Utility of Circulating Tumor DNA in the Management of Patients With GI Stromal Tumor: Analysis of 243 Patients

PURPOSE GI stromal tumor (GIST) is the most common sarcoma of the GI tract. Management of patients with GIST is determined by KIT, PDGFRA, or other genomic alterations. Tissue-based next-generation sequencing (NGS) analysis is the standard approach for diagnosis, prognosis, and treatment selection. However, circulating tumor DNA (ctDNA)–based NGS is a novel and noninvasive alternative. METHODS ctDNA sequencing results were evaluated in blood samples from 243 de-identified patients within the Guardant360 database. Under an approved institutional review board protocol, a retrospective analysis was performed on 45 single-institution patients. RESULTS Of 243 patients, 114 (47%) were women, and the median age was 59 years (range, 17-90 years). Patients with no alterations and variations of uncertain significance were excluded. Of the 162 patients with known pathogenic mutations, KIT was the most common (56%), followed by NF (7%), PDGFRA (6%), PI3KCA (6%), KRAS (5%), and others (6%). Most tumors harbored an actionable KIT or PDGFRA mutation. Our institutional cohort (n = 45) had 16 (35%) KIT exon 11 mutations, 3 (6%) KIT exon 9 mutations, and 1 (2%) PDGFRA mutation detected on ctDNA. Resistance mutations were observed in KIT exon 17 (8 patients), exon 13 (3 patients), and in both (3 patients). Our comparison of ctDNA with tissue NGS revealed a positive predictive value (PPV) of 100%. Failure of concordance was observed in patients with localized or low disease burden. From the time of ctDNA testing, the median overall survival was not reached, whereas the median progression-free survival was 7 months. CONCLUSION ctDNA provides a rapid, noninvasive analysis of current mutations with a high PPV for patients with metastatic GIST. ctDNA-based testing may help to define the optimal choice of therapy on the basis of resistance mutations and should be studied prospectively

Severe Bilateral Ischemic Retinal Vasculitis Following Cataract Surgery

This report describes two cases of severe, bilateral ischemic retinal vasculitis following cataract surgeries at different surgical centers. In both cases, the patient underwent bilateral cataract surgeries, performed 1 week apart for each eye. In the perioperative period following the second of the two surgeries, both patients developed severe, bilateral intraocular inflammation and profound vision loss. The underlying cause of this adverse response remains unknown. The authors suggest that the severe inflammatory reaction could be related to an intraoperative intracameral vancomycin injection

Abstract B123: Prevalence of COVID-19 among hematology/oncology patients and providers of a community-facing county health system during the B1.1.529 (“Omicron”) SARS-CoV-2 variant wave

Abstract Introduction: The SARS-CoV-2 (COVID-19) pandemic continues in the United States, and patients actively receiving chemotherapy are known to be at enhanced risk for developing symptomatic disease. Our study evaluated the prevalence of COVID-19 among patients and providers of our community-facing county health system during the B1.1.529 (“Omicron”) COVID-19 variant wave. Methods: We retrospectively analyzed patients that received care and clinical providers whom worked at the Jackson Memorial Hospital Hematology/Oncology clinic in Miami, Florida from December 1st, 2021 through April 30th, 2022. After categorizing basic demographic factors for individuals whom tested positive for COVID-19 during the study timeframe, we analyzed additional risk factors leading to COVID-19 positivity including, but not limited to, vaccination status, previous COVID-19 positivity, and active receipt of chemotherapeutics. We then analyzed outcomes related to COVID-19, including treatment with advanced COVID-19 therapies such as oral or intravenous antivirals, monoclonal antibodies, convalescent plasma, steroids, or interleukin-6 inhibitors; interactions with inpatient services including emergency department (ED)/urgent care visits, inpatient and/or ICU admissions, and deaths from COVID-19. We finally assessed quality outcomes such as delay in cancer-directed therapy. This study was approved by the University of Miami IRB and Jackson Health System Clinical Trials Office. Results: 498 patients and 18 providers were retrospectively analyzed during the study timeframe. 49 patients tested positive for COVID-19 (9.84%), while 6 providers tested positive (33.3%) (p = 0.015). Patients whom tested positive were 51.0% female (n = 25), 26.5% Black (n = 13), 73.5% Hispanic/Latinx (n = 36), and 2.05% Asian (n = 1). Only 6.12% patients had tested positive for COVID-19 previously (n = 3), and 42.9% were considered unvaccinated (n = 21) while 14.3% were boosted (n = 7). 73.5% (n = 36) presented with symptomatic disease, 46.9% (n = 23) sought care at an ED/urgent care, 32.6% (n = 13) were admitted to the hospital, 6.12% were admitted to the ICU (n = 3), and 16.3% (n = 8) received advanced therapeutics. There were 2 (8.0%) COVID-19-related deaths (and another outside our study timeframe) among 23 non-COVID-19 related deaths in the patient population (p = 0.75). More than half of the patients whom tested positive experienced a cancer treatment delay (n = 27/49; 55.1%). Conclusions: The prevalence of COVID-19 positivity in our patient cohort during the initial Omicron wave mirrored local, state, and national trends, however a statistically significant greater proportion of our providers tested positive. COVID-19 positivity conferred appreciable disparities in the presentation of disease as well as receipt of cancer treatment. COVID-19 positivity was more likely to result in symptomatic disease and ED/urgent care visit in cancer patients without previous COVID infection and unvaccinated status. COVID-19 accounted for 8.0% of our clinic’s total mortality. Citation Format: Aliya Khan, Samuel A. Kareff, Priscila Barreto-Coelho, Sunil Iyer, Brian Pico, Michele Stanchina, Giselle Dutcher, José Monteiro de Oliveira Novaes, Aparna Nallagangula, Gilberto Lopes. Prevalence of COVID-19 among hematology/oncology patients and providers of a community-facing county health system during the B1.1.529 (“Omicron”) SARS-CoV-2 variant wave [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr B123

Variants near TERT and TERC influencing telomere length are associated with high-grade glioma risk.

Glioma, the most common central nervous system cancer in adults, has poor prognosis. Here we identify a new SNP associated with glioma risk, rs1920116 (near TERC), that reached genome-wide significance (Pcombined = 8.3 × 10(-9)) in a meta-analysis of genome-wide association studies (GWAS) of high-grade glioma and replication data (1,644 cases and 7,736 controls). This region has previously been associated with mean leukocyte telomere length (LTL). We therefore examined the relationship between LTL and both this new risk locus and other previously established risk loci for glioma using data from a recent GWAS of LTL (n = 37,684 individuals). Alleles associated with glioma risk near TERC and TERT were strongly associated with longer LTL (P = 5.5 × 10(-20) and 4.4 × 10(-19), respectively). In contrast, risk-associated alleles near RTEL1 were inconsistently associated with LTL, suggesting the presence of distinct causal alleles. No other risk loci for glioma were associated with LTL. The identification of risk alleles for glioma near TERC and TERT that also associate with telomere length implicates telomerase in gliomagenesis

Inherited variant on chromosome 11q23 increases susceptibility to IDH-mutated but not IDH-normal gliomas regardless of grade or histology.

IntroductionRecent discoveries of inherited glioma risk loci and acquired IDH mutations are providing new insights into glioma etiology. IDH mutations are common in lower grade gliomas and secondary glioblastomas and uncommon in primary glioblastomas. Because the inherited variant in 11q23 has been associated with risk of lower grade glioma and not with glioblastomas, we hypothesized that this variant increases susceptibility to IDH-mutated gliomas, but not to IDH-wild-type gliomas.MethodsWe tested this hypothesis in patients with glioma and controls from the San Francisco Adult Glioma Study, the Mayo Clinic, and Illumina controls (1102 total patients, 5299 total controls). Case-control additive associations of 11q23 risk alleles (rs498872, T allele) were calculated using logistic regression, stratified by tumor IDH status (mutated or wild-type) and by histology and grade. We also adjusted for the recently discovered 8q24 glioma risk locus rs55705857 G allele.ResultsThe 11q23 glioma risk locus was associated with increased risk of IDH-mutated gliomas of all histologies and grades (odds ratio [OR] = 1.50; 95% confidence interval [CI] = 1.29-1.74; P = 1.3X10(-7)) but not with IDH-wild-type gliomas of any histology or grade (OR = 0.91; 95% CI = 0.81-1.03; P = 0.14). The associations were independent of the rs55705857 G allele.ConclusionA variant at the 11q23 locus increases risk for IDH-mutated but not IDH-wild-type gliomas, regardless of grade or histology