Invited Commentary: Ten-Year Outcome of a Randomized Trial: Cytoreduction and HIPEC with Mitomycin C Versus Oxaliplatin for Appendiceal Neoplasm with Peritoneal Dissemination, by Levine et al.

The current publication in Annals of Surgical Oncology by Levine and colleagues reports the long-term outcomes of 121 patients with peritoneal metastases from appendiceal neoplasm who underwent cytoreduction and were then randomly assigned to receive hyperthermic intraperitoneal chemotherapy (HIPEC) with mitomycin C or oxaliplatin. Their original publication from 2018 reported short-term toxicities in patients treated with HIPEC using mitomycin C (40 mg) or oxaliplatin (200 mg/m2) under hyperthermic conditions administered over 120 min.¹ The authors showed that mitomycin C was associated with significantly higher rates of transient leukopenia and oxaliplatin was associated with significantly higher rates of transient thrombocytopenia. In a follow-up publication analyzing quality-of-life outcomes in the study cohort, the authors reported that patients treated with oxaliplatin during HIPEC had better short-term quality of life.² In this 10-year outcome analysis, the authors report the progression-free and overall survivals in this cohort with reference to mitomycin C compared with oxaliplatin, and outcomes based on the histologic grade of the primary appendiceal neoplasm codified as low- versus high-grade. In this context, the authors use a grading system initially developed and reported from their institution in 2006 in which peritoneal metastases from low-grade mucinous appendiceal neoplasms (LAMN), high-grade mucinous appendiceal neoplasms (HAMN), and well-differentiated mucinous carcinomas of the appendix (also referred to as intermediate grade) were classified as mucinous carcinoma peritonei-L (low grade), and well-differentiated mucinous carcinomas with signet-ring features or high grade or poorly differentiated tumors were classified as MCP-H (high grade).³ In the current random assignment study, approximately 70% of patients had low-grade neoplasms, and if we presume the complexion of patients remained fairly consistent at that institution over time then most of those patients likely had peritoneal metastases from a primary LAMN or HAMN. This is important as we try to synthesize the data and determine how it relates, if at all, to the larger question on the role of HIPEC in the management of patients with peritoneal metastases from other gastrointestinal neoplasms such as colorectal cancer. …