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解锁贝伐单抗的潜力:相对脑血容量作为胶质母细胞瘤异柠檬酸脱氢酶野生型患者提高生存率的预测生物标志物。

Unlocking Bevacizumab's Potential: rCBV as a Predictive Biomarker for Enhanced Survival in Glioblastoma IDH-Wildtype Patients.

作者信息

Álvarez-Torres María Del Mar, Balaña Carmen, Fuster-García Elies, Puig Josep, García-Gómez Juan Miguel

机构信息

Instituto Universitario de Tecnologías de la Información y Comunicaciones, Universitat Politècnica de Valencia, 46022 Valencia, Spain.

Applied Research Group in Oncology (B-ARGO Group), Institut Catala d'Oncologia (ICO), Institut Investigació Germans Trias i Pujol (IGTP), 08916 Badalona, Spain.

出版信息

Cancers (Basel). 2023 Dec 28;16(1):161. doi: 10.3390/cancers16010161.

Abstract

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.

摘要

背景

异常的血管结构和血管生成是异柠檬酸脱氢酶野生型胶质母细胞瘤的标志,这表明这些肿瘤适合抗血管生成治疗。贝伐单抗在两项临床试验取得有前景的结果后,于2009年获得美国食品药品监督管理局(FDA)批准。然而,其用于复发性胶质母细胞瘤仍然是一个有争议的话题,因为它并不能普遍提高患者生存率。

目的

在本研究中,我们旨在分析肿瘤血管生成对贝伐单抗疗效的影响,并提出将高血管生成肿瘤区域的术前最大相对脑血容量(rCBVmax)作为预测生物标志物,以选择最能从治疗中获益的患者。

方法

分析了106例异柠檬酸脱氢酶野生型胶质母细胞瘤患者的临床和磁共振成像(MRI)数据。其中39例接受了贝伐单抗治疗,其余67例未接受二线治疗。采用ONCOhabitats方法自动计算rCBV。

结果

我们发现,接受贝伐单抗治疗的中度血管肿瘤患者的疾病进展后中位生存期比未接受任何二线治疗的患者长305天。这与高血管肿瘤患者形成对比,他们接受贝伐单抗治疗后疾病进展后中位生存期仅延长173天。此外,中度血管组对贝伐单抗的反应更好,疾病进展后6、12、18和24个月存活的患者比例更高。

结论

我们提出rCBVmax作为一种潜在的生物标志物,用于选择疾病进展后能从贝伐单抗治疗中更多获益的患者。此外,我们提出以7.5为阈值将患者分为中度和高血管组,以选择最佳的二线治疗方案。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2701/10778147/44ff128d3b6a/cancers-16-00161-g001.jpg

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