Revisiting the Role of Surgery in Brain Metastatic Small Cell Lung Cancer: Survival Benefit in Selected Patients

Revisiting the Role of Surgery in Brain Metastatic Small Cell Lung Cancer: Survival Benefit in Selected Patients | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Revisiting the Role of Surgery in Brain Metastatic Small Cell Lung Cancer: Survival Benefit in Selected Patients Ravit Gabay Yehezkely, Ariella R Eisenberg BSc¹, Ido Livneh, Rachel Grossman This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7943088/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose Small-cell lung cancer (SCLC) has a high propensity for early brain dissemination. With advances in focal therapies, the question arises whether surgery may have a role in selected patients with limited intracranial disease. Unlike in non–small cell lung cancer (NSCLC), the benefit of neurosurgical resection in SCLC remains uncertain. This study examined whether, in selected cases, surgical resection of brain metastases confers a meaningful survival advantage. Methods We retrospectively analyzed 39 patients with histologically confirmed SCLC and up to three brain metastases. Thirteen patients underwent resection followed by adjuvant therapy (surgery-group), and twenty-six were treated without surgery (non-surgical group) using radiotherapy and/or chemotherapy. To isolate the affect of extracranial disease, we applied a modified staging system classifying extracranial burden independently of intracranial status. Survival analyses were conducted using Kaplan–Meier estimates and Cox regression models. Results Median overall survival (OS) was 25.1 months in the surgery group versus 5.8 months in the non-surgical group (p = 0.001). On multivariable analysis, surgery was an independent predictor of longer OS (HR 4.88,95%CI 1.57–15.19, p = 0.006). The benefit of surgery persisted across both high and low Karnofsky Performance Scale (KPS) subgroups (p < 0.05). The median interval from SCLC diagnosis to brain metastasis onset was comparable between groups (8.7 vs. 9.1 months, p = 0.78). Conclusions When feasible, neurosurgical resection may substantially prolong survival in selected SCLC patients with limited brain metastases. This benefit appears independent of baseline performance or timing of brain involvement, warranting prospective validation and supporting surgery within a multimodal treatment approach. Figures Figure 1 Figure 2 Figure 3 Introduction Small cell lung cancer (SCLC) accounts for approximately 15% of all lung cancer cases. It is characterized by rapid growth, early systemic dissemination, and a particular affinity for the central nervous system [ 1 – 4 ]. Up to 60% of patients develop brain metastases, often early in the disease course [ 2 – 5 ]. Historically, because of its radiosensitivity and the frequent presence of multiple lesions, whole-brain radiotherapy (WBRT) has been the mainstay of treatment [ 6 – 8 ]. Yet WBRT is associated with significant neurocognitive toxicity, and modern neuro-oncology has shifted toward more localized treatments that preserve function [ 9 – 11 ]. Stereotactic radiosurgery (SRS) now offers durable control in selected patients, with reported median survival approaching 11 months for solitary lesions [ 12 – 15 ]. This trend mirrors a broader move in oncology toward personalized, lesion-directed therapy. While this shift is well established in non–small cell lung cancer (NSCLC), SCLC patients have largely been excluded from surgical clinical trials, reinforcing the notion that their disease is too diffuse for focal intervention [ 12 – 15 ]. Still, for selected patients with limited and surgically accessible intracranial disease, particularly when associated with a mass effect, surgical resection may provide not only symptomatic relief but also a potential survival benefit [ 16 – 18 ]. The present study was undertaken to re-examine this treatment paradigm. We aimed to identify whether surgical resection confers a survival advantage among SCLC patients with a limited number of brain metastases, while accounting for systemic disease burden using a modified staging approach. Methods Patient Selection: We reviewed institutional pathology records for patients with confirmed SCLC and radiologically verified brain metastases (≤ 3 lesions). Thirteen patients underwent surgical resection with adjuvant therapy (surgery group), and twenty-six patients received non-surgical management (non-surgical group) including WBRT, SRS, and/or chemotherapy. Patients with more than three brain metastases, leptomeningeal spread, or biopsy-only procedures were excluded from this cohort. This study was performed in line with the principles of the Declaration of Helsinki and was approved by the institutional review board (RMC 0083 − 25), and the requirement for informed consent was waived. Modified Staging Classification: In standard staging, any brain metastasis defines extensive-stage SCLC. To refine assessment of extracranial disease, we used a modified classification: modified limited disease (mLD) referred to disease confined to one hemithorax and regional lymph nodes; modified extensive disease (mED) indicated contralateral or multisite extracranial spread. This system, though not externally validated, allowed us to analyze intracranial outcomes independent of systemic extent. Data Collection: Clinical data were extracted from electronic medical records, including demographics, smoking history, comorbidities, KPS, presenting symptoms, and steroid use. Tumor features included number, laterality, and depth of brain metastases. Treatment data included WBRT dose, number and dose of SRS sessions, type of chemotherapy and immunotherapy. Overall survival (OS) was defined from the diagnosis of brain metastases to death or last follow-up. Time from initial SCLC diagnosis to the appearance of brain metastases was also calculated when available. Statistical Analysis: Group comparisons used Fisher’s exact or t-tests. Survival was estimated with Kaplan–Meier curves and compared by log-rank test. Variables with p < 0.1 in univariate analysis were entered into a Cox proportional hazards model. Statistical significance was defined as p < 0.05. Analyses were performed with SPSS v29.0 (IBM Corp.). Results Baseline Characteristics: Most patient demographics and disease characteristics were comparable between groups. The distribution of mLD and mED was similar (p = 0.32). Corticosteroid use tended to be higher in the non-surgical group (57.7% vs. 23.1%, p = 0.051). All patients in the non-surgical group had a smoking history, compared to 76.9% in the surgical group (p = 0.037). Headache at presentation was more frequent in the surgery group (30.8% vs. 3.8%, p = 0.035). No significant differences were found in lesion number, location, or laterality (Table 1 ). Table 1 Demographic, clinical, and radiographic characteristics of patients with SCLC brain metastases, treated with or without neurosurgical resection RT Group (n = 26) Non-Surgical Group (n = 13) P- Value Median OS (95% CI), mos 5.8 (1.7–9.9) 25.1 (23.2–27.0) 0.001 Sex, n (%) 0.157 Female 7 (26.9) 7 (53.8) Male 19 (73.1) 6 (46.2) Age, yrs Mean ± SD 64.77 ± 7.49 60.54 ± 9.33 0.134 Preoperative KPS score Mean ± SD 70.77 ± 16.95 82.31 ± 10.13 0.03 Modified SCLC Status n (%) 0.318 mLD 13 (50) 9 (69.2) mED 13 (50) 4 (30.8) Chronic comorbidity, n (%) Cardiovascular 14 (53.8) 5 (41.7) 0.728 Respiratory 5 (15.4) 1 (8.3) > 0.99 Endocrine/metabolic 17 (65.4) 4 (30.8) 0.087 Malignancy 1 (3.8) 1 (7.7) > 0.99 Other 4 (15.4) 2 (15.4) > 0.99 Smoking status, n (%) 24 (100) 10 (76.9) 0.037 Presenting symptoms, n (%) Motor/gait deficit 2 (7.7) 4 (30.8) 0.153 Headache 1 (3.8) 4 (30.8) 0.035 Language deficit 3 (11.5) 1 (7.7) > 0.99 Vision deficit 0 (0.0) 2 (15.4) 0.105 Other 14 (53.8) 6 (61.5) 0.74 Preoperative steroids, n (%) 0.051 Administered 15 (57.7) 3 (23.1) Not administered 11 (42.3) 10 (76.9) Tumor features, n (%) Side 0.244 Left 7 (26.9) 7 (53.8) Right 8 (30.8) 3 (23.1) Bilateral 11 (42.3) 3 (23.1) Depth 0.38 Superficial 23 (88.5) 10 (76.9) Deep 3 (11.5) 3 (23.1) Location 0.237 Frontal 8 (30.8) 4 (30.8) Temporal 1 (3.8) 0 (0.0) Parietal 1 (3.8) 4 (30.8) Occipital 3 (11.5) 1 (7.7) Periventricular 1 (3.8) 0 (0.0) Cerebellar 6 (23.1) 4 (30.8) Basal Ganglia 2 (7.7) 0 (0.0) Multiple 4 (15.4) 0 (0.0) Postoperative complications, n (%) N/A 1 (7.7) Adjuvant therapy, n (%) Radiotherapy 0.005 WBRT 16 (61.5) 2 (15.4) SRS 5 (19.2) 1 (7.7) Both 0 (0.0) 1 (7.7) Not administered 5 (19.2) 9 (69.2) Chemotherapy 24 (92.3) 11 (84.6) 0.589 Immunotherapy 7 (28.0) 3 (23.1) > 0.99 RT: radiotherapy, OS: overall survival, CI: confidence interval, mos: months, yrs: years, SD: standard deviation, KPS: Karnofsky Performance Scale, SCLC: small cell lung cancer, mLD: Modified limited disease, mED: Modified extensive disease, N/A: not applicable, WBRT: whole-brain radiotherapy, SRS: stereotactic radiosurgery. Interval from Primary Diagnosis to Brain Metastasis: The median time between primary diagnosis of small cell lung cancer and the onset of brain metastases was similar in both groups (8.7 vs. 9.1 months, p = 0.78), indicating comparable disease dynamics between cohorts and suggesting that the observed survival differences were not related to earlier or later CNS dissemination. Survival Outcomes: Median OS was significantly longer for patients who underwent resection (25.1 months) compared to those treated non-surgically (5.8 months; p = 0.001), (Fig. 1 ). Multivariate analysis confirmed surgery as an independent predictor of OS (HR 4.88, 95% CI 1.57–15.19, p = 0.006). Higher KPS scores trended toward improved OS (HR 0.98, p = 0.097). Receiving brain RT showed a non-significant trend toward reduced mortality (HR 0.53, p = 0.218), (Table 2 ). Table 2 Multivariable Cox proportional hazards regression model evaluating predictors of overall survival in patients with brain metastases from SCLC Variable Hazard Ratio (HR) 95% Confidence Interval p-value Group 4.884 1.57–15.19 0.006 Preoperative KPS score 0.98 0.96–1.00 0.097 Radiotherapy to brain 0.53 0.19–1.46 0.218 Smoking status 1.23 0.24–6.14 0.804 SCLC: small cell lung cancer, KPS: Karnofsky Performance Scale. Subgroup Analysis: When stratified by KPS, the survival advantage of surgery persisted. For patients with KPS ≤ 70, median OS was 25.8 months with surgery versus 6 months without (p = 0.046), (Fig. 2 ). In those with KPS > 70, surgery again predicted better OS (25.1 vs. 9.5 months, p = 0.033), (Fig. 3 ). Discussion Our results indicate that, even in an aggressive malignancy such as SCLC, surgical resection may play a meaningful role in selected patients with limited brain disease. The magnitude of survival difference, nearly fivefold, suggests that local control may affect outcomes more than previously appreciated. These findings align with recent studies by Gaebe et al. [ 5 ] and Wang et al. [ 4 ], which also reported favorable outcomes for local treatment in similar contexts. The time from initial diagnosis to brain involvement was comparable between groups, arguing against lead-time bias as the explanation for improved OS. The use of a modified staging system, though exploratory, provided a way to analyze outcomes beyond the binary limited/extensive classification. Similar efforts to refine staging have been described by Steindl et al. [ 19 ] and Rusthoven et al. [ 17 ]. While this approach is unvalidated, it may help clarify prognosis in future studies. Selection bias is inevitable in retrospective designs. Patients offered surgery often have accessible lesions, better systemic control, or receive more intensive supportive care. Yet baseline characteristics and extracranial disease stage were balanced between groups, and surgical resection remained a significant factor in multivariate analysis, supporting its potential independent impact. The lack of detailed data on systemic treatment response remains a limitation, as differences in chemotherapy sensitivity might partly explain outcomes. This factor has been emphasized in recent molecular analyses [ 20 , 21 ]. Future work incorporating molecular subtypes and treatment response will better define who benefits most from surgery. Beyond the statistical findings, this study reflects a shifting paradigm in the management of SCLC: from treating it as a uniformly systemic disease to recognizing biologically diverse subgroups. With the emergence of novel immunotherapeutic agents such as tarlatamab [ 9 ], combining systemic and local treatments is becoming increasingly rational. In this evolving landscape, surgical resection may complement rather than compete with modern oncologic strategies for carefully selected patients. Conclusions In this single center cohort, surgical resection was associated with a significant and durable survival advantage in patients with SCLC presenting with up to three brain metastases. The benefit persisted regardless of baseline functional status or timing of intracranial disease. Although limited by its retrospective nature, this work suggests that surgery should be considered within a multidisciplinary framework when lesions are surgically accessible and systemic disease is under control. Prospective multicenter studies are warranted to validate these findings and refine patient selection. Declarations Conflict of Interest Statement: The authors have no relevant financial or non-financial interests to disclose. Contribution All authors contributed to the study conception, design, material preparation and data collection. Analysis were performed by Ravit Gabay Yehezkely and Rachel Grossman. The first draft of the manuscript was written by Ravit Gabay Yehezkely and Rachel Grossman and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. Clinical trial number not applicable Ethics and Consent declarations This study was performed in line with the principles of the Declaration of Helsinki and was approved by the institutional review board (RMC 0083 − 25), and the requirement for informed consent was waived. Funding: None Author Contribution All authors contributed to the study conception, design, material preparation and data collection. Analysis were performed by Ravit Gabay Yehezkely and Rachel Grossman. The first draft of the manuscript was written by Ravit Gabay Yehezkely and Rachel Grossman and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. 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Semin Cancer Biol 86:450–462. 10.1016/j.semcancer.2022.05.010 Liu Q, Zhang J, Guo C, Wang M, Wang C, Yan Y, Sun L, Wang D, Zhang L, Yu H, Hou L, Wu C, Zhu Y, Jiang G, Zhu H, Zhou Y, Fang S, Zhang T, Hu L, Li J, Liu Y, Zhang H, Zhang B, Ding L, Robles AI, Rodriguez H, Gao D, Ji H, Zhou H, Zhang P (2024) Proteogenomic characterization of small cell lung cancer identifies biological insights and subtype-specific therapeutic strategies. Cell 187: 184–203 e128 10.1016/j.cell.2023.12.004 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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16:40:14","extension":"png","order_by":11,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":16749,"visible":true,"origin":"","legend":"","description":"","filename":"OnlineFig1.png","url":"https://assets-eu.researchsquare.com/files/rs-7943088/v1/f1dd33d5afe1373d5e18c982.png"},{"id":95320746,"identity":"2908025c-0bbd-4dce-bb0a-de13abab9d7a","added_by":"auto","created_at":"2025-11-06 16:40:14","extension":"png","order_by":12,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":17961,"visible":true,"origin":"","legend":"","description":"","filename":"OnlineFig2.png","url":"https://assets-eu.researchsquare.com/files/rs-7943088/v1/bc98753e6898e68dc1328362.png"},{"id":95320752,"identity":"75edb011-3c35-4602-aae8-5b1ff714fd63","added_by":"auto","created_at":"2025-11-06 16:40:14","extension":"png","order_by":13,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":16499,"visible":true,"origin":"","legend":"","description":"","filename":"OnlineFig3.png","url":"https://assets-eu.researchsquare.com/files/rs-7943088/v1/a3f45d8a5ef06242094ac81f.png"},{"id":95320755,"identity":"5f7e2390-1a14-4e65-ad07-8928953b40d9","added_by":"auto","created_at":"2025-11-06 16:40:14","extension":"xml","order_by":14,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":93470,"visible":true,"origin":"","legend":"","description":"","filename":"ce9709cbc8024639bdc7fb68c37a929d1structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-7943088/v1/5597f2ed63e20a0757e73368.xml"},{"id":95320756,"identity":"e7d696ae-aa35-49fe-bd89-2a6246443ee2","added_by":"auto","created_at":"2025-11-06 16:40:14","extension":"html","order_by":15,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":100562,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7943088/v1/79b7f7c229dfe9921e58a826.html"},{"id":95320737,"identity":"bd181c69-8fd4-4129-8356-f02fab054922","added_by":"auto","created_at":"2025-11-06 16:40:14","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":291174,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan-Meier survival curves of overall survival (months) in patients with brain metastases from small cell lung cancer treated with surgical resection (n = 13, solid;) versus non-surgical treatment (n = 26, dashed; p = 0.001).\u003c/p\u003e","description":"","filename":"Fig1.png","url":"https://assets-eu.researchsquare.com/files/rs-7943088/v1/5160e905cdbcb3219d662967.png"},{"id":95320742,"identity":"7e7825f8-3a0b-4a6d-9f93-365a914b605c","added_by":"auto","created_at":"2025-11-06 16:40:14","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":314400,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan-Meier survival curves of overall survival (months) in patients with preoperative KPS ≤ 70 and brain metastases from small cell lung cancer, treated with surgical resection (n = 13, solid;) versus non-surgical treatment (n = 26, dashed).Median OS: 25.8 vs. 6 months (p = 0.046).\u003c/p\u003e","description":"","filename":"Fig2.png","url":"https://assets-eu.researchsquare.com/files/rs-7943088/v1/b528ab626b4a7b902e9c6b71.png"},{"id":95524013,"identity":"d0b65c4d-2e39-494f-a8d7-2d41c8a463de","added_by":"auto","created_at":"2025-11-10 10:01:55","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":305348,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan-Meier survival curves of overall survival (months) in patients with preoperative KPS \u0026gt; 70 and brain metastases from small cell lung cancer, treated with surgical resection (n = 13, solid;) versus non-surgical treatment (n = 26, dashed). \u0026nbsp;Median OS: 25.1 vs. 9.5 months (p = 0.033).\u003c/p\u003e","description":"","filename":"Fig3.png","url":"https://assets-eu.researchsquare.com/files/rs-7943088/v1/f54a3ca01e9e59542bb0f4b0.png"},{"id":95934191,"identity":"889c300e-f9b0-49e5-926d-c52c52a62d92","added_by":"auto","created_at":"2025-11-14 15:08:54","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1692802,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7943088/v1/807ad51c-1bf1-49ac-9da4-50dbb6ad11ef.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Revisiting the Role of Surgery in Brain Metastatic Small Cell Lung Cancer: Survival Benefit in Selected Patients","fulltext":[{"header":"Introduction","content":"\u003cp\u003eSmall cell lung cancer (SCLC) accounts for approximately 15% of all lung cancer cases. It is characterized by rapid growth, early systemic dissemination, and a particular affinity for the central nervous system [\u003cspan additionalcitationids=\"CR2 CR3\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Up to 60% of patients develop brain metastases, often early in the disease course [\u003cspan additionalcitationids=\"CR3 CR4\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Historically, because of its radiosensitivity and the frequent presence of multiple lesions, whole-brain radiotherapy (WBRT) has been the mainstay of treatment [\u003cspan additionalcitationids=\"CR7\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Yet WBRT is associated with significant neurocognitive toxicity, and modern neuro-oncology has shifted toward more localized treatments that preserve function [\u003cspan additionalcitationids=\"CR10\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eStereotactic radiosurgery (SRS) now offers durable control in selected patients, with reported median survival approaching 11 months for solitary lesions [\u003cspan additionalcitationids=\"CR13 CR14\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. This trend mirrors a broader move in oncology toward personalized, lesion-directed therapy. While this shift is well established in non\u0026ndash;small cell lung cancer (NSCLC), SCLC patients have largely been excluded from surgical clinical trials, reinforcing the notion that their disease is too diffuse for focal intervention [\u003cspan additionalcitationids=\"CR13 CR14\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Still, for selected patients with limited and surgically accessible intracranial disease, particularly when associated with a mass effect, surgical resection may provide not only symptomatic relief but also a potential survival benefit [\u003cspan additionalcitationids=\"CR17\" citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe present study was undertaken to re-examine this treatment paradigm. We aimed to identify whether surgical resection confers a survival advantage among SCLC patients with a limited number of brain metastases, while accounting for systemic disease burden using a modified staging approach.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003ePatient Selection:\u003c/h2\u003e\u003cp\u003e We reviewed institutional pathology records for patients with confirmed SCLC and radiologically verified brain metastases (\u0026le;\u0026thinsp;3 lesions). Thirteen patients underwent surgical resection with adjuvant therapy (surgery group), and twenty-six patients received non-surgical management (non-surgical group) including WBRT, SRS, and/or chemotherapy. Patients with more than three brain metastases, leptomeningeal spread, or biopsy-only procedures were excluded from this cohort. This study was performed in line with the principles of the Declaration of Helsinki and was approved by the institutional review board (RMC 0083\u0026thinsp;\u0026minus;\u0026thinsp;25), and the requirement for informed consent was waived.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eModified Staging Classification:\u003c/h3\u003e\n\u003cp\u003eIn standard staging, any brain metastasis defines extensive-stage SCLC. To refine assessment of extracranial disease, we used a modified classification: \u003cem\u003emodified limited disease\u003c/em\u003e (mLD) referred to disease confined to one hemithorax and regional lymph nodes; \u003cem\u003emodified extensive disease\u003c/em\u003e (mED) indicated contralateral or multisite extracranial spread. This system, though not externally validated, allowed us to analyze intracranial outcomes independent of systemic extent.\u003c/p\u003e\n\u003ch3\u003eData Collection:\u003c/h3\u003e\n\u003cp\u003eClinical data were extracted from electronic medical records, including demographics, smoking history, comorbidities, KPS, presenting symptoms, and steroid use. Tumor features included number, laterality, and depth of brain metastases. Treatment data included WBRT dose, number and dose of SRS sessions, type of chemotherapy and immunotherapy. Overall survival (OS) was defined from the diagnosis of brain metastases to death or last follow-up. Time from initial SCLC diagnosis to the appearance of brain metastases was also calculated when available.\u003c/p\u003e\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\u003ch2\u003eStatistical Analysis:\u003c/h2\u003e\u003cp\u003eGroup comparisons used Fisher\u0026rsquo;s exact or t-tests. Survival was estimated with Kaplan\u0026ndash;Meier curves and compared by log-rank test. Variables with p\u0026thinsp;\u0026lt;\u0026thinsp;0.1 in univariate analysis were entered into a Cox proportional hazards model. Statistical significance was defined as p\u0026thinsp;\u0026lt;\u0026thinsp;0.05. Analyses were performed with SPSS v29.0 (IBM Corp.).\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003eBaseline Characteristics:\u003c/h2\u003e\u003cp\u003eMost patient demographics and disease characteristics were comparable between groups. The distribution of mLD and mED was similar (p\u0026thinsp;=\u0026thinsp;0.32). Corticosteroid use tended to be higher in the non-surgical group (57.7% vs. 23.1%, p\u0026thinsp;=\u0026thinsp;0.051). All patients in the non-surgical group had a smoking history, compared to 76.9% in the surgical group (p\u0026thinsp;=\u0026thinsp;0.037). Headache at presentation was more frequent in the surgery group (30.8% vs. 3.8%, p\u0026thinsp;=\u0026thinsp;0.035). No significant differences were found in lesion number, location, or laterality (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eDemographic, clinical, and radiographic characteristics of patients with SCLC brain metastases, treated with or without neurosurgical resection\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eRT Group (n\u0026thinsp;=\u0026thinsp;26)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNon-Surgical Group (n\u0026thinsp;=\u0026thinsp;13)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eP- Value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMedian OS (95% CI), mos\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5.8 (1.7\u0026ndash;9.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e25.1 (23.2\u0026ndash;27.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSex, n (%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.157\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFemale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7 (26.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e7 (53.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e19 (73.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e6 (46.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eAge, yrs\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e64.77\u0026thinsp;\u0026plusmn;\u0026thinsp;7.49\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e60.54\u0026thinsp;\u0026plusmn;\u0026thinsp;9.33\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.134\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003ePreoperative KPS score\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e70.77\u0026thinsp;\u0026plusmn;\u0026thinsp;16.95\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e82.31\u0026thinsp;\u0026plusmn;\u0026thinsp;10.13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.03\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003eModified SCLC Status n (%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.318\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003emLD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e13 (50)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e9 (69.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003emED\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e13 (50)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e4 (30.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003eChronic comorbidity, n (%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCardiovascular\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e14 (53.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e5 (41.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.728\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRespiratory\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5 (15.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1 (8.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026gt;\u0026thinsp;0.99\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEndocrine/metabolic\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e17 (65.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e4 (30.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.087\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMalignancy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (3.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1 (7.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026gt;\u0026thinsp;0.99\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOther\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4 (15.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e2 (15.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026gt;\u0026thinsp;0.99\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSmoking status, n (%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e24 (100)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e10 (76.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.037\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003ePresenting symptoms, n (%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMotor/gait deficit\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 (7.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e4 (30.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.153\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHeadache\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (3.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e4 (30.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.035\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLanguage deficit\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3 (11.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1 (7.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026gt;\u0026thinsp;0.99\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVision deficit\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0 (0.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e2 (15.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.105\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOther\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e14 (53.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e6 (61.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.74\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003ePreoperative steroids, n (%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.051\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAdministered\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e15 (57.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e3 (23.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNot administered\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e11 (42.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e10 (76.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eTumor features, n (%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSide\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.244\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLeft\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7 (26.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e7 (53.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRight\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8 (30.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e3 (23.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBilateral\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e11 (42.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e3 (23.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eDepth\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.38\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSuperficial\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e23 (88.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e10 (76.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDeep\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3 (11.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e3 (23.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eLocation\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.237\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFrontal\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8 (30.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e4 (30.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTemporal\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (3.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0 (0.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eParietal\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (3.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e4 (30.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOccipital\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3 (11.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1 (7.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePeriventricular\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (3.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0 (0.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCerebellar\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6 (23.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e4 (30.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBasal Ganglia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 (7.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0 (0.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMultiple\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4 (15.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0 (0.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003ePostoperative complications, n (%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1 (7.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eAdjuvant therapy, n (%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eRadiotherapy\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.005\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eWBRT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e16 (61.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e2 (15.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSRS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5 (19.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1 (7.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBoth\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0 (0.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1 (7.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNot administered\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5 (19.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e9 (69.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eChemotherapy\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e24 (92.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e11 (84.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.589\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eImmunotherapy\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7 (28.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e3 (23.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026gt;\u0026thinsp;0.99\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003eRT: radiotherapy, OS: overall survival, CI: confidence interval, mos: months, yrs: years, SD: standard deviation, KPS: Karnofsky Performance Scale, SCLC: small cell lung cancer, mLD: Modified limited disease, mED: Modified extensive disease, N/A: not applicable, WBRT: whole-brain radiotherapy, SRS: stereotactic radiosurgery.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eInterval from Primary Diagnosis to Brain Metastasis:\u003c/h3\u003e\n\u003cp\u003eThe median time between primary diagnosis of small cell lung cancer and the onset of brain metastases was similar in both groups (8.7 vs. 9.1 months, p\u0026thinsp;=\u0026thinsp;0.78), indicating comparable disease dynamics between cohorts and suggesting that the observed survival differences were not related to earlier or later CNS dissemination.\u003c/p\u003e\n\u003ch3\u003eSurvival Outcomes:\u003c/h3\u003e\n\u003cp\u003eMedian OS was significantly longer for patients who underwent resection (25.1 months) compared to those treated non-surgically (5.8 months; p\u0026thinsp;=\u0026thinsp;0.001), (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Multivariate analysis confirmed surgery as an independent predictor of OS (HR 4.88, 95% CI 1.57\u0026ndash;15.19, p\u0026thinsp;=\u0026thinsp;0.006). Higher KPS scores trended toward improved OS (HR 0.98, p\u0026thinsp;=\u0026thinsp;0.097). Receiving brain RT showed a non-significant trend toward reduced mortality (HR 0.53, p\u0026thinsp;=\u0026thinsp;0.218), (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eMultivariable Cox proportional hazards regression model evaluating predictors of overall survival in patients with brain metastases from SCLC\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVariable\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eHazard Ratio (HR)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003e95% Confidence Interval\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003ep-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGroup\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e4.884\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1.57\u0026ndash;15.19\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.006\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePreoperative KPS score\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.98\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.96\u0026ndash;1.00\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.097\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRadiotherapy to brain\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.53\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.19\u0026ndash;1.46\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.218\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSmoking status\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1.23\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.24\u0026ndash;6.14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.804\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003eSCLC: small cell lung cancer, KPS: Karnofsky Performance Scale.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\u003ch2\u003eSubgroup Analysis:\u003c/h2\u003e\u003cp\u003eWhen stratified by KPS, the survival advantage of surgery persisted. For patients with KPS\u0026thinsp;\u0026le;\u0026thinsp;70, median OS was 25.8 months with surgery versus 6 months without (p\u0026thinsp;=\u0026thinsp;0.046), (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). In those with KPS\u0026thinsp;\u0026gt;\u0026thinsp;70, surgery again predicted better OS (25.1 vs. 9.5 months, p\u0026thinsp;=\u0026thinsp;0.033), (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eOur results indicate that, even in an aggressive malignancy such as SCLC, surgical resection may play a meaningful role in selected patients with limited brain disease. The magnitude of survival difference, nearly fivefold, suggests that local control may affect outcomes more than previously appreciated. These findings align with recent studies by Gaebe et al. [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e] and Wang et al. [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e], which also reported favorable outcomes for local treatment in similar contexts.\u003c/p\u003e\u003cp\u003eThe time from initial diagnosis to brain involvement was comparable between groups, arguing against lead-time bias as the explanation for improved OS. The use of a modified staging system, though exploratory, provided a way to analyze outcomes beyond the binary limited/extensive classification. Similar efforts to refine staging have been described by Steindl et al. [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e] and Rusthoven et al. [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. While this approach is unvalidated, it may help clarify prognosis in future studies.\u003c/p\u003e\u003cp\u003eSelection bias is inevitable in retrospective designs. Patients offered surgery often have accessible lesions, better systemic control, or receive more intensive supportive care. Yet baseline characteristics and extracranial disease stage were balanced between groups, and surgical resection remained a significant factor in multivariate analysis, supporting its potential independent impact. The lack of detailed data on systemic treatment response remains a limitation, as differences in chemotherapy sensitivity might partly explain outcomes. This factor has been emphasized in recent molecular analyses [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Future work incorporating molecular subtypes and treatment response will better define who benefits most from surgery.\u003c/p\u003e\u003cp\u003eBeyond the statistical findings, this study reflects a shifting paradigm in the management of SCLC: from treating it as a uniformly systemic disease to recognizing biologically diverse subgroups. With the emergence of novel immunotherapeutic agents such as tarlatamab [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e], combining systemic and local treatments is becoming increasingly rational. In this evolving landscape, surgical resection may complement rather than compete with modern oncologic strategies for carefully selected patients.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eIn this single center cohort, surgical resection was associated with a significant and durable survival advantage in patients with SCLC presenting with up to three brain metastases. The benefit persisted regardless of baseline functional status or timing of intracranial disease. Although limited by its retrospective nature, this work suggests that surgery should be considered within a multidisciplinary framework when lesions are surgically accessible and systemic disease is under control. Prospective multicenter studies are warranted to validate these findings and refine patient selection.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003ch2\u003eConflict of Interest Statement:\u003c/h2\u003e\u003cp\u003eThe authors have no relevant financial or non-financial interests to disclose.\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003ch2\u003eContribution\u003c/h2\u003e\u003cp\u003eAll authors contributed to the study conception, design, material preparation and data collection. Analysis were performed by Ravit Gabay Yehezkely and Rachel Grossman. The first draft of the manuscript was written by Ravit Gabay Yehezkely and Rachel Grossman and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003ch2\u003eClinical trial number\u003c/h2\u003e\u003cp\u003enot applicable\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eEthics and Consent declarations\u003c/strong\u003e\u003cp\u003eThis study was performed in line with the principles of the Declaration of Helsinki and was approved by the institutional review board (RMC 0083\u0026thinsp;\u0026minus;\u0026thinsp;25), and the requirement for informed consent was waived.\u003c/p\u003e\u003c/p\u003e\u003ch2\u003eFunding:\u003c/h2\u003e\u003cp\u003eNone\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eAll authors contributed to the study conception, design, material preparation and data collection. Analysis were performed by Ravit Gabay Yehezkely and Rachel Grossman. The first draft of the manuscript was written by Ravit Gabay Yehezkely and Rachel Grossman and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eHirsch FR, Paulson OB, Hansen HH, Larsen SO (1983) Intracranial metastases in small cell carcinoma of the lung. Prognostic aspects. 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Cell 187: 184\u0026ndash;203 e128 \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.cell.2023.12.004\u003c/span\u003e\u003cspan address=\"10.1016/j.cell.2023.12.004\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-7943088/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7943088/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e\u003cp\u003eSmall-cell lung cancer (SCLC) has a high propensity for early brain dissemination. With advances in focal therapies, the question arises whether surgery may have a role in selected patients with limited intracranial disease. Unlike in non\u0026ndash;small cell lung cancer (NSCLC), the benefit of neurosurgical resection in SCLC remains uncertain. This study examined whether, in selected cases, surgical resection of brain metastases confers a meaningful survival advantage.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eWe retrospectively analyzed 39 patients with histologically confirmed SCLC and up to three brain metastases. Thirteen patients underwent resection followed by adjuvant therapy (surgery-group), and twenty-six were treated without surgery (non-surgical group) using radiotherapy and/or chemotherapy. To isolate the affect of extracranial disease, we applied a modified staging system classifying extracranial burden independently of intracranial status. Survival analyses were conducted using Kaplan\u0026ndash;Meier estimates and Cox regression models.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eMedian overall survival (OS) was 25.1 months in the surgery group versus 5.8 months in the non-surgical group (p\u0026thinsp;=\u0026thinsp;0.001). On multivariable analysis, surgery was an independent predictor of longer OS (HR 4.88,95%CI 1.57\u0026ndash;15.19, p\u0026thinsp;=\u0026thinsp;0.006). The benefit of surgery persisted across both high and low Karnofsky Performance Scale (KPS) subgroups (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). The median interval from SCLC diagnosis to brain metastasis onset was comparable between groups (8.7 vs. 9.1 months, p\u0026thinsp;=\u0026thinsp;0.78).\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e\u003cp\u003eWhen feasible, neurosurgical resection may substantially prolong survival in selected SCLC patients with limited brain metastases. This benefit appears independent of baseline performance or timing of brain involvement, warranting prospective validation and supporting surgery within a multimodal treatment approach.\u003c/p\u003e","manuscriptTitle":"Revisiting the Role of Surgery in Brain Metastatic Small Cell Lung Cancer: Survival Benefit in Selected Patients","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-06 16:40:09","doi":"10.21203/rs.3.rs-7943088/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"da5e9e31-8c0d-4753-97cf-0824e43bf30d","owner":[],"postedDate":"November 6th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-11-14T15:08:33+00:00","versionOfRecord":[],"versionCreatedAt":"2025-11-06 16:40:09","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7943088","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7943088","identity":"rs-7943088","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}