Radio-hyperthermo-chemotherapy (RHC), which combines radiotherapy, hyperthermia, and chemotherapy, for malignant soft-tissue tumors was introduced with the aim of decreasing local recurrence after surgery. We performed various experiments to apply this trimodal therapy to soft-tissue sarcomas, and herein review progress at our institution.
In vitro application of hyperthermia (42-43°C) resulted in apoptosis and selectively decreased the number of cells in the G1 phase, which are thought to exhibit radioresistance. Moreover, simultaneous administration of hyperthermia (42°C) with cisplatin increased the concentration of the anti-tumor agent within the cells, resulting in significant inhibition of DNA synthesis. These findings reinforced the synergic effects of hyperthermia and chemotherapy/radiotherapy.
We began using RHC combination therapy for highly malignant soft-tissue tumors in the early 1990s. Between 1990-1999, we treated 44 patients (21 cases of undifferentiated pleomorphic sarcoma; 7 cases of high grade lipoasarcoma; among others). The local control rate was 97.6% (29 cases were marginal resection; 5 cases were intralesional resection).
Regarding histological analysis, we reviewed 20 cases from 2004-2013. Total necrosis occurred in 15% of patients, while 30% of patients were considered to exhibit over 90% necrosis, and 45% of patients exhibited 50-90% necrosis.
Moreover, we performed a matched control analysis with a nationwide database to yield more objective evidence by eliminating selective bias. Overall survival at 5 years was 81.2% and 79.3% in the RHC and database groups, respectively (
p=0.52). There was a significant difference in local control rate at 5 years between the two groups (97.3% vs. 87.1% in the RHC and database groups, respectively;
p=0.04), despite patients in the RHC group undergoing surgery with closer margins.
Thus, RHC neoadjuvant therapy inhibits local recurrence, demonstrating a new strategy for treating soft-tissue sarcoma following less invasive surgery, potentially resulting in limb preservation and averting amputation.
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