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  • 1
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    The impact of socioeconomic factors and survivorship on radiation induced hypothyroidism in a single institution cohort study.
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 15_suppl ( 2020-05-20), p. e24065-e24065
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. e24065-e24065
    Abstract: e24065 Background: To determine factors associated with the development of post-treatment hypothyroidism (HY) in the head and neck (HN) population as well as evaluate the impact of socio-economic factors and survivorship program. Methods: We collected demographics, insurance coverage, disease staging, treatment characteristics, and details of thyroid function measurement as well as supplementation for all HN oncology patients (n = 608) who presented between January 2011 and January 2019 at Levine Cancer Institute, Charlotte, North Carolina. Insurance was categorized as Government (Medicaid or Medicare), Private, or Uninsured. Patient malignancies were grouped as oropharynx, oral cavity, larynx/hypopharynx, nasopharynx, nasal cavity/sinus, or primary salivary gland. Thyroid function was evaluated by use of laboratory thyroid stimulating hormone (TSH) values. Timing of thyroid supplementation was standardized to start of treatment. Details of thyroid hormone supplementation was collected. Data was analyzed with Chi-square and ANOVA methods, using SAS 9.4 (Cary, NC). Results: 483 patients (79%) had post treatment surveillance with TSH. The patients (n = 125, 21%) with no identifiable thyroid surveillance did not have any racial or socioeconomic disparities identified. Caucasian and African American thyroid surveillance rates were similar at 79% and 81%, respectively. There was no difference based on insurance: Government 81%, Uninsured 81%, and Private 76%. Of patients with thyroid surveillance, 203 (42%) developed post-treatment HY. The mean and median time frame until HY identification was 544 days and 450 days, respectively. A mean and median dose of thyroid hormone supplementation of 75 mcg of levothyroxine. Most patients had lower rates of thyroid dysfunction with TSH levels between 5-10. Fewer African Americans (24%) developed HY than Caucasians (47%). Patients with laryngeal cancer were at greatest risk to develop HY (57%), followed by oropharynx (40%) and oral cavity (40%). Staging did not demonstrate a significant difference between development of HY. Conclusions: This study is the largest cohort of HN patients to be evaluated for post HN treatment induced HY. Oncology team providers and primary care physicians should be aware of the significant rates of HY. In our institution we identified a consistency of care provided regardless of socioeconomic and racial factors.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2020.38.15_suppl.e24065
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
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  • 2
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    Molecular features of gliomas with high tumor mutational burden.
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 15_suppl ( 2020-05-20), p. 2549-2549
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. 2549-2549
    Abstract: 2549 Background: TMB-H in gliomas is caused by molecular alterations or alkylator treatment- induced genomic changes characterized by a large number of G:C 〉 A:T transitions. Our study describes the molecular features of TMB-H gliomas. Methods: Gliomas were tested with NextGen sequencing (592 genes), MGMT promoter methylation (MGMT-m) fragment analysis and IHC at Caris Life Sciences. Microsatellite instability (MSI) was test by NGS, FA/IHC. The GC:AT transition rate was calculated as the prevalence of G:A and C:T changes seen in each tumor and 〉 80% was regarded as high transition(TR-H). TMB values were compared using Wilcoxon Rank Sum. TMB-H was defined as the top quartile of all TMB values (TMB 〉 9). Results: TMB in the 3129 gliomas ranged from 0 to 372 mutations/MB (mean: 8.5, median: 6). TMB-H was observed in 31% of glioblastomas, 16% of astrocytomas (astro) (22% of grade III, 7% of grade I/II) and 22% of oligodendrogliomas (oligo) (32% of grade III and 15% of grade I/II). MGMT-m (58% vs. 47%; p=0.0001), pathogenic (p) or likely p (lp) EGFR (14% vs 10%, p=0.004) and PIK3CA mutations (13% vs. 9%, p=0.002), as well as p/lp in 30 other genes were more prevalent in TMB-H cases (p 〈 0.01). In the 613 TMB-H tumors, TR-H was seen in 12% (73) and was strongly associated with increased TMB (median TMB 52 in TR-H vs. 9 in TR-L,) and MSI-H (7.3% vs. 1.1%), both p 〈 0.0001. Tumors with both TR-H and MSI-H had a mTMB of 114 vs. 49 in TR-H /MSS tumors. MSI-H and TR-L tumors had an mTMB of 23 vs. 9 in MSS /TR-L tumors (p 〈 0.0001). All 5 POLE-MT tumors had TMB of 〉 100 (median 264) and TR-L; 4 of the 5 were also MSI-H. PDL1 IHC had no correlation with TMB, MSI or transition rates. In 89 paired samples taken 〉 150 days apart (regardless of intervening treatment), acquisition of TMB-H was seen in 11 pairs: 8 glioblastomas, 2 grade II/III astro and 2 oligo. In the paired tumors that acquired TMB-H status compared to those that did not, a significantly higher prevalence of MGMT-m (82% vs. 37%, p=0.008) and IDH mutation (64% vs. 19%, p=0.004) were seen. 10 of the 11 recurrent tumors with acquisition of TMB-H had TR-H while none in the other 78 pairs. Conclusions: TMB varies significantly in gliomas and associates with POLE, TR-H and MSI-H, but not with an increase of PD-L1. POLE-mutated tumors had the highest TMB levels. TR-H, an indicator of alkylator-induced phenotype, is associated with a higher TMB than MSI-H, however, TR-H may synergize with MSI-H to further increase TMB. Tumors with an IDH mutation and MGMT-m are more prevalent in tumors with high TMB gain. Further understanding of molecular and immune profile of the TMB-H may facilitate more individualized treatment planning.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2020.38.15_suppl.2549
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
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  • 3
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    Investigation of leptomeningeal disease in high grade glioma and characterization of molecular alterations.
    American Society of Clinical Oncology (ASCO) ; 2023
    In:  Journal of Clinical Oncology Vol. 41, No. 16_suppl ( 2023-06-01), p. 2070-2070
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. 2070-2070
    Abstract: 2070 Background: Leptomeningeal disease (LMD) is a challenging complication of high grade glioma (HGG) and questions remain regarding risk factors, molecular associations, and optimal treatment. Here we report updated results on a larger cohort from our previously reported multicenter study (Shoaf 2022, Neuro-Oncology). Methods: Patients with molecularly-profiled HGG (Caris Life Sciences; Phoenix, AZ) with LMD at 3 institutions were included. NextGen Sequencing of DNA (592 gene or whole exome) and RNA (whole transcriptome) were tested. Medical records were reviewed for clinicopathologic characteristics and outcome. Kaplan-Meier estimates of survival were performed using Cox’s proportional hazard model. Mann-Whitney U or Chi-square tests were applied for molecular comparison as appropriate and adjusted for multiple comparisons. Results: Seventy-two patients (female: 20, male: 52; median age: 54.5y) were identified, comprising 65 grade 4 tumors (glioblastoma [GBM]: 62; gliosarcoma: 2; H3K27M diffuse midline glioma: 1), 5 grade 3 tumors (astrocytoma: 4; pleomorphic xanthoastrocytoma: 1), and 1 astrocytoma NOS. LMD diagnosed at glioma diagnosis (n=23) vs. recurrence (n=44) was associated with longer post-LMD survival [pLMD-OS: 16.9m vs. 5.5m, p 〈 0.0001] but similar overall survival [mOS: 16.9m vs. 20.9m; p=0.36] . Pathology-diagnosed LMD (n=15) vs. MRI-diagnosed LMD (n=54) was associated with longer post-LMD survival [pLMD-OS: 15.2m vs. 6.2m, p=0.0002] but similar overall survival [mOS: 16.9m vs. 20.9m; p=0.72] . Post-LMD survival [pLMD-OS: 8.7m vs. 6.8m, p=0.33] and overall survival [mOS: 21.1m vs. 20.9m, p=0.20] were similar for supratentorial (n=45) vs. infratentorial/spinal (n=10) locations, and post-LMD survival did not significantly differ for symptomatic (n=40) vs. asymptomatic (n=22) patients [pLMD-OS: 6.6m vs. 10.5m, p=0.13). pTERT mutation (73%), MGMT methylation (38%), EGFR amplification (31%), and PTEN mutation (28%) were the most prevalent molecular alterations in this group. Comparison of grade 4 LMD tumors with an independent GBM cohort (n=5431) suggested a male predominance (73.4% vs. 58.5%, p=0.016) and a trend towards more frequent mutations in RB1 (25% vs. 9.2%, p=0.002) and MDM4 (12.7% vs. 4.3%, p=0.01) and amplification of WIF1 (6.1% vs. 0.3%, p=0.006), CHIC2 (17.0% vs. 5.2%, p=0.002), and LGR5 (5.9% vs. 0.4%, p=0.012). The expression of immune checkpoint-related genes was similar, although a trend towards immunologically “colder” tumors in the LMD cohort was observed. However, these effects were not significant after correcting for multiple comparisons. Conclusions: LMD is more common in male patients and may be associated with various genomic alterations and tumor microenvironment differences. Overall survival does not differ from patients without LMD, but these differences may provide clues to the pathogenesis and treatment resistance of GBM.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2023.41.16_suppl.2070
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
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  • 4
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    The mutational landscape of older patients with IDH wild-type glioblastoma (GBM).
    American Society of Clinical Oncology (ASCO) ; 2021
    In:  Journal of Clinical Oncology Vol. 39, No. 15_suppl ( 2021-05-20), p. e14033-e14033
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 15_suppl ( 2021-05-20), p. e14033-e14033
    Abstract: e14033 Background: Advanced age is associated with poorer outcomes in GBM and current NCCN guidelines distinguish older GBM patients (≥70 years, oGBM) from their younger counterparts ( 〈 70 years, yGBM). We aim to characterize age-related comprehensive mutational profiles with the long-term goal of improving treatment strategies, outcomes, and rational clinical trial design. Specifically, we focused on IDH-wildtype (WT) oGBM, investigated if oGBM are more likely to acquire temozolomide-induced hypermutations, and finally, compared the frequency of high-tumor mutational burden (TMB) between oGBM vs. yGBM. Methods: Comprehensive molecular profiles of 1,657 adult IDH-WT GBM tumors tested at Caris Life Sciences (Phoenix, AZ) were queried. Tests included NGS of DNA (NextSeq, 592 Genes and NovaSEQ, WES) and RNA (NovaSeq) sequencing. SBS11 gene signature (i.e temozolomide-induced hypermutational profile) was queried using SigProfiler (Alexandrov 2020, Nature). Significance was determined by X 2 and Fisher-Exact and p adjusted for multiple comparisons ( q) was 〈 0.05. Results: We identified 1,657 patients (range 21-89 years old, median 61 years) with IDH-wildtype GBM, 22% (360) of whom were ≥ 70 years. There was a slight male predominance (60%) for all ages. The most prevalent alterations in oGBM were TERT promoter mutation (105/131,80%), MGMT promoter methylation (pMe) (175/346, 51%), and PTEN mutation (129/349, 37%). EGFR amplification was seen in 35% (125/356) and EGFRvIII in 23% (81/360); Overall, fusions were seen in 12% (44 of 360) oGBM; events 〉 1% included MET (3.6%), FGFR3 (3.1%), EGFR (2.6%) and ROS1 (1.4%). 17% (56/349) of oGBM had positive PD-L1 by IHC. High TMB ( 〉 10mt/Mb) tumors were rare (3.1%) and MSI-high tumors even rarer (0.8%) in oGBM. When compared to yGBM, MGMT pMe was more prevalent (51% vs 38%, risk ratio (RR) 1.35 [1.19-1.52], q 〈 0.05) and NF1 mutations were less frequent in oGBM (21% v 34%, RR 0.62 [0.50-0.77], q 〈 0.05). No significant differences were seen in other key markers examined. The prevalence of SBS11 gene signature across all ages (data available for 1,141 patients) was 1.2% and was comparable across the age spectrum; no significant difference seen in the MGMT pMe group when oGBM was compared to yGBM (3.9% vs. 1.8 %, p= 0.3). Conclusions: This study represents the largest comprehensive molecular characterization of older IDH-WT GBM patients. We show that molecular profiles of IDH-WT GBM are remarkably similar across the age spectrum, including immunotherapy-associated markers, gene fusion landscape, EGFR amplification, and TMB. The significantly higher prevalence of MGMT pMe and lower NF-1 mutation rate in the older population bear significant prognostic and therapeutic implications.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2021.39.15_suppl.e14033
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2021
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  • 5
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    Distinct molecular features and potential therapeutic strategies for spinal cord gliomas.
    American Society of Clinical Oncology (ASCO) ; 2023
    In:  Journal of Clinical Oncology Vol. 41, No. 16_suppl ( 2023-06-01), p. 2056-2056
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. 2056-2056
    Abstract: 2056 Background: Spinal cord gliomas (SCG) are rare primary CNS tumors with varied prognosis. Standard treatment remains poorly defined, as no clear survival advantage exists with extensive resection, radiation, or chemotherapy. Mounting evidence suggests that tumors from different regions of the CNS harbor unique molecular signatures. In a retrospective study, we comprehensively characterized molecular alterations to identify potential therapeutic strategies in the largest cohort of SCG reported to date. Methods: We performed centralized pathology review and analyzed SCG with next-generation sequencing of DNA (592 gene NextSeq or WES, Novaseq), RNA (WTS, NovaSeq) and pyrosequencing (MGMT promoter methylation, MGMTme). We estimated tumor microenvironment cell infiltration by quanTIseq & Epithelial-Mesenchymal Transition (EMT) by RNAseq. We used X2/Fisher’s-exact/Mann-Whitney U tests for comparison & determined significance (p 〈 0.05), adjusting for multiple comparison by the Benjamini-Hochberg method (q 〈 0.05). Results: We analyzed 39 surgically accessible SCG (19 high grade, 17 low grade, 3 NOS); ependymomas were excluded. The most common alterations were mutations in H3F3A (31%), TP53 (25%), ATRX (21%), NF1 (18%) & BRAF fusion (19%). H3F3A mutations occurred exclusively in high grade SCG (63%, q 〈 0.05) while BRAF fusions occurred exclusively in low grade SCG (60%, p 〈 0.05). TP53 mutations were more prevalent in high grade SCG (50% vs. 8%, p 〈 0.05). Compared to intracranial gliomas (n = 6732), SCG harbor significantly more frequent H3F3A (31% vs. 1.6%), KRAS mutations (10% vs. 0.7%) & BRAF fusions (19% vs. 0.7%) but less frequent TERT (4.3% vs. 66%) & PTEN (0 vs. 27%) mutations or EGFR amplification (0 vs. 28%) (all q 〈 0.05). SCG rarely harbor the canonical intracranial alterations IDH1 (2.6% vs. 17%), EGFRvIII (0 vs. 17%) or MGMTme (19% vs. 47%) (p 〈 0.05). SCG have greater penetration of immune infiltrates of DCs (median cell fraction/MCF: 13% vs. 9%), T regs (positive percent: 47% vs. 26%) & B cells (MCF: 9% vs. 7%), with less penetration of monocytes (MCF: 0 vs. 2%) (q 〈 0.05). EMT score associates with high grade glioma in intracranial disease (q 〈 0.05) but does not recapitulate in SCG (p 〉 0.05). Conclusions: Clinical management of SCG is currently drawn from experience with intracranial gliomas. Our results identify unique molecular features of SCG suggesting an underlying biology distinct from intracranial gliomas. In SCG, H3F3A mutations are exclusive to high grade while BRAF fusions are exclusive to low grade; SCG rarely harbor canonical intracranial alterations such as IDH1, EGFR or MGMTme; and SCG have greater penetration of DCs with less penetration of monocytes. We provide a biological explanation for limited effectiveness of current therapies in SCG with potential implications for chemotherapy, targeted and immunotherapy. Our work underscores the need for investigations dedicated uniquely to SCG.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2023.41.16_suppl.2056
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
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  • 6
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    Biological and prognostic relevance of epigenetic regulatory genes in high-grade gliomas (HGGs).
    American Society of Clinical Oncology (ASCO) ; 2022
    In:  Journal of Clinical Oncology Vol. 40, No. 16_suppl ( 2022-06-01), p. 2019-2019
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. 2019-2019
    Abstract: 2019 Background: Gliomagenesis is regulated by dynamic epigenetic modifications of DNA methylation, deregulation of histones and alteration of the human Switch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complexes. These epigenetic genes are responsible for treatment resistance by inducing stemness of glioma cells and immune cells with in the tumor microenvironement (TME). We evaluated the key chromatin remodeling (CR) genes and their interactions with other regulatory genes that are of prognostic importance. Methods: 1856 HGGs underwent molecular profiling at Caris Life Sciences (Phoenix, AZ). Analyses included next-generation sequencing of DNA (592 Genes, NextSeq or WES, NovaSeq) and RNA (WTS, NovaSeq). Cell infiltration in the TME was estimated by quanTIseq. X 2 /Fisher’s-exact/Mann-Whitney U tests were used for comparison, and significance was determined as p-value adjusted for multiple comparison by the Benjamini-Hochberg method (q 〈 0.05). Overall survival (OS) was calculated from the start of temozolomide (TMZ) to last contact using insurance claims data. Results: In a cohort of 1856 HGGs, 181 (9.8%) displayed 〉 =1 mutation of 19 CR genes considered, including mutations (mt) of histone methyltransferases (HM) comprising SETD2 (62, 3.4%), KMT2D (18, 1.0%), KMT2C (11, 0.6%); SWI/SNF complexes (SSNF) including ARID1A (32, 1.74%), ARID2 (15, 0.82%), SMARCA4 (14, 0.76%) and ARID1B (12, 0.66%); and others including ( DNMT3A, 0.94%, ASLXL1: 13, 0.98%). When compared to CR-WT, CR-mt HGGs showed higher prevalence of Tumor Mutational Burden-High (TMB-H) (23% vs. 1.3%), MSI-H/dMMR (13% vs. 0.2%), gLOH (9.5% vs 4.3%), and mts in IDH1/2 (29% vs. 14%), TP53 (55% vs. 36%), MSH6 (8.8% vs. 0.6%), and PIK3CA (18.8% vs. 8.3%) (all q 〈 0.05). Investigation of CR-mt subgroups showed that SSNF mt had the highest MGMT-promoter methylation (68%) and IDH1/2 mt (46%), while HM and others showed similar prevalence. In IDH-WT and MSS HGGs, the CR association with TMB-H, MSH6, TP53 and PIK3CA persisted (q 〈 0.05). When studying the immune profile, CR-mt HGGs showed significantly lower expression of immune-related genes including PD-L1 (Fold change: 0.76), PD-L2 (0.72), IDO1 (0.65), TIM3 (0.76) and CD86 (0.77) and colder TME as manifested by lower infiltrations of M2 (0.87) and higher Treg (1.27, all q 〈 0.05); such effects were not observed in the subgroup of IDH WT/MSS tumors. Among TMZ-treated HGG tumors, CR mt was associated with improved OS (33 months vs 22m, HR: 0.713, 95% CI: 0.581-0.876, p =.001). In the IDH WT/MSS subgroup this effect was also observed (31.6m vs 19.2m, HR: 0.764, 95% CI: 0.59-0.99, p = 0.041). Conclusions: Nearly 10% of HGGs carry mts in CR genes. CR-mt HGGs possess significantly more favorable genetic alterations and colder TME compared to the CR-WT HGGs and showed better OS when treated with TMZ. Multivariate modeling and analysis of associations with specific targeted therapies is underway.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2022.40.16_suppl.2019
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
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  • 7
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    Is there a role for empiric radiation without a confirmatory biopsy for a subset of patients with radiographically-malignant primary brain tumors?: An analysis of short-term morbidity and mortality.
    American Society of Clinical Oncology (ASCO) ; 2015
    In:  Journal of Clinical Oncology Vol. 33, No. 15_suppl ( 2015-05-20), p. e13001-e13001
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 33, No. 15_suppl ( 2015-05-20), p. e13001-e13001
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2015.33.15_suppl.e13001
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2015
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  • 8
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    Use of immunotherapy in recurrent glioblastoma.
    American Society of Clinical Oncology (ASCO) ; 2017
    In:  Journal of Clinical Oncology Vol. 35, No. 15_suppl ( 2017-05-20), p. e13523-e13523
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 15_suppl ( 2017-05-20), p. e13523-e13523
    Abstract: e13523 Background: With the recent explosion of interest in immunotherapy to treat cancer, it has moved into management of glioblastoma (GBM). Several trials are ongoing, investigating use of checkpoint inhibition for newly diagnosed and recurrent GBM. Methods: We reviewed the records of patients with recurrent glioblastoma (including gliosarcoma). Six of the eight patients demonstrated PD-1 positivity via immunohistochemical (IHC) staining. Two patients demonstrated PD-L1 positivity as 2+ staining intensity via IHC. Patients were managed with checkpoint inhibitors for at least four weeks. When feasible, patients had tumor profiling of initial tumor and recurrent tumor. Patients were followed for response, progression, and survival. Results: Eight patients were identified with recurrent GBM who received immunotherapy with checkpoint inhibitors. They ranged from first through fifth recurrence following radiation and temozolomide. Three patients received pembrolizumab. Of those, two were PD-L1 positive. Five patients received nivolumab, and all were PD-1 positive. There were no partial or complete responses. Five of the eight subjects died, and the median survival time among the 8 subjects was 3.6 months. Six of eight subjects progressed on treatment, and the median PFS was 2.2 months. Bevacizumab was given to two patients for suspected “tumor flare” while on nivolumab. Four of the eight patients had tumor profiling completed at initial diagnosis and recurrence. Treatment was well-tolerated with only minimal toxicity observed. Conclusions: Despite increasing interest in utilizing these medications for recurrent glioblastoma, overall survival in our cohort was consistent with historical control (3 to 5 months). Additionally, we did not witness any responses.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2017.35.15_suppl.e13523
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2017
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  • 9
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    Mutations of H3.3 and H3.1 in a large cohort of glioma tumors.
    American Society of Clinical Oncology (ASCO) ; 2019
    In:  Journal of Clinical Oncology Vol. 37, No. 15_suppl ( 2019-05-20), p. e13540-e13540
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 15_suppl ( 2019-05-20), p. e13540-e13540
    Abstract: e13540 Background: Mutations in the histone genes H3.3 and H3.1 are driver events in pediatric and adult gliomas and carry diagnostic and prognostic importance for tumors originating from midline structures. Patients with tumors affected by these mutations are notoriously difficult to treat, and the prevalence and molecular correlates of H3 mutations in a large glioma population have not been systematically reported. We aim to survey a large cohort of gliomas for H3-mutations. Methods: Consecutive gliomas submitted for tumor profiling at Caris Life Sciences from 2015- 2018 were analyzed. NextGen sequencing was done on 592 genes (NextSEQ Illumina); MGMT promoter methylation was tested by pyrosequencing; and EGFRvIII and gene fusions were tested by RNA-sequencing (ArcherDx FusionPlex). Results: Of the 1763 tumors analyzed, 41 harbored H3F3A alterations, including 33 with the K27M mutation (4 arose from the spinal cord, 1 from cerebellum, 1 from brain stem, 4 from thalamus, and 23 from brain, NOS). Eight G34R mutations were identified. A HIST1H3B-K27M was detected in a tumor from the brain stem. Overall, H3 mutations were more prevalent in pediatric tumors (8 of 26, 31%) than adult tumors (34 of 1737, 2%). All H3 mutations seen in pediatric tumors were from grade IV tumors. Among the 34 H3-mutated adult tumors, histology differed. There were 2 grade II tumors (diffuse astrocytoma), 1 low grade glioma from the spinal cord, 1 anaplastic ganglioglioma and 2 anaplastic astrocytomas. In the investigated cohort, H3-mutations were mutually exclusive of IDH1/2 mutations and EGFR alterations. Significantly higher mutation rates were seen in H3-mutated tumors for TP53 (69%. Vs. 37%), ATRX (46% vs. 24%), NF1 (23% vs. 12%) , PDGFRA (17% vs. 1%), FGFR1 (12% vs. 1%), FBXW7 (5% vs. 0), BLM (3% vs. 0) and TSC2 (2% vs.0) compared with H3-WT (p 〈 0.05). The H3-WT tumors were more enriched for MGMT-methylation (53% vs. 26%) and PTEN mutation (22% vs. 7%) (p 〈 0.05). In H3-mutated tumors that were MGMT-methylated (n = 10), most H3-mutations seen were G34R (n = 8) while K27M (n = 2) was largely exclusive. Conclusions: This survey of a large cohort of gliomas revealed a heterogeneous distribution of H3 mutations. The co-occurring molecular alterations seen in H3-mutated tumors further support the hypothesis that these tumors are a distinct molecular entity. By better characterizing these associations, we are closer to developing more insight into novel treatment strategies for a class of tumors with historically dismal prognosis.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2019.37.15_suppl.e13540
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
    detail.hit.zdb_id: 2005181-5
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    Online Resource
    Risk factors for hospitalization for cancer patients with SARS-CoV-2 infection.
    American Society of Clinical Oncology (ASCO) ; 2021
    In:  Journal of Clinical Oncology Vol. 39, No. 15_suppl ( 2021-05-20), p. e18753-e18753
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 15_suppl ( 2021-05-20), p. e18753-e18753
    Abstract: e18753 Background: Cancer patients are more susceptible to developing severe disease associated with SARS-CoV-2 infection. Herein, data from a high-volume cancer center is presented highlighting risk factors associated with hospitalization with COVID-19 disease. Methods: Cancer patients in the Levine Cancer Institute COVID19 database who were tested for SARS-CoV-2 due to clinical illness from March 1, 2020 to October 29, 2020 with 90 days follow-up are described here. Patients’ demographic and clinical information were retrospectively entered into a REDCap database from chart reviews. Differences in distributions were identified between hospitalized and non-hospitalized patients using the chi-squared test with uni- and multivariable logistic regression models. Statistical significance was set at p 〈 0.05. Results: 228 patients with SARS-CoV-2 infection were identified, of whom 103 (45%) were hospitalized. Median age was 63 years (range 28-95). Race distribution for infection showed White 65%, followed by Black 26.8% and Hispanic ethnicity 16.7% , with a similar distribution for hospital admission. Median length of stay was 10 days (range 1-91) with no readmissions within 90 days. The most common underlying malignancies were breast (29.8%), hematologic (21.1%) and genitourinary (12.3%). The most common preexisting conditions included hypertension (55.7%), diabetes (27.2%) and cardiac disease (3.9%). The most common presenting symptoms were cough (50.2%), fever (38.4%), fatigue (37.8%) and shortness of breath (36.4%). Maximum oxygen requirements for hospitalized patients were ambient air (34%), nasal canula (34%), high/medium flow nasal canula (10%), non-invasive ventilation (13%) and mechanical ventilation (10%). Case fatality rate was 10% with diagnosis of COVID-19, including 21.4% of those admitted to the hospital and 51.7% of those admitted to the ICU. Univariable logistic regression analysis showed that age, sex, prior chemotherapy, upper gastrointestinal cancers, hematologic cancers, number of medical conditions, cardiac disease, chronic lung diseases, hypertension, and diabetes increased risk of hospitalization. Table shows results of multivariate analysis. Conclusions: The COVID-19 pandemic has caused high case fatality rates in our cancer patients. We identified age, cardiac disease, hematologic malignancy and receipt of chemotherapy within 4 weeks of diagnosis as risk factors for hospitalization. These data may help in prioritizing early intervention in vulnerable subgroups to improve survival outcomes. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2021.39.15_suppl.e18753
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2021
    detail.hit.zdb_id: 2005181-5
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Online Resource
    Open Access Request
    Availability (electronic / print)
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