Emerging new evidence for the treatment of pulmonary sarcomatoid carcinoma
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PROVIDER: S-EPMC10089887 | biostudies-literature | 2023 Feb
REPOSITORIES: biostudies-literature
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Project description:PurposePulmonary sarcomatoid carcinoma (PSC) is a rare aggressive subtype of non-small cell lung cancer (NSCLC) with limited therapeutic strategies. We attempted to elucidate the evolutionary trajectories of PSC using multiregional and longitudinal tumor samples.Materials and methodsA total of 31 patients were enrolled in this study and 11 longitudinal samples were available from them. Using whole exome sequencing data, we analyzed the mutational signatures in both carcinomatous and sarcomatous areas in primary tumors of the 31 patients and longitudinal samples obtained from 11 patients. Furthermore, digital droplet polymerase chain reaction (ddPCR), and programmed death-ligand 1 (PD-L1) immunohistochemistry using the Ventana SP263 assay were performed.ResultsTP53 was identified as the most frequently altered gene in the primary (74%) and metastatic (73%) samples. MET exon 14 skipping mutations, confirmed by ddPCR, and TP53 mutations were mutually exclusive; whereas, MET exon 14 skipping mutations frequently co-occurred with MDM2 amplification. Metastatic tumors showed dissimilar genetic profiles from either primary component. During metastasis, the signatures of APOBEC decreased in metastatic lesions compared with that in primary lesions. PSC showed higher MET and KEAP1 mutations and stronger PD-L1 protein expression compared with that recorded in other NSCLCs.ConclusionDecreased APOBEC signatures and subclonal diversity were detected during malignant progression in PSC. Frequent MET mutations and strong PD-L1 expression distinguished PSC from other NSCLCs. The aggressiveness and therapeutic difficulties of PSC were possibly attributable to profound intratumoral and intertumoral genetic diversity. Next-generation sequencing could suggest the appropriate treatment strategy for PSC.
| S-EPMC11016656 | biostudies-literature
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.
| S-EPMC11002509 | biostudies-literature
Project description:Pulmonary sarcomatoid carcinoma (PSC) is a rare subset of NSCLC that accounts for about 0.5-1% of all primary lung carcinoma, and its malignant biological behavior is more aggressive than other pathological types of lung cancer. Recent studies have reported a variety of gene mutations associated with the occurrence, development and treatment of PSC, especially the mesenchymal-epithelial transition (MET) proto-oncogene alterations, including the exon 14 (METex14) skipping mutations as well as the amplification and overexpression of MET gene, which are associated with molecularly targeted therapy for PSC. METex14 skipping mutation is the most common and well-studied mutation type, occurring in about 22-31.8% of PSC patients, while the prevalence of MET amplification is reported as 4.8-13.6% and MET ovexpression is about 20.2%. Molecular pathology tests, including IHC and NGS, are valuable in determining the prognosis of patients with PSC and helping to determine the treatment. The existing clinical data have confirmed the efficacy of MET-TKI in PSC patients with MET alteration, among which the clinical study of Savolitinib has enrolled the largest proportion of PSC patients and achieved relatively good efficacy, but more clinical researches are still needed. The multi-disciplinary team may maximize the optimal treatment options for patients with the advanced PSC.
| S-EPMC9539670 | biostudies-literature
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.
| S-EPMC10196425 | biostudies-literature
Project description: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.
| S-EPMC8975648 | biostudies-literature
Project description:Pulmonary sarcomatoid carcinoma (PSC) is a group of five rare non-small cell lung cancer subtypes. In the present study, the clinical characteristics and outcomes of patients with PSC registered in the Surveillance, Epidemiology and End Results (SEER) database were investigated. For this purpose, data for patients with PSC (n=1,723) who received their initial diagnosis between 1988 and 2016 were collected from the SEER database. Survival analysis was performed using the Kaplan-Meier curves and the log-rank test. Subsequently, multivariate analyses with the Cox proportional hazards model were used to identify significant independent predictors. A nomogram model was established to predict survival performance using the concordance index (C-index). From the total cohort, patients with pulmonary blastoma demonstrated improved 1-year overall survival (OS) rate compared with other pathological types (P<0.001). The 2-year overall survival rates of the 'only radiotherapy' cohort and the 'no specific treatment' cohort were 9.1 and 5.4% (P<0.001), respectively. Radiotherapy significantly improved the OS rate in stage I-III patients with PSC (P<0.001) when stratified by stage. After matching the propensity scores, the 'surgery combined with radiotherapy' group comprised 156 patients and the 'surgery-only' group had 247 patients (1:1.6). However, no significant differences in prognosis were found between the 2 subgroups (P=0.052). The multivariate Cox analysis demonstrated that older age (≥76 years old), male, unmarried, pathological type, larger tumor size (≥56 mm), later tumor node metastasis stages and treatment modalities were independent prognostic factors. A nomogram model was established to predict the survival of patients with PSC. This model incorporated the seven aforementioned independent prognostic factors (C-index for survival, 0.75; 95% confidence interval, 0.74-0.76). Radiotherapy needs to considered for stage I-III patients with PSC who undergo radiation therapy without surgical resection.
| S-EPMC7202303 | biostudies-literature
Project description:BackgroundPulmonary sarcomatoid carcinoma (PSC) is a kind of rare lung cancer. We aim to analyze the clinical characteristics and prognostic factors of patients with PSC.MethodsFrom January 1, 2006 to December 31, 2015, 119 patients in the Cancer Hospital Chinese Academy of Medical Sciences were diagnosed with PSC, and they received treatment. We retrospectively collected information on gender, age, body mass index (BMI), symptoms, family history, smoking history, tumor size, tumor location, tumor diameter, tumor-node-metastasis (TNM), pathological type, and other factors to analyze the relationship between these factors and 1-, 3-, 5-year, and overall survival (OS).ResultsMale patients who had a smoking history (n=76) comprised the main group of PSC. Median patient age was 60.67±10.50 years (range, 26-89 years). The majority of these patients (n=82) presented with respiratory symptoms. The median survival of patients who died of PSC was 11.87 months (6.38-21.48 months). The 1-, 3-, and 5-year survival rates were 61.3%, 34.5%, and 31.9%, respectively. Patients with a lower T stage and without lymph node metastasis and distant metastasis had a better OS (P<0.05). Other clinical characteristics and the difference in treatments did not influence the prognosis significantly (P>0.05).ConclusionsPSC is a rare malignant neoplasm of the lung with poor prognosis. Surgery is a major therapeutic method for this disease entity. TNM-stage is the main factors affecting prognosis.
| S-EPMC9641323 | biostudies-literature
Project description:Pulmonary sarcomatoid carcinoma (PSC) is classified as poorly differentiated, and non-small cell lung carcinomas that contained a component of sarcoma or sarcoma-like differentiation are rare. The underlying carcinogenetic mechanism governing PSC remains unclear. The current study investigated the underlying carcinogenetic mechanism of PSC based on the hypothesis that it involves the epithelial-mesenchymal transition (EMT) process. Mutation analysis of PSCs, including carcinosarcoma, pleomorphic carcinoma and epithelial carcinoma specimens, was performed using targeted deep sequencing, whole transcriptome analysis and digital spatial profiling (DSP). PSCs exhibit a distinct mutation profile, with TP53, SYNE1 and APC mutations. Therefore, clustering of the gene expression profiles allowed the PSCs to be distinguished from the epithelial carcinomas. Increased gene expression of fibronectin in PSC was an important contributor to differential profiles. Pathway analysis revealed enhanced activity of the integrin-linked kinase (ILK) signaling pathway in the PSCs. DSP analysis using 56 antibodies of marker proteins confirmed significantly higher expression of fibronectin in PSCs. Intratumor heterogeneity of fibronectin expression was observed in sarcoma components. In conclusion, epithelial-mesenchymal transition process mediated by ILK signaling may be associated with carcinogenetic mechanisms of PSC. Overexpression of fibronectin mediated by ILK signaling appears to serve a role in the EMT involved in the PSC transformation process.
| S-EPMC7933776 | biostudies-literature
Project description:PurposePulmonary sarcomatoid carcinoma (PSC) is recognized for its aggressiveness and poor prognosis. The role of radical radiotherapy in PSC remains uncertain due to its scarcity and limited data. In the absence of an effective systemic agent, this study aims to explore the possibility of cure and to investigate potential prognostic factors and treatment outcomes.Materials and methodsFrom January 2005 to December 2021, 149 PSC patients were identified. Among 62 patients who received radiotherapy for lung lesions, 25 who underwent palliative radiotherapy and 16 who underwent surgery were excluded.ResultsThe median patient age was 71 years. The majority were male, and 17 patients (81.0%) were diagnosed at an advanced stage. After radical radiotherapy, distant metastasis (47.6%) was the most common site of failure, while the local recurrence rate was quite low (9.5%). Eventually, five patients (26.3%) demonstrated either a partial response or complete remission, including three complete remissions with durable responses. The median progression-free survival (PFS) and overall survival were 4.6 months and 7.9 months, respectively. Univariate and multivariate analyses revealed that a tumor size >5 cm was associated with a worse prognosis (p = 0.045), while a radiation dose >58 GyEQD2 was significantly associated with better PFS (p = 0.038).ConclusionThis study demonstrates clinical outcomes after radical radiotherapy in managing PSC, suggesting tumor size and radiation dose could be a predictor of a systemic response. Given the known bad prognosis but complete remission could be achieved in certain subgroups, future research should explore the potential strategies using radical radiotherapy for this challenging patient population.
| S-EPMC10556836 | biostudies-literature
Project description:A 14-year-old, neutered male domestic shorthair cat presented for acute monoparesis with physical exam findings and biochemical data supportive of a distal arterial thromboembolism. Thoracic radiographs revealed an alveolar pattern in the right middle lung lobe and multifocal nodules in other lung lobes. A pulmonary mass was found on necropsy, which was composed of both carcinomatous and sarcomatous components, confirmed with cytokeratin and vimentin immunohistochemistry. Using the World Health Organization classification scheme for mixed pulmonary tumors, this tumor would be characterized as a pleomorphic squamous cell carcinoma under the umbrella term of pulmonary sarcomatoid carcinoma. The World Health Organization classification of mixed pulmonary tumors and its application to previously reported mixed pulmonary tumors in companion animals is discussed. This is the first reported case of this tumor type in a cat, as well as the first report of this tumor type associated with an arterial thromboembolism in any veterinary species.
| S-EPMC7822706 | biostudies-literature