Monitoring pediatric CNS non-germinomatous germ cell tumors via cerebrospinal fluid circulating tumor DNA.

BACKGROUND: Accurate molecular and clinical stratification of patients with central nervous system (CNS) non-germinomatous germ cell tumors (NGGCTs) remains challenging, impeding the development of personalized therapeutic approaches. Herein, we investigated the translational significance of cerebrospinal fluid (CSF) circulating tumor DNA (ctDNA) in pediatric NGGCTs to identify characteristic features of CNS NGGCTs and to identify a subset of patients for whom the presence of residual disease is a risk factor and an indicator of shorter progression-free survival (PFS) and overall survival (OS). METHODS: Medical records of patients with CNS NGGCTs between January 1, 2018 and December 31, 2022 were reviewed retrospectively. RESULTS: The cohort consisted of 11 male and six female patients. Tumor markers were elevated in four of the five people who underwent surgery. The remaining 12 patients were diagnosed with malignant NGGCTs according to elevated tumor markers. Among them, ctDNA before chemotherapy as well as ctDNA clearance were consistently associated with PFS and OS (p < .05). By setting a ctDNA positivity threshold of 6%, patients with high ctDNA (above the threshold) levels, which had limitation due to the selection based on optimal statistic from the survival analysis, had significantly inferior 5-year PFS and OS compared to those with low levels (below the threshold). ctDNA or ctDNA clearance combined with the presence of residual disease predicted significantly worse OS and PFS (p < .05). CONCLUSIONS: CSF ctDNA might allow the study of genomic evolution and the characterization of tumors in pediatric NGGCTs. CSF ctDNA analysis may facilitate the clinical management of pediatric NGGCT patients, and aid in designing personalized therapeutic strategies.

Pediatric sellar teratoma - Case report and review of the literature.

BACKGROUND: Intracranial teratoma represents a rare neoplasm, occurring predominantly during childhood. Characteristic symptoms depend on the location but are mainly hydrocephalus, visual disturbances, hypopituitarism, and diabetes insipidus. Initial diagnosis can be challenging due to similar radiological features in both teratomas and other lesions such as craniopharyngiomas. Gross total resection is recommended if feasible and associated with a good prognosis. CASE DESCRIPTION: A 10-year-old girl presented with newly diagnosed growth retardation, fatigue, cephalgia and bilateral hemianopia. Further laboratory analysis confirmed central hypothyroidism and hypercortisolism. Cranial magnetic resonance imaging showed a cystic space-occupying lesion in the sellar and suprasellar compartment with compression of the optic chiasm without hydrocephalus present, suspicious of craniopharyngioma. Subsequently, an endonasal endoscopic transsphenoidal near-total tumor resection with decompression of the optic chiasm was performed. During postoperative recovery the patient developed transient diabetes insipidus, the bilateral hemianopia remained unchanged. The patient could be discharged in a stable condition, while hormone replacement for multiple pituitary hormone deficiency was required. Surprisingly, histopathology revealed conspicuous areas of skin with formation of hairs and squamous epithelia, compatible with a mature teratoma. CONCLUSIONS: We present an extremely rare case of pediatric sellar teratoma originating from the pituitary gland and a review of literature focusing on the variation in presentation and treatment. Sellar teratomas are often mistaken for craniopharyngioma due to their similar radiographic appearances. However, the primary goal of treatment for both pathologies is to decompress eloquent surrounding structures such as the optic tract, and if applicable, resolution of hydrocephalus while avoiding damage to the pituitary stalk and especially the hypothalamic structures. If feasible, the aim of surgery should be gross total resection.

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

PURPOSE: Primary 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. METHOD: This 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. RESULTS: This 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). CONCLUSION: Hemorrhage indicates worse prognosis. Intratumoral hemorrhage and ADC ratios differentiate germinoma from NGGCTs. Larger cohorts and advanced MR techniques are needed for future study.

RARE INTRACRANIAL MULTIFOCAL NON-GERMINOMATOUS GERM CELL TUMOR IN AN 18-YEAR-OLD MALE: A CASE REPORT.

Intracranial germ cell tumors are rare brain tumors that are distinguished based on their histology and selected tumor markers. Non-germinomatous germ cell tumors are a diverse group of such tumors having the poorest prognosis. Most commonly, they are located in the suprasellar and pineal regions. Since the exact treatment protocol has not yet been established, there is currently no standardized modality of management. We present a case of intracranial multifocal non-germinomatous germ cell tumor in an 18-year-old male, along with relevant literature review. We describe initial diagnostic and treatment procedures in a young adult presented with diplopia and ataxic gait. Neuroradiological findings and elevated alpha fetoprotein and beta chain of the human chorionic gonadotropin tumor markers indicated the possible mixed germ cell tumor. Chemotherapy regimen was adjusted accordingly, biopsy was not performed. The patient's clinical condition improved significantly and his alpha fetoprotein values decreased remarkably after initiation of chemotherapy. In conclusion, initial evaluation with neuroimaging, tumor markers, and cytology from cerebrospinal fluid is important as guidance to further treatment and prognosis. In selected cases, biopsy may not be indicated to start adjuvant chemotherapy. We emphasize the importance of specific treatment modality selection based mainly on tumor markers, regardless of the precise histologic classification.

Outcomes of intracranial non-germinomatous germ cell tumors: a retrospective Asian multinational study on treatment strategies and prognostic factors.

PURPOSE: Non-germinomatous germ cell tumors (NGGCTs) are rare pediatric conditions. This multicenter study using Asian multinational patient data investigated treatment outcomes and prognostic factors for NGGCTs. METHODS: Medical records of 251 patients with NGGCTs treated from 1995 to 2015 were retrospectively analyzed from participating centers in Asian countries (Korea, Taiwan, Singapore, and Japan). RESULTS: The median follow up was 8.5 years (95% CI 7.8-9.9). In the total cohort, 5-year event-free survival (EFS) and overall survival (OS) rates were 78.2% and 85.4%, respectively. In 17.9% of the patients, diagnosis was determined by tumor markers alone (alpha-fetoprotein ≥ 10 ng/mL (Korea) or > 25 ng/mL (Taiwan and Singapore), and/or ß-human chorionic gonadotropin (ß-hCG) ≥ 50 mIU/mL). Patients with immature teratomas and mature teratomas comprised 12.0% and 8.4%, respectively. The 5-year EFS rate was higher in patients with histologically confirmed germinoma with elevated ß-hCG (n = 28) than those in patients with malignant NGGCTs (n = 127). Among malignant NGGCTs, patients with choriocarcinoma showed the highest 5-year OS of 87.6%, while yolk sac tumors showed the lowest OS (68.8%). For malignant NGGCT subgroups, an increase in serum ß-hCG levels by 100 mIU/mL was identified as a significant prognostic factor associated with the EFS and OS. CONCLUSION: Our result shows excellent survival outcomes of overall CNS NGGCT. However, treatment outcome varied widely across the histopathologic subgroup of NGGCT. Hence, this study suggests the necessity for accurate diagnosis by surgical biopsy and further optimization of diagnosis and treatment according to the histopathology of NGGCTs. Future clinical trials should be designed for individualized treatments for different NGGCTs subsets.

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

BACKGROUND: 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). METHODS: 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 20 years. 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 6.57 years (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. CONCLUSION: 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.

Canadian patterns of practice for intracranial germ cell tumors in adolescents and young adults.

INTRODUCTION: The study objectives were to describe patterns of practice for intracranial germ cell tumors (IGCT) in adolescents and young adults (AYA) and to determine factors associated with practice patterns. METHODS: A survey was written containing questions on the management of two 17-year old males, one with localized pineal germinoma and the other with localized pineal non-germinomatous germ cell tumor (NGGCT). An invitation to participate anonymously in the survey was e-mailed to 119 oncologists who treat brain tumors across Canada. RESULTS: Seventy-two (61%) of the 119 oncologists participated in the study. For the germinoma case, the most common treatment approaches were whole ventricular radiotherapy (WVRT) and chemotherapy (CH) (56%), WVRT alone (15%), and craniospinal radiotherapy (CSRT) alone (10%); for physicians recommending WVRT + CH, most frequently selected whole ventricular doses were 24 Gy (57%) and 18 Gy (20%). Chemotherapy was included in the treatment of germinoma by 96% of pediatric physicians vs. 54% of adult physicians (P = 0.001). The most common treatment approaches for NGGCT were CSRT + CH (44%), WVRT + CH (21%), and pineal gland RT + CH (15%). The selection of craniospinal vs. smaller-volume RT was not associated with the physicians' specialty, percentage of practice treating brain tumors, number of IGCTs seen, or size of institution. CONCLUSIONS: There is wide variation in the management of IGCT in AYA across Canada. A 17-year old male with a localized pineal germinoma is highly likely to receive chemotherapy if managed by a pediatric oncologist, while the same patient is much less likely to receive chemotherapy if managed by an adult oncologist.

Re-induction chemotherapy regimens in patients with recurrent central nervous system mixed malignant germ cell tumors.

BACKGROUND: The lack of a standard treatment approach has contributed to poor outcomes of patients with recurrent central nervous system (CNS) mixed malignant germ cell tumors (MMGCT). There are no data in the literature supporting optimal re-induction chemotherapy regimens that should be used for patients with recurrent CNS MMGCT. METHODS: We conducted a literature review to explore the response rate of patients with recurrent CNS MMGCT to different re-induction chemotherapy regimens by searching PubMed from 1985 through November 2017. Tumors were classified according to Japanese, European, and North American prognostic group classifications determined at initial presentation. RESULTS: Forty-two responses to various re-induction chemotherapy regimens reported in 38 patients were included. Two patients were inevaluable and their responses to re-induction chemotherapy were excluded. Thirty-five responses to various re-induction chemotherapy regimens were evaluable in 33 patients following a first relapse. Six (17%) responses were reported as complete or continuous complete responses, seven (20%) partial responses, two (6%) were stable disease, two (6%) were mixed responses, and 18 (51%) were progressive disease. Five of ten patients treated without platinum-based chemotherapy experienced tumor progression. There was a trend towards a higher rate of tumor progression among histological poor prognostic group patients, and among patients relapsing within 24 months of initial diagnosis; however, it was not statistically significant. CONCLUSIONS: The histological prognostic group and time to relapse may affect the response to re-induction chemotherapy. However, further studies with larger sample size are needed to examine these associations and determine the optimal re-induction chemotherapy regimens for patients with recurrent MMGCT.

Intracranial non-germinomatous germ cell tumors in children and adolescents: how can the experience from an uppermiddle-income country contribute to the worldwide effort to improve outcomes?

Background: Non-germinomatous germ cell tumors (NGGCT) accounts for one third of intracranial GCT. While the germinoma group have an excellent overall survival, the standard of practice for children with NGGCT is still under evaluation. Aims: Describe the results of the of the Brazilian consortium protocol. Methods: Since 2013, 15 patients with a diagnosis of NGGCT by histopathology and/or serum/cerebrospinal fluid (CSF) tumor markers, ßHCG >200mlU/ml and/or positive alpha-fetoprotein were treated with neoadjuvant chemotherapy with carboplatin, cyclophosphamide and etoposide followed by ventricular radiotherapy (RTV) of 18Gy with boost (32Gy) to the primary site. Metastatic patients underwent craniospinal irradiation (CSI) and "slow responders" to the four initial cycles of CT, to autologous stem cell transplantation (ASCT) followed by CSI. Results: Mean age, 13.1 years. Thirteen males. Primary sites: pineal (n=12), suprasellar (n=2) and bifocal (n=1). Four patients were metastatic at diagnosis. Eight patients had CSF and/or serum alpha-fetoprotein levels > 1,000ng/ml. Tumor responses after chemotherapy demonstrated complete in six cases and partial in seven, with "second-look" surgery being performed in five cases, and two patients presenting viable lesions being referred to ASCT. The main toxicity observed was hematological grades 3/4. Two patients with metastatic disease, one with Down Syndrome and AFP > 1,000ng/ml and the other with choriocarcinoma and pulmonary metastases, developed progressive disease resulting in death, as well as two other patients without evidence of disease, due to endocrinological disorders. Event-free and overall survival at 2 and 5 years were 80% and 72.7%, respectively, with a mean follow-up of 48 months (range, 7-107). Conclusions: Despite the small number of patients, in our series, treatment with six cycles of chemotherapy and RTV with focal boost for localized disease (n=11) and ACST for identified slow responders (n=2) seem to be effective strategies contributing to the overall effort to improve outcomes of this group of patients.

Primary Intracranial Germ Cell Tumors: A Study with an Integrated Clinicopathological Approach.

Background and Objective: Primary intracranial germ cell tumors (ICGCTs) are rare and are histologically classified as germinomas and non-germinomatous with distinctive prognostic and therapeutic implications. ICGCTs, essentially due to the inherent difficulty of surgical access, pose different challenges and management connotations than their extracranial counterparts. This is a retrospective analysis of histologically verified ICGCTs, which was undertaken to evaluate various clinicopathological features and their implications on patient management. Materials and Methods: Eighty-eight histologically diagnosed cases (over 14 years) of ICGCT at our institute formed the study cohort and were classified into germinoma and non-germinomatous germ cell tumors (NGGCTs). Additionally, germinomas were further subdivided on the basis of 1) tumor marker (TM) levels, as germinoma with normal TM, mildly elevated TM, and markedly elevated TM and 2) radiology features, as germinomas with typical radiology and atypical radiological features. Results: ICGCT with age ≤6 years (P = 0.049), elevated TM (P = 0.047), and NGGCT histology (P < 0.001) showed significantly worse outcomes. Furthermore, germinomas with markedly elevated TM and certain atypical radiological features showed prognosis akin to NGGCT. Conclusions: Analysis of our largest single cancer center Indian patient cohort of ICGCT shows that inclusion of age ≤6 years, raised TM, and certain radiological features may assist clinicians in overcoming the limitations of surgical sampling, with better prognostication of histologically diagnosed germinomas.

A Case of Non-Germinomatous Germ Cell Tumors of the Frontal Lobe Arising From the Lateral Ventricle With a Synchronous Pineal Lesion.

Non-germinomatous germ cell tumours (NGGCT) are rare intracranial tumours that account for 1% to 3% of cases. They are usually seen in the pineal and suprasellar regions. NGGCT of the frontal lobe arising from the lateral ventricle with a synchronous pineal lesion is uncommon. We present a case of NGGCT with multifocal lesions in the pineal gland, frontal lobe, and pons treated with chemotherapy followed by craniospinal irradiation (CSI).

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

CNS germ cell tumors (GCTs) preferentially occur in pediatric and adolescent patients. GCTs are located predominantly in the neurohypophysis and the pineal gland. Histopathologically, GCTs are broadly classified into germinomas and non-germinomatous GCTs (NGGCTs). In general, germinoma responds well to chemotherapy and radiation therapy, with a 10-year overall survival (OS) rate of approximately 90%. In contrast, NGGCTs have a less favorable prognosis, with a five-year OS of approximately 70%. Germinomas are typically treated with platinum-based chemotherapy and whole-ventricular radiation therapy, while mature teratomas can be surgically cured. Other NGGCTs require intensive chemotherapy with radiation therapy, including whole brain or craniospinal irradiation, depending on the dissemination status and protocols. Long-term treatment-related sequelae, including secondary neoplasms and cerebrovascular events, have been well recognized. These late effects have a tremendous impact in later life, especially since patients are mostly affected in childhood or young adults. Intending to minimize the treatment burden on patients, the identification of biomarkers for treatment stratification and evaluation of treatment response is of critical importance. Recently, tumor cell content in germinomas has been shown to be closely related to prognosis, suggesting that cases with low tumor cell content may be safely treated with a less intensive regimen. Among the copy number alterations, the 12p gain is the most prominent and has been shown to be a negative prognostic factor in NGGCTs. MicroRNA clusters (mir-371-373) were also revealed to be a hallmark of GCTs, demonstrating the potential for the application of liquid biopsy in the diagnosis and detection of recurrence. Recurrent mutations have been detected in the MAPK or PI3K pathways, most typically in KIT and MTOR and low genome-wide methylation has been demonstrated in germinoma; this most likely reflects the cell-of-origin primordial germ cells for this tumor type. These alterations can also be leveraged for liquid biopsies of cell-free DNA and may potentially be targeted for treatment in the future. Advancements in basic research will be translated into clinical practice and can directly impact patient management. Additional understanding of the biology and pathogenesis of GCTs will lead to the development of better-stratified clinical trials, ultimately resulting in improved treatment outcomes and a reduction in long-term treatment-related adverse effects.

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

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

Detecting non-germinomatous germ cell tumor component by arterial spin labeling perfusion-weighted MR imaging in central nervous system germ cell tumor.

PURPOSE: Differentiating between germinoma and non-germinomatous germ cell tumor (NGGCT) is important because sensitivity to chemotherapy and/or radiotherapy is quite different between these two subgroups. In this study, we evaluated whether the arterial spin labeling (ASL) based perfusion-weighted imaging (PWI) could provide additional information for the differential diagnosis between germinoma and NGGCT. METHOD: Between 2011 and 2018, 20 patients with central nervous system (CNS) germ cell tumor (GCT) who underwent preoperative MR imaging including ASL-PWI were enrolled in this study. Relative tumor blood flow (rTBF) was evaluated on ASL-PWI by manually placing regions of interest at gadolinium enhanced part of the tumors and normal subcortical white matter. Presence of intratumoral T1 hyperintense foci and apparent diffusion coefficient (ADC) were also evaluated. The final diagnosis was made by the combination of tumor markers and the histological diagnosis. RESULTS: Among 20 patients of CNS-GCT, 11 were diagnosed as germinoma and 9 were diagnosed as NGGCT. In the germinoma subgroup, the rTBF ranged from 0.90 to 1.71 (mean 1.21, median 1.09), while it ranged from 1.14 to 5.75 (mean 3.91, median 3.31) in NGGCT subgroup. The receiver operating characteristic (ROC) curve showed that calculating rTBF is useful for differentiating between germinoma and NGGCT (area under the curve (AUC) 0.929, P = 0.0012) compared to intratumoral T1 hyperintense foci (AUC 0.788, P = 0.0304) and ADC (AUC 0.919, P = 0.0016). CONCLUSIONS: High rTBF obtained by ASL-PWI implied the presence of NGGCT component. This information might help in deciding the chemotherapy/radiotherapy intensity.

Analysis of therapeutic effect of pediatric patients with intracranial primary non-germinomatous germ cell tumors / 中华放射肿瘤学杂志

Objective:To investigate the clinical features of pediatric patients with intracranial primary non-germinomatous germ cell tumors (NGGCT) and evaluate the treatment outcomes and prognostic factors of NGGCT.Methods:Clinical data of 40 children with NGGCT who were treated with radiotherapy (RT) at our department between November 2008 and June 2019 were retrospectively analyzed. Ninety percent of them received craniospinal irradiation (CSI). All children received platinum-based chemotherapy. Survival analysis was conducted using the Kaplan-Meier estimate. The prognostic factors were analyzed by log-rank test.Results:The primary sites were pineal gland, sellar / suprasellar region and basal ganglia. The median age of onset was 108 months (20-204 months). The median follow-up time was 33 months (8-131 months), and the 3-year and 5-year overall survival (OS) rates were 82.0%. The 3-year and 5-year progression-free survival (PFS) rates were 78.6% and 73.0%. Univariate analysis showed that increased alpha-fetoprotein (AFP) ( P=0.02), age at first diagnosis>10 years ( P=0.006), metastasis at first diagnosis ( P<0.001), and the pathological type (choriocarcinoma, yolk sac tumor and / or embryonal carcinoma) ( P=0.036) were independent adverse prognostic factors. Conclusions:Increased AFP, age>10 years at first diagnosis, tumor metastasis and pathological type were independent adverse prognostic factors of NGGCT. The overall prognosis of NGGCT children is worse than that of their counterparts with germinoma, and multidisciplinary intensive therapy is needed to improve survival.

Outcomes for pediatric patients with central nervous system germ cell tumors treated with proton therapy.

PURPOSE: We assessed outcomes after proton therapy (PT) for central nervous system germinomas or non-germinomatous germ cell tumors (NGGCTs) in children. PATIENTS AND METHODS: We identified children with germ cell tumors of the central nervous system who received proton therapy in 2006-2009 and extracted information on tumor response, treatment failures, and toxicity. RESULTS: Of the 20 identified patients (median age 12 years [range 3-16]), 9 had germinoma and 11 NGGCTs; 19 patients received three-dimensional conformal PT and 1 scanning-beam PT. Fourteen patients had craniospinal irradiation (CSI), 4 had ventricular irradiation that excluded the 4th ventricle, and 2 had whole-ventricle irradiation. All received involved-field boosts. At a median follow-up interval of 5.6 years (range, 0.3-8.2 years), 1 patient with germinoma had an out-of-field failure in the 4th ventricle and 2 with NGGCT died from disease progression after CSI. Rates of local control, progression-free survival, and overall survival at 5 years were 89%, 89%, and 100% for patients with germinoma; corresponding rates for NGGCTs were 82%, 82%, and 82%. The most common late toxicity (9 patients [45%]) was endocrinopathy. CONCLUSIONS: PT for CNS germ cell tumors is associated with acceptable disease control rates and toxicity profiles.

Growing Teratoma Syndrome of the Pineal Gland Recognized Very Early during Chemotherapy in a Child with a Non-Germinomatous Germ-Cell Tumor / 임상소아혈액종양

The growing teratoma syndrome (GTS) is defined as the development of mature low-grade elements in the absence of a recurrent non-germinomatous germ-cell tumor (NGGCT) after partial response to multimodal treatment. It is uncommon and may occur in intracranial NGGCTs. Here, we report that a 7-year-old boy with intracranial NGGCT presented with precocious puberty and developed growing teratoma syndrome only 2 weeks after the first cycle of chemotherapy.

Growing Teratoma Syndrome of the Pineal Gland Recognized Very Early during Chemotherapy in a Child with a Non-Germinomatous Germ-Cell Tumor / 임상소아혈액종양

The growing teratoma syndrome (GTS) is defined as the development of mature low-grade elements in the absence of a recurrent non-germinomatous germ-cell tumor (NGGCT) after partial response to multimodal treatment. It is uncommon and may occur in intracranial NGGCTs. Here, we report that a 7-year-old boy with intracranial NGGCT presented with precocious puberty and developed growing teratoma syndrome only 2 weeks after the first cycle of chemotherapy.