Haematological and nutritional prognostic biomarkers for patients receiving CROSS or FLOT

Background: Neoadjuvant carboplatin and paclitaxel with radiotherapy (CROSS) and perioperative docetaxel, oxaliplatin, calcium folinate and fluorouracil (FLOT) are widely used for gastric (GC), gastrooesophageal junction (GOJ) and oesophageal cancers (OC). Prognostic and predictive markers for response and survival outcomes are lacking. This study evaluates dynamic neutrophil-lymphocyte ratios (NLR), plateletlymphocyte ratios (PLR), albumin and body mass index (BMI) as predictors of survival, response and toxicity. Methods: This multi-centre retrospective observational study across 5 Sydney hospitals included patients receiving CROSS or FLOT from 2015 to 2021. Haematological results and BMI were recorded at baseline and pre-operatively, and after adjuvant treatment for FLOT. Toxicities were also recorded. An NLR >_2 and PLR >_200 was used to stratify patients. Univariate and multivariate analyses were performed to determine predictors of overall survival (OS), disease free survival (DFS), rates of pathological complete response (pCR) and toxicity. Results: One hundred sixty-eight patients were included (95 FLOT, 73 FLOT). A baseline NLR >_2 was predictive for worse DFS (HR 2.78, 95% CI: 1.41-5.50, P<0.01) and OS (HR 2.90, 95% CI: 1.48-5.67, P<0.01). Sustained elevation in NLR was predictive for DFS (HR 1.54, 95% CI: 1.08-2.17, P=0.01) and OS (HR 1.65, 95% CI: 1.17-2.33, P<0.01). An NLR >_2 correlated with worse pCR rates (16% for NLR >_2, 48% for NLR <2, P=0.04). A baseline serum albumin <33 was predictive of worse DFS and OS with a HR of 6.17 (P=0.01) and 4.66 (P=0.01) respectively. Baseline PLR, BMI, and dynamic changes in these markers were not associated with DFS, OS or pCR rates. There was no association of the aforementioned variables with toxicity. Conclusions: This demonstrates that a high inflammatory state represented by an NLR >_2, both at baseline and sustained, is prognostic and predictive of response in patients receiving FLOT or CROSS. Baseline hypoalbuminaemia is predictive of poorer outcomes.