bluuebunny/crossref_metadata_2025_split huggingface dataset:
RONC-09. The comparison of dosimetric parameters for predicting radiation-induced cataract in pediatric patients
Authors: Leangcharoensap Siriphan , Thephamongkhol Kullathorn , Treechairusame Teeradon , Suntornpong Nan , Rongthong Warissara 
Published: June 2022

Abstract
OBJECTIVE: The lens dose constraint for pediatric patients was still unknown due to conflicting data of dosimetric parameter. The aim of this study was to compare predictive ability for radiation-induced cataract between the maximum point dose of lens (Lens Dmax) ≥7 Gy, lens mean dose (Lens Dmean) ≥7 Gy, Lens Dmax ≥10 Gy, and Lens Dmean ≥10 Gy. METHOD: Patients 3-18 years received cranial irradiation or radiation therapy at head and neck area with three-dimentional conformal radiation therapy (3DCRT), intensity modulated radiation therapy (IMRT), or volumetric modulated arc therapy (VMAT) between 2010 and 2019 at our institute were included. Patients who have no eye exam before radiation or within 6 months of radiation (baseline) and/or have no follow-up eye examination after complete radiation &gt;6 months (follow-up) were excluded. Receiver operating characteristic (ROC) curves were used to identify the dosimetric parameter of potential predictors and to access their predictability. Univariate and multivariate analyses were performed using cox regression analysis to identify correlation between potential factors and cataract. RESULTS: Sixty-three patients (122 eyes) were analyzed. Cataracts were detected in 14 eyes (11.5%). The median follow-up time was 4 years (range 0.5-10 years). The median time to develop cataract was 2.5 years (range 0.3-7 years). Three (21.4%) patients developed cataract grade ≥3. Lens Dmean ≥10 Gy had highest predictive ability for predicting radiation-induced cataract in pediatric patients. The area under the ROC curve (AUC) were 0.591 for Dmax ≥ 7 Gy, 0.597 for Dmean ≥ 7 Gy, 0.642 for Dmax ≥ 10 Gy, and 0.698 for Dmean ≥ 10 Gy. Univariate analysis showed significant effect of age, diagnosis, and Lens Dmean on cataract formation. On multivariate analysis, cataract remained significantly predicted by diagnosis and Lens Dmean. CONCLUSION: Lens Dmean ≥10 Gy had highest predictive ability for predicting radiation-induced cataract in pediatric patients.
RONC-14. Olfactory Perception During Proton Radiation and Differences in Frequency of Olfactory Perceptions Based on Proton Craniospinal Irradiation Technique for Pediatric Brain Tumor Patients.
Authors: Ioakeim-Ioannidou Myrsini , Erfani Parsa , Urell Tobias , Daartz Juliane , Berv Julia , Leahy Shannon , Fullerton Barbara , Bolton Rachel , Yock Torunn , Tarbell Nancy , Yeap Beow , MacDonald Shannon 
Published: June 2022

Abstract
BACKGROUND: Unusual olfactory perception has been reported during brain radiation treatments but is infrequent and does not typically interfere with the ability to deliver treatment or cause notable distress. Methods: We performed a retrospective review of 127 pediatric patients treated with proton radiation therapy (PRT) for primary brain tumors in a single institution between 2016-2021. Patients received PRT to the brain as part of craniospinal irradiation (CSI) followed by a boost to the brain. Proton CSI was delivered with 3D-CRT protons (n=53) or pencil beam scanning technique (PBS) (n=74). Within the PBS group, treatment delivery to the CSI utilized a single PA field (n=24) or two posterior oblique fields (n=50). We collected data on abnormal olfactory sensations, nausea/vomiting, and the use of medical intervention for those symptoms. Results: Our cohort included 80 males and 47 females. The median age of patients was 10 years old (range, 3 – 21). Seventy-one patients received concurrent chemotherapy. Prior to PRT, 31 patients were nauseous. During the radiation course, 104 patients developed worsening nausea while 63 patients reported emesis. Four patients vomited while receiving radiation. Seventeen patients reported olfactory perceptions during CSI. We found a higher rate of olfactory perception in patients treated with PBS (n=16, 22%) than 3D-CRT (n=1, 2%) (p=0.001) and, within the PBS group, patients treated with a single PA field (n=11, 46%) than two oblique fields (n=5, 10%) (p=0.002). Seventy-eight patients required intervention including addition of anti-emetic or anti-anxiety medication. Two patients required sedation due to the malodorous smell during CSI. We did not find any significant difference in nausea/vomiting based on treatment technique. Conclusions: PBS and PBS technique influence olfactory perceptions but not the occurrence of the rate of nausea/vomiting. Further studies should be performed to validate these findings and determine techniques to minimize unpleasant olfactory perceptions.
RONC-15. FEASIBILITY AND EFFECTIVENESS OF REIRRADIATION IN CHILDREN AND ADOLESCENTS WITH RELAPSED OR RESISTANT BRAIN TUMORS
Authors: Campello Anna , Mussano Anna , Vallero Stefano , Bertin Daniele , Peretta Paola , Morana Giovanni , Sciortino Paola , Ricci Federica , Bertero Luca , Fagioli Franca 
Published: June 2022

Abstract
Few reports exist about reirradiation (RT2) for recurrent brain tumors in pediatric patients.A monocentric retrospective analysis of 22 patients with reirradiated CNS neoplasms was conducted with the objective to describe clinical outcomes and toxicities associated with RT2. Median age at diagnosis and RT2 was 8.5 years and 11.5 years respectively. Primary diagnoses included ependymoma (n=7, 32%), medulloblastoma (n=5, 23%), DIPG (n=4, 18%), glioblastoma (N=2, 9%), and others (N=4, 18%). The median interval between the first radiotherapy and RT2 was 16.5 months. Two patients underwent in-field RT2 for a secondary tumor. RT2 was administered with a curative intent in 13 patients, with a palliative-only treatment in the remaining 9. Sixteen patients received brain RT2 and 3 patients spine RT2, with a median cumulative dose of 19.9 Gy and 30 Gy respectively. Three patients received combined RT2. Volumetric Modulated Arc Therapy(VMAT) was the most frequent technique used (60%). Eight patients showed neurological symptoms before RT2, 6 had clinical benefit with RT2. Among patients who were asymptomatic before RT2, 5 later showed progressive neurological symptoms (at least partly attributable to RT2). Radionecrosis was radiologically detected in 6 patients, but accompanied by symptoms only in 3. Median event-free survival (EFS) and overall survival(OS) after RT2 was 4.7 and 8.7 months respectively, similarly to previous results. One-year EFS and OS was 13% and 36% respectively. As previously reported, OS appeared to be longer for patients with &gt;12 months elapsed time between first irradiation and RT2 (1-year OS=45% versus 0%, p=0.07). In our cohort RT2 appeared feasible and provided short-term disease control with tolerable short-term toxicity, while providing relief in most symptomatic patients. Larger prospective studies are needed to understand which subsets of patients may benefit from either curative or palliative reirradiation, to provide respectively a longer survival and a significantly improved symptom control.
RONC-17. Feasibility of proton therapy with and without simultaneous chemotherapy in CNS malignancies of children and adolescents
Authors: Schuermann Eicke , Tippelt Stephan , Zeller Julia , Geismar Dirk , Jazmati Danny , Peters Sarah , Timmermann Beate , Mikasch Ruth , Fleischhack Gudrun 
Published: June 2022

Abstract
BACKGROUND: Proton therapy (PT) is a valuable alternative to photon radiotherapy in treatment of CNS tumors in children and adolescents. The aim of this study was to investigate the feasibility of recent treatment strategies with a particular focus on the acute toxicity of a simultaneous radiotherapy and chemotherapy (sRCT). PATIENTS AND METHODS: We investigated 199 patients (116 male, 83 female, median age 7.4 years) who received in total 200 cycles of PT (60.5% at new diagnosis, 39.5% at relapse) from September 2013 to February 2017. Entities included ependymomas (34%), medulloblastomas (16%), low grade gliomas (13%), ATRTs (12%), craniopharyngiomas (9%), germ cell tumors (6%), and other entities (10%). SRCT was administered in 52 (26%) treatment cycles. The target tumor was predominantly localized infratentorial (53%), supratentorial (23.5%) and supra-/intrasellar (18%). 38 patients received additional CSI and 8 patients a boost to metastases. Data were collected retrospectively based on patient records. Toxicity was documented according to CTCAE version 4.03. RESULTS: Severe adverse events (SAE ≥ grade 3) occurred in 33.5% of all patients, in particular in form of hematotoxicity (64.1%) and infections (26.8%). In-patient treatment for unexpected SAEs was necessary in 33 patients (16.5%). In the group treated with sRCT 15 out of 52 (28.8%) patients couldn’t receive the recommended dose or time schedule of planned chemotherapy due to SAEs. Comparing the SAE frequency in both groups, the children who have been treated with sRCT had a significantly higher risk of SAEs than the patients who have received proton therapy only (63.5% vs. 23.0%, p=0.001). CONCLUSIONS: PT and concomitant chemotherapy are feasible, but require an interdisciplinary team with continuous out-/inpatient management of patients, as the risk of toxicity is significantly increased. Risk-adapted adjustment of simultaneous chemotherapy is necessary to reduce relevant interruptions of radiotherapy.
Funded by the German Childhood Cancer Foundation
SWK-02. Palliative sedation in pediatric patients suffering from brain tumors: choosing the best drugs to improve end of life
Authors: Podda Marta , Schiavello Elisabetta , Clerici Carlo Alfredo , Biassoni Veronica , Simonetti Fabio , Massimino Maura 
Published: June 2022

Abstract
INTRODUCTION: For terminally-ill children with brain tumors care focuses on quality of life, and patient management fundamentally affects grieving families. We describe our experience of palliative sedation (PS) for children with refractory symptoms caused by solid tumors, focusing on BT (brain tumor). METHODS: Retrospective data on all children treated for cancer who died between 1/2016-12/2020 in our Institution were collected. RESULTS: Of the 29 patients eligible for the study, M/F 17/12, the median duration of disease was 12.5 months(range 3-51) and the median age at death was 8.5 years(range 1-22). Fifteen had BT (5 DIPG, 2 Ependymoma, 8 high-grade-glioma). The reasons for starting PS in BT were: seizures(5), central respiratory failure(6), locked-in-syndrome(1), decerebration(1). Midazolam was combined in 16 cases with other drugs (neuroleptics, alpha-2 agonists, antihistamines) to achieve adequate sedation. Ten/15 with BT received antiepileptic therapy, apart midazolam. BT patients received oral benzodiazepins before PS less frequently than those with other cancers (p = 0.0033). Throughout the period of PS and on the day of death, patients with BT were given lower doses of midazolam and morphine. Mean dose of midazolam was 0.027 mg/kg/h (range 0.0069-0.06) for patients with BT, 0.055 mg/kg/h (range 0.01-0.38) for the others, while the mean morphine doses were 0.048 mg/kg/h (range 0-0.08) and 0.09 mg/kg/h (range 0.013-0.13), respectively. CONCLUSIONS: BT patients require less intensive analgesic-sedative therapies because their already impaired state of consciousness. Optimizing pharmacological treatments demands a medical team that knows how drugs (even developed for other indications) work. Emotional-relational aspects are important too, any action to lower a patient’s consciousness should be explained to the family. Guidelines on PS in pediatrics could help, providing they acknowledge that any child’s death is always a unique case.
SWK-05. Clinical social work in pediatric neuro-oncology – A research project on the social dimension using social diagnostics
Authors: Krottendorfer Kerstin , Rosenmayr Verena , Weiler-Wichtl Liesa Josephine , Pletschko Thomas , Peyrl Andreas , Leiss Ulrike 
Published: June 2022

Abstract
PURPOSE: A neuro-oncological disease of a child represents a high psychosocial burden for the whole family (Wiener, Kazek et al. 2015). A biopsychosocial and family-oriented approach for the treatment of children and their families focusing on medical, psychological and social care is significant in the course of the disease. Studies show that existential problems or lack of social support are risk factors. Therefore, this research investigates the impact of a pediatric neuro-oncological disease on the social dimension using a standardized social assessment. RESEARCH DESIGN: The project is based on a retrospective cross-sectional study (04/2015-12/2021) including consecutive patients with high- or low-grade gliomas at the Medical University of Vienna - Department of Pediatrics (n= 160). By using a specialized and standardized social diagnostic tool (DISAPO) starting at the onset of disease, the clinical social worker surveys the social situation (social network, work situation, financial and housing situation, legal status, insurance status, etc.) with the parents. Based on the assessed social situation the clinical social work interventions (CSWI) are recorded throughout the child′s treatment. The results are statistically evaluated including medical data. RESULTS: The results of the DISAPO show that in the course of the disease all families need CSWI in one or more areas of the social dimension: disease-related interventions: 100%, work intervention: 80,6% (n=129), living situation: 43,8% (n=70), social support: 39,4% (n=63), socioeconomic interventions: 19,4% (n=31), residence law aspects: 18,8% (n=30). CONCLUSION: These results emphasize that in case of a pediatric neuro-oncological disease the social dimension is always affected and comprehensive CSWI are highly needed. For a holistic care of the patients and their families a biopsychosocial standard-of-care including all professions is indispensable. In addition, a standardized approach for assessment and intervention showed that needs could be assessed more adequately and interventions more targeted.
SWK-09. Baseline Survey of Hematology/Oncology/Cellular Therapy Staff/Faculty Perceptions of Palliative Care
Authors: Hemenway Molly , Raybin Jennifer , Waters Melissa 
Published: June 2022

Abstract
Recent literature has shown that pediatric oncology patients and families prefer early integration of palliative care, yet the perception persists by staff and providers that palliative care has a negative connotation. We examined the baseline views of staff at our tertiary care center, prior to expansion of a formal palliative care service. We will describe baseline survey results in a diverse group of hematology/oncology/cellular therapy staff/faculty. This quality improvement project was conceived by the unit-based palliative care committee to compare baseline and follow-up survey results. We report the baseline results of a convenience sample of providers with varied roles. A validated survey for staff perception of palliative care found in the literature was utilized. After institutional qualitative review board approval, the survey was emailed to members of the inpatient and outpatient units. Demographic data collected included gender, level of education, role, patient population, length of career globally and locally. Perception of palliative care was evaluated by asking questions regarding 1) overlap with disease focused care, 2) risks/benefits of palliative care, and 3) timing of palliative care consults. Results were tabulated and graphed for dissemination to the unit-based palliative care committee. A follow-up survey is planned after integration of the developing formal palliative care service. Longitudinal comparison with statistical analysis will be completed at that time. Although most participants disagreed that palliative care is not consistent with curative care and that early palliative care does not induce parental anxiety, yet is perceived by the lay public as end-of-life care. Strong agreement was demonstrated with items regarding integration of palliative care early in the disease trajectory to decrease suffering. Participants also predominantly agreed that education for patients/families and staff/faculty would ameliorate misconceptions about palliative care. Future evaluation after increased palliative care penetration will provide comparison data.
TBIO-03. Angiogenesis in Pituitary Adenoma
Authors: Yoshida Daizo , Nomura Ryutaro , Teramoto Akira 
Published: June 2022

Abstract
The role of angiogenesis in pituitary tumor development used to be questioned, since pituitary tumors have been usually found to be less vascularized than the normal pituitary tissue. Nevertheless, a significantly higher degree of vasculature has been shown in invasive or macropituitary prolactinomas when compared to nonin- vasive and microprolactinomas. We should know VEGF was found firstly in pituitary anterior lobe, then tumor angiogenesis must occur. Meanwhile the vascular arrange- ment raised by VEGF is irregular, that sometimes lead to pituitary apoplexy. In this chapter, hypoxia inducible factors (HIF), transcription factors regulating expression of several genes related to oxygen homeostasis are in response to hypoxic stress. We focus on tumor angiogenesis regulated by the signaling cascade in tumor angiogenesis in pituitary tumor.
TBIO-06. Study of cell free DNA extracted from CSF enables molecular classification of embryonal brain tumors
Authors: Mathieu Chicard , Iddir Yasmine , Masliah-Planchon Julien , Combaret Valérie , Saint-Charles Alexandra , Baulande Sylvain , Delattre Olivier , Waterfall Joshua , Bourdeaut Franck , Schleiermacher Gudrun 
Published: June 2022

Abstract
Liquid biopsies are revolutionary tools to detect tumour-specific genetic alterations in body fluids. Here, we assess whether the circulating tumor DNA (ctDNA) in Cerebral Spinal Fluid (CSF) could be used for the tumor genetic profiling of pediatric embryonal brain tumors (EBT). Cell free DNA extracted from CSF from 4-5 lumbar puncture droplets from patients with Medulloblastoma (n=18), ATRT (n=3), ETMR(n=1), FOXR2 EBT (n=2) or other pediatric EBT (n=1) (cfDNA mean quantity 48 ng/ml ; range 5.6 - 442 ng/ml) and matched genomic DNA from primary tumors were sequenced by WES (Illumina 100PE) using Nimblegen Medexome Capture. SNVs/mutations were called using GATK-UnifiedGenotyper, GATK-HaplotypeCaller and Samtools. Copy Number profiles were generated with CNVkits. 10/13 cfDNA WES yielded satisfactory depth (&gt;10x). A mean of 466 (range 93-945) SNVs were detected in the primary tumor and 474 (range 18-922) in the CSF. A mean of 416 (range 18-872) commons SNVs were observed between the cfDNA and the primary tumor, comprising classical medulloblastoma genes such as SMO or MLL2. Interestingly, several SNVs were observed either in the tumor only (mean 50 ; range 3-115) or in CSF only (mean 58 ; range 0-148) suggesting a clonal heterogeneity. For 5 cases, Copy Number profiles were also available, allowing the detection of MYCN amplification or 19q13 miRNA cluster amplification. Altogether, we demonstrate the feasibility of WES on CSF with a low input of ctDNA. These results may pave the way for new tumor monitoring tools.
TBIO-07. Pediatric tumor classification through genome-wide methylation profiling of extracellular vesicle DNA
Authors: Ricklefs Franz , Maire Cecile , Fita Krys , Fritzsche Friederike , Kammler Gertrud , Westphal Manfred , Lamszus Katrin , Schüller Ulrich 
Published: June 2022

Abstract
BACKGROUND: Genome-wide methylation profiling reliably classifies pediatric central nervous system (CNS) tumors. Extracellular vesicles (EVs) are released by pediatric CNS tumor cells (pCC) and contain high molecular weight tumor DNA, rendering EVs a potential biomarker source to identify tumor subgroups, stratify patients and monitor therapy by liquid biopsy. We investigated, whether the DNA in pCC-derived EVs reflects genome-wide tumor methylation profiles and allows tumor subtype classification. Currently, the tests are being expanded to include blood samples (n=80 patients). METHODS: DNA was isolated from EVs secreted by pediatric CNS tumor cells (pCC) as well as from the shortly cultured tumor cells and from the original tumor samples (n=4 patients). Pediatric Fibroblasts and EVs derived thereof were used as a non-tumorous control. EVs were classified by nanoparticle analysis (NTA), immunoblotting, imaging flow cytometry (IFCM and electron microscopy. Genome-wide DNA methylation profiling was performed using an 850k Illumina EPIC array and results were classified according to the DKFZ brain tumor classifier and further analysed by t-SNE and Copy number alteration analysis (CNA). RESULTS: The size range of pCC-derived EVs was 120-150 nm, as measured by NTA. The majority of secreted EVs exhibited high expression of common EV markers (i.e. CD9, CD63 and CD81), as characterized by IFCM. Genome-wide DNA methylation profiling of pCC-derived EVs correctly identified the methylation class of the original tumor (i.e. pilocytic astrocytoma, medulloblastoma). In addition, t-SNE analysis and copy number alterations matched the pattern of the parental pCC and original tumor samples. CONCLUSION: EV DNA faithfully reflects the tumor methylation class and copy number alterations present in the parental cells and the original tumor. Methylation profiling of circulating tumor EV DNA could become a useful tool to detect and classify pediatric CNS tumors.
TBIO-09. EZHIP is not expressed within the developing mouse or human brain
Authors: Talal Younes Subhi , Weaver Kristin , Collier Anderson , Herrington Betty 
Published: June 2022

Abstract
The protein EZHIP, first described as part of the genetic signature of group A posterior fossa ependymoma (PFA), functions in a manner analogous to the onco-histone H3K27M, itself first described in diffuse midline glioma (DMG). These two proteins modulate activity of the Polycomb repressive complex 2 (PRC2), resulting in global loss of H3K27 trimethylation. Thus, both PFA and DMG are characterized by global loss of the H3K27me3 mark, and PRC2 modulation is critical to oncogenesis of these tumors. However, the precise mechanism(s) of EZHIP and H3K27M-induced tumorigenesis is not known. One possibility is that EZHIP is expressed within the developing brain where it acts to modulate cellular development. In turn, EZHIP overexpression or H3K27M mutation could co-opt this developmental program to drive tumorigenesis. Relatedly, whether EZHIP is expressed in the cell of origin for PFA or DMG is not known. In order to evaluate these hypotheses, we defined the landscape of EZHIP expression in both murine and human developing brain. Leveraging single cell RNA sequencing databases, we show that EZHIP is not expressed within the developing mouse brain, a finding that is consistent across separate datasets. Similarly, EZHIP is not expressed in the developing murine cerebellum, where the cell of origin for PFA is located. Furthermore, we examined bulk RNA sequencing datasets of the developing human brain. Similar to our findings in the mouse brain, EZHIP is not expressed at any time point or spatial location within the developing human brain. Taken together, these data reject the above hypothesis, that EZHIP or H3K27M co-opt an endogenous PRC2 inhibitory developmental program. Similarly, these results show that EZHIP is not expressed within the cell of origin for PFA or DMG. Further studies will seek to understand the endogenous function of EZHIP by further defining its normal expression pattern and function.