Efficacy and Toxicity of Different Target Volume Delineations of Radiotherapy Based on the Updated RTOG/NRG and EORTC Guidelines in Patients with High Grade Glioma: A Randomized, Controlled Clinical Trial

Purpose/Objective(s)Postoperative radiotherapy with concomitant and adjuvant temozolomide (TMZ) is the standard of care for newly diagnosed high grade glioma, but the optimal method for target volume delineations for intensity modulated radiation therapy (IMRT) is still unclear. We hypothesized that compared with the EORTC guidelines, IMRT based on the updated RTOG/NRG guidelines was equally effective, without increasing toxicities for patients with high-grade glioma. The purpose of this randomized phase 2 study was to compare the efficacy and toxicity of IMRT based on different target volume delineations (updated RTOG/NRG versus EORTC guidelines) with concomitant and adjuvant TMZ for patients with high grade glioma.Materials/MethodsA total of 302 patients with newly diagnosed high-grade glioma (WHO grade 3-4) were randomly assigned (1:1) to receive postoperative IMRT based on either updated RTOG/NRG guidelines (RTOG/NRG group, n = 151) or EORTC guideline (EORTC group, n = 151), with concomitant and adjuvant TMZ. In the RTOG/NRG group, an initial volume consisting of enhancement, postoperative cavity, plus surrounding edema (or fluid-attenuated inversion recovery [FLAIR] abnormality defined by magnetic resonance imaging [MRI]) and a 2-cm margin received 46 Gy in 23 fractions followed by a boost of 14 Gy in 7 fractions to the area of enhancement plus the cavity and a 2-cm margin. In the EORTC group, a single planning volume was used to deliver 60 Gy in 30 fractions to the area of enhancement and the cavity with a 2-cm margin. The primary end point was overall survival (OS). Secondary end points included progression-free survival (PFS) and toxicities associated with each treatment.ResultsNo statistically significant differences were observed between groups for 1-year OS (71.8% for RTOG/NRG group and 69.9% for EORTC group, respectively; P = 0.759) or 1-year PFS (46.7% for RTOG/NRG group and 43.6% for EORTC group, respectively; P = 0.674). Efficacy did not differ by MGMT methylation status. There were no differences in grade 3-4 toxicities (leukopenia, lymphopenia, neutropenia, thrombocytopenia, fatigue, nausea and vomiting) between the two groups. No grade 5 toxicities were observed in both groups. Multivariate analyses showed that tumor MGMT status (methylated vs unmethylated) and WHO grade (grade 3 vs grade 4) were associated with OS and PFS. However, radiation type (RTOG/NRG group vs EORTC), sex, age, and Karnofsky scale did not significantly influence OS or PFS.ConclusionCompared with EORTC guidelines for postoperative radiotherapy, IMRT based on RTOG/NRG guidelines was equally effective, without increasing toxicities for patients with high-grade glioma. This trial is registered with chictr.org.cn, number ChiCTR2100046667. Postoperative radiotherapy with concomitant and adjuvant temozolomide (TMZ) is the standard of care for newly diagnosed high grade glioma, but the optimal method for target volume delineations for intensity modulated radiation therapy (IMRT) is still unclear. We hypothesized that compared with the EORTC guidelines, IMRT based on the updated RTOG/NRG guidelines was equally effective, without increasing toxicities for patients with high-grade glioma. The purpose of this randomized phase 2 study was to compare the efficacy and toxicity of IMRT based on different target volume delineations (updated RTOG/NRG versus EORTC guidelines) with concomitant and adjuvant TMZ for patients with high grade glioma. A total of 302 patients with newly diagnosed high-grade glioma (WHO grade 3-4) were randomly assigned (1:1) to receive postoperative IMRT based on either updated RTOG/NRG guidelines (RTOG/NRG group, n = 151) or EORTC guideline (EORTC group, n = 151), with concomitant and adjuvant TMZ. In the RTOG/NRG group, an initial volume consisting of enhancement, postoperative cavity, plus surrounding edema (or fluid-attenuated inversion recovery [FLAIR] abnormality defined by magnetic resonance imaging [MRI]) and a 2-cm margin received 46 Gy in 23 fractions followed by a boost of 14 Gy in 7 fractions to the area of enhancement plus the cavity and a 2-cm margin. In the EORTC group, a single planning volume was used to deliver 60 Gy in 30 fractions to the area of enhancement and the cavity with a 2-cm margin. The primary end point was overall survival (OS). Secondary end points included progression-free survival (PFS) and toxicities associated with each treatment. No statistically significant differences were observed between groups for 1-year OS (71.8% for RTOG/NRG group and 69.9% for EORTC group, respectively; P = 0.759) or 1-year PFS (46.7% for RTOG/NRG group and 43.6% for EORTC group, respectively; P = 0.674). Efficacy did not differ by MGMT methylation status. There were no differences in grade 3-4 toxicities (leukopenia, lymphopenia, neutropenia, thrombocytopenia, fatigue, nausea and vomiting) between the two groups. No grade 5 toxicities were observed in both groups. Multivariate analyses showed that tumor MGMT status (methylated vs unmethylated) and WHO grade (grade 3 vs grade 4) were associated with OS and PFS. However, radiation type (RTOG/NRG group vs EORTC), sex, age, and Karnofsky scale did not significantly influence OS or PFS. Compared with EORTC guidelines for postoperative radiotherapy, IMRT based on RTOG/NRG guidelines was equally effective, without increasing toxicities for patients with high-grade glioma. This trial is registered with chictr.org.cn, number ChiCTR2100046667.