Clinical and Radiographic Improvement of Neurodegenerative Langerhans Cell Histiocytosis (ND-LCH) Following Dabrafenib (P3.266)
Bibliographic record
Abstract
Objective: We report two children with V600E+ ND-LCH enrolled on BRF116013 with clinical and radiographic improvement after 8 weeks of dabrafenib treatment. Background: Neurodegenerative LCH is a potentially devastating disorder with limited therapeutic options. The identification of BRAF mutations in LCH has led to investigations of BRAF inhibitors. BRF116013 (NCT01677741) is an ongoing first-in-children trial of dabrafenib for advanced BRAF V600+ tumors. Design/Methods: Two patients with ND-LCH and biopsy-confirmed BRAFV600E+LCH were treated on BRF116013 with dabrafenib 5.25 mg/kg/day, with MRI brain obtained at baseline and 2 months after. Image processing was performed by a single observer blinded to identity and scan date. Cerebellar lesions were segmented using a multimodal tissue classifier based on T2-weighted and FLAIR images. Results: At baseline, both children demonstrated progressive neurologic involvement, including ataxia, limited mobility and fine motor and speech decline. Patient 1 had neurologic onset 3 years prior, with failure of 3 therapies including ARA-C. Patient 2 had neurologic onset 2 years prior with progressive decline in coordination and school performance after 2 therapies including ARA-C. Brain MRI at BRF116013 initiation revealed cerebellar and generalized pontine involvement in both patients with extension to the midbrain in patient 1. At 8 weeks, brain MRI revealed resolution of pontine and midbrain lesions in both, with significant reduction of cerebellar lesional volume (8.0 to 3.5 cc in patient 1 (56[percnt] reduction) and 1.3 to 0.3 cc (77[percnt] reduction) in patient 2. Toxicities through Week 8 were all grade 1. Patient 1 experienced recovery of independent mobility and Patient 2 experienced improved mobility and coordination. Conclusion: These preliminary results suggest that dabrafenib may be a promising new therapy for ND-LCH, with rapid improvement seen following years of neurologic decline. Further investigation of this therapy in ND-LCH is warranted.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
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".