Pulmonary Carcinosarcoma Research Articles

EP.06C.08 Presentations and Outcomes of Pulmonary Carcinosarcoma: Results of Comparing Pulmonary Carcinosarcoma and Primary Lung Sarcoma

EP.06C.08 Presentations and Outcomes of Pulmonary Carcinosarcoma: Results of Comparing Pulmonary Carcinosarcoma and Primary Lung Sarcoma

Resection of Simultaneous Pulmonary Carcinosarcoma and Squamous Cell Carcinoma of the Lung: a Case Report

Resection of Simultaneous Pulmonary Carcinosarcoma and Squamous Cell Carcinoma of the Lung: a Case Report

Successful right lower bilobectomy for endobronchial carcinosarcoma rapidly occluding the trachea: a case report

Background: Endobronchial carcinosarcoma is an extremely rare type of pulmonary carcinosarcoma. It is defined by coexisting histologic elements of carcinomatous parenchyma and sarcomatous stroma and the most common finding was squamous cell carcinoma. Although it is also characterized by polypoid growth without invasion of the adjoining bronchial mucosa, because the polypoid often shows necrosis, it hampers prompt diagnosis by adequate tissue samples and treatment.

Pulmonary Carcinosarcoma is a Rare Cancer with a Poor Prognosis – A Retrospective Study

Pulmonary Carcinosarcoma is a Rare Cancer with a Poor Prognosis – A Retrospective Study

Clinical features and prognostic factors of pulmonary carcinosarcoma: A nomogram development and validation based on surveillance epidemiology and end results database.

Pulmonary carcinosarcoma (PCS) is a rare but aggressive malignant disease in the lung. It is characterized by coexisting histologic elements of carcinomatous and sarcomatous components. This study aimed to comprehensively understand the clinical features of PCS and develop a nomogram for prognostic prediction of PCS patients. Data were collected from the Surveillance Epidemiology and End Results (SEER) database between 1975 and 2018. Propensity-score matching (PSM) was used to match the demographic characteristic of the PCS vs. pulmonary sarcoma (PS). Cancer-specific survival (CSS) and overall survival (OS) were the main endpoints of the survival of patients and were evaluated using the Kaplan Meier curves and Cox proportional hazards regression. We further randomly split enrolled PCS patients from SEER into the training and validation sets. All independent predictors for OS of the training set were integrated to create a predictive nomogram. The performance of the nomogram was determined by discrimination, calibration ability, clinical usefulness, and risk stratification ability both in the training and validation cohorts. In addition, the clinical data of PCS patients from the West China Hospital were also retrospectively analyzed by this model. A total of 428 PCS patients and 249 PS patients were enrolled from SEER. Compared to pure PS, PCS was associated with significantly better survival in the unmatched cohorts, whereas non-significantly better survival after PSM. In subgroup analysis, PCS showed significantly worse survival than pure PS in subgroups among the race, marital status, and radiation treatment. A nomogram was constructed for PCS patients' survival prediction by combining the independent risk factors, including gender, stage, surgery, radiation, and chemotherapy. The nomogram showed good discrimination, calibration, and predictive power in the training and validation sets. Risk stratification analysis indicated that the nomogram scores efficiently divided PCS patients into low and high-risk groups. PCS is a rare malignant disease of the lung with distinct clinical features. It had a comparable survival compared with pure PS in the matched cohorts. In addition, a nomogram was developed and validated for predicting the OS in PCS patients.

CASE REPORT OF RAPIDLY DECOMPENSATING PRIMARY PULMONARY CARCINOSARCOMA

CASE REPORT OF RAPIDLY DECOMPENSATING PRIMARY PULMONARY CARCINOSARCOMA

Molecular and expressional characterization of tumor heterogeneity in pulmonary carcinosarcoma.

The genetic concordance and heterogeneity of the two components of pulmonary carcinosarcoma (PCS), carcinoma, and sarcoma, have not been fully elucidated because of its rare occurrence. We performed targeted sequencing of the carcinoma and sarcoma components of four PCSs to identify genetic similarities and differences. Formalin-fixed paraffin-embedded tissue samples were macroscopically or microscopically dissected. DNA was extracted from each component, and genetic alterations were analyzed separately. Moreover, we performed RNA-seq analysis on both components of one PCS to compare differences in gene expression profiles. The carcinoma part consisted of adenocarcinoma in two cases, squamous cell carcinoma in one, and adenosquamous carcinoma in the last. TP53 mutation was observed in three samples from the trunk, although it was detected only in the sarcoma part in one case. No specific driver gene mutation was observed; however, KRAS mutations were observed in one case in the trunk. RNA-seq analysis revealed that the rhabdomyosarcoma component expressed various genes related to muscle development, whereas the carcinoma component did not; and that gene expression overall was completely different between the two components. Our study revealed that the two different components of PCS shared common gene mutations in most cases. Although gene expression was different among components, if driver genes such as KRAS were detected in PCS, molecular targeted therapy could be beneficial even when the tumor contains a sarcoma component.

Pulmonary Carcinosarcoma: A Rare Disease With Challenging Diagnosis and Treatment

Pulmonary carcinosarcoma (PCS) is a rare type of non-small cell cancer. Overall, middle-aged and older smokers are the most affected age and sex groups. The diagnosis of PCS is difficult due to the absence of characteristic imaging findings. Additionally, preoperative biopsies do not usually reflect the heterologous nature of this tumor. Given the rarity of such tumors and the challenging diagnosis, the prognostic factors have not been established, and the overall prognosis remains poor. The valid therapeutic options are still limited. Here, we report a rare case of metastatic PCS that was accidentally discovered by imaging and properly diagnosed after surgical resection. The clinicopathological features, diagnostic tools, genetic theories, prognosis, and therapeutic options of this rare cancer are also discussed.

High homology of carcinomatous component and sarcomatous component in pulmonary carcinosarcoma and heterogeneity of gene expression among different patients.

e20534 Background: Pulmonary carcinosarcoma (PCS) is a rare subtype of non-small-cell lung cancer (NSCLC) which is highly aggressive and currently has no optimal treatment. Previous studies have shown that some potential markers for targeted therapy and immunotherapy have been detected in PCS patients. A few studies and cases have used microdissection to separate the carcinomatous component (CaC) and sarcomatous component (SaC) component of PCS and performed DNA-based next-generation sequencing (NGS) and confirmed that the two components are highly homologous. There are no studies yet to analyze the differences between CaC and SaC in PCSs from multiple aspects including DNA, RNA, and protein expression assays. Methods: 10 tumor tissues from 5 PCS patients were divided into CaCs and SaCs by microdissection, DNA-based NGS with a 520 gene panel, RNA-based NGS with a 115 gene panel, and Immunohistochemistry (IHC) were performed on these samples. The same type of detection results for different components of the tumors were used for comparative analysis, and the overall DNA test results of the two components were used to compare with detection data of NSCLC and lung sarcoma in the TCGA database respectively. Results: No significant differences were found between CaC and SaC at both DNA, RNA, and IHC assays. The most commonly mutated genes in this cohort of patients were TP53 (10/10, 100%), KRAS (6/10, 60%), LRP1B (5/10, 50%), RBM10, PTPRT, AKT2 (both are 4/10, 40%). Notably, all the mutated genes detected were more similar to those detected in NSCLC rather than mutated genes commonly found in sarcomas. In addition, regardless of DNA or RNA sequencing, no landmark fusion variants were detected in the four available sarcoma tissues. Single sample gene set enrichment analysis (ssGSEA) was used to analyze the RNA results of the matched CaC and SaC of the three patients, no difference in RNA expression among different types of tissues in the same patient was found, but gene expression heterogeneity among the 3 patients was very high. IHC results showed that the positive rates of PD-L1, CD3 and CD8 in the 5 CaCs were 40%, 100% and 100%, while this value was 80%, 100% and 100% in the 5 SaCs. PD-L1 showed a trend of high expression rate in SaC tissues of PCS patients. Conclusions: This study showed that the CaC and SaC tissues of the same PCS patient were both highly homologous in terms of DNA, RNA and protein expression, but the RNA expression was highly heterogeneous among different patients. The landscape of genetic alterations revealed that PCSs are molecularly more likely to arise from NSCLC rather than lung sarcomas, which suggests that for these patients, it may be suitable to choose a treatment plan for the pathological type of the carcinomatous component.

Tumor agnostic efficacy of selpercatinib in patients with RET fusion+ solid tumors: A global, multicenter, registrational trial update (LIBRETTO-001).

3094 Background: Selpercatinib, a first-in-class highly selective and potent RET kinase inhibitor, is approved in multiple countries for the treatment of lung and thyroid cancer with RET fusions and medullary thyroid cancer with RET mutations. We provide an efficacy and safety update with more patients (pts) and longer follow-up (data cut-off: 24Sep2021) in RET fusion+ solid tumors with histologies other than lung/thyroid. Methods: The phase 1/2 LIBRETTO-001 trial (NCT03157128) enrolled pts with locally advanced/metastatic RET fusion+ solid tumors. Following dose escalation, pts received the recommended dose of 160 mg orally twice daily. The efficacy analysis set consisted of pts enrolled ≥6 months (mo) prior to the cut-off date. If a pt achieved response, an additional ≥6 mo follow-up from the initial response was required. There was no additional follow-up required for non-responders. Response was assessed per RECIST 1.1. Primary endpoint was objective response rate (ORR) by independent review committee (IRC). Secondary endpoints included ORR by investigator (INV), duration of response (DoR), progression-free survival (PFS), time to response (TTR), and safety. Results: Forty-five pts with 14 unique RET fusion+ tumor types received ≥1 dose of selpercatinib: 12 pancreatic, 10 colon, 4 salivary, 3 unknown primary, 3 sarcoma, 2 each of breast, carcinoma of the skin, xanthogranuloma, and cholangiocarcinoma, and 1 each of lung carcinoid, rectal neuroendocrine, small intestine, ovarian, and pulmonary carcinosarcoma. Median age was 53 years (range 21-85). Forty-one pts received prior systemic therapy (median prior lines: 2, range 0-9); 31% received ≥3 lines. In 41 efficacy-evaluable pts, confirmed ORR by IRC was 44% (18/41, 95% CI: 29-60). Clinical benefit was observed in 63% (26/41) of pts: 2 complete responses (breast, small intestine), 16 partial responses, and stable disease ≥16 weeks in 8 pts by IRC. Responses were observed across a variety of fusion partners. Median TTR was 1.9 mo by IRC. Median DoR was 24.5 mo (95% CI: 9.2-NE) with 50% (9/18) of responses ongoing at a median follow-up of 14.9 mo by IRC. Median PFS by IRC was 13.2 mo (95% CI: 7.4-26.2), with 34.1% alive and progression-free at a median follow-up of 16.4 mo. No new safety signals were identified in this cohort compared to broader safety database. Three grade 5 AEs were observed (unrelated to treatment by INV), and 4 pts discontinued treatment due to AEs (1 deemed related to treatment by INV). Conclusions: Selpercatinib continued to demonstrate durable antitumor activity in pts with RET fusion+ cancers across multiple tumor types. No new safety signals were identified. These results emphasize the importance of comprehensive genomic profiling to identify actionable oncogenic drivers, including RET fusions. The LIBRETTO-001 study continues to enroll pts. Clinical trial information: NCT03157128.

A look towards the clonal origin of metastatic pulmonary carcinosarcoma: Report of a patient with an unexpected long-term survival

Pulmonary carcinosarcoma is a rare histological subtype of non-small cell lung cancer, defined by the combination of epithelial and mesenchimal elements. Prognosis is usually dismal, with a median survival of about 6 months. The use of immunotherapy by blockade of PD1/PD-L1 immune checkpoint signaling has been shown to improve patients' survival. However, local aggressiveness and distant metastases are frequent. Spread to the gastrointestinal tract is seldom reported. The genetic landscape of the disease has only recently begun to emerge, pointing at TP53, KRAS, EGFR and MET as the most common mutated genes. We describe the case of a metastatic patient with 37 months overall survival, treated by an aggressive multimodal approach combining surgery, chemotherapy, radiotherapy and immunotherapy. To shed new light on the molecular basis for sarcomatoid component in lung carcinoma, we performed next generation sequencing analysis of the squamous and sarcomatoid component by the two sites. We demonstrated a clonal origin and hypermutability of the sarcomatous elements that may account for the good response to immunotherapy. Moreover, we identified some mutations involving TP53 and EGFR genes, targetable by already available drugs. We depicted a model of how a squamous cell carcinoma can differentiate during its natural history into sub-clonal populations with different features and may ultimately result in a neoplasm (i.e. pulmonary carcinosarcoma) showing clonal heterogeneity. Our data might contribute to a better understanding of the pathogenesis and molecular mechanisms of this rare tumor and open new ways for a more tailored approach.

Resection of blastomatoid pulmonary carcinosarcoma in an elderly man

Resection of blastomatoid pulmonary carcinosarcoma in an elderly man

A Rare Case of Pulmonary Carcinosarcoma with Unusual Presentation: A Diagnostic Dilemma

Pulmonary carcinosarcoma is a rare malignancy of the lung and has poor prognosis than non-small cell lung cancer. Effective treatment has not been developed for non-resect able advanced stage. We report a case in a 51-year-old female who presented with a right sided massive pleural effusion. Pleural biopsy tissue histology and immunohistochemistry revealed carcinosarcoma.

Abstract CT011: Efficacy and safety of selpercatinib in RET fusion-positive cancers other than lung or thyroid cancers

Abstract Introduction: Selpercatinib, a first-in-class highly selective and potent RET kinase inhibitor, is approved in multiple countries for the treatment of RET fusion-positive lung or thyroid cancers. RET fusions are also implicated in the pathogenesis of other cancers. Selpercatinib's efficacy and safety were thus explored in patients (pts) with RET fusion-positive non-lung/non-thyroid cancers in a global, multicenter, registrational trial. Methods: Adults with locally advanced or metastatic RET fusion-positive non-lung/non-thyroid solid tumors enrolled in the phase 1/2 LIBRETTO-001 trial (NCT03157128) were included in this analysis (data cut-off: 19 March 2021). Following dose escalation, pts received the recommended dose of 160 mg orally, twice daily. Pts enrolled long enough to allow 6-month follow-up from their first dose comprised the efficacy-evaluable population. Response was assessed (RECIST 1.1) by investigators. The primary endpoint was objective response rate (ORR). Secondary endpoints included duration of response (DoR), time to response, and safety. Results: Thirty-two pts with RET fusion-positive non-lung/non-thyroid cancers included 12 unique tumor types: 9 pancreatic, 9 colon, 2 each of breast, salivary, sarcoma, and unknown primary, and 1 each of carcinoid, rectal neuroendocrine, small intestine, xanthogranuloma, ovarian, and pulmonary carcinosarcoma. The median age was 48 years (range 22-85). Twenty-nine pts received prior systemic therapy (median prior lines: 2, range 0-9). The ORR was 47% (N=15/32, 95% CI: 29-65). Objective responses were observed in 9 unique cancer types including colon, pancreatic, carcinoid, small intestine, salivary, xanthogranuloma, breast, ovarian, and sarcoma, and 5 additional patients had stable disease lasting ≥ 16 weeks. Median time to response was 1.9 months (range 0.7-7.3). Median DoR was not reached (median follow-up time of 13 months). Responses were ongoing in 73% (11/15) of pts. Safety among this population was consistent with the overall selpercatinib safety database. No patients in this cohort discontinued due to treatment-related AEs. Conclusion: Selpercatinib demonstrated promising antitumor activity in RET fusion-positive non-lung/non-thyroid cancers, including multiple treatment-refractory GI malignancies. Broad-based genomic profiling is essential to identify actionable oncogenic drivers, including RET fusions. The safety and efficacy of selpercatinib will continue to be explored in pts with these cancers in the ongoing LIBRETTO-001 study. Citation Format: Vivek Subbiah, Bhavana Konda, Todd Bauer, Caroline McCoach, Gerald Falchook, Masayuki Takeda, Jyoti Patel, Jared Weiss, Nir Peled, Lyudmila Bazhenova, Victoria Soldatenkova, Pearl French, Nora Drove, Oliver Gautschi, Alexander Drilon. Efficacy and safety of selpercatinib in RET fusion-positive cancers other than lung or thyroid cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr CT011.

Pulmonary Carcinosarcoma Diagnosed on CryoProbe® Biopsy

Pulmonary sarcomatoid carcinomas (PSC) are an uncommon form of non-small cell lung cancer and are found in 0.4% of all lung malignancies. The five histologic variants include: Pleomorphic carcinoma, spindle cell carcinoma, giant cell carcinoma, carcinosarcoma and pulmonary blastoma.

Lung Carcinosarcoma Report of One Case Treated With Immunotherapy with Review

Pulmonary Carcinosarcoma is an uncommon malignant biphasic tumor that accounts for less than 1% of all lung cancers. It is defined by coexisting histologic elements of carcinomatous and sarcomatous components. We report a case of advanced stage pulmonary carcinosarcoma in a 83-year-old patient, treated with immunotherapy with good response lasted for more than one year.

Uncontrollable Hiccup After Resection of Pulmonary Carcinosarcoma

Uncontrollable Hiccup After Resection of Pulmonary Carcinosarcoma

Next-Generation Sequencing Analysis Identified Genomic Alterations in Pathological Morphologies of 3 Cases of Pulmonary Carcinosarcoma.

BackgroundPulmonary carcinosarcomas (PCSs) are a heterogeneous group of non-small-cell 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.MethodsIn this study, the clinical and molecular characterization in 3 pulmonary sarcomatoid carcinomas (PSCs) were presented using microscope analysis and next-generation sequencing (NGS) analysis.ResultsThe 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.ConclusionOur 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.

The characteristic of tumor immune microenvironment in pulmonary carcinosarcoma.

Pulmonary carcinosarcoma (PCS) is a rare but aggressive neoplasm, due to late diagnosis and early metastasis. Surgery combined with radiotherapy is a standard treatment. However, PCS features an easy relapse after surgery resection and resistance to chemotherapy and radiotherapy. Tumor immune microenvironment reflects tumor immunophenotyping and affects immunotherapy efficiency. This review summarized current studies on the characteristic of tumor immune microenvironment in PCS and discussed the potential of immunotherapy combined with other regimes strategy as a candidate for treatments in PCS.

Clinicopathologic features and genomic analysis of pulmonary blastomatoid carcinosarcoma

BackgroundThis study was designed to investigate the clinicopathologic features of pulmonary blastomatoid carcinosarcoma and explore the genomic profiles of epithelial and mesenchymal components in this tumor.MethodsThree cases of pulmonary blastomatoid carcinosarcoma were enrolled in this study. Clinicopathologic information and prognostic data were retrospectively reviewed. Diagnostic immunohistochemistry was performed. The epithelial and mesenchymal components were microdissected to investigate the genomic profiles by performing capture-based targeted next generation sequencing.ResultsThe epithelial components in patient one consisted of low-grade and high-grade fetal lung adenocarcinoma. Low-grade epithelial cells showed nuclear expression of β-catenin and missense mutation of CTNNB1. The epithelial components in another two patients consisted of high-grade fetal lung adenocarcinoma/enteric adenocarcinoma. The epithelial cells showed membrane staining of β-catenin and harbored no mutation of CTNNB1. The mesenchymal components in all three tumors were composed of primitive round/spindle cells without definite differentiation and showed cytoplasmic dot positive of β-catenin and no corresponding mutation. Within a tumor, both components exhibited relatively comparable molecular profile. In patient one, 4 mutations: RB1, FAT3, PTCH1 and LRP1B were shared by both epithelial and mesenchymal components. Epithelial component had additional mutations in BCOR, CTNNB1, CTCF, FAT1 and DICER1. In patient two, 12 mutations were shared. The epithelial component had BRCA2 mutation and the mesenchymal had mutations in CREBBP, ALK, DNMT3A, ASXL2, MYCN and RICTOR. Patient three had 6 shared mutations. The epithelial component had an additional mutation in KAT6A and the mesenchymal had an additional mutation in APC. Collectively, we observed heterogeneity between epithelial and mesenchymal components of the same tumor.ConclusionsBlastomatoid carcinosarcoma showed characteristic morphology and immunophenotype. Parallel detection of genetic abnormalities in epithelial and mesenchymal components could provide further evidence for tumor differentiation, molecular targeting and differential diagnosis.