Regional Hyperthermia Improves Localised Soft Tissue Sarcoma Survival

Adding regional hyperthermia to neoadjuvant chemotherapy boosts outcomes in patients with localised high-risk soft tissue sarcoma

medwireNews: Patients with localised, high-risk soft tissue sarcoma derive a survival benefit from the addition of regional hyperthermia to neoadjuvant chemotherapy, according to phase III study results published in JAMA Oncology.

“For patients who are candidates for neoadjuvant treatment, adding regional hyperthermia may be warranted”, the study authors write.

Over a median follow-up of 11.3 years, progression-free survival (PFS) was significantly better for the 162 patients who received regional hyperthermia in addition to neoadjuvant chemotherapy than for the 167 given just the chemotherapy regimen. The median PFS times were 67.3 and 29.2 months, respectively, giving a hazard ratio (HR) of 0.65.

Participants given regional hyperthermia also had a significantly reduced risk of death from the disease or its treatment, with a median survival of 15.4 years, compared with 6.2 years in the chemotherapy alone group. And at the 5-year timepoint, 62.7% of hyperthermia-treated patients were alive versus 51.3% of those given chemotherapy alone; the corresponding rates at 10 years were 52.6% and 42.7%.

The survival advantage afforded by adding regional hyperthermia was observed across all prespecified subgroups and stratification criteria, including age, tumour size, grade and site, histological subtype, and receipt of radiotherapy.

The authors of an accompanying commentary say that while the survival definition used in the trial helps “to avoid the potential confounding of death due to causes unrelated to sarcoma” and “is useful to quantify the benefits of hyperthermia in a rare disease, an improvement in overall survival would more strongly justify an investment in hyperthermia to establish thermochemotherapy as a new standard of care at sarcoma centers.”

But Mark Dewhirst and David Kirsch, from Duke University School of Medicine in Durham, North Carolina, USA, add that “the impressive activity of regional hyperthermia” in this study “should stimulate further clinical trials in hyperthermia, which is a field that is heating up with the implementation of technological advances and strong biological rationale.”

For the EORTC 62961-ESHO 95 trial, Rolf Issels, from LMU Munich in Germany, and co-investigators enrolled patients aged 18–70 years with localised high-risk soft tissue sarcoma, defined by the presence of a tumour with a diameter of at least 5 cm, a French Federation Nationale des Centers de Lutte Contre le Cancer grade of 2 or 3, and deep extension to the fascia.

Participants were randomly assigned to receive four 3-week cycles of neoadjuvant chemotherapy comprising doxorubicin , ifosfamide and etoposide , with or without regional hyperthermia (42°C for 60 minutes) given alongside ifosfamide on days 1 and 4 of each cycle. The majority of patients in both study arms (91–92%) went on to receive surgery, with around two-thirds also undergoing postoperative external beam radiotherapy, after which the protocol specified a repeat of the allocated treatment as postinduction therapy.

References

Issels RD, Lindner LH, Verweij J, et al. Effect of neoadjuvant chemotherapy plus regional hyperthermia on long-term outcomes among patients with localized high-risk soft tissue sarcoma. The EORTC 62961-ESHO 95 randomized clinical trial. JAMA Oncol; Advance online publication 15 February 2018 . doi:10.1001/jamaoncol.2017.4996 

Dewhirst MW, Kirsch D. Technological advances, biologic rationales, and the associated success of chemotherapy with hyperthermia in improved outcomes in patients with sarcoma. JAMA Oncol; Advance online publication 15 February 2018 . doi:10.1001/jamaoncol.2017.4941

medwireNews is an independent medical news service provided by Springer Healthcare. © 2018 Springer Healthcare part of the Springer Nature group