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4017 Background: First-line mCCA treatment is chemotherapy and immunotherapy. Based on the phase 2 FIGHT-202 trial, pemigatinib was the first FGFR1-3 inhibitor approved in second line and beyond for mCCA with FGFR2 rearrangement. Results from the phase 3, randomized, global FIGHT-302 trial evaluating pemigatinib as first-line therapy are reported here (NCT03656536). Methods: Patients (pts) aged ≥18 y with previously untreated mCCA with FGFR2 rearrangement were randomized 1:1 to receive oral pemigatinib (13.5 mg once daily q21) or intravenous chemotherapy (1000 mg/m 2 gemcitabine + 25 mg/m 2 cisplatin d1,8 q21 ≤8 cycles) stratified by previous receipt of 1 chemotherapy cycle, geographic region, and tumor burden. Pemigatinib crossover was allowed for control arm pts progressing on chemotherapy. Primary end point was progression-free survival (PFS). Secondary efficacy, safety, and exploratory end points were also analyzed. Results: After prescreening >4000 pts, only 196 had FGFR2 rearrangement and were screened; 167 were randomized to receive pemigatinib (n=83) or chemotherapy (n=84) before closing the study early due to slow accrual. Baseline characteristics and demographics were similar between arms. Median PFS (mPFS) with pemigatinib versus chemotherapy was 8.3 versus 6.8 mo, respectively (hazard ratio [95% CI], 0.58 [0.39-0.87]; nominal P =.0078); secondary efficacy endpoints generally supported primary results (Table). Median OS was similar, although these results are confounded by FGFR inhibitor administration as second-line treatment. In the crossover group (n=42, second-line pemigatinib), mPFS was 8.1 mo. Safety was consistent with previous results (Table). Exploratory analyses of genetic co-alterations associated with treatment response will be presented. Conclusions: FIGHT-302 was the first phase 3 trial of a targeted therapy for untreated mCCA. Pemigatinb demonstrated superior activity and prolonged mPFS compared with first-line chemotherapy. The results confirm the current management paradigm of pemigatinib administration after disease progression on chemotherapy. Clinical trial information: NCT03656536 . Pemigatinib Gemcitabine + cisplatin mPFS (95% CI), mo a 8.3 (6.5-12.2) 6.8 (6.1-8.3) Objective response rate, n/N (%) a 39/83 (47) 13/84 (15.5) Median duration of response (95% CI), mo a 14.2 (8.7-24.7) 6.3 (4.3-not estimable) Median overall survival (95% CI) a,b , mo 24.4 (18.6-35.9) 25.0 (18.7-34.2) Treatment related TEAEs, n/N c (%) 80/83 (96) 70/73 (96) Serious TEAEs, n/N (%) c,d 23/83 (28) 17/73 (23) Grade ≥3 TEAEs, n/N (%) c 65/83 (78) 49/73 (67) TEAEs leading to treatment discontinuation, n/N (%) c 5/83 (6) 8/73 (11) Fatal TEAE, n/N (%) c,d 3/83 (4) 0 a All randomized pts. b Interpretation limited by second-line treatment with FGFR inhibitor in gemcitabine + cisplatin arm. c Pts who received ≥1 study dose. d None deemed treatment related.

1557 Background: Immunotherapy is now a standard-of-care treatment for lung cancer across most stages. Access to immunotherapy and molecular diagnostic tests in conflict-affected countries such as Syria remains poorly described. As the principal cancer center in Syria, Al-Bairouni University Hospital (ABUH) provides care for nearly three-quarters of all cancer cases nationally. We conducted this study to evaluate access to immunotherapy and molecular diagnostic services at ABUH. Methods: A mixed-methods study was performed between 2022 and 2024 at ABUH. This study included a retrospective cohort of all patients diagnosed with lung adenocarcinoma. Quantitative data included disease stage at diagnosis, molecular testing rates, and immunotherapy utilization. In addition, a qualitative patient survey was thematically analyzed to explore barriers to treatment access in a separate cohort of patients with mixed tumor types. Results: Among 2,920 patients diagnosed with lung cancer, 1,393 (47.7%) had lung adenocarcinoma. The median age at diagnosis was 61 years; 79.7% of patients were male. Smoking history was as follows: Current 792 (56.9%), Former 268 (19.2%), never smoked 318 (22.8%) At presentation, 3 patients (0.2%) had stage I disease, 40 (2.9%) stage II, 174 (12.5%) stage III, and 778 (55.8%) stage IV disease, staging was unknown for the rest of the patients. EGFR mutation testing was performed by ABUH for 226/1393 patients (16.2%) only, with positive results identified in 124 cases (8.9%). PD-L1 testing was conducted by ABUH in only 32/1393 patients (2.3%) and was positive in 23 (1.65%). Of all patients with lung adenocarcinoma, only 5 patients (0.6%) with stage IV disease received immunotherapy. All were treated with nivolumab. Thematic analysis of qualitative data (35 patients) revealed that high treatment costs and limited drug availability are the primary barriers to accessing immunotherapy. Conclusions: This study represents the first evaluation of access to immunotherapy for patients with lung cancer in Syria. Even at ABUH, the country's main cancer center, access to immunotherapy and molecular testing remains markedly limited. International collaboration is necessary to expand diagnostic infrastructure, standardize data reporting, and enhance financial protection mechanisms. These are critical steps toward achieving better cancer care in Syria.

1024 Background: Invasive lobular carcinoma (ILC) is a distinct breast cancer (BC) subtype with dissemination patterns differing from invasive breast carcinoma of no special type (IBC-NST). While genomic differences between ILC and IBC-NST have been described, the extent to which molecular and immune profiles vary by metastatic organ and histology is poorly characterized. Methods: We conducted a retrospective analysis to evaluate organ- and histology-specific molecular features of metastatic BC (mBC). Patients with metastatic IBC-NST or pure ILC underwent NGS (592, NextSeq; WES/WTS, NovaSeq; Caris Life Sciences). Tumor mutational burden (high ≥10 mut/Mb), PD-L1 expression (22C3), and immune cell fractions (RNAseq deconvolution, quanTIseq) were assessed. Analyses were restricted to sites with ≥10 biopsies per histology. Comparisons used chi-square or Mann–Whitney U tests with multiple testing correction (q < 0.05). Results: A total of 2645 mBC biopsies (605 ILC; 2040 IBC-NST) were analyzed (Table). In ILC, ERBB2 mut frequency differed by metastatic site (q<0.01), with higher prevalence in liver (32.7%) and lower in gastrointestinal (GI) lesions (3.7%). In IBC-NST, ESR1 and GATA3 mut and FGFR1 amplification were enriched in liver metastases, whereas PD-L1 expression was highest in skin (20.7%) and lowest in liver (5.0%). No organ-specific differences were observed for PIK3CA, AKT, PTEN, BRCA1/2 or RB1 . Across metastatic sites, both ILC and IBC-NST showed differences in B cells, macrophages (M1/M2), neutrophils, NK cells, dendritic cells, CD8+ T cells, and Tregs (all q < 0.05); CD4+ T-cell differences were observed only in IBC-NST (q = 0.002). In organ-specific ILC vs IBC-NST comparisons, CDH1 mut were more frequent in ILC across sites, along with higher PIK3CA mut in skin (ILC 51.3% vs IBC-NST 34.4%) and higher ERBB2 mut in liver (32.7% vs 3.3%), whereas a higher TP53 mut frequency was observed in IBC-NST in skin (28.5% vs 52.3%) and lymph nodes (LND) (23.5% vs 55.5%) (all q < 0.01). Conclusions: mBC exhibits marked organ-specific molecular and immune heterogeneity that differs by histology. These findings support histology- and site-aware interpretation of metastatic biopsies and may inform biomarker assessment and treatment decisions in advanced disease. BC-NST ILC Skin LND Bone Breast Liver Perit. CNS q-value Skin LND Bone Breast GI Liver GYN Perit. CNS q-value N (specimens) 785 401 109 361 220 15 44 - 172 84 62 56 56 54 43 37 11 - ERBB2 mut (%) 3.2 3.1 3.2 2.3 3.3 7.1 2.5 1.0 7.1 7.4 16.4 15.4 3.7 32.7 2.4 5.7 11.1 <0.01 ESR1 mut (%) 9.4 5.2 8.3 16.0 28.2 7.1 2.4 0.0 7.8 7.2 8.9 9.8 16.7 26.0 4.9 20.0 0.0 0.9 FGFR1 amp (%) 10.1 6.6 5.6 12.8 16.5 0.0 9.7 0.02 4.4 3.4 6.7 6.1 2.4 5.6 7.7 18.5 0.0 1.0 IHC-PD-L1 (%) 20.7 - 5.3 16.0 5.0 11.1 10.3 0.02 8.9 - 5.0 5.7 6.1 0.0 0.0 0.0 14.3 1.0 TMB-High (%) 10.7 10.1 8.8 8.8 8.5 14.3 21.4 0.8 27.6 11.0 19.6 28.0 11.3 19.6 9.8 32.4 22.2 0.8 Perit: peritoneum; CNS: central nervous system; GYN: genital tract.

<title>RESUMEN</title> <p>A pesar de que la Práctica Basada en la Evidencia (PBE) ha estandarizado los tratamientos psicológicos, la realidad clínica sigue enfrentándose a una barrera persistente: la dificultad de traducir los resultados de ensayos clínicos grupales a la singularidad de cada paciente en contextos reales. Como respuesta, la Salud Mental de Precisión (SMP) propone una evolución del modelo actual, integrando el cuidado basado en la medición y la toma de decisiones basada en datos para ajustar la intervención a las necesidades específicas de cada persona, gracias en gran medida a desarrollos tecnológicos recientes como la Inteligencia Artificial (IA). En este contexto, el presente artículo persigue dos objetivos fundamentales. En primer lugar, sintetiza los pilares operativos de la SMP, analizando cómo la medición rutinaria y las predicciones algorítmicas pueden potenciar el juicio clínico del profesional. En segundo lugar, se introduce el proyecto NOVA (Navigating Outcomes via Analytics), un proyecto traslacional diseñado para superar las barreras actitudinales, tecnológicas, estadísticas y contextuales de la implementación de herramientas de SMP en España. Se discute sobre los pasos necesarios para cerrar la brecha entre la innovación tecnológica y la práctica asistencial en psicología, acelerando la adopción sostenible de una psicología de precisión en el mundo real.</p>

Abstract Background Whether outcomes of germline BRCA1/2 (gBRCA1/2)-associated breast cancer differ compared with sporadic tumors is controversial. We explored the impact of gBRCA1/2 pathogenic variant (PV) status beyond established prognostic features. Methods We conducted 2 retrospective, matched cohort studies comparing gBRCA1/2 PV carriers and noncarriers with HER2-negative, stage I-III breast cancer (Clinical Outcomes Quality Database [COQD] cohort: 185 carriers, 555 noncarriers; Young Women’s Breast Cancer Study [YWS] cohort: 113 carriers, 226 noncarriers). Matching factors were age, stage, hormone receptor status, and year of diagnosis. Clinicopathological features, treatments, and survival outcomes were compared between carriers and noncarriers. Results Most patients in COQD had stage I-II disease (87.2%), and more carriers than noncarriers had genetic testing before diagnosis (33% vs 5.6%, P &lt; .001). In YWS, 22.7% of patients had stage III tumors, and few were tested before diagnosis (14.8% of carriers vs 1.7% of noncarriers; P &lt; .001). Carriers in COQD received chemotherapy more often than noncarriers (81.1 vs 67.0%, P &lt; .001), including platinum (P = .010); the proportion was similar for carriers and noncarriers in YWS. After adjusting for chemotherapy, relapse-free survival was longer in carriers than noncarriers in COQD (adjusted hazard ratio = 0.48 [95% CI = 0.26 to 0.87], P = .016), and a favorable trend was observed for other survival outcomes in both cohorts. Triple-negative tumors appeared to drive the differences. Conclusions We observed a trend toward improved outcomes in gBRCA1/2 PV carriers compared with noncarriers. These findings suggest that carriers should not receive more aggressive treatment solely based on their germline mutation status. Prospective clinical trials in this population are warranted.

Abstract We describe early experience with beta-lactam therapeutic drug monitoring (TDM) in a high-volume outpatient parenteral antimicrobial therapy program. In selected patients, TDM informed dose optimization and toxicity mitigation. Illustrative cases highlight feasibility and emerging lessons supporting beta-lactam TDM in outpatient care.

Abstract Introduction Sedation is routinely administered to facilitate comfort and tolerance of life support for critically ill adults dependent on invasive mechanical ventilation. Isoflurane, a widely used anesthetic during surgery, has properties that may also benefit ICU patients requiring continuous sedation. However, efficacy as a sedative and safety in this population is not well established. Methods We conducted two identically designed multicenter randomized trials, INSPIRE ICU1 and INSPIRE ICU2, at hospitals across the US. Ventilator-dependent adults were randomly assigned in a 1.5:1 ratio to receive either inhaled isoflurane or intravenous propofol as the first-line sedative for up to 48 ± 6 hours, targeting a sedation depth between Richmond agitation-sedation scale (RASS) -1 (drowsy) to -4 (responsive only to physical stimuli). Isoflurane was administered via an anesthetic conserving device (Sedaconda ACD-S). In both arms, opioids were permitted at the lowest dose required to achieve freedom from pain. The primary outcome was the percentage of time at target sedation level, assessed as a noninferiority outcome with pre-specified margin of 15%. Secondary outcomes included opioid exposure, wake-up time after end of treatment, time to extubation, and proportion of time with spontaneous breathing effort. Results A total of 470 combined participants were included in the two trials. In each trial, 142 patients were randomly assigned to isoflurane and 93 to propofol. In INSPIRE ICU1, percentage of time within target sedation depth was 77.1 [53.2, 89.9] % with isoflurane and 80.9 [58.2, 96.4] % with propofol (difference -1.5 [-8.9, &gt;99] %; p &lt; 0.01 for noninferiority). In INSPIRE ICU2, percentage of time within target sedation depth was 72.6 [66.4, 78.9] % with isoflurane and 74.5 [67.5, 81.5] % with propofol (difference -1.9 [-9.4, &gt;99] %; p &lt; 0.01 for noninferiority). In both trials, patients assigned to isoflurane received significantly less opioid, measured as fentanyl equivalents, during the treatment period. In INSPIRE ICU2, participants receiving isoflurane were significantly likelier to exhibit spontaneous breathing efforts, but this finding was not replicated in INSPIRE ICU1. There were no significant differences in time to wake-up or time to extubation between groups in either trial. No episodes of malignant hyperthermia or propofol infusion syndrome were reported. Adverse events were comparable in type and frequency between groups. Conclusions In two US multicenter trials, isoflurane was noninferior to propofol for maintaining target sedation depth in adults undergoing invasive ventilation, and was associated with significantly lower opioid exposure. (NCT05327296, NCT05312385) This abstract is funded by: Sedana Medical

ABSTRACT Objective This study examines the knowledge, beliefs, and perceptions of asthma among caregivers in Bogotá, Colombia, a middle‐income country (MIC). It provides insights into how these factors influence self‐management and adherence. Methods Trained facilitators conducted focus groups composed of caregivers of asthmatic children. Interview data were analyzed and coded using a process of open coding transcription, followed by inductive thematic‐based coding. The basic codes were then elaborated into a framework of thematic categories within NVivo. Results Sixteen caregivers were divided into two focus groups. Knowledge, beliefs, and perceptions about asthma and inhalation therapy, interactions between caregivers and other individuals, the use of traditional and natural medicine, and the availability of essential medications for asthma therapy were highlighted by the participant caregivers. Although some of the issues identified in these topics are similar to those described in high‐income countries, there are some differences, particularly regarding the fears of patients developing addiction to medications due to the use of inhalation therapy in childhood, the lifelong requirement of inhalation therapy, and the use of traditional versus natural medicine. Conclusions The present study's findings provide insights into how caregivers understand asthma and its treatment in their children. These insights can serve as a basis for more targeted and effective educational interventions in Colombia and other countries with similar socio‐economic and cultural conditions.