Lymphocyte dynamics during and after chemo-radiation correlate to dose and outcome in stage III NSCLC patients undergoing maintenance immunotherapy. (March 2022)

• Record Type: Journal Article
• Authors: Cho, Yeona; Kim, Yejin; Chamseddine, Ibrahim; Lee, Won Hee; Kim, Hye Ryun; Lee, Ik Jae; Hong, Min Hee; Cho, Byung Chul; Lee, Chang Geol; Cho, Seungryong; Kim, Jin Sung; Yoon, Hong In; Grassberger, Clemens
• Is Part Of: Radiotherapy and oncology. Volume 168(2022)
• Page Start: 1
• Page End: 7
• Publication Date: 2022-03
• Subjects: Radiation-induced lymphopenia -- Voxel-based analysis -- Absolute lymphocyte counts -- Immune checkpoint inhibitor -- Survival outcome; Oncology -- Periodicals; Radiotherapy -- Periodicals; Tumors -- Periodicals; Medical Oncology -- Periodicals; Neoplasms -- radiotherapy -- Periodicals; Radiotherapy -- Periodicals; Radiothérapie -- Périodiques; Cancérologie -- Périodiques; Tumeurs -- Périodiques; Electronic journals; 616.9940642
• DOI: 10.1016/j.radonc.2022.01.007
• Languages: English
• ISSNs: 0167-8140

Abstract

Highlights: Most patients undergoing CCRT and adjuvant ICI experienced lymphopenia. Some patients had persistent lymphopenia even 3 months after treatment. Patients with persistent lymphopenia showed inferior PFS and OS. Lymphocyte recovery is correlated to the ALC at previous timepoints. Dose to the aortic arch shows strong associations with G3+ lymphopenia. Abstract: Purpose: We investigated the dynamics of lymphocyte depletion and recovery during and after definitive concurrent chemoradiotherapy (CCRT), dose to which structures is correlated to them, and how they affect the prognosis of stage III non-small cell lung cancer (NSCLC) patients undergoing maintenance immunotherapy. Methods and materials: In this retrospective study, absolute lymphocyte counts (ALC) of 66 patients were obtained before, during, and after CCRT. Persistent lymphopenia was defined as ALC < 500/μL at 3 months after CCRT. The impact of regional dose on lymphocyte depletion and recovery was investigated using voxel-based analysis (VBA). Results: Most patients ( n = 65) experienced lymphopenia during CCRT: 39 patients (59.0%) had grade (G) 3+ lymphopenia. Fifty-nine patients (89.3%) recovered from treatment-related lymphopenia at 3 months after CCRT, whereas 7 (10.6%) showed persistent lymphopenia. Patient characteristics associated with persistent lymphopenia were older age and ALC before and during treatment. In multivariable Cox regression analysis, recovery from lymphopenia was identified as a significant prognostic factor for Progression Free Survival (HR 0.35, 95% CI 0.13–0.93, p = 0.034) and Overall Survival (HR 0.24, 95% CI 0.08–0.68, p = 0.007). Voxel-based analysis showed strong correlation of dose to the upper mediastinum with lymphopenia at the end of CCRT, but not at 3 months after CCRT. Conclusion: Recovery from lymphopenia is strongly correlated to improved survival of patients undergoing CCRT and adjuvant immunotherapy, and is correlated to lymphocyte counts pre- and post-CCRT. VBA reveals high correlation of dose to large vessels to lymphopenia at the end of CCRT. Therefore, efforts should be made not only for preventing lymphocyte depletion during CCRT but also for helping lymphocyte recovery after CCRT.