Recurrence pattern after concomitant radio-chemotherapy in newly diagnosed glioblastoma patients: Correlation with MGMT promoter methylation status

Abstract

2027 Background: Temozolomide (TMZ), concomitant with and adjuvant to radiotherapy (RT), has become the standard treatment for newly diagnosed glioblastoma (GBM). The aim of the present analysis was to evaluate the recurrence pattern in GBM patients (pts) treated with this treatment and to assess its correlation with MGMT promoter methylation status. Methods: A review was made of brain MRI images available in 95 GBM pts enrolled from January 2005 to January 2007, all of whom had been prospectively treated with TMZ (75 mg/m2/day) concomitant with standard RT (60 Gy/30F), followed by adjuvant TMZ (150–200 mg/m2 days 1–5, q28, maximum 12 cycles if MRI findings were negative or until progression if MRI appeared positive. An analysis was made of the correlation between MGMT promoter methylation status (assessed with methylation specific PCR) and the recurrence pattern. Results: After a median follow-up of 18 months (range: 6.6 - 44.8), 79 pts (83%) presented GBM recurrence: 57 pts (72%) had recurrence within, and 17 pts (22%) exclusively outside, the RT field; 5 pts (6%) had recurrence both within and outside the field. The median progression free survival (PFS) of pts with recurrence within, within plus outside, and only outside the RT field was 9.2, 8.7, and 14.9 months, respectively (in+in&out vs out p=0.025). The median survival time (MST) was 17.3 months (95%CI: 15.1–20), 14.8 months (95%CI: 10.8-NA), and 26.1 months (95%CI: 19-NA) in pts with recurrence within, within and outside, and only outside the RT field respectively (in+in&out vs out: p=0.013). Recurrence outside the RT field was reported in 15% of unmethylated pts and 42% of methylated pts (p=0.01). About 20% of GBM pts treated with TMZ concomitant and adjuvant to RT may develop recurrence outside the RT field. In pts with methylated MGMT promoter status with a longer PFS and OS, the incidence of recurrence outside the RT field is significantly higher. Conclusions: These data, of value in the development of surveillance strategies for GBM patients, may be an useful aid in selecting treatment for GBM pts in clinical trials. No significant financial relationships to disclose.