Gestasyonel Trofoblastik Hastalıklara Güncel Yaklaşım
Özet
Gestasyonel trofoblastik hastalıklar (GTH), gebelik sonrası trofoblastik dokunun anormal proliferasyonu ile karakterize, benign ve malign formları kapsayan heterojen bir hastalık grubudur. Bu grup; komplet mol hidatiform (KMH), parsiyel mol hidatiform (PMH), invaziv mol, koryokarsinom, plasental yerleşimli trofoblastik tümör (PSTT) ve epiteloid trofoblastik tümör (ETT)’ü içerir. GTH, gebeliğe özgü neoplastik hastalıklar arasında en yüksek tedavi başarısına sahip olup, erken tanı ve uygun izlemle %95’in üzerinde sağkalım oranına ulaşılmaktadır. GTH’nin insidansı bölgesel farklılıklar gösterir. Türkiye’de tahmini oran 1000 gebelikte 1–1,5’tir. Risk faktörleri arasında ileri anne yaşı (>40 yıl), önceki mol öyküsü, düşük sosyoekonomik durum ve A (anne) – O (baba) kan grubu uyumsuzluğu sayılabilir. Komplet mol, genellikle maternal kromozomların kaybı ve paternal dizomi sonucu diploid (46XX veya 46XY) genotip ile oluşur. Parsiyel mol ise triploid (69XXY) yapıda olup, embriyonik kalıntı içerebilir. Klinik olarak vajinal kanama, uterusun gebelik haftasına göre büyük olması, hipertiroidizm veya preeklampsi benzeri semptomlar ve yüksek β-hCG düzeyleriyle ortaya çıkar. Ultrasonografide “kar fırtınası” görünümü komplet molü, embriyo içeren kistik yapı ise parsiyel molü düşündürür. Tanı β-hCG ölçümü, pelvik ultrasonografi ve histopatolojik inceleme ile konur. GTH’nin malign formları, yani gestasyonel trofoblastik neoplaziler (GTN); invaziv mol, koryokarsinom, PSTT ve ETT’dir. Bu tümörler uterusla sınırlı kalabileceği gibi uzak metastazlar da yapabilir. Akciğer en sık metastaz yeridir (%80), bunu vajina, beyin ve karaciğer izler. FIGO evrelemesi GTN’yi yayılım düzeyine göre dört evreye ayırırken, WHO skorlama sistemi (yaş, gebelik tipi, β-hCG düzeyi, metastaz sayısı vb.) prognozu belirler. Skor ≤6 düşük risk, ≥7 yüksek risk olarak kabul edilir. Tedavide evre ve risk durumuna göre yaklaşım değişir. Düşük riskli GTN olgularında tek ajanlı kemoterapi (metotreksat veya aktinomisin D) ile tam yanıt oranı %98’in üzerindedir. Yüksek riskli olgularda çok ajanlı EMA/CO (etoposid, metotreksat, aktinomisin D, siklofosfamid, vinkristin) protokolü uygulanır. PSTT ve ETT kemoterapiye dirençli olabildiğinden primer tedavi cerrahi (histerektomi) olmalıdır. Son yıllarda, dirençli ve nüks olgularda immünoterapi (PD-1 inhibitörleri; örn. pembrolizumab) kullanımına yönelik başarılı sonuçlar bildirilmiştir. Ayrıca trofoblastik hücre dışı DNA (cfDNA) ve yapay zekâ destekli ultrasonografi uygulamaları, erken tanı ve nüks izlemi için umut verici gelişmelerdir. Tedavi sonrası β-hCG düzeyleri haftalık olarak negatifleşene kadar izlenmeli, ardından düşük risklilerde 6 ay, yüksek risklilerde 12 ay süreyle aylık kontroller yapılmalıdır. Bu dönemde yeni gebelik önerilmez. Sonuç olarak, gestasyonel trofoblastik hastalıklar ve neoplaziler erken tanı, uygun evreleme ve etkin tedavi ile tamamen kür sağlanabilen hastalık grubudur. Modern kemoterapi ve immünoterapi yaklaşımlarıyla, özellikle yüksek riskli ve metastatik olgularda bile yaşam oranları dramatik biçimde iyileşmiştir.
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