Araştırma Makalesi
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İnoperable Hepatosellüler karsinom’da lokorejyonel tedavi yanıtını öngörmek için albümin ve CRP ilişkili immüno-nutrisyon belirteçlerin kullanımı

Yıl 2025, Cilt: 18 Sayı: 1, 8 - 8
https://doi.org/10.31362/patd.1471860

Öz

Amaç: Controlling nutritional status (Conut) skor, lenfosit-albümin faktörü (LA), Albümin-bilirubin skor (ALBİ), high sensitif modifiye Glasgow prognostik skor (Hs-mGPS), Glasgow prognostik skoru (GPS) gibi albümin ve C-reaktive protein (CRP) ilişkili inflamasyon belirteçleri ile HCC’de lokorejyonel tedavi yanıtı arasındaki ilişkiyi inceledik.
Gereç ve yöntem: Yüz seksen HCC hastasından lokorejyonel tedavi uygulanan 63 hasta bu çalışmaya dahil edildi. Tedavi sonrası dördüncü-sekizinci hafta aralığındaki rutin laboratuvar testleri kaydedilerek albümin ve CRP ilişkili immüno-nutrisyon skorları hesaplandı. Prognostik belirteçlerin cut-off değerleri Roc analizi ile belirlendi. Bu belirteçlerin genel sağkalım (OS) ve tedavi sonrası hastalıksız sağkalım (DFS) için prediktif ve prognostik değeri analiz edildi.
Bulgular: Yaş ortalaması 63 (min-max:26-87) olan hastaların 59’u (%93,7) erkekti. Ortalama takip süresi 25 ay olup 53 hasta merhumdu (%84,1). Median genel sağkalım (mOS):18,56 ay (min-max:13,13-23,99); lokorejyonel tedavi sonrası mDFS:7ay (min-max:3,63-10,37) olarak belirlendi. Yaş (p=0,019), Conut (p=0,001), GPS (p=0,028), Hs-mGPS (p=0,012), LA (p=0,017) ve ALBI (p=0,002) ile mOS arasında istatistiksel anlamlı ilişki bulundu. Conut (p=0,002), GPS (p<0,001), Hs-mGPS (p=0,002), LA (p=0,002) ve ALBI (p=0,001) ile median hastalıksız sağkalım (mDFS) arasındaki ilişki istatistiksel olarak anlamlı bulundu. Multivariate analiz sonucunda; ≥65 yaş olanların (HR:2,10; %95 CI:1,02-4,30; p=0,042) ve hiç sistemik tedavi almayanların (HR:4,11; %95 CI:1,35-12,56; p=0,013) ölüm riskinin arttığı belirlendi (p<0,001). Bir diğer anlamlı sonuç ise GPS’nin ‘2’ olmasının (HR:6,62; %95 CI:1,13-38,62; p=0,036) yüksek progresyon riskini öngördüğü idi (p<0,001).
Sonuç: Lokorejyonel tedavi uygulanan HCC’li hastalarda; yaş, Conut skor, GPS, HsmGPS, LA ve ALBI skorun, hastaların mOS ve mDFS için önemli prediktif faktörler olduğunu saptadık. Tüm bu sonuçlar oluşturduğumuz prognostik modellemenin klinik pratikte kullanımının yararlı olabileceğini düşündürmektedir.

Proje Numarası

2

Kaynakça

  • Reig M, Forner A, Rimola J, et al. BCLC strategy for prognosis prediction and treatment recommendation: The 2022 update. J Hepatol. 2022;76(3):681-693. doi:10.1016/j.jhep.2021.11.018
  • Mauro E, Forner A. Barcelona Clinic Liver Cancer 2022 update: Linking prognosis prediction and evidence-based treatment recommendation with multidisciplinary clinical decision-making. Liver Int. 2022;42(3):488-491. doi:10.1111/liv.15180
  • Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71(3):209-249. doi:10.3322/caac.21660
  • Chen X, Liu X, Du S. Unveiling the Role of Tumor-Infiltrating T Cells and Immunotherapy in Hepatocellular Carcinoma: A Comprehensive Review. Cancers (Basel). 2023;15(20):5046. Published 2023 Oct 19. doi:10.3390/cancers15205046
  • Llovet JM, Villanueva A, Marrero JA, et al. Trial Design and Endpoints in Hepatocellular Carcinoma: AASLD Consensus Conference. Hepatology. 2021;73(Suppl 1):158-191. doi:10.1002/hep.31327
  • Singal AG, Lampertico P, Nahon P. Epidemiology and surveillance for hepatocellular carcinoma: New trends. J Hepatol. 2020;72(2):250-261. doi:10.1016/j.jhep.2019.08.025
  • Scheiner B, Pomej K, Kirstein MM, et al. Prognosis of patients with hepatocellular carcinoma treated with immunotherapy - development and validation of the CRAFITY score. J Hepatol. 2022;76(2):353-363. doi:10.1016/j.jhep.2021.09.035
  • Johnson PJ, Berhane S, Kagebayashi C, et al. Assessment of liver function in patients with hepatocellular carcinoma: a new evidence-based approach-the ALBI grade. J Clin Oncol. 2015;33(6):550-558. doi:10.1200/JCO.2014.57.9151
  • Singal AG, Hoshida Y, Pinato DJ, et al. International Liver Cancer Association (ILCA) White Paper on Biomarker Development for Hepatocellular Carcinoma. Gastroenterology. 2021;160(7):2572-2584. doi:10.1053/j.gastro.2021.01.233
  • Cabibbo G, Maida M, Genco C, et al. Natural history of untreatable hepatocellular carcinoma: A retrospective cohort study. World J Hepatol. 2012;4(9):256-261. doi:10.4254/wjh.v4.i9.256
  • de Franchis R; Baveno VI Faculty. Expanding consensus in portal hypertension: Report of the Baveno VI Consensus Workshop: Stratifying risk and individualizing care for portal hypertension. J Hepatol. 2015;63(3):743-752. doi:10.1016/j.jhep.2015.05.022
  • Schima W, Ba-Ssalamah A, Kurtaran A, Schindl M, Gruenberger T. Post-treatment imaging of liver tumours. Cancer Imaging. 2007;7 Spec No A(Special issue A):S28-S36. Published 2007 Oct 1. doi:10.1102/1470-7330.2007.9047
  • Kim S, Mannelli L, Hajdu CH, et al. Hepatocellular carcinoma: assessment of response to transarterial chemoembolization with image subtraction. J Magn Reson Imaging. 2010;31(2):348-355. doi:10.1002/jmri.22038
  • Kim SK, Lim HK, Kim YH, et al. Hepatocellular carcinoma treated with radio-frequency ablation: spectrum of imaging findings. Radiographics. 2003;23(1):107-121. doi:10.1148/rg.231025055
  • Johnson PJ, Berhane S, Kagebayashi C, et al. Assessment of liver function in patients with hepatocellular carcinoma: a new evidence-based approach-the ALBI grade. J Clin Oncol. 2015;33(6):550-558. doi:10.1200/JCO.2014.57.9151
  • Lu LH, Wei W, Li SH, Zhang YF, Guo RP. The lymphocyte-C-reactive protein ratio as the optimal inflammation-based score in patients with hepatocellular carcinoma underwent TACE. Aging (Albany NY). 2021;13(4):5358-5368. doi:10.18632/aging.202468
  • Yamamoto T, Kawada K, Hida K, et al. Combination of lymphocyte count and albumin concentration as a new prognostic biomarker for rectal cancer. Sci Rep. 2021;11(1):5027. Published 2021 Mar 3. doi:10.1038/s41598-021-84475-4
  • Devan AR, Nair B, Aryan MK, et al. Decoding Immune Signature to Detect the Risk for Early-Stage HCC Recurrence. Cancers (Basel). 2023;15(10):2729. Published 2023 May 12. doi:10.3390/cancers15102729
  • Bargellini I, Bozzi E, Campani D, et al. Modified RECIST to assess tumor response after transarterial chemoembolization of hepatocellular carcinoma: CT-pathologic correlation in 178 liver explants. Eur J Radiol. 2013;82(5):e212-e218. doi:10.1016/j.ejrad.2012.12.009
  • Tacher V, Lin M, Duran R, et al. Comparison of Existing Response Criteria in Patients with Hepatocellular Carcinoma Treated with Transarterial Chemoembolization Using a 3D Quantitative Approach. Radiology. 2016;278(1):275-284. doi:10.1148/radiol.2015142951
  • Refolo MG, Messa C, Guerra V, Carr BI, D'Alessandro R. Inflammatory Mechanisms of HCC Development. Cancers (Basel). 2020;12(3):641. Published 2020 Mar 10. doi:10.3390/cancers12030641
  • Schobert IT, Savic LJ, Chapiro J, et al. Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios as predictors of tumor response in hepatocellular carcinoma after DEB-TACE. Eur Radiol. 2020;30(10):5663-5673. doi:10.1007/s00330-020-06931-5
  • Young S, Rubin N, D'Souza D, et al. Inflammatory Scores: Correlation with Clinical Outcomes in Hepatocellular Carcinoma Patients Undergoing Transarterial Radioembolization. Cardiovasc Intervent Radiol. 2022;45(4):461-475. doi:10.1007/s00270-022-03080-8
  • Takagi K, Yagi T, Umeda Y, et al. Preoperative Controlling Nutritional Status (CONUT) Score for Assessment of Prognosis Following Hepatectomy for Hepatocellular Carcinoma. World J Surg. 2017;41(9):2353-2360. doi:10.1007/s00268-017-3985-8
  • Harimoto N, Yoshizumi T, Inokuchi S, et al. Prognostic Significance of Preoperative Controlling Nutritional Status (CONUT) Score in Patients Undergoing Hepatic Resection for Hepatocellular Carcinoma: A Multi-institutional Study. Ann Surg Oncol. 2018;25(11):3316-3323. doi:10.1245/s10434-018-6672-6
  • Pravisani R, Mocchegiani F, Isola M, et al. Controlling Nutritional Status score does not predict patients' overall survival or hepatocellular carcinoma recurrence after deceased donor liver transplantation. Clin Transplant. 2020;34(3):e13786. doi:10.1111/ctr.13786
  • Liu Y, Shi M, Chen S, et al. Intermediate stage hepatocellular carcinoma: Comparison of the value of inflammation-based scores in predicting progression-free survival of patients receiving transarterial chemoembolization. J Cancer Res Ther. 2021;17(3):740-748. doi:10.4103/jcrt.jcrt_29_21
  • Zhao Y, Huang F, Liu S, et al. Prediction of therapeutic response of unresectable hepatocellular carcinoma to hepatic arterial infusion chemotherapy based on pretherapeutic MRI radiomics and Albumin-Bilirubin score. J Cancer Res Clin Oncol. 2023;149(8):5181-5192. doi:10.1007/s00432-022-04467-3

Use of albumin and CRP related immuno-nutritional markers for prediction of locoregional response to treatment in unresectable hepatocellular carcinoma

Yıl 2025, Cilt: 18 Sayı: 1, 8 - 8
https://doi.org/10.31362/patd.1471860

Öz

Purpose: We examined the relationship between albumin and C reactive protein (CRP)-related inflammation markers such as Controlling nutritional status (Conut) score, lymphocyte-albumin factor (LA), albumin-bilirubin score (ALBI), highly sensitive modified Glasgow prognostic score (Hs-mGPS), Glasgow prognostic score (GPS) and locoregional treatment response in HCC.
Materials and methods: One hundred and eighty HCC patients and 63 patients who underwent locoregional therapy were included in this study. Routine laboratory tests between the fourth and eighth week after treatment were recorded and albumin and CRP-related immuno-nutrition scores were calculated. Cut-off values of prognostic markers were determined by Roc analysis. The predictive and prognostic value of these markers for overall survival (OS) and disease-free survival (DFS) after treatment were analyzed.
Results: The mean age was 63 years (min-max:26-87) and 59 (93.7%) of the patients were male. The mean follow-up period was 25 months and 53 patients were deceased (84.1%). Median overall survival (mOS):18.56 months (min-max:13.13-23.99); median disease-free survival (mDFS):7 months (min-max:3.63-10.37) after locoregional treatment. Age (p=0.019), Conut (p=0.001), GPS (p=0.028), Hs-mGPS (p=0.012), LA (p=0.017) and ALBI (p=0.002) were significantly correlated with mOS. Conut (p=0.002), GPS (p<0.001), Hs-mGPS (p=0.002), LA (p=0.002) and ALBI (p=0.001) were significantly correlated with mDFS. Multivariate analysis revealed that those aged ≥65 years (HR:2.10; 95% CI:1.02-4.30; p=0.042) and those who received no systemic therapy (HR:4.11; 95% CI:1.35-12.56; p=0.013) had an increased risk of death (p<0.001). Another significant result was that a GPS of '2' (HR:6.62; 95% CI:1.13-38.62; p=0.036) predicted a higher risk of progression (p<0.001).
Conclusion: In this study, we found that age, Conut score, GPS, HsmGPS, LA and ALBI score significantly predicted mOS and mDFS in locoregionally treated HCC patients. All these results suggest that our prognostic modelling may be useful in clinical practice.

Etik Beyan

Pamukkale Üniversitesi Tıp Fakültesi girişimsel olmayan etik kurul onayı alındı. (Sayı:E-60116787-020-507040, 20.03.2024 tarih, ve E.507040sayı numaralı kurul toplantısı)

Destekleyen Kurum

yok

Proje Numarası

2

Teşekkür

Prof. Dr. Gamze Gököz Doğu ve diğer yardımcı araştırmacılar

Kaynakça

  • Reig M, Forner A, Rimola J, et al. BCLC strategy for prognosis prediction and treatment recommendation: The 2022 update. J Hepatol. 2022;76(3):681-693. doi:10.1016/j.jhep.2021.11.018
  • Mauro E, Forner A. Barcelona Clinic Liver Cancer 2022 update: Linking prognosis prediction and evidence-based treatment recommendation with multidisciplinary clinical decision-making. Liver Int. 2022;42(3):488-491. doi:10.1111/liv.15180
  • Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71(3):209-249. doi:10.3322/caac.21660
  • Chen X, Liu X, Du S. Unveiling the Role of Tumor-Infiltrating T Cells and Immunotherapy in Hepatocellular Carcinoma: A Comprehensive Review. Cancers (Basel). 2023;15(20):5046. Published 2023 Oct 19. doi:10.3390/cancers15205046
  • Llovet JM, Villanueva A, Marrero JA, et al. Trial Design and Endpoints in Hepatocellular Carcinoma: AASLD Consensus Conference. Hepatology. 2021;73(Suppl 1):158-191. doi:10.1002/hep.31327
  • Singal AG, Lampertico P, Nahon P. Epidemiology and surveillance for hepatocellular carcinoma: New trends. J Hepatol. 2020;72(2):250-261. doi:10.1016/j.jhep.2019.08.025
  • Scheiner B, Pomej K, Kirstein MM, et al. Prognosis of patients with hepatocellular carcinoma treated with immunotherapy - development and validation of the CRAFITY score. J Hepatol. 2022;76(2):353-363. doi:10.1016/j.jhep.2021.09.035
  • Johnson PJ, Berhane S, Kagebayashi C, et al. Assessment of liver function in patients with hepatocellular carcinoma: a new evidence-based approach-the ALBI grade. J Clin Oncol. 2015;33(6):550-558. doi:10.1200/JCO.2014.57.9151
  • Singal AG, Hoshida Y, Pinato DJ, et al. International Liver Cancer Association (ILCA) White Paper on Biomarker Development for Hepatocellular Carcinoma. Gastroenterology. 2021;160(7):2572-2584. doi:10.1053/j.gastro.2021.01.233
  • Cabibbo G, Maida M, Genco C, et al. Natural history of untreatable hepatocellular carcinoma: A retrospective cohort study. World J Hepatol. 2012;4(9):256-261. doi:10.4254/wjh.v4.i9.256
  • de Franchis R; Baveno VI Faculty. Expanding consensus in portal hypertension: Report of the Baveno VI Consensus Workshop: Stratifying risk and individualizing care for portal hypertension. J Hepatol. 2015;63(3):743-752. doi:10.1016/j.jhep.2015.05.022
  • Schima W, Ba-Ssalamah A, Kurtaran A, Schindl M, Gruenberger T. Post-treatment imaging of liver tumours. Cancer Imaging. 2007;7 Spec No A(Special issue A):S28-S36. Published 2007 Oct 1. doi:10.1102/1470-7330.2007.9047
  • Kim S, Mannelli L, Hajdu CH, et al. Hepatocellular carcinoma: assessment of response to transarterial chemoembolization with image subtraction. J Magn Reson Imaging. 2010;31(2):348-355. doi:10.1002/jmri.22038
  • Kim SK, Lim HK, Kim YH, et al. Hepatocellular carcinoma treated with radio-frequency ablation: spectrum of imaging findings. Radiographics. 2003;23(1):107-121. doi:10.1148/rg.231025055
  • Johnson PJ, Berhane S, Kagebayashi C, et al. Assessment of liver function in patients with hepatocellular carcinoma: a new evidence-based approach-the ALBI grade. J Clin Oncol. 2015;33(6):550-558. doi:10.1200/JCO.2014.57.9151
  • Lu LH, Wei W, Li SH, Zhang YF, Guo RP. The lymphocyte-C-reactive protein ratio as the optimal inflammation-based score in patients with hepatocellular carcinoma underwent TACE. Aging (Albany NY). 2021;13(4):5358-5368. doi:10.18632/aging.202468
  • Yamamoto T, Kawada K, Hida K, et al. Combination of lymphocyte count and albumin concentration as a new prognostic biomarker for rectal cancer. Sci Rep. 2021;11(1):5027. Published 2021 Mar 3. doi:10.1038/s41598-021-84475-4
  • Devan AR, Nair B, Aryan MK, et al. Decoding Immune Signature to Detect the Risk for Early-Stage HCC Recurrence. Cancers (Basel). 2023;15(10):2729. Published 2023 May 12. doi:10.3390/cancers15102729
  • Bargellini I, Bozzi E, Campani D, et al. Modified RECIST to assess tumor response after transarterial chemoembolization of hepatocellular carcinoma: CT-pathologic correlation in 178 liver explants. Eur J Radiol. 2013;82(5):e212-e218. doi:10.1016/j.ejrad.2012.12.009
  • Tacher V, Lin M, Duran R, et al. Comparison of Existing Response Criteria in Patients with Hepatocellular Carcinoma Treated with Transarterial Chemoembolization Using a 3D Quantitative Approach. Radiology. 2016;278(1):275-284. doi:10.1148/radiol.2015142951
  • Refolo MG, Messa C, Guerra V, Carr BI, D'Alessandro R. Inflammatory Mechanisms of HCC Development. Cancers (Basel). 2020;12(3):641. Published 2020 Mar 10. doi:10.3390/cancers12030641
  • Schobert IT, Savic LJ, Chapiro J, et al. Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios as predictors of tumor response in hepatocellular carcinoma after DEB-TACE. Eur Radiol. 2020;30(10):5663-5673. doi:10.1007/s00330-020-06931-5
  • Young S, Rubin N, D'Souza D, et al. Inflammatory Scores: Correlation with Clinical Outcomes in Hepatocellular Carcinoma Patients Undergoing Transarterial Radioembolization. Cardiovasc Intervent Radiol. 2022;45(4):461-475. doi:10.1007/s00270-022-03080-8
  • Takagi K, Yagi T, Umeda Y, et al. Preoperative Controlling Nutritional Status (CONUT) Score for Assessment of Prognosis Following Hepatectomy for Hepatocellular Carcinoma. World J Surg. 2017;41(9):2353-2360. doi:10.1007/s00268-017-3985-8
  • Harimoto N, Yoshizumi T, Inokuchi S, et al. Prognostic Significance of Preoperative Controlling Nutritional Status (CONUT) Score in Patients Undergoing Hepatic Resection for Hepatocellular Carcinoma: A Multi-institutional Study. Ann Surg Oncol. 2018;25(11):3316-3323. doi:10.1245/s10434-018-6672-6
  • Pravisani R, Mocchegiani F, Isola M, et al. Controlling Nutritional Status score does not predict patients' overall survival or hepatocellular carcinoma recurrence after deceased donor liver transplantation. Clin Transplant. 2020;34(3):e13786. doi:10.1111/ctr.13786
  • Liu Y, Shi M, Chen S, et al. Intermediate stage hepatocellular carcinoma: Comparison of the value of inflammation-based scores in predicting progression-free survival of patients receiving transarterial chemoembolization. J Cancer Res Ther. 2021;17(3):740-748. doi:10.4103/jcrt.jcrt_29_21
  • Zhao Y, Huang F, Liu S, et al. Prediction of therapeutic response of unresectable hepatocellular carcinoma to hepatic arterial infusion chemotherapy based on pretherapeutic MRI radiomics and Albumin-Bilirubin score. J Cancer Res Clin Oncol. 2023;149(8):5181-5192. doi:10.1007/s00432-022-04467-3
Toplam 28 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Gastroenteroloji ve Hepatoloji, Radyoloji ve Organ Görüntüleme
Bölüm Araştırma Makalesi
Yazarlar

Melek Özdemir 0000-0003-1894-9743

Gamze Gokoz Dogu 0000-0001-8142-0362

Burcu Yapar Taşköylü 0000-0003-4755-2753

Atike Gökçen Demiray 0000-0003-4397-5468

Serkan Değirmencioğlu 0000-0002-1213-2778

Arzu Yaren 0000-0003-1436-8650

Muhammet Arslan 0000-0001-5565-0770

Burçin Çakan Demirel 0000-0003-0734-0692

Tolga Doğan 0000-0003-1281-942X

Taliha Güçlü Kantar 0000-0002-7836-4272

Semra Taş 0000-0002-9441-9210

Bedriye Açıkgöz Yıldız 0000-0001-7976-3358

Gamze Serin Özel 0009-0002-3631-6771

Ceren Mordağ Çiçek 0000-0002-9140-1453

Proje Numarası 2
Erken Görünüm Tarihi 11 Kasım 2024
Yayımlanma Tarihi
Gönderilme Tarihi 5 Mayıs 2024
Kabul Tarihi 4 Kasım 2024
Yayımlandığı Sayı Yıl 2025 Cilt: 18 Sayı: 1

Kaynak Göster

AMA Özdemir M, Gokoz Dogu G, Yapar Taşköylü B, Demiray AG, Değirmencioğlu S, Yaren A, Arslan M, Çakan Demirel B, Doğan T, Güçlü Kantar T, Taş S, Açıkgöz Yıldız B, Serin Özel G, Mordağ Çiçek C. Use of albumin and CRP related immuno-nutritional markers for prediction of locoregional response to treatment in unresectable hepatocellular carcinoma. Pam Tıp Derg. Kasım 2024;18(1):8-8. doi:10.31362/patd.1471860
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