Promising benefits of MET inhibition combined with EGFR/ALK tyrosine kinase inhibitor in heavily treated non-small cell lung cancer patients with EGFR-mutant/ALK rearrangement and MET overexpression: a retrospective cohort study

Introduction

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) represent the standard first-line treatment for patients with EGFR mutant non-small cell lung cancer (NSCLC) (1,2). Nevertheless, most patients ultimately develop resistance to EGFR TKIs, leading to disease progression and treatment failure (3,4). Aberrant activation of the mesenchymal-epithelial transition (MET) signaling axis has emerged as a critical clinical mechanism of such resistance. The MET proto-oncogene encodes a receptor tyrosine kinase on chromosome 7 that is activated by hepatocyte growth factor (HGF) and signals through downstream PI3K-AKT and RAS-MAPK pathways to promote tumor growth, survival, and metastasis (5,6).

MET alterations in NSCLC primarily encompass MET exon 14 skipping (METex14), MET amplification, MET overexpression, and MET gene fusions (7). While METex14 is a validated oncogenic driver and a definitive indication for MET inhibitor therapy (8). MET amplification has also been identified as an important molecular marker for developing treatment strategies after EGFR-TKI resistance (5). In contrast, the prognostic and predictive significance of MET overexpression remains a subject of debate. Notably, in EGFR mutant NSCLC tumors that have progressed on EGFR-TKI therapy, approximately 50% exhibit MET protein overexpression (9). Consequently, there is an unmet clinical need to develop and validate novel therapeutic strategies to improve outcomes in this subgroup.

Several clinical programs, including INSIGHT, TATTON, and SAVANNAH, have explored dual inhibition of EGFR and MET to overcome MET overexpression-driven resistance, demonstrating significant efficacy and favorable safety profiles (10-13). In addition to small molecule inhibitors, telisotuzumab vedotin (Teliso V), a first-in-class antibody drug conjugate targeting MET, has shown encouraging anti-tumor activity and tolerable toxicity in EGFR mutant patients with concomitant MET overexpression (14,15). Taken together, these data support MET overexpression as a clinically actionable biomarker and highlight the therapeutic potential of EGFR and MET co-targeting. Despite these advancements, EGFR TKI monotherapy remains the conventional first-line choice for EGFR mutant patients in routine practice, and there are limited real-world data regarding the benefits of adding MET inhibition in later lines of therapy (1). Therefore, this study aims to evaluate the clinical efficacy and safety of EGFR TKI and MET inhibitor dual targeted therapy in NSCLC patients with EGFR mutations and MET overexpression. We present this article in accordance with the STROBE reporting checklist (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2026-0448/rc).

Methods

Study design

This single-center retrospective study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Ethics Committee of Shanghai Pulmonary Hospital (approval No. K25-540). Informed consent was obtained from all participants. The patients included in this study were sourced from Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China. The inclusion criteria were as follows: (I) patients diagnosed with advanced NSCLC harboring EGFR mutations or anaplastic lymphoma kinase (ALK) rearrangement between 2022 and 2024; (II) patients who had achieved prior response or disease control with EGFR/ALK-targeted therapy and subsequently developed radiologically confirmed disease progression, as assessed according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1); and (III) patients who underwent post-progression pathological and molecular reassessment confirming MET overexpression by immunohistochemistry (IHC) and subsequently received a combination of EGFR/ALK TKIs and MET inhibitors. A total of 49 patients were initially screened. The exclusion criteria included: (I) insufficient treatment duration without efficacy assessment during the follow-up period (n=6); (II) incomplete clinical or pathological data (n=15); and (III) loss to follow-up (n=5). Ultimately, 23 patients were included in the final analysis (Figure 1).

Figure 1 Flowchart of patient selection and enrollment. ALK, anaplastic lymphoma kinase; EGFR, epidermal growth factor receptor; NSCLC, non-small cell lung cancer.

Data collection

Pretreatment clinical staging was performed according to the eighth edition of the American Joint Committee on Cancer (AJCC) lung cancer staging system. Relevant clinical data, including demographic information and perioperative details, were extracted from electronic medical records. During the treatment period, patients underwent chest enhanced computed tomography (CT) or positron emission tomography (PET)-CT scans every two cycles to assess therapeutic efficacy. Radiological responses following combination treatment were evaluated using the RECIST v1.1. According to RECIST v1.1, complete response (CR) was defined as the disappearance of all target lesions, with no evidence of new lesions for at least 4 weeks. Partial response (PR) was defined as a ≥30% reduction in the sum of the longest diameters of target lesions, sustained for at least 4 weeks. Stable disease (SD) was characterized by the absence of sufficient shrinkage to qualify as PR or sufficient increase to qualify as progressive disease (PD), with tumor size remaining stable. PD was defined as a ≥20% increase in the sum of the longest diameters of target lesions, or the appearance of new lesions. The objective response rate (ORR) was calculated as the proportion of patients achieving CR or PR, reflecting the overall efficacy of the treatment.

Pathology and molecular assessments

All included patients underwent post-progression molecular and pathological reassessment before dual-targeted therapy. MET overexpression was assessed by routine clinical IHC scoring at our center, with IHC 2+ or 3+ considered positive. The same scoring criteria were applied to all patients and MET IHC results were reviewed by two experienced thoracic pathologists. MET IHC scoring in this study was based on both staining intensity and the proportion of positive tumor cells. Staining intensity was categorized into four levels: no staining, weak staining, moderate staining, and strong staining. The scoring system was as follows: a score of 0 was assigned for no staining or if fewer than 50% of tumor cells exhibited any staining intensity. A score of 3+ was assigned when more than 50% of the tumor cells exhibited strong staining. A score of 2+ was given if more than 50% of the tumor cells showed moderate staining, with less than 50% exhibiting strong staining. A score of 1+ was assigned when ≥50% of the tumor cells exhibited weak staining or stronger, with less than 50% showing moderate or strong staining.

Endpoints and follow-up

Progression-free survival (PFS) was defined as the time from the initiation of treatment to the first documented event of recurrence, metastasis, or the last follow-up. Overall survival (OS) was defined as the time from treatment initiation to death or the last follow-up. Patient follow-up was conducted through outpatient records or telephone interviews, continuing until death or the last follow-up on December 9, 2025.

Statistical analysis

Continuous variables were presented as mean ± standard deviation for normally distributed data, while non-normally distributed data were expressed as median and interquartile range. Categorical variables were reported as frequencies and percentages. The Kaplan-Meier method was used to generate PFS and OS curves. All statistical analyses were conducted using R software version 4.4.1.

Results

Patients characteristics

A total of 23 patients with NSCLC were enrolled, all of whom were diagnosed with adenocarcinoma. The cohort comprised 18 females (78.3%) and 5 males (21.7%), with a median age of 66.9 years. Only one patient (4.35%) reported a history of smoking. All patients presented with advanced disease, specifically stage IVA or IVB. Brain metastases were present in 8 patients (34.8%) and bone metastases in 11 patients (47.8%). Regarding line of therapy, 5 patients (21.7%) received the second-line therapy, whereas 18 patients (78.3%) were treated beyond second-line therapy. The MET inhibitors administered included capmatinib (n=8, 34.78%), bozitinib (n=7, 30.4%), tepotinib (n=5, 21.7%), and glumetinib (n=3, 13.0%). Prior or concurrent exposure to EGFR or ALK TKIs involved first-generation TKIs (n=3, 13.04%), second-generation TKIs (n=5, 21.74%), and third-generation TKIs (n=15, 65.2%). Demographic, treatment, survival, driver alteration, and MET overexpression data were complete for all 23 patients. Human epidermal growth factor receptor 2 (HER2) expression was missing in 9 patients (39.1%) and programmed death-ligand 1 (PD-L1) expression in 7 patients (30.4%); these values were reported as “not available (N/A)” and were not imputed. Detailed baseline characteristics are summarized in Table 1 and Table S1.

Mutation profile

Among the 620 EGFR-mutant patients at our center, the majority had the L858R mutation (47.42%), followed by the 19-del mutation (45.48%). Regarding PD-L1 expression, 36.13% of patients had no expression, 15% exhibited 1–50% expression, and 6.13% showed ≥50% expression. For MET overexpression, 17.1% of patients had 2+ expression, and 4.84% had 3+ expression. HER2 overexpression was observed in 20% of patients at the 1+ level, while 8.87% had no expression, and only 1.13% exhibited 3+ overexpression (Table S2).

Among the 23 patients who met the inclusion and exclusion criteria and were included in the analysis, activating EGFR mutations were detected in 20 patients (87.0%), comprising L858R (n=14, 60.9%) and exon 19 deletions (n=6, 26.1%). Three patients (13.0%) lacked activating EGFR mutations, of whom two harbored ALK rearrangements (n=2, 8.7%). Other EGFR alterations identified in the cohort included T790M (n=1, 4.3%) and G719X (n=1, 4.3%). All patients demonstrated MET protein overexpression as determined by IHC, with MET IHC 2 plus observed in 14 patients (60.9%) and MET IHC 3 plus in 9 patients (39.1%). HER2 IHC results were available in 14 patients (60.9%), of whom 7 patients (30.4% of the overall cohort) had HER2 expression of at least 1+. PD-L1 status was evaluated in 16 patients (69.6%): PD-L1 ≥50% in 3 patients (13.0%), 1–49% in 7 patients (30.4%), and 0% in 1 patient (4.3%). Additionally, tumor protein p53 (TP53) alterations were identified in 9 patients (39.1%). These molecular characteristics are summarized in Figure 2.

Figure 2 Pathological features and treatment history of patients with MET overexpression. This chart illustrates the distribution of MET expression levels (2+ and 3+) in the patient cohort, along with their prior therapies and the duration of dual-target therapy treatment. Activating EGFR mutation: the presence of activating mutations in the EGFR gene (e.g., exon 19 deletions, L858R mutation, etc.). ALK rearrangement: the presence or absence of ALK gene rearrangements. EGFR T790M/G719X: specific mutations in EGFR (T790M or G719X) that can confer resistance to EGFR inhibitors. MET overexpression: overexpression of the MET receptor, indicated by the “+” sign (e.g., 2+ or 3+). HER2 overexpression: overexpression of HER2. PD-L1 expression: percentage of cells showing expression of PD-L1, which may be used as a biomarker for immunotherapy response. TP53: the status of the TP53 tumor suppressor gene (wild-type or mutated). Prior therapies: the list of therapies that the patient has previously received, which may include EGFR/ALK inhibitors, chemotherapy, immunotherapy, and others. MET inhibitor: the type of MET inhibitor used in the patient’s treatment (e.g., capmatinib, tepotinib, etc.). EGFR/ALK-TKI: the type of EGFR or ALK TKIs used, classified by generation (first-, second-, or third-generation). Time on MET inhibitor + EGFR/ALK-TKI (days): the total duration in days that the patient was on the combination of MET inhibitors and EGFR/ALK-TKI treatment. ALK, anaplastic lymphoma kinase; BOR, best overall response; CTx, chemotherapy; EGFR, epidermal growth factor receptor; gen., generation; HER2, human epidermal growth factor receptor 2; IO, immunotherapy; MET, mesenchymal-epithelial transition; N/A, not available; PD, progressive disease; PD-1, programmed cell death protein 1; PD-L1, programmed death-ligand 1; PR, partial response; SD, stable disease; TKI, tyrosine kinase inhibitor; TP53, tumor protein p53; VEGF, vascular endothelial growth factor.

Treatment regimens and treatment-related adverse events

Prior systemic therapies were heterogeneous, encompassing chemotherapy, EGFR or ALK TKIs across various generations, immunotherapy with or without chemotherapy, and anti-vascular endothelial growth factor (VEGF) or EGFR combinations. These treatment sequences are depicted chronologically in Figure 2 using distinct colored blocks. Most patients had undergone multiple prior lines of therapy before initiation of the MET inhibitor and EGFR or ALK TKI combination, and a substantial proportion (15/23, 65.2%) had received prior third-generation EGFR TKIs. The duration of combination therapy ranged from 27 to 385 days. At the time of data cutoff, 14 of 23 patients (60.9%) remained on treatment, while the remaining 9 patients discontinued therapy due to PD (Figure 2).

Treatment-related adverse events were recorded in 19 patients (82.6%), including MET inhibitor-related adverse events in 17 patients (73.9%) and EGFR/ALK TKI-related adverse events in 9 patients (39.1%) (Table S3). Grade ≥3 treatment-related adverse events occurred in 4 patients (17.4%). Dose reduction was required for MET inhibitors in 6 patients (26.1%) and for EGFR/ALK TKIs in 2 patients (8.7%), while treatment interruption occurred in 5 patients (21.7%) and 2 patients (8.7%), respectively. No treatment-related deaths or permanent treatment discontinuations were observed. Among MET inhibitor-related adverse events, edema was the most common toxicity, occurring in 11 patients (47.8%), followed by increased transaminases in 4 patients (17.4%), gastrointestinal symptoms, rash, and headache in 2 patients each (8.7%), and electrocardiographic QT interval prolongation in 1 patient (4.3%) (Table S4). Given the retrospective nature of this study, mild or transient toxicities may have been underreported.

Tumor response and survival outcomes

Among 23 evaluable patients, the best overall responses were as follows: 16 patients (69.6%) achieved a PR, 6 patients (26.1%) had SD, and 1 patient (4.3%) experienced PD after 27 days of dual-targeted therapy due to the appearance of new pulmonary nodules, which led to treatment discontinuation. The ORR for the entire cohort was 69.6%. Among the 21 patients who received an EGFR TKI concurrently with a MET inhibitor, the ORR was 66.7% (14/21). These individual responses are summarized in the waterfall plot in Figure 3, where each bar represents the maximum percentage change in target lesion size for a single patient. At the time of data cutoff, the median follow-up duration was 7.0 months. A total of 9 PFS events and 1 death were observed. The median PFS was 6.9 months, whereas the median OS was not reached because of the limited number of death events (Figure 4). Due to the limited number of events and substantial late censoring, 95% confidence intervals for certain survival endpoints could not be reliably estimated.

Figure 3 Changes in tumor diameter and response rates among patients receiving combined MET and EGFR/ALK inhibitors. The waterfall plot shows the percentage change in tumor size, categorizing the responses into PR, SD, and PD. Patient 9 exhibited PD due to a new pulmonary nodule. +, positive. ALK, anaplastic lymphoma kinase; EGFR, epidermal growth factor receptor; EGFRm, EGFR mutation; MET, mesenchymal-epithelial transition; PD, progressive disease; PR, partial response; SD, stable disease.

Figure 4 PFS (A) and OS (B) for patients undergoing dual-target therapy. The Kaplan-Meier survival curves depict median PFS and OS for the cohort, with the median PFS of 6.9 months, whereas the median OS was not reached at data cutoff. ALK, anaplastic lymphoma kinase; EGFR, epidermal growth factor receptor; MET, mesenchymal-epithelial transition; OS, overall survival; PFS, progression-free survival.

Notably, patients with PD-L1 expression ≥50% exhibited a 100% response rate. In contrast, those with PD-L1 expression between 1% and 50% and 0 showed ORRs of 71.43% and 66.67%, respectively. MET overexpression at the 3+ level was associated with an 88.89% response rate, while the 2+ level showed a lower response rate of 57.14%. HER2 overexpression did not seem to significantly impact response rates, with most patients showing lower ORRs in the 2+ and 3+ levels. Additionally, EGFR-mutant patients treated with third-generation EGFR-TKIs during dual-target therapy had the highest ORR (80%), compared to 66.67% for first-generation EGFR-TKIs and 0% for second-generation EGFR-TKIs (Table S5). These subgroup analyses should be interpreted with caution given the limited sample size.

Representative case presentations and therapeutic efficacy

Patient 18 was a 75-year-old female never smoker harboring an EGFR exon 19 deletion. Following disease progression on first-line treatment with a third-generation EGFR TKI, a repeat biopsy confirmed MET overexpression (IHC 3+), HER2 negativity, and a PD-L1 expression of 1 to 50 percent. Upon enrollment, the patient received combination therapy consisting of a MET inhibitor and a third-generation EGFR TKI. Radiographic evaluation at 6 weeks identified a PR, characterized by a 56.84 percent reduction in the sum of target lesion diameters. Notably, a more pronounced response was observed in the intracranial metastases, with substantial shrinkage and near complete resolution of most brain lesions (Figure 5A,5B). At the time of data cutoff, the patient remained on treatment with an ongoing response exceeding 3.5 months and tolerable treatment-related toxicity.

Figure 5 Imaging showing the effects of treatment on primary and metastatic lesions. (A,B) Pre- and post-treatment brain metastases in Patient 18, with significant reduction in lesion size. (C,D) Pulmonary lesions in Patient 7, illustrating substantial shrinkage and complete resolution of pleural effusion.

Patient 7 was a 66-year-old female with an EGFR exon 19 deletion, MET overexpression (MET 2+), and a PD-L1 expression of 1 to 50 percent. The clinical history involved multiple lines of therapy, including first- and second-generation EGFR TKI followed by a third-generation EGFR TKI. After disease progression, the patient received third-line chemotherapy combined with immune checkpoint inhibition and anti-angiogenic therapy. Upon further disease progression, treatment was initiated with a MET inhibitor plus a third-generation EGFR TKI. Radiographic assessment after 2 months revealed a 33.3 percent reduction in tumor burden, achieving a PR. Furthermore, a complete resolution of pleural effusion was observed (Figure 5C,5D). As of the data cutoff, the patient maintained SD status with an ongoing response duration of 12 months.

Discussion

In this retrospective cohort study of patients with advanced EGFR-TKI-resistant NSCLC and tumor MET overexpression, combined MET inhibitor plus EGFR or ALK TKI therapy demonstrated encouraging clinical activity, yielding an ORR of 69.6% and a median PFS of 6.9 months. The cohort was largely composed of older, female, never-smoking patients with advanced disease and multiple prior systemic treatments, including a high proportion previously exposed to third-generation EGFR TKIs. These findings provide real-world evidence that concurrent EGFR and MET blockade may represent a potentially effective and tolerable strategy for managing EGFR-TKI resistance associated with MET overexpression.

MET overexpression mediates resistance to EGFR TKI therapy via several distinct yet complementary mechanisms. First, elevated MET signaling facilitates the phosphorylation and activation of ERBB3 (HER3), which reengages the PI3K-AKT and RAS-MAPK pathways independent of EGFR, thereby effectively bypassing EGFR blockade (5). Second, ligand-dependent activation of MET by HGF drives autocrine or paracrine bypass signaling that restores downstream pathway activity despite EGFR inhibition (16). Third, overexpressed MET participates in receptor cross-phosphorylation and complex formation with EGFR family members, amplifying downstream signaling flux and reducing cellular reliance on EGFR signaling alone (6). Finally, under the selective pressure of EGFR inhibition, preexisting MET-high subclones can clonally expand and predominate at progression, leading to the clinical phenotype of MET-mediated resistance (17). Collectively, these processes provide a robust biological rationale for dual targeted therapy with EGFR TKI and MET inhibitors in appropriately selected patients.

Our findings are aligned with recent clinical trial data supporting dual targeted therapy with EGFR TKI and MET inhibitors. The multi-arm phase Ib TATTON study evaluated Osimertinib in combination with several agents and demonstrated that patients with EGFR mutant NSCLC whose tumors harbored MET overexpression or amplification could achieve clinically meaningful antitumor responses with osimertinib plus the MET inhibitor savolitinib, accompanied by an acceptable safety profile (11). The phase II SAVANNAH trial further investigated Osimertinib combined with Savolitinib in patients with EGFR mutant NSCLC and MET abnormalities. The study found that dual targeted therapy has shown a trend toward improved efficacy in patients resistant to third-generation EGFR-TKIs who exhibit high threshold levels of MET overexpression (IHC, ≥90% of tumor cells 3+) or amplification [fluorescence in situ hybridization (FISH), MET gene copy number ≥10] (13). Similarly, the INSIGHT program reported that tepotinib in combination with gefitinib for patients with MET overexpression or amplification following EGFR TKI resistance showed a trend towards improving survival compared to standard chemotherapy (10,12). In addition to prospective clinical trials, real-world evidence has also supported the clinical value of combined EGFR and MET inhibition after acquired MET dysregulation. Acker et al. provided real-world evidence that EGFR/MET co-inhibition may benefit EGFR-mutant NSCLC patients with acquired MET copy-number gain after EGFR inhibition. Although their cohort was defined by MET amplification or polysomy rather than MET protein overexpression by IHC, their findings complement our results and support dual EGFR/MET blockade after EGFR-TKI resistance (18). Although our real-world cohort differs from these researches in baseline characteristics, MET assessment methods, the specific MET inhibitors applied, the collective evidence suggests that dual EGFR and MET targeting represents a potentially effective and tolerable strategy for patients with EGFR-resistant NSCLC who develop MET overexpression.

The clinical landscape of dual EGFR and MET inhibition in NSCLC has been significantly advanced by recent landmark trials. The phase 3 SACHI trial demonstrated that the combination of savolitinib and osimertinib provides superior efficacy compared to standard chemotherapy in patients with MET-amplified tumors who progressed on prior EGFR TKI therapy, significantly extending median PFS (19). Furthermore, the FLOWERS trial explored this strategy in the first-line setting, showing that osimertinib plus savolitinib yielded a remarkable ORR of 90.5% and a median PFS of 19.6 months, compared to 60.9% and 9.3 months for osimertinib monotherapy in treatment-naive patients with MET-aberrant disease (20). The remarkable therapeutic outcomes of these dual targeted therapies align with the findings in our study, further underscoring the potent efficacy of this combination treatment strategy.

In our cohort, the combined regimen was generally tolerable. Treatment-related adverse events occurred in 19 patients (82.6%), and grade ≥3 events occurred in 4 patients (17.4%). The most common MET inhibitor-related adverse event was edema, followed by increased transaminases, gastrointestinal symptoms, rash, and headache, and electrocardiographic QT interval prolongation. Most toxicities were low grade and clinically manageable; notably, no treatment-related deaths occurred, and no patients required permanent treatment discontinuation due to adverse effects. These findings are broadly consistent with the safety profiles reported in prior combination studies, such as TATTON and SAVANNAH, which frequently identified peripheral edema, gastrointestinal disturbances, and transaminase elevations as common side effects of EGFR and MET blockade (10-13). However, it is important to acknowledge that due to the retrospective nature of this study, the incidence of adverse events may be underestimated. Some mild or manageable toxicities may not have been comprehensively documented in the medical records, and there is a potential for recall bias among patients and their families during follow-up visits. Consequently, systematic prospective reporting of toxicity grades, dose modifications, and treatment discontinuations will be essential in future studies to fully characterize the safety and tolerability of EGFR and MET co-targeting.

This study has several limitations. First, its single-center retrospective design makes it inherently vulnerable to selection bias, which may affect the representativeness of the patient population. Second, the small sample size may result in insufficient statistical power to definitively establish the efficacy and safety of dual targeted therapy in patients with EGFR-resistant and MET-overexpressing advanced NSCLC. Third, heterogeneity in treatment regimens, including the utilization of various MET inhibitors and the diverse number of prior therapeutic lines, complicates the interpretation of our data and limits the generalizability of the findings. Consequently, future prospective, multi-center studies with standardized MET assessment and uniform treatment protocols are needed to validate these observations.

From a clinical perspective, our findings underscore the importance of routine molecular reassessment upon disease progression during EGFR TKI therapy to identify the primary resistance mechanism. In patients with documented MET overexpression, dual blockade of the EGFR and MET pathways represents a rational and viable therapeutic strategy to overcome resistance and achieve sustained disease control, while maintaining a manageable safety profile.

Conclusions

In summary, these real-world data indicate that combined EGFR TKI and MET inhibition can produce meaningful antitumor activity with an acceptable safety profile in patients with advanced NSCLC who have developed resistance to EGFR TKIs and demonstrate MET overexpression.

Acknowledgments

The authors thank all the patients and their families for participating in this study, and the clinical and pathology teams at Shanghai Pulmonary Hospital for their support in patient management and data collection.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2026-0448/rc

Data Sharing Statement: Available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2026-0448/dss

Peer Review File: Available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2026-0448/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2026-0448/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. This single-center retrospective study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Ethics Committee of Shanghai Pulmonary Hospital (approval No. K25-540). Informed consent was obtained from all participants.

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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