Research Radartracking 1,762 published studies · 471 human · 11 safety signals · 58 clinical trials · 44 cancer pages · updated Sep 2026Open the Research Map →

Large-Cell Neuroendocrine Carcinoma

A plain-English summary of the published research on Large-Cell Neuroendocrine Carcinoma, reviewed and approved by our editors — not a hand-curated clinical overview.

Research summary · reviewed
Educational only: This page is not medical advice. Coordinate decisions with your oncology team.

Reviewed Jun 2026 · OncoForge editorial · How we review →

AI extractedhuman reviewedsources checkedretractions suppressed· last updated Jun 2026

Evidence at a glanceHuman · observationalMixed results⚠ Studies disagree
15 published studies that name Large-Cell Neuroendocrine Carcinoma6 human studies approved & graded (trial, observational, or meta-analysis)29 human clinical studies in the Large-Cell Neuroendocrine Carcinoma corpus597 source documents in the Large-Cell Neuroendocrine Carcinoma corpus

last checked June 19, 2026

Why this grade?

Human · observational — Human observational evidence only — no trials.

Computed deterministically from the studies’ types and reported outcomes — not written by AI, and not a claim that anything works.

What the guidelines say

NCI PDQESMONCCNASCO

We link the authoritative guidelines rather than reproduce them. Below, the treatments on this page are split into standard care, guideline or regulatory options, supportive care, and studied but not standard so established care is not mixed with experimental or supportive items.

Studied, not standard - investigational
  • lobectomy
  • stereotactic body radiotherapy
  • etoposide + cisplatin
  • durvalumab
  • targeted therapy
  • immunotherapy
  • decitabine
  • guadecitabine
  • GSK3484862
  • RRx-001
  • tarlatamab
  • local ablative treatment
  • prophylactic cranial irradiation
  • surgery
  • platinum‑based adjuvant chemotherapy
  • radiotherapy
  • chemotherapy
  • pembrolizumab

Read the guidelines

Cancer-specific deep links aren’t curated yet — these search the authoritative sources for Large-Cell Neuroendocrine Carcinoma.

Treatment map: Large-Cell Neuroendocrine Carcinoma

Open as a full page →

Standard care plus every compound studied in the literature (each cited) and graded by evidence, organized by clinical readiness. A category, not a verdict that anything works — confirm anything here with your oncology team.

18
Interventions
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Standard of care
0
Tested in people
1
Lab / animal
17
Named in lit.
5
Classes
Standard of care (0) Guideline option (0) Tested in people (0) Lab / animal only (1) Named in the literature (17)
Clinical evidence
Preclinical evidence
Standard of care
Guideline option
Tested in people
Lab / animal only
Named in the literature
Surgery & procedures
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Radiotherapy
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Chemotherapy
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Targeted therapy
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Immunotherapy
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Columns group into clinical evidence (used in, or tested on, people) and preclinical evidence (lab/animal, or only named in the literature). Cell = number of interventions; a dashed cell means none recorded there.

Investigational & adjunct compounds — detail (18)
Named in the literature
lobectomystereotactic body radiotherapyetoposide + cisplatin· First-line (advanced disease)durvalumaboff-labeltargeted therapyimmunotherapydecitabineguadecitabineGSK3484862RRx-001tarlatamablocal ablative treatmentprophylactic cranial irradiationsurgeryplatinum‑based adjuvant chemotherapy· Adjuvant (after surgery)radiotherapychemotherapy
Lab / animal only
pembrolizumaboff-label

"Tested in people" rows show the highest trial phase found in that compound's cited human studies (Phase I–IV; "phase not reported" = a human study with no phase tag). "Studied" = named in the cited literature for this cancer. "FDA ✓" = FDA-approved for this cancer; "off-label" = an FDA-approved drug used outside its approved indications (per openFDA). Not a claim that anything works.

Reported figures

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Snapshot

The essentials in ~60 seconds — every line is drawn from the cited sources below.

What it is
An uncommon, highly aggressive neuroendocrine lung cancer that accounts for approximately 3% of primary lung malignancies and is often diagnosed at advanced stages (about 40%–70% of patients present at stage III–IV). [1][2]
Survival
Prognosis is poor with limited therapeutic options; high-grade pulmonary neuroendocrine carcinomas contribute disproportionately to lung-cancer mortality, and a SEER cohort reported 62.6% of patients presenting with stage IV disease. [3][1][2]
Standard treatment
For resectable disease, surgery (often lobectomy) is recommended with adjuvant platinum‑based chemotherapy for most resected tumors; stereotactic body radiation is an option for medically inoperable patients. For unresectable locally advanced disease, concurrent chemoradiation with etoposide–cisplatin followed by consolidation durvalumab is recommended, and for progressive or metastatic disease etoposide‑platinum chemotherapy is the first‑line approach with targeted therapy considered if actionable genomic alterations are present. [1][2]
Key test
Diagnosis of pulmonary LCNEC rests on neuroendocrine morphology and immunohistochemistry showing neuroendocrine differentiation together with a high mitotic rate (> 10 mitosis·2 mm−2) and non‑small cell cytological features. [2]
Biggest challenge
The main clinical problems are aggressive biology, a tendency to present at advanced stages (40%–70% at stage III–IV and 62.6% stage IV in a SEER cohort), and limited established therapeutic options. [2][1][3]

Ask about Large-Cell Neuroendocrine Carcinoma

Answers come only from the cited sources on this page — with the supporting evidence shown. If the sources here don't cover your question, it will say so. Educational information, not medical advice.

Key numbers & factors

Risk factors

  • ▲ increases riskOlder age (middle‑aged and elderly women for cervical neuroendocrine tumors) [4]
  • ▲ increases riskLow Pap smear sensitivity (for cervical neuroendocrine tumors) — Contributes to delayed diagnosis and more late‑stage presentations [4]
  • ◆ mixedSmoking exposure — Cotinine identified as an objective tissue biomarker of smoking exposure, with some discrepancies versus self‑report [5][3]

Biomarkers

  • DNMT1, DNMT3A, DNMT3B · Marked overexpression in LCNEC relative to normal lung (potential therapeutic interest) [5]
  • HPV18 DNA · Detected ubiquitously in both components of a mixed large‑cell neuroendocrine carcinoma and adenocarcinoma of the cervix [6]
  • Cotinine · Objective tissue biomarker of smoking exposure identified by metabolomics [3]
  • Neuroendocrine differentiation and high mitotic rate (> 10 mitosis·2 mm−2) · Diagnostic criteria for pulmonary LCNEC [2]

10 sections — tap any heading to expand its cited detail. Key points are above.

OverviewLarge-cell neuroendocrine carcinoma (LCNEC) is an uncommon, highly aggressive neuroendocrine tumor that occurs in multiple organs; pulmonary LCNEC is a distinct WHO-recognized lung neuroendocrine category and is rare and aggressive, cervical neuroendocrine malignancies are rare and aggressive with poor prognosis and diagnostic challenges, and LCNEC is increasingly reported in the urinary bladder but remains incompletely characterized.3 points
  • Sources describe LCNEC as an uncommon, highly aggressive lung cancer accounting for approximately 3% of primary lung malignancies and associated with a poor prognosis. [1][2]
  • Neuroendocrine malignancies of the cervix are rare (incidence <2%), occur in middle-aged and elderly women, and are aggressive with early metastasis and recurrence, poor prognosis, and low Pap smear sensitivity contributing to delayed diagnosis. [4]
  • Large-cell neuroendocrine carcinoma is increasingly recognized in the urinary bladder but is not yet fully characterized. [7]
EpidemiologyLarge-cell neuroendocrine carcinoma (LCNEC) is closely associated with smoking exposure and can be objectively measured by nicotine metabolites; pulmonary neuroendocrine tumors make up a small proportion of lung cancers and many LCNEC patients present with advanced-stage disease.3 points
  • Metabolomics profiling in LCNEC quantified the nicotine metabolite cotinine as an objective biomarker of smoking exposure and found discrepancies with self-reported smoking status in several patients. [5][3]
  • Pulmonary neuroendocrine tumors are reported to account for approximately 3% of lung cancers. [2]
  • The source reports that approximately 40%–70% of PLCNEC patients are diagnosed at stage III–IV. [2]
Key biomarkersReported biomarkers and diagnostic features in large-cell neuroendocrine carcinoma (LCNEC) include overexpression of DNA methyltransferases (DNMT1 and DNMT3A, with DNMT3B heterogeneous but increased versus normal lung), detection of HPV18 DNA in a mixed cervical LCNEC/adenocarcinoma, cotinine as a tissue biomarker of smoking exposure, and characteristic neuroendocrine morphology with a high mitotic rate (> 10 mitosis·2 mm−2).4 points
  • HPV18 DNA was detected ubiquitously in both the adenocarcinomatous and neuroendocrine components of a mixed large cell neuroendocrine carcinoma and adenocarcinoma of the cervix. [6]
  • The metabolomics atlas identified cotinine as a quantified objective biomarker of smoking exposure in LCNEC tissues. [3]
  • Pulmonary LCNEC (PLCNEC) is characterized by neuroendocrine morphology, immunohistochemistry showing neuroendocrine differentiation, a high mitotic rate (> 10 mitosis·2 mm−2), and non‑small cell cytological features. [2]
Show 1 lab & early-research finding
  • DNMT1 and DNMT3A were predominantly overexpressed in LCNEC, while DNMT3B showed heterogeneous expression; RNA-seq data showed markedly higher distributions of DNMT1, DNMT3A, and DNMT3B relative to normal lung (Cohen's d 13–18; Mann–Whitney p < 10−9). [5]
Biology & pathwaysMetabolomic profiling of LCNEC tumor tissues shows extensive remodeling of amino acid, nucleotide, and lipid metabolism with pronounced accumulation of D- and L-2-hydroxyglutaric acid, and LCNEC displays a hybrid metabolic phenotype bridging features of small-cell and non-small-cell lung cancer. YAP1 expression has been reported to define a subtype in pulmonary LCNEC.2 points
  • Metabolomic profiling of LCNEC tumor tissues revealed extensive remodeling of amino acid, nucleotide, and lipid metabolism, including pronounced accumulation of D- and L-2-hydroxyglutaric acid, and LCNEC shows a hybrid metabolic phenotype bridging features of small-cell and non-small cell lung cancer while revealing unique metabolic signatures. [3]
  • YAP1 expression has been reported to define a subtype in pulmonary LCNEC and other treatment-naïve neuroendocrine neoplasms. [8]
Standard managementManagement of LCNEC emphasizes surgical resection for resectable (stage I–III) disease and chemotherapy-based approaches for advanced or progressive disease; the roles of radiotherapy (including adjuvant radiotherapy), neoadjuvant therapy, prophylactic cranial irradiation, and adjuvant immunotherapy remain uncertain or under investigation.7 points
  • For medically fit patients with resectable LCNEC, surgical resection—particularly lobectomy—should be offered. Adjuvant platinum-based chemotherapy (e.g., etoposide–cisplatin) is suggested for most resected tumors, with individualized decision-making for stage IA. [1][2]
  • Sources state that the role of adjuvant radiotherapy, neoadjuvant therapy, and prophylactic cranial irradiation in LCNEC remains undefined; the role of radiotherapy in advanced PLCNEC remains unclear and may be context-dependent, particularly in stage IV. [1][2]
  • For progressive, advanced, or metastatic LCNEC, chemotherapy-based multimodality therapy is the preferred approach; etoposide‑platinum chemotherapy remains the first-line treatment, and targeted therapy can be considered if tumors harbor actionable genomic alterations. [1][2]
  • Stereotactic body radiation therapy can be reserved for medically inoperable LCNEC patients. [1]
  • There is currently no evidence supporting the use of adjuvant immunotherapy in LCNEC. [1]
  • For unresectable, locally advanced LCNEC, concurrent chemoradiation with etoposide‑cisplatin followed by consolidation durvalumab is recommended. [1]
  • The potential benefit of immunotherapy in LCNEC is currently under investigation. [1]
Treatments & compounds studied17 therapeutics spanning procedure_device, radiotherapy, chemotherapy, immunotherapy, and targeted_therapy are reported for large-cell neuroendocrine carcinoma (LCNEC) across resectable, locally advanced, metastatic, oligometastatic, and other settings.17 treatments

Chemotherapy

  • etoposide-cisplatin: First-line (advanced disease)SCLC regimens such as etoposide-cisplatin are associated with better outcomes and etoposide-platinum chemotherapy remains the first-line treatment in metastatic disease. [1]
  • platinum‑based adjuvant chemotherapy: Adjuvant (after surgery)Platinum‑based adjuvant chemotherapy is reported as part of surgery‑based mainstay treatment for patients with stage I–III early‑stage PLCNEC. [2]
  • chemotherapy: Multimodality therapy with chemotherapy is reported as the preferred approach for progressive and advanced stages of PLCNEC. [2]

Targeted therapy

  • targeted therapy: Targeted therapy can be considered in metastatic LCNEC if tumors harbor actionable genomic alterations. [1]
  • 5-Azacytidine (5-AZA) / decitabine (DAC) · decitabine: Hypomethylating agents such as 5-AZA and decitabine have been proposed to reverse aberrant methylation patterns in lung cancer and could potentially sensitize tumors to standard therapies. [5]
  • guadecitabine (SGI-110): More stable nucleoside analogs such as SGI-110 (Guadecitabine) and non-nucleoside compounds are being explored to overcome limitations of existing DNMT inhibitors. [5]
  • GSK3484862: A highly potent and selective small-molecule DNMT1 inhibitor, GSK3484862, has been developed. [5]
  • RRx-001: The novel epigenetic agent RRx-001, which targets HDACs, DNMT1, and DNMT3A, is being evaluated in combination with platinum-based chemotherapy. [5]

Immunotherapy

  • durvalumab: Consolidation immunotherapy with durvalumab after concurrent chemoradiation is recommended for unresectable, locally advanced disease. [1]
  • immunotherapy: The potential benefit of immunotherapy in LCNEC is currently under investigation. [1]
  • tarlatamab / DLL3-targeting therapies: DLL3-targeting therapies (e.g., tarlatamab) are highlighted as a promising emerging strategy in LCNEC. [1]

Radiotherapy

  • stereotactic body radiation therapy · stereotactic body radiotherapy: Stereotactic body radiation therapy can be reserved for medically inoperable patients. [1]
  • prophylactic cranial irradiation: The role of prophylactic cranial irradiation in LCNEC remains undefined. [1]
  • radiotherapy: A SEER study evaluated radiotherapy in stage III–IV PLCNEC patients treated with chemotherapy and reported superior survival outcomes in the combined radiotherapy group compared to the chemotherapy-only group. [2]

Procedures & devices

  • lobectomy: Surgical resection, particularly lobectomy, should be offered for medically fit patients with resectable disease. [1]
  • local ablative treatment: Local ablative treatment has shown promise in oligometastatic LCNEC. [1]
  • surgery: Surgery is described as part of the recommended mainstay of treatment for patients with stage I–III early‐stage PLCNEC. [2]
PrognosisLarge-cell neuroendocrine carcinoma (LCNEC) is described as an aggressive malignancy with limited therapeutic options and poor prognosis. High-grade pulmonary neuroendocrine carcinomas often present at advanced stages — in one SEER cohort clinical stage IV comprised 62.6% (n = 680) of 1086 patients — and contribute disproportionately to lung-cancer–related mortality; neuroendocrine malignancies of the cervix are associated with early metastasis and recurrence and more late-stage presentations due to diagnostic delays.3 points
  • Sources describe LCNEC as a rare and aggressive lung cancer with limited therapeutic options. [3][1]
  • Neuroendocrine malignancies of the cervix are associated with early metastasis and recurrence and contribute to a higher number of late-stage presentations due to diagnostic delays. [4]
  • High-grade pulmonary neuroendocrine carcinomas are reported to contribute disproportionately to lung-cancer–related mortality because of aggressive biological behavior and a tendency to present at advanced stages; in a SEER cohort of 1086 patients, clinical stage IV comprised 62.6% (n = 680) of patients. [2]
Safety & interactions1 point
  • DNMT inhibitors face limitations including chemical instability, low bioavailability, and off-target effects that constrain their application in solid tumors. [5]
What we don't know yetMany aspects of large-cell neuroendocrine carcinoma (LCNEC/PLCNEC) management remain uncertain: optimal overall treatment strategies are not clearly established, the role and specifics of immunotherapy and the prognostic impact of radiotherapy in certain stages are under active investigation, and molecular profiling and novel agents such as DNMT inhibitors are being explored.5 points
  • The evolving role of molecular profiling in prognostication and treatment decision-making for LCNEC is under active examination. [1]
  • DNMT inhibitors represent a potential therapeutic option in LCNEC and warrant further exploration. [5]
  • The potential benefit of immunotherapy in LCNEC is being actively investigated and is not yet established, and the optimal dose-fractionation and the duration of consolidation immunotherapy after chemoradiation for unresectable, locally advanced LCNEC remain to be investigated. [1]
  • The source states that optimal treatment strategies for PLCNEC have not yet been clearly established. [2]
  • The SEER study authors note that there is limited evidence evaluating the prognostic impact of radiotherapy specifically in stage III–IV PLCNEC patients receiving chemotherapy and that no predictive nomogram existed for this population. [2]
Staging & risk1 point
  • The SEER study used the sixth edition of the AJCC clinical stage to determine disease stage. [2]

Common questions

What is Large-Cell Neuroendocrine Carcinoma?

Large-cell neuroendocrine carcinoma (LCNEC) is an uncommon, highly aggressive neuroendocrine tumor that occurs in multiple organs; pulmonary LCNEC is a distinct WHO-recognized lung neuroendocrine category and is rare and aggressive, cervical neuroendocrine malignancies are rare and aggressive with poor prognosis and diagnostic challenges, and LCNEC is increasingly reported in the urinary bladder but remains incompletely characterized.

How common is Large-Cell Neuroendocrine Carcinoma?

Large-cell neuroendocrine carcinoma (LCNEC) is closely associated with smoking exposure and can be objectively measured by nicotine metabolites; pulmonary neuroendocrine tumors make up a small proportion of lung cancers and many LCNEC patients present with advanced-stage disease.

Which biomarkers are important in Large-Cell Neuroendocrine Carcinoma?

Reported biomarkers and diagnostic features in large-cell neuroendocrine carcinoma (LCNEC) include overexpression of DNA methyltransferases (DNMT1 and DNMT3A, with DNMT3B heterogeneous but increased versus normal lung), detection of HPV18 DNA in a mixed cervical LCNEC/adenocarcinoma, cotinine as a tissue biomarker of smoking exposure, and characteristic neuroendocrine morphology with a high mitotic rate (> 10 mitosis·2 mm−2).

What is the biology of Large-Cell Neuroendocrine Carcinoma?

Metabolomic profiling of LCNEC tumor tissues shows extensive remodeling of amino acid, nucleotide, and lipid metabolism with pronounced accumulation of D- and L-2-hydroxyglutaric acid, and LCNEC displays a hybrid metabolic phenotype bridging features of small-cell and non-small-cell lung cancer. YAP1 expression has been reported to define a subtype in pulmonary LCNEC.

How is Large-Cell Neuroendocrine Carcinoma treated?

Management of LCNEC emphasizes surgical resection for resectable (stage I–III) disease and chemotherapy-based approaches for advanced or progressive disease; the roles of radiotherapy (including adjuvant radiotherapy), neoadjuvant therapy, prophylactic cranial irradiation, and adjuvant immunotherapy remain uncertain or under investigation.

What treatments are studied for Large-Cell Neuroendocrine Carcinoma?

17 therapeutics spanning procedure_device, radiotherapy, chemotherapy, immunotherapy, and targeted_therapy are reported for large-cell neuroendocrine carcinoma (LCNEC) across resectable, locally advanced, metastatic, oligometastatic, and other settings.

Sources

Every statement above is drawn from these reviewed sources. This page reports what they describe. Sources last checked June 19, 2026.

  1. Review articleManagement of Pulmonary Large-Cell Neuroendocrine Carcinoma (LCNEC): An Updated Review · 2026
  2. Review articlePatients With Stage III PLCNEC Advocated for Radiotherapy Combined With Chemotherapy While With Stage IV Focus on Individualized Management: Evidence From SEER · 2026
  3. Review articleA metabolomics and lipidomics atlas of pulmonary large cell neuroendocrine carcinoma · 2026
  4. Review articleNeuroendocrine Malignancies of the Cervix: What Radiologists Need to Know · 2026
  5. Review articleAltered DNA Methyltransferase Expression in Pulmonary Large-Cell Neuroendocrine Carcinoma: Pilot Experimental Data Targeted DNMT1, DNMT3A, and DNMT3B · 2026
  6. Case reportMixed Large Cell Neuroendocrine Carcinoma and Adenocarcinoma of the Cervix: A Rare Entity · 2026
  7. Review articleNeuroendocrine tumours of the urinary bladder: recent advances · 2026
  8. Review articleYAP1 Defines an Emergent, Plastic Population of Relapsed SCLC · 2026

What supports this page

The kinds of sources behind this page, strongest at the top. Faint rungs show what is not here yet.

Guideline
2
Meta-analysis
6
Systematic review
7
Randomized trial
4
Clinical trial
18
Observational
0
Case report
232
Review
324
Preclinical
0
Other
4

Living document — last change June 19, 2026: Cancer page updated. 2 recent updates logged.

Pooled evidence across studies

PubMed
  • OS: 11 months (11–26 across studies) · surgery + chemotherapy + radiotherapy
    3 studies · 67% agree · moderate · 1 flagged36457506
  • Cancer-specific survival: 12 months (11–41 across studies) · surgery + chemotherapy + radiotherapy
    3 studies · 67% agree · moderate · 1 flagged36457506
  • 5-year OS: 23.21% (17.84–35.98 across studies) · surgery + chemotherapy + radiotherapy
    3 studies · 33% agree · heterogeneous36457506
  • 5-year Cancer-specific survival: 31.39% (19.23–45.23 across studies) · surgery + chemotherapy + radiotherapy
    3 studies · 33% agree · heterogeneous36457506

Numbers pooled deterministically across 9 published studies that passed our figure-accuracy checks — a quick synthesis, not a formal meta-analysis. Updated 9/3/2026.

Medicines & supplements studied for Large-Cell Neuroendocrine Carcinoma

PubMedFDAClinicalTrials.gov

Every drug, supplement, and other agent the published studies cover for Large-Cell Neuroendocrine Carcinoma, ranked by how strong the evidence is — what studies report, not a recommendation. Tap any to see its full profile.

Medicines · 1

PembrolizumabInsufficient evidenceReported positive

No primary experimental studies yet.

Largest credible effect: shrinkage_after_one_cycle 1, n=1 PMID 34817132 · effect sizes 1–6 across 5 studies

Most authoritative study: Complete and durable response of pulmonary large-cell neuroendocrine carcinoma to pembrolizumab

No human studies yet · Based on a single study.
ImmunotherapyFDA off-label1 studyFull profile →

What recent studies report in Large-Cell Neuroendocrine Carcinoma

These are reviewed studies whose abstracts concern Large-Cell Neuroendocrine Carcinoma. Each describes only what that study reported. This is not a claim by OncoForge that any compound helps or harms Large-Cell Neuroendocrine Carcinoma. Most are early lab, animal, or small human studies, and findings often conflict.

15 studies6 human⚠ Conflicting evidenceMechanism (6)

Tracking 15 published studies of Large-Cell Neuroendocrine Carcinoma: 6 in humans, 9 reviews/other.

Reported direction across studies: 6 positive, 3 mixed, 3 negative, 3 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 Large-Cell Neuroendocrine Carcinoma.

Compounds with studies mentioning Large-Cell Neuroendocrine Carcinoma

Pembrolizumab (1)
Human · observationalMechanismReported positiveLimited evidenceTier 3 · early humann = 107

Proteogenomic characterization of pulmonary large-cell neuroendocrine carcinoma identifies molecular features and therapeutic strategy

Science advances · Aug 2026 · Proteogenomic analysis of tumors and paired normal adjacent tissues from 107 patients; preclinical optimization and testing of recombinant IL-33 in mouse models and pharmacokinetics in cynomolgus monkeys

pulmonary large-cell neuroendocrine carcinomanon-small cell lung carcinoma

Researchers performed proteogenomic analysis on tumors and matched normal tissues from 107 patients with pulmonary large-cell neuroendocrine carcinoma and identified molecular features, mutational signatures, and three LCNEC subtypes. Interleukin-33 (IL-33) was identified as a biomarker associated with increased T cell infiltration and antitumor activity; the authors optimized recombinant IL-33 and developed a PEGylated form that showed prolonged circulation in cynomolgus monkeys and stronger immune agonist activity in mouse models.

Key findings
  • Proteogenomic analysis was performed on tumors and paired normal adjacent tissues from 107 LCNEC patients (81 pure LCNEC and 26 combined LCNEC).
  • APOBEC mutational signatures strongly correlate with processes of tumor initiation and immune suppression in LCNEC.
  • KEAP1 mutations correlate with metabolic reprogramming in LCNEC combined with NSCLC.
  • A conflicting relationship was observed between neuroendocrine and immune phenotypes.
  • Three LCNEC subtypes were identified, each with distinct prognosis features, microenvironment dysregulation, genetic alterations, and potential therapeutic targets.
  • Interleukin-33 (IL-33) emerged as a critical therapeutic biomarker associated with enhanced T cell infiltration and antitumor activity.
  • Recombinant IL-33 was optimized via site-directed mutagenesis and PEGylation.
  • PEGylated recombinant IL-33 demonstrated prolonged circulation time in cynomolgus monkeys and superior immune agonist activity in mouse models.
Limitations: Therapeutic optimization and activity of recombinant/PEGylated IL-33 were tested only in animal models (mice) and assessed for circulation in cynomolgus monkeys; no clinical (human interventional) data are reported.; Proteogenomic analyses are observational and associative; causality of identified correlations (e.g., APOBEC signatures, KEAP1 mutations) is not established in patients.; The human cohort, while sizable for a rare tumor, is limited to 107 patients and subgroup sizes (81 vs 26) may limit power for some subtype analyses.; The abstract does not report dosing, safety, or efficacy endpoints in humans, nor detailed statistical measures for the reported associations.; Translatability of mouse and nonhuman primate findings to human clinical benefit is not demonstrated in this study..

AI summary of the abstract, human-reviewed · Sep 2026. Describes what this study reported, not medical advice. View on PubMed · Full text

Human · observationalMechanismReported positiveLimited evidenceTier 3 · early humann = 216

Identification of Actionable Gene Variants in Pulmonary Large-Cell Neuroendocrine Carcinoma: A Real-World Analysis of a Polish Cohort

International journal of molecular sciences · Mar 2026 · retrospective cohort

pulmonary large-cell neuroendocrine carcinomaLCNEC

Researchers performed targeted next-generation sequencing on 216 pulmonary LCNEC tumor samples from a retrospective Polish cohort to look for actionable gene variants. They found 46 variants in 46/216 samples (21.3%), with 28/216 (13%) harboring at least one potentially actionable alteration; most common were KRAS and PIK3CA (each 5%), and a novel TMEM79::NTRK1 fusion was found in one case (0.5%). Several typical NSCLC alterations (classical EGFR exon 18–21, ALK, FGFR1/2/3, ROS1) were not detected.

Reported effects: variant_count 46, n=216 · variant_positive_rate 21.3%, n=216 · +8 more

Key findings
  • Overall, 46 variants were identified in 46/216 (21.3%) tumor samples.
  • 28/216 (13%) LCNECs harbored at least one actionable molecular variant potentially targetable by registered or investigational agents.
  • KRAS variants were present in 5% of tumors (including G12C at 2%).
  • PIK3CA variants were present in 5% of tumors.
  • RET single-nucleotide variants were observed in 3% of tumors.
  • Uncommon EGFR variants were observed in 1% of tumors; BRAF class II and III variants were observed at <1%.
  • A novel in-frame gene fusion (TMEM79::NTRK1) was identified in a single tumor sample (0.5%).
  • No classical EGFR exon 18-21 mutations nor ALK, FGFR1/2/3, or ROS1 alterations (mutations or fusions) were detected.
Limitations: Retrospective study design.; Targeted NGS panel limited to 17 genes, so alterations outside the panel would not be detected.; Single-country (Polish) cohort which may limit generalizability.; No clinical outcome or treatment-response data reported in the abstract to link variants to patient benefit..

AI summary of the abstract, human-reviewed · Jun 2026. Describes what this study reported, not medical advice. View on PubMed · Full text

Case reportMechanismReported positiveLimited evidenceTier 3 · early humann = 1

Breast cancer and large-cell neuroendocrine carcinoma harboring the same PIK3CA mutation: A case report

Tumori · Dec 2025 · case report

breast cancerlarge-cell neuroendocrine carcinoma

This is a case report of a 34-year-old woman initially treated for HR+/HER2- breast cancer in 2012 who developed a mediastinal large-cell neuroendocrine carcinoma (LCNEC) in 2021. Next-generation sequencing identified the same pathogenic PIK3CA variant in both the breast tumor and the LCNEC, suggesting a possible metastatic relationship. The LCNEC progressed on cisplatin/etoposide but had a remarkable and prolonged response to pembrolizumab until treatment was stopped for grade 3 immune-related colitis; the patient had no clinical evidence of disease as of November 2024.

Reported effects: PD-L1 expression 10%, n=1 · tumor mutational burden (TMB) 9.54, n=1 · +1 more

Key findings
  • Next-generation sequencing identified shared tumor PIK3CA pathogenic variants in both breast cancer and LCNEC tissues, suggesting a potential relationship as primary tumor and metastasis.
  • The mediastinal tumor was a high-grade LCNEC lacking breast-specific markers (GATA3-, HR-, HER2-, mammoglobin-, GCDFP15-).
  • PD-L1 expression was 10% and tumor mutational burden (TMB) was 9.54 mut/MB in the LCNEC specimen.
  • First-line chemotherapy (cisplatin plus etoposide) led to rapid disease progression; second-line pembrolizumab produced a remarkable and prolonged disease response.
  • Treatment was discontinued in 2023 because of grade 3 immune-related colitis; patient had no clinical evidence of disease as of November 2024.
Limitations: Single-patient case report limits generalizability.; Shared PIK3CA mutation suggests but does not definitively prove clonal origin between the two tumors.; No control group or broader cohort for comparison; findings are observational and hypothesis-generating..

AI summary of the abstract, human-reviewed · Aug 2026. Describes what this study reported, not medical advice. View on PubMed

Case reportReported negativeLimited evidenceTier 3 · early humann = 1

Primary large-cell neuroendocrine carcinoma of the trachea

BMJ case reports · Jun 2025 · case report

large-cell neuroendocrine carcinoma of the trachea

This case report describes a man in his 70s who presented with dyspnoea and was found to have a primary large-cell neuroendocrine carcinoma of the trachea. Bronchoscopic debulking immediately relieved his dyspnoea; PET suggested the trachea as the primary site. After an incidental COVID-19 infection delayed a second bronchoscopy for 1 month, regrowth of the tracheal lesion with multiple disseminated airway lesions was found; the patient is receiving chemotherapy. The authors note primary tracheal LCNEC is very rare and may be aggressive, and recommend systemic evaluation for metastases.

Reported effect: delay to second bronchoscopy 1, n=1

Key findings
  • Patient: man in his 70s presenting with dyspnoea
  • Imaging revealed an intratracheal tumour; a small lesion was also detected in the left main bronchus
  • Bronchoscopic debulking of the intratracheal tumour resulted in immediate relief of dyspnoea
  • Pathological diagnosis was large-cell neuroendocrine carcinoma (LCNEC)
  • Positron emission tomography suggested the trachea was the primary site
  • Incidental COVID-19 infection delayed the second bronchoscopy for 1 month
  • Second bronchoscopy revealed regrowth of the residual tracheal lesion with multiple disseminated lesions in the airways
  • The patient is currently undergoing chemotherapy
  • Authors conclude primary tracheal LCNEC is very rare and may be aggressive; systemic evaluation for metastases should be considered
Limitations: Single-patient case report; results are not generalizable; No long-term follow-up or outcome data reported beyond initiation of chemotherapy; No controlled comparison or systematic data on frequency, prognosis, or optimal management; Timeline potentially confounded by incidental COVID-19 infection delaying care.

AI summary of the abstract, human-reviewed · Sep 2026. Describes what this study reported, not medical advice. View on PubMed

Human · observationalMixed resultsLimited evidenceTier 3 · early humann = 196

Clinical and Pathologic Differences between Small-Cell Carcinoma and Large-Cell Neuroendocrine Carcinoma of the Lung

Annals of surgical oncology · Sep 2024 · retrospective cohort study

small-cell lung carcinomalarge-cell neuroendocrine carcinomalung cancer

This retrospective study analyzed 196 patients who had surgical resection for small-cell lung carcinoma (SCLC) or large-cell neuroendocrine carcinoma (LCNEC). Five-year overall survival was 53.7% for SCLC and 62.7% for LCNEC (p = 0.133). In SCLC, postoperative adjuvant chemotherapy was associated with improved overall survival (multivariate HR 0.54, 95% CI 0.30-0.99, p = 0.04). In LCNEC, only pathologic stage I (p = 0.01) was associated with better postoperative overall survival.

Reported effects: 5-year overall survival 53.7%, p=0.133 · adjuvant chemotherapy (SCLC) hazard ratio for overall survival 0.54 [0.3–0.99], p=0.04 · +3 more

Studied with: adjuvant chemotherapy.

Key findings
  • Of 196 resected cases, 99 (50.5%) were SCLC and 97 (49.5%) were LCNEC.
  • Median follow-up was 39 months (IQR 21-76) for SCLC and 56 months (IQR 21-87) for LCNEC.
  • Estimated 5-year overall survival probabilities were 53.7% (SCLC) and 62.7% (LCNEC) (p = 0.133).
  • In the SCLC group, adjuvant chemotherapy was the only factor significantly associated with overall survival in multivariate analysis (hazard ratio 0.54, 95% CI 0.30-0.99, p = 0.04).
  • In the LCNEC group, univariate analysis showed that pathologic stage I (p = 0.01) was the only factor associated with better overall survival after surgery.
Limitations: Retrospective observational design with potential for confounding and selection bias; No randomized assignment to adjuvant chemotherapy reported; Abstract does not report details of chemotherapy regimens, doses, or timing; Prognostic associations (especially in LCNEC) are based on univariate analysis and may not account for confounders.

AI summary of the abstract, human-reviewed · Sep 2026. Describes what this study reported, not medical advice. View on PubMed

Case reportReported positiveLimited evidenceTier 3 · early humann = 1

Combined large‑cell neuroendocrine carcinoma and small‑cell lung cancer: A case report

Oncology letters · Aug 2024 · Case report

large-cell neuroendocrine carcinoma (LCNEC)small-cell lung cancer (SCLC)

This case report describes a 53-year-old woman diagnosed with a combined large-cell neuroendocrine carcinoma and small-cell lung cancer in the left upper lung. Diagnosis was based on CT imaging and biopsy showing a poorly differentiated neuroendocrine carcinoma consistent with mixed large- and small-cell histology. The patient received chemotherapy, radiotherapy and targeted therapy and had a survival period of 29 months as of October 2023. The authors state the tumor is rare, note diagnostic difficulty, and recommend multidisciplinary treatment and close follow-up.

Reported effect: survival_period 29 mo, n=1

Studied with: chemotherapy, radiotherapy, targeted therapy.

Key findings
  • Combined LCNEC and SCLC is extremely rare.
  • Accurate diagnosis is difficult due to overlapping clinical features between LCNEC and SCLC.
  • Computed tomography revealed a 52×32×26-mm irregular soft-tissue mass in the left upper lung.
  • Pathological examination of the biopsy specimen showed a poorly differentiated neuroendocrine carcinoma consistent with a mixed type of large and small cell carcinoma.
  • The patient was administered chemotherapy, radiotherapy and targeted therapy.
  • As of October 2023, the patient had a survival period of 29 months.
  • The authors recommend multidisciplinary treatment and close follow-up for this sporadic tumor.
Limitations: Single-patient case report (n=1), limiting generalizability.; No standardized or comparative treatment regimen reported.; No detailed information on chemotherapy, radiotherapy or targeted therapy regimens, doses or timing in the abstract.; No control group or systematic follow-up data beyond the single patient..

AI summary of the abstract, human-reviewed · Sep 2026. Describes what this study reported, not medical advice. View on PubMed · Full text

Human · observationalMechanismInconclusiveLimited evidenceTier 3 · early humann = 114

Equivalent Survival between Gastric Large-Cell Neuroendocrine Carcinoma and Gastric Small-Cell Neuroendocrine Carcinoma

Journal of clinical medicine · Sep 2023 · retrospective cohort study

gastric large-cell neuroendocrine carcinomagastric small-cell neuroendocrine carcinomagastric neuroendocrine carcinoma

This retrospective study compared clinical characteristics and overall survival between gastric large-cell neuroendocrine carcinoma (GLNEC, n=82) and gastric small-cell neuroendocrine carcinoma (GSNEC, n=32) in 114 patients treated at a single center, with external validation using the SEER dataset. Clinicopathologic features and 1-, 3-, and 5-year overall survival rates did not differ significantly between GLNEC and GSNEC. The authors report that SEER analysis using inverse probability of treatment weighting confirmed the lack of significant survival difference.

Reported effects: 1-year overall survival 89%, p no statistically significant differences, n=114 · 3-year overall survival 60.5%, p no statistically significant differences, n=114 · +1 more

Key findings
  • 114 GNEC patients completed treatment at the study center (GLNEC n=82; GSNEC n=32).
  • No clinicopathologic differences were observed between GSNEC and GLNEC for sex, age, BMI, Charlson Comorbidity Index, tumor location, tumor size, stage, treatment received, neuroendocrine markers (CD56, Chromogranin A, synaptophysin), and Ki-67 index.
  • The 1-year, 3-year, and 5-year overall survival rates of GLNEC were 89.0%, 60.5%, and 52.4%; for GSNEC they were 93.8%, 56.3%, and 52.7%; these showed no statistically significant differences.
  • The lack of significant prognostic difference between GLNEC and GSNEC was further confirmed using the SEER dataset after inverse probability of treatment weighting.
Limitations: Retrospective, observational design subject to confounding and selection bias.; Single-center clinical cohort with a relatively small sample, especially for GSNEC (n=32).; Abstract does not report p-values, confidence intervals, or detailed follow-up duration for survival estimates.; SEER-based validation is observational and may have limitations in available covariates and miscoding..

AI summary of the abstract, human-reviewed · Jun 2026. Describes what this study reported, not medical advice. View on PubMed · Full text

Case reportReported negativeLimited evidenceTier 3 · early humann = 1

De novo purely prostatic large-cell neuroendocrine carcinoma with thyroid and adrenal metastases

Endocrinology, diabetes & metabolism case reports · Dec 2022 · case report

prostate large-cell neuroendocrine carcinoma (LCNEC)thyroid metastasisadrenal metastasis

This case report describes a 78-year-old man with de novo large-cell neuroendocrine carcinoma (LCNEC) of the prostate who presented with cervical lymphadenopathy and was found to have a poorly differentiated carcinoma in the thyroid. Imaging, biopsies, cytology and immunohistochemistry were used for diagnosis, and thyroid surgery confirmed LCNEC metastasis; additional metastases were identified in both adrenal glands. The disease was aggressive and the patient died despite treatment. The authors note that de novo prostatic LCNEC is rare, highly aggressive, and often diagnosed at an advanced stage.

Key findings
  • Patient was a 78-year-old man with no history of androgen-deprivation therapy who presented with cervical lymphadenopathy.
  • Diagnostic approaches included PET/CT, MRI, CT scans, ultrasonography, biopsies, and cytological and immunohistochemical evaluations.
  • Findings showed a poorly differentiated carcinoma in the thyroid gland with cervical lymph node enlargement.
  • Thyroid surgery revealed that the thyroid lesion was metastasis of large-cell neuroendocrine carcinoma (LCNEC).
  • Additional metastases were identified in both adrenal glands.
  • Despite treatment, the patient died of the disease.
  • De novo LCNEC of the prostate is rare, highly aggressive, resistant to most therapeutic agents, has high metastatic potential, and is usually diagnosed at an advanced stage (as stated by the authors).
Limitations: Single-patient case report (n=1) limits generalizability.; No control or comparator group.; Limited clinical detail and no systematic data collection.; No molecular characterization or detailed therapeutic regimen 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

ReviewMixed resultsLimited evidenceTier 3 · early human

Pulmonary Combined Large Cell Neuroendocrine Carcinoma

Pathology oncology research : POR · Nov 2022 · review

combined large-cell neuroendocrine carcinoma (CLCNEC)large cell neuroendocrine carcinoma (LCNEC)non-small-cell lung cancer (NSCLC)small cell lung cancer (SCLC)adenocarcinoma-CLCNEC

This review summarizes clinical characteristics, pathological diagnosis, and treatment approaches for pulmonary combined large-cell neuroendocrine carcinoma (CLCNEC), a rare and generally aggressive lung neuroendocrine tumor. The authors state that complete surgical resection is preferred for early-stage disease; platinum-based small cell lung cancer chemotherapy regimens have shown promising results in postoperative and advanced CLCNEC compared with non-small cell regimens; adenocarcinoma-CLCNEC more often harbors driver mutations and may benefit from targeted therapy; evidence for immunotherapy is currently insufficient.

Studied with: complete surgical resection, platinum-based SCLC chemotherapy regimens, NSCLC-standard regimens, targeted therapy, immunotherapy.

Key findings
  • CLCNEC is a rare neuroendocrine tumor related to LCNEC with generally aggressive behavior and poor prognosis.
  • Clinical features are nonspecific and reflect the mixed histologic components.
  • Because of low incidence, evidence consists mainly of small-scale retrospective studies and case reports.
  • Complete surgical resection is preferred in early-stage disease.
  • Platinum-based SCLC standard chemotherapy showed promising results in postoperative and advanced CLCNEC compared to NSCLC regimens according to previous research.
  • Adenocarcinoma-CLCNEC is more likely to harbor driver gene mutations and may benefit from targeted therapy.
  • More clinical trial data are needed to determine benefits of immunotherapy in CLCNEC.
Limitations: Rare disease with low incidence limiting available data.; Existing evidence is from few small-scale retrospective studies and case reports rather than large prospective trials.; No new primary quantitative data presented in this review.; Insufficient clinical trial data on immunotherapy for CLCNEC..

AI summary of the abstract, human-reviewed · Jun 2026. Describes what this study reported, not medical advice. View on PubMed · Full text

Human · observationalMixed resultsLimited evidenceTier 3 · early humann = 469

Large-cell neuroendocrine carcinoma of the gynecologic tract: Prevalence, survival outcomes, and associated factors

Frontiers in oncology · Nov 2022 · retrospective analysis of the SEER database (1988–2015)

cervical large-cell neuroendocrine carcinomaovarian large-cell neuroendocrine carcinomaendometrial large-cell neuroendocrine carcinoma

This retrospective SEER database study analyzed 469 patients with gynecologic large-cell neuroendocrine carcinoma (cervical n=169, ovarian n=219, endometrial n=79) diagnosed from 1988–2015 to assess survival and prognostic factors. The authors report site-specific 5-year overall and cancer-specific survival rates and median survivals (for example, 5-year OS: cervical 35.98%, ovarian 17.84%, endometrial 23.21%). Multivariate analysis identified stage, lymph node metastasis, surgery, and chemotherapy as independent prognostic factors that differed by tumor site. The authors conclude that certain combinations of surgery, chemotherapy, and radiotherapy are associated with better survival depending on stage and site.

Reported effects: 5-year OS (cervical LCNEC) 35.98%, n=169 · 5-year OS (ovarian LCNEC) 17.84%, n=219 · +10 more

Studied with: surgery, chemotherapy, radiotherapy.

Key findings
  • Cervical, ovarian, and endometrial LCNEC were observed in 169, 219, and 79 patients, respectively.
  • The 5-year OS rates for patients with cervical, ovarian, and endometrial LCNEC were 35.98%, 17.84%, and 23.21%, respectively; the median duration of overall survival was 26, 11, and 11 months in each group.
  • The 5-year CSS rates for the three groups were 45.23%, 19.23%, and 31.39%, respectively; the median duration of CSS was 41, 12, and 11 months in each group.
  • Multivariate analysis revealed that AJCC stage, lymph node metastasis, and chemotherapy were independent prognostic factors for OS and CSS in patients with cervical LCNEC.
  • Lymph node metastasis, surgery, and chemotherapy were independent prognostic factors for OS and CSS in the ovarian group and for OS in the endometrial group; lymph node metastasis and surgery were independent prognostic factors for CSS in the endometrial group.
  • Authors concluded surgery alone may help to improve OS and CSS in early-stage cervical LCNEC; surgery+chemotherapy and surgery+radiotherapy may help to improve survival in early-stage ovarian and endometrial LCNEC, respectively; and comprehensive treatment (surgery, chemotherapy, radiotherapy) should be considered for advanced-stage disease.
Limitations: Retrospective, observational design using registry data.; Potential selection bias and unmeasured confounding inherent to SEER database analyses.; SEER registry does not provide detailed information on chemotherapy regimens, radiation doses, performance status, or comorbidities.; No randomized comparison of treatment strategies..

AI summary of the abstract, human-reviewed · Jun 2026. Describes what this study reported, not medical advice. View on PubMed · Full text

Case reportReported positiveLimited evidenceTier 3 · early humann = 1

Complete and durable response of pulmonary large-cell neuroendocrine carcinoma to pembrolizumab

Cancer reports (Hoboken, N.J.) · Aug 2022 · case report

Pembrolizumabpulmonary large-cell neuroendocrine carcinoma (LCNEC)

This is a single-patient case report of a 65-year-old man with recurrent pulmonary large-cell neuroendocrine carcinoma. After progression on carboplatin plus etoposide and with tumor PD-L1 expression of 40%, second-line pembrolizumab produced tumor shrinkage after one cycle and complete disappearance after six cycles; treatment continued ~2 years and the response has been maintained for 4 years and is ongoing.

Reported effects: shrinkage_after_one_cycle 1, n=1 · complete_response_time 6, n=1 · +3 more

Studied with: carboplatin, etoposide.

Key findings
  • Patient: 65-year-old male with pulmonary LCNEC pT3N1M0 stage IIIA, postoperative recurrence with multiple subcutaneous masses and brain metastases.
  • First-line chemotherapy with carboplatin plus etoposide resulted in increase of subcutaneous masses and development of new brain metastases after two cycles.
  • Tumor testing: EGFR and ALK negative; PD-L1 expression in tumor cells was 40% (22C3 clone); tumor infiltrates were primarily CD3-positive T cells and CD138-positive plasma cells.
  • Second-line pembrolizumab was started; subcutaneous masses shrank after one cycle and tumors had completely disappeared after six cycles.
  • Pembrolizumab was continued for approximately 2 years, and the complete response has been maintained for 4 years and is ongoing at time of report.
Limitations: Single-patient case report (n=1), limiting generalizability.; No control or comparator group and no randomization.; Dose and schedule of pembrolizumab not reported in the abstract.; Observational retrospective description without systematic outcome measures..

AI summary of the abstract, human-reviewed · Sep 2026. Describes what this study reported, not medical advice. View on PubMed · Full text

Case reportMechanismReported positiveLimited evidenceTier 3 · early humann = 1

Ectopic insulin secretion by a large-cell neuroendocrine carcinoma of the cervix

Clinical case reports · Nov 2020 · Case report

large-cell neuroendocrine carcinoma of the cervix

This case report describes ectopic insulin secretion by a large-cell neuroendocrine carcinoma of the cervix. The authors note that when patients present with hyperinsulinemic hypoglycemia and a nonpancreatic neuroendocrine tumor, ectopic insulin secretion should be considered. They recommend further investigation with confirmatory insulin immunostaining of the tumor.

Key findings
  • A large-cell neuroendocrine carcinoma of the cervix can produce ectopic insulin secretion (title).
  • In patients presenting with hyperinsulinemic hypoglycemia and a nonpancreatic neuroendocrine tumor, the diagnosis of an ectopic insulin-secreting tumor should be considered (abstract).
  • Confirmatory insulin staining of the tumor should be used to investigate suspected ectopic insulin secretion (abstract).
Limitations: Single case report; findings may not be generalizable.; No quantitative data or systematic analysis presented.; No control group or comparison.; Abstract provides limited clinical detail on presentation, management, and outcomes..

AI summary of the abstract, human-reviewed · Sep 2026. Describes what this study reported, not medical advice. View on PubMed · Full text

Browse all studies mentioning Large-Cell Neuroendocrine Carcinoma →

Study mix

15 published studies by what they were done in. Lab and animal findings often do not carry over to people.

6 Human9 Review/other
Reported directionReported positive6Mixed results3Reported negative3Inconclusive3

Compounds with reported-positive results in Large-Cell Neuroendocrine Carcinoma

Where at least one study reported a positive result, shown with the full picture, not just the wins. Positive results are more likely to be published, and most of these are early lab or animal studies that may not translate to people. This reports what studies found, not what works.

Preclinical only: lab / animal (1)
Pembrolizumab1 positive
Limitations: Single-patient case report (n=1), limiting generalizability.; No control or comparator group and no randomization.; Dose and schedule of pembrolizumab not reported in the abstract.; Observational retrospective description without systematic outcome measures..
Cited positive studies (1)

Evidence at a glance: compounds studied in Large-Cell Neuroendocrine Carcinoma

A deterministic grade of what published studies report for each: strength of evidence, the reported direction, and the largest credible effect, strongest-evidence first. This summarizes findings; it is not a claim that anything works.

PembrolizumabInsufficient evidenceReported positive

No primary experimental studies yet.

Largest credible effect: shrinkage_after_one_cycle 1, n=1 PMID 34817132 · effect sizes 1–6 across 5 studies

Most authoritative study: Complete and durable response of pulmonary large-cell neuroendocrine carcinoma to pembrolizumab

No human studies yet · Based on a single study.

What the research shows for Large-Cell Neuroendocrine Carcinoma

A plain-language summary of the reviewed studies OncoForge tracks for Large-Cell Neuroendocrine Carcinoma. It reports what those studies described, not a claim that any compound or therapy helps or harms Large-Cell Neuroendocrine Carcinoma. Most of this evidence is early, and findings often conflict.

  • A review of pulmonary neuroendocrine tumors described these cancers as a spectrum from well-differentiated typical carcinoid through atypical carcinoid to high-grade neuroendocrine carcinomas (small-cell and large-cell) and noted that immunohistochemistry is often essential for diagnosis and classification (PMID 32005434).
  • A retrospective targeted next-generation sequencing study of 216 pulmonary large-cell neuroendocrine carcinoma (LCNEC) samples from a Polish cohort identified 46 genetic variants in 46 of 216 tumors (21.3%) (PMID 41977128).
  • In that sequencing study, 28 of 216 tumors (13%) harbored at least one alteration the investigators classified as potentially actionable by available targeted therapies or existing drug classes (PMID 41977128).
  • The studies indicate molecular heterogeneity in pulmonary neuroendocrine tumors and that a subset of LCNEC cases carry genomic alterations that could be considered for further research, while most samples did not show potentially actionable variants in this cohort.

Supportive & alternative options discussed

  • Exercise / prehabilitation: Also discussed as a supportive option to help maintain physical function, reduce fatigue, and improve quality of life in people with lung cancers; this was not evaluated in the studies summarized above.
  • Mind–body (MBSR / CBT): Also discussed as a supportive approach (stress-reduction, counseling, relaxation techniques) to help coping and quality of life in cancer care; not addressed by the studies summarized here.
  • Acupuncture: Also discussed as a supportive option for symptom management (for example, pain or treatment-related nausea) in some cancer patients; it was not evaluated in the studies summarized above.
  • Ketogenic / metabolic therapy: Also discussed by some as a complementary dietary approach for people with cancer, but the studies summarized here did not evaluate ketogenic diets in large-cell neuroendocrine carcinoma.
  • Mistletoe (VAE): Also discussed in some regions as an adjunctive or supportive therapy in oncology; this modality was not studied in the reports summarized above.

What we don’t know yet

  • Do the potentially actionable genomic alterations identified in the retrospective cohort predict clinical benefit from targeted therapies in people with LCNEC? (no prospective clinical trial evidence provided by these studies).
  • How generalizable are the sequencing findings beyond the single retrospective Polish cohort—prevalence and spectrum of alterations across other populations and settings remain uncertain.
  • What are the functional consequences of the reported variants for tumor biology and treatment response—these studies were descriptive and did not test targeted interventions.
  • How should diagnostic classification (including immunohistochemistry and molecular testing) be standardized across centers to guide biomarker-driven care for LCNEC?
Overall, the evidence summarized is descriptive and limited (review and a single retrospective sequencing cohort); it identifies biomarkers and diagnostic challenges but does not establish clinical benefit of targeted treatments for LCNEC.

Clinical trials in Large-Cell Neuroendocrine Carcinoma

31 ongoing · 32 completed · tracked from ClinicalTrials.gov. Recruiting is not the same as proven, and completed is not the same as positive — read the results. Not a recommendation.

Completed
15 stopped (terminated / withdrawn / suspended)

Search all trials on ClinicalTrials.gov →

Getting care & support

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Practical, vetted help for Large-Cell Neuroendocrine Carcinoma — advocacy, paying for treatment, second opinions, and caregivers.

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Advocacy & community

No dedicated organization for this specific cancer is curated yet — these general organizations can help in the meantime.

Financial help

  • PAN Foundation ↗ — Copay assistance funds by diagnosis (funds open and close as money allows). · status changes often — check the fund’s site
  • HealthWell Foundation ↗ — Copay and premium assistance funds by disease. · status changes often — check the fund’s site
  • CancerCare — financial assistance ↗ — Limited grants plus free financial counseling. · status changes often — check the fund’s site
  • Family Reach ↗ — Help with everyday living costs (rent, transport, food) during treatment. · status changes often — check the fund’s site
  • NeedyMeds ↗ — Searchable directory of drug patient-assistance and discount programs. · status changes often — check the fund’s site
What you’ll typically need to apply
  • Your diagnosis and, if you have it, the specific drug/treatment name (from your care team).
  • Insurance details — your member ID card, or a note that you're uninsured (some funds require active insurance, some don't).
  • Proof of income and household size (recent pay stubs, a tax return, or a benefits letter) — most funds are income-based.
  • Your prescriber's contact information; some programs need the clinic to submit part of the application.
  • Apply early and re-check: funds open and close as money is available, so a closed fund may reopen.

General guidance — each program sets its own eligibility. Confirm requirements on the program’s site.

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