Adjuvant radiotherapy after lymphadenectomy in melanoma patients: Final results of an intergroup randomized trial (ANZMTG 0.1.02/TROG 02.01).

9001 Background: The role of adjuvant radiotherapy following lymphadenectomy in melanoma patients identified as at high risk for further recurrence has been controversial. This final report of a multicenter randomized trial updates survival and lymph node field (LNF) control, and reports long term treatment toxicity, lymphedema and quality of life (QOL) (Lancet Oncol 2012;13:589-97). Methods: Patients at high risk of LNF relapse (≥1 parotid, ≥2 cervical or axillary or ≥3 groin positive nodes; or extra-nodal spread of tumour; or minimum metastatic node diameter of 3cm (neck or axilla) or 4cm (groin)) received adjuvant radiotherapy (ART) (48Gy in 20 fractions) or observation (OBS). LNF relapse, as a 1st relapse, was the primary endpoint; morbidity, QOL, patterns of relapse, disease free and overall survival were secondary endpoints. A target sample size of 250 enabled detection of a difference in 3 year relapse rates of 30% and 15% to be detected (2-sided logrank test, power of 80%). Results: 250 patients from 16 centres were randomized from Mar 02 to Sept 07 (123 ART; 127 OBS) with 217 fully eligible (109 ART, 108 OBS). Mean follow-up 73 months (range 21–116). LNF recurrence was reduced in the ART arm (HR=0.52 (0.31- 0.88) p=0.023) but there was no difference in survival (HR=1.13 (0.82 – 1.55) p =0.21). QOL was assessed by comparison of area under the curve from baseline to 5 years (or recurrence) with the FACT-G tool using both total score and the 4 major domains (physical, social, emotional and functional wellbeing), no difference. Regional symptoms (standardised questionnaire) were higher in the ART arm (p=0.035). Limb volumes were higher in the ART arm (leg 7.3% difference p=0.014, arm 3.4% p=0.25). Grade 2-4 RT toxicity was common for head + neck: skin (33%); axilla: skin (44%), subcutaneous tissue (41%); Groin: skin (46%), subcutaneous tissue (67%), other (38%). Conclusions: RT reduced the risk of LNF relapse by 52% but there was no impact on survival. In the ART arm loco-regional symptoms were worse, limb volumes were somewhat increased and Grade 2 - 4 long term RT toxicity was relatively common. However QOL as assessed by a validated tool (FACT-G) was similar in both groups. Clinical trial information: NCT00287196.