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Clinical characteristics and outcome of a large cohort of patients with primary central nervous system (CNS) tumors and tropomyosin receptor kinase (TRK) fusion.

2022· article· en· W4286294939 on OpenAlexaff
Audrey‐Anne Lamoureux, Michael J. Fisher, Lauriane Lemelle, Elke Pfaff, Stefan M. Pfister, Dominik Sturm, David Jones, Daniel Orbach, Scott Raskin, Alexander Drilon, Michal Zápotocký, Christina Coleman Abadi, Marc Barritault, Pierre Leblond, Uri Tabori, Jordan R. Hansford, Craig Erker, François Doz, Theodore W. Laetsch, Sébastien Perreault

Bibliographic record

VenueJournal of Clinical Oncology · 2022
Typearticle
Languageen
FieldMedicine
TopicGlioma Diagnosis and Treatment
Canadian institutionsIzaak Walton Killam Health CentreHospital for Sick ChildrenUniversity of TorontoSickKids FoundationCentre Hospitalier Universitaire Sainte-Justine
Fundersnot available
KeywordsTrk receptorMedicineInternal medicineOncologyEpendymomaGastroenterologyPathologySurgeryNeurotrophinReceptor

Abstract

fetched live from OpenAlex

2052 Background: TRK fusions are detected in less than 3% of central nervous system (CNS) tumors. Given their rarity, there are limited data on the clinical course of affected patients. Methods: We contacted 166 oncology centers worldwide to retrieve data on patients with TRK fusion-driven CNS tumors. Data extracted included demographics, histopathology, TRK gene fusion, treatment modalities and outcomes. Results: Ninety-two patients with TRK fusion-driven primary CNS tumors were identified including 76 pediatric patients (82.6%), 15 adults (16.3%) and 1 not specified (1.1%). Median age at diagnosis was 4.4 years (range 0.0–78.3) and 58.7 % were male. NTRK2 gene fusions were found in 45 patients (48.9%), NTRK1 and NTRK3 aberrations were detected in 27 (29.3%) and 20 (21.7%), respectively. Tumor types included 56 high-grade gliomas (HGG; 60.9%), 20 low-grade gliomas (LGG; 21.7%), 4 embryonal tumors (4.3%) and 12 others (13.0%). Median follow-up was 40.5 months (range 3–226). During the course of their disease, 75 (81.5%) patients underwent surgery with a treatment intent, 67 (72.8%) patients received chemotherapy, 50 (54.3%) patients received radiation therapy, while 47 (51.1%) patients received NTRK inhibitors (6 as first line treatment). There were significant differences in the median progression-free (PFS) and overall survival (OS) between pediatric patients compared to adults. The pediatric median PFS was 32 months (95% CI: 15.5–48.5) compared to 8 months for the adult (95% CI: 4.5–11.5, p = 0.015). The pediatric median OS was 182 months (95% CI: 25.1–338.9) compared to 24 months (95% CI: 18.3–29.7 p < 0.001) for adult patients. There was no difference in the PFS of LGG compared to HGG. However, the OS was significantly worse for the HGG when compared to LGG (p = 0.039). The median OS for LGG was not reached and the median OS for HGG was 70 months (95% CI 7.5–132.5). Nineteen patients with HGG (38.0 % 19/50 evaluable patients) died compared to only one patient with LGG (5.6% 1/18 evaluable patients, p = 0.014). Conclusions: We report the largest cohort of patients with TRK fusion-driven primary CNS tumors. These results will help us to better understand clinical evolution and compare outcomes with ongoing clinical trials.

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)0.000
metaresearch head score (Gemma)0.001
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 score0.003
Threshold uncertainty score0.006

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

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 head0.036
GPT teacher head0.370
Teacher spread0.334 · 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".

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Citations0
Published2022
Admission routes1
Has abstractyes

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