Hepatoselüler kanserli hastalarda lokal bölgesel tedaviler ve sorafenib kombinasyonun etkinlik ve güvenilirliği: Tek merkez deneyimi
Yıl 2025,
Cilt: 64 Sayı: 1, 71 - 76, 12.03.2025
Harun Muğlu
,
Erdem Sünger
,
Mehmet Haluk Yücel
,
Maral Martin Mıldanoğlu
,
Ebru Engin Delipoyraz
,
Jamshid Hamdard
,
Hakan Özçelik
,
Özgür Açıkgöz
,
Ahmet Bilici
,
Ebru Karcı
,
Omer Fatih Olmez
,
Özcan Yıldız
,
Cengiz Erol
Öz
Amaç: Hepatoselüler karsinom, dünya genelinde önemli bir sağlık sorunu olan bir karaciğer kanseridir. Çoğu hasta unrezektabl evrede tanı alır. Lokal bölgesel tedaviler ve sorafenib gibi sistemik tedaviler, Hepatoselüler kanser tedavisinde kullanılan önemli yöntemlerdir. Bu çalışmada, Lokal bölgesel tedaviler ve sorafenib kombinasyonunun Hepatoselüler kanser hastalarındaki etkinliği ve güvenilirliği retrospektif olarak araştırılmıştır.
Gereç ve Yöntem: 2018 2023 yılları arasında Medipol Mega Üniversite Hastanesi’nde takip edilen 20 Hepatoselüler kanser tanılı hasta çalışmaya dahil edildi. Hastaların tümüne Lokal bölgesel tedaviler ve sorafenib tedavisi uygulandı. Progresyonsuz sağkalım ve genel sağkalım süreleri, yan etkiler ve prognostik faktörler değerlendirildi.
Bulgular: Kombinasyon tedavi sonrası objektif yanıt oranı %90, hastalık kontrol oranı %95 olarak bulundu. Ortanca progresyonsuz sağkalım 11,1 ay, ortanca genel sağkalım 18,6 ay olarak saptandı. Çok değişkenli analizde, progresyonsuz sağkalım için lokal bölgesel tedavi tipi ve nakil varlığı, genel sağkalım için ise ECOG performans durumu bağımsız prognostik faktörler olarak belirlendi. En sık görülen yan etki dermatolojik yan etkiler oldu.
Sonuç: Çalışmamız, Hepatoselüler Kanser hastalarında Lokal bölgesel tedaviler ve sorafenib kombinasyonunun güvenli ve etkili olabileceğini göstermektedir. Bu kombinasyon, progresyonsuz sağkalım ve genel sağkalım sürelerini uzatabilir. Ancak, bu konuda daha büyük, prospektif çalışmalara ihtiyaç vardır.
Kaynakça
- Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in
2008: GLOBOCAN 2008. International journal of cancer, 2010;127(12):2893-917.
- Njei B, Rotman Y, Ditah I, Lim JK. Emerging trends in hepatocellular carcinoma incidence and mortality.
Hepatology, 2015;61(1):191-9.
- Couri T, Pillai A. Goals and targets for personalized therapy for HCC. Hepatology international, 2019;13:125-
37.
- Llovet JM, Real MI, Montaña X, Planas R, Coll S, Aponte J, et al. Arterial embolisation or chemoembolisation
versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised
controlled trial. The Lancet, 2002;359(9319):1734-9.
- Riaz A, Gates VL, Atassi B, Lewandowski RJ, Mulcahy MF, Ryu RK, et al. Radiation segmentectomy: a novel
approach to increase safety and efficacy of radioembolization. International Journal of Radiation Oncology*
Biology* Physics, 2011;79(1):163-71.
- Ozkan ZG, Poyanli A, Ucar A, Kuyumcu S, Akyuz F, Keskin S, et al. Favorable survival time provided with
radioembolization in hepatocellular carcinoma patients with and without portal vein thrombosis. Cancer
Biotherapy and Radiopharmaceuticals, 2015;30(3):132-8.
- Salem R, Thurston KG. Radioembolization with 90Yttrium microspheres: a state-of-the-art brachytherapy
treatment for primary and secondary liver malignancies: part 1: technical and methodologic considerations.
Journal of vascular and interventional radiology, 2006;17(8):1251-78.
- Niu G, Chen X. Vascular endothelial growth factor as an anti-angiogenic target for cancer therapy. Current
drug targets, 2010;11(8):1000-17.
- Kaseb AO, Morris JS, Hassan MM, Siddiqui AM, Lin E, Xiao L, et al. Clinical and prognostic implications of
plasma insulin-like growth factor-1 and vascular endothelial growth factor in patients with hepatocellular
carcinoma. Journal of clinical oncology, 2011;29(29):3892-9.
- Zhang W, Kim R, Quintini C, Hashimoto K, Fujiki M, Diago T, et al. Prognostic role of plasma vascular
endothelial growth factor in patients with hepatocellular carcinoma undergoing liver transplantation. Liver
Transplantation, 2015;21(1):101-11.
- Labeur TA, Ten Cate DW, Bart Takkenberg R, Azahaf H, van Oijen MG, van Delden OM, et al. Are we SHARP
enough? The importance of adequate patient selection in sorafenib treatment for hepatocellular carcinoma.
Acta Oncologica, 2018;57(11):1467-74.
- Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc J-F, et al. Sorafenib in advanced hepatocellular
carcinoma. New England journal of medicine, 2008;359(4):378-90.
- Dufour J-F, Hoppe H, Heim MH, Helbling B, Maurhofer O, Szucs-Farkas Z, et al. Continuous administration of
sorafenib in combination with transarterial chemoembolization in patients with hepatocellular carcinoma:
results of a phase I study. The oncologist, 2010;15(11):1198-204.
- Chung YH, Han G, Yoon JH, Yang J, Wang J, Shao GL, et al. Interim analysis of START: Study in Asia of the
combination of TACE (transcatheter arterial chemoembolization) with sorafenib in patients with hepatocellular
carcinoma trial. International journal of cancer, 2013;132(10):2448-58.
- Erhardt A, Kolligs F, Dollinger M, Schott E, Wege H, Bitzer M, et al. TACE plus sorafenib for the treatment of
hepatocellular carcinoma: results of the multicenter, phase II SOCRATES trial. Cancer chemotherapy and
pharmacology, 2014;74:947-54.
- Shim JH, Park JW, Kim JH, An M, Kong SY, Nam BH, et al. Association between increment of serum VEGF
level and prognosis after transcatheter arterial chemoembolization in hepatocellular carcinoma patients.
Cancer science, 2008;99(10):2037-44.
- Park J-W, Koh YH, Kim HB, Kim HY, An S, Choi J-I, et al. Phase II study of concurrent transarterial
chemoembolization and sorafenib in patients with unresectable hepatocellular carcinoma. Journal of
hepatology, 2012;56(6):1336-42.
- Kudo M, Imanaka K, Chida N, Nakachi K, Tak W-Y, Takayama T, et al. Phase III study of sorafenib after
transarterial chemoembolisation in Japanese and Korean patients with unresectable hepatocellular
carcinoma. European journal of cancer, 2011;47(14):2117-27.
- Gadaleta C, Mattioli V, Colucci G, Cramarossa A, Lorusso V, Canniello E, et al. Radiofrequency ablation of 40
lung neoplasms: preliminary results. American journal of roentgenology, 2004;183(2):361-8.
- Gadaleta CD, Solbiati L, Mattioli V, Rubini G, Fazio V, Goffredo V, et al. Unresectable lung malignancy:
combination therapy with segmental pulmonary arterial chemoembolization with drug-eluting microspheres
and radiofrequency ablation in 17 patients. Radiology, 2013;267(2):627-37.
Efficacy and safety of combined locoregional therapy and sorafenib in hepatocellular carcinoma: Single center experience
Yıl 2025,
Cilt: 64 Sayı: 1, 71 - 76, 12.03.2025
Harun Muğlu
,
Erdem Sünger
,
Mehmet Haluk Yücel
,
Maral Martin Mıldanoğlu
,
Ebru Engin Delipoyraz
,
Jamshid Hamdard
,
Hakan Özçelik
,
Özgür Açıkgöz
,
Ahmet Bilici
,
Ebru Karcı
,
Omer Fatih Olmez
,
Özcan Yıldız
,
Cengiz Erol
Öz
Aim: Hepatocellular carcinoma represents a significant global health concern, with a substantial proportion of patients presenting at an unresectable stage. Locoregional therapies and systemic agents such as sorafenib have emerged as pivotal modalities in the management of Hepatocellular carcinoma. This retrospective study aimed to evaluate the efficacy and safety of combining Locoregional therapies with sorafenib in patients diagnosed with Hepatocellular carcinoma.
Materials and Methods: A cohort of 20 Hepatocellular carcinoma patients followed at Medipol Mega University Hospital between 2018 and 2023 was retrospectively analyzed. All patients underwent Locoregional therapies in conjunction with sorafenib treatment. Progression free survival and overall survival rates, adverse events, and prognostic factors were assessed.
Results: Upon receiving combination therapy, an objective response rate of 90% and a disease control rate of 95% were observed. Median progression free survival was determined to be 11,1 months, while median overall survival was 18,6 months. Multivariate analysis revealed that Locoregional therapies type and transplantation status were independent prognostic indicators for progression free survival, whereas ECOG performance status was an independent prognostic factor for overall survival. Dermatological adverse events were the most frequently reported.
Conclusion: Our findings suggest that the concurrent administration of Locoregional therapies and sorafenib may offer a safe and effective therapeutic strategy for patients with Hepatocellular carcinoma. This combined approach has the potential to prolong progression free survival and overall survival. However, to definitively establish the clinical benefits of this regimen, larger scale, prospective trials are warranted.
Kaynakça
- Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in
2008: GLOBOCAN 2008. International journal of cancer, 2010;127(12):2893-917.
- Njei B, Rotman Y, Ditah I, Lim JK. Emerging trends in hepatocellular carcinoma incidence and mortality.
Hepatology, 2015;61(1):191-9.
- Couri T, Pillai A. Goals and targets for personalized therapy for HCC. Hepatology international, 2019;13:125-
37.
- Llovet JM, Real MI, Montaña X, Planas R, Coll S, Aponte J, et al. Arterial embolisation or chemoembolisation
versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised
controlled trial. The Lancet, 2002;359(9319):1734-9.
- Riaz A, Gates VL, Atassi B, Lewandowski RJ, Mulcahy MF, Ryu RK, et al. Radiation segmentectomy: a novel
approach to increase safety and efficacy of radioembolization. International Journal of Radiation Oncology*
Biology* Physics, 2011;79(1):163-71.
- Ozkan ZG, Poyanli A, Ucar A, Kuyumcu S, Akyuz F, Keskin S, et al. Favorable survival time provided with
radioembolization in hepatocellular carcinoma patients with and without portal vein thrombosis. Cancer
Biotherapy and Radiopharmaceuticals, 2015;30(3):132-8.
- Salem R, Thurston KG. Radioembolization with 90Yttrium microspheres: a state-of-the-art brachytherapy
treatment for primary and secondary liver malignancies: part 1: technical and methodologic considerations.
Journal of vascular and interventional radiology, 2006;17(8):1251-78.
- Niu G, Chen X. Vascular endothelial growth factor as an anti-angiogenic target for cancer therapy. Current
drug targets, 2010;11(8):1000-17.
- Kaseb AO, Morris JS, Hassan MM, Siddiqui AM, Lin E, Xiao L, et al. Clinical and prognostic implications of
plasma insulin-like growth factor-1 and vascular endothelial growth factor in patients with hepatocellular
carcinoma. Journal of clinical oncology, 2011;29(29):3892-9.
- Zhang W, Kim R, Quintini C, Hashimoto K, Fujiki M, Diago T, et al. Prognostic role of plasma vascular
endothelial growth factor in patients with hepatocellular carcinoma undergoing liver transplantation. Liver
Transplantation, 2015;21(1):101-11.
- Labeur TA, Ten Cate DW, Bart Takkenberg R, Azahaf H, van Oijen MG, van Delden OM, et al. Are we SHARP
enough? The importance of adequate patient selection in sorafenib treatment for hepatocellular carcinoma.
Acta Oncologica, 2018;57(11):1467-74.
- Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc J-F, et al. Sorafenib in advanced hepatocellular
carcinoma. New England journal of medicine, 2008;359(4):378-90.
- Dufour J-F, Hoppe H, Heim MH, Helbling B, Maurhofer O, Szucs-Farkas Z, et al. Continuous administration of
sorafenib in combination with transarterial chemoembolization in patients with hepatocellular carcinoma:
results of a phase I study. The oncologist, 2010;15(11):1198-204.
- Chung YH, Han G, Yoon JH, Yang J, Wang J, Shao GL, et al. Interim analysis of START: Study in Asia of the
combination of TACE (transcatheter arterial chemoembolization) with sorafenib in patients with hepatocellular
carcinoma trial. International journal of cancer, 2013;132(10):2448-58.
- Erhardt A, Kolligs F, Dollinger M, Schott E, Wege H, Bitzer M, et al. TACE plus sorafenib for the treatment of
hepatocellular carcinoma: results of the multicenter, phase II SOCRATES trial. Cancer chemotherapy and
pharmacology, 2014;74:947-54.
- Shim JH, Park JW, Kim JH, An M, Kong SY, Nam BH, et al. Association between increment of serum VEGF
level and prognosis after transcatheter arterial chemoembolization in hepatocellular carcinoma patients.
Cancer science, 2008;99(10):2037-44.
- Park J-W, Koh YH, Kim HB, Kim HY, An S, Choi J-I, et al. Phase II study of concurrent transarterial
chemoembolization and sorafenib in patients with unresectable hepatocellular carcinoma. Journal of
hepatology, 2012;56(6):1336-42.
- Kudo M, Imanaka K, Chida N, Nakachi K, Tak W-Y, Takayama T, et al. Phase III study of sorafenib after
transarterial chemoembolisation in Japanese and Korean patients with unresectable hepatocellular
carcinoma. European journal of cancer, 2011;47(14):2117-27.
- Gadaleta C, Mattioli V, Colucci G, Cramarossa A, Lorusso V, Canniello E, et al. Radiofrequency ablation of 40
lung neoplasms: preliminary results. American journal of roentgenology, 2004;183(2):361-8.
- Gadaleta CD, Solbiati L, Mattioli V, Rubini G, Fazio V, Goffredo V, et al. Unresectable lung malignancy:
combination therapy with segmental pulmonary arterial chemoembolization with drug-eluting microspheres
and radiofrequency ablation in 17 patients. Radiology, 2013;267(2):627-37.