ABSTRACT
SMARCA4‐deficient thoracic tumor (SDTT) is a malignant tumor with a poor prognosis that often presents with distant metastases at the time of clinical diagnosis. Skeletal muscle metastasis is a rare subtype of metastasis patterns, and there are limited studies about SDTT metastasis in skeletal muscle. Herein, we retrospectively analyzed the data of stage IV patients diagnosed with SDTT from May 2009 to June 2024. The clinical and genomic data, imaging features, and treatment information were collected. As a result, the study included 145 patients with metastatic SDTT, 17 with skeletal muscle metastases, and 128 without. The rate of skeletal muscle metastasis in SDTTs was 11.7%. Multivariate Cox regression analysis showed that skeletal muscle metastases (p = 0.014, hazard ratio 95% confidence interval [HR 95% CI] [2.90, 1.25–6.75]) and first‐line chemoimmunotherapy (p < 0.001, HR 95% CI [0.31, 0.17–0.56]) were independent prognostic variables. Furthermore, patients with skeletal muscle metastases had a significantly shorter median overall survival (OS) than those without (13.20 vs. 18.6 months, p = 0.021) in metastatic SDTTs. The mutation rate of STK11 and KRAS was higher in the skeletal muscle metastasis group (62.50% vs. 15.52%, p = 0.008; 50.00% vs. 8.62%, p = 0.009). In conclusion, SDTTs exhibited a high rate of skeletal muscle metastases. Skeletal muscle metastases and first‐line chemoimmunotherapy were independent prognostic factors for OS in SDTTs.
Keywords: chemoimmunotherapy, genomic feature, prognosis, skeletal muscle metastasis, SMARCA4‐deficient thoracic tumors
What's new?
SMARCA4‐deficient thoracic tumors (SDTTs) are aggressive and usually fatal, being characterized by inactivation of the SMARCA4 tumor suppressor gene and loss of SMARCA4 (BRG1) protein expression. SDTTs frequently present with distant metastases at diagnosis. Here, the authors investigated clinical and genomic features of distant skeletal metastases in stage IV SDTT patients. More than 11 percent of patients experienced skeletal muscle metastases, which were associated with significantly shorter survival and increased STK11 and KRAS mutation rates. First‐line chemoimmunotherapy improved outcomes. The findings identify skeletal muscle metastases as an adverse prognostic factor in SDTT and highlight the importance of tailored treatment strategies.
SMARCA4‐deficient thoracic tumors (SDTTs) are aggressive and usually fatal, being characterized by inactivation of the SMARCA4 tumor suppressor gene and loss of SMARCA4 (BRG1) protein expression. SDTTs frequently present with distant metastases at diagnosis. Here, the authors investigated clinical and genomic features of distant skeletal metastases in stage IV SDTT patients. More than 11 percent of patients experienced skeletal muscle metastases, which were associated with significantly shorter survival and increased STK11 and KRAS mutation rates. First‐line chemoimmunotherapy improved outcomes. The findings identify skeletal muscle metastases as an adverse prognostic factor in SDTT and highlight the importance of tailored treatment strategies.
Abbreviations
- 8th, AJCC
8th edition of the American Joint Committee on Cancer staging system
- 95% CI
95% confidence intervals
- BRG1
brahma‐related gene 1
- CR
complete response
- DoR
duration of response
- ECOG
Eastern Cooperative Oncology Group performance status
- FFPE
formalin‐fixed, paraffin‐embedded
- HR
hazard ratios
- IHC
immunohistochemistry
- IQR
interquartile range
- NCCN
National Comprehensive Cancer Network
- NGS
next‐generation sequencing
- OS
overall survival time
- PD
progressive disease
- PD‐L1
programmed death‐ligand 1
- PET/CT
positron emission tomography/computed tomography
- PR
partial response
- RECIST 1.1
Response Evaluation Criteria in Solid Tumors version 1.1
- SD
disease stability
- SDTT
SMARCA4‐deficient thoracic tumor
- SMARCA4‐dNSCLCs
SMARACA4‐deficient non‐small cell lung cancers
- SMARCA4‐dUCs
SMARACA4‐deficient thoracic undifferentiated carcinomas
- SUVmax
standardized uptake value maximum
- TMB
tumor mutational burden
- WHO
World Health Organization
1. Introduction
SMARCA4‐deficient thoracic tumors (SDTTs) are rare, primary malignancies of the chest that exhibit a negative immunohistochemical result for brahma‐related gene 1 (BRG1) [1]. Notably, SDTTs include two subtypes: SMARCA4‐deficient non‐small cell lung cancers (SMARCA4‐dNSCLCs) and SMARCA4‐deficient thoracic undifferentiated carcinomas (SMARCA4‐dUCs), which are newly recognized by the World Health Organization (WHO) [1, 2]. SDTTs are common in elderly male patients with a smoking history, high tumor mutational burden (TMB), and low expression of programmed death‐ligand 1 (PD‐L1) [3, 4, 5, 6]. Advanced SDTTs are malignant and have a poorer prognosis, with a median overall survival time (OS) of approximately 9.5–12 months [7, 8]. About 40%–69% of patients were stage IV at initial diagnosis, and 20%–50% of patients had distant metastases, with common metastatic sites being the adrenal glands (15%–22%), bones (30%–39%), and liver (8%–11%) and brain (16%–19%) [6, 7, 8, 9].
It has been reported that SMARCA4/BRG1 protein deficiency is associated with the SMARCA4 truncating mutations, conferring unique biological behaviors, invasion, and metastasis patterns in tumors [10, 11, 12, 13, 14]. A previous study has also reported that muscle metastases could be detected in SDTTs [6]. Consequently, metastasis to skeletal muscles commonly originates from lung cancers, gastrointestinal tumors, urological tumors, and malignant melanoma [15, 16, 17]. Moreover, about 1%–3% of patients with advanced lung cancer have skeletal muscle metastasis [18, 19, 20, 21]. However, due to the rarity of skeletal muscle metastases, there is a lack of long‐term survival, genetic characterization, and effective treatment options for patients with skeletal muscle metastases.
We explored the metastatic pattern of SDTTs and found a high incidence of skeletal muscle metastasis. Based on this, we explored this population's clinical features, prognostic differences, genomic features, imaging, and chemoimmunotherapy efficacy.
2. Materials and Methods
2.1. Population
The study population was retrospectively analyzed from the electronic medical records of patients identified at the Sun Yat‐sen University Cancer Center (SYSUCC) from May 2019 to June 2024 in China.
Inclusion criteria: (1) primary tumor in the chest; (2) cytological and histological diagnosis of SMARCA4/BRG1‐deficient tumor by immunohistochemistry (IHC) demonstrating a loss of nuclear SMARCA4/BRG1 immunoreactivity, characterized by either a complete absence or a profound diffuse reduction of expression (Figure S1); (3) whole‐body imaging, such as positron emission tomography/computed tomography (PET/CT) or CT to detect the presence or absence of skeletal muscle metastases; (4) and clinical stage IV, according to the 8th edition of the American Joint Committee on Cancer staging system (8th, AJCC).
Exclusion criteria: (1) a combination of other active tumors, including muscle primary tumors, (2) patients who were lost to follow‐up or who had lost baseline data, (3) and other active tumors were present.
2.2. Methods and Endpoints
Patients' baseline characteristics, including clinical stage, age, gender, smoking status, Eastern Cooperative Oncology Group performance status (ECOG), TNM stage, histology, distant metastatic sites, first‐line treatment, and genomic changes were gathered. Tumor response and progression to treatment were regularly performed according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) [22]. Notably, tumor response was defined as complete response (CR), partial response (PR), disease stability (SD), or progressive disease (PD). The primary endpoint was OS, defined as the time from diagnosis to death from any cause. The second endpoint was duration of response (DoR), the time from the first objective response (PR or CR) to disease progression or relapse.
Patients with SDTTs underwent complete next‐generation sequencing (NGS). Formalin‐fixed, paraffin‐embedded (FFPE) tumor tissue samples and matched whole blood DNA were collected from patients for analysis. DNA extraction, library construction, and high‐throughput sequencing were performed using the SYSUCC platform (Supporting Information: Methods and Materials). The sequencing coverage and quality statistics for each sample are summarized in Table S1.
2.3. Statistical Analyses
Categorical variables were compared using the Chi‐square test or Fisher exact test. Continuous variables were compared using the Student unpaired t‐test. Survival analysis was conducted using the Kaplan–Meier method, and the differences were compared using the log‐rank test. Association between baseline characteristics such as sites of distant metastasis and treatment outcomes were investigated using univariate and multivariate Cox proportional hazards regression analysis to calculate hazard ratios (HR) and their corresponding 95% confidence intervals (95% CI). Genes with p value (Fisher exact test) < 0.05, |log2(Odds Ratio) | > 1 and adjusted p value < 0.2 were selected as differential genes. Furthermore, all statistical tests were two‐sided, and a level of p < 0.05 was considered statistically significant. Statistical analyses were performed using R version 4.4.0.
3. Result
3.1. Clinical Characteristics
Two hundred and ninety‐one patients were histologically diagnosed with SDTTs at Sun Yat‐sen University Cancer Center from May 2019 to June 2024. Among those excluded, 110 patients were in clinical stages I–III, 30 patients without follow‐up information, and6 without baseline information. Finally, 145 patients diagnosed with metastatic SDTTs were screened according to the inclusion and exclusion criteria (Figure 1). The median age was 62 years (interquartile range [IQR], 56–67), and 94.5% (137/145) were male. In total, 75.9% (110/145) of the population had smoking history, and 65.5% (95/145) were in the IVB stage. Most patients (94.5%, 137/145) had an ECOG score of 0–1. At the time of initial diagnosis of metastatic SDTTs, patients exhibited different distant metastatic sites, including brain (n = 44, 30.3%), liver (n = 25, 17.2%), bone (n = 64, 44.1%), adrenal (n = 48, 33.1%), and skeletal muscle (n = 15, 10.3%). Moreover, 53.8% (78/145) patients received first‐line treatment based on chemoimmunotherapy, including chemoimmunotherapy alone (n = 60, 41.4%) and chemoimmunotherapy plus antiangiogenic therapy (n = 18, 12.4%). Forty patients did not receive chemoimmunotherapy and 27 had not available antitumor therapy records. Among the 40 patients, the treatments included chemotherapy (n = 13), chemotherapy plus antiangiogenic therapy (n = 15), targeted therapy (n = 8), and so on (n = 4) (Table S2).
FIGURE 1.
Flowchart of patient inclusion. [Color figure can be viewed at wileyonlinelibrary.com]
3.2. High Prevalence of Skeletal Muscle Metastases of SDTTs
Among the 145 cases of metastatic SDTTs, skeletal muscle metastasis occurred in 17 cases, with an incidence rate of skeletal muscle metastases of 11.7% (17/145). Fifteen (10.3%) patients had skeletal muscle metastases at the time of initial diagnosis while skeletal muscle metastases occurred during treatment in another two patients (1.4%) (Table 1). The limbs were the most common organs (58.8%, 10/17) of skeletal muscle metastases. Additionally, skeletal muscle metastases were mainly detected by PET/CT (14/17, 82.4%). The average size of the skeletal muscle metastases was 31.2 mm, and the average standardized uptake value maximum (SUVmax) of PET/CT was 11.5. Thirteen patients had single skeletal muscle metastasis, while four had multiple skeletal muscle metastases (Table 1). Notably, the clinical characteristics were not significantly different between patients with or without skeletal muscle metastasis (Table S3).
TABLE 1.
Sites of skeletal muscle metastases in SDTTs.
| Characteristics | Skeletal muscle metastases (n) |
|---|---|
| n = 17 | |
| Initial diagnosis with skeletal muscle tumor | |
| Yes | 15 |
| No | 2 |
| Imaging examination methods | |
| CT | 3 |
| PET‐CT | 14 |
| Size of lung tumor (mean) (mm) | 48.4 |
| Size of skeletal muscle tumor (mean) (mm) | 31.2 |
| SUVmax of lung tumor (mean) | 25.3 |
| SUVmax of skeletal muscle tumor (mean) | 11.5 |
| Amount of skeletal muscle tumor | |
| Single | 13 |
| Multiple | 4 |
| Side of body of skeletal muscle tumor | |
| Left | 10 |
| Right | 4 |
| Bilateral | 3 |
| Location of skeletal muscle tumor | |
| Head and neck region | 1 |
| Trunk | 6 |
| Upper limb | 2 |
| Lower limb | 5 |
| Trunk and limb | 3 |
| Local symptom of skeletal muscle tumor | |
| Yes | 4 |
| No | 13 |
| Local treatment of skeletal muscle tumor | |
| Yes | 2 |
| No | 15 |
Abbreviations: CT: computed tomography; PET‐CT: positron emission tomography‐computed tomography; SUV: standard uptake value.
3.3. Imaging Features
Imaging data from several individuals were presented to better understand the radiological characteristics of skeletal muscle metastases. Figure 2A,B showed an enhanced CT scan of the primary lung tumor, a big mass in the left lung compressing the bronchus, and skeletal muscle metastases in the right subscapularis. Figure 2C–E and F–H depicted 18F‐FDG PET/CT images of skeletal muscle metastatic lesions in the gluteus and teres minor, respectively. Moreover, the skeletal muscle metastatic lesions exhibited significant FDG uptake on fusion PET/CT (SUVmax 12.5 and SUVmax 8.6). The areas of skeletal muscle metastases were clear to detect with 18F‐FDG PET/CT.
FIGURE 2.
CT and PET/CT Imaging in SDTT patients with Skeletal muscle Metastases. Lung tumor lesions and skeletal muscle metastases of Enhanced CT images (A, B, red arrow) and PET/CT (C–H, red arrow). [Color figure can be viewed at wileyonlinelibrary.com]
3.4. Survival Analysis and Treatment
One hundred and forty‐five patients were included in univariate Cox regression analysis. Univariate Cox regression analysis suggested that age (p = 0.029, HR 95% CI [1.76, 1.06–2.91]), clinical stage (p = 0.016, HR 95% CI [2.05, 1.15–3.67]), skeletal muscle metastasis (p = 0.025, HR 95% CI [2.12, 1.10–4.10]), and first‐line chemoimmunotherapy (p < 0.001, HR 95% CI [0.36, 0.20–0.64]) were associated with OS (Figure S2). These prognostic factors were included in the multivariate Cox regression analysis. The multivariable model incorporated 118 patients with complete records, excluding 27 with unknown treatment status to minimize potential bias in the core variable analysis. The result confirmed that the presence of skeletal muscle metastases (p = 0.014, HR 95% CI [2.90, 1.25–6.75]) and first‐line chemoimmunotherapy (p < 0.001, HR 95% CI [0.31, 0.17–0.56]) were independent factors for OS (Figure 3A). That is, patients with skeletal muscle metastases or without first‐line chemoimmunotherapy had poor survival outcomes.
FIGURE 3.
Multivariate Cox (A) analysis and Kaplan–Meier curves stratified by chemoimmunotherapy (B) and skeletal muscle metastasis (C) of OS in SDTTs. OS: overall survival; SDTTs: SMARCA4‐deficient thoracic tumors; ECOG: Eastern Cooperative Oncology Group performance status; SMARCA4‐deficient non‐small cell lung cancer (SMARCA4‐dNSCLC); SMARCA4‐deficient undifferentiated thoracic tumors (SMARCA4‐dUTs); NA: not available. *p < 0.05. [Color figure can be viewed at wileyonlinelibrary.com]
As mentioned above, 78 patients received first‐line chemoimmunotherapy, 40 did not (Table S2). Most clinical characteristics were not significantly different between patients with or without first‐line chemoimmunotherapy (Table S4). The patients receiving first‐line chemoimmunotherapy (n = 48) have longer median OS than those without (n = 78; 22.47 vs. 8.17 months; p < 0.001) (Figure 3B). In addition, the median OS of patients with skeletal muscle metastasis (n = 17) was 13.2 months (95% CI, 4.17‐NA months). This was shorter than 18.6 months (95% CI, 16.97‐NA months) of those without skeletal muscle metastasis (n = 128), which was statistically significant (p = 0.021) (Figure 3C).
Of the 17 patients with skeletal muscle metastases, 11 patients were dead by the final follow‐up and 10 patients had treatment efficacy evaluation records (Figure 4A,B). The follow‐up time ranged from 1.03 to 20.4 months. Two patients passed away shortly after receiving chemotherapy alone or chemotherapy combined with antiangiogenic therapy, and the best therapeutic response was PD. Seven of the eight patients treated with chemoimmunotherapy showed PR (n = 3) or SD (n = 4) as the best response (Figure 4B). The average DoR of chemoimmunotherapy was 4.6 months, with the range of OS ranging from 3.3 to 15.9 months. Additionally, chemoimmunotherapy could show efficacy at both the primary and skeletal muscle metastatic sites. There was a significant reduction in lung and skeletal muscle tumors following the second and fifth cycles of therapy compared to baseline, with PR demonstrating the best response (Figure S3).
FIGURE 4.
Therapeutic effect and gene mutations after skeletal muscle metastases in SMARCA4‐deficient thoracic tumors patients. Swimming map (A), waterfall plot of efficacy (B) of treatments following skeletal muscle metastases and genetic landscape (C) with (N = 8) and without skeletal (N = 58) muscle metastases. C: chemotherapy, I: immunotherapy, A: antiangiogenic therapy, T: targeted therapy; values marked in * and bold represent statistically significant differences (p < 0.05). [Color figure can be viewed at wileyonlinelibrary.com]
3.5. Genetic Characteristics
To investigate genetic differences between patients with and without skeletal muscle metastases, NGS results on tumor tissues from 8 patients with skeletal muscle metastases and 58 patients without skeletal muscle metastases were performed (Figure 4C). Among the patients without skeletal muscle metastases in SDTTs, SMARCA4, STK11, and TP53 mutations were identified in 82.76% (48/58), 15.52% (9/58), and 82.76% (48/58) of cases, respectively. These mutations were identified in 62.50% (5/8), 62.50% (5/8), and 50.00% (4/8) of cases with skeletal muscle metastases, respectively. It showed that patients with skeletal muscle metastases had a higher proportion of STK11 mutations (62.50% vs. 15.52%, p = 0.008) (Table S5). KRAS mutation patterns also differed between groups. Patients with skeletal muscle metastases showed a higher mutation rate (4/8 vs. 5/58, 50.00% vs. 8.62%, p = 0.009), with the p.G12C subtype accounting for 100% (4/4) of cases (Table S5, Figure S4). Conversely, those without metastases exhibited lower frequency and greater diversity, including p.G12C (60%, 3/5), p.G12V (20%, 1/5), and p.Q61H (20%, 1/5) (Figure S4).
4. Discussion
Our study revealed a high incidence of skeletal muscle metastases in metastatic SDTTs, and PET/CT was a better diagnostic tool. Patients with a pattern of skeletal muscle metastases had a worse prognosis. First‐line chemoimmunotherapy might bring better survival benefits for SDTTs. STK11 and KRAS gene mutation rates were significantly higher for patients with skeletal muscle metastases.
Skeletal muscle metastasis was a rare location of metastasis in solid tumors, with an estimated chance of less than 5% [18, 19, 20, 21]. In a large meta‐analysis, the probability of skeletal muscle metastases in advanced lung cancer was about 1%–3% [21]. While in gastrointestinal and renal cancers, approximately 2%–3% were reported [23]. In our study, the probability of skeletal muscle metastasis in SDTTs was up to 10%, which was identified and summarized for the first time and summarized them. The “seed and soil” hypothesis suggested skeletal muscle's harsh oxidative stress environment typically discourages tumor growth, contributing to low metastasis rates [24, 25]. However, SMARCA4‐deficient tumor cells, with enhanced mitochondrial function and increased NADPH [26], might enhance antioxidant capacity, potentially explaining their higher incidence of skeletal muscle metastases.
The limbs were the most common site of SDTTs with skeletal muscle metastases, occurring in 58.8%. The limbs were also showed same result in NSCLC [27, 28]. Skeletal muscle metastases showed a notable metabolic uptake on PET/CT in our study. In current lung cancer diagnosis, CT scan of the abdomen and chest and bone scan was the standard tools following National Comprehensive Cancer Network (NCCN) guidelines [29]. However, if there were no local symptoms at the metastasis site, limbs would not be scanned, thus missing the diagnosis of skeletal muscle metastasis. This could explain why most skeletal muscle metastasis was discovered by PET/CT in our study. Therefore, PET/CT could be a better option for patients with SDTTs in clinical practice.
According to our research, patients in SDTTs with muscle metastases had a shorter OS. Previous case analyses had explored the prognosis of skeletal muscle metastases, but comparative studies on prognostic differences between skeletal muscle and other metastatic sites remain limited [15, 30]. Therefore, our research demonstrated for the first time that skeletal muscle metastases were an independent prognostic factor for shorter OS compared with other metastases. Previous studies have shown that chemoimmunotherapy offers superior clinical advantages of progression‐free survival (PFS) than chemotherapy alone in SDTTs [8, 31]. Our study demonstrated that first‐line chemoimmunotherapy led to superior clinical benefits of OS in advanced SDTTs patients. Besides, our research provided a rationale for first‐line chemoimmunotherapy as a treatment approach for SDTTs, especially those with skeletal muscle metastases.
Previous research on SMARCA4‐dNSCLC had shown primarily SMARCA4 mutations and co‐mutations in KRAS, TP53, KEAP1, and STK11 [5, 10]. While concurrent mutations may influence tumor aggressiveness and treatment resistance, the genomic landscape of skeletal muscle metastases has not been well characterized. In this study, we observed a higher STK11 and KRAS mutation rate in SDTT patients with skeletal muscle metastases. Given that concurrent SMARCA4 and STK11 mutations are linked to poor clinical outcomes [11, 32], the prognostic impact of this specific association in skeletal muscle metastases warrants further validation.
For the different molecular subtypes of KRAS mutation, a relatively high mutation rate of KRAS p.G12C was observed in skeletal muscle metastases in our study. Highly specific KRAS p.G12C inhibitors, like garsorasib, that bind irreversibly to KRAS G12C protein, are effective in the solid tumors with KRAS G12C mutation [33, 34]. However, given the limited sample and the absence of KRAS inhibitor in skeletal muscle metastases, real‐world clinical evidence for this specific population remains limited. Future large‐scale, multi‐center studies are warranted to further validate these findings and refine the therapeutic landscape.
There are some limitations in this study. Due to the low prevalence of SDTTs, the sample size of patients with skeletal muscle metastases was modest. And NGS results were not available for all patients. However, with the small sample size, we still had some meaningful findings that needed to be confirmed in a larger population.
Author Contributions
Xueyuan Chen: conceptualization, investigation, resources, data curation, methodology, formal analysis, writing – original draft, writing – review and editing, visualization. Mengting Shi: conceptualization, writing – original draft, methodology, writing – review and editing, data curation, resources, visualization, funding acquisition, formal analysis. Yuwen Yang: data curation, resources, formal analysis, methodology, writing – review and editing, conceptualization, investigation, writing – original draft, visualization. Lin Zhang: conceptualization, investigation, writing – original draft, methodology, writing – review and editing, formal analysis, data curation, resources, visualization. Tingting Liu: investigation, resources, data curation, formal analysis. Bijing Xiao: investigation, formal analysis, data curation, resources. Silang Mo: investigation, formal analysis, data curation, resources. Yuanzheng Ma: data curation, resources, formal analysis, investigation. Gang Chen: data curation, resources. Ting Zhou: resources, data curation. Yunpeng Yang: data curation, resources. Zhixiong Lin: software, validation. Yuanyuan Zhao: conceptualization, resources, writing – review and editing, supervision, project administration.
Funding
This work was supported by the National Natural Science Foundation of China (Grant No. 82503939).
Ethics Statement
Our study was approved by the Ethics Committee of Sun Yat‐sen University Cancer Center and was conducted in accordance with the Declaration of Helsinki (B2023‐721‐01). All patients' individual consent for this retrospective analysis was waived.
Conflicts of Interest
The authors declare no conflicts of interest.
Supporting information
Table S1: Sequencing coverage and quality statistics.
Table S2: Baseline characteristics of all patients diagnosed initially metastatic SMARCA4‐deficient thoracic tumors.
Table S3: Characteristics of patients with and without skeletal muscle metastases in SMARCA4‐deficient thoracic tumors.
Table S4: Characteristics of patients with and without first‐line chemoimmunotherapy in SMARCA4‐deficient thoracic tumors.
Table S5: Comparison of gene mutation with and without skeletal muscle metastasis.
Figure S1: Representative Immunohistochemistry (IHC) for the expression (A) and loss (B) of SMARCA4 protein expression in primary tumor in the chest.
Figure S2: Univariate Cox regression analysis of overall survival in SDTTs: SMARCA4‐Deficient Thoracic Tumors; ECOG: Eastern Cooperative Oncology Group performance status; SMARCA4‐deficient non‐small cell lung cancer (SMARCA4‐dNSCLC); SMARCA4‐deficient undifferentiated thoracic tumors (SMARCA4‐dUTs). *p < 0.05 Cases with missing clinical data for specific variables were excluded only from the respective subgroup analyses.
Figure S3: CT changes of lung and skeletal muscle metastases masses after immunotherapy combined with chemotherapy.
Figure S4: Distribution of KRAS mutation status and subtypes in SDTTs with and without skeletal muscle metastases.
Acknowledgments
We gratefully acknowledge the support and contributions of the patients, medical staff, colleagues, and funding agencies who made this cancer research project possible.
Chen X., Shi M., Yang Y., et al., “Skeletal Muscle Metastasis in Patients With SMARCA4‐Deficient Thoracic Tumors: A Retrospective Cohort Study,” International Journal of Cancer 159, no. 6 (2026): 1546–1555, 10.1002/ijc.70537.
The abstract of this article has been submitted as a poster presentation for the IASLC 2025 World Conference on Lung Cancer (Control# 2357).
Contributor Information
Zhixiong Lin, Email: zxlin2@stu.edu.cn.
Yuanyuan Zhao, Email: zhaoyy@sysucc.org.cn.
Data Availability Statement
The datasets generated and analyzed during the current study are available from the corresponding author. R code is publicly available on GitHub (https://github.com/chenxueyuan888/R‐code.git). Further information is available from the corresponding author upon request.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Table S1: Sequencing coverage and quality statistics.
Table S2: Baseline characteristics of all patients diagnosed initially metastatic SMARCA4‐deficient thoracic tumors.
Table S3: Characteristics of patients with and without skeletal muscle metastases in SMARCA4‐deficient thoracic tumors.
Table S4: Characteristics of patients with and without first‐line chemoimmunotherapy in SMARCA4‐deficient thoracic tumors.
Table S5: Comparison of gene mutation with and without skeletal muscle metastasis.
Figure S1: Representative Immunohistochemistry (IHC) for the expression (A) and loss (B) of SMARCA4 protein expression in primary tumor in the chest.
Figure S2: Univariate Cox regression analysis of overall survival in SDTTs: SMARCA4‐Deficient Thoracic Tumors; ECOG: Eastern Cooperative Oncology Group performance status; SMARCA4‐deficient non‐small cell lung cancer (SMARCA4‐dNSCLC); SMARCA4‐deficient undifferentiated thoracic tumors (SMARCA4‐dUTs). *p < 0.05 Cases with missing clinical data for specific variables were excluded only from the respective subgroup analyses.
Figure S3: CT changes of lung and skeletal muscle metastases masses after immunotherapy combined with chemotherapy.
Figure S4: Distribution of KRAS mutation status and subtypes in SDTTs with and without skeletal muscle metastases.
Data Availability Statement
The datasets generated and analyzed during the current study are available from the corresponding author. R code is publicly available on GitHub (https://github.com/chenxueyuan888/R‐code.git). Further information is available from the corresponding author upon request.