TY - JOUR
T1 - Early imaging marker of progressing glioblastoma
T2 - a window of opportunity
AU - Gatson, Na Tosha N.
AU - Bross, Shane P.
AU - Odia, Yazmin
AU - Mongelluzzo, Gino J.
AU - Hu, Yirui
AU - Lockard, Laura
AU - Manikowski, Jesse J.
AU - Mahadevan, Anand
AU - Kazmi, Syed A.J.
AU - Lacroix, Michel
AU - Conger, Andrew R.
AU - Vadakara, Joseph
AU - Nayak, Lakshmi
AU - Chi, T. Linda
AU - Mehta, Minesh P.
AU - Puduvalli, Vinay K.
N1 - Funding Information:
We acknowledge Dr. Susan Chang , Director of the UCSF Division of Neuro-Oncology and Director of the 2019 Society for Neuro-Oncology Clinical Trials Course, Dr. Mark Gilbert , Chief of the Neuro-Oncology Branch (NOB) at the National Institutes of Health, Dr. Priya Kumthekar of Northwestern University Feinberg School of Medicine, and to Dr. Prakash Chinnaiyan , Professor, Oakland University William Beaumont School of Medicine for dedicating their time and critical review of the research. The members of the NRG Brain Tumor & Neurosurgery Committees , and the NCI Brain Malignancies Steering Committee for their involvement in critical assessment of this work. To Geisinger Research Institute leadership, Dr. David Ledbetter , and Department Chair, Dr. Neil Holland, for allowing the dedicated research time. Finally, thanks to my donors: Mr. Jeff Erdly, Mr. Jerry Sandel , The Lowe Family, and The Comp Family.
Publisher Copyright:
© 2020, Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2020/7/1
Y1 - 2020/7/1
N2 - Purpose: Therapeutic intervention at glioblastoma (GBM) progression, as defined by current assessment criteria, is arguably too late as second-line therapies fail to extend survival. Still, most GBM trials target recurrent disease. We propose integration of a novel imaging biomarker to more confidently and promptly define progression and propose a critical timepoint for earlier intervention to extend therapeutic exposure. Methods: A retrospective review of 609 GBM patients between 2006 and 2019 yielded 135 meeting resection, clinical, and imaging inclusion criteria. We qualitatively and quantitatively analyzed 2000+ sequential brain MRIs (initial diagnosis to first progression) for development of T2 FLAIR signal intensity (SI) within the resection cavity (RC) compared to the ventricles (V) for quantitative inter-image normalization. PFS and OS were evaluated using Kaplan–Meier curves stratified by SI. Specificity and sensitivity were determined using a 2 × 2 table and pathology confirmation at progression. Multivariate analysis evaluated SI effect on the hazard rate for death after adjusting for established prognostic covariates. Recursive partitioning determined successive quantifiers and cutoffs associated with outcomes. Neurological deficits correlated with SI. Results: Seventy-five percent of patients developed SI on average 3.4 months before RANO-assessed progression with 84% sensitivity. SI-positivity portended neurological decline and significantly poorer outcomes for PFS (median, 10 vs. 15 months) and OS (median, 20 vs. 29 months) compared to SI-negative. RC/V ratio ≥ 4 was the most significant prognostic indicator of death. Conclusion: Implications of these data are far-reaching, potentially shifting paradigms for glioma treatment response assessment, altering timepoints for salvage therapeutic intervention, and reshaping glioma clinical trial design.
AB - Purpose: Therapeutic intervention at glioblastoma (GBM) progression, as defined by current assessment criteria, is arguably too late as second-line therapies fail to extend survival. Still, most GBM trials target recurrent disease. We propose integration of a novel imaging biomarker to more confidently and promptly define progression and propose a critical timepoint for earlier intervention to extend therapeutic exposure. Methods: A retrospective review of 609 GBM patients between 2006 and 2019 yielded 135 meeting resection, clinical, and imaging inclusion criteria. We qualitatively and quantitatively analyzed 2000+ sequential brain MRIs (initial diagnosis to first progression) for development of T2 FLAIR signal intensity (SI) within the resection cavity (RC) compared to the ventricles (V) for quantitative inter-image normalization. PFS and OS were evaluated using Kaplan–Meier curves stratified by SI. Specificity and sensitivity were determined using a 2 × 2 table and pathology confirmation at progression. Multivariate analysis evaluated SI effect on the hazard rate for death after adjusting for established prognostic covariates. Recursive partitioning determined successive quantifiers and cutoffs associated with outcomes. Neurological deficits correlated with SI. Results: Seventy-five percent of patients developed SI on average 3.4 months before RANO-assessed progression with 84% sensitivity. SI-positivity portended neurological decline and significantly poorer outcomes for PFS (median, 10 vs. 15 months) and OS (median, 20 vs. 29 months) compared to SI-negative. RC/V ratio ≥ 4 was the most significant prognostic indicator of death. Conclusion: Implications of these data are far-reaching, potentially shifting paradigms for glioma treatment response assessment, altering timepoints for salvage therapeutic intervention, and reshaping glioma clinical trial design.
KW - FLAIR signal intensity (SI)
KW - Imaging biomarker
KW - Neurologic Assessment in Neuro-Oncology (NANO)
KW - Progressed glioblastoma
KW - Response Assessment in neuro-Oncology (RANO)
KW - Signal Assessment in Neuro-Oncology (SANO)
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U2 - 10.1007/s11060-020-03565-x
DO - 10.1007/s11060-020-03565-x
M3 - Article
C2 - 32602020
AN - SCOPUS:85087286691
SN - 0167-594X
VL - 148
SP - 629
EP - 640
JO - Journal of neuro-oncology
JF - Journal of neuro-oncology
IS - 3
ER -