Article
Establishing a threshold for extent of resection to improve progression free survival in WHO grade II gliomas: a retrospective multicenter assessment of 188 cases
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Published: | June 18, 2018 |
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Objective: The beneficial impact of a gross total resection (GTR) on patient outcome in low grade glioma (LGG) surgery has been emphasized in the literature. Since GTR is not always feasible in the vicinity of eloquent areas the aim of this study was to evaluate prognosis according to different levels of extent of resection (EOR) in a multicenter cohort.
Methods: IMRI guided resections of WHO grade II LGG from 2001-2014 were retrospectively collected from five academic centers including clinical parameters (e.g. age, histopathology, adjuvant treatments, neurologic deficits), molecular pathology (IDH1) and imaging data. EOR was evaluated in semi-quantitative fashion in EOR clusters (100%, ≥95%, ≥75%, ≥50%, <50%) by a neuroradiologist blinded to clinical outcome. In a stepwise approach EOR clusters were compared using Kaplan-Meier estimates and LoG-Rank test for PFS to establish a EOR threshold which was then evaluated in a multivariate Cox-regression model. Multiple imputations with weighted estimators were applied to compensate for missing IDH1 values.
Results: Out of n=288 cases screened n=188 cases with available imaging were analyzed. This included 109 astrocytomas (58%), 39 oligodendrogliomas (21%) and 40 oligoastrocytomas (21%). Repeated surgery was performed in non-malignant progression in 43 cases (23%). 95 cases (51%) were <40 years at presentation. IDH1 mutations were found in 120 cases (64%) with missing information on IDH1 in 51 cases (27%). Adjuvant therapy was applied in 53 cases (28%). EOR was 100% in 67(36%), ≥95% in 40(21%), ≥75% in 34(18%), ≥50% in 20(11%) and <50% in 27(14%) cases. Mild neurologic deficits were found in 19 cases(10%), severe deterioration in 7 cases(4%) postoperatively. Mean PFS was 4.4 years(95%C.I. 3.8-5.1) and significantly correlated with EOR(p<0.0001). In cluster-wise comparison an EOR <75% showed a significant negative influence on PFS (p<0.001). Interestingly, an EOR of ≥95% did not differ from a GTR (p=0.663). Multivariate analysis identified EOR≥75%(p<0.006) and recurrent surgery(p=0.014) as positive and adjuvant treatment(p<0.008) as negative independent prognosticators of PFS.
Conclusion: This study corroborated the positive impact of EOR on PFS in a multicenter series of WHO grade II gliomas. Our data supports the surgical goal to achieve GTR whenever feasible. If not feasible, survival benefits could still be detected for a 75% EOR threshold. Repeated surgery in non-malignant progression was an appropriate treatment option.