Single-Arm Phase II Study of Conformal Radiation Therapy and Temozolomide plus Fractionated Stereotactic Conformal Boost in High-Grade Gliomas

Boccadoro, Mario; Apicella, G.; Manfrida, S.; Mangiola, Annunziato; Fiorentino, Alba; Azario, L.; D’Agostino, Giuseppe; Frascino, V.; Dinapoli, N.; Mantini, Giovanna; Albanese, Alessio; Bonis, Pasquale De; Chiesa, S.; Valentini, Vincenzo; Anile, Carmelo; Cellini, Numa

doi:10.1007/s00066-010-2101-x

Cited by 31 publications

(17 citation statements)

References 38 publications

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“…In a recent phase II study that applied a fractionated stereotactic boost up to 69.4 Gy (fraction dose 2.5 Gy) after 50.4-59.4 Gy standard radiotherapy with temozolomide, the mean OS and PFS of 28 and 10 months were reported [1]. The favorable results of this first prospective trial using a stereotactic boost with simultaneous temozolomide suggest the important role of combined treatment.…”

Section: Discussionmentioning

confidence: 86%

Integrated boost IMRT with FET-PET-adapted local dose escalation in glioblastomas

et al. 2012

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Section: Discussionmentioning

confidence: 86%

Integrated boost IMRT with FET-PET-adapted local dose escalation in glioblastomas

et al. 2012

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“…Despite of improvements in chemo-and radiotherapy, long-term prognosis is still poor for many patients with newly diagnosed or recurrent cancer diseases [3,28,36,38].…”

Section: Introductionmentioning

confidence: 99%

Small interfering RNA targeting HIF-1α reduces hypoxia-dependent transcription and radiosensitizes hypoxic HT 1080 human fibrosarcoma cells in vitro

et al. 2011

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Background: Hypoxia inducible factor-1 has been identified as a potential target to overcome hypoxia-induced radioresistance The aim of the present study was to investigate whether selective HIF-1 inhibition via small interfering RNA (siRNA) targeting hypoxia-inducible factor 1α (HIF-1α) affects hypoxia-induced radioresistance in HT 1080 human fibrosarcoma cells. Material and Methods: HIF-1α expression in HT 1080 human fibrosarcoma cells in vitro was silenced using HIF-1α siRNA sequence primers. Quantitative real-time polymerase chain reaction assay was performed to quantify the mRNA expression of HIF-1α. HIF-1α protein levels were studied by Western blotting at 20% (air) or after 12 hours at 0.1% O 2 (hypoxia). Cells were assayed for clonogenic survival after irradiation with 2, 5, or 10 Gy, under normoxic or hypoxic conditions in the presence of HIF-1α-targeted or control siRNA sequences. A modified oxygen enhancement ratio (OER´) was calculated as the ratio of the doses to achieve the same survival at 0.1% O 2 as at ambient oxygen tensions. OER´ was obtained at cell survival levels of 50%, 37%, and 10%. Results: HIF-1α-targeted siRNA enhanced radiation treatment efficacy under severely hypoxic conditions compared to tumor cells treated with scrambled control siRNA. OER was reduced on all survival levels after treatment with HIF-1α-targeted siRNA, suggesting that inhibition of HIF-1 activation by using HIF-1α-targeted siRNA increases radiosensitivity of hypoxic tumor cells in vitro. Conclusion: Inhibition of HIF-1 activation by using HIF-1α-targeted siRNA clearly acts synergistically with radiotherapy and increase radiosensitivity of hypoxic cells in vitro.Hintergrund und Ziel: Hypoxia-inducible Factor-1 (HIF-1) wurde als potentielles therapeutisches Target identifiziert. Ziel der Arbeit war es, zu untersuchen, ob die selektive HIF-1-Inhibition mittels Small Interfering RNA (siRNA) gegen HIF-1α die Strahlensensibilität von hypoxischen HT-1080-Zellen beeinflussen kann. Material und Methodik: Die HIF-1α-Expression in humanen HT-1080-Fibrosarkomzellen wurde mittels RNA-Interferenz nach Transfektion der Zellen mit siRNA unter hypoxischen Bedingungen (0,1% O 2 , 12 h), bzw. Normoxie (20% O 2 ) in vitro inhibiert. Die HIF-1α-Genexpression wurde mit quantitativer Realtime-Polymerasekettenreaktion (qRT-PCR), das HIF-1α-Protein mittels Western Blot quantifiziert. Das klonogene Überleben wurde nach Bestrahlung unter Hypoxie und Normoxie bestimmt und daraus eine Oxygen Enhancement Ratio (OER´) bei den Überlebensniveaus 50%, 37% and 10% berechnet. Resultate: HIF-1α-siRNA erhöht die Strahlensensibilität unter hypoxischen Bedingen, verglichen mit HT-1080-Zellen, die mit Kontroll-siRNA behandelt wurden. Die OER` war bei allen Überlebensniveaus reduziert. Schlussfolgerung: Eine selektive Inhibition der HIF-1-Aktivierung durch HIF-1α-siRNA wirkt synergistisch mit einer Bestrahlung und erhöht die Strahlensensitivität hypoxischer Tumorzellen in vitro.Schlüsselwörter: Hypoxia-inducible factor-1α · Small Interfering RNA · Hypoxie ·...

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“…The aim of this analysis was to evaluate compliance, toxicity, and outcomes in GBM patients over 65 years enrolled in 4 prospective phase II trials with radiochemotherapy. 19,20,[22][23][24] …”

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confidence: 99%

Can Elderly Patients With Newly Diagnosed Glioblastoma be Enrolled in Radiochemotherapy Trials?

Fiorentino

Boccadoro²,

Bonis

et al. 2015

American Journal of Clinical Oncology

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Single-Arm Phase II Study of Conformal Radiation Therapy and Temozolomide plus Fractionated Stereotactic Conformal Boost in High-Grade Gliomas

Abstract: FSCRT boost plus temozolomide is well tolerated and seems to increase survival compared to the standard treatment in patients with HGG.

Cited by 31 publications

References 38 publications

Integrated boost IMRT with FET-PET-adapted local dose escalation in glioblastomas

Integrated boost IMRT with FET-PET-adapted local dose escalation in glioblastomas

Small interfering RNA targeting HIF-1α reduces hypoxia-dependent transcription and radiosensitizes hypoxic HT 1080 human fibrosarcoma cells in vitro

Can Elderly Patients With Newly Diagnosed Glioblastoma be Enrolled in Radiochemotherapy Trials?

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