bluuebunny/crossref_metadata_2025_split huggingface dataset:
GCT-05. UPDATED REPORT ON TREATMENT MODALITIES IN METASTATIC GERMINOMA IN CHILDREN: A MULTI-INSTITUTIONAL ANALYSIS
Authors: Shatara Margaret , Thia Alexia , Abu-Arja Mohammad H , Su Jack M , MacDonald Shannon , Perkins Stephanie , Gorsi Hamza , Govender Dinisha , Dholaria Hetal , Schwartz Jonathan , Foo Jen Chun , Rajagopal Revathi , Bartels Ute , O’Halloran Katrina , Sleightholm Richard , Lafay-Cousin Lucie , Cansanay Rose Daynielle A , Schlosser Mary-Pat , Cappellano Andrea M , Dassi Natália , Fisher Michael J , Amayiri Nisreen , Yilmaz Yasin , Czogala Malgorzata , Graham Richard , Baglivo Sofia Jares , Ronsley Rebecca , Mastronuzzi Angela , Michaiel George , Khan Sara , Magnum Ross , Hoffman Lindsey M , Knowles Truman , Mueller Sabine , Zaghloul Mohamed S , Abdelhaleem Nada A , El-ayadi Moatasem , Abdelbaki Mohamed S 
Published: June 2024

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.
GCT-09. VENTRICULAR RELAPSES OF INTRACRANIAL GERM CELL TUMORS FOLLOWING FOCAL RADIOTHERAPY
Authors: Dassi Natália , Abdelbaki Mohamed S , Cappellano Andrea M 
Published: June 2024

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.
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
Authors: Biassoni Veronica , Raimondo Paolo , Schiavello Elisabetta , Terenziani Monica , Nigro Olga , Gattuso Giovanna , Spreafico Filippo , Meazza Cristina , Podda Marta , Chiaravalli Stefano , Luksch Roberto , Puma Nadia , Ferrari Andrea , Casanova Michela , Bergamaschi Luca , Sironi Giovanna , Vennarini Sabina , Massimino Maura 
Published: June 2024

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.
GCT-26. INTRACRANIAL NON-GERMINOMATOUS GERM CELL TUMOR WITH MALIGNANT TRANSFORMATION TO EMBRYONAL RHABDOMYSARCOMA
Authors: Long Clayton , Mangum Ross , Keller Lisa , Bristol Ruth E , Ahmed Safia K , Kuwabara Michael , Tiwari Nishant , Hoffman Lindsey M 
Published: June 2024

Abstract

BACKGROUND
Non-germinomatous germ cell tumors (NGGCT) constitute 35%- 45% of intracranial germ cell tumors. Growing teratoma syndrome has been observed in patients with NGGCTs after starting chemotherapy. While growing teratomas are typically benign, this process can rarely involve malignant transformation and result in poor prognosis. We present the case of a patient with pineal NGGCT and growing teratoma syndrome with malignant transformation to embryonal rhabdomyosarcoma.

CASE REPORT
A 13-year-old male presented with headaches and vision changes. An MRI brain demonstrated a 26 x 25 x 19 mm (AP X TR X CC) mixed solid and cystic pineal mass with no evidence of metastatic disease. Due to elevated alpha fetoprotein levels in the serum and cerebrospinal fluid, he was diagnosed with intracranial NGGCT. Treatment was initiated with alternating cycles of Carboplatin/Etoposide and Ifosfamide/Etoposide. After 2 cycles of chemotherapy, a complete biochemical response was noted but MRI showed increased tumor size (presumed growing teratoma syndrome). The patient underwent complete tumor resection. Histology showed embryonal rhabdomyosarcoma as a somatic malignancy arising in a mature teratoma. Further molecular characterization revealed somatic NF1 and KRAS pathogenic mutations that are consistent with the primary diagnosis. Methylation profiling, however, did not exhibit a match with any known malignancies. Continued complete response was noted following two additional chemotherapy cycles. The patient is planned for six total chemotherapy cycles followed by high-dose craniospinal radiation with boost to the primary tumor.

CONCLUSIONS
Malignant transformation is a rare phenomenon in NGGCT. There is no standard of care for these patients. Further studies are needed to define ideal therapy for this patient population.
GCT-28. THE IMPACT OF RESIDUAL TUMOR ON THE OUTCOMES OF CENTRAL NERVOUS SYSTEM GERMINOMA
Authors: Baroni Lorena V , Alderete Daniel , Abdelbaki Mohamed S 
Published: June 2024

Abstract

BACKGROUND
The inclusion of chemotherapy in the treatment backbone of central nervous system germinoma has helped reduce the field and dose of radiotherapy. Typically, patients wirh residual disease after chemotherapy are treated with higher doses of radiotherapy, which may not be necessary. Hence, we aimed to assess the impact of residual disease at different points during therapy on the outcomes of germinoma patients.

METHODS
We performed an extensive review of all germinoma patients diagnosed at Hospital Garrahan in Argentina over the last 20 years. We evaluated the chemotherapy response after 2 cycles and 4 cycles of chemotherapy and after radiotherapy.

RESULTS
Thirty nine germinoma were included (localized 34; disseminated 5). All patients were treated as per the SIOP-CNS-GCT-96 strategy. At the end of 2 cycles of chemotherapy, 21 patients achieved a complete response (CR), 10 had a partial response (PR), and 8 patients didn’t have MRI evaluation. At the end of 4 chemotherapy cycles, 10 additional patients achieved a CR, 7 still had a PR, while one patient didn’t have MRI evaluation. Only 3 patients had residual tumour after radiotherapy; one had a second-look surgery that didn’t show any evidence of viable tumour. None of the patients with residual tumour at the end of chemotherapy or radiotherapy relapsed with a median follow up of 6.3 years.

CONCLUSION
Residual tumor at the end of both chemotherapy and radiotherapy does not have an impact on the outcomes. Clinical trials in germinomas may need to investigate administering the same dose of radiotherapy for patients regardless of the presence of residual disease at the end of chemotherapy. Furthermore, patients with no residual disease at the end of two cycles of chemotherapy may benefit from moving directly to radiotherapy without the need to receive two additional cycles of chemotherapy.
HGG-03. TRUNCATING MUTATIONS IN PPM1D COOPERATE WITH PI3K ALTERATIONS TO DRIVE PEDIATRIC DIFFUSE MIDLINE GLIOMAS
Authors: Kebede Adam F , Morin Eric , Kundu Ipsita , Blumenshine Olivia , Rendo Veronica , Phoenix Timothy N , Bandopadhayay Pratiti 
Published: June 2024

Abstract
Mutations in PPM1D – coding for the phosphatase WIP1 - are present in 8 -12% of all Diffuse Midline Glioma (DMG), H3 K27-altered – a universally fatal subtype of pediatric high-grade tumors. PPM1D mutations are mutually exclusive with TP53 mutations and mainly lead to a truncation of its C-terminal regulatory domain. Truncated PPM1D (PPM1Dtr) has increased protein stability and impairs the p53-dependent DNA Damage Response (DDR) by dephosphorylating its numerous targets (e.g p53, H2A.X, CHK1) which contributes to its oncogenicity. However, because wildtype p53 is present in PPM1Dtr tumors, its activation is suppressed but not completely ablated suggesting that PPM1D mutant tumors may evolve differently from p53 mutant ones. Our analysis of whole genome sequencing datasets indeed found that PPM1D mutations uniquely co-occur with alterations in the PI3K/mTOR pathway suggesting potential cooperativity in enhancing tumorigenesis. Using mouse neural stem cells (mNSCs) as an isogenic model system, we have engineered specific combinations of oncogenic alterations to study their impact on cell proliferation, PI3K/mTOR pathway activation and response to DNA damage and replication stress. We find that PPM1Dtr cooperates with PIK3CA alterations to increase proliferation and signaling through the PI3K/mTOR pathway. Notably, in an in utero electroporation model, mutant PIK3CA accelerates the development of high-grade tumors that infiltrate deep into the brainstem. Our study also indicates a vulnerability to inhibition of the PI3K/mTOR pathway in PPM1Dtr-PI3K co-altered tumors. Future work will aim at 1) exploring the mechanism of cooperation and impact on replicative stress response and 2) developing and testing a rational therapeutic strategy for PPM1D-mutant tumors.
HGG-47. SPATIAL SINGLE-CELL PROTEOMIC ANALYSIS MAPS THE DISTINCT PEDIATRIC-TYPE DIFFUSE HIGH-GRADE GLIOMA TUMOR ENTITIES AND DEFINES THEIR TUMOR AND IMMUNE MICROENVIRONMENTS
Authors: Petrilli Lucia Lisa , Spinozzi Giulio , Crocco Lucia Di , Salanitro Antonio , Rossi Sabrina , Bressan Dario , Cerimele Alfredo , Diomedi-Camassei Francesca , Miele Evelina , Cacchione Antonella , Baldo Giada Del , Colafati Giovanna Stefania , Carai Andrea , Locatelli Franco , Mastronuzzi Angela , Vinci Maria 
Published: June 2024

Abstract
Paediatric-type diffuse high-grade gliomas (pDHGG) are a group of molecularly and clinically defined tumor entities of the central nervous system. The investigation of the spatial organization of pDHGG tissues may provide new insights to decipher their heterogeneous nature and identify vulnerabilities in their aggressive behaviour. Here we exploit Imaging Mass Cytometry (IMC), a spatial biology approach enabling multiplex tissue phenotyping at single-cell resolution. We used 16 total formalin-fixed paraffin-embedded (FFPE) tissues from 4 patients including 1 Diffuse hemispheric glioma H3G34-mutant (DHG-H3G34), 1 Diffuse pediatric-type high-grade glioma H3-wildtype and IDH-wildtype (DHGG-WT) and 2 Diffuse midline glioma H3K27-altered (DMG-H3K27, 1 H3.3K27M and 1 H3.1K27M). Classical pathology assessment and DNA methylation profile were also performed. For IMC staining, 2 metal-tag custom-designed antibody panels (tumour and immune) of 31 antibodies were used. The panels include antibodies for differentiated and stem-cell markers, extracellular matrices, immune markers and H3K27M and H3.3G34R variants. An IMC analysis pipeline was developed: images are extracted in tiff format from the proprietary MCD files produced by Hyperion instrument, filtered to remove hot pixels via top-hat and OpenCV in Python, segmented using steinbock and analysed using the IMC Data Analysis toolbox in R, using docker. A total of 209 mm2 of tissue were analysed. IMC analysis showed that DHG-H3G34 displays a higher heterogeneity in terms of cell phenotypes compared to the other tumor entities. Moreover, immune infiltrate of T, B cells, NK and monocytes was observed in the DHG-H3G34 and DHGG-WT tissues, while the DMG-H3K27 had low/no immune infiltrate with the H3.3K27M showing higher PDL-1 expression. Analysis of longitudinal and multi-region samples highlighted trajectories of tumor evolution and identification of extracellular matrix niches in tumor core versus the infiltrative front. Our study provides novel insights into pDHGG complex biology by investigating their tissue architecture, spatial organization and cell-cell interactions.
IMG-03. PRE-TREATMENT EVIDENCE OF ABNORMAL SUPRATENTORIAL WHITE MATTER IN CHILDREN WITH POSTERIOR FOSSA TUMOURS USING DIFFUSION MRI
Authors: Drabek-Maunder Emily , Mankad Kshitij , Aquilina Kristian , Dean Jamie A , Nisbet Andrew , Clark Chris A 
Published: June 2024

Abstract

BACKGROUND
Over half of childhood brain tumours originate in the posterior fossa, which includes low-grade (e.g. pilocytic astrocytoma) and high-grade (e.g. medulloblastoma) tumours. Even though overall survival rates of paediatric brain tumours have substantially increased, survivors face neuropsychological impairments impacting behaviour, cognition, language and motor skills. Post-treatment outcomes are associated with structural changes within the brain, but it is unclear if observed microstructural damage is caused exclusively by radiotherapy or if there is earlier damage from the tumour and related effects. Diffusion MRI is a non-invasive technique that can be used to better understand white matter microstructure by quantifying water diffusion in the brain. Diffusion tensor imaging (DTI) can be used to assess white matter damage.

METHODS
In this work, we used DTI to understand white matter microstructure in 8 posterior fossa tumour patients prior to surgery. We compared individual patients to age- and sex-matched healthy controls in a one-against-many approach.

RESULTS
We demonstrate the presence of supratentorial white matter abnormalities prior to treatment in 3 patients. Before treatment, all patients are found to have significantly enlarged lateral ventricles relative to total brain volume (p&lt;0.05). Patients with ventricle volumes &gt;4% relative to brain volume correspond to significant changes in DTI parameters found in pre-treatment images, suggesting that hydrocephalus impacts white matter microstructure before surgery. Observed white matter changes are complex and patient-dependent, patients demonstrate compression (increased fractional anisotropy; FA) or diffuse oedema and damage (decreased FA). These white matter abnormalities persist over time, which could lead to cumulative damage, for example when adjuvant treatment involves radiotherapy.

CONCLUSIONS
To improve patient outcomes, pre-treatment imaging could be considered during individual treatment planning and risk evaluation to avoid further injury to white matter. Pre-treatment white matter abnormalities may have a bearing on neurocognitive patient outcomes, which will be the focus of future work.
IMG-20. IDENTIFICATION OF PRE-OPERATIVE IMAGING FEATURES ASSOCIATED WITH COGNITIVE IMPAIRMENT IN CHILDREN WITH BRAIN TUMOURS USING A LANGUAGE MODELLING SYSTEM COMBINED WITH MACHINE LEARNING ANALYSIS
Authors: Dockrell Simon , Tsakiroglou Anna Maria , Vaughan Kate , Albutt Lesley , Kilday John-Paul , Kamaly-Asl Ian , McCabe Martin , Fergie Martin , Stivaros Stavros 
Published: June 2024

Abstract

BACKGROUND
Cognitive impairments caused by paediatric brain tumours negatively impact future quality-of-life. Impairments of processing speed and working memory are important contributors to challenges these children encounter in education. Inconsistent image acquisition and poor imaging quality can restrict advanced radiomic analysis in historical datasets. We developed and refined a language modelling human image-analysis support system, passing data to specific machine learning techniques that can utilise datasets with many data points in a limited population.

METHODS
Medical records of children treated for brain tumours with surgery and radiotherapy in Manchester between 2000-2020 were reviewed with imaging accessible from 2006-2020. Pre-operative MRI scans were reviewed for 52 patients along with their most recent processing speed and/or working memory test scores. 274 radiological variables analysing tumour features and damage to brain structures were reported per patient using a standardised reporting tool. Univariate analysis was performed using Linear Regression with time-to-test analysed as a covariate. Multivariate analysis used Elastic Net Regression.

RESULTS
Univariate analysis revealed risk factors for slower processing speed included midline shift, tumour in the corpus callosum, right temporal periventricular white matter oedema, diffusion changes in the left frontal lobe or amygdala and FLAIR changes in the left caudate nucleus (p&lt;0.005). Risk factors for impaired working memory included midline shift, cortical tumour location, left periventricular white matter oedema and diffusion or FLAIR changes in the left frontal lobe (p&lt;0.005). Despite the limited population size and review of only pre-operative features, multivariate analysis produced multiple predictive models able to outperform chance when predicting processing speed and working memory outcomes.

CONCLUSIONS
This study provides evidence that a radiological language modelling approach can be utilised for outcome prediction. It identified imaging features predictive of cognitive impairments prior to surgery and radiotherapy. Further work is needed to assess inter-observer variability and validate these findings.
IMG-26. USING [18F]FET-PET/CT SCAN TO DIFFERENTIATE RADIONECROSIS FROM RECURRENCE/NEW TUMOURS: THE CASE OF A CNS SARCOMA
Authors: Pilotto Chiara , Coassin Elisa , Borsatti Eugenio , Tuniz Francesco , Pegolo Enrico , D’Agostini Serena , De Colle Cristina , Rombi Barbara , Vindigni Marco , Vitullo Angelo , Toniutti Maristella , Tanzi Giorgia , Mascarin Maurizio , Cogo Paola Elisa , Liguoro Ilaria 
Published: June 2024

Abstract

CASE REPORT
A 5-year-old girl diagnosed with a posterior fossa standard-risk medulloblastoma underwent surgery followed by proton therapy (PT) 23.4 Gy(RBE) (1.8 Gy(RBE)/fr) to the craniospinal axis plus a boost of 30.6 Gy(RBE) (1.8 Gy(RBE)/fr) to the tumor bed and maintenance chemotherapy according to HIT-SIOP PNET 4 protocol. The patient remained disease-free for 4 years after the end of treatmen. MRI showed a new left temporo-occipital lesion 8x10x10 mm which was irradiated from cranial field during the craniospinal phase but outside of the boost area, consistent with inoperable recurrence. She was then re-irradiated with a second course of PT 50.4 Gy(RBE) (1.8 Gy(RBE)/fr) and subsequently started on temozolomide. Periodic MRI scans showed progressive reduction of the lesion for 10 months, when new lesion progression occurred within the re-irradiated fieled. Considering the stable clinical conditions of the patient, the minimal size of the lesion, and the uncertain nature between actinic damage or cancer, a watchful waiting approach was adopted. Few months later, the area increased. [18F]FET-PET/CT evaluation documented an uptake of the drug compatible with metabolically active lesion. A biopsy was performed, and histology showed a CNS sarcoma. Genetical testing excluded cancer predisposition syndromes. Chemotherapy with bevacizumab and irinotecan was started, but the MRI showed significant progression of the disease and the patient died 6 months after the diagnosis.

CONCLUSION
MRI is the main diagnostic method in the follow up of CNS neoplasms, but it has limitations in discriminating recurrences/secondary tumours and tissue changes due to previous treatments, particularly radiotherapy. Recently, the use of [18F]FET-PET/CT is being investigated, but literature is still poor in children and most cases refer to high-grade gliomas. It is desirable to study it further, as it may play a relevant role in differentiating equivocal cases, as in our patient.