Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 24
Filter
1.
Cureus ; 16(4): e59293, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38813335

ABSTRACT

Resistance to tyrosine kinase inhibitors (TKIs) in non-small cell lung carcinoma (NSCLC) remains a significant clinical challenge. Osimertinib, a third-generation TKI, has demonstrated efficacy in overcoming resistance, but novel resistance mechanisms continue to emerge. This case report presents a unique instance of histologic transformation from NSCLC to carcinosarcoma, representing a previously unreported manifestation of osimertinib resistance. We describe the clinical course of a 63-year-old female with epidermal growth factor receptor (EGFR)-mutant NSCLC who initially responded to osimertinib but eventually developed carcinosarcoma. The transformation was associated with additional EGFR mutations and alterations in RB and TP53. Despite aggressive treatment, the patient's condition deteriorated, emphasizing the limited therapeutic options for carcinosarcoma. This case underscores the need for further research to elucidate the molecular mechanisms behind histologic transformation and explore novel therapeutic strategies to address osimertinib resistance in NSCLC. Understanding and addressing these mechanisms are crucial for improving outcomes in patients facing this challenging form of resistance.

2.
Front Oncol ; 13: 1145021, 2023.
Article in English | MEDLINE | ID: mdl-36969031

ABSTRACT

Epidermal growth factor receptor (EGFR) mutations have been frequently detected in patients with pulmonary adenocarcinoma. EGFR Exon 19Del and 21L858R mutations are the two most common EGFR mutations. EGFR-tyrosine kinase inhibitors (TKIs) are widely employed to treat patients with non-small cell lung cancer (NSCLC) harboring EGFR mutations. Recently, there has been rapid growth in clinical trials assessing neoadjuvant targeted therapy, indicating good application prospects owing to high efficiency and low toxicity. Herein, we discuss the case of a 56-year-old male patient who was initially diagnosed with stage IIIA pulmonary adenocarcinoma (AJCC,8th edition) of the left lower lung with an EGFR Exon 19Del mutation. The patient was treated with osimertinib but failed to undergo timely review and surgery. Subsequently, the patient underwent two cycles of neoadjuvant chemotherapy (NAC) combined with neoadjuvant targeted therapy. After the tumor load and size had significantly decreased, radical surgery was successfully performed under thoracoscopy. However, postoperative pathology revealed carcinosarcoma, pT2aN0M0, stage IB, and the pathological response was 50%. The present case report provides practical clinical evidence for the application of neoadjuvant targeted therapy combined with chemotherapy for locally advanced primary pulmonary carcinosarcoma with EGFR mutation.

3.
Front Med (Lausanne) ; 9: 988830, 2022.
Article in English | MEDLINE | ID: mdl-36330063

ABSTRACT

Background: 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. Methods: 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. Results: 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. Conclusion: 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.

4.
Cureus ; 14(7): e26901, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35983399

ABSTRACT

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.

5.
Tumori ; 108(6): NP5-NP10, 2022 Dec.
Article in English | MEDLINE | ID: mdl-35168438

ABSTRACT

INTRODUCTION: 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. CASE DESCRIPTION: 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. CONCLUSIONS: 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.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Carcinoma , Carcinosarcoma , Lung Neoplasms , Neoplasms, Second Primary , Humans , Carcinoma, Non-Small-Cell Lung/therapy , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/therapy , Lung Neoplasms/drug therapy , Carcinosarcoma/diagnosis , Carcinosarcoma/genetics , Carcinosarcoma/therapy , Lung/pathology
6.
Cancer Manag Res ; 14: 103-106, 2022.
Article in English | MEDLINE | ID: mdl-35023973

ABSTRACT

Pulmonary carcinosarcoma (PC) is a rare and highly malignant type of non-small cell lung cancer (NSCLC) that is insensitive to radiotherapy and chemotherapy and has a poor prognosis. Here, we report a case of an 88-year-old patient with inoperable PC and a history of cerebral infarction who was treated with first-line anlotinib combined with stereotactic body radiation therapy (SBRT). The therapeutic response has sustained for 10 months. Our work suggests that SBRT combined with anlotinib may be a safe and effective treatment strategy for octogenarians with PC.

7.
Thorac Cancer ; 12(9): 1445-1448, 2021 05.
Article in English | MEDLINE | ID: mdl-33687154

ABSTRACT

Pulmonary carcinosarcoma is a rare lung tumor accounting for <1% of primary lung cancers, characterized by biphasic components with both carcinomatous and sarcomatous mesenchymal features. This report describes a case of pulmonary carcinosarcoma in an octogenarian who was treated with stereotactic body radiation therapy (SBRT) and whose therapeutic response was sustained for 2 years. Along with other treatment modalities, SBRT might be considered for the treatment of medically inoperable localized stage pulmonary carcinosarcoma.


Subject(s)
Carcinosarcoma/radiotherapy , Lung Neoplasms/radiotherapy , Aged, 80 and over , Carcinosarcoma/pathology , Humans , Lung Neoplasms/pathology , Male , Radiosurgery
8.
J Thorac Cardiovasc Surg ; 162(1): 274-284, 2021 Jul.
Article in English | MEDLINE | ID: mdl-32711968

ABSTRACT

OBJECTIVE: Primary pulmonary sarcomas (PPS) and pulmonary carcinosarcomas (PCS) are rare aggressive lung malignancies. We reviewed our 21-year experience with the surgical and nonsurgical treatment of both tumors, comparing their clinical, histopathologic, and treatment results. METHODS: All patients with PPS or PCS who underwent surgical and nonsurgical treatment between 1998 and 2019 at our cancer center were retrospectively reviewed. Multivariable Cox proportional hazards model was constructed. RESULTS: In total, 100 patients were analyzed: 45 with PPS and 55 with PCS. Among patients with PPS, 31 of 45 (69%) underwent surgery with 1 (3%) operative mortality. For patients with PCS, 29 of 55 (53%) underwent surgery with no operative mortality. Patients with PPS were younger than PCS (P < .01). Fewer patients were smokers among PPS (58%) versus PCS (93%) (P < .01). For resected PPS, mean tumor size was 8.2 ± 4.1 cm (range 2.2-18.0) compared with 10.1 ± 5.0 cm (range 3.9-17.0) for unresected PPS. Tumor size for resected PCS was 6.2 ± 2.6 cm (range 2.0-10.5) versus 6.8 ± 3.5 cm (range 1.2-13.5) for unresected PCS. Of resected patients, 5 of 31 (16%) with PPS and 9 of 29 (31%) with PCS were node positive. Overall survival estimates were as follows: for PPS, median survival and 5-year overall survival for resected versus unresected cases were 39.6 months/28.7% versus 4.9 months/7.8%. For PCS, survival estimates were 23.6 months/31.0% versus 14.9 months/28.2%, respectively. In multivariable analyses (N = 100), age, smoking history, histology, and surgery were risk factors of survival. CONCLUSIONS: At initial evaluation, PPS and PCS presented with large-sized tumors and usually were not stage I. Surgery had a positive impact on survival among patients with PPS. Whenever feasible, surgical resection, even in locally advanced disease, may yield long-term survival in these aggressive lung tumors, although the level of evidence is low.


Subject(s)
Carcinosarcoma , Lung Neoplasms , Sarcoma , Adult , Aged , Aged, 80 and over , Carcinosarcoma/epidemiology , Carcinosarcoma/mortality , Carcinosarcoma/pathology , Carcinosarcoma/therapy , Female , Humans , Lung/surgery , Lung Neoplasms/epidemiology , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Lung Neoplasms/therapy , Male , Middle Aged , Pneumonectomy/mortality , Retrospective Studies , Risk Factors , Sarcoma/epidemiology , Sarcoma/mortality , Sarcoma/pathology , Sarcoma/therapy , Treatment Outcome
9.
Onco Targets Ther ; 13: 7963-7972, 2020.
Article in English | MEDLINE | ID: mdl-32848420

ABSTRACT

BACKGROUND: Pulmonary 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. 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.

10.
Immunotherapy ; 12(5): 323-331, 2020 04.
Article in English | MEDLINE | ID: mdl-32212951

ABSTRACT

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.


Subject(s)
Carcinosarcoma/immunology , Immunotherapy/trends , Lung Neoplasms/immunology , Lung/pathology , Animals , Carcinosarcoma/therapy , Drug Resistance, Neoplasm/immunology , Humans , Immunity , Lung Neoplasms/therapy , Tumor Escape , Tumor Microenvironment
11.
Clin Lung Cancer ; 21(2): 160-170, 2020 03.
Article in English | MEDLINE | ID: mdl-31455596

ABSTRACT

INTRODUCTION: Pulmonary carcinosarcoma (PC) is a rare malignant neoplasm composed of epithelial and mesenchymal components. It accounts for < 1% of thoracic cancers and is not fully understood. This study examined Surveillance, Epidemiology, and End Results (SEER) data to describe demographic and clinical characteristics of patients with PC and assessed survival outcomes by treatment modality and stage. PATIENTS AND METHODS: SEER data were reviewed to identify patients diagnosed with primary PC (1973-2012). Overall survival (OS) and disease-specific survival (DSS) were analyzed by univariate/multivariable Cox proportional hazards models and Kaplan-Meier methods. RESULTS: A total of 411 patients were included. Median age was 67 (range, 24-96) years. Disease stage at the time of initial diagnosis was known for 74.7% of the identified patients (307/411). Of these patients, 23.1% had localized disease. Survival was significantly better for patients with localized disease (OS: 31 vs. 6 months, P < .001; DSS: 54 vs. 8 months, P < .001). Additionally, patients who received surgery alone had significantly improved OS (20 months; P < .001) and DSS (32 months; P < .001) compared to patients who received combined surgery and radiotherapy (OS: 7 months; DSS: 8 months) or radiotherapy alone (OS: 4 months; DSS: 4 months). CONCLUSION: Treatment with surgery alone resulted in superior survival outcomes compared to other treatment modality combinations, regardless of patient age and disease stage. Within the limitations of this study, providers may wish to consider these findings when devising patient treatment plans.


Subject(s)
Carcinosarcoma/pathology , Lung Neoplasms/pathology , SEER Program/statistics & numerical data , Adult , Aged , Aged, 80 and over , Carcinosarcoma/mortality , Carcinosarcoma/therapy , Combined Modality Therapy , Female , Follow-Up Studies , Humans , Lung Neoplasms/mortality , Lung Neoplasms/therapy , Male , Middle Aged , Prognosis , Retrospective Studies , Survival Rate , Young Adult
12.
Interact Cardiovasc Thorac Surg ; 30(1): 4-10, 2020 01 01.
Article in English | MEDLINE | ID: mdl-31518405

ABSTRACT

OBJECTIVES: Pulmonary carcinosarcoma (PCS) is a rare neoplasm. This study explored the clinicopathological characteristics and survival outcomes of PCS. METHODS: The Surveillance, Epidemiology and End Results (SEER) database (1988-2014) was queried for PCS. Overall survival (OS) was evaluated by multivariable Cox regression and nomograms were constructed to predict 3-year OS for PCS. Prognostic performance was evaluated using concordance index and area under the curve analysis. In M0 surgically treated patients, interaction assessments were performed using likelihood ratio tests. Subgroup analysis was performed according to patient age. The clinical features of PCSs were further compared to other non-small-cell lung cancers (NSCLCs). RESULTS: Multivariable analysis identified age [hazard ratio (HR) 1.03, 95% confidence interval (CI) 1.01-1.04], surgery (HR 0.53, 95% CI 0.36-0.77) and chemotherapy (HR 0.51, 95% CI 0.36-0.73) as significantly associated with OS. The nomogram had a concordance index of 0.747 and an area under the curve of 0.803. The association between age and OS was stronger in those receiving pneumonectomy (P = 0.04 for interactions) compared to those that did not (HR 5.14, 95% CI 1.64-16.07), and was associated with a poorer outcome compared to lobectomy amongst the elderly (age ≥ 70 years). Patients with PCS were more likely to receive surgical treatment and had lower lymphatic metastasis compared to adenocarcinoma, squamous cell carcinoma and large cell carcinoma (all P < 0.05). CONCLUSIONS: PCS had unique clinical features compared to common types of NSCLCs in terms of lymphatic invasion and surgical treatment. Pneumonectomy was associated with poorer survival in elderly patients.


Subject(s)
Carcinosarcoma/mortality , Lung Neoplasms/mortality , Aged , Carcinosarcoma/pathology , Carcinosarcoma/surgery , Female , Humans , Lung Neoplasms/pathology , Lung Neoplasms/surgery , Male , Middle Aged , Neoplasm Staging , Nomograms , Pneumonectomy/mortality , Prognosis , Proportional Hazards Models , Retrospective Studies , SEER Program
13.
Cureus ; 11(9): e5643, 2019 Sep 13.
Article in English | MEDLINE | ID: mdl-31700745

ABSTRACT

Pulmonary carcinosarcoma is an unusual biphasic tumor of the lung with carcinomatous and sarcomatous components. We report a case in a 71-year-old female who presented with a 13-cm lung mass. Microscopic examination revealed squamous cell carcinoma and chondrosarcoma with focal spindle cell atypia. In the most recent version of the World Health Organization (WHO) classification, carcinosarcoma is included in the category of sarcomatous neoplasms with a poorer prognosis than non-small cell lung carcinoma.

14.
Pathol Int ; 69(5): 282-287, 2019 May.
Article in English | MEDLINE | ID: mdl-30864171

ABSTRACT

Carcinosarcoma is a clonal tumor developed through sarcomatoid changes in a carcinoma via the epithelial-mesenchymal transition (EMT). Here, we present an extremely rare case of pulmonary carcinosarcoma characterized by components suggesting pluripotency, namely neuroendocrine, myogenic, and chondrogenic differentiation, based on immunohistochemical analysis. A 42-year-old Japanese man was admitted to our hospital. Analysis of tumor tissue after right upper lobe lobectomy revealed a transition between carcinomatous and sarcomatous components. Immunohistochemical analysis suggested immortality owing to complete loss of p53 and diffuse expression of p16 in both the carcinomatous and sarcomatous components. There were also scattered cell groups expressing aldehyde dehydrogenase 1 family member A1, SOX2, CD133, and c-kit, suggesting the possible presence of cancer stem cells. Our findings in this case suggested that the EMT may play a key role in mediating the immortality of tumor cells in carcinosarcoma and facilitating the pluripotency of cancer stem cells.


Subject(s)
Carcinosarcoma/pathology , Epithelial-Mesenchymal Transition , Lung Neoplasms/pathology , Tumor Suppressor Protein p53/metabolism , Adult , Biomarkers, Tumor/metabolism , Carcinosarcoma/metabolism , Cell Differentiation , Humans , Lung Neoplasms/metabolism , Male , Neoplastic Stem Cells/pathology , Pluripotent Stem Cells/pathology
15.
BMC Pulm Med ; 18(1): 193, 2018 Dec 12.
Article in English | MEDLINE | ID: mdl-30541518

ABSTRACT

BACKGROUND: Pulmonary carcinosarcoma (PCS) is a rare primary lung malignancy and has a poor prognosis among lung tumor histological subtypes. However, an appropriate treatment strategy has not been developed for unresectable PCS. CASE PRESENTATION: A 65-year-old man who was diagnosed with PCS was treated by surgical removal of the primary lung lesion, followed by six cycles of adjuvant chemotherapy with cisplatin plus irinotecan. Following the chemotherapy, he experienced a relapse with brain metastasis, which induced the rapid onset of left leg paralysis. Radical surgical resection and stereotactic radiosurgery to the resection cavity were performed. However, meningeal dissemination and new lung metastases occurred after a year and half. To control these multiple metastatic lesions, the patient was treated with the multiple kinase inhibitor pazopanib. No change was observed in the meningeal dissemination, while the metastatic lung lesions were prominently reduced in size following treatment with pazopanib. Consequently, the patient showed a partial response to pazopanib treatment, although the dose of pazopanib was reduced by half as a result of thrombocytopenia. CONCLUSION: This is the first report of metastatic PCS showing an evident therapeutic response to tumor-targeted therapy. We suggest that pazopanib may be a therapeutic option for patients with metastatic PCS.


Subject(s)
Brain Neoplasms , Carcinosarcoma , Lung Neoplasms , Meningeal Neoplasms , Pneumonectomy/methods , Pyrimidines , Sulfonamides , Thrombocytopenia , Aged , Angiogenesis Inhibitors/administration & dosage , Angiogenesis Inhibitors/adverse effects , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/adverse effects , Brain Neoplasms/secondary , Brain Neoplasms/surgery , Carcinosarcoma/pathology , Carcinosarcoma/physiopathology , Carcinosarcoma/therapy , Chemotherapy, Adjuvant/methods , Dose-Response Relationship, Drug , Humans , Indazoles , Lung Neoplasms/pathology , Lung Neoplasms/physiopathology , Lung Neoplasms/therapy , Male , Meningeal Neoplasms/drug therapy , Meningeal Neoplasms/secondary , Neoplasm Staging , Pyrimidines/administration & dosage , Pyrimidines/adverse effects , Radiosurgery/methods , Sulfonamides/administration & dosage , Sulfonamides/adverse effects , Thrombocytopenia/chemically induced , Thrombocytopenia/prevention & control , Treatment Outcome
16.
Lung Cancer ; 122: 146-150, 2018 08.
Article in English | MEDLINE | ID: mdl-30032823

ABSTRACT

OBJECTIVES: Pulmonary carcinosarcoma is a rare lung malignancy and little analysis has been performed to identify associated genomic alterations. We used next-generation sequencing (NGS) to analyze a pulmonary carcinosarcoma harboring an epidermal growth factor receptor (EGFR) mutation. MATERIALS AND METHODS: The lung carcinosarcoma used for this study contained components of adenocarcinoma and chondrosarcoma and originated from a 73-year-old female. Both components carried deletion mutations in exon 19 of EGFR and both had equally strong EGFR protein expression. This study analyzed the biological and genetic characteristics of both components, using NGS and immunohistochemical (IHC) staining. RESULTS AND CONCLUSION: IHC staining revealed that both total EGFR and deletion mutation specific EGFR proteins were equally expressed in both components. Intriguingly, identification of genomic alterations with NGS found five identical alterations in four genes (EGFR, CBLB, TP53, and MEN1) that were shared by the two components, and that each component had a large number of individual alterations. Additionally, we focused on an alpha-thalassemia/mental retardation syndrome X-linked (ATRX) mutation which was only present in the sarcoma component. ATRX protein expression was also only detected in the sarcoma component. This is the first report of the exhaustive genomic alterations in a pulmonary carcinosarcoma harboring an EGFR mutation. The results show that our case had the same EGFR status in both components. The EGFR mutation is the driver mutation in both components. In our case, we found that TP53 may be a common alteration and ATRX may be a specific alteration in the sarcoma component.


Subject(s)
Carcinosarcoma/diagnosis , Lung Neoplasms/diagnosis , Sequence Deletion/genetics , Tumor Suppressor Protein p53/genetics , X-linked Nuclear Protein/genetics , Aged , ErbB Receptors/genetics , Female , Genome/genetics , High-Throughput Nucleotide Sequencing , Humans , Immunohistochemistry
17.
Oncotarget ; 8(56): 96453-96459, 2017 Nov 10.
Article in English | MEDLINE | ID: mdl-29221220

ABSTRACT

Immunotherapy has recently become a new focus for the treatment of malignant tumors following the surgery, chemotherapy, radiotherapy, and molecular targeted therapy. Nivolumab, a human monoclonal antibody, is the first programmed cell death protein-1 (PD-1) inhibitor, which can prohibit the interaction of its ligand (PD-L1), restoring the immune response of T cells, and enhancing the recognition of tumor cells by the immune system. Pulmonary carcinosarcoma is an uncommon but highly aggressive tumor type with a poor prognosis. We described a case of pulmonary carcinosarcoma, with the positive expression of PD-L1, obtained a significant benefit from Nivolumab treatment in a 64-year-old Chinese man, which give us a clue that patients with pulmonary carcinosarcoma may benefit fromanti-PD-1 immunotherapy.

18.
Lung Cancer ; 113: 93-101, 2017 11.
Article in English | MEDLINE | ID: mdl-29110857

ABSTRACT

INTRODUCTION: Pulmonary Sarcomatoid Carcinoma (PSC) is a rare subset of NSCLC, associated with worse prognosis and resistant to platinum-based regimens. Recent investigations have shown high levels of PD-L1 expression in PSC, providing a rationale for the potential use of immunotherapy. In this study, we investigated whether the PD-L1 expression was related to clinico-pathologic and molecular characteristics. MATERIALS AND METHODS: Fortythree surgically-resected PSCs were selected from 2006 to 2014 and clinical information retrieved. PD-L1 expression was analyzed by immunohistochemistry and correlated with the clinic-pathologic features and driver gene mutations analyzed by Next-Generation-Sequencing. Correlation of clinical, pathological and genetic variants with PD-L1 expression positivity were tested by Fisher's exact test analysis. RESULTS: About 25% of PSCs showed a significant expression of PD-L1 (positive staining defined as staining in ≥10% of tumor cells). PD-L1 expression was associated with aggressive pathological features of PSCs including N2-involvement (PD-L1 positive in 83.3% of N2-PSCs vs in 16.2% of N0/N1-PSCs, p=0.003) and presence of either local (p=0.038) and distant metastases (p=0.022). Furthermore, PD-L1 expression was significantly associated with the overall mutational load of the tumors (PD-L1 positivity only in PSCs with at least one mutational event) and in particular with the presence of KRAS mutation (PD-L1 positive in 44.4% of KRAS-Mut PSCs vs 12.0% in KRAS-Wild PSCs). The correlation between PD-L1 expression and KRAS-mutation were found at univariate analysis (p=0.031), even considering PD-L1 as a continuous variable (p=0.018), and confirmed at multivariate analysis (p=0.035). The mutational status of the other genes explored in the NGS-panel (EGFR, APC, PTEN, PIK3CA, TP53 and STK11) did not correlate with PD-L1 expression. CONCLUSIONS: PD-L1 expression significantly correlates with overall mutational load and KRAS mutational status in pulmonary sarcomatoid carcinomas.


Subject(s)
B7-H1 Antigen/biosynthesis , Carcinoma, Non-Small-Cell Lung/genetics , Lung Neoplasms/genetics , Mutation , Proto-Oncogene Proteins p21(ras)/genetics , Aged , Carcinoma, Non-Small-Cell Lung/metabolism , Carcinoma, Non-Small-Cell Lung/pathology , Female , Humans , Immunohistochemistry , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Male , Middle Aged , Multivariate Analysis , Prognosis , Survival Analysis
19.
J Thorac Oncol ; 11(8): 1282-1292, 2016 08.
Article in English | MEDLINE | ID: mdl-27156442

ABSTRACT

INTRODUCTION: Pulmonary sarcomatoid carcinoma (PSC) is a rare and aggressive subset of non-small cell lung cancer with limited treatment options. The molecular characterization of PSC has been strongly hampered by the relative rarity of these tumors. However, understanding the molecular and genetic bases of PSCs is critical to pave the way to new treatment options. In this work, we aimed to explore the complexity of the genetic asset of PSC and investigate its prognostic impact on survival in a large cohort of patients with PSC. METHODS: Next-generation sequencing analysis of a panel of 26 genes with potential clinical relevance was performed on surgical specimens of 49 PSCs. The prognostic impact of genetic profiles on patient survival and the association between the genetic alterations and clinicopathological features were tested. RESULTS: Fifty-five somatic mutations were detected in 13 genes. Thirty-nine PSCs (80%) showed at least one mutation. Survival probability decreased in patients with mutated PSC compared with in those with PSC without mutations (p = 0.02). In particular, mutations in Kirsten rat sarcoma viral oncogene homolog gene (KRAS), alone or in combination with tumor protein p53 gene (TP53) mutations, were associated with decreased survival probability and with the occurrence of local metastases at recurrence. Finally, comparison of our results with data in The Cancer Genome Atlas showed that PSCs have a mutational profile similar to that of smokers' lung adenocarcinoma. CONCLUSIONS: Overall, our analysis provides further information on the mutational profiles of PSCs and demonstrates for the first time a role of KRAS mutations in driving the aggressiveness of this type of cancer.


Subject(s)
High-Throughput Nucleotide Sequencing , Lung Neoplasms/genetics , Mutation , Proto-Oncogene Proteins p21(ras)/genetics , Sarcoma/genetics , Adult , Aged , Aged, 80 and over , Biomarkers , ErbB Receptors/genetics , Female , Genes, p53 , Humans , Lung Neoplasms/mortality , Male , Middle Aged , Prognosis , Proto-Oncogene Proteins c-met/genetics , Sarcoma/mortality
20.
China Oncology ; (12): 59-61, 2010.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-403712

ABSTRACT

Background and purpose: Carcinosarcoma of the lung is a rare malignant pulmonary neoplasm,which including epithelial and parenchymal malignant structure with a poor prognosis. The purpose of this study was to describe the clinicopathologic characteristics and the survival of pulmonary carcinosarcoma. Methods: From Jan.1980 to Dec. 2006, 64 patients with pulmonary carcinosarcoma who underwent surgical treatment were retrospectively analyzed. Results: The overall 5-year survival rate of the patients was 14.1%. There was significant difference between stage Ⅰ/Ⅱ and stage Ⅲ/Ⅳ disease (28.6% vs 2.8%, P=0.003), respectively. The 5-year survival rates of lobectomy, pneumonectomy and palliative resection were 3 3.3 %, 2.8% and 0% ( P=0.003 ), respectively. Conclusion:p-TNM and operative pattern were correlated with survival. Early diagnosis and radical operation are important to the survival of the patients with pulmonary carcinosarcoma.

SELECTION OF CITATIONS
SEARCH DETAIL
...