapy (HITHOC) 

Advanced cervical cancer

Weak evidence of tumor response among people with recurrent and/or metastatic cervical cancer treated with carboplatin and whole-body hyperthermia

• Poor response (14%) and survival (23% survival at 12 months and 4% at 24 months) among people with recurrent cervical cancer after cisplatin-based chemoradiation or neoadjuvanttherapy used before a main treatment, such as chemotherapy, radiation therapy, and hormone therapy before surgery chemotherapy followed by surgery and radiotherapy then treated with concurrent platinum-based chemotherapy and hyperthermia in a small uncontrolled triala 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 design⁶⁸Heijkoop ST, van Doorn HC et al. Results of concurrent chemotherapy and hyperthermia in patients with recurrent cervical cancer after previous chemoradiation. International Journal of Hyperthermia. 2014 Feb;30(1):6-10.
• Response rates comparable to palliative chemotherapy regimens among people with recurrent and/or metastatic cervical cancer treated with carboplatin and whole-body hyperthermia in a small uncontrolled trial;⁶⁹Richel 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. see concerns about renal toxicity in Safety and precautions ›

Advanced colorectal cancer

No evidence of an effect on peritoneal metastases among people with resected colon cancer treated with adjuvanttreatment applied after initial treatment for cancer, especially to suppress secondary tumor formation HIPEC

• No evidence of an effect on peritoneal metastases among people with resected colon cancer treated with adjuvant HIPEC followed by routine adjuvant chemotherapy compared to chemotherapy alone in a mid-sized RCTrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects⁷⁰Klaver CEL, Wisselink DD et al. Adjuvant hyperthermic intraperitoneal chemotherapy in patients with locally advanced colon cancer (COLOPEC): a multicentre, open-label, randomised trial. Lancet Gastroenterology & Hepatology. 2019 Oct;4(10):761-770.

Preliminary evidence of longer survival and fewer peritoneal metastases after target organ resection among people with advanced colon cancer treated with HIPEC

• Longer survival and fewer peritoneal metastases after target organ resection among people with advanced colon cancer considered at high risk for peritoneal spread treated with HIPEC compared to resection alone in a small controlled triala study design in which people are assigned to either an experimental group or a control group to compare the outcomes from different treatment; assignment is not random, and so this is not as strong a study design as a randomized controlled trial, but still stronger than an uncontrolled trial⁷¹Sammartino P, Sibio S et al. Long-term results after proactive management for locoregional control in patients with colonic cancer at high risk of peritoneal metastases. International Journal of Colorectal Disease. 2014 Sep;29(9):1081-9.

Weak evidence of tumor response among people with metastatic colorectal cancer treated with chemotherapy plus whole-body hyperthermia

• A partial response among 3 of 11 people with metastatic colorectal cancer recalcitrant to previous chemotherapy treated with chemotherapy plus whole-body hyperthermia in a small uncontrolled trial⁷²Hildebrandt B, Drager J et al. Whole-body hyperthermia in the scope of von Ardenne’s systemic cancer multistep therapy (sCMT) combined with chemotherapy in patients with metastatic colorectal cancer: a phase I/II study. International Journal of Hyperthermia. 2004;20(3):317–333.

Advanced ovarian cancer

Modest evidence of longer survival after cytoreductive surgery among people with ovarian cancer treated with HIPEC

• Moderately longer survival and less progression during 10 years of follow up after interval cytoreductive surgery among people with primary epithelial stage 3 ovarian cancer treated with HIPEC compared to surgery alone in a mid-sized RCT⁷³Aronson SL, Lopez-Yurda M et al. Cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy in patients with advanced ovarian cancer (OVHIPEC-1): final survival analysis of a randomised, controlled, phase 3 trial. Lancet Oncology. 2023 Oct;24(10):1109-1118.
• Longer overall survival and better 3-year survival among women with advanced ovarian cancer with disease recurrence after initial treatment then treated with cytoreductive surgery (CRS) and HIPEC then systemic chemotherapy compared to CRS alone and systemic chemotherapy in a mid-sized RCT⁷⁴Spiliotis J, Halkia E et al. Cytoreductive surgery and HIPEC in recurrent epithelial ovarian cancer: a prospective randomized phase III study. Annals of Surgical Oncology. 2015 May;22(5):1570-5.

Advanced pancreatic cancer

Preliminary evidence of tumor response after failed chemotherapy among among people with advanced or metastatic pancreatic cancer treated with chemotherapy and hyperthermia

• Better survival after recurrence and a weak trend toward better overall survival among people with advanced pancreatic ductal adenocarcinoma pretreated with gemcitabine further treated with regional hyperthermia with cisplatin added to gemcitabine compared to gemcitabine alone in a mid-sized RCT⁷⁵Issels RD, Boeck S et al. Regional hyperthermia with cisplatin added to gemcitabine versus gemcitabine in patients with resected pancreatic ductal adenocarcinoma: the HEAT randomised clinical trial. European Journal of Cancer. 2022 Dec 30;181:155-165.
• 4.3-month median time to second progression and 12.9-month median overall survival after failed gemcitabine monotherapy among people with advanced or metastatic pancreatic cancer treated with gemcitabine and cisplatin chemotherapy plus regional hyperthermia in a small uncontrolled trial⁷⁶Tschoep-Lechner KE, Milani V et al. Gemcitabine and cisplatin combined with regional hyperthermia as second-line treatment in patients with gemcitabine-refractory advanced pancreatic cancer. International Journal of Hyperthermia. 2013;29(1):8-16.
• 18% partial response, 53% stable disease, 29% progressive disease, 3.9-month progression-free survival, and 8.9-month overall survival among people with progressive metastatic pancreatic cancer after gemcitabine treatment then treated with gemcitabine-oxaliplatin chemotherapy plus locoregional hyperthermia in a small uncontrolled trial⁷⁷Volovat C, Volovat SR, Scripcaru V, Miron L. Second-line chemotherapy with gemcitabine and oxaliplatin in combination with loco-regional hyperthermia (EHY-2000) in patients with refractory metastatic pancreatic cancer—preliminary results of a prospective trial. Romanian Reports in Physics. 2014;66:166-174.

Bladder cancer

Preliminary evidence of comparable disease-free survival or rates of complete response among people with recurrent non–muscle-invasive bladder cancer treated with radiofrequency-induced thermo-chemotherapy effect (RITE) compared to institutional standard second-line therapy

• Comparable disease-free survival or rates of complete response at 3 months among people with recurrent non–muscle-invasive bladder cancer, although a weak trendan apparent change due to a therapy, close to but not achieving full statistical significance (this is the CancerChoices definition; other researchers and studies may define this differently toward better disease-free survival among people without carcinoma in situ (CIS) and worse survival among people with CIS, treated with radiofrequency-induced thermo-chemotherapy effect (RITE) compared to institutional standard second-line therapy in a mid-sized RCT⁷⁸Tan WS, Panchal A et al. Radiofrequency-induced thermo-chemotherapy effect versus a second course of bacillus Calmette-Guérin or institutional standard in patients with recurrence of non–muscle-invasive bladder cancer following induction or maintenance bacillus Calmette-Guérin therapy (HYMN): a phase iii, open-label, randomised controlled trial. European Urology. 2019 Jan;75(1):63-71.

Good evidence of comparable risk of bladder tumor progression after transurethral resection of bladder tumor treatment (TURBt) among people with non-muscle-invasive bladder cancer treated with either hyperthermia intravesical chemotherapy (HIVEC) with mitomycin C or bacillus Calmette-Guérin (BCG) vaccine

• Comparable risk of bladder tumor progression after transurethral resection of bladder tumor treatment (TURBt) among people with non-muscle-invasive bladder cancer treated with either hyperthermia intravesical chemotherapy (HIVEC) with mitomycin C or bacillus Calmette-Guérin (BCG) vaccine in a network meta-analysisa statistical analysis that combines the results of two or more research studies; the results of smaller research studies addressing the same or similar questions can be analyzed as though they are one bigger, more powerful study of 15 RCTs⁷⁹Zeng N, Xu MY et al. Hyperthermia intravesical chemotherapy acts as a promising alternative to bacillus Calmette-Guérin instillation in non-muscle-invasive bladder cancer: a network meta-analysis. Frontiers in Oncology. 2023 May 12;13:1164932.

Esophageal cancer

Weak evidence of tumor response among people with residual or recurrent esophageal cancer treated with radiofrequency capacitive heating system-based hyperthermia with chemotherapy

• Complete response in 3 and stable disease in 5 of 11 people with residual or recurrent esophageal cancer treated with radiofrequency capacitive heating system-based hyperthermia combined with cisplatin/5-fluorouracil, an oral fluoropyrimidine and irinotecan in a small uncontrolled trial⁸⁰Nishimura S, Saeki H et al. Hyperthermia combined with chemotherapy for patients with residual or recurrent oesophageal cancer after definitive chemoradiotherapy. Anticancer Research. 2015 Apr;35(4):2299-303.

Pleural cancer

Modest evidence of better survival among people with primary or secondary malignant pleural effusions treated with hyperthermic intrapleural or intrathoracic chemotherapy (HITHOC)

• Better survival among people with primary or secondary malignant pleural effusions treated with HITHOC compared to controls in a meta-analysis of 5 RCTs⁸¹Zhou H, Wu W, Tang X, Zhou J, Shen Y. Effect of hyperthermic intrathoracic chemotherapy (HITHOC) on the malignant pleural effusion: a systematic review and meta-analysis. Medicine (Baltimore). 2017 Jan;96(1):e5532.

Stomach (gastric) cancer

Modest and somewhat conflicting evidence of better treatment outcomes after surgery among people with stomach cancer treated with hyperthermic chemotherapy (HIPEC)

• Less disease progression, better progression-free survival, and fewer metachronous peritoneal metastases among people with gastric cancer treated with HIPEC combined with radical surgery compared to surgery alone in a mid-sized RCT⁸²Reutovich 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.
• No evidence of an effect on relapse-free survival or overall survival after radical gastrectomy among people with locally advanced gastric cancer treated with HIPEC and adjuvant chemotherapy regimen (SOX) compared to SOX alone in a small RCT⁸³Fan B, Bu Z et al. Phase II trial of prophylactic hyperthermic intraperitoneal chemotherapy in patients with locally advanced gastric cancer after curative surgery. BMC Cancer. 2021 Mar 2;21(1):216.
• Better survival after cytoreductive surgery among people with peritoneal carcinomatosis from gastric cancer treated with HIPEC compared to surgery alone in a small RCT⁸⁴Yang XJ, Huang CQ et al. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy improves survival of patients with peritoneal carcinomatosis from gastric cancer: final results of a phase III randomized clinical trial. Annals of Surgical Oncology. 2011 Jun;18(6):1575-81.
• Better 5-year survival after curative gastrectomy with extended lymphadenectomy among people with T2-4 gastric cancer treated with hyperthermic chemotherapy peritoneal perfusion compared to normal temperature chemotherapy peritoneal perfusion in a small RCT⁸⁵Yonemura Y, de Aretxabala X et al. Intraoperative chemohyperthermic peritoneal perfusion as an adjuvant to gastric cancer: final results of a randomized controlled study. Hepatogastroenterology. 2001 Nov-Dec;48(42):1776-82. PMID: 11813623.
• No evidence of an effect on 5-year survival after potentially curative gastrectomy among people with advanced gastric cancer with tumors invading deeper than the serosa but with no peritoneal metastasis treated with prophylactic continuous hyperthermic peritoneal perfusion (P-CHPP) compared to people who did not meet the inclusion criteria for P-CHPP in a mid-sized controlled trial⁸⁶Kunisaki C, Shimada H et al. Lack of efficacy of prophylactic continuous hyperthermic peritoneal perfusion on subsequent peritoneal recurrence and survival in patients with advanced gastric cancer. Surgery. 2002 May;131(5):521-8.
• Better 3-year and 5-year survival after curative surgery among people with advanced gastric cancer treated with hyperthermic intraperitoneal chemotherapy (HIPEC) compared to no HIPEC in a mid-sized observationala type of study in which individuals are observed or certain outcomes are measured, but no attempt is made to affect the outcome (for example, no treatment is given); an example is a study that records people’s diets, but doesn’t try to alter their diets, and looks for patterns of disease or other outcomes related to different foods study⁸⁷Murata S, Kaida S et al. A propensity-matched analysis comparing hepatic recurrence after curative gastrectomy followed by adjuvant HIPEC to surgery alone for advanced gastric cancer. Journal of Clinical Oncology. 2016;34(Suppl. 15):4056.
• Better 5-year survival after surgical resection among people with serosa-invasive gastric cancer treated with intraperitoneal hyperthermo-chemo-perfusion (IHCP) compared to no IHCP, but only among people with less than stage 4 cancer, in a mid-sized observational study⁸⁸Kim JY, Bae HS. A controlled clinical study of serosa-invasive gastric carcinoma patients who underwent surgery plus intraperitoneal hyperthermo-chemo-perfusion (IHCP). Gastric Cancer. 2001;4(1):27-33.
• Better 5-year survival after surgery among people with advanced gastric cancer with peritoneal metastases treated with continuous hyperthermic peritoneal perfusion compared to no further treatment after surgery in a small observational study⁸⁹Hirose K, Katayama K et al. Efficacy of continuous hyperthermic peritoneal perfusion for the prophylaxis and treatment of peritoneal metastasis of advanced gastric cancer: evaluation by multivariate regression analysis. Oncology. 1999;57(2):106-14.
• Better survival after curative resection of advanced gastric cancer among people with pathologically confirmed serosal invasion-positive tumors, but no evidence of an effect among people with serosal invasion-negative tumors, treated with continuous hyperthermic peritoneal perfusion with mitomycin C and cisplatin compared to no further treatment in a mid-sized observational study⁹⁰Yonemura Y, Ninomiya I et al. Prophylaxis with intraoperative chemohyperthermia against peritoneal recurrence of serosal invasion-positive gastric cancer. World Journal of Surgery. 1995 May-Jun;19(3):450-4; discussion 455.
• Better 5-year survival after potentially curative resection of gastric cancer among people with macroscopic serosal invasion but no macroscopic peritoneal metastasis treated with continuous hyperthermic peritoneal perfusion with mitomycin C (CHPP-M) compared to no CHPP-M in a small RCT⁹¹Kaibara N, Hamazoe R, Iitsuka Y, Maeta M, Koga S. Hyperthermic peritoneal perfusion combined with anticancer chemotherapy as prophylactic treatment of peritoneal recurrence of gastric cancer. Hepatogastroenterology. 1989 Apr;36(2):75-8.
• Better 3-year survival among people with peritoneal recurrence of gastric cancer with serosal invasion after gastric surgery treated with continuous hyperthermic peritoneal perfusion with mitomycin C compared to controls in a small RCT and observational study⁹²Koga S, Hamazoe R et al. Prophylactic therapy for peritoneal recurrence of gastric cancer by continuous hyperthermic peritoneal perfusion with mitomycin C. Cancer. 1988 Jan 15;61(2):232-7.

Modulated electro-hyperthermia and intravenous vitamin C: preliminary evidence of better survival among people with refractory advanced non-small-cell lung cancer treated with intravenous vitamin C concurrent with modulated electrohyperthermia (mEHT)

• Longer progression-free survivalthe time during and after treatment of a disease that a patient lives without disease progression (worsening) and overall survival, plus a higher 3-month disease control rate, among people with refractory advanced (stage 3b or 4) non-small-cell lung cancer treated with intravenous vitamin C concurrent with mEHT 3 times a week for 25 treatments in total and best supportive care compared to best supportive care alone in a small RCT⁹³Ou J, Zhu X et al. A randomized phase II trial of best supportive care with or without hyperthermia and vitamin C for heavily pretreated, advanced, refractory non-small-cell lung cancer. Journal of Advanced Research. 2020;24:175-82.

Hyperthermia combined with radiotherapy

Cancer as a whole

Weak evidence of tumor response among people with various types of cancer with superficial recurrences treated with radio-hyperthermia

• 60% complete response and 0% partial response at 45 days, then 40% local control and 0% stable disease at 18 months after previous radiotherapy among people with cancers other than breast or head and neck cancer or melanoma with superficial recurrences treated with radio-hyperthermia in a small uncontrolled trial⁹⁴Gabriele P, Ferrara T et al. Radio hyperthermia for re-treatment of superficial tumours. International Journal of Hyperthermia. 2009 May;25(3):189-98.

Bladder cancer

Weak evidence of tumor response among elderly people with muscle-invasive bladder cancers treated with radiotherapy and radiofrequency hyperthermia

• 68.7% free from local and/or distant failure and 67.5% overall survival at 5 years among elderly people with muscle-invasive bladder cancers unfit for surgery or chemoradiotherapy treated with radiotherapy and radiofrequency hyperthermia in a small uncontrolled trial⁹⁵Datta NR, Stutz E et al. A pilot study of radiotherapy and local hyperthermia in elderly patients with muscle-invasive bladder cancers unfit for definitive surgery or chemoradiotherapy. Frontiers in Oncology. 2019;9:889.

Brain cancer

Preliminary evidence of lower mortality among people with brain cancer treated with hyperthermia and radiotherapy

• Lower mortality among people with anaplastic astrocytoma or glioblastoma multiforme treated with thermoradiotherapy and brachytherapy compared to brachytherapy alone in a small RCT⁹⁶Stea B, Rossman K et al. Interstitial irradiation versus interstitial thermoradiotherapy for supratentorial malignant gliomas: a comparative survival analysis. International Journal of Radiation Oncology, Biology, Physics. 1994 Oct 15;30(3):591-600.
• 8.4-month overall survival, with 67% survival at 6 months and 30% survival at 12 months, among people with recurrent high grade gliomas treated with re-irradiation with hyperthermia in a small uncontrolled trial⁹⁷Heo J, Kim SH, Oh YT, Chun M, Noh OK. Concurrent hyperthermia and re-irradiation for recurrent high-grade gliomas. Neoplasma. 2017;64(5):803-808.

Breast cancer

Weak evidence of clinical response and local control among people with recurrent breast cancer treated with radiotherapy and hyperthermia

• 86% clinical response rate and 25% locoregional control at 3 years among people with irresectable locoregional recurrent breast cancer after previous irradiation then treated with reirradiation and hyperthermia in a mid-sized uncontrolled trial⁹⁸Oldenborg S, Griesdoorn V et al. Reirradiation and hyperthermia for irresectable locoregional recurrent breast cancer in previously irradiated area: size matters. Radiotherapy and Oncology. 2015 Nov;117(2):223-8.
• 70% complete response and local control of 53% at 1 year, 40% at 3 years, and 39% at 5 years after re-irradiation among people with an irresectable macroscopic breast cancer recurrence treated with hyperthermia in a mid-sized uncontrolled trial⁹⁹Linthorst 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.
• 71% complete response among people with recurrent breast cancer with macroscopic tumors, and 73% local control, for a median of 32 months, among people with either macro- or microscopic tumors, treated with reirradiation with local hyperthermia in a mid-sized uncontrolled trial¹⁰⁰van der Zee J, van der Holt B et al. Reirradiation combined with hyperthermia in recurrent breast cancer results in a worthwhile local palliation. British Journal of Cancer. 1999 Feb;79(3-4):483-90.
• 66% survival and 78% local control at 3 years and 65% local control at 5 years after resection or clinically complete remission among people with previously irradiated persistent locoregional recurrent breast cancer treated with re-irradiation and hyperthermia in a small uncontrolled trial¹⁰¹Oldenborg S, Van Os RM et al. Elective re-irradiation and hyperthermia following resection of persistent locoregional recurrent breast cancer: a retrospective study. International Journal of Hyperthermia. 2010;26(2):136-44.
• 28-month median overall survival, with 71% survival at 1 year and 54% at 2 years among extensively pretreated women with locally recurrent breast cancer after primary modified radical mastectomy treated with combined hyperthermia and radiation therapy in a small uncontrolled trial¹⁰²Hehr T, Lamprecht U et al. Thermoradiotherapy for locally recurrent breast cancer with skin involvement. International Journal of Hyperthermia. 2001 Jul-Aug;17(4):291-301.
• 65.9% complete response and 29.5% partial response at 45 days, then 72.7% local control and 20.5% stable disease at 18 months among people with breast cancer with superficial recurrences after previous radiotherapy then treated with radio-hyperthermia in a small uncontrolled trial¹⁰³Gabriele P, Ferrara T et al. Radio hyperthermia for re-treatment of superficial tumours. International Journal of Hyperthermia. 2009 May;25(3):189-98.
• Complete response among 56% of previously irradiated and 47% of unirradiated tumors among people with locoregional recurrence of breast cancer treated with local hyperthermia combined with external irradiation at a lower dose than typical in a small uncontrolled trial¹⁰⁴Li G, Mitsumori M et al. Local hyperthermia combined with external irradiation for regional recurrent breast carcinoma. International Journal of Clinical Oncology. 2004 Jun;9(3):179-83.
• 95% tumor response rate and 5% recurrence rate but no evidence of an effect on survival, possibly due to the systemic tumor burden existing outside of the treated fields, among people with extensive recurrences on the chest wall of advanced carcinoma of the breast comprising diffuse lesions which had failed previous therapy, including radiotherapy among most people, treated with radiation therapy and multiple field patchwork hyperthermia in a small uncontrolled trial¹⁰⁵Engin K, Tupchong L et al. Multiple field hyperthermia combined with radiotherapy in advanced carcinoma of the breast. International Journal of Hyperthermia. 1994 Sep-Oct;10(5):587-603.
• 41% complete response, sustained for greater than 12 months among 67% of people, and 23% partial response 1 month after treatment among people with locally recurrent, previously irradiated adenocarcinoma of the breast treated with irradiation and externally applied microwave hyperthermia in a small uncontrolled trial¹⁰⁶Phromratanapongse P, Steeves RA, Severson SB, Paliwal BR. Hyperthermia and irradiation for locally recurrent previously irradiated breast cancer. Strahlentherapie und Onkologie. 1991 Feb;167(2):93-7.

Cervical cancer

Preliminary evidence of comparable event-free survival after radiotherapy among people with locally advanced cervical cancer treated with either hyperthermia or chemotherapy

• Comparable event-free survival after radiotherapy among people with locally advanced cervical cancer treated with either hyperthermia or chemotherapy (cisplatin) in a small RCT¹⁰⁷Lutgens LC, Koper PC et al. Radiation therapy combined with hyperthermia versus cisplatin for locally advanced cervical cancer: results of the randomized RADCHOC trial. Radiotherapy and Oncology. 2016 Sep;120(3):378-382.

Esophageal cancer

Preliminary evidence of better survival among people with esophageal cancer treated with hyperthermia and radiation

• Better 5-year survival among people with esophageal cancer treated with hyperthermia, chemotherapy and radiation treatment before surgery compared to chemotherapy alone in a small observational study¹⁰⁸Kuwano H, Sumiyoshi K et al. Preoperative hyperthermia combined with chemotherapy and irradiation for the treatment of patients with esophageal carcinoma. Tumori. 1995;81(1):18-22.
• 19-month median progression-free survival and 29-month median overall survival among people with esophageal cancer treated with hyperthermia and radiotherapy in a small uncontrolled trial¹⁰⁹Liming S, Yongling J, Qiner W, Xianghui D. Regional hyperthermia combined with radiotherapy for esophageal squamous cell carcinoma with supraclavicular lymph node metastasis. Oncotarget. 2017 Jan 17;8(3):5339–5348.

Head and neck cancer

Weak evidence of tumor response and control after previous radiotherapy among people with head and neck cancer with superficial recurrences treated with radio-hyperthermia

• 40% complete response and 13.3% partial response at 45 days, then 33.3% local control and 40% stable disease at 18 months after previous radiotherapy among people with head and neck cancer with superficial recurrences treated with radio-hyperthermia in a small uncontrolled trial¹¹⁰Gabriele P, Ferrara T et al. Radio hyperthermia for re-treatment of superficial tumours. International Journal of Hyperthermia. 2009 May;25(3):189-98.

Melanoma

Weak evidence of tumor response among people with melanoma with superficial recurrences treated with radio-hyperthermia

• 33.3% complete response and 25% partial response at 45 days, then 50% local control and 16.7% stable disease at 18 months among people with melanoma with superficial recurrences treated with radio-hyperthermia in a small uncontrolled trial¹¹¹Gabriele P, Ferrara T et al. Radio hyperthermia for re-treatment of superficial tumours. International Journal of Hyperthermia. 2009 May;25(3):189-98.

Prostate cancer

Weak evidence of tumor response among people with locally advanced prostate cancer treated with radiotherapy and regional hyperthermia

• 27% biochemical relapse among people with locally advanced prostate carcinoma treated with conformal external beam irradiation (EBRT) and either regional hyperthermia (coaxial transverse electrical magnetic system) or interstitial hyperthermia (multi-electrode current source system), comparing favorably to radiation alone, in a small uncontrolled trial¹¹²Van Vulpen M, De Leeuw AA et al. Radiotherapy and hyperthermia in the treatment of patients with locally advanced prostate cancer: preliminary results. BJU International. 2004 Jan;93(1):36-41.
• 88-month median survival among people with locally advanced adenocarcinoma of the prostate treated with external beam radiotherapy and regional hyperthermia in a small uncontrolled trial¹¹³Algan O, Fosmire H et al. External beam radiotherapy and hyperthermia in the treatment of patients with locally advanced prostate carcinoma. Cancer. 2000 Jul 15;89(2):399-403.

Hyperthermia combined with both radiation and chemotherapy

Advanced cervical cancer

Weak evidence of tumor response among people with advanced-stage cervical cancer treated with platinum-based chemotherapy, radiotherapy, brachytherapy, and hyperthermia

• 79% overall survival at 12 months among people with advanced-stage cervical cancer treated with platinum-based chemotherapy followed by full-dose radiotherapy, brachytherapy, and 5 hyperthermia treatments in a small uncontrolled trial¹¹⁴Heijkoop ST, Franckena M et al. Neoadjuvant chemotherapy followed by radiotherapy and concurrent hyperthermia in patients with advanced-stage cervical cancer: a retrospective study. International Journal of Hyperthermia. 2012;28(6):554-61.

Advanced esophageal cancer

Weak evidence of tumor response among people with metastatic esophageal squamous cell carcinoma treated with intensity-modulated radiotherapy and hyperthermia, plus chemotherapy for most people

• 34.9% progression-free survival and 42.5% overall survival at 3 years among people with upper and middle thoracic esophageal squamous cell carcinoma with supraclavicular lymph node metastasis treated with intensity-modulated radiotherapy and hyperthermia, plus chemotherapy for most people, in a small uncontrolled trial¹¹⁵Sheng 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.

Advanced head and neck cancer

Weak evidence of tumor response among people with head and neck cancer treated with radiotherapy, cisplatin, and hyperthermia

• 51% overall survival and 54% disease-free survival at 2 years among people with carcinomas of the head and neck with N2 or N3 metastatic cervical lymph nodes treated with radiation therapy, cisplatin, and hyperthermia in a small uncontrolled trial¹¹⁶Serin M, Erkal HS, Cakmak A. Radiation therapy, cisplatin and hyperthermia in combination in management of patients with carcinomas of the head and neck with N2 or N3 metastatic cervical lymph nodes. Radiotherapy and Oncology. 1999;50(1):103-106.
• 38% nodal complete response and overall survival at 1 year among people with recurrent carcinomas of the head and neck with metastatic cervical lymph nodes treated with radiation therapy, cisplatin, and hyperthermia in a small uncontrolled trial¹¹⁷Serin M, Erkal HS, Cakmak A. Radiation therapy, cisplatin and hyperthermia in combination in management of patients with recurrent carcinomas of the head and neck with metastatic cervical lymph nodes. International Journal of Hyperthermia. 1999;15(5):371-381.

Hyperthermia with chemotherapy combined with surgery

Adrenocortical cancer

Weak evidence of longer survival than expected among people with adrenocortical carcinoma treated with cytoreduction surgery and HIPEC with cisplatin

• Mean disease-free survival of 19 months among people with adrenocortical carcinoma confined to the peritoneum treated with cytoreduction surgery and HIPEC with cisplatin in a small uncontrolled trial¹¹⁸Hughes 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.

Colorectal cancer

No evidence of an effect on overall survival among people with colorectal cancer at high risk for developing colorectal peritoneal metastases treated with surgery and HIPEC in a mid-sized study

• No evidence of an effect on overall survival among people with colorectal cancer at high risk for developing colorectal peritoneal metastases treated with second-look surgery (exploration of the entire abdominal cavity and resection of all peritoneal implants if resectable) and HIPEC compared to simple surveillance in a mid-sized RCT¹¹⁹Goéré D, Glehen O et al. Second-look surgery plus hyperthermic intraperitoneal chemotherapy versus surveillance in patients at high risk of developing colorectal peritoneal metastases (PROPHYLOCHIP–PRODIGE 15): a randomised, phase 3 study. Lancet Oncology. 2020 Sep;21(9):1147-1154.

Desmoplastic small round cell tumors and other tumors

Weak evidence of tumor response among people with desmoplastic small round cell tumors, peritoneal tumor, and other tumors treated with cytoreductive surgery and HIPEC

• 30.9-month median disease-free survival and 57.5-month median overall survival among children (median age at diagnosis of 14.8 years) with peritoneal tumor spread from mesothelioma, desmoplastic small round cell tumors, and other tumors treated with cytoreductive surgery with HIPEC in a small uncontrolled trial¹²⁰Scalabre A, Philippe-Chomette P et al. Cytoreductive surgery and hyperthermic intraperitoneal perfusion with chemotherapy in children with peritoneal tumor spread: a French nationwide study over 14 years. Pediatric Blood & Cancer. 2018 Apr;65(4).
• 79% overall 3-year survival and 14.0-month median recurrence-free survival among people with desmoplastic small round cell tumors treated with cytoreductive surgery and HIPEC with cisplatin in a small uncontrolled trial¹²¹Hayes-Jordan AA, Coakley BA et al. Desmoplastic small round cell tumor treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: results of a phase 2 trial. Annals of Surgical Oncology. 2018 Apr;25(4):872-877.

Lung cancer

Weak evidence of tumor response among people with lung cancer with advanced pleural spread treated with thoracoscopic intrapleural perfusion hyperthermic chemotherapy and radical surgery

• 19-month mean survival time among people with lung cancer with advanced pleural spread treated with thoracoscopic intrapleural perfusion hyperthermic chemotherapy and radical surgery (panpleuropneumonectomy) in a small uncontrolled trial¹²²Shigemura N, Akashi A, Ohta M, Matsuda H. Combined surgery of intrapleural perfusion hyperthermic chemotherapy and panpleuropneumonectomy for lung cancer with advanced pleural spread: a pilot study. Interactive Cardiovascular and Thoracic Surgery. 2003 Dec;2(4):671-5.

Peritoneal sarcomatosis or rhabdomyosarcomas

Weak evidence of tumor response among people with peritoneal sarcomatosis or advanced peritoneal rhabdomyosarcomas treated with cytoreductive surgery and HIPEC

• 29.3-month median overall survival and 35.3% 5-year overall survival among people with peritoneal sarcomatosis treated with cytoreductive surgery and HIPEC in a meta-analysis of 16 uncontrolled studies¹²³Wong LCK, Li Z et al. Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) in peritoneal sarcomatosis—a systematic review and meta-analysis. European Journal of Surgical Oncology. 2022 Mar;48(3):640-648.
• Complete response (no evidence of disease) after a median follow up of 12 months among children 5 and younger with advanced peritoneal rhabdomyosarcomas treated with cytoreductive surgery and HIPEC in a small uncontrolled study¹²⁴Gesche J, Beckert S. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: A safe treatment option for intraperitoneal rhabdomyosarcoma in children below 5 years of age. Pediatric Blood & Cancer. 2019 Feb;66(2):e27517.

Uterine sarcoma

Weak evidence of tumor response after cytoreductive surgery among people with uterine sarcoma treated with intraperitoneal hyperthermic chemotherapy perfusion

• 65% overall survival and 30% progression-free survival at 5 years after cytoreductive surgery among people with uterine sarcoma treated with intraperitoneal hyperthermic perfusion of either cisplatin+mitomycin C or cisplatin+doxorubicin in a small uncontrolled trial¹²⁵Kusamura S, Raspagliesi F et al. Uterine sarcoma treated by cytoreductive surgery and intraperitoneal hyperthermic perfusion: a feasiblity study. Journal of Chemotherapy. 2004 Nov;16 Suppl 5:19-22.

Pancreatic cancer

Weak evidence of tumor response after cytoreductive surgery among people with pancreatic cancer treated with HIPEC

• 75% survival at 1 year (4 studies), 50.4% survival at 2 years (4 studies), 24.0% survival 3 years (3 studies), 20.4% survival at 5 years (3 studies), with an 11-month median time to relapse or progression after cytoreductive surgery among people with pancreatic cancer treated with HIPEC in a meta-analysis of uncontrolled trials¹²⁶Frassini S, Calabretto F et al. Intraperitoneal chemotherapy in the management of pancreatic adenocarcinoma: a systematic review and meta-analysis. European Journal of Surgical Oncology. 2022 Sep;48(9):1911-1921.

Hyperthermia combined with chemotherapy, radiation, and surgery

Weak evidence of tumor response among people with high-risk soft-tissue sarcoma of the extremities treated with chemotherapy combined with regional hyperthermia followed by surgery, radiation, and adjuvant chemotherapy

• 21% objective response, 105-month median overall survival, 57% overall survival and 48% local failure-free survival at 5 years, and 79% limb preservation among people with high-risk soft-tissue sarcoma of the extremities treated with 4 cycles of etoposide, ifosfamide, and doxorubicin combined with regional hyperthermia followed by surgery, radiation, and adjuvant chemotherapy in a small uncontrolled trial¹²⁷Schlemmer M, Wendtner CM et al. Thermochemotherapy in patients with extremity high-risk soft tissue sarcomas (HR-STS). International Journal of Hyperthermia. 2010;26(2):127-35.

Whole-body hyperthermia and chemotherapy

Colorectal cancer

Weak evidence of tumor response among people with metastatic colorectal cancer with disease progression treated with whole-body hyperthermia and chemotherapy

• An overall response rate of 20% among people with metastatic colorectal cancer with disease progression during or within 3 months of chemotherapy regimen further treated with chemotherapy and whole-body hyperthermia in a small uncontrolled trial¹²⁸Hegewisch-Becker S, Gruber Y et al. Whole-body hyperthermia (41.8 C) combined with bimonthly oxaliplatin, high-dose leucovorin and 5-fluorouracil 48-hour continuous infusion in pretreated metastatic colorectal cancer: a phase II study. Annals of Oncology. 2002;13(8):1197–1204.

Mesothelioma

Weak evidence of tumor response among people with mesothelioma treated with whole-body hyperthermia and chemotherapy

• 29.6-week median progression-free survival time of s and 76.6-week median overall survival time among chemonaive people with non-metastatic mesothelioma treated with whole-body hyperthermia and ICE (ifosfamide, carboplatin, and etoposide) chemotherapy in a small uncontrolled trial¹²⁹Bakhshandeh A, Bruns I et al. Ifosfamide, carboplatin and etoposide combined with 41.8 degree C whole body hyperthermia for malignant pleural mesothelioma. Lung Cancer 2003;39(3):339–345.

Sarcoma

Weak evidence of tumor response among people with sarcoma treated with whole-body hyperthermia and chemotherapy

• 28.4% overall response rate (moderately higher among people with no prior treatment), 32.6% stable disease, and median survival of 393 days among people with metastatic sarcoma treated with whole-body hyperthermia and ‘ICE’ chemotherapy in a small uncontrolled trial¹³⁰Westermann 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.
• 58% partial remissions, 25% disease stabilization among adults with refractory sarcoma treated with whole-body hyperthermia and ‘ICE’ chemotherapy in a small uncontrolled trial¹³¹Wiedemann 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.
• 12% partial responses and 4 objective tumor responses lasting more than 4 months, plus stable disease for 38 month in 1 person with previously rapidly growing chondrosarcoma pulmonary metastases, among people with chemotherapy-resistant metastatic sarcoma treated with whole-body hyperthermia and chemotherapy (BCNU) in a small uncontrolled trial¹³²Bull JM, Cronau LH et al. Chemotherapy resistant sarcoma treated with whole body hyperthermia (WBH) combined with 1-3-bis(2-chloroethyl)-1-nitrosourea (BCNU). International Journal of Hyperthermia. 1992;8(3),297–304.

Hyperthermia combined with sorafenib

Weak evidence of tumor response among people with advanced liver cancer (hepatocellular carcinoma) treated with deep locoregional electro-hyperthermia and sorafenib

• A median progression-free survival of 5.2 months and overall survival of 10.4 months among people with advanced hepatocellular carcinoma treated with deep locoregional electro-hyperthermia and sorafenib in a small uncontrolled trial¹³³Gadaleta-Caldarola G, Infusino et al. Sorafenib and locoregional deep electro-hyperthermia in advanced hepatocellular carcinoma: a phase II study. Oncology Letters. 2014;8(4):1783-1787.

Electro-hyperthermia with thermo-active agents combined with chemotherapy

Weak evidence of tumor response among people with chemo-refractory malignant primary liver cancer treated with deep electro-hyperthermia with thermo-active agents and chemotherapy

• Median survival of 20.5 weeks among people with chemo- refractory malignant primary liver cancer who had exhausted other treatment options, including surgery, treated with deep electro-hyperthermia with thermo-active agents and chemotherapy in a small uncontrolled trial¹³⁴Ferrari VD, Ponti SD et al. Deep electro-hyperthermia (EHY) with or without thermo-active agents in patients with advanced hepatic cell carcinoma: phase II study. Journal of Clinical Oncology. 2007;5(18):suppl15168.

Modulated electro-hyperthermia (mEHT) combined with traditional Chinese medicine

Preliminary evidence of higher objective response rate among people with peritoneal carcinomatosis with malignant ascites treated with local mEHT combined with the traditional Chinese medicine ‘Shi Pi’ herbal decoction

• Higher objective response rate among people with peritoneal carcinomatosis with malignant ascites treated with local mEHT combined with the traditional Chinese medicine ‘Shi Pi’ herbal decoction compared to standard intraperitoneal chemoinfusion in a mid-sized RCT¹³⁵Pang CLK, Zhang X et al. Local modulated electro-hyperthermia in combination with traditional Chinese medicine vs. intraperitoneal chemoinfusion for the treatment of periotoneal carcinomatosis with malignant ascites: a phase II randomized trial. Molecular and Clinical Oncology. 2017;6(5):723-732.

Hyperthermia combined with androgen suppression therapy and radiotherapy 

Weak evidence of tumor response among people with locally advanced prostate cancer treated with androgen suppression therapy and conformal radiotherapy plus local hyperthermia

• 87% 5-year overall survival and a 49% 5-year biochemical progression-free survival among people with locally advanced prostate cancer treated with androgen suppression therapy and conformal radiotherapy plus local hyperthermia in a small uncontrolled trial¹³⁶Maluta S, Dall’Oglio S et al. Conformal radiotherapy plus local hyperthermia in patients affected by locally advanced high risk prostate cancer: preliminary results of a prospective phase II study. International Journal of Hyperthermia. 2007 Aug;23(5):451-6.

Microwave inactivation in situ with curettage and bone grafting

Weak evidence of tumor response and better function and pain scores among people with primary or metastatic tumor of the proximal humerus treated with intraoperative microwave inactivation in situ followed by curettage and bone grafting

• 67.3% 5-year overall survival and 71.4% 5-year tumor-specific survival, with better function and pain scores after treatment compared to before surgery, among people with primary or metastatic tumor of the proximal humerus treated with intraoperative microwave inactivation in situ followed by curettage and bone grafting assisted with internal fixation in a small uncontrolled trial¹³⁷Pang CG, Huang ZF et al. Microwave-induced hyperthermia in situ in the treatment of tumors of proximal humerus: long-term results with functionary sparing surgery. Journal of Orthopaedic Surgery and Research. 2023 Jun 13;18(1):433.

Preliminary evidence of immune activation after neoadjuvant chemotherapy among people with soft-tissue sarcoma treated with regional hyperthermia

• Higher markers of immune activation (tumor-infiltrating lymphocytes) and related tumor response after neoadjuvant chemotherapy among people with high-risk soft-tissue sarcoma treated with regional hyperthermia compared to chemotherapy alone in a mid-sized RCTrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects¹³⁸Issels RD, Noessner E et al. Immune infiltrates in patients with localised high-risk soft tissue sarcoma treated with neoadjuvant chemotherapy without or with regional hyperthermia: A translational research program of the EORTC 62961-ESHO 95 randomised clinical trial. European Journal of Cancer. 2021 Oct 16;158:123-132.

Preliminary evidence of some higher markers of immune activation after surgery for colorectal cancer among people treated with fever-range whole-body hyperthermia

• Higher levels of heat shock proteins compared to controls and lower tumor necrosis factor alpha and procalcitonin but no evidence of an effectoverall, one or more studies did not demonstrate that a treatment or intervention led to an expected outcome; this does not always mean that there is no effect in clinical practice, but that the studies may have been underpowered (too few participants) or poorly designed. Larger, well-designed studies provide more confidence in making assessments. on interleukin 6/10, human leukocyte antigen-DR, or LPS binding protein after surgery for colorectal cancer among people treated with fever-range whole-body hyperthermia compared to controls in a small RCT¹³⁹Sulyok I, Fleischmann E et al. Effect of preoperative fever-range whole-body hyperthermia on immunological markers in patients undergoing colorectal cancer surgery. British Journal of Anaesthesia. 2012 Nov;109(5):754-61.

• Higher peak concentrations of vitamin C (ascorbic acid) among people with stage 3–4 non-small cell lung cancer treated with intravenous vitamin C (IVAA) simultaneously with mEHT compared to IVAA before or after mEHT or IVAA alone in a small randomized comparison triala study in which two different treatments are compared for their effects¹⁴⁰Ou J, Zhu X et al. A phase I-II clinical trial to evaluate the safety, pharmacokinetics and efficacy of high dose intravenous ascorbic acid synergy with mEHT in Chinese patients with stage III-IV non-small cell lung cancer. Annals of Oncology. 2017;28:iii12‐iii13.

Preliminary evidence of better scores on symptoms specific to nasopharyngeal carcinoma during and after chemoradiotherapy among people with nasopharyngeal carcinoma treated with non-invasive extracorporeal radiofrequency (ERF) hyperthermia

• Better scores on symptoms specific to nasopharyngeal carcinoma (pain, swallowing, speech, social eating, opening mouth, dry mouth, sticky saliva) during and after chemoradiotherapy among people with nasopharyngeal carcinoma treated with non-invasive extracorporeal radiofrequency (ERF) hyperthermia compared to chemoradiotherapy alone in a small RCTrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects¹⁴¹Zhao C, Chen J, Yu B, Chen X. Improvement in quality of life in patients with nasopharyngeal carcinoma treated with non-invasive extracorporeal radiofrequency in combination with chemoradiotherapy. International Journal of Radiation Biology. 2014 Oct;90(10):853-8.

No evidence of an effect on chemoradiotherapy toxicity among people with cervical cancer and HIV treated with modulated electrohyperthermia (mEHT)

• No evidence of an effect on chemoradiotherapy toxicity among people with cervical cancer and HIV treated with modulated electrohyperthermia (mEHT) compared to chemoradiotherapy alone in a mid-sized RCT¹⁴²Minnaar CA, Kotzen JA et al. Analysis of the effects of mEHT on the treatment-related toxicity and quality of life of HIV-positive cervical cancer patients. International Journal of Hyperthermia. 2020;37(1):263-272.

• Better cognitive function scores among people with cervical cancer and HIV treated with modulated electrohyperthermia (mEHT) compared to chemoradiotherapy alone in a mid-sized RCTrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects¹⁴³Minnaar CA, Kotzen JA et al. Analysis of the effects of mEHT on the treatment-related toxicity and quality of life of HIV-positive cervical cancer patients. International Journal of Hyperthermia. 2020;37(1):263-272.

• Less fatigue among people with cervical cancer and HIV treated with modulated electrohyperthermia (mEHT) compared to chemoradiotherapy alone in a mid-sized RCTrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects¹⁴⁴Minnaar CA, Kotzen JA et al. Analysis of the effects of mEHT on the treatment-related toxicity and quality of life of HIV-positive cervical cancer patients. International Journal of Hyperthermia. 2020;37(1):263-272.

• Less pain among people with cervical cancer and HIV treated with modulated electrohyperthermia (mEHT) compared to chemoradiotherapy alone in a mid-sized RCTrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects¹⁴⁵Minnaar CA, Kotzen JA et al. Analysis of the effects of mEHT on the treatment-related toxicity and quality of life of HIV-positive cervical cancer patients. International Journal of Hyperthermia. 2020;37(1):263-272.
• Longer time to pain progression after external beam radiation among people with painful bony metastasis from a variety of primary tumor types treated with hyperthermia compared to radiation alone in a small RCT¹⁴⁶Chi MS, Yang KL et al. Comparing the effectiveness of combined external beam radiation and hyperthermia versus external beam radiation alone in treating patients with painful bony metastases: a phase 3 prospective, randomized, controlled trial. International Journal of Radiation Oncology, Biology, Physics. 2018;100(1):78-87.
• Lower pain scores after chemotherapy (5-FU) before surgery, bypass surgery with intraoperative bolus infusion of 5-FU and then multi-agent chemotherapy plus sandostatin and external beam irradiation after surgery among people with stage 4 pancreatic adenocarcinoma treated with a single session of intraoperative hyperthermia directly on the tumor compared to no hyperthermia in a small controlled triala study design in which people are assigned to either an experimental group or a control group to compare the outcomes from different treatment; assignment is not random, and so this is not as strong a study design as a randomized controlled trial, but still stronger than an uncontrolled trial¹⁴⁷Kouloulias VE, Kouvaris JR et al. Intraoperative hyperthermia in conjunction with multi-schedule chemotherapy (pre-, intra- and post-operative), by-pass surgery, and post-operative radiotherapy for the management of unresectable pancreatic adenocarcinoma. International Journal of Hyperthermia. 2002 May-Jun;18(3):233-52.
• Lower pain scores after radiotherapy among people with bony metastases treated with hyperthermia compared to baseline in an uncontrolled triala 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 design¹⁴⁸Ariyafar T, Mahdavi SR et al. Evaluating the effectiveness of combined radiotherapy and hyperthermia for the treatment response of patients with painful bony metastases: a phase 2 clinical trial. Journal of Thermal Biology. 2019 Aug;84:129-135.

Preliminary evidence of better quality of life and performance status among people with advanced cancer treated with a hyperthermia

• Better quality of life after treatment with gemcitabine and cisplatin among people with advanced non-small cell lung cancer treated with radiofrequency hyperthermia compared to gemcitabine and cisplatin alone in a small RCTrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects¹⁴⁹Shen H, Li XD et al. The regimen of gemcitabine and cisplatin combined with radio frequency hyperthermia for advanced non-small cell lung cancer: a phase II study. International Journal of Hyperthermia. 2011;27(1):27-32.
• Better quality of life and performance status (Karnofsky scores) after chemotherapy (5-FU) before surgery, bypass surgery with intraoperative bolus infusion of 5-FU, and then multi-agent chemotherapy plus sandostatin and external beam irradiation after surgery among people with stage 4 pancreatic adenocarcinoma treated with a single session of intraoperative hyperthermia directly on the tumor compared to no hyperthermia in a small controlled triala study design in which people are assigned to either an experimental group or a control group to compare the outcomes from different treatment; assignment is not random, and so this is not as strong a study design as a randomized controlled trial, but still stronger than an uncontrolled trial¹⁵⁰Kouloulias VE, Kouvaris JR et al. Intraoperative hyperthermia in conjunction with multi-schedule chemotherapy (pre-, intra- and post-operative), by-pass surgery, and post-operative radiotherapy for the management of unresectable pancreatic adenocarcinoma. International Journal of Hyperthermia. 2002 May-Jun;18(3):233-52.

Preliminary evidence of better social and emotional functioning among people with cervical cancer and HIV treated with modulated electrohyperthermia

• Better social and emotional functioning among people with cervical cancer and HIV treated with modulated electrohyperthermia (mEHT) compared to chemoradiotherapy alone in a mid-sized RCT¹⁵¹Minnaar CA, Kotzen JA et al. Analysis of the effects of mEHT on the treatment-related toxicity and quality of life of HIV-positive cervical cancer patients. International Journal of Hyperthermia. 2020;37(1):263-272.

Radiation therapy, cisplatin, and ultrasound hyperthermia: weak evidence of fewer presenting symptoms among people with recurrent carcinomas of the head and neck with metastatic cervical lymph nodes treated with radiation therapy, cisplatin, and ultrasound hyperthermia

• Fewer (palliation) presenting symptoms among 90% of people with recurrent carcinomas of the head and neck with metastatic cervical lymph nodes treated with radiation therapy, cisplatin, and ultrasound hyperthermia in a small uncontrolled triala 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 design¹⁵²Serin M, Erkal HS, Cakmak A. Radiation therapy, cisplatin and hyperthermia in combination in management of patients with recurrent carcinomas of the head and neck with metastatic cervical lymph nodes. International Journal of Hyperthermia. 1999;15(5):371-381.

Modulated electro-hyperthermia (mEHT) with traditional Chinese medicine: preliminary evidence of higher quality of life among people with peritoneal carcinomatosis with malignant ascites treated with local modulated electro-hyperthermia (mEHT) combined with the traditional Chinese medicine ‘Shi Pi’ herbal decoction

• Higher quality of life among people with peritoneal carcinomatosis with malignant ascites treated with local modulated electro-hyperthermia (mEHT) combined with the traditional Chinese medicine ‘Shi Pi’ herbal decoction compared to standard intraperitoneal chemoinfusion in a mid-sized RCTrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects¹⁵³Pang CLK, Zhang X et al. Local modulated electro-hyperthermia in combination with traditional Chinese medicine vs. intraperitoneal chemoinfusion for the treatment of periotoneal carcinomatosis with malignant ascites: a phase II randomized trial. Molecular and Clinical Oncology. 2017;6(5):723-732.

Modulated electrohyperthermia with intravenous vitamin C 

Preliminary evidence of better quality of life among people with refractory advanced (stage 3b or 4) non-small-cell lung cancer treated with intravenous vitamin C concurrent with modulated electrohyperthermia

• Better quality of life among people with refractory advanced (stage 3b or 4) non-small-cell lung cancer treated with intravenous vitamin C concurrent with modulated electrohyperthermia 3 times a week for 25 treatments in total and best supportive care compared to best supportive care alone in a small RCT¹⁵⁴Ou J, Zhu X et al. A randomized phase II trial of best supportive care with or without hyperthermia and vitamin C for heavily pretreated, advanced, refractory non-small-cell lung cancer. Journal of Advanced Research. 2020;24:175-82.

Weak evidence of higher functioning among people with stage 3–4 non-small cell lung cancer treated with intravenous vitamin C (IVAA) and modulated electrohyperthermia

• Higher functioning among people with stage 3–4 non-small cell lung cancer treated with intravenous vitamin C (IVAA) with modulated electrohyperthermia (mEHT) compared to baseline in a small randomized comparison triala study in which two different treatments are compared for their effects¹⁵⁵Ou J, Zhu X et al. A phase I-II clinical trial to evaluate the safety, pharmacokinetics and efficacy of high dose intravenous ascorbic acid synergy with mEHT in Chinese patients with stage III-IV non-small cell lung cancer. Annals of Oncology. 2017;28:iii12‐iii13.

• Longer recurrence-free survival after a complete transurethral resection of bladder tumor (TURBT) for primary or recurrent superficial transitional cell carcinoma among people treated with adjunctiveconnected or added to a main treatment or therapy, not used alone mitomycin C and microwave-induced hyperthermia compared to mitomycin C alone in a small RCTrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects¹⁵⁶Colombo R, Da Pozzo LF et al. Multicentric study comparing intravesical chemotherapy alone and with local microwave hyperthermia for prophylaxis of recurrence of superficial transitional cell carcinoma. Journal of Clinical Oncology. 2003 Dec 1;21(23):4270-6.
• A higher rate of recurrence-free survival after intravesical adjuvant therapy with pirarubicin (THP) after transurethral resection of bladder tumors (TURBT) among people with urothelial carcinoma of the bladder treated with hyperthermia compared to the same treatment without hyperthermia in a mid-sized controlled triala study design in which people are assigned to either an experimental group or a control group to compare the outcomes from different treatment; assignment is not random, and so this is not as strong a study design as a randomized controlled trial, but still stronger than an uncontrolled trial¹⁵⁷Zhou J, Li L et al. Efficacy analysis of a novel thermochemotherapy scheme with pirarubicin for intermediate- and high-risk nonmuscle-invasive bladder cancer: a single-institution nonrandomized concurrent controlled trial. International Journal of Hyperthermia. 2019;36(1):868-875.

Anal cancer: preliminary evidence of lower risk of recurrence after chemoradiotherapy among people with anal cancer treated with hyperthermia

• Lower risk of recurrence (better disease-free survival) after chemoradiotherapy among people with anal cancer treated with hyperthermia compared to chemoradiotherapy alone in a mid-sized controlled triala study design in which people are assigned to either an experimental group or a control group to compare the outcomes from different treatment; assignment is not random, and so this is not as strong a study design as a randomized controlled trial, but still stronger than an uncontrolled trial¹⁵⁸Ott OJ, Schmidt M et al. Chemoradiotherapy with and without deep regional hyperthermia for squamous cell carcinoma of the anus. Strahlentherapie und Onkologie. 2019 Jul;195(7):607-614.

Stomach cancer: preliminary evidence of lower risk of recurrence after radical gastrectomy among people with stomach (gastric) cancer treated with hyperthermic chemotherapy

• Lower risk of recurrence (longer disease-free survival) after radical gastrectomy among people with stage 3 gastric cancer treated with HIPEC using cisplatin and and oral S-1 compared to standard intravenous cisplatin and oral S-1 in a mid-sized RCTrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects¹⁵⁹Liu L, Sun L, Zhang N et al. A novel method of bedside hyperthermic intraperitoneal chemotherapy as adjuvant therapy for stage-III gastric cancer. International Journal of Hyperthermia. 2022;39(1):239-245.

Risk of recurrence

Preliminary and somewhat conflicting evidence of lower risk of recurrence among people with cervical cancer treated with hyperthermia

• Lower risk of recurrence (greater disease-free survival) at 6 months after chemoradiotherapy among people with stage 2B–3B squamous cell carcinoma of the cervix treated with modulated electro-hyperthermia compared to chemoradiotherapy alone in a mid-sized RCTrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects¹⁶⁰Minnaar CA, Kotzen JA et al. The effect of modulated electro-hyperthermia on local disease control in HIV-positive and -negative cervical cancer women in South Africa: early results from a phase III randomised controlled trial. PLoS One. 2019 Jun 19;14(6):e0217894.
• A weak trendan apparent change due to a therapy, close to but not achieving full statistical significance (this is the CancerChoices definition; other researchers and studies may define this differently toward lower risk of recurrence (longer overall disease-free survival) but no evidence of an effectoverall, one or more studies did not demonstrate that a treatment or intervention led to an expected outcome; this does not always mean that there is no effect in clinical practice, but that the studies may have been underpowered (too few participants) or poorly designed. Larger, well-designed studies provide more confidence in making assessments. on 5-year disease-free survival after chemoradiotherapy among people with locally advanced cervical cancer treated with regional whole-pelvis hyperthermia compared with chemoradiotherapy alone in a mid-sized RCT¹⁶¹Harima Y, Ohguri T et al. A multicentre randomised clinical trial of chemoradiotherapy plus hyperthermia versus chemoradiotherapy alone in patients with locally advanced cervical cancer. International Journal of Hyperthermia. 2016 Nov;32(7):801-8.
• No evidence of an effect on disease-free survival after interstitial brachytherapy among people with advanced cervical cancer treated with interstitial hyperthermia and compared to interstitial brachytherapy alone in a mid-sized RCT¹⁶²Zolciak-Siwinska A, Piotrkowicz N et al. HDR brachytherapy combined with interstitial hyperthermia in locally advanced cervical cancer patients initially treated with concomitant radiochemotherapy—a phase III study. Radiotherapy and Oncology. 2013;109(2):194-199.

Risk of cancer

Modest evidence of higher rate of clearance of high risk human papillomavirus (HPV)—a risk factor for gynecological cancer—among people treated with local hyperthermia, comparable to rates after cryotherapy or large loop excision of the transformation zone

• Higher rate of clearance of high risk human papillomavirus (HPV) among people treated with local hyperthermia using an intravaginal probe at 44℃ compared to 37℃ (normal body temperature) in a small RCT¹⁶³Yang Y, Zhang L et al. Local Hyperthermia at 44°C is effective in clearing cervical high-risk human papillomaviruses: a proof-of-concept, randomized controlled clinical trial. Clinical Infectious Diseases. 2021 Nov 2;73(9):1642-1649.
• Comparable effects on HPV clearance or visual inspection of precancerous cervical lesions among women positive for cervical precancer treated with either thermal ablation, cryotherapy, or large loop excision of the transformation zone in a mid-sized RCT¹⁶⁴Pinder LF, Parham GP et al. Thermal ablation versus cryotherapy or loop excision to treat women positive for cervical precancer on visual inspection with acetic acid test: pilot phase of a randomised controlled trial. Lancet Oncology. 2020 Jan;21(1):175-184.

• Lower risk of recurrence (better disease-free survival) at 5 years after treatment with cisplatin chemotherapy and radiotherapy among people with nasopharyngeal carcinoma with metastatic foci in cervical lymph nodes treated with microwave hyperthermia compared to chemoradiotherapy alone in a mid-sized RCTrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects¹⁶⁵Kang M, Liu WQ, Qin YT, Wei ZX, Wang RS. Long-term efficacy of microwave hyperthermia combined with chemoradiotherapy in treatment of nasopharyngeal carcinoma with cervical lymph node metastases. Asian Pacific Journal of Cancer Prevention. 2013;14(12):7395-400.
• Lower risk of recurrence (better disease-free survival) after induction chemotherapy before radical surgery with postoperative radiotherapy among people with locally advanced resectable oral squamous cell carcinoma treated with ultrasonic thermal therapy compared to induction chemotherapy alone before surgery and radiotherapy in a mid-sized RCT¹⁶⁶Ren G, Ju H et al. A multicenter randomized phase II trial of hyperthermia combined with TPF induction chemotherapy compared with TPF induction chemotherapy in locally advanced resectable oral squamous cell carcinoma. International Journal of Hyperthermia. 2021;38(1):939-947.

• Longer biochemical disease-free survival after intensity-modulated radiotherapy (IMRT) plus neoadjuvant androgen deprivation therapy (ADT) among people with high-risk prostate carcinoma treated with regional hyperthermia compared to no hyperthermia in a mid-sized observationala type of study in which individuals are observed or certain outcomes are measured, but no attempt is made to affect the outcome (for example, no treatment is given); an example is a study that records people’s diets, but doesn’t try to alter their diets, and looks for patterns of disease or other outcomes related to different foods study¹⁶⁷Nakahara S, Ohguri T et al. Intensity-modulated radiotherapy with regional hyperthermia for high-risk localized prostate carcinoma. Cancers (Basel). 2022 Jan 13;14(2):400.
• Better 5-year biochemical disease-free survival after definitive radiotherapy among people with high-risk or very high-risk prostate cancer treated with regional hyperthermia for 1 minute or longer at 43°C in 90% of intra-rectal measurement points, but no evidence of an effectoverall, one or more studies did not demonstrate that a treatment or intervention led to an expected outcome; this does not always mean that there is no effect in clinical practice, but that the studies may have been underpowered (too few participants) or poorly designed. Larger, well-designed studies provide more confidence in making assessments. among people at 43°C in only 50% of measurement points in a mid-sized observational study¹⁶⁸Yahara K, Ohguri T et al. Definitive radiotherapy plus regional hyperthermia for high-risk and very high-risk prostate carcinoma: thermal parameters correlated with biochemical relapse-free survival. International Journal of Hyperthermia. 2015;31(6):600-8.

See “Dosing” in How do experts use hyperthermia? ›

• Lower risk of recurrence (longer disease-free survival) after chemotherapy among people with high-risk soft tissue sarcoma treated with regional hyperthermia compared to chemotherapy alone in a mid-sized RCTrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects¹⁶⁹Issels RD, Lindner LH et al. Neo-adjuvant chemotherapy alone or with regional hyperthermia for localised high-risk soft-tissue sarcoma: a randomised phase 3 multicentre study. Lancet Oncology. 2010;11(6):561-570.
• Lower risk of recurrence (longer disease-free survival) after complete macroscopic resection and chemotherapy among people with abdominal and retroperitoneal soft tissue sarcomas treated with regional hyperthermia compared to resection and chemotherapy alone in a mid-sized subgroup analysis of an RCT¹⁷⁰Angele MK, Albertsmeier M et al. Effectiveness of regional hyperthermia with chemotherapy for high-risk retroperitoneal and abdominal soft-tissue sarcoma after complete surgical resection: a subgroup analysis of a randomized phase-III multicenter study. Annals of Surgery. 2014 Nov;260(5):749-54; discussion 754-6.

Hyperthermia combined with chemotherapy

Bladder cancer

Preliminary evidence of better recurrence-free survival among people with bladder cancer treated with regional hyperthermic chemotherapy

• Better recurrence-free survival among people with high-risk non-muscle-invasive bladder cancer treated with recirculating hyperthermic intravesical chemotherapy (HIVEC) with mitomycin C compared to immunotherapy (bacillus Calmette-Guerin) in a small RCTrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects¹⁷¹Guerrero-Ramos F, González-Padilla DA et al. Recirculating hyperthermic intravesical chemotherapy with mitomycin C (HIVEC) versus BCG in high-risk non-muscle-invasive bladder cancer: results of the HIVEC-HR randomized clinical trial. World Journal of Urology. 2022 Apr;40(4):999-1004.
• 78% recurrence-free survival among people with intermediate- and high-risk nonmuscle invasive bladder cancer treated with intravesical mitomycin C combined with regional hyperthermia in a small uncontrolled triala 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 design¹⁷²Geijsen ED, de Reijke TM et al. Combining mitomycin C and regional 70 MHz hyperthermia in patients with nonmuscle invasive bladder cancer: a pilot study. Journal of Urology. 2015 Nov;194(5):1202-8.
• 67% bladder cancer recurrence and 13% upper tract recurrence during more than 3 years of follow up among people with bacillus Calmette-Guérin refractory non-muscle-invasive bladder cancer at high risk of recurrence and/or progression treated with deep pelvic hyperthermia and intravesical mitomycin C in a small uncontrolled trial¹⁷³Inman BA, Stauffer PR, Craciunescu OA, Maccarini PF, Dewhirst MW, Vujaskovic Z. A pilot clinical trial of intravesical mitomycin-C and external deep pelvic hyperthermia for non-muscle-invasive bladder cancer. International Journal of Hyperthermia. 2014 May;30(3):171-5.

Weak evidence of lower risk of bladder tumor recurrence after transurethral resection of bladder tumor treatment (TURBt) among people with non-muscle-invasive bladder cancer treated with hyperthermia intravesical chemotherapy (HIVEC) with mitomycin C

• Aweak trendan apparent change due to a therapy, close to but not achieving full statistical significance (this is the CancerChoices definition; other researchers and studies may define this differently toward lower risk of bladder tumor recurrence after transurethral resection of bladder tumor treatment (TURBt) among people with non-muscle-invasive bladder cancer treated with hyperthermia intravesical chemotherapy (HIVEC) with mitomycin C compared to bacillus Calmette-Guérin (BCG) vaccine in a network meta-analysisa statistical analysis that combines the results of two or more research studies; the results of smaller research studies addressing the same or similar questions can be analyzed as though they are one bigger, more powerful study of 32 RCTs¹⁷⁴Zeng N, Xu MY et al. Hyperthermia intravesical chemotherapy acts as a promising alternative to bacillus Calmette-Guérin instillation in non-muscle-invasive bladder cancer: a network meta-analysis. Frontiers in Oncology. 2023 May 12;13:1164932.

Weak evidence of lower risk of recurrence but also higher risk of progression to muscle infiltration among among people with non-muscle invasive bladder cancer (NMIBC) who fail bacillus Calmette-Guérin (BCG) therapy treated with hyperthermia intravesical chemotherapy (HIVEC)

• 62.9% recurrence-free survival at 12 months, with an 87.1% bladder preservation rate, but also 12.9% progression to muscle infiltration among people with non-muscle invasive bladder cancer (NMIBC) who fail bacillus Calmette-Guérin (BCG) therapy and a theoretical indication for cystectomy but were ineligible for surgery or refused it, who were treated with hyperthermia intravesical chemotherapy (HIVEC) in a small uncontrolled trial¹⁷⁵Pignot G, Baboudjian M et al. Efficacy of hyperthermic intravesical chemotherapy (HIVEC) in patients with non-muscle invasive bladder cancer after BCG failure. World Journal of Urology. 2023 Nov;41(11):3195-3203.

Colon cancer: preliminary evidence of longer recurrence-free survival after target organ resection among people with advanced colon cancer treated with regional hyperthermic intraperitoneal chemotherapy (HIPEC)

• Less local recurrence after target organ resection among people with advanced colon cancer considered at high risk for peritoneal spread treated with hyperthermic intraperitoneal chemotherapy (HIPEC) compared to resection alone in a small controlled triala study design in which people are assigned to either an experimental group or a control group to compare the outcomes from different treatment; assignment is not random, and so this is not as strong a study design as a randomized controlled trial, but still stronger than an uncontrolled trial¹⁷⁶Sammartino P, Sibio S et al. Long-term results after proactive management for locoregional control in patients with colonic cancer at high risk of peritoneal metastases. International Journal of Colorectal Disease. 2014 Sep;29(9):1081-9.

Pancreatic cancer: no evidence of an effect on recurrence among people with advanced pancreatic ductal adenocarcinoma pretreated with gemcitabine further treated with regional hyperthermia

• No evidence of an effectoverall, one or more studies did not demonstrate that a treatment or intervention led to an expected outcome; this does not always mean that there is no effect in clinical practice, but that the studies may have been underpowered (too few participants) or poorly designed. Larger, well-designed studies provide more confidence in making assessments. on recurrence (disease-free survival) among people with advanced pancreatic ductal adenocarcinoma pretreated with gemcitabine further treated with regional hyperthermia with cisplatin added to gemcitabine compared to gemcitabine alone in a mid-sized RCT¹⁷⁷Issels RD, Boeck S et al. Regional hyperthermia with cisplatin added to gemcitabine versus gemcitabine in patients with resected pancreatic ductal adenocarcinoma: the HEAT randomised clinical trial. European Journal of Cancer. 2022 Dec 30;181:155-165.

Stomach (gastric) cancer: preliminary evidence of lower risk of recurrence after surgery among people with stomach cancer treated with hyperthermic chemotherapy

• Lower risk or recurrence (better hepatic recurrence-free survival and peritoneal recurrence-free survival) after curative surgery among people with advanced gastric cancer treated with hyperthermic intraperitoneal chemotherapy (HIPEC) compared to surgery alone in a mid-sized observationala type of study in which individuals are observed or certain outcomes are measured, but no attempt is made to affect the outcome (for example, no treatment is given); an example is a study that records people’s diets, but doesn’t try to alter their diets, and looks for patterns of disease or other outcomes related to different foods study¹⁷⁸Murata S, Kaida S et al. A propensity-matched analysis comparing hepatic recurrence after curative gastrectomy followed by adjuvant HIPEC to surgery alone for advanced gastric cancer. Journal of Clinical Oncology. 2016;34(Suppl. 15):4056.
• Less peritoneal recurrence after surgery among people with advanced gastric cancer with peritoneal metastases treated with continuous hyperthermic peritoneal perfusion compared to surgery alone in a small observational study¹⁷⁹Hirose K, Katayama K et al. Efficacy of continuous hyperthermic peritoneal perfusion for the prophylaxis and treatment of peritoneal metastasis of advanced gastric cancer: evaluation by multivariate regression analysis. Oncology. 1999;57(2):106-14.

Hyperthermia combined with chemotherapy and surgery

Colorectal cancer: no evidence of an effect on risk of recurrence among people with colorectal cancer at high risk for developing colorectal peritoneal metastases treated with surgery and hyperthermic intraperitoneal chemotherapy (HIPEC)

• No evidence of an effect on risk of recurrence (disease-free survival) among people with colorectal cancer at high risk for developing colorectal peritoneal metastases treated with second-look surgery (exploration of the entire abdominal cavity and resection of all peritoneal implants if resectable) and HIPEC compared to simple surveillance in a mid-sized RCT of high quality¹⁸⁰Goéré D, Glehen O et al. Second-look surgery plus hyperthermic intraperitoneal chemotherapy versus surveillance in patients at high risk of developing colorectal peritoneal metastases (PROPHYLOCHIP–PRODIGE 15): a randomised, phase 3 study. Lancet Oncology. 2020 Sep;21(9):1147-1154.

Peritoneal sarcomatosis: weak evidence of lower risk of recurrence among people with peritoneal sarcomatosis treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC)

• 12-month median disease-free survival and 21.8% 5-year disease-free survival among people with peritoneal sarcomatosis treated with cytoreductive surgery and HIPEC in a meta-analysis of 16 uncontrolled studies¹⁸¹Wong LCK, Li Z et al. Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) in peritoneal sarcomatosis—a systematic review and meta-analysis. European Journal of Surgical Oncology. 2022 Mar;48(3):640-648.

Regional hyperthermia with radiation therapy

Breast cancer: weak evidence of lower risk of recurrence among among people with locally advanced breast cancer and no prior radiotherapy treated with simultaneous hyperthermia and radiotherapy

• 7% recurrence at an average follow-up of 79 months among people with locally advanced breast cancer and no prior radiotherapy treated with simultaneous hyperthermia and radiotherapy in a small uncontrolled trial¹⁸²Varma 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.

Prostate cancer: weak evidence of lower risk of recurrence (biochemical disease-free survival) among people with locally advanced prostate cancer treated with radiotherapy plus regional hyperthermia

• Higher than 50% 6-year biochemical disease-free survival after radical prostatectomy among people with locally advanced primary prostatic carcinoma (95% survival) or local recurrence (60% survival) treated with radiation therapy plus regional hyperthermia (some patients also received short term hormonal therapy) in a small uncontrolled study¹⁸³Tilly W, Gellermann J et al. Regional hyperthermia in conjunction with definitive radiotherapy against recurrent or locally advanced prostate cancer T3 pN0 M0. Strahlentherapie und Onkologie. 2005 Jan;181(1):35-41.
• 36-month median biochemical disease-free survival among people with locally advanced adenocarcinoma of the prostate treated with external beam radiotherapy and regional hyperthermia in a small uncontrolled trial¹⁸⁴Algan O, Fosmire H et al. External beam radiotherapy and hyperthermia in the treatment of patients with locally advanced prostate carcinoma. Cancer. 2000 Jul 15;89(2):399-403.

Hyperthermia combined with chemotherapy, radiation, and surgery: weak evidence of comparable risk of recurrence to amputation, but with 79% limb preservation among people with high-risk soft-tissue sarcoma of the extremities treated with chemotherapy combined with regional hyperthermia followed by surgery, radiation, and adjuvant chemotherapy

• Comparable 5-year distant disease-free survival to amputation but with 79% limb preservation among people with high-risk soft-tissue sarcoma of the extremities treated with four cycles of etoposide, ifosfamide, and doxorubicin combined with regional hyperthermia followed by surgery, radiation, and adjuvant chemotherapy in a small uncontrolled trial¹⁸⁵Schlemmer M, Wendtner CM et al. Thermochemotherapy in patients with extremity high-risk soft tissue sarcomas (HR-STS). International Journal of Hyperthermia. 2010;26(2):127-35.