Abstract A034 LIBERTY: LIquid Biopsy for rElapsed/RefracTorY neuroblastoma - a pilot study of characterization of circulating tumor DNA alterations in patients with relapsed and refractory neuroblastoma using a clinically validated liquid biopsy platform
Bibliographic record
Abstract
Abstract Introduction Detection of tumor-derived targetable alterations from peripheral blood samples represents a unique opportunity for patients (pts) with hard-to-biopsy neuroblastoma (NBL). The overall aim of LIBERTY is to describe the molecular alteration landscape identified by circulating tumor DNA (ctDNA) profiling in pts with relapsed/refractory NBL by providing rapid turnaround results to Canadian patients, using a clinically validated commercial liquid biopsy platform. Methods LIBERTY is a prospective non-interventional study of molecular profiling of ctDNA for pts with relapsed, refractory or not amenable to biopsy NBL, treated in a Canadian oncology center. The Tempus next-generation sequencing xF+ assay is performed on ctDNA extracted from blood collected at a single timepoint. The 523-gene panel includes single nucleotide variants, insertions and deletions, copy number variants and chromosomal rearrangements, using 30-50 ng of input DNA. An analytically validated report of genomic findings is returned to the study team and may be used to inform treatment recommendations. Results To date, 15 pts have been enrolled (6 male), with a median age of 6.7 y (range, 2.8-24.6). Disease status at enrolment was primary refractory/progressive NBL (n=2), first relapse (n=4), second or greater relapse (n=9). Nine pts were primarily treated at the Hospital for Sick Children. Remote consent was performed for remaining 6 pts, with blood sample being collected at and shipped from their institution to TEMPUS. Thirteen of 15 (86.6%) pts had been previously enrolled in another pediatric precision oncology program (KiCS (n=10), PROFYLE (n=1), KiCS/PROFYLE (n=2)), which provided sequencing results of tumor tissue-derived DNA. Median turnaround time was 13 days from blood draw to available report (range, 9-27). ctDNA extraction and sequencing led to generation of a research report for 14/15 pts. Biologically relevant variants, as defined by the TEMPUS knowledge database as variants with functional significance or association with disease state, and may have relevant therapeutic, prognostic or diagnostic evidence, were reported for 8/14 (57%), with a median variant allele fraction of 10.6% (range, 0.2%-47.4%). At least one biologically relevant variant was a novel finding for 6 pts (not in previous tumor tissue sequencing (n=5); no previous sequencing (n=1)) and in 3 pts, was deemed therapeutically actionable – variants in PIK3R1, RET, CHEK2 for SK-0010; ALK for SK-0013; PTPN11 for SK-0015. For one pt with ALK p.F1174L, ctDNA sequencing led to a change in therapy in the context of first relapse. Conclusion Using a commercially available liquid biopsy tool within the confines of a research study for pts with relapsed/refractory NBL is feasible in an expansive country like Canada. Remote consent and shipping of blood samples directly from pt’s institution facilitated access from across the country. Enrolment in LIBERTY gave pts timely access to ctDNA next-generation sequencing and led to identification of novel findings with implications for therapy. Citation Format: Sarah Cohen-Gogo, Gabriel Revon-Riviere, Jathishinie Jegathisawaran, Adam Shlien, Anita Villani, Meredith Irwin, Daniel A. Morgenstern. LIBERTY: LIquid Biopsy for rElapsed/RefracTorY neuroblastoma - a pilot study of characterization of circulating tumor DNA alterations in patients with relapsed and refractory neuroblastoma using a clinically validated liquid biopsy platform [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 A034.
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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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
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".