Clinical UM Guideline

This document addresses hyperthermia for cancer therapy. Hyperthermia is a type of cancer treatment in which body tissue is exposed to high temperatures using external and internal heating devices. Hyperthermia is routinely used with other forms of cancer therapy. Hyperthermia may make cancer cells more sensitive to chemotherapy and radiation therapy or harm other cancer cells radiation cannot damage.

Note: This document does not address hyperthermic intraperitoneal chemotherapy (HIPEC), hyperthermic limb perfusion, radiofrequency ablation to treat tumors outside the liver or locally ablative techniques for treating primary and metastatic liver malignancies.

For information regarding radiofrequency ablation to treat tumors outside the liver or locally ablative techniques for treating primary and metastatic liver malignancies see the following documents:

• CG-SURG-61 Cryosurgical, Radiofrequency, Microwave or Laser Ablation to Treat Solid Tumors Outside the Liver
• CG-SURG-78 Locoregional Techniques for Treating Primary and Metastatic Liver Malignancies

Medically Necessary:

Local hyperthermia, using either external or interstitial modalities, in combination with radiation therapy is considered medically necessary for the treatment of individuals with primary or metastatic cutaneous or subcutaneous superficial tumors (for example, superficial recurrent melanoma, chest wall recurrence of breast cancer, and cervical lymph node metastases from head and neck cancer); and

When criteria above are met, local hyperthermia is considered medically necessary when used no more than twice weekly.

Not Medically Necessary:

Local hyperthermia, using either external or interstitial modalities, in conjunction with radiation therapy is considered not medically necessary for all other uses not identified as medically necessary.

Local hyperthermia is considered not medically necessary when given more than two times per week.

Intraluminal/endocavitary hyperthermia is considered not medically necessary in the treatment of malignancies.

Regional deep tissue hyperthermia is considered not medically necessary in the treatment of malignancies.

Whole-body hyperthermia is considered not medically necessary in the treatment of malignancies.

Hyperthermia in conjunction with chemotherapy is considered not medically necessary.

The following codes for treatments and procedures applicable to this guideline are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.

Local hyperthermia (superficial external, interstitial)
When services may be Medically Necessary when criteria are met:

When services are Not Medically Necessary:
For the procedure and diagnosis codes listed above when criteria are not met or for all other diagnoses not listed; or when the code describes a procedure or situation designated in the Clinical Indications section as not medically necessary.

Other hyperthermia (deep, intracavitary, whole body)
When services are Not Medically Necessary:
For the following procedure codes, or when the code describes a procedure designated in the Clinical Indications section as not medically necessary.

Hyperthermia is a type of cancer treatment in which body tissue is exposed to moderately high tumor heating using external or internal heating devices. Clinical studies suggest tumor cells may be more sensitive to increased temperature as compared with normal cells, that heat may enhance the tumoricidal effects of radiation or chemotherapy and overcome acquired drug resistance, and that elevated temperatures can stimulate certain components of the immune system, which may aid in destroying cancer cells. There are potential risks associated with hypothermia therapy. An increase in temperature results in enhanced blood flow and may aid in the dissemination of malignant cells and increased delivery of nutrients to the existing tumor (Alshaibi, 2020; Szasz, 2019). A number of methods of hyperthermia are currently under study, including local, regional, and whole-body hyperthermia.

Local Hyperthermia in Conjunction with Radiation Therapy for Superficial Malignancies

In local hyperthermia, heat is applied to a small area, such as a tumor, using various techniques that deliver energy to heat the tumor. Different types of energy may be used to apply heat, including microwave, radiofrequency, and ultrasound. Depending on the tumor location, there are several approaches to local hyperthermia. External approaches are used to treat tumors in or just below the skin. External applicators are positioned around or near the tumor, and energy is focused on the tumor to raise the temperature. Interstitial techniques are used to treat tumors deep within the body, such as brain tumors. This technique allows the tumor to be heated to higher temperatures than external techniques. Radiofrequency ablation is a type of interstitial hyperthermia using radio waves to heat and kill cancer cells.

A literature search focused on randomized controlled trials (RCTs) of hyperthermia in superficial malignancies. A variety of studies were published in the 1990s that examined the role of hyperthermia in breast cancer (Vernon, 1996), melanoma (Overgaard, 1995), head and neck cancer (Datta, 1990; Emami, 1996; Valdagni, 1994) and a variety of superficial tumors (Perez, 1991). Not all trials reported positive results, presumably in part related to the difficulty in delivering consistent thermal doses.

Jones and colleagues (2005) reported on a trial of 109 individuals, with a variety of different types of superficial tumors, who were randomized to receive radiation therapy with or without a well-defined and consistent dose of hyperthermia. The majority had breast cancer with chest wall involvement. Other groups included those with head and neck cancer and melanoma. Hyperthermia was associated with significantly improved local control (66%) compared to the control group (42%) (p=0.02). Survival was not significantly different between the two groups.

One of the most common superficial tumors is breast cancer. Vernon (1996) published a combined analysis of five RCTs initiated between 1988 and 1991. A total of 306 individuals were randomized to receive radiation therapy with or without hyperthermia. The primary outcome was complete response rate, which was achieved in 59% of those receiving hyperthermia compared to 41% in the control group.

The National Comprehensive Cancer Network (NCCN) clinical practice guideline on breast cancer (V4. 2022) does not address hyperthermia therapy.  

Intraluminal/Endocavitary Hyperthermia in Conjunction with Radiation Therapy

Intraluminal or endocavitary methods may be used to treat tumors within or near body cavities, such as the esophagus or rectum. Probes are placed inside the cavity and inserted into the tumor to deliver energy and heat the area directly.

The Dutch Deep Hyperthermia trial was an RCT designed to evaluate the role of once weekly hyperthermia in 114 women with locally advanced cervical cancer (Stage IIB, IIIB or IV). Franckena (2008) published long-term results (12-year) in which the primary end point was local control. Local control was improved in the hyperthermia group compared to the control group (56% vs 37%; p=0.01). Additionally, the improved local control translated to improved survival rates at 12 years (37% vs 20%; p=0.03). The toxicities were similar in both groups. The same group of authors, Franckena (2009), reported on the outcomes of hyperthermia in a prospective case series of 378 individuals with locally advanced cervical cancer. The complete response, local control, and survival rates were similar to the results in the randomized Dutch Deep Hyperthermia Trial. The authors concluded that radiation in conjunction with hyperthermia can be considered as an alternative to chemoradiation therapy in those with locally advanced cervical cancer. However, in the United States, the standard treatment of locally advanced cervical cancer is chemoradiation, and there is inadequate data comparing radiation and hyperthermia to this standard treatment.

The Dutch Deep Hyperthermia trial also enrolled individuals with bladder cancer. An initial improvement in local control rates disappeared during follow up (van der Zee, 2000).

A Cochrane Review (Lutgens, 2010), assessed the role of hyperthermia as an adjunct to radiotherapy in the treatment of locally advanced cervix cancer. The authors reported:

The limited number of patients available for analysis, methodological flaws and a significant over-representation of patients with stage IIIB prohibit drawing definite conclusions regarding the impact of adding hyperthermia to standard radiotherapy.

Regional, Whole Body or Deep Tissue Hyperthermia in Conjunction with Radiation Therapy

In regional hyperthermia, various approaches may be used to heat large areas of tissue, such as a body cavity, organ, or limb. Regional deep tissue hyperthermia may be used to treat cancers within the body, such as cervical or bladder cancer. External applicators are positioned around the body cavity or organ to be treated, and microwave, electromagnetic (electrohyperthermia or mEHT) or radiofrequency energy is focused on the area to raise its temperature.

Whole body hyperthermia (WBH) has been proposed as a therapy, most commonly as an adjunct to radiotherapy or chemotherapy, to treat metastatic cancer that has spread throughout the body. WBH is achieved with either radiant heat or extracorporeal technologies that raise the body temperature to 107-108°F. In radiant WBH, heat is externally applied to the whole body using hot water blankets, hot wax, inductive coils, or thermal chambers. The individual is sedated throughout the WBH procedure, which lasts approximately 4 hours. Extracorporeal WBH is achieved by re-infusion of extracorporeally heated blood. A circuit of blood is created outside the body by accessing an artery, usually the femoral artery, and creating an extracorporeal loop. The circulating blood is passed through a heating device, usually a water bath or hot air, and the heated blood is then re-injected into a major vein. The desired body temperature is adjusted and controlled by changing the volume flow of the warmed re-infused blood. Extracorporeal hyperthermia treatments are conducted under general anesthesia. Lassche and associates (2019) conducted a review of phase I/II studies which evaluated the use of WBH combined with systemic therapy to treat metastasized solid malignancies (n=14). The authors noted that the promising results documented following combination of WBH and chemotherapy were at the cost of a high proportion of individuals suffering from grade 3 or 4 chemotherapy toxicity. There is no evidence that WBH provides additional clinical value over standard chemotherapy alone and it is unlikely to become part of routine clinical care.

A literature search focusing on RCTs identified a single study of regional hyperthermia with radiation therapy in 80 individuals with non-small cell lung cancer (Mitsumori, 2007). This trial failed to show any substantial benefit from the addition of hyperthermia to radiotherapy in the treatment of locally advanced non-small cell lung cancer. The literature search did not identify any RCTs of deep tissue hyperthermia.

Hyperthermia in Conjunction with Chemotherapy with or without Radiation Therapy

Issels and colleagues (2010) reported on an RCT designed to assess the safety and efficacy of neo-adjuvant regional hyperthermia in conjunction with chemotherapy. A total of 341 individuals were enrolled in the trial between July 21, 1997 and November 30, 2006 at nine European and North American centers. Individuals with localized high-risk soft tissue sarcoma were randomly assigned to receive either chemotherapy consisting of etoposide, ifosfamide, and doxorubicin (EIA) alone (n=172), or combined with regional hyperthermia (EIA plus regional hyperthermia) (n=169) in addition to local therapy. Of all the enrollees, 151 subjects (89.3%) in the EIA plus regional hyperthermia group and 146 (84.9%) in the EIA alone group completed induction chemotherapy. In the combined treatment group, 129 subjects (76.3%) received seven to eight regional hyperthermia treatments, 33 (19.5%) received one to six regional hyperthermia treatments, and 7 (4.1%) received none. Most of the study subjects (90.6%) also underwent surgery (155 EIA plus regional hyperthermia vs 154 EIA alone). Approximately two-thirds of the individuals underwent a tumor resection and others underwent amputation. A total of 108 subjects in the combined treatment group and 106 in the EIA alone group received radiotherapy; 61 subjects in the combined treatment group and 64 in the EIA alone group did not receive radiotherapy. The primary reason for not receiving radiotherapy was an abdominal or retroperitoneal tumor location. More subjects in the combined treatment group completed full post-induction chemotherapy as compared to the EIA alone group (89 [52.7%] versus 71 [41.3%]; p=0.020). A similar number did not receive post-induction therapy (43 in the combined treatment group vs 47 in the EIA alone group) due to non-compliance. Also, in the combined treatment group 60 subjects (35.5%) received seven to eight regional hyperthermia treatments, 28 (16.6%) received one to six regional hyperthermia treatments and 66 did not receive any regional hyperthermia. Reasons for not receiving regional hyperthermia were side effect related or intolerance to heat treatment. The overall duration of study treatment was 32.4 weeks for the combined treatment group versus 29.1 weeks in the EIA alone group. The primary outcome of the study was local progression-free survival which was defined as “the time from randomization to confirmed local progression, relapse, or death, whichever occurred first and irrespective of any occurrence of distant metastases.” Secondary endpoints were disease-free survival, overall survival, tumor response after induction therapy, treatment toxicity, and long-term complications.

Subjects were observed as more likely to experience local progression or death in the EIA alone group compared with the EIA plus regional hyperthermia group (relative hazard [RH] 0.58, 95% confidence interval [CI], 0.41-0.83; p=0.003). For disease-free survival the relative hazard was 0.70 (95% CI, 0.54-0.92; p=0.011) for EIA plus regional hyperthermia compared with EIA alone. The treatment response rate in the group that received regional hyperthermia was 28.8%, compared with 12.7% in the group who received chemotherapy alone (p=0.002). After a median follow-up time of 34 months, 132 subjects had local progression (56 EIA plus regional hyperthermia vs 76 EIA). A total of 153 individuals died during the follow-up period of 128 months with 2 deaths attributed to treatment in the combined treatment group, and 1 death was attributed to treatment in the EIA alone group. A higher incidence of hematological toxicity (leukopenia 72.6% versus 63.5%, p=0.005) was noted in the combined therapy group compared with EIA alone. When all individuals who were assigned to treatment were analyzed, there was no evidence of a difference in overall survival between the EIA alone group and the combined treatment group. Among the 269 individuals who completed induction therapy (4 cycles EIA plus 8 regional hyperthermias vs 4 cycles EIA alone) there was a significant difference in overall survival in the combined therapy group compared with the EIA alone group (hazard ratio [HR] 0.66, p=0.038). The authors indicated that this was the first randomized phase 3 trial to show that regional hyperthermia increases the benefit of chemotherapy. Although study results may show promise, there is a need for additional controlled studies to confirm these early findings.

In 2018, Issels and colleagues evaluated whether the initial improvement in local progression-free survival translated into improved survival rates in the long-term. A total of 329 individuals with a median follow-up of more than 11 years were included in the study. By December 2014, 174 individuals (77 in the chemotherapy plus regional hyperthermia group and 97 in the chemotherapy alone group) had died due to disease or treatment. More deaths were attributable to the treatment in the group which received chemotherapy plus regional hyperthermia compared to the group which received chemotherapy alone (5 deaths, 3.1% versus 2 deaths, 1.2% respectively). Survival was significantly improved in the chemotherapy plus regional hyperthermia group compared to the chemotherapy alone group (15.4 years versus 6.2 years; HR 0.73; 95% CI, 0.54-0.98; p=0.04 respectively). There was an 11.4% improvement in the 5-year survival rate and a 9.9% improvement in the 10-year survival rate in the chemotherapy plus regional hyperthermia group compared to the chemotherapy group alone. However, while the risk of death from sarcoma was significantly lower, the risk of death from a non-sarcoma cause was significantly higher. These results suggest there was no gain in OS survival in the chemotherapy plus regional hyperthermia group. In addition, several confounding variables were noted, including that the results related to sarcoma specific survival are confounded by the median number of cycles of chemotherapy which each group received 5 cycles in the chemotherapy only group and 8 cycles in the chemotherapy plus regional hyperthermia group. These limitations as well as the lack of gain in OS did not support that regional hyperthermia provided clinical benefit in those undergoing chemotherapy.

Chen and colleagues (2012) enrolled 358 individuals with malignant pleural effusion in an RCT designed to evaluate the safety and efficacy of intrapleural chemotherapy consisting of cisplatin and OK-432 (picinbanil) plus hyperthermia. Two study groups across four Chinese cancer centers consisted of 179 subjects each. Those in group A received the intrapleural combination of cisplatin and OK-432 with hyperthermia, while Group B received the same intrapleural combination without hyperthermia. Quality of life scores increased in both groups as compared to prior treatment. The survival follow-up period varied from 3 to 24 months. A total of 26 subjects in group A and 24 in group B were lost to follow-up. The median survival in group A (8.9 months) and group B (6.2 months) were similar (p>0.05).

Several studies (Heijkoop, 2012; Westermann, 2012) have evaluated a triple combination therapy consisting of regional hyperthermia, chemotherapy and brachytherapy for the treatment of advanced cancer of the cervix. Westermann and colleagues (2012) enrolled 68 women with advanced cervical cancer in a small prospective registry study in the USA, Norway and the Netherlands. Treatment consisted of a triple combination of regional whole pelvis hyperthermia (four weekly sessions), chemotherapy (at least four courses of weekly cisplatin) and radiotherapy (brachytherapy and external beam radiotherapy). At a median follow-up of 81 months, tumors returned in 28 women resulting in 21 deaths. The 5-year recurrence-free survival in the study was 57.5% and 5-year overall survival was 66.1%. The authors indicated that survival results with the addition of whole pelvic HT to RT and chemotherapy for advanced cervical cancer were comparable to historical controls. This study was limited by a small size and lack of a concurrent control group.

Heijkoop and colleagues (2012) also studied triple combination therapy consisting of hyperthermia, chemotherapy, and radiotherapy in a pilot study of women with advanced stage cervical cancer. A total of 43 women were treated with platinum-based chemotherapy, followed by radiotherapy, brachytherapy and five hyperthermia treatments. A total of 67% completed all six planned courses of chemotherapy. At the end of chemotherapy, 83.7% achieved a complete or partial response. At the end of treatment, the complete response rate was 81.4%. The median follow-up time was 29.8 months (range 4.1-124.8). Overall survival rate at 12 months was 79%. The authors recommended proceeding to a phase II trial to obtain additional information. This trial was limited by a small size and lack of a comparator.

Schroeder and colleagues (2012) evaluated the impact of regional hyperthermia with neoadjuvant chemoradiation on rates of complete pathological response (pCR) and sphincter-sparing surgery for locally advanced rectal cancer. Between 2007 and 2010, 106 individuals received treatment consisting of neoadjuvant chemoradiation either with (n=61) or without (n=45) regional hyperthermia in a non-randomized fashion. A retrospective comparison was performed between the two groups: 45 subjects received standard treatment consisting of 5040 cGy in 28 fractions to the pelvis and 5-fluorouracil (RCT group) and 61 subjects received the same treatment in combination with regional hyperthermia (HRCT group). A pCR occurred in 6.7% of the RCT group and in 16.4% of the HRCT group. Those who received at least four hyperthermia treatments (n=40) achieved a significantly higher pCR rate (22.5%) than the remaining 66 subjects (p=0.043). Rates of sphincter-sparing surgery were similar in both groups. The authors conclude that “a randomised trial comparing RCT and HRCT with well-defined inclusion criteria for high-risk patients is warranted.”

A Phase II study combining hyperthermia concurrent with neoadjuvant chemoradiotherapy (nCRT) for advanced rectal cancer (Barsukov, 2013) enrolled 64 previously untreated individuals. Hyperthermia was combined with chemoradiotherapy and subsequent resection was performed in 59 subjects (92.2%). A total of 5 individuals (7.8%) were deemed inoperable. Median follow up was 24.9 months. The 2-year overall survival was 91% and 2-year disease-free survival was 83%. Study limitations include lack of randomization and lack of a control group.

Ranieri and colleagues (2017) published a prospective pilot study evaluating the efficacy, safety, and survival of anti-angiogenic-based chemotherapy associated to regional deep capacitive hyperthermia in metastatic cancer subjects. A total of 23 subjects with metastatic colorectal (n=16), ovarian (n=5), and breast (n=2) cancer were enrolled in this study. Out of those subjects, 18 (78%) completed the study. The authors found that 28% of subjects achieved stable disease, 11% achieved partial response, and 33% achieved complete response. In addition, the results showed higher numbers of chemotherapy cycles (p=0.015) and number of hyperthermia sessions (p<0.001) performed were associated with a better response. The authors conclude that these results need to be confirmed in larger studies.

In 2017, van der Horst and colleagues conducted a systematic review of the clinical benefit of hyperthermia and/or chemotherapy in subjects with pancreatic cancer. The search yielded 14 studies with 395 subjects. Out of the 395 subjects 248 received regional hyperthermia (n=189), intraoperative hyperthermia (n=39), or whole body hyperthermia (n=20), combined with chemotherapy, radiotherapy, or both. Results showed that overall response rate was better for hyperthermia groups; however, the quality of the studies was low level due to no randomization and some studies being retrospective. The authors concluded that randomized control trials are needed to establish efficacy. 

Yea and colleagues (2022) published a systematic review and meta-analysis of studies comparing chemoradiotherapy with hyperthermia to chemoradiotherapy alone in locally advanced cervical cancer (LACC). Two studies, both RCTs, met the review’s inclusion criteria. The studies included a total of 536 individuals; 268 were in the chemoradiotherapy group and 268 were in the chemoradiotherapy plus hyperthermia group. In a pooled analysis of study findings, individuals in the chemoradiotherapy plus hyperthermia group had significantly better five-year OS than those in the chemoradiotherapy-only group (HR, 0.67, 95% CI, 0.47 to 0.96, p=0.03). The rates of local relapse-free survival did not differ significantly between the two groups (HR, 0.74, 95% CI, 0.49 to 1.12, p=0.16). There were no significant differences between groups on toxicity outcomes. The review is limited by the small number of relevant trials; only two studies were included in pooled analyses.  

There has also been interest in combining hyperthermia with intravesicular chemotherapy in individuals with bladder cancer. However, published evidence is very limited.

Peer Reviewed Publications:

1. Alshaibi HF, Al-Shehri B, Hassan B, et al. Modulated electrohyperthermia: a new hope for cancer patients. Biomed Res Int. 2020; 2 020:8814878.
2. Barsukov YA, Gordeyev SS, Tkachev SI, et al. Phase II study of concomitant chemoradiotherapy with local hyperthermia and metronidazole for locally advanced fixed rectal cancer. Colorectal Dis. 2013; 15(9):1107-1114.
3. Chang P, Sapozink MD, Grunberg SM, et al. Unresectable primary and recurrent head and neck tumors; effect of hyperthermia and carboplatin-preliminary experience. Radiology. 2000; 214(3):688-692.
4. Chen WJ, Yuan SF, Yan QY, et al. Intrapleural chemo- and hyperthermotherapies for malignant pleural effusion: a randomized prospective study. Cancer Invest. 2012; 30(2):126-130.
5. Datta NR, Bose AK, Kapoor HK. Head and neck cancers: results of thermoradiotherapy versus radiotherapy. Int J Hyperthermia. 1990; 6(3):479-486.
6. Dewhirst MW, Kirsch D. Technological advances, biologic rationales, and the associated success of chemotherapy with hyperthermia in improved outcomes in patients with sarcoma. JAMA Oncol. 2018; 4(4):493-494.
7. Emami B, Scott C, Perez CA, et al. Phase III study of interstitial thermoradiotherapy compared with interstitial radiotherapy alone in the treatment of recurrent or persistent human tumors. A prospectively controlled randomized study by the Radiation Therapy Group. Int J Radiat Oncol Biol Phys. 1996; 34(5):1097-1104.
8. Franckena M, Lutgens LC, Koper PC, et al. Radiotherapy and hyperthermia for treatment of primary locally advanced cervix cancer: results in 378 patients. Int J Radiat Oncol Biol Phys. 2009; 73(1):242-250.
9. Franckena M, Stalpers LJ, Koper PC, et al. Long-term improvement in treatment outcome after radiotherapy and hyperthermia in locoregionally advanced cervix cancer: an update of the Dutch Deep Hyperthermia Trial. Int J Radiat Oncol Biol Phys. 2008; 70(4):1176-1182.
10. Heijkoop ST, Franckena M, Thomeer MG, et al. Neoadjuvant chemotherapy followed by radiotherapy and concurrent hyperthermia in patients with advanced-stage cervical cancer: a retrospective study. Int J Hyperthermia. 2012; 28(6):554-561.
11. Issels RD, Lindner LH, Verweij J, et al.; European Organization for the Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group and the European Society for Hyperthermic Oncology. 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 Oncol. 2018; 4(4):483-492.
12. Issels RD, Lindner LH, Verweij J, et al. European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group (EORTC-STBSG); European Society for Hyperthermic Oncology (ESHO). Neo-adjuvant chemotherapy alone or with regional hyperthermia for localized high-risk soft-tissue sarcoma: a randomised phase 3 multicentre study. Lancet Oncol. 2010; 11(6):561-570.
13. Jones EL, Oleson JR, Prosnitz LR, et al. Randomized trial of hyperthermia and radiation for superficial tumors. J. Clinical Oncology. 2005; 23(13):3079-3085.
14. Killock D. Sarcoma: Local hyperthermia improves survival. Nat Rev Clin Oncol. 2018; 15(5):266.
15. Kok HP, Cressman ENK, Ceelen W, et al. Heating technology for malignant tumors: a review. Int J Hyperthermia. 2020; 37(1):711-741.
16. Lassche G, Crezee J, Van Herpen CML. Whole-body hyperthermia in combination with systemic therapy in advanced solid malignancies. Crit Rev Oncol Hematol. 2019; 139:67-74.
17. Lutgens L, van der Zee J, Pijls-Johannesma M, et al. Combined use of hyperthermia and radiation therapy for treating locally advanced cervix carcinoma. Cochrane Database Syst Rev. 2010; (3):CD006377.
18. Mansmann U, Lindner LH, Issels R. Regional hyperthermia with neoadjuvant chemotherapy for treatment of soft tissue sarcoma-reply. JAMA Oncol. 2019; 5(1):114.
19. Mitsumori M, Zeng ZF, Oliynychenko P, et al. Regional hyperthermia combined with radiotherapy for locally advanced non-small cell lung cancers: a multi-institutional prospective randomized trial of the International Atomic Energy Agency Int J Clin Oncol. 2007; 12(3):192-198.
20. Overgaard J, Gonzalez Gonazalez D, et al. Randomized trial of hyperthermia as adjuvant to radiotherapy for recurrent or metastatic malignant melanoma. European Society for Hyperthermic Oncology. Lancet 1995; 345(8949):540-543.
21. Perez CA; Pajak T; Emami B, et al. Randomized phase III study comparing irradiation and hyperthermia with irradiation alone in superficial measurable tumors. Final report by the Radiation Therapy Oncology Group. Am J Clin Oncol. 1991; 14(2):133-141.
22. Ranieri G, Ferrari C, Di Palo A, et al. Bevacizumab-based chemotherapy combined with regional deep capacitive hyperthermia in metastatic cancer patients: a pilot study. Int J Mol Sci. 2017; 18(7). pii: E1458.
23. Roussakow S. Regional hyperthermia with neoadjuvant chemotherapy for treatment of soft tissue sarcoma. JAMA Oncol. 2019; 5(1):113-114.
24. Schroeder C, Gani C, Lamprecht U, et al. Pathological complete response and sphincter-sparing surgery after neoadjuvant radiochemotherapy with regional hyperthermia for locally advanced rectal cancer compared with radiochemotherapy alone. Int J Hyperthermia. 2012; 28(8):707-714.
25. Sun R, Wei LJ. Regional hyperthermia with neoadjuvant chemotherapy for treatment of soft tissue sarcoma. JAMA Oncol. 2019; 5(1):112-113.
26. Szasz AM, Minnaar CA, Szentmártoni G, et al. Review of the clinical evidences of modulated electro-hyperthermia (mEHT) method: an update for the practicing oncologist. Front Oncol. 2019; 9:1012.
27. Valdagni 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. Int J Radiat Oncol Biol Phys. 1994; 28(1):163-169.
28. van der Horst A, Versteijne E, Besselink MGH, et al. The clinical benefit of hyperthermia in pancreatic cancer: a systematic review. Int J Hyperthermia. 2018; 34(7):969-979.
29. van der Zee J, González D, van Rhoon GC. Comparison of radiotherapy alone with radiotherapy plus hyperthermia in locally advanced pelvic tumours: a prospective, randomised, multicentre trial. Dutch Deep Hyperthermia Group. Lancet. 2000; 355(9210):1119-1125.
30. Vernon CC, Hand JW, Field S, et al. Radiotherapy with or without hyperthermia in the treatment of superficial localized breast cancer: results from five randomized controlled trials. International Collaborative Hyperthermia Group. Int J Radiat Oncol Biol Phys. 1996; 35(4):731-744.
31. Westermann A, Mella O, Van Der Zee J, et al. Long-term survival data of triple modality treatment of stage IIB-III-IVA cervical cancer with the combination of radiotherapy, chemotherapy and hyperthermia - an update. Int J Hyperthermia. 2012; 28(6):549-553.
32. Yea JW, Park JW, Oh SA et al. Chemoradiotherapy with hyperthermia versus chemoradiotherapy alone in locally advanced cervical cancer: a systematic review and meta-analysis. Int J Hyperthermia. 2021;38(1):1333-1340.

Government Agency, Medical Society, and Other Authoritative Publications:

1. NCCN Clinical Practice Guidelines in Oncology™ (NCCN). © 2022 National Comprehensive Cancer Network, Inc. For additional information visit the NCCN website at: http://www.nccn.org/index.asp. Accessed on December 14, 2022.
   • Breast Cancer (V.4.2022). Revised June 21, 2022.

1. American Cancer Society. Hyperthermia to Treat Cancer. Revised May 3, 2016. Available at: https://www.cancer.org/treatment/treatments-and-side-effects/treatment-types/hyperthermia.html. Accessed on December 20, 2022.
2. National Cancer Institute. National Institutes of Health. Hyperthermia in cancer treatment: Questions and answers. Updated June 17, 2021. Available at: http://www.cancer.gov/cancertopics/factsheet/Therapy/hyperthermia. Accessed on December 20, 2022.

Local Hyperthermia
Modulated electro-hyperthermia (mEHT)
Regional Deep Tissue Hyperthermia
Regional Perfusion Hyperthermic Techniques
Systemic Thermotherapy
Thermal Therapy
Whole Body Hyperthermia (WBH)