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February 04, 2020; 94 (5) Article

Olfactory function as an independent prognostic factor in glioblastoma

Sied Kebir, Elke Hattingen, Michael Niessen, Laurèl Rauschenbach, Rolf Fimmers, Thomas Hummel, Niklas Schäfer, Lazaros Lazaridis, Christoph Kleinschnitz, Ulrich Herrlinger, Björn Scheffler, Martin Glas
First published December 12, 2019, DOI: https://doi.org/10.1212/WNL.0000000000008744
Sied Kebir
From the Division of Clinical Neurooncology (S.K., L.L., M.G.), Department of Neurology (C.K.), West German Cancer Center (S.K., L.R., B.S., M.G.), and Department of Neurosurgery (L.R.), University Hospital Essen, University Duisburg-Essen; Division of Clinical Neurooncology, Department of Neurology and Center of Integrated Oncology (S.K., M.N., N.S., U.H., M.G.), and Institute for Medical Biometry, Informatics, and Epidemiology (R.F.), University of Bonn Medical Center; Department of Neuroradiology (E.H.), Goethe University Hospital, Frankfurt Am Main; Department of Otorhinolaryngology, Smell and Taste Clinic (T.H.), TU Dresden; DKFZ-Division Translational Neurooncology at the West German Cancer Center (S.K., B.S., M.G.), German Cancer Research Center (DKFZ), Heidelberg; and German Cancer Consortium (S.K., B.S., M.G.), Partner Site University Hospital Essen, Germany.
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Elke Hattingen
From the Division of Clinical Neurooncology (S.K., L.L., M.G.), Department of Neurology (C.K.), West German Cancer Center (S.K., L.R., B.S., M.G.), and Department of Neurosurgery (L.R.), University Hospital Essen, University Duisburg-Essen; Division of Clinical Neurooncology, Department of Neurology and Center of Integrated Oncology (S.K., M.N., N.S., U.H., M.G.), and Institute for Medical Biometry, Informatics, and Epidemiology (R.F.), University of Bonn Medical Center; Department of Neuroradiology (E.H.), Goethe University Hospital, Frankfurt Am Main; Department of Otorhinolaryngology, Smell and Taste Clinic (T.H.), TU Dresden; DKFZ-Division Translational Neurooncology at the West German Cancer Center (S.K., B.S., M.G.), German Cancer Research Center (DKFZ), Heidelberg; and German Cancer Consortium (S.K., B.S., M.G.), Partner Site University Hospital Essen, Germany.
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Michael Niessen
From the Division of Clinical Neurooncology (S.K., L.L., M.G.), Department of Neurology (C.K.), West German Cancer Center (S.K., L.R., B.S., M.G.), and Department of Neurosurgery (L.R.), University Hospital Essen, University Duisburg-Essen; Division of Clinical Neurooncology, Department of Neurology and Center of Integrated Oncology (S.K., M.N., N.S., U.H., M.G.), and Institute for Medical Biometry, Informatics, and Epidemiology (R.F.), University of Bonn Medical Center; Department of Neuroradiology (E.H.), Goethe University Hospital, Frankfurt Am Main; Department of Otorhinolaryngology, Smell and Taste Clinic (T.H.), TU Dresden; DKFZ-Division Translational Neurooncology at the West German Cancer Center (S.K., B.S., M.G.), German Cancer Research Center (DKFZ), Heidelberg; and German Cancer Consortium (S.K., B.S., M.G.), Partner Site University Hospital Essen, Germany.
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Laurèl Rauschenbach
From the Division of Clinical Neurooncology (S.K., L.L., M.G.), Department of Neurology (C.K.), West German Cancer Center (S.K., L.R., B.S., M.G.), and Department of Neurosurgery (L.R.), University Hospital Essen, University Duisburg-Essen; Division of Clinical Neurooncology, Department of Neurology and Center of Integrated Oncology (S.K., M.N., N.S., U.H., M.G.), and Institute for Medical Biometry, Informatics, and Epidemiology (R.F.), University of Bonn Medical Center; Department of Neuroradiology (E.H.), Goethe University Hospital, Frankfurt Am Main; Department of Otorhinolaryngology, Smell and Taste Clinic (T.H.), TU Dresden; DKFZ-Division Translational Neurooncology at the West German Cancer Center (S.K., B.S., M.G.), German Cancer Research Center (DKFZ), Heidelberg; and German Cancer Consortium (S.K., B.S., M.G.), Partner Site University Hospital Essen, Germany.
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Rolf Fimmers
From the Division of Clinical Neurooncology (S.K., L.L., M.G.), Department of Neurology (C.K.), West German Cancer Center (S.K., L.R., B.S., M.G.), and Department of Neurosurgery (L.R.), University Hospital Essen, University Duisburg-Essen; Division of Clinical Neurooncology, Department of Neurology and Center of Integrated Oncology (S.K., M.N., N.S., U.H., M.G.), and Institute for Medical Biometry, Informatics, and Epidemiology (R.F.), University of Bonn Medical Center; Department of Neuroradiology (E.H.), Goethe University Hospital, Frankfurt Am Main; Department of Otorhinolaryngology, Smell and Taste Clinic (T.H.), TU Dresden; DKFZ-Division Translational Neurooncology at the West German Cancer Center (S.K., B.S., M.G.), German Cancer Research Center (DKFZ), Heidelberg; and German Cancer Consortium (S.K., B.S., M.G.), Partner Site University Hospital Essen, Germany.
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Thomas Hummel
From the Division of Clinical Neurooncology (S.K., L.L., M.G.), Department of Neurology (C.K.), West German Cancer Center (S.K., L.R., B.S., M.G.), and Department of Neurosurgery (L.R.), University Hospital Essen, University Duisburg-Essen; Division of Clinical Neurooncology, Department of Neurology and Center of Integrated Oncology (S.K., M.N., N.S., U.H., M.G.), and Institute for Medical Biometry, Informatics, and Epidemiology (R.F.), University of Bonn Medical Center; Department of Neuroradiology (E.H.), Goethe University Hospital, Frankfurt Am Main; Department of Otorhinolaryngology, Smell and Taste Clinic (T.H.), TU Dresden; DKFZ-Division Translational Neurooncology at the West German Cancer Center (S.K., B.S., M.G.), German Cancer Research Center (DKFZ), Heidelberg; and German Cancer Consortium (S.K., B.S., M.G.), Partner Site University Hospital Essen, Germany.
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Niklas Schäfer
From the Division of Clinical Neurooncology (S.K., L.L., M.G.), Department of Neurology (C.K.), West German Cancer Center (S.K., L.R., B.S., M.G.), and Department of Neurosurgery (L.R.), University Hospital Essen, University Duisburg-Essen; Division of Clinical Neurooncology, Department of Neurology and Center of Integrated Oncology (S.K., M.N., N.S., U.H., M.G.), and Institute for Medical Biometry, Informatics, and Epidemiology (R.F.), University of Bonn Medical Center; Department of Neuroradiology (E.H.), Goethe University Hospital, Frankfurt Am Main; Department of Otorhinolaryngology, Smell and Taste Clinic (T.H.), TU Dresden; DKFZ-Division Translational Neurooncology at the West German Cancer Center (S.K., B.S., M.G.), German Cancer Research Center (DKFZ), Heidelberg; and German Cancer Consortium (S.K., B.S., M.G.), Partner Site University Hospital Essen, Germany.
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Lazaros Lazaridis
From the Division of Clinical Neurooncology (S.K., L.L., M.G.), Department of Neurology (C.K.), West German Cancer Center (S.K., L.R., B.S., M.G.), and Department of Neurosurgery (L.R.), University Hospital Essen, University Duisburg-Essen; Division of Clinical Neurooncology, Department of Neurology and Center of Integrated Oncology (S.K., M.N., N.S., U.H., M.G.), and Institute for Medical Biometry, Informatics, and Epidemiology (R.F.), University of Bonn Medical Center; Department of Neuroradiology (E.H.), Goethe University Hospital, Frankfurt Am Main; Department of Otorhinolaryngology, Smell and Taste Clinic (T.H.), TU Dresden; DKFZ-Division Translational Neurooncology at the West German Cancer Center (S.K., B.S., M.G.), German Cancer Research Center (DKFZ), Heidelberg; and German Cancer Consortium (S.K., B.S., M.G.), Partner Site University Hospital Essen, Germany.
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Christoph Kleinschnitz
From the Division of Clinical Neurooncology (S.K., L.L., M.G.), Department of Neurology (C.K.), West German Cancer Center (S.K., L.R., B.S., M.G.), and Department of Neurosurgery (L.R.), University Hospital Essen, University Duisburg-Essen; Division of Clinical Neurooncology, Department of Neurology and Center of Integrated Oncology (S.K., M.N., N.S., U.H., M.G.), and Institute for Medical Biometry, Informatics, and Epidemiology (R.F.), University of Bonn Medical Center; Department of Neuroradiology (E.H.), Goethe University Hospital, Frankfurt Am Main; Department of Otorhinolaryngology, Smell and Taste Clinic (T.H.), TU Dresden; DKFZ-Division Translational Neurooncology at the West German Cancer Center (S.K., B.S., M.G.), German Cancer Research Center (DKFZ), Heidelberg; and German Cancer Consortium (S.K., B.S., M.G.), Partner Site University Hospital Essen, Germany.
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Ulrich Herrlinger
From the Division of Clinical Neurooncology (S.K., L.L., M.G.), Department of Neurology (C.K.), West German Cancer Center (S.K., L.R., B.S., M.G.), and Department of Neurosurgery (L.R.), University Hospital Essen, University Duisburg-Essen; Division of Clinical Neurooncology, Department of Neurology and Center of Integrated Oncology (S.K., M.N., N.S., U.H., M.G.), and Institute for Medical Biometry, Informatics, and Epidemiology (R.F.), University of Bonn Medical Center; Department of Neuroradiology (E.H.), Goethe University Hospital, Frankfurt Am Main; Department of Otorhinolaryngology, Smell and Taste Clinic (T.H.), TU Dresden; DKFZ-Division Translational Neurooncology at the West German Cancer Center (S.K., B.S., M.G.), German Cancer Research Center (DKFZ), Heidelberg; and German Cancer Consortium (S.K., B.S., M.G.), Partner Site University Hospital Essen, Germany.
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Björn Scheffler
From the Division of Clinical Neurooncology (S.K., L.L., M.G.), Department of Neurology (C.K.), West German Cancer Center (S.K., L.R., B.S., M.G.), and Department of Neurosurgery (L.R.), University Hospital Essen, University Duisburg-Essen; Division of Clinical Neurooncology, Department of Neurology and Center of Integrated Oncology (S.K., M.N., N.S., U.H., M.G.), and Institute for Medical Biometry, Informatics, and Epidemiology (R.F.), University of Bonn Medical Center; Department of Neuroradiology (E.H.), Goethe University Hospital, Frankfurt Am Main; Department of Otorhinolaryngology, Smell and Taste Clinic (T.H.), TU Dresden; DKFZ-Division Translational Neurooncology at the West German Cancer Center (S.K., B.S., M.G.), German Cancer Research Center (DKFZ), Heidelberg; and German Cancer Consortium (S.K., B.S., M.G.), Partner Site University Hospital Essen, Germany.
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Martin Glas
From the Division of Clinical Neurooncology (S.K., L.L., M.G.), Department of Neurology (C.K.), West German Cancer Center (S.K., L.R., B.S., M.G.), and Department of Neurosurgery (L.R.), University Hospital Essen, University Duisburg-Essen; Division of Clinical Neurooncology, Department of Neurology and Center of Integrated Oncology (S.K., M.N., N.S., U.H., M.G.), and Institute for Medical Biometry, Informatics, and Epidemiology (R.F.), University of Bonn Medical Center; Department of Neuroradiology (E.H.), Goethe University Hospital, Frankfurt Am Main; Department of Otorhinolaryngology, Smell and Taste Clinic (T.H.), TU Dresden; DKFZ-Division Translational Neurooncology at the West German Cancer Center (S.K., B.S., M.G.), German Cancer Research Center (DKFZ), Heidelberg; and German Cancer Consortium (S.K., B.S., M.G.), Partner Site University Hospital Essen, Germany.
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Citation
Olfactory function as an independent prognostic factor in glioblastoma
Sied Kebir, Elke Hattingen, Michael Niessen, Laurèl Rauschenbach, Rolf Fimmers, Thomas Hummel, Niklas Schäfer, Lazaros Lazaridis, Christoph Kleinschnitz, Ulrich Herrlinger, Björn Scheffler, Martin Glas
Neurology Feb 2020, 94 (5) e529-e537; DOI: 10.1212/WNL.0000000000008744

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Abstract

Objective To determine the role of olfactory function in patients with glioblastoma multiforme (GBM) as a prognostic clinical measure.

Methods In a prospective case-control study, olfactory testing was performed in 73 patients with primary GBM at baseline during first-line treatment and at later follow-ups. An age-matched control cohort consisted of 49 patients with neurologic diseases, excluding those known to affect olfactory function per se. Depending on the olfactory testing score, patients were allotted to a hyposmia group (HG) or normosmia group (NG). MRI analysis was performed to assess whether tumor location affects olfactory pathways.

Results Patients with GBM had olfactory dysfunction significantly more often compared to the control cohort (p = 0.003). Tumor location could not explain this finding since no relevant difference in MRI-based olfactory pathway involvement was found between HG and NG (p = 0.131). Patients with olfactory dysfunction had significantly worse overall survival (OS) and progression-free survival (PFS) compared to those without dysfunction (median OS 20.9 vs 40.6 months, p = 0.035; median PFS, 9 vs 19 months, p = 0.022). Multivariate analysis in patients without MRI-based involvement of olfactory pathways confirmed olfaction is an independent prognostic factor for OS (hazard ratio [HR] 0.43; p = 0.042) and PFS (HR 0.51; p = 0.049).

Conclusion This pilot study provides the first indication that olfactory dysfunction is frequently observed in GBM and may be associated with worse survival outcome in GBM. However, validation of these results in an independent cohort is needed.

Glossary

CCNU=
lomustine;
CI=
confidence interval;
GBM=
glioblastoma multiforme;
HG=
hyposmia group;
HR=
hazard ratio;
KPS=
Karnofsky Performance Scale;
MGMT=
O6-methylguanine-DNA methyltransferase;
NG=
normosmia group;
OB=
olfactory bulb;
OS=
overall survival;
PFS=
progression-free survival;
RMS=
rostral migratory stream;
SSc=
Sniffin' Sticks score;
SVZ=
subventricular zone

Footnotes

  • Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • ↵* Shared last authorship.

  • Received March 15, 2019.
  • Accepted in final form August 1, 2019.
  • © 2019 American Academy of Neurology
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Letters: Rapid online correspondence

  • Reader response: Olfactory function as an independent prognostic factor in glioblastoma
    • L. Nicolas Gonzalez Castro, MD, PhD, Neuro-Oncology, Dana-Farber Cancer Institute
    Submitted February 27, 2020
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