Demographic Trends, Coalterations, and Imatinib Resistance across Genomic Variants in Gastrointestinal Stromal Tumors: An AACR Project GENIE Analysis.

INTRODUCTION: Gastrointestinal stromal tumors (GIST) are the most common mesenchymal neoplasm of the gastrointestinal tract, the treatment of which represents a significant breakthrough in targeted cancer therapy. Given its overall rare nature, analysis of genomic differences and clinical implications between demographic groups has not been previously completed, but American Association for Cancer Research (AACR) Project GENIE makes such an analysis possible. METHODS: Anonymized demographic, clinical, and genomic data from 1,559 GIST patients was analyzed using cBioPortal and custom Python scripts, with no exclusions from the cohort. Data included patient demographics, genomic alterations, and co-occurrence information, and was classified according to clinical implications using the OncoKB database. Analysis involved Chi-squared tests for differences in genomic alterations across various demographic factors and mutual exclusivity analysis to identify co-mutation patterns. RESULTS: Male patients exhibited higher mutation rates at PDGFRA (14.56% vs 8.05%; p<0.001), while female patients had higher rates at NF1 (7.46% vs 3.23%; p=0.001). Asian patients showed higher alteration rates at KIT (85.59%; p=0.002). Co-occurrence analysis revealed KIT alterations frequently co-occurred with CDKN2A (q<0.001), MTAP (q=0.045), and PTEN (q=0.056), while showing mutual exclusivity with PDGFRA (q<0.001), NF1 (q<0.001), and BRAF (q=.015). CDKN2A alterations co-occurred with MTAP (q<0.001) and PIK3CA (q=.015), while being mutually exclusive with TP53 (q=.002) and NF1 (q=.007). Trends were similar among patients who had received no prior medical treatment. Imatinib-resistant mutations were more common in male patients (25.6% vs 18.9%; p=.0056) and those under 55 (27.3% vs 20.9%; p=.0228). Among patients with imatinib-resistant mutations, 77.78% had sunitinib resistance, while 70.25% maintained sensitivity to ripretinib. CONCLUSION: Sex and race/ethnic differences in genomic alterations, as well as co-mutations, were prevalent among patients with GIST. Variations in mutational profiles highlight the importance of distinct genetic drivers that may be targeted to treat different patient populations.

Racial and Sex Differences in Genomic Profiling of Intrahepatic Cholangiocarcinoma.

BACKGROUND: Racial and sex disparities in the incidence and outcomes of patients with intrahepatic cholangiocarcinoma (iCCA) exist, yet potential genomic variations of iCCA based on race and sex that might be contributing to disparate outcomes have not been well studied. METHODS: Data from the American Association for Cancer Research Project GENIE registry (version 15.0) were analyzed to assess genetic variations in iCCA. Adult patients (age >18 years) with histologically confirmed iCCA who underwent next-generation sequencing were included in the analytic cohort. Racial and sex variations in genomic profiling of iCCA were examined. RESULTS: The study enrolled 1068 patients from 19 centers (White, 71.9%; Black, 5.1%; Asian, 8.4%, other, 14.6%). The male-to-female ratio was 1:1. The majority of the patients had primary tumors (73.7%), whereas 23.0% had metastatic disease sequenced. While IDH1 mutations occurred more frequently in White versus Black patients (20.8% vs. 5.6%; p = 0.021), FGFR2 mutations tended to be more common among Black versus White populations (27.8% vs. 16.1%; p = 0.08). Males were more likely to have TP53 mutations than females (24.3% vs. 18.2%, p = 0.016), whereas females more frequently had IDH1 (23.3% vs 16.0 %), FGFR2 (21.0% vs. 11.3%), and BAP1 (23.4% vs. 14.5%) mutations than males (all p < 0.05). Marked variations in the prevalence of other common genomic alterations in iCCA were noted across different races and sexes. CONCLUSION: Distinct genomic variations exist in iCCA across race and sex. Differences in mutational profiles of iCCA patients highlight the importance of including a diverse patient population in iCCA clinical trials as well as the importance of recognizing different genetic drivers that may be targetable to treat distinct patient cohorts.

Feasibility of targeting the cingulate gyrus using high-intensity focused ultrasound on a cadaveric specimen: illustrative case.

BACKGROUND: Cancer is commonly associated with pain. For patients with advanced cancer and intractable pain, ablative neurosurgical procedures can significantly improve pain and transition patients out of inpatient settings. These procedures are normally invasive, and this poses an important risk in this population. Cingulotomy has been reported to improve pain perception and contribute substantially to the quality of life of cancer patients with refractory pain. OBSERVATIONS: One fresh human cadaver specimen was used for the setup. The cingulate gyrus was targeted using intraoperative magnetic resonance images, and osseous aberrations were corrected after coregistration with the preoperative head computed tomography. After accounting for sinuses, membrane folds, and calcifications, a total of 737 elements were available for thermal ultrasound ablation. On high-power sonications, the total energy delivered reached a peak temperature of 57°C (15,050 J, 350 W, 45 seconds) in the right cingulate and 52°C (13,000 J, 405 W, 46 seconds) in the left cingulate. LESSONS: Despite the limitations of using a cadaver model (temperature, vascularization), cingulotomy appears to be feasible using high-intensity focused ultrasound. https://thejns.org/doi/10.3171/CASE2459.

The Role of Delirium on Short- and Long-Term Postoperative Outcomes Following Major Gastrointestinal Surgery for Cancer.

INTRODUCTION: The growing burden of an aging population has raised concerns about demands on healthcare systems and resources, particularly in the context of surgical and cancer care. Delirium can affect treatment outcomes and patient recovery. We sought to determine the prevalence of postoperative delirium among patients undergoing digestive tract surgery for malignant indications and to analyze the role of delirium on surgical outcomes. METHODS: Medicare claims data were queried to identify patients diagnosed with esophageal, gastric, hepatobiliary, pancreatic, and colorectal cancers between 2018 and 2021. Postoperative delirium, occurring within 30 days of operation, was identified via International Classification of Diseases, 10th edition codes. Clinical outcomes of interested included "ideal" textbook outcome (TO), characterized as the absence of complications, an extended hospital stay, readmission within 90 days, or mortality within 90 days. Discharge disposition, intensive care unit (ICU) utilization, and expenditures also were examined. RESULTS: Among 115,654 cancer patients (esophageal: n = 1854, 1.6%; gastric: n = 4690, 4.1%; hepatobiliary: n = 6873, 5.9%; pancreatic: n = 8912, 7.7%; colorectal: n = 93,325, 90.7%), 2831 (2.4%) were diagnosed with delirium within 30 days after surgery. On multivariable analysis, patients with delirium were less likely to achieve TO (OR 0.27 [95% CI 0.25-0.30]). In particular, patients who experienced delirium had higher odds of complications (OR 3.00 [2.76-3.25]), prolonged length of stay (OR 3.46 [3.18-3.76]), 90-day readmission (OR 1.96 [1.81-2.12]), and 90-day mortality (OR 2.78 [2.51-3.08]). Furthermore, patients with delirium had higher ICU utilization (OR 2.85 [2.62-3.11]). Upon discharge, patients with delirium had a decreased likelihood of being sent home (OR 0.40 [0.36-0.46]) and instead were more likely to be transferred to a skilled nursing facility (OR 2.17 [1.94-2.44]). Due to increased utilization of hospital resources, patients with delirium incurred in-hospital expenditures that were 55.4% higher (no delirium: $16,284 vs. delirium: $28,742) and 90-day expenditures that were 100.7% higher (no delirium: $2564 vs. delirium: $8226) (both p < 0.001). Notably, 3-year postoperative survival was adversely affected by delirium (no delirium: 55.5% vs. delirium: 37.3%), even after adjusting risk for confounding factors (HR 1.79 [1.70-1.90]; p < 0.001). CONCLUSIONS: Postoperative delirium occurred in one in 50 patients undergoing surgical resection of a digestive tract cancer. Delirium was linked to a reduced likelihood of achieving an optimal postoperative outcome, increased ICU utilization, higher expenditures, and a worse long-term prognosis. Initiatives to prevent delirium are vital to improve postoperative outcomes among cancer surgery patients.

COVID-19 Vaccination Rates and Vaccine Hesitancy Among Spanish-Speaking Free Clinic Patients.

We sought to assess COVID-19 vaccination rates, as well as attitudes and beliefs towards the vaccine, of patients in a Spanish-speaking student-run free clinic in Columbus, Ohio. A cross-sectional study was performed. Surveys were distributed to all individuals over 18 years who presented to La Clínica Latina between July, 2022 and September, 2022. A convenience sample was used: patients in the waiting room and their accompanying family members or friends were invited to participate. Subjects were excluded if under the age of 18 or over the age of 75, or if non-Spanish speaking. Of the 158 individuals who agreed to participate in our study, 146 responded to the question regarding vaccination status, revealing 90.4% of respondents had received a COVID-19 vaccination. Most respondents learned about the vaccine from social media (26.4%) or television (22.7%). The majority of participants sought answers to questions surrounding the vaccine by asking their doctor (49.1%). The most common reason among unvaccinated participants for not undergoing vaccination was fear of an adverse reaction to the vaccine (n = 11). We found that a large proportion (90.4%) of individuals seeking care at a Spanish-speaking free clinic were vaccinated against COVID-19. Our study also provides perspective on the means of health knowledge acquisition and behaviors in this predominantly Latinx patient population in central Ohio. We can utilize our results to optimize and tailor clinic services and initiatives for COVID-19 boosters to meet the needs of this community.