Neoadjuvant chemotherapy plus radiation versus chemotherapy plus regional hyperthermia in high-grade soft tissue sarcomas: a retrospective comparison

Abstract

Purpose: Localized adult high-grade soft tissue sarcomas (STS) usually require multimodality treatment including surgery, radiotherapy, chemotherapy and hyperthermia. If maximal preoperative tumorshrinkage is envisaged, neoadjuvant chemotherapy þ radiation (CRT) is often applied, however at the expense of relatively high toxicities and increased postoperative complication rates. This study aims to compare preoperative CRT with neoadjuvant chemotherapy þ regional hyperthermia (HCT) regarding histopathological response, toxicity and outcome. Methods: In this retrospective analysis, 61 consecutive high-grade STS patients treated between 2009 and 2016 were included. All patients were treated within a prospective treatment protocol. 28 patients received neoadjuvant CRT 33 patients HCT. CRT consisted of four cycles doxorubicin/ifosfamide and two cycles ifosfamide concomitant to 50.4 Gray external beam radiotherapy. HCT consisted of 4-6 cycles doxorubicin/ifosfamide with deep regional hyperthermia administered biweekly during each cycle. Association of treatment modality with overall survival (OS), local control (LC) and freedom from distant metastases (FFDM) was evaluated by Kaplan-Meier and log-rank analyses. Results: The overall patient characteristics were well balanced. Histopathological tumor response did not differ significantly between both groups (p ¼ .67), neither did higher-grade toxicities during neoadjuvant treatment. Wound dehiscence (p ¼ .018) and surgical hospital re-admissions (p < .001) were both significantly more frequent in the CRT group. Two-year OS, LC and FFDM rates of all patients were 93, 85 and 71% with no significant differences between CRT and HCT. Conclusion: Compared to CRT, HCT seems equally efficient and appears to bear less surgical complications. Interpretation should be cautious due to the low number of patients and the retrospective nature of this study.

The Role of Hyperthermia in the Multidisciplinary Treatment of Malignant Tumors

“…Furthermore, there were no significant differences in overall survival (OS), local control, and freedom from distant metastases over 2 years between the 2 groups. 54,55…”

“…Furthermore, there were no significant differences in overall survival (OS), local control, and freedom from distant metastases over 2 years between the 2 groups. 54,55 In a more recent trial, the prospectively randomized NCT 00003052 phase III multicenter trial, 341 patients with untreated localized high-risk STS were enrolled, of whom 169 received neoadjuvant chemotherapy consisting of etoposide, ifosfamide, and adriamycin (EIA) plus regional hyperthermia, and the remainder received EIA alone. After induction therapy, the tumor response was evaluated by imaging, and the best local treatment (surgery and/or RT) was selected, followed by another 4 cycles of induction therapy.…”

Combination therapy with Olaratumab/doxorubicin in advanced or metastatic soft tissue sarcoma -a single-Centre experience

“…They could show a significant effect of additional hyperthermia on local PFS, DFS, and OS with an improvement of overall survival and local progression-free survival [22]. A retrospective analysis of the radiooncologic department at the Charité-Universitätsmedizin Berlin also demonstrated a comparable therapeutic response of hyperthermia and radiation therapy in STS in a neoadjuvant setting with a reduced rate of surgical complications in the former group [23]. For that reason, in selected patients we combined doxorubicin/olaratumab with regional hyperthermia in the cohort of patients with borderline resectable localized tumours.…”

Hyperthermia in Cancer Care: A Literature Review

“…One RCT (yielding three publications), [13][14][15] five observational studies [56][57][58][59][60] , and seven single-arm trials [61][62][63][64][65][66][67] were identified. Additionally, one single-arm trial 68 included deep seated sarcomas, and one observational study mixed soft tissue tumours.…”