ORCID Profile
0000-0002-0668-9529
Current Organisation
Erasmus MC
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Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22487442.V1
Abstract: Supplementary Data from Temozolomide and Radiotherapy versus Radiotherapy Alone in Patients with Glioblastoma, i IDH /i -wildtype: i Post Hoc /i Analysis of the EORTC Randomized Phase III CATNON Trial
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22487439.V1
Abstract: Supplementary Figure from Temozolomide and Radiotherapy versus Radiotherapy Alone in Patients with Glioblastoma, i IDH /i -wildtype: i Post Hoc /i Analysis of the EORTC Randomized Phase III CATNON Trial
Publisher: American Association for Cancer Research (AACR)
Date: 11-03-2022
DOI: 10.1158/1078-0432.CCR-21-4283
Abstract: In a post hoc analysis of the CATNON trial (NCT00626990), we explored whether adding temozolomide to radiotherapy improves outcome in patients with IDH1/2 wildtype (wt) anaplastic astrocytomas with molecular features of glioblastoma [redesignated as glioblastoma, isocitrate dehydrogenase–wildtype (IDH-wt) in the 2021 World Health Organization (WHO) classification of central nervous system tumors]. From the randomized phase III CATNON study examining the addition of adjuvant and concurrent temozolomide to radiotherapy in anaplastic astrocytomas, we selected a subgroup of IDH1/2wt and H3F3Awt tumors with presence of TERT promoter mutations and/or EGFR lifications and/or combined gain of chromosome 7 and loss of chromosome 10. Molecular abnormalities including MGMT promoter methylation status were determined by next-generation sequencing, DNA methylation profiling, and SNaPshot analysis. Of the 751 patients entered in the CATNON study, 670 had fully molecularly characterized tumors. A total of 159 of these tumors met the WHO 2021 molecular criteria for glioblastoma, IDH-wt. Of these patients, 47 received radiotherapy only and 112 received a combination of radiotherapy and temozolomide. There was no added effect of temozolomide on either overall survival [HR, 1.19 95% confidence interval (CI), 0.82–1.71] or progression-free survival (HR, 0.87 95% CI, 0.61–1.24). MGMT promoter methylation was prognostic for overall survival, but was not predictive for outcome to temozolomide treatment either with respect to overall survival or progression-free survival. In this cohort of patients with glioblastoma, IDH-wt temozolomide treatment did not add benefit beyond that observed from radiotherapy, regardless of MGMT promoter status. These findings require a new well-powered prospective clinical study to explore the efficacy of temozolomide treatment in this patient population.
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.C.6532518.V1
Abstract: AbstractPurpose: In a i ost hoc /i analysis of the CATNON trial (NCT00626990), we explored whether adding temozolomide to radiotherapy improves outcome in patients with i IDH1/2 /i wildtype (wt) anaplastic astrocytomas with molecular features of glioblastoma [redesignated as glioblastoma, isocitrate dehydrogenase–wildtype ( i IDH /i -wt) in the 2021 World Health Organization (WHO) classification of central nervous system tumors]. Patients and Methods: From the randomized phase III CATNON study examining the addition of adjuvant and concurrent temozolomide to radiotherapy in anaplastic astrocytomas, we selected a subgroup of i IDH1/2 /i wt and i H3F3A /i wt tumors with presence of i TERT /i promoter mutations and/or i EGFR /i lifications and/or combined gain of chromosome 7 and loss of chromosome 10. Molecular abnormalities including i MGMT /i promoter methylation status were determined by next-generation sequencing, DNA methylation profiling, and SNaPshot analysis. Results: Of the 751 patients entered in the CATNON study, 670 had fully molecularly characterized tumors. A total of 159 of these tumors met the WHO 2021 molecular criteria for glioblastoma, i IDH /i -wt. Of these patients, 47 received radiotherapy only and 112 received a combination of radiotherapy and temozolomide. There was no added effect of temozolomide on either overall survival [HR, 1.19 95% confidence interval (CI), 0.82–1.71] or progression-free survival (HR, 0.87 95% CI, 0.61–1.24). i MGMT /i promoter methylation was prognostic for overall survival, but was not predictive for outcome to temozolomide treatment either with respect to overall survival or progression-free survival. Conclusions: In this cohort of patients with glioblastoma, i IDH /i -wt temozolomide treatment did not add benefit beyond that observed from radiotherapy, regardless of i MGMT /i promoter status. These findings require a new well-powered prospective clinical study to explore the efficacy of temozolomide treatment in this patient population. /
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22487439
Abstract: Supplementary Figure from Temozolomide and Radiotherapy versus Radiotherapy Alone in Patients with Glioblastoma, i IDH /i -wildtype: i Post Hoc /i Analysis of the EORTC Randomized Phase III CATNON Trial
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22487430.V1
Abstract: Supplementary Figure from Temozolomide and Radiotherapy versus Radiotherapy Alone in Patients with Glioblastoma, i IDH /i -wildtype: i Post Hoc /i Analysis of the EORTC Randomized Phase III CATNON Trial
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22487427
Abstract: Supplementary Figure from Temozolomide and Radiotherapy versus Radiotherapy Alone in Patients with Glioblastoma, i IDH /i -wildtype: i Post Hoc /i Analysis of the EORTC Randomized Phase III CATNON Trial
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22487424
Abstract: Supplementary Figure from Temozolomide and Radiotherapy versus Radiotherapy Alone in Patients with Glioblastoma, i IDH /i -wildtype: i Post Hoc /i Analysis of the EORTC Randomized Phase III CATNON Trial
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22487433.V1
Abstract: Supplementary Figure from Temozolomide and Radiotherapy versus Radiotherapy Alone in Patients with Glioblastoma, i IDH /i -wildtype: i Post Hoc /i Analysis of the EORTC Randomized Phase III CATNON Trial
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22487433
Abstract: Supplementary Figure from Temozolomide and Radiotherapy versus Radiotherapy Alone in Patients with Glioblastoma, i IDH /i -wildtype: i Post Hoc /i Analysis of the EORTC Randomized Phase III CATNON Trial
Publisher: Springer Science and Business Media LLC
Date: 19-03-2021
DOI: 10.1007/S00401-021-02291-6
Abstract: Somatic mutations in the isocitrate dehydrogenase genes IDH1 and IDH2 occur at high frequency in several tumour types. Even though these mutations are confined to distinct hotspots, we show that gliomas are the only tumour type with an exceptionally high percentage of IDH1 R132H mutations. Patients harbouring IDH1 R132H mutated tumours have lower levels of genome-wide DNA-methylation, and an associated increased gene expression, compared to tumours with other IDH1/2 mutations (“non-R132H IDH1/2 mutations”). This reduced methylation is seen in multiple tumour types and thus appears independent of the site of origin. For 1p/19q non-codeleted glioma (astrocytoma) patients, we show that this difference is clinically relevant: in s les of the randomised phase III CATNON trial, patients harbouring tumours with IDH mutations other than IDH1 R132H have a better outcome (hazard ratio 0.41, 95% CI [0.24, 0.71], p = 0.0013). Such non-R132H IDH1/2-mutated tumours also had a significantly lower proportion of tumours assigned to prognostically poor DNA-methylation classes ( p 0.001). IDH mutation-type was independent in a multivariable model containing known clinical and molecular prognostic factors. To confirm these observations, we validated the prognostic effect of IDH mutation type on a large independent dataset. The observation that non-R132H IDH1/2-mutated astrocytomas have a more favourable prognosis than their IDH1 R132H mutated counterpart indicates that not all IDH-mutations are identical. This difference is clinically relevant and should be taken into account for patient prognostication.
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22487421
Abstract: Supplementary Figure from Temozolomide and Radiotherapy versus Radiotherapy Alone in Patients with Glioblastoma, i IDH /i -wildtype: i Post Hoc /i Analysis of the EORTC Randomized Phase III CATNON Trial
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22487442
Abstract: Supplementary Data from Temozolomide and Radiotherapy versus Radiotherapy Alone in Patients with Glioblastoma, i IDH /i -wildtype: i Post Hoc /i Analysis of the EORTC Randomized Phase III CATNON Trial
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22487430
Abstract: Supplementary Figure from Temozolomide and Radiotherapy versus Radiotherapy Alone in Patients with Glioblastoma, i IDH /i -wildtype: i Post Hoc /i Analysis of the EORTC Randomized Phase III CATNON Trial
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22487424.V1
Abstract: Supplementary Figure from Temozolomide and Radiotherapy versus Radiotherapy Alone in Patients with Glioblastoma, i IDH /i -wildtype: i Post Hoc /i Analysis of the EORTC Randomized Phase III CATNON Trial
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22487427.V1
Abstract: Supplementary Figure from Temozolomide and Radiotherapy versus Radiotherapy Alone in Patients with Glioblastoma, i IDH /i -wildtype: i Post Hoc /i Analysis of the EORTC Randomized Phase III CATNON Trial
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.C.6532518
Abstract: AbstractPurpose: In a i ost hoc /i analysis of the CATNON trial (NCT00626990), we explored whether adding temozolomide to radiotherapy improves outcome in patients with i IDH1/2 /i wildtype (wt) anaplastic astrocytomas with molecular features of glioblastoma [redesignated as glioblastoma, isocitrate dehydrogenase–wildtype ( i IDH /i -wt) in the 2021 World Health Organization (WHO) classification of central nervous system tumors]. Patients and Methods: From the randomized phase III CATNON study examining the addition of adjuvant and concurrent temozolomide to radiotherapy in anaplastic astrocytomas, we selected a subgroup of i IDH1/2 /i wt and i H3F3A /i wt tumors with presence of i TERT /i promoter mutations and/or i EGFR /i lifications and/or combined gain of chromosome 7 and loss of chromosome 10. Molecular abnormalities including i MGMT /i promoter methylation status were determined by next-generation sequencing, DNA methylation profiling, and SNaPshot analysis. Results: Of the 751 patients entered in the CATNON study, 670 had fully molecularly characterized tumors. A total of 159 of these tumors met the WHO 2021 molecular criteria for glioblastoma, i IDH /i -wt. Of these patients, 47 received radiotherapy only and 112 received a combination of radiotherapy and temozolomide. There was no added effect of temozolomide on either overall survival [HR, 1.19 95% confidence interval (CI), 0.82–1.71] or progression-free survival (HR, 0.87 95% CI, 0.61–1.24). i MGMT /i promoter methylation was prognostic for overall survival, but was not predictive for outcome to temozolomide treatment either with respect to overall survival or progression-free survival. Conclusions: In this cohort of patients with glioblastoma, i IDH /i -wt temozolomide treatment did not add benefit beyond that observed from radiotherapy, regardless of i MGMT /i promoter status. These findings require a new well-powered prospective clinical study to explore the efficacy of temozolomide treatment in this patient population. /
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22487421.V1
Abstract: Supplementary Figure from Temozolomide and Radiotherapy versus Radiotherapy Alone in Patients with Glioblastoma, i IDH /i -wildtype: i Post Hoc /i Analysis of the EORTC Randomized Phase III CATNON Trial
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Pim French.