Clinical outcomes of sorafenib treatment in Child-Pugh B hepatocellular carcinoma patients: a retrospective single-center study

Öz

Aim: Hepatocellular carcinoma (HCC) is a leading cause of liver-related mortality, particularly in patients with cirrhosis. Sorafenib is one of the primary systemic therapies for advanced HCC. This study aimed to evaluate the clinical outcomes and prognostic factors associated with sorafenib treatment in this patient population. Material and Methods: This retrospective, single-center study included 28 patients with Child-Pugh B HCC who were treated with sorafenib. Patient characteristics, overall survival (OS), and progression-free survival (PFS) were analyzed. Kaplan-Meier survival analysis and Cox regression were used to assess prognostic factors, including transarterial chemoembolization (TACE), transarterial radioembolization (TARE), and tumor size. Results: Among the 28 patients, 85.7% were male and 89.3% had cirrhosis. Biopsy was performed in 64.3% of cases, and extrahepatic spread was observed in only 3.6%. Tumor size exceeded 5 cm in 67.9% of patients. Disease control was achieved in 57.1% with stable disease (SD), 10.7% showed partial response (PR), and 32.1% experienced progressive disease (PD). Median OS and PFS were 8.1 and 5.9 months, respectively. Cox regression analysis did not identify TACE, TARE, or tumor size as statistically significant prognostic factors. Conclusion: Sorafenib led to disease stabilization in over half of the patients, although one-third experienced disease progression. Compared to the SHARP and Asia-Pacific trials, our study yielded different outcomes, likely due to the exclusive inclusion of patients with Child-Pugh B score of 7. These findings underscore the need for improved patient selection, potential combination therapies, and the identification of predictive biomarkers to enhance treatment efficacy.

Anahtar Kelimeler

• Hepatocellular Carcinoma
• Sorafenib
• Child-B

Destekleyen Kurum

The authors received no financial support for the research and/or authorship of this article.

Etik Beyan

This study was approved by Gülhane Training and Research Hospital Ethics Committee with protocol number 2024/506

Child-Pugh B hepatoselüler karsinom hastalarında sorafenib tedavisinin klinik sonuçları ve prognostik faktörleri: retrospektif tek merkezli bir çalışma

Öz

Amaç: Hepatoselüler karsinom (HCC), özellikle sirozu bulunan hastalarda karaciğere bağlı mortalitenin başlıca nedenlerinden biridir. Sorafenib, ileri evre HCC tedavisinde kullanılan birincil sistemik ajanlardan biridir. Bu çalışma, Sorafenib tedavisi uygulanan hastalarda klinik sonuçları ve prognostik faktörleri değerlendirmeyi amaçlamaktadır. Gereç ve Yöntemler: Bu retrospektif, tek merkezli çalışmaya, Sorafenib ile tedavi edilen 28 Child-Pugh B HCC hastası dahil edilmiştir. Hastaların demografik ve klinik özellikleri, genel sağkalım (OS) ve progresyonsuz sağkalım (PFS) değerlendirilmiştir. Kaplan-Meier sağkalım analizleri ve Cox regresyon testleri ile transarteryel kemoembolizasyon (TACE), transarteryel radyoembolizasyon (TARE) ve tümör boyutu gibi olası prognostik faktörler analiz edilmiştir. Bulgular: Çalışmaya dahil edilen 28 hastanın %85,7’si erkek ve %89,3’ü sirozlu olup, %64,3’üne biyopsi yapılmıştır. Ekstrahepatik yayılım %3,6 oranında saptanmıştır. Hastaların %67,9’unda tümör boyutu 5 cm’nin üzerindedir. Sorafenib tedavisi sonrası hastaların %57,1’inde stabil hastalık (SD), %10,7’sinde kısmi yanıt (PR), %32,1’inde ise progresyon (PD) gözlenmiştir. Ortanca OS 8,1 ay, PFS ise 5,9 ay olarak hesaplanmıştır. Cox regresyon analizinde TACE, TARE ve tümör boyutunun sağkalım üzerinde anlamlı etkisi bulunmamıştır. Sonuç: Sorafenib tedavisi, hastaların çoğunda hastalığın stabil seyretmesini sağlamış olmakla birlikte, önemli bir hasta grubunda progresyon gelişmiştir. Bu durum, hasta seçiminin daha dikkatli yapılması ve kombine tedavi stratejilerinin değerlendirilmesi gerektiğini göstermektedir. SHARP ve Asya-Pasifik çalışmalarıyla karşılaştırıldığında farklı sonuçlar elde edilmesinin nedeni, bu çalışmaya yalnızca Child-Pugh B (puan 7) hastalarının dahil edilmesidir. Bulgular, tedavi stratejilerinin optimize edilmesi ve prognostik biyobelirteçlerin belirlenmesinin önemini vurgulamaktadır.

Anahtar Kelimeler

• hepatosellür kanser
• sorafenib
• child-b

Kaynakça

1. McGlynn KA, Petrick JL, El-Serag HB. Epidemiology of Hepatocellular Carcinoma. Hepatology 2021; 73: 4-13.
2. Zhang BH, Yang BH, Tang ZY. Randomized controlled trial of screening for hepatocellular carcinoma. J Cancer Res Clin Oncol 2004; 130: 417-22.
3. Takayama T, Makuuchi M, Hirohashi S, Sakamoto M, Yamamoto J, Shimada K et al. Early hepatocellular carcinoma as an entity with a high rate of surgical cure. Hepatology 1998; 28: 1241-6.
4. Kudo M, Imanaka K, Chida N, Nakachi K, Tak WY, Takayama T et al. Phase III study of sorafenib after transarterial chemoembolisation in Japanese and Korean patients with unresectable hepatocellular carcinoma. Eur J Cancer 2011; 47: 2117-27.
5. Liu L, Cao Y, Chen C, Zhang X, McNabola A, Wilkie D et al. Sorafenib blocks the RAF/MEK/ERK pathway, inhibits tumor angiogenesis, and induces tumor cell apoptosis in hepatocellular carcinoma model PLC/PRF/5. Cancer Res 2006; 66: 11851-8.
6. Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 2008; 359: 378-90.
7. Cheng AL, Kang YK, Chen Z, Tsao CJ, Qin S, Kim JS et al. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol 2009; 10: 25-34.
8. Pressiani T, Boni C, Rimassa L, Labianca R, Fagiuoli S, Salvagni S et al. Sorafenib in patients with Child-Pugh class A and B advanced hepatocellular carcinoma: a prospective feasibility analysis. Ann Oncol 2013; 24: 406-11.

9. Nakano M, Tanaka M, Kuromatsu R, Nagamatsu H, Tajiri N, Satani M et al. Sorafenib for the treatment of advanced hepatocellular carcinoma with extrahepatic metastasis: a prospective multicenter cohort study. Cancer Med 2015; 4: 1836-43.
10. Geschwind JF, Gholam PM, Goldenberg A, Mantry P, Martin RC, Piperdi B et al. Use of Transarterial Chemoembolization (TACE) and Sorafenib in Patients with Unresectable Hepatocellular Carcinoma: US Regional Analysis of the GIDEON Registry. Liver Cancer 2016; 5: 37-46.
11. Park JW, Kim YJ, Kim DY, Bae SH, Paik SW, Lee YJ et al. Sorafenib with or without concurrent transarterial chemoembolization in patients with advanced hepatocellular carcinoma: The phase III STAH trial. J Hepatol 2019; 70: 684-91.
12. Ricke J, Klümpen HJ, Amthauer H, Bargellini I, Bartenstein P, de Toni EN et al. Impact of combined selective internal radiation therapy and sorafenib on survival in advanced hepatocellular carcinoma. J Hepatol 2019; 71: 1164-74.