Effectiveness of Regional Hyperthermia With Chemotherapy for High-Risk Retroperitoneal and Abdominal Soft-Tissue Sarcoma After Complete Surgical Resection

Abstract

Objective To determine whether regional hyperthermia (RHT) in addition to chemotherapy improves local tumor control after macroscopically complete resection of abdominal or retroperitoneal high-risk sarcomas. Background Within the prospectively randomized EORTC 62961 phase- III trial, RHT and systemic chemotherapy significantly improved local progression-free survival (LPFS) and disease-free survival (DFS) in patients with abdominal and extremity sarcomas. That trial included macroscopically complete and R2 resections. Methods A subgroup analysis of the EORTC trial was performed and long-term survival determined. From 341 patients, 149 (median age 52 years, 18–69) were identified with macroscopic complete resection (R0, R1) of abdominal and retroperitoneal soft-tissue sarcomas (median diameter 10 cm, G2 48.3%, G3 51.7%). Seventy-six patients were treated with EIA (etoposide, ifosfamide, doxorubicin) + RHT (≥5 cycles: 69.7%) versus 73 patients receiving EIA alone (≥5 cycles: 52.1%, P = 0.027). LPFS and DFS as well as overall survival were determined. Results RHT and systemic chemotherapy significantly improved LPFS (56% vs 45% after 5 years, P = 0.044) and DFS (34% vs 27% after 5 years, P = 0.040). Overall survival was not significantly improved in the RHT group (57% vs 55% after 5 years, P = 0.82). Perioperative morbidity and mortality were not significantly different between groups. Conclusions In patients with macroscopically complete tumor resection, RHT in addition to chemotherapy resulted in significantly improved local tumor control and DFS without increasing surgical complications. Within a multimodal therapeutic concept for abdominal and retroperitoneal high-risk sarcomas, RHT is a treatment option beside radical surgery and should be further evaluated in future trials.

Doxorubicin loaded dual pH- and thermo-responsive magnetic nanocarrier for combined magnetic hyperthermia and targeted controlled drug delivery applications

“…17,18 Hyperthermia is also often used as an adjuvant therapy with radio-or chemotherapy, 19 as heat makes cancer cells more sensitive to the effect of radiation 15 and antineoplastic agents. 16,20 An enhanced therapeutic efficacy of chemotherapy in combination with hyperthermia has been demonstrated in many clinical trials, [21][22][23][24] resulting in a synergistic effect of the cancer therapy. Increased anti-cancer drug accumulation in tumour and thermal enhancement of drug cytotoxicity mainly caused by an improved intracellular uptake of drugs due to an increased cell membrane permeability, inhibition of DNArepair of the chemically induced lethal or sublethal damages, and acceleration of the cytotoxic chemical reaction, are among the most important mechanisms behind the synergistic effect of thermo-chemotherapy.…”

Neoadjuvant chemotherapy in soft tissue sarcomas: latest evidence and clinical implications

“…A subgroup analysis of patients with retroperitoneal and abdominal sarcomas confirmed the effectiveness of improving local tumour control (56% versus 45% after 5 years) and disease-free survival (34% versus 27% after 5 years) in patients who had macroscopically complete tumour resection. 78 These results were recently updated by analysing 9-year follow-up data and presented in abstract form. 79 A significantly prolonged overall survival was observed in patients receiving regional hyperthermia compared with patients receiving only chemotherapy (63% versus 51% after 5 years).…”

Behandlung retroperitonealer Sarkome in Deutschland

“…Systemische Therapien gehören nach aktuellem Kenntnisstand nicht zur Standardtherapie, können jedoch in Einzelfällen zur Anwendung kommen, ggf. auch in Kombination mit einer regionalen Hyperthermie [10].…”