ORLANDO Adjuvant radiotherapy following lymphadenectomy improved lymph node field control for patients with melanoma who were at an increased risk of relapse in an ongoing, multicenter trial.
Dr. Michael A. Henderson and his colleagues did not observe a significant difference in relapse-free or overall survival benefit between 109 patients randomized to adjuvant radiotherapy after surgery and 108 controls assigned to observation only.
The study was positive in terms of the primary end point, however. At a mean follow-up of 39 months, "radiotherapy patients were significantly less likely to develop a lymph node field relapse," Dr. Henderson said at the annual meeting of the American Society of Clinical Oncology. The hazard ratio was 0.56 vs. observation (P = .041).
An intent-to-treat analysis of an initial 248 patients "demonstrates an even larger and more significant advantage in lymph node field control" in the radiotherapy vs. observation patients (HR, 0.47; P = .005), said Dr. Henderson, a surgical oncologist at Peter MacCallum Cancer Centre in Melbourne. He had no disclosures.
In all, relapses in all-local, in-transit, or distant sites occurred in 161 patients during follow-up. This total included 62 patients with a first relapse in a lymph node field. There were 120 deaths (all but 2 due to melanoma), and about 40 patients have active disease.
This intergroup study from ANZMTG (Australia and New Zealand Melanoma Trials Group) and TROG (Trans-Tasman Radiation Oncology Group) included patients from 22 centers. Median age was 58 years in the radiotherapy group and 57 years in the observation arm. Men accounted for about 75% of each arm.
After 31 patients were excluded for "major eligibility infractions," the 217 remaining participants received 48 Gy of adjuvant radiotherapy in 20 fractions over 4 weeks or observation following complete resection of their palpable lymph nodes. Radiotherapy was delivered to axillae, groin, or parotid and neck lymph node fields.
"This is the first multicenter, randomized, controlled trial of adjuvant radiotherapy after resection of node metastases," said study discussant Dr. Antoni Ribas, before outlining several concerns.
"Is local control a reasonable goal in the treatment of stage III melanoma?" he asked rhetorically. "Yes, if it's well tolerated. We know the really important event is systemic metastasis, which is what kills patients, and that will have to be balanced along with possible toxicities."
Quality of life measures and long-term effects of radiation are pending in the trial, and may ultimately guide how patients are counseled about an adjuvant radiotherapy option, said Dr. Ribas of the medicine and surgery faculties at the University of California, Los Angeles. He is a consultant and/or adviser to Pfizer Inc., MannKind Corp., and Sanofi-Pasteur Inc., and receives honoraria from these companies and Amgen Inc., as well as research funding from Pfizer.
The "early radiotherapy toxicity appears acceptable," Dr. Henderson said. At 2 weeks after radiotherapy, grade 3 toxicities included 18 cases of radiation dermatitis and two reports of pain. At 6 weeks post radiotherapy, five cases of radiation dermatitis, two reports of pain, and one case of fatigue were reported. There were no early grade 4 toxicities.
"Similarly, late radiotherapy toxicities were also uncommon," he continued. Grade 3 or 4 late toxicities in the radiotherapy arm included four reports of pain, four cases of skin toxicity, three reports of subcutaneous tissue toxicity, and one report each of bone, joint, and nerve damage toxicity.
The intent-to-treat analysis also showed no difference in relapse-free survival (P = .53) or overall survival (P = .14). Overall survival at 5 years was 38% in the radiotherapy group vs. 44% in the observation group, Dr. Henderson said.
A meeting attendee noted that the radiotherapy group's survival curve was below the observation group's curve and said, "At this immature stage of the trial, I don't think radiotherapy can be recommended." Dr. Henderson had no comment.