ArticlesAdjuvant radiotherapy versus observation alone for patients at risk of lymph-node field relapse after therapeutic lymphadenectomy for melanoma: a randomised trial
Introduction
Standard treatment protocols for many solid tumours include adjuvant radiotherapy on the basis of data that show improved local control and, in some situations, improved survival. For primary cutaneous melanoma, the commonest and usually first site of recurrence after definitive excision of the primary tumour is in the draining lymph-node field. After therapeutic lymphadenectomy for isolated lymph-node field relapse, patients with substantial disease burden in the regional lymph-node field have a high risk of recurrence,1, 2, 3 which can cause morbidity including pain, ulceration, malodour, lymphoedema, and impaired function, particularly in the leg. Further lymph-node field relapse is predicted by extranodal spread of melanoma, increased number of tumour-positive lymph nodes, and increasing size of involved nodes.4, 5, 6 The use of adjuvant radiotherapy after lymphadenectomy to reduce the risk of further relapse is controversial. In many centres it is recommended in patients considered to be at high risk of further relapse; however, evidence from randomised studies is scarce. In 1993, the Radiation Therapy Oncology Group initiated a randomised trial of post-operative adjuvant radiotherapy (RTOG 93.02), but the trial was halted after failure to accrue sufficient patients, with no results reported. Some retrospective single institution studies and several reviews suggest that radiotherapy after therapeutic lymphadenectomy improves lymph-node field control; however, the effect of radiotherapy on survival is much less clear.7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19
In 1996, the Trans-Tasman Radiation Oncology Group (TROG) initiated a phase 2 trial20 (TROG 96.06) of adjuvant radiotherapy for melanoma patients with completely resected lymph-node disease judged to be at substantial risk of further melanoma relapse. Regional control was good, with few toxic effects.20, 21
With the same radiotherapy regimen as TROG 96.06, we did a randomised trial to compare adjuvant radiotherapy with observation alone in patients at high risk of lymph-node field relapse who had undergone therapeutic lymphadenectomy for metastatic melanoma in regional lymph nodes. The study was started in 2002, by the Australian and New Zealand Melanoma Trials Group and TROG (ANZMTG 01.02/TROG 02.01).
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Patients
Patients from 16 hospitals in Australia, four in New Zealand, one in the Netherlands, and one in Brazil were considered for inclusion. Patients were eligible if they had palpable metastatic lymph-node field disease; had a complete cervical, axillary, or inguinal lymphadenectomy; were at high risk of further lymph-node field relapse; had an ECOG performance status of 0 or 1; were aged 18 years or older; had a life expectancy in the absence of melanoma of 2 years or more; were staged (by CT scan
Results
From March 20, 2002, to Sept 21, 2007, 250 patients from 16 institutions (six did not accrue any patients) in Australia (222 patients), New Zealand (14 patients), the Netherlands (12 patients), and Brazil (two patients) were randomly assigned. The accrual rate (average 3·7 patients per month) was generally uniform throughout the accrual period. Two patients (one from each group) withdrew consent soon after randomisation and were excluded from all analyses (figure 1). The intention-to-treat
Discussion
The results of our study suggest that the use of adjuvant radiotherapy after complete surgical resection for isolated lymph-node field melanoma relapse in patients at high risk of relapse substantially reduced the risk of further lymph-node field relapse, although there was no effect on overall survival. As used in this trial, adjuvant radiotherapy was associated with acceptable early toxic effects.
The first study to investigate the role of adjuvant radiotherapy in melanoma patients with
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Both authors contributed equally