W. R. Doerfler1, J. Miller-Ocuin1, M. Zenati1, H. Zeh1 1University Of Pittsburgh,Department Of Surgery,Pittsburgh, PA, USA
Introduction:
The lack of effective therapy and poor prognosis for pancreatic ductal adenocarcinoma (PDA) necessitates identification of prognostic factors that improve patient risk stratification and inform treatment strategies. Elevation of the neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) in patients with metastatic PDA is predictive of shortened overall survival (OS). We hypothesized NLR and PLR would correlate with improved clinical outcomes in patients with operable PDA treated with neoadjuvant therapy in a randomized phase II clinical trial.
Methods:
Patients with resectable or borderline resectable PDA were randomized to receive 2 months of neoadjuvant gemcitabine/nab-paclitaxel (GemAbx) or GemAbx + hydroxychloroquine (HCQ), an autophagy inhibitor, prior to undergoing pancreatectomy. Pre- and post-treatment peripheral blood NLR and PLR values were calculated. Primary outcome was OS and secondary outcome was histopathologic response (<50% vs. >50% tumor destruction). OS was determined and hazard ratios for covariates were determined using Cox regression.
Results:
54 patients were included in the analysis [n=27 (GemAbx), n=27 (GemAbx + HCQ)]. Patients with lower pre-treatment NLR appeared to have increased overall survival [(HR=0.690; 95% CI (0.411 – 1.158)] but this did not reach statistical significance (p=0.160). This trend was not affected by receipt of the G-CSF analog filgrastim during treatment (p=0.883). There appeared to be a direct correlation between treatment-related change in NLR and increased histopathologic response [OR =1.501; 95% CI (0.9101-2.478); p=0.112]. A similar trend with change in PLR was also observed [OR = 0.592; 95% CI (0.2717-1.291); p=0.118]. Patients in whom neoadjuvant chemotherapy resulted in >50% histopathologic response had longer median overall survival on Kaplan Meier curves (30 months vs 18 months; p =0.060).
Conclusion:
Patients with PDA treated with neoadjuvant chemotherapy had improved OS with lower pre-treatment NLR and PLR. Patients with greater histopathologic response to neoadjuvant therapy had improved median OS, and histopathologic response appeared to correlate with differences in pretreatment in NLR and PLR. Considering the small sample size of this pilot trial, these results are very encouraging.