# Frailty, nutritional status, and inflammation as determinants of chemotherapy delivery and outcomes in pancreatic cancer patients receiving gemcitabine plus nab-paclitaxel

## TL;DR

This study explores how frailty and inflammation affect chemotherapy delivery and outcomes in pancreatic cancer patients treated with gemcitabine plus nab-paclitaxel.

## Contribution

This is one of the first studies to evaluate composite frailty and neutrophil-to-lymphocyte ratio (NLR) together in pancreatic cancer patients receiving GnP.

## Key findings

- Composite frailty was linked to reduced chemotherapy dose intensity but not to severe adverse events or survival.
- Higher NLR was associated with shorter treatment duration and worse survival outcomes.
- In frail patients, NLR ≥5 predicted worse survival, while in non-frail patients, both NLR ≥3 and ≥5 were significant.

## Abstract

Pancreatic cancer has high mortality, and optimizing chemotherapy delivery in frail patients is challenging. Frailty and systemic inflammation are increasingly recognized as prognostic factors; however, their roles in patients receiving gemcitabine plus nab-paclitaxel (GnP) are not well defined. We aimed to evaluate the impact of a composite frailty index (modified frailty index [mFI] ≥2 and prognostic nutritional index [PNI]<45) and neutrophil-to-lymphocyte ratio (NLR) on treatment delivery, toxicity, and survival.

We retrospectively analyzed patients with locally advanced or metastatic pancreatic adenocarcinoma treated with first-line GnP at a tertiary center. Composite frailty was defined as an mFI ≥2 and a PNI <45. The primary endpoint was reduced relative dose intensity (RDI <75%) during the first 8 weeks. Secondary endpoints included time-to-discontinuation (TTD), overall survival (OS), severe toxicities, and the prognostic value of NLR cutoffs (≥3, ≥5).

Among 114 patients, 34 (29.8%) had composite frailty. Composite frailty was associated with reduced RDI <75% (odds ratio [OR] 2.65, 95% confidence interval [CI] 1.02–7.16, p=0.049), but not with severe adverse events, TTD, or OS. Higher NLR was associated with shorter TTD and worse OS. Secondary analyses showed that in frail patients, NLR ≥5 (but not ≥3) predicted inferior OS (hazard ratio [HR] 3.11, 95% CI 1.34–7.21, p=0.008). In non-frail patients, both NLR ≥3 and ≥5 were significantly associated with poor OS.

To our knowledge, this study is among the first to collectively evaluate composite frailty and NLR in pancreatic cancer patients treated with GnP. Frailty was mainly associated with chemotherapy delivery, whereas NLR provided stronger prognostic information for survival. These complementary markers may support treatment optimization and personalized care for vulnerable patients.