The role of tumor markers for relapse detection in central nervous system non-germinomatous germ cell tumors (CNS-NGGCT): A pool analysis of cooperative group clinical trials.

Abstract

2503 Background: CNS-NGGCT are rare tumors that have been successfully treated with multimodal therapies. With a 5-yr EFS and OS of 72-84% and 82-93% respectively, surveillance and relapse detection is essential. Tumor marker (TM) elevation has proven to be a highly sensitive method of relapse detection in extra-cranial-NGGCT. We aim to determine the role of TM for relapse surveillance in children and adolescents with CNS-NGGCTs. Methods: European and North American data from germ cell tumor trials (SIOP GCT96, SFOP-TGM TC 90/92, COG-ACNS0122 and COG-ACNS1123) were pooled for analysis. Additionally, patients treated in the UK, Germany and France under strict protocol-guidelines were included. Details regarding imaging, pathology and TM elevation at diagnosis and relapse were collected. We report the proportion of relapses detectable by TM elevation. Results: Four-hundred and eighty-four patients enrolled in prospective cooperative group CNS-NGGCT trials from 1989 to 2016 were pooled for analysis. One-hundred and thirteen (23%) patients experienced a relapse/progression (SIOP GCT96: n = 57; SFOP TGM TC 90-92 n = 23, COG-ACNS0122 n = 16 & COG-ACNS1123 n = 17) and constitute the population of this report. Median age at diagnosis was 13 (range:1-30) years. The most common primary location was pineal in n = 60 (53%) patients. The site of relapse was available for 100 patients, 48 patients relapsed locally, 36 relapsed with distant disease, combined relapses were seen in 22 patients and 4 patients relapsed with TM elevation alone. TM in serum and/or CSF at diagnosis was available in 93(82%) patients, and in 90(80%) patients at the time of relapse. Eighty-four patients had TM available at both timepoints. At diagnosis 81 (96%) patients had TM elevation and 3 (4%) had negative TM. At relapse, 74(94%) patients with positive TM at diagnosis had TM elevation, while 7(6%) had TM negative. Conversely, 2/3 patients with negative TM at diagnosis, relapsed with elevated TM. Conclusions: Herein, we have assembled the largest prospective cohort to date of relapsed intracranial germ cell tumors. TM are highly sensitive detecting relapse/progression in CNS-NGGCT patients with elevated TM at diagnosis. The routine use of TM for relapse surveillance in patients with CNS-NGGCT can decrease the frequency of cross-sectional imaging, therefore, reducing lengthy hospital visits, sedation procedures and decreasing health-care costs.