“Photodynamic therapy [PDT] has the potential to provide a great service in an area that is very desperately in need of that,” pronounced Harry T. Whelan, MD, Professor of Neurology at the Medical College of Wisconsin in Milwaukee. With no clear standard of care and poor 5-year survival rates, there certainly is room for improvement in caring for patients with brain tumors, and PDT may play a future role. From its use in canine models in the mid-1990s to its application in patients approximately 10 years later, PDT has been emerging as a topic of interest. In this article, Dr. Whelan takes a backward glance at the origins of PDT for brain tumors, describes the clinical challenges to its use in the skull, and outlines the objectives of his phase I study for PDT in children with brain cancer, the second most common childhood cancer after leukemia.
Gliomas are among the most challenging of brain tumor subtypes. The location of a benign tumor in the eloquent areas of the brain could potentially render it inoperable, the presence of a blood–brain barrier limits the ability of systemically administered medications to reach the target site, and the intricate neuronal network makes targeted therapy challenging. Patients with high-grade gliomas (HGGs) in particular have a generally poor prognosis, and surgery is rarely curative.
The use of PDT for brain tumors such as HGGs and glioblastoma multiforme (GBM) moves away from the more traditional resection and systemic chemotherapy methods. With light-mediated activation of a photosensitizer that is selectively accumulated in the target tissue, PDT causes destruction of tumor cells through the production of singlet oxygen or superoxide and induces cell damage through direct and indirect cytotoxicity. Therefore, photosensitizers are the first critical element in PDT procedures, and the activation procedure is the second step, explained Dr. Whelan.
Whelan HT, Schmidt MH, Segura AD et al.. The role of photodynamic therapy in posterior fossa brain tumors: a preclinical study in a canine glioma model. J Neurosurg 1993;79:562–568.
Schmidt MH, Meyer GA, Reichert KW et al.. Evaluation of photodynamic therapy near functional brain tissue in patients with recurrent brain tumors. J Neurooncol 2004;67:201–207.
Fouladi M, Hunt DL, Pollack IF et al.. Outcome of children with centrally reviewed low-grade gliomas treated with chemotherapy with or without radiotherapy on Children’s Cancer Group high-grade glioma study CCG-945. Cancer 2003;98:1243–1252.
Cohen KJ, Pollack IF, Zhou T et al.. Temozolomide in the treatment of high-grade gliomas in children: a report from the Children’s Oncology Group. Neuro Oncol 2011;13:317–323.
Stupp R, Hegi ME, Gilbert MR, Chakravarti A. Chemoradiotherapy in malignant glioma: standard of care and future directions. J Clin Oncol 2007;25:4127–4136.
Stylli SS, Kaye AH, MacGregor L et al.. Photodynamic therapy of high grade glioma: long term survival. J Clin Neurosci 2005;12:389–398.