Prognostic scores in pulmonary large cell neuroendocrine carcinoma: A retrospective cohort study
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ABSTRACT:
SUBMITTER: Akdag G
PROVIDER: S-EPMC10839983 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
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Project description:BackgroundThe hemoglobin (Hgb)/red cell distribution width (RDW) ratio (HRR) is a simple prognostic marker for small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), but no data are available for pulmonary large cell neuroendocrine carcinoma (PLCNEC). This study aimed to assess the potential prognostic role of preoperative HRR in PLCNEC.MethodsThis single-center retrospective study included patients with PLCNEC who underwent surgery at Shanghai Pulmonary Hospital from January 2012 to August 2016. The follow-up was censored in August 2020. The participants were grouped as low/high HRR according to their optimal value calculated using a receiver operating characteristic (ROC) curve. Univariable and multivariable Cox analysis were performed to identify the risk factors for overall survival (OS).ResultsA total of 80 patients with PLCNEC were included. The optimal cutoff values were 0.969 for HRR. Compared with the high HRR group, the low HRR group had a lower mean Hgb (12.1 vs. 14.1 g/dL, P<0.001), lower mean albumin-globulin ratio (AGR) (1.4 vs. 1.6, P=0.017), and higher median RDW (14.5% vs. 12.9%, P<0.001). The median OS was 30.0 months [95% confidence interval (CI): 13.4 to 46.5 months]. Participants in the low HRR group exhibited a poorer OS than those with high HRR (20.3 months, 95% CI: 14.5 to 26.1 months vs. not reached, P<0.001). The multivariable analysis showed that low HRR was significantly associated with poor OS [hazard ratio (HR) =3.16, 95% CI: 1.69 to 5.93, P<0.001].ConclusionsLow HRR is associated with poor OS in patients with PLCNEC and can be used as an inexpensive prognostic factor in patients undergoing PLCNEC resection.
| S-EPMC8848384 | biostudies-literature
Project description:BackgroundLarge cell neuroendocrine carcinoma (LCNEC) is a high-grade malignant pulmonary neuroendocrine tumour. The distinction of pulmonary large cell carcinoma (LCC) and LCNEC is based on the presence of neuroendocrine morphology and the expression of at least one neuroendocrine marker in at least 10% of tumour cells in the latter. According to the current classification, LCC with neuroendocrine morphology and without neuroendocrine marker expression is classified as LCC. This subgroup we have named LCNEC-null and aimed to analyze its characteristics.Methods31 surgical samples resected in West China Hospital of Sichuan University between 2017 to 2021 were collected, including 7 traditional LCCs, 11 LCNEC-nulls and 13 LCNECs. Each case was conducted to immunohistochemistry and 425-panel-NGS.ResultsCompared to other LCCs, detailed analysis of LCNEC-nulls revealed biological features similar to those of LCNECs, especially for immunohistochemistry and molecular analysis: 1. diffusive, coarse granular and high expression of Pan-CK; 2. rare PD-L1 expression; 3. High rate of p53 expression and Rb deficiency 4. abundant genetic alterations are similar to LCNEC. All characteristics above deviated from traditional LCC, indicating they have the same origin as LCNEC. Furthermore, LCNEC could be genetically divided into two subtypes when we reclassified LCNEC-null as LCNEC, and the mutational type and prognosis differed significantly.ConclusionsWe consider that LCNEC-null should be reclassified as LCNEC based on analysis above. In addition, two genetic types of LCNEC with different prognosis also indicate two mechanism of tumour formation.
| S-EPMC8832809 | biostudies-literature
Project description:BackgroundThe study was conducted to compare the clinicopathological characteristics, survival outcomes, and metastatic patterns between pulmonary large cell neuroendocrine carcinoma (LCNEC) and other non-small cell lung cancer (ONSCLC), and to identify the prognostic factors of LCNEC.MethodsData of patients diagnosed with LCNEC and ONSCLC from 2004 to 2014 were obtained from the Surveillance, Epidemiology, and End Results dataset. Pearson's chi-square tests were used to compare differences in clinicopathological characteristics. The Kaplan-Meier method was used for survival analysis. A propensity score was used for matching and a Cox proportional hazards model was used for multivariate and subgroup analyses.ResultsA total of 2368 LCNEC cases and 231 672 ONSCLC cases were identified. LCNEC incidence increased slightly over time. Except for marital status, LCNEC patients had obviously different biological features to ONSCLC patients. Survival analysis showed that LCNEC had poorer outcomes than ONSCLC. Multivariate analysis revealed that female gender, black race, surgery, radiation, and chemotherapy were protective factors for LCNEC. Matched subgroup analysis further demonstrated that most subgroup factors favored ONSCLC, especially in early stage. Early-stage LCNEC patients had a higher risk of lung cancer-specific death than early-stage ONSCLC patients. Moreover, metastatic patterns were different between LCNEC and ONSCLC. LCNEC patients with isolated liver metastasis or combined invasion to other organs had poorer survival rates.ConclusionsLCNEC has totally different clinicopathological characteristics and metastatic patterns to ONSCLC. LCNEC also has poorer survival outcomes, primarily because of isolated liver metastasis or combined invasion to other organs. Most subgroup factors are adverse factors for LCNEC.
| S-EPMC6449250 | biostudies-literature
Project description:BackgroundYAP1 (Yes-associated protein 1), an important effector of the Hippo pathway, acts as an oncogene and is overexpressed in various malignant tumors. However, the function and expression pattern of YAP1 in pulmonary large cell neuroendocrine carcinoma (LCNEC) have not been systematically established. This study aimed to explore the relationship between YAP1 expression and neuroendocrine differentiation markers and their prognostic significance in LCNEC.Materials and methodsYAP1 protein and neuroendocrine markers (INSM1, NeuroD1 and DLL3) expression were examined by immunohistochemical (IHC) staining in 80 resected pulmonary LCNEC cases. The possible association between these markers and clinicopathological features was evaluated and survival analyses were performed.ResultsYAP1 was highly expressed in 25% LCNECs (20/80) , especially at a relatively higher T stage (p = 0.015). YAP1 expression was negatively correlated with INSM1 (χ2=11.53, p = 0.001) and DLL3(χ2=8.55, p = 0.004), but not with NeuroD1 (p = 0.482). For survival analyses, YAP1 expression was associated with worse disease-free survival (DFS) and overall survival (OS) (median DFS: 13 months vs. not reached (NR), p = 0.0096; median OS: not reached, NR vs. NR, p = 0.038), and was an unfavorable prognostic factor for DFS (HR:3.285; 95%CI: 1.526-7.071, p = 0.002) and OS (HR: 2.864, 95% CI: 0.932-8.796, p = 0.066).ConclusionsYAP1 was found to be conversely correlated with neuroendocrine markers and a prognostic factor for worse survival in resected LCNEC patients, and mechanisms need to be further investigated.
| S-EPMC9478447 | biostudies-literature
Project description:BackgroundImmune checkpoint inhibitors (ICI)-based combination strategies have improved the survival outcomes in advanced non-small cell lung cancers; however, data regarding their efficacy remains limited for uncommon histological types, including large-cell carcinoma (LCC) and large-cell neuroendocrine carcinoma (LCNEC).MethodsWe retrospectively analyzed a total of 60 patients with advanced LCC and LCNEC - 37 treatment-naïve and 23 pre-treated - who received pembrolizumab with or without chemotherapy. Treatment and survival outcomes were analyzed.ResultsOf the 37 treatment-naïve patients who received first-line pembrolizumab combined with chemotherapy, the 27 patients with LCC had an overall response rate (ORR) of 44.4% (12/27) and a disease control rate (DCR) of 88.9% (24/27); whereas 10 patients with LCNEC had an ORR of 70% (7/10) and DCR of 90% (9/10). The median progression-free survival (mPFS) was 7.0 months (95% confidence intervals [CI]: 2.2-11.8) and median overall survival (mOS) was 24.0 months (95%CI: 0.0-50.1) for first-line pembrolizumab plus chemotherapy of LCC (n = 27), whereas mPFS was 5.5 months (95%CI: 2.3-8.7) and mOS was 13.0 months (95%CI: 11.0-15.0) for first-line pembrolizumab plus chemotherapy of LCNEC (n = 10). Of the 23 pre-treated patients who received subsequent-line pembrolizumab with or without chemotherapy, mPFS was 2.0 months (95% CI: 0.6-3.4) and mOS was 4.5 months (95% CI: 0.0-9.0) for LCC and mPFS was 3.8 months (95% CI: 0.0-7.6) and mOS was not reached for LCNEC.ConclusionOur study provides real-world clinical evidence of the anti-tumor activity of pembrolizumab plus chemotherapy in advanced LCC and LCNEC, indicating that this regimen could serve as a treatment option, particularly as first-line therapy, for improving the survival outcomes of patients with these rare histological subtypes of lung cancer.Trial registrationNCT05023837(ESPORTA, 27/08/2021).
| S-EPMC10186661 | biostudies-literature
Project description:BACKGROUND:The aim of this study was to identify subgroups with good or bad prognosis in patients with pulmonary large cell neuroendocrine carcinoma (LCNEC) based on immunostaining patterns with neuroendocrine markers and compare them with small cell lung carcinoma (SCLC). METHODS:From January 2001 to December 2017, of all patients with resected LCNEC and SCLC, we selected patients whose pathological tumor sizes were ≤30 mm in diameter (defined as small-sized tumors) and who underwent complete resection with lymphadenectomy. We classified patients with small-sized LCNEC (sLCNEC) into two subgroups based on immunostaining patterns with three neuroendocrine markers (chromogranin A, synaptophysin, and NCAM) and compared them to small-sized SCLC (sSCLC). RESULTS:A total of 48 patients with sLCNEC and 39 patients with sSCLC were enrolled. Of 48 patients with sLCNEC, 21 were categorized as the small-sized triple-positive group (sTP), whose patients were positive for the three neuroendocrine markers, and 27 patients were categorized as the small-sized nontriple-positive group (sNTP), whose patients were not positive for all three neuroendocrine markers. The percentage of lymph node metastasis was significantly lower in sNTP than in sTP and sSCLC. There was no significant difference in overall survival, but recurrence-free survival (RFS) and tumor-specific survival (TSS) were significantly poorer in sTP and sSCLC than in sNTP. Multivariate analysis revealed sTP and sSCLC were independent prognostic factors for poorer RFS and TSS than those of sNTP. CONCLUSIONS:The sNTP subgroup had a good prognosis and the sTP subgroup a poor prognosis. There were some similarities in clinicopathological features between sTP and sSCLC.
| S-EPMC6825905 | biostudies-literature
Project description:BackgroundThe optimal systemic treatment for pulmonary large-cell neuroendocrine carcinoma (LCNEC) remains controversial, and recent advances in LCNEC molecular subtype classification have provided potential strategies for assisting in treatment decisions. Our study aimed to investigate the impact of treatment regimens, molecular subtypes and their concordance on clinical outcomes of patients diagnosed with LCNEC.Patients and methodsAll patients diagnosed with advanced pulmonary LCNEC in Peking Union Medical College Hospital (PUMCH) between January 2000 and October 2021 were enrolled in this retrospective study. The tumor samples were collected and sequenced using a tumor-specific gene panel, while clinical information was retrieved from the medical records system. The survival and therapeutic response were analyzed and compared between different subgroups classified by treatment regimen (SCLC or NSCLC-based), molecular subtype (type I or II) or the combination.ResultsIn univariate subgroup analysis categorized only by treatment regimen or molecular subtype, there were no differences identified in DCR, ORR, PFS, or OS. Nevertheless, the group with consistent treatment regimen and molecular subtype exhibited significantly longer OS than that of the inconsistent group (median OS 37.7 vs. 8.3 months; p = 0.046). Particularly, the OS of patients with type II LCNEC treated with SCLC-based regimen was significantly prolonged than that of others (median 37.7 vs. 10.5 months; p = 0.039).ConclusionsCollectively, our study revealed the clinical outcomes of different treatment regimens for LCNEC patients highly depend on their molecular subtypes, highlighting the need for sequencing-guided therapy.
| S-EPMC10807557 | biostudies-literature
Project description:BackgroundLung large cell neuroendocrine carcinoma (LCNEC) is an aggressive disease with poor prognosis and short-term survival, which lacks effective prognostic indicators. The study aims to investigate the molecular subtypes and prognostic markers of lung LCNEC.MethodsPatients diagnosed with lung LCNEC at Sun Yat-sen University Cancer Center (SYSUCC) between November 2007 and January 2021 were screened. Baseline clinical data were collected and routine blood indexes including lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and systemic immune-inflammation index (SII) were calculated. Immunohistochemistry (IHC) of ASCL1, NEUROD1, POU2F3, YAP1 were done to perform molecular subtyping, while CD56, Syn, CgA, CD3, CD8, CD20, CD68, and CD163 were also stained on tissue samples. Then prognostic factors of lung LCNEC were explored.ResultsOne hundred and fifty-one lung LCNEC patients were identified, 103 of whom had complete clinical information, available routine blood and biochemical indexes were eventually included in the present study. Tumor tissue specimens were available from 64 patients. Positive expression rates of ASCL1, NEUROD1, and YAP1 were 82.8%, 50.0%, and 28.1%, respectively. No POU2F3+ cases were detected. Forty (62.5%) patients co-expressed with two or three markers. High LMR (>3.3) was an independent predictor of favorable prognosis of disease-free survival (DFS) [hazard ratio (HR), 0.391; 95% confidence interval (CI): 0.161-0.948; P=0.04] and overall survival (OS) (HR, 0.201; 95% CI: 0.071-0.574; P=0.003). Notably, high LMR was correlated with higher intra-tumoral CD3+ (P=0.004), CD8+ (P=0.01), and CD68+ (P<0.001) immune cell infiltration compared to low LMR in lung LCNEC.ConclusionsOur study validated molecular subtypes by IHC in lung LCNEC, and co-expression was found among different subtypes, with no prognostic effect. High blood LMR level was associated with a favorable prognosis in lung LCNEC, which might partly reflect a hot tumor tissue immune microenvironment. Our findings may benefit clinical practice, and further studies are warranted.
| S-EPMC11484736 | biostudies-literature
Project description:ObjectivesPulmonary large-cell neuroendocrine carcinoma (LCNEC) and small-cell lung cancer (SCLC) are both classified as pure and combined subtypes. Due to the low incidence and difficult diagnosis of combined LCNEC (C-LCNEC) and combined SCLC (C-SCLC), few studies have compared their clinical features and prognosis.Materials and methodsWe compared the clinical features, mutation status of driver genes (EGFR, ALK, ROS1, KRAS, and BRAF), and prognosis between C-LCNEC and C-SCLC. Univariate and multivariate Cox regression analyses were applied for survival analysis.ResultsWe included a total of 116 patients with C-LCNEC and 76 patients with C-SCLC in the present study. There were significant differences in distribution of smoking history, tumor location, pT stage, pN stage, pTNM stage, visceral pleural invasion (VPI), and combined components between C-LCNEC and C-SCLC (P<0.05 for all). C-SCLC was more advanced at diagnosis as compared to C-LCNEC. The incidence of EGFR mutations in C-LCNEC patients was higher than C-SCLC patients (25.7 vs. 5%, P=0.004). We found that tumor size, pN stage, peripheral CEA level, and adjuvant chemotherapy were independently prognostic factors for DFS and OS in C-LCNEC patients, while peripheral NSE level, pT stage, pN stage, VPI and adjuvant chemotherapy were independently associated with DFS and OS for C-SCLC patients (P<0.05 for all). Propensity score matching with adjustment for the confounders confirmed a more favorable DFS (P=0.032) and OS (P=0.019) in patients with C-LCNEC in comparison with C-SCLC patients upon survival analysis.ConclusionsThe mutation landscape of driver genes seemed to act in different way between C-SCLC and C-LCNEC, likely by which result in clinical phenotype difference as well as better outcome in C-LCNEC.
| S-EPMC8493068 | biostudies-literature
Project description:Pulmonary large cell neuroendocrine carcinoma (LCNEC), which accounts for approximately 1% of all lung cancers, is a rare and highly aggressive malignancy with a poor prognosis. Therefore, it is important to devise an effective treatment strategy. In the treatment of locally advanced complex LCNEC, it is unique to first administer radiotherapy combined with albumin-bound paclitaxel plus carboplatin, followed by durvalumab for immune maintenance treatment after concurrent radiotherapy and chemotherapy to achieve complete remission. We report a 54-year-old man who smoked and who felt chest tightness for 2 weeks and was diagnosed as having combined pulmonary LCNEC. For patients with locally advanced pulmonary LCNEC, chemoradiotherapy increases overall survival. After surgical resection and chemoradiotherapy, our patient achieved complete remission. Durvalumab was then started to consolidate the treatment. After six courses of immune maintenance therapy, the patient developed grade 2 immune-related pneumonitis and took prednisone orally until the symptoms resolved, and then reached complete remission again. The patient achieved complete remission, which was a challenge with this rare carcinoma, through albumin-bound paclitaxel plus platinum-based chemotherapy combined with radiotherapy and durvalumab for immune maintenance therapy. This approach may provide a treatment option for locally advanced combined pulmonary LCNEC.
| S-EPMC8573517 | biostudies-literature