gms | German Medical Science

Objective Glioblastoma is an orphan disease with a grave prognosis. Despite recent advances in the therapy, median survival is still restricted to about 15 months. Novel therapies in the recurrent situation have so far failed phase III evaluations. Therefore, new treatment concepts are needed. One concept may be interstitial photodynamic therapy (iPDT), using the endogenous heme precursor 5-aminolevulinic acid (ALA) which causes mitochondrial and nuclear DNA damage, as well as an immunological effect. This combination between immunologic targeting and local therapy is singular in the treatment of GBM. To evaluate early effectiveness of this therapy, MRI may be a useful tool. We therefore analyzed early MRI findings of patients with recurrent malignant glioma treated by iPDT in a compassionate use setting

Methods: The clinical implementation of iPDT has been shown to be feasible, accurate, and safe even for treatment of deep seated tumors. Therefore we have initiated a phase II b clinical, multicentric, randomized controlled trial (sponsored by Deutsche Krebshilfe, EudraCT-Nr: 2015-002727-25). The ethic commission vote was positive. Patients will be randomized 1:1 and treated in two arms. The treatment arm will receive 5-ALA HCl (20 mg/kg bw) orally 3.5 – 4.5 hours prior to induction anesthesia. A stereotactic biopsy will be performed in order to verify recurrence. If the result is positive, and if the patient is randomized to the PDT arm, iPDT is performed. All patients will receive further treatment of recurrent glioblastoma at the investigator´s discretion (best possible care). A retrospective databank analysis was performed of our compassionate series, treated by iPDT, as well. MRI was performed within 48h post surgery. The MRI was analyzed in the context of routine diagnostics.

Results: With our planned trial we want to investigate the efficacy and safety of iPDT with 5-ALA in recurrent glioblastoma regarding progression free survival (PFS), measured as time from the day of randomization until diagnosis of progressive disease. Secondary endpoints, among others, will be the OAS and the quality of life. As pilot seven patients with diagnosis of recurrent malignant Glioma, treated by PDT in a compassionate setting between 02/2011-05/2014 were analyzed. A median OAS from first diagnosis of 24 months was reached. Early postoperative MRI showed a restriction of diffusion as well as subsidence in ADC value which could be well correlated to treatment volume planned ex ante. The SWI demonstrated the products of heme decomposition.

Conclusion: We hope to prove iPDT with this multicenter randomized trial to be a valid additional treatment option in the therapy of recurrent malignant glioma. We already saw an effect of ALA PDT in the targeted tissue in the retrospective analyzes. Especially ADC subsidence appears to be a useful indicator of early therapy effects and will be useful to monitor correct planning of the treatment volume. The reasons for ADC subsidence are unclear to date but may be related to tumor cell swelling, necrosis or early apoptosis.