Citations

Abstract Sinonasal cancers are malignant neoplasms arising from the nasal cavity and paranasal sinuses, including squamous cell carcinoma (SCC), adenocarcinoma, and undifferentiated carcinoma. Due to their rarity, comprehensive genomic data remain limited. Treatments include surgery, radiation, and chemotherapy, with ongoing trials investigating agents like cetuximab, cisplatin, and Tazemetostat. We analyzed sinonasal cancer cases from the American Association for Cancer Research (AACR) Project Genomics Evidence Neoplasia Information Exchange (GENIE) database via cBioPortal (v16.1-public, accessed July 22, 2024). Common gene mutations, correlations, and mutual exclusivities were assessed using statistical analyses with false discovery rate correction. Of 2,595 head and neck cancer samples, 122 (4.7%) were sinonasal carcinoma: 70 (57.4%) SCC, 31 (25.4%) undifferentiated carcinoma, and 21 (17.2%) adenocarcinomas. The most frequent mutations were TP53 (tumor protein 53; 40%), PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha; 14%), KMT2D (lysine methyltransferase 2D; 11%), and CDKN2A (cyclin-dependent kinase inhibitor 2A; 9%). Subtype-specific mutations included IDH2 (isocitrate dehydrogenase; 230%) in undifferentiated carcinoma and FAT1 (15%) in adenocarcinoma. TP53 frequently co-occurred with PRKDC (protein kinase, DNA-activated, catalytic subunit; p = 0.020), while KMT2D co-occurred with PIK3CA (p = 0.018). TP53, PIK3CA, and KMT2D mutations are prevalent in sinonasal carcinoma, highlighting potential targets for therapy. Tazemetostat, targeting KMT2D-related DNA (deoxyribonucleic acid) methylation, and cetuximab, targeting the PIK3CA signaling cascade, may offer therapeutic benefits. Further research on mutation-specific therapies could improve treatment strategies.

Abstract Olfactory neuroblastoma (ONB) is a rare head and neck cancer arising from the upper nasal cavity, with limited systemic therapeutic options due to a poor understanding of its genomic landscape. This study aims to utilize a patient-level genomic repository to identify potential therapeutic targets and improve disease modeling in ONB. Retrospective genomic analysis. Data analysis was performed using the American Association for Cancer Research (AACR) Project Genomics Evidence Neoplasia Information Exchange (GENIE) database. Patients with confirmed ONB who have undergone targeted sequencing within GENIE. Data were analyzed for recurrent somatic mutations, along with their clinical and demographic correlations, with significance set at p < 0.05. A high prevalence of mutations in TP53 (tumor protein p53) and FRK (fibroblast growth factor receptor kinase) genes was identified. A moderate prevalence of mutations in NOTCH3 (notch receptor 3), SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4), RET (rearranged during transfection), and CTCF (CCCTC-binding factor) was also identified. The mutation patterns differed between pediatric and adult ONB cases. Specific mutations were enriched in metastatic tumors compared with primary tumors. This study provides a genomic profile for ONB, identifying key mutations and potential therapeutic targets. The identification of frequently mutated genes like TP53 and FRK suggests potential targets for novel therapies. The observation that certain genes are mutated in pediatric ONB but not adult ONB (and vice versa), and the presence of specific mutations in metastatic tumors that are absent in primary tumors, offers valuable insights for future precision medicine and the design of targeted therapeutic interventions for these distinct clinical presentations.

PURPOSE Initial reports indicate that access to contemporary therapies currently used in North America for the treatment of multiple myeloma (MM) varies internationally. No studies have quantitatively reported the extent of disparities in the access to MM therapies worldwide, with a goal to investigate access to MM therapies and barriers globally. METHODS From June 18 to July 15, 2023, an electronic survey was distributed to 176 oncologists treating MM outside the United States. MM drugs were categorized by accessibility, with the cutoff for adequate access set at 60% of respondents affirming easy/moderate access. RESULTS Ninety-five (54%) respondents from 33 countries completed the survey. Fifty-one percent of the respondents were from university-based academic programs, and 17% of the responders treated only plasma cell disorders. Most respondents had adequate access to noncellular MM therapies, except for isatuximab, ixazomib, selinexor, and elotuzumab. Among the cellular therapies, 17% had access to Chimeric Antigen Receptor T-cell therapy, whereas 23% had access to approved T-cell engagers (TCEs). Financial stress on patients and health care systems has emerged as a primary barrier to global inaccessibility of treatment drugs. CONCLUSION Global access to novel MM therapies remains challenging, and we have identified barriers and suggested strategies to bridge this gap.

e16072 Background: Gastric cancer is a leading cause of mortality worldwide, with pronounced variations in outcomes across populations. This study investigates U.S. trends in age-adjusted mortality rates (AAMRs) for gastric cancer from 1999 to 2023, examining differences by gender, race, region, and urbanization to uncover critical patterns and inequities. Methods: Data were extracted from the CDC WONDER database using ICD-10 code C16 to identify gastric cancer-related deaths in adults aged 25 and older. AAMRs per 1,000,000 population were calculated and stratified by year, gender, race/ethnicity, geographic region, and urban-rural classification. Trends were analyzed using Joinpoint regression to determine annual percentage changes (APC) and 95% confidence intervals (CI). Statistical significance was set at p < 0.05. Results: From 1999 to 2023, there were 312,300 gastric cancer deaths (185,391 men, 126,909 women). Overall, AAMRs declined consistently, with APCs of -3.4 for the period 1999 to 2007, -2.2 for 2007 to 2018, and -1.2 for 2018 to 2023. Men showed a more pronounced decline, with APCs of -3.6 for 1999 to 2009 and -2.2 for 2009 to 2023, compared to women, who had APCs of -3.1 for 1999 to 2008, -1.9 for 2008 to 2018, and -0.8 for 2018 to 2023. Non-Hispanic Black populations experienced a decline in AAMR with an APC of -3.3 for 1999 to 2020, while Hispanic/Latino and Asian/Pacific Islander populations showed declines with APCs of -2.8 for 1999 to 2011 and -3.8 for 1999 to 2020, respectively. Metropolitan areas saw AAMR reductions with APCs of -3.3 for 1999 to 2008 and -2.2 for 2008 to 2020, while non-metropolitan areas had larger initial declines with an APC of -3.6 for 1999 to 2006 but slower decreases with an APC of -2.0 for 2006 to 2020. Geographically, the Northeast had the highest AAMR (62.9), followed by the West (61.7), South (57.4), and Midwest (50.9). Hawaii recorded the highest state-level AAMR (96.5), while Wyoming had the lowest (36.6). States in the top 90th percentile included Alaska, California, and New York, whereas Utah, Idaho, and Iowa were among the lowest. Conclusions: Gastric cancer mortality in the U.S. has declined over the past two decades, but the pace of reduction has slowed in recent years. Significant disparities persist across gender, racial, and geographic groups, underscoring the need for targeted interventions to address these inequities and improve outcomes in vulnerable populations.

Abstract Purpose Gastric cancer is a leading cause of mortality worldwide, with pronounced variations in outcomes across populations. This study investigates U.S. trends in age-adjusted mortality rates (AAMRs) for gastric cancer from 1999 to 2023, examining differences by sex, race, region, and urbanization to uncover critical patterns and inequities. Methods Data were extracted from the CDC WONDER database using ICD-10 code C16 to identify gastric cancer-related deaths in adults aged 25 and older. AAMRs per 1,000,000 population were calculated and stratified by year, sex, race/ethnicity, geographic region, and urban-rural classification. Trends were analyzed using Joinpoint regression to determine annual percentage changes (APC) and 95% confidence intervals (CI). Statistical significance was set at p < 0.05. Results From 1999 to 2023, there were 312,300 gastric cancer deaths (185,391 men, 126,909 women). Overall, AAMRs declined consistently, with APCs of -3.4 for the period 1999 to 2007, -2.2 for 2007 to 2018, and − 1.2 for 2018 to 2023. Men showed a more pronounced decline, with APCs of -3.6 for 1999 to 2009 and − 2.2 for 2009 to 2023, compared to women, who had APCs of -3.1 for 1999 to 2008, -1.9 for 2008 to 2018, and − 0.8 for 2018 to 2023. Non-Hispanic Black populations experienced a decline in AAMR with an APC of -3.3 for 1999 to 2020, while Hispanic/Latino and Asian/Pacific Islander populations showed declines with APCs of -2.8 for 1999 to 2011 and − 3.8 for 1999 to 2020, respectively. Metropolitan areas saw AAMR reductions with APCs of -3.3 for 1999 to 2008 and − 2.2 for 2008 to 2020, while non-metropolitan areas had larger initial declines with an APC of -3.6 for 1999 to 2006 but slower decreases with an APC of -2.0 for 2006 to 2020. Geographically, the Northeast had the highest AAMR (62.9), followed by the West (61.7), South (57.4), and Midwest (50.9). Hawaii recorded the highest state-level AAMR (96.5), while Wyoming had the lowest (36.6). States in the top 90th percentile included Alaska, California, and New York, whereas Utah, Idaho, and Iowa were among the lowest. Conclusion Gastric cancer mortality in the U.S. has declined over the past two decades, but the pace of reduction has slowed in recent years. Significant disparities persist across sex, racial, and geographic groups, underscoring the need for targeted interventions to address these inequities and improve outcomes in vulnerable populations.

Background: Nasopharyngeal carcinoma (NPC) is a rare head and neck cancer arising from the mucosal lining of the nasopharynx, for which systemic therapeutic options remain scarce, reflecting the limited characterization of its genomic profile. This study utilized a large patient-level genomic repository to characterize genetic alterations, identify potential therapeutic targets, and improve disease modeling in NPC. Methods: A retrospective analysis of NPC samples was conducted using the AACR Project GENIE database. Targeted sequencing data were analyzed for recurrent somatic mutations, tumor mutational burden, and chromosomal copy number variations, with significance set at p < 0.05. Results: Frequent mutations were identified in KMT2D (20%), TP53 (16%), CYLD (9.6%), NFKBIA (6.4%), and PIK3CA (5.6%), implicating the p53, NF-κB, and PI3K pathways in NPC development. Notably, significantly distinct mutational profiles were observed based on both sex and race, with female patients exhibiting higher frequencies of PIK3C2G, ETV6, and CDKN1B mutations and non-Asian patients showing enrichment in KDM5A, CCND2, and TP53 mutations. Conclusions: This study presents a detailed genomic profile of NPC, identifying key mutations within established cancer-associated pathways. The identification of frequently mutated pathways (p53, NF-κB, and PI3K) suggests potential targets for novel therapies. Furthermore, distinct mutational landscapes in female and Asian NPC patients offer possibilities for precision therapeutic interventions.

Background/objective: HCM is a structural disorder of the myocardium that leads to sudden cardiac death in young adults. We synthesized an updated understanding of the role of Cardiac Myosin Inhibitors (CMIs) in HCM by pooling data from RCTs. Methods: We identified six published RCTs, involving 826 participants. Data were extracted pertaining to study characteristics; primary outcomes of interest–(1) change from baseline in resting left ventricular outflow tract (LVOT) peak gradient, (2) change from baseline in Valsalva LVOT peak gradient, and (3) improvement of ≥1 NYHA class–and secondary outcomes. These were pooled using Review Manager 5.4, employing a random-effects model, and reported as odds ratios (ORs) or mean differences (MDs). Results: We found statistically significant between-group difference favoring CMIs in change from baseline in LVOT peak gradient: at rest (MD −39.33; −53.01 to −25.64), post-Valsalva (MD −48.99; −53.96 to −44.03), and post-exercise (MD −37.11; −44.34 to −29.87); ≥1 NYHA class improvement (OR 4.10; 2.79–6.02), change from baseline in peak oxygen uptake (MD −37.11; −44.34 to −29.87), LVOT gradient ≤30 mm hg (RR 14.89; 7.47–29.67), participants eligible for septal reduction therapy (RR 0.26; 0.18–0.36), and change from baseline in KCCQ-CSS score (MD 8.54; 5.36–11.71). Subgrouping by intervention type (mavacamten vs. aficamten) revealed non-significant results for all primary outcomes. Conclusions: CMIs can contribute to improving key efficacy outcomes for patients with HCM while reducing incidence of SRT.

Background We automated subarachnoid hemorrhage volume (SAHV) calculation with artificial intelligence (SAHVAI) and created 3‐dimensional volumetric images (SAHVAI‐3D) using noncontrast head computed tomography data for patients with aneurysmal SAH. We also defined 4‐dimensional SAHVAI (SAHVAI‐4D), representing SAHV over time. We aimed to compare automated SAHVAI values and computational times to manual SAHV measurement methods, explore the potential of imaging biomarkers to identify at‐risk brain regions for delayed cerebral ischemia and explore potential insights in future neurotherapeutic interventions for patient recovery after SAH. Methods A training set of 10 consecutive patients with aneurysmal SAH was used to manually compute SAHV, SAHVAI‐3D, and SAHVAI‐4D, including 92 noncontrast computed tomography scans (182 slices each). The SAHVAI deep learning algorithm generated automated SAHV values in cubic centimeters. A 3‐dimensional SAH brain map was created for each patient for the SAHVAI and manual evaluations. Blood volumetric outputs were analyzed and compared to neurologic outcomes at discharge, including delayed cerebral ischemia events, symptomatic vasospasm, and areas with the thickest SAH blood concentration. Results SAHVAI quantified SAHV in a mean of 6.7 seconds per scan, significantly faster than the manual method, which took >60 minutes per scan (Fisher exact test, P <0.001). SAHVAI demonstrated an accuracy of 99.8%, Dice score of 0.701, false‐positive rate of 0.0005, and negative predictive value of 0.999. The mean absolute error between SAHVAI and manual methods was 5.67 mL. SAHVAI‐3D brain map and total SAHV at admission were inversely associated with Glasgow Coma Scale (R 2 = 0.23, P = 0.017) and directly associated with length of hospital stay (R 2 = 0.175, P = 0.004), especially in regions with dense blood concentration. Conclusion SAHVAI‐3D and SAHVAI‐4D brain mapping techniques represent innovative imaging biomarkers for SAH. These advancements enable rapid evaluation and targeted interventions, potentially improving patient care in SAH management.

The role of second-look endoscopy and debridement (SLED) remains uncertain in children due to the perceived need for additional general anesthesia following their initial functional endoscopic sinus surgery (FESS) while mitigating risks and healthcare costs. This comprehensive review synthesizes current evidence on SLED in children, focusing on its practice pattern and treatment outcomes. This review was designed and performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews Protocol. Independent queries of the PubMed Central, MEDLINE, and Bookshelf databases were performed. A total of 53 relevant, unique articles were initially identified; 12 articles were ultimately deemed appropriate for inclusion in final analysis. The most common indication for FESS was chronic rhinosinusitis or recurrent sinus infections while that for SLED under general anesthesia varied from institutional practice patterns to surgeon preference. No meaningful comparison of outcomes was possible as the “success rates” of FESS with or without SLED were largely based on unvalidated questionnaires and equally subjective surgeon assessments. Even when looking at outcomes based on revision rates, FESS with SLED was considered successful between 60.5% and 95.6% of the time, with a mean of 84.2%, while FESS without SLED was successful between 71.0% to 96.4% of the time, with a mean of 86.3%. However, no randomized, controlled studies were available in the pediatric literature pertaining to FESS with or without SLED. Moreover, it became apparent that previous conclusions on the utility of SLED were based on the outcomes of FESS following one single SLED under general anesthesia vs. no SLED. As such, there is an unmet need to examine the utility of serial, office-based SLED in children to better elucidate its utility in pediatric FESS.