Interstitial photodynamic therapy (iPDT) of brain tumours (Conference Presentation)

Abstract

THIS IS FOR THE SESSION "CAPABILITIES OF 5-ALA" The accumulation of the fluorescent photosensitizer protoporphyrin IX (PpIX) after systemic administration of 5-ALA proved high tumor selectivity and led to intra-operative fluorescence guidance during resection of malignant glioma. 5-ALA therefore also promises to be useful for PDT of malignant glioma. Preclinical investigations resulted in the establishment of an appropriate treatment planning strategy and treatment parameters. This can be outlined as follows: interstitial placement of cylindrical diffuser fibers (1 to 4 cm diffuser length) by stereotaxy after careful planning on CT/MRI scans, such that fibers are approximately 1 cm apart and as close as 3-4 mm from the contrast uptaking tumor border. Aim of the irradiation parameters (200 mW/cm diffuser length for 1 hour) is to reach >95% photobleaching of PpIX in at least one optical penetration depth (approx. 3 mm) from the fibers. The therapeutic penetration depth can be expected to reach significantly deeper and kill glioma cells within parts of the infiltration zone, which are no more highlighted by Gd-contrast uptake. So far, inoperable de novo and recurrent malignant glioma with sizes up to 3 cm in diameter proved amenable in clinical investigations. Intriguing longterm progression free and overall survivals led to the design of prospective clinical trials, which are expected to start recruitment in 2019. Further research should focus on individualizing treatment parameters, further improve PpIX accumulation, including the sensitization of cancer stem cells and explore the role of immune stimulation by PDT, including the possible synergistic effect of immune checkpoint inhibitors.