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

  • Author Footnotes
    1 These authors have contributed equally to this work.
    Yeona Cho
    Footnotes
    1 These authors have contributed equally to this work.
    Affiliations
    Department of Radiation Oncology, Gangnam Severance Hospital, Yonsei University College of Medicine, Yonsei University Health System, Seoul, Republic of Korea
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  • Author Footnotes
    1 These authors have contributed equally to this work.
    Yejin Kim
    Footnotes
    1 These authors have contributed equally to this work.
    Affiliations
    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
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  • Ibrahim Chamseddine
    Affiliations
    Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, United States
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  • Won Hee Lee
    Affiliations
    Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University Health System, Yonsei University College of Medicine, Seoul, Republic of Korea
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  • Hye Ryun Kim
    Affiliations
    Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea
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  • Ik Jae Lee
    Affiliations
    Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University Health System, Yonsei University College of Medicine, Seoul, Republic of Korea
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  • Min Hee Hong
    Affiliations
    Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea
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  • Byung Chul Cho
    Affiliations
    Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea
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  • Chang Geol Lee
    Affiliations
    Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University Health System, Yonsei University College of Medicine, Seoul, Republic of Korea
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  • Seungryong Cho
    Affiliations
    Department of Nuclear and Quantum Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea
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  • Jin Sung Kim
    Correspondence
    Corresponding authors at: Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University Health System, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea, (J.S. Kim and H.I. Yoon). Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, 02114 Boston, MA, United States (C. Grassberger).
    Affiliations
    Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University Health System, Yonsei University College of Medicine, Seoul, Republic of Korea
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  • Hong In Yoon
    Correspondence
    Corresponding authors at: Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University Health System, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea, (J.S. Kim and H.I. Yoon). Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, 02114 Boston, MA, United States (C. Grassberger).
    Affiliations
    Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University Health System, Yonsei University College of Medicine, Seoul, Republic of Korea
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  • Clemens Grassberger
    Correspondence
    Corresponding authors at: Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University Health System, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea, (J.S. Kim and H.I. Yoon). Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, 02114 Boston, MA, United States (C. Grassberger).
    Affiliations
    Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, United States
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  • Author Footnotes
    1 These authors have contributed equally to this work.
Published:January 13, 2022DOI:https://doi.org/10.1016/j.radonc.2022.01.007

      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.

      Keywords

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