Combination of FOSCAN® mediated fluorescence guided resection and photodynamic treatment as new therapeutic concept for malignant brain tumors

Abstract

Abstract Photodynamic therapy (PDT), the combination of tumor-selective photosensitizers (PS) and light at the appropriate wavelength is under investigation for adjuvant therapy in brain tumors. Malignant brain tumors carry a lethal prognosis with a median survival of 15 months despite surgery, radiotherapy and chemotherapy. Recently photodynamic diagnosis mediated by FOSCAN® (meta-tetrahydroxyphenylchlorin – mTHPC) was introduced by our institution for intraoperative photo diagnosis (PDD) and fluorescence guided resection (FGR) for a more radical tumor removal. Twenty-six patients suffering from malignant brain tumors were sensitized with 0.15 mg/kg m-THPC body weight and underwent a combination of fluorescent guided resection followed by intraoperative PDT (20 J/cm2 at 652 nm) after 4 days. Intraoperative fluorescence was induced by a UV light source at 370–440 nm. A standard neurosurgical microscope was optimized for fluorescence detection. Intraoperative PDT was performed by lasers at 652 nm and 20 J/cm2. The fluorescence sensitivity and specificity in 172 tissue samples were 87.9% and 95.7%, respectively. Tumor could be predicted to an accuracy of 90.7%. Photodynamic diagnosis (PDD) proved to be useful in tumor resection accounting for a radical resection in 75% under fluorescenceguided resection as compared to 52% in the control group. The median survival time for the PDD/PDT group was 9 months as compared to the matched pair control group of 3.5 months, respectively. The side effects consisted of two severe toxic reactions to sunlight due to unintentional exposure to direct sunlight and one patient experienced a transitional brain swelling. Our results indicate that fluorescence guided surgery is feasible and proved to be of significant help in delineating tumor margins and in resection of residual tumor that could not be detected by the surgeon. The addition of intraoperative PDT significantly enhanced survival.