Introduction
Extent of resection matters
Materials and methods
Research protocol and literature search with PRISMA
Results
Study | Year | Study type | No. of patients | ALA | Intraoperative MRI | Tumor type | Gross total resection rates with | Survival | Comment/conclusion | ||
---|---|---|---|---|---|---|---|---|---|---|---|
ALA | MRI | Both | |||||||||
Coburger et al. | 2014 | Prospective, single-center, histology-based assessment | 45 | Yes | Yes (1.5 T) | 34 HGG, 11 metastatic lesions | n/a | n/a | n/a | n/a | Sensitivity for tumor detection: ALA (91%) vs. iMRI (66%); specificity for tumor detection: ALA (91%) vs. iMRI (60%) |
Coburger et al. | 2015 | Prospective, single-center, combined with retrospective match-paired assessment | 33 | Yes | Yes (1.5 T) | Glioblastoma | n/a | 82% | 100% | PFS and OS = n.s. between groups | Significant increase in EoR when combining ALA and iMRI without higher complications rates. |
Coburger et al. | 2017 | Prospective, single-center, histology-based assessment | 33 | Yes | Yes (1.5 T) | Glioblastoma | n/a | n/a | n/a | n/a | “Only 5-ALA showed a significant correlation to histopathological findings compared to iMRI and linear array intraoperative ultrasound” |
Eyüpoglu et al. | 2012 | Prospective, single-center | 37 | Yes | Yes (1.5 T) | High-grade glioma | 71.7% | n/a | 100%* | n/a | “After initial resection with ALA, MRI assisted in finding tumor remnant which after locating it, demonstrated fluorescence. iMRI was helpful for discriminating low-grade portions of allegedly secondary high-grade tumors” (* for tumors in the vicinity of eloquent regions) |
Eyüpoglu et al. | 2016 | Prospective (n = 30) and retrospective (n = 75), single-center | 105 | Yes | Yes (1.5 T) | Glioblastoma | n/a | n/a | 100% (n = 30, supramarginal resection) | Median survival time 18.5 months (vs. 14 months in the control arm) | No iMRI or FGS in retrospective cohort |
Gessler et al. | 2015 | Prospective, single-center | 32 | Yes | Yes (0.15 T) | Glioblastoma | n/a | n/a | 97% | OS 80.7 weeks, PFS 61.3 weeks | Sensitivity and specificity of iMRI and 5-ALA to detect remaining tumor tissue were 75 and 100% for iMRI and 70 and 100% for 5-ALA fluorescence “in 52.6% of the cases; each one of the modalities was the only indicator of further tumor tissue in 26.3% (iMRI) or 21.1%(5-ALA) of the cases, while the other did not indicate residual tumor, when the surgeon thought to have achieved GTR already.” |
Hauser et al. | 2016 | Prospective, single-center | 14 | Yes | Yes (0.15 T) | Glioblastoma | 9% | n/a | 82% | Mean OS 15.3 months, 6-month PFS 36.4% | iMRI demonstrated 91.6% of tumor remnant after FGS; however, only 64.3% of these were confirmed as actual tumor after histological examination |
Nickel et al. | 2017 | Prospective, multicenter | 162 | Yes | Yes (n/a) | High-grade glioma | 74% | 94% | 95% | n/a | GTR with no imaging 73% and with 5-ALA alone 74% |
Quick-Weller et al. | 2016 | Prospective, single-center | 7 | Yes | Yes (0.15 T) | Recurrent glioblastoma | n/a | n/a | 100% | Median OS 27.8 months, since repeat surgery 7.6 months | Absence of fluorescence in one patient. “5-ALA is a powerful surgical tool, but in the case of recurrent GBM, re-surgery should be performed under the combined help of 5-ALA and iMRI in order to achieve most radical tumor resection to prolong patients’ survival.” |
Roder et al. | 2014 | Retrospective, single-center | 117 | Yes (n = 47) | Yes (n = 27; 1.5 T) | Glioblastoma | 46% | 74% | n/a | No statistical difference between groups | Thirty-two percent of patients in the iMRI group received ALA. Residual volume after iMRI (0.5 cm3) was lower than both 5-ALA (1.9 cm3) and white-light surgery (4.9 cm3). This is a historic comparison, and differences can be multifactorial. |
Schatlo et al. | 2015 | Retrospective, single-center | 200 | Yes | Yes (0.15 T) | High-grade gliomas | n/a (n = 58) | n/a | 45% (n = 55) | Median OS 13.8 months and PFS 7 months vs. 17.9 and 10.6 months (no iMRI vs. iMRI) | Historic comparison (2003–2011). Large groups of patients before FGS era and introduction of concomitant radio-/chemotherapy with TMZ |
Tsugu et al. | 2011 | Retrospective, single-center | 33 | Yes | Yes (1.5 T) | Low- and high-grade gliomas | 55% | 56%* | 40% | n/a | * Included 12 ALA negative low-grade gliomas |
Yamada et al. | 2015 | Prospective, single-center | 97 | Yes | Yes (0.3 T) | High-grade gliomas | n/a | n/a | 52% | n/a | “5-ALA-induced tissue fluorescence had 92% positive predictive value (PPV) for presence of glioma in the histopathological specimen.” “Neurochemical navigation with 5-ALA is useful adjunct during iMRI-guided resection of intracranial malignant gliomas, which allows identification of the tumor extension beyond its radiological borders.” |
Discussion
5-Aminolevulinic acid
Intraoperative MRI
5-Aminolevulinic acid-induced fluorescence vs. gadolinium contrast enhancement in MRI
Resection rates
Study | Stummer et al. | Stummer et al. | Diez Valle et al. | Schucht et al. | Della Puppa et al. | Schucht et al. |
---|---|---|---|---|---|---|
Year | 2000 | 2006 | 2011 | 2012 | 2013 | 2014 |
No. of patients | 50 | 135 | 36 | 103 | 25 | 67 |
Study design | Prospective, single-center | Prospective, multicenter two-arm randomized | Prospective, single-center | Prospective, single-center | Prospective, single-center | Prospective, single-center |
Eloquent region | Eloquent and non-eloquent | Eloquent and non-eloquent | Eloquent and non-eloquent | Eloquent and non-eloquent | Eloquent and non-eloquent | Solely eloquent (motor) |
Monitoring and mapping | No | No | Yes | Yes | Yes | Yes |
Resection rate | 65% | 65% | 83.3% | 96% | 80% | 76% |