Real-World Outcomes of Irinotecan–Bevacizumab Therapy in Recurrent Brain Tumors: A Retrospective Cohort Study

Abstract

Abstract Aim: Although the irinotecan–bevacizumab (IB) combination is a frequently used treatment option in recurrent brain tumors, clinical benefit shows heterogeneity among patient subgroups. This study aimed to evaluate clinical and prognostic factors associated with early-stage mortality and overall survival (OS) in patients receiving IB treatment. Material and Methods: Seventy-eight brain tumor patients who received IB treatment between 2015 and 2023 were retrospectively evaluated. Patients with complete clinical and radiological data were included in the study. The demographic, clinical, and pathological characteristics of the patients were recorded. The timing of the initiation of IB therapy was categorized according to whether it was started at the first recurrence or at the second and subsequent recurrences. Factors associated with early-stage mortality (≤6 months) were determined using log-linear regression analysis, while independent prognostic factors affecting GSK were determined using the Cox proportional hazards regression model. Results: The mean age of patients was 53.01±12.78 years, and the mean follow-up period was 9.47 months. The mortality rate within the first 6 months was determined to be 44.9%. Early-stage mortality was found to be significantly associated with multilobular tumor localization (p=0.037) and initiation of IB therapy at ≥2nd stage (p=0.036). In the log-linear regression analysis, the probability of survival beyond 6 months was 5.05 times lower (RR=0.198, 95% CI: 0.054-0.735) in multilobular localization, while in those who started IB at ≥2nd node, it was 4.40 times lower (RR=0.227, 95% CI: 0.069-0.748). In the multivariate Cox regression analysis, starting IB at ≥2nd line (HR: 2.35, 95% CI: 1.09-5.07, p=0.029), the presence of IDH mutation (HR: 1.98, 95% CI: 1.09-3.58, p=0.025), and age (HR: 1.03, 95% CI: 1.01-1.05, p=0.015) were identified as independent prognostic factors for GSK. Conclusion: This retrospective cohort study based on real-world data demonstrates that the clinical benefit of the IB combination shows significant heterogeneity across patient subgroups. Multilobar tumor location and initiation of IB therapy in the late stages of recurrence are associated with early mortality and poorer survival. Our findings emphasize that IB therapy in recurrent brain tumors should be administered in a personalized manner, considering patient selection and treatment sequence, rather than as a routine approach.

Keywords

• Glioblastoma multiforme
• brain tumors
• bevacizumab
• irinotecan
• overall survival

Nüks Beyin Tümörlerinde İrinotekan–Bevacizumab Tedavisinin Gerçek Yaşam Sonuçları: Retrospektif Bir Kohort Çalışması

Öz

Özet Amaç: Nüks beyin tümörlerinde irinotekan–bevacizumab (İB) kombinasyonu sıklıkla kullanılan bir tedavi seçeneği olmakla birlikte, klinik fayda hasta alt grupları arasında heterojenlik göstermektedir. Bu çalışmada, İB tedavisi alan hastalarda erken dönem mortalite ve genel sağkalım (GSK) ile ilişkili klinik ve prognostik faktörlerin değerlendirilmesi amaçlanmıştır. Materyal-Metod: 2015-2023 yılları arasında İB tedavisi alan 78 beyin tümörü hastası retrospektif olarak değerlendirildi. Klinik ve radyolojik verileri eksiksiz olan hastalar çalışmaya dahil edildi. Hastaların demografik, klinik ve patolojik özellikleri kaydedildi. İB tedavisinin başlama zamanı birinci nükste veya ikinci ve daha sonraki nükslerde başlanmasına göre kategorize edildi. Erken dönem mortalite (≤6 ay) ile ilişkili faktörler log-lineer regresyon analizi ile, GSK'yı etkileyen bağımsız prognostik faktörler ise Cox orantısal risk regresyon modeli ile belirlendi. Bulgular: Hastaların yaş ortalaması 53.01±12.78 yıl, ortalama takip süresi 9.47 aydı. İlk 6 ay içinde mortalite oranı %44.9 olarak saptandı. Erken dönem mortalite, multilobüler tümör lokalizasyonu (p=0.037) ve İB tedavisinin ≥2. nükste başlanması (p=0.036) ile anlamlı ilişkili bulundu. Log-lineer regresyon analizinde multilobüler lokalizasyonda 6 aydan uzun sağkalım olasılığı 5.05 kat (RR=0.198, %95 GA: 0.054-0.735), ≥2. nükste İB başlananlarda ise 4.40 kat (RR=0.227, %95 GA: 0.069-0.748) daha düşük saptandı. Çok değişkenli Cox regresyon analizinde İB'nin ≥2. nükste başlanması (HR: 2.35, %95 GA: 1.09-5.07, p=0.029), İDH mutasyon varlığı (HR: 1.98, %95 GA: 1.09-3.58, p=0.025) ve yaş (HR: 1.03, %95 GA: 1.01-1.05, p=0.015) GSK açısından bağımsız prognostik faktörler olarak belirlendi. Sonuç: Bu gerçek yaşam verilerine dayalı retrospektif kohort çalışması, İB kombinasyonunun klinik faydasının hasta alt gruplarına göre belirgin heterojenlik gösterdiğini ortaya koymaktadır. Multilobüler tümör yerleşimi ve İB tedavisinin geç nüks basamaklarında başlanması, erken mortalite ve daha kötü sağkalım ile ilişkilidir. Bulgularımız, nüks beyin tümörlerinde İB tedavisinin rutin bir yaklaşım olarak değil, hasta seçimi ve tedavi hattı dikkate alınarak bireyselleştirilmiş biçimde uygulanması gerektiğini vurgulamaktadır.

Anahtar Kelimeler

• Glioblastoma multiforme
• bevacizumab
• irinotecan

Kaynakça

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