BACKGROUND: Foreign scholars use thermotherapy, a new pathway for synthetic therapy of tumor, to perform hyperpyrexia combined with chemical drug radiotherapy of intraperitoneal infiltration and metastasis or to study on the therapeutic effect of metaphase and advanced stage tumor. Especially, establishing thermal biology and thermal dosiology is a scientific and quantified track for synthetic therapy of thermal radiotherapy, thermal chemotherapy and hyperthermal perfusion of tumor.OBJECTIVE: To analyze the thermal dose effect of regional radiofrequency (RF) hyperthemia combined with radiotherapy, chemotherapy and thermal perfusion on metaphase and advanced stage tumor.DESIGN: Controlled observation.SETTING: Key Department of Traditional Chinese and Western Medicine for Tumor, the 107 Hospital of Chinese PLA (General Center for Non-traumatic Treatment and Diagnosis of Tumor).PARTICIPANTS: Totally 1 455 patients with metaphase and advanced-stage tumor admitted to the General Center for Non-traumatic Treatment and Diagnosis of Tumor, the 107 Hospital of Chinese PLA between June and September 2006 who received conservative palliative treatment in the Department of Internal Medicine were recruited in this study. They were all confirmed by pathology and imageology. ECOG was scored 2 to 4 points. Informed consents of detection and treatment were obtained from all the involved patients. The study was approved by the Hospital Ethics Committee.According to the therapeutic regimen, the patients were assigned into thermal perfusion group (n =53), thermal radiotherapy group (n =874), thermal chemotherapy group (n =458) and simple hyperthemia group (n =70).METHODS: After admission, patients in each group were performed peritoneal and pelvic cavity perfusion,intensity-modulated radiation therapy, routine chemotherapy and integrated traditional and western medicine palliative therapy, respectively. Meanwhile, they received RF hyperthemia using in vitro endogenic magnetic field hyperthermia system. A thermocouple was placed in the abdominal cavity. Temperature at 3 different sites in the abdominal cavity was collected, and meanwhile two different sites for measuring temperature at rectum and external acoustic meatus were monitored. The maximal temperature (Tmax), minimal temperature (Tmin) and the average temperature (Tave) of therapeutic target were recorded. 40 ℃/min was used as thermal dose, thermal perfusion was performed once a week, and RF hyperthemia was conducted twice a week, 60 minutes once. Target temperature was 39.5 to 43 ℃, and the thermal dose of 40 ℃/min was calculated out. Intensity-modulated radiation therapy was conducted within 1 hour before heating at (3-5)Gy/time, 3 to 4 times a week. Total dose was DT 30 to 50Gy. Thermal perfusion was conducted 2 to 3 times a week, and intensity-modulated radiation therapy was conducted once to twice a week and 6 to 8 times a course of treatment. The thermal effect of each patient was analyzed at different temperature and different diseases.MAIN OUTCOME MEASURES: ① To analyze the effect of effective thermal dose. ② To evaluate the therapeutic effect and the improvement of quality of life according to World Health Organization (WHO) objective therapeutic effect evaluation criteria and Zubrod-ECOG-WHO scores. ③To observe the changes in abdominal dropsy.RESULTS: Altogether 1 455 patients with metaphase and advanced stage participated in the final analysis. ①After perfusion, body temperature was over 39.5 ℃ in most cases after 15-minute warming, over 40.0 ℃ after another 25-minute warming, over 41.0 ℃ after additional 35-minute arming, and even to 43.0 ℃ after frequent such a thermal therapy. Temperature over 41 ℃ was found in 91 cases, at 40 ℃-40.9 ℃ in 414 cases and at 39.5 ℃-39.9 ℃ in 950 cases. ② The thermal effect of 40 ℃/min could obviously improve the therapeutic effects of graded intensity-modulated radiation therapy, low-dose chemotherapy and thermal perfusion group. The total effective rate of thermal perfusion group, thermal radiotherapy group, thermal chemotherapy group and simple hyperthemia group was 81.6%, 81.9%, 80% and 50%, respectively. The clinical therapeutic effect of 40 ℃-40.9 ℃ and 39.5 ℃-39.9 ℃ in the thermal perfusion group, thermal radiotherapy group and thermal chemotherapy group was significantly better than that in the simple hyperthemia group (P ＜ 0.05). ③ Comparison of Zubrod-ECOG-WHO score of patients before and after therapy: After therapy, Zubrod-ECOG-WHO score was enhanced in 76.3% patients. ④The changes in abdominal dropsy of patients before and after therapy: After therapy, abdominal dropsy changed in 75% patients.⑤The therapeutic effects of different diseases at different temperature: For the same disease, the therapeutic effects over 41 ℃ and at 40 ℃-40.9 ℃ were significantly different from those at 39.5 ℃-39.9 ℃(P ＜ 0.05); However, the therapeutic effects over 41 ℃ were not significantly different from those at 40 ℃-40.9 ℃ (P ＞ 0.05).CONCLUSION: ①The effects of regional RF hyperthemia combined with intensity-modulated radiation therapy are confirmed in the treatment of metaphase and advanced-stage of tumor. ② The therapeutic effects strengthen correspondingly with 40 ℃/min thermal dose increase or temperature increase.