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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.

Fig. 2. A) The lymphocyte count before, during and after concurrent chemoradiotherapy(CCRT). B) Voxel-based analysis of the differences between patients with and without G3+ lymphopenia 3 months post-RT. 

Affiliations

Yeona Cho  1 , Yejin Kim  2 , Ibrahim Chamseddine  3 , Won Hee Lee  4 , Hye Ryun Kim  5 , Ik Jae Lee  4 , Min Hee Hong  5 , Byung Chul Cho  5 , Chang Geol Lee  4 , Seungryong Cho  6 , Jin Sung Kim  7 , Hong In Yoon  8 , Clemens Grassberger  9
1 Department of Radiation Oncology, Gangnam Severance Hospital, Yonsei University College of Medicine, Yonsei University Health System, Seoul, Republic of Korea.
2 Department of Nuclear and Quantum Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea; Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, United States; Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University Health System, Yonsei University College of Medicine, Seoul, Republic of Korea.
3 Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, United States.
4 Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University Health System, Yonsei University College of Medicine, Seoul, Republic of Korea.
5 Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea.
6 Department of Nuclear and Quantum Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea.
7 Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University Health System, Yonsei University College of Medicine, Seoul, Republic of Korea. Electronic address: JINSUNG@yuhs.ac.
8 Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University Health System, Yonsei University College of Medicine, Seoul, Republic of Korea. Electronic address: yhi0225@yuhs.ac.
9 Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, United States. Electronic address: Grassberger.Clemens@mgh.harvard.edu.