Thein, Kyaw Zin

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.

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.

Introduction: Management of newly diagnosed multiple myeloma (NDMM), which accounts for 1% of all cancers, is an area in dire need of therapeutic innovation. In recent years, the introduction of novel agents is one of the major advances in the management of patients with NDMM, in both transplant- eligible and transplant- ineligible candidates. Studies have combined daratumumab, a human IgGκ monoclonal antibody that targets CD38 which is highly expressed on myeloma cells, with proteasome inhibitors and immunomodulatory agents-based regimens in the first-line treatment of NDMM. The purpose of our study is to explore and consolidate the efficacy of upfront daratumumab combination regimen in patients with NDMM. Methods: We systematically conducted a comprehensive literature search using MEDLINE, EMBASE databases and meeting abstracts from inception through June 2019. Phase III RCTs utilizing daratumumab in patients with newly diagnosed/ untreated multiple myeloma were incorporated in the analysis. A generic inverse variance method was used to calculate the estimated pooled hazard ratio (HR) for progression-free survival (PFS) with 95% confidence interval (CI). Mantel-Haenszel (MH) method was used to calculate the estimated pooled risk ratio (RR) for overall response rate (ORR), including stringent complete response (sCR), CR and very good partial response (VGPR). Heterogeneity was assessed with Cochran's Q -statistic. Random effects model was applied. Results: Three phase III RCTs with a total of 2,528 patients with NDMMwere included.Studies compared daratumumab (D) + bortezomib (V) + melphan (M) + prednisone (P) vs VMP, D + lenalidomide (R) + dexamethasone (d) vs Rd, and DVd + thalidomide (T) vs VTd. The randomization ratio was 1:1 in all studies. The I2statistic for heterogeneity was 0, suggesting homogeneity among RCT. The pooled HR for PFS was statistically significant at 0.52 (95% CI: 0.44-0.61; P < 0.0001). The PFS benefit was observed in all ISS categories, types of immunoglobulin (Ig) and standard risk cytogenetic; ISS I cohort (HR, 0.55; 95% CI: 0.37- 0.82; P = 0.003), ISS II cohort (HR, 0.43; 95% CI: 0.33- 0.55; P < 0.0001), ISS III cohort (HR, 0.63; 95% CI: 0.48- 0.82; P = 0.0006), IgG cohort (HR, 0.56; 95% CI: 0.40- 0.77; P = 0.0003), non-IgG cohort (HR, 0.52; 95% CI: 0.28- 0.97; P = 0.04), and standard risk cytogenetic cohort (HR, 0.43; 95% CI: 0.35- 0.53; P < 0.0001). The pooled HR for PFS in high risk cytogenetic cohort was not statistically significant at 0.76 (95% CI: 0.53- 1.10; P = 0.15). The pooled RR for ORR was 1.13 (95% CI: 1.01-1.26; P = 0.03), sCR was 2.02 (95% CI: 1.33-3.08; P = 0.001), CR was 1.46 (95% CI: 1.20-1.79; P = 0.0002),and VGPR was 1.01 (95% CI: 0.82-1.25; P = 0.93). The pooled RR for negative minimal residual disease (MRD) was 2.54 (95% CI: 1.24-5.20; P = 0.01). Conclusions: Upfront combination regimen with daratumumab significantly improved PFS, ORR, sCR and CR along with negative MRD, compared to control arm in patients with NDMM. The improvement in PFS was noted across all subgroups except in high-risk cytogenetic group. More randomized studies are required to explore further novel agents and to formulate optimal combination regimen to improve survival in this high-risk cytogenetic subset. Disclosures No relevant conflicts of interest to declare.

250 Background: Testicular germ cell tumor survivors (TGCTSs) contend with treatment side effects for decades after cure, and many have metabolic syndrome (MTS), a modifiable cardiometabolic risk factor. Because reliably predicting MTS could prompt interventionreducing risk, we analyzed clinical data and body composition in computed tomography (CT) scans to identify associations. Methods: In a retrospective review of 196 TGCTSs treated at a single institution from 1970 to 2007, we collected patient (pt) demographics, clinical data, body fat composition measures, and evidence from CT scans from baseline through posttreatment. NIH Image J was used to analyze cross-sectional CT images and measured subcutaneous adipose tissue, visceral adipose tissue, and skeletal muscle. Visceral fat-to-muscle ratio (VMR), visceral-to-subcutaneous fat ratio (VSR), and change in VMR and VSR from baseline to 3 to 5 years posttreatment (ΔVMR and ΔVSR) were calculated. We also gathered posttreatment glucose, blood pressure, lipid data, and body weight and height measured at time of scans. The 2001 U.S. National Cholesterol Education Program Adult Treatment Panel III guideline defined MTS. Univariate and multivariate logistic regression analyses identified associations. Results: Of the 167 pts included in the final analysis, 37.7% had MTS, 76.6% were white, and 68.9% had chemotherapy. Pts with MTS had significantly higher VMRs (p = .007) and VSRs (p = .021) than those without. Pts receiving chemotherapy and radiotherapy were significantly more likely to have MTS (p = .044 and p = .037). A multinomial logistic regression model including year of diagnosis, age, race, tumor histology, treatment, VSR, and VMR identified the association of high VMR and VSR with MTS; ΔVMR and ΔVSR were not statistically significant predictors. Conclusions: Body composition analyses identified VMR and VSR as significant predictors of MTS.