Pure Germinoma Research Articles

Pituitary germinoma after resection of a mature third ventricular teratoma: illustrative case.

Metachronous intracranial germ cell tumors (iGCTs)-unrelated, histologically different iGCTs occurring at different time points-occurring within the same patient remain a rarity. Herein, the authors report such a case and discuss the literature and potential pathophysiological mechanisms leading to this phenomenon. A 9-year-old boy presented with new-onset impaired balance, headaches, nausea, visual disturbances, and left facial paresis. Magnetic resonance imaging (MRI) scans revealed a suspected pineal region teratoma originating from the pineal gland with consecutive obstructive hydrocephalus. A mature teratoma was diagnosed and resected. Postoperative recovery was good, and the patient could return to his normal daily activities. However, a new, slowly progressive lesion in the sellar region with an enlarged infundibular stalk was detected on follow-up MRI 3.5 years after initial pineal region teratoma resection. Biopsy revealed a newly developed pure germinoma. The patient was treated with radiotherapy plus chemotherapy and remained relapse free at the last follow-up. Sixteen other cases have reported a surgically resected primary mature teratoma, wherein patients developed metachronous germinomas during follow-up. Different theories try to elaborate this phenomenon, yet none can completely account for it. Although rare, metachronous iGCT is a phenomenon neurosurgeons should be aware of. In patients treated for iGCT, close long-term clinical, imaging, and laboratory follow-up is recommended. https://thejns.org/doi/10.3171/CASE2443.

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

GCT-13. OUTCOMES OF INTRACRANIAL GERMINOMA TREATED AT A SINGLE UK PROTON CENTRE ACCORDING TO UK CHILDREN’S CANCER AND LEUKAEMIA GROUP (CCLG) GUIDELINES

Abstract BACKGROUND After SIOP-CNS-GCT II closed in 2018, the CCLG recommended, with caveats, following the standard trial arms: 4 cycles of chemotherapy (Etoposide-Carboplatin alternating with Etoposide-Ifosfamide) followed by whole ventricular radiotherapy (WVRT) (24Gy/15fractions) and boost (16Gy/10fr) to the primary site(s) for localised germinoma and craniospinal irradiation (CSI) (24Gy/15fr) followed by boost (16Gy/10fr) to primary and metastatic sites for metastatic disease. Since 04/2021, the CCLG formally recommended omitting the boost for localised unifocal germinoma in complete radiological response after chemotherapy. From autumn 2022, we also omitted boosts to completely responded primary sites for localised bifocal germinoma. METHODS Retrospective reviewed of all patients referred to our proton centre 12/2018–06/2023. We collected patient, tumour and treatment factors, acute toxicities (CTCAE grade≥3), and event-free survival(EFS) from radiotherapy until 09/2023. RESULTS Forty-two patients (36M:6F) were included, 23 localised and 19 (including 3 incompletely staged) treated as metastatic. Primary sites: 21 pineal, 8 pituitary/suprasellar, 10 bifocal and 3 atypical (optic nerve, periventricular, thalamic). Diagnosis was by histopathology in 40 and bifocal disease with negative CSF and serum markers in 2. Median age was 15 years (IQR 13-16), median follow-up 13 months (IQR 6-15). Patients were treated according to CCLG guidance, apart from three patients with metastatic pure germinoma, of whom one received 2 cycles Cisplatin-Etoposide, and two received 5 and 3 cycles of Vinblastine before CSI, and one patient with metastatic germinoma plus teratoma who received 2 cycles of Cisplatin-Etoposide and non-germinoma radiotherapy doses (30Gy/20fr CSI, 24Gy/15fr cranial boosts). No patient had subsequent surgery. All remained progression free at last follow-up. Eight patients developed acute grade 3 toxicities: 3 vomiting (2 CSI, 1 WVRT), and 5 lymphopenia (all CSI). CONCLUSIONS Disease control was excellent, with no relapses to date. Proton therapy was well tolerated with low rates of acute high grade toxicities.

Long-term outcomes following proton therapy for non-metastatic central nervous system germinoma in children and adolescents

Background/PurposeRadiation is a key component in the treatment of central nervous system pure germinoma (PG) in children and adolescents. Proton therapy (PT) improves normal tissue sparing and potentially reduces adverse effects (AE). The aim of this study was to present the largest single institution experience utilizing PT for the management of PG. Materials MethodsWe enrolled 35 non-metastatic patients with PG that were treated with PT at our institution between July 2007 – September 2021. Most received induction chemotherapy (n = 31, 89 %) and whole ventricular irradiation with an involved field boost (n = 29, 83 %). The most common total dose was 30 CGE (n = 18, 51.4 %). We utilized the cumulative incidence method to estimate local control (LC), freedom from distant metastases (FFDM), freedom from progression (FFP), and overall survival (OS). Treatment related toxicity was assessed per CTCAE version 5. ResultsMedian follow-up was 6.2 years (range, 0.9–––15.2). The 10-year Kaplan-Meier estimates for LC, FFDM, FFP, and OS were 100 %, 100 %, 100 %, and 94 % respectively. The most common AE were hearing impairment requiring hearing aids (n = 3), transient hypersomnia requiring medication (n = 3), and new onset endocrinopathy (n = 1). Of the 23 evaluable patients ≥ 18 years old at last follow-up, 8 were high school graduates/in college, 8 college graduates, and 7 others gainfully employed. ConclusionsWhen utilized in modern multimodality treatment of non-metastatic PG, the precise dosimetry of PT does not compromise disease control. Although serious radiation side effects are rare, the 100% cure rate supports further investigation into selective radiation dose and volume de-escalation.

Primary intracranial germ cell tumors in adolescents and adults: Results of an international, multicenter, retrospective cohort study.

2061 Background: Primary Intracranial Germ Cell Tumors (iGCT) are rare. Previous prospective and retrospective studies mainly included pediatric patients (pts) with a median age of 10-14 years. The aim of this retrospective analysis was to evaluate characteristics, treatment and outcome of adolescents and adults with iGCT. Methods: Data were collected from 10 institutions in Germany and Switzerland. Pts aged >/= 16 years at first diagnosis or at relapse with a primary iGCT were included. Objective responses were evaluated by local investigators. Statistics (Cox proportional hazard model, progression-free survival (PFS) and overall survival (OS) analyzed by Kaplan-Meier method) were performed with SPSS v29. Results: We identified 75 pts (92.0% male) with a median age of 23 years (range 16-60, 94.7% >/= 18 years). At first diagnosis, histology was pure germinoma in 70.7%, pure teratoma in 10.7%, other non-germinomatous GCT (NGGCT) in 13.3%, unknown in 5.3% of pts. Localized, bifocal, and metastatic disease was found in 72.0, 6.7, and 21.3% of pts. As part of their first line (1L) treatment, 69.3%, 80.0%, and 62.7% received surgery, radiotherapy, and chemotherapy, respectively. High dose chemotherapy/ autologous stem cell transplantation (HDCT/ASCT) was part of 1L treatment in n=3 pts with NGGCT. Trimodal and bimodal treatment was performed in 48.0% and 32.0% of pts. Response to 1L therapy was complete remission (CR) in 61.3%, partial remission tumor marker negative (PRm-) in 16.0%, PRm+ in 4.0%, PR with tumor marker status unknown in 4.0%, progressive disease (PD) in 2.7%, and unknown in 12.0%. Relapse occurred in 13/75 pts (17.3%) with unknown histology (n=4), teratoma (n=2), other NGGCT (n=4), and germinoma (n=3). In 2 pts. in whom germinoma was diagnosed at time of first diagnosis, at time of recurrence PNET and Yolk sac tumor were histologically proven. Median time to relapse was 19.0 months (mo.; range 3-223). HDCT/ASCT as salvage treatment was performed in 5 pts with NGGCT and in one pt with germinoma as 2L (n=5) or 3L (n=1). NGGCT histology was associated with increased risk for recurrence or death (p=0.012 and 0.039).3-year PFS was 90.7% (germinoma: 98.1%, NGGCT: 73.9%) and 5-year OS was 92.0% (germinoma: 98.1%; NGGCT: 78.3%). Median follow-up time was 60 mo (range 0-339). Conclusions: Disease characteristics, treatment and outcomes of adolescent/ adult iGCT pts are comparable to those reported in pediatric pts. High cure rates are achieved in pts with pure germinoma and current treatment concepts. In pts with NGGCT further investigation is needed to improve survival outcomes.

Double Localization of a Cerebral Germinoma: Case Report

Germinal cell tumors are embryonic tumors located mainly in the gonads, and their cerebral localization is rare, representing less than 1% of intracranial neoplasia. Clinical expression can be polymorphous, while imaging provides a highly suggestive radiological semiology. We report the case of a 31-year-old patient presenting with diabetes insipidus evolving for one year and associated with decreased visual acuity. Cerebro-medullary MRI revealed a tumoral process in the pineal region associated with thickening of the pituitary region. Tumor markers (β HCG and AFP) in plasma and CSF were negative, confirming the diagnosis of pure germinoma without the need for biopsy. Treatment is mostly based on radiotherapy, and sometimes on a combination of radiotherapy and chemotherapy. The latter was our therapeutic choice, with a good clinical and biological evolution.

Plasma miRNA expression profile in pediatric pineal pure germinomas.

Pure germinomas account for 40% of pineal tumors and are characterized by the lack of appreciable tumor markers, thus requiring a tumor biopsy for diagnosis. MicroRNAs (miRNA) have emerged as potential non-invasive biomarkers for germ cell tumors and may facilitate the non-invasive diagnosis of pure pineal germinomas. A retrospective chart review was performed on all patients treated at the Children's Cancer Hospital Egypt diagnosed with a pineal region tumor between June 2013 and March 2021 for whom a research blood sample was available. Plasma samples were profiled for miRNA expression, and DESeq2 was used to compare between pure germinoma and other tumor types. Differentially expressed miRNAs were identified. The area under the curve of the receive;r operating characteristic curve was constructed to evaluate diagnostic performance. Samples from 39 pediatric patients were available consisting of 12 pure germinomas and 27 pineal region tumors of other pathologies, including pineal origin tumors [n = 17; pineoblastoma (n = 13) and pineal parenchymal tumors of intermediate differentiation (n = 4)] and others [n = 10; low-grade glioma (n = 6) and atypical teratoid rhabdoid tumor (n = 4)]. Using an adjusted p-value <0.05, three miRNAs showed differential expression (miR-143-3p, miR-320c, miR-320d; adjusted p = 0.0058, p = 0.0478, and p = 0.0366, respectively) and good discriminatory power between the two groups (AUC 90.7%, p < 0.001) with a sensitivity of 25% and a specificity of 100%. Our results suggest that a three-plasma miRNA signature has the potential to non-invasively identify pineal body pure germinomas which may allow selected patients to avoid the potential surgical complications.

Primary Co-Occurrence of Gonadal and Extragonadal Central Nervous System (CNS) Germ Cell Tumors (GCTs): Case Report and Review of the Literature

Background: The primary co-occurrence of gonadal and extragonadal central nervous system (CNS) germ cell tumors (GCTs) has rarely been reported in the literature, and a common opinion on the underlying etiopathogenetic mechanism is lacking. Objective: We aim to investigate the pathophysiological mechanisms and genetic pathways underlying the primary co-occurrence of gonadal and CNS GCTs. Methods: We reviewed data from 29 consecutive patients with a diagnosis of CNS GCT, evaluated in our Hospital over the past 23 years, and searched for those who had at least a primary gonadal co-occurrence of GCT. A systematic review of the literature according to the PRISMA guidelines was also conducted. For a comprehensive and detailed search, PubMed, Ovid MEDLINE, and Ovid EMBASE databases have been consulted. Boolean operators and MeSH terms were used to find studies. Only articles published between 2000 and 2023 were considered. Results: Including our Institutional case report, a total of 7 patients with both testicular NGGCTs and CNS GCTs were identified (5 patients with metachronous tumors and patients with synchronous presentation). The average age at tumor diagnosis was 17 years. The cerebral histotypes reported were mixed GCTs (3 cases; 43%), pure germinomas (3 cases, 43%), and one yolk sac tumor (14%). Two out of seven cases (29%) were syndromic, one suffering from Down Syndrome and the other from Testicular Dysgenesis Syndrome. Regarding the etiology and molecular mechanism of GCT development, several gene mutations have been reported in the literature. Particularly, genetic alterations in the MAPK and/or PI3K/AKT/mTOR pathway, together with mutations of the KIT gene, have been shown to guarantee survival and transformation of mismigrated totipotent primordial germ cells, while suppressor genes allow their resistance against apoptotic death. Aberrant chromosomes have also been reported to be responsible for oncogenic transformation. It is also known that CNS and testicular GCTs share some genetic/epigenetic profiles. Conclusions: The primary co-occurrence of testicular NGGCT and extragonadal CNS GCTs is extremely rare. Genetic factors seem to play a paramount role in their etiopathogenesis. Additional research is needed to elucidate molecular mechanisms of oncogenesis in such patients.

PAEDIATRIC-07 IMAGING OF PINEAL REGION TUMOURS IN CHILDREN

Abstract Pineal tumors comprise between 3% and 8% of all pediatric brain tumors. Pineal region tumors can be divided into four categories: Germ cell tumors, pineal cysts, pineal parenchymal tumors, and tumors of the supporting tissues of the pineal gland or adjacent structures (such as pineal gliomas, dermoids, and epidermoids). The most common pineal region tumors are germ cell tumors, most are pure germinomas. Other variants such as nongerminomatous germ cell tumors, mixed germ cell tumors, teratomas, embryonal cell carcinoma, yolk sac tumor, and choriocarcinoma constitute the remainder. Germinomas are hyperdense on CT and enhance homogenously. The typical appearance on CT is a calcified pineal gland surrounded by noncalcified tumor. On MRI, these lesions have homogenous signal isointense to gray matter on all sequences with intense contrast enhancement. These tumors may infiltrate the thalami and midbrain. Spinal dissemination is seen in up to 36% of cases. Pineocytomas are well-differentiated tumors that retain morphologic features of the pineal parenchymal cells. They are slow-growing, circumscribed, but noncapsulated tumors. They are more commonly solid tumors, although cystic variants have been described. Solid tumors are either hypointense or isointense to gray matter and T2-hyperintense. Enhancement is homogenous and calcification is common. Cystic variants are often indistinguishable from pineal cysts. Pineoblastomas are malignant, unencapsulated tumors that resemble embryonal tumors NOS, but are distinct from such tumors in other locations due to their photosensory differentiation. On MRI, these lesions are hypointense to isointense on T1-weighted images and variable low, high, or mixed signal on T2-weighted images. They have lobulated contours and enhance homogenously. They calcify less often than pineocytomas. The “exploded pattern” of calcification with peripheral displacement of pineal gland calcification is considered more typical of pineal parenchymal tumors, differentiating them from germ cell tumors.

Outcomes Following Proton Therapy for Non-Metastatic Central Nervous System Germinoma in Children and Adolescents

Radiation is a key component in the treatment of central nervous system pure germinoma (PG) in children and adolescents. Compared to photons, proton therapy (PT) improves normal tissue sparing and potentially reduces adverse effects, but there are sparse data on long-term patient outcomes. Herein, we present the largest reported single institution experience utilizing PT for the management of PG. We performed an IRB-approved retrospective review of a prospective database containing 35 patients with non-metastatic PG treated with PT between July 2007 and September 2021. The median age at treatment was 13 years. All patients had > 6 months of follow up. Two patients were diagnosed based on cerebral spinal fluid B-HCG levels and the remaining 33 patients through histopathology. Eleven patients had bifocal or multifocal intracranial disease. Most patients (n = 31, 88.6%) received induction chemotherapy with carboplatin + etoposide (n = 25, 80.6%) with all demonstrating a radiographic response to neoadjuvant therapy. Twenty-nine were treated with whole ventricular irradiation (WVI) with an involved field (IF) boost, 2 with craniospinal irradiation + WVI + IF, 2 with IF, 1 with CSI + IF, and 1 with whole brain + IF. Among this subgroup, the most common total dose was 30 GyRBE (n = 18, 51.4%). Of the 4 patients that did not receive chemotherapy, 3 received WVI + IF and 1 was treated with CSI + WVI + IF. The total dose in the patients not receiving chemotherapy was 45 GyRBE. Twenty-nine patients were treated with double scattered PT (DS) and 6 patients with pencil beam scanning PT (PBS). We utilized the cumulative incidence method to estimate local control (LC), freedom from distant metastases (FFDM), freedom from progression (FFP), and overall survival (OS). Treatment related toxicity was assessed according to the CTCAEv5. Median follow up was 6.2 years (Range: 0.9-15.2 years). The 10-year KM estimates for LC, FFDM, FFP, and OS were 100%, 100%, 100%, and 97% respectively. One patient developed acute lymphocytic leukemia 8 months after treatment and died. The sole ³ grade 3 radiation-related toxicity was a cavernoma with hemorrhage 3.6 years post treatment requiring surgical resection. The most common adverse events were hearing impairment requiring hearing aids (n = 3), hypersomnia requiring medication (n = 3), and new onset endocrinopathy (n = 1). Of the 22 evaluable patients ³18 years old at last follow up, 7 were high school graduates/in college, 8 college graduates, and 5 others gainfully employed. The use of proton therapy in the multi-modality approach to non-metastatic PG does not compromise local control. Although serious side effects are rare and treatment has minimal impact on survivors' early educational/career trajectory, the 100% cure rate supports further investigation into selective radiation dose and volume de-escalation.

Multi-Institutional Phase I Feasibility Trial of Vertebral Body Sparing CSI for Pediatric Brain Tumors

Craniospinal irradiation (CSI) is an essential part of curative treatment for several pediatric brain tumors. Proton CSI allows for sparing of the organs anterior to the vertebral bodies (VBs), but this technique still includes the entire VB in the target for growing children. providing no advantage in marrow sparing or adverse effects on growth. Advances in proton therapy including Proton Beam Scanning (PBS) allow for delivery of proton CSI with substantial vertebral body sparing (VBS). We sought to determine the feasibility of VBS CSI using PBS based on the effects on tumor control and growth, and the occurrence of grade III/IV hematologic toxicity. Clinical and treatment characteristics were recorded for 20 pediatric patients with medulloblastoma (n = 14) or germ cell tumor (GCT) (n = 6) who received proton VBS CSI without concurrent chemotherapy or with concurrent single-agent vincristine in a multi-institutional clinical trial. The following standard variables were extracted for each patient: age, histology, radiation dose, chemotherapy regimen, and growth hormone replacement status. Complete blood counts (CBC) with differential and data on height/weight were recorded at baseline pre-RT, weekly during RT, and after completion of cancer treatment. Hematologic toxicity was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4 (CTCAE v4). Median age of 13 male and 7 female patients receiving proton VBS CSI was 10 years (range: 5.1 - 15.1). All GCT patients (n = 6, 30%) received pre-RT chemo. Median CSI dose was 23.4 Gy (range: 21.0 - 37.8), and total dose to tumor bed was 54 Gy in 18 patients (90%) while 2 patients with pure germinoma received a total dose of 36 and 37.5 Gy, respectively. 11 patients (55%) did not receive concurrent vincristine. At a median follow up of 26.4 months (range: 12.5 - 56.3) from the start of RT, no patients relapsed. 17 patients (85%) developed grade ≥3 hematologic toxicity including grade 3 lymphopenia (n = 16), leukopenia (n = 9), neutropenia (n = 8), anemia (n = 1), and grade 4 neutropenia (n = 1). The patient who developed grade 4 neutropenia had low white blood counts prior to RT. 14 patients (70%) received post-RT chemo. No patients required platelet transfusion during RT. Those findings are similar to historical controls. 4 patients started growth hormone replacement therapy after RT. No patients developed spine deformities after the completion of treatment. Proton VBS CSI is a feasible and well tolerated treatment for children with brain tumors. Longer follow up is needed to assess for late effects on tumor control. It is too early to assess for height in this cohort but for the patients that had longer follow up, normal height was achieved.

Occult neurohypophyseal germinoma discovered during the course of long-term diabetes insipidus: illustrative case.

The authors report a case of occult neurohypophyseal germinoma detected in a patient with long-term diabetes insipidus. Central diabetes insipidus is the initial symptom in 95% of cases of neurohypophyseal germinoma. In occult neurohypophyseal germinomas, no abnormalities are seen on magnetic resonance imaging (MRI) at the onset of symptoms. It can take several months or even years for these changes to be detected on MRI. A 20-year-old male was diagnosed with central diabetes insipidus at the age of 17 years, and gonadal and adrenal corticosteroid insufficiency was noted at the age of 19 years. Head MRI showed an enlarged and enhanced pituitary stalk. He was referred to our department for a suspected neoplastic lesion. Endoscopic transsphenoidal biopsy indicated a pure germinoma. He was treated with chemotherapy and radiotherapy and then was discharged. In this case, new imaging findings appeared 19 months after the onset of diabetes insipidus, and the pathological diagnosis was made after almost 24 months. Because the patient had a history of growth hormone deficiency and had a positive test result for diabetes insipidus, occult neurohypophyseal germinoma was suspected, and periodic contrast-enhanced MRI monitoring was deemed essential.

OTHR-09. A RETROSPECTIVE COHORT STUDY EXAMINING RADIOLOGIC AND CLINICAL CHARACTERISTICS OF CHILDREN AND ADOLESCENTS WITH ATYPICAL/COMPLEX PINEAL CYSTS

Abstract INTRODUCTION The significance of atypical or complex pineal cysts (CPC) on magnetic resonance imaging (MRI) is often unclear, and the appropriate management has not been well defined. We conducted a retrospective cohort study of children and adolescents (0-18 years of age) with complex pineal cysts noted on brain MRIs obtained at Children’s Hospital Los Angeles (CHLA) prior to 05/31/2022. METHODS We retrospectively reviewed electronic medical records at CHLA to identify patients &amp;lt;18 years of age who were diagnosed with CPC upon MRI between January 1, 2010 and May 31, 2022. CPC were defined as cysts that are multi-cystic, enhancing, ≥1 cm in size, have a solid component, or exhibit restricted diffusion. Patients were identified by an automated Boolean search of a radiology report database; individual reports were then reviewed for eligibility. Patients with normal pineal glands or simple (&amp;lt;1 cm) pineal cysts were excluded. Electronic medical records were evaluated for patient chief complaint, initial clinical and radiographic symptoms, tumor markers (beta-human chorionic gonadotropin and alpha-fetoprotein), and final diagnosis. RESULTS We identified a cohort of 175 patients; 106 (61%) were female. Mean age at initial MRI was 8.36 years of age (SD 5.36). Tumor markers were measured in 52 patients (30%). The most common presenting symptoms for patients were headache (34%), seizures (26%), nausea/vomiting (19%), weakness/fatigue (17%), and dizziness (12%). Additional presenting symptoms included ataxia, sensory changes, and anxiety. Pineal malignancies were identified in 4 patients (2.2%), which consisted of a pituitary pure germinoma, a pineal region parenchymal tumor, and two pineoblastomas. The remaining 98% of patients (171 patients) either had a benign pineal cyst or were categorized as unknown. CONCLUSION Most CPC are not associated with malignant neoplasms and represent incidental findings with scant clinical significance.

Surgical outcome of pineal region lesions in paediatric population

Introduction. Pineal region pathologies are heterogenous, spectrum ranging from benign, infective to malignant in nature such as parenchymal, germ cell, glial, melanomas, metastatic, tubercular, etc. These lesions are commoner in the pediatric age group and have a variable outcome. The goal of this study is to present our experience regarding the surgical outcomes of pineal region lesions in the paediatric population. Objective. The objective of this study is to access the surgical outcome of pineal region lesions in the paediatric population Methods and Material. Eighty cases of pineal region lesions in the paediatric population (upto 15 years of age) operated in the neurosurgery department, G.B Pant Hospital New Delhi via either Occipital transtentorial or Supracerebellar Infratentorial approaches were retrospectively analyzed. Results. There were four main groups of lesions with pineal parenchymal tumours (35 cases) being the commonest. Glial tumours were the next most common contributing 29 cases. Germ cell tumours comprise 7 and miscellaneous 9 cases. The outcome showed graded improvement with the extent of tumour removal and 57 patients(71.25%) improved following surgery. The clinical status of 20 patients(25%) remained unchanged and 3(3.75%) deteriorated from their pre-operative status. 3 patients(3.75%) died in the immediate post-operative period and 11(13.75%) died due to recurrent disease. Conclusion. A graded increase in survival was noted with increasing the degree of resection and postoperative adjuvant therapy in malignant pineal tumours whereas benign pineal lesions can be managed with surgery. Pure germinomas are the only tumour for which the survival rate was unrelated to extent of tumour resection.

Influence of growth hormone therapy on germinoma survivors.

Due to the effectiveness of growth hormone therapy (GHT), the number of cancer survivors receiving GHT has increased. Previous studies had indicated that GHT was not associated with the increasing risks of tumor recurrence and development with second neoplasm (SN) in cancer survivors. However, to date, research on those risks in germinoma survivors is still limited. The aim of this study is to evaluate the impact of GHT in relation to tumor recurrence and development with SN in pure germinoma survivors. This retrospective cohort study was approved by the Ethical Committee for Epidemiology of our institution. Seventy-three consecutive patients who underwent a biopsy of the lesion and were diagnosed with pure germinoma were retrospectively studied. They (median age, 15.0years) were followed up more than 1year after biopsy (median follow-up period, 14.3years). The following data was obtained from the medical records of the patients: age, sex, preoperative magnetic resonance imaging findings, hormonal replacement, and events including tumor recurrence and/or SN. In our patient series, 16 patients (21.9%) who were more likely to have neurohypophysial lesion and receive multiple hormonal therapies had received GHT. No significant differences in the rates of tumor recurrence and development with SN were observed between the patients who had and had not received GHT. Moreover, the recurrence-free survival and overall survival rates were not different between the patients who had and had not received GHT. GHT did not increase the risks of tumor recurrence and development with SN in pure germinoma survivors.

Multi-institutional analysis of central nervous system germ cell tumors in patients with Down syndrome.

Primary germ cell tumors (GCTs) are the most common central nervous system (CNS) neoplasm in patients with Down syndrome (DS). However, a standard of care has not been established due to paucity of data. A retrospective multi-institutional analysis was conducted, in addition to a comprehensive review of the literature. Ten patients from six institutions (five USA, one Brazil) were identified, in addition to 31 patients in the literature from 1975 to 2021. Of the 41 total patients (mean age 9.9years; 61% male), 16 (39%) had non-germinomatous germ cell tumors (NGGCTs), 16 (39%) had pure germinomas, and eight (19.5%) had teratomas. Basal ganglia was the most common tumor location (n=13; 31.7%), followed by posterior fossa (n=7; 17%). Nine patients (22%) experienced disease relapse or progression, of which four died from tumor progression (one germinoma, three teratomas). Sixteen patients (39%) experienced treatment-related complications, of which eight (50%) died (five germinomas, three NGGCTs). Of the germinoma patients, two died from chemotherapy-related sepsis, one from postsurgery cardiopulmonary failure, one from pneumonia, and one from moyamoya following radiation therapy (RT). Of the NGGCT patients, one died from chemotherapy-related sepsis, one from postsurgical infection, and one from pneumonia following surgery/chemotherapy/RT. Three-year overall survival was 66% for all histological types: 62% germinomas, 79% for NGGCTs, and 53% for teratomas. Patients with DS treated for CNS GCTs are at an increased risk of treatment-related adverse events. A different therapeutic approach may need to be considered to mitigate treatment-related complications and long-term neurocognitive sequelae.

GCT-15. Multi-institutional analysis and literature review of central nervous system germ cell tumors in patients with Down syndrome

Abstract BACKGROUND: A standard-of-care has not been established for the management of patients with Down syndrome (DS) who develop primary central nervous system (CNS) germ cell tumors (GCTs) – the most common CNS neoplasm in DS – despite being more susceptible to treatment-related adverse events. METHODS: Data from large academic institutions were collected and a comprehensive review of the medical literature was conducted. RESULTS: Ten patients from six institutions (five USA, one Brazil) were reviewed. Additionally, thirty-one patients were identified in the literature from 1975-2021. Of the 41 total patients, mean age was ten years (range, birth to 35 years); males were predominant (61%). Basal ganglia were the most common tumor location (n=12; 29%), followed by posterior fossa (n=7; 17%). Sixteen patients had non-germinomatous germ cell tumors (NGGCTs) (39%), 14 had pure germinomas (34%), and eight had teratomas (20%); histology was unreported for two (5%). Nine patients (22%) experienced disease relapse, of which four died from tumor progression (one germinoma versus three teratoma). Fifteen patients (37%) experienced treatment-related complications - seven died (four germinoma versus three NGGCT). Of the germinoma patients, two died from chemotherapy-related sepsis, one from post-surgery cardiopulmonary failure, and one from Moyamoya following radiation-therapy (RT) only. Of the NGGCT patients, one died from chemotherapy-related sepsis, one from post-surgical infection, and one from pneumonia following surgery/chemotherapy/RT. Three-year overall survival (OS) was 66% for all histological types - 62% germinoma, 79% for NGGCT, and 53% for teratoma. Three-year OS for patients who received RT or chemotherapy was 71% and 75% respectively. Twenty-seven patients remain alive at latest follow-up (mean follow-up from diagnosis: 46.8 months). CONCLUSIONS: Patients with DS treated for CNS GCTs are at an increased risk of treatment-related adverse events. A different therapeutic approach may need to be considered for this patient population to mitigate treatment-related complications and long-term neurocognitive sequelae.

GCT-17. Recurrence of CNS germ cell tumors (GCTs) along biopsy and ventriculostomy tracts

Abstract BACKGROUND: Central nervous system (CNS) germinoma relapses are rare. However, the latest Children’s Oncology Group (COG), ACNS1123 stratum 2, described three relapses along the biopsy tract out of eight total relapses; two along the biopsy and endoscopic third ventriculostomy (ETV) tract and one along the biopsy tract and external ventricular drain. Given these findings, we sought to describe other cases of GCT recurrence along surgical tracts. METHODS: We performed a literature review from 1980-2021 to identify cases of GCT recurrence along biopsy and ventriculostomy tracts. RESULTS: Three patients with pineal lesions were identified (13, 14, and 34-years old). All underwent ETV, cerebrospinal fluid (CSF) sampling, and tumor biopsy. Two patients had uncomplicated postoperative courses. One developed persistent hydrocephalus and underwent repeat ventriculostomy. Two were diagnosed with pure germinoma and treated with focal radiotherapy of 45 Gy alone or chemotherapy and radiation (50.4 Gy to the tumor volume and 36 Gy to adjacent high-risk area). The third was treated with methotrexate and corticosteroids. All three had recurrence on surveillance MRI (1-3 years after diagnosis). One had recurrence at the ventriculostomy bur hole site, and two had recurrence along the ventriculostomy tract. On biopsy, all three lesions were germinomas. One received pre-radiation chemotherapy and palliative radiation (36 Gy to surgical bed and 30.6 Gy to surrounding high-risk area). Another received chemotherapy and craniospinal radiation of 15 Gy. The third had a complicated post-biopsy course. He ultimately underwent chemotherapy and radiation (24 Gy). All were still alive at time of report. Two were disease free at 12 and 18 months, while one was still receiving chemotherapy. CONCLUSION: Recurrence along the biopsy or ventriculostomy tract is rarely reported in the literature. Future evaluation to determine the incidence could inform if biopsy and ventriculostomy tracts should be included in the radiation therapy field.

Central Nervous System Tumors in Children.

Central Nervous System Tumors in Children.

Clinical Outcomes and Diagnostic Consistency of Serum and CSF Tumor Markers in Pediatric Intracranial Germ Cell Tumors in Thailand: A Multicenter Study.

The diagnostic and treatment outcomes of intracranial germ cell tumors (ICGCTs) among low and middle income countries are limited. A total of 63 ICGCTs patients with a median age of 11.6 years were studied. A 30 (47.6%) and 33 (52.4%) patients were classified as pure germinomas and nongerminomatous germ cell tumors (NGGCTs), respectively. The concordances between serum and cerebrospinal fluid (CSF) alpha-fetoprotein (84.3%) and beta-human chorionic gonadotropin (68.4%) were addressed. The 5-year overall survival (OS) and event-free survival (EFS) rates of pure germinomas versus NGGCTs were 83.9 versus 69.1% and 74.6 versus 57.7%, respectively. Patients undergoing radiation had higher 5-year OS and EFS than those without radiation treatment with P < .001. Chemotherapy combined with radiation is a cornerstone treatment to achieve outcomes. Adverse prognostic factors included age <8 years, surgery, and nonradiation treatment. Either serum or CSF tumor markers were adequately required as a diagnostic test among patients with ICGCTs.