Phase 2 Trial of Hypofractionated High-Dose Intensity Modulated Radiation Therapy With Concurrent and Adjuvant Temozolomide for Newly Diagnosed Glioblastoma

Iuchi, Toshihiko; Hatano, Kazuo; Kodama, Takashi; Sakaida, Tsukasa; Yokoi, Sana; Kawasaki, Koichiro; Hasegawa, Yuzo; Hara, Ryusuke

doi:10.1016/j.ijrobp.2013.12.011

Cited by 85 publications

(57 citation statements)

References 30 publications

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“…Patients with high-grade gliomas who received high-dose radiation therapy had a higher rate of CSFD than those who had received lower doses [27]. The most frequent pattern of recurrence for patients who had received hypofractionated, high-dose, intensity modulated radiation therapy (IMRT) was dissemination (45.6%) [28]. A higher rate of CSFD at recurrence in the high-dose groups seems somewhat paradoxical.…”

Section: Discussionmentioning

confidence: 99%

Cerebrospinal fluid dissemination of high-grade gliomas following boron neutron capture therapy occurs more frequently in the small cell subtype of IDH1R132H mutation-negative glioblastoma

et al. 2017

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We have used boron neutron capture therapy (BNCT) to treat patients in Japan with newly diagnosed or recurrent high-grade gliomas and have observed a significant increase in median survival time following BNCT. Although cerebrospinal fluid dissemination (CSFD) is not usually seen with the current standard therapy of patients with glioblastoma (GBM), here we report that subarachnoid or intraventricular CSFD was the most frequent cause of death for a cohort of our patients with high-grade gliomas who had been treated with BNCT. The study population consisted of 87 patients with supratentorial high-grade gliomas; 41 had newly diagnosed tumors and 46 had recurrent tumors. Thirty of 87 patients who were treated between January 2002 and July 2013 developed CSFD. Tumor histology before BNCT and immunohistochemical staining for two molecular markers, Ki-67 and IDH1R132H, were evaluated for 20 of the 30 patients for whom pathology slides were available. Fluorescence in situ hybridization (FISH) was performed on 3 IDH1R132H-positive and 1 control IDH1R132H-negative tumors in order to determine chromosome 1p and 19q status. Histopathologic evaluation revealed that 10 of the 20 patients’ tumors were IDH1R132H-negative small cell GBMs. The remaining patients had tumors consisting of other IDH1R132H-negative GBM variants, an IDH1R132H-positive GBM and two anaplastic oligodendrogliomas. Ki-67 immunopositivity ranged from 2 to 75%. In summary, IDH1R132H-negative GBMs, especially small cell GBMs, accounted for a disproportionately large number of patients who had CSF dissemination. This suggests that these tumor types had an increased propensity to disseminate via the CSF following BNCT and that these patients are at high risk for this clinically serious event.

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Section: Discussionmentioning

confidence: 99%

Cerebrospinal fluid dissemination of high-grade gliomas following boron neutron capture therapy occurs more frequently in the small cell subtype of IDH1R132H mutation-negative glioblastoma

et al. 2017

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“…No acute hematological toxicities were observed during treatment; however, 33% of patients experienced neutropenia or thrombocytopenia requiring cycle delays as well as inability to achieve full dose adjuvant TMZ. In a Japanese phase II trial with extremely fractionated dose-painting radiotherapy (4/5/8.5 Gy/fr., total dose 32/40/68 Gy) with TMZ, early hematological tolerance was good [34]. Hematological toxicities occurred during adjuvant treatment with chemotherapy or antiepileptic drugs: grade 3 or 4 anemia in 8 (17.8%), grade 3 or 4 lymphopenia in 21 (45.7%), grade 3 or 4 neutropenia in 3 (6.5%), and grade 3 thrombocytopenia in 1 (2.2%) patient.…”

Section: Clinical Studiesmentioning

confidence: 99%

Hematological Toxicity of Hypofractionated Radiotherapy: A Review of the Available Evidence

Spałek

2018

Oncol Res Treat

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Hypofractionated radiotherapy is commonly used to treat many cancers. The number of indications for this fractionation schedule is increasing. Knowledge of the potential hematological toxicity arising from hypofractionated irradiation is vital since many patients receive further systemic treatment. This review analyzes the available evidence on the effect of hypofractionated radiotherapy on hematological toxicity. However, radiobiological data on bone marrow responses to high doses of radiation per fraction are sparse. Additional biological effects may also play an significant role in bone marrow function and recovery after hypofractionated radiotherapy. Clinical data show a good early hematological tolerance of hypofractionated radiotherapy (both large field and for stereotactic body radiotherapy). There are, however, no data available that assess late hematological toxicity. Evidence on acute hematological toxicity after hypofractionated radiotherapy does not suggest any significant impact of altered fractionation on early treatment tolerance, although further research to assess this problem is needed. The effect of hypofractionation on late hematological tolerance is unknown because the data are still lacking.

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“…A prior phase I trial examining hypofractionated RT to a dose of 52.5 Gy in 15 fractions combined with peri-RT TMZ found no instances of irreversible grade 3 or higher acute toxicity [207]. In a phase II trial of hypofractionated high-dose IMRT with concurrent and adjuvant TMZ, necrosis was noted in nearly half of the treated patients in the high-dose field and also in the subventricular zone, which led to deterioration in the performance status of long-term survivors [208]. The results of the NCIC CTG CE.6/EORTC 26062-22061/TROG 08.02 phase III study are eagerly awaited which will help to define the role of TMZ with concurrent hypofractionated RT in elderly patients.…”

Section: Open Questions For Considerationmentioning

confidence: 99%

Success and Failures of Combined Modalities in Glioblastoma Multiforme: Old Problems and New Directions

Corso

Bindra

2016

Seminars in Radiation Oncology

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Phase 2 Trial of Hypofractionated High-Dose Intensity Modulated Radiation Therapy With Concurrent and Adjuvant Temozolomide for Newly Diagnosed Glioblastoma

Cited by 85 publications

References 30 publications

Cerebrospinal fluid dissemination of high-grade gliomas following boron neutron capture therapy occurs more frequently in the small cell subtype of IDH1R132H mutation-negative glioblastoma

Cerebrospinal fluid dissemination of high-grade gliomas following boron neutron capture therapy occurs more frequently in the small cell subtype of IDH1R132H mutation-negative glioblastoma

Hematological Toxicity of Hypofractionated Radiotherapy: A Review of the Available Evidence

Success and Failures of Combined Modalities in Glioblastoma Multiforme: Old Problems and New Directions

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