bluuebunny/crossref_metadata_2025_split huggingface dataset:
NFS-04. GENETIC COUNSELLING IN A MULTI-TUMOR PREDISPOSITION SYNDROME: A NOVEL FOUR-GENERATION TUNISIAN PEDIGREE
Authors: Abdelmoula Nouha Bouayed , Abdelmoula Balkiss 
Published: June 2024

Abstract

BACKGROUND
Cancer predisposition syndromes associated with an increased risk of CNS tumors and colorectal polyposis are heterogeneous inherited disorders associated with multiples genes. The delineation of the inheritance pattern and the management of the genetic testing are recommended for optimal care of patients and their families. Our aim was to report a cancer predisposition brain tumor-polyposis syndrome in a four-generation Tunisian consanguineous pedigree characterized by uncommon tumors localizations.

METHODS
The index case was a 43-year-old infertile woman presented to our genetic counselling because of a suspected familial cancer predisposition syndrome. She consulted for digestive symptoms with epigastralgia. Six adenomatous polyposis of the colon were confirmed histologically. Her sister died of colon cancer at the age of 50. She developed a malignant mesenteric recurrence after surgical resection of a moderately differentiated adenocarcinoma infiltrating the meso fat with lymph node metastases. Their three sisters and brother did not have any cancer. From the same third generation, only one cousin died of a brain cancer identified as a glioblastoma at the age of 43. Their maternal grandmother and her two brothers died of respectively breast, laryngeal and urothelial cancers. The second generation and fourth generation involved healthy members.

RESULTS
Analysis of the pedigree of this family indicated an autosomal recessive mode of inheritance of the brain tumor-polyposis syndrome. Clinically, there was uncommon association with breast, laryngeal and urothelial cancers in the first generation and brain/colon cancers in the third generation.

CONCLUSIONS
A recessive multi-tumor predisposition syndrome related to high microsatellite instability resulting in a mismatch repair deficiency seems to be the most reliable diagnosis in this family. Familial NTHL1 tumor and MUTYH associated polyposis syndromes were also suspected. NGS-based testing, from whole exome sequencing to multigene panel testing, is suggested as the most accurate genetic testing in such heterogeneous multi-tumor predisposition syndromes.
NFS-08. CLINICAL AND MOLECULAR FEATURES OF HIGH-GRADE GLIOMA IN CHILDREN AND ADULTS WITH NEUROFIBROMATOSIS TYPE 1: A PRELIMINARY ANALYSIS
Authors: Kotch Chelsea , Solomon David A , Wallace Keri , de Blank Peter M , Li Yimei , Mbonglou Franziska , Reddy Alyssa T , Gutmann David H , Piotrowski Anna F , Fisher Michael J 
Published: June 2024

Abstract

BACKGROUND
Individuals with neurofibromatosis type 1 (NF1) are at increased risk for developing high-grade glioma (HGG) relative to the general population. Despite the elevated incidence in NF1, adequately powered studies of HGG have not been performed to date, limiting understanding of the clinical course, prevalent treatment approaches, recurrent molecular features, and outcomes.

METHODS
Patients with NF1 and pathologic or molecularly confirmed high grade glioma and high-grade astrocytoma with piloid features at Children’s Hospital of Philadelphia, University of California San Francisco, Washington University, and Cincinnati Children’s Hospital Medical Center diagnosed between 2005 to 2021 were included. Retrospective clinical, molecular, treatment, and imaging data were collated and analyzed.

RESULTS
Thirty-four patients met eligibility criteria, 13 (38%) were female. The median age at diagnosis was 22.7 years; 10 were pediatric (children &lt;18 years of age). The most common diagnoses included high-grade astrocytoma (7), anaplastic astrocytoma (8), glioblastoma multiforme (5), and high-grade astrocytoma with piloid features (5). Fifteen (44%) of tumors underwent biopsy only and 4 (12%) were gross totally resected. Nine tumors (26%) were considered to have transformed from a pre-existing low-grade lesion. In the 22 cases with molecular testing, the most prevalent genetic variants involved the NF1, CDKN2A/B, ATRX, TP53, and SUZ12 genes. Frontline treatment approach varied; however, 26 individuals (76%) received radiation as part of their initial therapy. Overall survival at 2 years was 52% (95% CI 33-67) across all ages and 70% (95% CI 33-89) in children. There was no significant difference in overall survival at 2 years by extent of tumor resection at diagnosis.

CONCLUSIONS
High grade glioma in individuals with NF1 demonstrate a high prevalence of alterations in the CDKN2A/B and ATRX genes, with a poor overall survival despite radiation-inclusive treatment regimens. Collection of additional patient data from collaborating institutions is ongoing to support further analyses.
NFS-11. PHASE II STUDY OF AXITINIB IN PATIENTS WITH NEUROFIBROMATOSIS TYPE 2-RELATED SCHWANNOMATOSIS AND PROGRESSIVE VESTIBULAR SCHWANNOMAS
Authors: Garcia Mekka R , Hagiwara Mari , Yaffe Anna , Mitchell Carole , Akshintala Srivandana , Nicolaides Theodore , Phadnis Sheetal S , Yohay Kaleb , Feng Yang , Goldberg Judith D , Allen Jeffrey C , Karajannis Matthias A 
Published: June 2024

Abstract

BACKGROUND
Axitinib is an oral multi-receptor tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor (VEGFR), platelet derived growth factor receptor (PDGFR), and c-KIT. These represent a clinically and/or preclinically validated molecular targets in vestibular schwannoma (VS).

METHODS
Eligible participants were age &gt;5 years with a clinical diagnosis of neurofibromatosis type 2-related schwannomatosis (NF2-SWN) and at least one volumetrically measurable, progressive VS. Axitinib was given continuously in 28-day cycles for up to of 12 cycles. Primary endpoint was objective volumetric response rate to axitinib, hearing response was a secondary endpoint, along with validated quality of life assessments (NFTI-QOL).

RESULTS
Twelve participants were enrolled and eight completed 12 cycles, including two pediatric patients. Two patients were non-evaluable due to coming off study prior to the first scheduled response evaluation: one withdrew from the study for personal reasons and one for non-compliance. Due to slowing accrual, the study closed prior to meeting planned enrollment of 17 evaluable patients. Ten patients were evaluable for the primary endpoint, defined as ≥20% decrease in VS volume, with two volumetric responses observed; both were reached after three cycles and sustained during treatment. Best volumetric response was −53.9% after nine cycles. Hearing response was evaluable in nine participants, with three hearing responses observed, one of which was sustained during treatment. All participants experienced drug-related toxicities, the most common were diarrhea, hematuria and skin toxicity, not exceeding grade 2, as well as hypertension, not exceeding grade 3. NFTI-QOL scores remained stable or improved during treatment in all participants.

CONCLUSIONS
Axitinib therapy targeting VEGFR, PDGFR and c-KIT is feasible in this population and associated with volumetric and hearing responses in a subset of patients. The convenience of oral administration appears to be offset, however, by increased toxicity and lower response rates compared to VEGF-A targeted therapy with bevacizumab.
NFS-26.RB1-ALTERED SUBTYPE (GROUP A) PINEOBLASTOMA AS A PART OF «TRILATERAL RETINOBLASTOMA» PHENOMENON: NEURO-ONCOLOGICAL AND OPHTHALMIC-ONCOLOGICAL VIEW
Authors: Levashov Andrey Sergeevich , Serov Yuriy Alexandrovich , Ushakova Tatyana Leonidovna , Stroganova Anna Mikhailovna , Ryzhova Marina Vladimirovna , Gorelyshev Sergey Kirillovich , Kadirov Shavkat Umidovich , Terentyeva Alexandra Igorevna , Grigoryeva Marina Vladimirovna , Polyakov Vladimir Georgievich , Gorovtsova Olga Valeryevna , Grigorenko Vasiliy Andreevich 
Published: June 2024

Abstract

BACKGROUND
RB1-altered subtype (Group A) pineoblastoma as a part of «Trilateral retinoblastoma» is an extremely rare phenomenon. But over the past 10 years, the incidence of this disease has been increasing. Optimal therapeutic strategy is unknown. The aim of this study was to estimate the incidence of this phenomenon among patients with retinoblastoma, age at onset of retinoblastoma/RB1-altered pineoblastoma and genetic, gender, age predisposition.

DESIGN/METHODS
From 2019 to 2023 years 256 pediatric patients with de novo retinoblastoma were treated in the FSBI «N.N.Blokhin National Medical Research Center of Oncology». RB1-altered pineoblastoma was revealed in 9 cases (3,5% of all patients, 9,5% among patients with bilateral retinoblastoma, 6,6% for patient with the onset of retinoblastoma under the age of 12 months). Diagnosis was determined according to familial history, retinal camera and MRI data, histology, immunohistochemistry and Illumina Infinium methylation EPIC Bead Chip method (FFPE tumor samples), NGS and MLPA methods for detection of RB1 germline mutation status (blood samples). Therapeutic options for patients with RB1-altered subtype pineoblastoma were presented as like–COGARET0321, like–HIT–MED2017/2020, selective intra-arterial chemotherapy, intravitreal chemotherapy, transpupillary thermotherapy, brachytherapy.

RESULTS
Gender ratio was 1:2 (3 male and 6 female). In all cases, intraocular retinoblastoma was bilateral. Family history was revealed in two cases. Age at onset of retinoblastoma: less than 6 months in 8 cases, all cases less 2 years, median 3±1,9 months [1,5-20,5]. Median age at onset of RB1-altered subtype pineoblastoma was 20,5±7,3 months [1,5-57,5]. A synchronous variant of the disease was identified in 5 cases, metachronous in 4. Pineoblastoma of pineal region was detected in 7 cases, suprasellar region in 2. Six out of 9 patients are alive, median follow-up 16,5±5,1 months [1,5-43,0].

CONCLUSION
It is necessary to expand both regional and international interdisciplinary cooperation to develop an optimal algorithm for the diagnosis and treatment of this disease.
QOL-01. FEASIBILITY AND EFFICACY OF DIETARY AND LIFESTYLE INTERVENTIONS FOR HYPOTHALAMIC OBESITY DURING CHILDHOOD: A SYSTEMATIC REVIEW
Authors: van Roessel Ichelle , van den Brink M , Dekker J , van Essen B G Ruitenburg- , Tissing W J E , van Santen H M 
Published: June 2024

Abstract

BACKGROUND
Hypothalamic obesity may be encountered in children with genetic or syndromal disease or after (treatment of) a suprasellar tumor. There is currently no effective treatment for hypothalamic obesity, and dietary and lifestyle interventions are the cornerstone of obesity treatment. The obesity in patients with HD is the consequence of decreased satiety feelings (hyperphagia), in combination with a decreased resting energy expenditure and increased fat storage due to hyperinsulinemia. We searched the literature for evidence on feasibility and efficacy of dietary and lifestyle interventions for childhood hypothalamic obesity.

METHODS
A systematic search was conducted in Pubmed, EMBASE, Cochrane and CINAHL. Studies assessing the feasibility, safety or efficacy of any dietary or lifestyle intervention in children with hypothalamic overweight or obesity, were included. Risk of bias was assessed with an adapted Cochrane Risk of Bias Tool.

RESULTS
In total, twelve studies were included, with a total number of 118 patients (age 1 – 19 years) of whom one with craniopharyngioma, one with ROHHAD-NET syndrome, 50 with monogenic obesity and 66 with Prader-Willi syndrome. Four studies reported on feasibility: all diets were judged to be feasible. Seven studies reported on the effect of a dietary intervention; a well-balanced restrictive caloric diet (30% fat, 45% carbohydrates and 25% protein) and various hypocaloric diets (8-10 kcal/cm/day) were effective in terms of weight stabilization or decrease. No negative effect on linear growth was reported. Four studies reported on specific lifestyle interventions. Combined dietary and lifestyle intervention resulted in decreased BMI, however BMI returned to baseline values in the long-term.

CONCLUSIONS
Hypocaloric diet or restrictive macronutrient diet with lower percentage of carbohydrates seems feasible and effective for childhood hypothalamic obesity. Lifestyle interventions only resulted in BMI decrease in short-term, indicating that additional guidance is needed to successfully implement lifestyle interventions in this group of patients.
QOL-04.IN VIVO MODELLING RECAPITULATES RADIOTHERAPY DELIVERY AND LATE-EFFECT PROFILE FOR CHILDHOOD MEDULLOBLASTOMA
Authors: Castle Jemma , Shaw Gary , Weller Dominic , Fielder Edward , Egnuni Teklu , Singh Mankaran , Skinner Roderick , von Zglinicki Thomas , Clifford Steven C , Short Susan , Miwa Satomi , Hicks Debbie 
Published: June 2024

Abstract

BACKGROUND
Medulloblastoma (MB) is the most common malignant paediatric brain tumour, with 5-year survival rates &gt;70%. Survivors frequently suffer a wide-range of late-effects due to their tumour and its treatment. Cranial radiotherapy (CRT) to the whole-brain, with posterior fossa boost (PFB), underpins treatment for non-infants, however, radiotherapeutic insult to normal brain tissue has deleterious consequences to neurocognitive and physical functioning, and causes accelerated ageing/frailty. Unfortunately, approaches to ameliorate radiotherapy-induced late-effects are lacking and a paucity of appropriate model systems hinders their development.

METHODS
We have developed a clinically-relevant in vivo model system that recapitulates the radiotherapy dose, delivery and late-effect profile of childhood medulloblastoma, at an equivalent developmental stage. Consistent with human regimens, age-equivalent (postnatal days 28-37) C57Bl/6J mice received targeted, CT image-guided, CRT (human-equivalent 38 Gy, n=12) or CRT with PFB (human-equivalent 49 Gy, n=12), via the small animal radiation research platform (SARRP) and were longitudinally assessed for over a year. Late-effects were compared to a sham-irradiated group (n=12).

RESULTS
CRT was well tolerated, independent of PFB receipt, and no mice suffered severe acute toxicity. Mice were significantly more frail following irradiation (frailty index; p=0.0002) and had reduced physical functioning; time to fall from a rotating rod and grip strength were significantly lower (rotarod; p=0.026 and grip strength; p=0.006, respectively). Neurocognitive deficits were consistent with those observed in childhood MB survivors; irradiated mice displayed significantly worse working memory (Y-maze; p=0.009) and exhibited spatial memory deficits (Barnes maze; p=0.029). Receipt of PFB did not induce a more severe late-effect profile.

CONCLUSION
We conclude that our in vivo model of childhood MB radiotherapy recapitulates the late-effect profile of MB survivors. Our clinically-relevant model will facilitate both the elucidation of novel/target mechanisms underpinning MB late-effects and the development of novel interventions for their amelioration.
QOL-05. MEMANTINE FOR PREVENTION OF COGNITIVE LATE EFFECTS IN CHILDREN RECEIVING CRANIAL RADIATION THERAPY FOR FOCAL BRAIN TUMORS: A PILOT STUDY
Authors: Conklin Heather M , Khan Raja B , Ashford Jason M , Owens Christina , Simmons Andrea , Bosley Christina , Hsu Chia-Wei , Pan Haitao , Gajjar Amar , Merchant Thomas E 
Published: June 2024

Abstract

BACKGROUND
Childhood brain tumor survivors treated with cranial irradiation are at significant risk for cognitive late effects that negatively impact quality of life. Memantine (an NMDA receptor antagonist), taken during radiotherapy for brain metastases in adults, resulted in reduced cognitive declines. This is the first investigation of feasibility, acceptability, and preliminary efficacy of memantine for reducing cognitive late effects in children undergoing radiation therapy.

METHODS
In a randomized, double-blind, controlled trial (MEMCRT; NCT03194906) children took memantine (20 mg/d) or placebo for 12 weeks. During the medication phase, participants received weekly phone calls to assess adherence using pill counts and monitor side effects using the SAFTEE structured interview. At baseline, 6 weeks (end of radiation therapy), and 12 weeks (end of medication), participants completed a brief battery of cognitive measures.

RESULTS
30 patients (age at irradiation=11.93±2.87; 47% male) were included; memantine (n=16) and placebo (n=14) groups did not differ in age, sex, race, socioeconomic status or baseline IQ (ps&gt;.26). Study participation (71% of those approached) and medication adherence (88% completed 12 weeks, with 97% of medication taken) were high. Side effects were minimal (only one CTCAE≥ 3; headache in the placebo group) with no difference between groups in change in side effect severity from baseline to any medication week, across any symptom inquiry (ps&gt;.23). At 12 weeks, Cohen’s d effect sizes (ES) indicate the memantine group had better performance on measures of processing speed (Cogstate Identification ES=.61), academic fluency (Woodcock Johnson-IV Reading Fluency ES=.45; Math Fluency ES=.81), and fatigue (PedsQL Multidimensional Fatigue Scale ES=.72).

CONCLUSIONS
Study findings indicate memantine used as a neuroprotectant during radiation therapy for children with focal brain tumors is feasible and acceptable, with preliminary evidence for better cognitive outcomes that require validation in a larger, definitive trial.
QOL-08. THE LONG-TERM UTILITY OF METHYLPHENIDATE FOR THE PRESERVATION OF INTELLECTUAL DEVELOPMENT IN CHILDHOOD SURVIVORS OF BRAIN TUMOUR
Authors: Hagan Alexander J , Verity Sarah J 
Published: June 2024

Abstract

BACKGROUND
Enduring neurocognitive late effects are a common consequence of childhood brain tumour survivorship. Conceptual modelling of intelligence suggests initial deficits to processing speed and attention lead to the subsequent plateauing of intellectual and academic development. The utility of methylphenidate in improving attentional and processing speed deficits within the early phase of recovery has been previously reported. The longer-term contribution of methylphenidate in preserving intellectual ability through ameliorating these early deficits is yet to be evaluated.

METHODS
Twenty-nine childhood survivors were matched retrospectively with a no-treatment synthetic control. Intellectual assessments were conducted prior to starting methylphenidate and a minimum of 12 months thereafter. For the no-treatment control group, intellectual data were collected retrospectively from archival records, employing a similar assessment period. Linear Mixed Models were used to assess the influence of methylphenidate on intellectual trajectories between groups and fatigue scores over time.

RESULTS
Methylphenidate was associated with raw score improvements across all intellectual indices compared to no-treatment controls. Linear Mixed Modelling reported a borderline significant improvement in Processing Speed (t = 1.98, p =.05) for the methylphenidate group. In comparison, a borderline significant (p =.05) within-group decrease in Working Memory scores was reported for the no-treatment group. There was a significant within-group decrease in pooled PedsQL MFS scores between assessments for the treatment group (t = -4.01, p &lt;.01), with the most notable decrease observed in Sleep/Rest Fatigue (t = -10.17, p &lt;.01).

CONCLUSIONS
Methylphenidate may pose a valuable long-term rehabilitative strategy in preserving Processing Speed in childhood survivors of brain tumour. Whilst our sample size is small, there is tentative evidence for the utility of methylphenidate in alleviating fatigue experienced by childhood survivors.
QOL-10. PHYSICAL ACTIVITY LEVELS AND PATTERNS IN SURVIVORS OF CHILDHOOD CENTRAL NERVOUS SYSTEM TUMOURS
Authors: Keating Rachael , Curry Sarah , Hussey Juliette 
Published: June 2024

Abstract

BACKGROUND
Engaging in regular physical activity (PA) has multiple positive health benefits and for survivors of childhood cancer can additionally result in reduced severity of late-effects. There is a lack of objectively measured PA data in survivors of childhood central nervous system (CNS) tumours. The aims of this study were to objectively measure PA levels and patterns in survivors of childhood CNS tumours and to determine whether survivors were meeting the World Health Organisation (WHO) recommended PA guidelines of 60 minutes of moderate to vigorous intensity physical activity (MVPA) daily.

METHODS
Survivors of childhood CNS tumours aged between 6-17 years, between 3 months and 5 years post treatment, were provided with Actigraph GT3X accelerometers to assess their PA patterns over a seven day recording period.

RESULTS
Twenty-six participants were recruited with a mean age of 12.75 (SD 3.29) years. Participants met the WHO PA guidelines for a mean of 3.18 (SD 2.56) days during the assessment week. Participants spent a mean daily time of 591.77 (SD 146.91) minutes in sedentary behaviour and 129.45 (SD 54.14) minutes in light intensity PA. A significant association was found between PA and age (p&lt;0.001, CI[-8.48, -3.05]), child participants engaged in significantly less sedentary time and significantly more MVPA daily than adolescent participants. No significant differences in PA patterns were identified between participants in early survivorship versus those in late survivorship (≥ 2 years post treatment), (p=0.095 – p=0.513).

CONCLUSIONS
The majority of survivors of childhood CNS tumours do not meet the WHO recommended daily PA guidelines and lead significantly sedentary lives. PA patterns differed significantly between child and adolescent participants. Further research is required on interventions to support engagement in PA particularly for adolescent survivors of CNS tumours, with a focus on how this can be implemented into clinical practice.