Abstract
BACKGROUND: Laser light in malignant brain tumours has been used in conjunction with photosensitizing drugs to both guide surgical resection (Photodynamic Diagnosis (PDD)) and to also enhance the extent of tumour destruction (Photodynamic Therapy (PDT)). Photosensitizing drugs given pre-operatively are taken up by rapidly dividing cells, resulting in fluorescence on exposure to low visible wavelength (blue) light (PDD) or generate cytotoxic singlet oxygen species upon exposure to high visible wavelength (red) light (PDT). PDT potentially offers benefit for patients with Glioblastoma Multiforme (GBM) where it’s highly invasive & heterogeneous nature makes complete resection impossible. As 5-ALA has European & US regulatory approval for PDD in GBM surgery, it is the most obvious candidate for PDT. A newer agent, Temoporfin, has demonstrated greater phototoxicity in animal models and enhances survival over matched pair (no PDT) controls in humans. This retrospective analysis aims to establish whether PDT with Temoporfin confers a greater degree of survival for GBM patients compared to using PDT with 5-ALA while undergoing a standard regime of care (surgical debulking, followed by Temozolomide with radiotherapy). MATERIAL AND METHODS: Clinical data were gathered retrospectively from procedure and electronic medical records for patients undergoing PDT following surgical debulking of GBM from September 2009 to December 2012. Survival of those who underwent intra-operative treatment with Temoporfin was compared to those who were treated with 5-ALA, along with data on demographics, Karnofsky Performance Score, Charlson Co-Morbidity Index and lesion size. RESULTS: Median overall survival from point of surgery and PDT therapy for those treated with Temoporfin (n=6) was 4.2 mths (range, 1.2–32.3 mths), with 2-year survival rates of 16.7%. This was compared to those treated with 5-ALA (n=9) where median overall survival was 6.0 mths (range, 1.8–39.7 mths), with 2-year survival rates of 11.1%. No significant difference in survival was demonstrated between the two groups (log-rank test, p=0.835) and multivariate Cox regression analysis showed no statistically significant independent covariates. CONCLUSIONS: Despite evidence suggesting increased phototoxicity in animal models, these data demonstrate no difference in survival outcome between GBM patients treated with Temoporfin and those treated with 5-ALA. This may reflect inherent difficulties relating to laser light dispersion through brain tissue, even when using more penetrant red-light. However, the small number of patients in this retrospective analysis is a limitation to inferences that can be drawn. Nevertheless, given 5-ALA’s widespread regulatory approval, it remains the best opportunity for ongoing research into PDT for GBM.