Pre-, Intra-, and Posttreatment Serum Albumin Predicts for Clinical Radiation Pneumonitis in Locally Advanced Non-Small Cell Lung Cancer Patients Treated with Radiochemotherapy

Abstract

Limited data exists on pretreatment immune parameters such as neutrophil-to-lymphocyte ratios (NLR) in patients receiving radiotherapy, especially during or after treatment. We sought to correlate pretreatment (pre-RT – within 90d), intratreatment (intra-RT), and posttreatment (post-RT – within 90 d) NLRs and albumin levels to radiation pneumonitis (RP) and overall survival (OS) of locally advanced lung cancer patients treated with definitive chemoradiotherapy. Hematologic values of 125 patients with locally advanced lung cancer treated between 2009-2018 were collected. Given the retrospective nature, the following were the sample sizes for each parameter: pre-RT/intra-RT/post-RT NLRs n = 80/76/39, respectively; pre-RT/intra-RT/post-RT albumin n = 82/52/73, respectively. NLRs and differences between pre-RT and intra-RT NLRs (delta-NLR) were calculated. RP was recorded as RTOG grade ≥3 RP requiring steroid medication. Kaplan-Meier statistics, univariate Cox regressions (UVA), and logistic models were used. The median age of the cohort was 58.9 years (54.1-65.2) with median follow up of 1.96 years (0.05-10.61) after RT. The majority of patients were stage IIIA/IIIB (80%) with median lung V20Gy of 28% (21-30). Median pre-RT/intra-RT/post-RT NLR was 2.92 (0.5-17), 12.13 (1.8-43), and 5.6 (0.91-40), respectively. 64 (95.2%) patients had increasing NLR during treatment, with the absolute median increase of 8.4 (3.1-15.22), a median 2.6x increase (0.7-4.9). The absolute median increase between post-RT and pre-RT NLRs was +2.2 (+0.4-5.2), a median 1.8x increase (1.2-2.4) with 80.6% (25/31) of patients experiencing a higher post-RT NLR. Median pre-RT/intra-RT/post-RT albumin was 4.2 g/dL (3.2-4.9), 3.98 g/dL (2.74-4.70), and 3.85 g/dL (2.46-4.62), respectively. 59.5% (22/37) and 75.5% (40/53) had a decrease of their albumin levels from pre-to-intra-RT and pre-to-post-RT, respectively, by a median -0.18 (-0.4 to 0.11) and -0.29 (-0.6 to 0), respectively. Five-year OS for the entire cohort was 33.3%. Higher intra-RT and post-RT albumin levels were correlated with improved OS (HR 0.36, p = 0.001 and 0.03, respectively), however pre-RT/intra-RT/post-RT NLR were not (p = 0.36/0.34/0.15 respectively). 5-year OS stratified by median post-RT albumin level (3.85) was 49.8% vs. 19.6% (p = 0.01). Twenty patients (16%) experienced RP. There was a trend towards higher pre-RT NLR predicting development of RP (p = 0.057). Decrease in albumin level from pre- to post-RT predicted for RP (p = 0.04). The majority of patients experienced an increased neutrophil-predominant inflammatory response and a decreased serum albumin level during chemoradiotherapy. Contrary to the current literature, higher NLRs did not predict for poorer OS, but higher albumin level during and after radiotherapy was correlated with improved OS. Higher pre-RT NLR and decrease in albumin level during radiation were correlated with clinical grade 3+ RP, and should be explored further.