Abstract 770: Exploitation of treatment induced tumor lysis to enhance sensitivity of ctDNA analysis: a first-in-human pilot study
Notice bibliographique
Résumé
Abstract Background: Blood based liquid biopsies examining circulating tumour DNA (ctDNA) have increasing applications in non-small cell lung cancer (NSCLC). Limitations in sensitivity, especially in patients with limited disease burden, remains a barrier to ctDNA replacing tissue-based testing. There is a paucity of data regarding the optimal time to measure ctDNA, specifically the dynamics of ctDNA levels in the hours to days following a new and effective treatment. We hypothesize that chemotherapy or radiation will yield an increased abundance of ctDNA in plasma by inducing tumor lysis, allowing for the detection of genetic alterations that were occult in baseline testing. Methods: Two prospective cohorts of twenty patients (pts) with stage III/IV NSCLC were enrolled. Cohort 1 (C1) contained patients starting the first cycle of platinum doublet chemoradiation (C1a, n=10) or the first cycle of platinum doublet cytotoxic chemotherapy ± immunotherapy without concurrent radiation (C1b, n=10). Cohort 2 (C2) contained patients receiving palliative radiation. Consenting patients provided baseline samples, the first ≤ 14 days prior to starting treatment and one immediately prior to treatment. In C1, subsequent samples were collected (A) 2-3, (B) 4-6, (C) 18-72 and (D) 42-96 hours post initiation of chemotherapy. Pts in C2 had samples collected immediately prior to radiotherapy fractions 2, 3, and 4. Samples were analyzed for ctDNA using the 36-gene amplicon-based NGS Inivata InVisionFirst®-Lung assay. Results: Complete results were available for the first 28 of 40 enrolled pts, C1a - 8 pts, C1b - 8 pts, C2 - 12 pts. Detectable ctDNA was present at baseline in 21 pts (75%), 4 additional pts (14.3%) had detectable ctDNA in post treatment samples (C1a - 2pts, C1b - 1pt, C2 - 1pt). Three of the patients with detectable ctDNA at baseline (10.7%) had new genetic alterations detected in post treatment samples. A total of 7/28 pts (25%) had new genetic alterations detected in the post treatment samples. Mutant molecule numbers increased with treatment in 19 of 25 (76%) pts with detectable ctDNA, C1 - 11 of 15 pts (73.3%) and C2 - 8 of 10 pts (80%). ctDNA levels peaked a median of 2.2 hours (interquartile range (IQR): 1.5 - 2.9 hours) after the initiation of chemotherapy and a median of 1 day (IQR: 1-2 days) after radiation was commenced. The percentage increase in ctDNA levels was a median of 39.3% (IQR: -20.5 to +112.8%) in C1, with median increases of 22.0% and 39.3% in C1a and C1b, respectively. C2 had a median increase of 81.9% (IQR: 0 to +161.5%). Conclusion: ctDNA levels increase in the hours to days after starting a new treatment. ctDNA testing in the acute post treatment phase can yield results that were not evident in pretreatment testing. Application of this principle could improve ctDNA utility as an alternate to tissue-based testing and/or improve sensitivity for the detection of treatment-resistant clones. Citation Format: Daniel Breadner, Mark David Vincent, Rohann Correa, Morgan Black, Andrew Warner, Melody Qu, Diane Logan, Michael Sanatani, Jawaid Younus, Brian Yaremko, George Rodrigues, Phillip Blanchette, Joanna Laba, Edward Yu, David Goodale, Lori Lowes, Vasudeva Bhat, Albert Gratton, James Sinfield, Susan Archer, Clive Morris, Emma Green, Greg Jones, Alison Allan, David Palma, Jacques Raphael. Exploitation of treatment induced tumor lysis to enhance sensitivity of ctDNA analysis: a first-in-human pilot study [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 770.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,002 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,001 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,001 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,007 | 0,002 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».