Response of canine soft tissue sarcomas to radiation or radiation plus hyperthermia: a randomized phase II study

Abstract

Sixty-four dogs with spontaneous soft tissue sarcomas without evidence of metastases were stratified by tumour volume and randomized to receive graded doses of radiotherapy (XRT) alone or radiotherapy plus hyperthermia (HT). An improvement in duration of local control was achieved with the addition of hyperthermia as compared with XRT alone (Wilcoxon, p = 0.040; log rank, p = 0.064). Overall frequency of late complications was not different for the two treatment arms when comparing across equivalent XRT dose groups. Frequency of distant metastases after therapy completion was not significantly different for the two treatment arms at 1 year (7.4% for XRT versus 20% for HT plus XRT) or 2 years (11.5% for XRT versus 25% for HT plus XRT) post therapy. These results suggest that a therapeutic gain was achieved for this group of tumour-bearing animals. Uni- and multivariate analyses were performed to examine the potential for various factors to influence treatment outcome. Patient related variables included tumour stage, histologic subtype and grade and tumour site. Treatment related variables included total radiation dose and 15 descriptors of temperature distributions achieved during hyperthermia. When considering patient related factors, tumour histology, grade and location were important predictors of time to minimum volume, but only tumour location influenced time to tumour regrowth. When considering treatment related factors, radiation dose was not significantly correlated with time to minimum volume or time to local regrowth, but it was correlated with probability for late normal tissue damage in the XRT alone group (p = 0.005). For the hyperthermia treatments, 13 of 15 tumour temperature distribution descriptors were correlated with time to minimum volume, but none were correlated with time to local regrowth. These results suggest that caution should be used in interpreting the value of temperature distribution descriptors in predicting for long-term local control after hyperthermia and radiotherapy, based on analysis of short-term responses.

Prognostic Factors for Cutaneous and Subcutaneous Soft Tissue Sarcomas in Dogs

“…3,7,11,23,32,34,40,48,49 Grade II tumors occur with intermediate frequency. 23,38,40 Grade II tumors with complete margins also appear to rarely, if ever, recur. 40 Grade II tumors with close margins recur more frequently than grade I tumors (14 of 41, 35%), and when they recur, they have a shorter tumor-free interval than grade I tumors.…”

“…23,38,40 They are considered to have the greatest potential for recurrence and metastasis; however, information on these tumors in humans and dogs is necessarily based on studies with relatively small numbers of grade III tumors to evaluate. 48 Recurrence of grade III STS with complete surgical margins has been observed following wide surgical excision, 6,48 but the rate of recurrence when surgical margins are complete appears to be infrequent.…”

“…Indeed, much of the information regarding prognosis of STS has been gathered from studies designed for other purposes, such as comparing efficacy of two or more treatment modalities. 11,23,28,38,46,48 In these studies, the objective is to assess a treatment strategy rather than just assess prognostic variables. These studies are subjected to a variety of selection and treatment biases that confound evaluation of prognostic variables.…”

“…53 It was first applied to canine cutaneous and subcutaneous STSs in the late 1980s. 32,37,38 It takes into account tissue differentiation, MI, and necrosis ( Table 2).…”

Letter to the editor

“…In a separate canine clinical trial where hyperthermia was administered 3-4 h after radiotherapy, higher normal tissue temperatures in the region surrounding the tumour were associated with lower incidence of distant metastases [29].…”