Abstract P136: Response to alpelisib in an adolescent with <i>PIK3CA</i>-mutated metastatic gastrointestinal stromal tumour
Notice bibliographique
Résumé
Abstract Introduction Gastrointestinal stromal tumours (GISTs) are mesenchymal neoplasms that arise in the gastrointestinal tract. While most GISTs are driven by mutations in cKIT or PDGFR, approximately 10% lack these variants and are referred to as ‘wild-type’. Wild-type GISTs are commonly succinate dehydrogenase (SDH)-deficient and are characterized by indolent, multi-focal disease at presentation. On occasion, patients experience symptomatic disease progression warranting treatment ; imatinib or sunitinib offer minimal benefit. PIK3CA mutations have recently been described in a small proportion of GIST. Case report A previously healthy 16-year-old female presented with a five-month history of vomiting and weight loss, compatible with gastric outlet obstruction. Computerized tomography demonstrated a large gastric mass, and multiple liver and peritoneal metastases. Biopsy showed nests of epithelioid cells with round nuclei, vesicular chromatin, and eosinophilic cytoplasm. The lesional cells were immunoreactive for CD117, DOG1, CD34, and smooth muscle actin, while negative for SDH-B immunohistochemistry, in keeping with SDH-deficient GIST. Germline and somatic panel sequencing were performed through the SickKids Cancer Sequencing Program along with RNA sequencing by Illumina TruSight RNA Pan-Cancer NGS analysis. Somatic analysis revealed a PIK3CA p.Glu545Lys (E545K) mutation at 0.12 variant allele fraction (VAF). The patient was also found to have germline heterozygous pathogenic splice variant in the SDHB gene c.75+1 G>T (p?). In the light of the molecular findings and no alternative curative options, compassionate access to alpelisib was sought. The patient started drug at the recommended adult dose of 300 mg by mouth daily, and after completing two 28-day cycles, showed marked improvement in her abdominal distension and discomfort. Her appetite improved with documented nutritional weight gain. Reimaging at this time showed a 20% reduction in the sum of maximum dimensions of target lesions (per RECIST 1.1). Repeat imaging after five months on treatment confirmed continued improvement with 25% reduction compared to baseline.The patient did not experience hypersensitivity, severe cutaneous adverse reactions, hyperglycemia or pneumonitis. She currently continues on alpelisib monotherapy. Conclusion We describe the first report of a clinically meaningful response to a PIK3CA inhibitor in an adolescent patient with advanced metastatic SDH-deficient GIST harbouring a somatic activating PIK3CA hotspot mutation. There is still much to be learned about the biology of pediatric/wild-type GIST. In these rare cases, we recommend referral to specialized centers and incorporation of comprehensive next generation sequencing into care. Sequencing should be performed both on germline and somatic DNA to evaluate for a cancer predisposition syndrome, along with possible druggable targets in PIK3CA, cKIT or PDGFRA. We believe that the lack of routine comprehensive genomic analysis may underestimate the frequency of such rare variants. Citation Format: Sarah Cohen-Gogo, Nisha Kanwar, Furqan Shaikh, Reto M. Baertschiger, Adam Shlien, David Malkin, Juan Putra, Ailish Coblentz, Anita Villani, Abha A. Gupta, Daniel A. Morgenstern. Response to alpelisib in an adolescent with PIK3CA-mutated metastatic gastrointestinal stromal tumour [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2021 Oct 7-10. Philadelphia (PA): AACR; Mol Cancer Ther 2021;20(12 Suppl):Abstract nr P136.
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 | 0,000 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,001 |
| Bibliométrie | 0,001 | 0,000 |
| Études des sciences et des technologies | 0,001 | 0,000 |
| Communication savante | 0,000 | 0,001 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,002 | 0,002 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 0,000 |
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 ».