2392 - Higher Baseline Monocyte and Neutrophil Counts Are Associated with Significantly Worse Overall Survival in NSCLC Patients Treated with Curative-Intent Chemoradiation

Purpose/Objective(s): In the era of adjuvant immune checkpoint inhibitors (ICIs) for non-small cell lung cancer (NSCLC) in patients undergoing chemoradiation (CRT), immune function plays a key role. The immune system can be impaired through mechanisms such as neutrophilia, which shield tumor cells from cytotoxic T lymphocytes and natural killer cells, and tumor-associated macrophages, which arise from the differentiation of peripheral monocytes and are known for their negative prognostic impact. Higher neutrophil and monocyte counts have previously been associated with worse outcomes in surgical series. These immune factors can also diminish the effectiveness of adjuvant immunotherapy, thereby limiting its potential benefits in NSCLC. Leukocyte measurements from peripheral blood offer insights into immune function. We analyzed blood biomarkers in patients with NSCLC before and after curative-intent CRT, aiming to assess the impact of CRT on biomarker levels and identify prognostic factors for survival.

Materials/Methods: Eligibility for this retrospective, single-center, observational study required clinico-pathological diagnosis of NSCLC and definitive treatment with CRT +/- Durvalumab. Data was obtained from an ongoing, prospective thoracic malignancy cohort database and cross-checked with electronic medical records. Statistical analyses were performed in R version 4.4.1.

Results: In total, 133 patients who received curative-intent CRT for NSCLC between January 2012 and July 2022 were identified.121 patients had stage III NSCLC, 6 stage II and 6 stage IV. Most (131) patients received 60 Gy in 30 fractions, while 2 patients received 55 Gy in 20 fractions. 3D conformal RT technique was used in 94 patients, and volumetric modulated arc therapy (VMAT) was used in 39 (from 2018 onwards). Median follow up was 4.64 years; median overall survival from start date of CRT was 2.6 years (95%CI: 1.7-3.4). At baseline, mean Hb was 131.2g/L, WCC 11.9x10^9/L, neutrophils 6.5x10^9/L, lymphocytes 2.3x10^9/L and monocytes 0.6 x10^9/L. Mean difference in Hb, neutrophil count and monocyte count between baseline and 0-4 weeks post CRT was -30.4, -3.6 and -0.2 respectively. Higher baseline neutrophil and monocyte counts were associated with poorer prognosis: in univariate analysis HRs 1.2 (95% CI 1.1-1.2) for neutrophils and 3.1 (95% CI 1.6-6.0) for monocytes, and in multivariate analysis HR 1.2 (95% CI 1.1-1.3) for neutrophils and HR 2.0 (95%CI 1.0-4.2) for monocytes.

Conclusion: To the best of our knowledge, this is the first report highlighting the negative impact of high absolute monocyte count in NSCLC patients treated with curative-intent CRT. Elevated baseline neutrophil and monocyte counts were identified as key prognostic factors, offering potential biomarkers for identifying high-risk patients and possible therapeutic targets.