Impact on survival of early tumor growth between surgery and radiotherapy in patients with de novo glioblastoma

Barros, Amaury De; Attal, Justine; Roques, Marjorie; Nicolau, Julien; Sol, Jean‐Christophe; Cohen-Jonathan-Moyal, Elizabeth; Roux, Franck‐Emmanuel

doi:10.1007/s11060-019-03120-3

Cited by 17 publications

(10 citation statements)

References 45 publications

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“…An overly lengthy delay would be deleterious, or without influence and even beneficial, depending on studies. [33][34][35][36][37] When focusing on molecular aspects, patients with GBM with dual mechanisms of MGMT inactivation had longer OS (P = .002) and PFS (P = .03). In the hypermethylated group (Group 1 + 2; n = 68), patients with loss of chromosome 10q had longer OS from 8-month follow-up than patients without 10q loss (P = .009).…”

Section: Discussionmentioning

confidence: 99%

Dual MGMT inactivation by promoter hypermethylation and loss of the long arm of chromosome 10 in glioblastoma

et al. 2020

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Background Epigenetic inactivation of O6‐methylguanine‐methyltransferase (MGMT) gene by methylation of its promoter is predictive of Temozolomid (TMZ) response in glioblastoma (GBM). MGMT is located on chromosome 10q26 and the loss of chromosome 10q is observed in 70% of GBMs. In this study, we assessed the hypothesis that the dual inactivation of MGMT, by hypermethylation of MGMT promoter and by loss the long arm of chromosome 10 (10q), may confer greater sensitivity to TMZ. Methods A total of 149 tumor samples from patients diagnosed with GBM based on the WHO 2016 classification were included in this retrospective study between November 2016 and December 2018. Methylation status of MGMT promoter was evaluated by pyrosequencing and status of chromosome 10q was assessed by array comparative genomic hybridization. Results Glioblastoma patients with chromosome 10q loss associated with hypermethylation of MGMT promoter had significantly longer overall survival (OS) (P = .0024) and progression‐free survival (PFS) (P = .031). Indeed, median OS of patients with dual inactivation of MGMT was 21.5 months compared to 12 months and 8.1 months for groups with single MGMT inactivation by hypermethylation and by 10q loss, respectively. The group with no MGMT inactivation had 9.5 months OS. Moreover, all long‐term survivors with persistent response to TMZ treatment (OS ≥ 30 months) displayed dual inactivation of MGMT. Conclusions Our data suggest that the molecular subgroup characterized by the dual inactivation of MGMT receives greater benefit from TMZ treatment. The results of our study may be of immediate clinical interest since chromosome 10q status and methylation of MGMT promoter are commonly determined in routine practice.

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Section: Discussionmentioning

confidence: 99%

Dual MGMT inactivation by promoter hypermethylation and loss of the long arm of chromosome 10 in glioblastoma

et al. 2020

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“…Late initiation of RT could lead to reduced radiosensitivity. De Barros et al compared preoperative, immediate postoperative and preradiotherapy MRI images of 75 patients, among which 72% had an early tumor regrowth ( 14 ). Patients with no early tumor growth had a better OS than those with early tumor regrowth by 6.9 months.…”

Section: Discussionmentioning

confidence: 99%

“…From the radiobiological point of view, the efficacy of RT decreases as the tumor size increases, especially for highly proliferative tumors with rapid growth such as GBM (9)(10)(11)(12)(13). It is suggested that longer delay between surgery and postoperative treatment is a detrimental factor for early tumor regrowth and associated with poorer prognosis (14)(15)(16).…”

Section: Original Articlementioning

confidence: 99%

Survival impact of delaying postoperative chemoradiotherapy in newly-diagnosed glioblastoma patients

Zhang¹,

Xu²,

Ni³

et al. 2020

Transl Cancer Res TCR

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Background: Maximal safe resection followed by adjuvant chemoradiotherapy (CRT) with temozolomide (TMZ) is the standard treatment for newly diagnosed glioblastoma multiforme (GBM) patients. Time of initiation of postoperative adjuvant therapy has been demonstrated to impact on prognosis. For GBM patients, the optimal interval between definitive surgery and CRT is still uncertain. Current study aims to find whether the delayed initiation of CRT after surgery has a negative impact on patients' outcome.

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“…In the time between surgery and radiotherapy, remnant tumour cells remain untreated causing rapid early progression (REP), which is associated with a shorter survival [5][6][7][8][9][10][11][12][13]. This highlights the limitations of the current glioblastoma treatment pathway and the desperate need for new strategies.…”

Section: Introductionmentioning

confidence: 99%

Early Therapeutic Interventions for Newly Diagnosed Glioblastoma: Rationale and Review of the Literature

et al. 2022

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Purpose of Review Glioblastoma is the commonest primary brain cancer in adults whose outcomes are amongst the worst of any cancer. The current treatment pathway comprises surgery and postoperative chemoradiotherapy though unresectable diffusely infiltrative tumour cells remain untreated for several weeks post-diagnosis. Intratumoural heterogeneity combined with increased hypoxia in the postoperative tumour microenvironment potentially decreases the efficacy of adjuvant interventions and fails to prevent early postoperative regrowth, called rapid early progression (REP). In this review, we discuss the clinical implications and biological foundations of post-surgery REP. Subsequently, clinical interventions potentially targeting this phenomenon are reviewed systematically. Recent Findings Early interventions include early systemic chemotherapy, neoadjuvant immunotherapy, local therapies delivered during surgery (including Gliadel wafers, nanoparticles and stem cell therapy) and several radiotherapy techniques. We critically appraise and compare these strategies in terms of their efficacy, toxicity, challenges and potential to prolong survival. Finally, we discuss the most promising strategies that could benefit future glioblastoma patients. Summary There is biological rationale to suggest that early interventions could improve the outcome of glioblastoma patients and they should be investigated in future trials.

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Impact on survival of early tumor growth between surgery and radiotherapy in patients with de novo glioblastoma

Cited by 17 publications

References 45 publications

Dual MGMT inactivation by promoter hypermethylation and loss of the long arm of chromosome 10 in glioblastoma

Dual MGMT inactivation by promoter hypermethylation and loss of the long arm of chromosome 10 in glioblastoma

Survival impact of delaying postoperative chemoradiotherapy in newly-diagnosed glioblastoma patients

Early Therapeutic Interventions for Newly Diagnosed Glioblastoma: Rationale and Review of the Literature

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