Abstract 909: Defining molecular and laboratory predictive biomarkers of response to cisplatin-based neoadjuvant chemotherapy (NC) in muscle-invasive bladder cancer (MIBC) - preliminary results and future plans
Notice bibliographique
Résumé
Abstract Background: MIBC is common, yet there has been little progress in its research, with no new therapeutic agents approved in years. The optimal therapeutic modalities and treatment sequence are not entirely well-defined. Cisplatin-based NC prior to definitive radical cystectomy (RC) increases overall survival (OS), yet is only active in a proportion of patients (pts). A pathological complete response (pCR) at RC is associated with improved OS, but there are currently no molecular biomarkers predicting which pts are likely to achieve pCR, and thus treatment decisions are currently based solely on clinical parameters. Methods: Since micro-RNAs (miRNAs) are known to be key-players in cancer, we chose to study the differences in miRNA expression patterns between 7 pts who achieved pCR and 9 pts who did not respond (‘responders’ and ‘non-responders’, respectively), using commercial micro-arrays (Agilent ®) and quantitative RT-PCR. In a different cohort, we performed a retrospective chart review of 29 pts with MIBC receiving NC to find associations between clinical, biochemical or radiological characteristics and pCR. As the peripheral blood neutrophil-to-lymphocyte ratio (NLR) is thought to non-specifically correlate with systemic inflammatory burden, we analyzed its levels before and during NC as well as prior to RC. Results: The trend of change in NLR was significantly different between responders and non-responders (p=0.039), the former exhibiting a sustained decrease in NLR throughout chemotherapy up until RC, and the latter exhibiting a transient decrease in NLR by mid-NC, followed by an increase to above baseline. One miRNA was significantly lower in responders than in non-responders (q value=0.048, corrected for multiple comparisons), and five miRNAs with the identical seed sequence (thus potentially targeting the same mRNAs) were also all lower in responders, one with borderline significance (q value=0.1, corrected). Conclusions: These findings suggest that chemo-sensitivity of MIBC is determined by both inherent molecular characteristics as well as the immune/inflammatory system, and raises the question whether the response to NC could be enhanced by decreasing the systemic inflammatory burden. We will corroborate these results in larger pts cohorts and search for potential targets of these miRNAs. We also plan to initiate a prospective multi-center clinical trial in which both intra-tumoral and circulating miRNAs, as well as micro-environment/systemic inflammatory markers, will be monitored and assessed in order to establish predictive factors for pCR with NC. Citation Format: Raya Leibowitz-Amit, Jo-An Seah, Raanan Berger, Srikala S. Sridhar. Defining molecular and laboratory predictive biomarkers of response to cisplatin-based neoadjuvant chemotherapy (NC) in muscle-invasive bladder cancer (MIBC) - preliminary results and future plans. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 909. doi:10.1158/1538-7445.AM2014-909
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 | 0,002 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,000 | 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) | 0,001 | 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 ».