体部伽玛刀联合微波加热治疗直肠癌术后局部复发的临床观察

目的：评价体部伽玛刀联合微波加热治疗对直肠癌术后局部复发患者的临床疗效及毒副反应。方法：对直肠癌术后局部复发的３６例患者应用体部伽玛刀联合微波加热治疗。伽玛刀治疗方案：５０％ ～８０％处方剂量线,４～６Ｇｙ／次,每周５次,总剂量３６～４２Ｇｙ,生物等效剂量５６～６７Ｇｙ。微波加热治疗方案：伽玛刀治疗期间予以微波加热治疗,每周２次,共４次。每次热疗均在伽玛刀治疗前进行,热疗温度保持在４０～４３℃范围,持续加热时间１.５～２ｈ。治疗结束后１个月复查盆腔ＣＴ。结果：完全缓解７例,部分缓解２５例,稳定３例,进展１例,近期总有效率８８.９％。１、２和３年生存率分别为１０００％、８３.３％和６０.８％。主要毒副反应为下消化道反应,其中Ⅲ级反应２例。其余均为Ⅰ ～Ⅱ级。结论：体部伽玛刀联合微波加热治疗直肠癌术后局部复发患者的疗效好,毒副反应轻。     

Retrospective analysis of hyperthermia for use in the palliative treatment of cancer: a multi-modality evaluation.

Forty-two patients with local or superficial metastatic or recurrent malignant tumors were treated in a non-randomized Phase I/II study to assess the tumoricidal effects of heat combined with radiation and/or chemotherapy. Radiation doses administered averaged 3130 +/- 350 cGy; chemotherapeutic agents employed included bleomycin, mitomycin-C, adriamycin, and cis-platin, heat was induced by radiative or interstitial microwave applicators operating at frequencies ranging from 95 to 900 MHz. Forty-one of the forty-two patients were evaluated for initial therapeutic effects yielding the following response distributions: local hyperthermia with radiation--42% complete response (CR), 44% partial response (PR), and 15% no response (NR); local hyperthermia with chemotherapy--0% CR, 50% PR and 50% NR. Long-term response duration was evaluated for local hyperthermia with radiation, yielding mean time to recurrence of 9.4 months for CR's and mean time to progression of 3.4 months for PR's. In retrospective analysis, we examined the correlations of previously established response-predictor variables of tumor volume and minimum thermal dose with both initial and long-term response rates. Initial complete response rates were correlated directly with non-site-specific minimum thermal dose, varied inversely with tumor volume and exhibited a positive correlation for a limited histologic type/treatment site combination. Surprisingly, long-term response did not correlate either with tumor volume or thermal dose. The frequency of thermally induced complications, which did not correlate with any measured thermal parameters, was found to be 42%, expressed on a per-patient basis.     

248例恶性肿瘤微波热疗近期疗效报告

为观察微波热疗对恶性肿瘤的疗效，１９９１年９月至１９９４年１２月，对２４８例晚期恶性肿瘤进行微波加热配合放疗和化疗或单独热疗的临床观察。加温是采用９１５ＭＨｚ微波治疗机进行。全组近期总有效率６８．１％（１６９／２４８），单纯热疗有效率６４．５％（６０／９３），放疗加热疗有效率６９．１％（９４／１３６），化疗加热疗有效率６０．０％（３／５），热疗加放疗加化疗有效率８５．７％（１２／１４）。     

Combined treatment with radiation and hyperthermia in metastatic malignant melanoma

In 24 patients with metastatic malignant melanoma, combined treatment with radiation and hyperthermia was administered to 38 localizations, radiation alone to 8 comparative localizations and hyperthermia alone to 3 localizations. Hyperthermia was administered during one hour by using a 433 MHz microwave generator. The heat treatment was given within 30 min following irradiation. Although an intratumoral temperature of 43 degrees C was aimed, considerable variations occurred during one session and from session-to-session. Radiation schedules consisted in either one large fraction (6-8 Gy) once a week in 14-21 days or two fractions (4-5 Gy) twice a week in 21 days. In the group of patients receiving irradiation once a week, three heat treatments were administered. In the twice-a-week radiation schedule, six heat sessions were given. The overall complete response (CR) rate in patients receiving combined treatment was 50%. In the group of patients treated with hyperthermia and irradiation schedules of 8 Gy per fraction, the CR rate was 83%. Irradiation alone achieved 38% CR rate but some of these CR relapsed during follow-up whereas the comparative area treated with radiation and heat remained under control at this time. The lesions treated with heat alone did not show any response to treatment. Enhancement of the acute skin reactions was generally observed. However, because the total doses were relatively low, this enhancement did not constitute a clinical problem. CR appears to occur more frequently in small tumor sizes. The highest and lowest temperature ever registered during any session of hyperthermia did not seem to correlate with the tumor response.     

Long-term results of thermoradiotherapy for superficial, subsurface tumors using a 430 MHz microwave heating system

Superficial, subsurface tumors of 93 patients were treated with thermoradiotherapy using a 430 MHz microwave heating system (HTS-100). All patients had malignant tumors, and all were treated with a combination of hyperthermia and radiation. Satisfactory temperature data for each thermal parameter were achieved within a 5 cm depth for each tumor. The overall complete response (CR) rate was 39.8%; in the less than or equal to 3 cm (depth of tumor), the CR rate was 66.7%, in the 3-5 cm group, the CR rate was 42.9%. In the multivariate analysis, duration of local control correlated with tumor responses (CR). There were no instances of prominent late complications that were observed for greater than or equal to 6 months. This study suggests that the HTS-100 may improve tumor response and the duration of local control of superficial and subsurface tumors.     

Chestwall recurrences of breast cancer: results of combined treatment with radiation and hyperthermia

In 35 patients with chestwall recurrences of breast carcinoma, 45 lesions were treated with combined radiation and hyperthermia. The majority of the lesions received 6 fractions of 4 Gy, twice a week during 3 weeks. Hyperthermia was administered within 30 min after irradiation, aiming a tumor temperature of 43 degrees C during one hour. The percentage of complete response (CR) was 57%. In small lesions, the percentage of CR was 80%. The mean duration of the response was 7 months. Response rate increased with increasing temperature. Particularly, mean temperature and isoeffect thermal dose correlated very well with response rate. In nine cases, comparative lesions were treated with either radiation alone or radiation combined with hyperthermia. The response rates were 3/9 and 7/9, respectively. Acute skin reactions were enhanced by the combined treatment. However, late skin reactions were not increased. Although the prognosis of patients with chestwall recurrences is determined by the presence of distant metastases, local control remains an important objective. Combined treatment with radiation and hyperthermia offers the possibility of obtaining a high local control rate particularly in relatively small lesions.     

热疗加放疗治疗局部复发乳腺癌的疗效分析

目的评价热疗加放疗治疗局部复发乳腺癌的疗效.方法回顾性分析热疗加放疗治疗的85处病灶,其中39处病灶曾接受过放疗,未曾放疗的部位给予59.5±6.8 Gy(40～70 Gy)照射,曾放疗的病灶实施43.0±12.4 Gy(12～74.4 Gy)照射;热疗每周1次或1周2次,平均每例患者的热疗次数为4.5(2～9)次.结果治疗1个月后CR率为92.0%,过去未曾放疗的病灶CR率为47.1%(16/34),曾放疗过病灶的CR率为56.1%(23/41),虽然曾放疗组的剂量(43.0±12.4 Gy)明显低于未放疗组的剂量(59.5±6.8 Gy),但两组间CR率差异无显著性(P=0.40).治疗后4周时弥散/多发型病变较肿块/结节型病变的CR率高,而6个月后弥散/多发型的局部控制率却明显降低.结论局部热疗配合放疗可以提高复发乳腺癌的局部控制率,特别是对曾经接受过放疗的区域可以降低放疗的剂量.弥散/多发型肿块较肿块/结节型的病灶对治疗的反应较早,但是很容易在短时期内复发.     

An assessment of local hyperthermia in clinical practice

A total of 116 small superficial tumours have been treated by radiation alone, hyperthermia alone, or radiation and hyperthermia combined in a Phase I/II study. Most tumours were metastases or local recurrences of adenocarcinoma of breast but other histologies were involved including melanoma. Hyperthermia was delivered predominantly by microwaves, but radiofrequency and ultrasound methods were also used. Rigorous thermal dosimetry, based on measurements from invasive multipoint thermocouple arrays, has shown that 58 per cent of hyperthermal treatments reached a minimum dose within tumour equivalent to 20 min at 43 degrees C (minEq43); 24 per cent reached at least 60 minEq43. Minima of 20 minEq43 were achieved successfully on every intended occasion in a quarter of the 75 tumours heated, and on one/two occasions in 39; unfortunately, this minimum threshold was not reached at any point monitored at any hyperthermia session in 17(23 per cent) tumours. Tumours that received radiation and effective hyperthermia were more likely to disappear completely (CR rate 86 per cent) than those that were irradiated but inadequately heated (CR rate 35 per cent) (P less than 0.001) or were treated by the same doses of radiation alone (CR rate 35 per cent) (P less than 0.05). This improvement with hyperthermia became more apparent with suboptimal radiation doses. A small but measurable growth delay was imposed by heat alone with a poor complete response rate (11 per cent). The real-time use of a thermal dose unit in clinical practice facilitates hyperthermal treatment comparisons and provides an important parameter for checking the technical performance of a heat delivery system. The results of this study emphasizes the need for improvements in intratumour temperature distribution, in order to establish minimum threshold temperatures to enhance tumour response rates.     

热放化综合治疗鼻咽癌颈淋巴结转移的临床随机研究

目的 :随机分组比较热放化综合与放化配合治疗鼻咽癌颈淋巴结转移癌的临床疗效。方法 :35例行放疗 化疗 热疗与 32例行放疗 化疗对照 ,观察肿瘤的消退率和皮肤反应。结果 :颈转移淋巴结的全消率在热放化组为 6 5 71% (2 3/35 ) ,放化组为 4 0 6 2 % (13/32 ) ;放射的皮肤反应两组相似。结论 :热疗配合放疗和化疗较放疗和化疗能显著提高鼻咽癌颈淋巴结转移癌的全消率 (P <0 0 5 ) ,热疗不会加重皮肤的放射反应。     

Local microwave hyperthermi and irradiation in cancer therapy: Preliminary observations and directions for future clinical trials

This report outlines the preliminary experience at the Mallinckrodt Institute of Radiology with hyperthermia and irradiation. Twenty-nine lesions were treated with 400 rad fraction given every 72 hours (twice weekly) for a total dose of 2000 to 4000 rad followed by byperthermia (2450 M z or 915 MHz microwaves, 42.0°–43°C, 90 minutes, every 72 hours.) In addition, 6 lesions were treated with threeof 500 rad fofiowed by hypertbermia and 12 with irradiation alone (three doses of 600, 700 or 800 rad every 72 hours). In the lesions treated with 2000 to 4000 rad and heat, nine of 12 recurrent epidermoid carcinomas of the hea and neck showed complete regression (7%) and one more than 50% response. Four of five metastatic melanoma nodules showed complete regression of the tumors and one over 80% response. Of nine recurrent adenocarcinoma of the breast nodules in the chest wall treated with 3200 to 4000 rad, five lesions exhibited complete regression and two others about 80%. Four of five metastatic melanoma nodules and three soft tissue sacomas had complete tumor regression. Of the six lesions treated with 1500 red and hypertbermia, two metastatic melanomas showed comppletel regression (CR), and three tumors exhibited partial regression. Despite the fact that the majority of the patients had been previously treated with defimitive radiotherapy, the retreatment with moderate doses of irradiation and beat) has been well tolerated. Of the 35 sites treated, four (11%) developed blisters, seven (20%) erythema only, three (8%) moist desquamation and 27 (77%) dry desquamation. There has been one instance of severe necrosis of soft tissues in the upper neck, in a patient previously treated with 5000 rad and surgery. Additio ial clinical trials are warranted to assess the potential value of hyperthermia alone or combined with irradiation in the treatment of selected cancer patients.     

Thermoradiotherapy of malignant melanoma

From 1978 through February 1986, 49 measurable lesions in 18 patients with recurrent primary or metastatic malignant melanomas were treated with a combination of radiation therapy and hyperthermia. The primary sites were head and neck (eight), chest wall (two), pelvis (one), upper extremities (three), and lower extremities (35). Because of the length of the study, the dose and fractionation of radiation therapy varied (dose per fraction from less than 400 cGy to 800 cGy and a total dose of 2000 cGy to 6000 cGy). This variation was mostly dependent on the prior course of radiation therapy of these lesions. The hyperthermia technique used in these patients was superficial local microwave hyperthermia; a minority of patients were treated with ultrasound. Complete response was achieved in 29 lesions (59–2 per cent) and partial response in six lesions (12 per cent). In a separate analysis of 67 lesions with superficial malignant melanoma who were treated by radiation therapy alone, a 24 per cent complete response and a 34 per cent partial response were achieved. Detailed analyses are presented in regard to dose per fraction, total radiation dose, and the size of lesions.     

Interstitial thermoradiotherapy: thermal dosimetry and clinical results

From August 1977 to August 1986, 72 patients with advanced primary or recurrent cancers were treated using interstitial thermoradiotherapy. Sites treated included the pelvis in 49 patients, the head and neck in 15, and other sites in six. Median tumor volume was 52 cm3, and all but nine patients had received prior irradiation. In 69 patients, hollow stainless steel catheters were implanted and used as electrodes with a 0.5 MHz radiofrequency (RF) generator, whereas in three patients, standard plastic Henschke tubes were used with a commercially available interstitial microwave (MW) system operating at 915 MHz. Most patients were heated intraoperatively for 30 minutes, aiming for a minimum measured intratumoral temperature (Tmin) of 42 degrees C. The implant was occasionally preceded by external irradiation, and after hyperthermia, the catheters were afterloaded with 192Ir for brachytherapy. Tmin exceeded 42 degrees, 42.5 degrees, 43 degrees, and 44 degrees in 25, 16, 12, and 3, respectively, of 70 patients with temperature data available, and the probability of successful heating was independent of tumor volume or site. Twenty-five of 69 (36%) evaluable patients achieved a complete response (CR). Probability of CR demonstrated a significant univariate dependence upon Tmin, radiation dose, site treated, and tumor volume, but multivariate analysis showed only three significant predictor variables: tumor volume, radiation dose, and Tmin. The probability of a CR ranged from 95% for patients with small tumors receiving high doses of radiation and adequate heat, to 5% for patients with large tumors receiving low radiation doses and less than adequate heat. Of 25 patients with CR, 10 relapsed; median response duration was less than 18 months, depended marginally upon disease site, and was independent of Tmin, radiation dose, and tumor volume. Seventeen patients sustained a complication, of which nine were severe enough to require hospitalization or surgery. All severe complications occurred in patients with pelvic tumors. The probability of a complication of any severity had a significant univariate association with maximum intratumoral temperature (Tmax) and tumor size. We conclude that interstitial thermoradiotherapy offers the promise of heating large tumors in locations where externally applied hyperthermia has not been successful.     

Thermoradiotherapy of malignant melanoma

From 1978 through February 1986, 49 measurable lesions in 18 patients with recurrent primary or metastatic malignant melanomas were treated with a combination of radiation therapy and hyperthermia. The primary sites were head and neck (eight), chest wall (two), pelvis (one), upper extremities (three), and lower extremities (35). Because of the length of the study, the dose and fractionation of radiation therapy varied (dose per fraction from less than 400 cGy to 800 cGy and a total dose of 2000 cGy to 6000 cGy). This variation was mostly dependent on the prior course of radiation therapy of these lesions. The hyperthermia technique used in these patients was superficial local microwave hyperthermia; a minority of patients were treated with ultrasound. Complete response was achieved in 29 lesions (59.2 per cent) and partial response in six lesions (12 per cent). In a separate analysis of 67 lesions with superficial malignant melanoma who were treated by radiation therapy alone, a 24 per cent complete response and a 34 per cent partial response were achieved. Detailed analyses are presented in regard to dose per fraction, total radiation dose, and the size of lesions.     

Analysis of prognostic variables in hyperthermia treatment of 161 patients

From 1977-1982, 161 patients were treated using hyperthermia as an adjuvant in Phase I trials. Microwave applicators (MW), capacitively coupled plates (RF plates), interstitial localized current fields (LCF), and magnetic induction heating (MI) techniques were used together with radiation in 135 patients, with chemotherapy in 10 patients, and alone in 16 patients. Tumor volume response categories were no response (NR, less than 50% decrease); partial response (PR, 50% less than or equal to volume decrease less than 100%); and complete response (CR, complete disappearance). The CR rates and total response rates (CR + PR) were 38/160 (24%) and 90/160 (56%), respectively. There were highly significant differences among techniques in CR vs PR + NR (p = .001), and in CR + PR vs NR (p less than .0005). Response did not vary significantly with histologic category. Overall toxicity was 16%, and did not vary significantly with technique (p = .193). In the patient group treated with hyperthermia and radiation, multivariate analysis revealed that a set of three variables had prognostic importance for CR: technique (p = .011), radiation dose (p = .019), and tumor volume (p = .001, negatively correlated). A good correlation also existed between CR and the minimum tumor temperature averaged over all treatments, TMIN (p less than .0005). Temperature variables themselves were correlated with tumor volume. Minimum T correlated negatively with volume (p = .017) and TMAX correlated positively with volume (p = .026). In fewer than 50% of patients could minimum T greater than 40.7 degrees C be achieved. Our conclusions are: TMIN, tumor volume, radiation dose, and heating technique have prognostic value for initial response; variation in CR vs technique reflects variation in tumor volume treated and in minimum temperature achieved with these techniques; and acute toxicity of treatment is infrequent, but serious toxicity is possible with the interstitial technique.     

Effect of hyperthermia combined with external radiation therapy in primary non-small cell lung cancer with direct bony invasion

Purpose : Local control in lung cancer directly invading the bone is extremely poor. Effects of regional hyperthermia combined with conventional external beam radiation therapy were evaluated. Materials and methods : Thirteen patients with non-small lung cancer (NSCLC) with direct bony invasion were treated with hyperthermia plus irradiation (hyperthermia group). The treatment outcome was compared with the historical treatment results in 13 patients treated with external radiation therapy alone (radiation alone group). In patients with no distant metastasis, radiation therapy at a total dose of 60-70Gy was administered to both groups. Hyperthermia was performed for 45-60min immediately after irradiation for two-four sessions with radiofrequency capacitive heating devices. Results : For primary response, 10 of the 13 tumours responded to the treatment (3 CR, 7 PR) in the hyperthermia group, whereas seven tumours responded (1 CR, 6 PR) in the radiation alone group. The 2-year local recurrence-free survival rate for clinical M 0 patients in the hyperthermia group and that in the radiation alone group were 76.1 and 16.9%, respectively. Three patients died of distant metastases within 2 years in the hyperthermia group, but two out of three tumours histologically disappeared, even in the autopsy examination. The 2-year overall survival rate for clinical M 0 patients in the hyperthermia group and that in the radiation alone group were 44.4 and 15.4%, respectively. No severe pulmonary complication was observed in either group. Conclusions : Regional hyperthermia combined with conventional irradiation could be a tool to improve local control in patients with NSCLC deeply invading the chest wall.     

‘Patchwork’ fields in thermoradiotherapy for extensive chest wall recurrences of breast carcinoma

Summary Chest wall lesions of advanced breast carcinoma in 23 patients were treated with thermoradiotherapy with clinical intent between January 1987 and March 1992. Treatment consisted of external 915 MHz microwave hyperthermia with commercially available applicators and radiation therapy to doses between 32–58 Gy. Twenty-three large, diffuse lesions were treated with multiple field patchwork hyperthermia. All lesions were diffuse with or without multiple nodules 3 cm depth. All lesions had failed previous therapy. The mean number of hyperthermia fields per patient was 3.2 ± 0.4 (range of 2–7). The complete response rate was 91% in this group of extensive, diffuse lesions treated by the patchwork technique. Mean total radiation dose administered concurrently with multiple field patchwork hyperthermia was 42 ± 1 Gy. The recurrence rate was 5%. The mean survival in patients who had a complete response was 9.0 ± 1.3 months. The reduced survival among patchwork treated patients was due to the extensive tumor burden existing outside of the treated fields in these patients. The skin reactions were minor, causing minimal discomfort. There was no evidence of increased thermal damage to skin, or of tumor recurrence at junctions of hyperthermia field overlap. It is concluded that extensive, diffuse lesions of chest wall recurrence of advanced carcinoma of the breast can be treated effectively with multiple field patchwork thermotherapy.Presented in part at the 15. San Antonio Breast Cancer Symposium (December 1992).     

Microwave-induced local hyperthermia in combination with radiotherapy of human malignant tumors

Since 1976, two groups of patients have been treated with local microwave hyperthermia immediately following ionizing radiation. Group A patients had measurable multiple lesions assigned radiotherapy only, microwave hyperthermia only, or combined treatment. Ionizing radiation in 200-600 rad fractions was used 2-5 times per week to a total of 1800-4200 rad in 5-14 fractions. Group B patients had combination treatment only, with radiation fractions of 200-600 rad 2-5 times per week to a total of 2000-4800 rad total in 6-20 fractions. Both groups received hyperthermia (42-44 C) 2-3 times per week, maximum ten sessions in four weeks. The 19 patients treated have had squamous cell carcinoma, adenocarcinoma, malignant melanoma, plasmacytoma, epithelioid sarcoma, and undifferentiated carcinoma. After more than 150 hyperthermia sessions, we find: (1) local hyperthermia with microwave alone or in combination with ionizing radiation can be used with excellent normal tissue tolerance provided local tissue temperatures are carefully monitored and controlled; (2) a higher level of heat induction in tumor tissue as compared to surrounding normal tissues; (3) repeated hyperthermia at 42-43.5 C for 45 minutes per session immediately following photon irradiation yields a favorable therapeutic result, occasionally dramatic. Local microwave hyperthermia in combination with radiotherapy offers the possibility of substantial impact on clinical cancer therapy, whether of curative or palliative intent.     

Solid tumor models for the assessment of different treatment modalities: XXIII. A new approach to the more effective utilization of radiotherapy alternated with chemotherapy

This study with the rat hepatoma 3924A demonstrated the marked improvement in tumor cure rates and control of tumor growth that can be achieved by the addition of cyclophosphamide (CP) to multiple fractions of radiation per day (MFD) schedules given intermittently. MFD radiation was delivered over a 2-day period followed by CP (150 mg/kg or 0.9 g/m2) 1 day later; this combined course was repeated at 11-day intervals (to allow for gastrointestinal tract and bone marrow recovery) for a total of 3 courses over a 23-day period. Cure rates of 30, 50 and 60% were achieved with total radiation doses of 4500, 6000 and 7500 rad, respectively, when the MFD radiation was given with CP. No cures and no complete responses were realized when the same intermittent MFD schedules for radiation were employed up to 9000 rad without CP. Other groups of 10 animals each were treated with daily fractions of 100, 150, 188, 250 and 375 rad given on days 0-9, 11-20 and 22-31. A 150 mg/kg or 0.9 g/m2 dose of CP was given after each course of daily radiation on days 10, 21 and 32 in the combined treatment groups. No complete responses or tumor cures occurred with radiation alone given daily for total radiation doses, which were increased from 3000 to 11,250 rad. Only the highest radiation dose given, 375 rad per day to a total of 11,250 rad, resulted in a complete response rate and tumor cure rate of 50% when CP was added. The addition of CP to the daily fractionation schedules reduced the total dose needed to give a growth delay of 100 days by 39% (5600 rad versus 9200 rad). The addition of CP to the intermittent MFD schedules further reduced the total dose needed to give a growth delay of 100 days to 4200 rad. Major improvements in some types of cancer treatment may be realized if we can develop clinical protocols for the alternate use of chemotherapy and radiotherapy as we have done successfully in our experimental program. The finding that intermittent MFD radiation schedules are as effective as daily schedules when given alone suggests that greater flexibility of patient management in clinical radiotherapy may be possible without a major loss of therapeutic effectiveness. These alternated fractionated schedules offer the possibility of optimizing treatment in terms of patient convenience and economy as well as the potential for improving the effectiveness of the interaction of radiotherapy with radiosensitizers, radioprotectors, and hyperthermia in addition to chemotherapy.     

Hyperthermia in combination with radiotherapy: a review of five years experience in the treatment of superficial tumors

Facilities for regional tumor hyperthermia has been in use at RPMI since 1976, and have been routinely used to treat patients according to protocol since 1977. Hyperthermia delivery has been exclusively by microwave using 434 MHz, 915 MHz and 2450 MHz. Greatest success at reaching tumor temperatures of 43-44 degrees C with minimal skin heating was obtained using 915 MHz. The majority of the patients were treated with this frequency. Approximately 125 patients have been treated and 70 have achieved completion of therapy and follow-up. Follow-up has been at least one month and several patients have been followed for one to two years. Initially, for entry into the hyperthermia protocol, patients were required to have three or more lesions. One lesion on each patient was treated with 800 rad fractions repeated three times on a 72 hour schedule. The second lesion was treated with 700 rad fractions and the third with 500 rad plus hyperthermia on the same schedule. Twelve patients with multiple melanoma lesions completed this study. One of 12 patients showed no response to the combination of hyperthermia plus radiotherapy, while four showed no response to radiotherapy alone. Of eight patients who survived three months, all lesions treated by hyperthermia plus radiotherapy responded completely, while only five lesions treated by radiotherapy alone so responded. In a second study, 58 patients with superficial tumors were treated by a protocol where hyperthermia was added to optimal conventional radiotherapy. Of the total, 43 patients had complete tumor response at follow-up varying from one month to 18 months. A subgroup of 24 of these patients had two lesions, one of which was treated with hyperthermia in addition to radiotherapy while the other served as control, receiving radiotherapy only. Nineteen lesions demonstrated complete response to hyperthermia plus radiotherapy, while only 14 of the controls had complete response. None of the lesions treated with hyperthermia responded less well than those treated by radiotherapy alone. Morbidity, as measured by skin reaction, was rarely increased in the heated field.