Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. 2060-2060
    Abstract: 2060 Background: Dysregulation of the JAK/STAT pathway in newly-diagnosed high-grade gliomas (nHGG) is linked to enhanced survival and proliferation of tumor cells. Ruxolitinib, a small molecule inhibitor of JAK1, JAK2, and JAK3, limits glioma growth in preclinical models. This concept was explored in a phase I trial (NCT03514069), whose final report on toxicity is presented here. Methods: This non-randomized prospective study included 60 WHO Grade 3-4 nHGG patients who received standard of care (SOC) therapy along with ruxolitinib in a 3+3 dose-escalation design; level 1 of 10 mg BID, level 2 of 15 mg BID, level 3 of 20 mg BID, level -1 of 5 mg BID. The primary study objective was the determination of the maximum tolerated dose (MTD) of ruxolitinib in combination with chemoradiation. The secondary objective was the determination of safety, overall survival (OS), and progression-free survival (PFS). The exploratory aims were to investigate relationships between clinical outcomes and genomic signatures. Results: 60 patients were enrolled, with a median age of 60.5 years (range 22-78). 23 (38%) patients were female and 37 (62%) were male. 29 (48%) were MGMT unmethylated and received ruxolitinib with radiation of 60 Gy over 6 weeks. 31 (52%) patients were MGMT methylated and received ruxolitinib with 75 mg/m 2 of temozolomide (TMZ) with radiation of 60 Gy over 6 weeks. The 1-year OS rate was 77% for all GBM patients; 62% for arm 1 (unmethylated MGMT) and 93% for arm 2 (methylated MGMT). Median OS for arm 1 was 18.1 months (10.1, NA) and was not reached for arm 2. MTD for both cohorts was 20 mg BID. No dose-limiting toxicities were observed. Toxicities attributable to study medications included four grade 4 AEs including seizure, respiratory distress, somnolence, and thromboembolic event along with 14 grade 3 adverse events (AEs), including respiratory distress, seizure, gait disturbance, weakness, thrombocytopenia, cognitive disturbance, urinary retention, and meningitis. Conclusions: Ruxolitinib therapy is safe and feasible in combination with TMZ and radiation. Efficacy of ruxolitinib plus SOC appears promising compared to historical benchmarks for both MGMT methylated and MGMT unmethylated cohorts. A randomized phase 2 trial is planned. Clinical trial information: NCT03514069 .
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
    detail.hit.zdb_id: 2005181-5
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 2
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 15_suppl ( 2019-05-20), p. e13550-e13550
    Abstract: e13550 Background: It is known that in the setting of glioblastoma (GBM) having a methylated O6-Methylguanine Methyltransferase (MGMT) gene promoter confers a greater response to Temozolomide (TMZ) and an increased progression free survival (PFS) and overall survival (OS). Recent literature has uncovered interesting results when dichotomizing patients by demographics (i.e. age and gender) and analyzing response to the various available GBM therapies. Our primary objective is to analyze the effect of both age and MGMT status on OS and PFS in patients with newly diagnosed GBM. Understanding the role of MGMT on age in the setting of GBM can allow for a better understanding of disease course and treatment. Methods: 464 adult patients with newly diagnosed GBM and documented MGMT status were analyzed from a single major tertiary care institution between 2012 and 2018. Patients were stratified into four groups based on age (above or below 65 years) and MGMT status. A univariate Cox model was used to analyze the effect of age and MGMT status on PFS and OS, where our reference group was the group with the highest OS ( 〈 65/methylated). Results: The median age of the whole dataset was 63.4 years, and 65.2 years for patients who were MGMT methylated. Patients less than 65 years and were MGMT methylated had the best prognosis with a PFS and an OS of 10.9 months and 18.9 (Table), respectively. Patients above the age of 65 were more likely to be MGMT methylated (p = 0.002). There was an association between IDH1-mutant status and MGMT methylation (p = 0.006). Conclusions: Using MGMT status and age of the patient, our model predicts outcomes that can vary from 7.4 months to 18.9 months (HR = 3.41 p 〈 0.001).[Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
    detail.hit.zdb_id: 2005181-5
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 3
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 15_suppl ( 2019-05-20), p. e13565-e13565
    Abstract: e13565 Background: Radiotherapy and concurrent chemotherapy with Temozolomide (TMZ) have myelosuppressive effect, and thrombocytopenia is commonly seen in this patient population seen in 5-10% of glioblastoma (GBM) patients. There is a lack of data analyzing the thrombocytopenia and it’s on the progression free survival (PFS) or overall survival (OS) of these patients. The primary objective of this study was to identify the degree of thrombocytopenia in newly diagnosed GBM patients receiving concurrent TMZ based chemoradiation (CRT). Secondary objectives included associations between thrombocytopenia PFS, and OS. Methods: We retrospectively reviewed 484 newly diagnosed GBM patients who underwent surgery followed by standard of care CRT. We also analyzed the association between platelet counts and age, sex, MGMT methylation status, and extent of surgical resection. Platelet count was collected at the time of surgery, CRT start date, and two, four, six, and ten weeks post-CRT start date. Patients were grouped into quartiles according to their platelets count. Results: Of the 484 patients collected, 308 were males, 139 had gross total resection of the tumor, 229 patients were older than 65 years, and 171 (42.1%) were MGMT methylated. In a univariate analysis, a platelet count less than 180,000 (lowest quartile) was associated with higher mortality (HR 1.63, P 〈 0.001) but had no significant association with PFS (HR 1.16, P = 0.48). Among the 118 patients who had platelet count lower than 180,000, 4 had platelets count less than 100,000 necessitating their TMZ to be stopped during CRT. In a multivariate analysis model adjusting for age, gender, MGMT status, and type of surgery, platelet counts less than 180,000 was also associated with significantly higher mortality (HR 1.60, P 〈 0.001). Conclusions: Our study concluded that patients who had platelet counts less than 180,000 at the time of surgery or CRT with TMZ had significantly higher mortality (HR 1.60, P 〈 0.001) but had no association with PFS (HR 1.16, P = 0.48).[Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
    detail.hit.zdb_id: 2005181-5
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 4
    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
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 5
    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. 2048-2048
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 33, No. 15_suppl ( 2015-05-20), p. 2048-2048
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2015
    detail.hit.zdb_id: 2005181-5
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 6
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 15_suppl ( 2019-05-20), p. e13567-e13567
    Abstract: e13567 Background: Albumin levels are widely used to estimate patients’ nutritional status. Low perioperative albumin levels are associated with worse outcomes. Moreover, Prognostic Nutritional Index (PNI), which is calculated from serum albumin levels and peripheral blood lymphocyte count as follows: PNI = (Albumin x 10) + (0.005 x ALC), has been used to predict both short and long term outcomes in patients with wide variety of tumors. The primary objective of this study was to characterize perioperative albumin levels and PNI in newly diagnosed GBM patients. Secondary objectives included associations between albumin levels and PNI on progression free survival (PFS) and overall survival (OS). Methods: We retrospectively reviewed 568 newly diagnosed GBM patients who underwent surgery followed by standard of care chemoradiation. We analyzed the association between albumin and PNI on age, sex, MGMT methylation status, and extent of surgical resection on PFS and OS using a multivariate Cox proportional hazard model. Results: Of the 568 patients collected, 355 (62.5%) were males, 158 (27.8%) had gross total resection of the tumor, and 197(42.5%) were MGMT methylated. Both albumin and PNI were associated with OS but not PFS. The hazard ratio (HR) for OS among the top 2 quartiles of both albumin level and PNI were significantly higher than the bottom two quartiles. The median albumin level was 4.0 and the median PNI was 40. The point for significant high hazard ratio (HR) was around median value for both Albumin and PNI based on restricted cubic spine Cox regression models. The Kaplan-Meir (KM) estimated median OS was 15.2 months for albumin 〉 4, and 7.6 for albumin ≤4. The KM estimated median OS was 14.6 months for PNI 〉 40, and 5.7 for PNI≤40 (P logrank 〈 0.001 for both). While controlling for other factors that may also be associated with early death including age, gender, surgery type and MGMT status, HR = 1.9 (95% CI = 1.4- = 2.6) for Albumin 〈 4, and HR = 2.1 (95% CI = 1.5- 3.0) for PNI 〈 40 compared to their counterpart. Conclusions: Glioblastoma patients with perioperative albumin 〉 4 had a median OS of 15.2 months and 7.6 months for albumin ≤4, and a median OS of 14.6 months for PNI 〉 40 and 5.7 months for PNI≤40 (P logrank 〈 0.001 for both).
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
    detail.hit.zdb_id: 2005181-5
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 7
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. 2067-2067
    Abstract: 2067 Background: Novel therapeutic strategies are urgently needed in newly-diagnosed glioblastoma (GBM). Ibrutinib, an oral small molecule inhibitor of BTK, is currently being investigated for several B-cell malignancies and solid tumors. Preclinical evidence suggests ibrutinib in inhibiting cancer stem cell in glioblastoma. We sought to investigate the safety and tolerability of ibrutinib in nGBM. Methods: A non-randomized, prospective phase I trial was conducted in nGBM patients with Karnofsky performance status ≥70% and normal organ function, who received standard of care chemoradiation plus ibrutinib in a 3+3 dose-escalation design (level 1: 420 mg daily, level 2: 560 mg daily, level -1: 280 mg daily). Primary study objective was to determine maximum tolerated dose (MTD) of ibrutinib in combination with radiotherapy (RT) of 60 Gy over 6 weeks with/without 75 mg/m 2 of temozolomide (TMZ). Secondary objective was to determine safety, overall survival (OS), and progression-free survival. Results: 26 patients were enrolled, with 12 (46%) females. Median age was 61.5 years (range 76-22). 15 (58%) patients were MGMT methylated and 11 (42%) were unmethylated. Dose-limiting toxicities (DLTs) were observed at all dose levels of ibrutinib plus RT (ibru+RT) cohort. MTD of ibrutinib was noted to be 420 mg daily with RT+TMZ. All MGMT methylated and 2 unmethylated patients received ibrutinib+RT+TMZ. Remaining 9 unmethylated received ibru+RT. In ibru+RT+TMZ, median cycles of TMZ were 4 (range 0-6) and of ibrutinib were 3 (range 0-26). EGFR amplification status was available for 22 patients, of which 8 (36%) were amplified. Survival outcomes are described, stratified using log-rank test. Conclusions: 420 mg of Ibrutinib daily is safe and feasible in combination with TMZ and radiation in nGBM. Outcomes of ibrutinib appears promising compared to historical survival data in the MGMT methylated cohorts. Further trials are planned. Clinical trial information: NCT03535350 . [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
    detail.hit.zdb_id: 2005181-5
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 8
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 15_suppl ( 2012-05-20), p. 2100-2100
    Abstract: 2100 Background: Anaplastic oligodendroglial tumors include both anaplastic oligodendroglioma (AO), and anaplastic oligoastrocytoma (AOA), histological categories of WHO grade 3 gliomas. There is limited data on specific prognostic factors for patients with these tumors. Methods: After obtaining IRB approval, the Cleveland Clinic Brain Tumor and Neuro-Oncology Center’s database was used to identify patients with histologically confirmed AO and AOA at the time of diagnosis. Multivariable analysis was conducted with use of a Cox proportional hazards model and a stepwise selection algorithm that used p 〈 0.05 both as the criteria for entry and retention in the model to identify independent predictors of survival. Results: Chart records of 139 patients, 52% of whom were male, diagnosed between 1992 and 2009 were included for analysis. Median age at presentation was 47 years (range, 18-83 years). 22% of patients had biopsy only, 35% had gross total resection, 43% had near total resection or subtotal resection. Following surgery, 30% of patients were treated with chemotherapy (CT) alone, 14% were treated with radiotherapy (RT) and 47% received both CT and RT. Median progression free survival and median overall survival (OS) were 29.0 and 58.7 months respectively. On multivariate analysis, four factors were identified as independent predictors of OS: age at diagnosis (≥50 vs. 〈 50, p=0.004), Hypothyroidism (p=0.009), multifocal disease (p=0.005) and 1p 19q co-deletion (p 〈 0.001). Choice of initial therapy did not impact survival in this cohort of patients. Conclusions: Older age, hypothyroidism and multifocal disease were associated with higher mortality. 1p, 19q co-deletion was associated with lower mortality. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2012
    detail.hit.zdb_id: 2005181-5
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 9
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 15_suppl ( 2019-05-20), p. e13569-e13569
    Abstract: e13569 Background: Standard post-surgical glioblastoma (GBM) treatment, per Stupp protocol, includes six-weeks of concurrent Temozolomide chemoradiation followed by at least six cycles of adjuvant-Temozolomide. Previous investigations into epidermal growth factor receptor (EGFR) amplification as a prognostic factor in GBM have yielded contradicting results, requiring further investigation. The primary aim of this study was to determine the degree to which EGFR amplification, in newly diagnosed GBM, impacted progression free survival (PFS) and overall survival (OS). Methods: Data from 582 patients who underwent surgical intervention for GBM at a tertiary care institution between 2012 and 2018 were analyzed. Only adult patients who underwent treatment per Stupp protocol and had pathological analysis on EGFR and CEP7 were included. Amplification and non-amplification status was calculated by a ratio of EGFR/CEP7 〉 2 and 〈 2, respectively. PFS and OS outcomes were compared using Cox proportional hazard models stratified by surgery type and sex. Results: Of the original 582 patients, 122 were treated per Stupp protocol and had documented EGFR analysis. Of patients who were EGFR amplified, 41 (58.5%) were male and 25 (48.1%) were female (p = 0.38) and median amplification was 1.07 and 1.16 (p 〈 0.001), respectively. EGFR non-amplified patients had a PFS hazard ratio, HR = 0.70 (95% CI = 0.44 – 1.12, p = 0.14); and an OS HR = 0.60 (95% CI = 0.35 – 1.03, p = 0.065). When the EGFR/CEP7 ratio was stratified by quartile, it was found that Q4 compared to Q1 (Q4 〉 6.50 vs 0 〈 Q1 ≤ 1.06) had a PFS HR = 2.1 (95% CI = 1.11 – 4.07, p = 0.024); and an OS HR = 2.48 (95% CI = 1.10 – 5.60, p = 0.028). Conclusions: There was no statistical difference in prevalence of EGFR amplification by sex. However, despite statistical significance, there was minimal difference in median degree of amplification by sex (0.09). Trends begin to show that patients who were EGFR non-amplified had better PFS and OS outcomes than patients who were EGFR amplified, although this was not statistically significant. Patients with very high EGFR amplification (Q4) had significantly poorer PFS and OS outcomes than patients with very low EGFR amplification (Q1).
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
    detail.hit.zdb_id: 2005181-5
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 10
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 15_suppl ( 2019-05-20), p. e13564-e13564
    Abstract: e13564 Background: Standard glioblastoma (GBM) management includes radiotherapy, chemotherapy, and steroids; all of which can result in immunosuppression and a low absolute lymphocyte count (ALC). Previous literature identified an association between low CD4 and worse progression free survival (PFS) and overall survival (OS). There remains a lack of research addressing predictors of immunosuppression in patients with GBM. The primary objective of this study is to identify the degree of immunosuppression, measured by ALC, in GBM patients receiving concurrent temozolomide chemoradiation (CRT). Secondary objectives include associations between ALC, PFS, and OS, and whether there are any predictors of immunosuppression in patients with GBM. Methods: We retrospectively reviewed 231 newly diagnosed GBM patients who underwent surgery followed by standard of care CRT. We also analyzed the association between ALC and age, sex, MGMT methylation status, and extent of surgical resection. ALC was collected at the time of surgery, CRT start date, and two, four, six, and ten weeks post-CRT start date. Common Terminology Criteria for Adverse Events (CTCAE) protocol version 5.0 was then used to grade low ALC as grade 0, 1, 2, 3, or 4. Results: Of the 231 patients analyzed, 139 were males, 74 underwent gross total resection of the tumor, 129 patients were less than 65 years, and 79 (42.5%) were MGMT methylated. 37 patients had grade 3-4 low ALC. In a univariate analysis, grade 3-4 low ALC at 4 weeks (±14 days) post-CRT start was associated with higher mortality (HR 1.54, P = 0.028) but had no significant association with PFS (HR 1.22, P = 0.29). Logistic regression analysis was used to identify risk factors for grade 3-4 low ALC and its association with survival. None of the risk factors that we tested such as age, gender, type of surgery, or molecular markers including MGMT, IDH, or EGFR were associated with low ALC. Conclusions: Our study demonstrated that patients with ALC grade 3 or 4 at 4 weeks (±14 days) of CRT had a significantly higher mortality (HR 1.54, P = 0.028) but had no significant association with PFS (HR 1.22, P = 0.29).
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
    detail.hit.zdb_id: 2005181-5
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. Further information can be found on the KOBV privacy pages