OBJECTIVEHigh-grade glioma (HGG) prognosis remains dismal, with inevitable, mostly local recurrence. Regimens for improving local tumor control are therefore needed. Photodynamic therapy (PDT) using porfimer sodium has been investigated but was abandoned due to side effects and lack of survival benefits. Intracellular porphyrins induced by 5-aminolevulinic acid (5-ALA) are approved for fluorescence-guided resections (FGRs), but are also photosensitizers. Activated by light, they generate reactive oxygen species with resultant cytotoxicity. The authors present a combined approach of 5-ALA FGR and PDT.METHODSAfter 5-ALA FGR in recurrent HGG, laser diffusors were strategically positioned inside the resection cavity. PDT was applied for 60 minutes (635 nm, 200 mW/cm diffusor, for 1 hour) under continuous irrigation for maintaining optical clarity and ventilation with 100% oxygen. MRI was performed at 24 hours, 14 days, and every 3 months after surgery, including diffusion tensor imaging and apparent diffusion coefficient maps.RESULTSTwenty patients were treated. One surgical site infection after treatment was noted at 6 months as the only adverse event. MRI revealed cytotoxic edema along resection margins in 16 (80%) of 20 cases, mostly annular around the cavity, corresponding to prior laser diffusor locations (mean volume 3.3 cm3). Edema appeared selective for infiltrated tissue or nonresected enhancing tumor. At the 14-day follow-up, enhancement developed in former regions of edema, in some cases vanishing after 4–5 months. Median progression-free survival (PFS) was 6 months (95% CI 4.8–7.2 months).CONCLUSIONSCombined 5-ALA FGR and PDT provides an innovative and safe method of local tumor control resulting in promising PFS. Further prospective studies are warranted to evaluate long-term therapeutic effects.

BACKGROUND Five-aminolevulinic acid (5-ALA) is well established for fluorescence-guided resections of malignant gliomas by eliciting the accumulation of fluorescent protoporphyrin IX (PpIX) in tumors. Because of the assumed time point of peak fluorescence, 5-ALA is recommended to be administered 3 h before surgery. However, the actual time dependency of tumor fluorescence has not yet been evaluated in humans and may have important implications. OBJECTIVE To investigate the time dependency of PpIX by measuring fluorescence intensities in tumors at various time points during surgery. METHODS Patients received 5-ALA (20 mg/kg b.w.) 3 to 4 h before surgery. Fluorescence intensities (FI) and estimated tumor PpIX concentrations (CPPIX) were measured in the tumors over time with a hyperspectral camera. CPPIX was assessed using hyperspectral imaging and by evaluating fluorescence phantoms with known CPPIX. RESULTS A total of 201 samples from 68 patients were included in this study. On average, maximum values of calculated FI and CPPIX were observed between 7 and 8 h after 5-ALA administration. FI and CPPIX both reliably distinguished central strong and marginal weak fluorescence, and grade III compared to grade IV gliomas. Interestingly, marginal (weak) fluorescence was observed to peak later than strong fluorescence (8-9 vs 7-8 h). CONCLUSION In human in Situ brain tumor tissue, we determined fluorescence after 5-ALA administration to be maximal later than previously thought. In consequence, 5-ALA should be administered 4 to 5 h before surgery, with timing adjusted to internal logistical circumstances and factors related to approaching the tumor.

No abstract

The combination of iMRI and awake craniotomy is demanding but well tolerated by patients. Careful preoperative evaluation is essential to ensure compliance. There is no adverse effect through iMRI on the awake patient or the results of cortical stimulation. Since the introduction of the iMRI in our department in 2005, all awake craniotomies were done in this setting. The implementation of these 2 techniques into our procedures is demanding, and necessitates thorough preparation but has broadened our basis for surgical decision making. However, to substantiate our positive perception, more clinical data are being compiled.

No abstract