Long-term results of carmustine wafer implantation for newly diagnosed glioblastomas: a controlled propensity-matched analysis of a French multicenter cohort

Pallud, Johan; Audureau, Étienne; Noël, G.; Corns, Robert; Lechapt‐Zalcman, Emmanuèle; Duntze, J.; Pavlov, Vladislav; Guyotat, Jacques; Hieu, P. Dam; Reste, Pierre-Jean Le; Faillot, Thierry; Litré, Claude‐Fabien; Desse, Nicolas; Petit, Audrey; Emery, Évelyne; Voirin, Jimmy; Peltier, Johann; Caire, François; Vignes, Jean‐Rodolphe; Barat, Jean-Luc; Langlois, Olivier; Dezamis, Edouard; Párraga, Eduardo; Zanello, Marc; Nader, E.; Lefranc, Michel; Bauchet, Luc; Devaux, Bertrand; Menei, Philippe; Métellus, Philippe

doi:10.1093/neuonc/nov126

Cited by 63 publications

(53 citation statements)

References 33 publications

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“…As patients aged >65 years who were not treated with BCNU wafers had a numerically higher rate of complete resection at surgery for recurrent GBM (62.5 vs. 45.8%), yet a lower PFS2 than elderly patients with BCNU wafer implantation (7.6 vs. 9.2 months), we argue that the comparability of the groups may be flawed and that the positive effect of BCNU on survival may be underestimated in our study. The 1.6-month improvement in median survival after implantation of BCNU wafers for first recurrent GBM and the 1.3-month improvement in OS in the older BCNU group over the control older non-BCNU group are roughly comparable with the available data, which showed an improvement in OS of 2-2.4 months [10,20] . Curiously, comparing survival data between the younger and the older BCNU group, there was no significant difference in OS (19.0 vs. 17.2 months), which might be explained by the fact that only patients in good condition (Karnofsky performance score ≥ 70) underwent a second tumor resection with wafer implantation, independent of age.…”

Section: Discussionsupporting

confidence: 79%

Safety and Effectiveness of Bis-Chloroethylnitrosourea Wafer Chemotherapy in Elderly Patients with Recurrent Glioblastoma

Klein

Juratli²,

Radev³

et al. 2017

Oncology

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Objective: To assess the safety and effectiveness of bis-chloroethylnitrosourea (BCNU) wafers in elderly patients with recurrent glioblastoma (GBM). Methods: Patients with recurrent GBM operated on between 2007 and 2014 were divided into 3 groups: >65 years with BCNU wafer implantation, >65 years without BCNU wafer implantation, and ≤65 years with BCNU wafer implantation. We compared survival and complications. Results: A total of 79 patients were identified: 24 in the older BCNU group (median age 68.2 years, 33.3% with a methylated MGMT promoter), 16 in the older non-BCNU group (median age 68.6 years, 31.3% with a methylated MGMT promoter), and 39 in the younger BCNU group (median age 56.8 years). Survival after progression was 9.2 months in the elderly BCNU group and 7.6 months in the elderly non-BCNU group (p = 0.34); overall survival was 17.2 and 15.9 months, respectively (p = 0.35). We found a tendency toward a higher rate of seizures and pneumonia in the older BCNU group. Conclusion: BCNU wafer implantation after resection of recurrent GBM is a reasonably safe treatment in patients aged >65 years. Seizures and systemic infections may occur more frequently, but the trade-off is still favorable as survival may be influenced positively. Higher age should not be regarded as a contraindication for BCNU wafers.

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Section: Discussionsupporting

confidence: 79%

Safety and Effectiveness of Bis-Chloroethylnitrosourea Wafer Chemotherapy in Elderly Patients with Recurrent Glioblastoma

Klein

Juratli²,

Radev³

et al. 2017

Oncology

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“…However, the highly infiltrative nature of this tumor, as well as its aggressiveness, leads to systematic failure of current therapeutics. Despite few improvements resulting from the development of second-line treatments such as antiangiogenic agents, the overall prognosis remains dismal and the median survival is 15 to 18 months (2). Furthermore, the neurological dysfunctions induced by tumor progression strongly impair the quality of life of patients (3).…”

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confidence: 99%

Endoplasmic reticulum proteostasis in glioblastoma—From molecular mechanisms to therapeutic perspectives

et al. 2017

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“…Treatment modalities usually include maximal resection, radiotherapy, and chemotherapy with the common use of temozolomide as first-line treatment (Stupp et al, 2005). However, GBM remain incurable and median survival remains close to 18 months (Pallud et al, 2015). As most malignant and fast-growing tumors, GBM cells are exposed to high cellular stress levels due to inadequate blood supply, hypoxia, nutrient deprivation, as well as to immune reactions and to various therapeutic treatments.…”

Section: Er Stress In Primary Brain Cancersmentioning

confidence: 99%

Signaling the Unfolded Protein Response in primary brain cancers

et al. 2016

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The Unfolded Protein Response (UPR) is an adaptive cellular program used by eukaryotic cells to cope with protein misfolding stress in the Endoplasmic Reticulum (ER). During tumor development, cancer cells are facing intrinsic (oncogene activation) and extrinsic (limiting nutrient or oxygen supply; exposure to chemotherapies) challenges, with which they must cope to survive. Primary brain tumors are relatively rare but deadly and present a significant challenge in the determination of risk factors in the population. These tumors are inherently difficult to cure because of their protected location in the brain. As such surgery, radiation and chemotherapy options carry potentially lasting patient morbidity and incomplete tumor cure. Some of these tumors, such as glioblastoma, were reported to present features of ER stress and to depend on UPR activation to sustain growth, but to date there is no clear general representation of the ER stress status in primary brain tumors. In this review, we describe the key molecular mechanisms controlling the UPR and their implication in cancers. Then we extensively review the literature reporting the status of ER stress in various primary brain tumors and discuss the potential impact of such observation on patient stratification and on the possibility of developing appropriate targeted therapies using the UPR as therapeutic target.

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Long-term results of carmustine wafer implantation for newly diagnosed glioblastomas: a controlled propensity-matched analysis of a French multicenter cohort

Abstract: Carmustine wafer implantation during surgical resection followed by the standard chemoradiation protocol for newly diagnosed glioblastoma in adults resulted in a significant progression-free survival benefit.

Cited by 63 publications

References 33 publications

Safety and Effectiveness of Bis-Chloroethylnitrosourea Wafer Chemotherapy in Elderly Patients with Recurrent Glioblastoma

Safety and Effectiveness of Bis-Chloroethylnitrosourea Wafer Chemotherapy in Elderly Patients with Recurrent Glioblastoma

Endoplasmic reticulum proteostasis in glioblastoma—From molecular mechanisms to therapeutic perspectives

Signaling the Unfolded Protein Response in primary brain cancers

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