gms | German Medical Science

Objective: Despite an established treatment protocol (EORTC/NCIC temozolomide trial) for de-novo glioblastoma (GBM) clinical prognosis remains dismal. In this pilot study, we evaluated the clinical outcome of stereotactic interstitial photodynamic therapy (iPDT) as primary treatment in 15 selected patients suffering from complex located, small sized de-novo GBMs.

Method: Adult patients with histologically proven de novo GBM (n=15) not suitable for gross total resection, and a contrast enhancing diameter in the range of 3.5 cm were included. Tumors infiltrating the midline, basal ganglia, or the ventricular system were excluded. 5-Aminolevulinic acid (5-ALA) was used as a photosensitizer (dose: 20 or 30 mg/kg). A modified 3-D treatment-planning software was used to calculate both, the treatment-volume and the exact position of the light diffusers within the lesion. Light diffusers were stereotactically implanted and irradiation was performed with a wavelength of 633 nm (median dose: 12960J). Outcome after iPDT was compared with a positively selected patient population undergoing complete tumor resection. All patients of the iPDT and the resection group underwent the EORTC/NCIC temozolomide trial protocol. Survival (OS) and progression free survival (PFS) was analyzed with the Kaplan Meier method and compared with log-rank statistics. Written informed consent was obtained from all patients.

Results: Median age of the iPDT group and the resection group was 68 and 56 years, respectively. MGMT-promotor methylation was seen in the range of 40% in both groups. Median follow-up after iPDT (resection) was 36.0 (37.0) months. Median PFS was 16.0 months after iPDT and 10.2 months after complete resection (p=0.0008). Six out of 15 patients of the iPDT group experienced progression free survival > 30 months (range: 30-70 months). Two- (three) year OS was 55% (55%) after iPDT and 36% (21%) after resection (p=0.02). MGMT-promoter methylation status was the strongest prognostic/predictive factor in both groups. Side effects after iPDT included transient aphasia (n=4) and pulmonary embolism (n=2).

Conclusions: Long-term PFS in a considerable number of patients after iPDT pointed to the induction of so far unknown tumor-controlling processes which might overcome limitations of conventional treatment concepts. Understanding of the underlying mechanisms is required to identify patients most suitable for that new treatment strategy.