Abstract 4023: Co-occurring mutations in recurrent/persistent head and neck squamous cell carcinoma (HNSCC) patients
Notice bibliographique
Résumé
Abstract Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer and lacks effective targeted therapies. HPV(-) patients have a 50-60% recurrence rate and could benefit from adjuvant therapy. Although HPV(+) patients have a significantly better survival, 20% have persistent/recurrent disease. Therefore, biomarkers could potentially help identify patients that would benefit from adjuvant targeted agents. Our objective was to evaluate if the mutational and biomarker analysis of tumor samples from OPSCC patients predict recurrence and/ or persistence in patients undergoing definitive therapy with curative intent. 44 advanced stage OPSCC patients that underwent comprehensive genomic profiling by Caris Life Sciences were included in this retrospective study. Next Generation Sequencing (NGS) on genomic DNA from FFPE tumors was performed using the Illumina Nextseq (592-gene, n=17)/MiSeq (44-gene, n=23) platform. Tumors were analyzed for total mutational load (TML), CNV’s and microsatellite instability status. IHC for tumor protein expression of ERCC1, PD-L1, RRM1, TrkA/B/C, TS and TUBB3 was performed using automated platforms. The ASCO/CAP scoring criteria and the cutoff points from published evidence was used in IHC evaluation. Of the 44 patients, 27 were HPV(+) tumors and 11 had HPV(-) disease. Patients with lack of progression free survival data were excluded. Only 4 patients in the entire cohort harbored a pathogenic PIK3CA mutation. Among HPV(+) patients, 22 patients were TP53 WT and 2 patients were found to be TP53 mutant. Although there was no significant change in the TML in smokers compared to nonsmokers (mean 8.77 vs 6.5, respectively; p=0.253), TML was higher in HPV(-) smokers compared to HPV(+) nonsmokers (mean 10.33 vs 6.5, p=0.0661). Our study presented a higher incidence of recurrent/persistent disease in the Caucasians (60%) in comparison to African-Americans (21%). Considering the sample size in the current study, the racial difference in outcomes appears likely to be present regardless of HPV status or disease state. The co-occurrence of multiple deleterious mutations was observed in 70% of the non-responders. Particularly, mutations in CHEK2, PTCH, MUTYH were noted in 50% of the recurrent/persistent patients. CNV mutations in SMAD2, MALT1, NFKBIA in 50% of the recurrent/persistent patients were found. The co-occurrence of multiple mutations were absent in responders in spite of an appreciable sample size in the responder group (n=12). This study also affirmed an improved prognosis in patients with HPV(+), with higher expression of TUBB3, and with positive expression of PD-1 in the tumors. Co-occurrence of multiple deleterious mutations were associated with patients who did not respond to therapy. Therefore, combination rescue therapies that can target multiple pathways to abrogate the mutational effects can aid/enhance therapeutic benefits in HNSCC patients. Citation Format: Alok R. Khandelwal, Kelsey Poorman, Tara Moore-Medlin, Xiaohui Ma, Abhijit Gundale, Ronald Horswell, San Chu, Michelle Winerip, Cherie-Ann O. Nathan. Co-occurring mutations in recurrent/persistent head and neck squamous cell carcinoma (HNSCC) patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4023.
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) | 0,000 | 0,000 |
| Bibliométrie | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,001 | 0,000 |
| Communication savante | 0,001 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,004 | 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 ».