Concurrent temozolomide and dose-escalated intensity-modulated radiation therapy in newly diagnosed glioblastoma

Christina I. Tsien, Doris Brown, Daniel Normolle, Matthew Schipper, Morand Piert, Larry Junck, Jason Heth, Diana Gomez-Hassan, Randall K. Ten Haken, Thomas Chenevert, Yue Cao, Theodore Lawrence

Research output: Contribution to journalArticlepeer-review

86 Scopus citations


Purpose: To determine the maximum-tolerated dose (MTD) of radiation (RT) with concurrent temozolomide 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 to 81 Gy, assigned to patients by the time-to-event continual reassessment method, were delivered over 6 weeks with concurrent daily temozolomide (75 mg/m2) followed by adjuvant cyclic temozolomide (200 mg/m2 d1-5 q28d ×6 cycles). Treatment was based on gadolinium-enhanced MRI. Pretreatment MET-PET scans were obtained for correlation with eventual sites of failure. Results: A total of 38 patients were analyzed with a median follow-up of 54 months for patients who remain alive. Late CNS grade ≥III toxicity was observed at 78 (2 of 7 patients) and 81 Gy (1 of 9 patients). None of 22 patients receiving 75 or less Gy developed RT 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 showed an increased risk of noncentral failure (P < 0.001). Conclusions: Patients with GBM can safely receive standard temozolomide 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.

Original languageEnglish (US)
Pages (from-to)273-279
Number of pages7
JournalClinical Cancer Research
Issue number1
StatePublished - Jan 1 2012
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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