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Peritoneal Surface Malignancies

E371: Navigating Neutropenia: Risk Factors and Outcomes Following Hyperthermic Intraperitoneal Chemotherapy with Mitomycin C

Introduction: Hyperthermic intraperitoneal chemotherapy (HIPEC) is a crucial treatment modality for managing peritoneal surface malignancies, substantially improving therapeutic outcomes. Mitomycin C (MMC) is a prominent chemotherapeutic agent in HIPEC protocols. However, MMC administration introduces challenges, primarily the risk of neutropenia that can produce significant clinical sequelae. Risk factors for developing MMC-related neutropenia in the setting of HIPEC-MMC are not well described in the literature, thus we reviewed our institutional experience of HIPEC-MMC.

Methods: Patients who underwent cytoreduction and MMC HIPEC (30+10 mg flat dosing, 90-minute perfusion) for appendiceal or colorectal peritoneal carcinomatosis at a single quaternary care center from October 2020 to October 2023 were retrospectively reviewed with IRB approval. Data were extracted from electronic health records and analyzed using JMP (version 16.2). Descriptive statistics and inferential methods were applied for associations, where relevant. Logistic regression was used to identify risk factors for the development of neutropenia, defined as an absolute neutrophil count (ANC) < 2000/mm3. 

Results: Overall, 31 patients underwent MMC HIPEC. The sex distribution was even (n=15 women), with median age 55 years. Most patients (n=18) had appendiceal primaries, median peritoneal cancer index score was 22, twenty-two patients (71%) achieved completeness of cytoreduction score of 0 or 1, and median post-operative length of stay was 14 days. Pre-operative neutropenia related to neoadjuvant treatment was identified in 4 patients (13%), and post-operative neutropenia was observed in 18 patients (58%), with 14 of these patients requiring filgrastim for absolute neutrophil count (ANC) recovery. Pre-operative ANC was not associated with post-operative neutropenia. Development of post-operative fever was associated with neutropenia (9 of 11 patients, p=0.047), and all 4 patients who developed anastomotic leak were neutropenic (p=0.069). On logistic regression, factors independently associated with post-operative neutropenia were per-year increase in age (OR 1.11, 95% CI 1.00-1.23) and female sex (OR 8.76, 95% CI 1.05-73.4).

Conclusions: These results demonstrate that older, women patients are at particularly high risk of post-operative neutropenia after HIPEC with MMC. This may influence the threshold for and consideration of early ANC rescue with filgrastim, as delay in correction of significant neutropenia may predispose to anastomotic leak.

Learning Objectives:

  • 1. Elucidate high-risk post-operative neutropenia from mitomycin HIPEC
  • 2. Identify high-risk patients for neutropenia from mitomycin HIPEC
  • 3. Track the associated complications of mitomycin HIPEC