Correlation of Clinical Features to DNA Methylation-Based Prognostic Subtypes in Chordoma Patients
Notice bibliographique
Résumé
Background: Chordomas are rare aggressive primary bone cancers affecting the skull-base and spine. Despite standard of care treatment with radical surgical resection and radiotherapy, the overall survival at 10 years is only 40%, with most patients experiencing disease recurrence. Moreover, many experience devastating neurological morbidity that significantly impairs quality of life. Much of the research on chordomas points to a dichotomization in outcomes with some experiencing rapid recurrence and mortality despite maximal treatment, while others experience progression-free survival of up to 10 to 20 years. We have previously identified robust DNA methylation-based prognostic subtypes of chordomas, a poorer performing immune-infiltrated subtype and a better performing cellular subtype. Here, we have aimed to further characterize these prognostic subtypes with an extensively annotated clinical database to potentially identify factors that correlate with each subtype and, therefore, can be used as markers of chordoma subtype. Methods: A total of 68 patients from a multi-institutional 20-year series were identified. These patients’ tumor samples had undergone whole genome DNA methylation profiling on the Illumina EPIC array. Extensive clinical data was extracted for all patients. Baseline clinical features, including clinical features (age, sex, pain, or neurological deficit at presentation, tumor size and diameter, tumor location), treatment details (extent of resection, complications, histological subtype, adjuvant radiotherapy), outcomes parameters (recurrence, metastasis, status of disease control) and imaging parameters (dural invasion, vascularity, soft-tissue extension, bony destruction) were analyzed using chi-squared or Kruskal–Wallis test. Results: Of all the variables tested, age of onset ( p -value = 0.012), location (skull base vs. spine vs. sacral: p -value = 0.0365) and histological subtype (classical vs. chondroid: p -value = 0.0132) were the only significant predictors of subgroup placement; older age, spinal location, and classical histological typing were predictors of immune infiltrated chordoma subtype, which has a poorer clinical performance. Sex, tumor size, degree of neurological deficit upon presentation, treatment experience such as extent of resection, complications or use of radiotherapy did not differ between the two groups. As expected, death from chordoma was significantly different between subtypes ( p -value = 0.0056). Notably, imaging characteristics of the tumor did not correlate with subtype. Conclusion: Overall, there are limited variables that correlate with methylation subtype after thorough assessment of clinical factors, meaning that the newly identified epigenetic chordoma subtypes cannot be reliably identified using clinical or imaging features of the patient and their tumor alone in the absence of molecular data. This is not unexpected as historically it has been very difficult to prognosticate chordomas using clinical factors and further underscores the value of molecular subgroups for this devastating disease. Currently, we are developing a model that utilizes both the DNA methylation subtype of chordoma along with clinical factors that were significant in this analysis to provide comprehensive composite 5-year and 10-year disease-specific survival risk values. We expect that chordoma prognostication using a multifactorial model considering DNA methylation subtype and clinical factors may allow us to most reliable prognosticate patients and thereby best tailor their treatment to their disease. Publication History Article published online: 01 February 2023 © 2023. Thieme. All rights reserved. Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany
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 | 0,002 |
| 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 | 0,000 | 0,000 |
| Communication savante | 0,000 | 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) | 0,002 | 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 ».