Long-term survival of a SMARCA4-deficient undifferentiated thoracic tumor with brain metastasis successfully treated with multimodal treatment: a case report and literature review

Abstract

Background

SMARCA4-deficient undifferentiated thoracic tumor (SMARCA4-UT) is a rare and highly aggressive malignancy characterized by early distant metastasis and a poor prognosis, with a median overall survival (OS) of only 4–7 months. Traditional therapies offer limited benefit, while emerging data suggest the efficacy of combined immunotherapy, chemotherapy, and anti-angiogenic approaches.

Case summary

We report a case of a 52-year-old male with a heavy smoking history who presented with loss of consciousness and limb convulsions. Imaging revealed brain metastasis and a thoracic tumor. After surgical removal of the brain lesion and a lung biopsy, the patient was diagnosed with SMARCA4-UT, showing no targetable driver mutations and a programmed death-ligand 1 (PD-L1) tumor proportion score (TPS) < 1%. The patient underwent first-line treatment with tislelizumab, bevacizumab, carboplatin, and paclitaxel. Despite discontinuation of bevacizumab due to a tumor cavity, the patient achieved partial remission (PR) after six cycles. Notably, consolidative thoracic radiotherapy (TRT) was administered following systemic disease control to enhance local control. After 5 months of maintenance therapy, oligoprogression of the primary lung lesion was detected and the progression-free survival (PFS) of first-line treatment reached 14 months. The patient then performed salvage surgery for local lesion and continued with maintenance treatment. As of May 2025, the patient has survived for 31 months since the initial diagnosis.

Conclusion

Multimodal therapy integrating chemoimmunotherapy, anti-angiogenesis, consolidative radiotherapy, and salvage surgery achieved durable survival in SMARCA4-UT with brain metastasis. It highlights the potential of combining systemic and local therapies, providing valuable insights for managing this challenging disease.

Introduction

SMARCA4-deficient undifferentiated thoracic tumor (SMARCA4-UT) is an emerging entity among rare malignant tumors with rapid progression and poor prognosis, which was first reported by Le Loarer et al. (2015) in October 2015. This aggressive neoplasm demonstrates a predilection for young adults with significant smoking history and pre-existing pulmonary emphysema or bullous lung pathology (Crombe et al. 2019; Matsushita and Kuwamoto 2018). It often presents as a compressive and infiltrative chest mass, and the majority have metastasized to the adrenal glands, bones, and brain at the time of initial diagnosis(Stewart et al. 2020), with a median survival time of 4–7 months(Rekhtman et al. 2020).

At present, there are no established treatment guidelines for SMARCA4-UT. Traditional treatment schemes such as surgery, chemotherapy, and radiation therapy have shown limited efficacy. Luo et al. (2023) documented that among 11 SMARCA4-UT patients, 9 relapsed within one year after surgery. Le Loarer et al. (2015) found that two patients underwent surgical resection, and although the tumor margins were macroscopically negative, the tumors recurred within one month. Despite patients being able to undergo complete resection, the outcome remains disappointing. Moreover, Perret et al. (2019)described 76.7% of patients received chemotherapy with or without radiotherapy and showed no response to the treatment. Iijima et al. (2020) administered chemotherapy as both first-line and second-line treatments to a SMARCA4-UT patient, which did not demonstrate sufficient therapeutic effects. These studies suggest that SMARCA4-UT appears to be resistant to conventional chemotherapy and radiotherapy.

In recent years, a few patients with SMARCA4-UT have been reported to be successfully treated with immunotherapy. In a 69-year-old SMARCA4-UT patient with a programmed death-ligand 1 (PD-L1) positivity rate of 60%, pembrolizumab as first-line treatment effectively inhibited tumor growth without adverse reactions(Takada et al. 2019). Henon et al. (2019) reported a case of SMARCA4-UT with PD-L1 negativity, after experiencing progression following radiotherapy and chemotherapy, achieved a 72% partial response (PR) to pembrolizumab compared to the baseline. However, Gantzer et al. (2022) identified that two SMARCA4-UT patients died quickly within 10 weeks after the diagnosis and had immune checkpoint inhibitors (ICIs) as their only treatment. He also reported that some SMARCA4-UT patients had no tertiary lymphoid structures, consistent with an immune desert phenotype. Due to most studies were case reports, immunotherapy in SMARCA4-UT remains controversial.

Currently, the combination of chemotherapy, immunotherapy, and anti-angiogenic treatment may be a viable option. An increasing amount of clinical and preclinical evidence supports the synergistic effect of chem-immunotherapy with anti-angiogenic therapy (Lee et al. 2020). Chemotherapy directly kills cancer cells, while anti-angiogenic treatment leads to vascular regression, thereby depriving cancer cells of nutrients (Abdallah et al. 2024). Beyond this, Anti-angiogenic treatment may have immune-modulating activity, capable of reprogramming the tumor microenvironment from an immunosuppressive to an immune-permissive phenotype (Tan et al. 2023). Kawachi et al. (2021) reported that three patients achieved PR to the treatment of atezolizumab, bevacizumab, carboplatin, and paclitaxel (ABCP), with one patient having a progression-free survival (PFS) of approximately 17 months. However, although systemic therapies can achieve disease control, maintaining long-term remission is challenging due to the high incidence of oligoprogression or tumor recurrence. Herein, we report a case of SMARCA4-UT with brain metastasis that achieved long-term survival (31 months from initial diagnosis) through a multimodal treatment strategy, significantly exceeding the typical prognosis of this disease.

Case presentation

A 52-year-old man reported episodes of unconsciousness with limb convulsions for 2 days. The patient had a smoking history (Brinkman index: 1800) but did not have a family history of cancer. Physical examination revealed decreased breath sounds in the right lung. Brain magnetic resonance imaging (MRI) on October 18, 2022, shows a nodular lesion in the right frontal lobe, approximately 2.3 × 2.2 cm in size, with a high probability of being a metastatic tumor (Fig. 1A). Chest computed tomography (CT) scan showed emphysema, a 4.3 × 4.2 cm space-occupying lesion in the posterior segment of the upper lobe of the right lung, with mediastinal lymph node enlargement (Fig. 1B).

Fig. 1.

Initial brain MRI and chest CT images. A A metastatic lesion in the right frontal lobe (solid tumor, dmax = 23 × 22 mm); B A primary tumor in the right lung upper lobe (solid tumor, dmax = 43 × 42 mm) and mediastinal lymph node metastases (dmax = 15 × 10 mm)

After admission, the patient still had recurrent seizures after dehydration, cranial pressure reduction, and antiepileptic treatment, indicating a poor therapeutic response. On October 20, 2022, the patient underwent a right frontal lobe lesion resection. Under the microscope, the postoperative tumor tissue exhibited an undifferentiated morphology. The tumor cells showed marked pleomorphism, with abundant eosinophilic cytoplasm, large nuclei with dense staining, and some nuclei were eccentric with abundant cytoplasm, presenting a striated muscle-like morphology. Initial immunohistochemical analysis revealed that the tumor cells were positive for Vimentin, while GFAP, NeuN, Syn, CgA, TTF-1, Napsin A, CK, and CK7 were all negative in the tumor cells. Combining the pathological features and imaging findings, we preliminarily speculated that the cranial space-occupying lesion was not the primary site but likely a metastatic tumor originating from the lung. One month after surgery, a CT-guided biopsy of the lung tumor was performed. The pathological histological features of the biopsy specimen were similar to those of brain tumors, with diffuse and sheet-like proliferation of the tumor, accompanied by coagulative necrosis. The tumor cells were relatively monotonous, with eosinophilic cytoplasm and partial rhabdoid appearance. Immunohistochemical results showed the following: BRG1(−), INI-1(+), Vim(+), P53(+, mutant), SALL-4(+), TTF-1(−), NapsinA(−), P40(focal +), CK(−), CK7(−), Ki67(80%), CK5/6(−), HMB-45(−), SSTR2(−), SATB2(−) (Fig. 2). Subsequently, supplementary immunohistochemical analyses were conducted on the brain tumor. The results indicated: BRG1 (−), INI-1 (+), Vim (+), P53 (+, mutated), HMB-45 (−), SSTR2 (−), SATB2 (−). These findings ultimately confirmed that the patient was a SMARCA4-UT with brain metastasis. Additionally, no driver gene alterations were found in a routine ten-gene mutation test (EGFR, ALK, ROS1, KRAS, BRAF, RET, HER2, NRAS, PIK3CA, and MET) and PD-L1 tumor proportion score (TPS) was lower than 1% (clone22C3). Abdominal CT, neck lymph node ultrasound, and bone scan all returned normal findings. Tumor marker test results revealed neuron-specific enolase (NSE) was 24.7 ng/mL (reference range, 0.0–16.3 ng/mL), whereas other tumor markers, such as carcinoembryonic antigen (CEA), cancer antigen 125 (CA125), squamous cell carcinoma antigen (SCC), cytokeratin 19 fragment (CYFRA21-1), and cancer antigen 199 (CA199), were within the normal ranges. He was finally diagnosed with SMARCA4-UT (cT4N2M1b, Stage IVA, 8th edition American Joint Committee on Cancer) with no targetable driver mutations and a PD-L1 TPS < 1%. Upon consultation with a multidisciplinary team, he was treated with tislelizumab, bevacizumab, carboplatin, and taxotere treatment as the first-line therapy. The patient underwent two cycles of treatment, and a cavity inside the tumor occurred. Due to concerns about the risk of hemoptysis, bevacizumab was discontinued. After six cycles, the response was PR according to Response Evaluation Criteria in Solid Tumors (RECIST1.1) guidelines (Fig. 3A–C). Subsequently, he was administered consolidative thoracic radiotherapy (TRT) at a total dose of 60.48 Gy in 28 fractions and a maintenance phase (taxotere, tislelizumab, and bevacizumab) for six more months (Fig. 3D–F). However, in January 2024, blood laboratory tests revealed NSE increased to 17.3 ng/mL, chest CT showed an enlarged right upper lung lesion while other lesions were stable, and positron-emission tomography-computed tomography (PET-CT) scan indicated abnormal uptakes in the primary lesion and mediastinal lymph node metastases (SUVmax is 6.9) (Fig. 3G). The patient was diagnosed with tumor recurrence. The PFS of first-line treatment was 14 months. Then, he underwent right upper lobe resection and mediastinal lymph node dissection. The surgical procedure commenced with a large anterolateral incision. Given the presence of adhesions between the mass and the thoracic cavity, a thoracoscope was inserted to facilitate the operation. Upon exploration, it was revealed that the tumor had invaded the chest wall, interlobar fissure, and the dorsal segment of the right lower lobe. Consequently, the involved chest wall muscles, the right upper lobe, and the affected lung tissue in the dorsal segment of the right lower lobe were resected en bloc. The tumor in the surgical specimen measured approximately 5 × 4 × 3 cm in size, with a cystic and solid, grayish-white cut surface. Under the microscope, most areas of the tumor showed necrosis, with only a small number of viable tumor cells remaining (about 10%). The surgical margins were found to be negative, and no cancerous cells were detected in the dissected lymph nodes (including groups 2, 4, 7, 10, 11, and 12). Notably, necrotic components were observed in lymph node groups 10 and 12. Immunohistochemical examination revealed complete loss of SMARCA4 expression. Other immunohistochemical features included positivity for INI-1 and SALL-4, partial expression of TTF-1 and EMA, no expression of Napsin A and CK7, and the proliferation index Ki-67 was 40%. Subsequently, we continued with maintenance treatment (taxotere, tislelizumab, and bevacizumab) to date. Throughout the treatment period, no obvious signs of tumor recurrence were observed in brain MRI scans. As of May 2025, the patient survived for 31 months from the initial diagnosis (Fig. 4).

Fig. 2.

Histological results of SMARCA4-UT tumors. A, B The biopsy specimen shows diffuse sheets of proliferating with coagulation necrosis. The tumor cells are relatively monotonous, with eosinophilic cytoplasm and partial rhabdoid appearance (hematoxylin and eosin-stained, 10 × 10 and 10 × 40); C The tumor cells are negative for BRG1 (immunostaining, 10 × 10); D The tumor cells are positive for INI-1 (immunostaining, 10 × 10)

Fig. 3.

Imaging changes during the treatment process. A Pretreatment CT scan of the patient; B CT scan after two cycles of tislelizumab, bevacizumab, carboplatin, and taxotere treatment; C CT scan after four cycles of tislelizumab, carboplatin, and taxotere treatment; D Radiotherapy target delineation; E CT scan after TRT; F CT scan after last maintenance treatment. G PET-CT images of tumor recurrences

Fig. 4.

Treatment timeline of the patient

Throughout the treatment course, the patient demonstrated good tolerance. During the third cycle of tislelizumab, bevacizumab, carboplatin, and taxotere treatment, CT scans indicated the formation of lung cavities. Due to concerns about the risk of hemoptysis, we discontinued bevacizumab. During TRT, the patient experienced grade 2 leukopenia(Common Terminology Criteria for Adverse Events, version 5.0), which improved after administration of leukocyte-boosting therapy. During the postoperative maintenance treatment phase, next generation sequencing of the patient's bronchoalveolar lavage fluid indicated a pulmonary fungal infection, and the patient received antifungal therapy. Other clinical assessments, such as liver and kidney function, myocardial enzymes, thyroid function, and electrocardiogram, all remained within normal ranges.

Discussion

SMARCA4 is a tumor suppressor gene located at 19p13.2. It encodes the tumor suppressor and transcriptional regulator BRG1, which is a subunit of the Switch/Sucrose non-fermentable (SWI/SNF) chromatin-remodeling complex (Mittal and Roberts 2020). It plays a crucial role in gene transcription, proliferation, differentiation, and DNA repair (Centore et al. 2020; Mardinian et al. 2021) and exhibits a high frequency of mutations in tumors (Abou Alaiwi et al. 2020). In 2021, the World Health Organization (WHO) defined SMARCA4-UT in its 5th edition of the Classification of Thoracic Tumors as a new rare malignant tumor entity with an aggressive clinical course (Nicholson et al. 2022), which was different from SMARCA4-deficient non-small cell lung cancer (NSCLC) due to its unique clinical, histological, immunohistochemical, and prognostic features (Wang et al. 2024). SMARCA4-UT predominantly occurs in male adults ranging from 28 to 90 years of age with a history of heavy smoking (Chatzopoulos and Boland 2021). Patients typically present with large, invasive, and compressive thoracic tumors, often associated with necrotic lymphadenopathy. Distant metastasis is common, with frequent involvement of lymph nodes, bones, brain, and adrenal glands (Perret et al. 2019). Histologically, these tumors are characterized by poorly differentiated cells, often with small cell, epithelioid, or rhabdoid appearance (Sauter et al. 2017). Immunohistochemically, the hallmark of the diagnosis is loss of BRG1 expression, regardless of whether the SMARCA4 gene mutation is detected (Kwon and Jang 2023). Additional supportive findings include BRM deficiency, INI-1 positive, epithelial markers (CK, CAM5.2, and EMA) expressed negatively or weakly, and stem cell markers (SALL-4, CD34, and SOX2) expressed in many cases (Longo et al. 2024; Shinno, Ohe, and Lung Cancer Study Group of the Japan Clinical Oncology, 2024). Generally speaking, the clinical presentation and radiological features of SMARCA4-UT are non-specific. It is essentially a pathological diagnosis (Shi et al. 2022). In this case, the patient was a middle-aged male with a long history of smoking. He presented initially with an epileptic seizure, and imaging revealed space-occupying lesions in both the brain and lungs. Given that the brain metastasis had caused significant mass effect and that conservative treatment had failed to improve the epileptic symptoms, we prioritized surgical intervention to alleviate symptoms. Postoperative pathology of the brain lesion confirmed a metastatic tumor. Imaging findings initially led us to suspect a primary origin in the lung. One month after the surgery, we performed a lung biopsy via percutaneous puncture. Pathological examination of the lung lesion revealed diffusely distributed tumor cells with a primitive appearance, eosinophilic staining, partial nuclear displacement, and extensive coagulative necrosis. Immunohistochemical analysis showed loss of BRG1 protein expression and positivity for INI-1 protein. Markers commonly associated with thoracic malignancies, malignant melanoma, and meningioma were all negative, leading to a final diagnosis of SMARCA4-UT. It is worth noting that if we had employed a more aggressive biopsy strategy at the initial presentation (such as early bronchoscopic or percutaneous lung biopsy) to confirm the primary lung lesion sooner, we might have avoided the brain metastasis resection and initiated systemic therapy earlier, potentially improving the patient's prognosis.

SMARCA4-UT is highly aggressive with a poor prognosis, with a median overall survival of 4–7 months (Rekhtman et al. 2020; Sauter et al. 2017). Presently, the standard treatment has not been established, and therapeutic strategies are still in the exploratory phase. We summarized various treatments and their effect on SMARCA4-UT in Table 1. SMARCA4-UT is rarely co-mutated with certain targetable driver oncogenes, such as EGFR, ALK, MET, ROS1, and RET, but more commonly co-occurs with other gene mutations, including KRAS, TP53, STK11, and KEAP1 (Alessi et al. 2021; Dagogo-Jack et al. 2020). Thus, no effective targeted treatment regimen is available in clinical practice. Chemotherapy is a commonly used method for treating tumors. In SMARCA4-UT, a typical chemotherapy regimen involves various combinations of paclitaxel, carboplatin, gemcitabine, cisplatin, and etoposide (Jiang et al. 2023), yet the therapeutic efficacy is limited. Chemotherapy can enhance the immune environment, thereby potentiating the antitumor effects of ICIs (Takada et al. 2019; Yin et al. 2024). Numerous studies have demonstrated the efficacy of immunotherapy in patients with SMARCA4-UT, both as monotherapy (Henon et al. 2019; Iijima et al. 2020; Shi et al. 2022) and in combination with chemotherapy (Anzic et al. 2021; Kawachi et al. 2021). Two SMARCA4-UT patients underwent conversion surgery after treatment with ICIs plus chemotherapy, achieving a complete pathologic response (Pan et al. 2018). A retrospective study indicated that chemoimmunotherapy significantly improved the median PFS compared to traditional chemotherapy as a first-line treatment (26.8 vs. 2.73 months, p = 0.0437) (Lin et al. 2023). The immunotherapeutic response in SMARCA4-UT appears independent of PD-L1 expression, which is typically low or negative (Zhou et al. 2020). A case with PD-L1 TPS 1% exhibited more than 9 months of PFS with chemoimmunotherapy (Dong et al. 2024). Additionally, the combination of anti-PD-L1 antibodies and anti-angiogenic drugs has shown synergistic effects (Hanna et al. 2021). A SMARCA4-UT patient with vertebral and chest wall invasion successfully underwent conversion surgery after treatment with ABCP (Kunimasa et al. 2021). In our case, sensitive mutations in lung cancer-related ten genes showed negative results, resulting in ineligibility for targeted therapy. We chose to treat a patient using tislelizumab with bevacizumab, carboplatin and taxotere for first-line treatment. Chest CT scan after two cycles of treatment shows an increase in tumor size and the formation of a cavity within the tumor. However, considering the patient's tumor marker NSE has decreased and the patient's mental state has significantly improved, pseudoprogression of the tumor is suspected. Due to concerns about the risk of hemoptysis, we discontinued bevacizumab and administered a combination therapy with taxotere, tislelizumab, and carboplatin. A follow-up CT scan showed the primary tumor had shrunk. He experienced a durable response (more than 14 months) despite having PD-L1 < 1%.

Table 1.

The effect of various treatments on SMARCA4-UT

Reference	Age/sex	Smoking	TNM	PD-L1 (%)	Therapy(first-line to subsequent lines)	Outcome
Iijima et al. (2020)	76/M	Current smoker (49 pack-years)	IV	0	Carboplatin and paclitaxel	PR to bone metastasis
					Open surgery and radiation for bone	–
					Carboplatin and etoposide	PD
					Nivolumab	22 months PR to August 2019
Takada et al. (2019)	70/F	Unknown	IV	> 60	Pembrolizumab for 8 cycles	PR
Henon et al. (2019)	58/F	Unknown	IV	0	Radiotherapy and carboplatin and paclitaxel	–
					Pembrolizumab	11 months PR to March 2019
Kawachi et al. (2021)	73/F	Current smoker (53 pack-years)	IVB	40	ABCP for 3 cycles then AB maintenance	PR after 2 cycles of ABCP No PD for 17 months
	59/M	Current smoker (39 pack-years)	IVB	0	ABCP for 3 cycles then AB maintenance	PR after 2 cycles of ABCP No PD for 10 months
	64/F	Past smoker (44 pack-years)	IVB	80	ABCP for 4 cycles	PR after 3 cycles of ABCP
					Brain Radiotherapy then AB maintenance	No PD for 2 months
Kunimasa et al. (2021)	51/M	Current smoker (22.5 pack-years)	IVA	0	ABCP for 6 cycles	PR
					Conversion surgery	No recurrence for 9 months
Shi et al. (2022)	50/M	Current smoker (36 pack-years)	IVA	90	Tislelizumab for 7 cycles	7 cycles of PR to August 2022
Anzic et al. (2021)	41/M	Current smoker	IV	100	Pembrolizumab for 8 cycles	mixed response
					Pembrolizumab and ipilimumab for 4 cycles	mixed response
					Carboplatin and paclitaxel for 2 cycles	–
					Radiotherapy with doxorubicin and ifosfamide for 6 cycles	died in August 2020
Dong et al. (2024)	56/M	smoker (Brinkman index: 600)	IB	5	Surgury	PD after 3 months
					TEP for 3 cycles then tislelizumab maintenance	No PD for 9 months
Takei et al. (2024)	40/M	Current smoker(2 pack per day for 25 years)	IIB	1	Cisplatin, vinorelbine and radiation	PR
					Conversion surgery	PD after postoperative day 36
					ABCP for 4 cycles	PD after 4 cycles of ABCP
Takei et al. (2024)	74/M	Current smoker(1 pack per day for 54 years)	IIIA	0	Carboplatin, paclitaxel and radiation	PR
					Conversion surgery	No PD for 12 months

ABCP, Atezolizumab, bevacizumab, carboplatins and paclitaxel; TEP, Tislelizumab, etoposide and cisplatin; AB, Atezolizumab and bevacizumab; PR, Partial response; PD, Progressive disease

Traditionally, radiotherapy has been viewed as a local treatment primarily used for palliative symptom relief in advanced lung cancer. Nowadays, an increasing amount of evidence supports that the use of TRT can improve survival rates in patients with advanced NSCLC who have achieved disease control after initial systemic therapy (Chan et al. 2020; Zeng et al. 2020). A phase II clinical study has shown that TRT before maintenance chemotherapy can double the PFS of limited metastatic NSCLC compared to maintenance chemotherapy alone, with no difference in toxicity (Iyengar et al. 2018). In the prospective NRG-LU002 study (Sun et al. 2024), the combination of icotinib (a first-generation EGFR TKI) with TRT was found to significantly improve overall survival (OS) (24.4 vs. 26.2 months, p = 0.029) in NSCLC patients who had oligometastatic disease and EGFR-sensitive mutations and this group also had a better rate of local control. Moreover, Takei et al. (2024) reported a SMARCA4-UT with clinical T4N1M0 stage III treated with chemoradiotherapy, the 7.4 cm maximum diameter of the tumor shrank to 4.7 cm. The patient in this case study was treated with consolidative TRT for residual lung lesions and mediastinal lymph nodes with a total radiation dose reaching 60.48 Gy in 30 fractions after achieving PR with combined therapy. Though the tumor showed only modest radiological reduction post-radiotherapy, the subsequent 5-month maintenance period without progression suggests a potential synergistic effect with prior systemic therapy. Regarding whether PFS and OS are beneficial, we look forward to clinical trials in SMARCA4-UT patients to provide answers.

Based on the current National Comprehensive Cancer Network (NCCN) guidelines (Riely et al. 2024), for low-volume progressive metastatic NSCLC, both surgery and radiotherapy targeting the site of oligorecurrence are appropriate options. Han et al. (2020) found that surgical intervention was linked to improved post-recurrence survival compared to non-surgical approaches (chemotherapy, radiotherapy, chemoradiotherapy, and supportive care) in patients with pulmonary oligorecurrence following curative resection of NSCLC. Studies (Sugimura et al. 2007) have indicated that patients with isolated pulmonary recurrence who underwent surgical treatment had a median survival of 32.8 months, in contrast to 13.4 months for those who received non-surgical treatment. In our case, after maintenance therapy, the patient developed oligorecurrence at the site of the original lung tumor. Considering that the patient had previously undergone radiotherapy at this site, surgical resection and postoperative maintenance therapy were performed, and to date, there has been no recurrence of the tumor.

We report a case of SMARCA4-UT achieving long-term survival through multimodal therapy. However, there were some limitations of this case report. The patient did not receive testing for SMARCA4, despite the routine ten-gene mutation screening. The SMARCA4 mutation was identified as the loss of BRG1 expression based on immunohistochemical staining results, even though SMARCA4 encodes the latter. Moreover, given that SMARCA4-UT remains a rare and heterogeneous entity, the efficacy of multimodal regimens needs to be validated in larger cohorts. Future prospective studies should explore the optimal combinations of chem immunotherapy, antiangiogenic drugs, radiation therapy, and surgical treatment to establish evidence-based guidelines.

Conclusion

This case report details a patient with brain metastasis from SMARCA4-UT who achieved a 31-month survival, significantly exceeding the typical median survival of 4–7 months. Despite PD-L1 expression < 1% and the absence of targetable mutations, a multimodal treatment strategy—first-line tislelizumab, bevacizumab, carboplatin, and paclitaxel, followed by consolidative TRT and salvage surgery for oligoprogression—was effective. This case underscores that combining chemoimmunotherapy, anti-angiogenic therapy, radiotherapy, and surgery may offer substantial benefits for patients with SMARCA4-UT. Larger prospective studies are needed to validate these regimens and establish guidelines for this rare and aggressive malignancy.

Author contributions

YG and SW wrote the main manuscript text. QH and FH prepared the figures. All authors have browsed and agreed with the final manuscript.

Funding

None.

Data availability

No datasets were generated or analysed during the current study.

Declarations

Conflict of interest

The authors declare no competing interests.

Ethical approval

The study was conducted following local legislative and institutional requirements. The patient provided written informed consent for study participation. Written informed consent has also been obtained from the patient to publish any potentially identifiable images or data in this article.

Consent to participate

Informed consent was obtained from all individual participants included in the study.

Consent for publication

The authors affirm that human research participants provided informed consent for publication of the images in Fig. 1–3.