Researchers affiliated with EORTC-ESHO Intergroup Trial (NCI-00003052) have reported that neoadjuvant chemotherapy with regional hyperthermia (RHT) improves outcomes of patients with high-risk soft tissue sarcoma (STS) compared with standard neoadjuvant chemotherapy. The results of this randomized study were presented on September 22, 2009 at Europe’s largest cancer congress, ECCO 15-ESMO 34, in Berlin.[1]

Soft tissue sarcomas are a diverse group of tumors with varying sensitivity to radiation therapy and chemotherapy. It is estimated that 60% of STS occur in the extremities, making amputation an option. Limb-sparing treatments have been increasingly utilized due to the lack of evidence that amputation improves survival. One of the techniques studied is delivery of chemotherapy via isolated limb perfusion. Isolated limb perfusion with chemotherapy was first used in patients with melanoma with some success. Some studies have suggested that RHT improves response rates to chemotherapy in patients with STS. For many years, blood was heated outside the body and returned to the affected area with chemotherapy. More recently, sophisticated electromagnetic energy has been used to heat tumors that are below the surface. With this approach, tissue in and around the tumor is heated to between 104-109 degrees Fahrenheit. The heat kills cancer cells, improves blood flow and makes cancer cells more sensitive, thereby improving the efficacy of chemotherapy. The apparatus used in the current study was the BSD 2000 hyperthermia system (http://www.bsdmc.com/bsd2000.html).

A Phase II study of neoadjuvant chemotherapy combined with RHT in adults with high-risk STS showed that response was correlated with survival, but the impact of RHT could not be determined.[2] These observations led to the design of the present study.

Researchers in Europe conducted a Phase III study that involved 341 patients with locally advanced high-risk STS patients. All patients underwent chemotherapy both before and after surgery and radiation. Half of the patients in the study were randomized to undergo RHT along with chemotherapy, and half received the same chemotherapy without RHT. Neoadjuvant chemotherapy consisted of etoposide, ifosfamide, and doxorubicin (EIA) given every three weeks for four cycles. Chemotherapy with or without RHT was given before and after surgery and radiotherapy.

The median follow-up was 34 months. Overall response rate to EIA chemotherapy was 28.8% in the RHT group and 12.7% in the control group. Local progression-free survival was improved by 42% in the RHT group. Median disease-free survival was 32 months in the RHT group and 18 months in the control group. On an intent-to-treat basis, overall survival was not improved. However, for the patients who completed all four cycles of induction therapy, overall survival was improved by 34% in the RHT group.

The researchers concluded that the heat therapy significantly improves overall response rates, time to progression, local progression-free survival, and disease-free survival. The most common side effect of the therapy was mild to moderate discomfort. One patient experienced severe burns.

Comments: This is an important study as it is the only study to document the benefit of RHT in patients with STS.

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