The Definition and Delineation of the Target Area of Radiotherapy Based on the Recurrence Pattern of Glioblastoma After Temozolomide Chemoradiotherapy.

Lin Zheng,Xiaofeng Zhou,Yang Yang,Qichun Wei,Qianqian Yu,Chao Li,Zhi-Rui Zhou,Minghan Shi

doi:10.3389/fonc.2020.615368

Abstract

Radiotherapy is an important treatment for glioblastoma (GBM), but there is no consensus on the target delineation for GBM radiotherapy. The Radiation Therapy Oncology Group (RTOG) and European Organisation for Research and Treatment of Cancer (EORTC) each have their own rules. Our center adopted a target volume delineation plan based on our previous studies. This study focuses on the recurrence pattern of GBM patients whose target delineations did not intentionally include the T2/fluid-attenuated inversion recovery (FLAIR) hyperintensity area outside of the gross tumor volume (GTV). We prospectively collected 162 GBM cases and retrospectively analysed the clinical data and continuous dynamic magnetic resonance images (MRI) of 55 patients with recurrent GBM. All patients received concurrent radiotherapy and chemotherapy with temozolomide (TMZ). The GTV that we defined includes the postoperative T1-weighted MRI enhancement area and resection cavity. Clinical target volume 1 (CTV1) and CTV2 were defined as GTVs with 1 and 2 cm margins, respectively. Planning target volume 1 (PTV1) and PTV2 were defined as CTV1 and CTV2 plus a 3 mm margin with prescribed doses of 60 and 54 Gy, respectively. The first recurrent contrast-enhanced T1-weighted MRI was introduced into the Varian Eclipse radiotherapy planning system and fused with the original planning computed tomography (CT) images to determine the recurrence pattern. The median follow-up time was 15.8 months. The median overall survival (OS) and progression-free survival (PFS) were 17.7 and 7.0 months, respectively. Among the patients, 44 had central recurrences, two had in-field recurrences, one had marginal recurrence occurred, 11 had distant recurrences, and three had subependymal recurrences. Five patients had multiple recurrence patterns. Compared to the EORTC protocol, target delineation that excludes the adjacent T2/FLAIR hyperintensity area reduces the brain volume exposed to high-dose radiation (P = 0.000) without an increased risk of marginal recurrence. Therefore, it is worthwhile to conduct a clinical trial investigating the feasibility of intentionally not including the T2/FLAIR hyperintensity region outside of the GTV.

Highlights

Glioblastoma (GBM) is the most common primary malignant central nervous system tumor with an incidence of approximately 3.20/100,000, accounting for 46.1% of all gliomas [1]
Planning target volume 1 (PTV1) and PTV2 were defined as Clinical target volume 1 (CTV1) and CTV2 plus a 3 mm margin, respectively
Eight patients refused to continue chemotherapy because of Radiation Therapy Oncology Group (RTOG) grade 3–4 toxicity, and seven patients returned to their local hospital to continue treatment

Summary

Introduction

Glioblastoma (GBM) is the most common primary malignant central nervous system tumor with an incidence of approximately 3.20/100,000, accounting for 46.1% of all gliomas [1]. The current standard treatment includes maximal safe resection of the tumor, followed by local radiotherapy and concurrent and adjuvant chemotherapy with temozolomide (TMZ) [2, 3]. The GBM radiotherapy protocols of Radiation Therapy Oncology Group (RTOG) or European Organisation for Research and Treatment of Cancer (EORTC) are commonly used. Clinical target volume 1 (CTV1) is defined as a 2 cm expansion from GTV1. Planning target volume 1 (PTV1) is expanded 0.3–0.5 cm from CTV1 and varies in different centers. The EORTC protocol is as follows [5]: one target volume of 60 Gy in 30 fractions is prescribed. GTV includes the T1-weighted MRI enhancement area and resection cavity but does not intentionally include the peritumoral edema area. PTV is treated with 0.3–0.5 cm expansion according to each center

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Conclusion