Clinical results of radiofrequency hyperthermia combined with radiation in the treatment of radioresistant cancers (original) (raw)
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International Journal of Radiation Oncology Biology Physics, 1990
From March 1984 to February 1988.70 patients with 179 separate treatment fields containing superficially located (~3 cm from surface) recurrent or metastatic malignancies were stratified based on tumor size, histology, and prior radiation therapy and enrolled in prospective randomized trials comparing two versus six hyperthermia treatments as an adjunct to standardized courses of radiation therapy. A total of 165 fields completed the combined hyperthermiaradiation therapy protocols and were evaluable for response. No statistically significant differences were observed between the two treatment arms with respect to tumor location; histology: initial tumor volume; patient age and pretreatment performance status; extent of prior radiation therapy, chemotherapy, hormonal therapy. or immunotherapy; or concurrent radiation therapy. The means for all fields of the averaged minimum, maximum, and average measured intratumoral temperatures were 40.2"C, 44.8"C, 42.5"C. respectively, and did not differ significantly between the fields randomized to two or six hyperthermia treatments. The treatment was well tolerated with an acceptable level of complications. At 3 weeks after completion of therapy, complete disappearance of all measurable tumor was noted in 52% of the fields, ~50% tumor reduction was noted in 7% of the fields, ~50% tumor reduction was noted in 21% of the fields, and continuing regression (monotonic regression to ~50% of initial volume) was noted in 20% of the fields. No significant differences were noted in tumor responses at 3 weeks for fields randomized to two versus six hyperthermia treatments (p = 0.89). Cox regression analyses were performed to identify pretreatment or treatment parameters that correlated with duration of local control. Tumor histology, concurrent radiation dose, and tumor volume all correlated with duration of local control. The mean of the minimum intratumoral temperatures (~41°C vs. 241°C) was of borderline prognostic significance in the univariate analysis, and added to the power of the best three covariate model. Neither the actual number of hyperthermia treatments administered nor the hyperthermia protocol group (two versus six treatments) correlated with duration of local control. The development of thermotolerance is postulated to be, at least in part, responsible for limiting the effectiveness of multiple closely spaced hyperthermia treatments.
International Journal of Radiation Oncology*Biology*Physics, 1992
240 superficially located recurrent/metastatic malignant lesions (173 patients) were enrolled in a prospective randomized study of one versus two byperthermia fractions per week. In the majority of patients, the dose of radiation therapy was less than 4000 cGy over 4 to S weeks. Stratification was by tumor size, site, and histology. The goal of the hyperthermia sessions were 42.S"C for 45-60 min minimum i&a-tumor measured temperature. Hyperthermia was given after radiation within 30-60 min. External applicators, both microwave (over 90% of treatments) and ultrasound, were used. Overall, complete response rate in 222 evahmble lesions was 56.3% (125/222) with a minimum follow-up of 6 months and a maximum follow-up of 52 months. The complete response rate for once a week versus twice a week hyperthermia group was 54.7% and 57.8%, respectively. The severe complication rate was 18% (41/222). There was no difference between the two treatment arms. Cox regression analyses were performed to study the prognostic significance of patient characteristics, tumor characteristics, and treatment parameters. Detailed analysis and results are presented.
Cancer treatment reviews, 2015
Hyperthermia, one of the oldest forms of cancer treatment involves selective heating of tumor tissues to temperatures ranging between 39 and 45°C. Recent developments based on the thermoradiobiological rationale of hyperthermia indicate it to be a potent radio- and chemosensitizer. This has been further corroborated through positive clinical outcomes in various tumor sites using thermoradiotherapy or thermoradiochemotherapy approaches. Moreover, being devoid of any additional significant toxicity, hyperthermia has been safely used with low or moderate doses of reirradiation for retreatment of previously treated and recurrent tumors, resulting in significant tumor regression. Recent in vitro and in vivo studies also indicate a unique immunomodulating prospect of hyperthermia, especially when combined with radiotherapy. In addition, the technological advances over the last decade both in hardware and software have led to potent and even safer loco-regional hyperthermia treatment deliv...
International Journal of Radiation Oncology*Biology*Physics, 1995
Hospital and Clinic has investigated the efficacy and safety of 8 MHz radiofrequency (RF) capacitive hyperthermia using the Thermotron RF-K This study reports the thermometric and clinical results of 119 patients treated with RF hyperthermia in combination with radiotherapy (RT). Methods and Materials: Of 119 patients, 69 received high-dose RT and 50 patients received low-dose RT because of previous irradiation to the treatment site. The most common anatomic sites treated were within the pelvic cavity or head and neck area. Thirty-three percent and 24% of tumors treated were > 7 cm and > 10 cm in largest diameter, respectively. Forty percent of the patients had deep-seated tumors (depth > 6 cm). Hyperthermia was given as soon as possible after RT twice weekly, allowing at least 72 h between treatments. The objective was to raise intratumoral temperatures to 42-43°C or above for 30-50 min while keeping normal tissue temperatures below 40-41°C. Results: Of 119 patients, 40% achieved a T;;;;;-; tumor temperature of > 42°C and 40% achieved 40-42°C-Higher TG) tumor temperatures were observed as tumor size increased. Tumors > 10 cm in largest diameter had a Tz of 42.2"C. Tumor depth was not a significant factor for the tumor temperatures achieved. Of 119 patients, 11% achieved complete response and 38% achieved partial response. Of the noresponse patients, 34% had symptomatic palliation and 15% had stable disease for at least 12 months after treatment. We were able to treat tumors of patients with subcutaneous fat as thick as 3 cm by precooling the fat for 20 min with lo-15°C saline-filled boluses prior to the initiation of heating. During treatment, 60% of patients complained of varying degrees of pain and 19% had pain that was a factor in limiting treatment. Vital signs were relatively stable and not a factor in limiting treatment. Conclusion: The Thermotron RF-8 is a useful hyperthermia device that can raise tumor temperatures to a therapeutic level (i.e., 42C) in a significant proportion of patients with superficial, subsurface, and deep. seated tumors, with minimal adverse effects, complications, and systemic stress. Further clinical studies using improved thermometry systems are warranted.
International Journal of Radiation Oncology*Biology*Physics, 1991
Center. To test this system in combination with interstitial radiotherapy and to study the interactions of interstitial radiotherapy and interstitial hyperthermia, animal experiments were performed using rhabdomyosarcoma type RI transplanted in the flanks of female Wag/Rij rats. Using the 27 MHz system, it appeared feasible to obtain hyperthermic temperatures. In this experiment a thermal dose of 44°C for 30 minutes was delivered by controlling the temperature at the periphery of the tumor to 44°C. The interstitial heating applicators were inserted in four standard afterloading catheters implanted with a fixed spacing of 7 mm; the same catheters were used for the radioactive sources for interstitial radiotherapy treatment following the interstitial hyperthermia sessions. Interstitial radiotherapy was given by means of four Ir19* wires with an average activity of 4.5 -10' Bq/cm. Minimum tumor doses of 20 to 115 Gy with a mean dose rate of 47 cGy/hour were applied. Interstitial hyperthermia alone resulted in a growth delay (GDl) of 6 + 2 days without significant reduction of tumor volume. The 50% tumor cure dose after interstitial radiotherapy alone was 95 f 9 Gy. Combination of interstitial hyperthermia and interstitial radiotherapy resulted in reduction of the 50% tumor cure dose to 48 rt 13 Gy. The dose-effect data for cure for these modalities are compared to existing data for external irradiation and external hyperthermia in the same tumor model. It was found that the addition of hyperthermia to different modes of irradiation, that is, either to single dose or protracted radiotherapy, results in a common level of radiosensitivity through impaired repair of sublethal damage. This study demonstrates the feasibility of the 27 MHz heating system in achieving hyperthermic temperatures; in the combined modality experiments a thermal enhancement factor of 2.0 f 0.3 (mean f standard deviation) was observed.
A Randomized Trial of Hyperthermia and Radiation for Superficial Tumors
International Journal of Radiation Oncology*Biology*Physics, 2005
Purpose Randomized clinical trials have demonstrated hyperthermia (HT) enhances radiation re sponse. These trials, however, generally lacked rigorous thermal dose prescription and administration. We report the final results of a prospective randomized trial of superficial tumors (::5 3 em depth) comparing radiotherapy versus HT combined with radiotherapy,using the parameter describing the number of cumulative equivalent minutes at 43°C exceeded by Authors•disclosures of potentialcon 90% of monitored points within the tumor (CEM 43°C T) as a measure of thermal dose.
Radiofrequency capacitive hyperthermia for deep-seated tumors. II. Effects of thermoradiotherapy
Cancer, 1987
The thermometry results of radiofrequency (RF) capacitive hyperthermia for 60 deep-seated tumors in 59 patients are reported. Hyperthermia was administered regionally using two RF capacitive heating equipments which the authors have developed in cooperation with Yamamoto Vinyter Company Ltd., (Osaka, Japan). Intratumor temperatures were measured by thermocouples inserted through angiocatheters which were placed 5 cm to 12 cm deep into the tissues. Tumor center temperatures were measured for 307 treatments in all tumors; thermal distributions within tumors and surrounding normal tissues were obtained for 266 treatments of 53 tumors by microthermocouples. Thermometry results obtained were summarized as follows. A maximum tumor center temperature greater than 43 degrees C and 42 degrees C to 43 degrees C was obtained in 23 (38%) and 14 (23%) of the 60 tumors respectively. The time required to reach 43 degrees C in the tumor center was within 20 minutes after the start of hyperthermia in 87% of tumors heated to more than 43 degrees C. Temperature variations within a tumor exceeded 2 degrees C in 81% of tumors heated to more than 43 degrees C. The lowest tumor temperature greater than 42 degrees C was achieved in six of the 53 tumors (11%). Of 42 tumors in which temperatures of the subcutaneous fat, surrounding normal tissues, and the tumor center were compared, 24 (57%) showed the highest temperature in the tumor center and ten (24%) in the subcutaneous fat. When the heating efficacy was assessed in terms of a maximum tumor center, it great deal depended on the treatment site, tumor size, thickness of subcutaneous fat, and tumor type. Tumors in the head and neck, thorax, lower abdomen, and pelvis could be heated better than tumors in the upper abdomen. Greater heating efficacy was shown in patients with large, hypovascular tumors, and with the subcutaneous fat measuring less than 15 mm thick. The predominant limiting factor for power elevation was pain associated with heating. Systemic signs including increases in pulse rate and body temperature were not serious and seldom became limiting factors for power elevation. Our thermometry results indicate that the advantages of deep RF capacitive heating are its applicability to various anatomic sites and negligible systemic effects. The disadvantages are that its primary usefulness is limited to patients with thin subcutaneous fat and with large or hypovascular tumors.