PET guided chemotherapy – monitoring metabolic effects of temozolomide chemotherapy in malignant gliomas and of long-term adjuvant chemotherapy in patients with glioblastoma

Aims: One general trend in oncology is to monitor biological effects of chemotherapy. [11C]methionine (MET)-PET may be a helpful tool to differentiate responders from non-responders and may provide valuable information for making treatment decisions, especially in non-responders. Therefore, MET-PET might have the potential to predict clinical outcome.

A further focus of interest is the monitoring of metabolic effects in glioblastomas (GBM) when adjuvant temozolomide (TMZ) chemotherapy is been administered longer than 12 cycles; recent TMZ adjuvant chemotherapy recommendations suggest up to 6–12 cycles in the standard dosage after maximal resection of the GBM and concomitant radio-/TMZ-therapy.

Patients and Methods: Sequential MET-PET studies were performed before and after the 3rd cycle of TMZ chemotherapy in 15 patients with malignant gliomas, and in 12 patients also after the 6th cycle. Long term-outcome was assessed by calculating the time-to-progression (TTP) in months.

Additionally, we observed two patients with GBM treated with adjuvant TMZ therapy up to 20 and 27 cycles, respectively. Due to a stable clinical status TMZ was discontinued and reduced, respectively. Three MET-PET follow-up scans in both patients were performed until the change of adjuvant therapy regimen, and, to image these effects, two additional MET-PET scans were performed afterwards in both patients. Additionally, to measure proliferative activity of the GBM two [18F]fluoro-L-thymidine (FLT)-PET scans was performed in one patient after the change of adjuvant therapy regimen.

Results: The median TTP was significantly longer in malignant glioma patients with decline of methionine uptake than in patients with increasing methionine uptake (23 vs. 3.5 months; p=0.01, log rank test).

After discontinuation and dose reduction of adjuvant TMZ therapy in two patients with GBM the metabolic activity of the tumor as measured by MET- and FLT-PET increased.

Conclusions: First, a reduction of MET uptake during TMZ treatment predicts favorable clinical outcome. Secondly, MET- and FLT-PET is able to monitor metabolic effects of long-term adjuvant TMZ therapy more than 12 cycles in patients with GBM after discontinuation and dose reduction, respectively. PET imaging offers a new method to follow the biological activity of malignant glioma and has to be studied in a larger patient group to establish its clinical value.