Pulmonary Sarcomatoid Carcinoma Patients Research Articles

Advances in immunotherapy for pulmonary sarcomatoid carcinoma

Pulmonary sarcomatoid carcinoma (PSC) is a rare, poorly differentiated non-small cell lung cancer (NSCLC) that contains sarcomatoid components or sarcomatoid differentiation, and accounts for less than 1% of all lung tumors. Compared to other types of NSCLC, PSC has more invasive biological behavior, is prone to metastasis, and has a higher recurrence rate after early surgery. Its greater resistance to traditional treatments leads to a poorer prognosis compared to other NSCLCs. Immunotherapy offers the possibility of long-term survival for PSC patients.

Clinical characteristics and prognosis analysis of pulmonary sarcomatoid carcinoma

Objective: To summarize the clinical characteristics, treatment, and outcomes of patients with pulmonary sarcomatoid carcinoma (PSC) in order to improve clinicians' understanding of this disease. Methods: The clinical data of patients diagnosed with PSC in our hospital from January 1, 2015 to November 30, 2023 were retrospectively analyzed. According to whether radical resection was performed, the patients were divided into resectable group and unresectable group. The characteristics and treatments of PSC in different groups were compared. The survival curves were drawn by Kaplan-Meier method to compare the prognosis of different groups of patients. Results: A total of 43 PSC patients were included, including 32 males, with an average age of (62.79±9.59) years, and 31 smokers. Peripheral-type tumors were more common, with imaging showing predominantly solid soft tissue masses, and the maximum diameter of the tumor was more than 5 cm in 14 patients. Among the 23 patients who underwent NGS gene testing, the KRAS mutation rate was 43.5%, the TP53 mutation rate was 30.4%, and the MET mutation rate was 8.7%, all of which were MET-14 exon skipping mutations. PD-L1 expression was detected in 13 patients, 10 of whom showed high expression. The median overall survival (mOS) of the 43 patients with PSC was 24.6 months (13.0-52.7 months). Among them, 22 patients underwent radical lobectomy plus mediastinal lymph node dissection, 13 patients had postoperative recurrence, and 7 patients died during follow-up. The median disease-free survival (mDFS) was 12.3 months, the mOS was not achieved and the 1-year OS rate was 77.3 %. Twenty-one patients had unresectable locally advanced or advanced stage, and 15 patients died. The mDFS was 2.5 months, the mOS was 6.2 months, and the 1-year OS rate was 42.9 %. Seventeen patients received immunotherapy, and 1 patient received targeted therapy with the MET inhibitor glumetinib. Conclusions: PSC has a higher incidence in the elderly, smokers, and males, is highly malignant and has a poor prognosis. Based on its molecular biological characteristics, PD-L1 expression and tumor molecular detection can be performed to guide treatment options.

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

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. 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. 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. 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.

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

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. 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". 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. 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.

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

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. 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. 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). 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.

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.

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.

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.

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.

The Correlation Between Histologic, Immunophenotypic, and Molecular Characteristics of Pulmonary Sarcomatoid Carcinoma Reveals That Sarcomatoid Change Is Potentially Derived From Epithelial Carcinoma Cells Undergoing Epithelial-Mesenchymal Transition.

Pulmonary sarcomatoid carcinoma (PSC) is characterized by biphasic tumors with epithelial and mesenchymal phenotype. Little is known about the correlation between histologic, immunophenotypic features and the genetic profile of PSC. We analyzed the expression of epithelial-mesenchymal transition-related markers, adenocarcinoma (ADC) and squamous cell carcinoma lineage-specific markers of 205 PSC cases. The alteration of 5 targeted genes was detected by amplification-refractory mutation system-polymerase chain reaction. The intensity of cytokeratin staining was stronger in epithelial carcinoma (EC) than that of the sarcomatoid component (SC) of pleomorphic carcinoma, while vimentin was positive in only 16.3% (17/104) of EC of pleomorphic carcinoma. There is no significant difference between thyroid transcription factor 1 (TTF-1) expression in the SC (46.5%, 33/71) of pleomorphic carcinoma with ADC components and pure PSC (44.2%, 42/95) without p40 expression ( P =0.858). Four cases with ALK rearrangement were confirmed to co-express ALK fusion protein in both the SC and EC. The incidence of EGFR/ALK/KRAS mutation was similar between pleomorphic carcinoma with ADC components (40.6%, 26/64) and TTF-1 + pure PSC (38.2%, 13/34) ( P =0.583). However, higher proportions of TTF-1 + /p40 - PSC patients (44.8%, 39/87) had EGFR/ALK/KRAS mutation than those with TTF-1 - /p40 - PSC (16.7%, 4/24) ( P =0.031). The incidence of EGFR mutation was significantly higher in TTF-1-positive (18.4%, 16/87) than TTF-1-negative (2.7%, 2/74) PSC ( P =0.002). No EGFR and ALK abnormality were observed in 24 pleomorphic carcinoma cases with squamous cell carcinoma components or pure PSC with p40 expression. Our study reveals a close correlation between SC and EC components of pleomorphic carcinoma in terms of immunophenotypic and genetic features, which suggests that pleomorphic carcinoma is potentially derived from the sarcomatoid change of EC cells undergoing epithelial-mesenchymal transition.

MET alterations in advanced pulmonary sarcomatoid carcinoma.

Pulmonary sarcomatoid carcinoma (PSC) is a rare subset of NSCLC that accounts for about 0.5-1% of all primary lung carcinoma, and its malignant biological behavior is more aggressive than other pathological types of lung cancer. Recent studies have reported a variety of gene mutations associated with the occurrence, development and treatment of PSC, especially the mesenchymal-epithelial transition (MET) proto-oncogene alterations, including the exon 14 (METex14) skipping mutations as well as the amplification and overexpression of MET gene, which are associated with molecularly targeted therapy for PSC. METex14 skipping mutation is the most common and well-studied mutation type, occurring in about 22-31.8% of PSC patients, while the prevalence of MET amplification is reported as 4.8-13.6% and MET ovexpression is about 20.2%. Molecular pathology tests, including IHC and NGS, are valuable in determining the prognosis of patients with PSC and helping to determine the treatment. The existing clinical data have confirmed the efficacy of MET-TKI in PSC patients with MET alteration, among which the clinical study of Savolitinib has enrolled the largest proportion of PSC patients and achieved relatively good efficacy, but more clinical researches are still needed. The multi-disciplinary team may maximize the optimal treatment options for patients with the advanced PSC.

PSC subtyping based on TTF-1 and p40 expression reveals distinct molecular characteristics and therapeutic strategies.

Pulmonary sarcomatoid carcinoma (PSC) is a unique form of poorly differentiated nonsmall cell lung cancer (NSCLC) and is notorious for its highly malignant nature and dismal prognosis. To introduce effective treatment for PSC patients, precise subtyping of PSC is demanding. In our study, TTF-1 and P40 immunohistochemistry (IHC) staining were applied to 56 PSC patients with multiomics data. According to IHC results, we categorized these patients into three subgroups and profiled their molecular contexture using bioinformatic skills. IHC results classified these patients into three subgroups: TTF-1 positive subgroup (n=27), P40 positive subgroup (n=15) and double-negative subgroup (n=14). Spindle cell samples accounted for 35.71% (5/14) of double-negative patients, higher than others (P=.034). The three subgroups were heterogeneous in the genomic alteration spectrum, showing significant differences in the RTK/RAS pathway (P=.004) and the cell cycle pathway (P=.030). The methylation profile of the double-negative subgroup was between the other two subgroups. In similarity analysis, the TTF-1 and p40 subgroups were closely related to LUAD and LUSC, respectively. The TTF-1 positive subgroup had the highest leukocyte fraction (LF) among several cancer types, and the tumor mutation burden (TMB) of the p40 positive subgroup ranked third in the TMB list, suggesting the applicability of immunotherapy for PSC. The study established a new subtyping method of PSC based on IHC results and reveals three subgroups with distinct molecular features, providing evidence for refined stratification in the treatment of PSC.

Genomic Variations and Immune-Related Features of TMB, PD-L1 Expression and CD8+ T Cell Infiltration in Chinese Pulmonary Sarcomatoid Carcinoma.

BackgroundPulmonary sarcomatoid carcinoma (PSC) is a rare and distinct subtype of lung cancer characterized by its aggressiveness and dismal prognosis. However, genomic landscape and immune contexture have not been fully elucidated among PSC patients.MethodsIn the present study, whole-exome-sequencing (WES) analyses were performed to depict genomic landscape of 38 independent PSC samples. Tumor mutation burden (TMB) was calculated with the total number of non-synonymous SNVs and indel variants per megabase of coding regions. PD-L1 expression and CD8+ T cell density were evaluated by immunohistochemistry in PSC samples. Their associations with genomic mutation were further assessed in genes with most frequent mutation. Overall survival (OS) of PSC patients with top mutated genes and high and low TMB, PD-L1 and CD8+ TIL expressions were further compared. Subgroup analyses of OS stratified by morphology and pathological type were conducted. Their correlation with TMB, PD-L1 and CD8+ T cell were further assessed.ResultsWe identified a cohort of genomic and somatic mutation in PSC patients. Subgroup patients with distinct clinicopathological features were found to harbor different genomic mutations and immunologic features. Besides, genomic profiles influenced outcomes, with SARS mutation associated with worsened prognosis.ConclusionThrough the mapping of genetic and immunologic landscape, we find the heterogeneity among the subgroups of PSC. Our findings may provide opportunities for therapeutic susceptibility among Chinese PSC patients.

16P Camrelizumab monotherapy or plus apatinib for PD-L1-positive advanced pulmonary sarcomatoid carcinoma: A single-arm, open-label, multicenter, phase II study

As a rare and highly aggressive malignancy, pulmonary sarcomatoid carcinoma (PSC) is insensitive to chemotherapy or radiotherapy and no optimal treatment has been established yet. Because of the high expression of programmed death-ligand 1 (PD-L1), immune checkpoint inhibitors (ICIs) were documented to possess encouraging efficacy in PSC patients (pts). Here we evaluated camrelizumab (Camre) in treating PD-1-positive PSC. Apatinib (Apa) may be used simultaneously with Camre based on the PD-L1 level, as the combination of Camre and Apa exhibited treatment potential in lung cancer in previous study.

Multimodality Treatment of Pulmonary Sarcomatoid Carcinoma: A Review of Current State of Art.

Pulmonary sarcomatoid carcinoma (PSC) is an unconventional non-small-cell lung cancer (NSCLC) that is currently managed under guidelines used for conventional NSCLC and has poor survival. Surgery is the optimal choice for resectable PSC, and the prevalence of mutations in this type of tumor laid the foundation for novel systemic therapies such as targeted therapy and immunotherapy. PSC is resistant to chemotherapy and radiotherapy, and the effects of the 2 therapies are controversial. Targeted therapies have been reported to confer survival benefits, and savolitinib, an oral selective MET tyrosine-kinase inhibitor, has been approved in metastatic patients with MET exon 14 skipping mutations. Expression and positive rate of programmed death ligand 1 in PSC are high; our previous research has also revealed a high mutational burden and a T-cell-inflamed microenvironment of PSC. Correspondingly, immune checkpoint inhibitors have shown preliminary antitumor effects (overall response rates of 40.5% (15/37) and 31.6% (6/19) in two retrospective studies, respectively) in PSC patients. In summary, patients should receive operations at an early stage and multimodality treatments are needed to maximize the benefits of patients with advanced disease.

The Prognosis of Pulmonary Sarcomatoid Carcinoma: Development and Validation of a Nomogram Based on SEER.

Background: The rarity of pulmonary sarcomatoid carcinoma (PSC) and the lack of prospective clinical trials have led to limited knowledge of its clinical characteristics. This study aimed to evaluate the survival and prognostic factors of PSC and to build a nomogram for clinical practice. Methods: Eligible patients diagnosed from 2010 to 2016 were selected from the Surveillance, Epidemiology, and End Results (SEER) database. We compared the clinical characteristics and survival times of PSC patients with those of lung adenocarcinoma (LADC) and lung squamous cell carcinoma (LSCC) patients. We also used univariate and multivariable Cox regression to estimate mortality hazard ratios among patients with PSC, while a visual nomogram was established to judge the prognosis. Discrimination, calibration, clinical utility, and reproducibility were validated by Harrell's concordance index (C-index), the area under the curve (AUC), calibration curves, and decision curve analysis (DCA). Results: A total of 400 PSC patients (0.42%) were identified in the SEER database, whereas 58 474 and 33 637 patients were diagnosed with LADC and LSCC, respectively. Age, T stage, grade, surgery, and radiation were shown to be significant prognostic factors in the Cox regression analyses and were included in the nomogram as predictors. The C-index of the nomogram in the validation set was 0.759. The AUC also demonstrated the good performance of the nomogram, and DCA demonstrated its good clinical applicability. Conclusion: We established a novel nomogram to predict the prognosis of PSC, which can help clinicians make tailored decisions and adjust follow-up management strategies, and can provide accurate and individualized survival predictions.

Immune checkpoint inhibitors plus chemotherapy in patients with locally advanced or metastatic pulmonary sarcomatoid carcinoma: a multicentric real-world study.

Immune checkpoint inhibitors (ICIs) have demonstrated promising efficacy as monotherapy in patients with pulmonary sarcomatoid carcinoma (PSC). We performed the current multi-institutional, real-world study to assess the efficacy of ICIs plus chemotherapy in patients with PSC. All consecutive patients with locally advanced or metastatic PSC from three centers treated with ICIs between January 2018 and July 2021 were enrolled. Programmed death ligand 1 (PD-L1) expression was stained and evaluated using immunohistochemical with 22C3. Single-cell RNA sequencing (scRNA-seq) was performed in two patients with PSC and two patients with adenocarcinoma to understand the cell-type-specific transcriptome landscape of cancer cells and tumor microenvironment (TME) of PSC. A cohort of 42 PSC patients was identified. In the overall population, the objective response rate (ORR) was 73.8%, median progression-free survival (mPFS) was 10.3 months and median overall survival was not reached and 2-year survival rate was 51.2%. For 34 treatment-naïve patients who received first-line ICIs plus chemotherapy, the ORR was 70.6%, mPFS was 10.3 months and 2-year survival rate was 57.8%. In patients with PD-L1 tumor proportion score (TPS) < 1%, 1-49%, and ⩾50%, the ORR was 33.3%, 72.7%, and 85.7% and mPFS was 6.0, 6.7, and 10.3 months, respectively. Notably, two patients with transformed PSC from lung adenocarcinoma after epidermal growth factor receptor-tyrosine kinase inhibitor treatment also responded well to ICIs plus chemotherapy. scRNA-seq revealed immune-cell-inflamed TME, lower intratumoral heterogeneity, and activated immune response pathway in PSC. Our study demonstrated remarkable efficacy of ICIs plus chemotherapy as first-line therapy for patient with locally advanced or metastatic PSC.

P14.06 Toripalimab in Combination With Bevacizumab and Platinum-Based Chemotherapy in Patients with Untreated Advanced PSC: A Phase II Study

Although immunotherapy has emerged as a standard treatment for advanced non-small cell lung cancer (NSCLC) without driver gene mutation, there are still insufficient data on the efficacy of immunotherapy for patients with pulmonary sarcomatoid carcinoma (PSC). Due to a high tumor mutation burden and great prevalence of programmed cell death ligand 1 (PD-L1) in PSC than other subtypes of NSCLC, immunotherapy may provide promising efficacy in advanced PSC patients. Multiple immune-monotherapy or combination with chemotherapy case studies and doublet immunotherapy based on a phase II study (NCT03022500) suggested the survival benefit of immunotherapy in advanced PSC. Blood-vessel invasion as an independent factor associated with PD-L1 expression and poor prognosis in PSC, early application of anti-angiogenesis may enhance patients' response to immunotherapy. The application of anti-programmed cell death protein 1 (PD-1) antibody combined with platinum-based chemotherapy plus anti-angiogenesis in untreated advanced PSC is worth exploring. Toripalimab, a humanized IgG4 monoclonal antibody against PD-1, achieved partial response (PR) for second-line advanced PSC in a recent case report (Jiao Y Oral Oncology 2020). Based on these pieces of evidence, we explore the combination of toripalimab with platinum-based chemotherapy and bevacizumab in patients with untreated advanced PSC. This is an open-label, multicenter, single-arm, phase II study that aims to evaluate the efficacy and safety of toripalimab combination with platinum-based chemotherapy and bevacizumab in patients with untreated advanced PSC. Key eligibility criteria include age 18-75 years with Eastern Cooperative Oncology Group performance status of 0-2, histologically confirmed PSC, at least 1 measurable lesion per RECIST v1.1 that not received radiotherapy, and no prior anti-PD-1 or anti-PD-L1 therapy for stage IV PSC. Patients will be excluded if they have evidence of mutations in either EGFR, ROS-1, ALK, or c-MET. 27 untreated advanced PSC patients at 5 sites will be enrolled in Chengdu city, Sichuan province of China. All patients will receive toripalimab (240 mg, d1) combined with bevacizumab (7.5 mg/kg, d1) and nab-paclitaxel (260 mg/m2, d1 or 130 mg/m2, d1,8) plus carboplatin (AUC= 4-5, d1) of a 21-day cycle for a maximum of 6 cycles. Patients will continue to receive maintenance therapy with toripalimab and bevacizumab until disease progression or died of two years. The primary endpoint is progression-free survival (PFS) by investigator assessment per RECIST v1.1. Secondary endpoints include objective response rate (ORR), disease control rate (DCR), overall survival (OS), the patient-reported outcome (PRO), and safety data per NCI-CTC AE 4.0.3. Enrollment for this trial is open in April of this year and will continue for 12 months. Not applicable. Not applicable.