Surgery of Motor Eloquent Glioblastoma Guided by TMS-Informed Tractography: Driving Resection Completeness Towards Prolonged Survival

Frontiers in Oncology, vol. 12, pp. 874631

Abstract

Background Surgical treatment of patients with glioblastoma affecting motor eloquent brain regions remains critically discussed given the risk–benefit dilemma of prolonging survival at the cost of motor-functional damage. Tractography informed by navigated transcranial magnetic stimulation (nTMS-informed tractography, TIT) provides a rather robust estimate of the individual location of the corticospinal tract (CST), a highly vulnerable structure with poor functional reorganisation potential. We hypothesised that by a more comprehensive, individualised surgical decision-making using TIT, tumours in close relationship to the CST can be resected with at least equal probability of gross total resection (GTR) than less eloquently located tumours without causing significantly more gross motor function harm. Moreover, we explored whether the completeness of TIT-aided resection translates to longer survival. Methods A total of 61 patients (median age 63 years, m = 34) with primary glioblastoma neighbouring or involving the CST were operated on between 2010 and 2015. TIT was performed to inform surgical planning in 35 of the patients (group T; vs. 26 control patients). To achieve largely unconfounded group comparisons for each co-primary outcome (i.e., gross-motor functional worsening, GTR, survival), (i) uni- and multivariate regression analyses were performed to identify features of optimal outcome prediction; (ii), optimal propensity score matching (PSM) was applied to balance those features pairwise across groups, followed by (iii) pairwise group comparison. Results Patients in group T featured a significantly higher lesion-CST overlap compared to controls (8.7 ± 10.7% vs. 3.8 ± 5.7%; p = 0.022). The frequency of gross motor worsening was higher in group T, albeit non-significant (n = 5/35 vs. n = 0/26; p = 0.108). PSM-based paired-sample comparison, controlling for the confounders of preoperative tumour volume and vicinity to the delicate vasculature of the insula, showed higher GTR rates in group T (77% vs. 69%; p = 0.025), particularly in patients with a priori intended GTR (87% vs. 78%; p = 0.003). This translates into a prolonged PFS in the same PSM subgroup (8.9 vs. 5.8 months; p = 0.03), with GTR representing the strongest predictor of PFS (p = 0.001) and OS (p = 0.0003) overall. Conclusion The benefit of TIT-aided GTR appears to overcome the drawbacks of potentially elevated motor functional risk in motor eloquent tumour localisation, leading to prolonged survival of patients with primary glioblastoma close to the CST.

Authors 16

1. Carolin Weiß Lucas corresponding

   University of Cologne · University Hospital Cologne

   Affiliation as printed

   Department of General Neurosurgery, Center of Neurosurgery, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany

2. Andrea Maria Faymonville

   University of Cologne · University Hospital Cologne · University Medical Centre Mannheim

   Affiliation as printed

   Department of General Neurosurgery, Center of Neurosurgery, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany

   Department of Neurosurgery, University Hospital Mannheim, Mannheim, Germany

3. Ricardo Loução

   Forschungszentrum Jülich · University of Cologne · University Hospital Cologne

   Affiliation as printed

   Department of General Neurosurgery, Center of Neurosurgery, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany

   Department of Stereotaxy and Functional Neurosurgery, Center of Neurosurgery, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany

   Institute of Neuroscience and Medicine (INM-4), Forschungszentrum Julich, Juelich, Germany

   Institute of Neuroscience and Medicine (INM‐4), Forschungszentrum Julich, Juelich, Germany

4. Catharina Schroeter

   University of Cologne · University Hospital Cologne

   Affiliation as printed

   Department of General Neurosurgery, Center of Neurosurgery, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany

5. Charlotte Nettekoven

   University of Cologne · University Hospital Cologne

   Affiliation as printed

   Department of General Neurosurgery, Center of Neurosurgery, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany

6. Ana‐Maria Oros‐Peusquens

   Forschungszentrum Jülich

   Affiliation as printed

   Institute of Neuroscience and Medicine (INM-4), Forschungszentrum Julich, Juelich, Germany

   Institute of Neuroscience and Medicine (INM‐4), Forschungszentrum Julich, Juelich, Germany

7. Karl‐Josef Langen

   Forschungszentrum Jülich

   Affiliation as printed

   Institute of Neuroscience and Medicine (INM-4), Forschungszentrum Julich, Juelich, Germany

   Institute of Neuroscience and Medicine (INM‐4), Forschungszentrum Julich, Juelich, Germany

8. Nadim Jon Shah Aachen Department of Neurology

   RWTH Aachen University · Forschungszentrum Jülich · Jülich Aachen Research Alliance

   Affiliation as printed

   Department of Neurology, RWTH Aachen University, Aachen, Germany

   Institute of Neuroscience and Medicine (INM-4), Forschungszentrum Julich, Juelich, Germany

   JARA - BRAIN - Translational Medicine, Aachen, Germany

   Institute of Neuroscience and Medicine (INM‐4), Forschungszentrum Julich, Juelich, Germany

   JARA ‐ BRAIN ‐ Translational Medicine, Aachen, Germany

9. Gabriele Stoffels

   Forschungszentrum Jülich

   Affiliation as printed

   Institute of Neuroscience and Medicine (INM-4), Forschungszentrum Julich, Juelich, Germany

   Institute of Neuroscience and Medicine (INM‐4), Forschungszentrum Julich, Juelich, Germany

10. Volker Neuschmelting

    University of Cologne · University Hospital Cologne

    Affiliation as printed

    Department of General Neurosurgery, Center of Neurosurgery, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany

11. Tobias Blau Aachen Department of Neurology

    RWTH Aachen University · University of Cologne · University Hospital Cologne

    Affiliation as printed

    Department of Neurology, RWTH Aachen University, Aachen, Germany

    Institute of Neuropathology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany

12. Hannah Neuschmelting

    Essen University Hospital

    Affiliation as printed

    Institute of Pathology and Neuropathology, University Hospital Essen, Essen, Germany

13. Martin Hellmich

    University of Cologne · University Hospital Cologne

    Affiliation as printed

    Institute for Diagnostic and Interventional Radiology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany

14. Martin Köcher

    Forschungszentrum Jülich · University of Cologne · University Hospital Cologne

    Affiliation as printed

    Department of General Neurosurgery, Center of Neurosurgery, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany

    Department of Stereotaxy and Functional Neurosurgery, Center of Neurosurgery, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany

    Institute of Neuroscience and Medicine (INM-4), Forschungszentrum Julich, Juelich, Germany

    Institute of Neuroscience and Medicine (INM‐4), Forschungszentrum Julich, Juelich, Germany

15. Christian Grefkes

    Forschungszentrum Jülich · University of Cologne · University Hospital Cologne

    Affiliation as printed

    Institute for Medical Statistics and Computational Biology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany

    Institute of Neuroscience and Medicine (INM-4), Forschungszentrum Julich, Juelich, Germany

    Institute of Neuroscience and Medicine (INM‐4), Forschungszentrum Julich, Juelich, Germany

16. Roland Goldbrunner

    University of Cologne · University Hospital Cologne

    Affiliation as printed

    Department of General Neurosurgery, Center of Neurosurgery, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany