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Multimodality Treatment of Pulmonary Sarcomatoid Carcinoma: A Review of Current State of Art.

ABSTRACT: Pulmonary sarcomatoid carcinoma (PSC) is an unconventional non-small-cell lung cancer (NSCLC) that is currently managed under guidelines used for conventional NSCLC and has poor survival. Surgery is the optimal choice for resectable PSC, and the prevalence of mutations in this type of tumor laid the foundation for novel systemic therapies such as targeted therapy and immunotherapy. PSC is resistant to chemotherapy and radiotherapy, and the effects of the 2 therapies are controversial. Targeted therapies have been reported to confer survival benefits, and savolitinib, an oral selective MET tyrosine-kinase inhibitor, has been approved in metastatic patients with MET exon 14 skipping mutations. Expression and positive rate of programmed death ligand 1 in PSC are high; our previous research has also revealed a high mutational burden and a T-cell-inflamed microenvironment of PSC. Correspondingly, immune checkpoint inhibitors have shown preliminary antitumor effects (overall response rates of 40.5% (15/37) and 31.6% (6/19) in two retrospective studies, respectively) in PSC patients. In summary, patients should receive operations at an early stage and multimodality treatments are needed to maximize the benefits of patients with advanced disease.

SUBMITTER: Zhang L

PROVIDER: S-EPMC8975648 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Multimodality Treatment of Pulmonary Sarcomatoid Carcinoma: A Review of Current State of Art.

Zhang Lin L Lin Weihao W Yang Zhenlin Z Li Renda R Gao Yibo Y He Jie J

Journal of oncology 20220325

Pulmonary sarcomatoid carcinoma (PSC) is an unconventional non-small-cell lung cancer (NSCLC) that is currently managed under guidelines used for conventional NSCLC and has poor survival. Surgery is the optimal choice for resectable PSC, and the prevalence of mutations in this type of tumor laid the foundation for novel systemic therapies such as targeted therapy and immunotherapy. PSC is resistant to chemotherapy and radiotherapy, and the effects of the 2 therapies are controversial. Targeted t ...[more]

PMID: 35368903

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Project description:Background and objectivePulmonary sarcomatoid carcinoma (PSC) is a subset of non-small cell lung cancer (NSCLC) with highly malignant, aggressive, and heterogeneous features. Patients with this disease account for approximately 0.1-0.4% of lung cancer cases. The absence of comprehensive summaries on the basic biology and clinical treatments for PSC means there is limited systematic awareness and understanding of this rare disease. This paper provides an overview of the biological characteristics of PSC and systematically summarizes various treatment strategies available for patients with this disease.MethodsFor this narrative review, we have searched literature related to the basic biology and clinical treatment approaches of PSC by searching the PubMed database for articles published from July 16, 1990 to August 29, 2023. The following keywords were used: "pulmonary sarcomatoid carcinoma", "genetic mutations", "immune microenvironment", "hypoxia", "angiogenesis", "overall survival", "surgery", "radiotherapy", "chemotherapy", and "immune checkpoint inhibitors".Key content and findingsClassical PSC comprises epithelial and sarcomatoid components, with most studies suggesting a common origin. PSC exhibits a higher tumor mutational burden (TMB) and mutation frequency than other types of NSCLC. The tumor microenvironment (TME) of PSC is characterized by hypoxia, hypermetabolism, elevated programmed cell death protein 1/programmed cell death-ligand 1 expression, and high immune cell infiltration. Treatment strategies for advanced PSC are mainly based on traditional NSCLC treatments, but PSC exhibits resistance to chemotherapy and radiotherapy. The advancement of genome sequencing has introduced targeted therapies as an option for mutation-positive PSC cases. Moreover, due to the characteristics of the immune microenvironment of PSC, many patients positively respond to immunotherapy, demonstrating its potential for the management of PSC.ConclusionsAlthough several studies have examined and assessed the TME of PSC, these are limited in quantity and quality, presenting challenges for research into the clinical treatment strategies for PSC. With the emergence of new technologies and the advancement of clinical research, for example, savolitinib's clinical study for MET exon 14 skipping mutations positive PSC patients have shown promising outcomes, more in-depth studies on PSC are eagerly anticipated.

Project description:Key clinical messageIn conclusion author highlights the tumor cell genetic testing or molecular pathological diagnosis plays a key role in the individualized treatment of PSC, which could benefit patients with advanced PSC.AbstractAn uncommon form of non-small-cell lung cancer (NSCLC) with a poor prognosis is pulmonary sarcomatoid carcinoma (PSC). Surgical resection is currently the preferred treatment, but guidelines for adjuvant chemotherapy have not yet been established, especially for the advanced stage. The development of molecular subgroups in the field of tumors may be advantageous to advanced PSC patients with the ongoing progress of genomics and immunology. A 54-year-old man presented to Xishan People's Hospital of Wuxi City with recurrent intermittent dry cough with fever for 1 month. Further examinations suggested the diagnosis of PSC occupying almost the entire right interlobar fissure area combined with malignant pleural effusion (Stage IVa). Pathological examination confirmed the diagnosis of PSC with ROS1 overexpressing via genetic testing. However, after three cycles of chemo-, antiangiogenetic- and immunochemical therapy, the lesion was localized, and pleural effusion disappeared, the patient subsequently received an operation which was performed as R0 resection. Unfortunately, the patient became deteriorated quickly followed by extensive metastatic nodules in the thoracic cavity. Although the patient continued to receive chemo- and immunochemical-therapy, it did not limit the progress of the tumor, leading to widespread metastasis, and eventually died of multiple organ failure. For PSC patients with Stage IVa, chemo-, antiangiogenetic- and immunochemical-therapy performs well in clinical efficacy, and comprehensive panel-based genetic testing may offer PSC patients a somewhat better prognosis. However, blindly implementing surgical treatment may bring harm to the patient and affect long-term survival. It's essential to know the surgical indications precisely by NSCLC guidelines.

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Multimodality Treatment of Pulmonary Sarcomatoid Carcinoma: A Review of Current State of Art.

Publications

Multimodality Treatment of Pulmonary Sarcomatoid Carcinoma: A Review of Current State of Art.

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