Kardiaözofageal Kanserlerde Neoadjuvan Tedavinin Yeri
Özet
Özofagus kanseri, yüksek ölüm oranlarıyla seyreden ve dünya genelinde önemli bir halk sağlığı problemi olan kötü prognozlu bir hastalıktır. Hastalığın tedavisinde ana yöntem cerrahi müdahale olmasına rağmen, tek başına cerrahi uygulanan durumlarda uzun dönem sağkalım sonuçları beklenenin altındadır. Bu durum, cerrahi öncesi evreyi küçülterek tam rezeksiyon şansını artırmayı ve mikrometastazları önlemeyi amaçlayan neoadjuvan (ameliyat öncesi) tedavilerin gerekliliğini ortaya çıkarmıştır. Hastalığın klinik ve radyolojik evrelemesinde Siewert ve Nishi sınıflandırmaları ile AJCC/UICC ve JES gibi TNM sistemleri kullanılmaktadır. Erken evre (T1N0) tümörlerde neoadjuvan tedavi sağkalımı artırmayıp morbiditeyi artırdığı için doğrudan cerrahi önerilirken, lokal ileri evre tümörlerde çoklu yaklaşımlar tercih edilmektedir. Günümüzde neoadjuvan tedavide kemoradyoterapi (CROSS çalışması), kemotherapy (MAGIC, ACCORD, FLOT rejimleri) ve henüz araştırma aşamasında olan immünoterapi (PALACE-1, PERFECT) seçenekleri bulunmaktadır. Siewert tip 3 tümörlerde radyasyon morbiditesinden kaçınmak adına FLOT rejimi ile neoadjuvan kemoterapi ön plana çıkarken, skuamöz hücreli karsinomlarda neoadjuvan kemoradyoterapi belirgin sağkalım avantajı sunmaktadır. Sonuç olarak, tedavi seçimi tümörün histolojik tipine, yayılımına ve hastanın komorbiditelerine göre kişiselleştirilmelidir.
Esophageal cancer is a significant global public health issue with a poor prognosis and high mortality rates, and although surgical intervention remains the primary treatment, long-term survival outcomes for surgery alone are sub-optimal. This limitation has underscored the necessity of neoadjuvant therapies, which aim to downstage the disease, maximize the chances of complete R0 resection, and eradicate micrometastases before surgery. Clinical and radiological staging relies on Siewert and Nishi classifications, alongside AJCC/UICC and JES TNM systems. While early-stage (T1N0) tumors warrant direct surgery because neoadjuvant approaches increase morbidity without improving survival, locally advanced stages benefit from multimodal therapies. Current neoadjuvant strategies include chemoradiotherapy (guided by the CROSS trial), perioperative chemotherapy (such as MAGIC, ACCORD, and the highly effective FLOT regimens), and emerging immunotherapies (investigated in PALACE-1 and PERFECT trials). For Siewert type III tumors, neoadjuvant chemotherapy via the FLOT regimen is preferred to avoid radiation-induced morbidity, whereas squamous cell carcinomas derive a more pronounced survival benefit from neoadjuvant chemoradiotherapy. Consequently, optimal therapeutic selection must be meticulously personalized, factoring in the specific tumor topography, histological type, nodal involvement, and patient-specific comorbidities.
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