Intracranial Germ Cell Tumors Research Articles

A Case of Pituitary Germinoma With Complete Recovery of Visual Field

Abstract Central nervous system germ cell tumours (GCTs) are rare, accounting for 0.1-3.4% of all primary brain malignancies. Intracranial GCTs (ICGCTs) usually arise within the pineal recess (50-65%), sellar-suprasellar region (25-35%) and rarely in the basal ganglia-thalamus (5-10%). A peakonset occurs during the second decade of life with a median age at diagnosis between10-12 years and a male predominance. Histologically, ICGCTs are classified into germinomas accounting for two thirds of cases and non-germinomatous GCTs. ICGCTs present with clinical features dependent on their location and tumour size. Symptoms most often arise from compressed optic structures, increased intracranial pressure and central endocrine abnormalities, particularly diabetes insipidus (DI). Clinical findings combined with elevated tumour marker levels within the serum and/or cerebrospinal fluid (CSF) can be diagnostic. Case: A 30-year-old lady who survived a childhood leukaemia presented as an emergency with a two-month history of headaches, dizziness and near-complete visual loss. Cranial MRI identified a large sellar mass with suprasellar extension compressing the optic chiasma and hypothalamus. Biochemical and endocrine profiles confirmed diabetes insipidus, hypocortisolaemia and hypothyroidism all requiring hormone replacement. Visual field examination revealed total left visual loss and a right temporal hemianopia. Cerebrospinal fluid analysis identified an elevated human chorionic gonadotropin (HCG) level at 16 IU/L (normal <2), with a normal alpha-fetoprotein (AFP) level. Both tumour markers were normal in the serum. Emergency Etoposide-Cisplatin (Em-EP) chemotherapy was initiated for a suprasellar GCT followed by the EPOMB-ITMTX regimen [Etoposide-Cisplatinwith intrathecal Methotrexate (ITMTX) alternating with Vincristine-Methotrexate-Bleomycin]. After four cycles EPOMB-ITMTX, the vision was fully restored, brain MRI demonstrated an excellent radiological response and the CSF HCG normalised. Our patient received volumetric-modulated arc cranial radiotherapy (VMAT) with a total 54 Gy in 16 fractions. She remains well without disease recurrence for 14 months. Tumour markers are normal with stable MRI brain and whole-spine. Endocrine follow-up confirms recovery in all pituitary axes except the gonadotrophins for which she remains on hormone replacement therapy. Conclusion: This case demonstrates an excellent outcome for a young adult diagnosed with a suprasellar GCT treated with chemotherapy followed by stereotactic radiotherapy. It highlights the importance in keeping a high clinical index of suspicion in young adults presenting with a midline intracranial tumour, visual dysfunction and an endocrinopathy. CSF analysis identified an elevated tumour marker level, which bypasses the need for a histological diagnosis.

The Third Eye Sees Double: Cohort Study of Clinical Presentation, Histology, Surgical Approaches, and Ophthalmic Outcomes in Pineal Region Germ Cell Tumors

Intracranial germ cell tumors (GCTs) predominantly occur in the adolescent and young adult population and are most frequently located at the pineal gland. Tumor masses in the pineal region may cause ophthalmic symptoms due to compression to the midbrain, frequently presenting with Parinaud syndrome and hydrocephalus due to aqueductal compression. We conducted a single-institution cohort study of primary, pineal region GCTs to characterize the clinical presentation, as well as associated ophthalmic and hydrocephalus outcomes. Fifty-six primary pineal GCTs were identified. Among the 40 isolated pineal region GCTs, 15 were germinomas while 25 were nongerminomatous GCTs. Among 43 cases of hydrocephalus, endoscopic third ventriculostomy was the primary treatment in 27 cases, which was successful in 23 but failed and required additional treatment for the rest. Pineal tumor mass was significantly larger in cases with hydrocephalus compared with those without, and the 20-mm diameter of the tumor was the crucial point for obstructive hydrocephalus. Ophthalmic symptoms were commonly observed at presentation, which included diplopia (74.3%), upward-gaze palsy (69.7%), and Argyll Robertson pupil (40%). These symptoms tended to remain, and the existence of these symptoms at presentation predicted the remaining symptoms in the follow-up. Intracranial GCTs presenting with ophthalmic abnormalities appear to be at increased risk of residual posttreatment symptoms, while second-look surgery presents a significant risk factor for the development of new deficits. Hydrocephalus often accompanies pineal region GCTs, and in most cases both cerebrospinal fluid diversion and tissue diagnosis can be successfully achieved via endoscopic third ventriculostomy.

Clinical outcomes of pediatric patients with autism spectrum disorder and other neurodevelopmental disorders and intracranial germ cell tumors.

Intracranial germ cell tumors (IGCTs) are rare tumors of the central nervous system with peak incidence around puberty. Given the developmental origins of IGCTs, we investigated the prevalence of neurodevelopmental disorders (NDDs) in patients with IGCTs and characterized outcomes for patients with NDD and IGCTs. A retrospective review of medical records was conducted for 111 patients diagnosed with IGCTs between 1998 and 2018 and evaluated at the Massachusetts General Hospital. Kaplan-Meier method and log-rank test was used for survival analyses. Cox regression analyses were performed for parameters associated with progression-free survival (PFS). Median age at IGCT diagnosis was 12.8 years (range: 4.3-21.7) and median follow-up was 6.5 years (range: 0.2-20.5). Eighteen patients were diagnosed with NDDs prior to IGCT diagnosis, including five patients with autism spectrum disorder (ASD). Of the 67 patients with pure germinomas, four (6.0 %) had prior ASD diagnoses. Patients with NDD had significantly inferior PFS in the nongerminomatous germ cell tumor (NGGCT) cohort. On univariate and multivariable analyses, craniospinal irradiation (CSI) was significantly associated with improved PFS in the NGGCT cohort. Our study found an ASD prevalence in the pure germinoma cohort more than threefold greater than the national prevalence, suggesting an association between ASD and pure germinomas. Furthermore, patients with NDD and NGGCT had worse PFS, possibly due to fewer patients with NDD receiving CSI. Future prospective studies with larger cohorts are needed to examine associations between NDDs and IGCTs, and further characterize outcomes for patients with NDDs and IGCTs.

Intracranial germ cells tumour: a single institution experience in Argentina.

Intracranial germ cell tumor (iGCT) represents a rare and heterogeneous group, with variable incidence and diverse treatment strategies. Although multiagent chemotherapy with reduced radiotherapy strategy has been applied by several cooperative groups in North America and Western Europe, there is a paucity of data to understand if this combined regimen is suitable in low-middle income countries (LMIC). We evaluate the outcome in a cohort of iGCT treated by SIOP-CNS-GCT-96 strategy at hospital J.P Garrahan in Argentina over the last 20years. Radiation field and dose included focal radiotherapy (FRT) before 2009 or focal radiotherapy plus whole ventricular radiotherapy (WVRT) after 2009 for localized germinoma and FRT or FRT plus WVRT or CSI for non germinomatous germ cell tumors (NGGCT) RESULTS: Sixty iGCT were identified; 39 germinoma and 21 NGGCT. Median follow-up was 6.57years (range 0.13-20.5). 5-year PFS and OS were 83.5% (95% CI [165.53-223.2]) and 88.7% (95% CI [169.84-223.2]) for the germinoma group, while for the NGGCT group were 75% (95% CI [133.27-219.96]) and 64.2% (95% CI [107.38-201.81]) respectively. The localized germinoma group showed poor results between 2000 and 2009 with 5-year PFS and OS of 69 and 75% respectively, and an excellent outcome between 2010 and 2019 with a 5-years PFS and OS of 92.8 and 100%. A univariable analysis identified this difference in survival as related to the field of radiotherapy, specifically whole ventricular radiotherapy. FRT increased the risk of recurrence in localized germinoma, involving not only ventricular relapses; but spinal cord and disseminated disease as well. There were no relapses of localized NGGCT after FRT and FRT plus WVRT. Herein we demonstrate that intensive chemotherapy followed by FRT plus WVRT for germinoma is a feasible and effective strategy, warranting further study in the developing world.

In Silico Molecular Docking Analysis of α-Pinene: An Antioxidant and Anticancer Drug Obtained from Myrtus communis

Background: Testis-specific protein on Y chromosome (TSPY) is the output of a tandem gene cluster. TSPY expression has been observed in gonadoblastoma and numerous distinct kinds of germ cell tumors, such as carcinoma in situ/intratubular germ cell neoplasia, seminoma, and extragonadal intracranial germ cell tumors (GCT). Myrtus communis extract rich in α-pinene showed high antioxidant and anticancer activity against a TSPY. Methods: The molecular weight and theoretical isoelectric of the TSPY proteins were calculated, using the ExPASSY ProtParam tools. Some software like mega 6, BioEdit, NEB cutter (New England Biolabs), and CAP3 were used to analyze clustering and find restriction enzymes on the TSPY sequence. To evaluate the nucleotide diversity of all sequences, the number of diverse situations and Tajima’s and Watterson’s estimators of theta were assessed. Nucleotide polymorphism can be measured by several parameters, such as haplotypes diversity, nucleotide diversity, theta using Dnasp software. To find interaction networks of protein-protein search tool for the retrieval of interacting genes/proteins (STRING) tools and to predict 3D structure, SWISS-MODEL was used; however, for docking protein-peptide based on interaction, Swiss Dock, Galaxy web, and CABS-dock software were employed. Results: We report a high (0.91) dN/dS index, positive Tajima's D, Fu, and Li’s tests, and a non-significant D test suggesting the occurrence of old modifications or a decrease of newborn mutations in the TSPY gene family. Interestingly, several hub proteins produced a strong chain or an operative module within their protein groups, such as nucleosome assembly protein (1NAP1L), RBMXL2, TBL1Y, and AMELY, which are all associated with the same cellular appliance elements and/or genetic uses. The docking of the TSPY target with α-pinene using docking revealed that the computationally-prognosticated lowest energy networks of TSPY are established by intermolecular hydrogen bonds and stacking interactions. Conclusions: The results of this study demonstrated that α-pinene interacts with the TSPY protein target and could be developed as a promising candidate for the new anticancer agent.

Precise detection of the germinomatous component of intracranial germ cell tumors of the basal ganglia and thalamus using placental alkaline phosphatase in cerebrospinal fluid.

The disadvantages of biopsy for lesions in the basal ganglia and thalamus include a risk of various complications, difficulty in selecting the target tissue in some cases due to indistinct neuroimaging findings and limited availability of sample tissue. Placental alkaline phosphatase (PLAP) plays a decisive role in the diagnosis and management of intracranial germ cell tumors (IGCTs) in the basal ganglia and thalamus. The present study aimed to demonstrate the ability, specificity, and optimal use of PLAP values obtained from cerebrospinal fluid (CSF). Twenty patients with lesions in the basal ganglia and thalamus were enrolled in this study: 11 had IGCTs and 9 had non-IGCTs. The values of PLAP and other established tumor markers in the CSF were measured in all patients before treatment. The mean follow-up period was 76.0months (range, 3-168) for all lesions. PLAP was elevated in all 11 patients with IGCTs in the basal ganglia or thalamus, whereas none of the patients with non-IGCT exhibited elevated PLAP. Thus, the sensitivity and specificity of PLAP were both 100%. Our data demonstrated that the PLAP value can specifically identify the germinomatous component even in cases of IGCTs in the basal ganglia or thalamus with high sensitivity and specificity. PLAP is undoubtedly beneficial for the safe and timely detection of the germinomatous component of IGCTs in the basal ganglia and thalamus, because reliance on PLAP measurement enables us to avoid invasive surgical procedures and facilitates the prompt initiation of chemoradiation therapy.

Mature Teratoma in the Third Ventricle: A Case Report and Review of the Literature

Introduction: Germ Cell Tumors (GCT) represent less than 4% of primary brain tumors. They comprise Germaniums, Non-Germinomatous Germ Cell Tumors and Teratomas. Teratomas represent less than 20% of intracranial GCT. They are tumors of multipotential cells derived from all 3 germ cell layers, frequently arising in midline structures, most commonly in the pineal and suprasellar regions, with a clear excess of male cases and frequently found in children and young adults. We report a case of a mature teratoma in the third ventricle in a 37-year-old male. Case Report: We report a case of a 37-year-old male with a history of headache lasting up to 9 days and refractory to pharmacological treatment. The CT scan revealed a 20mm round hypodense lesion in the anterior third ventricle, with a punctate hyperdensity in the inferior pole causing biventricular hydrocephalus with no periventricular lucency and the MRI showed a well-defined encapsulated mass lesion attached to the roof of the third ventricle, isointense in T1WI with circumferential enhancement and hyperintense in T2WI. Gross total resection was performed. Histopathologic evaluation revealed a mature teratoma. There was no evidence of recurrence on follow up MRI at 2 years. Conclusion: Intracranial teratomas typically originate in midline structures from optic chiasm to pineal region. Presentation after the first two decades of life is exceptional. Complete surgical resection is the only curative treatment for pure mature teratomas. We report the case of a mature teratoma in a 37-year-old male with unusual radiological findings.

Introduction of Proton Beam Therapy in Intracranial Germ Cell Tumors in India

Introduction of Proton Beam Therapy in Intracranial Germ Cell Tumors in India

Misdiagnosis of elevation of β-hCG in cystic craniopharyngioma: illustrative case

BACKGROUNDCraniopharyngiomas and germ cell tumors (GCTs) are both rare intracranial tumors commonly present in childhood or middle age. They share similar clinical and radiological features. GCTs commonly give rise to tumor markers in the cerebrospinal fluid, hence guiding the treatment plan.OBSERVATIONSThis article reports the case of a 5-year-old boy with a large sellar and suprasellar mass with obstructive hydrocephalus. Laboratory studies showed increased beta-human chorionic gonadotrophin (β-hCG) levels in the cystic fluid, suggestive of choriocarcinoma. He underwent 3 cycles of chemotherapy but showed a poor response. Further aspiration followed by tumor debulking was performed, and histopathological examination revealed craniopharyngioma.LESSONSThis case report indicates that β-hCG, commonly regarded as a specific tumor marker for choriocarcinoma, is detectable in other forms of suprasellar tumors. The authors highlight clinical and radiological features of suprasellar tumors that can be misdiagnosed as intracranial GCTs. The relevance of tumor markers and indications for histopathological confirmation are discussed.

Behavior Disorder and Social Function Impairment in Children with Basal Ganglia Germ Cell Tumors.

PurposeBasal ganglia intracranial germ cell tumors (iGCTs) can specifically destroy the basal ganglia network, leading to several cognitive, learning, behavioral, and social impairments. This study aimed to investigate the behavior and social disorders of patients with basal ganglia iGCTs.Patients and MethodsWe recruited 30 newly diagnosed iGCTs patients (and their parents) for the current study. The Child Behavior Checklist/6–18 was used to evaluate emotional and behavioral problems. The Conner’s Parent Rating Scales was used to assess symptoms of hyperactivity/impulsivity and conduct problems. The health-related quality of life (HRQoL) was assessed using the Pediatric Quality of Life Inventory 4.0 Generic Core Scale. Performance status was assessed using the Lansky play-performance scale and Karnofsky performance scale. The effects of basal ganglia lesions on these scores were examined.ResultsPatients with basal ganglia iGCTs (n = 10) had more behavioral problems (attention problems, aggressive behavior, learning problems, hyperactivity index), social function impairment, anxiety/depression, and poorer HRQoL compared to patients with non-basal ganglia iGCTs (n = 20). There was no significant difference in the Lansky play-performance/Karnofsky performance scale scores.ConclusionThis study demonstrates the effects of basal ganglia lesions on behavioral and emotional outcomes, social functions, and HRQoL of patients with iGCTs. The results may help to understand the function of basal ganglia and provide evidence for the benefit of early psychological intervention to improve the treatment for this rare disease.

GCT-37. PREVALENCE OF AUTISM SPECTRUM DISORDER AND OTHER NEURODEVELOPMENTAL DISORDERS IN PEDIATRIC PATIENTS WITH INTRACRANIAL GERM CELL TUMORS

PURPOSE/OBJECTIVE(s)Intracranial germ cell tumors (IGCTs) are rare tumors of the central nervous system with peak incidence around puberty. Due to the developmental origins of IGCTs, we investigated the prevalence of neurodevelopmental disorders (NDDs), including autism spectrum disorder (ASD), in our retrospective institutional cohort of patients diagnosed with IGCTs.MATERIALS/METHODSA retrospective review of medical records was conducted for 105 patients who were diagnosed with IGCTs and treated at Massachusetts General Hospital between 1998 and 2016. All patients with ASD had thorough neuropsychological assessment at the time of radiotherapy that confirmed their diagnoses.RESULTSMedian age at diagnosis was 12.8 years (range: 4.3–21.6) and median follow-up time was 4.7 years (range: 0.4–15.8). Seventeen patients with IGCTs were diagnosed with NDDs prior to cancer diagnoses, including five patients with ASD, and three patients with chromosomal abnormalities, including one patient with Down syndrome. Interestingly, four of five patients with ASD developed pure germinomas, giving an ASD prevalence rate of 6.5% and 2.3% in the pure germinoma and NGGCT cohorts, respectively. All other patients had no known diagnoses of NDDs.CONCLUSIONSOur study found 17 patients with IGCTs were diagnosed with NDDs prior to their cancer diagnoses. An ASD prevalence of 6.5% in the pure germinoma cohort is more than three-fold greater than the national prevalence, suggesting there may be an association between ASD and pure germinomas. Future prospective studies with larger cohorts are still needed to examine associations between NDDs and ASD and IGCTs.

GCT-08. PROTON BEAM RADIOTHERAPY FOR PEDIATRIC AND YOUNG-ADULT PATIENTS WITH INTRACRANIAL GERM CELL TUMOR

BACKGROUNDTo reduce treatment-related adverse events in pediatric and young-adult patients with brain tumors, proton beam radiotherapy (PBT) has recently been performed instead of conventional X-ray radiotherapy. However, whether PBT is as effective as X-ray radiotherapy has not been sufficiently investigated, especially in patients receiving whole-ventricular irradiation.METHODSWe report a retrospective observation of 15 patients with intracranial germ cell tumors (GCT), who received PBT at our institution from April 2014 to September 2019. We evaluated their clinical course, short-term adverse events, and prognosis. RESULTS/CONCLUSIONFifteen patients (9 males and 6 females; median age 13 years) who received PBT following induction chemotherapy were analyzed. Nine patients received 23.4–27.0 GyE of whole-ventricular irradiation due to GCT in the pituitary gland, pineal body, or hypothalamic area. Three patients received 23.4 GyE of whole-brain irradiation: one of them had boost irradiation for basal ganglia. Three patients received 30.6 GyE of craniospinal irradiation (CSI). Six of the 15 patients experienced nausea (grade 2, according to the CTCAE version 4.0). Four patients, including two who received CSI, showed myelosuppression: decrease in white blood cell count, lymphocyte cell count, and neutrophil count (grade 3). No other severe short-term adverse events of >grade 2 was observed in any of the patients. At a median follow-up of 21 months (2‐62 months) after irradiation. all patients are alive without recurrence. Our results may be encouraging and further investigations with a larger scale is warranted.

GCT-69. VOLUMETRIC CHANGE BEFORE CHEMORADIOTHERAPY AND INFLUENCE OF DIAGNOSTIC RADIATION EXPOSURE IN INTRACRANIAL GERMINOMAS

BACKGROUNDSpontaneous regression in intracranial germ cell tumors has been reported in some literatures, but the mechanism has not been well known. We retrospectively measured the tumor volume before chemoradiotherapy and analyzed factors that influence reduction of tumor volume.PATIENTS AND METHODSPlural MRI scans were done before the first course of chemotherapy regimen in 27 patients with primary intracranial germinomas. Their age ranged from 8 to 31 years. 35 lesions from them were enrolled and included 13 pineal, 4 neurohypophyseal, 4 basal ganglia, 4 bifocal type, and 2 multiple lesions. All regions were verified as pure germinoma or HCG-producing germinoma by histopathological examination. Tumor volume of 35 lesions was analyzed by volumetric assessment based on MRI. Ratio of volumetric change between the first MRI and the scan immediately before chemotherapy was defined as shrinking rate (%). Period between disease onset and the first chemotherapy was 20 to 47 days. Diagnostic radiation dose was calculated in each case.RESULTSInitial tumor volume ranged from 0.962 to 72.356 cubic centimeters (mean: 8.27). Diagnostic radiation dose: 40.5 to 910.1 mGy. Shrinking rate ranged from -57.8 to 85.4% (mean: 30.8). In 10 regions, shrinking rate was within 30%. Shrinking rate was significant positively influenced by diagnostic radiation dose (p<0.05) and negatively influenced by initial volume (p<0.05). But, other factors such as age, sex, histopathological parameters did not influence tumor shrinkage.CONCLUSIONThis study shows that the volume of intracranial germ cell tumors is changing dynamically before chemoradiotherapy in many cases. Diagnostic exposure to low-dose radiation influences tumor shrinkage of intracranial germinomas.

GCT-13. THE TREATMENT OUTCOMES OF INTRACRANIAL GERM CELL TUMORS WITH KSPNO PROTOCOL: SINGLE CENTER RETROSPECTIVE ANALYSIS

Dho et al. (BTRT, 2017) reported that 1.1% (127/11,827) of primary brain tumors are intracranial germ cell tumors (iGCT) in Korea. We analyzed the epidemiology and treatment results of germ cell tumors in our institution. From 2004 to 2019, among 6494 patients with intracranial neoplasms the 61 (0.9%) patients with iGCTs were enrolled: histologically diagnosed in 50 patients and clinically in 11 respectively. Pediatric patients underwent treatment according to the KSPNO protocol, and adult patients were treated with bleomycin, etoposide, and cisplatin regimens. The median age was 20 years (range: 1–42) and the follow-up period was 7.7 months (range: 10.0–203.4 months), respectively. The tumors arise most frequently in the pineal area (n=30, 49.2%). There were no significant differences in outcomes between protocols, but in KSPNO protocol group showed lower tumor recurrence rate (11.5% vs. 20%, p=0.494) and mortality (0% vs. 5.2%, p=0.503). According to the pathological subtype, the outcomes showed statistically significant differences between germinoma and non-germinomatous germ cell tumor (NGGCT) groups. The 10-year progression-free survival was 93.2% and 67.1% in the germinoma and the NGGCT group, respectively (p=0.009). The NGGCT pathological type (p=0.021) was a significant recurrence associated factor in multivariate analysis. Significant adverse events (CTCAE version 5.0 grade≥3) were showed in 14 patients (7 patients in both KSPNO and other treatment protocol groups). Pure germinoma has a higher survival rate and a lower recurrence rate than NGGCT. And KSPNO protocol might be safe and effective. For appropriate treatment for iGTCs, a multidisciplinary approach might be needed.

GCT-12. INTRACRANIAL GROWING TERATOMA SYNDROME: CLINICAL IMPLICATION FROM SINGLE UNIVERSITY EXPERIENCES

In general, intracranial germ cell tumors (GCT) are sensitive to chemotherapy, radiation therapy, and have favorable outcomes. However, a rare chemotherapeutic retro conversion phenomenon, known as intracranial growing teratoma syndrome (iGTS), shown a poorer prognosis. We analyze the diagnostic characteristics and the result of treatment response for the patients with iGTS treated in our institutes (SNUH and SNUBH, from 1997 to 2019). The electronic medical records and PACS were used for reviewing the clinical information, follow-up MRI images, tumor markers (alpha-fetoprotein, human chorionic gonadotropin, in serum or cerebrospinal fluids), and pathological findings. Out of 328 intracranial GCT patients, seventeen were finally identified as iGTS. Sixteen out of 17 patients were non-germinomatous GCTs, and 1 were germinomas. Initial pathology was common in order of immature teratoma (26.7%), other than immature teratoma (11.5%), and germinoma (0.5%). All of the tumors showed typical ‘honeycomb appearance’ in their follow-up MRI images. Sixteen out of 17 tumors were surgically resected as 2nd look surgery. Among them, 13 tumors were gross totally resected. Twelve were alive without evidence of recurrences during follow-up periods, and the other was dead from the progression of the disease. Among the other than the gross total resection group (n=4), two patients were dead, one recurred the tumor, and the other is following up with stable disease after adjuvant radiation therapy. Early detection and total resection of the tumor as possible might be meaningful for favor prognosis, especially in non-germinomatous GCTs patients.

GCT-31. DIAGNOSTIC CAPABILITY OF CSF-PLAP ON INTRACRANIAL GERM CELL TUMOR

BACKGROUNDSince the majority of intracranial germ cell tumor(GCT) is sensitive for chemoradiation, biopsy specimens are usually tiny and not enough for accurate pathological diagnosis. To supply complementary diagnostic information, a-fetoprotein or human chorionic gonadotropin-b are important biomarkers. Recently CSF-placental alkaline-phosphatase(PLAP) is also reported as an additional biomarker in intracranial GCT. This study’s purpose is to evaluate the significance of CSF-PLAP.METHODSCSF-PLAP was obtained from the patients with the intraventricular and periventricular tumor before any adjuvant therapy. Definitive diagnoses were made by histopathological information and/or their clinical courses; GCT(germinoma or non-germinomatous GCT(NGGCT)) or other tumors. In GCT, the relationship between CSF-PLAP and tumor reduction volume was evaluated. Tumor volumes were calculated on gadolinium-enhanced T1-weighted magnetic resonance imaging before and after initial chemoradiotherapy.RESULTSBetween 2005 and 2019, 42 patients were studied: 24 with GCT and 18 with others. CSF-PLAP value in patients with GCT was significantly higher than those with others: the Specificity was 88% and the sensitivity was 95% at the cutoff value of 8.0 pg/ml. For GCT patients, CSF-PLAP value tended to be higher in germinoma(n=12, mean 4756 pg/ml), compared to the value in NGGCT(n=7, mean 332 pg/ml), although there was no statistical difference. There was a significant positive correlation between initial CSF-PLAP value and tumor reduction volume.CONCLUSIONCSF-PLAP is a useful tumor marker for GCT differentiating from the other tumors located in intraventricular and periventricular region and CSF-PLAP value might correlate with the volume of germinomatous component of the tumor.

GCT-27. CLINICAL FEATURES AND PROGNOSTIC FACTORS OF NONGERMINOMATOUS GERM CELL TUMORS IN 111 CONSECUTIVE PATIENTS IN A SINGLE INSTITUTION: IMPACT OF IRRADIATION AND CHEMOTHERAPY CYCLES ON SURVIVAL

BACKGROUNDLimited data is available in intracranial nongerminomatous germ cell tumors (NGGCTs) in Chinese population. Here we aimed to retrospectively assess the clinical-pathological and prognostic factors of NGGCTs in a single large institution in China.METHODSFrom June 2003 to December 2018, 111 consecutive NGGCTs were treated in Guangdong Sanjiu Brain Hospital, China.RESULTSThe median follow-up was 36.2 months (range, 1.2 to 131.2 months). Three-year EFS and OS for 111 NGGCTs patients were 78.5%±4.5% and 82.8%±4.0%, respectively. 98 patients received CSI plus boost yielded better survival than those who received reduced-volume radiotherapy or no radiotherapy (3y OS, 86.7% vs. 51.4%, p=0.007). Patients had at least four cycles of chemotherapy were strongly associated with improved 3-year OS, compared to those received less than 4 cycles (94.1% vs. 63.6%, p＜0.001). There was no significant difference in survival of patients stratified by age, surgery, hydrocephalus, as well as tumor diameter. Multivariate analysis identified chemotherapy cycles less than 4 was the only prognostic factor that conferring a worse OS (p=0.003). Patients both received CSI and at least 4 courses of chemotherapy were correlated with lower incidence of relapse (p=0.044).CONCLUSIONSMultimodal approach including CSI and enough courses of chemotherapy was effective and should be recommended for the treatment of newly diagnosed NGGCTs in Chinese population.

GCT-59. EPIDEMIOLOGY OF PEDIATRIC INTRA-CRANIAL GERM CELL TUMORS: COMPARING THE INCIDENCE OF INTRA-CRANIAL GERM CELL TUMORS IN THE NATIVE JAPANESE POPULATION AND IMMIGRANT JAPANESE POPULATIONS ABROAD

Pediatric intra-cranial germ cell tumors (iGCTs) occur at an incidence of 0.6–1.2 cases/million/year in Western countries. The incidence is reported up to 5 times higher in the Japan. It is unknown whether this increased incidence is due to tumor biology or environment. The incidence of iGCTs in children ages 0–19 years was evaluated from 12/1/96-12/1/2016 in stable Japanese immigrant populations living abroad compared to current native Japanese registry data. Medulloblastoma incidence was used as a control to account for assumptions in the data. A review of the Brain Tumor Registry of Japan from 1984–2004 revealed an incidence of 2.5 cases/million/year and a lower incidence of medulloblastoma at 1.1 cases/million/year. Sites outside of Japan included Vancouver, Canada, Lima, Peru, and San Paolo, Brazil and together included a population of 853,174 Japanese persons. Within this population, 0 cases of iGCT were identified over a 20-years. The ratio of medulloblastoma to iGCT cases in Japan was identified as 1:2 while the ratio was 2:1, 6.5:1, and 5:1, respectively, in the other three locations. The data suggests increased incidence in the native Japan may not translate to higher incidence in immigrant Japanese populations abroad and a clear genetic component was not found in this preliminary data set. A more precise and comprehensive study is needed to determine the cause of this difference in incidence. This study also emphasizes the importance of national and state registries and is a call to collaborate on state and country level epidemiology studies.

GCT-72. ANALYSIS OF microRNA EXPRESSION PROFILE OF INTRACRANIAL GERM CELL TUMORS: A PROMISING TOOL FOR DIFFERENTIAL DIAGNOSIS

INTRODUCTIONOne of the major limitations of pathological diagnosis for intracranial germ cell tumors (iGCTs) is tumor heterogeneity, which cannot be evaluated using limited amount of tumor tissues. In this study, we performed comprehensive analysis of microRNA (miRNA) of iGCTs to identify miRNAs profile to help determine tumor diagnosis.METHODSRNA was extracted from frozen samples of 16 germinoma and 14 NGGCTs. Five non-iGCT pediatric brain tumor tissues were used as control. miRNA expression analysis was performed using a 3D-Gene Human miRNA Oligo Chip ver.22 (Toray Industries, Inc) which was designed to detect 2565 miRNAs. The miRNA expression profile was analyzed using t-SNE dimensionality reduction and weighted average difference method (WAD).RESULTSDifferent histological subtypes of the iGCTs and control samples were clustered into distinct classes. Furthermore, we found that the germinoma, NGGCTs and control samples may be readily distinguished by expression patterns of miR-200 and miR-371a-3p: a high expression of miR-200 was observed in the NGGCTs, whereas a high expression of miR-371a-3p was observed in all cases of germinoma and some of NGGCTs. Neither of miR-200 nor miR371-3p was highly expressed in control samples.CONCLUSIONOur data indicated that germ cell tumor and other pediatric brain tumors, and also germinoma and NGGCT can be distinguished by expression patterns of 2 micro RNA, miR-200 and miR-371a-3p. These 2 microRNA may serve as a useful tool for supporting the pathological diagnosis of iGCTs.

EPID-17. A SINGLE INSTITUTE EXPERIENCE IN THE REGISTRATION STUDY OF PEDIATRIC SOLID TUMOR IN JAPAN CHILDREN’S CANCER GROUP

A larger scale prospective registration study has been conducted nationwide in Japan since 2011, called as “registration study in pediatric solid tumor”, in Japan Children’s Cancer Group (JCCG). In this study, clinical data and surgical specimen are collected into the National Center for Child Health. Kyoto University Hospital has participated in this study since IRB approval in 2011. We reviewed our registered patients to the registration study and assessed the current status. 40 patients with pediatric brain tumors participated in this study from 2011 to 2020. There were 13 intracranial germ cell tumors, 9 medulloblastomas, 6 gliomas in 4 diffuse midline gliomas, 4 pilocytic astrocytoma, and 4 other types of tumor. The informed consent was obtained from 36 patients by pediatricians and 3 patients by neurosurgeons. Twenty-five surgical specimens were collected for central review. The reasons of no surgical specimens were nonsurgical management in 6 patients and no enough FFPE sample in 3 patients. There was no discrepancy between central review and institutional diagnosis. The status of clinical data entry was complete in 13 patients and uncomplete in 9 patients. These registration data including pathological diagnosis, molecular diagnosis, treatment, clinical information in patients with pediatric brain tumor are very important to realize current status. To conduct this study certainly, the collaboration among pediatrician, neurosurgeon, and supporting staff should be needed in collecting specimens and clinical data.