Prognosis of severe lymphopenia after postoperative radiotherapy in non-small cell lung cancer: Results of a long-term follow up study

Purpose: To investigate the incidence and prognosis of severe radiation-induced lymphopenia (sRIL) after postoperative radiotherapy (PORT) for resected NSCLC. Patients and methods: Between 1998 and 2017, 170 patients treated with PORT for NSCLC were retrospectively reviewed. Lymphopenia was divided into tertiles with severe lymphopenia defined as absolute lymphocyte counts (ALC) < 0.37 × 10³/ul. Results: sRIL was observed in 32.3% of patients. Multivariable logistic regression analysis indicated sRIL was associated with planning target volume radiation fraction numbers (OR 1.09, p = 0.005) and total lung mean dose (OR 1.12, p = 0.006). With a median follow-up time of 12.2 years, the median progression-free survival and overall survival were 14.8 months and 28.4 months respectively in patients with sRIL, vs. 21.7 months (p = 0.008) and 48.3 months (p = 0.01) respectively in patients without sRIL. Multivariable analyses indicated sRIL significantly decreased OS (HR 1.95, p < 0.01). Since PORT for stage I-II NSCLC was done largely for positive margins, which may confound the contribution of severe RIL, we analyzed stage III separately and found that sRIL also significantly decreased OS (HR 1.88, p = 0.004) in multivariable analysis. Conclusion: For this long-term outcome study, severe RIL correlated with total lung mean dose and radiation fractionation numbers, and was a strong prognostic factor for poor survival in PORT patients, particularly in patients with stage III NSCLC, highlighting the importance of an intact immune system for post-radiation immunologic disease surveillance.