EANO, SNO and Euracan consensus review on the current management and future development of intracranial germ cell tumors in adolescents and young adults

Abstract

The incidence of intracranial germ cell tumors (iGCT) is much lower in European and North American (E&NA) than in Asian population. However, E&NA cooperative groups have simultaneously developed with success treatment strategies with specific attention paid to long-term sequelae. Neurological sequelae may be reduced by establishing a diagnosis with an endoscopic biopsy and/or cerebrospinal fluid (CSF) and/or serum analysis, deferring the need to perform a radical surgery. Depending on markers and/or histological characteristics, patients are treated as either germinoma or non-germinomatous germ cell tumors (NGGCT). Metastatic disease is defined by a positive CSF cytology and/or distant drops in craniospinal MRI. The combination of surgery and/or chemotherapy and radiation therapy is tailored according to grouping and staging. With more than 90% 5-year event-free survival (EFS), localized germinomas can be managed without aggressive surgery, and benefit from chemotherapy followed by whole ventricular irradiation with local boost. Bifocal germinomas are treated as non-metastatic entities. Metastatic germinomas may be cured with craniospinal irradiation. With a 5-year EFS over 70%, NGGCT benefit from chemotherapy followed by delayed surgery in case of residual disease, and some form of radiotherapy. Future strategies will aim at decreasing long-term side effects while preserving high cure rates.

Roles of Tumor Markers in Central Nervous System Germ Cell Tumors Revisited with Histopathology-Proven Cases in a Large International Cohort

“…Tumor markers (human chorionic gonadotropin (HCG) and alpha fetoprotein (AFP)) in serum and cerebrospinal fluid (CSF) are useful for diagnosis [ 8 ], the evaluation of treatment response [ 9 ], and detecting recurrence after treatment [ 10 ]. GCTs have been shown to transform histologically following treatment, with associated fluctuations in tumor markers [ 11 ].…”

Biomarkers for risk-based treatment modifications for CNS germ cell tumors: Updates on biological underpinnings, clinical trials, and future directions

“…First, classifications differ in Europe, North America, and Japan. In Europe/North America, NGGCT is defined according to a case presentation in which tumor markers are elevated or according to histopathological confirmation of NGGCTs when tumor markers are normal ( 10 ). In Japan, NGGCT is further subdivided into two classes: an intermediate prognosis group and a poor prognosis group ( 3 , 11 )., The intermediate prognosis group includes immature teratomas, teratomas with somatic-type malignancy, and mixed tumors (mainly composed of germinomas and teratomas).…”

“…Tumor markers (HCG and AFP) are examined in blood serum and cerebrospinal fluid (CSF) from lumbar puncture or ventricular drainage when it is safe to obtain the sample for the latter. If tumor markers are elevated, patients are diagnosed with NGGCTs; if not, patients require a biopsy for histopathological diagnosis (6)(7)(8)(9)(10). In Japan, treatment stratification is unique in that it is based on three prognostic subgroups (i.e., germinoma, intermediate prognosis, and poor prognosis subgroups) that are determined according to histopathological confirmation (Table 1) (11,12).…”

Childhood brain tumors: It is the child’s brain that really matters

“…Within this statistic there are significant variations between European countries. Clinical trials have shown remarkable advances, such as intra-cranial germ cell tumors ( 5 ) and medulloblastoma ( 6 ), which have improved with combined standard approaches of well delivered chemotherapy, radiotherapy and rational approaches to surgery. Radiotherapy research and trials in the past decades have focussed upon optimising radiation doses to the tumour and surrounding brain to minimise the cognitive consequences ( 7 ).…”