Nervous System Germ Cell Tumors Research Articles

CNS Germ Cell Tumors: Molecular Advances, Significance in Risk Stratification and Future Directions.

Central Nervous System Germ Cell Tumors (CNS GCTs) represent a subtype of intracranial malignant tumors characterized by highly heterogeneous histology. Current diagnostic methods in clinical practice have notable limitations, and treatment strategies struggle to achieve personalized therapy based on patient risk stratification. Advances in molecular genetics, biology, epigenetics, and understanding of the tumor microenvironment suggest the diagnostic potential of associated molecular alterations, aiding risk subgroup identification at diagnosis. Furthermore, they suggest the existence of novel therapeutic approaches targeting chromosomal alterations, mutated genes and altered signaling pathways, methylation changes, microRNAs, and immune checkpoints. Moving forward, further research is imperative to explore the pathogenesis of CNS GCTs and unravel the intricate interactions among various molecular alterations. Additionally, these findings require validation in clinical cohorts to assess their role in the diagnosis, risk stratification, and treatment of patients.

Primary Co-Occurrence of Gonadal and Extragonadal Central Nervous System (CNS) Germ Cell Tumors (GCTs): Case Report and Review of the Literature

Background: The primary co-occurrence of gonadal and extragonadal central nervous system (CNS) germ cell tumors (GCTs) has rarely been reported in the literature, and a common opinion on the underlying etiopathogenetic mechanism is lacking. Objective: We aim to investigate the pathophysiological mechanisms and genetic pathways underlying the primary co-occurrence of gonadal and CNS GCTs. Methods: We reviewed data from 29 consecutive patients with a diagnosis of CNS GCT, evaluated in our Hospital over the past 23 years, and searched for those who had at least a primary gonadal co-occurrence of GCT. A systematic review of the literature according to the PRISMA guidelines was also conducted. For a comprehensive and detailed search, PubMed, Ovid MEDLINE, and Ovid EMBASE databases have been consulted. Boolean operators and MeSH terms were used to find studies. Only articles published between 2000 and 2023 were considered. Results: Including our Institutional case report, a total of 7 patients with both testicular NGGCTs and CNS GCTs were identified (5 patients with metachronous tumors and patients with synchronous presentation). The average age at tumor diagnosis was 17 years. The cerebral histotypes reported were mixed GCTs (3 cases; 43%), pure germinomas (3 cases, 43%), and one yolk sac tumor (14%). Two out of seven cases (29%) were syndromic, one suffering from Down Syndrome and the other from Testicular Dysgenesis Syndrome. Regarding the etiology and molecular mechanism of GCT development, several gene mutations have been reported in the literature. Particularly, genetic alterations in the MAPK and/or PI3K/AKT/mTOR pathway, together with mutations of the KIT gene, have been shown to guarantee survival and transformation of mismigrated totipotent primordial germ cells, while suppressor genes allow their resistance against apoptotic death. Aberrant chromosomes have also been reported to be responsible for oncogenic transformation. It is also known that CNS and testicular GCTs share some genetic/epigenetic profiles. Conclusions: The primary co-occurrence of testicular NGGCT and extragonadal CNS GCTs is extremely rare. Genetic factors seem to play a paramount role in their etiopathogenesis. Additional research is needed to elucidate molecular mechanisms of oncogenesis in such patients.

Intriguing Cases of Rare Malignancies of Childhood and Adolescence- A Series of Six Cases

Intracranial teratomas constitute the majority of congenital Central Nervous System (CNS) germ cell tumours. Pure mature or immature teratomas present with giant intracranial masses that cause irreversible brain damage and impair the quality of life. Two such cases are reported here: the first involves a four-month-old female infant with a large right hemispheric lesion, and the second involves a three-month-old female infant with a similar large right hemispheric space-occupying lesion. Both underwent craniotomy but ultimately succumbed to death within a few days after the operation. Immature teratomas of the ovaries are the second most common malignant germ cell tumour following dysgerminoma, with good prognosis and excellent overall survival rates. One such case is presented here, involving a 16-year-old adolescent female with a history of irregular and painful menstruation presenting with a large abdomino-pelvic mass that was determined to be of ovarian origin through imaging studies. Alveolar Soft Part Sarcoma (ASPS) is a rare soft-tissue sarcoma with a poor prognosis, demonstrated in a 17-year-old girl who presented with a painless left thigh mass that was clinically misdiagnosed as a benign intramuscular lipoma. Another case involves a 14-year-old boy with Ewing sarcoma of the ring finger, an extremely rare hand tumour with a high potential for misdiagnosis and delayed treatment, accompanied by a focus of pulmonary metastasis. The final case involves a poorly differentiated carcinoma of the Ileum in a 17- year-old girl who was eventually lost to follow-up checkups.

10121-BT-8 CLINICOPATHOLOGICAL ANALYSIS OF CENTRAL NERVOUS SYSTEM GERM CELL TUMORS -387CASES IN THE JCCG COHORT AND THE IGCT CONSORTIUM COHORT

Abstract BACKGROUND Central nervous system germ cell tumors (CNS GCTs) are rare primary tumors that tend to occur in East Asian boys. In Japan, the Japan Children's Cancer Group (JCCG) and the CNS GCT Genome Analysis Consortium (iGCT Consortium) have been accumulating clinical and pathological data on CNS-GCT cases. METHODS Statistical analyses were performed on 178 cases in the JCCG's Solid Tumor Observational Study (2016-2022) and 209 cases in the iGCT Consortium (2011-2021) for age, gender, site of origin, and pathological diagnosis. RESULTS There were 306 primary cases and 44 recurrent cases, 296 (77%) males and 90 (23%) females, with a median age of 13 years, 11 years for JCCG and 16 years for iGCT Consortium, with differences between these two cohorts. The most common pathological diagnosis was germinoma in 200 cases (52%). Non-germinomatous germ cell tumors (NGGCTs) in 167 cases (43%), of which 69 cases (18%) were mixed GCT with germinoma, 34 cases were immature teratoma, mature teratoma in 32 cases (8%), yolk sac tumor in 20 cases (5%), mixed GCT without germinoma in 5 cases (1%), choriocarcinoma in 5 cases (1%), embryonal carcinoma in 2 cases (0.5%). The median age of patients with germinoma was 15 years, while with other histological types was 12 years. The pineal gland was the most common site (208 cases, 56%) and 114 cases (31%) occurred in the neurohypophysis. 38 cases of them were bifocal. Tumor development in the basal ganglia occurred in 40 cases (11%), and multiple lesions were seen in 37 cases (10%). In the neurohypophysis, the male-to-female ratio was 1:1, while in the pineal region was 11:1. In the neurohypophysis, 67% had germinoma and 9% had teratoma, whereas, in the pineal regions, 50% had germinoma and 19% had teratoma. CONCLUSIONS CNS GCT is closely correlated with age, sex, site of origin, and histology.

A novel lactate dehydrogenase-based risk score model to predict the prognosis of primary central nervous system germ cell tumor treated with chemoradiotherapy

BackgroundThe prognostic role of lactate dehydrogenase (LDH) has been confirmed in many malignant tumors, but the role of serum LDH in primary central nervous system germ cell tumor (GCT) remains unknown. This study aimed to assess the prognostic value of LDH in GCT patients and develop a nomogram to predict prognosis in patients undergoing chemoradiotherapy. MethodsA total of 161 patients with GCT were included in this study. Using a restricted cubic spline (RCS) model, the optimal cutoff point for LDH was determined to be 217 U/L. The survival of GCT patients was evaluated using the Kaplan-Meier method and log-rank test to analyze the effects of LDH levels. Univariate Cox regression, multivariate Cox regression, and LASSO Cox regression were conducted to identify prognostic factors, which were incorporated into a nomogram for predicting overall survival (OS). The predictive accuracy of the nomogram was assessed using the C-index, calibration curve, area under the time-dependent receiver operating characteristic curve (time-dependent AUC), and risk group stratification. The net benefits of the nomogram at different threshold probabilities were quantified using decision curve analysis (DCA). ResultsThe high-LDH group had significantly shorter OS compared to the low-LDH group (P = 0.016). Based on the SYSUCC cohort, three variables were shown to be significant factors for OS and were incorporated in the nomogram: LDH, histopathology, and dissemination. It showed good discrimination ability, with C-index of 0.789 (95% CI, 0.671–0.907). Additionally, the clinical usefulness of the nomogram was confirmed by calibration curves and time-dependent AUC. DCA further highlighted the potential of the nomogram to guide clinical treatment strategies for patients. Moreover, there was a significant difference in OS among patients categorized into different risk groups (P < 0.001). ConclusionLDH levels may serve as a reliable predictor for assessing the therapeutic effect of chemoradiotherapy in GCT. The developed nomogram exhibits high accuracy in predicting survival outcomes, aiding in the classification of prognostic groups, and supporting informed clinical decision-making.

Clinicopathological spectrum of central nervous system germ cell tumors: A single-institution retrospective study.

Central nervous system germ cell tumors (CNSGCTs) though rare is the second most common extragonadal site for GCTs. To determine the clinicopathological features of CNSGCTs diagnosed at our center. A retrospective study of all histologically diagnosed CNSGCTs, during 2006-2019. The patients' data were retrieved from the hospital information systems and analyzed. Data on categorical variables were analyzed as percentages, and data on continuous variables calculated as mean. Chi-square test or Fisher's exact test was used to study association between variables. Of the total 34 cases with CNSGCT, age ranged from 1 to 27 years, majority in the second decade (19/34; 56%). Male: female (M: F) ratio was 1.6:1. Single site involvement was seen in 27 cases (27/34; 79%), whereas seven (7/34; 21%) showed bi/multifocal involvement. Among the unifocal cases, common sites involved were suprasellar (12/27; 44.4%), closely followed by the pineal (10/27; 37%). All multifocal tumors affected suprasellar compartment, being bifocal with pineal in four cases. A male gender predilection was noted among pineal region (9/10;90%) and multifocal tumors (5/7;71%). Germinoma was the commonest subtype (21/34; 61.8%) with male gender predilection (17/21; 81%) (M: F =4.3:1), with female predilection seen among mixed GCTs (MGCTs) (8/10; 80%) (M: F =1:4) and suprasellar location (M: F =1:2). Serum tumor markers (25 cases) and CSF markers (7 cases) were concordant with histology in all, except two cases. Though histology and immunohistochemistry were diagnostic, correlation between serum and/or CSF marker was essential to rule out GCT component(s) that may be missed on biopsy due to sampling error.

Unraveling the impact of upfront chemotherapy and proton beam therapy on treatment outcome and follow-up in central nervous system germ cell tumors: a single center experience.

Germ cell tumors (GCT) account for a minority of central nervous system (CNS) malignancies, highly prevalent in adolescents and young adults. Despite their aggressive biological behavior, prognosis is excellent in most cases with risk stratified treatment, consisting in a combination of chemotherapy and radiotherapy. Whole ventricular irradiation (WVI) and craniospinal irradiation, the treatment of choice for localized and metastatic disease, pose significant risk of collateral effects, therefore proton beam radiation (PBT) has been recently proposed for its steep dose fallout. We report our experience in a consecutive series of 17 patients treated for CNS GCT at our Institution from 2015 to 2021. Most frequent lesion location were sellar/suprasellar (35%) and bifocal germinoma (35%), followed by pineal (18%) and thalamic (12%). Two patients (12%), had evidence of disseminated disease at the time of diagnosis. At the latest follow-up all but one patient showed complete response to treatment. The only relapse was successfully rescued by additional chemotherapy and PBT. PBT was well tolerated in all cases. No visual, neurological or endocrinological worsening was documented during and after treatment. Neuropsychological evaluation demonstrated preservation of cognitive performance after PBT treatment. Our data, albeit preliminary, strongly support the favourable therapeutic profile of PBT for the treatment of CNS germ cell tumors.

512P Heterozygous germline Fanconi anemia-related gene mutations increase susceptibility to central nervous system germ cell tumors

512P Heterozygous germline Fanconi anemia-related gene mutations increase susceptibility to central nervous system germ cell tumors

Distinct patterns of copy number alterations may predict poor outcome in central nervous system germ cell tumors

We have previously reported that 12p gain may predict the presence of malignant components and poor prognosis for CNS germ cell tumor (GCT). Recently, 3p25.3 gain was identified as an independent predictor of poor prognosis for testicular GCT. Eighty-one CNS GCTs were analyzed. Copy number was calculated using methylation arrays. Five cases (6.2%) showed 3p25.3 gain, but only among the 40 non-germinomatous GCTs (NGGCTs) (5/40, 12.5%; p = 0.03). Among NGGCTs, those with a yolk sac tumor component showed a significantly higher frequency of 3p25.3 gain (18.2%) than those without (1.5%; p = 0.048). NGGCTs with gain showed significantly shorter progression-free survival (PFS) than those without (p = 0.047). The 3p25.3 gain and 12p gain were independent from each other. The combination of 3p25.3 gain and/or 12p gain was more frequent among NGGCTs with malignant components (69%) than among those without (29%; p = 0.02). Germinomas containing a higher number of copy number alterations showed shorter PFS than those with fewer (p = 0.03). Taken together, a finding of 3p25.3 gain may be a copy number alteration specific to NGGCTs and in combination with 12p gain could serve as a marker of negative prognosis or treatment resistance. Germinoma with frequent chromosomal instability may constitute an unfavorable subgroup.

Cytological features of central nervous system germ cell tumours and tumours of the sellar region.

Germ cell tumours of the central nervous system and tumours of the sellar region represent a diverse group of neoplasms. These tumours affect both paediatric and adult patients and represent some of the most common central nervous system tumours as well as rare entities. Diagnosis frequently relies on tissue sampling, and intraoperative consultation is often needed to guide surgical management. The focus of this article is to provide a reference for the intraoperative cytology of these entities. The cytological features of these tumours as well as their differential diagnoses are described.

Primary central nervous system germ cell tumors in children and young adults: A review of controversies in diagnostic and treatment approach

Primary central nervous system (CNS) germ cell tumors (GCT) are a rare heterogenous group of cancers, arising most commonly in the second decade of life. Through several clinical trials conducted around the world by various groups, the treatment approach for CNS GCT has advanced substantially with generally improved overall outcomes. In recent years, the goal of clinical trials has been focused on reduction of the radiotherapy burden and minimization of long-term toxicity. This review summarizes the current diagnostic and treatment regimens for CNS GCT, examines the controversies associated with these approaches, gaps in contemporary knowledge, and underscores the challenges we face. We also explore future directions in the management of CNS GCT with the ultimate overall aim of preserving curative outcomes, identifying novel biomarkers, and mitigating neurocognitive, endocrine, and psychological toxicity through prospective clinical studies.

PEDT-6 A RANDOMIZED CONTROLLED CLINICAL STUDY OF RADIOTHERAPY COMBINED WITH CHEMOTHERAPY IN PATIENTS WITH NEWLY DIAGNOSED CENTRAL NERVOUS SYSTEM GERM CELL TUMOR, JCCG CNSGCT2021

Abstract Background Central nervous system (CNS) germ cell tumors account for 15.3% of all CNS tumors in children and adolescents and young adults. Five histologic types and mixed types exist and can be classified into the following clinical risk groups: germinomas, malignant germ cell tumors, and other germ cell tumors. In germinomas, platinum-based chemotherapy and whole ventricle/brain irradiations 23.4 Gy/13 fraction are the standard of care, but late adverse events related to radiation therapy are a problem. In malignant germ cell tumors, chemotherapy with alkylating agents and platinum, craniospinal irradiation (CSI), and local radiation therapy (local dose 50-59.4 Gy/25-33 fractions) have become the standard of care, but the 10-year OS is poor at about 60% and late radiation therapy-related adverse events are an issue. For various reasons, it is not easy to establish a standard of care for mature teratomas and immature teratomas, which constitute the other germ cell tumors, but it is essential to collect knowledge on tumor characteristics and prognosis. Methods and Patients The Japan Children's Cancer Group Brain Tumor Committee has planned a study to validate the classification by histological diagnosis and ancillary tumor markers, a phase III study to test the non-inferiority of radiation dose reduction to standard therapy for germinomas, a phase II study to test the superiority of high-dose chemoradiation with methotrexate intrathecal injection excluding CSI to standard therapy for malignant germ cell tumors, observational studies to elucidate pathogenesis of other germ cell tumors. Discussion If these hypotheses are proven, it is expected to reduce late adverse events and prolong survival with radiotherapy in children and adolescent/young adult generation patients.

PD-L1 and PD-1 expression in pediatric central nervous system germ cell tumors

Central nervous system (CNS) germ cell tumors (GCTs) represent 2–3% of all primary CNS tumors. The majority are germinomas, which are radiosensitive and have an excellent prognosis. Contrarily, CNS non-germinomatous GCTs (NGGCTs) have less favorable prognosis and require more aggressive treatment. The expression of checkpoint/immune markers in CNS GCTs, particularly NGGCTs, is unknown. We previously reported a case of a patient whose intracranial NGGCT (predominantly choriocarcinoma) responded to immune checkpoint inhibition therapy. This case led us to evaluate our archive of intracranial GCTs for expression of PD-L1 and PD-1. With IRB approval, we searched the pathology archives at our institution for CNS GCTs. Demographic, radiologic, clinical, and histologic information was extracted from the medical records. Immunohistochemistry for lymphocytic markers (CD4, CD8, CD20), PD-1, and PD-L1 was performed. PD-L1 was considered positive if greater than 1% of tumor cells were positive and PD-1 was reported as a percentage of positive inflammatory cells. Fifty cases were identified, including 28 germinomas (mean age at diagnosis: 15.5 years; 17 males, 11 females), and 22 NGGCTs (mean age at diagnosis: 12.0 years, 21 males, 1 female). Germinomas were mostly suprasellar (17/28) and NGGCTs were predominantly pineal (17/22). Twenty-two germinomas (79%) were positive for PD-L1 expression, and 13 NGGCTs (57%) were positive for PD-L1. Cases of choriocarcinoma showed the most diffuse PD-L1 expression. PD-1 expression was seen in lymphocytes among 27/28 of the germinomas and 20/23 of the NGGCTs (ranging from 1–40% of lymphocytes). As expected, larger quantities of inflammatory cells were present in cases of germinoma. We demonstrate immune activity in CNS GCTs, and our results suggest that immune checkpoint inhibitors may be efficacious in the treatment of intracranial GCTs. Among NGGCTs, cases of choriocarcinoma showed the highest expression of PD-L1 in tumor cells, suggesting that this subtype may have the greatest benefit from checkpoint blockade.

Endoscopic aqueductal membrane fenestration was effective for intractable hydrocephalus after removal of a nongerminomatous germ cell tumor exhibiting growing teratoma syndrome: a case report

BackgroundPrimary central nervous system (CNS) germ cell tumors (GCTs) are rare neoplasms predominantly observed in the pediatric and young adult populations. A mixed GCT including immature teratoma exhibiting growing teratoma syndrome is presented. The pathogenesis of growing teratoma syndrome remains unclear, and its treatment strategy has not been established. GCTs are often located within the ventricles, causing hydrocephalus, which sometimes improves after removal of the tumor due to restoration of cerebrospinal fluid (CSF) flow. On the other hand, even if the flow route of CSF from the third ventricle to arachnoid granulations on the brain surface quadrigeminal cistern is restored after removal of the tumor, hydrocephalus may not improve.Case presentationA case whose intractable hydrocephalus improved after penetrating the aqueductal membrane via endoscopy is described. An 11-year-old boy was treated for pineal intracranial growing teratoma syndrome (IGTS). The tumor grew rapidly in a short period, and hydrocephalus progressed despite endoscopic third ventriculostomy (ETV). Although the obstruction was removed by radiation, chemotherapy, and total tumor resection, the hydrocephalus did not improve. Endoscopic membrane perforation was performed because a membrane-like structure was seen at the entrance of the cerebral aqueduct on magnetic resonance imaging. The hydrocephalus improved immediately after the operation, and the patient’s consciousness disturbance also improved significantly.ConclusionThe purpose of this report is to update the current knowledge and standards of management for patients with growing teratoma syndrome, as well as to drive future translational and clinical studies by recognizing the unmet needs concerning hydrocephalus.

Intracranial germinoma in the lateral ventricle with polydipsia and polyuria: a case report and literature review.

Central nervous system germ cell tumors (CNSGCTs) are rare neoplasms which usually develop in the midline structures. They are occasionally involved in off-midline structures of the brain. Here, we report an extremely rare case of an intracranial germinoma in the lateral ventricle. The patient was a 10-year-old boy with a 1-year history of polydipsia and polyuria. Brain magnetic resonance imaging (MRI) showed a relatively homogeneously enhancing lesion in the lateral ventricle, and the posterior pituitary gland was not hyperintense on T1-weighted imaging. Subependymoma was suspected, and tumor removal operation was performed; however, because the intraoperative pathological investigation revealed germinoma, we could only perform partial removal of the tumor. Postoperative histology also confirmed germinoma. Then, the patient received chemotherapy, followed by radiation therapy. MRI showed no recurrence for 6years after treatment. Intracranial germinoma in the lateral ventricle is extremely rare. The diagnosis is occasionally challenging, especially when the tumors are located in atypical locations. This paper presents a literature review of previously described CNSGCTs of the lateral ventricle to improve awareness of CNSGCTs in atypical locations. We also consider the relationship between imaging findings and clinical manifestations.

Pathogenesis of central nervous system germ cell tumors.

Intracranial germ cell tumors (IGCTs) are clinically rare. They are more common in children and adolescents and the incidence in Asia is higher than in Western countries. Histologically, IGCTs are divided into germinoma and non-germinomatous germ cell tumor (NGGCT). Germinoma is sensitive to radiotherapy and chemotherapy and therefore, patients with germinoma have a good prognosis. However, NGGCTs, especially those with malignant components, are not sensitive to radiotherapy and chemoradiotherapy, leading to a poor prognosis. The pathogenesis of IGCTs is not fully understood. By summarizing previous literature, we found that the occurrence of IGCTs may be related to the following factors: chromosomal instability, MAPK and/or PI3K pathway changes, and DNA hypomethylation in pure germ cell tumors.

Imaging diagnosis of central nervous system germ cell tumors

Imaging diagnosis of central nervous system germ cell tumors

Multi-institutional analysis of central nervous system germ cell tumors in patients with Down syndrome.

Primary germ cell tumors (GCTs) are the most common central nervous system (CNS) neoplasm in patients with Down syndrome (DS). However, a standard of care has not been established due to paucity of data. A retrospective multi-institutional analysis was conducted, in addition to a comprehensive review of the literature. Ten patients from six institutions (five USA, one Brazil) were identified, in addition to 31 patients in the literature from 1975 to 2021. Of the 41 total patients (mean age 9.9years; 61% male), 16 (39%) had non-germinomatous germ cell tumors (NGGCTs), 16 (39%) had pure germinomas, and eight (19.5%) had teratomas. Basal ganglia was the most common tumor location (n=13; 31.7%), followed by posterior fossa (n=7; 17%). Nine patients (22%) experienced disease relapse or progression, of which four died from tumor progression (one germinoma, three teratomas). Sixteen patients (39%) experienced treatment-related complications, of which eight (50%) died (five germinomas, three NGGCTs). Of the germinoma patients, two died from chemotherapy-related sepsis, one from postsurgery cardiopulmonary failure, one from pneumonia, and one from moyamoya following radiation therapy (RT). Of the NGGCT patients, one died from chemotherapy-related sepsis, one from postsurgical infection, and one from pneumonia following surgery/chemotherapy/RT. Three-year overall survival was 66% for all histological types: 62% germinomas, 79% for NGGCTs, and 53% for teratomas. Patients with DS treated for CNS GCTs are at an increased risk of treatment-related adverse events. A different therapeutic approach may need to be considered to mitigate treatment-related complications and long-term neurocognitive sequelae.

GCT-15. Multi-institutional analysis and literature review of central nervous system germ cell tumors in patients with Down syndrome

Abstract BACKGROUND: A standard-of-care has not been established for the management of patients with Down syndrome (DS) who develop primary central nervous system (CNS) germ cell tumors (GCTs) – the most common CNS neoplasm in DS – despite being more susceptible to treatment-related adverse events. METHODS: Data from large academic institutions were collected and a comprehensive review of the medical literature was conducted. RESULTS: Ten patients from six institutions (five USA, one Brazil) were reviewed. Additionally, thirty-one patients were identified in the literature from 1975-2021. Of the 41 total patients, mean age was ten years (range, birth to 35 years); males were predominant (61%). Basal ganglia were the most common tumor location (n=12; 29%), followed by posterior fossa (n=7; 17%). Sixteen patients had non-germinomatous germ cell tumors (NGGCTs) (39%), 14 had pure germinomas (34%), and eight had teratomas (20%); histology was unreported for two (5%). Nine patients (22%) experienced disease relapse, of which four died from tumor progression (one germinoma versus three teratoma). Fifteen patients (37%) experienced treatment-related complications - seven died (four germinoma versus three NGGCT). Of the germinoma patients, two died from chemotherapy-related sepsis, one from post-surgery cardiopulmonary failure, and one from Moyamoya following radiation-therapy (RT) only. Of the NGGCT patients, one died from chemotherapy-related sepsis, one from post-surgical infection, and one from pneumonia following surgery/chemotherapy/RT. Three-year overall survival (OS) was 66% for all histological types - 62% germinoma, 79% for NGGCT, and 53% for teratoma. Three-year OS for patients who received RT or chemotherapy was 71% and 75% respectively. Twenty-seven patients remain alive at latest follow-up (mean follow-up from diagnosis: 46.8 months). CONCLUSIONS: Patients with DS treated for CNS GCTs are at an increased risk of treatment-related adverse events. A different therapeutic approach may need to be considered for this patient population to mitigate treatment-related complications and long-term neurocognitive sequelae.

GCT-02. Imaging response assessment for Central Nervous System Germ Cell Tumours: consensus recommendations from the European Society for Paediatric Oncology Brain Tumour Group (SIOPE-BTG) and North American Children’s Oncology Group (COG)

Abstract BACKGROUND: Central nervous system (CNS) germ cell tumours (GCT) comprise a heterogeneous and relatively rare group of neoplasms. Improving the ability to conduct international clinical trials for CNS GCT requires use of homogeneous, common objective disease assessments and standardised response criteria. Currently, different criteria are employed between European and North American protocols for assessing radiological disease response. METHODS: An international working group of the European Society for Paediatric Oncology (SIOPE) Brain Tumour Group (BTG) and North American Children’s Oncology Group (COG) was therefore established to develop consensus recommendations for imaging response assessment for CNS GCT. The working group first reviewed existing literature and current practices and identified major challenges regarding imaging assessment. RESULTS: New clinical imaging standards were defined for the most common sites of intracranial GCT disease (suprasellar/pineal/bifocal), as well as for definition of loco-regional extension. In particular, clear standards were highlighted for definition of partial response (PR) and complete response (CR) to induction chemotherapy at different sites. Furthermore, growing teratoma syndrome (GTS) was clearly defined [apparent radiological increase in non-germinomatous GCT (NGGCT) size during induction chemotherapy despite normalising/normalised AFP/HCG markers – requiring surgery], to avoid such potential cases being classified as progressive disease (PD). CONCLUSION: This consensus will allow more consistent prospective neuroradiological evaluation of response to therapy for patients with CNS GCT and facilitate direct comparison of treatment outcomes across international studies. Ultimately, it may allow international trials to be developed and undertaken across a larger group of collaborating nations, which will be essential to answer many of the remaining questions for this rare but diverse group of tumours.