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

 Yeona Cho  ;  Yejin Kim  ;  Ibrahim Chamseddine  ;  Won Hee Lee  ;  Hye Ryun Kim  ;  Ik Jae Lee  ;  Min Hee Hong  ;  Byung Chul Cho  ;  Chang Geol Lee  ;  Seungryong Cho  ;  Jin Sung Kim  ;  Hong In Yoon  ;  Clemens Grassberger 
 RADIOTHERAPY AND ONCOLOGY, Vol.168 : 1-7, 2022-03 
Journal Title
Issue Date
Carcinoma, Non-Small-Cell Lung* / therapy ; Chemoradiotherapy / adverse effects ; Humans ; Immunotherapy / adverse effects ; Lung Neoplasms* / radiotherapy ; Lymphocytes ; Lymphopenia* / chemically induced ; Retrospective Studies
Absolute lymphocyte counts ; Immune checkpoint inhibitor ; Radiation-induced lymphopenia ; Survival outcome ; Voxel-based analysis
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.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Radiation Oncology (방사선종양학교실) > 1. Journal Papers
Yonsei Authors
Kim, Jinsung(김진성) ORCID logo https://orcid.org/0000-0003-1415-6471
Kim, Hye Ryun(김혜련) ORCID logo https://orcid.org/0000-0002-1842-9070
Yoon, Hong In(윤홍인) ORCID logo https://orcid.org/0000-0002-2106-6856
Lee, Ik Jae(이익재) ORCID logo https://orcid.org/0000-0001-7165-3373
Lee, Chang Geol(이창걸) ORCID logo https://orcid.org/0000-0002-8702-881X
Cho, Byoung Chul(조병철) ORCID logo https://orcid.org/0000-0002-5562-270X
Cho, Yeona(조연아) ORCID logo https://orcid.org/0000-0002-1202-0880
Hong, Min Hee(홍민희) ORCID logo https://orcid.org/0000-0003-3490-2195
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