Landmark Trials in Selected Central Nervous System Tumors

Abstract

This chapter contains a summary of some key findings from a selection of 24 trials related to adult low- and high-grade gliomas, meningiomas, and brain metastasis.

In adult lower-grade glioma, the Cancer Genome Atlas Research Network performed a detailed molecular analysis of 293 gliomas to determine if clinically distinct biologic classes of disease could be identified and key findings are discussed. An Intergroup Trial by Shaw et al. evaluated lower- versus high-dose radiation therapy, and the EORTC 22845 evaluated early versus delayed radiotherapy, and both trials are included. The RTOG 9802 and RTOG 0424 trials studied combining chemotherapy with radiation therapy and are discussed.

In adult anaplastic glioma and glioblastoma, RTOG 69-01 was an early study that evaluated the role of radiation therapy and is included. A meta-analysis by Brown et al. that studied the role of extent of resection for patients with glioblastoma is discussed. Both the RTOG 9402 and EORTC 26951 trials studied the addition of chemotherapy to radiation therapy and are included. The Glioma Meta-Analysis Trialists Group conducted a meta-analysis for patients with high-grade glioma to evaluate the role of systemic chemotherapy, and the CATNON trial studied the role of adding temozolomide to radiation therapy in adult patients with 1p/19q non-co-deleted anaplastic glioma, and both studies are discussed. An EORTC trial by Stupp et al. demonstrated a survival improvement associated with adding temozolomide to adjuvant radiation therapy in patients with glioblastoma and is included. Finally, a randomized trial evaluating the role of tumor treatment fields (TTFs) is discussed.

In meningioma, Goldsmith et al. performed an analysis of 140 patients treated with subtotal resection followed by radiation therapy between 1967 and 1990 at University of California, San Francisco, and is included. The NRG Oncology RTOG 0539 trial was a prospective phase 2 trial that assigned patients with meningioma into one of three prognostic categories and evaluated treatment approaches based on WHO grade, recurrence status, and extent of resection. We discuss the first report on clinical outcomes of NRG Oncology RTOG 0539, which focused on patients in the intermediate-risk category.

In brain metastasis, two studies by Patchell et al., the first that evaluated the role of surgical resection for patients with a solitary brain metastasis and the second that evaluated the role of postoperative whole brain radiation therapy, are included. The recursive partitioning analysis (RPA) and updated Graded Prognostic Assessment (GPA) that developed prognostic and stratification parameters for patients with brain metastasis are discussed. Multiple trials that evaluated the role of stereotactic radiosurgery (SRS) including RTOG 90-05 and RTOG 95-08 are included. Brown et al. conducted a randomized trial of SRS combined with WBRT compared with treatment with SRS alone, and a meta-analysis by Tsao et al. demonstrated that the addition of WBRT to SRS improved local control and distant brain control but did not improve overall survival compared with SRS alone, and both these studies are discussed. Finally, a prospective observational trial by Yamamoto et al. that evaluated the role of SRS in patients with up to ten metastatic lesions is included.

There are hundreds of trials to choose from, and therefore, no claim toward completeness can be made in the current format. These trials relate to the multidisciplinary management of central nervous system tumors from the perspective of a radiation oncologist. Readers are encouraged to refer to the full manuscript of these trials for a greater understanding. This material is provided for educational purposes only, and with the goal of encouraging further study about the landmark trials that have impacted oncology.