Atezolizumab with bevacizumab, paclitaxel and carboplatin was effective for patients with SMARCA4-deficient thoracic sarcoma

Kawachi, Hayato; Kunimasa, Kei; Kukita, Yoji; Honma, Keiichiro; Kawamura, Takahisa; Inoue, Tomio; Tamiya, Motohiro; Kuhara, Hanako; Nishino, Kazumi; Mizote, Yu; Akazawa, Takashi; Tahara, Hideaki; Kumagai, Toru

doi:10.2217/imt-2020-0311

Cited by 37 publications

(42 citation statements)

References 24 publications

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“…In this study, we found that SMARCA4-related genes were enriched in the PPAR signaling pathway and identified a strong correlation among SMARCA4, CD274, and PDCD1. Furthermore, the expression levels of SMARCA4 were found to be positively correlated with immunotherapy, which were consistent with the study reported by Peng et al [ 22 ], and was further confirmed in the patients with thoracic sarcoma and pancreatic cancer[ 19 , 45 ].…”

Section: Discussionsupporting

confidence: 90%

Delineation of a SMARCA4-specific competing endogenous RNA network and its function in hepatocellular carcinoma

Zhang¹,

Sun²,

Wu³

et al. 2022

World J Clin Cases

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BACKGROUND Hepatocellular carcinoma (HCC) is a common malignancy worldwide, and the mortality rate continues to rise each year. SMARCA4 expression has been associated with poor prognosis in various types of cancer; however, the specific mechanism of action of SMARCA4 in HCC needs to be fully elucidated. AIM To explore the specific mechanism of action of SMARCA4 in HCC. METHODS Herein, the expression level of SMARCA4 as well as its association with HCC prognosis were evaluated using transcriptome profiling and clinical data of 18 different types of cancer collected from The Cancer Genome Atlas database. Furthermore, SMARCA4-high and -low groups were identified. Thereafter, gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed to identify the function of SMARCA4, followed by construction of a SMARCA4-specific competing endogenous RNA (ceRNA) network using starBase database. The role of SMARCA4 in immunotherapy and its association with immune cells were assessed using correlation analysis. RESULTS It was observed that SMARCA4 was overexpressed and negatively correlated with prognosis in HCC. Further, SMARCA4 expression was positively associated with tumor mutational burden, microsatellite stability, and immunotherapy efficacy. The SNHG3/THUMP3-AS1-miR-139-5p-SMARCA4 ceRNA network was established and could be assumed to serve as a stimulatory mechanism in HCC. CONCLUSION The findings of this study demonstrated that SMARCA4 plays a significant role in progression and immune infiltration in HCC. Moreover, a ceRNA network was detected, which was found to be correlated with poor prognosis in HCC. The findings of this study could contribute towards the identification of predictive markers for immunotherapy and a novel mechanism of action for HCC treatment.

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Section: Discussionsupporting

confidence: 90%

Delineation of a SMARCA4-specific competing endogenous RNA network and its function in hepatocellular carcinoma

Zhang¹,

Sun²,

Wu³

et al. 2022

World J Clin Cases

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“…7,8 Although the efficacy of anti-angiogenic agents in sarcoma has not been established, it has been reported that treatment with atezolizumab, bevacizumab, carboplatin, and paclitaxel was effective in thoracic SMARCA4-deficient undifferentiated tumors. 9 Our patient was treated with atezolizumab, carboplatin, and nab-paclitaxel, excluding anti-angiogenic agents for hemoptysis, and achieved stable disease for 7 months.…”

Section: Discussionmentioning

confidence: 90%

“…It has been reported that the therapeutic effect was obtained using the anti‐PD‐L1 antibody in thoracic SMARCA4‐deficient undifferentiated tumors, regardless of the degree of PD‐L1 expression 7,8 . Although the efficacy of anti‐angiogenic agents in sarcoma has not been established, it has been reported that treatment with atezolizumab, bevacizumab, carboplatin, and paclitaxel was effective in thoracic SMARCA4‐deficient undifferentiated tumors 9 . Our patient was treated with atezolizumab, carboplatin, and nab‐paclitaxel, excluding anti‐angiogenic agents for hemoptysis, and achieved stable disease for 7 months.…”

Section: Discussionmentioning

confidence: 99%

SMARCA4‐deficient undifferentiated tumor that responded to chemotherapy in combination with immune checkpoint inhibitors: A case report

et al. 2022

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Thoracic SMARCA4‐deficient undifferentiated tumors are a new type of neoplasm that commonly occur in the mediastinum, progress rapidly, and show a poorer prognosis. We report a case of thoracic SMARCA4‐deficient undifferentiated tumor in the right thoracic cavity in a patient with a history of heavy smoking and presenting with respiratory distress and hemoptysis. Imaging showed pleural effusion and thickening. A diagnostic right pleural biopsy yielded multiple white nodules and pale bloody pleural effusion accumulated in the right thoracic cavity. Histopathologically, the tumor cells were large, some exhibited rhabdoid cytology, and they were surrounded by an infiltration of inflammatory cells. These tumor cells were negative for SMARCA4, p40, NUT, and claudin‐4, leading to establishing a diagnosis of thoracic SMARCA4‐deficient undifferentiated malignancy. We treated the patient with atezolizumab, carboplatin, and nab‐paclitaxel. The patient achieved stable disease at 7 months during this study. Although there is no standard treatment of this disease, our reported treatment may contribute to improved prognosis, requiring further research.

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“…SMARCA4‐UT is generally insensitive to cytotoxic chemotherapy; therefore, in this case, we did not administer adjuvant chemotherapy. Although three recent cases of unresectable SMARCA4‐UTs receiving combined immunotherapy, including atezolizumab, showed a strong effect (up to 17 months progression‐free survival), 5 there are no reports on the efficacy of immune checkpoint inhibitors (ICI) as adjuvant chemotherapy. Owing to the aggressive growth of these tumours, once symptoms appear, continuing treatment is frequently difficult, with decreased patient performance status.…”

Section: Discussionmentioning

confidence: 99%

A dramatic course after the resection of an SMARCA4‐deficient undifferentiated tumour

Iguchi

Mizuguchi

Chung

et al. 2022

Respirology Case Reports

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Thoracic SMARCA4‐deficient undifferentiated tumours are ordinarily found as a huge mass with systemic metastasis, and the prognosis is poor. The potential of immunotherapy for these unresectable tumours has been reported. An asymptomatic 68‐year‐old man with a smoking history had a left lung mass without distant metastasis and underwent complete resection. Two months after surgery, with no adjuvant therapy, he developed multiple distant metastases with aphasia and died 4 months after surgery. Adjuvant treatment may be necessary with immune checkpoint inhibitors, with a closer follow‐up to detect recurrence without symptoms.

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Atezolizumab with bevacizumab, paclitaxel and carboplatin was effective for patients with SMARCA4-deficient thoracic sarcoma

Cited by 37 publications

References 24 publications

Delineation of a SMARCA4-specific competing endogenous RNA network and its function in hepatocellular carcinoma

Delineation of a SMARCA4-specific competing endogenous RNA network and its function in hepatocellular carcinoma

SMARCA4‐deficient undifferentiated tumor that responded to chemotherapy in combination with immune checkpoint inhibitors: A case report

A dramatic course after the resection of an SMARCA4‐deficient undifferentiated tumour

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