Abstract B020: Improved outcome for patients with alternative lengthening of telomeres (ALT) neuroblastoma randomized to tandem myeloablative therapy on COG ANBL0532
Bibliographic record
Abstract
Abstract Background: Overall survival (OS) of high-risk neuroblastoma (HRNB) patients with alternative lengthening of telomeres (ALT) tumors (∼23% of patients) is low. Event-free survival (EFS) of HRNB patients in COG ANBL0532 was higher for tandem relative to single ASCT.We sought to determine if ALT HRNB patients on ANBL0532 benefited from tandem ASCT. Methods:We assessed telomere maintenance mechanisms (TMM), defined as per Cancer Res 80:2663, 2020, in 204 primary tumors from ANBL0532 patients as TERT+ (high TERT mRNA), ALT (positive for telomeric DNA C-circle assay) or ultrabright telomere foci (UTF), or no TMM. Due to non-proportional hazards, survival comparisons used the Improved Two-Stage Procedure (J Stat Comput Simul. 2017; 87:1877). Results: TMM status was: ALT n=48 (23.5%), TERT+ n=140 (68.6%), TMM negative n=16 (7.8%). Patients with TERT+ tumors more frequently progressed early, but 8-year OS was superior for TERT+ compared to ALT (58.1±4.6% vs 41.6±8.2%; p=0.0007), while 8-year OS for TMM negative was 67.7±12.2%. The 8-year OS for TERT+ patients randomized to single (n=67) vs tandem (n=59) ASCT was 56.9±6.7% vs 71.8±6.5% (p=0.32) and for ALT patients randomized to single (n=20) vs tandem (n=19) ASCT was 26.9±11.5% vs 61.1±13.5% (p=0.011).For patients on ANBL0532 who received dinutuximab post-consolidation therapy, the 8-year OS for TERT+ patients who underwent single (n=52) vs tandem (n=43) ASCT was 53.5±7.6% vs 75.8±7.8% (p=0.10) while for ALT patients who underwent single (n=13) vs tandem (n=10) ASCT it was 23.1±14.3% vs 77.8±16.4% (p=0.022). Conclusions:As previously reported, patients with ALT HRNB have inferior OS relative to TERT+ HRNB.TMM negative HRNB patients had apparently higher OS than ALT or TERT+ but small numbers preclude formal analyses. OS was significantly improved in ALT HRNB by tandem ASCT.These data support use of tandem myeloablative therapy for patients with ALT neuroblastoma until effective targeted therapies become available. Citation Format: Balakrishna Koneru, Trevor Burrow, Kristyn McCoy, Jonas Nance, Arlene Naranjo, Fan F. Zhang, Meredith S. Irwin, Julie R. Park, C. Patrick Reynolds. Improved outcome for patients with alternative lengthening of telomeres (ALT) neuroblastoma randomized to tandem myeloablative therapy on COG ANBL0532 [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pediatric Cancer Research; 2024 Sep 5-8; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl):Abstract nr B020.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot 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.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 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 source (direct Gemma or distilled Codex), 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".