Germ Cell Tumors Research Articles

GCT-05. UPDATED REPORT ON TREATMENT MODALITIES IN METASTATIC GERMINOMA IN CHILDREN: A MULTI-INSTITUTIONAL ANALYSIS

Abstract BACKGROUND Primary intracranial germ cell tumors (GCTs) are rare heterogeneous tumors; germinoma accounts for two-thirds of cases. While neoadjuvant chemotherapy followed by response-based reduced radiotherapy dose and field is the established approach for managing localized CNS germinomas, controversy persists regarding the treatment of primary metastatic disease. Additionally, limited research exists on the utilization of neoadjuvant chemotherapy in primary metastatic germinoma. METHODS A retrospective multi-institutional analysis was conducted to assess overall survival (OS) and event-free survival (EFS) among patients diagnosed with metastatic germinoma who were treated with various modalities. RESULTS We identified 88 patients, including 63 males and 25 females. The median age at presentation was 13.5 years. All patients, who had undergone both brain and spine MRIs, had their diagnoses confirmed through a biopsy, positive CSF cytology, and/or positive CSF tumor markers at presentation. Primary Tumor location was pineal (n=37), suprasellar (n=27), bifocal (n=14) and others (n=9). Eight patients underwent subtotal resection. Craniospinal irradiation (CSI; 21-24 Gy) was administered to 71 patients (81%), while eight patients (9%) received whole ventricular irradiation (WVI; 23.4-30 Gy). Whole brain radiation was given to four patients (5%; 24 Gy), and two patients (2%) had unknown fields. Boosts to primary and/or metastatic sites were administered in all but seven patients. Notably, thirty patients (34%) received CSI without neoadjuvant chemotherapy. At the end of therapy, 69 patients had complete response, 10 partial response and the response was unknown in six. Three patients did not receive irradiation, all died of disease progression. The median follow-up was 64 months (range 6-159 months), yielding an OS of 96.6%. Ongoing multi-institutional data collection and analysis will be presented at the meeting. CONCLUSION Our study is one of the largest studies to date in metastatic germinoma and may provide insight into the role of neoadjuvant chemotherapy with lower CSI doses.

QOL-42. ANALYSIS OF LATE EVENTS AFTER RADIATION THERAPY FOR PRIMARY PEDIATRIC BRAIN TUMORS

Abstract BACKGROUND Late events after radiation therapy for primary brain tumors consist of secondary malignant neoplasms (SMN) and tumor recurrences. The incidence and biology of late events are not very well described. Therefore, we aimed to identify late events in our institutional cohort and describe their biology. METHODS A retrospective chart review of all irradiated pediatric brain tumor patients treated between 2000 and 2015 at our institution was performed to obtain demographics and clinical data of late events. Late events were defined as intracranial intraaxial SMN or tumor recurrence occurring later than 3 years after radiation therapy. A whole-genome methylation array was employed to identify the methylation class of the late event. RESULTS In the observed period, 267 patients received some form of cranial radiotherapy for primary brain tumor; high-grade glioma (HGG, n=66), medulloblastoma (n=74), ependymoma (n=50), germ-cell tumors (GCT, n=22), low-grade glioma (LGG, n=24), and other diagnoses (n=31). Out of the 174 patients who were alive and without an event after 3 years from the radiation therapy, 30 developed late events (16.8%), and 27 of them were histologically verified. Verified late events consisted of 8 SMNs (29.6%) and 19 primary tumor recurrences. SMNs were mainly radiation-induced gliomas (RIG, n=7) and one atypical teratoid/rhabdoid tumor (ATRT) after craniopharyngioma. All RIG tumors clustered with the “pediatricHGG_RTK1” methylation class. Tumor recurrences consisted of medulloblastomas (Group 4 and Wnt), ependymomas (PFA and ST_ZFTA), GCTs, gliomas (one NF1-associated HGG, one H3-altered thalamic glioma, one diffuse astrocytoma with BRAF-V600E mutation), and craniopharyngiomas. The overall survival rate 5 years after a late event was 39.7%, with a worse survival rate for SMN patients (14.3%) compared to those with recurrences (44.9%) (p=0.05). CONCLUSIONS Late events affected 16.8% of long-term survivors. Strikingly, SMNs represented almost 30% of late events and were associated with a very poor prognosis.

GCT-18. GERMINOMAS OF THE CENTRAL NERVOUS SYSTEM (CNS): 20 YEARS EXPERIENCE WITH WHOLE VENTRICULAR IRRADIATION (WVI) AT FONDAZIONE IRCCS ISTITUTO NAZIONALE DEI TUMORI, MILAN

Abstract BACKGROUND Intracranial germ cell tumors account for 1-3% of pediatric CNS tumors, with germinomas constituting up to 65%, their prognosis being favourable compared to the non-germinomatous counterpart. METHODS After an unsuccessful experience with focal irradiation, from 2001 to 2021 we treated 68 patients (51 males/17 females, median age at diagnosis 16 years) with 4 PEB cycles (cisplatin 25 mg/sqm days 1-4, etoposide125 mg/sqm days 1-4, bleomycin 18 mg/sqm day 2, cycles every 21 days) followed by whole ventricular irradiation (WVI) 30,6 Gy/36Gy if CR/PR-SD. Patients with metastatic disease received craniospinal irradiation only (CSI 24 Gy+16Gy TB-tumor bed/WVI). RESULTS Fifty-nine patients had localized disease: 23 pineal, 22 suprasellar, 13 bifocal, 1 in the basal ganglia and 9 were metastatic. Suprasellar localization was associated with longer diagnostic delay. Five, 10 and 20 years OS and EFS were 100%, 97.5%, 97.5% and 95.3%, 92.8%.92.8% respectively. There was no statistical difference according to age at diagnosis, site and metastatic/bifocal disease. During follow-up 13/59 patients (22%) revealed moderate (2)/slight (11) impairment of the pulmonary function at spirometry assessment. Audiometric tests were available for 59 patients: 42 were normal (71%), 11 had a slight deficit, 4 moderate and 2 severe. Neurocognitive homogeneous evaluations were available only for 9 patients, so no clear correlation can be done, except observing the lowest scores in the patient with basal ganglia involvement. New endocrine deficits appeared in 9 patients after the treatment. CONCLUSIONS WVI tailored on response to chemotherapy proved effective in curing children CNS germinoma. Cisplatin and bleomycin-containing regimens induce high-response rates with known but in our experience limited sides effects. New collaborative protocols will investigate the reduction of the doses of irradiation and the use of less toxic drugs in order to achieve the same cure rates with less side effects.

LMIC-17. DIAGNOSTIC DELAY IN CHILDREN WITH CNS TUMORS IN A TERTIARY HOSPITAL IN MEXICO

Abstract BACKGROUND Delays in diagnosis of central nervous system (CNS) tumors have been associated with increased morbidity and mortality. We aimed to describe the time intervals for diagnosis and explore factors related to diagnostic delays in a tertiary public hospital in a middle-income country. METHODS A retrospective study was carried out, collecting data from patients diagnosed with brain tumors between 2000 and 2021 at the National Medical Center “20 de Noviembre” in Mexico City. The data were analyzed using descriptive statistics. RESULTS Data were collected from 163 patients with a median age of 8 years (range 0-18 years). 81 (49.7%) patients were diagnosed with gliomas, 47 (28.8%) with embryonal tumors, 20 (12.3%) with ependymomas, 10 (6.1%) with germ cell tumors of the central nervous system, 3 (1.8%) with choroid plexus carcinoma, and 2 (1.2%) with other diagnoses. The median time of symptom start and first visit with a physician was 20 days (rage 1 to 180 days). The median time in which the patients arrived at the tertiary hospital after the first visit to a physician was 184 days (range 1 to 2520). The population served by the institution, included the 32 states, with 153 patients (93.9%) coming from an urban location, with easy access to medical services. 145 (89%) of the 163 patients had parents with a medium socio-economic level (urban housing, all basic services, at least one of the parents with higher education.) Of the patients studied, 75 (46%) died, 18 (11%) abandoned treatment, 65 (39.9%) survived and 5 (3.1%) were lost to follow-up. CONCLUSION An important delay was found in the start of treatment from the moment patients begin symptoms. The identified delays warrant local and national strategies that allow prompt referrals.

GCT-09. VENTRICULAR RELAPSES OF INTRACRANIAL GERM CELL TUMORS FOLLOWING FOCAL RADIOTHERAPY

Abstract BACKGROUND Non-germinomatous germ cell tumors (NGGCTs) require treatment involving combinations of chemotherapy, surgery, and radiotherapy. The radiotherapy field is typically focal in Europe and craniospinal in North America. Unlike germinomas, there are conflicting results for the effectiveness of ventricular field irradiation, and there is not enough data documenting the histology and tumor markers for tumors that relapse along the ventricles in patients who receive focal irradiation. METHODS We performed a literature review for English-language literature from 1998 to 2024 to to analyze the incidence, histopathology and tumor marker levels for NGGCT patients who initially received chemotherapy followed by focal radiotherapy and ended up having of ventricular relapses. RESULTS We identified 47 cases with relapsed NGGCT. However, only 8 cases were along the ventricles. Six of these were ventricular only, including two presumed germinomas based on tumor markers, three biopsy-proven germinomas, and only one case with bHCG levels exceeding ≥1000 IU/l. Two had combined relapses involving both the ventricular and spinal regions; one had pathology-proven germinoma but with elevated alpha-fetoprotein, and the other exhibited bHCG levels between 50 and 200 IU/l. CONCLUSION Ventricular relapses in NGGCT patients who receive focal radiotherapy should be investigated further. Whole ventricular radiotherapy may be required to prevent the relapse of germinoma elements. However, further information is essential before making any changes in the radiotherapy doses and fields.

NURS-18. GERMINOMA PATIENTS – MORE PRONE TO PSYCHIATRIC DISORDERS, ALLERGIES, AND WEIGHT PROBLEMS? AN INSTITUTIONAL REVIEW

Abstract BACKGROUND Germinoma are the most frequent type of intracranial germ cell tumour. Within nursing clinical practice an increased prevalence of psychiatric manifestations, allergies, and weight gain throughout treatment and into survivorship within the germinoma population has been observed. There is only limited literature about these problems available. METHODS A retrospective review of clinical presentation, psychiatric co-morbidity, therapeutic course, and follow-up of 27 Germinoma patients (6.2-17 years) diagnosed and treated at a tertiary care center from 2008-2021 was performed. In addition, the presence and occurrence of allergies and weight changes throughout their therapy was reviewed. RESULTS Nearly half of the Germinoma patients (n=11) (suprasellar, pineal, basal ganglia) were diagnosed with pre-existing psychiatric co-morbidity (anxiety, depression, mood disorder and eating disorder) as per DSM-5 criteria, more commonly verified after their brain tumour diagnosis and persistent beyond treatment. Three of 27 (11%) patients indicated allergies (medication, food) at diagnosis. Seventeen of the 27 (63%) patients presented with allergies throughout their therapy (medication, tape, cleaning products, blood products). Six (35%) of those patients developed anaphylactic reaction to Etoposide and/or blood products. Eight of the patients (suprasellar & pineal) were found to have a significant weight gain throughout their treatment and two (pineal & suprasellar) were found to have significant weight loss, the rest of the cohort remained stable. The impact of tumour location (suprasellar, pineal) on the specific problems is ongoing. CONCLUSION The findings of this retrospective review could guide clinical practice. The potential higher incidence of psychiatric disorders should prompt practitioners to upfront screening and throughout therapy to ensure adequate support. Allergy prevalence in pediatrics is variable but an allergy occurrence of 35% is elevated in comparison to the general population and therefore increased awareness of allergies within this population is important for the bedside nurse. Lastly, early involvement of dieticians to aid in weight management seems crucial.

RADT-08. BASAL GANGLIA TOXICITY FOLLOWING PROTON THERAPY OF THE PINEAL REGION WITH BILATERAL ACTION-INDUCED MYOCLONUS

Abstract INTRODUCTION We sought to evaluate the toxicity profile for children receiving 54Gy to the pineal region with a significant dose delivered to posterior thalamus and basal ganglia. METHODS We performed a retrospective review of patients treated at a single institution with intensity modulated proton therapy (IMPT) receiving 54Gy to the pineal region. Multiple beam angles were utilized for planning. Patient characteristics and dosimetric data were correlated with late-toxicity and imaging. RESULTS From 2021-2023, six children were treated, and at a median follow-up of 13 months [9-26], all patients remain disease-free. Three patients had non-germinomatous germ cell tumors, 1 low-grade glioma, 1 atypical teratoid rhabdoid tumor (ATRT), and 1 embryonal tumor with multilayered rosettes. Age range was 2.4 to 16.8 years. All patients received chemotherapy prior to IMPT. Neuropsychological evaluation indicated range of intellectual functioning (mean = 98.3 [83-118]). One patient, a 4-year-old female with ATRT, developed T2 changes within the globus pallidus and thalamus on 3 month follow-up. At 5 months, she developed bilateral action-induced myoclonus with corresponding enhancing lesions in the globus pallidus bilaterally. Neuropsychological evaluation at 5 months post-treatment indicated memory impairments. She was treated with dexamethasone without improvement. Between 912 months post-treatment, tremors improved with physical therapy and imaging showed near complete resolution of enhancement within globus pallidus. CONCLUSION One of six children developed grade 3 toxicity manifesting as bilateral action-induced myoclonus with imaging changes in the globus pallidus bilaterally following IMPT and exhibited related neuropsychological deficits. While brainstem toxicity from IMPT is well documented, globus pallidus toxicity is not well characterized. Given the contiguous neuronal tracts with the brainstem, it is logical to apply similar treatment planning techniques, i.e. minimizing hotspots within the globus pallidus and thalamic “core” structures, and being cognizant of LET/RBE effects for treatment involving the pineal region in young children.

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-21. MULTINATIONAL ANALYSIS OF PEDIATRIC RELAPSED/REFRACTORY CENTRAL NERVOUS SYSTEM NON-GERMINOMATOUS GERM CELL TUMORS

Abstract BACKGROUND Patients with relapsed/refractory central nervous system (CNS) non-germinomatous germ cell tumors (NGGCTs) have poor prognosis. We explored prognostic factors to guide the management of these patients. METHODS We performed a multinational retrospective study of relapsed/refractory CNS NGGCTs. Data were summarized using standard descriptive statistics. Overall survival (OS) was evaluated using Kaplan-Meier and Fisher’s exact test to estimate odds ratios (OR) and 95% confidence intervals (CI). RESULTS We identified 31 patients from eight centers. The median age at initial diagnosis was 11 years (interquartile range (IQR): 9-15.3). Twenty patients (64.5%) suffered a relapse, and 11 patients (35.5%) had refractory disease. The median follow-up time since relapse/progression was 17.5 months (range:1-295). The median time to relapse/progression was 12.1 months (IQR: 5.5-27.5). Ten patients (32.3%) received high-dose chemotherapy (HDCx) with stem cell rescue. Sixteen patients (51.6%) received re-irradiation at relapse/progression. Nine patients (29%) achieved complete remission (CR). Ten patients (32.3%) were alive at the time of the last follow-up. Among the ten survivors, the median serum and cerebrospinal fluid (CSF) alpha-fetoprotein levels were 2.3 ng/dl (range: 0-17) and 2.1 ng/dl (range: 0-55), respectively, the median serum and CSF beta-human chorionic gonadotropin were 23 IU/L (0-168) and 139 IU/L(0-601), none underwent gross total resection, eight received HDCx, and seven received radiotherapy (craniospinal irradiation (n=6), abdominal radiotherapy (n=1)). HDCx (OR=19.8, 95%CI: 2.7-145.7; p=0.01) and achieving CR at the end of relapse treatment (OR=160, 95%CI: 8.9-2880.5; p=<0.001) were associated with a survival benefit. Re-irradiation (OR=3.3 95%CI: 0.53-20.9; p=0.24) was not associated with a survival benefit. CONCLUSIONS A subset of patients with relapsed NGGCTs are salvageable at relapse. HDCx and achieving CR at the end of relapse therapy were associated with a survival benefit. More studies are required to identify these patients who would benefit from salvage therapy.

QOL-30. NEUROPSYCHOLOGICAL FUNCTIONING AFTER WHOLE VENTRICULAR OR CRANIOSPINAL PROTON RADIATION FOR PEDIATRIC INTRACRANIAL GERM CELL TUMORS

Abstract BACKGROUND In Western countries, intracranial germ cell tumors (ICGT) represent 3-5% of central nervous system tumors, with peak incidence in the second decade of life. Compared to those receiving photon radiation therapy, pediatric patients receiving proton radiation therapy demonstrate stronger neurocognitive outcomes, particularly in verbal and visual reasoning. Ongoing treatment advances aim to reduce morbidity, such as neurocognitive late effects. This study characterizes memory functioning for patients with intracranial germinoma treated with either whole ventricular (WV) or craniospinal (CSI) proton radiation therapy. METHODS 29 patients received proton radiation therapy (17 WV, 12 CSI) for an ICGT (20 germinoma, 8 NGGCT, 1 mixed GCT; 3 disseminated at diagnosis). Age at diagnosis was 5-21 years (M=14.14; SD=3.91) with age at neuropsychological evaluation 8-25 years (M=17.66, SD=4.11). Evaluations occurred 0.71-7.85 years after diagnosis (M=3.52; SD=2.02). Patients (82.8% male, 65.5% white, 44.8% Very High Childhood Opportunity Index [COI]) had multiple additional interventions (surgeries, chemotherapy) prior to neuropsychological evaluation. RESULTS Patients in the WV group did not differ from patients in the CSI group on sex, COI, race, or ethnicity. Mean performance was stronger in the WV group than the CSI group for Full Scale IQ (FSIQ; t(27)=2.50, p=.019, Cohen’s d =0.94), Verbal Reasoning (VCI; t(24)=2.52, p=.019, d=1.0), Visual Memory (WRAML-2 Picture Memory Recognition; t(14)=2.51, p=.025, d=1.26), and Verbal Memory [(WRAML-2 Story Memory Delay, t(15.32)=2.82, p=.013, d=1.25); (WRAML-2 Story Memory Recognition, t(20)=2.34, p=.03, d=1.0)], all with large effect sizes. CONCLUSIONS Within this small ICGT sample with various medical treatments and comorbidities, demographic factors did not differ between groups, and WV proton radiation therapy appears to have less negative impact on aspects of reasoning and memory abilities compared to CSI proton radiation therapy.

QOL-32. COGNITIVE AND PSYCHOLOGICAL LATE EFFECTS IN CHILDREN AND ADOLESCENTS WITH PINEAL REGION TUMORS: A 35-YEAR-LONG EXPERIENCE IN A TERTIARY REFERRAL HOSPITAL

Abstract BACKGROUND Pineal region tumors (PRT) account for 2.8% of all central nervous system tumors in children and adolescents up to 19 years of age. Modern therapies allow more than 2/3 of patients to overcome their disease, but late effects impair quality of life of survivors. This study aimed to define the prevalence of cognitive and psychological late effects in PRT-survivors. METHODS Demographic information, medical variables, cognitive and psychological age-appropriated assessments of childhood and adolescence PRT-survivors, followed-up at Gaslini Children’s Hospital between 1988 and 2023, were retrospectively collected. Neurocognitive assessment was performed using the Wechsler scale. Psychological assessment was obtained using the Child Behavior Checklist, Beck Depression Inventory, State-Trait Anxiety Inventory, Trauma Symptom Checklist for children and Impact of Event Scale–Revised. RESULTS Sixty patients were included (53 males, 88%); median age at diagnosis was 12.8 years (Interquartile range, IQR, 9.0–15.7 years). Main entities were: germinoma (17, 28%), non-germinomatous germ cell tumor (16, 27%), bifocal germinoma (13, 22%), pineoblastoma (6, 10%), teratoma (3, 5%). 20/60 patients (33%) had neuroaxis spread, 48/60 (80%) presented hydrocephalus, 41/60 (68%) underwent surgery, 16/60 (27%) needed ventricular-peritoneal shunt, 51/60 (86%) received chemotherapy and 56/60 (93%) required radiotherapy. Median follow-up was 8.9 years (IQR 4.1–15.2). Six patients died, 5/6 died for progressive disease. Intelligence quotient (IQ) score was available for 43/60 patients with a median value of 91 (IQR 85-107). Complete cognitive and neuropsychological assessment was available for 25/60 patients showing presence of: anxiety symptoms (16/25, 64%), depression symptoms (20/25, 80%) and post-traumatic symptoms (7/25, 28%). CONCLUSIONS In our cohort, PRT-survivors showed IQ scores within expected average and a high frequency of anxiety and depression symptoms. Deeper insights into the mechanisms underlying cognitive and psychological late effects are needed, focusing on the role of demographics, treatments and disease-specific variables as well as on tumor location.

PALC-03. MEDICAL AID IN DYING: EXPERIENCE IN THE CENTER FOR CANCER AND BLOOD DISORDERS AT CHILDREN’S HOSPITAL COLORADO

Abstract BACKGROUND Medical Aid in Dying (MAiD) is now legal in 10 US states and Washington, DC, allowing terminally ill patients to self-administer medications to peacefully end their life. There is little published on pediatric hospitals’ approach to young adult patients requesting MAiD. METHODS We review the two patients who have participated in MAiD at the Center for Cancer and Blood Disorders at Children’s Hospital Colorado (CHCO). We also explore publicly available Colorado MAiD statistics. RESULTS Between 2017 and 2022, there have been 1,090 prescriptions written for MAiD medication in Colorado, 5 of which were for patients aged 18-34 (0.5%). Two of these patients were treated at CHCO. Patient A was a 26 year old male with a CNS non-germinomatous germ cell tumor whose treatment was complicated by mucormycosis and severe engraftment syndrome. He relapsed 23 months after completing therapy. He had neurologic decline including ataxia and blindness, at which time he requested MAiD. Patient B was a 24 year old male with multiply recurrent IDH-mutant medullary high grade glioma. With metastatic progression, he had many tumor-related symptoms including dysphagia, dysarthria, and weakness impacting his activities of daily living, so he requested MAiD. Both patients had multidisciplinary care conferences with neuro-oncology, social work, ethics, psychology, and palliative care. After completing psychological evaluation and all steps required by law, they were prescribed DDAMP2 (digoxin 50 mg, diazepam 1 gram, morphine 15 grams, and propranolol 2 grams). Both patients took the medications and died peacefully. Barriers encountered included infrequency of MAiD requests leading to unclear policies and processes. CONCLUSIONS Young adults represent a small but important subset of those seeking MAiD prescriptions. Despite challenges, patients were able to receive MAiD without delay in a compassionate manner. Our experience may be applicable to other pediatric hospitals facing these requests.

GCT-14. TREATMENT APPROACH FOR METASTATIC INTRACRANIAL GERMINOMA: A MULTI-INSTITUTIONAL EXPERIENCE

Abstract BACKGROUND Germinoma is the most common CNS germ cell tumor in children. Treatment with 24Gy craniospinal irradiation (CSI) with boost to 40Gy alone results in excellent survival irrespective of disease stage. For localized germinoma, recent studies have demonstrated the efficacy of neoadjuvant chemotherapy in decreasing the field/dose of radiation therapy (RT) needed for cure. For metastatic germinoma however, the optimal RT approach when combined with chemotherapy is unclear. Herein, we present our experience in treating patients with metastatic germinoma. METHODS We performed a retrospective, IRB-approved study of patients with metastatic germinoma diagnosed between 2001-2023 at Boston Children’s Hospital, Dana-Farber Cancer Institute, Brigham and Women’s Hospital, and Mass General Hospital. Clinical features, treatment plan, and outcomes were collected and analyzed using the Kaplan-Meier method and Fisher’s exact test. RESULTS Twenty-eight patients with metastatic germinoma were identified. Median age at diagnosis was 15.9 years (range:6.2-25.9). Metastasis was intracranial in 20, craniospinal in three and CSF-only in five patients. Six patients received CSI only. Twenty-two patients received neoadjuvant chemotherapy and CSI. Median number of chemotherapy cycles was 4 (range:3-6). Seventeen patients had complete response, four patients had partial response, and one patient had progressive disease with chemotherapy. All patients went on to receive CSI, with median dose of 21Gy (range:18-36Gy) with median IF boost to 36Gy (range:30-51.6Gy). Median duration of follow-up was 11 years (range:0.3-25.3). There were no recurrences or deaths within the cohort. Analysis of long-term outcomes data revealed no significant differences in frequency of endocrinopathies, CNS vasculopathies, or memory loss between the doses of RT. CONCLUSIONS Our data show that neoadjuvant chemotherapy followed by CSI is associated with excellent overall survival in patients with metastatic germinoma. Importantly, our experience suggests that in combination with neoadjuvant chemotherapy, 21Gy CSI may be sufficient as a curative dose in this patient population.

Establishment of human induced pluripotent stem cell line MURAi001-A from skin fibroblasts of a patient carrying a c.4404A > G mutation in the TET1 gene

Ten-Eleven Translocation methylcytosine dioxygenase 1 (TET1) is known to play a broad tumor suppressor role through demethylating and activating tumor suppressor genes. TET1 missense mutations are previously reported in many types of leukemia. Here, the human induced pluripotent stem cell line MURAi001-A was generated from skin fibroblasts derived from a 56-year-old female patient carrying the TET1 gene mutation c.4404A > G (p.I1468M), who had a history of ovarian germ cell tumor. The MURAi001-A cell line demonstrated embryonic-like characteristics as it expressed specific stemness markers, differentiated into the three germ layers, and retained normal karyotyping.

GCT-07. CONTRIBUTORS TO DELAYED TREATMENT OF NON-GERMINOMATOUS GERM CELL TUMORS IN CHINA: A TERTIARY-CENTER REVIEW

Abstract BACKGROUND Non-Germinomatous Germ Cell Tumors (NGGCT) are rare malignancies with potential for treatment delays. This study aims to identify risk factors and systemic challenges contributing to delayed management of NGGCT in China. METHODS We reviewed the clinical features and referral pattern of 56 consecutively diagnosed NGGCT patients at Shanghai Children’s Medical Center (SCMC) from 9/2018-2/2023. Patients were diagnosed by pathology (n=42), or by elevated markers alone (n=14, AFP>10ng/ml, and/or β-HCG>50mIU/ml). Patients were treated per COG ACNS0122. Delay of treatment was defined as chemotherapy initiated more than 6 months after symptom onset. RESULTS Forty-three males and 13 females were included. Median age at diagnosis was 9.17year (4month-16year). Primary tumor locations included the pineal region (n=31), sellar region (n=19), basal ganglia (n=5), and posterior fossa (n=1). Presenting symptoms included features of increased intracranial pressure (ICP, n=29), endocrine symptoms (n=21), blurred vision or squint (n=7), and hemiplegia (n=4). Delayed treatment occurred in 16 cases (29%), and was more likely in patients with non-pineal region primary (Chi-square p=0.003), and absence of symptoms pertaining to increased ICP (Chi-square p<0.001). Reasons for delay included lack of parental recognition on symptoms (n=7), misdiagnosis (n=3), and inappropriate/incomplete workup (n=6). As a national referral center, patients commuted a median of 483 km (range: 12-2943km) to SCMC (median 2 hospitals (1,5) before SCMC), including 10 patients with obvious hydrocephalus travelling before any CSF diversion procedure. Three-year Event-Free Survival (EFS) was 76.9% and Overall Survival was 86.0%. There was a trend to inferior outcome in patients with delay in treatment (3y EFS 69.6%) compared with those without (3year EFS 80.6%, p=0.112). CONCLUSIONS Delay in treatment is common for children with NGGCT managed at a tertiary referral center in China. Improving public awareness, training for primary-care clinicians, and establishing a national referral network are potential strategies to enhancing the outcome.

GCT-11. CENTRAL NERVOUS SYSTEM GERM TUMORS (CNS GCTS): RESULTS FROM A SINGLE INSTITUTION IN BRAZIL - SÃO PAULO UNIVERSITY

Abstract INTRODUCTION Central Nervous System Germ Tumors (CNS GCTs) are broadly classified as germinomatous (commonly called germinoma) and non-germinomatous germ cell tumors (NGGCTs) based on clinicopathological and laboratory characteristics, including tumor markers. OBJECTIVES Compare data from patients admitted from 2000 to 2023, with the usual presentation in the literature, identifying possible specific variables. METHODOLOGY Retrospective study involving 27 patients admitted to the institution without previous treatment. RESULTS In western countries, GCTs account for 3% to 4% of primary brain tumors in children, with a peak incidence between 10 and 19 years of age. In Japan and other Asian countries, one series reported that the incidence of GCTs in the CNS consists of approximately 15% of all pediatric CNS tumors. The genetic or environmental reasons for these differences remain unknown. In general, males have a higher incidence of GCT than females. Male patients have a preponderance of primary tumors of the pineal region. The data collected by our institution are compatible with those in the literature. CONCLUSION Our discussion and data analysis on GCTs are comparable to those presented in the literature, with the majority of cases treated being: adolescents between 10 and 15 years old, predominantly male and with a satisfactory response to therapy.

OTHR-24. CLINICAL COURSE OF ISOLATED PITUITARY STALK THICKENING IN PEDIATRIC PATIENTS AND RISK FACTOR FOR NEOPLASTIC ETIOLOGY: A SINGLE INSTITUTIONAL EXPERIENCE

Abstract BACKGROUND The incidence of pituitary stalk thickening (PST) has increased in recent years due to the increased utilization of diagnostic MRI of the brain. The etiology of PST includes germ cell tumors, Langerhans cell histiocytosis (LCH), and lymphocytic hypophysitis, among others. The clinical significance of PST, appropriate diagnostic workup, and clinical course for these patients is not well documented. We report our institutional experience with patients presenting with PST. METHODS After IRB approval, we reviewed lists of patients discussed in pediatric tumor boards from 2003-2023 to identify patients with PST. We excluded patients with other significant intracranial masses from our analysis. We followed the clinical course of these patients to collect applicable data. RESULTS A total of 20 patients were identified with PST, five patients were excluded due to additional MRI findings. The median age of diagnosis with PST was 14 years; 60% of cases were female. Seven patients had diabetes insipidus (DI), and five patients had other endocrinological abnormalities. Initial diagnostic workup included serum and CSF tumor markers (AFP, B-HCG), skeletal survey, CBC, and CMP. With this initial workup, no patients were diagnosed with neoplasm. All patients were followed with serial MRIs. Four patients (26.6%) displayed progression of PST, warranting biopsy. The median time from diagnosis to biopsy was seven months (range 4-26 months). Among four patients with biopsy, two had LCH, one had germinoma, and one inconclusive result. Among those diagnosed with neoplasm, 100% of them had DI. Three patients had complete resolution of PST during the follow-up period. Eight patients had stable PST during the median follow-up period of 19.5 months (Range 3-59 months). CONCLUSIONS Most isolated PST among pediatric patients remained stable during the follow-up period. The risk for neoplastic process was high among patients with increasing thickening of pituitary stalk and DI.

Unilateral Post-Chemotherapy Robot-Assisted Retroperitoneal Lymph Node Dissection for Stage II Non-Seminomatous Germ Cell Tumors: Sexual and Reproductive Outcomes.

We aimed to report sexual and reproductive outcomes following post-chemotherapy robot-assisted retroperitoneal unilateral lymph node dissection (PC-rRPLND) for non-seminomatous germ cell tumors (NSGCTs) at a high-volume cancer center. We collected records regarding sexual and reproductive outcomes of patients undergoing unilateral PC-rRPLND for stage II NSGCTs from January 2018 to November 2021. Preoperative and postoperative (at 12 months) ejaculatory function as well as erectile function, based on the International Index of Erectile Function-5 (IIEF-5) and Erection Hardness Score (EHS), were assessed. Only patients with a pre-operative IIEF-5 of ≥22 and EHS of ≥3 were included in this analysis. Overall, 22 patients undergoing unilateral PC-rRPLND met the inclusion criteria. Of these, seven (31.8%) patients presented an andrological disorder of any type after PC-rRPLND. Specifically, retrograde ejaculation was present in three (13.6%) patients and hypospermia was present in one (4.5%) patient. Moreover, three (13.6%) patients yielded erectile dysfunction (IIEF-5 < 22 and/or EHS < 3). Lastly, two (9.1%) succeeded in naturally conceiving a child after PC-rRPLND. Retrograde ejaculation is confirmed to be one of the most common complications of PC-rRPLND. Moreover, a non-negligible number of patients experience erectile dysfunction.

Interventional oncology in children: Where are we now?

Paediatric Interventional Oncology (IO) lags behind adult IO due to a scarcity of specific outcome data. The suboptimal way to evolve this field is relying heavily on adult experiences. The distinct tumour types prevalent in children, such as extracranial germ cell tumours, sarcomas, and neuroblastoma, differ strongly from those found in adults, presenting a completely different biological behaviour. Compounding this challenge, paediatric interventional radiology often employs adapted or off-label techniques, potentially compromising optimal outcomes. This review outlines the present indications for interventional radiology in paediatric cancer, from biopsy to supportive care, including complication management. It emphasises the role of locoregional approaches, and explores the status of common paediatric oncological diseases, highlighting areas where IO has made progress identifying potential opportunities for future advancements in this evolving field.

Remote Field Application of Digital Technology for Hearing Assessments in a Cohort of Pediatric Germ Cell Tumor Survivors.

Childhood cancer survivors treated with platinum-based chemotherapy are at risk of treatment-induced hearing loss. Accurate evaluation of hearing thresholds has historically been limited to clinical audiometry, which is logistically challenging and expensive to include in epidemiologic studies. We evaluated the feasibility of using a remote, tablet-based hearing assessment in a cohort of pediatric germ cell tumor survivors treated with platinum-based chemotherapy. Survivors from the GCT Outcomes and Late effects Data (GOLD) study were recruited to the pilot study (n = 100). Study personnel conducted remote hearing assessments of standard and extended high frequency thresholds using validated tablet-based audiometry (SHOEBOX, Inc.). T tests and Wilcoxon rank-sum tests evaluated differences in assessment characteristics between children and adults. Agreement between self-reported and measured hearing loss was calculated using Cohen κ. We were able to reach 136/168 (81%) eligible participants, of which 100 (74%) agreed to participate. Successful completion of the remote hearing assessment was high [97%; 20 children (ages 7-17), 77 adults (ages 18-31)]. The mean assessment length was 37.6 minutes, and the mean turnaround time was 8.3 days. We observed hearing loss at standard frequencies in 21% of participants. Agreement between self-reported and measured hearing loss was significant (P value = 1.41 × 10-7), with 83.5% concordance. Hearing loss measured using the remote assessment aligns with self-reporting and rates of hearing loss reported in the literature for this population. Remote application of tablet-based audiometry is a feasible and efficacious method for measuring hearing in epidemiologic studies with participants spread across large geographic areas.