Thoracic metastasectomy for adoptive immunotherapy of melanoma: a single-institution experience

Abstract

Objectives: Although refractory to chemotherapy, metastatic melanoma may respond to adoptive immunotherapy. As novel treatments evolve, surgeons may be asked to perform metastasectomy not only for palliation or potential cure but also for isolation of tumor-infiltrating lymphocytes. This study was undertaken to examine outcomes of patients with melanoma undergoing thoracic metastasectomy in preparation for investigational immunotherapy.

Methods: A retrospective review identified 107 consecutive patients who underwent 116 thoracic metastasectomy procedures from April 1998 to July 2009. Indications for surgical intervention included procurement of tumor-infiltrating lymphocytes, rendering of patients to no evaluable disease status, palliation, and diagnosis. Response Evaluation Criteria in Solid Tumors criteria were used to assess tumor response.

Results: Thoracotomy, lobectomy, and video-assisted thoracoscopic surgery with nonanatomic resection were the most common procedures. Major complications included 1 death and 1 coagulopathy-induced hemothorax. Seventeen patients were rendered to no evaluable disease status. Virtually all patients with residual disease had tumor specimens cultured for tumor-infiltrating lymphocytes; approximately 70% of tumor-infiltrating lymphocyte cultures exhibited antitumor reactivity. Of the 91 patients with residual or recurrent disease, 24 (26%) underwent adoptive cell transfer of tumor-infiltrating lymphocytes, of whom 7 exhibited objective responses (29% response rate and 8% based on intent to treat). Rapid disease progression precluded tumor-infiltrating lymphocyte therapy in most cases. Actuarial 1- and 5-year survival rates for patients rendered to no evaluable disease status or receiving or not receiving tumor-infiltrating lymphocytes were 93% and 76%, 64% and 33%, and 43% and 0%, respectively.

Conclusions: Relatively few patients currently having thoracic metastasectomy undergo adoptive cell transfer. Continued refinement of tumor-infiltrating lymphocyte expansion protocols and improved patient selection might increase the number of patients with melanoma benefiting from these interventions.

Figure 1

Flow diagram of patients undergoing thoracic metastasectomy for melanoma immunotherapy. Patients are classified according to status of TIL culture, TIL growth, TIL activity in vitro, and treatment with TIL or not. TIL, tumor-infiltrating lymphocytes; (a) TIL cultures per procedure; (b) Includes resection and no treatment twice for one patient; (c) One patient included in each group due to first resection and treatment followed by recurrence and second resection and no subsequent treatment; (d) Represents 24 individual patient treatments.

Figure 2

A) Overall survival of 107 patients undergoing thoracic metastasectomy for melanoma immunotherapy. The median survival was 13.2 months, with a 5-year survival rate of 22%. B) Survival of patients rendered NED after surgery. The median survival for these patients has not been reached. C) Survival of patients with residual disease following metastasectomy who received TIL therapy. Median survival of these patients was 14 months. D) Survival of patients with residual disease following metastasectomy who did not receive TIL therapy. Median survival of these patients was 10 months.