title: Complete resection of contrast-enhancing tumor volume is associated with improved survival in recurrent glioblastoma-results from the DIRECTOR trial.
abstract: BACKGROUND
  The role of reoperation for recurrent glioblastoma (GBM) remains unclear. Prospective studies are lacking. Here, we studied the association of clinical outcome with extent of resection upon surgery for recurrent GBM in the patient cohort of DIRECTOR, a prospective randomized multicenter trial comparing 2 dose-intensified temozolomide regimens at recurrence of GBM.
  
  
  METHODS
  We analyzed prospectively collected clinical and imaging data from the DIRECTOR cohort (N = 105). Volumetric analysis was performed on gadolinium contrast-enhanced MRI as well as fluid attenuated inversion recovery/T2 MRI and correlated with PFS after initial progression (PFS2) and post-recurrence survival (PRS). Quality of life was monitored by the EORTC QLQ-C30 and QLQ-BN20 questionnaires at 8-week intervals.
  
  
  RESULTS
  Seventy-one patients received surgery at first recurrence. Prognostic factors, including age, MGMT promoter methylation, and Karnofsky performance score, were balanced between patients with and without reoperation. Outcome in patients with versus without surgery at recurrence was similar for PFS2 (2.0 mo vs 1.9 mo, P = .360) and PRS (11.4 mo vs 9.8 mo, P = .633). Among reoperated patients, post-surgery imaging was available in 59 cases. In these patients, complete resection of contrast-enhancing tumor (N = 40) versus residual detection of contrast enhancement (N = 19) was associated with improved PRS (12.9 mo [95% CI: 11.5-18.2] vs 6.5 mo [95% CI: 3.6-9.9], P < .001) and better quality of life. Incomplete tumor resection was associated with inferior PRS compared with patients who did not undergo surgery (6.5 vs 9.8 mo, P = .052). Quality of life was similar in these 2 groups.
  
  
  CONCLUSIONS
  Surgery at first recurrence of GBM improves outcome if complete resection of contrast-enhancing tumor is achieved.
authors.affiliation: Department of Neurosurgery, Ludwig-Maximilians University Munich, Munich, Germany (B.S., J.C.T.); Department of Neurology, University Hospital Zurich, Zurich, Switzerland (M.W., G.T., H.-G.W.); Department of Neurology, University Hospital Tübingen, Tübingen, Germany (G.T.); Department of Neurosurgery, University Hospital Frankfurt, Frankfurt am Main, Germany (C.S.); Department of Neurology, University Hospital Regensburg, Regensburg, Germany (P.H.); Department of Neurosurgery, University Hospital Düsseldorf, Düsseldorf, Germany (M.C.S.); Department of Neurology, University Hospital Bonn, Bonn, Germany (U.H.); Department of Neurosurgery, University Hospital Saarland, Homburg/Saar, Germany (R.K.); Department of Neurology, Knappschaftskrankenhaus Bochum, Bochum, Germany (U.S.); Department of Oncology, Vienna General Hospital, Vienna, Austria (C.M.); Institute of Neuropathology, University Hospital Düsseldorf, Düsseldorf, Germany (G.R.); Department of Neurology, University Hospital Heidelberg, Heidelberg, Germany (W.W.).
authors.forename: Bogdana
authors.initials: B
authors.lastname: Suchorska
authors.affiliation: Department of Neurosurgery, Ludwig-Maximilians University Munich, Munich, Germany (B.S., J.C.T.); Department of Neurology, University Hospital Zurich, Zurich, Switzerland (M.W., G.T., H.-G.W.); Department of Neurology, University Hospital Tübingen, Tübingen, Germany (G.T.); Department of Neurosurgery, University Hospital Frankfurt, Frankfurt am Main, Germany (C.S.); Department of Neurology, University Hospital Regensburg, Regensburg, Germany (P.H.); Department of Neurosurgery, University Hospital Düsseldorf, Düsseldorf, Germany (M.C.S.); Department of Neurology, University Hospital Bonn, Bonn, Germany (U.H.); Department of Neurosurgery, University Hospital Saarland, Homburg/Saar, Germany (R.K.); Department of Neurology, Knappschaftskrankenhaus Bochum, Bochum, Germany (U.S.); Department of Oncology, Vienna General Hospital, Vienna, Austria (C.M.); Institute of Neuropathology, University Hospital Düsseldorf, Düsseldorf, Germany (G.R.); Department of Neurology, University Hospital Heidelberg, Heidelberg, Germany (W.W.).
authors.forename: Michael
authors.initials: M
authors.lastname: Weller
authors.affiliation: Department of Neurosurgery, Ludwig-Maximilians University Munich, Munich, Germany (B.S., J.C.T.); Department of Neurology, University Hospital Zurich, Zurich, Switzerland (M.W., G.T., H.-G.W.); Department of Neurology, University Hospital Tübingen, Tübingen, Germany (G.T.); Department of Neurosurgery, University Hospital Frankfurt, Frankfurt am Main, Germany (C.S.); Department of Neurology, University Hospital Regensburg, Regensburg, Germany (P.H.); Department of Neurosurgery, University Hospital Düsseldorf, Düsseldorf, Germany (M.C.S.); Department of Neurology, University Hospital Bonn, Bonn, Germany (U.H.); Department of Neurosurgery, University Hospital Saarland, Homburg/Saar, Germany (R.K.); Department of Neurology, Knappschaftskrankenhaus Bochum, Bochum, Germany (U.S.); Department of Oncology, Vienna General Hospital, Vienna, Austria (C.M.); Institute of Neuropathology, University Hospital Düsseldorf, Düsseldorf, Germany (G.R.); Department of Neurology, University Hospital Heidelberg, Heidelberg, Germany (W.W.).
authors.forename: Ghazaleh
authors.initials: G
authors.lastname: Tabatabai
authors.affiliation: Department of Neurosurgery, Ludwig-Maximilians University Munich, Munich, Germany (B.S., J.C.T.); Department of Neurology, University Hospital Zurich, Zurich, Switzerland (M.W., G.T., H.-G.W.); Department of Neurology, University Hospital Tübingen, Tübingen, Germany (G.T.); Department of Neurosurgery, University Hospital Frankfurt, Frankfurt am Main, Germany (C.S.); Department of Neurology, University Hospital Regensburg, Regensburg, Germany (P.H.); Department of Neurosurgery, University Hospital Düsseldorf, Düsseldorf, Germany (M.C.S.); Department of Neurology, University Hospital Bonn, Bonn, Germany (U.H.); Department of Neurosurgery, University Hospital Saarland, Homburg/Saar, Germany (R.K.); Department of Neurology, Knappschaftskrankenhaus Bochum, Bochum, Germany (U.S.); Department of Oncology, Vienna General Hospital, Vienna, Austria (C.M.); Institute of Neuropathology, University Hospital Düsseldorf, Düsseldorf, Germany (G.R.); Department of Neurology, University Hospital Heidelberg, Heidelberg, Germany (W.W.).
authors.forename: Christian
authors.initials: C
authors.lastname: Senft
authors.affiliation: Department of Neurosurgery, Ludwig-Maximilians University Munich, Munich, Germany (B.S., J.C.T.); Department of Neurology, University Hospital Zurich, Zurich, Switzerland (M.W., G.T., H.-G.W.); Department of Neurology, University Hospital Tübingen, Tübingen, Germany (G.T.); Department of Neurosurgery, University Hospital Frankfurt, Frankfurt am Main, Germany (C.S.); Department of Neurology, University Hospital Regensburg, Regensburg, Germany (P.H.); Department of Neurosurgery, University Hospital Düsseldorf, Düsseldorf, Germany (M.C.S.); Department of Neurology, University Hospital Bonn, Bonn, Germany (U.H.); Department of Neurosurgery, University Hospital Saarland, Homburg/Saar, Germany (R.K.); Department of Neurology, Knappschaftskrankenhaus Bochum, Bochum, Germany (U.S.); Department of Oncology, Vienna General Hospital, Vienna, Austria (C.M.); Institute of Neuropathology, University Hospital Düsseldorf, Düsseldorf, Germany (G.R.); Department of Neurology, University Hospital Heidelberg, Heidelberg, Germany (W.W.).
authors.forename: Peter
authors.initials: P
authors.lastname: Hau
authors.affiliation: Department of Neurosurgery, Ludwig-Maximilians University Munich, Munich, Germany (B.S., J.C.T.); Department of Neurology, University Hospital Zurich, Zurich, Switzerland (M.W., G.T., H.-G.W.); Department of Neurology, University Hospital Tübingen, Tübingen, Germany (G.T.); Department of Neurosurgery, University Hospital Frankfurt, Frankfurt am Main, Germany (C.S.); Department of Neurology, University Hospital Regensburg, Regensburg, Germany (P.H.); Department of Neurosurgery, University Hospital Düsseldorf, Düsseldorf, Germany (M.C.S.); Department of Neurology, University Hospital Bonn, Bonn, Germany (U.H.); Department of Neurosurgery, University Hospital Saarland, Homburg/Saar, Germany (R.K.); Department of Neurology, Knappschaftskrankenhaus Bochum, Bochum, Germany (U.S.); Department of Oncology, Vienna General Hospital, Vienna, Austria (C.M.); Institute of Neuropathology, University Hospital Düsseldorf, Düsseldorf, Germany (G.R.); Department of Neurology, University Hospital Heidelberg, Heidelberg, Germany (W.W.).
authors.forename: Michael C
authors.initials: MC
authors.lastname: Sabel
authors.affiliation: Department of Neurosurgery, Ludwig-Maximilians University Munich, Munich, Germany (B.S., J.C.T.); Department of Neurology, University Hospital Zurich, Zurich, Switzerland (M.W., G.T., H.-G.W.); Department of Neurology, University Hospital Tübingen, Tübingen, Germany (G.T.); Department of Neurosurgery, University Hospital Frankfurt, Frankfurt am Main, Germany (C.S.); Department of Neurology, University Hospital Regensburg, Regensburg, Germany (P.H.); Department of Neurosurgery, University Hospital Düsseldorf, Düsseldorf, Germany (M.C.S.); Department of Neurology, University Hospital Bonn, Bonn, Germany (U.H.); Department of Neurosurgery, University Hospital Saarland, Homburg/Saar, Germany (R.K.); Department of Neurology, Knappschaftskrankenhaus Bochum, Bochum, Germany (U.S.); Department of Oncology, Vienna General Hospital, Vienna, Austria (C.M.); Institute of Neuropathology, University Hospital Düsseldorf, Düsseldorf, Germany (G.R.); Department of Neurology, University Hospital Heidelberg, Heidelberg, Germany (W.W.).
authors.forename: Ulrich
authors.initials: U
authors.lastname: Herrlinger
authors.affiliation: Department of Neurosurgery, Ludwig-Maximilians University Munich, Munich, Germany (B.S., J.C.T.); Department of Neurology, University Hospital Zurich, Zurich, Switzerland (M.W., G.T., H.-G.W.); Department of Neurology, University Hospital Tübingen, Tübingen, Germany (G.T.); Department of Neurosurgery, University Hospital Frankfurt, Frankfurt am Main, Germany (C.S.); Department of Neurology, University Hospital Regensburg, Regensburg, Germany (P.H.); Department of Neurosurgery, University Hospital Düsseldorf, Düsseldorf, Germany (M.C.S.); Department of Neurology, University Hospital Bonn, Bonn, Germany (U.H.); Department of Neurosurgery, University Hospital Saarland, Homburg/Saar, Germany (R.K.); Department of Neurology, Knappschaftskrankenhaus Bochum, Bochum, Germany (U.S.); Department of Oncology, Vienna General Hospital, Vienna, Austria (C.M.); Institute of Neuropathology, University Hospital Düsseldorf, Düsseldorf, Germany (G.R.); Department of Neurology, University Hospital Heidelberg, Heidelberg, Germany (W.W.).
authors.forename: Ralf
authors.initials: R
authors.lastname: Ketter
authors.affiliation: Department of Neurosurgery, Ludwig-Maximilians University Munich, Munich, Germany (B.S., J.C.T.); Department of Neurology, University Hospital Zurich, Zurich, Switzerland (M.W., G.T., H.-G.W.); Department of Neurology, University Hospital Tübingen, Tübingen, Germany (G.T.); Department of Neurosurgery, University Hospital Frankfurt, Frankfurt am Main, Germany (C.S.); Department of Neurology, University Hospital Regensburg, Regensburg, Germany (P.H.); Department of Neurosurgery, University Hospital Düsseldorf, Düsseldorf, Germany (M.C.S.); Department of Neurology, University Hospital Bonn, Bonn, Germany (U.H.); Department of Neurosurgery, University Hospital Saarland, Homburg/Saar, Germany (R.K.); Department of Neurology, Knappschaftskrankenhaus Bochum, Bochum, Germany (U.S.); Department of Oncology, Vienna General Hospital, Vienna, Austria (C.M.); Institute of Neuropathology, University Hospital Düsseldorf, Düsseldorf, Germany (G.R.); Department of Neurology, University Hospital Heidelberg, Heidelberg, Germany (W.W.).
authors.forename: Uwe
authors.initials: U
authors.lastname: Schlegel
authors.affiliation: Department of Neurosurgery, Ludwig-Maximilians University Munich, Munich, Germany (B.S., J.C.T.); Department of Neurology, University Hospital Zurich, Zurich, Switzerland (M.W., G.T., H.-G.W.); Department of Neurology, University Hospital Tübingen, Tübingen, Germany (G.T.); Department of Neurosurgery, University Hospital Frankfurt, Frankfurt am Main, Germany (C.S.); Department of Neurology, University Hospital Regensburg, Regensburg, Germany (P.H.); Department of Neurosurgery, University Hospital Düsseldorf, Düsseldorf, Germany (M.C.S.); Department of Neurology, University Hospital Bonn, Bonn, Germany (U.H.); Department of Neurosurgery, University Hospital Saarland, Homburg/Saar, Germany (R.K.); Department of Neurology, Knappschaftskrankenhaus Bochum, Bochum, Germany (U.S.); Department of Oncology, Vienna General Hospital, Vienna, Austria (C.M.); Institute of Neuropathology, University Hospital Düsseldorf, Düsseldorf, Germany (G.R.); Department of Neurology, University Hospital Heidelberg, Heidelberg, Germany (W.W.).
authors.forename: Christine
authors.initials: C
authors.lastname: Marosi
authors.affiliation: Department of Neurosurgery, Ludwig-Maximilians University Munich, Munich, Germany (B.S., J.C.T.); Department of Neurology, University Hospital Zurich, Zurich, Switzerland (M.W., G.T., H.-G.W.); Department of Neurology, University Hospital Tübingen, Tübingen, Germany (G.T.); Department of Neurosurgery, University Hospital Frankfurt, Frankfurt am Main, Germany (C.S.); Department of Neurology, University Hospital Regensburg, Regensburg, Germany (P.H.); Department of Neurosurgery, University Hospital Düsseldorf, Düsseldorf, Germany (M.C.S.); Department of Neurology, University Hospital Bonn, Bonn, Germany (U.H.); Department of Neurosurgery, University Hospital Saarland, Homburg/Saar, Germany (R.K.); Department of Neurology, Knappschaftskrankenhaus Bochum, Bochum, Germany (U.S.); Department of Oncology, Vienna General Hospital, Vienna, Austria (C.M.); Institute of Neuropathology, University Hospital Düsseldorf, Düsseldorf, Germany (G.R.); Department of Neurology, University Hospital Heidelberg, Heidelberg, Germany (W.W.).
authors.forename: Guido
authors.initials: G
authors.lastname: Reifenberger
authors.affiliation: Department of Neurosurgery, Ludwig-Maximilians University Munich, Munich, Germany (B.S., J.C.T.); Department of Neurology, University Hospital Zurich, Zurich, Switzerland (M.W., G.T., H.-G.W.); Department of Neurology, University Hospital Tübingen, Tübingen, Germany (G.T.); Department of Neurosurgery, University Hospital Frankfurt, Frankfurt am Main, Germany (C.S.); Department of Neurology, University Hospital Regensburg, Regensburg, Germany (P.H.); Department of Neurosurgery, University Hospital Düsseldorf, Düsseldorf, Germany (M.C.S.); Department of Neurology, University Hospital Bonn, Bonn, Germany (U.H.); Department of Neurosurgery, University Hospital Saarland, Homburg/Saar, Germany (R.K.); Department of Neurology, Knappschaftskrankenhaus Bochum, Bochum, Germany (U.S.); Department of Oncology, Vienna General Hospital, Vienna, Austria (C.M.); Institute of Neuropathology, University Hospital Düsseldorf, Düsseldorf, Germany (G.R.); Department of Neurology, University Hospital Heidelberg, Heidelberg, Germany (W.W.).
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wick
authors.affiliation: Department of Neurosurgery, Ludwig-Maximilians University Munich, Munich, Germany (B.S., J.C.T.); Department of Neurology, University Hospital Zurich, Zurich, Switzerland (M.W., G.T., H.-G.W.); Department of Neurology, University Hospital Tübingen, Tübingen, Germany (G.T.); Department of Neurosurgery, University Hospital Frankfurt, Frankfurt am Main, Germany (C.S.); Department of Neurology, University Hospital Regensburg, Regensburg, Germany (P.H.); Department of Neurosurgery, University Hospital Düsseldorf, Düsseldorf, Germany (M.C.S.); Department of Neurology, University Hospital Bonn, Bonn, Germany (U.H.); Department of Neurosurgery, University Hospital Saarland, Homburg/Saar, Germany (R.K.); Department of Neurology, Knappschaftskrankenhaus Bochum, Bochum, Germany (U.S.); Department of Oncology, Vienna General Hospital, Vienna, Austria (C.M.); Institute of Neuropathology, University Hospital Düsseldorf, Düsseldorf, Germany (G.R.); Department of Neurology, University Hospital Heidelberg, Heidelberg, Germany (W.W.).
authors.forename: Jörg C
authors.initials: JC
authors.lastname: Tonn
authors.affiliation: Department of Neurosurgery, Ludwig-Maximilians University Munich, Munich, Germany (B.S., J.C.T.); Department of Neurology, University Hospital Zurich, Zurich, Switzerland (M.W., G.T., H.-G.W.); Department of Neurology, University Hospital Tübingen, Tübingen, Germany (G.T.); Department of Neurosurgery, University Hospital Frankfurt, Frankfurt am Main, Germany (C.S.); Department of Neurology, University Hospital Regensburg, Regensburg, Germany (P.H.); Department of Neurosurgery, University Hospital Düsseldorf, Düsseldorf, Germany (M.C.S.); Department of Neurology, University Hospital Bonn, Bonn, Germany (U.H.); Department of Neurosurgery, University Hospital Saarland, Homburg/Saar, Germany (R.K.); Department of Neurology, Knappschaftskrankenhaus Bochum, Bochum, Germany (U.S.); Department of Oncology, Vienna General Hospital, Vienna, Austria (C.M.); Institute of Neuropathology, University Hospital Düsseldorf, Düsseldorf, Germany (G.R.); Department of Neurology, University Hospital Heidelberg, Heidelberg, Germany (W.W.).
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Wirsching
mesh_terms: D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000401:mortality* / Q000473:pathology / Q000601:surgery; D003287:Contrast Media; D005260:Female; D005500:Follow-Up Studies; D005909:Glioblastoma / Q000401:mortality* / Q000473:pathology / Q000601:surgery; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000401:mortality* / Q000473:pathology / Q000601:surgery; D009367:Neoplasm Staging; D019635:Neurosurgical Procedures / Q000401:mortality*; D011379:Prognosis; D011446:Prospective Studies; D011788:Quality of Life; D012189:Retrospective Studies; D015996:Survival Rate; D047368:Tumor Burden; D055815:Young Adult
chemical_list: D003287:Contrast Media
keywords: DIRECTOR; outcome; re-operation; recurrent GBM; volumetry
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