Comparative outcomes of treatment with versus without definitive thoracic radiotherapy in locally advanced inoperable non-small cell lung cancer during the immunotherapy era: a Chinese real-world study

Introduction

Historically, concurrent chemoradiotherapy (cCRT) has been the standard for inoperable locally advanced non-small cell lung cancer (LA-NSCLC) (1,2). However, the therapeutic landscape has been reshaped by immunotherapy, with the PACIFIC trial establishing consolidation durvalumab after cCRT, marking a new era for LA-NSCLC treatment (3,4). For patients unable to tolerate cCRT, the GEMSTONE-301 trial showed that sequential chemoradiotherapy (sCRT) followed by sugemalimab maintenance is also effective (5,6). For patients with unresectable, epidermal growth factor receptor (EGFR) sensitive mutant LA-NSCLC, treatment has advanced. The LAURA trial demonstrated that using Osimertinib after definitive chemoradiotherapy (CRT) significantly improves progression-free survival (PFS) (7). This approach is now recommended by the latest National Comprehensive Cancer Network (NCCN) guideline (8). However, due to tumor heterogeneity and patient preferences, many real-world patients still receive non-radiotherapy-based systemic therapy. At the 2023 European Lung Cancer Conference (ELCC), Prof. Xing presented the MOOREA study, which examined real-world treatment patterns in stage III NSCLC. Results showed that only 41.3% unresected cases received CRT (9). Therefore, in the immune era, the necessity of thoracic radiotherapy (RT) and changes in its technical parameters, like timing and dose for patients at this stage, are critical clinical questions.

We initially compared the clinical efficacy of different treatment modalities for LA-NSCLC. Then, we identified the optimal treatment modality for these patients in real-world. Lastly, we explored the optimal timing and dose of RT in this population. We present this article in accordance with the STROBE reporting checklist (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2025-701/rc).

Methods

Patient selection

We reviewed patients with pathologically confirmed, inoperable stage II-III NSCLC (AJCC 9th edition) at our hospital from January 2018 to December 2022. Inclusion criteria: (I) pathologically diagnosed with NSCLC; (II) stage as II-III on whole-body examination; (III) received 1st-line immune checkpoint inhibitor (ICI) treatment before disease progression; (IV) no local treatment other than thoracic RT (including primary lesion and lymph node metastases) before progression; (V) radiation dose ≥50 Gy delivered in 1.8–2.0 Gy fraction. Exclusion criteria: (I) second primary tumor present; (II) multiple lung primaries; (III) local recurrence after local treatments; (IV) EGFR sensitive mutation (19del or 21L858R); (V) prior targeted therapy. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. This real-world study was approved by the ethics committee of Shanghai Chest Hospital (KS24053). Given the retrospective nature of the study and use of de-identified data, the requirement for informed consent was waived by the Ethics Committee of Shanghai Chest Hospital.

RT planning and delivery

All patients received intensity-modulated RT (IMRT) planned with computed tomography (CT)-based pinnacle. Those without supraclavicular metastasis were immobilized supine with arms raised and immobilized using a vacuum cushion; those with supraclavicular metastasis were positioned supine with arms at sides using a head-neck-shoulder mask. Planning used 4-dimensional CT (4D-CT) fused with pre-treatment positron emission tomography/CT (PET/CT). Grass tumor volume (GTV) included primary lesion and metastatic nodal disease. Internal target volume (ITV) was merged GTVs from 10 phases, then expanded 8 mm margin to form planning target volume (PTV). PTV received ≥50 Gy/25–30 Fx. Weekly cone beam CT (CBCT) monitored toxicity and positioning.

Patient classification

Patients were categorized into two groups: RT group and non-RT group. In the RT group, patients underwent thoracic RT before disease progression, with various modalities including chemoimmunotherapy (CIT) before thoracic RT (including cCRT or RT alone) and cCRT or sCRT followed by ICI maintenance. In contrast, the non-RT group comprised patients who received first-line systemic therapy with CIT or ICI without additional interventions before disease progression.

Data collection and treatment assessment

Baseline demographic and treatment data were extracted from electronic medical records. Patients were followed up every 3 months for 2 years and every 6 months for 3–5 years. Treatment response was assessed using chest enhanced CT scans, abdominal and supraclavicular lymph node ultrasonography, and cerebral magnetic resonance imaging (MRI). Bone emission CT scans were conducted every 6 months or as needed for patients with bone pain symptoms. Malignant pleural fluid was confirmed through pathological examination, and treatment response was evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST version 1.1).

Overall survival (OS) was calculated from the start of any anti-tumor intervention until death or the last follow-up. PFS was calculated from the start of any anti-tumor interventions until first disease progression or the last follow-up. Local recurrence-free survival (LRFS) was measured from the start of any anti-tumor interventions until the first local recurrence, death, or last follow-up. The objective response rate (ORR) included clinical complete response (CR) and partial response (PR). Disease control rate (DCR) included CR, PR and stable disease (SD). Duration of response (DoR) was calculated from the initial tumor response to tumor progression, death, or the last follow-up.

Statistical analysis

Survival data (OS, PFS, and LRFS) were analyzed via Kaplan-Meier and log-rank test; the reversed Kaplan-Meier method estimated the median follow-up time. Continuous variables were compared with independent sample t-tests, and categorical variables with chi-square tests. For dichotomizing continuous variables, the median served as the cut-off to minimize skewness and enhance clinical relevance. Effects and influencing factors were analyzed using Cox proportional hazards models. Propensity score-matched (PSM) analysis addressed baseline differences in outcomes. Age, sex, pathological types, tumor (T) stage, and node (N) stage (N2a, N2b matched separately) were considered in matching. We evaluated treatment-subgroup interactions by separately modeling each subgroup variable with treatment, then testing significance using Wald tests. Variables with P<0.10 in univariate analysis were entered into the multivariate model. Missing data were excluded without imputation. Statistical analysis was performed using SPSS (version 26.0), with statistical significance set at P≤0.05.

Results

Patient characteristics

A total of 410 eligible patients were enrolled, with 173 in the RT group and 237 in the non-RT group, as shown in Figure 1. In both groups of patients, over 90% had a performance status (PS) score of 0–1, and the incidence rates of comorbidities such as chronic obstructive pulmonary disease (COPD), cardiovascular disease, and diabetes were similar between the two groups. In the RT and non-RT groups, median ages were 65 and 57 years, respectively, with the majority being male (93% and 94% in the RT and non-RT groups). In the RT group, 63% had lung squamous cell carcinoma (LUSC), 29% had lung adenocarcinoma (LUAD), and the remaining 12% had other NSCLC types. In the non-RT group, the proportions of LUSC, LUAD, and others were 48%, 41%, and 11%. The majority of cases were at stage III, with only 3% and 4% at stage II in the RT and non-RT groups. Among stage III patients, the percentages of stage IIIA, IIIB, and IIIC were 21%, 57%, and 19% in the RT group and 20%, 51%, and 25% in the non-RT group. In the RT group, programmed cell death 1 ligand (PD-L1) expression levels were distributed as follows: <1% (22%), 1–49% (19%), ≥50% (16%), and undetected (43%). In the non-RT group, PD-L1 expression levels were distributed as follows: <1% (23%), 1–49% (32%), ≥50% (31%), and undetected (14%). In the RT group, 82 cases received CIT induction therapy prior to RT [excluding 9 patients who received prolonged induction therapy beyond the median PFS (mPFS) of the non-RT group], with 18 cases receiving cCRT after CIT induction therapy. Additionally, 53 cases underwent ICI maintenance after cCRT, and 29 received ICI maintenance after sCRT. In the RT group, most cases received a 60 Gy RT dose (82%), while 13% received 50 Gy. Only 2 cases received <50 Gy (46 and 47.3 Gy) RT, and 1 patient received a dose of >60 Gy (64 Gy). Baseline patient characteristics are presented in Table 1.

Figure 1 Flow diagram of patient selection. ICI, immune checkpoint inhibitor; NSCLC, non-small cell lung cancer.

Clinical outcomes—RT continues to be essential for LA-NSCLC in the immune era

Patients receiving thoracic RT before disease progression shows better prognosis than those without

With a median follow-up of 24.2 months, median OS (mOS) for the RT and non-RT groups was 55.5 and 26.6 months, respectively [P<0.001, hazard ratio (HR) =0.49, 95% confidence interval (CI): 0.34–0.70 (Figure 2, A1)]. The mPFS for the RT group was 21.3 months, compared to 14.1 months for the non-RT group [P<0.001, HR =0.55, 95% CI: 0.42–0.72 (Figure 2, A2)]. In the PSM dataset, prognostic outcomes were consistent with the total dataset. The mOS and mPFS for the RT and non-RT groups were 53.4 and 25.3 months, and 31.5 and 16 months, respectively [P=0.004, HR =0.56, 95% CI: 0.37–0.86 for OS (Figure 2, A3); P<0.001, HR =0.57, 95% CI: 0.41–0.79 for PFS (Figure 2, A4)]. Comparison of treatment-related adverse events (TRAEs) between the two groups revealed that the RT group had a higher incidence of grade 3–4 lymphopenia and a higher incidence of grade 1–2 radiation pneumonitis compared to the non-RT group. The incidence rates of other TRAEs were similar between the two groups (Table S1).

Figure 2 Key clinical outcomes, treatment response, and failure patterns. (A1) The OS of patients who received thoracic RT before disease progression (RT group) compared to those who did not receive RT (non-RT group) in the overall dataset; (A2) the PFS of patients who received thoracic RT before disease progression (RT group) compared to those who did not receive RT (non-RT group) in the overall dataset; (A3) the OS of patients who received thoracic RT before disease progression (RT group) compared to those who did not receive RT (non-RT group) in the PSM dataset; (A4) the PFS of patients who received thoracic RT before disease progression (RT group) compared to those who did not receive RT (non-RT group) in the PSM dataset; (B1) the LRFS of patients who received thoracic RT before disease progression compared to those who did not receive RT in the overall dataset; (B2) the LRFS of patients who received thoracic RT before disease progression compared to those who did not receive RT in the PSM dataset; (C1) the OS of patients without thoracic RT before disease progression in the PD-L1 ≥50% group compared to the PD-L1 <50% group; (C2) the OS of patients receiving thoracic RT before disease progression in the PD-L1 ≥50% group compared to the PD-L1 <50% group; (C3) the OS of patients with PD-L1 ≥50% in the RT group compared to the non-RT group; (D1) the treatment response of patients who received thoracic RT before disease progression compared to those who did not receive RT in the overall dataset; (D2) the treatment response of patients who received thoracic RT before disease progression compared to those who did not receive RT in the PSM dataset; (D3) the DoR of patients who received thoracic RT before disease progression compared to those who did not receive RT in the overall dataset; (D4) the DoR of patients who received thoracic RT before disease progression compared to those who did not receive RT in the PSM dataset; (E1) the failure pattern of patients who received thoracic RT before disease progression compared to those who did not receive RT in the overall dataset; (E2) the failure pattern of patients who received thoracic RT before disease progression compared to those who did not receive RT in the PSM dataset. *, P<0.05; **, P<0.01. DoR, duration of response; LRFS, local recurrence-free survival; OS, overall survival; PD-L1, programmed cell death 1 ligand; PFS, progression-free survival; PSM, propensity score-matched; RT, radiotherapy.

Patients receiving thoracic RT before disease progression experience improved LRFS compared to those without

Analysis of LRFS showed median LRFS (mLRFS) was not reached for the RT group, while it was 22.2 months for the non-RT group [P<0.001, HR =0.38, 95% CI: 0.28–0.52 (Figure 2, B1)]. Similarly, in the PSM dataset, mLRFS for the RT and non-RT groups were not reached and 23.8 months, respectively [P<0.001, HR =0.41, 95% CI: 0.27–0.60 (Figure 2, B2)].

Even among patients with high PD-L1 expression, RT group prognosis was superior to the non-RT group

In the non-RT group, mOS for the PD-L1 ≥50% subgroup was 50.4 months, surpassing the 24.9 months of PD-L1 <50% subgroup [P=0.01, HR =0.44, 95% CI: 0.26–0.77 (Figure 2, C1)]. Similarly, in the RT group, impact of PD-L1 expression on OS indicated a prognostic advantage for the PD-L1 ≥50% subgroup over the PD-L1 <50% subgroup, with mOS of 57.9 months and 38.9 months, respectively [P=0.048, HR =0.46, 95% CI: 0.23–0.95 (Figure 2, C2)]. Within the PD-L1 ≥50% subgroup, does prognosis differ between RT and non-RT groups? Among the 101 cases with high PD-L1 expression, 28 received thoracic RT while 73 did not. The RT group exhibited a mOS of 57.9 months, compared to 50.4 months for the non-RT group [P=0.05, HR =0.44, 95% CI: 0.18–1.00 (Figure 2, C3)]. PD-L1 expression levels did not appear to affect mPFS in either group (Figure S1A-1C).

The RT group exhibited superior immediate response and DoR compared to the non-RT group

Among the 173 cases in the RT group, one patient achieved CR (0.58%), 140 experienced PR (80.92%), 31 demonstrated SD (17.92%), and one patient had progression disease (PD) (0.58%). In the non-RT group (n=237), the occurrences of CR, PR, SD, and PD were one (0.42%), 154 (64.98%), 67 (28.27%), and 15 (6.33%), respectively. The ORR and DCR were 81.5% and 99.42% in the RT group, and 65.4% and 93.67% in the non-RT group, respectively (Table 2, Figure 2, D1,D2). Additionally, we provided data on the median time to best response and median DoR for both groups. The median DoR was 11.97 months for the RT group and 9.37 months for the non-RT group in the total dataset (P=0.008, Figure 2, D3). In the PSM dataset, the median DoR was 13.18 months for the RT group and 9.85 months for the non-RT group (P=0.04, Figure 2, D4).

The non-RT group had a higher local recurrence rate than RT group

At the last follow-up, 87 RT and 127 non-RT patients experienced disease progression. In the RT group, 42 cases exhibited local recurrence (24%, LR), 35 cases showed distant metastasis (20%, DM), and 10 cases had both LR and DM (5.8%, LR + DM). Conversely, in the non-RT group, LR, DM, and LR + DM occurred in 77 (32%), 25 (9.2%), and 25 (9.2%) cases, respectively. In both total and PSM datasets, the non-RT group had higher LR compared to RT group (Figure 2, E1,E2).

Exploring combination modalities of RT and ICI, and the optimal timing of RT

CIT induction before cCRT provides advantages for LA-NSCLC patients

Within the RT group, 82 cases underwent cCRT or sCRT followed by ICI maintenance, 64 received CIT induction followed by RT alone, 18 had CIT induction followed by cCRT, and 9 received prolonged induction therapy (excluded from the treatment pattern analysis). CIT induction followed by cCRT trended towards the best OS (Figure 3, A1). Pairwise comparison showed notably superior OS with CIT induction before cCRT compared to CRT followed by ICI maintenance [P=0.09, HR =0.31, 95% CI: 0.13–0.78, (Figure 3, A2)]. CIT induction followed by RT alone tended towards a poorer prognosis compared to standard care (Figure 3, A3). No significant difference in PFS among treatment modalities (Figure S2A-2C). In the CIT induction followed by cCRT group, 55.6% cases achieved PR after CIT induction therapy; following further cCRT, a PR rate of 88.9% was achieved. The efficacy waterfall plot was shown in Figure 3, A4,A5.

Figure 3 Impact of radiotherapy and immunotherapy sequencing on outcomes and prognostic predictors for the CIT induction followed by RT group. (A1) The OS of the three types treatment modalities; (A2) the OS of patients in the group receiving ICI induction before cCRT compared to the group receiving cCRT or sCRT followed by ICI maintenance; (A3) the OS of patients in the group receiving ICI induction before RT alone compared to the group receiving cCRT or sCRT followed by ICI maintenance; (A4) efficacy waterfall plot for patients receiving CIT induction; (A5) efficacy waterfall plot for patients receiving induction therapy with CIT followed by cCRT; (B1) forest plot of univariable and multivariable COX prognostic regression analysis; (B2) the OS of patients receiving ≤4 cycles of CIT compared to those receiving >4 cycles of CIT. cCRT, concurrent chemoradiotherapy; CIT, chemoimmunotherapy; ICI, immune checkpoint inhibitor; OS, overall survival; RT, radiotherapy; sCRT, sequential chemoradiotherapy.

Thoracic RT shouldn’t be significantly delayed after CIT induction, 4 cycles may be appropriate

In the CIT induction group, univariate analysis suggested that pathology, tumor-node-metastasis (TNM) stage, PD-L1 expression level, CIT induction cycles, 1st-line therapy cycles and RT dose may be associated with OS, and further multivariate analysis suggested that the type of pathology and CIT induction cycles were independent prognostic predictors of OS (Figure 3, B1, Table S2). Among this group, 53 received ≤4 induction cycles, while 29 received >4 cycles. The mOS was not reached for the ≤4 cycles subgroup, while it was 30.1 months for the >4 cycles subgroup (P=0.04, HR =0.42, 95% CI: 0.18–0.97, Figure 3, B2). No significant difference in PFS between the two subgroups (Figure S3A). In addition, patients responding well to CIT induction followed by RT trended towards better OS compared to those responding poorly (including 11 cases of thoracic progressive disease with CIT induction) (P=0.09, HR =0.52, 95% CI: 0.24–1.14, Figure S3B). Immediate response did not significantly affect PFS (Figure S3C).

Analysis of thoracic RT dose

Further investigation is needed to determine the optimal RT dose, with little difference between 50 and 60 Gy in selected patients

Among the RT group, 142 received ≥60 Gy, while 31 received <60 Gy. The ≥60 Gy subgroup exhibited a tendency towards better PFS than the <60 Gy subgroup (P=0.051, HR =0.63, 95% CI: 0.33–1.11, Figure 4A). However, in the PSM dataset, there was no significant difference in PFS between the two groups (Figure 4B). There were no significant differences in the impact of RT dose on OS (Figure 4C,4D). Additionally, within the treatment modalities, OS and PFS did not exhibit significant differences between the two RT dose subgroups (Figure S4A-S4D). Comparison of baseline characteristics between the two dose groups showed that the <60 Gy group had a higher proportion of N3 disease and lower proportion of concurrent chemotherapy, while the rest of the characteristics were similar between the two dose groups (Table S3).

Figure 4 PFS and OS of patient with different RT dose. (A) The PFS of patients receiving ≥60 and <60 Gy RT dose in total data; (B) the PFS of patients receiving ≥60 and <60 Gy RT dose in PSM data; (C) the OS of patients receiving ≥60 and <60 Gy RT dose in total data; (D) the OS of patients receiving ≥60 and <60 Gy RT dose in PSM data. OS, overall survival; PFS, progression-free survival; PSM, propensity score-matched; RT, radiotherapy.

Discussion

Stage III NSCLC, highly heterogeneous, includes various T and N statuses (IIIA, IIIB, and IIIC), histological types, genotypes, and PD-L1 expression statuses, leading to significant efficacy variations. The 5-year survival rates are 36%, 26%, and 13% for stages IIIA, IIIB, and IIIC (10). As well, treatment decisions for patients at this stage pose greater challenges due to age, comorbidities, and tumor location variability, necessitating multidisciplinary discussions for optimal therapeutic strategy.

In both pre-immune and immune eras, treatment modalities for stage III NSCLC patients were varied. Abrão et al. reported real-life experiences of 3,363 patients with stage IIIA NSCLC over a 19-year period, finding that only 30.3% patients received standard CRT (11). At the 2023 ELCC conference, Xing et al. presented a prospective, non-intervention study evaluating real-world treatment patterns and outcomes for stage III NSCLC in China, noting that only 41.3% patients in the unresectable group received CRT (9). Additionally, in various clinical trials, LA-NSCLC is being included in advanced first-line systemic therapy without thoracic RT planned for these patients (12,13). Some patients in our study were part of clinical trial groups, leading to diverse treatment modalities. Hence, the question arises: should thoracic RT be omitted from first-line therapy for LA-NSCLC?

After the successful PACIFIC and GEMSTONE 301 trials (4,6) established consolidative ICI maintenance as a cornerstone of treatment for unresectable LA-NSCLC following concurrent cCRT/sCRT, the therapeutic landscape has become increasingly stratified by molecular phenotype. For patients with EGFR-sensitive mutations, the LAURA trial has further defined Osimertinib consolidation after definitive thoracic CRT as a new standard of care (7,8). In this study, which excluded patients with EGFR sensitive mutations, we compared the prognosis of patients with LA-NSCLC patients who did not receive thoracic RT before disease progression with those who underwent definitive thoracic RT. In both the overall and PSM cohorts, the RT group had significantly longer OS, PFS, and LRFS. Importantly, even among patients with high PD-L1 expression (PD-L1 ≥50%), those who received RT exhibited a markedly improved prognosis compared to the non-RT group. These real-world findings reaffirm the critical role of thoracic RT in the first-line management of unresectable LA-NSCLC. They underscore that RT remains an indispensable component of multimodal treatment, including in patients with high PD-L1 expression, who might otherwise be considered for CIT alone. Our results support the integration of thoracic RT into standard treatment paradigms for this patient population to improve survival and local control.

Nevertheless, a substantial proportion (20–30%) of patients are unable to complete the planned CRT regimen, primarily owing to intolerable adverse events or other reasons (14,15). Some with extensive primary disease struggle to start early RT due to high risks to surrounding organs like lungs, heart, and esophagus. Others patients with smaller lung volumes or underlying pulmonary or cardiac conditions are less radiation-tolerant. Could earlier ICI initiation maximize tumor shrinkage while protecting organs at risk? Systemic therapy with CIT before definitive CRT for maximal downsizing is also recommended (16,17). However, in the KEYNOTE-799 trial, pembrolizumab plus cCRT for inoperable LA-NSCLC didn’t significantly improves OS but carried increased TRAEs (18). We hypothesize that continuous ICI use throughout CRT could increase TRAEs risks, potentially masking therapeutic benefits. Determining the RT target area solely based on pre-treatment tumor size is unreasonable. A retrospective study by Prof. Bi et al. showed CIT before definitive CRT is feasible for bulky LA-NSCLC, reducing tumors while preserving normal lung function (19). In our study, patients receiving CIT induction before cCRT achieved the longest OS compared to those with CRT followed by ICI maintenance, or RT alone after CIT induction. The optimal timing for RT analysis found better prognosis with ≤4 CIT induction cycles compared to >4 cycles. Additionally, a higher proportion of cCRT in the ≤4 induction cycles group compared to the >4 cycles group (Figure S5). Bi’s study reported better DCR of 2 CIT induction cycles than >4 cycles (19). These suggest ≤4 cycles CIT before definitive cCRT and followed by ICI maintenance may be the optimal treatment for LA-NSCLC.

Furthermore, experts in RT have been investigating the optimal radiation dose for LA-NSCLC (20-23). In the pre-immune era, efforts focused on enhancing thoracic RT efficacy by increasing radiation dose. However, RTOG-0617 trial found that 74 Gy was not better than 60 Gy for stage III patients, possibly increasing TRAEs (23,24). Higher doses pose greater risks to organs due to the dose-response relationship for radiation (25,26). Given the side effects of RT and the synergistic interaction between ICI and RT, should we lower the radiation dose of thoracic RT while maintaining efficacy in the immune era? RT doses in PACIFIC and GEMSTONE 301 ranged from 54 to 66 Gy (4,6). Prof. Bi’s study showed doses of 60–70 Gy, with higher grade ≥3 pneumonitis (9.3%) than PACIFIC (4.2%) and GEMSTONE 301 (<4%) trials. Our analysis found no significant efficacy differences among different RT dose groups. Due to the variability in tumor radiosensitivity and tumor burden among patients, tumor response to different RT doses is diminished in clinical practice and multiple clinical trials have confirmed the immediate tumor reduction effect of CIT induction (27-29). In our study, CIT induction in half the RT group may have influenced efficacy with different RT doses. Consequently, some patients received CIT induction, potentially reducing tumor burden and mitigating the impact of 50–60 Gy on tumor control.

Certainly, this retrospective study has inherent limitations because it is susceptible to treatment disparities such as variations in systemic treatments, discrepancies in ICI drug selection, and differences in RT dose. Furthermore, the small sample size of subgroups within the RT group limits result generalizability. However, ongoing validation through our prospective study cohort is underway. The limited sample size prevented most subgroup analyses from undergoing PSM analyses. Although the overall sample size is not small, being a single-center study introduces bias, necessitating validation from other centers. However, this study is still the largest to date comparing treatment modalities’ efficacy in inoperable LA-NSCLC during the immune era.

Conclusions

Our findings affirm the continued importance of thoracic RT for inoperable LA-NSCLC. CIT prior to cCRT followed by ICI maintenance may represent a promising treatment strategy for LA-NSCLC patients. Further prospective studies are needed to validate this approach and to clarify the optimal RT dose, as preliminary comparisons between 50 and 60 Gy suggest potentially comparable efficacy in certain patient subgroups.

Acknowledgments

The authors are grateful to the patients, the patients’ families and the investigators who took part in this study.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2025-701/rc

Data Sharing Statement: Available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2025-701/dss

Peer Review File: Available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2025-701/prf

Funding: This work was supported by National Natural Science Foundation of China (Nos. 82202964, and 92059206).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2025-701/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. This real-world study was approved by the ethics committee of Shanghai Chest Hospital (KS24053). Given the retrospective nature of the study and use of de-identified data, the requirement for informed consent was waived by the Ethics Committee of Shanghai Chest Hospital.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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