bims-necame 2026-02-08 papers

bims-necame

Biomed News

on Metabolism in small cell neuroendocrine cancers

Issue of 2026–02–08
thirteen papers selected by
Grigor Varuzhanyan, UCLA

Next-generation anti-DLL3 radiopharmaceuticals targeting high-grade neuroendocrine lung and prostate cancers.
The flavonoid GL-V9 induces oxidative stress mediated apoptosis in small cell lung cancer by promoting STEAP3 degradation.
Anti-AMPAR limbic encephalitis as the initial presentation of metastatic small cell cancer.
Prognostic value of the baseline triglyceride-glucose-body mass index in small cell lung cancer undergoing chemoimmunotherapy: A multicenter retrospective study.
Genomic heterogeneity and clinical implications in gastrointestinal neuroendocrine carcinoma: MYC and KRAS as predictive biomarkers.
Characterization of tumor-associated microbiome in multifocal small intestinal neuroendocrine tumors (SI-NETs).
Gastroenteropancreatic neuroendocrine neoplasms in children and adults: a comparative review.
Androgen Receptor Positive EWSR1::FEV-Rearranged Prostatic Ewing Sarcoma Mimicking High-Grade Neuroendocrine Carcinoma.
Head-to-Head Comparison of [18F]MFBG and [68Ga]Ga-DOTA-TATE PET/CT in Suspected Recurrent/Refractory Neuroblastoma: Prospective Single-center Analysis.
Long-term survival in extensive-stage small cell lung cancer: a case report on the integration of interventional bronchoscopy and systemic immunotherapy.
Structural and functional insights into CD3 bispecific antibodies targeting DLL3 in cancer immunotherapy.
Pseudotime-Based derivation of a PET-Based metabolic progression index for prognostic stratification in Extensive-Stage SCLC.
Real-world evaluation of immunotherapy in multi-line treatment of small cell lung cancer.

Proc Natl Acad Sci U S A. 2026 Feb 10. 123(6): e2505785123

Next-generation anti-DLL3 radiopharmaceuticals targeting high-grade neuroendocrine lung and prostate cancers.

Salomon Tendler, Roberto De Gregorio, Paul Balderes, Alexa L Michel, Tran T Hoang, David Bauer, Kathryn M Tully, Joshua A Korsen, Ivo C Lorenz, Abdul G Khan, Lukas Carter, Olivia Vergnolle, Irina V Lebedeva, Elisabeth K Nyakatura, Lisa Bodei, Michael J Morris, John T Poirier, Charles M Rudin, Jason S Lewis.

  Delta-like ligand 3 (DLL3) is a tumor-selective cell surface protein upregulated in high-grade neuroendocrine tumors, including small-cell lung cancer (SCLC) and neuroendocrine prostate cancer (NEPC). Here, we report on the development of anti-DLL3 radioimmunoconjugates for use as either a diagnostic imaging tracer based on the positron-emitter zirconium-89 (89Zr) or a therapeutic agent utilizing the beta-emitter lutetium-177 (177Lu). To begin, we generated a panel of human monoclonal antibodies targeting human DLL3 by immunizing transgenic mice engineered with a human immunoglobulin repertoire. The panel was extensively screened to identify high-affinity internalizing monoclonal antibodies (mAbs) recognizing a diversity of DLL3 epitopes. Select mAbs were reformatted as fully human Fab-arm exchange-deficient IgG4 to reduce effector function and then produced by recombinant methods. A pilot immunoPET study was performed in athymic female nude mice bearing human NCI-H82 SCLC tumors to nominate a lead candidate. ImmunoPET identified [89Zr]Zr-DFO-TDI-Y-010 as the top-performing diagnostic tracer, with excellent in vivo biodistribution and tumor-to-background-organ ratios consistently >4. Therapeutic studies with [177Lu]Lu-CHX-A"-DTPA-TDI-Y-010 demonstrated strong antitumor effects, significantly improving (P <0.05) overall survival compared with the benchmark clone [177Lu]Lu-CHX-A"-DTPA-SC16.56 in two SCLC tumor models (NCI-H82 and Lu149) and achieving comparable overall survival in a NEPC tumor model.

Keywords:  DLL3; Lutetium-177; NEPC; SCLC; Theranostics

DOI:  https://doi.org/10.1073/pnas.2505785123
Free Radic Biol Med. 2026 Feb 02. pii: S0891-5849(26)00086-9. [Epub ahead of print]247 1-14

The flavonoid GL-V9 induces oxidative stress mediated apoptosis in small cell lung cancer by promoting STEAP3 degradation.

Jiawei Zhao, Xuefeng Zhang, Yanqing Zhou, Dongsheng Bai, Jiaying Du, Chen Zhou, Chunyang Gu, Yuxiang Wang, Yuan Gao, Na Lu, Yue Zhao.

  Small cell lung cancer (SCLC) is an aggressive malignancy characterized by limited therapeutic options. In this study, we identified GL-V9 as a potent anti-SCLC agent that induces apoptosis through oxidative stress. GL-V9 significantly reduced SCLC cell viability in a dose-dependent manner and triggered apoptosis both in vitro and in xenograft models. Mechanistically, GL-V9 increased reactive oxygen species (ROS) levels and lipid peroxidation while impairing mitochondrial function, suggesting that its cytotoxic effects are mediated by oxidative stress. Drug-target interaction analyses revealed that GL-V9 directly binds to STEAP3, a key regulator of iron metabolism, and promotes its degradation via the ubiquitin-proteasome pathway. The loss of STEAP3 disrupted iron homeostasis and exacerbated oxidative stress. In contrast, STEAP3 overexpression attenuated ROS accumulation, mitochondrial damage, and apoptosis both in vitro and in vivo. Further investigation demonstrated that STEAP3 degradation decreased the stability of CISD2, a [2Fe-2S] cluster-containing mitochondrial protein essential for redox balance. GL-V9 downregulated CISD2 in a STEAP3-dependent manner, and restoring CISD2 expression significantly rescued cells from GL-V9-induced oxidative stress and apoptosis. Clinically, both STEAP3 and CISD2 are upregulated in SCLC tumors, and their elevated expression correlates with poor patient survival. Co-expression analysis associated these proteins with pathways involved in oxidative stress and mitochondrial dysfunction. Overall, these findings suggest that GL-V9 induces apoptosis in SCLC by targeting STEAP3 for proteasomal degradation, thereby disrupting the STEAP3-CISD2 axis and promoting oxidative stress-driven cell death. This study identifies a previously unrecognized redox regulatory pathway in SCLC and proposes a potential therapeutic strategy centered on selective induction of oxidative stress.

Keywords:  Apoptosis; CISD2; GL-V9; Oxidative stress; STEAP3

DOI:  https://doi.org/10.1016/j.freeradbiomed.2026.02.001
BMJ Case Rep. 2026 Feb 02. pii: e268896. [Epub ahead of print]19(2):

Anti-AMPAR limbic encephalitis as the initial presentation of metastatic small cell cancer.

Chandra L Kakarala, Vishal Mehta, Nicole Lisek, Zhonglin Hao.

  A small proportion of small cell lung cancer (SCLC) presents as paraneoplastic limbic encephalitis (PLE). The most implicated antibody is anti-Hu, but others such as anti-ampiphysin, anti-CRMP5 and anti-SOX1 have been frequently detected. Autoimmune encephalitis mediated by antibodies against α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) is a rare but important neurological complication of SCLC. The incidence of SCLC presenting with anti-AMPAR antibody PLE is extremely low. Our case illustrates a rare presentation of SCLC with an intention to highlight the importance of evaluating for malignancy and associated paraneoplastic syndromes in patients with unexplained encephalopathy.

Keywords:  Lung cancer (oncology); Neurology

DOI:  https://doi.org/10.1136/bcr-2025-268896
Cancer Treat Res Commun. 2026 Jan 28. pii: S2468-2942(26)00029-8. [Epub ahead of print]46 101118

Prognostic value of the baseline triglyceride-glucose-body mass index in small cell lung cancer undergoing chemoimmunotherapy: A multicenter retrospective study.

Dongyong Zhu, Yusheng Guo, Weiwei Liu, Bingxin Gong, Yi Li, Shanshan Jiang, Yuanxi Li, Lianwei Miao, Lingli Li, Lian Yang.

   BACKGROUND: The prognostic role of the triglyceride-glucose-body mass index (TyG-BMI), a surrogate marker for insulin resistance, in small cell lung cancer (SCLC) patients treated with immune checkpoint inhibitors remains undefined.
METHODS: In this multicenter retrospective study, SCLC patients who initiated first-line chemoimmunotherapy or chemotherapy alone between March 2015 and December 2023 were enrolled. The association between baseline TyG-BMI index and survival was analyzed using Kaplan-Meier and Cox regression methods. A prognostic nomogram was developed and validated via time-dependent ROC and calibration analyses.
RESULTS: Among 437 patients, a low TyG-BMI index was significantly associated with improved overall survival (OS) in the chemoimmunotherapy cohort (P < 0.001). In the chemotherapy-alone cohort, a high index predicted worse progression-free survival (PFS, P = 0.031). The TyG-BMI index was an independent prognostic factor for both PFS (HR = 1.44, P = 0.005) and OS (HR = 1.42, P = 0.002). The nomogram demonstrated good predictive accuracy for OS (9-18 month AUCs: 0.72-0.73; C-index=0.66, 95 % CI: 0.63-0.69) and was well-calibrated.
CONCLUSION: The baseline TyG-BMI index is a treatment-specific prognostic biomarker. A low index identifies SCLC patients most likely to achieve long-term survival benefit from chemoimmunotherapy, offering a practical tool for risk stratification and therapeutic guidance.

Keywords:  Immune checkpoint inhibitors; Prognosis; Small-cell lung cancer; Triglyceride-glucose-body mass index

DOI:  https://doi.org/10.1016/j.ctarc.2026.101118
ESMO Gastrointest Oncol. 2025 Sep;9 100193

Genomic heterogeneity and clinical implications in gastrointestinal neuroendocrine carcinoma: MYC and KRAS as predictive biomarkers.

T Ozato, Y Kono, H Yamamoto, A Hirasawa, D Ennishi, S Tomida, S Toyooka, M Otsuka.

   Background: Gastrointestinal neuroendocrine carcinoma (GI-NEC) is a highly lethal malignancy with significant clinical and molecular heterogeneities. Given its rarity, large-scale studies are lacking, and research on its genomic landscape remains limited. Consequently, to date, no reliable biomarkers for treatment selection and prognosis have been identified. To address this gap in knowledge, we investigated the clinical impact of genomic features on GI-NEC.
Methods: We retrospectively analyzed 261 patients with advanced or recurrent GI-NEC using a nationwide comprehensive genomic profiling database. We analyzed the correlation between platinum-based chemotherapy and the clinical outcomes in 152 patients, focusing on time to treatment failure and overall survival. We integrated the sequencing data with clinical information to identify potential biomarkers predictive of chemotherapy efficacy and survival.
Results: In the GI-NECs analyzed, TP53 (85.8%) and RB1 (38.7%) were the most frequently mutated genes. Genetic alterations varied according to the primary tumor site, exhibiting co-occurring and mutually exclusive mutations. Notably, RB1 deficiency and CCNE1 amplification were mutually exclusive, particularly in esophageal and gastric NEC. MYC amplification was associated with a shorter time to treatment failure (P = 0.050), while KRAS alterations were significantly associated with a shorter overall survival (P = 0.001) in recurrent or unresectable GI-NECs.
Conclusion: This study underscored the clinical and genomic heterogeneity of GI-NEC and highlighted the need to integrate genomic and clinical data to achieve personalized medicine. MYC amplification and KRAS alterations may serve as valuable predictors of treatment response and prognosis in patients with GI-NEC.

Keywords:  KRAS alterations; MYC amplification; comprehensive genomic profiling; gastrointestinal neuroendocrine carcinoma; platinum-based chemotherapy

DOI:  https://doi.org/10.1016/j.esmogo.2025.100193
ESMO Gastrointest Oncol. 2025 Sep;9 100229

Characterization of tumor-associated microbiome in multifocal small intestinal neuroendocrine tumors (SI-NETs).

I T Lee, A Dohlman, T Gao, Z Zhang, Y Kasai, G E Kim, C Thirlwell, E Nakakura, M Meyerson, N Mäkinen.

   Background: Small intestinal neuroendocrine tumors (SI-NETs) are among the most common neoplasms of the small bowel; however, the molecular mechanisms underlying their pathogenesis are largely unknown. The multifocal nature of SI-NETs, their putative distinct genomic origins, and their enrichment in the distal ileum led us to hypothesize that environmental factors, such as pathogenic organisms, might play a role in the development of these lesions.
Materials and methods: To study the tumor-associated microbiome of multifocal SI-NETs and its potential role in pathogenesis, we used matched whole genome and transcriptome sequencing data from a cohort of 10 multifocal SI-NET patients, including 70 primary ileal NETs and their matched normal ileal mucosa and/or whole blood specimens.
Results: Microbial communities in the ileal tissue samples were primarily composed of bacteria. The most abundant genera included well-known gastrointestinal, oral, and mucosal bacteria. Ileal tissue samples from individual patients contained distinct patient-specific microbial communities. Although the microbiota composition did not show significant differences between ileal NET and normal ileal tissues, genus Propionibacterium was found to be enriched in the normal tissue specimens.
Conclusions: This study comprehensively characterizes the tissue-resident ileal microbiome of multifocal SI-NET patients. We provide clear evidence that the microbial communities in the ileum are largely patient specific, whereas our genus-level analyses suggest that SI-NET pathogenesis is unlikely driven by individual microorganisms present in the tumors at the time of surgical resection.

Keywords:  ileum; multifocality; small intestinal neuroendocrine tumors; tumor microbiome

DOI:  https://doi.org/10.1016/j.esmogo.2025.100229
Front Endocrinol (Lausanne). 2025 ;16 1736543

Gastroenteropancreatic neuroendocrine neoplasms in children and adults: a comparative review.

Michaela Kuhlen, Rainer Claus, Marianne E Pavel, Marina Kunstreich, Nehara Begum, Constantin Lapa, Antje Redlich.

   Background: Gastroenteropancreatic neuroendocrine neoplasms (GEPNENs) represent a biologically heterogeneous tumor group that is increasingly recognized in adults but remains exceptionally rare in children. While adult management is guided by evidence-based recommendations, pediatric practice relies mainly on registry data and extrapolation. A direct comparison is needed to identify shared principles, highlight divergences, and define research priorities.
Methods: We performed a structured literature review of pediatric GEPNENs (pancreatic, gastrointestinal [excluding appendix], and neuroendocrine neoplasms of unknown primary) and contrasted these findings with adult guidelines (ENETS 2023-2024, ESMO 2020-2024, ASCO 2023, NANETS 2018-2023) and pivotal clinical trials. Domains analyzed included epidemiology, clinical presentation, histological and molecular characteristics, treatment strategies, outcomes, and guideline frameworks.
Results: Pediatric GEPNENs are strongly enriched for hereditary cancer predisposition syndromes (MEN1, VHL, NF1, TSC) and show a predominance of well-differentiated NET G1-G2. In contrast, adults exhibit the full spectrum of NET G1-3 and NEC G3. Somatostatin receptor (SSTR) expression is frequent in both pediatric and adult NETs, supporting the use of somatostatin analogues (SSAs) and peptide receptor radionuclide therapy (PRRT) in advanced disease; SSTR expression declines with increasing grade. Surgical resection remains the only curative option in both populations, with pediatric practice prioritizing organ preservation and minimization of late effects. In adults, systemic therapy sequencing is structured by randomized trials, whereas pediatric use of systemic therapies is adapted case-by-case, with emerging but still limited evidence. Survival in localized pediatric NETs exceeds 90%, but remains poor in metastatic and high-grade disease, similar to adults.
Conclusions: Although histological frameworks are shared, pediatric GEPNENs differ from adult disease in genetics, site distribution, functional status, and survivorship challenges. Adult evidence may be cautiously adapted to pediatrics, but pediatric-specific guidelines and collaborative research are urgently needed to address unique biological and clinical features and to harmonize long-term care.

Keywords:  adults; children and adolescents; gastroenteropancreatic; management; neuroendocrine neoplasms

DOI:  https://doi.org/10.3389/fendo.2025.1736543
Int J Surg Pathol. 2026 Feb 03. 10668969251410957

Androgen Receptor Positive EWSR1::FEV-Rearranged Prostatic Ewing Sarcoma Mimicking High-Grade Neuroendocrine Carcinoma.

Tanisha Martheswaran, Ezra Baraban, John Gross, Andres Matoso.

  Ewing sarcoma (ES) is a rare aggressive neoplasm that is the second most common primary bone tumor of childhood and adolescence, with less frequent extraskeletal presentations. ES with EWSR1::FEV translocation is extremely rare and is characterized by extraskeletal location, varying morphology and immunophenotype, and an aggressive clinical course. We present a prostatic ES confirmed by EWSR1::FEV fusion, detailing its clinical presentation, histopathologic and immunophenotypic features, molecular profile, and management. A man in his mid-50s presented with urinary frequency and difficulty voiding. Imaging revealed a 4.4 cm prostatic mass with bladder invasion and right iliac lymphadenopathy. Serum PSA was within normal limits. Biopsy demonstrated a poorly differentiated epithelioid neoplasm with neuroendocrine features. Immunohistochemistry showed strong expression of keratins AE1/3 and CAM5.2, chromogranin, synaptophysin, NKX2.2, and CD99 (weak), while PSA was negative. NKX3.1 was focally positive in rare tumor cells and Ki67 was approximately 35%. Perineural invasion and intraductal spread were noted. The tumor was initially interpreted as poorly differentiated carcinoma with neuroendocrine features. The patient underwent radical prostatectomy, revealing a 5.5 cm tumor with perineural and lymphovascular invasion, and nodal metastasis. Next-generation sequencing confirmed an EWSR1::FEV fusion, establishing the diagnosis of ES. Immunostain for androgen receptor was strongly and diffusely positive in the primary tumor and in the nodal metastasis, which together with focal staining for NKX3.1 were suggestive of primary prostatic origin and invited consideration of androgen deprivation therapy. This report highlights a rare prostatic Ewing-family sarcoma harboring an EWSR1::FEV fusion and immunophenotypic features that mimic a neuroendocrine carcinoma.

Keywords:  Ewing sarcoma; adamantinoma-like Ewing sarcoma; neuroendocrine; prostate

DOI:  https://doi.org/10.1177/10668969251410957
Clin Nucl Med. 2026 Jan 20.

Head-to-Head Comparison of [18F]MFBG and [68Ga]Ga-DOTA-TATE PET/CT in Suspected Recurrent/Refractory Neuroblastoma: Prospective Single-center Analysis.

Qinfeng Xu, Yueran Chen, Jieping Song, Wanhua Guo, Guoqiang Shao.

   INTRODUCTION: To prospectively compare the diagnostic value of 18F-meta-fluorobenzylguanidine ([18F]MFBG) and [68Ga]Ga-DOTA-TATE PET/CT in pediatric patients with suspected recurrent/refractory neuroblastoma.
METHODS: Between December 2024 and March 2025, 28 children (18 boys, 10 girls; mean age ± SD 4.8 ± 2.5 y) underwent both tracers within 1 week at a single institution. Physiological biodistribution, image quality, lesion conspicuity, semiquantitative uptake (SUVmax), Curie score, and response classification were analyzed side-by-side.
RESULTS: [18F]MFBG showed higher background than [68Ga]Ga-DOTA-TATE in skeletal muscle but lower activity in articular metaphyses, pituitary, and kidneys. Heterogeneous distribution of [18F]MFBG was more common in the liver, while notable uptake differences were observed in the pancreas with [68Ga]Ga-DOTA-TATE. Patient-level concordance was high (both scans positive in 15, negative in 7); discordance occurred in 6 patients (2 MFBG+/DOTA-TATE-, 4 MFBG-/DOTA-TATE+). Region-level analysis encompassed 86 relapsed or metastatic regions in 17 patients. [18F]MFBG detected 80 regions (sensitivity 93.0%, specificity 96.4%, AUC 0.947), whereas [68Ga]Ga-DOTA-TATE detected 82 (sensitivity 95.4%, specificity 86.6%, AUC 0.910). Superior specificity of [18F]MFBG stemmed largely from its higher uptake in bone/marrow metastases compared with [68Ga]Ga-DOTA-TATE (median SUVmax 5.21 vs. 2.90, P <0.0001). Region-level concordance revealed 78 concordant positive sites and 39 discordant sites (9 MFBG+/DOTA-TATE-, 30 MFBG-/DOTA-TATE+). Aggregate Curie scores were identical (155 each). Because uptake patterns were complementary, combining both tracers improved visual confidence in heterogeneous tumors and refined treatment-response categorization.
CONCLUSIONS: [18F]MFBG and [68Ga]Ga-DOTA-TATE PET/CT imaging are effective for evaluating relapsed or metastatic neuroblastoma because they show lower uptake in normal organs and benign lesions. The 2 imaging modalities offer complementary value in tumor detection and assessment of treatment response due to tumor spatial heterogeneity.

Keywords:  PET; [18F]MFBG; [68Ga]Ga-DOTA-TATE; modified curies score system; neuroblastoma

DOI:  https://doi.org/10.1097/RLU.0000000000006308
Front Oncol. 2025 ;15 1733112

Long-term survival in extensive-stage small cell lung cancer: a case report on the integration of interventional bronchoscopy and systemic immunotherapy.

Ganxiu Deng, Shixuan Yan, Victor Bwembya, Xiaoping Zhu, Zhibing Luo, Changwen Deng.

  Small cell lung cancer (SCLC) is an aggressive malignancy with a poor prognosis, particularly in patients with extensive-stage disease (ES-SCLC). Although the incorporation of immune checkpoint inhibitors (ICIs) into first-line chemotherapy has modestly improved survival, long-term disease control remains rare. Central airway obstruction (CAO), a common complication of advanced SCLC, often leads to respiratory failure and interruption of systemic therapy, further compromising outcomes. We report the case of a 65-year-old man diagnosed with ES-SCLC based on endobronchial ultrasound-guided transbronchial needle aspiration. The patient initially responded to platinum-etoposide chemotherapy but experienced treatment interruption during the COVID-19 pandemic, followed by recurrent malignant airway obstruction and respiratory failure. Repeated bronchoscopic interventions, including tumor debulking, airway stent placement, electrocautery, laser therapy, and cryotherapy, were performed to restore airway patency and stabilize respiratory function, thereby enabling the resumption and continuation of systemic antitumor therapy. Subsequently, chemotherapy combined with the programmed cell death protein-1 (PD-1) inhibitor serplulimab was initiated, followed by maintenance immunotherapy. After local bronchoscopic ablation, transient elevations in circulating inflammatory cytokines, including interleukin-6 and interleukin-8, were observed, suggesting systemic immune activation. The patient achieved sustained partial remission, with preserved airway patency and good general condition. At five years after initial diagnosis, the patient remains alive with stable disease and without severe treatment-related adverse events. This case highlights the potential role of integrating bronchoscopic local interventions with systemic chemotherapy and immunotherapy to enable durable disease control and long-term survival in selected patients with ES-SCLC complicated by central airway obstruction.

Keywords:  case report; central airway obstruction; cryo-immunotherapy; interventional pulmonology; small-cell lung cancer; tumor microenvironment

DOI:  https://doi.org/10.3389/fonc.2025.1733112
Med Oncol. 2026 Feb 07. 43(3): 145

Structural and functional insights into CD3 bispecific antibodies targeting DLL3 in cancer immunotherapy.

Shanshan Chen, Guangshun Zhang, Xiangyi He, Yuze Li, Dong Li.

  CD3 bispecific antibodies (BsAbs) targeting delta-like ligand 3 (DLL3) have emerged as promising candidates in cancer immunotherapy by enabling T-cell-mediated tumor lysis. A critical unmet need is to establish structural correlates of their preclinical activity and clinical efficacy to guide rational drug optimization. This study systematically characterized three clinical-stage CD3×DLL3 BsAbs, Tarlatamab (AMG757), BI764532 and HPN328, via structural modeling, T-cell activation assays, cytokine profiling, and tumor cytotoxicity tests. Preclinical data were further correlated with clinical trial outcomes to verify the predictive value of in vitro models. Preclinical data demonstrate a strong correlation with clinical outcomes, confirming that in vitro assays can reliably predict therapeutic response. Notably, structural features including immune synapse (IS) distance and epitope binding are tightly correlated with efficacy and safety. HPN328 exhibited the most potent T-cell activation and tumor killing activity, which aligned with its clinical confirmed complete response rate (cORR) of 50% in small cell lung cancer. BI764532 demonstrated a balanceed efficacy (ORR 18% in SCLC), while Tarlatamab achieved an ORR range of 13-40% across clinical trials. IS distance and epitope binding are strongly correlated with efficacy and safety of DLL3-targeted BsAbs, providing a critical framework for optimizing T-cell engager design in cancer immunotherapy.

Keywords:  CD3 bispecific antibodies; Immune synapse; Immuno-oncology; Structural biology; T cell function

DOI:  https://doi.org/10.1007/s12032-025-03232-z
Ann Nucl Med. 2026 Feb 04.

Pseudotime-Based derivation of a PET-Based metabolic progression index for prognostic stratification in Extensive-Stage SCLC.

Ayşegül Aksu, Anılcan Us, Zeynep Gülsüm Güç, Kadir Alper Küçüker, Ahmet Alacacıoğlu, Bülent Turgut.



Keywords:  DmaxVox; Metabolic progression index; PET/CT; Pseudotime; SCLC

DOI:  https://doi.org/10.1007/s12149-026-02162-8
Curr Med Res Opin. 2026 Feb 06. 1-20

Real-world evaluation of immunotherapy in multi-line treatment of small cell lung cancer.

Min Li, Mengyun Min, Fei Deng.

   OBJECTIVE: To assess the real-world efficacy and safety of immunotherapy in small cell lung cancer (SCLC) across multiple lines of treatment.
METHODS: We conducted a single-center, retrospective cohort study analyzing clinical data from 397 SCLC patients treated at the Second People's Hospital of Yichang (January 2018-July 2024). Based on treatment strategies, patients were divided into four groups: (1) first-line immune checkpoint inhibitor (ICIs)-based combination therapy, (2) first-line chemotherapy, (3) later-line ICIs-based combination therapy after first-line chemotherapy, and (4) chemotherapy in all lines. Propensity score matching (PSM) was used to balance baseline characteristics. Survival outcomes and safety were evaluated.
RESULTS: After matching, baseline characteristics were comparable. In patients with extensive-stage SCLC (ES-SCLC), first-line ICIs‑based combination therapy significantly improved median overall survival (OS, 12.9 vs. 10.2 months; hazard ratio [HR] = 0.56, 95% CI 0.38-0.80; p = 0.00189) and median progression-free survival (PFS, 8.0 vs. 5.6 months; HR = 0.57, 95% CI 0.40-0.80; p = 0.00125) compared with chemotherapy alone. In the limited-stage cohort, first-line ICIs‑based combination therapy yielded numerically longer OSOS (40.0 vs. 15.5 months; p = 0.121), though results are preliminary and should be interpreted with caution given sample limitations. In the later-line setting, ICIs‑based combination therapy significantly extended median OS compared with chemotherapy (10.4 vs. 7.4 months; HR = 0.60, 95% CI 0.37-0.98; p = 0.0405). Exploratory analysis indicated longer OS with later-line versus first-line ICIs (22.6 vs. 12.6 months; HR = 2.44, 95% CI 1.12-5.33; p = 0.0255); however, this finding may be influenced by potential selection biases and guarantee-time bias and should be viewed as hypothesis-generating only. Immune-related adverse events (irAEs) occurred in 11.1-22.2%, indicating manageable toxicity.
CONCLUSION: Immunotherapy, whether first-line or later-line, improves survival in ES-SCLC with acceptable safety. Our exploratory results suggest that later-line immunotherapy may be associated with favorable survival trends; however, these findings are hypothesis-generating and require validation in prospective trials due to inherent selection biases.

Keywords:  Small cell lung cancer; immunotherapy; prognosis; propensity score matching; real-world study

DOI:  https://doi.org/10.1080/03007995.2026.2624887