Nervous System Germ Cell Tumors Research Articles

QOL-07. LONG-TERM FOLLOW-UP OF PHYSICAL FUNCTION AND SOCIAL CONDITIONS IN CENTRAL NERVOUS SYSTEM GERM CELL TUMORS

Abstract BACKGROUND This paper presents an analysis of iving and social conditions from a long-term follow-up of Phase II clinical trial for central nervous system germ cell tumors conducted between 1995 and 2003. METHODS A retrospective analysis was performed on 228 cases, including 161 germinomas, 66 non-germinomas, and 1 mature teratoma, over a median follow-up of 222 months. There were 56 recurrences and 39 deaths recorded. The analysis at the final follow-up included final educational level, employment status, activities of daily living (ADLs), marital and parental status, and hormone replacement therapy. The study targeted 157 cases with more than 10 years of follow-up data. RESULTS At 20 years post-treatment, survival rates were 91% for germinomas and 65% for non-germinomas. At the last follow-up, ages ranged from 19 to 58 years (median 36 years). The Karnofsky Performance Status (KPS) was 80 or higher in 118 cases, 70 in 7 cases, and 60 or lower in 32 cases. Educational achievements were: elementary school in 1 case, middle school in 8, high school in 52, university in 45, and graduate school in 2. Employment status showed 37 unemployed, 4 in school, 23 part-time, 80 full-time, and 2 homemakers. Childbirth was reported in 16 men (18%) and 4 women (16%). The frequency of a KPS≧80 at the final follow-up was higher in initial germinoma cases than in non-germinoma cases (80 vs 62%, p=0.04), and was also higher in cases without recurrence (83 vs 47%, p<0.0001). Only the proportion of growth hormone supplementation showed a significant correlation with KPS (≧80: 19% vs <80: 3%, p=0.03). CONCLUSION Long-term social outcomes are favorable for germinoma patients without recurrence, while non-germinoma patients who have recurred and survived face tougher conditions, indicating significant treatment impacts. Managing treatment intensity and ensuring comprehensive long-term follow-up are crucial.

NCOG-43. THE APPLICATION OF INDUCTION CHEMOTHERAPY COMBINED WITH RADIOTHERAPY IN YOUNG ADULTS WITH CNS GERM CELL TUMORS

Abstract BACKGROUND Central nervous system (CNS) germ cell tumors are rare brain neoplasms, accounting for approximately 0.3-0.5% of all CNS tumors. A combination of radiotherapy and chemotherapy is the standard of care (SOC) in pediatric patients. However, there is no SOC for young adult or adult patients. This study evaluates a regimen of induction chemotherapy followed by radiation in treating young adults with CNS germ cell tumors. METHOD Nine young adult patients diagnosed with pure CNS germinomas were identified in our institution. They underwent a treatment regimen of induction chemotherapies that were planned for four cycles and consisted of bleomycin (three doses per cycle), cisplatin (five doses per cycle) and etoposide (five doses per cycle) followed with whole brain and/or ventricular radiotherapy. The patients’ overall survival (OS), neurological function (including cognition), and adverse events (AE) were analyzed. RESULT Among the nine patients (seven males and two females), the median age is 20 years (range: 17-33 years). They received bleomycin, cisplatin and etoposide (median: two cycles, range: 1-4), and subsequent radiotherapy with plans based on tumor location by radiation oncologists, with a median radiotherapy dose of 45 Gy (range: 36-50.4). Seven patients had a complete response after chemotherapy. The median OS is 53 months (range: 39-121). There is no identifiable cognitive impairment by neurological exam. All patients experienced at least one, reversible, grade 3 AE of myelosuppression. All patients return to their normal baseline including employment. Results of neuropsychological evaluation and all AEs will be presented at the conference. CONCLUSION Induction chemotherapy followed by radiotherapy is potentially safe and effective with manageable and reversible side effects from chemotherapy without cognitive and functional impairment in the nine young adult patients with CNS germ cell tumors. A prospective study of this approach in a clinical trial setting is warranted.

GCT-15. CLINICAL AND MOLECULAR CHARACTERIZATION OF INFANTILE CENTRAL NERVOUS SYSTEM GERM CELL TUMORS

Abstract BACKGROUND The management of infantile central nervous system germ cell tumors (CNS-GCTs) presents unique challenges, including variable clinical presentations such as tumor size and propensity for hemorrhage. Moreover, data on the clinical and molecular features remain limited. METHODS We conducted a clinical and molecular analysis of CNS-GCTs in children aged 6 years or younger, registered with the Japan Children’s Cancer Group and the iGCT consortium. DNA methylation analysis was performed using the Illumina Methylation EPIC array to identify potential molecular prognostic indicators. RESULTS The cohort comprised 43 patients, with a median age at onset of 6.5 months (0–68 months). Notably, 23 patients (54%) were diagnosed before 1 year of age. The male-female ratio was 27:15. Most common tumor location was cerebellum (13 cases). The median AFP level was 538 ng/ml (0–206460). Pathologically, the tumors were predominantly diagnosed as teratomas and yolk sac tumors. Teratomas were more common in patients diagnosed before 1 year of age, while mixed GCTs were more frequent in those diagnosed after 3 years. Molecular analysis identified four cases as embryonal tumors, including three AT/RTs and one DICER1-mutant intracranial sarcoma. The 3-year overall survival rates varied significantly by diagnosis: mixed GCTs at 100%, teratomas at 90.6%, yolk sac tumors at 30.0%, and embryonal tumors at 0%. Notably, two patients with teratomas developed metachronous tumors more than 10 years post-diagnosis, with both secondary tumors exhibiting mutations in the MAPK pathway absent in the primary tumors. CONCLUSION Infantile CNS-GCTs exhibit distinct clinical and molecular profiles compared to those in older children and adults. Not all tumors classified as GCTs based on molecular characterization were GCTs; some were embryonal tumors, potentially impacting treatment strategy. The genetic analysis suggests that some metachronous GCTs may represent second primary tumors rather than recurrences.

GCT-25. THE IMPACT OF RESIDUAL DISEASE ON THE OUTCOMES OF CENTRAL NERVOUS SYSTEM GERMINOMAS – A MULTICENTER INSTITUTION EXPERIENCE

Abstract BACKGROUND Germinomas make up about two-thirds of central nervous system (CNS) germ cell tumors and are highly radio-sensitive with excellent survival rate of more than 90%. Current standard of care involves the combination of chemotherapy with reduced-dose radiotherapy. Typically, patients with residual disease receive a higher dose of radiotherapy. However, recent clinical trials showed that there were no differences in the outcomes between those who had complete response (CR) versus partial response (PR) to initial chemotherapy. Hence, we aimed to assess the outcomes of germinoma patients based on the responses to both chemotherapy and radiotherapy. METHODS A multicenter retrospective chart review of patients with germinoma from four large academic institutions was conducted. RESULTS Data from 41 germinoma patients treated between 2011 and 2022 were analyzed. Thirty-two patients had stable disease (SD)(2), PR(28), or CR(2) to chemotherapy. At the end of radiotherapy, 12 had CR, 5 had PR, and 13 had SD. All patients were alive at the time of review, with a median duration of survival from diagnosis of 78.85 months (range 3.90-278.67). One patient experienced radiographic progression following chemotherapy with SD noted following radiotherapy. CONCLUSION Relapses are extremely rare in patients who have residual disease at the end of therapy for germinoma. Future prospective clinical trials are needed to test the possibility of treating germinoma patients who have residual disease with a dose of radiotherapy comparable to that used in patients who achieve complete response.

GCT-10. OUTCOME OF CHILDREN AND ADOLESCENTS DIAGNOSED WITH GERMINOMA WITH HCGΒ VALUES BETWEEN 100-200 MUI/ML TREATED ACCORDING TO THE BRAZILIAN CNS GCT PROTOCOL

Abstract BACKGROUND Primary central nervous system (CNS) germ cell tumors (GCT) are rare tumors, classified according to histological components and tumor markers (TM) as Germinomas and Non-Germinomatous Germ Cell Tumors (NGGCT). The aim of this study is to assess the outcome of patients with Germinoma and HCGβ levels between 100-200mIU/ml treated according to the Brazilian CNS GCT Consortium Protocol. METHODS From 2013 to 2021, forty-three patients presented with histological and/or TM (serum and CSF) consistent with the diagnosis of germinoma, five of them with HCGβ levels between 100-200mIU/ml. The treatment plan performed was four cycles of carboplatin/etoposide followed by whole ventricular field irradiation (WVFI) of 18Gy with a boost to primary site(s) up to 30Gy and 24Gy craniospinal irradiation (CSI) for disseminated disease. RESULTS Average age 13.7 years (6.3-20.3 years), four males and one female. Diagnosis was made by TM (n=2), and biopsy +TM (n=3). The primary tumor location was pineal (n=2), suprasellar (n=1), and bifocal (n=2) with 1 case presenting ventricular spread at diagnosis. Three patients achieved complete response (CR) after two cycles of chemotherapy and one after four cycles. One patient showed partial radiological response (PR) with negative TM after four cycles and was submitted to a second-look surgery, with pathological report of residual scar tissue. Radiotherapy was performed as described in all patients with four patients receiving WVFI (18Gy+30Gy) and one CSI (24Gy+30Gy). In a mean follow-up of 64 months, overall and event-free survival was 100%. CONCLUSION Despite the small sample, the present study shows effectivity with excellent results and a possibility of increasing the cutoff and therefore reducing treatment for patients with HCGβ at levels up to 200mlU/ml currently treated in some protocols as NGGCT cases.

GCT-16. LONG-TERM OUTCOMES AND COMPLICATION MANAGEMENT IN CNS GERM CELL TUMORS: INSIGHTS FROM A PHASE II HISTOPATHOLOGY-STRATIFIED TREATMENT TRIAL

Abstract BACKGROUND This detailed examination merges outcomes from a Phase II clinical trial targeting central nervous system (CNS) germ cell tumors (GCTs) conducted between 1995 and 2003. It evaluates the impact of histopathologically driven treatment modalities on survival, recurrence, and post-treatment life and social outcomes, aiming to delineate the long-term effects of such stratified treatment approaches. METHODS The cohort comprised 228 patients, stratified into three groups based on histology: germinoma (n=161), intermediate prognosis (n=38), and poor prognosis (n=28), each receiving customized chemotherapy and radiation treatments. With a median follow-up duration of 222 months, this longitudinal study scrutinized survival rates, recurrence patterns, and a spectrum of socio-economic and health-related outcomes. RESULTS For the germinoma group, the 10- and 20-year event-free survival (EFS) rates stood impressively at 82% and 73%, respectively, with overall survival (OS) rates reaching 97% and 92%. The intermediate prognosis group witnessed 10- and 20-year EFS rates of 76% and 66%, and OS rates of 87% and 70%. The poor prognosis group recorded EFS rates of 49% at both intervals, with OS diminishing to 61% and 53%. Notably, germinomas localized in the basal ganglia exhibited high relapse rates absent initial whole-brain radiation, yet were effectively managed upon subsequent interventions. The comprehensive follow-up illuminated striking disparities in socio-economic achievements: higher educational attainments, more stable employment, and improved health outcomes were predominantly observed among patients without recurrence. Non-recurrent germinoma patients, in particular, showcased enhanced educational and employment status, vividly illustrating the profound impact of disease progression and treatment on life quality. CONCLUSIONS The findings highlight the critical importance of customized initial treatments for improving survival and life quality in CNS GCT patients, stressing the need for detailed long-term follow-up to address relapses and complications effectively. The study advocates for personalized care that balances treatment intensity to optimize long-term outcomes, enhancing post-treatment care.

GCT-01. CENTRAL NERVOUS SYSTEM GERM CELL TUMORS – GENERATING A CONSENSUS IN THEIR DIAGNOSIS AND MANAGEMENT

Abstract BACKGROUND Despite the excellent outcomes of central nervous system (CNS) germ cell tumors (GCTs), there still exists significant differences in how GCTs are diagnosed and managed in different parts of the world. Additionally, the long-term toxicities and morbidities of the current therapies, and their substantial negative impact on the social wellbeing of our patients should clearly indicate that the current achievements are not enough. Further, important molecular data have emerged over the past decade that we have not witnessed their translation into any of the ongoing clinical trials. METHODS A comprehensive review of all major CNS GCT clinical trials will be discussed, in addition to a detailed review of the several issues of debate. Moreover, the latest developments in molecular landscape of GCTs will be provided in order to identify the hurdles that affect their incorporation in GCT clinical trials. RESULTS Tumor marker cut-offs that differentiate between germinoma and non-germinomatous germ cell tumors are clearly different between the various groups around the world. Additionally, differences exist in the chemotherapy backbones, radiation therapy field and dose, and the appropriate regimens to treat some of the rarer GCTs. Furthermore, there is no clear guideline on how to treat patients who do not achieve complete response after chemotherapy. CONCLUSIONS Discussing the clear differences that exist in the diagnosis and management of CNS GCTs is a critical first step in generating a clear consensus between the North American, European, Asian, and Latin American groups, which will certainly guide future clinical trials, improve the outcomes as well as the long-term treatment effects for this group of patients.

Prognostic implications of distinctive imaging characteristics in primary intracranial germ cell tumors: A retrospective analysis

PurposePrimary central nervous system (CNS) germ cell tumors (GCTs) are rare brain tumors that encompass two subtypes: germinomas and non-germinomatous germ cell tumors (NGGCTs), NGGCTs have less favorable outcome and require multi-modality treatment. Biopsy is recommended for disease diagnosis, the specimen may not adequately reflect the entire tumor. This study aimed to assess distinct imaging characteristics to differentiate between GCT subgroups and to identify possible initial image and subgroup features that influence survival. MethodThis retrospective study, conducted from January 2006 to March 2023, analyzed patient data and MRI findings of primary CNS GCTs. It evaluated tumor characteristics including cysts, seeding, multifocality, and hemorrhage. Tumor volumes and apparent diffusion coefficient (ADC) values of both tumoral and normal-appearing contralateral white matter were measured. These factors were correlated with overall and 5-year survival rates. ResultsThis study included 51 participants with CGTs, comprising 19 germinoma and 32 NGGCTs cases. GCTs with hemorrhage had worse overall (P = 0.03) and 5-year (P = 0.01) survival rates. No survival difference between germinoma and non-hemorrhagic NGGCT. NGGCTs were more likely to bleed (P < 0.001) than germ cell tumor, especially those with choriocarcinoma or yolk sac tumor components (P = 0.001). The ADC ratios of germinomas were significantly lower than those of NGGCTs (P = 0.03 for whole tumor; P < 0.01 or solid part), The ADC ratios of choriocarcinoma were also lower than mixed tumor (P = 0.01; P = 0.02). ConclusionHemorrhage indicates worse prognosis. Intratumoral hemorrhage and ADC ratios differentiate germinoma from NGGCTs. Larger cohorts and advanced MR techniques are needed for future study.

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.

Primary central nervous system germ cell tumors in Central America and the Caribbean Region: an AHOPCA 20-year experience.

Primary central nervous system germ cell tumors (GCT) are rare neoplasms in pediatrics. Treatment depends on the histological subtype and extent of the disease. Overall survival (OS) is above 90% for germinomas and 70%-80% for nongerminomatous GCT (NGGCT) in high-income countries (HIC) while data are usually lacking for patients in Low-Middle Income country (LMIC). This study aims to describe the experience of treating patients with CNS GCT in four of eight countries, members of the Asociación de Hemato-Oncología Pediátrica de Centro América (AHOPCA), and determine their 5-year OS. We conducted a retrospective chart review of patients treated for CNS GCT. Epidemiological and clinical characteristics, histology, treatment modalities, and outcomes were analyzed. From 2001 to 2021, 48 patients were included: 22 from Guatemala, 18 from Nicaragua, three from the Dominican Republic, and five from El Salvador. Thirty-one (64.6%) were boys; the median age at diagnosis was 10.2 years (range: 1 to 17 years). Presenting symptoms were headaches (n = 24, 50%), visual disturbances (n = 17, 35.4%), vomiting (n = 12, 25%), nausea (n = 8, 16.7%), and diabetes insipidus (n = 7, 14.6%). Two patients with NGGCT presented with precocious puberty. Biopsy or tumor resection was performed in 38 cases (79.2%): 23 (88.4%) germinomas, 11 (78.6%) NGGCT, and four (50%) CNS GCT. Eight patients were diagnosed and treated based on CSF tumor marker elevation; four germinomas (BHCG 11.32-29.41 mUI/mL) and four NGGCT (BHCG 84.43-201.97 mUI/mL or positive AFP > 10 UI/mL). Tumor locations included suprasellar (n = 17, 35.4%), pineal (n = 13, 27.1%), thalamus/basal ganglia (n = 5, 10.4%), other (n = 12, 25%), and one bifocal. Four (8.3%) had metastatic disease, and six had positive CSF; staging data were incomplete in 25 patients (52%). Patients were treated with varied chemotherapy and radiotherapy modalities. Nine patients had incomplete data regarding treatment. Five-year OS was 65% (68% for germinoma, 50.6% for NGGCT, and 85.7% for unclassified GCT). Germinoma was the most common histology, and there was a male predominance. More than half of patients had incomplete staging data and treatment was variable across the region. OS is lower compared to HIC. Standardized treatment protocols will aid in adequate staging and treatment planning, prevent complications, and improve survival.

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.