Abstract P3-02-08: Detection of Circulating Tumor Cells Prior to Autologous Stem Cell Transplantation Is Predictive of Shorter Progression Free Survival in Metastatic Breast Cancer
Notice bibliographique
Résumé
Abstract Background: High dose chemotherapy (HDCT) in patients with metastatic breast cancer (MBC) followed by autologous hematopoietic stem cell transplantation (ASCT) offers high complete response rates compared to standard therapy. However, the bone marrow (BM) is a reservoir for disseminated tumor cells (DTC) and the inadvertent recruitment from BM of DTC, cancer stem cells (CSC), and non-leukocytes undergoing epithelial mesenchymal transition (EMT) during the CD34+ hematopoietic progenitor cell (HPC) mobilization could adversely impact clinical outcome. As epithelial cells in EMT possess stem-like properties, we evaluated the apheresis product for CSC and expression of EMT to ascertain if they had an impact on clinical outcome in the transplant setting. Methods: Twenty-one MBC patients treated with HDCT underwent apheresis to harvest HPC and subsequent ASCT. A peripheral blood (PB) sample was collected before apheresis (baseline) and again after ASCT (post-treatment) for enumeration of CTC by CellSearch (Veridex, LLC, Raritan, NJ). Furthermore, mononuclear cells (MNC) were isolated from 19 HPC-depleted apheresis products. An aliquot of MNC was further depleted of CD45+ leukocytes and then interrogated for expression of the EMT-inducing transcription factor TWIST1 by quantitative RT-PCR. Another aliquot of each MNC sample was analyzed by 6-color flow cytometry for the presence of CSC (CD326+CD44hiCD24lo) and with ALDH-1 activity (Aldefluor+ CSC), measured by Aldefluor (StemCell Technologies, Vancouver, BC). The logrank test was used to determine if progression-free survival (PFS) was associated with the number of CTCs at baseline and post-ASCT; baseline percentages of CSC and Aldefluor+ CSC; and expression of TWIST1 by non-leukocytes. Results: The median follow-up was 17 months with a median time to disease progression of 9.4 months. The median overall survival was 12.9 months. At follow-up, 7 patients had non-progressive disease (NPD) and 12 had progressive disease (PD). CTCs were detected in 6 pts (range, 1-115) at baseline and in 9 patients post-ASCT (range, 1-131). PD patients had statistically significantly higher % of CD326+ epithelial cells but not CSC within the HPC-depleted apheresis products when compared with identical apheresis products of NPD patients (0.20% vs. 0.11%; P=0.033). Aldefluor test was performed in 12 of 19 samples. Four samples with TWIST1 transcripts contained a significantly higher % of CD326+ Aldefluor+ CSC than the samples without TWIST (9.58% vs. 1.58%; P =0.007). The presence of CTC at baseline was associated with shorter progression-free survival (PFS) (P =0.027). However, PFS was not associated with the TWIST1 expression or with % of Aldefluor+ CSC detected in apheresis products. Conclusion: Baseline CTC number was predictive of PFS. HDCT followed by ASCT did not reduce the number of CTC in patients with MBC. Finally, leukocyte-depleted apheresis products that expressed EMT-inducing TWIST1 transcripts contained higher % CSCs suggesting a strong linkage between circulating epithelial cells undergoing EMT and the production of cancer stem cells. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-02-08.
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 | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,005 | 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 ».