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Response to Neoadjuvant Chemotherapy Combined With Regional Hyperthermia Predicts Long-Term Survival for Adult Patients With Retroperitoneal and Visceral High-Risk Soft Tissue Sarcomas

From the Department of Internal Medicine III, Diagnostic Radiology and Institute for Biostatistics and Epidemiology, Klinikum Grosshadern Medical Center, Ludwig-Maximilians-University; and the KKG Hyperthermia/GSF-National Research Center for Environment and Health, Munich, Germany.

Address reprint requests to C.-M. Wendtner, MD, Ludwig-Maximilians-Universität, Medizinische Klinik III, Klinikum Grosshadern, Marchioninistr 15, D-81377 Munich, Germany; email: Clemens.Wendtner{at}med3.med.uni-muenchen.de

PURPOSE: To determine the efficacy of neoadjuvant chemotherapy combined with regional hyperthermia (RHT) for local tumor control and overall survival (OS) in adult patients with retroperitoneal or visceral (RP/V) high-risk soft tissue sarcomas (HR-STS).

PATIENTS AND METHODS: From 1991 to 1997, 58 patients with HR-STS at RP/V sites were prospectively treated with four cycles of etoposide, ifosfamide, and doxorubicin combined with RHT followed by surgery, adjuvant chemotherapy, and radiation.

RESULTS: Objective response rate assessable in 40 patients was 13% (five partial responses). Including minor responses (n = 8), the radiographic response rate was 33%. The pathologic response rate assessable in 26 patients after surgical resection was 42%. Median OS was 31 months. At a median observation time of 74 months, 5-year probability of local failure-free survival (LFFS), distant metastasis-free survival, event-free survival, and OS were 25%, 51%, 20%, and 32%, respectively. Averaged minimum temperatures (T_min) and time-averaged temperatures achieved in 50% (T₅₀) and 90% (T₉₀) of all measured tumor sites differed significantly between responders and nonresponders (T_min, 39.3°C v 38.0°C; P = .002; T₅₀, 40.9°C v 40.3°C; P = .038; T₉₀, 40.1°C v 39.3°C; P = .017). At 5-year follow-up, probability of LFFS (59% v 0%; P < .001) and OS (60% v 10%; P < .001) was significantly in favor of patients responding to neoadjuvant thermochemotherapy.

CONCLUSION: Response to neoadjuvant chemotherapy combined with RHT is predictive for an improved local tumor control resulting in a long-term survival benefit for patients with HR-STS at unfavorable RP/V sites; however, the impact of RHT has to be defined in a randomized phase III trial.

Presented, in part, at the Thirty-Seventh Annual Meeting of the American Society of Clinical Oncology, San Francisco, CA, May 12-15, 2001.

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