Regional hyperthermia increases benefit of chemotherapy in patients with high-risk soft tissue sarcoma in EHSO EORTC trial 62961

Adult soft-tissue sarcoma (STS) have a relatively low incidence, approximately 10 390 new cases are reported each year in the United States, yet half of all patients with STS eventually die from the disease. The optimum treatment for high-risk STS in adults is unclear, however phase 2 studies have shown that chemotherapy with regional hyperthermia (RHT) improves local control compared with chemotherapy alone.

In an intergroup study with the European Society for Hyperthermic Oncology (EHSO), the EORTC Soft Tissue and Bone Sarcoma Group (STBSG) showed that RHT increases the benefit of etoposide, ifosamide, and doxorubicin (EIA) chemotherapy in patients with high-risk STS. Results of this study were recently reported online in Lancet Oncology.[1]

In the EHSO and EORTC STBSG study, a total of 341 patients with localized STS were were randomly assigned to receive EIA alone, 172 patients, or EIA plus RHT, 169 patients. All patients were included in the analysis of the primary endpoint, local progression free survival (LPFS).

The treatment response rate in the EIA plus RHT arm was better at 28.8% compared with 12.7% in the EIA alone arm (P=0.002). After a median follow-up of 34 months overall survival was better in patients who completed the preoperative induction in the EIA plus RHT arm compared to the patients in the EIA alone arm (P=0.038). All patients benefited from RHT in terms of LPFS (P=0.003) as well as disease-free survival (P=0.011), but the effect was particularly pronounced in the subgroup with an abdominal or retroperitoneal tumor location. RHT-related adverse events were pain, bolus pressure, and skin burn.

Leucopenia (grade 3 or 4) was more frequent in the EIA plus RHT arm compared with the EIA alone arm, and was reported for 128 of 165 patients in the EIA plus RHT arm and 106 of 167 patients in the EIA alone arm, p = 0.005. This might be a result of the heating field affecting the bone marrow, particularly in patients with large abdominal or pelvic tumors which accounted for 81% of the non-extremity tumors. Adverse events related to RHT included pain, bolus pressure, and skin burn.

According to the authors, “This randomised trial provides the first evidence that regional hyperthermia added to preoperative and postoperative chemotherapy is clinically more effective than chemotherapy alone in a specific population of patients with high-risk STS. This therapeutic strategy offers a new treatment option, and can be integrated in the multimodal treatment approach for these patients.”

John Bean
EORTC, Medical Science Writer


 

[1] Rolf D Issels, Lars H Lindner, Jaap Verweij, Peter Wust, Peter Reichardt, Baard-Christian Schem, Sultan Abdel-Rahman, Soeren Daugaard, Christoph Salat, Clemens-Martin Wendtner, Zeljko Vujaskovic, Rüdiger Wessalowski, Karl-Walter Jauch, Hans Roland Dürr, Ferdinand Ploner, Andrea Baur-Melnyk, Ulrich Mansmann, Wolfgang Hiddemann, Jean-Yves Blay, Peter Hohenberger, for the European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group (EORTC-STBSG) and the European Society for Hyperthermic Oncology (ESHO). Neo-adjuvant chemotherapy alone or with regional hyperthermia for localised high-risk soft-tissue sarcoma: a randomised phase 3 multicentre study. Lancet Oncology, DOI:10.1016/S1470-2045(10)70071-1

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