Relationships among tumor temperature, treatment time, and histopathological outcome using preoperative hyperthermia with radiation in soft tissue sarcomas.
The lack of an unambiguous thermal dosimetry continues to impede progress in clinical hyperthermia. In an attempt to define better this dosimetry, a model based on the cumulative minutes during which arbitrary percentages of measured tumor temperature points exceeded an index temperature was tested in patients with soft tissue sarcomas treated with preoperative hyperthermia and conventional radiation therapy. Patients received 5000-5040 cGy at 180-200 cGy per fraction. Hyperthermia was delivered 30-60 minutes after radiation therapy and given for 60 minutes. Patients were randomized between one and two hyperthermia treatments per week for a total of five or 10 treatments, respectively. Lesions were excised 4-6 weeks after completion of hyperthermia/radiation therapy. Successful treatment outcome was considered to be the finding of greater than 80% necrosis of the sarcoma upon histopathologic examination of the resected specimen. Forty-five patients were eligible with thermometry data available in 44 patients. An average of 19 interstitial sites were monitored each treatment per tumor. Sixty percent of tumors had a successful histopathologic outcome. Univariate analysis demonstrated that several descriptors of the temperature distribution were strongly related to treatment outcome; more strongly than nonthermometric factors, such as the number of treatments per week, tumor volume and patient age and more strongly than the commonly used temperature descriptors Tmin and Tmax. Descriptors that incorporated both temperature and time were also superior to the more commonly used descriptors Tmin and Tmax. Multivariate stepwise logistic regression analysis revealed that a descriptor of both the hyperthermia treatment time and the frequency distribution of intratumoral temperatures was the strongest predictor of histopathologic outcome and that the best predictive model combined this time/temperature descriptor and one versus two treatment per week grouping. The more conventional temperature descriptor, minimum measured tumor temperature, did not significantly enhance the predictive power of treatment group. Based on these results, we recommend that descriptors based on both the frequency distribution of intratumoral temperatures and hyperthermia treatment time be tested for relationships with treatment outcome in other clinical data bases. Furthermore, we recommend that temperature descriptors that are less sensitive to catheter placement and tumor boundary identification than Tmin and Tmax (such as T90, T50, and T10) be tested prospectively along with other important thermal variables in Phase II trials in further efforts to define a thermal dosimetry for spatially nonuniform temperature distributions.
Leopold, KA; Dewhirst, M; Samulski, T; Harrelson, J; Tucker, JA; George, SL; Dodge, RK; Grant, W; Clegg, S; Prosnitz, LR
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