Neutrophil count and efficacy of chemoradiation in patients with locally advanced unresectable pancreatic carcinoma: An ancillary study of in the LAP 07 trial.

Abstract

4120 Background: Predictive biomarkers of Overall Survival (OS) and Progression Free Survival (PFS) in locally advanced pancreatic cancer (LAPC) pts are mandatory. Baseline leukocyte, neutrophil and monocyte counts in addition to lymphocyte ratio (NLR) may predict OS in LAPC pts. Efficacy of chemoradiation (CRT) depending on neutrophil count was retrospectively analyzed in the largest Phase III cohort of LAPC. Methods: The international multicenter randomized LAP07 phase III trial (NCT00634725) has recruited 442 LAPC pts. We have studied the predictive and prognostic value of systemic inflammation, as defined: (i) baseline neutrophilia (neutrophil count > 7 G/L at first randomization) or (ii)increased absolute neutrophil count (IANC) after induction chemotherapy vs baseline. Univariate and multivariate Cox analysis evaluated the benefit of CRT for OS, PFS and Local Control (LC) in pts without systemic inflammation. Results: Patients with baseline neutrophilia (11%) had a worse OS (median 8.9 vs 13.3 months, p = 0.01). At 2nd randomization, 9% and 29% pts had baseline neutrophilia or IANC, respectively. Both neutrophilia (median OS 10.6 vs 16.1 months, p = 0.03) and IANC (median OS 14.6 vs 17.4 months, p = 0.02) predicted poor OS. Systemic inflammation predicted local resistance to CRT (p = 0.02, interaction = 0.015). After excluding pts with systemic inflammation, 1-year local control was 80% in CRT vs 54% in chemotherapy arms (p < 0.001). Pts without systemic inflammation in CRT arm had improved PFS vs chemotherapy arm (median 10.3 vs 8.3 months, p = 0.04). In multivariate analysis in this population, CRT increased PFS (HR = 0.66, 95%CI: 0.45 - 0.97, p = 0.03), after adjusting on age, tumor size, pain at enrollment, albumin, and CA 19.9 according to PROLAP nomogram parameters. Conclusions: In LAPC pts with tumor controlled after induction chemotherapy, systemic inflammation may help to better predict those who will benefit from CRT. This result may impact clinical management and the design of future clinical trials for LAPC. An external validation with a cohort from the ARCAD pancreas meta-analysis is under consideration. Clinical trial information: NCT00634725.