Prediction of Delayed Lymphopenia at the Time of Consolidation Immunotherapy After Chemoradiotherapy in Locally Advanced Non-Small Cell Lung Cancer

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<h3>Purpose/Objective(s)</h3> Consolidation immunotherapy becomes a new standard treatment after definitive chemoradiotherapy (CRT) in locally advanced non-small cell lung cancer (NSCLC). However, the efficacy of immunotherapy can be compromised by treatment-related immune suppression status. We aimed to evaluate clinical and dose-volumetric predictors of delayed lymphopenia at the time of consolidation immunotherapy after CRT in locally advanced NSCLC. <h3>Materials/Methods</h3> We retrospectively reviewed 318 patients with locally advanced non-small cell lung cancer who received definitive CRT from January 2012 to December 2020. Patients diagnosed between 2012 and 2018 were assigned as training set (n = 244), and rest were selected as validation set (n = 74). Absolute lymphocyte count (ALC) was recorded at baseline, during CRT, and 4 to 12 weeks after CRT. Dose-volume histogram parameters for planned target volume, whole body, heart, lung, great vessels, spleen, esophagus and thoracic vertebral bodies were evaluated. Dose-volume histogram parameters reported as mean, maximum and minimum dose with volume receiving 5 Gy (V5), 10 Gy (V10), 20 Gy (V20), 30 Gy (V30), 40 Gy (V40), 50 Gy (V50), and 60 Gy (V60). Overall survival (OS) was analyzed using Kaplan-Meier survival analysis, log-rank test, and Cox regression model. Area under the receiver operating characteristic curve (ROC) analysis and multivariate logistic regression were used to determine the predictors of severe lymphopenia. <h3>Results</h3> Grade 3 lymphopenia (ALC nadir < 500/mm³) were 81.1%, 48.1%, and 11.4% cases during CRT, 0 to 4 weeks, and 4 to 12 weeks after CRT, respectively. Kaplan-Meier survival curves and multivariate cox regression analysis revealed that patients with delayed lymphopenia (grade 3 lymphopenia during 4 to 12 weeks after CRT) was associated with inferior overall survival (<i>P</i> < 0.0001). On multivariable logistic regression models, age (OR = 1.116; <i>P</i> = 0.018), baseline ALC (OR = 0.998; <i>P</i> = 0.010), albumin nadir during CRT (OR = 0.111, <i>P</i> = 0.001), and lung V5 (OR = 1.089, <i>P</i> < 0.001) were significant predictors for delayed lymphopenia. The prediction nomogram was developed according to the above four independent variables. The AUC value of the nomogram model was 0.928. In the validation set (n = 74) the performance was 0.859. <h3>Conclusion</h3> Delayed lymphopenia is an independent predictor of poor overall survival. Age, baseline ALC, albumin nadir during CRT, and lung V5 revealed as the dominant contributor to delayed lymphopenia at the time of consolidation immunotherapy after definitive chemoradiotherapy.