Volumetric Study Reveals the Relationship Between Outcome and Early Radiographic Response During Bevacizumab-Containing Chemoradiotherapy for Unresectable Glioblastoma

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  • Kosuke Takigawa
    Department of Neurosurgery, Graduate school of Medical Sciences, Kyushu University
  • Nobuhiro Hata
    Department of Neurosurgerey, Graduate School of Medical Sciences, Kyushu University, Fukuoka
  • Yuhei Michiwaki
    Department of Neurosurgery, International university of health and welfare NARITA Hospital
  • Akio Hiwatashi
    Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
  • Hajime Yonezawa
    Department of Neurosurgery, Graduate School of Medical and Dental Sciences, Kagoshima University, Japan
  • Daisuke Kuga
    Department of Neurosurgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
  • Ryusuke Hatae
    Department of Neurosurgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
  • Yuhei Sangatsuda
    Department of Neurosurgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
  • Yutaka Fujioka
    Department of Neurosurgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka
  • Yusuke Funakoshi
    Department of Neurosurgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka
  • Ryosuke Otsuji
    Department of Neurosurgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka.
  • Aki Sako
    Kyushu University Hospital: Kyushu Daigaku Byoin
  • Osamu Togao
    Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka
  • Takashi Yoshiura
    Department of Radiology, Graduate School of Medical and Dental Sciences, Kagoshima University, Japan
  • Koji Yoshimoto
    Department of Neurosurgery, Graduate School of Medical and Dental Sciences, Kagoshima University, Japan.
  • Masahiro Mizoguchi
    Department of Neurosurgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka

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<title>Abstract</title> <p>Purpose: Although we have shown the clinical benefit of bevacizumab (BEV) in the treatment of unresectable newly diagnosed glioblastomas (nd-GBMs), the relationship between early radiographic response and survival outcome remains unclear. We performed a volumetric study of the early radiographic responses in nd-GBMs treated with BEV.Methods: Twenty-two patients with unresectable nd-GBM treated with BEV during concurrent temozolomide radiotherapy were analyzed. Early responses in fluid-attenuated inversion-recovery (FLAIR) and gadolinium-enhanced T1-weighted images (GdT1WI) were interpreted by an experienced neuroradiologist. Volumetric changes were evaluated using diffusion-weighted imaging (DWI) and GdT1WI according to the Response assessment in neuro-oncology (RANO) criteria. The results were categorized into improved (complete response [CR] or partial response [PR]) or non-improved (stable disease [SD] or progressive disease [PD]) groups; outcomes were compared using Kaplan-Meier analysis.Results: The volumetric GdT1WI improvement was a significant predictive factor for overall survival (OS) prolongation (<italic>p</italic>=0.0093, median OS: 24.7 vs. 13.6 months); however, FLAIR and DWI images were not predictive. The threshold for the neuroradiologist-interpretation of improvement in GdT1WI was nearly 20% of volume reduction, which was lesser than 50%, the definition of PR applied in RANO criteria; however, even less stringent neuroradiologist-interpretation could successfully predict OS prolongation (improved vs. non-improved: <italic>p</italic>=0.0067, median OS: 17.6 vs. 8.3 months). Significant impact of OS on the early response in volumetric GdT1WI was observed within the cut-off range of 20 to 50% (20%, <italic>p</italic>=0.0315; 30%, <italic>p</italic>=0.087; 40%, <italic>p</italic>=0.0456).Conclusions: Early response during BEV-containing chemoradiation can be a predictive indicator for patient outcome in unresectable nd-GBMs.</p>

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