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      Blood Lymphocytes as a Prognostic Factor for Stage III Non-Small Cell Lung Cancer with Concurrent Chemoradiation

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          Abstract

          We aimed to identify blood lymphocytes as a prognostic factor for survival in patients with locally advanced stage III non-small cell lung cancer (NSCLC) treated with concurrent chemoradiotherapy (CCRT). This is a secondary study of 196 patients enrolled in the Korean Radiation Oncology Group 0903 phase III clinical trial to evaluate the prognostic significance of circulating blood lymphocyte levels. The median total lymphocyte count (TLC) reduction ratio during CCRT was 0.74 (range: 0.29-0.97). In multivariate analysis, patient age (p=0.014) and gross tumor volume (GTV, p=0.031) were significant factors associated with overall survival, while TLC reduction (p=0.018) and pretreatment neutrophil-to-lymphocyte ratio (NLR; p=0.010) were associated with progression-free survival (PFS). In multivariate logistic regression analysis, pretreatment NLR, GTV, and heart V20 were significantly associated with TLC reduction. Immunohistochemical analysis of programmed death ligand 1 and CD8 expression on T cells was performed on 84 patients. CD8 expression was not significantly associated with the pretreatment lymphocyte count (p=0.673), and PDL1 expression was not significantly associated with OS or PFS. Univariate analysis revealed that high CD8 expression in TILs was associated with favorable OS and was significantly associated with favorable PFS (p=0.032). TLC reduction during CCRT is a significant prognostic factor for PFS, and heart V20 is significantly associated with TLC reduction. Thus, in the era of immunotherapy, constraining the volume of the radiation dose to the whole heart must be prioritized for the better survival outcomes.

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          Pembrolizumab versus Chemotherapy for PD-L1–Positive Non–Small-Cell Lung Cancer

          Martin Reck, Delvys Rodriguez-Abreu, Andrew G Robinson … (2016)
          Pembrolizumab is a humanized monoclonal antibody against programmed death 1 (PD-1) that has antitumor activity in advanced non-small-cell lung cancer (NSCLC), with increased activity in tumors that express programmed death ligand 1 (PD-L1).
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            Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial

            Tony Mok, Yi-Long Wu, Iveta Kudaba … (2019)
            First-line pembrolizumab monotherapy improves overall and progression-free survival in patients with untreated metastatic non-small-cell lung cancer with a programmed death ligand 1 (PD-L1) tumour proportion score (TPS) of 50% or greater. We investigated overall survival after treatment with pembrolizumab monotherapy in patients with a PD-L1 TPS of 1% or greater.
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              Durvalumab after Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer.

              Scott J Antonia, Augusto Villegas, Davey Daniel … (2017)
              Background Most patients with locally advanced, unresectable, non-small-cell lung cancer (NSCLC) have disease progression despite definitive chemoradiotherapy (chemotherapy plus concurrent radiation therapy). This phase 3 study compared the anti-programmed death ligand 1 antibody durvalumab as consolidation therapy with placebo in patients with stage III NSCLC who did not have disease progression after two or more cycles of platinum-based chemoradiotherapy. Methods We randomly assigned patients, in a 2:1 ratio, to receive durvalumab (at a dose of 10 mg per kilogram of body weight intravenously) or placebo every 2 weeks for up to 12 months. The study drug was administered 1 to 42 days after the patients had received chemoradiotherapy. The coprimary end points were progression-free survival (as assessed by means of blinded independent central review) and overall survival (unplanned for the interim analysis). Secondary end points included 12-month and 18-month progression-free survival rates, the objective response rate, the duration of response, the time to death or distant metastasis, and safety. Results Of 713 patients who underwent randomization, 709 received consolidation therapy (473 received durvalumab and 236 received placebo). The median progression-free survival from randomization was 16.8 months (95% confidence interval [CI], 13.0 to 18.1) with durvalumab versus 5.6 months (95% CI, 4.6 to 7.8) with placebo (stratified hazard ratio for disease progression or death, 0.52; 95% CI, 0.42 to 0.65; P<0.001); the 12-month progression-free survival rate was 55.9% versus 35.3%, and the 18-month progression-free survival rate was 44.2% versus 27.0%. The response rate was higher with durvalumab than with placebo (28.4% vs. 16.0%; P<0.001), and the median duration of response was longer (72.8% vs. 46.8% of the patients had an ongoing response at 18 months). The median time to death or distant metastasis was longer with durvalumab than with placebo (23.2 months vs. 14.6 months; P<0.001). Grade 3 or 4 adverse events occurred in 29.9% of the patients who received durvalumab and 26.1% of those who received placebo; the most common adverse event of grade 3 or 4 was pneumonia (4.4% and 3.8%, respectively). A total of 15.4% of patients in the durvalumab group and 9.8% of those in the placebo group discontinued the study drug because of adverse events. Conclusions Progression-free survival was significantly longer with durvalumab than with placebo. The secondary end points also favored durvalumab, and safety was similar between the groups. (Funded by AstraZeneca; PACIFIC ClinicalTrials.gov number, NCT02125461 .).
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                Author and article information

                Journal
                Journal ID (nlm-ta): Chonnam Med J
                Journal ID (iso-abbrev): Chonnam Med J
                Journal ID (publisher-id): CMJ
                Title: Chonnam Medical Journal
                Publisher: Chonnam National University Medical School
                ISSN (Print): 2233-7385
                ISSN (Electronic): 2233-7393
                Publication date (Print): January 2024
                Publication date (Electronic): 25 January 2024
                Volume: 60
                Issue: 1
                Pages: 40-50
                Affiliations
                [1 ]Department of Radiation Oncology, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Hwasun, Korea.
                [2 ]Department of Pathology, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Hwasun, Korea.
                [3 ]Department of Internal Medicine, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Hwasun, Korea.
                Author notes
                Corresponding Author: Sung-Ja Ahn. Department of Radiation Oncology, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, 322 Seoyong-ro, Hwasun-eup, Hwasun 58128, Korea. Tel: +82-61-379-7200, Fax: +82-61-379-7249, ahnsja@ 123456chonnam.ac.kr

                †These authors contributed equally to this work.

                Article
                DOI: 10.4068/cmj.2024.60.1.40
                PMC ID: 10828085
                PubMed ID: 38304134
                SO-VID: fcfd2121-e3f4-468b-90ec-38568ab8267d
                Copyright © © Chonnam Medical Journal, 2024
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 25 October 2023
                Date revision received : 17 November 2023
                Date accepted : 20 November 2023
                Categories
                Subject: Original Article

                ScienceOpen disciplines: Medicine
                Keywords: lymphocytes,tumor-infiltrating lymphocytes,chemoradiotherapy,non-small-cell lung carcinoma
                Data availability:
                ScienceOpen disciplines: Medicine
                Keywords: lymphocytes, tumor-infiltrating lymphocytes, chemoradiotherapy, non-small-cell lung carcinoma

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