Pulmonary Sarcomatoid Carcinoma Research Articles

73P Camrelizumab plus famitinib as first-line treatment in patient with locally advanced or metastatic pulmonary sarcomatoid carcinomas (CAPSTONE): A multi-center, single-arm, phase II study

73P Camrelizumab plus famitinib as first-line treatment in patient with locally advanced or metastatic pulmonary sarcomatoid carcinomas (CAPSTONE): A multi-center, single-arm, phase II study

Effectiveness and Safety of Immune Checkpoint Inhibitors Alone or in Combination With Chemotherapy in Pulmonary Sarcomatoid Carcinoma

IntroductionPulmonary sarcomatoid carcinoma (PSC) is a rare subtype of lung cancer associated with poor prognosis and resistance to conventional chemotherapy. Immune checkpoint inhibitors (ICIs), alone or in combination with chemotherapy, were found to have clinical benefits in PSC in recent studies. Nevertheless, because these studies included a small number of patients owing to disease rarity, larger studies are needed to evaluate the effectiveness and safety of ICI-based therapy for PSC. MethodsThis multicenter retrospective study evaluated patients with ICI-naive advanced or metastatic PSC who were treated with ICI-based therapy at 25 hospitals in Japan. ResultsA total of 124 patients were evaluated. The overall response rate, median progression-free survival (PFS), and median overall survival (OS) were 59.0%, 10.5 months, and 32.8 months, respectively. The PFS and OS rates at 24 months were 35.3% and 51.5%, respectively. Programmed death-ligand 1 expression, concomitant chemotherapy, and the treatment line were not significantly associated with PFS or OS. Immune-related adverse events (irAEs) were observed in 70 patients (56.5%), including 30 (24.2%) with grade 3 to 5 events. Patients with mild irAEs (grades 1–2) had longer PFS and OS than did those with severe (grades 3–5) or no irAEs. In a multivariate analysis, any-grade irAEs and the absence of liver metastases were independently associated with PFS, whereas any-grade irAEs and Eastern Cooperative Oncology Group performance status less than or equal to 1 were independently associated with OS. ConclusionsICI-based therapy was found to have promising effectiveness in patients with advanced or metastatic PSC, regardless of programmed death-ligand 1 expression, concomitant chemotherapy, or treatment line.

Genomic Landscape of Pulmonary Sarcomatoid Carcinoma.

Pulmonary 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. A 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. TP53 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. Decreased 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.

Recurrence of pulmonary sarcomatoid carcinoma presenting as haemothorax: a case report

Pulmonary sarcomatoid carcinoma (PSC) is a rare and highly invasive malignant tumour. It has similar clinical manifestations and imaging features to ordinary lung cancer. This current case report describes a 65-year-old male patient who had a mass in the apicoposterior segment of the left upper lobe with haemoptysis. Imaging studies revealed a central parenchymal mass surrounded by areas of ground-glass opacity, strongly indicating the presence of a pulmonary malignancy. Intraoperatively, the tumour was discovered to have invaded the chest wall and exhibited a significant propensity for bleeding. Consequently, a left upper lobe resection accompanied by extensive pleural debridement were performed. Subsequent postoperative histopathological examination confirmed the diagnosis of PSC. Unfortunately, 1 month after the surgery, the patient presented with left-sided haemothorax. Despite employing various haemostatic interventions, the patient eventually succumbed to haemorrhagic shock. This study provides a treatment strategy reference for patients with PSC presenting as haemothorax.

P2.22-01 Single-nuclei RNA Sequencing Reveals Heterogeneity and Malignancy in Pulmonary Sarcomatoid Carcinoma

P2.22-01 Single-nuclei RNA Sequencing Reveals Heterogeneity and Malignancy in Pulmonary Sarcomatoid Carcinoma

Survival analysis and nomogram for pulmonary sarcomatoid carcinoma: an SEER analysis and external validation

ObjectiveUncommon and particularly deadly, pulmonary sarcomatoid carcinoma (PSC) is an aggressive type of lung cancer. This research aimed to create a risk categorisation and nomogram to forecast the overall survival...

A rare case of pulmonary endobronchial spindle cell carcinoma with liver metastasis along with concurrent cutaneous neurofibroma

Spindle cell carcinoma is one of the histological variants of pulmonary sarcomatoid carcinoma. It is a rare, poorly differentiated, highly malignant, and rapidly growing non-small cell carcinoma of the lung. Information about pulmonary spindle carcinoma incidence, clinical features, and immunohistochemical markers are not well known compared to other variants of sarcomatoid carcinoma. Most sarcomatoid carcinoma features mimic non-small cell carcinoma, so it is easily misdiagnosed. Cutaneous neurofibroma with primary lung spindle cell carcinoma has not been reported in any previous literature. Here we report a rare endobronchial sarcoma with liver metastasis and concurrent skin neurofibroma.

Clinical outcomes of radical radiotherapy for pulmonary sarcomatoid carcinoma.

Pulmonary 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. From 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. The 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). This 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.

Preoperative CT findings and prognosis of pulmonary sarcomatoid carcinoma: comparison with conventional NSCLC of similar tumor size

BackgroundPulmonary sarcomatoid carcinoma (PSC) is a rare subtype of non-small cell lung cancer (NSCLC) but differs in terms of treatment strategies compared with conventional-NSCLC (c-NSCLC). However, preoperative CT differentiation between PSC and c-NSCLC remains a challenge. This study aimed to explore the CT findings and prognosis of PSC compared with c-NSCLC of similar tumor size.MethodsClinical data and CT findings of 31 patients with PSC and 87 patients with c-NSCLC were retrospectively analyzed. Clinical data included sex, age, and smoking history. CT findings included tumor size, tumor location, calcification, vacuole/cavity, pleural invasion, mean CT value, and low-attenuation area (LAA) ratio. Kaplan‒Meier curves and log-rank tests were used for survival analysis. A Cox regression model was constructed to evaluate prognostic risk factors associated with overall survival (OS). The Spearman correlation among clinicoradiological outcomes were analyzed.ResultsThe mean tumor size of PSC and c-NSCLC were both 5.1 cm. The median survival times of PSC and c-NSCLC were 8 months and 34 months, respectively (P < 0.001). Calcification and vacuoles/cavities were rarely present in PSC. Pleural invasion occurred in both PSC and c-NSCLC (P = 0.285). The mean CT values of PSC and c-NSCLC on plain scan (PS), arterial phase (AP), and venous phase (VP) were 30.48 ± 1.59 vs. 36.25 ± 0.64 Hu (P = 0.002), 43.26 ± 2.96 vs. 58.71 ± 1.65 Hu (P < 0.001) and 50.26 ± 3.28 vs. 64.24 ± 1.86 Hu (P < 0.001), the AUCs were 0.685, 0.757 and 0.710, respectively. Compared to c-NSCLC, PSC had a larger LAA ratio, and the AUC was 0.802, with an optimal cutoff value of 20.6%, and the sensitivity and specificity were 0.645 and 0.862, respectively. Combined with the mean CT value and LAA ratio, AP + VP + LAA yielded the largest AUC of 0.826. The LAA ratio were not independent risk factors for PSC in this study. LAA ratio was negatively correlated with PS (r = -0.29), AP (r = -0.58), and VP (r = -0.66). LAA showed a weak positive correlation with tumor size(r = 0.27).ConclusionsPSC has a poorer prognosis than c-NSCLC of similar tumor size. The mean CT value and LAA ratio contributes to preoperative CT differentiation of PSC and c-NSCLC.

The use of Anatomage table for metastases to the oral region

IntroductionThe Anatomage Table is a modern device characterized by virtual reality functionality that may be used to enhance the teaching of human anatomy to medical and allied health students. The purpose of the present study was to use the virtual dissection table (3D Anatomage) as an additional tool for education and information in cases of metastases to the oral region. Materials and methodsThe hospital database of Vercelli Hospital, Vercelli, Italy, was searched for metastases to the oral region. DICOM data of Computed tomography scans were retrieved and uploaded in the Anatomage Table device. The workstation was used to obtain images of the body surface, “dissection cuts,” or “vascular reconstructions,” modifying the filters. ResultsThe reconstructed images of three cases of metastases to the oral region from pulmonary adenocarcinoma, pulmonary sarcomatoid carcinoma, and breast ductal infiltrative adenocarcinoma were produced and presented. Different filters were used. DiscussionThe use of Anatomage Table, a touch interactive anatomy virtual dissection table used in anatomy education, thanks to the application of different filters, may represent a promising resource both for patients and students.

Novel model for cancer-specific survival of patients with pulmonary sarcomatoid carcinoma: A population-based analysis and external validation

Background/ObjectiveWe aimed to develop a comprehensive and effective nomogram for predicting cancer-specific survival (CSS) in patients with pulmonary sarcomatoid carcinoma (PSC). MethodsData for patients diagnosed with PSC between 2004 and 2018 from the Surveillance, Epidemiology, and End Results database were retrospectively collected and randomly divided into training and internal validation sets. We then retrospectively recruited patients diagnosed with PSC to construct an external validation cohort from the Southwest Hospital. A prognostic nomogram for CSS was established using independent prognostic factors that were screened from the multivariate Cox regression analysis. The performance of the nomogram was evaluated using area under the receiver operating characteristic (ROC) curves, Harrell's concordance index (C-index), calibration diagrams, and decision curve analysis (DCA). The clinical value of the nomogram and tumor, nodes, and metastases (TNM) staging system was compared using the C-index and net reclassification index (NRI). ResultsOverall, 1356 patients with PSC were enrolled, including 876, 377, and 103 in the training, internal validation, and external validation sets, respectively. The C-index and ROC curves, calibration, and DCA demonstrated satisfactory nomogram performance for CSS in patients with PSC. In addition, the C-index and NRI of the nomogram suggested a significantly higher nomogram value than that of the TNM staging system. Subsequently, a web-based predictor was developed to help clinicians obtain this model easily. ConclusionsThe prognostic nomogram developed in this study can conveniently and precisely estimate the prognosis of patients with PSC and individualize treatment, thereby assisting clinicians in their shared decision-making with patients.

Chemotherapy for advanced pulmonary sarcomatoid carcinoma: a population-based propensity score matching study

ObjectivesPulmonary sarcomatoid carcinoma (PSC) is a rare histological type of non-small cell lung cancer (NSCLC). There are no specific treatment guidelines for PSC. For advanced PSC (stage II-IV), the role of chemotherapy is still controversial. The purpose of this study was to investigate the effect of chemotherapy on the prognosis of advanced PSC.MethodsA total of 960 patients with advanced PSC from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2019 were enrolled in this study. To investigate the prognostic factors, the Cox proportional hazard regression model was conducted. A total of 642 cases were obtained after propensity score matching (PSM). The Kaplan‒Meier method was applied to compare overall survival (OS) and cancer-specific survival (CSS).ResultsFor all 960 cases included in this study, the Cox proportional hazard model was applied for prognostic analysis. Univariate and multivariate analyses showed that stage, T stage, N stage, M stage, surgery, and chemotherapy were prognostic factors for OS and CSS (P < 0.05). A total of 642 cases were obtained after PSM, with no significant difference between the two groups for all variables. Kaplan‒Meier curves indicated that for OS and CSS, the prognosis was significantly better in the chemotherapy group than in the no-chemotherapy group.ConclusionsFor advanced PSC, chemotherapy can significantly improve the OS and CSS of patients. Chemotherapy should be an important part of PSC treatment.

Heterogeneous Expression of PD-L1, B7x, B7-H3, and HHLA2 in Pulmonary Sarcomatoid Carcinoma and the Related Regulatory Signaling Pathways.

Immunotherapy has transformed lung cancer management, but PSC remains an aggressive subtype with a poor prognosis. This study investigates the differential expression of PD-L1 and alternative immune checkpoints (ICs; B7x, B7-H3, and HHLA2), and genetic alterations in PSCs. Tumor specimens of 41 PSC patients were evaluated. PD-L1, B7x, B7-H3, and HHLA2 were positive in 75.0%, 67.6%, 73.0%, and 91.9% of tumors, respectively. PD-L1 expression was significantly higher in the epithelial compared to the sarcomatoid component (median TPS: 50% vs. 0%, p = 0.010). Expression of PD-L1 in both components was only seen in 32.1% of patients. However, at least one IC was expressed in 92.9% of epithelial and 100% of sarcomatoid components. Furthermore, METex14 was detected in 19.5% of patients and was associated with a higher sarcomatoid percentage. Our preclinical studies revealed that METex14 induced PD-L1 expression via MAPK or PI3K/Akt pathways, and MET inhibitors decreased PD-L1 expression. Our findings demonstrate distinct expressions of ICs in PSC subcomponents. Thus, combination IC inhibition as a therapeutic strategy in PSC warrants further exploration. A high percentage of METex14 in PSC and its role in regulating PD-L1 expression reveal different therapeutic targets in this aggressive NSCLC subtype.

Individual risk and prognostic value prediction by machine learning for distant metastasis in pulmonary sarcomatoid carcinoma: a large cohort study based on the SEER database and the Chinese population.

This study aimed to develop diagnostic and prognostic models for patients with pulmonary sarcomatoid carcinoma (PSC) and distant metastasis (DM). Patients from the Surveillance, Epidemiology, and End Results (SEER) database were divided into a training set and internal test set at a ratio of 7 to 3, while those from the Chinese hospital were assigned to the external test set, to develop the diagnostic model for DM. Univariate logistic regression was employed in the training set to screen for DM-related risk factors, which were included into six machine learning (ML) models. Furthermore, patients from the SEER database were randomly divided into a training set and validation set at a ratio of 7 to 3 to develop the prognostic model which predicts survival of patients PSC with DM. Univariate and multivariate Cox regression analyses have also been performed in the training set to identify independent factors, and a prognostic nomogram for cancer-specific survival (CSS) for PSC patients with DM. For the diagnostic model for DM, 589 patients with PSC in the training set, 255 patients in the internal and 94 patients in the external test set were eventually enrolled. The extreme gradient boosting (XGB) algorithm performed best on the external test set with an area under the curve (AUC) of 0.821. For the prognostic model, 270 PSC patients with DM in the training and 117 patients in the test set were enrolled. The nomogram displayed precise accuracy with AUC of 0.803 for 3-month CSS and 0.869 for 6-month CSS in the test set. The ML model accurately identified individuals at high risk for DM who needed more careful follow-up, including appropriate preventative therapeutic strategies. The prognostic nomogram accurately predicted CSS in PSC patients with DM.

Integrated Clinical, Molecular and Immunological Characterization of Pulmonary Sarcomatoid Carcinomas Reveals an Immune Escape Mechanism That May Influence Therapeutic Strategies.

Pulmonary sarcomatoid carcinoma (PSC) has highly aggressive biological behaviour and poor clinical outcomes, raising expectations for new therapeutic strategies. We characterized 179 PSC by immunohistochemistry, next-generation sequencing and in silico analysis using a deep learning algorithm with respect to clinical, immunological and molecular features. PSC was more common in men, older ages and smokers. Surgery was an independent factor (p < 0.01) of overall survival (OS). PD-L1 expression was detected in 82.1% of all patients. PSC patients displaying altered epitopes due to processing mutations showed another PD-L1-independent immune escape mechanism, which also significantly influenced OS (p < 0.02). The effect was also maintained when only advanced tumour stages were considered (p < 0.01). These patients also showed improved survival with a significant correlation for immunotherapy (p < 0.05) when few or no processing mutations were detected, although this should be interpreted with caution due to the small number of patients studied. Genomic alterations for which there are already approved drugs were present in 35.4% of patients. Met exon 14 skipping was found more frequently (13.7%) and EGFR mutations less frequently (1.7%) than in other NSCLC. In summary, in addition to the divergent genomic landscape of PSC, the specific immunological features of this prognostically poor subtype should be considered in therapy stratification.

Comparison of clinical outcomes in patients with advanced pulmonary sarcomatoid carcinoma treated with immunotherapy-based regimen or chemotherapy: A study based on the SEER database and multicentric real-world settings.

e20573 Background: Pulmonary sarcomatoid carcinoma (PSC) is a rare pulmonary cancer characterised by early metastasis and invasion, predominantly diagnosed with locally advanced or metastasis, hindering the possibility of surgical intervention. However, a standardised treatment strategy for advanced PSC is yet to be established. Herein, we aimed to evaluate the effects of immunotherapy-based strategies or chemotherapy on patients with advanced PSC. Methods: We conducted a retrospective study to compare the clinical outcomes of immunotherapy-based regimens and chemotherapy in patients with advanced PSC using the Surveillance, Epidemiology, and End Results (SEER) database and data from three cancer centres. Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan–Meier method. Univariate and multivariate analyses were performed to identify prognostic factors. Results: In total, 202 patients with stage IV PSC were identified from the SEER database. The median OS was 5 months. The median follow-up time of PSC patients from three cancer centres was 27.5 months Considering all three cancer centres, first-line treatment with a first-line immunotherapy-based regimen and chemotherapy were administered to 12 and 16 patients, respectively. The median PFS was 2.1 (95% confidence interval [CI] [2.1, 4.1]) and 7.2 (95% CI [6.8, 7.6]) months for the chemotherapy- and immune-based groups, respectively (p &lt; 0.001). The median OS was 3.6 (95% CI [1.6, 5.6]) and 13.7 (95% CI [5.1, 22.3]) months for the chemotherapy and immune-based groups, respectively (p = 0.003). Multivariate analysis revealed that the immunotherapy-based regimen was an independent prognostic factor for PFS and OS (p &lt; 0.01, hazard ratio [HR] = 0.22, 95% CI [0.07,0.67] and p &lt; 0.01 HR = 0.27 95% CI [0.11,0.68], respectively). Conclusions: Conventional chemotherapy has limited benefits in patients with stage IV PSC. However, patients with advanced PSC who received first-line immunotherapy-based regimens exhibited a remarkable response. The immunotherapy-based regimen was an independent prognostic factor for PFS and OS.

Imaging features of intestinal metastasis from pulmonary sarcomatoid carcinoma

Imaging features of intestinal metastasis from pulmonary sarcomatoid carcinoma

A robust and accurate method to detect MET Exon 14–skipping mutation in pan-cancer samples using an NGS-based RNAseq approach.

e20575 Background: Met exon 14 skipping mutation(METex14) occurs in multiple cancer species, mainly in non-small cell lung cancer (NSCLC, 3~4%) and pulmonary sarcomatoid carcinoma (PSC, 22%). Several drugs expressed curative effect in previously treated patients who harboring METex14, such as savolitinib approved by NMPA, capmatinib and tepotinib licenced by FDA. Developing a quick and precise method which detect METex14 and help patients benefit from clinical drug treatment is a desiderative issue currently. Previous researches suggest that transcriptome-based RNA-seq method was superior to DNA-based NGS (exome, panel) and PCR method. Here We introduce a fast and accurate method to detect METex14 alternation in RNAseq data. Methods: We sequenced NGS-based Ribo-zero RNAseq (pair-end, 150bp×2) and METex14 ddPCR on 99 pan-cancer samples, of which 38 lung carcinoma (38%), 8 renal carcinoma (8%), 7 pancreatic carcinoma (7%). In 38 lung carcinoma, 35 NSCLC samples were consist by 29 lung adenocarcinoma (LUAD, 76%), 4 lung squamous carcinoma (LUSC, 10%) and 2 PSC (5%). Begin of the study, data quality control applied by Fastp and aligned to human hg19 genome by STAR subsequently. Next, MET exon14 related candidate soft-clipping reads were extracted from BAM files and translated to fastq file. Then we remapped the translated fastq file to hg19 genome with Blat using parameters ‘stepSize = 5, -repMatch = 2253, -minScore = 20, -minIdentity = 90’. Next, supporting reads were sequentially retained by: single end length longer than 18bp; block mapped reads of MET gene; the pair end reads mapped to genome if one end fall in the last 3bp of MET intron 13 and another end fall in at least initial 3bp of MET exon 15. Pair or single end support junction read, distance of junction site to reads end and site coverage were enrolled in a bayesian model to calculate METex14 confidence score (BMMETs). Threshold of our model was defined by the cut-point of max youden-index and 16 samples were validated METex14 by ddPCR. Finally, we would predict a sample with METex14 when score &gt; = 0.752. Results: Our method reported 15 TP samples, 1 FP sample and 1 FN samples (AUC 0.97, sensitivity 0.88, specificity 0.98) while STAR-fusion detected 14 TR samples and 6 FP sample and 2 FN samples (AUC 0.715, sensitivity 0.64, specificity 0.73). BMMETs FP sample scored approximately 0.739 that close to the threshold. Conclusions: Strategy of screen reliable METex14 supporting reads and using bayesian model to calculate a METex14 confidence score could robustly and efficiently predict METex14 event in NGS-based RNAseq data.

Demographics and Clinicopathologic Profile of Pulmonary Sarcomatoid Carcinoma with Survival Analysis and Genomic Landscape.

Background: Pulmonary sarcomatoid carcinoma (PSC) is a rare subtype of non-small cell lung cancer (NSCLC) with an aggressive clinical nature and poor prognosis. With novel targeted therapeutics being developed, new ways to effectively treat PSC are emerging. In this study, we analyze demographics, tumor characteristics, treatment modalities, and outcomes of PSC and genetic mutations in PSC. Methods: Data from the Surveillance, Epidemiology, and End Results (SEER) database were reviewed to analyze cases of pulmonary sarcomatoid carcinoma from 2000 to 2018. The molecular data with the most common mutations in PSC were extracted from the Catalogue Of Somatic Mutations in Cancer (COSMIC) database. Results: A total of 5259 patients with PSC were identified. Most patients were between 70 and 79 years of age (32.2%), male (59.1%), and Caucasian (83.7%). The male-to-female ratio was 1.45:1. Most tumors were between 1 and 7 cm in size (69.4%) and poorly differentiated (grade III) (72.9%). The overall 5-year survival was 15.6% (95% confidence interval (95% CI) = 14.4-16.9)), and the cause-specific 5-year survival was 19.7% (95% CI = 18.3-21.1). The five-year survival for those treated with each modality were as follows: chemotherapy, 19.9% (95% CI = 17.7-22.2); surgery, 41.7% (95% CI = 38.9-44.6); radiation, 19.1% (95% CI = 15.1-23.5); and multimodality therapy (surgery and chemoradiation), 24.8% (95% CI = 17.6-32.7). On multivariable analysis, age, male gender, distant stage, tumor size, bone metastasis, brain metastasis, and liver metastasis were associated with increased mortality, and chemotherapy and surgery were associated with reduced mortality (p < 0.001). The best survival outcomes were achieved with surgery. The most common mutations identified in COSMIC data were TP53 31%, ARID1A 23%, NF1 17%, SMARCA4 16%, and KMT2D 9%. Conclusions: PSC is a rare and aggressive subtype of NSCLC, usually affecting Caucasian males between 70 and 79. Male gender, older age, and distant spread were associated with poor clinical outcomes. Treatment with surgery was associated with better survival outcomes.

Survival outcomes and prognostic factors of lung cancer patients with the MET exon 14 skipping mutation: A single-center real-world study.

The MET exon 14 skipping (METex14) mutation is an important oncogenic driver in lung cancer. We performed a retrospective analysis of clinical data from lung cancer patients with the METex14 mutation to analyze their survival outcomes and associated prognostic factors. A one-step reverse transcription-polymerase chain reaction to examine the presence of the METex14 mutation was performed using RNA samples from 1374 lung cancer patients with no detected EGFR and ALK mutations. Pathological features and immunohistochemistry (IHC) results for c-MET were analyzed in patients with METex14-positive tumors. METex14 was identified in 69 patients with lung cancer, including 53 adenocarcinoma (ADC) and 16 non-ADC patients. In comparison with patients without the METex14 mutation, lung cancer patients harboring the METex14 mutation were generally elderly individuals, never-smokers, and had poor performance scores. A higher frequency of METex14 mutations was detected in pulmonary sarcomatoid carcinoma (PSC) patients (24.3%, n = 9/37). However, stage IV PSC patients with or without the METex14 mutations showed similarly poor overall survival (OS) (p = 0.429). For all 36 METex14-positive lung ADCs, multivariate analysis showed several poor prognostic factors, including strong c-MET IHC staining (p = 0.006), initial brain metastasis (p = 0.005), and administration of only supportive care (p < 0.001). After excluding seven patients who received only supportive care, we further analyzed 29 stage IV lung ADC patients with METex14 mutations who received anti-cancer treatment. Multivariate analysis showed that pemetrexed treatment (p = 0.003), lung radiotherapy (p = 0.020), initial brain metastasis (p = 0.005), and strong c-MET IHC staining (p = 0.012) were independent prognostic factors for OS in these patients. A higher frequency of METex14 mutations was detected in PSC patients. Stage IV PSC patients with or without the METex14 mutations had similarly poor overall survival. Pemetrexed-based chemotherapy, strong c-MET ICH staining, initial brain metastasis, and lung radiotherapy, may help predict survival outcomes in patients with advanced lung ADCs harboring the METex14 mutation.