Pretreatment inflammatory indices predict Bevacizumab response in recurrent Glioma.

Alicia Martínez-González,Pedro C Lara,Marta Lloret,Raquel Cabrera

doi:10.20517/cdr.2020.33

Abstract

Aim: It remains unclear what the best therapeutic option for recurrent glioma patients after Stupp treatment is. Bevacizumab (BVZ) is commonly administered in progression, but it appears that only some patients benefit. It would be useful to find biomarkers that determine beforehand who these patients are.Methods: The protocol included 31 high-risk progressing glioma patients after Stupp treatment who received BVZ 5-10 mg/kg every 14 days and temozolomide (3-19 cycles, 150-200 mg five days each 28-day cycle) during a mean of eight cycles of BVZ or until tumor progression or unacceptable toxicity. We analyzed the clinical outcome values of inflammatory indices measured before BVZ administration.Results: Lymphocyte level before BVZ administration was the best independent predictor of overall survival (HR = 0.34; 95%CI: 0.145-0.81; P = 0.015). The area under the receiver operating characteristic (ROC) curve was 0.823, with 1.645 being the optimal cut-off value, and 0.80 and 0.85 the sensitivity and specificity values, respectively. Responder and non-responder survival curves were also significantly different, considering the first and second tertiles as cut-off points. The number of BVZ cycles was not related to lymphopenia. Pretreatment neutrophil, platelet levels, platelet-to-lymphocyte ratio (PLR), and neutrophil-to-lymphocyte ratio (NLR) did not have independent predictive value. Inflammatory variables were not correlated with each other. However, patients with high NLR and PLR simultaneously (double positive PLR-NLR) showed a worse clinical outcome than the rest (P = 0.043).Conclusion: Pretreatment lymphocyte levels and double positive PLR-NLR could be used as non-invasive hematological prognostic markers for recurrent gliomas treated with bevacizumab. A close relationship emerged between inflammation and angiogenesis.

Highlights

Primary brain tumors constitute about 2% of all malignant tumors; half of them are high-grade gliomas[1,2] and some low-grade gliomas show aggressive transformation, becoming high-grade gliomas, including glioblastoma (GBM)[3]
Pretreatment lymphocyte levels and double positive platelet-to-lymphocyte ratio (PLR)-neutrophil-to-lymphocyte ratio (NLR) could be used as non-invasive hematological prognostic markers for recurrent gliomas treated with bevacizumab
A close relationship emerged between inflammation and angiogenesis

Summary

Introduction

Primary brain tumors constitute about 2% of all malignant tumors; half of them are high-grade gliomas[1,2] and some low-grade gliomas show aggressive transformation, becoming high-grade gliomas, including glioblastoma (GBM)[3]. GBM aggressiveness leads to a median survival time of around three months without treatment, and 12-15 months with all therapeutic interventions[4]. Standard treatment includes maximal safe surgical resection and the Stupp protocol: concomitant temozolomide (TMZ) (75 mg seven days/week) to radiotherapy (RT) and adjuvant TMZ (six cycles, 150-200 mg five days each 28-day cycle). Progression and recurrence are observed with a median time of 10 weeks after finishing the standard treatment[1]. When progression occurs after the Stupp protocol, there is no standard treatment[8]. Since BVZ can only cross the blood–brain barrier in disrupted areas[14], it is associated with non-enhancing tumor progression, improvement of clinical performance, and progression-free survival[15,16]. The reduction in tumor size following therapy is transient and it is unclear which patients are most likely to benefit from treatment[17,18]

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