Baseline Lymphocyte Counts Do Not Predict Oncologic Outcomes and Survival in Patients Receiving Short Course Total Neoadjuvant Therapy for Rectal Cancer

Abstract

Total neoadjuvant therapy (TNT) is increasingly utilized for patients with locally advanced rectal cancer. Prior studies have suggested that markers of systemic inflammation at baseline may predict treatment outcomes for patients receiving neoadjuvant long-course chemoradiation (LC-CRT). However, this has not been evaluated in patients receiving TNT with short-course radiation (SC-RT). We evaluated the prognostic value of baseline neutrophil-to-lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and monocyte to lymphocyte ratio (MLR) in rectal cancer patients receiving SC-TNT. Between 2010 and 2019, we identified 186 patients with rectal cancer who received SC-TNT at our institution. Of these, 141 patients had a pre-treatment complete blood counts available within 2 months prior to initiating therapy. All patients received neoadjuvant SC- RT 25 Gy/5 Fx to the pelvis followed by chemotherapy followed by delayed surgery +/- adjuvant chemotherapy based on pathologic features. Primary clinical outcomes of interest were pathologic complete response (pCR), loco-regional control (LRC), distant control (DC), disease-free survival (DFS), and overall survival (OS). Cox regression analysis was performed to determine potential associations between NLR, PLR, and MLR with clinical outcomes. NLR, PLR, and MLR were analyzed as both continuous and dichotomized variables. Multiple cutoff values were evaluated based on cohort mean, cohort median, and previously published values. Statistical analyses were performed using SPSS version 26. P <0.05 was considered statistically significant. The median baseline NLR was 2.5 (interquartile range 1.36). The median baseline PLR was 142.73 (interquartile range 82.11). The median baseline MLR was 2.56 (interquartile range 2.26). Median follow-up was 2.44 years (range 0.11 – 9.59 years). pCR was achieved in 34 patients (24.1%). Three-year actuarial LRC, DC, DFS, and OS were 93%, 84.2%, 78.9%, and 87.7%, respectively. NLR as a continuous variable was significantly associated with LRC, DFS, and OS on univariate analysis but not multivariate analysis. There was no other association found between NLR, PLR, or MLR with any other clinical outcomes of interest when analyzed as either continuous or dichotomous variables. In our SC-TNT cohort, baseline NLR, PLR, and MLR did not predict tumor response, oncologic outcomes, or overall survival in rectal cancer patients. Our data contrasts prior studies for LC-CRT, possibly due to differences in neutrophil or lymphocyte depletion with hypo-fractionated RT. Further studies are warranted to compare post-RT immune markers between LC-CRT and SC-RT. As hypo-fractionated RT use increases, identification and validation of biomarkers in rectal cancer patients undergoing neoadjuvant SCRT will become increasingly important.