Novel Application of Iterative Hyperthermic Intraperitoneal Chemotherapy for Unresectable Peritoneal Metastases from High-Grade Appendiceal Ex-Goblet Adenocarcinoma

Background: Peritoneal metastases (PMs) from appendiceal ex-goblet adenocarcinoma (AEGA) are associated with a poor prognosis. While cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has been shown to prolong survival, the majority of patients are ineligible for complete cytoreduction. We describe a novel approach to the management of such patients with iterative HIPEC (IHIPEC). Methods: Patients with signet ring/poorly differentiated AEGA with high Peritoneal Cancer Index (PCI) and extensive bowel involvement underwent IHIPEC with mitomycin C at 6-week intervals for a total of three cycles. Survival outcomes for these patients were compared with patients with high-grade appendiceal tumors matched for tumor burden who were treated with other conventional approaches, i.e. systemic chemotherapy only (SCO) or complete CRS + HIPEC. Results: Between 2016 and 2019, seven AEGA patients with high PCI (median 32.5 [range 21–36]) underwent 18 IHIPEC cycles (median cycles per patient 3 [2–3]) in combination with systemic chemotherapy (median 2 lines [1–3], 12 cycles [10–28]). IHIPEC was delivered laparoscopically in 14/18 cases. Postoperatively, the median length of stay was 1 day (1–8 days), no procedure-related complications were reported, and five (28%) 90-day readmissions for bowel obstruction were documented. Median overall survival after IHIPEC was better compared with a matched group of patients (n = 16) receiving SCO (24.6 vs. 7.9 months; p = 0.005), and similar to those (n = 7) who underwent CRS + HIPEC (24.6 vs. 16.5 months; p = 0.62). Conclusions: IHIPEC in combination with systemic chemotherapy is tolerable, safe, and may be associated with encouraging survival outcomes compared with SCO in selected patients with high-grade, high-burden AEGA PM.