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.

We have established a minimally invasive dog model of prostate cancer. This model may be valuable for studying prostate cancer progression and distant metastasis.

We assessed the value of fusion 18F-fluoromethylcholine (18F-choline) PET/MRI for image-guided (targeted) prostate biopsies to detect significant prostate cancer (Gleason ≥ 3 + 4) compared with standard (systematic 12-core) biopsies. Methods Within an ongoing prospective clinical trial, hybrid 18F-choline PET/CT and multiparametric 3T MRI (mpMRI) of the pelvis were performed in 36 subjects with a rising prostate-specific antigen for known (n = 15) or suspected (n = 21) prostate cancer before a prostate biopsy procedure. PET and T2-weighted MR volumes of the prostate were spatially registered using commercially available software. Biopsy targets were selected on the basis of visual appearance on MRI and graded as low, intermediate, or high risk for significant disease. Volumes of interest were defined for MR-identified lesions. 18F-choline uptake measures were obtained from the MR target and a mirrored background volume of interest. The biopsy procedure was performed after registration of real-time transrectal ultrasound with T2-weighted MR and included image-guided cores plus standard cores. Histologic results were determined from standard and targeted biopsy cores as well as prostatectomy specimens (n = 10). Results Fifteen subjects were ultimately identified with Gleason ≥ 3 + 4 prostate cancer, of which targeted biopsy identified significantly more (n = 12) than standard biopsies (n = 5; P = 0.002). A total of 52 lesions were identified by mpMRI (19 low, 18 intermediate, 15 high risk), and mpMRI-assigned risk was a strong predictor of final pathology (area under the curve = 0.81; P < 0.001). When the mean 18F-choline target-to-background ratio was used, the addition of 18F-choline to mpMRI significantly improved the prediction of Gleason ≥ 3 + 4 cancers over mpMRI alone (area under the curve = 0.92; P < 0.001). Conclusion Fusion PET/MRI transrectal ultrasound image registration for targeted prostate biopsies is clinically feasible and accurate. The addition of 18F-choline PET to mpMRI improves the identification of significant prostate cancer.

No abstract