Add-on regional hyperthermia prolongs survival in high-risk soft tissue carcinoma patients
Use of regional hyperthermia (RHT) in addition to neoadjuvant chemotherapy in the treatment of patients with localized high-risk soft tissue carcinoma confers benefits for local progression-free survival, according to the results of the EORTC 62961-ESHO 95 study.
“For patients who are candidates for neoadjuvant treatment, adding RHT may be warranted,” the investigators said.
The phase III study randomized 329 patients (median age 51 years; 55.3 percent male) with localized soft tissue sarcoma to neoadjuvant chemotherapy (NACT) consisting of doxorubicin, ifosfamide and etoposide either alone (n=167) or combined with RHT (n=162). During a median follow-up of 11.3 years, 220 patients (67 percent) had disease relapse and 188 (57 percent) died.
In multivariate Cox models, add-on RHT treatment was associated with a 35-percent improvement in the primary endpoint of local progression-free survival (hazard ratio [HR], 0.65; 95 percent CI, 0.49–0.86; p=0.002). [JAMA Oncol 2018;doi:10.1001/jamaoncol.2017.4996]
Furthermore, patients who received NACT plus RHT had prolonged survival rates compared with those given NACT alone (HR, 0.73; 0.54–0.98; p=0.04). Survival rates were 62.7 percent vs 51.3 percent at 5 years and 52.6 percent vs 42.7 percent at 10 years.
The investigators noted that the survival of patients with high-risk extremity tumours who were treated with NACT alone in the present EORTC 62961-ESHO 95 cohort was almost identical to those receiving short, full-dose preoperative chemotherapy as reported in the Italian Sarcoma-Intergroup adjuvant trials, and was further improved by almost 10 percent with the addition of RHT. [Ann Oncol 2016;27:2283-2288]
“Therefore, these results reinforced the significance of the additional benefit by RHT because they were not confounded by an insufficient efficacy of the chemotherapy regimen. The survival benefit was also observed in patients with less favourable, abdominal-retroperitoneal tumours, and was even more pronounced in grade 2 tumours, due to yet unknown mechanisms,” they added.
However, the investigators acknowledged that the study was not powered enough to show statistical evidence for all patient subgroups (eg, extremity vs abdominal and/or retroperitoneal sarcomas).
In an invited commentary on EORTC 62961-ESHO 95, Drs Mark Dewhirst and David Kirsch from the Duke University School of Medicine in North Carolina, US, pointed out that the trial represents the best example of RHT having a beneficial effect on patients treated with chemotherapy to date. [JAMA Oncol 2018;4:493-494]
“Given the potential impact of hyperthermia, it is surprising that it has not been embraced more widely in the oncology community. The reasons for lack of adoption include: (1) requirement of staff of highly skilled engineers and/or physicists to run instruments to deliver hyperthermia; and (2) control arms in many of the trials conducted to date did not include current state-of-the-art therapy,” they wrote.
Dewhirst and Kirsch highlighted the importance of identifying patients most likely to benefit from hyperthermia and exploring opportunities to use the treatment modality to achieve better results in the future.
“Promising approaches to improve thermal therapy include novel thermally triggered nanotechnologies that enhance tumour drug delivery several-fold and exploitation of immunomodulatory pathways. The final results of EORTC 62961-ESHO 95 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,” they added.