multiparametric mr-guided high dose adaptive radiotherapy with concurrent temozolomide in patients with newly diagnosed glioblastoma

Conditions: Glioblastoma

Summary: this study will investigate whether or not intensified radiation therapy adapted during the radiation treatment course to high-risk, treatment-resistant tumor regions will improve overall survival in patients with newly diagnosed glioblastoma (gbm) compared to conventional chemoradiotherapy.


Eligibility criteria:
inclusion criteria: * provision of signed and dated informed consent form * stated willingness to comply with all study procedures and availability for the duration of the study * newly diagnosed, histologically-confirmed supratentorial who grade iv gliomas including glioblastoma (all variants) and gliosarcoma. prior low-grade glioma without prior rt, now with malignant progression are eligible. * karnofsky performance status \>=70 * minimal life expectancy of 12 weeks * adequate bone marrow reserve (hemoglobin ≥ 10 g/dl, absolute neutrophils ≥ 1500/mm3, platelet count ≥ 100,000/mm3), acceptable liver function (total bilirubin ≤ 2 x upper limit of normal (uln) (unless elevated bilirubin is related to gilbert syndrome), and alt/ast ≤ 5 x uln) and renal function (serum creatinine ≤ 2.0 mg/dl) within 14 day prior to registration. eligibility level for hemoglobin may be reached by transfusion. * maximal contiguous diameter of tumor based on high b-value diffusion mri and dce perfusion mri ≤5 cm * patients must be registered within 6 weeks of most recent resection * females of child-bearing potential must have a negative pregnancy test within 14 days prior to registration. patients with reproductive potential must agree to use an effective contraceptive method during treatment and study participation. exclusion criteria: * recurrent glioma, or tumor involving the brainstem or cerebellum * prior use of gliadel wafers or any other intratumoral or intracavitary treatment is not permitted. prior chemotherapy for a different cancer is allowable if interval since last treatment cycle completion is \>3 years. * evidence of csf dissemination (positive csf cytology for malignancy or mri findings consistent with csf dissemination) * evidence of severe concurrent disease requiring treatment * prior invasive malignancy (except non-melanoma skin cancer or non-life limiting invasive malignancy that may not require treatment, such as low-risk prostate cancer) unless disease free for a minimum of 3 years (for example, carcinoma in situ of breast, oral cavity or cervix are all permissible) * patients unable to undergo mri exams (i.e. patients with non-compatible devices such as cardiac pacemakers, other implanted electronic devices, metallic prostheses, or ferromagnetic prostheses \[e.g. pins in artificial joints and surgical pins/clips\], or unable to receive gadolinium for mri, as per the standard department of radiology mri screening criteria) * patients treated with previous cranial or head/neck radiotherapy leading to significant radiation field overlap as determined by treating physician * multifocal disease (\>1 lobe of involvement) of discontiguous contrast enhancing disease as seen on conventional mri * pregnancy or lactation