title: Tumor temperature distributions predict hyperthermia effect.
abstract: Review of clinical hyperthermia (HT) trial results shows that there previously has not been a robust model relating efficacy of HT treatments to characteristics of the temperature distribution. Lack of a model has been an impediment in Phase II trials; these trials must include defining the prescription for HT treatment, optimizing the schedule of HT treatments, and defining quality assurance procedures. We propose a model that is based upon noting that the majority of a tumor volume is contained in the outermost "shell" of a solid tumor, across which shell the radial temperature distribution is assumed to be linear. Any linear distribution can be defined by coordinates of a point and a slope, and we choose the temperature at the radiographically defined edge of a tumor and the slope (dT/dr) across the outer shell as these determinants of the linear radial temperature distribution. A discriminant analysis of success or failure of treatment can then be based upon these two descriptors (Tedge, dT/dr). We have tested this model using data from patients with soft tissue sarcoma (Stage IIB or greater) that have entered an ongoing prospective trial of conventional preoperative radiotherapy (5000 cGy/25 Fx/5 wk) together with HT, the latter randomized to be given once or twice weekly during the 5 week course. Wide local excision of the primary tumor is done 1 month after completion of radiotherapy, and the extent of histologic change in the resected specimen is scored. Our model has an 86% predictive value for lack of complete or nearly complete necrosis in the resected specimen according to whether the time-averaged Tedge and slope during each HT treatment satisfy the equation Tedge + 1.2 (slope in degree C/cm) less than or equal to 40.6 degrees C in all but one treatment at most. Conversely, in 85% of cases with complete or nearly complete tumor necrosis, temperature distributions satisfied Tedge + 1.2 (slope in degree C/cm) greater than 40.6 degrees C during at least one HT treatment. Requiring greater than or equal to one third of treatments of a patient to satisfy the preceeding discriminant equation resulted in 80% of patients being correctly classified as a responder or nonresponder, with only one false positive prediction (patient incorrectly classified as a responder). The model can reveal systematic changes in the edge temperature distribution during the treatment course that are consistent with tumor perfusion changes inferred and measured by independent means.(ABSTRACT TRUNCATED AT 400 WORDS)
authors.affiliation: Duke University Medical Center, Durham, NC 27710.
authors.forename: J R
authors.initials: JR
authors.lastname: Oleson
authors.forename: M W
authors.initials: MW
authors.lastname: Dewhirst
authors.forename: J M
authors.initials: JM
authors.lastname: Harrelson
authors.forename: K A
authors.initials: KA
authors.lastname: Leopold
authors.forename: T V
authors.initials: TV
authors.lastname: Samulski
authors.forename: C Y
authors.initials: CY
authors.lastname: Tso
mesh_terms: D001831:Body Temperature; D002986:Clinical Trials as Topic; D003131:Combined Modality Therapy; D006801:Humans; D006979:Hyperthermia, Induced; D008954:Models, Biological; D009369:Neoplasms / Q000532:radiotherapy / Q000628:therapy*; D011379:Prognosis; D011897:Random Allocation; D012509:Sarcoma / Q000532:radiotherapy / Q000628:therapy; D012983:Soft Tissue Neoplasms / Q000532:radiotherapy / Q000628:therapy