Validation and next-generation update of a DNA methylation-based recurrence predictor for meningioma: A multicenter prospective study.
Обработка статьи · этапы, ошибки и управление
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Landry Alexander P, Wang Justin Z, Patil Vikas, Gui Chloe, Mamatjan Yasin, Patel Zeel, Yakubov Rebecca, Kaloti Ramneet, Habibi Parnian, Wilson Mark, Ajisebutu Andrew, Ellenbogen Yosef, Wei Qingxia, Singh Olivia, Sosa Julio, Mansouri Sheila, Wilson Christopher, Cohen-Gadol Aaron A, Virtanen Piiamaria, Burket Noah, Blackwell Matthew, Koenig Jenna, Alfonso Anthony, Davis Joseph, Zaazoue Mohamed A, Tabatabai Ghazaleh, Tatagiba Marcos, Behling Felix, Barnholtz-Sloan Jill S, Sloan Andrew E, Chotai Silky, Chambless Lola B, Mansouri Alireza, Ehret Felix, Capper David, Tsang Derek S, Aldape Kenneth, Gao Andrew, International Consortium on Meningiomas (ICOM), Nassiri Farshad, Zadeh Gelareh
Аннотация
METHODS: Genome-wide methylation profiles were generated with the Illumina EPICArray. The performance of our next-generation predictor was compared with our original model and standard-of-care 2021 WHO grade using time-dependent receiver operating characteristic curves. An nomogram was generated by incorporating our methylation predictor with WHO grade and the extent of resection.
RESULTS: A total of 1347 meningioma cases were utilized in the study, including 469 prospective cases from 3 institutions and an external cohort of 100 WHO grade 2 cases for model validation. Both the original and next-generation models significantly outperform the 2021 WHO grade in predicting early postoperative recurrence. Dichotomizing patients into grade-specific risk subgroups was predictive of outcomes within both WHO grades 1 and 2 tumors (P < .05), whereas all WHO grade 3 tumors were considered high-risk. Multivariable Cox regression demonstrated the benefit of adjuvant radiotherapy (RT) in high-risk cases specifically, reinforcing its informative role in clinical decision-making. Finally, our next-generation predictor contains nearly 10-fold fewer features than the original model, allowing for targeted arrays.
CONCLUSIONS: This next-generation DNA methylation-based meningioma outcome predictor significantly outperforms the 2021 WHO grading in predicting time to recurrence. We make this available as a point-and-click tool that will improve prognostication, inform patient selection for RT, and allow for molecularly stratified clinical trials.