e76a13d313d8ffbd8e5e464b25f9ae2d 302170.pdf f51f34977c5dd1eacd023cc3e53ff8258e5ed35d 302170.pdf 807765e2c3f4785910676717858b13eed8a98c3c61004701593776ea7bef4d2d 302170.pdf Title: Unlocking Bevacizumab’s Potential: rCBVmax as a Predictive Biomarker for Enhanced Survival in Glioblastoma IDH-Wildtype Patients Subject: Background: Aberrant vascular architecture and angiogenesis are hallmarks of glioblastoma IDH-wildtype, suggesting that these tumors are suitable for antiangiogenic therapy. Bevacizumab was FDA-approved in 2009 following promising results in two clinical trials. However, its use for recurrent glioblastomas remains a subject of debate, as it does not universally improve patient survival. Purposes: In this study, we aimed to analyze the influence of tumor vascularity on the benefit provided by BVZ and propose preoperative rCBVmax at the high angiogenic tumor habitat as a predictive biomarker to select patients who can benefit the most. Methods: Clinical and MRI data from 106 patients with glioblastoma IDH-wildtype have been analyzed. Thirty-nine of them received BVZ, and the remaining sixty-seven did not receive a second-line treatment. The ONCOhabitats method was used to automatically calculate rCBV. Results: We found a median survival from progression of 305 days longer for patients with moderate vascular tumors who received BVZ than those who did not receive any second-line treatment. This contrasts with patients with high-vascular tumors who only presented a median survival of 173 days longer when receiving BVZ. Furthermore, better responses to BVZ were found for the moderate-vascular group with a higher proportion of patients alive at 6, 12, 18, and 24 months after progression. Conclusions: We propose rCBVmax as a potential biomarker to select patients who can benefit more from BVZ after tumor progression. In addition, we propose a threshold of 7.5 to stratify patients into moderate- and high-vascular groups to select the optimal second-line treatment. Keywords: glioblastoma; predictive biomarker; angiogenesis; bevacizumab; rCBV Author: María del Mar Álvarez-Torres, Carmen Balaña, Elies Fuster-García, Josep Puig and Juan Miguel García-Gómez Creator: LaTeX with hyperref Producer: pdfTeX-1.40.25 CreationDate: Thu Dec 28 15:48:36 2023 CET ModDate: Thu Dec 28 15:53:02 2023 CET Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 15 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 5901283 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- OPETZR+VnURWPalladioL-Bold Type 1 Custom yes yes yes 10 0 YQOTQA+VnURWPalladioL Type 1 Custom yes yes yes 16 0 OHYQJB+URWPalladioL-Bold Type 1 Custom yes yes yes 21 0 XIKMYV+URWPalladioL-Roma Type 1 Custom yes yes yes 27 0 ROZNDK+URWPalladioL-Ital Type 1 Custom yes yes yes 32 0 LCJEVJ+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 49 0 GFAWRG+CMSY10 Type 1 Builtin yes yes yes 69 0 FCENGL+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 84 0 FCENGN+PalatinoLinotype TrueType WinAnsi yes yes no 87 0 FCENGP+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 90 0 FCENNN+PalatinoLinotype TrueType MacRoman yes yes no 93 0 FCENGL+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 110 0 FCENGM+PalatinoLinotype CID TrueType Identity-H yes yes yes 113 0 FCENGN+PalatinoLinotype TrueType WinAnsi yes yes no 119 0 FCENGP+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 122 0 FCENNN+PalatinoLinotype TrueType MacRoman yes yes no 125 0 OXWQKG+URWPalladioL-BoldItal Type 1 Custom yes yes yes 132 0 FCENGL+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 150 0 FCENGM+PalatinoLinotype CID TrueType Identity-H yes yes yes 153 0 FCENGN+PalatinoLinotype TrueType WinAnsi yes yes no 159 0 FCENGO+PalatinoLinotype,Italic CID TrueType Identity-H yes yes yes 162 0 FCENGP+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 168 0 FCENNN+PalatinoLinotype TrueType MacRoman yes yes no 171 0 FCENGL+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 184 0 FCENGM+PalatinoLinotype CID TrueType Identity-H yes yes yes 187 0 FCENGN+PalatinoLinotype TrueType WinAnsi yes yes no 193 0 FCENGO+PalatinoLinotype,Italic CID TrueType Identity-H yes yes yes 196 0 FCENGP+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 202 0 FCENNN+PalatinoLinotype TrueType MacRoman yes yes no 205 0 FCENGL+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 221 0 FCENGM+PalatinoLinotype CID TrueType Identity-H yes yes yes 224 0 FCENGN+PalatinoLinotype TrueType WinAnsi yes yes no 230 0 FCENGP+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 233 0 FCENNN+PalatinoLinotype TrueType MacRoman yes yes no 236 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2025-01-08 02:41:29 CET RepresentationInformation: 302170.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2025-01-07 10:34:14 CET Size: 5901283 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 442 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Material and Methods Destination: section.2 Children: Item: Title: Cohort Description Destination: subsection.2.1 Item: Title: Magnetic Resonance Imaging (MRI) Destination: subsection.2.2 Item: Title: MRI Processing and rCBV Calculation Destination: subsection.2.3 Item: Title: rCBV Threshold to Define Vascular Groups Destination: subsection.2.4 Item: Title: Statistical Analyses Destination: subsection.2.5 Children: Item: Title: Dataset Description: Distinctions between Moderate- and High-Vascularity Groups Destination: subsubsection.2.5.1 Item: Title: Analysis of Survival Differences among Groups Destination: subsubsection.2.5.2 Item: Title: Comparison of Responses to BVZ between Vascular Groups Destination: subsubsection.2.5.3 Item: Title: Results Destination: section.3 Children: Item: Title: Benefit of Providing BVZ for the Entire Cohort Destination: subsection.3.1 Item: Title: Cohort and Group Description Destination: subsection.3.2 Item: Title: Survival Differences between Vascular Groups Destination: subsection.3.3 Item: Title: Enhanced Responses to BVZ in Patients with Moderate-Vascular Tumors Destination: subsection.3.4 Item: Title: Discussion Destination: section.4 Item: Title: Conclusions Destination: section.5 Item: Title: References Destination: appendix.A. Info: Title: Unlocking Bevacizumab’s Potential: rCBVmax as a Predictive Biomarker for Enhanced Survival in Glioblastoma IDH-Wildtype Patients Author: María del Mar Álvarez-Torres, Carmen Balaña, Elies Fuster-García, Josep Puig and Juan Miguel García-Gómez Subject: Background: Aberrant vascular architecture and angiogenesis are hallmarks of glioblastoma IDH-wildtype, suggesting that these tumors are suitable for antiangiogenic therapy. Bevacizumab was FDA-approved in 2009 following promising results in two clinical trials. However, its use for recurrent glioblastomas remains a subject of debate, as it does not universally improve patient survival. Purposes: In this study, we aimed to analyze the influence of tumor vascularity on the benefit provided by BVZ and propose preoperative rCBVmax at the high angiogenic tumor habitat as a predictive biomarker to select patients who can benefit the most. Methods: Clinical and MRI data from 106 patients with glioblastoma IDH-wildtype have been analyzed. Thirty-nine of them received BVZ, and the remaining sixty-seven did not receive a second-line treatment. The ONCOhabitats method was used to automatically calculate rCBV. Results: We found a median survival from progression of 305 days longer for patients with moderate vascular tumors who received BVZ than those who did not receive any second-line treatment. This contrasts with patients with high-vascular tumors who only presented a median survival of 173 days longer when receiving BVZ. Furthermore, better responses to BVZ were found for the moderate-vascular group with a higher proportion of patients alive at 6, 12, 18, and 24 months after progression. Conclusions: We propose rCBVmax as a potential biomarker to select patients who can benefit more from BVZ after tumor progression. In addition, we propose a threshold of 7.5 to stratify patients into moderate- and high-vascular groups to select the optimal second-line treatment. 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