Large Cell Neuroendocrine Carcinoma Of Lung Research Articles

Prognostic factors and predictive models for patients with lung large cell neuroendocrine carcinoma: Based on SEER database.

Lung Large cell neuroendocrine carcinoma (LCNEC) is a rare, aggressive, high-grade neuroendocrine carcinoma with a poor prognosis, mainly seen in elderly men. To date, we have found no studies on predictive models for LCNEC. We extracted data from the Surveillance, Epidemiology, and End Results (SEER) database of confirmed LCNEC from 2010 to 2018. Univariate and multivariate Cox proportional risk regression analyses were used to identify independent risk factors, and then we constructed a novel nomogram and assessed the predictive effectiveness by receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). A total of 2546 patients with LCNEC were included, excluding those diagnosed with autopsy or death certificate, tumor, lymph node, metastasis (TNM) stage, tumor grade deficiency, etc., and finally, a total of 743 cases were included in the study. After univariate and multivariate analyses, we concluded that the independent risk factors were N stage, intrapulmonary metastasis, bone metastasis, brain metastasis, and surgical intervention. The results of ROC curves, calibration curves, and DCA in the training and validation groups confirmed that the nomogram could accurately predict the prognosis. The nomogram obtained from our study is expected to be a useful tool for personalized prognostic prediction of LCNEC patients, which may help in clinical decision-making.

P2.16-05 Durvalumab+EP in Advanced Large-Cell Neuroendocrine Carcinoma of Lung (aLCNEC): a Pilot Phase II study

P2.16-05 Durvalumab+EP in Advanced Large-Cell Neuroendocrine Carcinoma of Lung (aLCNEC): a Pilot Phase II study

SAT321 Ectopic ACTH Cushing's Syndrome Caused By A Large-cell Neuroendocrine Lung Carcinoma Responding To Desmopressin

Abstract Disclosure: S. Larose: None. D. Rioux: None. R. Albadine: None. A. Lacroix: None. Background: Ectopic ACTH secretion (EAS) is a less frequent cause of ACTH-dependent Cushing’s syndrome (CS), most often caused by a thoracic neuroendocrine tumor (NET). Large-cell neuroendocrine carcinomas (LCNEC) with EAS are rare and usually present a more severe phenotype of ACTH secretion and hypercortisolism. Clinical Case: We report the case of a 44-yo non-smoking man, who presented clinical and biochemical evidence of ACTH-dependent severe CS complicated by pulmonary emboli. In the context of an initial equivocal pituitary MRI, desmopressin and CRH stimulation tests were performed. Desmopressin produced a 157% increase in ACTH (basal: 59.0 pmol/L to peak: 151.9 pmol/L) and a 25% increase in cortisol from baseline; there was no stimulation of ACTH or cortisol during a CRH test and no suppression with high dose dexamethasone tests. Repeat pituitary MRI identified a 5 mm lesion, but inferior petrosal venous sinus sampling (IPSS) under desmopressin did not identify a central ACTH source. Thorax and abdominal imaging including Indium-111 octreoscan identified a left lung 3 mm micronodule which became more evident when pulmonary emboli resolved. In this context of probable ectopic ACTH secretion, the patient was treated with left inferior lung lobectomy for a suspected NET. Pathological studies confirmed a lung LCNEC with morphologic features of carcinoid tumor and strongly positive ACTH immunohistochemistry (IHC) in the primary lesion and lymph node metastasis. The patient was in CS remission after surgery and adjuvant chemotherapy, but developed a CS recurrence 9.5 years later, with a morning ACTH of 56.9 pmol/L, (N <11.0 pmol/L), a non-suppressed AM cortisol of 633 nmol/L after 1mg of dexamethasone overnight and urinary free cortisol of 1717 nmol/24 hours (N:< 789). Imaging showed signs of recurrence, with a hypermetabolic, 14 x 11 mm left hilar lymph node lesion on a TEP-DOTATATE scan in the left lung, near the surgical suture. An endobronchial ultrasound-guided biopsy confirmed the recurrence of the LCNEC. Surgery was performed and demonstrated again positive ACTH IHC of the lesion. The patient achieved remission of CS with secondary adrenal insufficiency, treated with hydrocortisone. Six months later, there was no response of ACTH or cortisol to a desmopressin test. Conclusion: This is the first report of LCNEC with morphologic feature of carcinoid tumor of the lung with ectopic ACTH secretion stimulated by desmopressin. Long delay prior to metastatic recurrence indicates relatively indolent NET. This case report indicates that response to desmopressin can occur in malignant LCNEC. Combining the desmopressin test with other dynamic tests, sellar MRI, IPSS and thoraco-abdominal functional imaging improves diagnostic accuracy of ectopic ACTH source. Presentation: Saturday, June 17, 2023

2190P First-line atezolizumab in combination with platinum etoposide in patients with metastatic lung large cell neuroendocrine carcinoma (LCNEC)

2190P First-line atezolizumab in combination with platinum etoposide in patients with metastatic lung large cell neuroendocrine carcinoma (LCNEC)

Development and Validation of a Nomogram for Patients with Lung Large Cell Neuroendocrine Carcinoma

Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a rarely high-grade neuroendocrine carcinoma of the lung with features of both small cell and non-small cell lung cancer. We aim to construct a prognostic nomogram combined with the clinical features and treatment options to predict disease-specific survival (DSS), meanwhile, evaluating the role of prophylactic cranial irradiation (PCI) in LCNEC by subgroup analysis. A total of 713 patients diagnosed with LCNEC from the US National Cancer Institute's Surveillance Epidemiology and End Results (SEER) registry between 2010 and 2016. Cox proportional hazards analysis was conducted to choose the significant predictors of DSS. External validation was performed using 77 patients with LCNEC in the West China Hospital Sichuan University between 2010 and 2018, subgroup analysis was carried out for the whole brain radiotherapy (WBRT) and PCI population. The predictive accuracy and discriminative capability were estimated by the concordance index (C-index), calibration curve and receiver operating characteristic (ROC) curve. The clinical applicability of the nomogram was verified through the decision curve analysis (DCA). Six independent risk factors for DSS were identified and integrated into the nomogram. The nomogram achieved good C- indexes of 0.803 and 0.767 in the training and validation group respectively. Moreover, the calibration curves of both cohorts for the probability of survival showed good agreement between prediction by nomogram and actual observation in 1-, 3- and 5-year DSS. The ROC curves demonstrated the prediction accuracy of the established nomogram (all AUC>0.8). DCA confirmed the better potential clinical practicality of the nomogram in the prediction of LCNEC survival than AJCC staging. A risk classification system was built which could perfectly classify LCNEC patients into high- and low-risk groups(p<0.001). Subgroup analysis showed that WBRT did not bring survival benefits, PCI appeared to have survival benefits in LCNEC patients without brain metastases (p>0.05). The prognostic nomogram developed in this study has certain prognostic value and clinical practicality for LCNEC patients. PCI might be investigated as a means of improving prognosis.

Efficacy and safety of immune checkpoint inhibitors in lung large-cell neuroendocrine carcinoma.

Lung large-cell neuroendocrine carcinoma (L-LCNEC) is a rare and highly aggressive neuroendocrine tumor. There is currently no standard therapeutic regimen, and systemic chemotherapy results in poor prognosis. Due to the rarity of L-LCNEC, the efficacy and safety of immune checkpoint inhibitors (ICIs) remain unclear. This study included 34 L-LCNEC patients administered ICIs at Zhejiang Cancer Hospital, from February 6, 2018 to February 6, 2023. The treatment responses were evaluated. Fisher's exact test was used to compare categorical variables, and the Kaplan-Meier method was used for survival analyses. Cox regression was used for multivariate analysis. The objective response rate (ORR) of 34 patients was 29.4%, the disease control rate (DCR) was 82.4%, the median progression-free survival (PFS) was 6.30 months, and the median overall survival (OS) was 14.77 months. The ORRs of combined LCNEC (n=7) and pure LCNEC (n=27) were 14.3% and 33.3%; the DCRs were 100% and 77.8%; the median PFSs were 12.48 and 5.6 months (P=0.032); and the median OSs were 21.27 and 14.73 months, respectively (P=0.233). The observed incidence of immune-related adverse events (irAEs) was 61.8%, primarily occurring in grades 1/2 (58.8%) and grade 3 (5.9%). Elevated aminotransferases (14.7%), pneumonia (8.8%), and fatigue (8.8%) were the most common irAEs. ICIs treatment showed efficacy and safety in advanced L-LCNEC, with the potential for greater benefits in the combined LCNEC subtype.

Development and Validation of A Prognostic Nomogram to Guide Decision-making in Lung Large Cell Neuroendocrine Carcinoma

Lung large cell neuroendocrine carcinoma (LCNEC) is a rare and highly malignant lung tumor with a poor prognosis. Currently, most research on LCNEC is based on retrospective studies and lacks validation in the real world. The study aims to identify independent risk factors and establish and validate a predictive model for the prognosis of LCNEC. Patient data were extracted from Surveillance, Epidemiology, and End Results (SEER) and our department's hospitalization records from 2010 to 2015 and 2016 to 2020, respectively. Kaplan-Meier analysis was used to evaluate overall survival (OS). OS is defined as the time from diagnosis to death or last follow-up for a patient. Univariate and multivariate Cox regression analyses were performed to identify significant prognostic factors and construct a Nomogram for predicting the prognosis of LCNEC. In total, 1892 LCNEC patients were included and divided into a training cohort (n=1288) and two validation cohorts (n=552, n=52). Univariate Cox regression analysis showed that age, gender, primary tumor site, laterality, T stage, N stage, M stage, surgery, and radiotherapy were factors that could affect the prognosis of LCNEC patients (P<0.05). Multivariate Cox analysis indicated that age, gender, primary tumor site, T stage, N stage, M stage, surgery, and radiotherapy were independent risk factors for the prognosis of LCNEC patients (P<0.05). Calibration curves and the concordance index (internal: 0.744±0.015; external: 0.763±0.020, 0.832±0.055) demonstrated good predictive performance of the model. Patients aged ≥65 years, male, with advanced tumor-node-metastasis (TNM) staging, and who have not undergone surgery or radiotherapy have a poor prognosis. Nomogram can provide a certain reference for personalized clinical decision-making for patients.

The role of immunotherapy in stage III large cell neuroendocrine carcinoma of the lung (LCNEC): A retrospective NCDB analysis.

e20568 Background: Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a rare lung cancer subtype. Despite advances in understanding lung cancer biology, a consensus on the use of consolidation immunotherapy (IO) in patients with LCNEC is still lacking. Methods: Using National Cancer Database (NCDB), we reviewed stage III lung LCNEC cases diagnosed from 2017 through 2019 with a follow-up through 2020. Several variables were incorporated into the multivariate logistic regression analysis, including age, gender, race, Charlson-Deyo comorbidity score (CDCS), insurance status, and IO use. Survival distribution was examined using the Kaplan-Meier analysis and compared by the log-rank test. Results: A total of 956 cases with a male:female ratio of 1.2:1, and a median age (±SD, range) of 66.4 (±9.7, 37–90) years—baseline characteristics are shown in the Table. In the univariate analysis, IO use (n = 184) resulted in a superior median overall survival (mOS; 30.6 vs. 20.3 months, HR 0.76, 95% CI 0.62-0.96, p = 0.02, compared to no IO use). Results from multivariate analysis further demonstrated survival benefit with IO use (HR 0.79, 95% CI 0.63-0.98, p = 0.03, compared to no IO use). Additionally, in the multivariate analysis, the female gender was associated with improved survival (HR 0.84, 95% CI 0.71-0.99, p = 0.04); while notable factors associated with reduced survival were age ≥75 years (HR 1.45, 95% CI 1.08-1.95, p = 0.01, compared to 18-64 years age group), CDCS of ≥1 (HR 1.19, 95% CI 1.004-1.420, p = 0.04, compared to zero), and Medicaid (HR 1.46, 95% CI 1.05-2.05, p = 0.02, compared to private insurance). There was no statistical significance for OS noted with age group 65-74 years (HR 1.09, 95% CI 0.84-1.42, p = 0.49, compared to 18-64 years age group); and race (African American, HR 1.001, 95% CI 0.77-1.29, P = 0.99, compared to White). Conclusions: This study shows that IO improves survival in stage III LCNEC. Despite the inherent limitations of the database, our findings are intriguing and warrant further evaluation through prospective clinical trials in order to assess and optimize the benefit of IO in this patient population. [Table: see text]

Pulmonary large cell neuroendocrine carcinoma (LCNEC): a population-based study addressing recent molecular-genetic advances and emerging therapeutic approaches.

Large cell neuroendocrine carcinoma (LCNEC) of the lung is a rare, aggressive cancer most commonly found in the lungs but not exclusively, with a worse prognosis than non-small cell lung carcinomas. Currently, LCNEC patients are treated using small cell and non-small cell protocols. This study aims to use the SEER database to identify demographic, clinical, pathological, and therapeutic factors affecting the prognosis and survival of patients with LCNEC of the lung. Demographic, clinical, and management data of patients with lung LCNEC were extracted from the SEER database for the period 2000-2018. In the USA, LCNEC has a higher incidence in elderly white men: M:F ratio = 1.2:1, Caucasian: 83.3%, mean age: 67 ± 10.2years. The most common treatment modality was chemotherapy only: 29.2%, followed by surgery: 21.5% (but in this group the statuses of chemotherapy were unknown), and combination surgery/chemotherapy: 8.8%. The overall and cause-specific 5-year survival was 17.5% (95% CI 16.3-18.8) and 21.9% (95% CI 20.5-23.4), respectively. By treatment, the best 5-year survival was for surgery alone (48%), followed by multimodality therapy (chemo + surgery + radiation) at 35% (95% CI 27-43). Age > 60years, male gender, size > 7cm, and nodal and liver metastasis were independent risk factors associated with increased mortality. Lung LCNEC is an aggressive neoplasm most common in older white males that presents at an advanced stage despite small primary tumors. Most patients die within 2years. The best predictor of survival is surgery with chemotherapy. Given its dismal prognosis, new treatment guidelines are needed for this aggressive cancer.

The prognosis analysis of organ metastatic patterns in lung large cell neuroendocrine carcinoma: A population-based study.

Lung large cell neuroendocrine carcinoma (LCNEC) is a rare and highly aggressive malignancy with a dismal prognosis. This study was designed to depict patterns of distant organ metastatic and to analyze prognosis of LCNEC patients. We gathered data from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2015. We conducted the Kaplan-Meier method to calculate overall survival (OS) and compare different variables. Cox proportional hazards regression models in univariate and multivariate analyses were employed to further explore prognostic factors. A total of 1335 LCNEC patients were eventually selected from the SEER database, of which 348 patients (26.0%) had single organ metastasis and 197 patients (14.8%) had multiple metastases. Our study indicates that patients with single organ metastasis generally have a poor prognosis, with a median OS of 8 months for both lung and brain metastasis with 1-year survival rates of 33% and 29% respectively. Patients with multiple metastases exhibited the worst prognosis, with a median OS of only 4 months and a 1-year OS of 8%. Multivariate analysis revealed that age, T stage, N stage, chemotherapy and radiation in metastatic patients were independently associated with OS. In conclusion, LCNEC exhibits a high metastatic rate when diagnosed. The most common metastatic organ is the brain in single-site metastatic patients. Patients with single or multiple metastases exhibit a significantly worse prognosis than those with non-organ metastases. In the group of single organ metastases, patients with brain and lung metastases had a better prognosis than those with bone and liver metastases.

Pulmonary Combined Large Cell Neuroendocrine Carcinoma.

Pulmonary combined large-cell neuroendocrine carcinoma (CLCNEC) is a rare neuroendocrine tumor pertained to lung large cell neuroendocrine carcinoma (LCNEC) with aggressive behavior and poor prognosis generally. The clinical features of CLCNEC are not specific including cough, expectoration, chest distress, chest pain, etc., which are prone to have different manifestations of the mixed components. Owing to the low incidence, there are few related small-scale retrospective studies and case reports. Currently, the treatment regimen of CLCNEC mainly refers to LCNEC that complete surgical resection is preferred in the early stage and according to previous researches, platinum-based small cell lung cancer (SCLC) standard treatment regimen showed promising results in postoperative and advanced CLCNEC as compared to that of non-small cell lung cancer (NSCLC). Adenocarcinoma-CLCNEC more likely harbor driver gene mutation, and may benefit from targeted therapy. As for immunotherapy, more clinical trial data are needed to support its benefits. This article will fill the gap and will provide new insight into the clinical characteristics, pathological diagnosis and treatment endeavors of CLCNEC.

Large cell neuroendocrine lung carcinoma – A challenging rare tumour

Large cell neuroendocrine lung carcinoma – A challenging rare tumour

1178P Integrated pathological analysis to develop a Gal-9 based immune survival stratification to predict the outcome of lung large cell neuroendocrine carcinoma

For large cell neuroendocrine lung carcinoma (LCNEC) therapy, immunotherapy might have unique advantage. The role of Gal-9 in LCNEC remains incompletely understood. Computer-extracted feature in pathology images may reflect immune infiltration. This study aimed to integrate pathological characteristics to develop a Gal-9 based immune risk score in the LCNEC. By mean of IHC, the expression of Gal-9 and other immune markers on both tumor cells and TILs in 122 surgical LCNEC samples were evaluated. The Gal-9 based immune risk model was built and the prognostic performance was evaluated. Then, the effects of Gal-9 and immune risk model on LCNEC immune infiltration were studied in GEO, validated in our cohort by Histology-based Digital-Staining which evaluated the immune cell proportion and image characteristics. In the LCNEC cohort for IHC, 43 (35.2%) were positive Gal-9 expression on tumor cells. The high Gal-9 protein expression on tumor cells indicated worse overall survival (P=0.029, HR=1.83, 95CI: 1.01-3.31). The immune risk model which consisted of Gal-9 on tumor cells, CD3, CD4, PD-L1 on tumor cells and PD-1was constructed and validated to discriminate high or low-risk LCNEC patients. The prognostic predictive performance of immune risk model was good with AUC of 1, 3, 5 years survival: 0.808, 0.763, 0.787 in whole cohort. High Gal-9 related enrichment pathways in LCNEC involved immune suppression and immune tolerance. The high-risk group demonstrated an immune-desert tumor filled with less T cells but more neutrophils (P=0.041). HD-staining pathology results from a total of 108369 cells validated that high-risk group has less stroma cells (13.9% vs 11.1%), but more tumor cells (63.9%% vs 59.6%), meanwhile, revealed that high-risk group has the higher tumor cell nucleic solidity (OR=3.048; 95%CI 1.513-6.138, P=0.002), but has lower nucleic solidity of the stroma cell (OR=0.253; 95%CI 0.097-0.665, P=0.005), lymphocyte (OR=0.081; 95%CI 0.017-0.392, P=0.002). Gal-9 is distinctively related to immune infiltration in LCNEC. The outcome of LNCEC can be predicted by integrated pathological analysis and Gal-9 based immune survival stratification.

EP14.05-006 The Impact of Adjuvant Chemotherapy on Survival of Stage I Lung Large Cell Neuroendocrine Carcinoma: A Meta-Analysis of Comparative Studies

Large Cell Neuroendocrine Carcinoma (LCNE) of the lung is a less common and aggressive cancer. The standard treatment of early stages is surgical resection. However, recurrences remain common with increased mortality. The role of adjuvant chemotherapy has been controversial in stage I, and the optimal adjuvant strategies remain undefined. One meta-analysis was conducted, revealing no benefit to chemotherapy in stage I. However, it was flawed using several studies analyzing the same NCDB data and one study that combined LCNE and small cell lung cancer.

Based on SEER Database: Population Distribution, Survival Analysis, and Prognostic Factors of Organ Metastasis of Lung Large Cell Neuroendocrine Carcinoma.

BackgroundThe incidence rate of lung large cell neuroendocrine carcinoma (LCNEC) in lung cancer is low, but the malignancy is high and the prognosis is poor. We used the Surveillance, Epidemiology, and End Results (SEER) database to determine the population distribution of organ metastasis in LCNEC, conduct survival analysis, judge prognostic factors, and provide direction for follow-up diagnosis and treatment.Materials and methodsBy logging into the SEER database, the data of lung LCNEC were retrieved and the target population was selected. According to the presence or absence of organ metastasis (bone, brain, liver, and lung), we divided the target population into the no organ metastasis group (n = 1,202) and the organ metastasis group (n = 870). By analyzing the clinicopathological data of patients and using the survival function, the corresponding median survival time was obtained, and the influencing factors of each group were analyzed. Then, the significant influencing factors were analyzed by multivariate Cox regression analysis to screen out the independent influencing factors.ResultIn the overall sample group, multivariate Cox regression analysis showed that sex, age, primary site surgery, bone metastasis, brain metastasis, liver metastasis, radiotherapy, and chemotherapy were independent prognostic factors. The 1-year survival rate was 13.8% in the bone metastasis group, 19.1% in the brain metastasis group, 13.8% in the liver metastasis group, and 20.3% in the intrapulmonary metastasis group. In the organ metastasis group, multivariate Cox regression analysis showed that sex, chemotherapy, radiotherapy sequence with surgery, primary site surgery, liver metastasis, and age at diagnosis were independent factors affecting the prognosis.ConclusionIn the overall sample of LCNEC, bone metastasis, brain metastasis, and liver metastasis all reduced the overall survival time, while the effect of intrapulmonary metastasis on the overall survival time was not statistically significant. Sex, chemotherapy, radiotherapy sequence with surgery, primary site surgery, liver metastasis, and age were independent factors affecting the prognosis of the LCNEC organ metastasis group. Women, chemotherapy, and radiotherapy sequence with surgery were favorable factors, while old age, liver metastasis, and male were unfavorable factors.

The genomic mutational landscape and its correlation with TMB, PD-L1 expression and CD8+ T cell infiltration in Chinese lung large cell neuroendocrine carcinoma

ObjectivesThe aim of this study was to illustrate the genomic mutational landscape, tumor mutation burden (TMB), PD-L1 expression, CD8+ T cell infiltration and their prognostic value in resectable Lung large cell neuroendocrine carcinoma (LCNEC). Materials and MethodsThe tumor tissues and corresponding normal tissues of 37 LCNEC patients undergoing surgical resection were collected and determined by whole exome sequencing (WES). Subsequently, the tumor samples were stained with the antibodies of PD-L1 and CD8 via multiplex immunohistochemistry (Multi IHC) to evaluate PD-L1 expression and CD8+ T cells infiltration in stroma and tumor regions. Univariate and multivariate analysis were applied to assess the association among genomic features, immune profiles, clinical data and prognosis of LCNEC patients. ResultsThe median TMB was 5.42 mutations per megabase. Mutations in Wnt (p = 0.049) and Hippo (p = 0.005) pathways were markedly associated with higher TMB value, mutations in p53 pathway were related with higher stromal PD-L1 expression (p = 0.041). LCNEC patients with KEAP1 mutation (p = 0.044) or without adjuvant radiochemotherapy (p = 0.023) had significantly shorter OS. Multivariate analysis showed that high stromal CD8 + T cells infiltration was an independent favorable factor for disease free survival (p = 0.030). The patient stratification of KEAP1 mutation status and stroma PD-L1 expression was independent prognostic factors for overall survival (p = 0.049). ConclusionThe investigation of prognostic factor in resectable LCNEC may provide guidance for timely intervention and new therapy strategy for LCENC patients.

Integrated pathological analysis to develop a Gal-9 based immune survival stratification to predict the outcome of lung large cell neuroendocrine carcinoma and its usefulness in immunotherapy.

This study aimed to integrate the cell spatial organization to develop a Gal-9-based immune survival stratification in the lung large cell neuroendocrine carcinoma (LCNEC) and investigate its potentials to immunotherapy.The expression of Gal-9 and other twelve immune markers were evaluated in 122 cases of surgical LCNEC samples from our center using immunohistochemistry. The Gal-9-based immune survival stratification risk score was constructed and its predictive performance was evaluated. Then, we thoroughly explored the effects of Gal-9 and immune risk score on LCNEC immune pathways, immune micro-environment and immunotherapy sensitivity in different cohort and platform, and made a validation in pathology images using Histology-based Digital-Staining (HDS).In 122 LCNEC samples, 43 cases were positive Gal-9 expression on tumor cells (Gal-9 TC). Increased Gal-9 TC predicted worse overall survival. Gal-9's interaction with other immune markers added to the immune suppression and immune tolerance in LCNEC. Immune protein marker-based risk score consisting of Gal-9, CD3, CD4, PD-L1, and PD-1 was developed and validated to robustly discriminate survival high-risk or low-risk in LCNEC patients. The high-risk group characterized by immune-desert tumor had less various T cells. The low-risk group featuring immune-inflamed tumor was more likely to respond to anti-PD1 immunotherapy. HDS in 122 LCNEC samples' 108,369 cells validated that the high-risk group had more tumor cells, less stromal cells, less lymphocytes, higher tumor cell nucleic solidity and lower stromal cells nucleic solidity.An integrated pathological analysis confirms the Gal-9 based immune survival stratification is distinctively related to micro-environment status involved in immune suppression and immune tolerance and could act as a combinatorial biomarker to predict the outcome of LCNEC. These findings may help effectively stratify LCNEC patients sensitive to immunotherapy.

1117P Mutational landscape of large cell neuroendocrine lung carcinoma: Molecular characterization using next generation sequencing

Large cell neuroendocrine lung carcinoma (LCNEC) is an aggressive subtype with an incidence around 3% of all lung cancer. The treatment approach for advanced patients remains controversial due to the lack of large randomized trials including this subtype. Owing to this fact, molecular characterization using next generation sequencing (NGS) technology has become a key tool for the molecular profiling of LCNEC.

Survival and prognosis of lung large cell neuroendocrine carcinoma

Only a few large-scale studies have focused on large cell neuroendocrine carcinoma, a rare type of pulmonary malignancy, and uniform diagnostic criteria and standardized treatments are lacking. This study aimed to assess the treatment outcomes and factors influencing patients' prognosis with large cell neuroendocrine carcinoma. The data of 55 patients with pathologically confirmed large cell neuroendocrine carcinoma, treated at our hospital from January 2013 to January 2018, were collected. Relationships between clinical characteristics, diagnoses, treatment outcomes, and prognoses were retrospectively analyzed. Patients were followed for a median of 18.5 (0.5-41.0) months. Thirty-four patients died before the final follow-up, resulting in a median overall survival of 17.9 (0.5-36.0) months, with 1-, 2-, and 3-year survival rates of 69.1%, 23.6%, and 1.8%, respectively. Single-factor analysis identified gender (P=0.036), smoking history (P=0.008), obstructive atelectasis (P=0.032), regional lymph node metastasis (P=0.020), and treatment selection (P=0.000) as factors influencing overall survival. Multifactor analysis identified treatment selection as an independent survival prognostic factor. Particularly, significant differences were observed between the combination therapies (surgery+chemotherapy, surgery+radiotherapy, surgery+radiotherapy+chemotherapy, and concurrent chemoradiotherapy) and single-therapy approaches (chemotherapy or radiotherapy alone; P<0.001), but not among the combination therapies (P=0.216). Male patients with large cell neuroendocrine carcinoma with a history of smoking, obstructive atelectasis, and regional lymph node metastasis have a particularly poor prognosis. Our observation of the treatment approach as an independent survival prognostic factor suggests that combination therapies may yield survival benefits to patients.

173 - An unusual case of ALK mutation in large-cell neuroendocrine carcinoma of lung and response to alectinib

173 - An unusual case of ALK mutation in large-cell neuroendocrine carcinoma of lung and response to alectinib