Neutropenia in colorectal cancer treated with oxaliplatin-based hyperthermic intraperitoneal chemotherapy: An observational cohort study

BACKGROUND The implications of neutropenia after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy(HIPEC) treatment have never been investigated.AIM To evaluate the occurrence of neutropenia and its effect on the risk of increased Clavien-Dindo morbidity as well as its effect on overall or disease-free survival.METHODS All patients with colorectal peritoneal metastases(1996-2015) completing cytoreductive surgery and oxaliplatin-based HIPEC treatment from a biinstitutional database(Uppsala and Sydney) were included in the study. ClavienDindo grade 3-4 morbidity differences between the neutropenia group vs nonneutropenia group were calculated and Kaplan-Meier curves with log rank test were rendered. Univariate and multivariable Cox regression models for diseasefree survival were implemented.RESULTS Two hundred and forty-six patients were identified – 32 postoperative any-grade neutropenia patients and 214 non-neutropenia patients. The neutropenia group had more combination oxaliplatin + irinotecan treatment than the nonneutropenia group(66% vs 13%, P = 0.0001). The neutropenia group was not associated with increased Clavien-Dindo grade 3-4 morbidity. Median overall survival was 53 mo vs 37 mo for the neutropenia and non-neutropenia group, P =0.07. Median disease-free survival was 16 mo vs 11 mo, respectively, P = 0.02.Neutropenia was an independent prognostic factor for disease-free survival withhazard ratio: 0.58, 95% confidence interval: 0.36-0.95, P = 0.03.CONCLUSION13% of patients developed neutropenia which was not associated with increased Clavien-Dindo grade 3-4 morbidity. Neutropenia was an independent positive prognostic factor for disease-free survival and was associated with more intense HIPEC treatment. This is in direct contrast to the current paradigm of decreasing the treatment intensity.