Predicting MET exon 14 skipping mutation in pulmonary sarcomatoid carcinoma by whole-tumour texture analysis combined with clinical and conventional contrast-enhanced computed tomography features.

Background: Pulmonary sarcomatoid carcinoma (PSC) is a rare, highly malignant type of non-small cell lung cancer (NSCLC) with a poor prognosis. Targeted drugs for MET exon 14 (METex14) skipping mutation can have considerable clinical benefits. This study aimed to predict METex14 skipping mutation in PSC patients by whole-tumour texture analysis combined with clinical and conventional contrast-enhanced computed tomography (CECT) features. Methods: This retrospective study included 56 patients with PSC diagnosed by pathology. All patients underwent CECT before surgery or other treatment, and both targeted DNA- and RNA-based next-generation sequencing (NGS) were used to detect METex14 skipping mutation status. The patients were divided into two groups: METex14 skipping mutation and nonmutation groups. Overall, 1,316 texture features of the whole tumour were extracted. We also collected 12 clinical and 20 conventional CECT features. After dimensionality reduction and selection, predictive models were established by multivariate logistic regression analysis. Models were evaluated using the area under the curve (AUC), and the clinical utility of the model was assessed by decision curve analysis. Results: METex14 skipping mutation was detected in 17.9% of PSCs. Mutations were found more frequently in those (I) who had smaller long- or short-axis diameters (P=0.02, P=0.01); (II) who had lower T stages (I, II) (P=0.02); and (III) with pseudocapsular or annular enhancement (P=0.03). The combined model based on the conventional and texture models yielded the best performance in predicting METex14 skipping mutation with the highest AUC (0.89). The conventional and texture models also had good performance (AUC =0.83 conventional; =0.88 texture). Conclusions: Whole-tumour texture analysis combined with clinical and conventional CECT features may serve as a noninvasive tool to predict the METex14 skipping mutation status in PSC.

Integrative genomic and transcriptomic profiling of pulmonary sarcomatoid carcinoma identifies molecular subtypes associated with distinct immune features and clinical outcomes.

Background: Pulmonary sarcomatoid carcinoma (PSC) is a rare and aggressive subtype of non-small cell lung cancer (NSCLC), characterized by the presence of epithelial and sarcoma-like components. The molecular and immune landscape of PSC has not been well defined. Methods: Multiomics profiling of 21 pairs of PSCs with matched normal lung tissues was performed through targeted high-depth DNA panel, whole-exome, and RNA sequencing. We describe molecular and immune features that define subgroups of PSC with disparate genomic and immunogenic features as well as distinct clinical outcomes. Results: In total, 27 canonical cancer gene mutations were identified, with TP53 the most frequently mutated gene, followed by KRAS. Interestingly, most TP53 and KRAS mutations were earlier genomic events mapped to the trunks of the tumors, suggesting branching evolution in most PSC tumors. We identified two distinct molecular subtypes of PSC, driven primarily by immune infiltration and signaling. The Immune High (IM-H) subtype was associated with superior survival, highlighting the impact of immune infiltration on the biological and clinical features of localized PSCs. Conclusions: We provided detailed insight into the mutational landscape of PSC and identified two molecular subtypes associated with prognosis. IM-H tumors were associated with favorable recurrence-free survival and overall survival, highlighting the importance of tumor immune infiltration in the biological and clinical features of PSCs.

Case report: Sintilimab combined with anlotinib as neoadjuvant chemotherapy for metastatic bone tumor resection in patients with PSC.

Background: Pulmonary sarcomatoid carcinoma (PSC) is a rare subtype of non-small-cell lung cancer (NSCLC), which is resistant to chemotherapy and radiotherapy with a poor prognosis. PSC is highly malignant and is prone to recurrence even after surgery. The programmed death-ligand 1 (PD-L1) tumor cell proportion score (TPS) 5%, TERT and TP53 gene mutations were detected in this patient accompanied by multiple metastatic sites. The anlotinib is a novel multitarget tyrosine kinase inhibitor (TKI) that could be effective for advanced NSCLC and some sarcoma patients. Limited clinical trials and case reports have shown that PSC patients with gene mutations and PD-L1 expression have good responses to multitarget antiangiogenic drug and immune checkpoint inhibitors (ICIs). In this article, we reported a case with metastatic PSC diagnosed by Computed Tomography (CT)-guided needle biopsy treated with immunotherapy combined with antiangiogenic drugs as a neoadjuvant chemotherapy (NACT). PSC is controlled and the patient achieves successfully limb salvage treatment by surgical resection. Therefore, targeted therapy and immunotherapy can provide sufficient surgical opportunities for limb salvage in the treatment of metastatic PSC patients. Case summary: A 69-year-old male diagnosed with malignant bone tumor in the proximal femur was admitted to our hospital in June 2022 with recurrent fever as well as swelling and pain in the left thigh for twenty days. The initial computed tomography (CT) scan of the chest showed a pulmonary cavity (20 mm × 30 mm) and scattered lung masses. Subsequently, he underwent a CT-guided needle biopsy to distinguish the essence of osteolytic bone destruction and soft tissue mass in the left proximal femur which showed metastatic sarcomatoid carcinoma histology. Genetic testing revealed TERT c.-124C mutation (abundance 8.81%), TP53 p.R342 mutation (abundance 11.35%), tumor mutational burden (TMB) 7.09 muts/Mb, microsatellite stability (MSS), and PD-L1 (SP263) TPS 5% were also detected. The patient was tentatively treated with a combination of antiangiogenic drug and PD-1 inhibitor. After one course, the tumor volume significantly reduced in magnetic resonance imaging (MRI) and pathological fracture occurred in the femur after combined treatment. The patient received proximal femoral tumor resection and prosthesis replacement after defervescence. Sequentially sintilimab with anlotinib were administered for over 1 year. Finally, the local tumor was well controlled, and no obvious drug-related adverse reactions were observed. The lesions in the lung remained in partial response (PR) for more than 16 months and complete response (CR) of metastatic tumor in the proximal femur was observed through imaging examinations. Conclusion: This is the first reported case of a metastatic PSC in femur showing a favorable response to the treatment consisting of anlotinib combined with sintilimab. This case suggests that antiangiogenic therapy combined with immunotherapy may benefit patients with metastatic PSC in the preoperative adjuvant therapy for limb salvage.

Effect of histological subtype on the efficacy of perioperative chemotherapy in pulmonary sarcomatoid carcinoma: a retrospective study based on SEER population.

Background: The efficacy of perioperative chemotherapy (PC) in pulmonary sarcomatoid carcinoma (PSC) is controversial. We conducted this study to investigate the effect of different histological subtypes on the efficacy of PC in PSC patients. Methods: Clinicopathological data of 811 PSC patients of different histological subtypes were collected from the Surveillance, Epidemiology, and End Results (SEER) database. Kaplan-Meier method and log-rank test were used to evaluate the effects of PC on the overall survival (OS) and cancer-specific survival (CSS) in different subtypes of PSC patients. Propensity score matching (PSM) was used to reduce potential confounding effects. Subgroup analyses were conducted to further investigate the efficacy of PC in patients with different characteristics. Results: A total of 210 (25.89%) enrolled PSC patients received PC. PC was not associated with OS or CSS benefit in pleomorphic carcinoma, giant cell carcinoma, or spindle cell carcinoma patients, neither before nor after matching. But survival benefit of PC was observed in carcinosarcoma patients both before (5-year OS: 48.79% vs. 38.75%, P=0.01) and after (5-year OS: 51.29% vs. 17.54%, P=0.003) matching. Subgroup analyses showed that in patients whose tumor larger than 4 cm, PC was still associated with improved survival in carcinosarcoma, but not in the other histological subtypes of PSC. Conclusions: The efficacy of PC varies between different subtypes of PSC. Survival benefit of PC was only observed in carcinosarcoma patients, but not in pleomorphic carcinoma, giant cell carcinoma, or spindle cell carcinoma patients. Histological subtype should be considered when treating PSC patients with PC.

Role of immunotherapy in pulmonary sarcomatoid carcinoma: review of current approaches and related biomarkers.

Pulmonary sarcomatoid carcinoma (PSC), a rare subtype of non-small cell lung cancer, is highly malignant and has a poor prognosis. Treatments for PSC are presently limited. Traditional treatments provide fewer benefits to PSC patients and are associated with early recurrence and metastasis. Surgical intervention is the preferred option for early-stage PSC patients, whereas chemotherapy, radiotherapy, immunotherapy, and other targeted therapies are recommended for advanced PSC patients. Targeted therapy is only effective in a small number of PSC patients. The initial efficacy of immune checkpoint inhibitors has been acceptable in patients with advanced PSC; therefore, much attention on related biomarkers has been sought. This article aimed to review the research progress of PSC immunotherapy and related diagnostic and prognostic biomarkers in recent years.

Advances in immunotherapy for pulmonary sarcomatoid carcinoma Pulmonary sarcomatoid carcinoma (PSC), a rare subtype of non-small cell lung cancer (NSCLC), is highly malignant and has a poor prognosis. Traditional treatments provide fewer benefits to PSC patients and are associated with early recurrence and metastasis. Targeted therapy is only effective in a small number of PSC patients. The initial efficacy of immune checkpoint inhibitors (ICIs) has been acceptable in patients with advanced PSC, therefore, much attention on related biomarkers has been sought. This article aimed to review the research progress of PSC immunotherapy and related diagnostic and prognostic biomarkers in recent years.

Biological characteristics and clinical treatment of pulmonary sarcomatoid carcinoma: a narrative review.

Background and Objective: Pulmonary sarcomatoid carcinoma (PSC) is a subset of non-small cell lung cancer (NSCLC) with highly malignant, aggressive, and heterogeneous features. Patients with this disease account for approximately 0.1-0.4% of lung cancer cases. The absence of comprehensive summaries on the basic biology and clinical treatments for PSC means there is limited systematic awareness and understanding of this rare disease. This paper provides an overview of the biological characteristics of PSC and systematically summarizes various treatment strategies available for patients with this disease. Methods: For this narrative review, we have searched literature related to the basic biology and clinical treatment approaches of PSC by searching the PubMed database for articles published from July 16, 1990 to August 29, 2023. The following keywords were used: "pulmonary sarcomatoid carcinoma", "genetic mutations", "immune microenvironment", "hypoxia", "angiogenesis", "overall survival", "surgery", "radiotherapy", "chemotherapy", and "immune checkpoint inhibitors". Key Content and Findings: Classical PSC comprises epithelial and sarcomatoid components, with most studies suggesting a common origin. PSC exhibits a higher tumor mutational burden (TMB) and mutation frequency than other types of NSCLC. The tumor microenvironment (TME) of PSC is characterized by hypoxia, hypermetabolism, elevated programmed cell death protein 1/programmed cell death-ligand 1 expression, and high immune cell infiltration. Treatment strategies for advanced PSC are mainly based on traditional NSCLC treatments, but PSC exhibits resistance to chemotherapy and radiotherapy. The advancement of genome sequencing has introduced targeted therapies as an option for mutation-positive PSC cases. Moreover, due to the characteristics of the immune microenvironment of PSC, many patients positively respond to immunotherapy, demonstrating its potential for the management of PSC. Conclusions: Although several studies have examined and assessed the TME of PSC, these are limited in quantity and quality, presenting challenges for research into the clinical treatment strategies for PSC. With the emergence of new technologies and the advancement of clinical research, for example, savolitinib's clinical study for MET exon 14 skipping mutations positive PSC patients have shown promising outcomes, more in-depth studies on PSC are eagerly anticipated.

Case report: Pathological complete response induced by immunochemotherapy in a case of Pulmonary Sarcomatoid Carcinoma staged IIIA-N2.

Pulmonary sarcomatoid carcinoma (PSC) represents a rare and highly aggressive variant of lung cancer, characterized by its recalcitrance to conventional therapeutic modalities and the attendant dismal prognosis it confers. Recent breakthroughs in immunotherapy have presented novel prospects for PSC patients; nevertheless, the utility of neoadjuvant/conversional immunotherapy in the context of PSC remains ambiguous. In this report, we present a middle-aged male presenting with Stage III PSC, notable for its high expression of the programmed death-ligand 1 (PD-L1), initially deemed as non-resectable for sizeable tumor mass and multiple lymph nodes metastases. The patient underwent a transformation to a resectable state after a regimen of three cycles of platinum-based chemotherapy plus immunotherapy. Following definitive surgical resection, the individual realized a pathological complete response (pCR), culminating in a significant prolongation of event-free survival (EFS). This case underscores the viability of employing immunochemotherapy as a neoadjuvant/conversional strategy for chosen cases of PSC.

[A Case of Multidomain Integrated Treatment Strategy 
for Complex Primary Pulmonary Sarcomatoid Carcinoma].

Pulmonary sarcomatoid carcinoma (PSC) is a rare and highly malignant tumor, which includes the following five pathologic types: pleomorphic carcinoma, spindle cell carcinoma, giant cell carcinoma, carcinosarcoma and pulmonary blastoma. The onset of PSC is occult with non-specific clinical symptoms and signs. The clinical manifestations include irritating cough, bloody sputum, dyspnea, chest pain and so on, which are closely related to the growth and invasion site of the tumor. PSC tends to metastasize early, so most patients are already in local advanced stage or advanced stage with a median survival of 9 months at the time of hospital visit. A patient with primary PSC which led to 90% stenosis in central airway was treated by combined method of vascular and tracheoscopic intervention in our respiratory center. This treatment prolonged the patient's survival time and got a satisfactory effect at 19-month follow-up after surgery. Herein we report the case for clinical reference.
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Spindle Cell Carcinoma Presenting as a Massive Pleural Effusion.

The lung's sarcomatoid carcinomas (SC) are a heterogeneous sporadic group of non-small cell lung carcinomas (NSCLCs) and are very challenging to diagnose and treat. Spindle cell carcinoma (SpCC) is a very rare subset of this group. Hence, the prognosis and treatments are unclear due to the limited literature available. The presentation of this cancer varies based on the site of the neoplasm and the complications and metastases observed at the time of diagnosis. Here, we report a 73-year-old man who presented to the emergency room after two months of worsening dyspnea and fatigue. Chest X-ray showed an extensive left-sided pleural effusion. A computed tomography (CT) scan of the chest showed a pleural-based mass that came back as SpCC, for which he was referred to a university hospital.

Extended radical resection and chest wall reconstruction for a pulmonary sarcomatoid carcinoma: a case report.

BACKGROUND: Pulmonary sarcomatoid carcinoma (PSC) is a rare and highly malignant type of non-small cell lung cancer (NSCLC), for which the treatment of choice is surgery. For peripheral PSC growing outward and invading the chest wall, a complete resection of the affected lung lobes and the invaded chest wall can improve long-term prognosis. However, when the extent of the resected chest wall is large, reconstruction is often required to reduce the risk of postoperative complications. Here, we present a case of PSC invading the chest wall treated with successful extended radical resection for lung cancer and chest wall reconstruction. CASE PRESENTATION: A 58-year-old male patient with a nodule in the right upper lobe that had been identified on physical examination 2 years before presentation presented to our hospital with a recent cough, expectoration, and chest pain. Imaging revealed a mass in the right upper lobe that had invaded the chest wall. Preoperative puncture pathology revealed poorly differentiated NSCLC. We performed extended radical resection for lung cancer under open surgery and reconstructed the chest wall using stainless steel wire and polypropylene meshes. The procedure was uneventful, and the patient was discharged 7 days postoperatively. Furthermore, the final pathology revealed PSC. CONCLUSIONS: This case underscores the feasibility of surgical R0 resection in patients with PSC with chest wall invasion and no lymph node metastasis, potentially enhancing long-term outcomes. The novel aspect of this case lies in the individualized chest wall reconstruction for a large defect, using cost-effective materials that offered satisfactory structural support and postoperative recovery, thereby providing a valuable reference for similar future surgical interventions.

Case report: Successful treatment of advanced pulmonary sarcomatoid carcinoma with BUBIB-ALK rearrangement and KRAS G12C mutation by sintilimab combined with anlotinib.

Pulmonary sarcomatoid carcinoma (PSC) is a rare and aggressive subtype of non-small cell lung cancer (NSCLC) that is characterized by poor differentiation and invasiveness. According to the World Health Organization, PSC exhibits sarcoma or sarcomatoid differentiation and typically presents with an insidious onset, lacking specific symptoms and signs. It is associated with high malignancy, early metastasis, short survival time, and a poor prognosis. Treatment for PSC follows a similar approach to NSCLC; however, it presents significant challenges due to its high resistance to chemotherapy. Previous research has demonstrated the coexistence of two or more target mutations in PSC, and the presence of multiple mutations is correlated with higher mortality rates compared to single mutations. This is supported by our case study of a male patient with advanced BUBIB-ALK rearrangement and KRAS G12C missense mutation. There is currently no standard treatment protocol available for patients with this condition. The patient showed rapid progression after 1 month of alectinib treatment and was intolerant to paclitaxel + cisplatin chemotherapy. Following this, successful disease control was achieved with a combination therapy of sintilimab and anlotinib. The patient achieved a progression-free survival (PFS) of over 20 months, and long-term follow-up is still ongoing for the patient. Based on our clinical experience, the combination of anlotinib and programmed death-1 (PD-1) inhibitors may be a promising strategy for PSC patients, particularly those with multi-target mutations who do not respond to ALK-TKI and are resistant to chemotherapy.

18F-FDG PET/CT imaging in pulmonary sarcomatoid carcinoma.

Background: Pulmonary sarcomatoid carcinoma (PSC) is a rare highly aggressive and poorly differentiated non-small cell carcinoma, and little is known about the information on the usefulness of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT). We investigated the clinical and 18F-FDG PET/CT features of PSC. Methods: We retrospectively analyzed 25 consecutive PSC patients who had undergone 18F-FDG PET/CT. Demographic data, PET/CT findings before treatment, pathological features, and prognosis in these patients were investigated to define correlates between maximal standard uptake value (SUVmax) and clinicopathological parameters. Results: From March 2017 to January 2023, twenty-five eligible patients with PSC were identified. There were 23 (92%) men, aged 68.5 ± 8.5 (range 56-90) years. Eighteen (72%) patients had a frequent smoking history. The mean size of PSCs was 59.3 ± 18.6 (range 29-97) mm, and 23 (92%) PSCs were Stage IV tumors. 20 (80%) lesions were located in the upper lung and 19 (76%) cases belonged to the peripheral type. Necrotic foci appeared in 21(84%) tumors. 11 (44%) PSCs invaded the pleura. All PSCs were FDG avid, and the mean of SUVmax was 11.8 ± 5.3 (range 4.8-25.5). Metastases were found on PET/CT in 24(96%) patients. The SUVmax of the lesions ≥ 5cm was higher than that of the lesions < 5cm (p=0.004), and the SUVmax of lesions with TTF-1 expression was higher than those of lesions without TTF-1 expression (p=0.009). All of the 25 primary lesions were considered malignant and confirmative, probable, and possible diagnosis of PSC was made in 2 (8%), 4 (16%), and 5(20%) patients, respectively on PET/CT. PSC was not considered in 14 (56%) patients, in PET/CT. The survival of patients with surgery didn't demonstrate a significantly good prognosis as compared with those without surgery (p=0.675). Conclusion: All PSCs had obvious FDG avidity. Although imaging diagnosis is still difficult, combined clinical and imaging features more than 40% of primary lesions were considered for the possibility of PSC in our group. Early histopathological diagnosis is necessary to help develop a reasonable regimen.

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

Introduction: Pulmonary 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. Methods: This multicenter retrospective study evaluated patients with ICI-naive advanced or metastatic PSC who were treated with ICI-based therapy at 25 hospitals in Japan. Results: A 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. Conclusions: ICI-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.

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

BACKGROUND/OBJECTIVE: We aimed to develop a comprehensive and effective nomogram for predicting cancer-specific survival (CSS) in patients with pulmonary sarcomatoid carcinoma (PSC). METHODS: Data 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). RESULTS: Overall, 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. CONCLUSIONS: The 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.

Genomic Landscape of Pulmonary Sarcomatoid Carcinoma.

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

A case report: A new promising treatment for pulmonary sarcomatoid carcinoma - Tislelizumab and Anlotinib combined with local radiotherapy.

Background: Pulmonary sarcomatoid carcinoma (PSC) is a rare pathological type of non-small cell lung cancer, only occurs in 0.1%-0.4 % of lung cancer patients. It has a poor prognosis and shows low response to conventional chemotherapy. Target therapy, immunotherapy, and other new approaches are worth exploring in PSC. Recently, patients with MET ex14 skipping mutation can obtain good therapeutic efficacy through target therapy. But there was no definitive treatment for patients without this special mutation. Case description: Now, we report a female PSC patient without MET ex14 skipping mutation in the cT4N2M1 stage treated with Tislelizumab and Anlotinib obtained remarkable effect for more than 2 years. Significantly, in this case, immunotherapy and antiangiogenic therapy continued to prolong the survival time of more than 10 months for the patient after being treated by local radiotherapy. This is the first case that reported the effectiveness of immunotherapy and antiangiogenic therapy combined with local radiotherapy in treating PSC and achieved more long-term clinical efficacy than other treatments. Conclusions: Thus, immunotherapy and antiangiogenic therapy combined with local radiotherapy may bring new hope to advanced PSC patients and is worth conducting further research. It provided an effective reference for the treatment of advanced PSC patients without METex14 skipping mutation. Moreover, this case also demonstrated the synergistic effect of radiotherapy and immunotherapy.

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.

Pembrolizumab combined with anlotinib improves therapeutic efficacy in pulmonary sarcomatoid carcinoma with TMB-H and PD-L1 expression: a case report and literature review.

Background: Pulmonary sarcomatoid carcinoma (PSC) is a unique subtype of non-small cell lung cancer (NSCLC) with a high degree of malignancy and poor therapeutic effects. With the widespread use of immune checkpoint inhibitors (ICIs) in recent years, few studies have reported that immunotherapy is effective against PSC. As a multi-target anti-vascular targeting agent, anlotinib showed a better anti-tumor effect in various cancer species. The paper reported the therapeutic and side effects of pembrolizumab combined with anlotinib in a patient with advanced PSC. Case presentation: This is a 73 year old female patient who underwent thoracoscopy right upper lobectomy and was diagnosed as locally advanced PSC. However, the patient experienced tumor recurrence and metastasis 7 weeks after surgery and was unable to tolerate chemoradiotherapy. Moreover, she detected TP53 mutation and found that tumor mutation burden (TMB) and PD-L1 were high expression. Therefore, the patient received pembrolizumab combined with anlotinib treatment. After 15 cycles of treatment, the tumor significantly shrank with no tumor activity. The evaluation of tumor efficacy is partial response (PR). During the treatment period, she experienced one-degree thyroid-stimulating hormone elevation and two-degree hand-foot syndrome. Pembrolizumab and anlotinib was continued for two years as a maintenance treatment. The patient had a good quality of life and no disease progression was observed. Currently, the patient is still alive without tumor progression and has overall survival exceeding 45 months and toxic side effects were tolerable. Conclusions: Combining ICIs and anti-angiogenic targeted therapy has brought new hope in treating advanced PSC. Additionally, TMB and PD-L1 expression could be potential predictive biomarkers of the efficacy in advanced PSC with immunotherapy.

Anlotinib combined with pembrolizumab as first-line treatment for advanced pulmonary sarcomatoid carcinoma: a case report and literature review.

Pulmonary sarcomatoid carcinoma (PSC) is an uncommon variant of non-small cell lung cancer (NSCLC), known for its unfavorable prognosis. Previous studies have elucidated that PSC generally exhibits a significant expression of programmed death-ligand 1 (PD-L1), an elevated tumor mutation burden, and marked vascular invasion. These factors imply the possible effectiveness of treatments like immunotherapy and anti-angiogenic therapy. The subject of this case was a 65-year-old male diagnosed with advanced PSC, characterized by high PD-L1 expression and devoid of known driver gene mutations. Owing to the restrictions imposed by the COVID-19 pandemic, the patient initially underwent home-based treatment with anlotinib, which led to symptomatic improvement after a single treatment cycle. Subsequent hospitalization allowed for the administration of anlotinib plus Pembrolizumab, resulting in a partial response. Radiotherapy was necessitated due to local disease progression. But after 15 cycles of treatment with Pembrolizumab, hyperprogression was observed. The patient's overall survival spanned 14 months, with no evident adverse reactions to the medications. Genomic analysis revealed potential associations between treatment efficacy and mutations in the TP53, NF1, and MET genes. This case underscores the effectiveness and safety of a first-line treatment regimen combining pan-target anti-angiogenic therapy (anlotinib) with anti-tumor immunotherapy.

Pulmonary Spindle Cell Carcinoma Presenting Anaplastic Lymphoma Kinase Rearrangement.

Pulmonary spindle cell carcinoma is a subtype of pulmonary sarcomatoid carcinoma and a very rare tumor type with a poor prognosis. A few case reports have documented patients with pulmonary sarcomatoid carcinoma with anaplastic lymphoma kinase rearrangement, and the efficacy and outcomes of anaplastic lymphoma kinase inhibitors remain unclear. Herein, we present the case of a 60-year-old woman with stage IVB disease who was diagnosed with a metastatic brain tumor. This patient showed high levels of programmed cell death ligand 1 expression and anaplastic lymphoma kinase rearrangement and received pembrolizumab as the first-line treatment. Three weeks later, pembrolizumab failed to reduce the size of the primary pulmonary tumor, and the patient's general condition did not improve. The patient received alectinib as the second-line treatment. Two months later, multiple brain metastases were observed. Hence, whole-brain irradiation was performed as treatment for multiple brain metastases, while another anaplastic lymphoma kinase inhibitor was administered; however, both treatments remained ineffective. The patient eventually died 9 months after the initiation of first-line treatment. The present case report describes the therapeutic course of a patient with pulmonary spindle cell carcinoma with an anaplastic lymphoma kinase rearrangement.