These are reviewed studies whose abstracts concern Pulmonary Large Cell Neuroendocrine Carcinoma (Lcnec). Each describes only what that study reported. This is not a claim by OncoForge that any compound helps or harms Pulmonary Large Cell Neuroendocrine Carcinoma (Lcnec). Most are early lab, animal, or small human studies, and findings often conflict.
5 studies3 human⚠ Conflicting evidenceMechanism (5)
Tracking 5 published studies of Pulmonary Large Cell Neuroendocrine Carcinoma (Lcnec): 3 in humans, 2 reviews/other.
Reported direction across studies: 1 positive, 2 mixed, 2 inconclusive.
Findings conflict — both supportive and negative/mixed results exist (see below). Human evidence is limited.
These counts summarize what the studies reported; they are not a measure of whether anything works for Pulmonary Large Cell Neuroendocrine Carcinoma (Lcnec).
Human · observationalMechanismMixed resultsLimited evidenceTier 3 · early humann = 590
Nature communications · Aug 2025 · cohort study (two independent clinical/genomic cohorts)
pulmonary large cell neuroendocrine carcinoma (LCNEC)small cell lung cancer (SCLC)non-small cell lung cancer (NSCLC)
The authors analyzed clinical and molecular data from 590 patients with pulmonary large cell neuroendocrine carcinoma across two cohorts. They identified two genomic subtypes (NSCLC-like with KEAP1/KRAS/STK11 mutations and SCLC-like with RB1/TP53 mutations) and report that 80% of tumors aligned with SCLC transcriptional profiles. The study found elevated FGL-1 and SPINK1 expression in NSCLC-like LCNECs and higher DLL3 in SCLC-like LCNECs, and noted fewer tumor-infiltrating lymphocytes in LCNEC compared with other lung cancers. Overall survival was comparable across chemotherapy, chemoimmunotherapy, and immunotherapy in this cohort.
Reported effect: proportion aligning with SCLC transcriptional profiles 80%, n=590
Key findings
- Study cohort: 590 patients across two independent cohorts.
- Comparable overall survival across treatment regimens (chemotherapy, chemoimmunotherapy, immunotherapy) without unexpected adverse events.
- Genomic analysis identified two LCNEC subtypes: NSCLC-like (KEAP1, KRAS, STK11 mutations) and SCLC-like (RB1, TP53 mutations).
- 80% of LCNEC tumors aligned with SCLC transcriptional profiles.
- Serial sampling showed stable mutational landscapes but shifting transcriptomic profiles over time.
- Elevated FGL-1 (a LAG-3 ligand) and SPINK1 expression were observed in NSCLC-like LCNECs; DLL3 levels were higher in SCLC-like LCNECs.
- Immunofluorescence confirmed FGL-1 expression in NSCLC-like LCNECs.
- H&E analyses indicated fewer tumor-infiltrating lymphocytes in LCNECs versus other lung cancers.
- Authors suggest these immunogenomic features support future investigation of LAG-3, SPINK1, and DLL3-targeted approaches.
Limitations: Observational cohort design — no randomized comparison of treatments reported in the abstract.; Abstract provides no quantitative survival or subgroup outcome measures (no effect sizes or statistical details reported).; Molecular associations (expression of FGL-1, SPINK1, DLL3) are descriptive and do not demonstrate therapeutic efficacy.; Functional or clinical validation of proposed targets is not presented in the abstract.; H&E-based assessment of tumor-infiltrating lymphocytes is a histologic surrogate and may lack detailed immunophenotyping..
Identifies immunogenomic subtypes and candidate targets (FGL-1/LAG-3, SPINK1, DLL3) in LCNEC that may guide future therapeutic investigations.
AI summary of the abstract, human-reviewed · Jun 2026. Describes what this study reported, not medical advice. View on PubMed · Full text
ReviewMechanismInconclusiveLimited evidenceTier 4 · clinical
Frontiers in medicine · Feb 2024
pulmonary large cell neuroendocrine carcinoma (LCNEC)small cell lung cancer (SCLC)
This narrative review summarizes current knowledge on diagnosis, molecular characteristics, and treatment strategies for pulmonary large cell neuroendocrine carcinoma (LCNEC). The authors state LCNEC is a high-grade neuroendocrine carcinoma (about 3% of primary lung cancer) with strong invasion, high heterogeneity, and very poor prognosis, and that diagnosis and treatment remain controversial and often refer to small cell lung cancer strategies. They note recent genetic analyses and emerging clinical trials provide increasing evidence to support more precise diagnosis and therapy and outline directions for future work.
Key findings
- LCNEC is a high-grade neuroendocrine carcinoma accounting for approximately 3% of primary lung cancer.
- LCNEC is characterized by strong invasion, high heterogeneity, and extremely poor prognosis.
- Diagnosis and treatment of LCNEC are controversial and currently often follow therapeutic strategies for SCLC rather than LCNEC-specific precision therapies.
- Recent genetic analyses and clinical trials of LCNEC have begun to emerge, offering more evidence to inform precise diagnosis and treatment.
- This review summarizes diagnosis, molecular characteristics, and treatment and suggests potential directions for future LCNEC diagnosis and treatment research.
Limitations: Narrative review article that presents synthesis rather than original experimental or clinical data.; Abstract provides no methodological details (e.g., search strategy, inclusion criteria) so it is unclear whether this is a systematic review.; No quantitative synthesis, primary outcome data, or novel trial results are reported in the abstract.; Conclusions are general and the abstract lacks specific molecular findings or treatment outcome metrics..
AI summary of the abstract, human-reviewed · Jun 2026. Describes what this study reported, not medical advice. View on PubMed · Full text
Human · observationalMechanismMixed resultsLimited evidenceTier 3 · early humann = 1875
Cancer medicine · Feb 2023 · Retrospective cohort analysis of SEER registry data (January 2010 to October 2018) using logistic and Cox regression; nomogram development and internal validation
pulmonary large cell neuroendocrine carcinoma (LCNEC)brain metastasislung neoplasmsbrain neoplasms
This retrospective study used SEER registry data (2010–2018) to identify factors associated with having brain metastasis at diagnosis and with cancer-specific survival (CSS) among pulmonary large cell neuroendocrine carcinoma (LCNEC) patients who had brain metastases. Younger age (<65) and N2 stage were associated with higher odds of brain metastasis at diagnosis. Among the 294 patients with brain metastases, older age, higher T and N stage, and liver metastasis were associated with worse CSS, while primary-site surgery and chemotherapy were associated with lower hazard of cancer-specific death. A nomogram to predict 6-, 12-, and 18-month CSS was constructed and internally evaluated by C-index, ROC, calibration curves, and decision curve analysis.
Reported effects: BM at diagnosis 15.7%, n=1875 · age <65 OR 1.564, n=1875 · +11 more
Key findings
- Total enrolled: 1875 patients; 294 (15.7%) had brain metastasis at diagnosis.
- Multivariate logistic regression: age <65 associated with greater chance of brain metastasis (odds ratio, OR = 1.564).
- Multivariate logistic regression: N2 staging associated with greater chance of brain metastasis (OR = 1.775).
- Cox regression (prognosis among LCNEC patients with BM): age ≥65 vs <65 associated with higher hazard for cancer-specific death (HR = 1.409).
- Cox regression: T staging associated with higher hazard for cancer-specific death (T1 vs T0: HR = 4.580; T2 vs T0: HR = 6.008; T3 vs T0: HR = 7.065; T4 vs T0: HR = 6.821).
- Cox regression: N staging associated with higher hazard for cancer-specific death (N2 vs N0: HR = 1.592; N3 vs N0: HR = 1.654).
- Cox regression: liver metastasis associated with higher hazard for cancer-specific death (HR = 1.410).
- Cox regression: primary site surgery associated with lower hazard for cancer-specific death (HR = 0.581).
- Cox regression: chemotherapy associated with lower hazard for cancer-specific death (HR = 0.452).
- A nomogram predicting 6-, 12-, and 18-month cancer-specific survival was constructed and evaluated; the model showed good performance by C-index, ROC curves, calibration curves, and decision curve analyses (no numeric values reported in abstract).
Limitations: Retrospective registry-based study subject to selection bias and unmeasured confounding.; Use of SEER data likely lacks detailed clinical variables (e.g., performance status, comorbidities, systemic therapy regimen/details, molecular markers) that could influence prognosis.; Potential for coding/misclassification errors inherent to administrative/registry data.; No evidence of external validation of the nomogram reported in the abstract..
AI summary of the abstract, human-reviewed · Jun 2026. Describes what this study reported, not medical advice. View on PubMed · Full text
ReviewMechanismInconclusiveLimited evidenceTier 4 · clinical
Pathology oncology research : POR · Oct 2022
pulmonary large cell neuroendocrine carcinoma (LCNEC)non-small-cell lung cancer (NSCLC)small cell lung cancer (SCLC)
This narrative review summarizes epidemiology, imaging, pathology, diagnosis, treatment, and prognosis of pulmonary large cell neuroendocrine carcinoma (LCNEC). It reports LCNEC is a rare (0.3%–3% of lung cancers), aggressive NSCLC subtype with clinical features often seen in elderly male smokers, peripheral upper-lobe tumors, frequent mediastinal/hilar lymph node enlargement, and diagnosis relying on histology and neuroendocrine immunohistochemical markers (CgA, Syn, CD56), with INSM1 and high Ki-67 helping diagnosis. The authors note that molecular typing has emerged recently and may assist diagnosis and subsequent treatment decisions.
Key findings
- LCNEC is a rare subtype of malignant pulmonary tumor with reported incidence of 0.3%-3% of lung cancers.
- Although classified as NSCLC, LCNEC is more aggressive than other NSCLC and biologically similar to SCLC.
- Most LCNEC patients are elderly smoking males and clinical manifestations are not specific.
- Tumors are often peripheral and in the upper lobes; mediastinal or hilar lymph node enlargement is common on imaging.
- Diagnosis is mainly based on pathology with histological features and immunohistochemistry; neuroendocrine markers chromogranin A (CgA), synaptophysin (Syn) and CD56 are usually diffusely positive.
- INSM1 expression and a high Ki-67 proliferation index are reported as helpful for diagnosis.
- Recent rise of LCNEC molecular typing may be helpful for diagnosis and guiding subsequent treatment.
Limitations: Narrative review without original patient-level data presented in this abstract; LCNEC is a rare disease, so the available evidence base is limited; Diagnostic heterogeneity and overlap with other tumor types may limit generalizability of conclusions.
AI summary of the abstract, human-reviewed · Jun 2026. Describes what this study reported, not medical advice. View on PubMed · Full text
Human · observationalMechanismReported positiveLimited evidenceTier 3 · early humann = 79
Translational oncology · May 2022
pulmonary large cell neuroendocrine carcinoma (LCNEC)
The authors performed immunohistochemistry on tissue microarrays from 79 resected LCNEC cases to measure ALDH1A1, E-cadherin and N-cadherin and to correlate expression with clinicopathologic features and survival. ALDH1A1 was positive in 75.9% of tumors and was positively correlated with E-cadherin but not with N-cadherin. Patients with ALDH1A1 expression had longer median disease-free survival (52 vs 12 months) and better overall survival, and multivariate analysis identified ALDH1A1 as an independent favorable prognostic factor.
Reported effects: ALDH1A1 positive expression 75.9%, n=79 · Spearman correlation with E-cadherin 0.229, p=0.007 · +4 more
Key findings
- ALDH1A1 was positively expressed in 75.9% (60/79 cases) of LCNEC patients.
- No significant difference in clinicopathological variables was observed between ALDH1A1-negative and ALDH1A1-positive groups.
- ALDH1A1 expression was positively correlated with E-cadherin (Spearman's rho = 0.229, p-value = 0.007) but not with N-cadherin.
- Patients with ALDH1A1 expression had significantly longer disease-free survival (median DFS: 52 vs 12 months, p = 0.028) and overall survival (median OS: not reached; p = 0.027) than ALDH1A1-negative patients.
- Multivariate analysis showed ALDH1A1 was an independent favorable prognostic factor for DFS (p = 0.032, HR: 0.438, 95% CI: 0.206-0.932) and OS (p = 0.025, HR: 0.279, 95% CI: 0.091-0.852).
Limitations: Observational IHC study on archived resected samples — correlation does not prove causation.; Moderate sample size (n=79) which may limit statistical power.; No external validation cohort reported.; No functional or mechanistic experiments to explain the observed associations (authors note mechanism needs further study)..
AI summary of the abstract, human-reviewed · Jun 2026. Describes what this study reported, not medical advice. View on PubMed · Full text