Based on this clinical report, megalocornea, partial callosal agenesis and mild bilateral occipital lobe hypoplasia should perhaps be included in the list of anomalies associated with partial trisomy 16q.

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INTRODUCTION:Urothelial Bladder Cancer (UBC) is the ninth worldwide most common cancer. In Italy the prevalence of the disease is about 10 percent, representing the third most prevalent cancer with 180,775 cases in men and 42,757 cases in women. The increase in the incidence requires continuous surveillance and care, resulting in a significant burden on Italian Healthcare System, making any improvement to the strategy for diagnosing and treating this disease important to the medical and scientific community. The aim of this study was to evaluate the burden of UBC in the Italian context, collecting and measuring the total costs of the disease.METHODS:An economic analysis in the National Health Service perspective was carried out, evaluating in six centers direct costs in terms of outpatient, inpatient and emergency care, pharmaceuticals and follow up procedures and indirect costs in terms of productivity losses. Data were collected through aggregated form reports, focusing on patients with an existing diagnosis of UBC who were taken in charge in the last year. Statistical analysis was conducted in order to explore variations between centers.RESULTS:Mean total annual cost per patients was EUR11,310, increasing for disease severity from EUR6,954 for superficial disease to EUR24,896 for metastatic stage. The analysis confirmed a proportional relation between disease severity and disability grade. The total burden of the disease considering all patients, including prevalence and incidence data coming from AIOM guidelines 2015, was EUR2,833,655,822, of which 15 percent is represented by estimated productivity losses.CONCLUSIONS:Our analysis represents the first economic burden study of UBC in the Italian context as well as the first real life evidence of the current therapeutic algorithm. This study opens the possibility for further analysis on the indirect costs components that represent a great burden for the society, especially for the stages of the disease with high disability grade.

Background: Lung cancer in the female population is a growing sanitary problem. Gender-related differences in susceptibility, pathogenesis and possible cure for this disease are interesting fields of basic and clinical investigation. Female sex, adenocarcinoma histology, non smoking history represent clinical features correlated with response to EGFR-TKIs. The use of these molecules in patients selected on a "clinical enrichment" basis are warranted. Patients and Methods: The mutational status of EGFR (exons from 18 to 21) and K-ras (exon 1) is routinely evaluated in patients with adenocarcinoma of the lung referred to our Institution. From January 2006 30 women with advanced NSCLC were observed: median age 60 yrs (37-80); smokers=12 pts (40%); non smokers=18 (60%). Adenocar-cinoma= 22 pts (73.3%); BAC =6 (20%); adenocarcinoma with BAC features= 2 (6.7%). Fifteen pts (50%) had stage IV disease at diagnosis and 5 of them (33.3%) showed brain metastases. Results: 9/30 (30%) EGFR mutations were detected: 5 in exon 19; 2 in exon 21; 2 in exon 20. 3/30 (10%) K-ras mutations were noted. 11 patients received TKIs (Gefitinib 250 mg/die or Erlotinib 150 mg/die orally) as second-line therapy for at least 2 months and were evaluable for activity: 5 PR (45%) and 6 PD (55%) were observed. All responding patients were non smokers; 3 had mutation in exon 19, 1 in exon 21 and 1 had Wild Type EGFR. All were WT K-ras. Among patients with PD: 1 had tumor with mutation in exon 21, 2 had tumors with K-ras mutation and 3 WT EGFR. Median progression-free survival was 5 months (range 2-14+ months); median overall survival was 27 months (range 8-108 months). Conclusions: In our "clinically enriched" population (women with adenocarcinoma) we can observed that: 1) 60% of patients were non smokers; 2) 17% had brain metastases at diagnosis; 3) the frequence of EGFR mutations is 30% (higher than that reported in caucasian non selected series); 4) the most frequent EGFR mutation was in exon 19. In patients receiving second-line TKIs response rate was 45%; all responding patients were non smokers and 4/5 (80%) had tumors with EGFR mutations. The study is ongoing. Updated results will be presented at the meeting.

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Background: Treatment (Tx) options for METex14 NSCLC have been limited to chemotherapy (Ctx), immunotherapy (IO), and multikinase inhibitors (MKi) until FDA approvals of selective MET inhibitors (METi) from 2020. BM are a further challenge to treat. We previously reported NGS timing in relation to start of first-line Tx (1L) for pts with METex14 NSCLC in the RW. Here we provide overall survival (OS) data, including subgroup analyses for pts with known BM prior to 1L initiation. Methods: Data originating from ~280 US cancer clinics (~800 sites of care) from the US electronic health record-derived de-identified Flatiron Health Foundation Medicine clinico-genomic database (FH-FMI CGDB) were evaluated. Pts were ≥18 yrs, diagnosed with advanced/metastatic NSCLC from Jan 1, 2011, with NGS-confirmed METex14, ≥1 line of Tx, and ≥90 days follow-up from 1L initiation to cutoff date (Dec 2020). Pts treated with capmatinib or tepotinib were excluded. We examined Tx patterns and OS for pts with and without known BM before starting 1L, and OS for pts with an NGS report before or on/after 1L initiation (time from 1L initiation to death or censoring, analyzed using Kaplan-Meier method with left truncation adjustment to mitigate bias due to the prerequisite for NGS testing). HRs were estimated using Cox regression models with covariates adjustment to estimate risk of death. Results: The analysis included 156 METex14 NSCLC pts: median age 75 yrs, 59% females, 85.3% non-squamous (NSQ), 9% squamous cell carcinoma (SQ), and 64% had history of smoking. A total of 31 pts (20%) had BM before 1L initiation: median age 73 yrs, 61% females, 94% NSQ, 0% SQ, and 71% had history of smoking. Overall, treatment patterns were similar for pts with and without known BM before 1L initiation (Ctx with or without IO, IO monotherapy, and MKi were all used in 1L). Median OS for pts with BM was 8.11 mo (95% CI, 6.0-19.8) and 14.39 mo (11.1-22.1) for pts without BM, corresponding to a 73% increase in risk of death for pts with BM vs pts without BM by univariate analysis (HR 1.73 [95% CI, 1.06-2.82]; P=0.03). Median OS for pts with an NGS report before and on/after 1L initiation was 13.3 mo (8.8-26.2) and 6.8 mo (0.03-19.8), respectively (P=0.45); HR by multivariate analysis was 0.78 (0.45-1.35) when comparing pts with NGS report before vs on/after 1L initiation. Conclusions: Tx patterns in 1L were similar for pts with or without BM at time of 1L initiation; presence of BM prior to 1L was associated with inferior outcomes. Numerically longer OS was observed in pts with NGS report prior to 1L initiation vs pts with NGS report on/after 1L, supporting further investigation of underlying causes. These data underline the ongoing unmet clinical need of METex14 NSCLC BM and the importance of investigating upfront comprehensive genomic testing in NSCLC. Citation Format: Xiuning Le, Stephen Robb, Nydia Caro, Simona Doria, Whitney C. Rhodes, Wen-Hsing Wu, Julia Kim, Vincent Prêtre, Fen Ye. Brain metastases (BM) and next-generation sequencing (NGS) timing: Real-world (RW) outcomes for patients (pts) with advanced non-small cell lung cancer (aNSCLC) and MET exon 14 skipping mutations (METex14) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 4118.