Re-irradiation for recurrent glioblastoma multiforme: a critical comparison of different concepts

Baehr, Andrea; Trog, Daniela; Oertel, Michael; Welsch, Sophie; Kröger, Kai; Grauer, Oliver; Haverkamp, Uwe; Eich, Hans Theodor

doi:10.1007/s00066-020-01585-0

Cited by 10 publications

(6 citation statements)

References 34 publications

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“…Regarding the full treatment scheme, total doses of 50-60 Gy are common in vivo. Thus, observable effects in our experiments following a single dose irradiation with 2 Gy that are significant but rather small could accumulate during fractionated treatment and therefore increase in a clinical relevant matter [70][71][72][73].…”

Section: Discussionmentioning

confidence: 84%

Dual mTOR/DNA-PK Inhibitor CC-115 Induces Cell Death in Melanoma Cells and Has Radiosensitizing Potential

Bürkel

Jost

Hecht

et al. 2020

IJMS

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CC-115 is a dual inhibitor of the mechanistic target of rapamycin (mTOR) kinase and the DNA-dependent protein kinase (DNA-PK) that is currently being studied in phase I/II clinical trials. DNA-PK is essential for the repair of DNA-double strand breaks (DSB). Radiotherapy is frequently used in the palliative treatment of metastatic melanoma patients and induces DSBs. Melanoma cell lines and healthy-donor skin fibroblast cell lines were treated with CC-115 and ionizing irradiation (IR). Apoptosis, necrosis, and cell cycle distribution were analyzed. Colony forming assays were conducted to study radiosensitizing effects. Immunofluorescence microscopy was performed to determine the activity of homologous recombination (HR). In most of the malign cell lines, an increasing concentration of CC-115 resulted in increased cell death. Furthermore, strong cytotoxic effects were only observed in malignant cell lines. Regarding clonogenicity, all cell lines displayed decreased survival fractions during combined inhibitor and IR treatment and supra-additive effects of the combination were observable in 5 out of 9 melanoma cell lines. CC-115 showed radiosensitizing potential in 7 out of 9 melanoma cell lines, but not in healthy skin fibroblasts. Based on our data CC-115 treatment could be a promising approach for patients with metastatic melanoma, particularly in the combination with radiotherapy.

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Section: Discussionmentioning

confidence: 84%

Dual mTOR/DNA-PK Inhibitor CC-115 Induces Cell Death in Melanoma Cells and Has Radiosensitizing Potential

Bürkel

Jost

Hecht

et al. 2020

IJMS

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“…The 3 RCTs [ 27 , 33 , 37 ] were of low RoB. Of the 28 non-randomised studies, 19 were of moderate RoB [ 18 , 25 , 28 , 29 , 31 , 32 , 34 , 35 , 38 , 40 , 43 , 45 , 48 – 54 ], and 9 were of serious RoB (and hence excluded from meta-analyses) [ 26 , 30 , 36 , 39 , 41 , 42 , 44 , 46 , 47 ].…”

Section: Resultsmentioning

confidence: 99%

“…Combination therapy improved PFS (4 studies [ 31 , 37 , 40 , 49 ], 236 participants; HR 0.52 (95% CI 0.38–0.72), p < 0.0001, I2 = 0%; low certainty) and OS (7 studies [ 31 , 37 , 38 , 40 , 43 , 49 , 50 ], 471 participants; HR 0.69 (95% CI 0.52–0.93), p = 0.02, I2 = 18%; low certainty) (Fig. 3 ).…”

Section: Resultsmentioning

confidence: 99%

Reirradiation versus systemic therapy versus combination therapy for recurrent high-grade glioma: a systematic review and meta-analysis of survival and toxicity

Marwah,

Xing,

Squire

et al. 2023

J Neurooncol

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Purpose This review compares reirradiation (reRT), systemic therapy and combination therapy (reRT & systemic therapy) with regards to overall survival (OS), progression-free survival (PFS), adverse effects (AEs) and quality of life (QoL) in patients with recurrent high-grade glioma (rHGG). Methods A search was performed on PubMed, Scopus, Embase and CENTRAL. Studies reporting OS, PFS, AEs and/or QoL and encompassing the following groups were included; reirradiation vs systemic therapy, combination therapy vs systemic therapy, combination therapy vs reRT, and bevacizumab-based combination therapy vs reRT with/without non-bevacizumab-based systemic therapy. Meta-analyses were performed utilising a random effects model. Certainty of evidence was assessed using GRADE. Results Thirty-one studies (three randomised, twenty-eight non-randomised) comprising 2084 participants were included. In the combination therapy vs systemic therapy group, combination therapy improved PFS (HR 0.57 (95% CI 0.41–0.79); low certainty) and OS (HR 0.73 (95% CI 0.56–0.95); low certainty) and there was no difference in grade 3 + AEs (RR 1.03 (95% CI 0.57–1.86); very low certainty). In the combination therapy vs reRT group, combination therapy improved PFS (HR 0.52 (95% CI 0.38–0.72); low certainty) and OS (HR 0.69 (95% CI 0.52–0.93); low certainty). In the bevacizumab-based combination therapy vs reRT with/without non-bevacizumab-based systemic therapy group, adding bevacizumab improved PFS (HR 0.46 (95% CI 0.27–0.77); low certainty) and OS (HR 0.42 (95% CI 0.24–0.72; low certainty) and reduced radionecrosis (RR 0.17 (95% CI 0.06–0.48); low certainty). Conclusions Combination therapy may improve OS and PFS with acceptable toxicities in patients with rHGG compared to reRT or systemic therapy alone. Particularly, combining bevacizumab with reRT prophylactically reduces radionecrosis. Registration: CRD42022291741.

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“…In addition, there may be vascular reactions, including thrombosis. GBM is often characterized by invasive growth, frequently affecting multiple lobes (26).…”

Section: Discussionmentioning

confidence: 99%

“…In addition, there may be vascular reactions, including thrombosis. GBM is often characterized by invasive growth, frequently affecting multiple lobes ( 26 ). The tumor invades through the brain, often along the corpus callosum to the contralateral frontal lobe.…”

Section: Discussionmentioning

confidence: 99%

Effects of postoperative radiotherapy and docetaxel and PD-1 inhibitors on the survival and safety of glioblastoma patients: a systematic review and meta-analysis

Yang¹,

Wang²,

Liu³

et al. 2022

Ann Transl Med

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Background: The present standard treatment rarely allows the complete removal of glioblastoma (GBM).So postoperative treatments are provided to prevent or delay tumor recurrence. The overall survival (OS) rate and safety of postoperative chemotherapy alone, or combined with radiotherapy (RT), or programmed cell death-1 (PD-1) inhibitor in GBM is still unclear. The present goal was to explore postoperative treatment's effect on the survival and safety of patients with GBM.Methods: We searched the mainstream online databases for clinical studies of RT and chemotherapy and PD-1 inhibitors in the treatment of GBM published up to May 2020. The patients in the experimental group accepted an anti-PD-1 drug alone and RT + chemotherapy, whereas the controlled patients were treated with docetaxel alone. The literature qualities were assessed using Cochrane Risk of Bias 2.0, and studies were assigned. The meta-analysis was conducted by RevMan 5.4 software.Results: A total of 927 articles were identified through the online database search. The articles unable to meet the inclusion criteria were excluded leaving 6 studies for inclusion in the study. Compared with docetaxel-based chemotherapy for GBM, combined RT chemotherapy and PD-1 inhibitor therapy had better OS [mean difference (MD), −1.75; 95% confidence interval (CI): −2.99 to −0.51; P=0.006] and progression-free survival (PFS) and a lower incidence of adverse reactions (MD, −7.03; 95% CI: −7.64 to −6.42; P<0.00001) above grade III.Conclusions: Postoperative combination of RT and chemotherapy and PD-1 inhibitors had some advantages over docetaxel in terms of effectiveness. More clinical trials are needed to confirm effectiveness.

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Re-irradiation for recurrent glioblastoma multiforme: a critical comparison of different concepts

Cited by 10 publications

References 34 publications

Dual mTOR/DNA-PK Inhibitor CC-115 Induces Cell Death in Melanoma Cells and Has Radiosensitizing Potential

Dual mTOR/DNA-PK Inhibitor CC-115 Induces Cell Death in Melanoma Cells and Has Radiosensitizing Potential

Reirradiation versus systemic therapy versus combination therapy for recurrent high-grade glioma: a systematic review and meta-analysis of survival and toxicity

Effects of postoperative radiotherapy and docetaxel and PD-1 inhibitors on the survival and safety of glioblastoma patients: a systematic review and meta-analysis

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