Quality of life after isolated limb infusion for in-transit melanoma of the extremity.

BACKGROUND: Isolated limb infusion (ILI) has been associated with persistent edema, numbness, pain, and functional impairment of the treated limb. However, health-related quality of life (HRQOL) has not yet been assessed using a validated questionnaire. METHODS: Functional Assessment of Cancer Therapy-Melanoma (FACT-M) questionnaires were collected from subjects enrolled a phase I ILI trial with temozolomide at baseline and 2, 6 weeks, and 3 months post-ILI. Of 28 enrolled patients, 19 patients received maximum tolerated dose of temozolomide and are included in the HRQOL analysis. Clinical and operative variables and treatment response data also were collected. RESULTS: HRQOL scores showed a trend of improvement from baseline through 3-months post-ILI as measured by FACT-M and the melanoma surgery scores. There were no differences in HRQOL when patients were stratified by disease burden, clinical toxicity level, and 3-month disease response. Additionally, fewer patients complained of pain, numbness, and swelling of the affected limb at 3 months post-ILI compared to baseline, and also these symptoms were improved at the immediate postoperative visit compared with baseline. CONCLUSIONS: Despite the known morbidity of ILI, we have demonstrated with a validated HRQOL questionnaire that HRQOL is not adversely impacted at therapeutic doses of temozolomide delivered intra-arterially from baseline through 3 months posttreatment. Patient centered-outcomes should be evaluated as a standard part of all future regional therapy trials using standardized melanoma-specific HRQOL questionnaires to more completely evaluate the utility of this type of treatment strategy.

Immunotherapy following regional chemotherapy treatment of advanced extremity melanoma.

PURPOSE: Following regional chemotherapy (RC) for melanoma, approximately 75 % of patients will progress. The role of immunotherapy after RC has not been well established. METHODS: A prospective, single-institution database of 243 patients with in-transit melanoma (1995-2013) was queried for patients who had progression of disease after RC with melphalan and subsequently received systemic immunotherapy. Fifteen patients received IL-2 only, 12 received ipilimumab only, and 6 received IL-2 followed by ipilimumab. Fisher's exact test was used to determine if there was a difference in number of complete responders after immunotherapy. RESULTS: With IL-2 alone, all patients progressed. After ipilimumab alone, three patients had a complete response and nine had progressive disease. Six additional patients received IL-2 first then ipilimumab. All six progressed on IL-2 but three went on to have a complete response to ipilimumab while three progressed. The use of ipilimumab at any time in patients who progressed after RC was associated with higher rate of complete response compared to use of IL-2 alone (33 vs. 0 %; p = 0.021). CONCLUSIONS: Patients with progression after regional therapy for melanoma may benefit from immunologic therapy. In this group of patients, immune checkpoint blockade with ipilimumab has a higher complete response rate than T cell stimulation with IL-2, with no complete responders in the IL-2 only group. Furthermore, the complete response rate for ipilimumab in our cohort is higher than reported response rates in the literature for ipilimumab alone, suggesting that the effects of immunotherapy may be bolstered by previous regional treatment.