Concurrent Temozolomide and Dose-Escalated Intensity-Modulated Radiation Therapy in Newly Diagnosed Glioblastoma

Abstract

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. Methods and Materials 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.

Concurrent chemoradiotherapy with weekly nedaplatin versus radiotherapy alone in elderly patients with non-small-cell lung cancer

“…The advent of IMRT enables dose distribution that is more conformal to tumoral well as gives permission to dose escalation to target volumes while sparing normal structures [8,9]. Nevertheless, the appearance of distant metastases affects the prognosis of patients.…”

The Helical Tomotherapy Experience on Radiotherapy of Glioblastoma Multiforme

“…For this reason, it is necessary to study further the alternative fraction protocols in patients with GBM. The results of dose escalation have been reported in small, single institution, phase I-II studies (14,15). In these studies, the overall survival has been reported as 20.1 months in patients treated with hypofractioned IMRT.…”

Can an 18F-ALF-NOTA-PRGD2 PET/CT Scan Predict Treatment Sensitivity to Concurrent Chemoradiotherapy in Patients with Newly Diagnosed Glioblastoma?

“…This may be a great help to the adjustment of the clinical therapy scheme (34) and personalized treatment. In addition, considering the ease of preparation and good imaging qualities, 18 FAlF-NOTA-PRGD2 may be a promising alternative to other RGD agents for PET imaging of integrin a v b 3 expression (14).…”