Efficacy of immunotherapy in sarcomatoid lung cancer, a case report and literature review

Kotlowska, M. Palka; Rueda, A. Gómez; Olmedo, María Eugenia; Benito, Amparo; Roldán, Almudena Santón; Fernández-Méndez, María Ángeles; Gorospe, Luis; Palacios, José; Garrido, Pilar

doi:10.1016/j.rmcr.2019.02.017

Cited by 28 publications

(24 citation statements)

References 41 publications

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“…12 Sarcoma components include rhabdomyosarcoma, chondrosarcoma, osteosarcoma, and combinations of these components. 13 In our study, all three male smokers were diagnosed with pulmonary carcinosarcoma, presenting as squamous cell carcinoma with sarcoma component. For immunohistochemistry, EMA, CK5/6, CK7, TIF1, P63, chromogranin A, CD56, and synaptophysin can be used as markers for carcinomatous components, and desmin, vimentin, and smooth muscle/sarcomeric actin can be used as markers for sarcomatous elements.…”

Section: Discussionmentioning

confidence: 68%

<p>Next-Generation Sequencing Analysis Identified Genomic Alterations in Pathological Morphologies of 3 Cases of Pulmonary Carcinosarcoma</p>

Фан¹,

Hu²,

Kong³

et al. 2020

OTT

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Background: Pulmonary carcinosarcomas (PCSs) are a heterogeneous group of non-smallcell lung carcinomas (NSCLCs) with aggressiveness and a poor prognosis. Although genetic mutations of some common lung cancer subtypes have been extensively studied, the molecular characteristics of PCSs and the existence of abnormal target genes are unknown. Methods: In this study, the clinical and molecular characterization in 3 pulmonary sarcomatoid carcinomas (PSCs) were presented using microscope analysis and next-generation sequencing (NGS) analysis. Results: The results revealed a carcinosarcomas subtype presenting squamous cell carcinoma and sarcoma components in all 3 cases. NGS analysis showed that 182, 316 and 230 shared mutations were detected between sarcoma and lung carcinoma from 3 patients. Two identical alterations in two genes (CSMD3 and RYR3) that were all shared by the two components in 3 patients. Tumor suppressor gene TP53 (5/6, 83%) showed the highest mutation frequency for driver genes here. Additionally, we focused on an LYST mutation which was mainly present in the sarcoma components. Moreover, the clonal evolution and signature analysis confirm that lung squamous cell carcinoma and sarcoma in each PCS patient may have come from a common ancestor, and mutagenesis was possibly related to indirect effects of tobacco, age or other unknown factors. Conclusion: Our results indicate that genetic analysis and molecular targeted therapy are necessary for the identification and treatment of these rare lung tumors. CSMD3 and LYST, as common mutation genes, may be a potential therapeutic target in PCS.

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Section: Discussionmentioning

confidence: 68%

<p>Next-Generation Sequencing Analysis Identified Genomic Alterations in Pathological Morphologies of 3 Cases of Pulmonary Carcinosarcoma</p>

Фан¹,

Hu²,

Kong³

et al. 2020

OTT

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“…At the same time, PSC also had a high expression of PD-L1, suggesting that targeting PD-1/PD-L1 might be a potential treatment regimen for PSC. Patients with PSC who received PD-1/PD-L1 inhibitors exhibited high response rates and prolonged overall survival (24)(25)(26)(27)(28)(29)(30)(31). Also some novel biomarkers were investigated to predict the survival outcome of PSC, such as CD8+ tumor-infiltrating lymphocytes, the epithelial−mesenchymal transition transcription factors (Twist1), the change of neutrophil-to-lymphocyte ratio, KRAS mutations and c-MET overexpression (32)(33)(34)(35)(36).…”

Section: Discussionmentioning

confidence: 99%

Survival Analysis and Prediction Model for Pulmonary Sarcomatoid Carcinoma Based on SEER Database

Chen

Qiao

et al. 2021

Front. Oncol.

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ObjectiveThis study aimed to investigate the incidence of the pulmonary sarcomatoid carcinoma (PSC), to compare the clinical characteristics and overall survival (OS) of patients with PSC and those with other non-small-cell lung cancer (oNSCLC), so as to analyze the factors affecting the OS of patients with PSC and construct a nomogram prediction model.MethodsData of patients with PSC and those with oNSCLC diagnosed between 2004 and 2015 from the Surveillance, Epidemiology, and End Results database were collected. The age-adjusted incidence of PSC was calculated. The characteristics of patients with PSC and those with oNSCLC were compared, then the patients were matched 1:2 for further survival analysis. Patients with PSC were randomly divided into training set and testing set with a ratio of 7:3. The Cox proportional hazards model was used to identify the covariates associated with the OS. Significant covariates were used to construct the nomogram, and the C-index was calculated to measure the discrimination ability. The accuracy of the nomogram was compared with the tumor–node–metastasis (TNM) clinical stage, and the corresponding area under the curve was achieved.ResultsA total of 1049 patients with PSC were enrolled, the incidence of PSC was slowly decreased from 0.120/100,000 in 2004 to 0.092/100,000 in 2015. Before PSM, 793 PSC patients and 191356 oNSCLC patients were identified, the proportion of male, younger patients (<65 years), grade IV, TNM clinical stage IV was higher in the PSC. The patients with PSC had significantly poorer OS compared with those with oNSCLC. After PSM, PSC still had an extremely inferior prognosis. Age, sex, TNM clinical stage, chemotherapy, radiotherapy, and surgery were independent factors for OS. Next, a nomogram was established based on these factors, and the C-indexs were 0.775 and 0.790 for the training and testing set, respectively. Moreover, the nomogram model indicated a more comprehensive and accurate prediction than the TNM clinical stage.ConclusionsThe incidence of PSC was slowly decreased. PSC had a significantly poor prognosis compared with oNSCLC. The nomogram constructed in this study accurately predicted the prognosis of PSC, performed better than the TNM clinical stage.

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“…Considering the similar TME of the epithelial and sarcomatoid components from the same patient demonstrated by fluorescent multiplex IHC, the two components could both have a possible favorable response to immunotherapy. In addition, cases of PSC with dramatic response to immune checkpoint inhibitors were reported 36 , 37 , despite the lack of large-scale clinical research. Therefore, immunotherapy could offer a new hope for patients with PSC and help improve patient outcomes in the future.…”

Section: Discussionmentioning

confidence: 99%

Integrated molecular characterization reveals potential therapeutic strategies for pulmonary sarcomatoid carcinoma

Yang

et al. 2020

Nat Commun

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Pulmonary sarcomatoid carcinoma (PSC) is a rare subtype of lung cancer with poor prognosis. Here, we perform multi-omics analysis of 56 PSC samples, 14 of which are microdissected to analyze intratumoral heterogeneity. We report the mutational landscape of PSC. The epithelial and sarcomatoid components share numerous genomic alterations, indicating a common progenitor. We find that epithelial-mesenchymal transition (EMT) plays important roles in the carcinogenesis of PSC. The pan-cancer analysis reveals high tumor mutation burden and leukocyte fraction of PSC. Integrated molecular classification shows three subgroups with distinct biology, prognosis and potential therapeutic strategies. Actionable mutations are enriched in C1 and C2, patients in C3 have a significantly longer overall survival, and C1 and C2 exhibit T-cell inflamed microenvironments. The three subgroups show molecular similarities to specific subtypes of conventional lung cancer. In conclusion, our study reveals the molecular characteristics and provides entry points for the treatment of PSC.

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Efficacy of immunotherapy in sarcomatoid lung cancer, a case report and literature review

Cited by 28 publications

References 41 publications

<p>Next-Generation Sequencing Analysis Identified Genomic Alterations in Pathological Morphologies of 3 Cases of Pulmonary Carcinosarcoma</p>

<p>Next-Generation Sequencing Analysis Identified Genomic Alterations in Pathological Morphologies of 3 Cases of Pulmonary Carcinosarcoma</p>

Survival Analysis and Prediction Model for Pulmonary Sarcomatoid Carcinoma Based on SEER Database

Integrated molecular characterization reveals potential therapeutic strategies for pulmonary sarcomatoid carcinoma

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