Is interstitial photodynamic therapy for brain tumors ready for clinical practice? A systematic review

Interstitial photodynamic therapy (iPDT), inserting optical fibers inside brain tumors, has been proposed for more than 30 years. While a promising therapeutic option, it is still an experimental treatment, with different ways of application, depending on the team performing the technique.

In this systematic review, we reported the patient selection process, the treatment parameters, the potential adverse events and the oncological outcomes related to iPDT treatment applied to brain tumors.

We performed a search in PubMed, Embase and Medline based on the following Mesh terms: "interstitial" AND "photodynamic therapy" AND "brain tumor" OR "glioma" OR glioblastoma" from January 1990 to April 2020. We screened 350 studies. Twelve matched all selection criteria.

251 patients underwent iPDT. Tumors were mainly de novo or recurrent high-grade gliomas (171 (68%) of glioblastomas), located supratentorial, with a median volume of 12 cm³. Hematoporphyrin derive agent (HpD) or protoporphyrin IX (PpIX) induced by 5-aminolevulinic acid (5-ALA) was used as a photosensitizer. Up to 6 optical fibers were introduced inside the tumor, delivering 200 mW/cm at a wavelength of 630 nm. Overall mortality was 1%. Transient and persistent morbidity were both 5%. No permanent deficit occurred using 5-ALA PDT. Tumor response rate after iPDT was 92% (IQR, 67; 99). Regarding glioblastomas, progression-free-survival was respectively 14.5 months (IQR, 13.8; 15.3) for de novo lesions and 14 months (IQR, 7; 30) for recurrent lesions, while overall survival was respectively 19 months (IQR, 14; 20) and 8 months (IQR, 6.3; 8.5). In patients harboring high-grade gliomas, 33 (13%) were considered long-term survivors (> 2 years) after iPDT.

Regardless of heterogeneity in its application, iPDT appears safe and efficient to treat brain tumors, especially high-grade gliomas. Stand-alone iPDT (i.e., without combined craniotomy and intracavitary PDT) using 5-ALA appears to be the best option in terms of controlling side effects: it avoids the occurrence of permanent neurological deficits while reducing the risks of hemorrhage and sepsis.