Background: In the next decades, the incidence of patients with glioblastoma (GBM) will increase due to the growth of the elderly population. Fluorescence-guided resection using 5-aminolevulinic acid (5-ALA) is widely applied to achieve maximal safe resection of GBM and is identified as a novel intraoperative marker for diagnostic tissue during biopsies. However, detailed analyses of the use of 5-ALA in resections as well as biopsies in a large elderly cohort are still missing. The aim of this study was thus to investigate the efficacy, outcome, and safety of surgically- treated GBM in the 5-ALA era in a large elderly cohort. Methods: All GBM patients aged 65 years or older who underwent neurosurgical intervention between 2007 and 2019 were included. Data on 5-ALA application, intraoperative fluorescence status, and 5-ALA-related side effects were derived from our databank. In the case of resection, the tumor resectability and the extent of resection were determined. Potential prognostic parameters relevant for overall survival were analyzed. Results: 272 GBM patients with a median age of 71 years were included. Intraoperative 5-ALA fluorescence was applied in most neurosurgical procedures (n = 255/272, 88%) and visible fluorescence was detected in most cases (n = 252/255, 99%). In biopsies, 5-ALA was capable of visualizing tumor tissue by visible fluorescence in all but one case (n = 91/92, 99%). 5-ALA administration did not result in any severe side effects. Regarding patient outcome, smaller preoperative tumor volume (<22.75 cm3), gross total resection, single lesions, improved postoperative neurological status, and concomitant radio-chemotherapy showed a significantly longer overall survival. Conclusions: Our data of this large elderly cohort demonstrate the clinical utility and safety of 5-ALA fluorescence in GBM for improved tumor visualization in both resections as well as biopsies. Therefore, we recommend the use of 5-ALA not only in resections, but also in open/stereotactic biopsies to optimize the neurosurgical management of elderly GBM patients.
Background: 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PpIX) fluorescence shows high sensitivity in detecting the tumor core of high-grade gliomas (HGG) but poor sensitivity for tissue of low-grade gliomas (LGG) and the margins of HGG. The characteristic emission peak for PpIX is known to be located at 635 nm. Recently, a second emission peak was described at 620 nm wavelength in LGG and the tumor infiltration zone of HGG. Methods: During surgery, samples from the tumor core and tumor infiltration zone of 43 WHO grade 2–4 gliomas were collected after preoperative 5-ALA administration, and their PpIX emission spectra, as well as fluorescence lifetimes, were determined by ex vivo analysis. Subsequently, the relative PpIX peak contribution (RPPC) was retrieved by calculating the integral of the two bands corresponding to the two emission peaks of PpIX (615–625 nm, 625–635 nm) and correlated with fluorescence lifetimes. Results: The mean RPPC decreased in samples with descending order of WHO grades, non-fluorescing samples, and infiltrative tumor regions, indicating a shift toward the 620 nm peak in porphyrin fluorescence. The porphyrin peak shift across all specimens correlated with lower fluorescence lifetimes (R: 0.854, R-squared: 0.729). Conclusions: The observed peak shift has important implications for fluorescence lifetime analyses since the lifetimes of other porphyrins contribute to the overall decay dynamics. Based on these initial data using fluorescence lifetime, this knowledge is of major importance, especially for detecting tissue from LGG that lack visible fluorescence, to further optimize the visualization of these tumor tissue using this promising imaging modality.
Background: Established clinical risk scores (CRSs) can estimate the prognosis of patients with colorectal liver metastases (CLM) after hepatic resection. However, their ability to predict outcome for patients undergoing neoadjuvant chemotherapy is limited, mainly because most included variables do not reflect a biologic response to neoadjuvant chemotherapy (NAC). This study aimed to evaluate the prognostic value of total metastases volume (TMV) and relative volume reduction (RVR) for patients with CLM undergoing perioperative chemotherapy and surgery. Methods: Liver metastases volume was semi-automatically measured on computed tomography images in 69 patients before and after NAC and compared to established CRS regarding progression-free survival (PFS) and overall survival (OS). Results: Patients with a TMV smaller than 29.5 ml before NAC and 7.5 ml after NAC showed a significantly longer PFS than those with a larger TMV (median, 31.0 vs. 13.7 months [p = 0.005] and 22.6 vs. 9.1 months [p = 0.013], respectively). An RVR after NAC of at least 73% was a positive predictor of PFS (median, 38.0 vs. 9.4 months; p = 0.004) and OS (mean, 59.5 vs. 92.5 months; p = 0.002). Conclusions: Total tumor volume and RVR of CLM seem to be superior to established CRS for patients undergoing neoadjuvant chemotherapy and surgery.
Proposing three-dimensional morphological criteria to measure tumor burden in colorectal liver metastases: Total metastases volume and relative volume reduction represent valuable prognostic parameters for patients undergoing neoadjuvant chemotherapy and surgery (