gms | German Medical Science

Objective: Recurrent malignant Glioma (RMG) is an orphan disease with few therapeutic options. Most current therapy regimens are based on compassionate use or on attending physician's individual treatment preference. Encouraged by the apparent efficacy of 5-ALA based photodynamic therapy (PDT) in malignant gliomas in in-vivo and in-vitro, we now report our experience with 5-ALA-PDT in malignant recurrent glioma.

Methods: Between 2011 and 2017 37 patients with diagnosis of malignant glioma were treated in a compassionate use setting and now analyzed retrospectively. All patients received 20 mg/kg bodyweight ALA orally 4 hours prior to surgery. A stereotactic biopsy was performed prior to PDT. PDT involved stereotactic implantation of light diffusors with a light distribution modelled to the tumor form. For illumination a 635 nm laser was used (Ceralas biolitec, Germany) for one hour with a constant power of 200 mW/cm diffusor length.

Results: Median age was 52 (22-74). The gender ratio was balanced with 17 female and 20 male patients. Median time of follow up was 27 months. Pretreatment consisted of in median one surgery followed by radiotherapy (34/37) with a median dose of 60 Gy. 34 patients had received chemotherapy. Temozolomide was used in 27 patients, Avastin was used in one patient in addition to temozolomide prior to PDT treatment. Histopathology was determined prior to ALA PDT by frozen section. Glioblastoma WHO Grade IV were found in 23, anaplastic Astrocytoma (WHO Grade III) in 7, anaplastic Oligoastrocytoma (WHO Grade III) in 2, anaplastic Oligodendroglioma (WHO Grade III) in 3 cases, and one gliosarcoma. After PDT, temozolomide rechallenge was tried in 4 patients. Combination therapies with temozolomide+ PCV+ Avastin were tried in 2 patients Avastin alone in 3 patients, CCNU alone in 4 patients, a combination of TMZ + CCNU in 3 patients, PCV alone in 2 patients and temozolomide plus Avastin in 2 patients. A median overall survival (OAS) determined from iPDT until death or loss to follow up was 24 months (95% CI (7,645-40,335))

Conclusion: We demonstrate that in a small heterogenic group of malignant glioma patients ALA PDT was well tolerated. A median OAS of 24 months suggest efficacy in RMG. A randomized multicenter study is presently commencing.