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Purpose: The local failure rate in patients with locoregionally advanced cervical cancer is 41-72% after radiotherapy (RT) alone, whereas local control is a prerequisite for cure. The Dutch Deep Hyperthermia Trial showed that combining RT with hyperthermia (HT) improved 3-year local control rates of 41-61%, as we reported earlier. In this study, we evaluate long-term results of the Dutch Deep Hyperthermia Trial after 12 years of follow-up., Methods and Materials: From 1990 to 1996, a total of 114 women with locoregionally advanced cervical carcinoma were randomly assigned to RT or RT+HT. The RT was applied to a median total dose of 68 Gy. The HT was given once weekly. The primary end point was local control. Secondary end points were overall survival and late toxicity., Results: At the 12-year follow-up, local control remained better in the RT+HT group (37% vs. 56%; p=0.01). Survival was persistently better after 12 years: 20% (RT) and 37% (RT+HT; p=0.03). World Health Organization (WHO) performance status was a significant prognostic factor for local control. The WHO performance status, International Federation of Gynaecology and Obstetrics (FIGO) stage, and tumor diameter were significant for survival. The benefit of HT remained significant after correction for these factors. European Organization for Research and Treatment of Cancer Grade 3 or higher radiation-induced late toxicities were similar in both groups., Conclusions: For locoregionally advanced cervical cancer, the addition of HT to RT resulted in long-term major improvement in local control and survival without increasing late toxicity. This combined treatment should be considered for patients who are unfit to receive chemotherapy. For other patients, the optimal treatment strategy is the subject of ongoing research.

Purpose: Claims for the value of hyperthermia as an adjunct to radiotherapy in the treatment of cancer have mostly been based on small Phase I or II trials. To test the benefit of this form of treatment, randomized Phase III trials were needed., Methods and Materials: Five randomized trials addressing this question were started between 1988 and 1991. In these trials, patients were eligible if they had advanced primary or recurrent breast cancer, and local radiotherapy was indicated in preference to surgery. In addition, heating of the lesions and treatment with a prescribed (re)irradiation schedule had to be feasible and informed consent was obtained. The primary endpoint of all trials was local complete response. Slow recruitment led to a decision to collaborate and combine the trial results in one analysis, and report them simultaneously in one publication. Interim analyses were carried out and the trials were closed to recruitment when a previously agreed statistically significant difference in complete response rate was observed in the two larger trials., Results: We report on pretreatment characteristics, the treatments received, the local response observed, duration of response, time to local failure, distant progression and survival, and treatment toxicity of the 306 patients randomized. The overall CR rate for RT alone was 41% and for the combined treatment arm was 59%, giving, after stratification by trial, an odds ratio of 2.3. Not all trials demonstrated an advantage for the combined treatment, although the 95% confidence intervals of the different trials all contain the pooled odds ratio. The greatest effect was observed in patients with recurrent lesions in previously irradiated areas, where further irradiation was limited to low doses., Conclusion: The combined result of the five trials has demonstrated the efficacy of hyperthermia as an adjunct to radiotherapy for treatment of recurrent breast cancer. The implication of these encouraging results is that hyperthermia appears to have an important role in the clinical management of this disease, and there should be no doubt that further studies of the use of hyperthermia are warranted.

One hundred and thirty-two patients received postoperative radiation therapy following radical hysterectomy and pelvic lymphadenectomy for carcinoma of the uterine cervix Stage IB and IIA. In 43 patients with negative lymph node the 5- and 10-year survival rate was 85%. The other 89 patients with positive lymph node had 5- and 10-year survival rates of 60% and 51%, respectively. Multifactorial analysis of prognostic factors in the group of patients with lymph node metastasis disclosed pathology, microscopic infiltration in the parametrium and vascular space invasion as independent prognostic factors, that is, the 5-year survival rates were: 66% for squamous cell carcinomas versus, 25% for adenocarcinomas (p value: 0.001), 76% negative parametrium versus 39% positive parametrium (p value: 0.008), 68% no vascular space invasion versus 43% if invasion was observed (p value: 0.04). Sites of failure in 37 recurrences out of 89 patients with lymph node metastasis were pelvic alone 9, distant metastases alone 15, and combined pelvic plus distant metastasis in 12 patients. In one patient the site of failure was unknown. These data warrant more intensive local and systemic treatment, particularly in patients with poor prognostic factors. In the whole group, severe complications were observed in 11 patients.

The effects of X ray and 14 MeV neutron irradiation on growing tibia of mice were studied. As reported in the literature, the age of the animal at irradiation was an important factor if the endpoint in analyzing the radiation effect is the absolute shortening, difference in length between unirradiated and irradiated tibia, achieved by the treatment. However, if the growth remaining at the moment of irradiation is taken into account no significant differences in effect were observed with aging, and the dose given appeared to be the overruling factor. This was valid for both X ray and neutron irradiation. Absorbed dose-response curves after X ray irradiation showed a shoulder in the lower range of absorbed doses, which was not the case for neutron irradiation. RBE values for 14 MeV neutrons as compared to 250 kV X rays varied from 3.6 to 2.0 depending on the single absorbed dose level. No differences in RBE were found with aging. A mathematical formula was derived which can predict the absolute shortening when the initial and final length of the tibia are known as well as the absorbed dose of irradiation to be administered.