Neo-adjuvant Chemotherapy-Induced Neutropenia Is Associated with Histological Responses and Outcomes after the Resection of Colorectal Liver Metastases

Background: Neutropenia, the major adverse event in chemotherapy, is associated with favourable clinical outcome in several solid tumours. We aimed to investigate the predictive value of neo-adjuvant chemotherapy (NAC)-induced neutropenia for the pathological response and prognosis in colorectal liver metastases (CRLM) patients.

Methods: A retrospective review was performed in 141 CRLM patients receiving NAC followed by liver resection. A logistic regression was applied to analyse potential predictors. A Cox proportional hazards analysis was used to analyse survival.

Results: Neutropenia due to NAC was observed in 42.6% (60/141) of all patients, and grade 3/4 neutropenia was noted in 31.7% (19/60). A pathological response (tumour regression grade (TRG) 1-3) was reported in 46.1% (65/141) of patients. Multivariate analysis showed that neutropenia significantly predicted the favourable pathological response (OR = 3.718, 95% CI 1.716-8.329, P = 0.001), as well as targeted therapy, good differentiation and preoperative CEA < 10 ng/ml as independent predictors of favourable histological response. Of the patients, 54.6% (77/141) had postoperative complications, including 28 major complications (28/77, 36.4%). Severe neutropenia significantly predicted postoperative major complications in multivariate analysis (OR = 4.077, 95% CI 1.184-14.038, P = 0.026). Compared to patients without neutropenia, patients with neutropenia had significantly better progression-free survival (PFS) (P = 0.007; mPFS, 10.2 months vs. 6.7 months). Patients with histological response had significantly better PFS than patients with no histological response (P = 0.001; mPFS, 10.0 months vs. 5.5 months). According to multivariate analyses, neutropenia was a significant predictor for better PFS (HR = 0.613, 95% CI 0.406-0.925, P = 0.020) but not OS.

Conclusions: For CRLM patients receiving NAC followed by liver resection, NAC-induced neutropenia was a significant predictor of favourable pathological response, postoperative major complications and better prognosis, which makes it useful for CRLM patients in guiding treatment approaches and prognosis assessments.