Adjuvant irradiation for axillary metastases from malignant melanoma

Abstract Purpose: To evaluate the outcome and treatment-related toxicity for patients with axillary lymph node metastases from malignant melanoma treated with surgery and radiation, with or without systemic therapy. Methods and Materials: The medical records of 89 consecutive patients with axillary lymph node metastases from malignant melanoma were retrospectively reviewed. All patients underwent axillary dissection and postoperative radiation to a median dose of 30 Gy at 6 Gy/fraction delivered twice weekly. In 3 patients referred with microscopic residual disease, a single boost (4–6 Gy) was given to a reduced field. All but 2 patients were referred because their axillary dissections revealed features believed to predict a 30–50% risk of subsequent axillary recurrence: lymph nodes ≥3 cm in size (54 patients), ≥4 lymph nodes positive (44), the presence of extracapsular extension (69), recurrent disease after initial surgical resection (23), or multiple risk factors (77). Fifty-one patients received systemic therapy before or after radiation therapy. Results: At a median follow-up of 63 months, 47 patients had relapsed and 43 patients had died. The actuarial overall and disease-free survival rates at 5 years were 50% and 46%, respectively. The actuarial axillary control and distant metastasis-free survival rates at 5 years were 87% and 49%, respectively. Univariate analysis revealed that the probability of axillary control was inferior when the axillary disease measured >6 cm in size (72% vs. 93%, p = 0.02), the location of the primary tumor was unknown (74% vs. 93%, p = 0.02), the axillary failure occurred within 18 months from diagnosis of the primary melanoma (84% vs. 100%, p = 0.04), or the Breslow thickness was >4 mm (80% vs. 96%, p = 0.04). Additionally, there was an inferior distant metastasis-free and disease-free survival when there were >2 nodes positive for metastatic disease, the primary lesion had a Breslow thickness >4 mm, or the axillary failure occurred within 18 months from diagnosis of the primary melanoma. On multivariate analysis, the significantly inferior distant metastasis-free and disease-free survival seen when >2 nodes were positive or the recurrence occurred within 18 months remained significant. The small number of axillary failures precluded multivariate analysis for axillary control; however, stratified analysis suggested that size >6 cm was the factor most closely associated with subsequent axillary failure. Twenty-six patients developed treatment-related arm edema. Classification according to the severity of edema yielded 5-year actuarial arm edema rates of 21%, 19%, and 1%, for Grade 1 (transient or asymptomatic), Grade 2 (requiring medical intervention), or Grade 3 (requiring surgical intervention) edema, respectively. Conclusion: Adjuvant radiation therapy using a hypofractionated regimen resulted in an 87% 5-year axillary control rate, superior to the 50–70% local control achieved with surgery alone for lymph node metastases from melanoma when high-risk features are present. Improvements are needed for patients with bulky nodal masses >6 cm in size. Mild-to-moderate arm edema was common, but manageable. The degree to which radiotherapy adds to the risk of arm edema after axillary dissection alone cannot be addressed in the present analysis.