Breaking barriers: harnessing hypofractionated radiotherapy to transform outcomes in low tumor mutation burden stage III non-small cell lung cancer - a retrospective study

BackgroundNon-Small Cell Lung Cancer (NSCLC) patients with low tumor mutational burden (TMB) showed low sensitive to conventional fractionated radiotherapy in our previous study. This study aimed to evaluate the efficacy and safety of hypofractionated radiotherapy (HFRT) in locally advanced NSCLC pa...

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Main Authors: Jingyun Yang, Tianxiang Cui, Yang Zhang, Guangpeng Chen, Xinxin Wang, Jianguo Sun, Anmei Zhang, Guanghui Li
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-04-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1557154/full
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author Jingyun Yang
Tianxiang Cui
Yang Zhang
Guangpeng Chen
Xinxin Wang
Jianguo Sun
Anmei Zhang
Guanghui Li
author_facet Jingyun Yang
Tianxiang Cui
Yang Zhang
Guangpeng Chen
Xinxin Wang
Jianguo Sun
Anmei Zhang
Guanghui Li
author_sort Jingyun Yang
collection DOAJ
description BackgroundNon-Small Cell Lung Cancer (NSCLC) patients with low tumor mutational burden (TMB) showed low sensitive to conventional fractionated radiotherapy in our previous study. This study aimed to evaluate the efficacy and safety of hypofractionated radiotherapy (HFRT) in locally advanced NSCLC patients with low-TMB compared to conventional fractionated radiotherapy (CFRT).MethodsWe retrospectively analyzed clinical outcomes of 74 locally advanced NSCLC patients with low-TMB undergoing definitive radiotherapy from January 2017 to July 2023, with 31 patients received HFRT (received radiation doses of >2Gy and ≤5 Gy per fraction) and 43 received CFRT (received radiation doses of 1.8-2 Gy per fraction). Progression-free survival (PFS), overall survival (OS) and objective response rate (ORR) to radiotherapy was analyzed in the two groups. Univariate analysis was performed to assess the impact of clinical characteristics on PFS. We also analyzed PFS in subgroups receiving HFRT or CFRT combined with immunotherapy and chemotherapy.ResultsSurvival analysis revealed the median PFS of 13 months in the HFRT group was significantly better than the 10 months in the CFRT group (p = 0.024). The 6-month and 12-month PFS rates were 80.6% and 61.3% for the HFRT group, versus 81.4% and 39.5% for the CFRT group, respectively. Median OS was 27 months in the HFRT group and 20 months in the CFRT group (p = 0.079). There were no statistically significant differences in major adverse events between the HFRT and CFRT groups (all p>0.05). In the subgroup receiving combined immunotherapy and chemotherapy, the median PFS was 10 months in the HFRT group and 9 months in the CFRT group (p = 0.092).ConclusionHFRT was superior to CFRT in prolonging PFS for patients with low-TMB locally advanced NSCLC. It was a safely and effective approach for these patients and was worth further prospective studies with larger sample sizes.
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spelling doaj-art-4d5d26e845f24d99b5fb35fa9e4606e92025-08-20T03:06:13ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-04-011610.3389/fimmu.2025.15571541557154Breaking barriers: harnessing hypofractionated radiotherapy to transform outcomes in low tumor mutation burden stage III non-small cell lung cancer - a retrospective studyJingyun YangTianxiang CuiYang ZhangGuangpeng ChenXinxin WangJianguo SunAnmei ZhangGuanghui LiBackgroundNon-Small Cell Lung Cancer (NSCLC) patients with low tumor mutational burden (TMB) showed low sensitive to conventional fractionated radiotherapy in our previous study. This study aimed to evaluate the efficacy and safety of hypofractionated radiotherapy (HFRT) in locally advanced NSCLC patients with low-TMB compared to conventional fractionated radiotherapy (CFRT).MethodsWe retrospectively analyzed clinical outcomes of 74 locally advanced NSCLC patients with low-TMB undergoing definitive radiotherapy from January 2017 to July 2023, with 31 patients received HFRT (received radiation doses of >2Gy and ≤5 Gy per fraction) and 43 received CFRT (received radiation doses of 1.8-2 Gy per fraction). Progression-free survival (PFS), overall survival (OS) and objective response rate (ORR) to radiotherapy was analyzed in the two groups. Univariate analysis was performed to assess the impact of clinical characteristics on PFS. We also analyzed PFS in subgroups receiving HFRT or CFRT combined with immunotherapy and chemotherapy.ResultsSurvival analysis revealed the median PFS of 13 months in the HFRT group was significantly better than the 10 months in the CFRT group (p = 0.024). The 6-month and 12-month PFS rates were 80.6% and 61.3% for the HFRT group, versus 81.4% and 39.5% for the CFRT group, respectively. Median OS was 27 months in the HFRT group and 20 months in the CFRT group (p = 0.079). There were no statistically significant differences in major adverse events between the HFRT and CFRT groups (all p>0.05). In the subgroup receiving combined immunotherapy and chemotherapy, the median PFS was 10 months in the HFRT group and 9 months in the CFRT group (p = 0.092).ConclusionHFRT was superior to CFRT in prolonging PFS for patients with low-TMB locally advanced NSCLC. It was a safely and effective approach for these patients and was worth further prospective studies with larger sample sizes.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1557154/fullnon-small cell lung cancerhypofractionated radiotherapyconventional fractionated radiotherapytumor mutation burdenprogression-free survival
spellingShingle Jingyun Yang
Tianxiang Cui
Yang Zhang
Guangpeng Chen
Xinxin Wang
Jianguo Sun
Anmei Zhang
Guanghui Li
Breaking barriers: harnessing hypofractionated radiotherapy to transform outcomes in low tumor mutation burden stage III non-small cell lung cancer - a retrospective study
Frontiers in Immunology
non-small cell lung cancer
hypofractionated radiotherapy
conventional fractionated radiotherapy
tumor mutation burden
progression-free survival
title Breaking barriers: harnessing hypofractionated radiotherapy to transform outcomes in low tumor mutation burden stage III non-small cell lung cancer - a retrospective study
title_full Breaking barriers: harnessing hypofractionated radiotherapy to transform outcomes in low tumor mutation burden stage III non-small cell lung cancer - a retrospective study
title_fullStr Breaking barriers: harnessing hypofractionated radiotherapy to transform outcomes in low tumor mutation burden stage III non-small cell lung cancer - a retrospective study
title_full_unstemmed Breaking barriers: harnessing hypofractionated radiotherapy to transform outcomes in low tumor mutation burden stage III non-small cell lung cancer - a retrospective study
title_short Breaking barriers: harnessing hypofractionated radiotherapy to transform outcomes in low tumor mutation burden stage III non-small cell lung cancer - a retrospective study
title_sort breaking barriers harnessing hypofractionated radiotherapy to transform outcomes in low tumor mutation burden stage iii non small cell lung cancer a retrospective study
topic non-small cell lung cancer
hypofractionated radiotherapy
conventional fractionated radiotherapy
tumor mutation burden
progression-free survival
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1557154/full
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