Charles J Puza1, Elizabeth Schell Bressler2, Alicia M Terando3, John Harrison Howard3, Michael C Brown4, Brent Hanks5, April K S Salama5, Georgia M Beasley4. 1. Department of Surgery, Duke University, Durham, North Carolina. Electronic address: Charles.puza@duke.edu. 2. Department of Pathology and Department of Dermatology, Duke University, Durham, North Carolina. 3. Division of Surgical Oncology, Ohio State University, Columbus, Ohio. 4. Department of Surgery, Duke University, Durham, North Carolina. 5. Division of Medical Oncology, Duke University, Durham, North Carolina.
Abstract
BACKGROUND: The emergence of immune checkpoint inhibitors (ICIs) has improved survival for patients with metastatic melanoma. The types of disease-response patterns to ICI therapy can be more complex relative to traditional chemotherapy and include mixed responses, pseudoprogression, and oligoprogression. The potential benefit of surgery after incomplete response to ICI therapy has not been explored. The purpose of this study was to explore outcomes of surgery after ICI therapy in patients with metastatic melanoma. METHODS: A retrospective study was conducted at two centers and included patients with melanoma who underwent surgery after treatment with monotherapy or combination therapy with anti-programmed cell death protein (PD) 1 and/or anti-cytotoxic T-lymphocyte associated protein (CTLA)-4 checkpoint blockade. RESULTS: Of 25 patients, nine received anti-CTLA-4 therapy, eight received anti-PD-1 therapy, and eight received both anti-CTLA-4 and anti-PD-1 therapies before surgery. Five patients were treated in the adjuvant setting and developed new lesions, whereas 20 patients were treated for metastatic disease and underwent surgery for persistent disease on imaging after ICI therapy. Twenty-five patients underwent 30 operations without complications. Twenty-seven of 30 masses were confirmed to be melanoma on pathology, one was a desmoid tumor and two were necrosis. At a median follow-up of 14.2 months, 2 patients died, 8 were alive with a known disease, and 15 continued to have no further evidence of disease. CONCLUSIONS: Surgery was well tolerated in this cohort of patients receiving ICI therapy for melanoma. Surgery may benefit select patients with an oligoprogressive disease after ICI therapy. After a mixed response, surgery remains the only definitive method to render some patients free of disease.
BACKGROUND: The emergence of immune checkpoint inhibitors (ICIs) has improved survival for patients with metastatic melanoma. The types of disease-response patterns to ICI therapy can be more complex relative to traditional chemotherapy and include mixed responses, pseudoprogression, and oligoprogression. The potential benefit of surgery after incomplete response to ICI therapy has not been explored. The purpose of this study was to explore outcomes of surgery after ICI therapy in patients with metastatic melanoma. METHODS: A retrospective study was conducted at two centers and included patients with melanoma who underwent surgery after treatment with monotherapy or combination therapy with anti-programmed cell death protein (PD) 1 and/or anti-cytotoxic T-lymphocyte associated protein (CTLA)-4 checkpoint blockade. RESULTS: Of 25 patients, nine received anti-CTLA-4 therapy, eight received anti-PD-1 therapy, and eight received both anti-CTLA-4 and anti-PD-1 therapies before surgery. Five patients were treated in the adjuvant setting and developed new lesions, whereas 20 patients were treated for metastatic disease and underwent surgery for persistent disease on imaging after ICI therapy. Twenty-five patients underwent 30 operations without complications. Twenty-seven of 30 masses were confirmed to be melanoma on pathology, one was a desmoid tumor and two were necrosis. At a median follow-up of 14.2 months, 2 patientsdied, 8 were alive with a known disease, and 15 continued to have no further evidence of disease. CONCLUSIONS: Surgery was well tolerated in this cohort of patients receiving ICI therapy for melanoma. Surgery may benefit select patients with an oligoprogressive disease after ICI therapy. After a mixed response, surgery remains the only definitive method to render some patients free of disease.
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