Heating soft-tissue sarcomas during chemotherapy was associated with a significant reduction in the risk of recurrence and death, according to data presented by Professor Rolf Issels, professor of medical oncology, Klinikum Grosshadern Medical Center, University of Munich in Germany.
Heating soft-tissue sarcomas during chemotherapy was associated with a significant reduction in the risk of recurrence and death, according to data presented by Professor Rolf Issels, professor of medical oncology, Klinikum Grosshadern Medical Center, University of Munich in Germany. The intent-to-treat population in this phase 3 study consisted of 341 patients with grade 2-3 soft-tissue sarcomas greater than 5 cm or with deep tumors. These patients are at high risk for local recurrence and metastases after resection, Prof Issels said.
More than half the patients had abdominal tumors; the remainder had tumors in their arms and legs. All patients received neoadjuvant and adjuvant chemotherapy and radiotherapy. Researchers randomized half to receive targeted heat in and around the tumor tissue during chemotherapy administration. The technique is called regional hyperthermia and involves using electromagnetic energy to heat the targeted tissue to a level between 104 and 109.4 degrees Fahrenheit. In addition to inducing apoptosis, the heat seems to make the cancer cells more susceptible to the cytotoxic chemotherapy agents.
All patients received 4 cycles of initial chemotherapy; those who also received heat treatments underwent a total of 8 sessions (4 during chemotherapy and 4 alone). Patients who received the combination therapy had significantly increased progression-free survival, which lasted a median of 120 months compared with 75 months for the control arm. Three years after treatment, patients in the combination group were 30% more likely to be alive and free of disease than those who received only chemotherapy (P = .011). This is significant because patients with soft-tissue sarcomas typically relapse within the first 3 years after treatment, Prof Issels said.
At 34 months’ follow-up, 44.9% of patients (n = 153) had died. “For the whole population group, we could not find any advantage for overall survival,” Prof Issels said. When investigators analyzed survival rates only for the 269 patients who completed all 4 cycles of chemotherapy or 4 cycles of chemotherapy plus 8 sessions of regional hyperthermia, they found that those in the combination group had a 44% reduction in the risk of death during the 34-month follow-up period. Prof Issels advised caution when considering these survival results, however, noting that they applied only to a subpopulation of the original intent-to-treat population.
In considering the entire study group, Prof Issels said, “The patients receiving the targeted heat therapy fared better on all outcome measurements.” At 2 years follow-up, he noted that 76% of patients who received heat therapy were alive and had no local progression compared with 61% in the control arm. The combination group also had a higher rate of tumor shrinkage (28.8% vs. 12.7%, respectively) and only 6.8% experienced tumor growth compared with 20% in the control arm. Nearly half (45%) of the patients experienced mild to moderate discomfort during heat therapy and 1 patient suffered severe burns. Approximately 18% of patients developed blisters. No one died as a result of regional hyperthermia therapy.
Dr Issels said this technique is currently being investigated in a number of locations, including Duke University in the United States. “This strategy has been in development for about 20 years, with about 150 leading groups studying it,” he said. He suggested that the results of this study indicate a need to increase the pace of its use and investigate it with different chemotherapy agents at a range of doses. He also said the results of this trial might lead other researchers to consider exploring the potential of regional hyperthermia in a variety of major cancers.
ECCO/ESMO Abstract 1 LBA