Patterns of Failure in Primary GBM Following High-Dose Radiation Therapy and Concurrent Temozolomide, Indicating a Potential Role for Methionine-PET in GTV Definition

To analyze patterns of failure following high-dose radiation therapy (RT) with concurrent temozolomide (TMZ) for primary glioblastoma multiforme (GBM) in comparison to pre-treatment 11C-methionine-PET (mPET) volumes. 30 patients with primary GBM were treated on an IRB-approved phase I protocol using concurrent TMZ (75 mg/m2) and high-dose RT (median 75 Gy) delivered in 6 weeks. mPET scans were obtained before treatment but were not used for target definition. Protocol defined treatment volumes were based on MRI alone: PTV1 = T1 contrast-enhancing lesion (GTV) + 0.5 cm; and PTV2 = GTV + 2 cm. PTV2 received 60 Gy. PTV1 received HDRT delivered in a simultaneous IMRT boost. We used in-house developed software tools (FIAT) to analyze patterns of failure. Tumor progression MRI (obtained at the time of failure) and pre-treatment mPET scans were co-registered to the radiation dose map. Failures were classified based on the percentage volume of progression region of interest (pROI) within the 95% (of prescription) isodose surface (95% IDS): “central” (>95% enclosed), “in-field” (80–95%), “marginal” (20–80%), or “distant” (<20%). mPET volumes which might have been considered in GTV definition (mPET-GTVs) were obtained by automatically thresholding regions showing 1.5 times the uptake of normal cerebellum, and coverage of this volume by the 95% IDS was retrospectively assessed. 18 patients have relapsed, and 16 had imaging available at the time of failure. 1 patient did not have a mPET scan prior to treatment. Of the sixteen failures, 9 failures were central, 2 were in-field, and 5 were marginal. In 12/15 cases, mPET-GTVs overlapped with the pROIs. In the 3 cases with no overlap, the mPET-GTVs were minimal (<1 cm3). In retrospect (see Table), 5/6 cases where mPET-GTV coverage was suboptimal resulted in non-central failures, while adequate mPET-GTV coverage resulted in non-central failures in only 2/9 cases. Functional imaging using mPET may have a potential role in improving target volume definition for IMRT boost although additional subjects are needed to validate these findings.