W. Lo¹, T. Beresnev¹, M. Merino³, M. Mulquin¹, Y. Shutack¹, D. Zlott¹, J. Hernandez¹, J. Davis¹, M. Hughes^{2  1}National Cancer Institute,Thoracic And GI Oncology Branch,Bethesda, MD, USA ²Eastern Virginia Medical School,Surgical Oncology,Norfolk, VA, USA ³National Cancer Institute,Pathology,Bethesda, MD, USA

Introduction:  Adrenocortical carcinoma (ACC) is an aggressive disease with 5-year survival estimated at 10-15%. While definitive therapy is complete surgical resection, recurrence occurs in up to 85% of patients. Systemic chemotherapy and molecular-targeted therapy have had minimal benefit for patients with advanced disease. The purpose of this study is to evaluate cytoreduction and HIPEC for safety in patients with advanced ACC confined to the peritoneal cavity, as well as evaluate the strategy for peritoneal progression-free survival.

Methods:  This single-institution, phase 2 clinical trial enrolled patients from April 2013 through September 2016. Eligible patients had histologically confirmed ACC and peritoneal disease deemed resectable by the operating surgeon and preoperative imaging. Comprehensive cytoreductive surgical resection was performed. Patients achieving CCR 0 or 1 proceeded with HIPEC using the closed-abdomen technique. Intraperitoneal cisplatin at 250 mg/m2 was circulated at 40°C for 90 minutes. Primary outcome was peritoneal progression-free survival (PFS). Secondary outcomes included overall survival (OS), adverse events, and treatment toxicity.

Results: Nine patients underwent cytoreduction and HIPEC. Mean operative time was 689 minutes (range 577 – 894 min). Median estimated blood loss was 500 mL (range 100 – 2000 mL). Median length of hospital stay after resection was 11 days. There were no perioperative mortalities or immediate reoperations. No treatment-related toxicities, grade 3 or 4 complications were observed. Thirty percent (n = 3) experienced infection-related complications. During a median follow-up period of 23.2 months, seven patients experienced peritoneal progression of disease and two patients died due to ACC. Median peritoneal PFS was 18.9 months from cytoreductive surgery and HIPEC. Median OS from date of initial diagnosis was 4.23 years. On univariate analysis, prior treatment with mitotane was associated with improved peritoneal PFS and OS. Tumor stage, initial disease-free interval after index resection, tumor functional status, type of initial resection, and prior treatment with etoposide, doxorubicin, and cisplatin (EDP) had no impact on peritoneal PFS or OS.

Conclusion: Recurrent ACC is an aggressive disease, and effective treatment strategies remain undefined. This study demonstrates that cytoreduction and HIPEC can be safely performed for patients with advanced ACC, and may result in a survival advantage for patients with disease confined to the peritoneum after receipt of adjuvant mitotane.