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Record W2941112345 · doi:10.1093/neuonc/noz036.159

LGG-16. PREDICTORS OF OUTCOME IN BRAF-V600E PEDIATRIC GLIOMAS TREATED WITH BRAF INHIBITORS: A REPORT FROM THE PLGG TASKFORCE

2019· article· en· W2941112345 on OpenAlexaff
Liana Nobre, Michal Zápotocký, Scott Ryall, Ana Guerreiro Stücklin, Julie Bennett, Lorena Baroni, David Sumerauer, Josef Zámečnı́k, Lenka Krsková, Adéla Mišove, Zdeněk Pavelka, Jaroslav Štěrba, Ofelia Cruz, Andrés Morales La Madrid, Palma Solano‐Páez, Eduardo Quiroga-Cantero, Adela Cañete, Julia Balaguer Guill, Maria Luisa Garrè, Samatha Mascelli, Valentina Iurilli, Péter Hauser, Didier Frappaz, Cécile Faure‐Conter, Jordan R. Hansford, Nisreen Amayiri, Helena Mörse, Magnus Sabel, Anne Grete Bechensteen, Jack Su, Murali Chintagumpala, Matthias A. Karajannis, Gurcharanjeet Kaur, Jonathan L. Finlay, Diana S. Osorio, Scott Coven, David D. Eisenstat, Bev Wilson, Frank K.H. van Landeghem, Helen Toledano, Sonika Dahiya, Karen Gauvain, Sarah Leary, Theodore Nicolaides, Elisabeth Finch, Sabine Mueller, Jean M. Mulcahy Levy, Nicholas K. Foreman, David W. Ellison, Álvaro Lassaletta, Valérie Larouche, Naureen Mushtaq, Till Milde, Cornelis Vantilburg, Olaf Witt, Duarte Salgado, Inga Harting, Miriam Bornhorst, Roger J. Packer, Mariana Fernandes, Sarah G. Injac, Abhi Bavle, Daniel Alderete, Vijay Ramaswamy, Michael Taylor, Peter B. Dirks, Tara McKeown, Ute Bartels, Éric Bouffet, Cynthia Hawkins, Uri Tabori

Bibliographic record

VenueNeuro-Oncology · 2019
Typearticle
Languageen
FieldMedicine
TopicGlioma Diagnosis and Treatment
Canadian institutionsUniversity of AlbertaUniversité LavalStollery Children's HospitalHospital for Sick Children
Fundersnot available
KeywordsMedicineOncologyInternal medicineCohortClinical trialChemotherapyV600EMutationGene

Abstract

fetched live from OpenAlex

The BRAF-V600E mutation is found in 15–20% of pediatric low grade gliomas (PLGG) and result in worse outcome and higher risk of transformation to high grade gliomas (PHGG). Although ongoing trials are assessing the role of BRAF inhibitors (BRAFi) in these children, data are still limited. We aimed to report overall response rates and predictors of outcome in childhood BRAF-V600E gliomas. We collected clinical, imaging and molecular information of patients treated with BRAFi outside trials from centers participating in the PLGG taskforce. Response was calculated by RANO criteria and follow up data were collected for all patients. Sixty-six patients were treated with BRAFi (55 PLGG and 11 PHGG); median follow-up time was 1.5 years (0.1-5y). In PLGG, objective response (tumor reduction of >25%) was observed in 77% compared to 15% in a cohort treated with conventional chemotherapy (pCDKN2A deletion was not associated with lack of response, while specific enhancing patterns correlated strongly with response to BRAFi. Two-year PFS for the BRAF-V600E PLGG was 74% vs 47% for BRAFi vs chemotherapy, respectively (p=0.02). Our data reveal rapid, dramatic and sustained response of BRAF-V600E PLGG to BRAFi. These are in contrast to BRAF-V600E PHGG and non-enhancing PLGG. Additional molecular analyses are being performed to identify poor responders and emerging mechanisms of resistance in these tumors.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.002
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.005
Threshold uncertainty score0.010

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.002
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.015
GPT teacher head0.273
Teacher spread0.258 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations0
Published2019
Admission routes1
Has abstractyes

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