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Early postoperative treatment versus initial observation in CNS WHO grade 2 and 3 oligodendroglioma: clinical outcomes and DNA methylation patterns

ABSTRACT: In the past decades, ample evidence has shown that combined radio-chemotherapy is superior to either radiotherapy or chemotherapy alone in oligodendroglioma. However, the survival benefit comes at the cost of immediate and long-term toxicities. Therefore, deferring postoperative therapy until progression may be a valid option to delay treatment-related side effects. Still, systematic data and reliable predictive biomarkers are limited. In this large retrospective series of oligodendroglioma cases, we could show that early postoperative treatment is not associated with improved PFS and OS while correcting for baseline differences between both groups. In addition, we performed whole-genome DNA methylation analyses and observed a predictive role of certain methylation patterns independent from MGMT promoter methylation status, extent of resection and CNS WHO grade. The results of this real-life study may serve as a benchmark for future trial planning in oligodendroglioma, and further studies should evaluate the predictive value of DNA methylation profiles.

ORGANISM(S): Homo sapiens

PROVIDER: GSE209579 | GEO | 2022/08/22

REPOSITORIES: GEO

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Project description:Treatment options and reliable predictive marker to determine patients at risk to develop postoperative LD and to define the optimal time point of liver resection are limited. Accordingly, there is an urgent need for an easily assessable preoperative test to predict postoperative liver function recovery, specifically as current markers are often expensive, time consuming and sometimes invasive. Emerging evidence suggests that microRNA (miRNA) signatures represent potent diagnostic, prognostic and treatment response biomarkers for several diseases. Using next-generation sequencing as an unbiased systematic approach 554 miRNAs were detected in preoperative plasma of 21 patients suffering from postoperative LD after liver resection and 27 matched controls. Subsequently, we identified a miRNA signature - consisting of miRNAs 151a-5p, 192-5p and 122-5p - that highly correlated with patients developing postoperative LD after liver resection. The predictive potential for postoperative LD was subsequently confirmed using real-time PCR in an independent validation cohort of 98 patients. Ultimately, a regression model of the two miRNA ratios 151a-5p to 192-5p and 122-5p to 151a-5p was found to reliably predict postoperative LD, severe morbidity, prolonged intensive care unit and hospital stay and even mortality prior to surgery with a remarkable accuracy, thereby outperforming established markers of postoperative LD. Ultimately, we documented that miRNA ratios closely followed liver function recovery after partial hepatectomy. Conclusion: Given the clinical relevance of predicting potentially fatal postoperative clinical outcome after liver resection, our data demonstrate the clinical utility of a novel miRNA-based biomarker to support the selection of patients undergoing partial hepatectomy. The dynamical changes during liver function recovery indicate a possible role in tailoring the optimal time point of surgery to each individual patient. Thereby, our data might help to tailor surgical strategies to the specific risk profile of individual patients.

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Early postoperative treatment versus initial observation in CNS WHO grade 2 and 3 oligodendroglioma: clinical outcomes and DNA methylation patterns

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