Erişkin diffüz gliomlarda Dünya Sağlık Örgütü derecesinin ötesinde izositrat dehidrogenaz durumu ve O⁶-Metilguanin-DNA metiltransferaz promotör metilasyonunun artımsal prognostik değeri: Gerçek yaşam kohort çalışması

Öz

Amaç: Erişkin diffüz gliomlarda prognostik değerlendirme giderek histolojik derecelendirme ile rutin olarak erişilebilen moleküler testlerin birlikte kullanımına dayanmaktadır. Bu çalışmada, izositrat dehidrogenaz (IDH) durumu ile O⁶-metilguanin-DNA metiltransferaz (MGMT) promotör metilasyonunun, klinik değişkenler ve Dünya Sağlık Örgütü (DSÖ) derecesinin ötesindeki artımsal prognostik katkısı değerlendirildi. Gereç ve Yöntemler: 2017–2022 yılları arasında cerrahi uygulanan 82 erişkin hastayı içeren retrospektif tek merkezli bir kohort çalışması gerçekleştirildi. Klinik ve cerrahi değişkenleri içeren model, bu değişkenlere DSÖ derecesinin eklendiği model ve moleküler belirteçlerin de dahil edildiği tam model olmak üzere önceden tanımlanmış üç iç içe Cox regresyon modeli karşılaştırıldı. Ayırt edicilik, kalibrasyon, yeniden sınıflandırma, bootstrap optimizm düzeltmesi ve IDH-vahşi tip tümörlerle sınırlı önceden belirlenmiş alt grup analizi değerlendirildi. Bulgular: Görünen uyum indeksi 0,738’den 0,878’e ve 0,885’e yükselirken, optimizm düzeltilmiş değerler sırasıyla 0,701, 0,829 ve 0,834 olarak bulundu. DSÖ derecesi ayırt edicilikteki temel iyileşmeyi sağladı. DSÖ derecesine ek olarak IDH ve MGMT’nin dahil edilmesi yalnızca küçük ve istatistiksel olarak belirsiz bir artış sağladı. IDH-vahşi tip durumu en güçlü olumsuz moleküler özellik olarak kalırken, MGMT metilasyonu için ne karma kohortta ne de IDH-vahşi tip alt grubunda bağımsız prognostik ilişki gösterilemedi. Sonuç: Bu gerçek yaşam kohortunda, DSÖ derecesi ve IDH durumu temel prognostik çerçeveyi oluştururken, MGMT metilasyonunun başlangıç risk ayrımına ek katkısı belirsiz kalmıştır. Bu bulgular, kapsamlı moleküler profillemenin her zaman erişilebilir olmadığı kaynakları değişken sağlık sistemlerinde özellikle önem taşımaktadır.

Anahtar Kelimeler

• Beyin neoplazmları
• diffüz gliom
• izositrat dehidrogenaz
• O⁶-Metilguanin-DNA metiltransferaz
• prognoz

Incremental prognostic value of isocitrate dehydrogenase status and O⁶-Methylguanine-DNA methyltransferase promoter methylation beyond World Health Organization grade in adult diffuse glioma: A real-world cohort study

Öz

Aim: Prognostic counseling in adult diffuse glioma increasingly combines histologic grading with routinely available molecular testing. We assessed the incremental prognostic contribution of isocitrate dehydrogenase (IDH) status and O⁶-methylguanine-DNA methyltransferase (MGMT) promoter methylation beyond clinical variables and World Health Organization (WHO) grade in routine neuro-oncology practice. Material and Methods: We conducted a retrospective single-center cohort study of 82 adults who underwent surgery between 2017 and 2022. Three prespecified nested Cox models compared clinical and surgical variables alone, the same variables plus grade, and the full model plus molecular markers. Discrimination, calibration, reclassification, bootstrap optimism correction, and a prespecified subgroup analysis restricted to IDH-wildtype tumors were evaluated. Results: Apparent concordance improved from 0.738 to 0.878 to 0.885, with optimism-corrected values of 0.701, 0.829, and 0.834. WHO grade provided the main improvement in discrimination. Adding IDH and MGMT beyond grade yielded only a small and statistically uncertain increase. IDH-wildtype status remained the dominant adverse molecular feature, whereas no independent prognostic association of MGMT methylation was detected in either the mixed cohort or the IDH-wildtype subgroup. Conclusion: In this real-world cohort, grade and IDH status formed the principal prognostic framework, whereas the additional contribution of MGMT methylation to baseline risk discrimination remained uncertain. These findings are most relevant to resource-variable settings in which comprehensive molecular profiling is not uniformly available.

Anahtar Kelimeler

• Brain neoplasms
• diffuse glioma
• isocitrate dehydrogenase
• O(6)-Methylguanine-DNA methyltransferase
• prognosis

Kaynakça

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