Adding regional hyperthermia to neoadjuvant chemotherapy improves survival in patients with localized, high-risk soft-tissue sarcoma, according to findings from an open-label trial.

"The survival benefit by adding regional heat to the area of the tumor opens a new therapeutic window for these patients," Dr. Rolf D. Issels of University Hospital, LMU Munich, Germany, reported. "The regional hyperthermia effect of improved survival is most likely due to immunological effects induced by the inflamed tumor."

In their online article in JAMA Oncology, Dr. Issels et al. note that such patients are at risk for local recurrence and distant metastases. Regional hyperthermia has been shown to improve local progression-free survival, but it is unclear whether this is also the case for overall survival.

The researchers randomized 329 patients to neoadjuvant chemotherapy (with doxorubicin, ifosfamide, and etoposide) alone or with hyperthermia. By a median follow-up of 11.3 years, 220 patients (67%) had experienced disease relapse and 188 (57%) had died.

Intention-to-treat analyses showed adding hyperthermia significantly improved both local progression-free survival (hazard ratio, 0.65) and overall survival (HR, 0.71).

The five-year survival rate in the hyperthermia group was 62.7% compared to 51.3% in those given chemotherapy alone. At 10 years, the corresponding rates were 52.6% and 42.7%.

The researchers conclude, "For patients who are candidates for neoadjuvant treatment, adding regional hyperthermia may be warranted."

Dr. Mark W. Dewhirst, the coauthor of an accompanying editorial, reported, "Modern clinical interest in using hyperthermia to increase the efficacy of radiotherapy and chemotherapy started in the early 1980s.

Although clinical trials were initiated very early, following provocative preclinical studies, there have been very few pivotal randomized trials that demonstrated the value of adjuvant hyperthermia."

He added that the current study "showing an impressive improvement in progression-free survival and overall survival of patients with locally advanced, high-grade sarcomas, who were treated with thermochemotherapy is the most definitive trial to date."

"The trial had a strong biological rationale, was properly powered and included rigorous quality control. It bodes well for the future of the field, where there remains promise for treating a variety of other tumor types."