Lymphocyte nadir and recovery dynamics for locally advanced thoracic malignancies undergoing concurrent chemo-irradiation: Establishment of organs-at-risk constraints

Abstract

Background and purpose: Radiotherapy-induced-lymphopenia (RIL) worsens outcome in thoracic malignancies on radiotherapy (RT). We hypothesised that post-RT absolute lymphocyte count (ALC) nadir and recovery were independently prognostic for overall survival (OS) and progression-free survival (PFS) in thoracic malignancies following radical chemo-irradiation. We also aimed to determine relevant organs-at-risk (OARs) constraints. Methods and materials: Two independent cohorts of stage III non-small-cell lung cancer (NSCLC) and stage II to III oesophageal cancer (EC) patients receiving chemo-irradiation from 2013 to 2022 were analysed. ALC nadir was defined as the lowest ALC on RT. ALC recovery index (ARI) was the ALC at 6 months/Pre-RT ALC. Effect of ALC nadir and ARI on OS and PFS were evaluated. RT dose of OARs was correlated with ALC nadir and ARI. OAR thresholds were then determined. Results: High ARI and ALC nadir were independently prognostic of improved OS and PFS for both cohorts. In NSCLC, thoracic spine V35Gy and ribs V35Gy were associated with ARI. Cut-off for thoracic spine V35Gy was 25.5 % while ribs V35Gy cut-off was 6.6 %. Thoracic spine V20Gy and Mean lung dose (MLD) were associated with ALC nadir in NSCLC. MLD cut-off was 16.5 Gy while T spine V20Gy cut off was 25.6 %. For EC, thoracic spine V35Gy was also associated with ARI. Similar to NSCLC, cut-off was 25.7 %. MLD and spleen V5Gy were associated with ALC nadir. MLD and Spleen V5Gy cut-off was 10.6 Gy and 7.2 % respectively. Conclusion: Post-RT lymphocyte nadir and recovery were both important for survival outcomes. Future prospective studies are warranted to validate whether abiding to lymphocyte sparing OARs constraints developed in the current study can improve lymphopenia and outcomes.