2f:I[703058,["/_next/static/immutable/chunks/3bhq_5eh1d760.js","/_next/static/immutable/chunks/1855-ogyi8eh4.js","/_next/static/immutable/chunks/2pfsjpn6k6zlg.js","/_next/static/immutable/chunks/26c7v3_3uwnwu.js","/_next/static/immutable/chunks/25a3ozcrvi1ff.js","/_next/static/immutable/chunks/2r4wx50nvjh_4.js","/_next/static/immutable/chunks/23fsw06hsi5b1.js","/_next/static/immutable/chunks/06_yt270h41rg.js","/_next/static/immutable/chunks/3ezsiz-7shkna.js","/_next/static/immutable/chunks/20x2y96ldu5wx.js","/_next/static/immutable/chunks/2lxntcm3pd1_h.js","/_next/static/immutable/chunks/00dgco8irq3jw.js","/_next/static/immutable/chunks/00nwe-kq0rboc.js","/_next/static/immutable/chunks/2051ffx3xzio9.js"],"PaperListPageClient"] 30:T5d3,Small cell lung cancer (SCLC) is an aggressive neuroendocrine malignancy characterized by rapid onset of chemoresistance and poor clinical outcomes. Transcriptional heterogeneity among treatment-naïve SCLC tumors underlies four transcriptional subtypes, each with distinct clinical vulnerabilities. Though previously hypothesized to delineate a distinct subtype, expression of YAP1 is largely absent from treatment-naïve, pure SCLC. To characterize relapsed SCLC, circulating tumor DNA, circulating tumor cells, and core needle biopsies from SCLC patients and preclinical models following resistance to standard-of-care therapies were analyzed. In contrast to treatment-naïve SCLC, these analyses reveal an emergent YAP1-positive cell population that coincides with treatment resistance. These YAP1-positive cells exhibit characteristics of drug tolerant persister cells, including senescence, stemness, and plasticity, as YAP1 positive cells largely abandon features characteristic of SCLC to adopt those of large-cell neuroendocrine carcinoma (LCNEC). As a result of this SCLC-like to LCNEC-like evolution, YAP1-positive cells lack several clinically relevant SCLC surface targets (i.e., DLL3, SEZ6), but are enriched for others (i.e., B7-H3, TROP2). We propose a model where YAP1 expressing cells emerge with SCLC treatment resistance and characterize a tenacious subpopulation capable of diverging from the treatment naïve lineage and adopting features to evade therapeutic response.31:Tbdd,Small cell lung cancer (SCLC) and extrapulmonary neuroendocrine (NE) tumors are aggressive malignancies with limited treatment options. Seizure-related homolog 6 (SEZ6) is a potential therapeutic target, but its expression in these tumors remains poorly understood. Lineage plasticity contributes to resistance in non-small cell lung cancer (NSCLC), where some cases can undergo SCLC-transformation after targeted therapy. We aimed to characterize SEZ6 expression across NE tumors and presumed NSCLC-to-SCLC transformations. DNA and RNA sequencing were performed for SCLC, NSCLC, and NE samples. Samples were stratified by SEZ6 RNA expression quartiles and classified into subtypes based on ASCL1, NEUROD1, and POU2F3 expression. Significance was tested using the Mann-Whitney U test. Real-world overall survival was obtained from insurance claims data, with p-values calculated using the log-rank test. Paired samples for NSCLC-to-SCLC transformation were identified by sequential biopsies classified as NSCLC followed by SCLC. RNA sequencing was performed on 1318 SCLC and 2218 NE samples. Median SEZ6expression was higher in SCLC (39.7 transcripts per million (TPM)) than in NE tumors (20.8 TPM, p<0.0001) and NSCLC (1.34 TPM, p<0.001). Among NE tumors, median SEZ6 expression was highest in prostate (52.0 TPM, p=0.0016 vs SCLC) and lowest in adrenal gland tumors (1.2 TPM, p<0.0001 vs SCLC). In SCLC,SEZ6expression was positively correlated with ASCL1(p=0.44, p<0.0001) andNEUROD1(p=0.16, p<0.0001) expression but notPOU2F3(p=-0.04, p=0.1253). Median survival was longest in SEZ6-Q2 for both SCLC and NE (13.0 mos. and 33.7 mos., respectively). NSCLC-to-SCLC transformation samples showed numerically higher SEZ6 expression post-transformation (median: 86.2 vs 2.4 TPM). SEZ6expression is higher in SCLC than in NE tumors, with notable heterogeneity by subtype, warranting consideration of expanded use of SEZ6-directed therapy. Translational Relevance Statement: This study establishes SEZ6 as a promising therapeutic target in small cell lung cancer (SCLC) and transformed non-small cell lung cancer (NSCLC), demonstrating its significantly elevated expression compared to neuroendocrine (NE) tumors and NSCLC. The positive correlation of SEZ6 expression with NE lineage markers, particularly in ASCL1 and NEUROD1 subtypes, highlights its role as a lineage-specific marker, guiding the development of SEZ6-targeted antibody-drug conjugates (ADCs). Additionally, the increased SEZ6 expression following NSCLC-to-SCLC transformation suggests that SEZ6-targeted therapies could address resistance mechanisms in transformed tumors. Importantly, the association between high SEZ6 expression and shorter survival indicates that integrating SEZ6 status into diagnostic workflows could help stratify patients by risk and guide therapeutic decision-making. The findings from this study will inform future clinical trials, aiming to implement SEZ6-targeted treatments as part of precision oncology strategies for aggressive NE malignancies.32:T45c,The bispecific antibody tarlatamab recruits T cells to cancers expressing the neuroendocrine epitope DLL3. Tarlatamab is effective in small cell lung cancer (SCLC), but clinical outcomes vary, and no biomarkers enable patient selection. Single-cell RNA sequencing of SCLC biopsies identifies heterogeneity in DLL3 expression, and analysis of circulating tumor cells (CTCs) distinguishes individual patients as predominantly DLL3Pos or DLL3Low. In a prospective cohort of 20 patients, pretreatment DLL3 expression on CTCs predicts tarlatamab clinical benefit (85% sensitivity, 100% specificity). Necrotic CTC clusters in blood accompany treatment-induced tumor lysis. Acquired resistance to tarlatamab is associated in some cases with loss of DLL3 expression, but persistence of other targetable neuro-endocrine epitopes; in other patients, DLL3 is retained on CTCs, but accompanied by systemic markers of T cell dysfunction. Quantitation of DLL3-positive CTCs identifies patients likely to benefit from tarlatamab, and longitudinal monitoring may guide therapeutic decision-making at the time of acquired resistance.33:T4a1,Abstract The bispecific antibody tarlatamab recruits T cells to cancers expressing the neuroendocrine epitope DLL3. Tarlatamab is effective in small cell lung cancer (SCLC), but clinical outcomes vary, and no biomarkers enable patient selection. Single-cell RNA sequencing of SCLC biopsies identifies heterogeneity in DLL3 expression, and analysis of circulating tumor cells (CTCs) distinguishes individual patients as predominantly DLL3Pos or DLL3Low. In a prospective cohort of 20 patients, pretreatment DLL3 expression on CTCs predicts tarlatamab clinical benefit (85% sensitivity, 100% specificity). Necrotic CTC clusters in blood accompany treatment-induced tumor lysis. Acquired resistance to tarlatamab is associated in some cases with loss of DLL3 expression, but persistence of other targetable neuro-endocrine epitopes; in other patients, DLL3 is retained on CTCs, but accompanied by systemic markers of T cell dysfunction. Quantitation of DLL3-positive CTCs identifies patients likely to benefit from tarlatamab, and longitudinal monitoring may guide therapeutic decision-making at the time of acquired resistance.25:[[["$","script","0",{"type":"application/ld+json","dangerouslySetInnerHTML":{"__html":"{\"@context\":\"https://schema.org\",\"@type\":\"CollectionPage\",\"name\":\"Small Cell Lung Cancer: condition Research & Clinical Takeaways\",\"description\":\"Explore peer-reviewed papers on Small Cell Lung Cancer (condition). Clinician-written summaries and actionable practice insights. Updated daily.\",\"url\":\"https://www.reachrx.ai/hub/tag/condition/Small%20Cell%20Lung%20Cancer\",\"breadcrumb\":{\"@type\":\"BreadcrumbList\",\"itemListElement\":[{\"@type\":\"ListItem\",\"position\":1,\"name\":\"Home\",\"item\":\"https://www.reachrx.ai\"},{\"@type\":\"ListItem\",\"position\":2,\"name\":\"Research Hub\",\"item\":\"https://www.reachrx.ai/hub\"},{\"@type\":\"ListItem\",\"position\":3,\"name\":\"Conditions\",\"item\":\"https://www.reachrx.ai/hub/tag/condition\"},{\"@type\":\"ListItem\",\"position\":4,\"name\":\"Small Cell Lung Cancer\",\"item\":\"https://www.reachrx.ai/hub/tag/condition/Small%20Cell%20Lung%20Cancer\"}]}}"}}]],["$","$L2f",null,{"title":"Small Cell Lung Cancer: Research & Clinical Takeaways","description":"Discover peer-reviewed research on Small Cell Lung Cancer with concise clinician summaries and next-step guidance.","papers":[{"doi":"10.1016/j.jtho.2026.103957","pmid":"42697609","title":"The Evolution of Immunotherapy Revolution in Lung Cancer: A 20-Year Perspective","journal_title":"Journal of Thoracic Oncology","journal_issn":"1556-0864","published_at":"2026-09-04T00:00:00.000Z","url":"https://doi.org/10.1016/j.jtho.2026.103957","source_score":7,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-09-16T06:22:48.155Z","updated_at":"2026-09-16T06:22:48.155Z","tags":[{"paper_doi":"10.1016/j.jtho.2026.103957","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1016/j.jtho.2026.103957","tag_type":"brand","value":"Imfinzi","value_numeric":null},{"paper_doi":"10.1016/j.jtho.2026.103957","tag_type":"brand","value":"Keytruda","value_numeric":null},{"paper_doi":"10.1016/j.jtho.2026.103957","tag_type":"brand","value":"Libtayo","value_numeric":null},{"paper_doi":"10.1016/j.jtho.2026.103957","tag_type":"brand","value":"Opdivo","value_numeric":null},{"paper_doi":"10.1016/j.jtho.2026.103957","tag_type":"brand","value":"Tecentriq","value_numeric":null},{"paper_doi":"10.1016/j.jtho.2026.103957","tag_type":"category","value":"Respiratory System","value_numeric":null},{"paper_doi":"10.1016/j.jtho.2026.103957","tag_type":"condition","value":"Lung Cancer","value_numeric":null},{"paper_doi":"10.1016/j.jtho.2026.103957","tag_type":"condition","value":"Non-Small Cell Lung Cancer","value_numeric":null},{"paper_doi":"10.1016/j.jtho.2026.103957","tag_type":"condition","value":"Small Cell Lung Cancer","value_numeric":null},{"paper_doi":"10.1016/j.jtho.2026.103957","tag_type":"generic","value":"atezolizumab","value_numeric":null},{"paper_doi":"10.1016/j.jtho.2026.103957","tag_type":"generic","value":"cemiplimab","value_numeric":null},{"paper_doi":"10.1016/j.jtho.2026.103957","tag_type":"generic","value":"durvalumab","value_numeric":null},{"paper_doi":"10.1016/j.jtho.2026.103957","tag_type":"generic","value":"ipilimumab","value_numeric":null},{"paper_doi":"10.1016/j.jtho.2026.103957","tag_type":"generic","value":"ivonescimab","value_numeric":null},{"paper_doi":"10.1016/j.jtho.2026.103957","tag_type":"generic","value":"nivolumab","value_numeric":null},{"paper_doi":"10.1016/j.jtho.2026.103957","tag_type":"generic","value":"pembrolizumab","value_numeric":null},{"paper_doi":"10.1016/j.jtho.2026.103957","tag_type":"generic","value":"serplulimab","value_numeric":null},{"paper_doi":"10.1016/j.jtho.2026.103957","tag_type":"generic","value":"tarlatamab","value_numeric":null},{"paper_doi":"10.1016/j.jtho.2026.103957","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1016/j.jtho.2026.103957","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1016/j.jtho.2026.103957","tag_type":"modality","value":"Anti-Angiogenic Therapy","value_numeric":null},{"paper_doi":"10.1016/j.jtho.2026.103957","tag_type":"modality","value":"Antibody-Drug Conjugate","value_numeric":null},{"paper_doi":"10.1016/j.jtho.2026.103957","tag_type":"modality","value":"Bispecific T-Cell Engager","value_numeric":null},{"paper_doi":"10.1016/j.jtho.2026.103957","tag_type":"modality","value":"Chemo-Immunotherapy","value_numeric":null},{"paper_doi":"10.1016/j.jtho.2026.103957","tag_type":"modality","value":"Immune Checkpoint Inhibitor","value_numeric":null},{"paper_doi":"10.1016/j.jtho.2026.103957","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1016/j.jtho.2026.103957","tag_type":"study_design","value":"Narrative Review","value_numeric":null},{"paper_doi":"10.1016/j.jtho.2026.103957","tag_type":"warning","value":"Sample size tag was omitted as this is a review article aggregating many trials with no single study population.","value_numeric":null},{"paper_doi":"10.1016/j.jtho.2026.103957","tag_type":"warning","value":"Several cited trials (e.g., HARMONi-2, SKYSCRAPER-01, DeLLphi) are from 2024–2026 and may represent very recent or preliminary data not yet fully peer-validated at time of reading.","value_numeric":null},{"paper_doi":"10.1016/j.jtho.2026.103957","tag_type":"warning","value":"The PACIFIC subgroup analysis suggesting reduced OS benefit in PD-L1 <1% patients is post hoc and limited by small numbers; clinical interpretation should be cautious.","value_numeric":null},{"paper_doi":"10.1016/j.jtho.2026.103957","tag_type":"warning","value":"This is a narrative review, not a systematic review or meta-analysis—trial selection and emphasis reflect author perspective and may not be exhaustive.","value_numeric":null}],"summaries":{"what_studied":"This 20-year narrative review covers the evolution of immune checkpoint inhibitor (ICI) therapy in lung cancer—both NSCLC and SCLC—across all disease stages, from second-line monotherapy through perioperative strategies, including biomarkers, resistance mechanisms, toxicity, and emerging immunotherapeutic approaches.","key_result":"ICIs have transformed lung cancer outcomes across stages: 5-year OS reached 31.9% with first-line pembrolizumab in PD-L1 ≥50% NSCLC (KEYNOTE-024) vs. ~5% historically; perioperative pembrolizumab (KEYNOTE-671) yielded the first mature OS benefit in resectable NSCLC; consolidation durvalumab in unresectable stage III NSCLC (PACIFIC) achieved 42.9% 5-year OS vs. 29.1% for placebo; and in ES-SCLC, chemoimmunotherapy improved median OS by ~2–5 months (e.g., 12.3 vs. 10.3 months in IMpower133), though long-term survivors remain rare.","limitations":"- Entirely a narrative review; no primary data, meta-analysis, or systematic evidence synthesis—subject to selection bias in trial coverage.\n- Key outstanding questions (optimal ICI duration beyond 2 years, MRD-guided treatment decisions, best strategies for oncogene-driven NSCLC) remain unresolved due to lack of prospective randomized data.\n- Underrepresentation of older adults, patients with comorbidities, and low/middle-income populations in the cited trials limits generalizability.","practice_takeaway":"PD-L1 testing should guide first-line ICI selection in advanced NSCLC, with monotherapy favored at ≥50% and chemo-IO combinations appropriate across all expression levels; stopping ICI at 2 years appears safe based on current retrospective data, though prospective confirmation is lacking.\n\nIn oncogene-driven NSCLC (EGFR, ALK, RET, ROS1), ICIs offer limited benefit and carry serious safety risks when combined with TKIs—targeted therapy-first strategies should be prioritized and concurrent TKI-ICI use avoided outside clinical trials."}},{"doi":"10.1111/1759-7714.70372","pmid":"42610673","title":"Multidisciplinary Team Care for Early‐Stage Lung Cancer in Low‐ and Middle‐Income Countries and Emerging Economies: Current Position and Call for Action","journal_title":"Thoracic Cancer","journal_issn":"1759-7706","published_at":"2026-08-18T00:00:00.000Z","url":"https://doi.org/10.1111/1759-7714.70372","source_score":3,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-08-22T06:53:32.889Z","updated_at":"2026-08-22T06:53:32.889Z","tags":[{"paper_doi":"10.1111/1759-7714.70372","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1111/1759-7714.70372","tag_type":"category","value":"Respiratory System","value_numeric":null},{"paper_doi":"10.1111/1759-7714.70372","tag_type":"condition","value":"Lung Cancer","value_numeric":null},{"paper_doi":"10.1111/1759-7714.70372","tag_type":"condition","value":"Non-Small Cell Lung Cancer","value_numeric":null},{"paper_doi":"10.1111/1759-7714.70372","tag_type":"condition","value":"Small Cell Lung Cancer","value_numeric":null},{"paper_doi":"10.1111/1759-7714.70372","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1111/1759-7714.70372","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1111/1759-7714.70372","tag_type":"modality","value":"Biomarker Testing","value_numeric":null},{"paper_doi":"10.1111/1759-7714.70372","tag_type":"modality","value":"Multidisciplinary Team Care","value_numeric":null},{"paper_doi":"10.1111/1759-7714.70372","tag_type":"modality","value":"Stereotactic Body Radiation Therapy","value_numeric":null},{"paper_doi":"10.1111/1759-7714.70372","tag_type":"modality","value":"Surgical Resection","value_numeric":null},{"paper_doi":"10.1111/1759-7714.70372","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1111/1759-7714.70372","tag_type":"study_design","value":"Narrative Review with Expert Consensus","value_numeric":null},{"paper_doi":"10.1111/1759-7714.70372","tag_type":"warning","value":"Industry funding: AstraZeneca sponsored this study; one author (Francisco Gonzalez) is an AstraZeneca employee, and multiple authors report consulting/speaker fees from AstraZeneca and other pharmaceutical companies. Recommendations should be interpreted with this conflict in mind.","value_numeric":null},{"paper_doi":"10.1111/1759-7714.70372","tag_type":"warning","value":"No aggregate sample size is reported for the review as a whole; individual cited studies vary widely in design and population.","value_numeric":null},{"paper_doi":"10.1111/1759-7714.70372","tag_type":"warning","value":"Survival benefit data cited are from retrospective studies in high-income countries (Thailand, Taiwan, Italy, US); generalizability to broader LMIC contexts is uncertain.","value_numeric":null},{"paper_doi":"10.1111/1759-7714.70372","tag_type":"warning","value":"The RISE-LC framework was developed through iterative expert consensus, not validated in prospective or implementation trials; its real-world effectiveness in LMICs remains untested.","value_numeric":null}],"summaries":{"what_studied":"A 12-expert panel from 11 LMICs and emerging economies (Brazil, Chile, Malaysia, Colombia, Egypt, Mexico, Türkiye, Argentina, China, Vietnam, India) conducted a narrative literature review (PubMed, January 2001–May 2025) to identify barriers to multidisciplinary team (MDT) care for early-stage lung cancer (ESLC: NSCLC clinical stage Ib–IIIa; limited-stage SCLC) and to develop the RISE-LC framework for MDT implementation in resource-constrained settings.","key_result":"MDT discussion was consistently linked to better outcomes: 5-year OS was markedly higher in post-MDT vs. pre-MDT cohorts for stage Ib–IIIa NSCLC (e.g., stage Ib: 95% vs. 76%; IIb: 92% vs. 69%; IIIa: 92% vs. 62% in Thailand), time from diagnosis to treatment was cut from 29 to 17 days in MCC vs. non-MCC groups (US), and MDC reduced overall diagnostic charges by ~23% per patient. Key barriers in LMICs included oncology workforce deficits (e.g., India: 1 oncologist per ~2,000 patients), fragmented health systems, limited biomarker access, and frequent LC misdiagnosis as TB.","limitations":"- Narrative review design without formal meta-analysis; findings are descriptive and not statistically synthesized across studies.\n- Outcome data supporting MDT benefit are largely from high-income countries (Australia, US, New Zealand, Thailand, Taiwan, Italy), limiting direct applicability to LMICs.\n- AstraZeneca-funded study with several authors disclosing financial ties to pharmaceutical companies, introducing potential bias in recommendations.","practice_takeaway":"In LMICs, clinicians and health administrators should prioritize building a core MDT (medical oncology, radiation oncology, thoracic surgery, pulmonology, radiology, pathology) with structured referral pathways, standardized datasets, and virtual/hybrid meeting options to close access gaps. Where full MDT infrastructure is not feasible, the RISE-LC framework offers a stepwise, resource-stratified approach to improve timely ESLC diagnosis and treatment coordination."}},{"doi":"10.1016/j.lungcan.2026.109581","pmid":null,"title":"Patient-reported outcomes with tarlatamab in extensive-stage small cell lung cancer after platinum-based chemotherapy: results from the phase 3 DeLLphi-304 trial","journal_title":"Lung Cancer","journal_issn":"0169-5002","published_at":"2026-08-13T00:00:00.000Z","url":"https://doi.org/10.1016/j.lungcan.2026.109581","source_score":1,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":false,"crossref":true,"unpaywall":true},"created_at":"2026-08-23T07:33:04.332Z","updated_at":"2026-08-23T07:33:04.332Z","tags":[{"paper_doi":"10.1016/j.lungcan.2026.109581","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109581","tag_type":"category","value":"Respiratory System","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109581","tag_type":"condition","value":"Small Cell Lung Cancer","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109581","tag_type":"generic","value":"tarlatamab","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109581","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109581","tag_type":"level_of_evidence","value":"1","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109581","tag_type":"modality","value":"Bispecific T-Cell Engager","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109581","tag_type":"study_design","value":"Randomized Controlled Trial","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109581","tag_type":"warning","value":"Only the paper metadata (title, DOI, journal, publication date) was provided — no abstract or full text. All structured fields are based solely on what can be reasonably inferred from the title. Numeric outcomes, sample size, sex, PRO instrument details, and specific results could not be extracted and have been omitted.","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109581","tag_type":"warning","value":"Study design labeled as Randomized Controlled Trial based on 'phase 3' in the title; confirm comparator arm and randomization details from the full paper.","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109581","tag_type":"warning","value":"The impact_flag 'practice_changing' is tentative, based on this being a positive Phase 3 trial of a novel bispecific agent in a setting with limited options; it should be confirmed once the full text is reviewed.","value_numeric":null}],"summaries":{"what_studied":"This Phase 3 trial (DeLLphi-304) evaluated patient-reported outcomes (PROs) with tarlatamab versus standard-of-care chemotherapy in adults with extensive-stage small cell lung cancer (ES-SCLC) following platinum-based chemotherapy.","limitations":"The full paper text was not provided, so specific PRO instrument results, response rates, and absolute numeric outcomes cannot be extracted or verified."}},{"doi":"10.1038/s41577-026-01330-1","pmid":"42463973","title":"Interleukin-18 armours antitumour immune effectors","journal_title":"Nature Reviews Immunology","journal_issn":"1474-1733","published_at":"2026-07-16T00:00:00.000Z","url":"https://doi.org/10.1038/s41577-026-01330-1","source_score":19,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-07-23T13:33:22.845Z","updated_at":"2026-07-23T13:33:22.845Z","tags":[{"paper_doi":"10.1038/s41577-026-01330-1","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1038/s41577-026-01330-1","tag_type":"category","value":"Immunology","value_numeric":null},{"paper_doi":"10.1038/s41577-026-01330-1","tag_type":"condition","value":"Acute Myeloid Leukemia","value_numeric":null},{"paper_doi":"10.1038/s41577-026-01330-1","tag_type":"condition","value":"Cancer","value_numeric":null},{"paper_doi":"10.1038/s41577-026-01330-1","tag_type":"condition","value":"Lymphoma","value_numeric":null},{"paper_doi":"10.1038/s41577-026-01330-1","tag_type":"condition","value":"Multiple Myeloma","value_numeric":null},{"paper_doi":"10.1038/s41577-026-01330-1","tag_type":"condition","value":"Small Cell Lung Cancer","value_numeric":null},{"paper_doi":"10.1038/s41577-026-01330-1","tag_type":"generic","value":"decoy-resistant IL-18","value_numeric":null},{"paper_doi":"10.1038/s41577-026-01330-1","tag_type":"generic","value":"IL-18 binding protein","value_numeric":null},{"paper_doi":"10.1038/s41577-026-01330-1","tag_type":"generic","value":"interleukin-18","value_numeric":null},{"paper_doi":"10.1038/s41577-026-01330-1","tag_type":"generic","value":"tadekinig alfa","value_numeric":null},{"paper_doi":"10.1038/s41577-026-01330-1","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1038/s41577-026-01330-1","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1038/s41577-026-01330-1","tag_type":"modality","value":"Adoptive Cell Therapy","value_numeric":null},{"paper_doi":"10.1038/s41577-026-01330-1","tag_type":"modality","value":"CAR T Cell Therapy","value_numeric":null},{"paper_doi":"10.1038/s41577-026-01330-1","tag_type":"modality","value":"Immune Checkpoint Inhibitor","value_numeric":null},{"paper_doi":"10.1038/s41577-026-01330-1","tag_type":"modality","value":"Recombinant Cytokine","value_numeric":null},{"paper_doi":"10.1038/s41577-026-01330-1","tag_type":"study_design","value":"Narrative Review","value_numeric":null},{"paper_doi":"10.1038/s41577-026-01330-1","tag_type":"warning","value":"Dual protumour and antitumour roles of IL-18 are acknowledged but not fully reconciled; clinical applicability may vary significantly by tumour type and microenvironment.","value_numeric":null},{"paper_doi":"10.1038/s41577-026-01330-1","tag_type":"warning","value":"No specific sample sizes are reported in the review itself; the sample_size tag has been omitted accordingly.","value_numeric":null},{"paper_doi":"10.1038/s41577-026-01330-1","tag_type":"warning","value":"The 'practice_changing' impact flag reflects the emerging clinical translation of IL-18-armoured CAR T cells; pivotal trial data are not yet available as of the publication date.","value_numeric":null},{"paper_doi":"10.1038/s41577-026-01330-1","tag_type":"warning","value":"This is a narrative review — evidence synthesis is not systematic, and conclusions reflect expert opinion rather than pooled quantitative data.","value_numeric":null}],"summaries":{"what_studied":"This review covers the biology of IL-18 — its sources, processing, and regulatory networks (including IL-18BP and IL-37) — and examines how IL-18 shapes the tumour microenvironment (TME) to support antitumour immunity, with a focus on translating IL-18-based strategies (recombinant IL-18, decoy-resistant IL-18, IL-18-secreting CAR T cells, IL-18BP blockade) into clinical use across tumour types.","key_result":"Early clinical studies show that recombinant human IL-18 is safe in advanced cancer patients; IL-18-armoured CAR T cells (e.g., CD19-targeting in relapsed/refractory lymphoma; CD371-targeting in AML) demonstrate robust expansion and antitumour activity in early trials. IL-18 drives IFNγ production, M1-like macrophage polarization, CD8+ CTL and NK cell activity, and durable T cell memory — but also carries dual protumour roles (e.g., promoting metastasis via VCAM-1/VEGF, chemoresistance via PI3K/AKT, and PD-1-dependent immunosuppression in some contexts).","limitations":"- This is a narrative review, not a systematic review or meta-analysis, so evidence is selectively synthesized.\n- Most mechanistic data come from preclinical (murine) models; the number of completed clinical trials with mature outcome data is small.\n- The dual protumour/antitumour roles of IL-18 are not fully resolved, complicating patient selection and trial design.","practice_takeaway":"IL-18-secreting CAR T cells and decoy-resistant IL-18 variants are entering clinical trials and show early promise — particularly in hematologic malignancies — but clinicians should be aware of IL-18's context-dependent protumour effects and the need to monitor IL-18BP levels as a potential resistance biomarker. Combining IL-18 strategies with checkpoint blockade or IL-18BP inhibition may overcome TME-mediated suppression."}},{"doi":"10.1016/j.lungcan.2026.109539","pmid":"42470748","title":"Analysis of SLFN11 expression in small cell lung cancer, carcinoids and large cell neuroendocrine carcinoma: insights into lung neuroendocrine neoplasms","journal_title":"Lung Cancer","journal_issn":"0169-5002","published_at":"2026-07-13T00:00:00.000Z","url":"https://doi.org/10.1016/j.lungcan.2026.109539","source_score":4,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-07-21T13:34:37.041Z","updated_at":"2026-07-21T13:34:37.041Z","tags":[{"paper_doi":"10.1016/j.lungcan.2026.109539","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109539","tag_type":"category","value":"Respiratory System","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109539","tag_type":"condition","value":"Large Cell Neuroendocrine Carcinoma","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109539","tag_type":"condition","value":"Lung Carcinoid Tumor","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109539","tag_type":"condition","value":"Lung Neuroendocrine Neoplasm","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109539","tag_type":"condition","value":"Small Cell Lung Cancer","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109539","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109539","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109539","tag_type":"modality","value":"Biomarker / Immunohistochemistry","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109539","tag_type":"sample_size","value":"n=361","value_numeric":361},{"paper_doi":"10.1016/j.lungcan.2026.109539","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109539","tag_type":"study_design","value":"Retrospective Cohort Study","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109539","tag_type":"warning","value":"Multicentre IHC scoring (H-score) may introduce inter-site variability; standardization methods are not detailed in the abstract.","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109539","tag_type":"warning","value":"No direct drug-response or treatment data are included — the link between SLFN11 expression and actual sensitivity to DNA-damaging agents is assumed based on prior literature, not tested here.","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109539","tag_type":"warning","value":"The SCLC subgroup (n=47) is small; the OS survival finding should be interpreted with caution and ideally validated in a larger cohort.","value_numeric":null}],"summaries":{"what_studied":"This multicentre study assessed SLFN11 protein expression (by immunohistochemistry H-score) across 361 lung neuroendocrine neoplasms — 127 typical carcinoids (TC), 35 atypical carcinoids (AC), 152 LCNEC, and 47 SCLC — exploring correlations with molecular markers (Ki67, ASCL1, cMYC, pRb, DLL3, etc.) and clinical outcomes including OS.","key_result":"SLFN11 expression followed a clear histologic gradient (median H-score: TC=0, AC=0, LCNEC=2.49, SCLC=35; p<0.001) and correlated with Ki67 (R²=0.187). In SCLC, high SLFN11 (≥ median) was associated with improved OS (13.9 vs 6.8 months; HR=0.48, 95% CI 0.26–0.90, p=0.020). SLFN11 was linked to ASCL1-high tumors across all subtypes but was not prognostic in TC/AC or LCNEC.","limitations":"- SCLC cohort was small (n=47), limiting statistical power for survival analysis.\n- Retrospective multicentre design with potential selection bias and IHC variability across centres.\n- Therapeutic implications (e.g., response to DNA-damaging agents) were not directly tested; clinical correlation is inferential.","practice_takeaway":"SLFN11 expression is highest in SCLC and lowest in carcinoids, suggesting its predictive value for DNA-damaging therapies is most relevant in SCLC, particularly in ASCL1-high tumors. Its role in LCNEC and carcinoids remains unclear and should not yet guide treatment decisions."}},{"doi":"10.1200/jco-26-01076","pmid":"42413070","title":"Brain-Only Progression After First-Line Therapy in Extensive-Stage Small Cell Lung Cancer: Treat the Sanctuary, Preserve the Backbone","journal_title":"Journal of Clinical Oncology","journal_issn":"0732-183X","published_at":"2026-07-07T00:00:00.000Z","url":"https://doi.org/10.1200/jco-26-01076","source_score":29,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-08-12T13:26:26.674Z","updated_at":"2026-08-12T13:26:26.674Z","tags":[{"paper_doi":"10.1200/jco-26-01076","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1200/jco-26-01076","tag_type":"category","value":"Oncology","value_numeric":null},{"paper_doi":"10.1200/jco-26-01076","tag_type":"condition","value":"Brain Metastases","value_numeric":null},{"paper_doi":"10.1200/jco-26-01076","tag_type":"condition","value":"Small Cell Lung Cancer","value_numeric":null},{"paper_doi":"10.1200/jco-26-01076","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1200/jco-26-01076","tag_type":"level_of_evidence","value":"7","value_numeric":null},{"paper_doi":"10.1200/jco-26-01076","tag_type":"modality","value":"Chemotherapy","value_numeric":null},{"paper_doi":"10.1200/jco-26-01076","tag_type":"modality","value":"Immunotherapy","value_numeric":null},{"paper_doi":"10.1200/jco-26-01076","tag_type":"modality","value":"Radiation Therapy","value_numeric":null},{"paper_doi":"10.1200/jco-26-01076","tag_type":"study_design","value":"Editorial / Commentary","value_numeric":null},{"paper_doi":"10.1200/jco-26-01076","tag_type":"warning","value":"Sex and sample size tags were omitted as no study population is described in this commentary.","value_numeric":null},{"paper_doi":"10.1200/jco-26-01076","tag_type":"warning","value":"The 'practice_changing' impact flag reflects the clinical strategy proposed, but the recommendation is expert opinion-level (Level 7 evidence) without supporting RCT data.","value_numeric":null},{"paper_doi":"10.1200/jco-26-01076","tag_type":"warning","value":"This is an editorial/commentary (DOI: 10.1200/jco-26-01076) with no original clinical trial data — no sample size, patient outcomes, or comparative statistics are available from the source text. Tags and summaries reflect the conceptual framework discussed rather than empirical findings.","value_numeric":null}],"summaries":{"what_studied":"This editorial/commentary addresses the clinical scenario of brain-only progression after first-line therapy in extensive-stage small cell lung cancer (ES-SCLC), focusing on whether systemic therapy should be continued ('preserving the backbone') while treating the CNS sanctuary site.","key_result":"The discussion centers on managing isolated CNS progression in ES-SCLC by directing local therapy to the brain while maintaining the current systemic regimen, rather than switching systemic agents prematurely.","limitations":"The source text is limited to a commentary/editorial without original trial data; no patient-level outcomes or comparative statistics are provided.","practice_takeaway":"When ES-SCLC patients progress in the brain only after first-line therapy, consider local CNS-directed treatment (e.g., radiation) while continuing the systemic backbone rather than immediately switching systemic regimens. This strategy treats the brain as a sanctuary site and may preserve effective systemic disease control."}},{"doi":"10.1016/j.jtho.2026.104052","pmid":null,"title":"PP01.54: SCLC Outcomes and Real-World Insight with Tarlatamab, a Multi-Center Experience","journal_title":"Journal of Thoracic Oncology","journal_issn":"1556-0864","published_at":"2026-07-03T00:00:00.000Z","url":"https://doi.org/10.1016/j.jtho.2026.104052","source_score":7,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":false,"crossref":true,"unpaywall":true},"created_at":"2026-07-17T13:24:14.674Z","updated_at":"2026-07-17T13:24:14.674Z","tags":[{"paper_doi":"10.1016/j.jtho.2026.104052","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1016/j.jtho.2026.104052","tag_type":"category","value":"Respiratory System","value_numeric":null},{"paper_doi":"10.1016/j.jtho.2026.104052","tag_type":"condition","value":"Small Cell Lung Cancer","value_numeric":null},{"paper_doi":"10.1016/j.jtho.2026.104052","tag_type":"generic","value":"tarlatamab","value_numeric":null},{"paper_doi":"10.1016/j.jtho.2026.104052","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1016/j.jtho.2026.104052","tag_type":"level_of_evidence","value":"4","value_numeric":null},{"paper_doi":"10.1016/j.jtho.2026.104052","tag_type":"modality","value":"Bispecific T-Cell Engager","value_numeric":null},{"paper_doi":"10.1016/j.jtho.2026.104052","tag_type":"study_design","value":"Real-World Evidence Study","value_numeric":null},{"paper_doi":"10.1016/j.jtho.2026.104052","tag_type":"warning","value":"Only the paper metadata (title, DOI, journal, date) was provided — no abstract, methods, results, or full text were available. All structured fields are based solely on the title and inferred study type; key numeric outcomes cannot be reported.","value_numeric":null},{"paper_doi":"10.1016/j.jtho.2026.104052","tag_type":"warning","value":"Sample size is unknown and could not be tagged.","value_numeric":null},{"paper_doi":"10.1016/j.jtho.2026.104052","tag_type":"warning","value":"Sex distribution of the study population is not determinable from available information.","value_numeric":null}],"summaries":{"what_studied":"This multi-center, real-world study evaluated outcomes of tarlatamab in patients with small cell lung cancer (SCLC), examining efficacy and tolerability outside of controlled trial settings.","limitations":"Real-world observational design limits causal inference; specific patient numbers, response rates, and survival data are not extractable from the abstract alone; potential selection bias across centers.","practice_takeaway":"Real-world multi-center data on tarlatamab in SCLC may help clinicians contextualize trial results in broader patient populations, but full quantitative outcomes are needed before firm practice conclusions can be drawn."}},{"doi":"10.1016/j.lungcan.2026.109501","pmid":"42361644","title":"Durvalumab plus etoposide–platinum in patients with epidermal growth factor receptor (EGFR)-mutated advanced NSCLC and neuroendocrine transformation after first-line osimertinib: ORCHARD","journal_title":"Lung Cancer","journal_issn":"0169-5002","published_at":"2026-06-18T00:00:00.000Z","url":"https://doi.org/10.1016/j.lungcan.2026.109501","source_score":10,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-28T13:27:06.742Z","updated_at":"2026-06-28T13:27:06.742Z","tags":[{"paper_doi":"10.1016/j.lungcan.2026.109501","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109501","tag_type":"brand","value":"Imfinzi","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109501","tag_type":"brand","value":"Tagrisso","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109501","tag_type":"category","value":"Respiratory System","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109501","tag_type":"condition","value":"Large Cell Neuroendocrine Carcinoma","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109501","tag_type":"condition","value":"Neuroendocrine Transformation","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109501","tag_type":"condition","value":"Non-Small Cell Lung Cancer","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109501","tag_type":"condition","value":"Small Cell Lung Cancer","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109501","tag_type":"generic","value":"durvalumab","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109501","tag_type":"generic","value":"etoposide","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109501","tag_type":"generic","value":"osimertinib","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109501","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109501","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109501","tag_type":"modality","value":"PD-L1 Inhibitor","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109501","tag_type":"modality","value":"Platinum-Based Chemotherapy","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109501","tag_type":"modality","value":"Topoisomerase II Inhibitor","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109501","tag_type":"sample_size","value":"n=14","value_numeric":14},{"paper_doi":"10.1016/j.lungcan.2026.109501","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109501","tag_type":"study_design","value":"Phase 2 Platform Trial (Single-Arm Module)","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109501","tag_type":"warning","value":"Platform trial module design may introduce patient selection differences compared to a standalone RCT.","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109501","tag_type":"warning","value":"Sample size of only 14 patients makes all efficacy estimates highly uncertain and limits any firm conclusions.","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109501","tag_type":"warning","value":"The primary endpoint used an 80% confidence interval rather than the conventional 95%, which is non-standard and should be interpreted cautiously.","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109501","tag_type":"warning","value":"The study is single-arm with no control group, so the incremental benefit of durvalumab over etoposide-platinum alone cannot be determined.","value_numeric":null}],"summaries":{"what_studied":"This phase 2 platform study (ORCHARD) evaluated durvalumab 1,500 mg IV Q3W plus etoposide-platinum Q3W (up to 4 cycles) in 14 patients with EGFR-mutated advanced NSCLC who developed neuroendocrine transformation (SCLC or large cell neuroendocrine carcinoma) after progression on first-line osimertinib.","key_result":"Confirmed ORR was 43% (80% CI: 24–63%; 6 partial responses); median DoR 4.3 months; median PFS 4.2 months (95% CI: 3.0–5.6); median OS 10.2 months (95% CI: 4.3–16.8). Grade ≥3 AEs occurred in 64% of patients, most commonly neutropenia.","limitations":"Extremely small sample size (n=14) limits statistical power and generalizability. Single-arm design with no comparator group. The 80% CI used for the primary ORR endpoint is non-standard and may overstate precision.","practice_takeaway":"Durvalumab plus etoposide-platinum yields a modest response (~43% ORR) in neuroendocrine-transformed EGFR-mutated NSCLC post-osimertinib, but responses are short-lived (median ~4 months) and most patients progress or die within a year. This regimen may serve as a bridge option while better therapies are sought for this rare resistance mechanism."}},{"doi":"10.1016/j.lungcan.2026.109472","pmid":"42217422","title":"Characteristics and clinical outcomes of a nationwide cohort of patients with small cell lung cancer following first-line treatment: Real-world evidence","journal_title":"Lung Cancer","journal_issn":"0169-5002","published_at":"2026-05-27T00:00:00.000Z","url":"https://doi.org/10.1016/j.lungcan.2026.109472","source_score":3,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-02T13:27:28.222Z","updated_at":"2026-06-02T13:27:28.222Z","tags":[{"paper_doi":"10.1016/j.lungcan.2026.109472","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109472","tag_type":"category","value":"Respiratory System","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109472","tag_type":"condition","value":"Small Cell Lung Cancer","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109472","tag_type":"impact_flag","value":"confirms_prior","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109472","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109472","tag_type":"modality","value":"Platinum-Based Chemotherapy","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109472","tag_type":"sample_size","value":"n=1284","value_numeric":1284},{"paper_doi":"10.1016/j.lungcan.2026.109472","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109472","tag_type":"study_design","value":"Multicenter Observational Cohort Study","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109472","tag_type":"warning","value":"Specific second-line or subsequent treatment regimens used in the cohort are not described in the abstract or results, limiting assessment of how treatment heterogeneity may have influenced survival outcomes.","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109472","tag_type":"warning","value":"The HR for PFS (HR 1.22, p=0.010) is reported without a confidence interval in the source text, reducing precision of that estimate.","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109472","tag_type":"warning","value":"The paper is published May 2026 but references a DOI with '2026' in the path — content is consistent with a recently published study, not a preprint, though this could not be independently verified.","value_numeric":null}],"summaries":{"what_studied":"A nationwide Spanish multicenter observational cohort (August 2016–June 2023) described characteristics and clinical outcomes of 1,284 SCLC patients (limited- and extensive-stage) following first-line oncological treatment, using the Spanish Thoracic Tumor Registry.","key_result":"Median OS was 16.5 months for CTFI ≥90 days vs. 10.2 months for CTFI <90 days (p<0.001); median PFS was 5.8 months (LS-SCLC) vs. 4.6 months (ES-SCLC, HR 1.22, p=0.010). Independent predictors of worse OS included ES-SCLC (HR 1.57), ECOG ≥2 (HR 1.43), while CTFI ≥90 (HR 0.34) and CTFI ≥180 (HR 0.20) were strongly protective.","limitations":"- Observational/registry design limits causal inference and may carry selection bias.\n- Ambispective design means historical data quality may vary across centers.\n- Second-line and beyond treatment details are not described, limiting interpretation of post-progression outcomes.","practice_takeaway":"Chemotherapy-free interval (CTFI) is one of the strongest prognostic tools in SCLC after first-line therapy — patients with CTFI ≥90 days live ~6 months longer. Performance status and disease stage at diagnosis should continue to guide treatment planning and clinical trial eligibility."}},{"doi":"10.1016/j.jtho.2026.103730","pmid":"42019833","title":"YAP1 defines an emergent, plastic population of relapsed small cell lung cancer","journal_title":"Journal of Thoracic Oncology","journal_issn":"1556-0864","published_at":"2026-04-23T00:00:00.000Z","url":"https://doi.org/10.2139/ssrn.5191737","source_score":40,"is_retracted":false,"is_open_access":true,"raw_metadata":{"ooir":{"day":"2026-04-23","doi":"10.1016/j.jtho.2026.103730","days":"30","issn":"1556-0864","rank":"3","field":"Clinical Medicine","score":"40","category":"Respiratory System","categories":["Respiratory System"],"_categories":["Respiratory System"]},"pubmed":{"doi":"10.1016/j.jtho.2026.103730","title":"YAP1 defines an emergent, plastic population of relapsed small cell lung cancer.","journal":"Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer","methods":"","results":"","abstract":"$30","keywords":["SCLC","YAP1","intratumoral heterogeneity","plasticity"],"pubmed_id":"42019833","conclusions":"","publication_date":"2026-04-23T00:00:00"},"crossref":{"DOI":"10.1016/j.jtho.2026.103730","URL":"https://doi.org/10.1016/j.jtho.2026.103730","ISSN":["1556-0864"],"link":[{"URL":"https://api.elsevier.com/content/article/PII:S1556086426001838?httpAccept=text/xml","content-type":"text/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https://api.elsevier.com/content/article/PII:S1556086426001838?httpAccept=text/plain","content-type":"text/plain","content-version":"vor","intended-application":"text-mining"}],"page":"103730","type":"journal-article","issue":null,"score":1,"title":["YAP1 defines an emergent, plastic population of relapsed small cell lung cancer"],"author":[{"given":"C. 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Published by Elsevier Inc. on behalf of International Association for the Study of Lung Cancer."}],"deposited":{"date-time":"2026-04-23T23:06:06Z","timestamp":1776985566000,"date-parts":[[2026,4,23]]},"issn-type":[{"type":"print","value":"1556-0864"}],"published":{"date-parts":[[2026,4]]},"publisher":"Elsevier BV","reference":null,"short-title":[],"update-policy":"https://doi.org/10.1016/elsevier_cm_policy","alternative-id":["S1556086426001838"],"article-number":"103730","content-domain":{"domain":["jto.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"original-title":[],"container-title":["Journal of Thoracic Oncology"],"published-print":{"date-parts":[[2026,4]]},"reference-count":0,"published-online":null,"references-count":0,"short-container-title":["Journal of Thoracic Oncology"],"is-referenced-by-count":0},"unpaywall":{"doi":"10.1016/j.jtho.2026.103730","is_oa":true,"title":"YAP1 Defines an Emergent, Plastic Population of Relapsed Small Cell Lung Cancer","updated":"2026-04-30T09:32:37+00:00","published_date":"2025-01-01","best_oa_location":{"url":"https://doi.org/10.2139/ssrn.5191737","pmh_id":null,"url_for_pdf":null,"url_for_landing_page":"https://doi.org/10.2139/ssrn.5191737"}}},"created_at":"2026-05-07T22:50:01.410Z","updated_at":"2026-05-14T15:13:26.918Z","tags":[{"paper_doi":"10.1016/j.jtho.2026.103730","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1016/j.jtho.2026.103730","tag_type":"category","value":"Respiratory System","value_numeric":null},{"paper_doi":"10.1016/j.jtho.2026.103730","tag_type":"condition","value":"Large Cell Neuroendocrine Carcinoma","value_numeric":null},{"paper_doi":"10.1016/j.jtho.2026.103730","tag_type":"condition","value":"Small Cell Lung Cancer","value_numeric":null},{"paper_doi":"10.1016/j.jtho.2026.103730","tag_type":"generic","value":"YAP1","value_numeric":null},{"paper_doi":"10.1016/j.jtho.2026.103730","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1016/j.jtho.2026.103730","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1016/j.jtho.2026.103730","tag_type":"modality","value":"Biomarker / Transcriptional Subtyping","value_numeric":null},{"paper_doi":"10.1016/j.jtho.2026.103730","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1016/j.jtho.2026.103730","tag_type":"study_design","value":"Translational/Preclinical Study","value_numeric":null},{"paper_doi":"10.1016/j.jtho.2026.103730","tag_type":"warning","value":"No explicit sample sizes (N) are reported in the abstract; the sample_size tag was omitted. Study design sits between translational and observational — level of evidence is estimated at 5.","value_numeric":null},{"paper_doi":"10.1016/j.jtho.2026.103730","tag_type":"warning","value":"Publication date (2026-04-20) is in the future relative to today's date (May 07, 2026), suggesting this is a very recently published or ahead-of-print article.","value_numeric":null},{"paper_doi":"10.1016/j.jtho.2026.103730","tag_type":"warning","value":"The impact_flag 'practice_changing' reflects the clinical implication of shifting therapeutic targeting at relapse, but this is based on translational/preclinical evidence — no interventional trial data are presented.","value_numeric":null},{"paper_doi":"10.1016/j.jtho.2026.103730","tag_type":"warning","value":"YAP1 is described as a protein/transcriptional marker, not a pharmacological agent; it is tagged under 'generic' as a molecular target for clarity, though it is not a traditional drug.","value_numeric":null}],"summaries":{"what_studied":"This study characterized YAP1-expressing cell populations in relapsed/treatment-resistant SCLC using circulating tumor DNA, circulating tumor cells, and core needle biopsies from patients and preclinical models after failure of standard-of-care therapies.","key_result":"YAP1-positive cells are largely absent in treatment-naïve SCLC but emerge with acquired resistance, exhibiting drug-tolerant persister features (senescence, stemness, plasticity) and shifting from an SCLC-like to a large-cell neuroendocrine carcinoma (LCNEC)-like phenotype — losing surface targets DLL3 and SEZ6 while gaining B7-H3 and TROP2 enrichment.","limitations":"No specific sample sizes are reported; findings rely heavily on preclinical models alongside clinical specimens, limiting direct clinical generalizability. The study is primarily descriptive/translational without interventional data on targeting YAP1-positive cells.","practice_takeaway":"At SCLC relapse, consider that tumors may shift to an LCNEC-like phenotype where DLL3- or SEZ6-targeted therapies may be less effective, while B7-H3- and TROP2-directed agents could be more relevant. Biopsy at relapse may help guide target selection."}},{"doi":"10.1016/j.lungcan.2026.109390","pmid":"41930543","title":"Real-world multi-institution analysis of tarlatamab in patients with small cell lung cancer","journal_title":"Lung Cancer","journal_issn":"0169-5002","published_at":"2026-03-31T00:00:00.000Z","url":"https://doi.org/10.1016/j.lungcan.2026.109390","source_score":20,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-05-07T22:50:01.795Z","updated_at":"2026-05-07T22:50:01.795Z","tags":[{"paper_doi":"10.1016/j.lungcan.2026.109390","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109390","tag_type":"brand","value":"Imdelltra","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109390","tag_type":"category","value":"Respiratory System","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109390","tag_type":"condition","value":"Small Cell Lung Cancer","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109390","tag_type":"generic","value":"tarlatamab","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109390","tag_type":"impact_flag","value":"confirms_prior","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109390","tag_type":"level_of_evidence","value":"4","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109390","tag_type":"modality","value":"Bispecific T-Cell Engager","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109390","tag_type":"sample_size","value":"n=102","value_numeric":102},{"paper_doi":"10.1016/j.lungcan.2026.109390","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109390","tag_type":"study_design","value":"Retrospective Cohort Study","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109390","tag_type":"warning","value":"The brand name 'Imdelltra' is assumed based on tarlatamab's FDA-approved trade name; the paper does not explicitly state it.","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109390","tag_type":"warning","value":"The trial-eligible evaluable subgroup size (n=34) is small, so between-group comparisons should be interpreted cautiously.","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109390","tag_type":"warning","value":"Time on treatment is used as a surrogate for PFS; actual progression-free or overall survival data are not reported.","value_numeric":null}],"summaries":{"what_studied":"A multicenter retrospective cohort study across 3 US institutions evaluated real-world outcomes of tarlatamab in 102 SCLC patients (May 2024–June 2025), comparing those who would have met clinical trial eligibility criteria (n=40 evaluable) versus those who would not (n=60, 59%), defined by poor PS, untreated brain mets, organ dysfunction, prior pneumonitis, and other comorbidities.","key_result":"Trial-eligible patients had higher rates of partial response or stable disease (70% vs 43%) and longer median time on treatment (4.8 vs 2.1 months; p=0.06). ICANS was significantly more common in trial-ineligible patients (33% vs 14%; p=0.038), while CRS rates were similar between groups (~60%).","limitations":"- Retrospective design with investigator-assessed response (no central review) limits outcome reliability.\n- Small sample size (n=102; only 80 evaluable for response) reduces statistical power.\n- Predominantly white cohort (92%) limits generalizability to diverse populations.","practice_takeaway":"Tarlatamab can be used in SCLC patients who would not have qualified for clinical trials, but expect lower response rates and higher ICANS risk in this group. Monitor trial-ineligible patients especially closely for neurologic toxicity."}},{"doi":"10.1016/j.lungcan.2026.108913","pmid":"41534317","title":"SEZ6 expression and lineage plasticity in small cell lung cancer and transformed non-small cell lung cancer","journal_title":"Lung Cancer","journal_issn":"0169-5002","published_at":"2026-01-15T00:00:00.000Z","url":"https://doi.org/10.1016/j.lungcan.2026.108913","source_score":13,"is_retracted":false,"is_open_access":false,"raw_metadata":{"ooir":{"day":"2026-01-12","doi":"10.1016/j.lungcan.2026.108913","days":"14","issn":"0169-5002","rank":"4","field":"Clinical Medicine","score":"13","category":"Respiratory System","categories":["Respiratory System"],"_categories":["Respiratory System"]},"pubmed":{"doi":"10.1016/j.lungcan.2026.108913","title":"SEZ6 expression and lineage plasticity in small cell lung cancer and transformed non-small cell lung cancer.","journal":"Lung cancer (Amsterdam, Netherlands)","methods":"","results":"RNA sequencing was performed on 1318 SCLC and 2218 NE samples. Median SEZ6expression was higher in SCLC (39.7 transcripts per million (TPM)) than in NE tumors (20.8 TPM, p<0.0001) and NSCLC (1.34 TPM, p<0.001). Among NE tumors, median SEZ6 expression was highest in prostate (52.0 TPM, p=0.0016 vs SCLC) and lowest in adrenal gland tumors (1.2 TPM, p<0.0001 vs SCLC). In SCLC,SEZ6expression was positively correlated with ASCL1(p=0.44, p<0.0001) andNEUROD1(p=0.16, p<0.0001) expression but notPOU2F3(p=-0.04, p=0.1253). Median survival was longest in SEZ6-Q2 for both SCLC and NE (13.0 mos. and 33.7 mos., respectively). NSCLC-to-SCLC transformation samples showed numerically higher SEZ6 expression post-transformation (median: 86.2 vs 2.4 TPM).","abstract":"$31","keywords":["Lineage plasticity","NSCLC","Neuroendocrine tumors","SCLC","SEZ6"],"pubmed_id":"41534317","conclusions":"","publication_date":"2026-01-15T00:00:00"},"crossref":{"DOI":"10.1016/j.lungcan.2026.108913","URL":"https://doi.org/10.1016/j.lungcan.2026.108913","ISSN":["0169-5002"],"link":[{"URL":"https://api.elsevier.com/content/article/PII:S0169500226000085?httpAccept=text/xml","content-type":"text/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https://api.elsevier.com/content/article/PII:S0169500226000085?httpAccept=text/plain","content-type":"text/plain","content-version":"vor","intended-application":"text-mining"}],"page":"108913","type":"journal-article","issue":null,"score":1,"title":["SEZ6 expression and lineage plasticity in small cell lung cancer and transformed non-small cell lung cancer"],"author":[{"given":"Jennifer A.","family":"Marks","sequence":"first","affiliation":[]},{"given":"Kieran","family":"Sweeney","sequence":"additional","affiliation":[]},{"given":"Andrew","family":"Elliott","sequence":"additional","affiliation":[]},{"given":"Brinda","family":"Gupta","sequence":"additional","affiliation":[]},{"given":"Ari","family":"VanderWalde","sequence":"additional","affiliation":[]},{"given":"Sonam","family":"Puri","sequence":"additional","affiliation":[]},{"given":"Misty Dawn","family":"Shields","sequence":"additional","affiliation":[]},{"given":"Jorge J.","family":"Nieva","sequence":"additional","affiliation":[]},{"given":"Heloisa P.","family":"Soares","sequence":"additional","affiliation":[]},{"given":"Patrick C.","family":"Ma","sequence":"additional","affiliation":[]},{"given":"Balazs","family":"Halmos","sequence":"additional","affiliation":[]},{"given":"Stephen V.","family":"Liu","sequence":"additional","affiliation":[]}],"issued":{"date-parts":[[2026,3]]},"member":"78","prefix":"10.1016","source":"Crossref","volume":"213","created":{"date-time":"2026-01-10T16:01:50Z","timestamp":1768060910000,"date-parts":[[2026,1,10]]},"indexed":{"date-time":"2026-01-14T05:20:12Z","timestamp":1768368012428,"date-parts":[[2026,1,14]]},"license":[{"URL":"https://www.elsevier.com/tdm/userlicense/1.0/","start":{"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000,"date-parts":[[2026,3,1]]},"delay-in-days":0,"content-version":"tdm"},{"URL":"https://www.elsevier.com/legal/tdmrep-license","start":{"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000,"date-parts":[[2026,3,1]]},"delay-in-days":0,"content-version":"tdm"},{"URL":"https://doi.org/10.15223/policy-017","start":{"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000,"date-parts":[[2026,3,1]]},"delay-in-days":0,"content-version":"stm-asf"},{"URL":"https://doi.org/10.15223/policy-037","start":{"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000,"date-parts":[[2026,3,1]]},"delay-in-days":0,"content-version":"stm-asf"},{"URL":"https://doi.org/10.15223/policy-012","start":{"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000,"date-parts":[[2026,3,1]]},"delay-in-days":0,"content-version":"stm-asf"},{"URL":"https://doi.org/10.15223/policy-029","start":{"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000,"date-parts":[[2026,3,1]]},"delay-in-days":0,"content-version":"stm-asf"},{"URL":"https://doi.org/10.15223/policy-004","start":{"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000,"date-parts":[[2026,3,1]]},"delay-in-days":0,"content-version":"stm-asf"}],"subject":[],"abstract":null,"language":"en","relation":{},"resource":{"primary":{"URL":"https://linkinghub.elsevier.com/retrieve/pii/S0169500226000085"}},"subtitle":[],"assertion":[{"name":"publisher","label":"This article is maintained by","value":"Elsevier"},{"name":"articletitle","label":"Article Title","value":"SEZ6 expression and lineage plasticity in small cell lung cancer and transformed non-small cell lung cancer"},{"name":"journaltitle","label":"Journal Title","value":"Lung Cancer"},{"name":"articlelink","label":"CrossRef DOI link to publisher maintained version","value":"https://doi.org/10.1016/j.lungcan.2026.108913"},{"name":"content_type","label":"Content Type","value":"article"},{"name":"copyright","label":"Copyright","value":"© 2026 Elsevier B.V. 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