Small Cell Lung Carcinoma Research Articles (Page 1)

Abstract Background Acute myeloid leukemia (AML) occasionally presents with extramedullary disease, but pulmonary involvement is rare and often misdiagnosed as primary lung carcinoma, particularly in chronic smokers. Accurate diagnosis requires histopathology supplemented by immunohistochemistry (IHC). Case presentation We report a 70-year-old chronic smoker who presented with cough, chest pain, weight loss, and a right hilar lung mass. Initial histology of a lung biopsy was suspicious for small-cell lung carcinoma (SCLC). However, laboratory findings revealed progressive cytopenias and circulating blasts. Bone marrow evaluation demonstrated florid myeloblast proliferation consistent with AML. Further IHC of the lung biopsy confirmed myeloid lineage (CD34 positivity, MPO, CD117) and excluded neuroendocrine or epithelial carcinoma markers (TTF-1, synaptophysin, chromogranin, cytokeratin AE1/AE3). A final diagnosis of AML with pulmonary involvement was established. Despite diagnosis, the patient deteriorated rapidly and died before initiation of therapy. Conclusion This case highlights the diagnostic dilemma of AML masquerading as primary lung cancer in smokers. It underscores the indispensable role of IHC in distinguishing hematologic malignancies from solid tumors, thereby avoiding misdiagnosis and inappropriate management. Clinicians should maintain a high index of suspicion for hematologic disease when atypical laboratory findings accompany pulmonary masses.

Intraductal carcinoma of the prostate (IDC-P) is a strong indicator of poor prognosis in prostate cancer (PCa). We utilized the Visium Spatial Gene Expression platform to characterize the gene expression profiles and copy number variations (CNVs) of IDC-P. Manually annotated IDC-P components were relatively enriched in a single transcriptomic cluster identified by principal component analysis, which exhibited elevated expression of FOLH1 (PSMA), PSCA and PLA2G2A. Differential gene expression analysis between IDC-P and non-IDC-P cancer tissues revealed up-regulation of pathways related to chemotaxis and leukocyte migration, as well as gene sets associated with small cell lung carcinoma, suggesting a potential link to treatment-related neuroendocrine prostate carcinoma. In contrast, non-IDC-P components showed increased expression of genes associated with extracellular matrix organization. InferCNV analysis identified distinct CNV patterns differentiating IDC-P from non-IDC-P cancer components in four out of six cases. However, no common CNV alterations were shared across these cases, indicating molecular diversity among IDC-P lesions. In the remaining cases, IDC-P clustered with Gleason pattern 5 carcinoma, and no CNV alterations distinguishing IDC-P from adjacent non-IDC-P components were identified. These findings suggest that IDC-P represents a biologically distinct component from conventional acinar adenocarcinoma and may reflect spatial tumour progression through pre-existing ductal structures. Our study also suggests that the molecular mechanisms underlying IDC-P progression may differ between patients, while the limited sample size (n = 6) warrants cautious interpretation and further validation in larger cohorts.

Abstract Disclosure: T. Aggarwal: None. R. Sandooja: None. A. Fingeret: None. J.B. Shank: None. M.B. Mulder: None. L.M. Vargas: None. Background: Endogenous hypercortisolism secondary to ectopic ACTH syndrome (EAS) is a rare condition with a reported incidence of 6-10%. The most common sources are bronchial carcinoid tumors, followed by small cell lung carcinoma. Pancreatic EAS is uncommon (7-14%) and in 12-18% of cases, the source remains occult. Cyclical ectopic Cushing syndrome (CS) is an exceptionally rare variant of EAS, with only a few cases reported in the literature. While no standard definition of cyclical CS exists, diagnosis usually requires at least two hypercortisolemic peaks interspersed with eucortisolemic troughs. Case Presentation: A 74-year-old male presented with a three-month history of progressive proximal muscle weakness, new onset type 2 diabetes mellitus, and severe hypokalemia requiring hospitalization. Axial imaging of the abdomen noted bilateral adrenal hyperplasia. Biochemical evaluation demonstrated an elevated baseline morning cortisol level of 27.2 µg/dL (n 6.7-22.6 µg/dl) with ACTH of 50.5 pg/mL (n 7.2-63.3 pg/mL). A 1mg and 8mg dexamethasone suppression test (DST) revealed non-suppressible cortisol levels of 53.3µg/dl (<1.8µg/dL) and 33.6 µg/dL (n <1.8 µg/dL) respectively. ACTH levels post 1 mg and 8 mg DST were 50.5 pg/mL and 40.7 pg/mL (n 7.2-63.3 pg/mL) respectively. Bedtime salivary cortisol levels were elevated > 0.1µg/dl on multiple occasions. Initial 24-hour urine free cortisol (UFC) levels were also elevated at 225 µg (n <60µg). MRI pituitary with dynamic protocol was unremarkable. Given the suspicion for EAS, PET DOTATATE was performed which identified a small focus of increased DOTATATE avidity in pancreatic tail which was confirmed on a CT abdomen with pancreas protocol. Subsequent UFC levels normalized at 44.8 µg (n <60µg) after one month but showed a marked elevation to over 1500 µg (n <60µg) the following month. The patient's reported symptoms, including proximal muscle weakness, correlated with his cortisol levels. After multidisciplinary discussion, the patient underwent bilateral adrenalectomy and distal pancreatectomy to address the biochemical and clinical consequences of recalcitrant cyclical CS. Intraoperative ACTH levels were unreliable due to the administration of dexamethasone during surgery. Pathology revealed a 5 mm pancreatic neuroendocrine tumor; however, definitive proof of ACTH secretion by the NET could not be established due to absence of direct ACTH staining.Conclusion: This case demonstrates the diagnostic and management challenges of cyclical EAS due to fluctuating biochemical testing and adds to the existing literature on this rare entity. Collaboration within a multidisciplinary team is crucial due to the heterogeneity of the patient's presentation and the rarity of the condition. Presentation: Sunday, July 13, 2025

In this study, we investigated human epidermal growth factor receptor 2 (HER2) aberrations, including gene amplification and mutation, and protein expression in 123 small cell lung carcinomas (SCLC) and 128 extrapulmonary small cell neuroendocrine carcinomas (EP-SCNC) samples. Among the EP-SCNC cohort, HER2 mutations were found in 5.5% of samples (7/128); urinary bladder (4 cases), and one case each in samples from the colon, anal canal, and uterine cervix. In SCLCs, HER2 mutations were rare, detected in only 0.8% (1/119) of cases. We also identified eight EP-SCNCs and five SCLC cases with HER2 gene variants of uncertain significance (VUS). HER2 gene amplification was detected in 2.3% (3/128) of EP-SCNCs, but no amplification was found in SCLCs. The differences in HER2 mRNA expression were not statistically significant among tumor groups in the EP-SCNCs and SCLCs cohorts. RNA-seq analysis revealed high HER2 mRNA expression in seven EP-SCNCs and four SCLCs. An immunohistochemistry (IHC) analysis of 10 available tumors with high mRNA expression revealed HER2 protein positivity in 8 cases. The prognostic value of HER2 overexpression in EP-SCNC patients was not established in our study. Furthermore, EP-SCNC patients with high HER2 mRNA expression were generally younger, with a mean age of 60years. These findings highlight the potential of HER2 as a therapeutic target in EP-SCNC, warranting further investigation into its clinical implications.

Merkel cell carcinoma (MCC) is an aggressive tumor mostly related to Merkel cell polyomavirus genomic integration. MCC can present either as a primary cutaneous tumor or as a lymph node metastasis without a primary skin tumor (MCCWOPT). The distinction between MCCWOPT and lymph node metastases of non-cutaneous neuroendocrine carcinomas remains challenging. The present study aims to determine whether the methylation profile can distinguish MCCWOPT from lymph node metastases of extracutaneous neuroendocrine carcinomas. Methylation profiles of twenty MCCWOPT were compared to 23 cutaneous MCC, 37 small-cell lung carcinomas, 17 and 34 well-differentiated neuroendocrine tumors of the ileum and pancreas. Among the controls, cutaneous MCC cases formed a cluster distinct from other extracutaneous neuroendocrine tumors. MCCWOPT clustered together with cutaneous MCC cases. Methylation profiling represents a promising additional tool for the diagnosis of MCCWOPT.

Abstract BACKGROUND Brain metastases (BM) are a common complication of many solid cancers, and their incidence is expected to rise as systemic treatments continue to improve and prolong patient survival. The efficacy of systemic therapies against BM is often hindered by the blood-brain barrier (BBB). The BBB restricts the brain entry of many drugs, in part due to active efflux by ABCB1 (P-glycoprotein) and ABCG2 (breast cancer resistance protein). The expression and functionality of these drug-transporting proteins at the BBB can vary. Previous work in mouse models has demonstrated that ABC transporters can restrict chemotherapy efficacy against glioblastoma (GBM) and melanoma BM, even when the BBB is compromised. However, while their expression has been clearly established in GBM patients, their presence in the various types of human BM is less well documented. We therefore set out to comprehensively assess the expression of ABCB1 and ABCG2 in human tissue of the most common BM. MATERIAL AND METHODS A retrospective pathology study has been conducted through PALGA, the nationwide network and registry of histopathology and cytopathology in the Netherlands. Data provided by PALGA were year of birth, age at diagnosis, localization of the lesion, and diagnosis, as made by the local pathologist. Tissue of the nine most common origins of brain metastases was requested: non-small cell lung carcinoma (NSCLC), small-cell lung carcinoma (SCLC), Her2 positive-, Her2 negative- and triple-negative breast cancer, melanoma, renal clear cell carcinoma, colon carcinoma, and ovarian carcinoma. Per origin, 10 pairs of the primary tumor and matched BM of the same patient were requested for comparison. Whenever possible, tissue was selected to be treatment-naïve to avoid potential confounding effects of systemic therapy on ABC transporter expression. Using immunohistochemistry, tissues were stained for ABCB1, ABCG2, IgG - as a proxy for barrier leakage - and the endothelial cell marker CD31. RESULTS In general, we find expression of ABCB1 and ABCG2 in the vasculature associated with brain metastases of all investigated primary origins. Expression levels did vary within and across different lesions. Interestingly, in some cases, we observed expression in the tumor-associated vasculature of primary tumors but not in the adjacent tumor-free tissue, suggesting a local tumor-induced expression of drug efflux transporters. CONCLUSION The brain metastasis associated vasculature expresses ABCB1 and ABCG2, which can impede the delivery of systemic therapies to brain metastases. Supported by Dutch Cancer Society (KWF) project grant 14736.

When salvage surgery for apparent "recurrence" of small-cell lung cancer leads to prolonged survival while correcting the initial diagnosis

Lung cancer was the second most common malignancy and the leading cause of cancer-related mortality worldwide in 2020, accounting for 1.8 million deaths. Delayed diagnosis often leads to advanced-stage presentation and poor long-term survival. Pancoast tumors, a rare subset of superior sulcus lung cancers, may present with atypical neurologic signs. We report a 55-year-old man with a 6-month history of right chest pain and progressive dyspnea. Physical examination was unremarkable apart from mild right eyelid ptosis without a full Horner’s syndrome. Chest X-ray and contrast-enhanced CT demonstrated an apical mass in the right upper lobe with lytic lesions of the first and second ribs. Bronchoscopic biopsy confirmed non–small cell lung carcinoma consistent with a Pancoast tumor. The patient underwent surgical resection of the apical mass with regional lymphadenectomy, followed by platinum-based chemotherapy. Postoperative imaging revealed residual disease, prompting additional chemotherapy cycles. At six-month follow-up, the patient experienced marked pain relief and partial resolution of ptosis, with no new metastatic foci on imaging. High clinical suspicion and a multidisciplinary radiologic and histopathologic approach are essential for early diagnosis and optimal management of Pancoast tumors.

P3.13.02 The Effectiveness of Anatomical Versus Non-Anatomical Resection for Treatment of Small Cell Lung Carcinoma

γ-Aminobutyric acid B receptor (GABABR)-IgG (immunoglobulin G) is an intermediate-risk paraneoplastic autoantibody often associated with seizures. We aimed to assess the clinical and oncological features of GABABR-IgG autoimmune encephalitis (AE) and evaluate the performance of antibody testing. Patients testing positive for GABABR-IgG in serum/cerebrospinal fluid (CSF) at Mayo Clinic Neuroimmunology Laboratory were identified. Archived sera were retested by cell-based assay (CBA) at 1:100 and 1:200 dilutions. A live-cell flow cytometry-based assay (LCFBA) was developed and validated using archived sera and CSF. True positivity included patients with classic presentations of GABABR-IgG AE or oncological explanations for antibody presence. Eighty-six patients (median age 63 years; 43 female) presented with classic presentations of GABABR-IgG AE: encephalopathy with prominent seizures (n = 55), status epilepticus (n = 23), and rapidly progressive dementia (n = 8). In addition, 44 patients (33%) had a false-positive result for GABABR-IgG characterized by non-specific symptoms/alternate diagnoses. Malignancy was identified in 78% of true-positive patients, predominantly small cell lung carcinoma (SCLC). Testing serum at 1:100 dilution on CBA and using tissue immunofluorescence assay (IFA) in serum and CSF improved the identification of true-positive patients (p < 0.001). CBA at 1:100 dilution performed better than conventional CBA (at 1:10 dilution, p < 0.001) and tissue IFA (p = 0.031). An in-house LCFBA showed 100% sensitivity and specificity in CSF, performing similarly to conventional CBA (p = 0.125) in CSF, but better than tissue IFA (p = 0.031). Furthermore, serum LCFBA performed better than conventional CBA (p = 0.022) and tissue IFA (p = 0.006). LCFBA had the highest diagnostic accuracy and was closely followed by CBA at 1:100 dilution. GABABR-IgG AE often presents as encephalopathy with seizures or status epilepticus in the context of an underlying SCLC. Multimodal evaluation using tissue IFA and fixed CBA at higher dilutions improves detection of true cases. LCFBA performs very well as a diagnostic test with very high sensitivity and specificity.

Inappropriate antidiuresis syndrome (SIAD) induced hyponatremia is the most common electrolyte disturbance found in cancer patients. Available treatment options are limited by their poor efficacy, tolerability, or cost. Urea is a promising alternative, but its use in the oncology setting remains insufficiently characterized. We aimed to evaluate the efficacy and safety of urea in the management of chronic SIAD-induced hyponatremia in patients with cancer. We conducted a retrospective observational study of patients diagnosed with SIAD and treated with oral urea at our Oncology Center between August 2021 and June 2023. Sodium levels were recorded before urea initiation, at the first reevaluation and at the last available follow-up. The cohort included 28 patients, mostly men (71%), with a mean age of 63.9 ± 10.0 years; 86% had metastatic disease. Lung cancer was the most frequent diagnosis, mostly small cell lung carcinoma. Urea treatment resulted in a statistically significant increase in serum sodium both in inpatients (mean increase of 2.4 ± 3.5 mmol/L after 12 (23) hours, p = 0.016) and outpatients (mean increase of 8.6 ± 6.6 mmol/L after 8 (11) days, p = 0.003). No cases of sodium overcorrection or clinically significant adverse events were reported. One patient complained of urea taste, with no impact on treatment adherence. Sodium normalization following cancer treatment allowed for urea discontinuation in 21% of cases. Median follow-up was 84 days (range 3 days-20.9 months). Our study suggests that urea may be a safe, effective, and well-tolerated option for the long-term management of SIAD-related hyponatremia in oncology patients, but further studies are necessary to confirm these observations.

The Switch/Sucrose Nonfermentable (SWI/SNF) complexes are chromatin remodeling factors that consist of multiple protein subunits. Each subunit plays a distinct role in gene regulation and is aberrantly expressed in tumors, such as neuroendocrine neoplasms (NENs). BRG1-associated factor 53B (BAF53B), which is also known as ACTL6B, is a neuron-specific subunit that acts as a regulator during neurogenesis. Because the BAF53B expression pattern in tumors is unknown, the present study investigated the expression in cell lines and tissues. Publicly available transcriptome data indicated that BAF53B mRNA was highly expressed in NEN-derived cell lines. We performed immunohistochemical staining on tissue microarrays of different types of NENs with neuroendocrine (NE) marker expression (n = 117) (small cell lung carcinoma (SCLC)lung carcinoid (LC), gastroenteropancreatic-NEN (GEP-NEN), esophageal neuroendocrine carcinoma (ENEC), medullary thyroid carcinoma (MTC), neuroblastoma (NB), and pheochromocytoma (PHEO)) and non-NENs (n = 178). While few positive cells were observed in many cases of non-NENs (e.g., lung adenocarcinoma), positive expression was found in cases of NENs (SCLC (14/19, 73.7%), LC (12/16, 75.0%), GEP-NEN (4/9, 44.4%), ENEC (1/2, 50.0%), MTC (24/27, 88.9%), NB (18/20, 90.0%), and PHEO (16/24, 66.7%)). In NCI-H889 cells, BAF53B knockdown did not affect the cellular viability, and its effect on NE marker expression was only marginal. However, a gene expression microarray analysis suggested that BAF53B-regulated genes were associated with the development and progression of NENs. Our analysis revealed that BAF53B was an immunohistochemical marker for specific NENs, indicating its potentially important role in the pathogenesis.

2759MO DAREON®-8: A phase I trial of first-line obrixtamig plus chemotherapy and atezolizumab in extensive-stage small cell lung carcinoma (ES-SCLC)

Background: Autoimmune enteric neuropathies (AENs) are rare but potentially reversible causes of severe gastrointestinal dysmotility, frequently overlooked or misdiagnosed as functional or obstructive disorders. They often present as gastroparesis, chronic constipation, or intestinal pseudo-obstruction, leading to diagnostic delays and poor outcomes. Methods: We conducted a narrative review of the literature using PubMed, EMBASE, and Scopus (2000–2024), focusing on clinical, diagnostic, immunologic, and therapeutic data relevant to AEN. Search terms included “autoimmune enteric neuropathy,” “enteric ganglionitis,” “gastrointestinal dysmotility,” “immunotherapy,” and “paraneoplastic.” Results: AENs require a multimodal diagnostic approach, including anti-neuronal antibody testing (e.g., anti-Hu, anti-CV2), full-thickness intestinal biopsy, and exclusion of structural disease. Paraneoplastic forms, especially those associated with small cell lung carcinoma, and idiopathic variants remain the most common. Immunomodulatory therapies such as corticosteroids, intravenous immunoglobulin (IVIG), azathioprine, and rituximab have shown variable success, particularly when initiated early. Recent advances include trials of subcutaneous immunoglobulin, interleukin inhibitors, JAK inhibitors, and neuro-regenerative strategies. However, evidence remains limited, predominantly comprising case reports and small series. Conclusions: This review highlights AENs as an under-recognized but treatable cause of gastrointestinal dysmotility, with emerging therapeutic strategies showing promise in refractory cases. Critical gaps persist regarding diagnostic consensus, biomarker validation, and standardized treatment. Multidisciplinary approaches, earlier serological testing, and prospective clinical trials are urgently needed. Enhancing clinician awareness could transform outcomes in.

Paraneoplastic neurological syndromes arise from autoimmune reactions against nervous system antigens due to a maladaptive immune response to a peripheral cancer. Patients with small cell lung carcinoma or malignant thymoma can develop an autoimmune response against the CV2/collapsin response mediator protein 5 (CRMP5) antigen, with approximately 80% of these patients experiencing painful neuropathies. Here we investigate the mechanisms underlying anti-CV2/CRMP5 autoantibodies (CV2/CRMP5-Abs)-related pain and find that patient-derived CV2/CRMP5-Abs bind to their target on rat dorsal root ganglia (DRG) and superficial laminae of the spinal cord, to induce DRG neuron hyperexcitability and mechanical hypersensitivity. These effects from patient-derived Abs are recapitulated in rats immunized with a DNA vaccine for CRMP5, in which therapeutic treatment with anti-CD20 depleting B cells ameliorates autoimmunity and neuropathy. Our data thus reveal a mechanism of neuropathic pain in patients with paraneoplastic neurological syndromes and implicates CV2/CRMP5-Abs as a potential target for treating paraneoplastic neurological syndromes.

ABSTRACT This study was conducted to investigate the in vitro differences in killing effects and cellular death pathways in human bronchial epithelial BEAS-2B cells, human lung adenocarcinoma A549 cells, human lung squamous carcinoma H520 cells, and human lung small cell carcinoma H446 cells mediated by hematoporphyrin derivative (HPD) at 630 nm laser wavelength. Our results showed that the viability of the BEAS-2B, A549, H520, and H446 cells gradually decreased with increasing HPD concentration after HPD-PDT. HPD-PDT induced an increase in intracellular ROS production (p < 0.05), with H520 > A549 > H446 > BEAS-2B. HPD-PDT resulted in intracellular chromatin fixation and dense nuclear staining and induced apoptosis, with apoptosis rates of H520 > A549 > H446 > BEAS-2B. The western blotting (WB) results showed that HPD-PDT could lead to reduced BCL-2 protein levels, upregulate BAX protein expression and activate caspase-3 protein, and induce autophagy, as evidenced by the increased expression of the autophagy-related proteins ATG5, Beclin-1 and LC3B in all cells tested. However, apoptosis-inducing proteins and autophagy proteins were statistically different in these four cell types. Our study confirms that HPD-mediated phototoxicity varied in the different cell lines, indicating that lung cancer cells die due to the interactions of different cell death pathways rather than the same well-defined mechanisms.

Small cell lung carcinoma is a malignant neuroendocrine neoplasm characterized by rapid progression and high metastatic potential. This article presents the case of a 31-year-old male patient with no history of smoking who experienced persistent hemoptysis for one year, accompanied by asthenia and odynophagia. Imaging studies revealed a pulmonary mass located in the upper lobe of the left lung, involving the left main bronchus and accompanied by satellite nodular lesions, some of them cavitated. A CT-guided biopsy showed small, round-shaped cells with hyperchromatic nuclei and high mitotic activity. Immunohistochemical analysis revealed positivity for cytokeratin, TTF-1, CD56, and a moderate Ki-67 proliferation index, confirming the diagnosis of small cell lung carcinoma. This case is atypical due to the patient’s young age, the peripheral location of the tumor, and the absence of classical risk factors such as smoking.

A 47-year-old man undergoing follow-up for previously treated squamous cell carcinoma of the lung was found to have two masses in the gallbladder and a new pulmonary nodule in the left upper lobe, different from the original tumor. Imaging findings suggested gallbladder masses atypical for primary gallbladder cancer. Endoscopic ultrasound-guided tissue acquisition of a hepatoduodenal ligament lymph node adjacent to the gallbladder revealed small cell carcinoma, distinct from the previously diagnosed squamous cell carcinoma. A transbronchial lung cryobiopsy confirmed small cell lung carcinoma of the left upper lobe. Based on these findings, the patient was diagnosed with metachronous small cell lung carcinoma with gallbladder metastases. To our knowledge, this is the first reported case of gallbladder metastases from small cell lung carcinoma arising after prior treatment of squamous cell carcinoma in the same patient. This case highlights the importance of histopathological evaluation of new lesions, even in patients with a history of lung cancer, to ensure accurate diagnosis and treatment planning.

Surgery is the standard treatment for early-stage pulmonary neuroendocrine tumors (NETs); however, long-term prognostic data are limited. This study aimed to establish the long-term outcomes of surgically resected pulmonary NETs. This study included 263 patients who underwent pulmonary resection between January, 1997 and December, 2019: 89 with small cell lung carcinoma (SCLC), 120 with large cell neuroendocrine carcinoma (LCNEC), 14 with atypical carcinoid (AC), and 40 with typical carcinoid (TC). We analyzed clinicopathological characteristics and long-term prognosis. The 5-year relapse-free survival (RFS) rates were 38.7%, 54.2%, 62.3%, and 85.0%, and the 10-year RFS rates were 24.5%, 39.8%, 20.8%, and 76.4% for SCLC, LCNEC, AC, and TC, respectively. All deaths from TC occurred more than 5years after surgery, whereas three of the four deaths from AC occurred after this period. Most patients with high-grade NETs had relapses within 3years after surgery, whereas patients with AC had relapses not only in the early phase but also in the late phase. The long-term prognosis of AC is comparable to that of high-grade NETs, suggesting that its biological characteristics might be more closely related to high-grade NETs than to TC.

BackgroundLung cancer continues to be the primary cause of cancer-related mortality globally, with combined small cell lung carcinoma (C-SCLC) constituting a relatively uncommon yet highly aggressive subset of this disease. Despite its clinical significance, limited efforts have been made to develop survival prediction models tailored to the clinical characteristics of C-SCLC patients. Additionally, the interpretability of existing models remains limited.MethodsThis study aimed to develop and validate an interpretable machine learning model for predicting survival outcomes in C-SCLC patients using clinical data from the SEER database and external validation with Chinese patient cohorts. Initially, we employed the Cox proportional hazards model for rigorous variable selection. Subsequently, through 10-fold cross-validation and grid search for optimal parameters, we selected the XGBoost model as the best-performing one among four candidates. Furthermore, we enhanced the model’s interpretability by incorporating the SHapley Additive exPlanations (SHAP) method, which helped us understand the contribution of each variable within the model.ResultsWe constructed a predictive model using data from 1,230 SEER patients and validated it externally with data from 154 Chinese patients. The XGBoost model demonstrated excellent performance in predicting survival outcomes at 1-year, 3-year, and 5-year. The AUC values for the external validation cohort were 0.849, 0.830, and 0.811, respectively. SHAP analysis revealed that N stage, T stage, radiotherapy, surgery, and gender are key factors influencing the ML model’s predictions. To enhance clinical utility, we have developed an interpretable web-based tool to predict patients’ 1-year survival probability.ConclusionThe XGBoost model, integrating demographic and clinical factors of C-SCLC patients, demonstrated excellent predictive performance. Our web-based prediction tool will promote the development of personalized treatment strategies and optimize clinical decision-making.