SMARCA4-deficient non-small cell lung carcinoma: clinicodemographic, computed tomography, and positron emission tomography-computed tomography features

Introduction

Over the past decade, there has been a dramatic advancement in the field of non-small cell lung carcinoma (NSCLC) treatment (1). Recent discoveries of mutation in multiple oncogenic driver genes in NSCLC enabled personalized targeted therapy and being readily adapted into clinical practice (2-6). However, despite the recent innovation, many patients still suffer from frequent tumor recurrence and metastasis due to inevitable drug resistance (7). Further study by La Fleur et al. have revealed that NSCLC is a complex entity consisting of multiple diseases at a molecular level, which are not only related with oncogenic-based mutations but also tumor suppressor genes mutation due to loss-of-function or deletions (8).

The SMARCA4 gene, which is responsible for the transcription activator BRG1, is one of the most common anomalous ATP-dependent catalytic subunits of SWI/SNF chromatin-remodeling complexes participating in the activation or repression of transcriptional processes in various types of cancer (9). Loss of the BAF (SWI/SNF) complex subunit (also known as BRG1) was first reported in 2000 by Wong et al. in various cell lines of prostatic, breast, and pancreatic carcinomas, proving the role of BAF (SWI/SNF) complex as a tumor suppressor gene (10). In thorax, SMARCA4 deficiency appears as two different phenotypes: SMARCA4-deficient undifferentiated tumor (SD-UT; formerly known as SMARCA4-deficient sarcoma) and SMARCA4-deficient non-small cell lung carcinoma (SD-NSCLC). Previous study of Reisman et al. have shown that SMARCA4 deficiency can be occasionally seen in conventional NSCLC with poorer prognosis (11). In 2015, Le Loarer et al. reported a case series of SD-UT in 19 patients with following features: young male smokers, a rapidly enlarging thoracic mass with rhabdoid morphological features, undifferentiated immunophenotype, and a very aggressive clinical course (12).

Currently, SD-NSCLC is recognized as relatively rare tumor, which occurs in 5–10% of NSCLC (13). According to the 8^th edition of World Health Organization (WHO) thoracic tumor classification system, only SD-UT is recognized as a separate disease entity, distinguished from SD-NSCLC (14). However, differentiation between SD-NSCLC and SD-UT may be difficult and sometimes impossible due to the shared biological continuum between both entities (15). In fact, these tumors are closely linked at a molecular level as they share the same genomic alterations, which is typical of smoking related NSCLC (KRAS, KEAP1, STK11) and a high tumor mutational load (12,16). For treatment of SD-NSCLC, radical surgical excision which resulted in complete remission in resectable cases has been reported (17); however, it is often presented at an advanced stage and generally insensitive to palliative treatment such as chemotherapy and radiotherapy (18). Recently, immune checkpoint blockade (ICB) has shown a promising but inconsistent response in SMARCA4-mutant NSCLC, from favorable to poor or even hyper-progression (19,20). Although yet to be evaluated, the presence of SMARCA4 mutations opens a wide variety of therapeutic possibilities using targeted therapy (21).

To the best of our knowledge, there have been only few studies regarding SD-NSCLC, especially with emphasis on the imaging features of computed tomography (CT), and positron emission tomography (PET)-CT (18,22). Therefore, the aim of our study was to retrospectively assess the clinical, demographic, and imaging features of SD-NSCLC, and compare with previous reported features of SD-UT to observe possible differentiating characteristics. We present this article in accordance with the STROBE reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-1606/rc).

Methods

Patient selection

The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The institutional review board of Samsung Medical Center approved this retrospective study (IRB file No.: 2023-02-010), and the requirement for patient consent to use clinical data was waived due to retrospective study design. We searched electronic medical records between January 2018 to November 2022, among patients who underwent transbronchial lung or lymph node biopsy, percutaneous core needle lung biopsy, and curative lung resection surgery at Samsung Medical Center, a tertiary referral hospital located in Seoul, Republic of Korea. By using the term “SMARCA4 deficient non-small cell lung cancer”, we found nine patients with pathological confirmation of SD-NSCLC.

Clinical and pathologic assessment

Two of the authors (J.H.K., Y.K.C.) reviewed electronic medical records for clinicopathologic data of the patients, as follows: age, sex, smoking history, and pack-years if available. In all nine patients, the histopathologic reports were recorded. Five patients underwent curative resection, and subsequently staged based on the 8^th edition of the American Joint Committee on Cancer (AJCC) TNM classification. Pathologic specimens were examined by pathologists who reported the pathologic findings using the latest edition of the WHO classification thoracic tumor classification system. In four patients without surgical resection, diagnosis of SD-NSCLC was confirmed through either percutaneous lung (n=1) or lymph node (n=3) biopsy.

Image acquisition

CT studies from various helical CT scanners (from 16- to 64-MDCT scanners) from several vendors were performed. The scanning parameters were 120 kVp and 100 to 150 mAs under automatic exposure control; beam width, 10 to 20 mm; and rotation time, 0.3 to 0.4 seconds. CT image data were reconstructed using standard soft-tissue algorithms, with a section thickness of 2.5 to 3.0 mm for axial images. Both contrast and noncontrast CT scans were obtained. Intravenous (IV) contrast medium injection was given in all patients: 1.5 mL/kg of body weight of iobitridol (300 mg I/mL; Xenetics, Guerbet, Aulnay-sous-Bois, France) was injected at an infusion rate of 3 mL/s using a power injector (MCT Plus, Medrad, Pittsburgh, USA). Both mediastinal (width, 400 HU; level, 20 HU) and lung (width, 1,500 HU; level, −700 HU) window settings were adapted during image review.

All nine patients included in our analysis performed both CT and PET-CT studies in our institution. Before PET-CT examinations, all patients fasted for at least 6 hours. Blood glucose level was measured before injection of ¹⁸F-fluorodeoxyglucose (FDG), targeting <150 mg/dL for the examination. Whole-body PET and noncontrast CT images were performed using two PET-CT scanners (Discovery LS and Discovery STe, GE Healthcare, Chicago, USA) 60 minutes after FDG injection (5.5 MBq/kg). A whole-body CT with Discovery LS scanner adapted continuous helical technique with 8-MDCT (140 keV; 40–120 mAs; section width, 5 mm). PET was acquired from the head to middle thigh for 4 minutes per frame in the 2D mode after CT scan. Attenuation-corrected PET images (4.3×4.3×3.9 mm) were reconstructed from the CT data using an ordered subset expectation maximum (OSEM) algorithm (28 subsets, 2 iterations). A whole-body CT with Discovery STe scanner adapted a continuous helical technique with 16-MDCT (140 keV; 30–170 mAs; section width, 3.75 mm). PET scans were obtained from the head to middle thigh for 2.5 minutes per frame in the 3D mode after CT scan. Attenuation-corrected PET images (3.9×3.9×3.3 mm) were reconstructed from the CT data using a 3D OSEM algorithm (20 subsets, 2 iterations). The standardized uptake value (SUV) was calculated based on the injected dose of FDG and body weight of the patient.

Image interpretation

CT studies were reviewed by three radiologists with thoracic CT interpretation experience of 5, 8 and 16 years, and all decisions were made by consensus. Multiple CT imaging features were assessed: tumor size (maximum, in mm), attenuation value (in HUs), net enhancement (attenuation difference between enhanced and unenhanced images), tumor margin (well or poorly defined), contour (round, lobulated, or spiculated), presence of necrotic component, calcification, and pleural tagging within the primary tumor. Tumor size was determined as the longest diameter among three planes (axial, coronal, and sagittal). When measuring tumor attenuation, the region of interest (ROI) covering more than half of the tumor diameter was adopted on both enhanced and unenhanced images and values were subtracted to calculate the net enhancement. Tumor margin was characterized as either well- or poorly-defined. A well-defined margin was defined as a distinct interface between a lesion and the surrounding parenchyma at more than 50% of the imaged circumference and otherwise considered as poorly defined. Contour was described as round, lobulated, or spiculated. A spiculated margin was defined as a thickening and distorted line radiating from the nodular surface. The tumor distribution was determined by dividing the lung into inner and outer regions at the midline on CT images. Tumors with their center located medial to the midline were considered central, and those located lateral to the midline were considered peripheral (23). Additional image findings such as enlarged lymph nodes in the hilum (>10 mm in short axis) and mediastinum (>10 mm in short axis), presence of pleural thickening or nodularity, and pleural effusion were also evaluated.

Due to high prevalence of smokers in SMARCA4-deficient tumor, we also evaluated the presence of emphysema and subsequently graded based on Fleischner Society CT-based visual classification (mild, moderate, confluent, and advanced destructive emphysema) (9,24). In PET-CT, the FDG uptake of the tumor was compared with that of the mediastinal blood pool. Positive uptake was defined as higher FDG uptake of the tumor than of the mediastinal blood pool. Then SUV was measured, and the maximum SUV (SUV_max) was determined. Furthermore, FDG uptake pattern were also evaluated and categorized into three patterns: diffuse, curvilinear, or crisscross patterns.

Statistical analysis

The presentation of continuous variables included the mean and range, while categorical variables were expressed as counts and percentages (%). All statistical analyses were performed using SPSS (version 25.0).

Results

Demographic and clinical findings

Demographic and clinical features of nine cases of SD-NSCLC are summarized in Table 1. All patients were male and the median age at the time of diagnosis was 64 years (range, 46–74 years). Only one (11.1%) patient had symptoms of hoarseness, cough, and sputum at initial presentation. Eight (88.9%) patients were asymptomatic and incidentally diagnosed through routine heath check-up. All nine patients were either current or ex-smokers (five current smokers, four ex-smokers; average pack-years, 51.9).

Imaging findings

Characteristic imaging features with detailed description of all cases of SD-NSCLC are summarized in Tables 2,3. In CT, tumors were in form of either solitary nodules (n=4, 44.4%) or masses (n=5, 55.6%). Median tumor size was 42 mm (range, 8–62 mm) and all tumors showed well-defined margins (n=9). Most tumors appeared as lobulated contour (n=8, 88.9%), and only one case showed spiculation. After IV injection of contrast medium, measured net enhancement values ranged from 8 to 43 HU (median, 24 HU). There was no evidence of necrotic change or calcification within the tumors in all nine cases. In seven (77.8%) patients, the tumors were located at the peripheral portion of the lung, and only two (22.2%) cases were located at the central portion. In seven (77.8%) cases, the tumors showed direct pleural and chest wall invasion, regardless of small tumor size (Figure 1). Five (55.6%) of nine patients showed enlarged lymph nodes in hilar, mediastinal, and supraclavicular areas, and two (22.2%) patients showed necrotic changes within the enlarged lymph nodes (Figure 2). All nine patients had smoking history, and five (55.6%) patients showed mild degree of centrilobular emphysema in CT, graded based on the Fleischner Society CT-based visual classification. For metastasis, four (44.4%) patients showed intra- or extrathoracic metastasis at the time of diagnosis. Metastases involved bone in three (33.3%) patients (all with multiple areas), and lung in one (11.1%) patient.

Figure 1 A representative case of SMARCA4-deficient non-small cell lung cancer. A 67-year-old man presented with left upper lobe nodule, incidentally detected during health check-up. Unenhanced and enhanced CT scan (A,B) shows a 26 mm sized relatively well-defined subpleural nodule in left upper lobe, and it shows heterogeneous enhancement (ΔHU =35). On axial and coronal enhanced CT scan (C-E) left upper lobe nodule shows invasion to adjacent chest wall. On MIP (F) and fusion image of PET-CT (G), the nodule shows diffuse and intense ¹⁸F-FDG uptake, showing SUV_max of 12.7. (H) The photograph of gross specimen shows 28×28×20 mm sized mass, and (I) photomicrograph obtained at low magnification shows invasion of the tumor (arrow; hematoxylin and eosin stain) to adjacent chest wall. Photomicrograph (hematoxylin and eosin stain) shows two different cores within the tumor; (K) areas with poorly differentiated adenocarcinoma (hematoxylin and eosin stain, ×100), (L) large pleomorphic tumor cells (hematoxylin and eosin stain, ×400). On BRG1 (SMARCA4) immunostaining (J), it shows a loss of SMARCA4 nuclear expression in tumor cells (*) in contrast with normally stained inflammatory cells (▲) (BRG1 immunohistochemical stain, ×400). CT, computed tomography; MIP, maximum-intensity-projection; PET, positron emission tomography; FDG, fluorodeoxyglucose; SUV_max, maximum standardized uptake value.

Figure 2 A 63-year-old man with SMARCA4-deficient non-small cell lung cancer. Unenhanced (A,D) and enhanced (B,E) CT scans show enhancing nodule with lobulated contour in right lower lobe periphery, and the nodule shows chest wall invasion (arrow). On enhanced CT (F), it shows multiple enlarged lymph nodes with necrotic changes in subcarinal and right interlobar areas. On MIP (G) and fusion image of PET-CT (C), the nodule shows diffuse intense FDG uptake (SUV_max =14.9). On MIP (G) right axillary, right hilar and right mediastinal also show FDG uptake (open arrows), suggesting metastasis. CT, computed tomography; MIP, maximum-intensity-projection; PET, positron emission tomography; FDG, fluorodeoxyglucose; SUV_max, maximum standardized uptake value.

FDG PET-CT and pathologic findings

FDG PET-CT was performed in all nine patients included in our analysis. FDG accumulation within the tumor was relatively intense, and the median value of measured SUV_max was 13.5 (range, 9.5–16.5). In all cases, there were diffuse uptake patterns, and no curvilinear nor crisscross patterns were observed.

All nine cases showed presence of differentiated histology in pathologic specimens (either glandular or squamous). Presence of differentiated histology in SD-NSCLC is known to be a distinct feature from SD-UT, as SD-UT are generally associated with undifferentiated or rhabdoid morphology (25). Moreover, all nine cases showed TTF1 negativity, which is known to be found in 80% of SWI/SNF-deficient lung adenocarcinoma, which led to further evaluation of SMARCA4 (BRG1) and SMARCA2 (BRM).

Treatment and prognosis

Five (55.6%) patients received surgical resection with mediastinal lymph node dissection, and the resection was complete with negative resection margin in all cases. Mediastinal nodal metastases were not observed. In two (22.2%) patients, tumor invasion of parietal pleura of the chest wall was observed, and other two patients showed superficial invasion of pleural connective tissue, not beyond the elastic layer of the visceral pleura. After surgical resection was performed, three (60%) of five patients had performed adjuvant chemotherapy. All five patients who had undergone the curative resection have survived and there was no recurrence on follow-up imaging studies.

Four (44.4%) patients who had intra- or extrathoracic metastatic disease at the time of diagnosis, palliative chemotherapy was performed instead of surgical resection. Two of four patients with chemotherapy showed poor clinical outcomes. One patient showed very poor clinical outcome (expired within 6 months of chemotherapy), and another patient showed rapid disease progression in the form of new metastasis involving bone, within 4 months after treatment. In other two patients with chemotherapy, the primary tumor and metastatic lesions showed overall decrease in size and extent during follow-up. In overall, eight of nine patients survived after median follow-up periods of 5.2 months (range, 2–10 months).

Discussion

Due to the rarity of SD-NSCLC, only a very limited number of research regarding CT and PET-CT imaging and clinicopathologic features of SD-NSCLC have been reported to date (26,27). To the best of our knowledge, our study is the largest to focus on the clinical, imaging, and pathologic findings of the SD-NSCLC. Our results showed that SD-NSCLC has a strong tendency to show a peripheral distribution, lobulated contour, high proportion of pleural invasion regardless of small size, and clinical predilection of male patients with smoking history. Currently, distinction between SD-NSCLC and SD-UT is required not only for the accurate diagnosis according to WHO classification of lung tumors, but also for the appropriate targeted therapies which is often crucial for patient survival (14,18). However, in small biopsies with poor morphology, unusual immune profiles and with sarcomatoid areas, differentiation between SMARCA4-deficient NSCLC and SMARCA4-UT is difficult and sometimes impossible (18). Genomic profiling is unlikely to add diagnostic value, since SMARCA4-deficient NSCLC usually harbor truncating SMARCA4 mutations (>90% of NSCLC with BRG1 loss harbor truncating SMARCA4 mutations) and shows overlapping molecular profiles with SMARCA4-UT (TP53, KRAS, STK11, and KEAP1 mutations) and high tumor mutation burden (18). It seems reasonable to assume the biological continuum between these two tumors, as they share genomic alterations typical of smoking related NSCLC (KRAS, KEAP1, STK11) (12,16).

Demographic features of SD-NSCLC in our study showed similarities in terms of male predominance and smoking history (five current smokers, four ex-smokers; average pack-years, 51.9) with reported features of SD-UT. This result also correlates with the previous studies of SD-NSCLC (13,28). However, in our study, most patients were asymptomatic, and the tumors were incidentally diagnosed during the routine health check-up. In five patients who underwent curative resection, three cases were detected at a relatively earlier stage. In contrast, patients with SD-UT are frequently symptomatic with most frequent symptoms being dyspnea. Also, indirect symptoms of regional invasion were frequently observed, such as superior vena cava syndrome, Pancoast syndrome, and hemoptysis (29).

According to our study, the majority of SD-NSCLC was manifested as relatively well-defined nodules or masses, showing lobulated contour and variable degree of enhancement. This result shows difference from previous study by Lou et al. (26). Lou et al. have reported 23 cases of SD-NSCLC in 2022, which mostly manifested as infiltrative masses and heterogenous densities with unclear margins (26). These image findings were in contrary to our study, and we believe such differences might be due to the fact that large proportion of our cohort were detected earlier phase during routine health check-up. Moreover, our study showed clearly distinguishable imaging features from SD-UT, which showed ill-defined margin in all patients (21 cases) (29). SD-NSCLC in our cohort did not show any calcification nor necrotic components, which was coherent with reported imaging features of SD-UT (29). Most of the SD-NSCLC were in the peripheral portion of the lung (n=7, 77.8%), and showed adjacent pleura and chest wall invasion regardless of small tumor size. It has been known that SD-NSCLC has highly aggressive behavior with vascular invasion and pleural metastasis (30), and high prevalence of pleural and chest wall metastasis might be due to SMARCA4 relation with trans-membrane glycoprotein CD44, which is closely related to metastasis (9,31). Furthermore, the incidence of pleural invasion was higher in our study when compared with the previous study of Heidinger et al. in terms of pleural invasion of pulmonary adenocarcinomas, according to CT features of primary tumor (32). In our study, the incidence of pleural invasion was observed to be 77.8%, whereas Heidinger et al. reported 24.6% in solid tumors and 4.7% in subsolid tumors (32). However, since our study included only small number of patients, further research with larger cohort would be necessary for more accurate comparison. Regarding metastatic potential of SD-UT, Crombé et al. have mentioned a striking tendency of SD-UT to cross compartments and to spread from mediastinum to pleura, neck, or lung apex in an infiltrative and compressive fashion (29). We assumed the same principle can be adopted to explain our cases of SD-NSCLC with relatively aggressive pleural and chest wall invasion regardless of tumor size.

In terms of nodal metastasis, four (44%) cases showed metastatic lymph nodes with two cases of necrosis within the lymph nodes in CT. In five cases with curative surgical resection, pathologic lymph node metastases were not observed in all cases. This result is similar to the previous pathologic study of SD-NSCLC, which reported lymph node metastases in 47% of all cases (13). Furthermore, based on previous study regarding tumor genomic features associated with pathologic lymph node metastasis in clinical stage I and II, an alteration in SMARCA4 gene was significantly associated with higher lymph node metastasis (33). Lymph node involvement in SD-UT is also known to show heterogeneous (necrotic) attenuation with ill-defined perinodal soft tissue infiltration (15,18). In previous study of SD-UT, almost all cases showed lymph node metastases with necrotic change (29). We believe that the correlation between SMARCA4 deficiency and pathologic lymph node metastasis with tendency for necrosis was also demonstrated through our analysis.

Proportion of distant metastases at the time of diagnosis in SD-NSCLC was similar to that of previous study of SD-UT (29). Our study revealed that four patients had intra- or extrathoracic metastasis at the time of diagnosis. Metastases involved the bone in three patients (all with multiple areas), and lung in one patient. We carefully hypothesized that SD-NSCLC and SD-UT may share similarity in terms of distant metastases, probably based on the molecular similarity in the molecular level. Also, in PET-CT, all tumors in lung parenchyma showed diffuse and intense FDG uptake with SUV_max value ranging from 9.5–16.5 in the lung parenchyma. This was coherent with previous study regarding SMARCA4-UT, which reported strong FDG avidity with mean SUV_max of 16.6 (range, 9.1–33.8) (29). Herein, we can assume that PET-CT features including SUV_max value and FDG uptake pattern of SD-NSCLC is in fact similar to that of SD-UT.

In terms of pathologic diagnosis of SD-UT and SD-NSCLC, SD-NSCLC is usually distinguished from SD-UT based on the morphology by well-differentiation in form of clear-cut adenocarcinoma or very rarely, squamous cell carcinoma (18). Unlike SD-UT, differentiated (glandular or squamous) histology is more frequent in SD-NSCLC (34). Also, SMARCA4 and SMARCA2 should be included in the workup of TTF1-negative adenocarcinoma of presumable pulmonary origin, as 80% of SMARCA4/SMARCA2-deficient lung adenocarcinomas are TTF1 negative (34). In contrary, SD-UT is known to consist of diffuse sheets of variably dis-cohesive, large, round to epithelioid cells with vesicular chromatin and prominent nucleoli (14). Unequivocal epithelial architecture (e.g., glandular or squamous differentiation) should be absent, except rare, combined cases in which conventional NSCLC is juxtaposed (14).

SD-NSCLC is known to be associated with overall poorer outcome independent of clinical stages (9,13). Inconsistent responses to ICB have been observed in SD-NSCLC with variable responses, from favorable, poor to even hyper-progression (18). This might be partly explained by the high co-occurrence of STK11 and KEAP1 mutations in SD-NSCLC that are known to blunt responses to immune checkpoint inhibitors (ICIs) (14). Regarding the relationship between SD-NSCLC and SD-UT, recent study by Lin et al. demonstrated survival benefit of ICI comparing to traditional chemotherapy in SD-UT, and the prognostic disparity between SD-NSCLC and SD-UT under different treatment settings (35). ICI-based treatment significantly improved progression-free survival (PFS) than chemotherapy in the first-line treatment of SD-UT (35). Moreover, patients of SD-UT and SD-NSCLC receiving ICI-based regimen as first-line treatment had significantly longer median overall survival than those having ICI-based regimen in latter line or no ICI treatment throughout clinical courses (35). These results indicated the promising efficacy of ICI in metastatic SD-UT, and its optimal effect may be achieved when used early in clinical courses (35). Regarding the prognostic disparity, no significant survival differences were observed in PFS between SD-UT and SD-NSCLC of under same treatment settings (35). However, some studies showed limited efficacy of ICI in SD-UT. Gantzer et al. reported that SD-UT mostly had an immune-desert tumor microenvironment (36). Only one out of four patients in Gantzer’s cohort turned out to have immune-rich tumor microenvironment responded to ICI (36). However, despite multimodal treatment therapy including chemotherapy and surgery, the clinical outcomes of most patients with SD-NSCLC and SD-UT have been discouraging to date (18,35). Due to the small sized cohort, the prognosis of each patient with SD-NSCLC could not be exactly compared with SD-UT. In our case series, eight (88.9%) of nine patients have survived. Although long-term clinical outcomes are not available, tumors with relatively low-grade TNM stage tend to show excellent short-term results. In five cases who have undergone curative resection with or without adjuvant chemotherapy, there was no evidence of recurrence during the follow-up periods. In patients with palliative chemotherapy without surgery, most patients showed an overall decrease in the extent of total tumor burden. However, like SD-UT behavior, early relapse or progression more frequently occurred (29). In the previous study of SD-UT, all patients died of their disease due to local complications, with a median survival of 5 months after initial diagnosis.

Our study has several limitations. First, our analysis was conducted based on a retrospective design with small number of patients due to rarity of disease entity. However, to our knowledge, this study is the largest cohort to provide detailed analyses of clinicodemographic, CT and PET-CT imaging features of SD-NSCLC. Second, our follow-up period was relatively short with a median value of 6 months. Larger cohort with long-term follow-up study is mandatory to better understand the tumor behavior and prognosis. Furthermore, studies focusing on the comparison of image finding with other histopathologic types and mutations of primary lung cancer are required to further validate our results.

Conclusions

In conclusion, SD-NSCLC is a rare type of primary lung cancer which shows similar demographic and clinical features with SD-UT. In male smokers presenting with peripherally located tumors and showing invasion of adjacent pleura or chest wall regardless of small tumor size, radiologists should be concerned about the possibility of SD-NSCLC.

Acknowledgments

Funding: None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-1606/rc

Data Sharing Statement: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-1606/dss

Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-1606/prf

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-1606/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 (as revised in 2013). The institutional review board of Samsung Medical Center approved this retrospective study (IRB file No.: 2023-02-010), and the requirement for patient consent to use clinical data was waived due to retrospective study design.

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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