Abstract P1-01-01: Analytical validation of a standardized scoring protocol for Ki67: Phase-3 of an international multicenter collaboration
Notice bibliographique
Résumé
Abstract Aims: (i) To determine if between-pathologist agreement for Ki67 is adequate for clinical application, following a standardised scoring protocol. (ii) To compare between-pathologist agreement of scoring hot-spots vs a global method averaging Ki67 across each section. Background: The nuclear proliferation biomarker Ki67 has multiple potential roles in breast cancer, including aiding decisions based on prognosis, but has unacceptable between-laboratory variability. The International Ki67 Working Group has undertaken a systematic program to determine whether Ki67 measurement can be analytically validated and standardized across labs. In phase 1 variability in visual interpretation was the most important source of variability. Phase 2 showed that significant improvements in agreement could be achieved when scoring the same tumors on tissue microarrays by following clearly defined scoring methods. We now assess whether acceptable performance can be achieved on core-cut biopsies using a standardised method. Methods: Three adjacent sections from each of 30 primary ER+ breast cancers were centrally stained for Ki67 to assemble three sets of 30 stained tumor sections, circulated around 22 laboratories in 11 countries. Ki67 was scored by 2 methods by all labs: (a) global: 4 fields of 100 cells each were selected to represent any heterogeneity (b) hotspot: the field with highest Ki67 staining percentage was selected and 500 cells scored. Ki67 scores were log2-transformed for statistical analyses and back-transformed for presentation. The primary objective was to assess if either method could achieve an intraclass correlation coefficient (ICC) significantly greater than 0.8, considered substantial to almost-perfect agreement. Secondary objectives were to assess which method had highest observed ICC and to assess whether pathologists identified the same "hotspots". Results: The ICC for the global method was 0.88 (95%CI: 0.81-0.93) and therefore met the prespecified success criterion. The ICC for the hotspot method was 0.84 (95%CI: 0.77-0.92) and therefore had a CI which extended below the success criterion. Across the 22 labs, geometric mean value of the 30 scores ranged from 14.4 to 27.9 for the global method and from 17.4 to 40.2 for the hotspot method. The overall mean (95% CI) of these values was 19.8 (18.5-21.3) and 26.4 (24.6-28.3), respectively. Visually, there was moderately strong agreement in location of selected hotspot in the core-cuts across laboratories. The impact of variability of the Ki67 scores for estimating prognosis using the integrated IHC4 + clinical treatment score will be assessed. After selection of the areas to score, the median times for cell counting were 3 and 4 minutes for the global and hotspot methods, respectively. Conclusions: The global method met the prespecified criterion of success; it should now be evaluated for clinical validity in appropriate cohorts of samples. The hotspot method showed slightly less agreement between labs. The time taken for scoring is practical using counting software we are making publicly available. Establishment of external quality assessment schemes is likely to improve the agreement between labs further. (Supported by a grant from the Breast Cancer Research Foundation). Citation Format: Dowsett M, Leung SCY, Zabaglo L, Arun I, Badve SS, Bane AL, Bartlett JMS, Borgquist S, Chang MC, Dodson A, Enos RA, Fineberg S, Focke CM, Gao D, Gown AM, Grabau D, Gutierrez C, Hugh JC, Kos Z, Lænkholm A-V, Lin M-G, Mastropasqua MG, Moriya T, Nofech-Mozes S, Osborne CK, Penault-Llorca FM, Piper T, Sakatani T, Salgado R, Starczynski J, Viale G, Hayes DF, McShane LM, Nielsen TO. Analytical validation of a standardized scoring protocol for Ki67: Phase-3 of an international multicenter collaboration. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-01-01.
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 | 0,229 | 0,133 |
| Méta-épidémiologie (sens strict) | 0,003 | 0,001 |
| Méta-épidémiologie (sens large) | 0,002 | 0,003 |
| Bibliométrie | 0,002 | 0,003 |
| Études des sciences et des technologies | 0,004 | 0,004 |
| Communication savante | 0,003 | 0,002 |
| Science ouverte | 0,006 | 0,006 |
| Intégrité de la recherche | 0,004 | 0,004 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,006 | 0,004 |
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 ».