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  • 1
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 80, No. 16_Supplement ( 2020-08-15), p. 1159-1159
    Abstract: Purpose: There is risk of clinical under-staging of muscle invasive bladder cancer (MIBC) by trans-urethral resection (TURBT) alone. Circulating biomarkers may improve the staging and pre-treatment risk stratification of patients with bladder cancer by discriminating non-muscle invasive (NMIBC) and MIBC. Methods: Peripheral blood from 74pts with BC (30NMIBC, 15 MIBC and 29 Met BC was collected in Streck BCT tubes and processed to obtain cfDNA. Total cfDNA quantity (ng/mlof plasma) was assessed by fluorimetry. cfDNA fragment size was measured by Bioanalyzer DNA analysis. Wilcoxon rank sum test, Cochran-armitage trend test, Fisher's exact t-test were used to compare cfDNA quantity and fragmentation pattern (small fragments are indicative of circulating tumor DNA) among pts with NMIBC, MIBC, met BC to predict invasiveness of BC. Results: There was no significant difference in cfDNA concentration between MIBC and met BC, however, cfDNA levels were significantly lower in pts with NMIBC vs MIBC and met BC. The difference was even more pronounced in case of cfDNA fragment (100-400bp) conc. Total cfDNA (ng/ml) was a good predictor in bladder cancer invasiveness, AUC 0.8 (95% CI 0.7-0.9). The risk of invasion was significantly lower inpatients with total cfDNA & lt 1.5 ng/ml and significantly higher in patients with cfDNA & gt 7.0ng/ml. In 18 pts with cfDNA & lt1.5ng/ml, only 1 pt (5.6%) had invasive cancer (at 1.2). The percent risk of invasive disease was 70.6% for cfDNA concentrations between 1.5-7.0ng/ml and 79.0% for cfDNA & gt 7.0. No invasion was observed among 13 pts with total cfDNA less than 1. This exploratory study suggests that cfDNA levels may correlate with BC stage and hence can be used in juxtaposition with TURBT, exam under anesthesia and CT to better predict clinical staging. Conclusions: Circulating cfDNA may be a dynamic, low-cost and minimally invasive biomarker that can be used in conjunction with TURBT to predict tumor invasiveness, reduce under-staging, and risk stratify patients for appropriate curative intent therapy. cfDNA variation with BC stagingcfDNA parametersTotalNMIBCMIBCMET BCp-value(N=74)(N=30)(N=15)(N=29)cfDNA_ng/ml of plasma7.3[2.9,12.5]1.3[0.48,7.4] 9.7[4.0,13.3]8.7[6.1,14.4] & lt;0.001bcfDNA fragment (100to400bp)_pg/ml of plasma76.9[0.00,5591.2]0.00[0.00,59.4] 3322.7[0.00,8405.2]3344.7[53.8,21930.3] & lt;0.001b Citation Format: Shinjini Ganguly, Jaleh Fallah, Hong Li, Wei Wei, Aysegul Balyimez, Claudia Marcela Diaz, Pat Rayman, Marcelo Lamenza, Priscilla Dann, Donna Company, Rahul Tendulkar, Jacob Scott, Mohamed Abazeed, Jorge A. Garcia, Moshe C. Ornstein, Brian R. Rini, Byron Lee, Petros Grivas, Omar Mian. Circulating cell-free DNA (cfDNA) levels and fragmentation patterns discriminate muscle invasive from non-muscle invasive urothelial cancer of the bladder [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1159.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2020
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  • 2
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 15_suppl ( 2020-05-20), p. 2537-2537
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. 2537-2537
    Abstract: 2537 Background: Clinical trials of bevacizumab monotherapy and TTFields monotherapy have shown activity but limited clinical benefit in patients (pts) with recurrent glioblastoma (GBM), with median progression-free survival (PFS) of 2-4 months and median overall survival (OS) of 6-9 months with either treatment modality. In a single-arm phase II clinical trial, the efficacy of the combination of bevacizumab and TTFields in pts with recurrent GBM was investigated. Methods: Pts with histologically confirmed GBM or other grade IV gliomas, who had disease progression after chemoradiation were enrolled in a phase II trial of the combination of bevacizumab and TTFields. Bevacizumab was given at a dose of 10 mg/Kg intravenously every 2 weeks and TTFields was worn by the pts continuously for more than 18 hours per day. Treatment was continued until disease progression or unacceptable toxicity. The primary endpoints were PFS at 6 months and OS at 12 months. Survival outcomes were assessed using the Kaplan-Meier method and compared by log rank test. Treatment-related adverse events were reported according to CTCAE, v4.0 criteria. Results: From April 2013 to December 2017, 25 pts were enrolled and 23 were evaluable: 18 (78%) men and 5 (22%) women, median age 60 years (range 17–78). 21 pts were Caucasian, 1 was African American and 1 of unknown race. After a median follow up of 31.6 months (range: 4.1-59.0 months), 21 out of 23 pts died (4 women and 17 men). The median PFS was 4.1 months (95%CI, 3.6-9.5) and the median OS was 10.5 months (95% CI, 8.2-14.9). The PFS rate at 6 and 12 months were 33% and 19%, respectively. The OS rate at 6 and 12 months were 82% and 46%, respectively. Women had better OS and PFS compared to men, however, the difference was not statistically significant which can be due to the small study population (table). Grade 3 and 4 toxicities considered definitely or probably related to the treatment included hypertension (n = 1) and cerebral infarction (n = 1). Other reported grade 3-4 toxicities (n = 7) included cough, dysphagia, muscle weakness, hyperglycemia, psychosis, seizure, lymphopenia, transaminitis, and muscle weakness considered unlikely to be treatment-related. Conclusions: The combination of bevacizumab and TTFields in is safe and feasible and has clinical efficacy in pts with recurrent GBM. Clinical trial information: NCT01894061 . [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
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  • 3
    Online Resource
    Online Resource
    American Society of Hematology ; 2016
    In:  Blood Vol. 128, No. 22 ( 2016-12-02), p. 3584-3584
    In: Blood, American Society of Hematology, Vol. 128, No. 22 ( 2016-12-02), p. 3584-3584
    Abstract: Introduction: Splenectomy has been a historically important diagnostic and therapeutic modality for splenic lymphomas, but with the advent of sensitive diagnostic tools and efficacious immunochemotherapy, its role has diminished. Our objective was to describe trends in the use of splenectomy for management of splenic lymphomas, and to determine the association of practice setting with choice of surgical treatment. Methods: Using the National Cancer Data Base (NCDB), a nationwide registry capturing 〉 80% of lymphomas in the United States, we selected non-Hodgkin lymphoma cases diagnosed in 2004-2013, with spleen recorded as the primary site. We identified the use of splenectomy and chemotherapy as part of the initial treatment. Splenectomy was assumed to be diagnostic when it was coincident with lymphoma diagnosis (0 days from diagnosis to surgery). Treatment facilities were designated by the NCDB as community, comprehensive community, academic/research, or integrated network cancer programs, depending on case volume and available services. We studied factors associated with the use of splenectomy in a multilevel mixed-effects logistic model (with random intercepts for each geographic region and each facility within it), reporting odds ratios (OR) and intraclass correlation (ICC) with 95% confidence intervals (CI). Linearized trends from log-binomial regression were expressed as average annual percent change (APC) in the proportion of patients (pts) undergoing splenectomy. Results: Among 6,504 of pts with splenic lymphomas, 48% were classified as splenic marginal zone (SMZL), 28% as diffuse large B-cell (DLBCL), 4% as mantle cell (MCL), 5% as follicular (FL), 4% as T-cell lymphoma (TCL, 52% being hepatosplenic γd-TCL), and 11% were other or unspecified histologies. Overall, 58% of pts underwent any splenectomy, and 33% a diagnostic splenectomy, but these proportions significantly varied by histology (χ2P 〈 .0001, Table). After a diagnostic splenectomy, 31% of DLBCL and 47% of MCL pts did not receive chemotherapy. Between 2004 and 2013, the proportion undergoing splenectomy significantly decreased for most histologies (Figure). This trend was most pronounced in SMZL (APC, -7.7%; Table), and MCL (APC, -8.4%), and it was paralleled by a significant increase in the use of chemotherapy for management of SMZL and TCL. Mortality at 30 days after splenectomy was 4% overall, varying from 〈 2% in SMZL/MCL/FL, 6% in DLBCL, to 10% in TCL (χ2P 〈 .0001). The proportion of pts undergoing splenectomy differed significantly according to type of treating hospital only in SMZL, where it was 39% for pts treated in "community", 52% in "comprehensive community", 50% in "academic/research", and 44% in "integrated network" centers (χ2P=.0004). In contrast, facility type was not associated with splenectomy use in DLBCL (P=.47), MCL (P=.55), FL (P=.75), or TCL (P=.15). The proportion of splenectomies performed for diagnosis was significantly lower in academic (51%) than in community (62%), comprehensive community (59%), or integrated network centers (60%, χ2P 〈 .0001) In a multivariable model in treated SMZL pts, those who had advanced-stage lymphoma or B symptoms, and those who were older, male, without comorbidities, with Medicaid, or with no insurance were significantly less likely to undergo splenectomy. There was evidence of significant clustering of treatment selection in each hospital (ICC, 24%; CI, 17-32%), but not in geographical regions (ICC, 2%; CI, 0.2-9.5%). Compared with academic/research centers, splenectomy was performed less frequently in smaller community centers (adjusted OR, 0.59; CI, 0.38-0.93, P=.022), but not in larger comprehensive community centers (OR, 0.97; CI, 0.72-1.32, P=.86). Conclusions: Although the use of splenectomy for management of splenic lymphomas has declined, nearly half of pts with splenic DLBCL, FL, or TCL still undergo surgery for diagnosis, highlighting the ongoing need for reliable, non-invasive diagnostic modalities. A substantial proportion of pts with DLBCL and MCL do not receive chemotherapy after surgery. Further research should elucidate the reasons for it, and associated outcomes in those groups. In SMZL, the use of splenectomy is facility-dependent after adjusting for patient- and lymphoma-related characteristics, with lower rate of splenectomy in smaller community centers, possibly reflecting availability of surgical expertise. Disclosures Olszewski: TG Therapeutics: Research Funding; Genentech: Research Funding; Bristol-Myers Squibb: Consultancy.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2016
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  • 4
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    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2016
    In:  Journal of Clinical Oncology Vol. 34, No. 15_suppl ( 2016-05-20), p. 2026-2026
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 34, No. 15_suppl ( 2016-05-20), p. 2026-2026
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2016
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  • 5
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 15_suppl ( 2021-05-20), p. 4516-4516
    Abstract: 4516 Background: Immunotherapy-based combination therapies (IO-X) are standard of care for metastatic RCC (mRCC) in the frontline setting. Limited data is available on the role of cytoreductive nephrectomy prior to IO-X in patients (pts) with mRCC (Bakouny, et al. GU ASCO 2020). We assessed the correlation between nephrectomy prior to IO-X and overall survival (OS) in pts with de novo mRCC. Methods: We pooled data from trials submitted for FDA review of a checkpoint inhibitor combination as first-line treatment for pts with mRCC. We only included trials with available data for stage at initial diagnosis (dx) to identify pts with stage IV disease at initial dx and to exclude those with nephrectomy in the non-metastatic setting. Kaplan-Meier method was used to estimate median OS in pts with de novo mRCC with and without nephrectomy prior to IO-X. Results: Five trials met inclusion criteria, all of which evaluated IO in combination with a kinase inhibitor. Data for stage at initial dx was available in 1708 pts who received IO-X. The majority of pts were male (72%) and White (80%). Among the 849 pts (50%) with stage IV RCC at initial dx, 523 pts (62%) had nephrectomy prior to IO-X. All pts had clear cell histology; Sarcomatoid differentiation was present in tumor pathology of 25% and 10% of pts with and without prior nephrectomy, respectively. Proportion of pts with favorable, intermediate and poor risk disease was 10%, 70% and 20%, respectively. OS appeared better in those with stage IV disease at dx who had prior nephrectomy compared to pts without nephrectomy (Hazard ratio (HR) = 0.53, 95% CI: 0.42, 0.68), even after adjusting for age and prognostic risk group (HR = 0.59, 95% CI: 0.46, 0.75) (see table). Conclusions: In this retrospective exploratory analysis, nephrectomy prior to IO-X in pts with new dx of stage IV RCC appeared to be associated with improved OS, even when controlling for age and prognostic risk group. The decision for nephrectomy is affected by factors such as medical comorbidities which could not be completely controlled. Results should be considered hypothesis generating.[Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2021
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  • 6
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2015
    In:  Journal of Clinical Oncology Vol. 33, No. 15_suppl ( 2015-05-20), p. 1521-1521
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 33, No. 15_suppl ( 2015-05-20), p. 1521-1521
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2015
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  • 7
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 29, No. 9 ( 2023-05-01), p. 1651-1657
    Abstract: On March 23, 2022, the FDA approved Pluvicto (lutetium Lu 177 vipivotide tetraxetan, also known as 177Lu-PSMA-617) for the treatment of adult patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen receptor pathway inhibition and taxane-based chemotherapy. The recommended 177Lu-PSMA-617 dose is 7.4 gigabecquerels (GBq; 200 mCi) intravenously every 6 weeks for up to six doses, or until disease progression or unacceptable toxicity. The FDA granted traditional approval based on VISION (NCT03511664), which was a randomized (2:1), multicenter, open-label trial that assessed the efficacy and safety of 177Lu-PSMA-617 plus best standard of care (BSoC; n = 551) or BSoC alone (n = 280) in men with progressive, PSMA-positive mCRPC. Patients were required to have received ≥1 androgen receptor pathway inhibitor, and one or two prior taxane-based chemotherapy regimens. There was a statistically significant and clinically meaningful improvement in overall survival (OS), with a median OS of 15.3 months in the 177Lu-PSMA-617 plus BSoC arm and 11.3 months in the BSoC arm, respectively (HR: 0.62; 95% confidence interval: 0.52–0.74; P & lt; 0.001). The most common adverse reactions (≥20%) occurring at a higher incidence in patients receiving 177Lu-PSMA-617 were fatigue, dry mouth, nausea, anemia, decreased appetite, and constipation. The most common laboratory abnormalities that worsened from baseline in ≥30% of patients receiving 177Lu-PSMA-617 were decreased lymphocytes, decreased hemoglobin, decreased leukocytes, decreased platelets, decreased calcium, and decreased sodium. This article summarizes the FDA review of data supporting traditional approval of 177Lu-PSMA-617 for this indication.
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2023
    detail.hit.zdb_id: 1225457-5
    detail.hit.zdb_id: 2036787-9
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  • 8
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 6_suppl ( 2021-02-20), p. 197-197
    Abstract: 197 Background: Patients (pts) enrolled in trials of androgen receptor inhibitors (ARI) in the non-metastatic castration resistant prostate cancer (nmCRPC) setting may or may not have received definitive treatment with prostatectomy and/or radiation therapy (Surg/RT). We investigated the characteristics and outcomes of pts with nmCRPC based on prior history of Surg/RT. Methods: Data were pooled from all trials of ARI in nmCRPC submitted to the FDA as of October 2020. Pts baseline characteristics were summarized by prior history of Surg/RT. The Kaplan-Meier method was used to estimate median metastatic-free survival (MFS) and overall survival (OS) of each treatment arm by prior history of Surg/RT status. Hazard Ratios (HR) with corresponding 95% confidence intervals (CI) were estimated using a Cox proportional hazards model stratified by trial and adjusted for baseline characteristics. Results: Three trials met the inclusion criteria. Of 4117 pts enrolled, 2251 (55%) had prior surg/RT. The median age at the time of enrollment was 72 and 76 years in pts with and without prior Surg/RT, respectively. The median time from initial diagnosis of prostate cancer to enrollment on the trials of ARI was 9.1 and 5.7 years in pts with and without prior Surg/RT, respectively. PSA doubling time and number of prior hormonal therapies were similar between the two groups with and without prior Surg/RT. History of prior Surg/RT varied by geographic region: 76% (N = 611/807) in North America, 50% (N = 1110/2229) in Europe, 39% (N = 220/570) in Asia/Pacific, 52% (135/262) in South America, and 73% (171/233) in Australia/New Zealand. ECOG performance status (PS) at the time of enrollment was 0 and 1 in 80% and 20% of the pts with prior Surg/RT, respectively. In pts without prior Surg/RT, ECOG PS was 0 in 65% and 1 in 35% of pts. Gleason score was ≥8 in 36% and 47% of pts with and without prior Surg/RT, respectively. MFS and OS results in pts with and without prior Surg/RT are in the table. Conclusions: In this retrospective analysis, MFS and OS was improved in pts who received ARIs compared to placebo, regardless of prior history of Surg/RT. Any relative differences based on prior history of Surg/RT can only be considered hypothesis generating. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2021
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  • 9
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 7_suppl ( 2019-03-01), p. 437-437
    Abstract: 437 Background: MDSCs play an important role in maintaining a tumor immunosuppressive microenvironment. The association of circulating levels of MDSCs with pCR (pT0N0) and outcomes was investigated in patients (pts) with non-metastatic UC undergoing cystectomy. Methods: Peripheral blood samples from pts with non-metastatic UC was collected. MDSCs were measured in freshly purified peripheral blood mononuclear cells, using flow cytometry. Total (T) MDSC was defined as CD33+/HLADR-. T-MDSC subtypes were polymorphonuclear (PMN-MDSC: CD15+/CD14-), monocytic (M-MDSC: CD15-/CD14+], and uncommitted (UC-MDSC: CD15-/CD14-] . MDSC populations were presented as % of live nucleated blood cells. Wilcoxon rank sum test was used to compare MDSCs between pCR groups. Kaplan-Meier and log-rank test were used to analyze RFS and OS. Results: MDSC data were available for 124 pts (106 male, 18 female), median age 68, 28 (23%) never smokers, 93 (75%) pure UC. Thirty four pts (27%) received intravesical BCG; 49 (39%) received neoadjuvant chemotherapy (NAC); 22 (19%) had pCR (pT0N0) following surgery. PMN-MDSC was the dominant subtype (42%) and frequency of UC-MDSC and M-MDSC was 40% and 17%, respectively. Circulating levels of T-MDSC and PMN-MDSC were significantly lower in pCR patients than those in non-pCR patients (Table). Sixteen deaths were observed and 21 pts recurred after surgery. The median follow-up time of patients alive was 18.7 months (range 0.3-42.4). The median OS or RFS of all patients was not reached. One-year and two-year OS rates were 94% and 83%, respectively. One-year and two-year RFS rates were 82% and 69%, respectively. There was no association between MDSC subtypes with OS or RFS. Conclusions: Total- and PMN-MDSC subtypes in blood were significantly correlated with pCR in pts with non-metastatic UC who undergo cystectomy. The relatively short follow-up may impact the association with RFS and OS; additional follow-up is needed. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
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  • 10
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. e14551-e14551
    Abstract: e14551 Background: In a retrospective study, we investigated the correlation between the molecular characteristics and treatment outcomes in pts with G2-3 glioma. Methods: Pts with G2-3 glioma and known IDH mutation status who were diagnosed between 1994 and 2017 were analyzed. In most of the pts, IDH mutation was determined by immunohistochemistry only. Overall survival (OS) was defined as the date of biopsy/surgical resection to the date of last follow up or death. OS was estimated by Kaplan-Meier method and compared by log rank test. Results: 606 pts with G2 (81%) or G3 (19%) glioma were included. The median age at diagnosis was 38 years (Interquartile range 27-52), 55% of the pts were male, 83% were white, 47% had IDH-mt tumor and 67% underwent surgical resection. The median follow-up was 55.6 months (mo). The median OS (mOS) in pts with IDH mutated (mt) and IDH wild type (wt) tumor were 201 and 128 mo, respectively. The predictors of worse OS in pts with IDH-mt tumor included G3, receipt of chemotherapy or radiation therapy (RT), bilateral disease and lack of 1p/19q codeletion. The determinants of worse OS in pts with IDH-wt tumor included male gender, receipt of chemotherapy or RT, history of prior malignancy, smoking, G3, astrocytoma histology, no surgical resection, EGFR amplification, and lack of 1p/19q codeletion. The mOS by IDH, 1p/19q, and MGMT status is summarized in the table. RT and chemotherapy were more commonly used among pts who had G3 glioma and those who underwent biopsy only. Conclusions: Tumor grade continues to be a determinant of pt outcomes in the setting of molecularly defined gliomas. Presence of 1p/19q codeletion is a predictor of favorable OS in pts with G2-3 glioma. Surgical resection is a determinant of OS in pts with IDH-wt G2-3 gliomas, but not in pts with IDH-mt tumor. The worse OS in pts who were treated with RT or chemotherapy is likely due to the use of these treatment modalities in more aggressive tumors and in those who only had biopsy. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
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