Concurrent Temozolomide and Dose-Escalated Intensity Modulated Radiation Therapy in Newly Diagnosed Glioblastoma
Menée sur 38 patients atteints d'un glioblastome nouvellement diagnostiqué (durée médiane de suivi : 54 mois), cette étude évalue la dose maximale tolérée de rayonnements dans un traitement combinant radiothérapie avec modulation d'intensité et chimiothérapie concomittante par témozolomide, et analyse le rôle d'une tomographie par émission de positons à base de méthionine C11 pour prédire le risque de récidive
Purpose:To determine the maximum tolerated dose (MTD) of radiation (RT) with concurrent temozolomide (TMZ) in patients with newly diagnosed glioblastoma (GBM), to estimate their progression free (PFS) and overall survival (OS), and to assess the role of 11C methionine PET (MET-PET) imaging in predicting recurrence. Experimental Design: Intensity modulated RT (IMRT) doses of 66-81 Gy, assigned to patients by the time-to-event continual reassessment method, were delivered over 6 wks with concurrent daily TMZ (75 mg/m2) followed by adjuvant cyclic TMZ (200 mg/m2 d1-5 q28d x6 cycles). Treatment was based on gadolinium-enhanced MRI. Pretreatment MET-PET scans were obtained for correlation with eventual sites of failure. Results:38 patients were analyzed with a median follow-up of 54 months for patients who remain alive. Late CNS grade>3 toxicity was observed at 78 (2 pts of 7) and 81 Gy (1 pt of 9). None of 22 patients receiving <75 Gy developed radiation necrosis. Median OS and PFS were 20.1(14.0, 32.5) and 9.0 (6.0, 11.7) months, respectively. Twenty-two of 32 patients with pretreatment MET PET uptake showed uptake beyond the contrast-enhanced MRI. Patients whose treatment did not include the region of increased MET-PET uptake demonstrated an increased risk of non-central failure (p<0.001). Conclusions:GBM patients can safely receive standard TMZ with 75 Gy in 30 fractions, delivered using IMRT. The median OS of 20.1 months is promising. Furthermore, MET-PET appears to predict regions of high risk of recurrence not defined by MRI, suggesting that further improvements may be possible by targeting metabolically active regions.