Citations

TPS6138 Background: Patients with early-stage oral cavity cancer (OCC; T1-2N0M0; AJCC 8th edition) have a 20-30% risk of occult nodal metastases despite clinical and radiographic evaluations. Standard-of-care treatment for most patients includes elective neck dissection (END), which requires surgical removal of the regional cervical lymph nodes, even though 70-80% of these necks are disease-free. Sentinel lymph node biopsy (SLN Bx), a less invasive procedure, could assess the first echelon lymph nodes as an alternative to END, potentially reducing morbidity and costs. A pivotal clinical trial comparing SLN Bx to END (NCT#04333537) is underway to inform efforts to establish optimal disease management for early-stage OCC. Methods: To assess the efficacy of SLN Bx in this population, we activated an international, multi-institutional, prospective phase II/III trial in July 2020, randomizing patients to two surgical arms: SLN Bx and END. A node-negative 18 F-FDG PET/CT imaging biomarker study with centralized read was required before randomization. OCC patients with a positive PET/CT remained in a registry to compare imaging findings with final neck pathology. Given the current evidence on morbidity for SLN Bx versus END, the phase II was designed to determine whether the change in patient-reported neck and shoulder function and related quality of life (QOL) from baseline to 6 months after surgery, using the Neck Dissection Impairment Index (NDII), showed a signal of superiority of SLN Bx compared to END (minimum important difference ³ 7.5; one-sided a = 0.10; 90% power). As of December 2024, 261 patients had been randomized and 203 were analyzed for the “Go/No-Go” decision to move forward into phase III. The phase III portion is a non-inferiority (NI) trial with disease-free survival (DFS) as the primary endpoint (NI margin hazard ratio 1.34 based on a 5% absolute difference in 2-year DFS; one-sided a = 0.05; 80% power, and two interim looks). The change in NDII from baseline to 6 months after surgery is a hierarchical co-primary endpoint for phase III. Phase III opened in October 2025 upon receiving a “Go” signal from phase II. Target accrual for phase III is 686 node-negative PET/CT patients, including those randomized in phase II (425 additional patients). In addition to sites requiring radiotherapy and imaging credentialing, quality assurance will include central pathology review of all negative SLN Bx cases and surgeon credentialing through an education course with SLN Bx and END case review by the surgical co-chairs. A surgical quality assurance working group will review all trial SLN Bx and END procedures. As of 01/12/26, 351 patients have been screened, and 273 of the planned 686 have been randomized. Clinical trial information: NCT#04333537 .

e23223 Background: Early-stage lung cancer is potentially curable with surgery, yet emergency or nonelective presentation represents a care-delivery phenotype reflecting failures in early diagnosis or access to care rather than tumor biology alone. The national impact of emergency presentation among surgically treated, presumed early-stage lung cancer patients is poorly defined. This study evaluates emergency versus elective presentation as a care-delivery phenotype and its association with perioperative morbidity, failure-to-rescue, and inpatient outcomes. Methods: A survey-weighted analysis of the National Inpatient Sample (2016–2023) was conducted. Adult lung cancer hospitalizations were identified using ICD-10-CM C34* in any diagnosis position. A presumed early-stage surgical cohort was defined by curative-intent lung resection without metastatic disease, malignant pleural effusion, or palliative care coding. The primary exposure was nonelective versus elective admission. Outcomes included in-hospital mortality; ICU-level care, defined by invasive mechanical ventilation, shock, or respiratory failure; major complications; failure-to-rescue; length of stay; and hospitalization cost and charges. Multivariable survey-weighted models adjusted for patient demographics, payer, neighborhood income, hospital characteristics, and year. Results: In the weighted cohort of 422,925 hospitalizations, nonelective admission occurred in 27.3%. After multivariable adjustment, nonelective admission was independently associated with higher odds of in-hospital mortality (adjusted odds ratio [aOR] 2.59, 95% CI 2.22–3.03), ICU-level care (aOR 4.53, 95% CI 4.32–4.76), and major complications (aOR 5.00, 95% CI 4.78–5.23), as well as longer length of stay (+2.42 days). Notably, failure-to-rescue among patients with major complications did not differ by admission type (aOR 0.90, 95% CI 0.77–1.05), indicating that excess mortality associated with nonelective presentation is driven by presentation severity and care pathway rather than differences in rescue quality. In unadjusted analyses, nonelective presentation was associated with higher mortality (2.21% vs 0.68%), greater ICU-level care use (33.8% vs 8.9%), more frequent major complications (45.0% vs 12.4%), and longer length of stay (7.84 vs 4.99 days) compared with elective admissions. Conclusions: In a procedure-defined, presumed early-stage lung cancer surgical cohort, nonelective admission identifies a common care-delivery failure phenotype associated with higher perioperative morbidity, ICU-level care, in-hospital mortality, and longer hospitalization. Emergency presentation represents a systems-level vulnerability in curative-intent lung cancer care and serves as a scalable and actionable marker for quality improvement and disparity-focused analyses.

e23193 Background: Small cell lung cancer (SCLC) is typically treated with outpatient systemic therapy; inpatient chemotherapy during acute hospitalization represents a high-risk care-delivery phenotype driven by delayed diagnosis, access barriers, or acute clinical decompensation rather than tumor biology alone. National data describing this care pathway and its inpatient outcomes remain limited. Methods: The U.S. National Inpatient Sample (2016–2023) was analyzed using survey weights. Adult hospitalizations meeting an ICD-10–based proxy definition for small cell lung cancer, defined by lung cancer diagnoses combined with neuroendocrine malignancy codes and excluding palliative care admissions, were identified. Inpatient chemotherapy was defined using ICD-10-PCS administration codes with prespecified sensitivity definitions. Outcomes included in-hospital mortality (primary), ICU-level care, sepsis, acute kidney injury, length of stay, hospitalization costs, and routine discharge. Multivariable survey-weighted logistic regression adjusted for patient demographics, payer, admission characteristics, and hospital factors. Results: The analytic cohort included 2,507 unweighted hospitalizations, representing 12,535 nationally weighted admissions. In multivariable analyses adjusting for demographics, payer, admission characteristics, and hospital factors, inpatient chemotherapy was independently associated with higher in-hospital mortality (adjusted odds ratio [aOR] 2.31, 95% CI 1.48–3.60) and greater ICU-level care (aOR 2.80, 95% CI 1.86–4.23). These associations were consistent across prespecified sensitivity analyses. In unadjusted analyses, inpatient chemotherapy occurred in 12.3%–19.3% of admissions annually from 2016–2023 and was associated with higher mortality (8.7% vs 5.2%), greater ICU-level care (11.8% vs 4.9%), longer length of stay (11.6 vs 7.0 days), higher costs ($38,446 vs $23,746), and lower routine discharge rates (42.8% vs 48.4%). Among 400 admissions with procedure-day data, chemotherapy was administered a mean of 3–5 days after admission. Late inpatient chemotherapy (day ≥2) was associated with higher mortality (10.6% vs 5.6%), greater ICU-level care (14.8% vs 9.2%), longer hospitalization (14.1 vs 8.0 days), and higher costs ($46,203 vs $28,025) compared with early chemotherapy (day 0–1), supporting inpatient chemotherapy as a marker of late care escalation rather than planned inpatient treatment. Conclusions: Inpatient chemotherapy identifies a high-risk care-delivery phenotype in hospitalized small cell lung cancer, with higher mortality, greater ICU-level care, and increased resource use, supporting its role as a marker of late care escalation or system-level barriers and a scalable quality indicator.

e21521 Background: Outcomes following tumor-infiltrating lymphocyte (TIL) therapy vary in real-world practice, and accessible predictors are needed to inform patient selection and timing of referral. We evaluated whether baseline disease burden, metastatic distribution, and treatment delivery factors are associated with outcomes following TIL therapy. Methods: We retrospectively analyzed patients with metastatic melanoma treated with TIL therapy across Mayo Clinic sites (N = 27 infused). Baseline disease burden was characterized using AJCC metastatic stage and organ-specific involvement. A composite high visceral burden variable was defined as the presence of M1d disease and/or liver metastases. Bridging therapy use prior to infusion was recorded. Post-infusion IL-2 exposure was categorized as low (0-2 doses) vs. high (3-6 doses). Best overall response (BOR) was summarized using RECIST-based standard criteria. Overall survival (OS) and progression-free survival (PFS) were measured from TIL infusion and estimated using Kaplan–Meier methods with univariable Cox regression. Results: Median age at infusion was 62.0 years; 59.3% were male. Melanoma subtypes included cutaneous (81.5%) and mucosal (18.5%). Bridging therapy was used in 48.1%. Baseline metastatic stage was M1a/M1b in 18.5%, M1c in 63.0%, and M1d in 18.5%. Median follow up was 8.3 months. BOR included complete response (18.5%), partial response (37.0%), stable disease (22.2%), and progressive disease (22.2%), yielding an objective response rate of 55.6% and disease control rate of 77.8%. Patients with high visceral disease burden experienced inferior OS vs. those without high visceral burden (median 5.2 vs 13.4 months; HR 4.77, 95% CI 1.22–18.63; p = 0.014). Bridging therapy was not associated with OS or PFS. Higher post-infusion IL-2 exposure (seen in 77.8% of patients) was associated with improved OS (median 9.0 vs 3.7 months; HR 0.16, 95% CI 0.04–0.67, p = 0.005), likely reflecting early post-infusion clinical tolerance rather than a causal treatment effect. Median PFS for the cohort was 3.6 months and did not differ by IL-2 exposure ( p = 0.3), metastatic stage ( p = 0.8), bridging therapy ( p = 0.7), liver metastases ( p = 0.2), or LDH above upper limit of normal ( p = 0.1). Conclusions: The above findings are hypothesis generating and will support evaluation in larger cohort. In this real-world cohort of patients treated with TIL therapy, baseline visceral disease burden was strongly associated with survival outcomes, while bridging therapy did not compromise post-infusion efficacy among patients proceeding to infusion. Post-infusion IL-2 exposure correlated with OS and likely reflects early treatment tolerance. These readily available clinical features may inform patient counseling, referral timing, and sequencing decisions as TIL therapy enters broader clinical use.

e20700 Background: Leptomeningeal metastases (LM) are a particularly challenging complication of EGFR-mutant non–small cell lung cancer (NSCLC) and are often associated with rapid neurologic decline. Intrathecal (IT) chemotherapy is frequently used in this setting, but its efficacy and safety have not been well defined. We conducted a systematic review and meta-analysis to assess neurologic response and treatment-related toxicity associated with IT chemotherapy in EGFR-mutant NSCLC with LM. Methods: We performed a PRISMA-guided search of MEDLINE, EMBASE, Cochrane CENTRAL, and targeted grey literature to identify prospective and retrospective studies reporting outcomes of IT chemotherapy in EGFR-mutant NSCLC with LM. Quantitative analyses were restricted to studies with extractable endpoints. Neurologic response and grade ≥3 toxicity were pooled using random-effects generalized linear mixed models with logit transformation. Heterogeneity was assessed using I² and τ². Prespecified sensitivity analyses examined neurologic response by route of administration (lumbar puncture vs Ommaya reservoir), concomitant EGFR-TKI use, and study design or era. Results: Four studies comprising 76 patients reported extractable neurologic response data. The pooled neurologic response rate was 81.9% (95% CI, 64.0%–92.0%), with moderate heterogeneity (I² = 63.4%, p = 0.04). Grade ≥3 toxicity was reported in three studies (n = 59), with a pooled incidence of 11.8% (95% CI, 3.2%–34.9%) and substantial heterogeneity (I² = 71.3%, p = 0.03). Myelosuppression was the most frequently reported severe adverse event, and no consistent signal of severe neurologic toxicity was identified. Exploratory sensitivity analysis suggested higher neurologic response in LP-treated cohorts compared with mixed LP/Ommaya cohorts; however, this finding was driven by a single small study and is likely influenced by limited sample size and selection bias and should be considered hypothesis-generating only. Neurologic response was otherwise consistent across study designs and eras. Stratification by concomitant EGFR-TKI use was limited by incomplete reporting. Median overall survival was variably reported and ranged from approximately 7 to 12 months. Conclusions: In EGFR-mutant NSCLC with leptomeningeal metastases, IT chemotherapy is associated with a high pooled neurologic response and relatively uncommon severe toxicity, although heterogeneity across studies remains substantial. The observed neurologic benefit appears consistent across study designs and is more likely related to underlying EGFR-sensitive disease biology than to a definitive effect of route of administration. These findings support further prospective evaluation of IT chemotherapy as part of multimodal treatment strategies in this high-risk population.

e18597 Background: TP53 mutations ( TP53 m) are uncommon in chronic-phase (CP) Philadelphia (Ph) chromosome–negative myeloproliferative neoplasms (MPN) but are increasingly reported in myelofibrosis (MF) and accelerated/blast phase (AP/BP). Their distribution, allelic configuration, and associated clinical outcomes have not been systematically synthesized. Methods: A PRISMA-guided search of EMBASE and PubMed (1974-July 1, 2025) identified cohort studies reporting adult Ph–negative MPNs with molecularly confirmed TP53 m. Case reports were excluded; Conference abstracts were included if cohort-level data were available. Extracted variables included demographics, MPN subtype, disease phase, TP53 allelic status (per International Consensus Classification), variant allele frequency (VAF), allogeneic hematopoietic cell transplantation (allo-HCT), median overall survival (mOS), and leukemic transformation. Given heterogeneity and lack of comparators, pooled proportions with (95% CI) were generated for descriptive variables; outcomes were summarized descriptively. Results: 10 retrospective studies met inclusion criteria. Pooled mean age was 61 years (95% CI 57.18–65.17) with male predominance (58%, 95 CI 53–63). TP53 m were uncommon in patients with Ph-negative MPN (3%, 95% CI 0–15%) but were higher in MF/AP/BP (10%, 95% CI 4–24%). Among patients with TP53 m, disease distribution included MF (35%, 95% CI 13–65%), AP/BP (33%, 95% CI 26–41%), essential thrombocythemia (ET) (10%, 95% CI 3–28%), and polycythemia vera (PV) (8%, 95% CI 4–14%). Multi-hit TP53 m accounted for 52% (95% CI 40–64%), while single-hit comprised 47% (95% CI 34–60%). The pooled mean TP53 VAF was 37.48% (95% CI 30.73–44.24%). Allo-HCT was used in 16% (95% CI 13–20%). One cohort reported leukemic transformation in 47% with a median follow-up of 9.6 months (m). Reported mOS in TP53 m CP-MF ranged from 11.6–18 m and was not reached in PV/ET, whereas AP/BP mOS ranged from 4.5–6 months. Conclusions: TP53 m Ph–negative MPNs are enriched in MF and AP/BP and frequently demonstrate multi-hit TP53 m with high VAF and associated with high leukemic transformation. Standardized molecular reporting and prospective studies are needed to refine prognostication and treatment strategies in TP53m MPN. Characteristics of patients with TP53 m MPN. Variable Pooled variables (95% CI) Age 61.18 years (57.18–65.17) Male/Female 58% (53–63)/42% (53–63) TP53 mutation in the cohort 3% (0–15) TP53 in MF/AP/BP 10% (CI 4–24) Primary myelofibrosis 35% (13–65) MPN in AP/BP 33% (26–41) Essential thrombocythemia 10% (CI 3–28) Polycythemia vera 8% (CI 4–14) Multi-hit/single-hit TP53 52% (CI 40–64) 47% (CI 34–60) TP53 VAF 37.48% (30.73–44.24) Abbreviations: MF: Myelofibrosis, AP: accelerated phase, BP: Blast phase, MPN: myeloproliferative neoplasm, VAF: Variant Allele Frequency.

9557 Background: High-dose interleukin-2 (IL-2) is administered following tumor-infiltrating lymphocyte (TIL) therapy, yet cardiotoxicity frequently limits dose delivery. The clinical significance of peri-dose troponin elevations during IL-2 remains poorly defined. We evaluated troponin kinetics during IL-2 dosing and their association with significant cardiac events and IL-2 interruption. Methods: We retrospectively analyzed patients with metastatic melanoma treated with TIL therapy followed by inpatient high-dose IL-2 at Mayo Clinic Rochester (N = 24; 87 IL-2 doses). High-sensitivity troponin and ECGs were obtained before and after each IL-2 dose. Clinically significant cardiac events were defined as QTc prolongation > 480 ms, arrhythmias (excluding isolated sinus tachycardia), new ECG abnormalities, vasopressor requirement, or cardiology consultation. Dose-level outcomes included cardiac events and subsequent IL-2 dose interruption. Paired troponin changes were assessed using Wilcoxon signed-rank testing. Dose-level associations were evaluated using clustered logistic regression to account for repeated IL-2 doses within patients. Results: 24 patients received 87 IL-2 doses (median 3 [IQR 2 - 5]). Median age was 63 years (IQR 54 - 70), and 58% were male. Baseline troponin median was 11 ng/L (IQR 6 - 21); 38% had baseline troponin > 14 ng/L. Post-dose troponin exceeded 14 ng/L in 16/24 patients (67%) and 48/87 doses (52%). Median delta troponin was 0 ng/L (IQR −1 to 6; range −24 to 133), with post-dose levels higher than pre-dose values ( p = 0.02). Clinically significant cardiac events occurred in 33% of patients; no post-IL-2 reductions in left ventricular ejection fraction were observed. At the dose level, cardiac events occurred only when post-dose troponin exceeded 14 ng/L (15/48 [31%] vs 0/39 doses; p < 0.001). In clustered logistic regression, post-dose troponin ≥15 ng/L was independently associated with cardiac events (OR 9.6, 95% CI 1.5 - 60.6; p = 0.02) and subsequent IL-2 dose interruption (OR 3.4, 95% CI 1.1 - 10.7; p = 0.04). When modeled continuously, each 1-unit increase in log-transformed post-dose troponin was associated with higher odds of cardiac events (OR 3.3, 95% CI 1.6 - 6.7; p = 0.001) and IL-2 interruption (OR 2.8, 95% CI 1.6 - 4.9; p < 0.001). Baseline troponin correlated with peak post-dose troponin (ρ = 0.44, p = 0.04). Conclusions: Peri-dose troponin elevations are common during post-TIL high-dose IL-2; however, higher post-dose troponin independently identifies clinically significant cardiac toxicity and predicts IL-2 interruption after accounting for repeated dosing within patients. Baseline troponin modestly predicts peak elevations, supporting standardized, risk-stratified troponin monitoring and prospective evaluation of toxicity-adaptive IL-2 delivery strategies in TIL therapy.

9510 Background: Although acute toxicities associated with adoptive cellular therapy using lifileucel are well described and largely occur within the first 2 weeks of treatment, adverse events beyond this early window remain incompletely characterized. We sought to characterize treatment-related adverse events (AEs) with emphasis on those starting or persisting ≥2 weeks after lifileucel infusion. Methods: We conducted a retrospective multicenter study across three centers (Moffitt Cancer Center, Massachusetts General Hospital, and Mayo Clinic). Patients with advanced melanoma treated with lifileucel were included. The primary endpoint was incidence and characterization of AEs occurring or persisting ≥2 weeks after standard of care lifileucel infusion. Results: Among 79 patients (median follow-up 11 months [95% CI, 9.6–15]), median age was 63 years (range 30–79), 59% were male (n = 47), 41% were female (n = 32), and ECOG PS was 0–1 in 98%. Patients received a median of 5 IL-2 doses (range 0–6). Of 79 patients, 78 experienced treatment-related adverse events that either persisted or occurred >2 weeks after cell infusion. A total of 308 delayed treatment-related adverse events were identified; 96 were new events (31%) and 212 (69%) were continued toxicities that started < 2 weeks after cell infusion. Lymphopenia was the most common delayed or persistent toxicity, occurring in a majority of patients (n = 68/79, 86%). Treatment-associated anemia (n = 59/79, 75%), fatigue (n = 56/79, 71%) and thrombocytopenia (n = 24/79, 30%) were also common. Viral infections occurred in 9.0% (n = 7), including CMV/EBV viremia (n = 1) and respiratory or gastrointestinal viral infections (metapneumovirus, parainfluenza, SARS-CoV-2, and norovirus). Hemophagocytic lymphohistiocytosis (HLH) occurred in 2 patients (n = 2/79, 3%) and was fatal in both cases. No other toxicity related deaths were noted. Autoimmune toxicities directly attributable to TIL included vitiligo in 9% (n = 7; median onset 41 days), uveitis in 5% (n = 4; median onset 26 days), and sensorineural hearing loss in 1% (n = 1; onset 28 days). All patients underwent TIL infusion in the inpatient setting; a total of 14 of 79 patients (18%) were re-admitted after discharge due to treatment-related toxicity (median time from infusion 19 days). Conclusions: In this multicenter real-world cohort, toxicities persisting beyond two weeks were largely driven by lymphodepleting chemotherapy–associated immunosuppression and cytopenias. These findings highlight the importance of structured post-discharge monitoring and support ongoing efforts to de-intensify lymphodepleting chemotherapy to improve safety while maintaining clinical benefit.

9551 Background: Lymphodepleting (LD) chemotherapy is required prior to tumor-infiltrating lymphocyte (TIL) therapy, yet the depth, kinetics, and completeness of peripheral T-cell recovery in practice remain poorly defined. Using a pooled, multi-institution cohort, we characterized longitudinal CD4 and CD8 T-cell reconstitution and the prevalence of CD4 lymphopenia following TIL therapy. Methods: We conducted a retrospective multicenter study across Mayo Clinic, Moffitt Cancer Center, and Massachusetts General Hospital of patients with metastatic melanoma treated with TIL (N = 41, median follow-up 7.6 months). Absolute CD4 and CD8 T-cell counts and CD4:CD8 ratios were assessed at baseline (pre-LD), week 4, month 3, and month 6 post-TIL. Clinically significant CD4 lymphopenia was defined as CD4 < 200 cells/µL. All patients received Pneumocystis jirovecii and antiviral prophylaxis, with antibacterial and antifungal prophylaxis administered per institutional protocols. Post-TIL infections were recorded. Paired changes from baseline were evaluated using Wilcoxon signed-rank testing. Results: Median age was 65 years (range 35-79), and 68% were male. At baseline, 16 patients (39%) had CD4 counts below the institutional lower limit of normal prior to LD. Eighteen patients (44%) received bridging therapy prior to TIL and had lower baseline CD4 and CD8 counts compared with those who did not ( p < 0.05 for both); however, post-TIL CD4 and CD8 recovery trajectories did not differ between groups. CD4 counts declined sharply following LD and demonstrated incomplete and heterogeneous recovery. Median CD4 decreased from 490 cells/µL at baseline to 250 at week 4, 290 at month 3, and 220 at month 6, remaining significantly below baseline at all post-TIL timepoints ( p < 0.05). Clinically significant CD4 lymphopenia was observed in 45% (10/22) of evaluable patients at month 3 and in 50% (44%, 7/16) at month 6. In contrast, CD8 counts increased early after TIL (median 240 to 590 cells/µL at week 4; p = 0.004) and remained higher than baseline at month 6. The CD4:CD8 ratio inverted from a median of 2.02 at baseline to 0.46 at week 4 and remained below 1.0 through month 6, reflecting sustained CD4 suppression despite CD8 recovery. Post-TIL infections occurred despite widespread prophylaxis, including bacterial (13%), viral (10%), and fungal (4.9%) infections. Conclusions: In a multi-institution cohort, LD chemotherapy preceding TIL is associated with profound and prolonged CD4 T-cell suppression, persistent CD4:CD8 inversion, and a high prevalence of CD4 < 200 cells/µL through 6 months. These findings identify delayed immune reconstitution as a common and clinically relevant consequence of TIL therapy and support prospective optimization of antimicrobial prophylaxis duration, vaccination timing, and immune monitoring strategies.

8077 Background: Small cell lung cancer (SCLC) is an aggressive malignancy with poor prognosis. This study evaluates national trends in surgical management of early-stage SCLC using the National Cancer Database (NCDB), aiming to identify factors associated with improved outcomes and assess the survival benefit of surgical resection. Methods: Patients diagnosed with clinical stage T1–T3 N0 M0 SCLC between 2004 and 2022 were identified from the NCDB. Exclusions included non-SCLC histologies, advanced or missing staging, non-lobectomy surgeries, and incomplete survival data. Propensity score matching (1:1) was used to balance surgical and non-surgical cohorts based on demographic, clinical, and socioeconomic variables. Kaplan-Meier and Cox regression analyses were used to evaluate overall survival, stratified by T stage. Results: Among 17,762 patients with early-stage SCLC, 3,234 (18.2%) underwent lobectomy with mediastinal lymph node dissection. Surgical rates increased from 5% in 2004, 17% in 2013 to 24% in 2021. Surgery was more common in T1 (26.5%) than T2 (11.4%) or T3 (4.6%) disease. After matching, surgery was associated with improved survival across all T stages, with no significant interaction between T stage and surgical benefit (p=0.43). Older age, male sex, and higher comorbidity scores predicted worse outcomes. Among surgical patients, 2.3% received neoadjuvant therapy and 71.6% received adjuvant treatment. Systemic therapy-both neoadjuvant (HR 0.63) and adjuvant (HR 0.69)-was significantly associated with improved survival. Conclusions: Lobectomy remains underutilized in early-stage SCLC but is linked to significantly improved survival. Albeit small patient's number, neoadjuvant systemic therapy further enhanced survival, supporting broader use of surgery and multimodal treatment in appropriately selected patients Univariable results 1 Multivariable results 2 Characteristic No. deaths Person-months HR (95% CI) p-value HR (95% CI) p-value Charlson score <0.001 <0.001 0 761 77727 1.00 (ref) 1.00 (ref) 1 623 60483 1.06 (0.95,1.18) 1.07 (0.96,1.20) 2 or more 350 27025 1.30 (1.15,1.48) 1.30 (1.13,1.48) Clinical T-stage 0.011 0.014 cT1N0M0 1266 124916 1.00 (ref) 1.00 (ref) cT2N0M0 406 33924 1.18 (1.06,1.32) 1.20 (1.06,1.35) cT3N0M0 62 6393 0.96 (0.75,1.24) 1.00 (0.76,1.31) Residual disease <0.001 <0.001 No residual tumor 1626 158838 1.00 (ref) 1.00 (ref) Residual tumor 92 4699 1.91 (1.55,2.36) 1.91 (1.52,2.40) Neoadjuvant systemic treatment 0.253 0.034 No 1629 154116 1.00 (ref) 1.00 (ref) Yes 30 3495 0.81 (0.56,1.16) 0.63 (0.41,0.97) Adjuvant radiation 0.067 <0.001 No 1209 118925 1.00 (ref) 1.00 (ref) Yes 452 40471 1.11 (0.99,1.23) 1.33 (1.18,1.51) Adjuvant systemic treatment <0.001 <0.001 No 563 44045 1.00 (ref) 1.00 (ref) Yes 1096 113566 0.75 (0.68,0.83) 0.69 (0.62,0.78)