Abstract A28: Targeted sequencing in 388 patients with high-risk or recurrent/refractory pediatric extracranial solid malignancies: An interim report from the GAIN Consortium/iCat2 Study
Notice bibliographique
Résumé
Abstract Background: Gene variants with potential therapeutic significance have been reported in 30-60% of childhood malignancies. The 12-institution Genomic Assessment Informs Novel therapy (GAIN) consortium is conducting the individualized cancer therapy 2 (iCat2) study (NCT02520713) with the objective of evaluating the impact of tumor profiling on outcome. We provide an interim report on patients enrolled on the ongoing GAIN/iCat2 study. Methods and Objectives: Patients are eligible if they have a high-risk, recurrent/refractory (RR), or difficult-to-diagnose extracranial solid tumor diagnosed at ≤30 years and adequate sample available for sequencing. A next-generation targeted panel assay is performed. Results are returned with a GAIN report containing clinical interpretation, including an individualized cancer therapy (iCat) recommendation if there is evidence supporting a link between an identified variant and response to molecularly targeted therapy. iCat recommendations are tiered from 1 to 5 based on the level of clinical and preclinical support, with tier 1 being the highest and tier 5 the lowest. Potential extraordinary responders are selected for further review based on having treatment duration of ≥1 year for chemotherapy or ≥4 months or a partial response for targeted therapy. Results: 388 eligible patients were enrolled by 1/1/2019 with the most common diagnoses being osteosarcoma, Ewing sarcoma, and rhabdomyosarcoma. 366 patients (94%) have had at least one successful sequencing result, with 349 having molecular and GAIN reports suitable for inclusion in this analysis. 68% of patients (237/349) have received iCat recommendations, with 41% (143/349) having the highest tier of 1-2 and 27% (94/349) having a highest tier of 3-5. Common genes for which tier 1-2 iCat recommendations were made include TP53 (15%), SMARCB1 (4%), PIK3CA (3%), CDK4 (2%), and KRAS (2%). Common alterations for which tier 3-5 recommendations were made include EWSR1 fusions (12%), MYC/MYCN amplifications (8%), and CDKN2A deletions (7%). Of 170 RR patients with treatment follow-up data entered as of June 2019, 15% (25/170) have received matched targeted therapy. Six of these (24%) are considered extraordinary responders. Of note, extraordinary responses were also seen with some second-line chemotherapy and multitargeted kinase inhibitors. Conclusions: The proportion of patients with clinically significant gene variants is higher in this study than in some previous reports. Providing an iCat recommendation for alterations in genes such as TP53 where evidence is mixed, increased availability of molecularly targeted therapy trials, and more evidence may all be responsible for this increased rate. Reassessment of iCat recommendation tiers based on current evidence is ongoing. Extraordinary responses occur in a subset of children with extracranial solid malignancies who receive matched targeted therapy. Study enrollment is ongoing with further assessments of the impact of tumor profiling on outcome planned. Citation Format: Laura B. Corson, Alanna J. Church, Deirdre Reidy, Pei-Chi Kao, Wenjun Kang, Navin Pinto, Luke Maese, Theodore W. Laetsch, AeRang Kim, Susan I. Vear, Margaret E. Macy, Mark A. Applebaum, Lobin A. Lee, Duong Doan, R. Seth Pinches, Seong Choi, Suzanne J. Forrest, Catherine M. Clinton, Brian D. Crompton, Laura E. MacConaill, Samuel L. Volchenboum, Neal I. Lindeman, Steven G. DuBois, Wendy B. London, Katherine A. Janeway. Targeted sequencing in 388 patients with high-risk or recurrent/refractory pediatric extracranial solid malignancies: An interim report from the GAIN Consortium/iCat2 Study [abstract]. In: Proceedings of the AACR Special Conference on the Advances in Pediatric Cancer Research; 2019 Sep 17-20; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Res 2020;80(14 Suppl):Abstract nr A28.
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 | 0,001 | 0,002 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,000 |
| Science ouverte | 0,000 | 0,001 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 0,001 |
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 ».