The Neutrophil-to-Lymphocyte Ratio is a Prognostic Biomarker in An Ethnically Diverse Patient Population with Advanced Pancreatic Cancer.

PURPOSE: The neutrophil-to-lymphocyte ratio (NLR) is associated with decreased overall survival in patients with pancreatic adenocarcinoma (PAC) in studies including few minority patients. We investigated the association between NLR and survival in patients with advanced PAC in an ethnically diverse population. METHODS: We retrospectively evaluated 226 patients with advanced PAC treated at Montefiore Medical Center between 2006 and 2015. Adjusted Cox proportion hazard regression models were utilized to derive effect estimates for survival duration. RESULTS: Patients with a NLR ≤ 5 (126 patients, median age 66 years) were more likely to be non-Hispanic Black (30.8% vs. 20%), while patients with a NLR > 5 (70 patients, median age 66 years) were more likely to be non-Hispanic White (21.4% vs. 12.2%) or Hispanic (44.3% vs. 34%). A NLR > 5 compared with a NLR ≤ 5 was significantly associated with a worse overall survival when adjusted for a priori and exploratory variables from the univariate analysis (median survival 7.4 vs. 12 months, HR 1.650, 95% CI 1.139, 2.390). CONCLUSIONS: In an ethnically diverse population, elevated NLR is an independent marker of poor prognosis and a potentially valuable factor in driving therapeutic decisions and defining prognosis for patients in the locally advanced or metastatic for PAC setting, meriting investigation in prospective clinical trials.

Comparing outcomes following total neoadjuvant therapy and following neoadjuvant chemoradiation therapy in patients with locally advanced rectal cancer.

BACKGROUND: There is recent interest in treating locally advanced rectal cancer (LARC) patients with total neoadjuvant therapy (TNT). However, whether TNT is associated with improved overall survival (OS) remains unknown. This study compares outcomes following TNT and following neoadjuvant chemoradiation therapy (nCRT) in patients with LARC, clinically defined cT3/4 or node positive disease, using the National Cancer Database. METHODS: LARC patients diagnosed between 2004-2015 were included. TNT was defined as multi-agent chemotherapy given at least 2 months before RT followed by pre-operative chemoradiation therapy and definitive surgery without adjuvant chemotherapy. nCRT was defined as pre-operative RT and chemotherapy started within 2 weeks from each other followed by definitive surgery with or without adjuvant chemotherapy. Kaplan-Meier curve with logrank test and multivariable Cox proportional hazards regression modelling were used to analyse the primary endpoint of overall survival (OS). Multivariable logistic regression modelling was used for secondary outcomes to determine if TNT is associated with pathological complete response (pCR), defined as ypT0N0, and negative circumferential resection margin (CRM). FINDINGS: Data from 372 TNT patients and 707 nCRT patients were analysed after a 2:1 propensity matching with replacement. Kaplan-Meier curve showed that OS with TNT was comparable to that with nCRT (p = 0•16). The 5-year OS rates for TNT and nCRT were 73•6% vs. 78•5% (p = 0•20). Multivariable Cox proportional hazards regression modelling confirmed no difference in OS between TNT and nCRT (HR = 1•21, p = 0•25). With TNT, 16•9% patients achieved pCR, whereas 13•1% patients achieved pCR with nCRT (p = 0•12). TNT was not found to be significantly associated with pCR (OR = 1•36, p = 0•13) or negative CRM (OR = 1•77, p = 0•19) in multivariable logistic regression modelling. INTERPRETATION: With results from current clinical trials pending, our data suggested that TNT and nCRT resulted in similar survival, while TNT led to higher pCR and CRM negative rate, albeit not statistically significant.

Human papillomavirus, radiation dose and survival of patients with anal cancer.

Purpose: To determine if anal cancer patients with HPV positive disease have different overall survival (OS) compared to those with HPV negative disease, and to elucidate differences in the association between radiation dose and OS.Patients and methods: We utilized the National Cancer Database (NCDB) registry to identify a cohort of non-metastatic anal cancer patients treated with curative intent between 2008 and 2014. Propensity score matching was used to account for potential selection bias between patients with HPV positive and negative disease. Multivariable Cox regression was used to determine the association between HPV status and OS. Kaplan-Meier methods were used to compare actuarial survival estimates.Results: We identified 5927 patients with tumor HPV status for this analysis, 3523 (59.4%) had HPV positive disease and 2404 (40.6%) had HPV negative disease. Propensity-matched analysis demonstrated that patients with HPV positive locally advanced (T3-4 or node positive) anal cancer had better OS (HR = 0.81 (95%CI: 0.68-0.96), p=.018). For patients with early stage disease (T1-2 and node negative) there was no difference in OS (HR = 1.11 (95%CI: 0.86-1.43), p=.43). In the unmatched cohort, we found a significant improvement in OS with increasing radiation dose only for patients with locally advanced, HPV negative disease (p<.001). In those patients, significant improvement in OS compared to the group receiving 30-45 Gy was seen for increasing doses up to 55-60 Gy, but not beyond 60 Gy.Conclusion: We found HPV to be a significant prognostic marker in anal tumors, especially for locally advanced disease. We further found that higher radiation dose up to 55-60 Gy was associated with better OS, but only for patients with locally advanced, HPV negative disease.

Bridging therapy effectiveness in the treatment of hepatocellular carcinoma prior to orthotopic liver transplantation.

BACKGROUND: Orthotopic liver transplantation (OLT) is the most effective treatment for hepatocellular carcinoma (HCC) in patients with underlying cirrhosis and portal hypertension. Availability of OLT is limited by donor-organ shortages, which increase patient waiting time until OLT. A variety of bridging therapies (BT) have been used to halt tumor progression in patients on the OLT waiting list. Despite complete radiologic responses following BT, viable tumor is often present in explants. METHODS: Treatment outcomes were evaluated in 50 patients who had a total of 125 BT for treatment of 93 nodules. Success of BT was assessed by radiologic response compared to histopathological examination of explanted livers. RESULTS: Pre-transplant treatments included: transcatheter arterial chemoembolization (TACE), alcohol ablation (ETOH), radiofrequency ablation (RFA), microwave ablation (MWA), selective internal radiation therapy (SIRT) and stereotactic body radiation therapy (SBRT). Fifty-nine (64%) nodules had a complete radiographic response to therapy; however, only 28 nodules (30%) had complete tumor necrosis (CTN) on explant examination. Ten nodules with CTN were treated with TACE alone. Seven of the 28 nodules with CTN were treated with TACE and RFA. Three of seven nodules treated with TACE and SIRT had CTN. Patients underwent a mean of 2.5 BTs. Six of 50 patients (12%) had no residual HCC in their explants. Five of those six patients (83%) had complete response (CR) on pre-transplant imaging. CONCLUSIONS: Although favorable radiologic responses are seen following BT, viable HCC is seen in the majority of liver explants and radiographic imaging cannot always accurately predict pathological response. This underscores the need for aggressive treatment of patients who otherwise may not be eligible for OLT.