Temperature elevation during brachytherapy for carcinoma of the uterine cervix: adverse effect on survival and enhancement of distant metastasis.

Possible effects of fever during intracavitary radiation therapy on patient survival, local-regional control or metastatic spread of disease were analyzed in a group of 398 patients with previously untreated, invasive carcinoma of the uterine cervix, managed with a combination of external beam irradiation and intracavitary radium (ICR) applications at Yale-New Haven Medical Center and affiliated hospitals from January 1953 through December 1977. Cox step-wise proportional hazard models were used to test for the influence of elevated temperatures during ICR placements, controlling for the influence of other pretreatment patient parameters, including FIGO stage, age, blood count, prior supracervical hysterectomy and number of prior pregnancies. Increasing maximum temperatures noted during ICR placements were associated with: decreased patient survival (p = 0.014) and increased frequency with time of distant metastasis as the initial sites of treatment failure (p = 0.038). When patients were dichotomized on the basis of maximum temperature during ICR, distant metastasis as the initial site(s) of treatment failure was noted twice as frequently in patients with maximum temperatures greater than or equal to 101.0 degrees F (12.5%; 10/80 patients) than in those with maximum temperatures less than 101.0 degrees F during ICR placement (6.3%; 20/318 patients). No statistically significant differences were noted between the two groups in their distributions by stage, age, histology, year of diagnosis, or pretreatment hemoglobin, and the sites of distant metastasis and time course for clinical detection were similar in both groups. These results are in agreement with prior clinical studies in cancer of the uterine cervix which noted a poor prognosis in patients with cancer of cervix who developed fever during treatment. In addition, the finding of an association between an increased frequency of distant metastasis and temperature elevation during the ICR provides, for the first time, clinical data supporting the reports of an alteration or enhancement of distant metastasis following the application of whole body hyperthermia in murine, rabbit and canine tumors.