tbuckley/cabot-search huggingface dataset:
MBCL-38. MEDULLOBLASTOMAS ASSOCIATED WITH APC GERMLINE MUTATION: A MULTICENTRIC FRENCH AND BELGIAN REVIEW
Authors: Aurore Surun, Laurence Brugières, Léa Guerrini-Rousseau, Pascale Varlet, Brigitte Lacour, Cécile Faure-Conter, Pierre Leblond, Anne-Isabelle Bertozzi-Salomon, Claire Berger, Nicolas Andre, Eric Sariban, Fabienne Prieur, Françoise Desseigne, Hélène Zattara-Cannoni, Marc Polivka, Marie-Bernadette Delisle, Alexandre Vasiljevic, Chrystelle Colas, François Doz, Franck Bourdeaut
Journal: Neuro-Oncology (2018)

Medulloblastoma may occur in a context of APC germline mutation and familial adenomatous polyposis. We aimed to describe clinical features of patients with medulloblastoma occurring in this context. We performed a multicentric retrospective review of French and Belgian patients treated for medulloblastoma with identified or highly suspected (personal or familial history) APC germline mutation. Genetic status, clinical and histological characteristics, treatments and outcome were reported. Eleven patients with known or suspected APC germline mutation, mostly on exon 15 (N=6/9 available data), were diagnosed with medulloblastoma at a median age of 10.6 years [6-32]. Medulloblastomas were mainly non-metastatic (N=9/11), classic (N=9/9 available data, central review ongoing), with no significant residual tumor after surgery (N=9/11). All patients underwent radiotherapy (median craniospinal dose: 35 Gy), combined with chemotherapy for 10 patients. No relapse was noticed (median follow-up: 11 years). Secondary tumors (N=8) occurred in 7 patients, including 1 lethal malignant Triton tumor in the irradiation field, 1 thyroid carcinoma, and 6 desmoid tumors (5 abdominal tumors, 1 occipital tumor in the irradiation field). Pre-symptomatic polyposis was diagnosed for 9 patients at a median age of 15.5 years, prior to medulloblastoma for 2 of them. Medulloblastomas associated with APC germline mutation have favorable clinical outcome, even for metastatic tumors, with no relapse in this small series of patients, in line with WNT-medulloblastomas’ profile. Yet, long-term survival is clouded by second tumor occurrence, with potential radiation-induced tumors. These findings raise the question of applying de-escalation therapeutic protocol for these patients with reduced intensity craniospinal irradiation.
DEV-07. THE LATIN-AMERICAN BRAIN TUMOR BOARD (LATB) TELECONFERENCE: RESULTS OF A WEB-BASED SURVEY TO EVALUATE PARTICIPANT EXPERIENCE AND THE PROGRAM
Authors: Mohammad H Abu Arja, Scott Coven, Joseph R Stanek, Andrés E Morales La Madrid, Alvaro Lassaletta, Ute Bartels, Ibrahim Qaddoumi, Jonathan L Finlay, Diana S Osorio
Journal: Neuro-Oncology (2018)

The LATB is a weekly teleconference operating over 3.5 years connecting pediatric neuro-oncologists from high-income countries with pediatric subspecialists from 20 Latin-American countries. This survey explored the participants’ experience utilizing this resource. A web-based questionnaire was distributed to 159 participants through email and www.Cure4Kids.org. Ninety-five respondents (60%) from all the 20 participating countries completed the survey. Sixty-one reported frequent-attendance (≥ 1 per month), 23 reported infrequent-attendance (< 1 per month), and 11 never participated. The main barriers to attendance were the subspecialist’s respective workload (64%), the timing of the teleconference (38%), and internet connectivity problems (29%). Subspecialist’s workload amount was more commonly reported as a barrier compared with other barriers, in both the frequent and infrequent-attendance groups (p<0.05), with the exception of the timing of the meeting in the infrequent-attendance group. More than 80% found the frequency and duration of the teleconference were sufficient. Utilizing Spanish as the primary language was reported to enhance the teleconference recommendations by 93% of the respondents. The recommendations were reported to always or almost always fit the local circumstances by 84%, moreover; 99% of attending respondents found the teleconference provides a continuing medical education opportunity. Finally, 83% agreed to the need to include more subspecialties into LATB especially: neuroradiology, neuropathology, neurosurgery, and radiation-oncology. Participants found that weekly, one-hour sessions were sufficient to review the requested cases. Utilizing the participants’ first language makes the recommendations clearer and easier to follow. Physician workload is the main barrier to participate in the teleconference.
Clinical outcomes and toxicity of chemoradiation with IMRT for anal cancer
Authors: J. Fonseca, N. Ferreira, C. Viveiros, G. Fernandez, C. Travancinha, L. Mirones, S. Esteves, I. Rosa, M. Limbert, J. Freire, F. Santos
Journal: Annals of Oncology (2018)

Introduction: Anal carcinoma is an uncommon diagnosis whose treatment carries risks of significant morbidity due to the complex target volume and multiple adjacent organs at risk. Intensity modulated radiation therapy (IMRT) offers the potential to reduce toxicity while maintaining or improving the dose distribution to the target volume. Our purpose was to evaluate the outcomes of our center since the implementation of IMRT in the treatment of squamous cell carcinoma (SCC) of the anal canal. Methods: Retrospective single-center study of patients with SCC of the anal canal treated with IMRT between 2011 and 2015. Overall survival (OS), disease free survival (DFS), colostomy free survival (CFS) and local control (LC) were calculated by the Kaplan-Meier method. Toxicity was evaluated according to Common Terminology Criteria for Adverse Events v4.0. Results: Thirty-five patients were included (males 78%, females 22%, median age 64 years). T stage distribution was Tx 8%, T1 6%, T2 40%, T3 40% and T4 6%. 63% had nodal involvement. 11% were HIV positive. Median follow-up time for surviving patients was 3 years (range 1-7 years). IMRT was used in all patients with median doses to the pelvis of 45 Gy and 59 Gy to the primary tumor, using a sequential boost. Most patients (95%) were treated with chemoradiation (CRT) and only 2 patients received RT alone. The most frequent chemotherapy regimen was 5-fluoracil and mytomycin C (94%). Median overall treatment time was 44 days. Three patients (9%) had a treatment break and one patient did not complete treatment due to severe acute toxicity. Thirty-two patients (91%) had complete response. Three patients had persistent disease and three patients developed local recurrence. These patients had abdominoperineal resection (APR), except one who refused surgery. Three-year LC was 82%. Three patients (9%) developed distant metastases as the site of first failure. Three-year OS, DFS and CFS were 84, 77% and 84%, respectively. On univariate analysis, age, sex, T stage, HIV status or nodal disease had no impact on the outcomes. Grade 3 acute skin toxicity was observed in 13 patients (37%) and one patient had grade 4 toxicity. Grades 1-2 gastrointestinal (GI) toxicity occurred in 14 patients (40%) and grade 3 toxicity in one patient. Genitourinary (GU) grade 1 acute toxicity was observed in 6 patients (17%). Major late GI toxicity (grade 3-4) was reported in 2 patients (6%) and grade 2 in 7 patients (20%). There was no relevant late skin or GU toxicity. Conclusion: Chemoradiation with IMRT achieves good clinical outcomes and low treatment-related morbidity with minor treatment interruptions and acceptable late sequelae. The small sample size may explain the lack of impact of the tested variables on univariate analysis and requires longer follow-up of our patients.
TBIO-30. MOLECULAR LANDSCAPE AND CLINICAL CORRELATIONS OF CNS SARCOMAS
Authors: Adriana Fonseca, Ben Ho, Jonathon Torchia, Sarah Leary, Mei Lu, Gino Sommers, Abha Gupta, Ronald Grant, Joe Norman, Lucie Lafay-Cousin, Cynthia Hawkins, Ute Bartels, Eric Bouffet, Annie Huang
Journal: Neuro-Oncology (2018)

Central nervous system (CNS) sarcomas are rare mesenchymal tumors accounting for less than 0.2% of intracranial (IC) tumors. Due to their rarity molecular insights they may be misdiagnosed as embryonal brain tumors, thus best clinical approach has been lacking 17 IC and 4 extracranial (EC) sarcomas were examined using methylation profiles and RNASeq analyses to define molecular features and clinicopathologic correlations. CNS sarcomas segregate into 3 sub-groups; the majority exhibited CIC (n=17) or EWS (n=9) fusions, a small subset (n=3) has no defining alteration. All IC EC sarcomas with the same molecular alterations indicating they were not distinct brain tumor types. Median age was 4.25-yrs, 10.6-yrs and 14-yrs for the CIC, EWS and undifferentiated subgroup respectively. The 5-yr PFS was 33%, 75% and 100% and OS was 49%,83% and 100% for the CIC, EWS and undifferentiated group respectively. IC and EC sarcomas represent a common molecular diseases, and should be treated using similar approaches.
HGG-38. DEVELOPMENT AND COMPREHENSIVE CHARACTERIZATION AND UTILIZATION OF PRECLINICAL MODELS OF PEDIATRIC HIGH GRADE GLIOMAS
Authors: Sridevi Yadavilli, Kathleen Knudson, Madhuri Kambhampati, Eshini Panditharatna, Michael Prados, Sabine Mueller, Suresh Magge, Lindsay Kilburn, Eugene Hwang, Roger Packer, Javad Nazarian
Journal: Neuro-Oncology (2018)

Midline high-grade gliomas (HGGs) are amongst the most challenging childhood cancers to treat. Recent advances in understanding the molecular drivers of these tumors have resulted from donated autopy or biopsy specimens. We have initiated a midline glioma preclinical initiative for producing in vitro and in vivo models that have well defined genomic profiles. We obtained 22 autopsy, 11 upfront biopsy (PNOC NCT 2274987) and 2 surgical resection samples. Collectively, specimens represented DIPGs (n=30) and thalamic HGGs (n=5). Single cell suspensions were generated for neurosphere culture and intracranial injection into mice. Specimens were considered viable if they resulted in two consecutive generations of murine tumor models or five in vitro passages. A total of 14 cell lines representing DIPG and thalamic glioma were generated and validated by short tandem repeat (STR) analysis. Orthotopic injections into non scid gamma (NSG) mice resulted in tumor formation (n=14) with molecular characteristics similar to the corresponding patient tumor. Eleven mouse implantations are still being monitored. In vivo models were validated by immunohistochemical staining for human mitochondria and H3K27M. Methylation and whole genome analysis of preclinical models were generated to assess similarities/shared pathways with human disease. In vitro and in vivo response to therapeutics including panobinostat and TAK228 was also assessed. A microdialysis procedure was optimized to assess blood brain barrier penetration of systemically administered therapeutics. Direct drug delivery was also evaluated using subcutaneously placed osmotic pumps with optimization of delivery rates, cannula depth and placement.
QOL-47. ApoE4 AS A GENETIC PREDICTOR FOR NEUROCOGNITIVE OUTCOMES IN PEDIATRIC BRAIN TUMOR SURVIVORS
Authors: Cassie Kline, Erin Felton, Lennox Byer, Schuyler Stoller, Joseph Torkildson, Karen Gauvain, David Samuel, Elizabeth Tong, John Liu, Heather Fullerton, Dena Dubal, Sabine Mueller
Journal: Neuro-Oncology (2018)

Long-term neurocognitive deficits in pediatric brain tumor survivors are challenging to both predict and treat. In a previous cohort analysis, we identified the genetic variant for ApoE4 reliably correlates with decreased neurocognitive function over time. Herein, we present case-control analyses comparing neurocognitive outcomes of ApoE4 carriers versus non-carriers in a group of pediatric brain tumor survivors. Utilizing an existing cohort of pediatric brain tumor patients from a diverse population, we isolated cases heterozygous for ApoE4 and matched these to controls carrying ApoE3. Priority was placed on matching cases and controls along variables previously identified to impact neurocognition – time from radiation and hydrocephalus or seizures at diagnosis. Student t-tests and lowess smoothing regression were used to compare outcomes in 6 neurocognitive domains over multiple time points. Twenty matched cases and controls were included in the analyses. At baseline, there were no statistically significant differences between cases and controls in any domain. Over time, ApoE3 controls performed statistically significantly higher across an increasing number of neurocognitive domains than ApoE4 carriers. Using smoothing regression, cases visibly performed worse over time as compared to controls and as seen by decreasing neurocognitive scores across all domains. ApoE4 carrier status strongly correlates with neurocognition function over time in pediatric brain tumor survivors. This effect appears across multiple domains and may show evidence of progressive deterioration with each year from treatment. Our results identify ApoE4 as a possible genetic predictor for neurocognitive outcomes in pediatric brain tumor survivors and support further investigation of this genetic variant.
Publisher Correction: Transcription factor Hoxb5 reprograms B cells into functional T lymphocytes
Authors: Mengyun Zhang, Yong Dong, Fangxiao Hu, Dan Yang, Qianhao Zhao, Cui Lv, Ying Wang, Chengxiang Xia, Qitong Weng, Xiaofei Liu, Chen Li, Peiqing Zhou, Tongjie Wang, Yuxian Guan, Rongqun Guo, Lijuan Liu, Yang Geng, Hongling Wu, Juan Du, Zheng Hu, Sheng Xu, Jiekai Chen, Aibin He, Bing Liu, Demin Wang, Yong-Guang Yang, Jinyong Wang
Journal: Nature Immunology (2018)
QOL-10. TIMING OF CENTRAL LINE REMOVAL IN PEDIATRIC NEURO-ONCOLOGY PATIENTS AFTER COMPLETION OF THERAPY
Authors: Zachary Prudowsky, Joseph Stanek, Mostafa Eltobgy, Mohamed AbdelBaki
Journal: Neuro-Oncology (2018)

Chemotherapy is frequently used to treat pediatric brain tumors, and central lines (CVLs) are often required for its delivery. CVLs are known to have their own side effects, including risk of blood stream infection, catheter-associated thrombosis, or catheter dysfunction requiring surgical repair or replacement. CVLs also require frequent flushing if not accessed for lab draws or medication administration. Current practice is to remove the CVL as soon as logistically possible once therapy is completed; however, disease recurrence does require line replacement, exposing patients to anesthesia and another invasive procedure. Our single-institution, IRB-approved study retrospectively reviewed pediatric neuro-oncology patients with CVLs over the past 10 years aiming to identify the best timing to remove CVLs after finishing therapy. Patients were subsequently stratified based on their diagnosis and respective tumor grade; rates of relapse and CVL-associated adverse events were also analyzed. Fifty-three patients were included in our study: 22 had low grade tumors, and 25 had high grade tumors, with the most common malignancy being medulloblastoma (14 patients). All but one of the CVLs were electively removed after completion of therapy. Tumor recurrence occurred 4 times with low grade and 8 times with high grade tumors, with recurrence happening anywhere between 95 and 1872 days after CVL removal, and CVL-related adverse events occurring approximately 1 in every 1,000 days. We found no significant differences in the timing of tumor recurrences to justify keeping the CVL for 3-6 months after therapy, which is a common practice in some large pediatric cancer centers.
FRI0303 Efficacy and safety of ustekinumab in patients with active systemic lupus erythematosus: results of a phase 2, randomised placebo-controlled study
Authors: R. van Vollenhoven, B.H. Hahn, G.C. Tsokos, C. Wagner, P. Lipsky, B. Hsu, M. Chevrier, R. Gordon, M. Triebel, S. Rose
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> IL12 and IL23 have been linked to SLE pathogenesis. <h3>Objectives</h3> The anti-IL12/23 monoclonal antibody ustekinumab (UST) was evaluated in pts with active SLE. <h3>Methods</h3> We conducted a Ph2, PBO-controlled study in 102 pts with active SLE. Pts were randomised(3:2) to UST IV~6 mg/kg or PBO at wk0, followed by UST SC 90 mg or PBO injections q8w, both added to standard care. Primary endpoint was proportion of pts achieving SLE responder index(SRI)−4 response at wk24. Secondary endpoints were change from baseline(BL) in SLEDAI-2K, PGA and BICLA response. Additional pre-specified endpoint analyses included no BILAG worsening(defined as no new BILAG A and ≤1 new BILAG B) and BILAG flare(≥1 new BILAG A or ≥2 new BILAG B). <h3>Results</h3> SRI-4 response occurred in 60% UST vs 31% PBO pts(p=0.005) at wk24 (table 1). UST pts had greater median change from BL in SLEDAI-2K and PGA vs PBO. No difference was observed in BICLA response at wk24; however, in the UST group vs PBO, more pts had no BILAG worsening, and the risk of a new BILAG flare was significantly lower(HR 0.11 [95% CI 0.01–0.94];p=0.0078). UST demonstrated improvement in musculoskeletal and mucocutaneous disease features vs PBO (table 1). Through wk24, 78% UST vs 67% PBO pts had ≥1 AE; 8.3%–9.5%, respectively, had ≥1 SAE; there were no deaths. The overall safety profile was comparable between UST and PBO. <h3>Conclusions</h3> UST treatment showed efficacy in pts with active SLE and was well-tolerated. UST may work via a novel mechanism of action in SLE. <h3>Disclosure of Interest</h3> R. van Vollenhoven Grant/research support from: Janssen Research and Development, LLC, B. Hahn Grant/research support from: Janssen Research and Development, LLC, G. Tsokos Grant/research support from: Janssen Research and Development, LLC, C. Wagner Employee of: Janssen Research and Development, LLC, P. Lipsky Grant/research support from: Janssen Research and Development, LLC, B. Hsu Employee of: Janssen Research and Development, LLC, M. Chevrier Employee of: Janssen Research and Development, LLC, R. Gordon Employee of: Janssen Research and Development, LLC, M. Triebel Employee of: Janssen Biologics, S. Rose Employee of: Janssen Research and Development, LLC
TBIO-04. A CENTRALIZED MOLECULAR DIAGNOSTIC SERVICE FOR PEDIATRIC BRAIN TUMORS IN JAPAN
Authors: Koichi Ichimura, Yoshiko Nakano, Takako Yoshioka, Junko Hirato, Mai Kitahara, Tomoko Shofuda, Sumihito Nobusawa, Kai Yamasaki, Yonehiro Kanemura, Hiroaki Sakamoto, Ryo Nishikawa, Junichi Hara
Journal: Neuro-Oncology (2018)

Molecular tests have now become an essential part of clinical management of pediatric brain tumor patients. We have established a central diagnosis system for pediatric brain tumors in Japan to provide standardized molecular diagnostic service. Tumor specimen are accepted from centers participating Japan Children’s Cancer Group (JCCG). The JCCG Datacenter at National Center for Child Health and Development (NCCHD) manages all patients’ specimen and information. Histology is centrally reviewed at Gunma University Hospital. Molecular tests are performed at either Osaka National Hospital (medulloblastoma), Gunma University Hospital (ETMR) or National Cancer Center (all the others). Medulloblastomas are classified by expression profiling using the nanostring technology, and mutations of CTNNB1, TP53 and TERT determined. Gliomas are examined for mutations of BRAF, H3F3A, HIST1H3B, FGFR1, IDH1/2 and TERT using pyrosequencing, as well as for BRAF fusion by RT-PCR as necessary. Supratentorial ependymomas are examined for the presence of RELA fusion by RT-PCR, and posterior fossa ependymomas are classified as PFA or PFB by DNA methylation analysis. Those tumors negative for the routine analyses may be subjected to RNA sequencing or targeted sequencing for 93 genes known to be mutated in brain tumors. As of August 2017, over 200 tumors have been molecularly diagnosed and the integrated diagnosis reported to each center. Our system is affordable utilizing minimum amount of high throughput technologies, and will hopefully improve the standard of diagnosis for pediatric brain tumors.
Childhood obesity: government’s plan targets energy drinks and junk food advertising
Authors: Jonathan Owen
Journal: BMJ (2018)

Banning the sale of energy drinks to children, encouraging primary school pupils to run a mile a day, and restricting junk food advertising are some of the new measures outlined in chapter 2 of the government’s childhood obesity plan.1

In a bid to halve childhood obesity by 2030 the government plans to prevent shops from displaying food high in fat, sugar, and salt at checkouts or including it in “two for one” promotions.

It will also consult on forcing restaurants, cafes, and takeaways to include calorie labelling on their menus, as well as new restrictions on television and online advertising. This could result …
GERM-16. A MULTI-CENTRE CLINICAL TRIAL OF CNS GERM CELL TUMOURS IN HONG KONG
Authors: Matthew MK Shing, Godfrey CF Chan, C W LUK, Dennis TL Ku, Anthony Liu, S C Ling
Journal: Neuro-Oncology (2018)

This clinical trial started from January 2008 and ended in June 2014. Patients who were suspected to have germinoma received a biopsy, followed by chemotherapy with carboplatin (600 mg per m2 on day 1) and etoposide (150 mg per m2 per day, day 1 to 3), alternating with ifosfamide (1.8 mg per m2 per day and etoposide 150 mg per m2 per day, day 1 to 5). They were assessed with MRI every 2 cycles. A total of 4 cycles of chemotherapy were given, followed by radiotherapy. The dose and volume of radiotherapy depend on the response and site of involvement. Patients with non-germinomatous germ cell tumours received operation to remove the tumour (if possible), chemotherapy as above for 6 cycles, reassessed by MRI once in two cycles, and cranio-spinal radiotherapy. The patients may need a second look operation if necessary. The data were reviewed on 31 May 2017. There were 45 patients, male to female ratio: 2.8:1, median age: 12.5 years of age (0.4 to 18.7). The pathology were germinoma (n=24) and non-germinomatous germ cell tumours (n=21). The locations of the tumours were suprasellar/sellar(n=13), pineal gland (n=20), suprasellar & pineal gland (n=7) and basal ganglia (n=4) and left frontal lobe (n=1). Five patients had metastatic diseases at presentation. Two patient had relapses. The median follow-up time was 6.75 years (2.43 to 9.54). PFS and OS at 5 years were 95.5% and 100% respectively. With a multi-disciplinary approach, a satisfactory outcome is achieved.