Department of Radiation Oncology, UPMC Hillman Cancer Center.
Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA.
Am J Clin Oncol. 2019 Jan;42(1):27-35. doi: 10.1097/COC.0000000000000470.
Despite multimodal treatment for high-grade gliomas, prognosis remains grim. Prior Radiation Therapy Oncology Group-Recursive Partitioning Analysis (RTOG-RPA) reports indicate based on pretreatment and treatment-related factors, a subset of patients experience a significantly improved survival. Since the development of the RTOG-RPA, high-grade gliomas have seen the widespread introduction of temozolomide and tumor oncogenetics. Here we aimed to determine whether the RTOG-RPA retained prognostic significance in the context of modern treatment, as well as generate an updated RPA incorporating both clinical and genetic variables.
Patients with histologically proven glioblastoma, gliosarcoma, anaplastic astrocytoma, and anaplastic oligodendroglioma treated with intensity-modulated radiation therapy (IMRT) between 2004 and 2017 were reviewed. The primary endpoint was overall survival from date of diagnosis. Primary analysis compared actual survival rates to that expected of corresponding RTOG-RPA class. Secondary analysis utilized the rpart function to recursively partition overall survival by numerous clinical and genetic pretreatment and treatment-related variables. A tertiary analysis recursively partitioned a subset of patients in which the status of all genetic markers were known.
We identified 878 patients with histologically proven high-grade glioma treated with IMRT and 291 patients in our genetic subset. Median overall survival for the entire cohort was 14.2 months (95% confidence interval, 13.1-15.3). Applying the RTOG-RPA to our cohort validated the relative prognostic ordering of the survival classes except class II. Generating our new RPA created 7 significantly different survival classes (P<0.001, χ=584) with median survival ranging from 96.4 to 2.9 months based on age, histology, O6-methylguanine-DNA methyltransferase methylation status, radiation fractions, tumor location, radiation dose, temozolomide status, and resection status. Our second RPA of our genetic subset generated 5 significantly different survival classes (P<0.001, χ=166) with survival ranging from 65.3 to 5.6 months based on age, isocitrate dehydrogenase 1 mutation status, O6-methylguanine-DNA methyltransferase methylation status, neurological functional classification, hospitalization during IMRT, temozolomide status, and Karnofsky performance status.
The RTOG-RPA retains partial prognostic significance, however, should be updated to reflect recent advancements. This series represents a large RPA analyzing both clinical and genetic factors and generated 7 distinct survival classes. Further assessment of patients with fully available genetic markers generated 5 distinct survival classes. These survival classifications need to be validated by a prospective data set and compared against the RTOG-RPA to determine whether they provide improved prognostic power.
尽管对高级别神经胶质瘤进行了多模式治疗，但预后仍然不容乐观。先前的放射治疗肿瘤学组-递归分区分析（RTOG-RPA）报告表明，根据治疗前和治疗相关因素，一部分患者的生存率显著提高。自 RTOG-RPA 发展以来，高强度聚焦超声治疗已广泛应用于替莫唑胺和肿瘤肿瘤遗传学。在这里，我们旨在确定 RTOG-RPA 在现代治疗背景下是否仍然具有预后意义，并生成一个包含临床和遗传变量的更新的 RPA。
回顾了 2004 年至 2017 年间接受调强放疗（IMRT）治疗的组织学证实的胶质母细胞瘤、胶质肉瘤、间变性星形细胞瘤和间变性少突胶质细胞瘤患者。主要终点是从诊断日期起的总生存。主要分析比较了实际生存率与相应 RTOG-RPA 类别的预期生存率。次要分析利用 rpart 函数根据许多临床和遗传治疗前和治疗相关变量递归划分总生存。第三项分析递归地划分了一组已知所有遗传标记状态的患者子集。
我们确定了 878 名接受 IMRT 治疗的组织学证实的高级别神经胶质瘤患者和 291 名遗传亚组患者。整个队列的中位总生存期为 14.2 个月（95%置信区间，13.1-15.3）。将 RTOG-RPA 应用于我们的队列验证了生存类别的相对预后排序，除了 II 类。生成我们的新 RPA 创建了 7 个显著不同的生存类（P<0.001，χ=584），中位生存期从 96.4 到 2.9 个月不等，基于年龄、组织学、O6-甲基鸟嘌呤-DNA 甲基转移酶甲基化状态、放疗次数、肿瘤位置、放疗剂量、替莫唑胺状态和切除状态。我们的遗传亚组的第二个 RPA 生成了 5 个显著不同的生存类（P<0.001，χ=166），生存时间从 65.3 到 5.6 个月不等，基于年龄、异柠檬酸脱氢酶 1 突变状态、O6-甲基鸟嘌呤-DNA 甲基转移酶甲基化状态、神经功能分类、IMRT 期间住院、替莫唑胺状态和卡诺夫斯基表现状态。
RTOG-RPA 仍然具有部分预后意义，但应进行更新以反映最新进展。本系列代表了一个大型的 RPA，分析了临床和遗传因素，并生成了 7 个不同的生存类。进一步评估具有完全可用遗传标记的患者生成了 5 个不同的生存类。这些生存分类需要通过前瞻性数据集进行验证，并与 RTOG-RPA 进行比较，以确定它们是否提供了更好的预后能力。
