scholarly journals ACTR-20. EFFICACY OF INITIAL TEMOZOLOMIDE FOR HIGH-RISK LOW GRADE GLIOMAS IN A PHASE II AINO (ITALIAN ASSOCIATION FOR NEURO-ONCOLOGY) STUDY: A POST-HOC ANALYSIS WITHIN MOLECULAR SUBGROUPS OF WHO 2016

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi16-vi17
Author(s):  
Roberta Rudà ◽  
Alessia Pellerino ◽  
Andrea Pace ◽  
Carmine Maria Carapella ◽  
Cristina Dealis ◽  
...  
Keyword(s):  
High Risk ◽  
Phase Ii ◽  
Response Rate ◽  
Long Term Results ◽  
Molecular Subgroups ◽  
Who Grade ◽  
Post Hoc Analysis ◽  
Grade Ii ◽  
Post Hoc ◽  
Who Grade Ii Gliomas

Abstract BACKGROUND The optimal management of high risk WHO grade II gliomas after surgery is still debated. The efficacy of initial temozolomide to delay radiotherapy and risk of cognitive defects could vary across the molecular subgroups of WHO 2016, but information on this issue are lacking. PATIENTS AND METHODS A post-hoc analysis has been performed on a cohort of high risk WHO grade II gliomas, who received initial temozolomide alone in phase II multicenter study, with the objective of re-evaluating the long-term results across the different molecular subgroups of the WHO 2016 classification. The primary endpoint of the study, carried out between 2007 and 2010, was response rate according to RANO, being seizure response, PFS and OS secondary endpoints. RESULTS Response rate (partial and minor responses) among oligodendrogliomas IDH-mutant and 1p/19q codeleted (76%) was significantly higher than that among diffuse astrocytomas either mutant (55%) or wild-type (36%). A reduction of seizure frequency >50% was observed in 87% patients and a seizure freedom in 72%. The probability of seizure reduction >50% was significantly associated with the presence of an IDH mutation. Median PFS, PFS at 5 and 10 years, median OS and OS at 5 and 10 years were all significantly longer in oligodendrogliomas IDH-mutant and 1p/19q codeleted. Of patients who did not recur or delay radiotherapy at recurrence for a median follow-up of 8.2 years, 67% and 59%, respectively, were oligodendrogliomas IDH-mutant and 1p/19q codeleted. CONCLUSIONS The post-hoc analysis of this phase II trial suggests that the beneficial effects of initial temozolomide prevail in oligodendrogliomas IDH-mutant and 1p/19q codeleted: thus, these tumors, when incompletely resected or progressive after surgery, especially when suffering from pharmacoresistant seizures, could receive temozolomide as initial treatment with radiotherapy and chemotherapy at recurrence. The trial was registered with EU Clinical Trials Register, EudraCT n. 2007/000386-38.

scholarly journals Phase II study of primary temozolomide chemotherapy in patients with WHO grade II gliomas

2003 ◽  
Vol 14 (12) ◽  
pp. 1715-1721 ◽  
Author(s):  
M. Brada ◽  
L. Viviers ◽  
C. Abson ◽  
F. Hines ◽  
J. Britton ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Who Grade ◽  
Grade Ii ◽  
Who Grade Ii Gliomas ◽  
Temozolomide Chemotherapy

scholarly journals RTID-05. INDIGO: A GLOBAL, RANDOMIZED, DOUBLE-BLIND, PHASE 3 STUDY OF VORASIDENIB (AG-881) VS PLACEBO IN PATIENTS WITH RESIDUAL/RECURRENT GRADE II GLIOMA WITH AN ISOCITRATE DEHYDROGENASE 1/2 (IDH1/2) MUTATION

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii194-ii194
Author(s):  
Ingo Mellinghoff ◽  
Martin van den Bent ◽  
Jennifer Clarke ◽  
Elizabeth Maher ◽  
Katherine Peters ◽  
...  
Keyword(s):  
High Risk ◽  
Dose Escalation ◽  
Objective Response ◽  
Data Monitoring Committee ◽  
Progression Free Survival ◽  
High Risk Population ◽  
Low Grade ◽  
Who Grade ◽  
Free Survival ◽  
Grade Ii

Abstract BACKGROUND Low-grade gliomas (LGGs; WHO grade II) are incurable and ultimately progress to high-grade gliomas. The current treatment options are surgery followed by observation (“watch and wait”) for patients with lower risk for disease progression or postoperative chemoradiotherapy (high-risk population). There are no approved targeted therapies. IDH1 and IDH2 mutations (mIDH1/2) occur in approximately 80% and 4% of LGGs, respectively, and promote tumorigenesis via neomorphic production of D-2-hydroxyglutarate. Vorasidenib, an oral, potent, reversible, brain-penetrant pan-inhibitor of mIDH1/2, was evaluated in 76 patients with glioma in two phase 1 studies (dose escalation and perioperative) and was associated with a favorable safety profile at daily doses below 100 mg. Preliminary clinical activity was observed in non-enhancing glioma patients in both studies, with an objective response rate (ORR) of 18.2% and median progression-free survival of 31.4 months in the dose escalation study. METHODS Approximately 366 patients will be randomized 1:1 to vorasidenib (50 mg QD) or matched placebo and stratified by 1p19q status (intact vs co-deleted). Key eligibility criteria: age ≥ 12 years; grade II oligodendroglioma or astrocytoma (per WHO 2016 criteria) not in need of immediate treatment and without high-risk features; centrally confirmed mIDH1/2 status; ≥ 1 surgery for glioma with most recent ≥ 1 year but ≤ 5 years before randomization, and no other anticancer therapy; Karnofsky performance status ≥ 80%; and centrally confirmed measurable, non-enhancing disease evaluable by magnetic resonance imaging. Crossover from placebo to the vorasidenib arm is permitted upon centrally confirmed radiographic progression per RANO-LGG criteria. Primary endpoint: progression-free survival assessed by independent review. Secondary endpoints: safety and tolerability, tumor growth rate assessed by volume, ORR, overall survival, and quality of life. Clinical data will be reviewed regularly by an independent data monitoring committee. The study is currently enrolling patients in the US, with additional countries planned (NCT04164901).

Identification of WHO II/III gliomas by 16 prognostic-related gene signatures using machine learning methods

2021 ◽  
Vol 28 ◽  
Author(s):  
YaMeng Wu ◽  
Yu Sa ◽  
Yu Guo ◽  
QiFeng Li ◽  
Ning Zhang
Keyword(s):  
Neural Network ◽  
Machine Learning ◽  
Overall Survival ◽  
High Risk ◽  
Who Grade ◽  
Machine Learning Methods ◽  
Medium Risk ◽  
Grade Ii ◽  
Fully Connected ◽  
Genome Atlas

Background: It is found that the prognosis of gliomas of the same grade has large differences among World Health Organization(WHO) grade II and III in clinical observation. Therefore, a better understanding of the genetics and molecular mechanisms underlying WHO grade II and III gliomas is required, with the aim of developing a classification scheme at the molecular level rather than the conventional pathological morphology level. Method: We performed survival analysis combined with machine learning methods of Least Absolute Shrinkage and Selection Operator using expression datasets downloaded from the Chinese Glioma Genome Atlas as well as The Cancer Genome Atlas. Risk scores were calculated by the product of expression level of overall survival-related genes and their multivariate Cox proportional hazards regression coefficients. WHO grade II and III gliomas were categorized into the low-risk subgroup, medium-risk subgroup, and high-risk subgroup. We used the 16 prognostic-related genes as input features to build a classification model based on prognosis using a fully connected neural network. Gene function annotations were also performed. Results: The 16 genes (AKNAD1, C7orf13, CDK20, CHRFAM7A, CHRNA1, EFNB1, GAS1, HIST2H2BE, KCNK3, KLHL4, LRRK2, NXPH3, PIGZ, SAMD5, ERINC2, and SIX6) related to the glioma prognosis were screened. The 16 selected genes were associated with the development of gliomas and carcinogenesis. The accuracy of an external validation data set of the fully connected neural network model from the two cohorts reached 95.5%. Our method has good potential capability in classifying WHO grade II and III gliomas into low-risk, medium-risk, and high-risk subgroups. The subgroups showed significant (P<0.01) differences in overall survival. Conclusion: This resulted in the identification of 16 genes that were related to the prognosis of gliomas. Here we developed a computational method to discriminate WHO grade II and III gliomas into three subgroups with distinct prognoses. The gene expression-based method provides a reliable alternative to determine the prognosis of gliomas.

Phase II study with the combination etoposide, doxorubicin, and cisplatin in advanced measurable gastric cancer.

1989 ◽  
Vol 7 (9) ◽  
pp. 1310-1317 ◽  
Author(s):  
P Preusser ◽  
H Wilke ◽  
W Achterrath ◽  
U Fink ◽  
L Lenaz ◽  
...  
Keyword(s):  
Survival Time ◽  
Median Survival ◽  
Phase Ii ◽  
Metastatic Disease ◽  
Median Survival Time ◽  
Response Rate ◽  
Response Duration ◽  
World Health ◽  
Who Grade ◽  
Median Response

In this phase II multicenter trial, 67 evaluable patients with advanced measurable gastric carcinoma were treated with a combination of etoposide, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), and cisplatin (EAP). The overall response rate was 64%, including 21% complete responses (CRs). In 55 patients with metastatic disease, 31 responses (51%) including eight CRs (15%) were achieved. Responses were seen in all metastatic sites, but the response rate was lower in patients with peritoneal carcinomatosis. In 12 patients with locoregional disease, six CRs and six partial responses (PRs) were observed. Eight CRs (three and five in patients with metastatic and locoregional disease, respectively) were pathologically confirmed. The overall median response duration was 7 months; it was 16 months for patients achieving CR (22 months for pathologically confirmed CR [pCR]), and 6 months for PR. The median survival time for all patients was 9 months, for the patients who achieved CR 17 months, for pCR 23 months, and for PR 9.5 months. Median survival time for all patients with metastatic disease was 8 months, and for locoregional disease 12.5 months. Six patients (9%) (four local, two metastatic disease) were alive at 2 years, and four patients are alive and disease free at 35+ to 56+ months. Main toxicities were leukopenia and thrombocytopenia, with 64% of patients developing grade 3 to 4 myelosuppression and 12% severe infections. Nonhematologic toxicities of World Health Organization (WHO) grade 4 were not observed.

Surgery for Diffuse WHO Grade II Gliomas: Volumetric Analysis of a Multicenter Retrospective Cohort From the German Study Group for Intraoperative Magnetic Resonance Imaging

Neurosurgery ◽  
2019 ◽  
Vol 86 (1) ◽  
pp. E64-E74 ◽  
Author(s):  
Moritz Scherer ◽  
Hajrulla Ahmeti ◽  
Constantin Roder ◽  
Florian Gessler ◽  
Christine Jungk ◽  
...  
Keyword(s):  
Regression Models ◽  
Cox Regression ◽  
Study Group ◽  
Incomplete Resection ◽  
Who Grade ◽  
German Study ◽  
Significant Survival ◽  
Idh Mutations ◽  
Grade Ii ◽  
Who Grade Ii Gliomas

Abstract BACKGROUND In diffuse WHO grade II gliomas (LGG), the extent of resection (EOR) required to achieve significant survival benefits remains elusive. OBJECTIVE To evaluate the association of residual volume (RV) and EOR with progression-free survival (PFS) or overall survival (OS) in LGG in a retrospective, multicenter series by the German study group of intraoperative MRI (GeSGIM). METHODS Consecutive cases were retrospectively assessed from 5 centers. Tumors were volumetrically quantified before and after surgery, and clinical data were analyzed, including IDH mutations and neurologic deficits. Kaplan–Meier estimates, accelerated failure time models (AFT), and multivariate Cox regression models were calculated to identify determinants of survival. RESULTS A total of 140 cases were analyzed. Gross total resection (GTR) was associated with significantly longer PFS compared to any incomplete resection (P = .009). A significant survival disadvantage was evident even for small (&gt;0-5 ml) residuals and increased for moderate (&gt;5-20 ml) and large remnants (&gt;20 ml) P = .001). Accordingly, PFS increased continuously for 20% incremental steps of EOR (P &lt; .001). AFT models supported the notion of a continuous association of RV and EOR with PFS. Multivariate Cox regression models confirmed RV (P = .01) and EOR (P = .005) as continuous prognosticators of PFS. Univariate analysis showed significant associations of RV and EOR with OS. CONCLUSION Our data support the hypothesis of a continuous relationship of RV and EOR with survival for LGG with superiority seen for GTR. Hence, GTR should be achieved whenever safely feasible, and resections should be maximized whenever tumor has to be left behind to spare function.

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