Abstract
Background
Glucose transporter 1 (GLUT1) is a transmembrane protein responsible for the transportation of glucose across the cell membrane that is often overexpressed in cancer. Due to a key role in cancer glucose metabolism and its membranous localization GLUT1 represents a potential therapeutic target. Our study was designed to elucidate the prevalence of GLUT1 expression and potential associations with tumor phenotype as well as patient outcome in different lung cancer subtypes.
Methods
A tissue microarray containing 858 resected lung cancers was analyzed for GLUT1 expression by immunohistochemistry.
Results
GLUT1 staining was significantly more prevalent and intense in squamous cell carcinoma (SCC, 97.3%) than in pulmonary adenocarcinoma (AC, 62.9%; P<0.001). Of the 225 SCCs, GLUT1 staining was observed in 219 (97.3%) tumors and considered strong in 75.6%, moderate in 15.1%, and weak in 6.7%. In 439 ACs, GLUT1 staining was seen in 276 (62.9%) tumors and considered strong in 14.6%, moderate in 16.4% and weak in 31.9%. High GLUT1 staining was significantly linked to advanced pT stage (P=0.03), nodal metastasis (P<0.001), high grade (P<0.001) and poor overall survival (OS) (P=0.01) in ACs. In SCCs, high GLUT1 staining was unrelated to pT, pN, and histologic grade but significantly linked to OS (P=0.03).
Conclusions
It is concluded that GLUT1 expression is commonly expressed in lung cancer and that a high level of expression is linked to unfavorable tumor features and/or poor prognosis in both AC and SCC.
Keywords: Glucose transporter type 1, lung neoplasms, immunohistochemistry, biomarkers, tumor
Highlight box.
Key findings
• Glucose transporter 1 (GLUT1) is commonly expressed in lung cancer and a high level of expression is linked to unfavorable tumor features and/or poor prognosis in both pulmonary adenocarcinoma (AC) and squamous cell carcinoma (SCC).
What is known and what is new?
• GLUT1 is a transmembrane protein responsible for the transportation of glucose across the cell membrane that has been found to be often overexpressed in cancer.
• Our study shows that GLUT1 is commonly overexpressed in lung cancer with a higher level of expression in SCC than in AC, and is associated with unfavorable tumor features and/or poor prognosis in both histological subtypes of the lung.
What is the implication, and what should change now?
• Should clinical GLUT1 inhibition become available in the future, non-small cell lung cancer could represent a promising indication.
Introduction
With approximately 125,000 annual cancer deaths in the U.S. alone, lung cancer remains the leading cause for cancer-related deaths worldwide (1). Non-small cell lung cancers (NSCLCs) account for the majority of lung cancer cases (~85%) and are considered one of the two major clinical types alongside the small cell lung carcinomas (SCLCs) (2). The most common histological NSCLC subtype are adenocarcinomas (ACs), followed by squamous cell carcinomas (SCCs) (3). New therapeutic strategies such as targeted therapy of oncogenic-driven NSCLC and immunotherapies to enhance the body’s own cancer defenses have fundamentally changed the treatment of NSCLC (4). However, the 5-year survival rate remains at around 20%, reflecting the poor overall prognosis associated with lung cancer (5). This underlines the urgent need for further systemic treatment options, as well as prognostic and predictive biomarkers to identify NSCLC patients who might benefit from alternative treatment approaches (6).
Glucose transporter 1 (GLUT1) has previously been proposed as a prognostic molecular marker and potential novel therapeutic target in lung cancer (7-9). GLUT1, being responsible for basal glucose uptake, is the most widely expressed member of the glucose transporter (GLUT) family (9). The membrane-bound GLUTs mediate the transportation of glucose across the cell membrane, a crucial step of the cellular energy metabolism (7,8). Cancer cells undergo metabolic reprogramming, switching from oxidative phosphorylation to a usually less effective glycolysis dominated metabolism (7,10). To meet the increased energy demand of cancer cells due to uncontrolled growth, the cells increase their glucose uptake by overexpressing glucose transporters such as GLUT1 (7). Elevated GLUT1 expression has been found in various cancer types and has been associated with poor patient prognosis in some of these cancers (11-14). Of particular interest, studies examining GLUT1 expression in pulmonary cancers, described varying expression levels in the different subtypes of lung cancer (15-17) and proposed a link between high expression and poor prognosis in NSCLC (18,19).
It was the aim of this study to gain further knowledge on the prevalence and potential prognostic role of GLUT1 expression in different NSCLC subtypes. Immunohistochemistry (IHC) was used to investigate the relationship between GLUT1 expression and clinicopathological parameters of tumor aggressiveness as well as patient outcome in more than 850 lung cancers in a tissue microarray (TMA) format. We present this article in accordance with the REMARK reporting checklist (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2025-422/rc).
Methods
Tissue microarrays (TMAs)
Our TMA set was composed of one sample each from 858 resected lung cancers. All samples were from the archives of the Institute of Pathology, University Medical Center Hamburg-Eppendorf, Germany. Available histopathological data including tumor stage (pT), grade, lymph node status (pN) and resection margin (R) are shown in Table 1. Clinical follow-up data [overall survival (OS)] were available from 431 patients with AC and 207 patients with SCC. Tissues were fixed in 4% buffered formalin and then embedded in paraffin. The TMA manufacturing process was described earlier in detail (20,21). Briefly, one tissue spot (diameter: 0.6 mm) per patient was taken from a cancer containing tumor block by using a semi-automated homemade tissue arrayer. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Ethic Committee Medical Council Hamburg (No. WF-049/09) and informed consent was not required for this study in accordance with local laws (§14 HambKhG).
Table 1. Study cohort (n=858).
| Tumor entity | Items | Values |
|---|---|---|
| Histological subtype | Adenocarcinoma | 470 (54.8) |
| Squamous cell carcinoma | 235 (27.4) | |
| Mesothelioma | 50 (5.8) | |
| Carcinoid | 52 (6.1) | |
| Large cell neuroendocrine carcinoma | 16 (1.9) | |
| Large cell carcinoma | 7 (0.8) | |
| Carcinosarcoma | 2 (0.2) | |
| Pleomorphic carcinoma | 14 (1.6) | |
| Adenosquamous carcinoma | 8 (0.9) | |
| Low-grade mucoepidermoid carcinoma | 1 (0.1) | |
| Lymphoepithelial carcinoma | 1 (0.1) | |
| SMARCA4-deficient undifferentiated tumor | 2 (0.2) | |
| Adenocarcinoma | Follow-up (months) | 15.2 (mean) |
| Censored (alive) | 383 (88.9) | |
| Failed (dead) | 48 (11.1) | |
| Gender | ||
| Female | 258 (55.8) | |
| Male | 204 (44.2) | |
| Stage | ||
| pT1 | 157 (36.0) | |
| pT2 | 165 (37.8) | |
| pT3 | 58 (13.3) | |
| pT4 | 56 (12.8) | |
| Nodal stage | ||
| pN0 | 280 (68.6) | |
| pN+ | 128 (31.4) | |
| Grade | ||
| 1–2 | 69 (37.9) | |
| 3 | 113 (62.1) | |
| Resection margin | ||
| R0 | 420 (93.8) | |
| R+ | 28 (6.2) | |
| Squamous cell carcinoma | Follow-up (months) | 14.9 (mean) |
| Censored (alive) | 172 (83.1) | |
| Failed (dead) | 35 (16.9) | |
| Gender | ||
| Female | 70 (30.3) | |
| Male | 161 (69.7) | |
| Stage | ||
| pT1 | 58 (25.5) | |
| pT2 | 66 (29.1) | |
| pT3 | 43 (18.9) | |
| pT4 | 60 (26.4) | |
| Nodal stage | ||
| pN0 | 134 (59.8) | |
| pN+ | 90 (40.2) | |
| Grade | ||
| 1–2 | 35 (38.0) | |
| 3 | 57 (61.9) | |
| Resection margin | ||
| R0 | 204 (90.7) | |
| R+ | 21 (9.3) |
Data are presented as n (%) unless otherwise specified. The percentages refer to the fraction of samples across each category. Because of cases with missing data, the numbers in the different categories do not always add up to the total number of cases. pN, pathological lymph node status; pT, pathological tumor stage; TMA, tissue microarray.
Immunohistochemistry (IHC)
Freshly cut TMA sections were immunostained on one day and in one experiment. Slides were deparaffinized with xylol, rehydrated through a graded alcohol series and exposed to heat-induced antigen retrieval for 5 minutes in an autoclave at 121 ℃ in pH 7.8 Tris-EDTA-Citrat (TEC) puffer. Endogenous peroxidase activity was blocked with Dako REAL Peroxidase-Blocking Solution (Agilent Technologies, Santa Clara, CA, USA; #S2023) for 10 minutes. Primary antibody specific for GLUT1 (recombinant rabbit monoclonal, MSVA-401R, MS Validated Antibodies GmbH, Hamburg, Germany; #4457-401R) was applied at 37 ℃ for 60 minutes at a dilution of 1:150. Bound antibody was then visualized using the Dako REAL EnVision Detection System Peroxidase/DAB+, Rabbit/Mouse kit (Agilent Technologies, Santa Clara, CA, USA; #K5007) according to the manufacturer’s directions. The sections were counterstained with hemalaun. For tumor tissues, the percentage of positive neoplastic cells was estimated, and the staining intensity was semi-quantitatively recorded (0, 1+, 2+, 3+) (22). For statistical analyses, the staining results were categorized into four groups. Tumors without any staining were considered negative. Tumors with 1+ staining intensity in ≤70% of tumor cells or 2+ intensity in ≤30% of tumor cells were considered weakly positive. Tumors with 1+ staining intensity in >70% of tumor cells, 2+ intensity in 31–70%, or 3+ intensity in ≤30% of tumor cells were considered moderately positive. Tumors with 2+ intensity in >70% or 3+ intensity in >30% of tumor cells were considered strongly positive. The evaluation was performed by an experienced pathologist (SS).
Statistical analysis
Statistical calculations were carried out using the JMP17® software (SAS®, Cary, NC, USA). Associations between GLUT1 immunostaining and tumor phenotype were investigated using contingency tables and the chi2-test. The Kaplan-Meier method was used to calculate survival curves. A log-rank test was applied to determine significant differences between groups. Cox proportional hazards regression analysis was conducted to determine the independence and significance between pathological, molecular and clinical variables.
Results
GLUT1 immunohistochemistry
Among normal tissues, GLUT1 immunostaining was weak in normal respiratory epithelium and absent in alveolar cells of the lung. GLUT1 staining was mostly membranous but some tumors showed cytoplasmic positivity. A GLUT1 staining was seen in 570 (70.81%) of the 805 interpretable cancers, including 194 (24.1%) with weak, 120 (14.9%) with moderate, and 256 (31.8%) with strong positivity. Representative images are shown in Figure 1. GLUT1 positivity was significantly more prevalent and intense in SCC (97.3% positive) than in AC (62.9%; P<0.001; Table 2). GLUT1 expression was also common in large cell neuroendocrine carcinomas (LCNEC, 93.7% positive) and large cell carcinomas (85.7%) as well as in malignant mesotheliomas (57.9%). GLUT1 staining was mostly absent in lung carcinoid tumors (7.7%). Of the 225 SCCs, GLUT1 staining was observed in 219 (97.3%) tumors and considered strong in 75.6%, moderate in 15.1% and weak in 6.7%. In 439 ACs, GLUT1 staining was seen in 276 (62.9%) tumors and considered strong in 14.6%, moderate in 16.4% and weak in 31.9%.
Figure 1.
GLUT1 immunostaining in normal and neoplastic lung tissue. GLUT1 staining was absent in the alveolar cells of lung (A), weak and predominantly membranous in (non-basal) cells of the respiratory epithelium (B), strong and predominantly membranous in an adenocarcinoma (C) and a squamous cell carcinoma (D), weak to moderate in an adenocarcinoma (E) and a squamous cell carcinoma (F) and absent in an adenocarcinoma (G) and a squamous cell carcinoma (H). Magnification: (A,C-H) 100×; (B) 400×. GLUT1, glucose transporter 1.
Table 2. GLUT1 immunostaining in lung cancer.
| Tumor entity | n | GLUT1 immunostaining results | P | |||
|---|---|---|---|---|---|---|
| Negative (%) | Weak (%) | Moderate (%) | Strong (%) | |||
| Adenocarcinoma | 439 | 37.1 | 31.9 | 16.4 | 14.6 | <0.001* |
| Squamous cell carcinoma | 225 | 2.7 | 6.7 | 15.1 | 75.6 | |
| Mesothelioma | 38 | 42.1 | 44.7 | 7.9 | 5.3 | |
| Carcinoid | 52 | 92.3 | 7.7 | 0.0 | 0.0 | |
| Large cell neuroendocrine carcinoma | 16 | 6.3 | 56.3 | 12.5 | 25.0 | |
| Large cell carcinoma | 7 | 14.3 | 57.1 | 0.0 | 28.6 | |
| Carcinosarcoma | 2 | 0.0 | 0.0 | 0.0 | 100 | |
| Pleomorphic carcinoma | 14 | 0.0 | 14.3 | 50.0 | 35.7 | |
| Adenosquamous carcinoma | 8 | 0.0 | 0.0 | 12.5 | 87.5 | |
| Low-grade mucoepidermoid carcinoma | 1 | 0.0 | 100 | 0.0 | 0.0 | |
| Lymphoepithelial carcinoma | 1 | 0.0 | 0.0 | 100 | 0.0 | |
| SMARCA4-deficient undifferentiated tumor | 2 | 0.0 | 100 | 0.0 | 0.0 | |
GLUT1, glucose transporter 1. *, adenocarcinoma versus squamous cell carcinoma.
High GLUT1 staining was significantly linked to advanced pT stage (P=0.03), nodal metastasis (P<0.001) and higher grade (P<0.001) in ACs but not significantly related to these parameters in SCCs (Table 3). Univariate outcome analysis revealed significant associations with OS in all lung tumors if tumor groups with negative, weak, moderate, and strong staining were compared (Figure 2A-2C). If tumors were categorized into low (negative/weak) and high expressors (moderate/strong), the differences in patient outcome became more apparent and reached significance in all lung tumors, ACs, and SCCs (Figure 2D-2F). Multivariate analysis showed that GLUT1 was not an independent prognostic factor for OS (Table 4).
Table 3. GLUT1 and cancer phenotype.
| Tumor entity | n | GLUT1 immunostaining results | P | |||
|---|---|---|---|---|---|---|
| Negative (%) | Weak (%) | Moderate (%) | Strong (%) | |||
| Adenocarcinoma | ||||||
| Stage | 0.03 | |||||
| pT1 | 144 | 47.2 | 32.6 | 10.4 | 9.7 | |
| pT2 | 158 | 33.5 | 34.8 | 15.8 | 15.8 | |
| pT3 | 54 | 33.3 | 22.2 | 25.9 | 18.5 | |
| pT4 | 53 | 28.3 | 32.1 | 20.8 | 18.9 | |
| Nodal stage | <0.001 | |||||
| pN0 | 262 | 44.3 | 30.2 | 14.1 | 11.5 | |
| pN+ | 120 | 21.7 | 35.0 | 21.7 | 21.7 | |
| Grade | <0.001 | |||||
| Grade 1–2 | 67 | 65.7 | 29.9 | 4.5 | 0.0 | |
| Grade 3 | 111 | 22.5 | 41.4 | 19.8 | 16.2 | |
| Squamous cell carcinomas | ||||||
| Stage | 0.07 | |||||
| pT1 | 56 | 7.1 | 1.8 | 12.5 | 78.6 | |
| pT2 | 66 | 1.5 | 7.6 | 19.7 | 71.2 | |
| pT3 | 37 | 0.0 | 2.7 | 21.6 | 75.7 | |
| pT4 | 58 | 1.7 | 10.3 | 6.9 | 81.0 | |
| Nodal stage | 0.48 | |||||
| pN0 | 125 | 2.4 | 4.0 | 15.2 | 78.4 | |
| pN+ | 89 | 3.4 | 9.0 | 14.6 | 73.0 | |
| Grade | 0.91 | |||||
| Grade 1–2 | 34 | 2.9 | 2.9 | 17.6 | 76.5 | |
| Grade 3 | 54 | 1.9 | 5.6 | 14.8 | 77.8 | |
| Total | 88 | 2.3 | 4.5 | 15.9 | 77.3 | |
GLUT1, glucose transporter 1; pN, pathological lymph node status; pT, pathological tumor stage.
Figure 2.
GLUT1 and prognosis in lung cancer. The panels show the impact of GLUT1 staining levels on overall survival in all lung cancers (A), AC (B), and SCC (C). The panels (D-F) describe the same patient cohorts after a dichotomous categorization of tumors into low (negative/weak) and high expression (moderate/strong) for all cancers (D), AC (E), and SCC (F). AC, adenocarcinoma; GLUT1, glucose transporter 1; SCC, squamous cell carcinoma.
Table 4. Multivariate analysis of GLUT1 expression.
| Tumor entity | Analyzable (n) | P value | |||
|---|---|---|---|---|---|
| pT stage | Nodal stage | Grade | GLUT1 expression | ||
| All subtypes | 269 | 0.46 | 0.03 | 0.36 | 0.29 |
| Adenocarcinoma of the lung | 148 | 0.01 | 0.051 | 0.71 | 0.40 |
| Squamous cell carcinoma of the lung | 68 | 0.57 | 0.09 | 0.77 | 0.20 |
GLUT1, glucose transporter 1; pT, pathological tumor stage.
Discussion
In this study, more than 850 lung tumors were examined for the expression pattern of GLUT1. We report a higher prevalence and intensity of GLUT1 expression in SCC (97.3% positivity in our study) than in AC (62.9% positivity), which is in line with previous studies describing a significant correlation between GLUT1 expression and a squamous cell histology. These differences may indicate potential metabolic differences between these NSCLC subtypes (15,17). Previous studies, analyzing smaller patient cohorts, reported a GLUT1 expression between 54.7–100.0% (23,24) in SCC and 18.7–100.0% (16,25) in AC. Possible reasons for these reported discrepancies in GLUT1 positivity rates between studies include, but are not limited to, differences in the IHC protocols and antibodies used, thresholds defining positivity and the composition of the patient cohorts. It is of note that the antibody used for our assay has previously been validated according to the guidelines of the International Working Group for Antibody Validation (IWGAV) by comparing with RNA expression data and results obtained by an independent second antibody on more than 600 samples from 76 different normal tissue types (26). The validation of antibodies on such a broad range of different normal tissues enables the evaluation of virtually all proteins and their posttranslational modifications for potential cross-reactivities.
Key result of our study is the significant correlation between high GLUT1 expression and unfavorable tumor features and/or poor prognosis in NSCLC as well as the subgroups of both AC and SCC. To date several studies have reported a link between high GLUT1 expression and an unfavorable tumor phenotype or poor prognosis in cohorts of NSCLCs without subclassification or in cohorts of ACs. Koh et al. (27) have demonstrated a significant association between high GLUT1 levels and lymphovascular invasion, advanced pT stage, nodal and distant metastasis, as well as poor OS in a series of 158 ACs. Maki et al. (28) linked GLUT1 expression to a larger tumor size, invasive growth, several molecular alterations and reduced survival in a series of 105 ACs. Ito et al. (23) showed a significant link of high GLUT1 expression with lymphatic and pleural invasion in non-squamous NSCLCs (n=325) and poor OS in NSCLC (n=445), while they could not find any associations between GLUT1 expression and clinicopathological features in 120 SCCs. Others reported on an aggressive tumor behavior or poor OS in GLUT1 positive lung cancers without differentiating between different histological subtypes (17). For the future, it appears desirable that studies investigating prognostic markers in NSCLC include markedly larger patient cohorts in order to obtain clearer and more unequivocal data.
A role of GLUT1 expression for conferring increased aggressiveness to tumor cells is also supported by data from other tumor entities and data obtained through functional studies. These studies have identified associations between GLUT1 expression and aggressive tumor features or poor prognosis in gastric (11), esophageal (12), pancreatic (13) and colorectal (14) cancer. Using the same methodological approach as in the present study, we have previously identified significant associations between high GLUT1 expression and aggressive phenotype in urothelial carcinoma, clear cell and papillary renal cell carcinoma, as well as colorectal, gastric, pancreatic and ovarian cancer (Büyücek et al., manuscript submitted). The best known and probably most important cancer promoting mechanisms associated with GLUT1 is its role in transmembrane glucose uptake, which enables alternative or additional energy production through glycolysis (10,29). However, GLUT1 upregulation in pulmonary cancer has been found to not only stimulate glycolysis (30), but also to play a role in cell cycle regulation (31), cell proliferation (31), inhibition of apoptosis (31), migration and invasion (32), as well as the induction of several other cancer-related signaling pathways. GLUT1 has been shown to increase the expression of different cyclins (31), to decrease the expression of p53 (31) and to promote the integrin ß1/Src/FAK signaling pathway in NSCLC (31). High GLUT1 expression has also been linked to KRAS (Kirsten rat sarcoma viral oncogene homolog) mutations and is suggested to confer immunogenic properties in lung AC (9). Moreover, GLUT1 can prevent EGFR degradation by interaction with the phosphor-epidermal growth factor receptor (p-EGFR) (32). In this context GLUT1 knock-down invoked decreased proliferation, migration and invasion in lung AC cells (32).
Alterations in glucose metabolism are considered a major factor for development and progression of lung cancer (30). Targeting glycolysis in lung cancers and thereby its energy supply, appears to be an approach with great potential for clinical application (30). As a key driver of glycolysis in cancer cells and due to its transmembrane localization, GLUT1 represents a promising therapeutic target (7). Based on cell assays and animal models, various GLUT1 Inhibitors have been identified and developed, including natural products such as flavones or polyphenols (8) and small molecules like Fasentin (33), WZB117 (34) or BAY-876 (35-37). For example, WZB117 led to a downregulation of glycolysis, induced cell-cycle arrest and significantly inhibited cell growth in lung cancer cell lines and reduced tumor growth in NSCLC mouse models (34). However, despite promising preclinical findings, none of the anti-GLUT1 compounds evaluated so far has advanced to clinical trials, highlighting the challenges in translating these experimental findings into viable treatment options.
Conclusions
In conclusion, our study shows that GLUT1 is commonly overexpressed in lung cancer with a higher level of expression in SCC than in AC. A high expression level of GLUT1 is associated with unfavorable tumor features and/or poor prognosis in both AC and SCC of the lung. Should clinical GLUT1 inhibition become available in the future, NSCLC could therefore represent a promising indication.
Supplementary
The article’s supplementary files as
Acknowledgments
We are grateful to Laura Behm, Melanie Steurer, Inge Brandt, and Sünje Seekamp for excellent technical assistance.
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. The study was approved by the Ethic Committee Medical Council Hamburg (No. WF-049/09) and informed consent was not required for this study in accordance with local laws (§14 HambKhG).
Footnotes
Reporting Checklist: The authors have completed the REMARK reporting checklist. Available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2025-422/rc
Funding: This work was supported by European Union’s Horizon 2020 programme through the I3LUNG project under the call topic “HORIZON-HLTH-2021-CARE-05-02” (grant No. 101057695).
Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2025-422/coif). All authors reported that this work was supported by European Union’s Horizon 2020 programme through the I3LUNG project under the call topic “HORIZON-HLTH-2021-CARE-05-02” (grant No. 101057695). D.B.E. was participant of unpaid Advisory Board of Cosinuss GmbH, received travel support by Metronic Gmbh and is presenter during workshops for Schleswig-Holstein Swimming Federation. M.R. received consulting fees from Amgen, AstraZeneca, Beigene, Boehringer-Ingelheim, BMS, Lilly, Merck, MSD, Mirati, Novartis, GSK, Pfizer, Roche, Regeneron, Sanofi, Daiichi-Sankyo, and Janssen; and for support for attending meetings and/or travel, and honoraria for lectures, presentations, speakers bureaus; as well as from Daiichi and Sanofi for participation on a Data Safety Monitoring Board or Advisory Board. S.v.W. received payments from AstraZeneca, Boehringer-Ingelheim, BMS, Intuitive, Johnson & Johnson, MSD, Novocure, Olympus, and Roche in the form of consulting fees; from AstraZeneca, Boehringer-Ingelheim, BMS, Covidien, Johnson & Johnson, MedXpert, MSD, Novocure, Olympus, and Roche for honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events; from AstraZeneca, Boehringer-Ingelheim, BMS, Covidien, Johnson & Johnson, Livsmed, MedXpert, MSD, Novocure, Olympus, and Roche for support for attending meetings and/or travel; and from Pfm medical for participation on a data safety monitoring board or advisory board. The authors have no other conflicts of interest to declare.
Data Sharing Statement
Available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2025-422/dss
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