PL01.5.A ASSOCIATION BETWEEN RESTING-STATE-NETWORK FUNCTIONAL CONNECTIVITY AND SURVIVAL IN RECURRENT GLIOMAS DIAGNOSED USING FET PET

Neuro-Oncology, vol. 26, pp. v1

Abstract

Abstract BACKGROUND Functional connectivity between glioma-infiltrated brain tissue and remote cortical regions has been linked to overall survival (OS) in patients with newly diagnosed glioblastoma. Here, we studied the association of functional connectivity between tumor and resting-state networks and OS in patients with recurrent gliomas. PATIENTS AND METHODS The study included 82 patients (age range, 26-81 years; median ECOG performance score, 0) with recurrent gliomas (CNS WHO grade 4 glioblastoma, n=57; CNS WHO grade 3 and 4 astrocytoma, n=12; CNS WHO grade 2 and 3 oligodendroglioma, n=13) who had undergone first-line therapy by current guidelines. In addition to the RANO criteria for anatomical MRI, diagnosis of glioma recurrence was confirmed by amino acid PET using the tracer O-(2-[18F]-fluoroethyl)-L-tyrosine (FET). FET PET and resting-state functional MRI were simultaneously acquired on a 3T hybrid PET/MR scanner. A seed-based dual regression analysis was performed to determine the functional connectivity between metabolically active recurrent tumors and a set of seven canonical resting state networks. RESULTS Average functional connectivity was significantly higher (p=0.028) in oligodendrogliomas (z-score, 6.9±1.9) and astrocytomas (z-score, 5.5±1.3) than in glioblastomas (z-score, 4.9±2.6) and was inversely related to the tumor grade (p=0.031). Univariate Cox regression analysis revealed a significant positive association between OS and tumor connectivity with the visual, somatomotor, and dorsal attention network (all p<0.05). Subsequent stepwise multivariate Cox regression analysis refined this association to the dorsal attention network alone (HR, 0.88; 95% CI, 0.80-0.97; p=0.007). Patients with the highest functional connectivity (z-score >8.3, n=21) had a median OS of 31.4 months, while those with the lowest functional connectivity (z-score <4.3, n=21) had a median OS of 10.6 months. Functional connectivity between tumors and the dorsal attention network showed an independent association with OS (p=0.002) in a multivariate model, including the metabolic tumor volume (p=0.003). CONCLUSION Recurrent gliomas exhibit significant functional connectivity to most of the major known resting-state networks, which was generally higher in astrocytomas and oligodendrogliomas. The data suggest that high functional connectivity between the tumor and the dorsal attention network is an independent prognostic factor for improved OS.

Authors 16

1. Michel Friedrich

   Forschungszentrum Jülich

   Affiliation as printed

   Institute of Neuroscience and Medicine (INM-3), Forschungszentrum Juelich , Juelich,

2. Jan‐Michael Werner

   University of Cologne · University Hospital Cologne

   Affiliation as printed

   Center of Integrated Oncology (CIO), Universities of Aachen, Bonn, Cologne , and Duesseldorf,

   Department of Neurology, Faculty of Medicine and University Hospital Cologne, University of Cologne , Cologne,

3. Jörg Steinbach

   University Hospital Frankfurt · Goethe University Frankfurt

   Affiliation as printed

   Department of Neuro-Oncology, University Hospital Frankfurt - Goethe-University , Frankfurt,

4. Michael Sabel

   Düsseldorf University Hospital · Heinrich Heine University Düsseldorf

   Affiliation as printed

   Center of Integrated Oncology (CIO), Universities of Aachen, Bonn, Cologne , and Duesseldorf,

   Department of Neurosurgery, Heinrich Heine University Medical Faculty and University Hospital Duesseldorf , Duesseldorf,

5. Ulrich Herrlinger

   University Hospital Bonn

   Affiliation as printed

   Center of Integrated Oncology (CIO), Universities of Aachen, Bonn, Cologne , and Duesseldorf,

   Department of Neurooncology, Center for Neurology, University Hospital Bonn , Bonn,

6. Marc Dieter Piroth

   Witten/Herdecke University · Helios Universitätsklinikum Wuppertal

   Affiliation as printed

   Department of Radiation Oncology, Helios University Hospital Wuppertal, Faculty of Health, Witten/Herdecke University , Wuppertal,

7. Gabriele Stoffels
   Affiliation as printed

   Institute of Neuroscience and Medicine (INM-)

8. Philipp Lohmann Aachen Department of Nuclear Medicine

   RWTH Aachen University · Universitätsklinikum Aachen

   Affiliation as printed

   Department of Nuclear Medicine, RWTH University Hospital Aachen, RWTH University Aachen , Aachen,

   Institute of Neuroscience and Medicine (INM-)

9. Nadim Jon Shah Aachen Department of Neurology

   RWTH Aachen University · Universitätsklinikum Aachen · Jülich Aachen Research Alliance

   Affiliation as printed

   Department of Neurology, RWTH University Hospital Aachen, RWTH University Aachen , Aachen,

   Institute of Neuroscience and Medicine (INM-)

   Juelich-Aachen Research Alliance (JARA), Section JARA-Brain , Juelich,

10. Maximilian Ingolf Ruge

    University of Cologne · University Hospital Cologne

    Affiliation as printed

    Center of Integrated Oncology (CIO), Universities of Aachen, Bonn, Cologne , and Duesseldorf,

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

11. Felix Manuel Mottaghy Aachen Department of Nuclear Medicine

    RWTH Aachen University · Universitätsklinikum Aachen · Maastricht University · Maastricht University Medical Centre

    Affiliation as printed

    Department of Nuclear Medicine, RWTH University Hospital Aachen, RWTH University Aachen , Aachen,

    Department of Radiology and Nuclear Medicine, Maastricht University Medical Center , Maastricht,

12. Roland Goldbrunner

    University of Cologne · University Hospital Cologne

    Affiliation as printed

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

    Center of Integrated Oncology (CIO), Universities of Aachen, Bonn, Cologne , and Duesseldorf,

13. Karl‐Josef Langen Aachen Department of Nuclear Medicine

    RWTH Aachen University · Universitätsklinikum Aachen

    Affiliation as printed

    Department of Nuclear Medicine, RWTH University Hospital Aachen, RWTH University Aachen , Aachen,

    Institute of Neuroscience and Medicine (INM-)

14. Gereon R. Fink

    Forschungszentrum Jülich · University of Cologne · University Hospital Cologne

    Affiliation as printed

    Department of Neurology, Faculty of Medicine and University Hospital Cologne, University of Cologne , Cologne,

    Institute of Neuroscience and Medicine (INM-3), Forschungszentrum Juelich , Juelich,

15. Martin Köcher

    University of Cologne · University Hospital Cologne

    Affiliation as printed

    Center of Integrated Oncology (CIO), Universities of Aachen, Bonn, Cologne , and Duesseldorf,

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

    Institute of Neuroscience and Medicine (INM-)

16. Norbert Galldiks

    Forschungszentrum Jülich · University of Cologne · University Hospital Cologne

    Affiliation as printed

    Center of Integrated Oncology (CIO), Universities of Aachen, Bonn, Cologne , and Duesseldorf,

    Department of Neurology, Faculty of Medicine and University Hospital Cologne, University of Cologne , Cologne,

    Institute of Neuroscience and Medicine (INM-3), Forschungszentrum Juelich , Juelich,