Photodynamic therapy in the treatment of intracranial gliomas: A review of current practice and considerations for future clinical directions

Invasive grade III and IV malignant gliomas remain difficult to treat with a typical survival time post-diagnosis hovering around 16 months with only minor extension thereof seen in the past decade, whereas some improvements have been obtained towards five-year survival rates for which completeness of resection is a prerequisite. Optical techniques such as fluorescence guided resection (FGR) and photodynamic therapy (PDT) are promising adjuvant techniques to increase the tumor volume reduction fraction. PDT has been used in combination with surgical resection or alternatively as standalone treatment strategy with some success in extending the median survival time of patients compared to surgery alone and the current standard of care. This document reviews the outcome of past clinical trials and highlights the general shift in PDT therapeutic approaches. It also looks at the current approaches for interstitial PDT and research options into increasing PDT's glioma treatment efficacy through exploiting both physical and biological-based approaches to maximize PDT selectivity and therapeutic index, particularly in brain adjacent to tumor (BAT). Potential reasons for failing to demonstrate a significant survival advantage in prior PDT clinical trials will become evident in light of the improved understanding of glioma biology and PDT dosimetry.