Germ Cell Tumors Research Articles

Endoscopic Third Ventriculostomy and Pineal Biopsy from a Single Entry Point.

Pineal neoplasms have a significant impact on children although they are relatively uncommon. They account for approximately 3-11% of all childhood brain tumors, which is considerably higher than the <1% seen in adult brain tumors. These tumors can be divided into three main categories: germ cell tumors, parenchymal pineal tumors, and tumors arising from related anatomical structures. Obtaining an accurate and minimally invasive tissue diagnosis is crucial for selecting the most appropriate treatment regimen for patients with pineal gland tumors. This is due to the diverse treatment options available and the potential risks associated with complete resection. In cases where patients present with acute obstructive hydrocephalus caused by a pineal gland tumor, immediate treatment of the hydrocephalus is necessary. The urgency stems from the potential complications of hydrocephalus, including increased intracranial pressure and neurological deficits. To address these challenges, a minimally invasive endoscopic approach provides a valuable opportunity. This technique allows clinicians to promptly relieve hydrocephalus and obtain a histological diagnosis simultaneously. This dual benefit enables a more comprehensive understanding of the tumor and assists in determining the most effective treatment strategy for the patient.

Ciprofloxacin prophylaxis during haematopoietic cell transplantation: a role for use in patients with germ cell tumours?

Introduction. Fluoroquinolone prophylaxis during haematopoietic cell transplantation (HCT) can lead to antimicrobial resistance (AMR). Identifying the groups of patients that have the highest likelihood of benefiting from prophylactic antimicrobials is important for antimicrobial stewardship (AMS).Hypothesis. We aimed to identify groups of HCT recipients that have the highest likelihood of benefiting from prophylactic fluroquinolones.Methods. All admissions for HCT in a tertiary centre between January 2020 and December 2022 (N = 400) were retrospectively studied. Allogeneic HCT (allo-HCT) recipients had prophylaxis with ciprofloxacin during the chemotherapy-induced neutropenia, while autologous HCT (auto-HCT) recipients did not. Bacteraemias were recorded when non-contaminant bacterial pathogens were isolated in blood cultures.Results. Allo-HCT was performed for 43.3 % (173/400) of patients and auto-HCT was performed for 56.7 % (227/400). A bacteraemia was documented in 28.3 % (113/400) of cases. Allo-HCT recipients were more likely to have a Gram-positive bacteraemia (20.8%, 36/173, vs 10.1%, 23/227, P = 0.03), while a difference was not observed for Gram-negative bacteraemias (18.5%, 32/173 vs 18.1%, 41/227, P = 0.91). Among auto-HCT recipients not receiving ciprofloxacin prophylaxis, patients with germ cell tumours had the highest probability (P for trend 0.09) of recording any bacteraemia (43.5%, 10/23) followed by patients with lymphomas (32.5%, 13/40), other auto-HCT indications (22.2%, 2/9), multiple myeloma (22.1%, 29/131) and multiple sclerosis (12.5%, 3/24). The higher number of bacteraemias in patients with germ cell tumours was primarily driven by Gram-negative pathogens.Conclusions. Ciprofloxacin prophylaxis was associated with a reduced incidence of Gram-negative bacteraemias in allo-HCT recipients. Auto-HCT recipients due to germ cell tumours, not receiving ciprofloxacin prophylaxis, recorded the highest incidence of bacteraemias and represent a possible target group for this intervention.

Mucinous cystadenoma and carcinoid tumor arising from an ovarian mature cystic teratoma in a 60 year-old patient: a case report

BackgroundMature cystic teratomas (MCT) of the ovary are benign ovarian germ cell neoplasms. Malignant transformation is possible but rare and ovarian carcinoid tumors in MCT are among the most extremely rare subtypes.Case presentationWe report a case of a 60-year-old Iranian woman suffering from postmenopausal bleeding and hypogastric pain for the last 40 days. An adnexal mass was detected during the physical examination. Ultrasound imaging showed a (55 × 58) mm mass in the left ovary. Total abdominal hysterectomy, bilateral salpingooophorectomy and comprehensive staging surgery were performed for the patient. Intraoperative frozen section of the left ovarian mass was indicative of a malignant tumor. She was diagnosed with a carcinoid tumor with benign mucinous cystadenoma arising on MCT of the ovary, confirmed in the histopathology and immunohistochemistry examination. The tumor was classified as low grade and no chemotherapy cycles were considered. The patient was followed up long-term and no recurrence was observed during 14 months of examinations.ConclusionOvarian carcinoids arising from MCT are rare neuroendocrine neoplasms, and proper diagnosis of these tumors requires careful histopathology evaluation and appropriate examination. Therefore, it is necessary to consider these tumors as a possible differential diagnosis and evaluate them in individuals (especially postmenopausal women) who have abdominal pain or abnormal bleeding and a palpable mass.

Pathogenesis and pathobiology of testicular germ cell tumours: a view from a developmental biological perspective with guidelines for pathological diagnostics.

Testicular germ cell tumours (GCT) are divided into three different subtypes (types I-III) regarding to their developmental origin, histological differences and molecular features. Type I GCT develop from disturbed primordial germ cells and most commonly occur in children and young adolescents, which is why they are referred to as prepubertal GCT. Type II GCT develop from a non-invasive germ cell neoplasia in situ (GCNIS) and show an isochromosome 12p (i12p) or gain of 12p material as a common and characteristic molecular alteration. Type III GCT originate from distorted postpubertal germ cells (e.g. spermatogonia) in adult patients and have changes on chromosome 9 with amplification of the DMRT1 gene. Type I GCT encompass prepubertal-type teratomas and yolk-sac tumours (YST). Type II GCT include seminoma, embryonal carcinoma, choriocarcinoma, postpubertal-type teratoma and postpubertal-type YST. Types I and II GCT both show similar morphology, but are separated from each other by the detection of a GCNIS and an i12p in type II GCT. For type II GCT it is especially important to detect non-seminomatous elements, as these tumours have a worse biological behaviour and need a different treatment to seminomas. In contrast to types I and II GCT, type III tumours are equivalent to spermatocytic tumours and usually occur in elderly men, with few exceptions in young adults. The development of types I and II GCT seems to depend not upon driver mutations, but rather on changes in the epigenetic landscape. Furthermore, different pluripotency associated factors (e.g. OCT3/4, SOX2, SOX17) play a crucial role in GCT development and can be used as immunohistochemical markers allowing to distinguish the different subtypes from each other in morphologically challenging tissue specimens. Especially in metastatic sites, a morphological and immunohistochemical diagnostic algorithm is important to detect small subpopulations of each non-seminomatous GCT subtype, which are associated with a poorer prognosis and need a different treatment. Furthermore, primary extragonadal GCT of the retroperitoneum or mediastinum develop from misguided germ cells during embryonic development, and might be challenging to detect in small tissue biopsies due to their rarity at corresponding sites. This review article summarises the pathobiological and developmental aspects of the three different types of testicular GCT that can be helpful in the histopathological examination of tumour specimens by pathologists.

Antibody-drug conjugates as a novel therapeutic modality to treat recurrent refractory germ cell tumors.

This review provides a rationale for using the Food and Drug Administration (FDA)-approved antibody-drug conjugates (ADCs) for implementing as therapy in recurrent refractory germ cell tumors similar to their position in the treatment of other types of chemoresistant solid tumors. Germ cell tumors (GCTs) originate from germ cells; they most frequently develop in ovaries or in the testes, while being the most common type of malignancy in young men. GCTs are very sensitive to cisplatin-based chemotherapy, but therapeutic resistance occurs in a considerable number of cases, which is associated with disease recurrence and poor patient prognosis. ADCs are a novel type of targeted antitumor agents that combine tumor antigen-specific monoclonal antibodies with chemically linked chemotherapeutic drugs (payload) exerting a cytotoxic effect. Several FDA-approved ADCs use as targeting moieties the antigens that are also detected in the GCTs, offering a benefit of this type of targeted therapy even for patients with relapsed/refractory testicular GCTs (rrTGCT) unresponsive to standard chemotherapy.

Clinical effects of neuroendoscopic infratentorial supracerebellar approach surgical technique for resecting pineal tumors: a retrospective study

ObjectivePineal tumors are relatively rare central nervous system lesions with a predilection for the pediatric population. This article aims to explore the clinical effects of neuroendoscopic infratentorial supracerebellar approach for resecting tumors in the pineal area. MethodsThis is a retrospective study that included patients who underwent neuroendoscopic infratentorial supracerebellar approach to resect nine tumors in the pineal area at the Department of Neurosurgery of the Second Hospital of Lanzhou University from December 2017 to October 2023. ResultsThe results of postoperative MRI revealed that all tumors were resected. Five patients received postoperative radiotherapy, three patients received radiotherapy along with chemotherapy, and one patient received neither radiotherapy nor chemotherapy. The pathological results showed that four patients were diagnosed with germinoma, two patients with teratoma, two patients with mixed germ cell tumors, and one patient with central neurocytoma. After surgery, one patient developed psychiatric symptoms, two patients developed binocular upward vision and diplopia, and one patient developed unstable walking and diplopia. With a follow-up of 1.7–4.8 years, all nine patients lived normally. Furthermore, none of them had tumor recurrence or death. ConclusionThe simple neuroendoscopic infratentorial supracerebellar approach has some safety and efficacy. It is suitable for tumors in the pineal region where the disease is mainly located below the Galen vein complex.

Amplifications of EVX2 and HOXD9-HOXD13 on 2q31 in mature cystic teratomas of the ovary identified by array comparative genomic hybridization may explain teratoma characteristics in chondrogenesis and osteogenesis

BackgroundTeratomas are a common type of germ cell tumor. However, only a few reports on their genomic constitution have been published. The study of teratomas may provide a better understanding of their stepwise differentiation processes and molecular bases, which could prove useful for the development of tissue-engineering technologies.MethodsIn the present study, we analyzed the copy number aberrations of nine ovarian mature cystic teratomas using array comparative genomic hybridization in an attempt to reveal their genomic aberrations.ResultsThe many chromosomal aberrations observed on array comparative genomic hybridization analysis reveal the complex genetics of this tumor. Amplifications and deletions of large DNA fragments were observed in some samples, while amplifications of EVX2 and HOXD9-HOXD13 on 2q31.1, NDUFV1 on 11q13.2, and RPL10, SNORA70, DNASE1L1, TAZ, ATP6AP1, and GDI1 on Xq28 were found in all nine mature cystic teratomas.ConclusionsOur results indicated that amplifications of these genes may play an important etiological role in teratoma formation. Moreover, amplifications of EVX2 and HOXD9-HOXD13 on 2q31.1, found on array comparative genomic hybridization, may help to explain the characteristics of teratomas in chondrogenesis and osteogenesis.

Primary hypothyroidism in a patient with germ cell tumor: A case report

Germ cell tumors (GCTs) are known to present with thyroid dysfunction, typically manifesting as hyperthyroidism due to human chorionic gonadotropin secretion. However, hypothyroidism among GCT patients is a relatively underexplored phenomenon, which could be attributable to low clinical suspicion and the potential masking of hypothyroidism by cancer-related symptoms. Moreover, the impact of hypothyroidism on cancer-related outcomes remains uncertain. Here, we present a case of incidentally detected primary hypothyroidism in a 16-year-old girl with an ovarian GCT. Remarkably, her condition improved at an unexpected rate after cancer-directed treatment. In our evaluation, we identified various causes of reversible hypothyroidism, all of which are comprehensively reviewed in this case report.

Assessment of Molecular Markers in Pediatric Ovarian Tumors: Romanian Single-Center Experience.

Pediatric ovarian tumors exhibit unique diagnostic and therapeutic challenges. This study evaluates the expression of SALL4 and OCT3/4 biomarkers in pediatric ovarian tumors and their associations with tumor subtype, stage, and clinical outcome. A retrospective analysis was conducted on 64 patients under 18 years old, examining demographic data, tumor characteristics, immunohistochemical staining, and clinical outcomes. Our results show that SALL4 was significantly expressed in adenocarcinoma, dysgerminoma (DSG), mixed germ cell tumors (GCTs), and immature teratoma, while OCT3/4 was highly expressed in DSG and mixed GCTs. Both markers are associated with a higher tumor grade and stage, indicating a more aggressive disease. The SALL4 positivity expression was correlated with high alpha fetoprotein (AFP) and lactate dehydrogenase (LDH) levels, while OCT3/4 positivity significantly predicted the risk of subsequent metastasis. The mean progression-free survival (PFS) was notably shorter in patients with positive markers. These findings underscore the diagnostic and prognostic value of SALL4 and OCT3/4 in pediatric ovarian tumors, aligning with previous research and supporting their use in clinical practice for better disease management and patient outcomes.

A Multicenter Evaluation of Treatment-associated Changes in Body Composition in Men With Germ Cell Tumors of the Testis: Implications for Adverse Events and Complications

ObjectivesTo characterize changes in body composition following cytotoxic chemotherapy for germ cell carcinoma of the testis (GCT) and quantify associations between body composition metrics and chemotherapy-associated adverse events (AEs) and post-retroperitoneal lymph node dissection (RPLND) complications. Materials and MethodsThis retrospective multi-center study included 216 men with GCT treated with cytotoxic chemotherapy and/or RPLND (2005-2020). We measured body composition including skeletal muscle (SMI), visceral adipose (VAI,), subcutaneous adipose (SAI), and fat mass (FMI) indices on computed tomography. We quantified chemotherapy-associated changes in body composition and evaluated associations between body composition and incidence of grade 3+ AEs and post-RPLND complications on multivariable logistic regression analyses. Results182 men received a median of 3 cycles of cisplatin-based chemotherapy. Following chemotherapy, median change in SMI was -6% (p=<0.0001), while VAI, SAI, and FMI increased by +13% (p=<0.0001), +11% (p=<0.0001), and +6% (p=<0.0001), respectively. 79 patients (43%) experienced at least one grade 3+ AE. A decrease in SMI following chemotherapy was associated with increased risk of grade 3+ AEs (p=0.047). 103 men with a median age of 28.5 years (IQR 23-35.5) underwent RPLND of whom 22 (21.3%) experienced at least one grade 3+ post-RPLND complication. No baseline body composition metrics were associated with post-RPLND complications. ConclusionsIn men with GCT of the testis, chemotherapy was associated with 6% loss of lean muscle mass and gains in adiposity. Lower skeletal muscle was associated with a higher incidence of chemotherapy-associated AEs. Body composition was not associated with the incidence of post-RPLND complications.

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

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

GCT-02. OPTIC PATHWAY PRIMARY GERMINOMA: DON´T MISS THE DIAGNOSIS

Abstract BACKGROUND Germ Cell tumors usually arise in the midline of brain; location in optic pathway (OP) is extremely rare. This case illustrates an OP primary Germinoma. METHODS A 9 years old female debuted with diminished visual acuity, it was diagnosed and treated as optic neuritis without improvement, a MRI evidenced a gadolinium enhancement with a very subtle thickening on the optic chiasm, along 3 non conclusive vascular like images in the left Virchow space. A differential diagnosis between endophytic Optic pathway glioma and germ cell tumor was made. RESULTS Assessment of AFP and Sub HCG in both blood and CFS was negative, endocrine evaluation confirmed Diabetes insipidus. A stereotaxic biopsy was performed and Pathology confirmed a Pure Germinoma. Non metastatic disease was confirmed as negative Spine MRI and acellular CFS. As a relevant familiar History the father had testicular Germinoma in his teenage. She was treated with 9 weeks of Carboplatin/V16 and radiotherapy as follows: whole ventricular 24 Gy and primary site 16.5 Gy for a total dose of 40.05 Gy. She is free of tumor at 3 follow up years with improvement in visual acuity and arginine vasopressin dependence. CONCLUSIONS This case illustrates a germ cell tumor primary arising in the optic pathway and aware us to consider it as a differential diagnosis with non-exophytic optic pathway Glioma being the biopsy mandatory to establish the correct diagnosis

NURS-14. DEVELOPMENT OF A CLINICAL PRACTICE INTERVENTION TO SUPPORT NURSES CARING FOR PATIENTS WITH DIABETES INSIPIDUS (DI) DURING CHEMOTHERAPY HYDRATION

Abstract BACKGROUND Pediatric neuro-oncology patients with germ cell tumors (GCT) and diabetes insipidus (DI) often require management with vasopressin (DDAVP). Fluid and sodium balance, ordinarily managed successfully with DDAVP, can be disrupted during chemotherapy and associated hydration. Patients with an intact thirst mechanism may be able to self-regulate fluid and salt balance under the right conditions, whereas patients without an intact thirst may experience sodium fluctuations if intravenous hydration exceeds the amount they drink independently. Patients may be unable to maintain adequate hydration and sodium levels due to nausea and/or sedating antiemetics. These factors create a unique clinical challenge for nurses. Nurses sought guidance in understanding DI and its impact on hydration during chemotherapy. METHODS Two nursing education sessions were held and focused on DI management. Nurses were surveyed pre and post education. The goals of the intervention were that the oncology nurse will be to describe the pathophysiology of diabetes insipidus, the role of desmopressin, the ability to differentiate between management of patients with and without an intact thirst mechanism, and the special care of a DI patient receiving chemotherapy. RESULTS Nurses reported an increased awareness post education of the need to closely assess patients and manage their DI in collaboration with clinicians. Routine chemotherapy management does not apply to this population, because drastic fluctuations in sodium and water balance put them at risk of other complications. Nurses identified the need to closely manage hydration, DDAVP, recording strict intake/output, monitoring sodium levels, assessing for nausea/vomiting and the degree of sedation from antiemetics. CONCLUSION Outcomes from this educational intervention were that nurses had an increased understanding of DI management in patients with GCT receiving chemotherapy. Future goals would be to implement a standard approach to hydration, DDAVP administration, and monitoring sodium levels in patients with GCT and DI.

OTHR-21. DEVELOPING A NEURO-ONCOLOGY PROGRAM FOR ADOLESCENTS AND YOUNG ADULTS IN CANADA – THE CANON EXPERIENCE

Abstract BACKGROUND Brain tumors are the leading cause of cancer-related death in adolescents and young adults (AYA). These tumors possess both pediatric-type and adult-type qualities, with up to 30% of gliomas harboring pediatric-type alterations. Specialized expertise and significant collaboration between pediatric and adult providers is needed to guide therapy for AYAs. To address this, we have developed the Canadian Adolescent and Young Adult Neuro-Oncology Network (CANON). METHODS In April 2021, we established a national virtual AYA tumor board integrating comprehensive molecular analysis of available tumors. Rounds included representatives from both pediatric and adult neuro-oncology, radiation oncology, neurosurgery, neuropathology and neuroradiology. We collected clinical data and recommendations from rounds. RESULTS In the first 2 years of rounds through CANON, 156 cases have been reviewed. Gliomas (108) accounted for most cases followed by medulloblastoma (18) and ependymoma (7). Sequencing was available in 47% of cases. Of those with molecular data available, the majority (36) had a pediatric-type alteration, followed by IDH mutation (10). Additional molecular analysis was recommended in 29% of cases presented. Of those with sequencing data available, 35% had a potentially targetable alteration identified. Despite this, only 8% were eligible for a clinical trial based on their diagnosis and age. Recurrent clinical questions included access to molecular analysis, use of “off-label” targeted agents, lack of clinical trial options for AYA patients and the practice variation in treatment of AYA tumors typically seen in childhood such as medulloblastoma and germ cell tumor. DISCUSSION Dedicated AYA rounds have highlighted many inequities in care of these patients, highlighting a need for inclusion of AYAs in clinical trials and further study of tumor biology and clinical outcomes of this cohort. AYAs with pediatric-type tumors would also benefit from management by dedicated physicians with expertise in these complex tumors.

QOL-34. POST-TRAUMATIC GROWTH AND COPING STRATEGIES AMONG ADOLESCENTS AND YOUNG ADULTS SURVIVORS OF PEDIATRIC BRAIN TUMORS

Abstract BACKGROUND Pediatric brain tumor survivors (PBTS) often report late psychosocial effects following the disease and the treatments. Recent studies have shown that PBTS can experience growth in their personal and interpersonal dimensions and develop coping strategies that allow them to deal with the stress caused by cancer diagnosis and subsequent therapies. This study aimed to describe post-traumatic growth (PTG) experiences and coping strategies among adolescents and young adults (AYA) survivors of pediatric brain tumors. METHODS AYA survivors were assessed using Post-Traumatic Growth Inventory (PTGI) and Coping Inventory for Stressful Situations (CISS) questionnaires. They received evaluation at a median age of 20.2 years (range 13.6-28.7), with a median of 92 months from diagnosis. RESULTS Among 22 AYA survivors (M =14; F=8), the diagnosed tumor types were: germ cell tumor (10/22), low-grade glioma (4/22), embryonal tumor (3/22), high-grade glioma (2/22), craniopharyngioma (2/22), and mesenchymal tumor of the meninges (1/22).The domains of PTG in which positive changes were most frequently reported were Personal Strength (25%), Appreciation for Life (25%), and New Possibilities (23%). The less impacted domain was Spiritual Growth (9%). As regards the most adopted coping style, 38% showed higher values in the Distraction scale, 31% in the Task-Oriented scale, 15% in the Avoidance scale, and 15% in the Social Diversion scale. CONCLUSIONS PTG and coping are important indicators of psychosocial adaptation to difficult or stressful events. To develop specific interventions that enhance PTG, it is essential to understand which factors influence growth in PBTS. Our preliminary data show that all AYA survivors report PTG after treatments, at least in some domains. Further analysis is needed to identify which coping styles may influence the development of PTG.

BIOM-14. UTILITY OF MIRNA-BASED LIQUID BIOPSY AND RADIOGRAPHIC IMAGING IN PEDIATRIC BRAIN TUMOR PATIENTS

Abstract BACKGROUND MRI is the current gold standard imaging technique for diagnostic evaluation and monitoring of pediatric CNS tumors; however, MRI measures can only provide inference into tumor biology and molecular stratification. miRNAs are an abundant and stable nucleic acid found circulating in blood and cerebrospinal fluid (CSF) and can be utilized as a tumor biomarker. METHODS We hypothesized that correlating miRNA biomarkers with radiological tumor measurements may provide improved diagnostic and monitoring for patients with pediatric brain tumors. Using a cohort of 54 pediatric brain tumors including low grade glioma, ependymoma, germ cell tumor, medulloblastoma, atypical teratoid rhabdoid tumor and high-grade glioma we attempted to combine MRI findings and circulating miRNA data. The miRNA expression was profiled in 33 CSF and 52 plasma samples using the HTG EdgeSeq platform. Clinically acquired, multi-parametric MRI scans at time-points close to liquid biopsy collection were collected retrospectively and used to generate volumetric tumor segmentations. Machine learning methods were implemented to evaluate combinatory features. RESULTS We identified unique miRNA targets that significantly correlated with MRI features, clinical findings, and patient outcomes. In both CSF and plasma, miRNA expression was found to correlate with diagnosis and clinical features including tumor grade and disease burden (p &amp;lt; 0.05). In CSF, miRNA expression was correlated with MRI features including cystic core presence, edema, leptomeningeal disease and tumor location (p &amp;lt;0.05). In plasma, differences in miRNA expression were related to MRI measurements including cystic core volume, location, and leptomeningeal disease (p &amp;lt; 0.05). Combination of miRNA targets for plasma or CSF with imaging-based features significantly improved histology specific multimodal diagnosis predictions. CONCLUSIONS These results demonstrate the potential utility of miRNAs as a pediatric brain tumor biomarker which when combined with imaging features can improve minimally and non-invasive diagnostics and the subsequent management of pediatric brain tumor patients.

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

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

Effect of delayed diagnosis on neuroendocrine function in individuals with suprasellar germ cell tumors.

The impact of delayed diagnosis on tumor-related prognosis appears to be minimal in individuals with intracranial germ cell tumors (iGCTs). However, its effect on neuroendocrine functions remains unclear. We aimed to assess the effects of delayed diagnosis on neuroendocrine function in individuals with suprasellar GCTs. We conducted a retrospective cohort study of 459 individuals with suprasellar GCTs and categorized them into two groups based on disease duration: delayed diagnosis (> 6 months) and non-delayed diagnosis (≤ 6 months). We compared endocrinological symptoms, neuroendocrine dysfunction and its grading (categorized into 0-3 grades based on severity), and recovery from neuroendocrine dysfunction in both groups. Patients with delayed diagnosis exhibited higher incidences of amenorrhea, slow growth, fatigue, and polyuria/polydipsia. Neuroendocrine dysfunction, including central adrenal insufficiency (CAI), central hypothyroidism (CHT), arginine vasopressin deficiency (AVP-D), growth hormone deficiency, hypogonadism, and hyperprolactinemia, was more pronounced in the delayed diagnosis group at diagnosis, the end of treatment, and the last follow-up. Furthermore, individuals with delayed diagnosis showed higher grades of neuroendocrine dysfunction at diagnosis (OR=3.005, 95% CI 1.929-4.845, p<0.001), end of oncologic treatment (OR=4.802, 95% CI 2.878-8.004, p<0.001), and last follow-up(OR=2.335, 95% CI 1.307-4.170, p=0.005) after adjusting for confounders. Finally, less recovery, particularly in CAI, CHT, and AVP-D, was seen among the group with delayed diagnosis after treatment. Among individuals with suprasellar GCTs, delayed diagnosis is associated with increased, more severe, and less recovered neuroendocrine dysfunction, emphasizing the importance of early diagnosis and treatment to reduce neuroendocrine dysfunction.

RADT-04. ASSESSMENT OF CLINICAL AND NEUROLOGICAL ALTERATIONS BEFORE RADIATION THERAPY IN CHILDREN WITH MALIGNANT BRAIN TUMORS

Abstract BACKGROUND Young patients with malignant brain tumors show neurocognitive alterations as both consequences of the tumor and of treatments received. A prospective study of longitudinal radiation damages after focal RT was activated in 2017. We present the first analysis correlating tumor localization, symptoms, neurological/endocrinological impairments, surgery/ies if adopted, and cognitive assessments at the time of enrollment. METHODS Sixty-six children eligible for focal RT were enrolled and underwent a neurocognitive assessment based on standardized tests (“impaired”/“non-impaired”). The database included demographical, clinical and pathological variables. The latter, together with MRI morphological scans, were used to define different kind of damage scores. The pattern of associations between clinical variables and damage scores was investigated. RESULTS Patients median age was 8 years; the most frequent tumor was Ependymoma (41%) and Posterior Fossa (29%) was the prevalent tumor site. All but 5 children (with Germ Cell Tumors), had undergone surgery and 32 had undergone chemotherapy before irradiation and evaluations. Ad-hoc scores of neurological deficits and endocrine alterations were created to characterize each patient. Moreover, structural abnormalities were quantified in a score for each cortical/subcortical region. Patients with posterior fossa Ependymomas and infratentorial tumors showed higher neurological damage scores. Endocrine alterations were more serious in supratentorial tumors, specifically in patients with Craniopharyngioma and Germ Cell tumors of the sellar region and ventricular system. Deficit scores were not associated to the presence of hydrocephalus and surgery, unlike endocrine alteration scores. The median number of child’s structural damaged areas was equal to 2 (IQR: 2-3). Tumor sites of patients with an impaired or non-impaired full-scale IQ or visual-perception index, was found to be different. CONCLUSIONS The analysis of baseline evaluations highlights damages preexisting to irradiations and generated by multiple factors. In light of these findings, damages over time could be better investigated by distinguishing multiple generating factors.

RADT-02. PROTON THERAPY IN PEDIATRIC ONCOLOGY IN SLOVAKIA: A COMPREHENSIVE ANALYSIS

Abstract INTRODUCTION Radiotherapy has been a cornerstone in pediatric oncology for decades. Recognizing the potential to mitigate side effects, proton therapy (PT) has gained prominence, becoming part of treatment in pediatric oncology in Slovakia since 2014. METHODOLOGY This retrospective analysis investigates a cohort of patients with CNS tumors treated at the National Institute of Children’s Diseases in Bratislava, who underwent PT at the Proton Center in Prague between 2014 and 2022. RESULTS Among 47 patients, embryonal tumors constituted the largest group (40%), followed by germ cell tumors (21%), ependymal tumors (19%), less common CNS tumors (10%), and glial tumors (8%). Acute complications included skin toxicity (38%), CNS toxicity (23%), GIT toxicity (14%), and blood count changes (8%). Notably, 22 patients experienced no acute toxicity. Late reactions, predominantly endocrine dysfunction (65%), featured central hypothyroidism (45%), ACTH deficiency (22%), GH deficiency (16%), and gonadotropin deficiency (10%). Ocular complications affected 55%, while tensive cephalea and post-radiation necrosis-related epileptic seizures were observed in limited cases. Disease recurrence was absent in 89% of patients, with 10% exiting due to disease progression. CONCLUSION This pioneering analysis highlights the unique experiences of Slovak pediatric patients undergoing PT at the Proton Center in Prague. The study emphasizes the dual impact of PT, enhancing survival rates while reducing adverse effects, thereby significantly contributing to a better quality of life for pediatric cancer patients.