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01-05-2018 | Original Article

The role of albumin–bilirubin grade and inflammation-based index in patients with hepatocellular carcinoma treated with stereotactic body radiotherapy

Authors: Eleni Gkika, Dominik Bettinger, Leo Krafft, Michael Schultheiss, Hannes Philipp Neeff, Lars Maruschke, Michaela Schulenburg, Sonja Adebahr, Simon Kirste, Ursula Nestle, Robert Thimme, Anca-Ligia Grosu, Thomas Baptist Brunner

Published in: Strahlentherapie und Onkologie | Issue 5/2018

Abstract

Purpose

We evaluated the prognostic accuracy of the albumin–bilirubin (ALBI) grade and the inflammation-based index (IBI) in estimating overall survival (OS) and toxicity in patients with hepatocellular carcinoma (HCC) treated with stereotactic body radiotherapy (SBRT).

Materials and methods

Forty patients with 47 HCC lesions with a Barcelona Clinic Liver Cancer (BCLC) classification stage B or C were treated with SBRT in 3–12 fractions. The ALBI grade and the IBI were calculated at different time points (baseline, during, at the end of treatment and at follow-up) and compared with the Child-Pugh (CP) score as well as other patient- and treatment-related parameters, concerning OS and toxicity.

Results

The median follow-up was 14.3 months for patients alive. The median OS from SBRT was 10 (95% confidence interval 8.3–11.6) months. The local control at 1 year was 79%. A lower IBI during treatment was associated with better OS (p = 0.034) but not CP and ALBI. Higher C‑reactive protein levels as well as higher alpha-fetoprotein concentrations correlated with worse survival (p = 0.001). Both higher ALBI (p = 0.02) and CTP (p = 0.001) at baseline correlated with a higher incidence of acute and late toxicities (CTC ≥2). Neither the mean radiation dose to the liver nor the dose to 700 cc of the liver correlated with the occurrence of toxicities.

Conclusions

In this analysis, a higher ALBI grade as well as a higher CP were predictors of higher incidence of toxicity, whereas a lower IBI during treatment correlated with a better OS. These results should be further evaluated in prospective studies.

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Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F (2015) Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 136(5):E359–E386. https://doi.org/10.1002/ijc.29210 CrossRefPubMed

Bruix J, Gores GJ, Mazzaferro V (2014) Hepatocellular carcinoma: clinical frontiers and perspectives. Gut 63(5):844–855. https://doi.org/10.1136/gutjnl-2013-306627 CrossRefPubMedPubMedCentral

European Association For The Study Of The Liver, European Organisation For Research And Treatment Of Cancer (2012) EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol 56(4):908–943. https://doi.org/10.1016/j.jhep.2011.12.001 CrossRef

M-LI PRN, Dawson JL, Pietroni MC, Williams R (1973) Transection of the oesophagus for bleeding oesophageal varices. Br J Surg 60(8):646–649CrossRef

Johnson PJ, Berhane S, Kagebayashi C, Satomura S, Teng M, Reeves HL, O’Beirne J, Fox R, Skowronska A, Palmer D, Yeo W, Mo F, Lai P, Inarrairaegui M, Chan SL, Sangro B, Miksad R, Tada T, Kumada T, Toyoda H (2015) Assessment of liver function in patients with hepatocellular carcinoma: a new evidence-based approach-the ALBI grade. J Clin Oncol 33(6):550–558. https://doi.org/10.1200/JCO.2014.57.9151 CrossRefPubMed

Pinato DJ, Sharma R, Allara E, Yen C, Arizumi T, Kubota K, Bettinger D, Jang JW, Smirne C, Kim YW, Kudo M, Howell J, Ramaswami R, Burlone ME, Guerra V, Thimme R, Ishizuka M, Stebbing J, Pirisi M, Carr BI (2016) The ALBI grade provides objective hepatic reserve estimation across each BCLC stage of hepatocellular carcinoma. J Hepatol. https://doi.org/10.1016/j.jhep.2016.09.008

Andreatos N, Amini N, Gani F, Margonis GA, Sasaki K, Thompson VM, Bentrem DJ, Hall BL, Pitt HA, Wilson A, Pawlik TM (2016) Albumin-bilirubin score: predicting short-term outcomes including bile leak and post-hepatectomy liver failure following hepatic resection. J Gastrointest Surg. https://doi.org/10.1007/s11605-016-3246-4

Sieghart W, Hucke F, Pinter M, Graziadei I, Vogel W, Muller C, Heinzl H, Trauner M, Peck-Radosavljevic M (2013) The ART of decision making: retreatment with transarterial chemoembolization in patients with hepatocellular carcinoma. Hepatology 57(6):2261–2273. https://doi.org/10.1002/hep.26256 CrossRefPubMed

Pinato DJ, Sharma R (2012) An inflammation-based prognostic index predicts survival advantage after transarterial chemoembolization in hepatocellular carcinoma. Transl Res 160(2):146–152. https://doi.org/10.1016/j.trsl.2012.01.011 CrossRefPubMed

10.

Pinato DJ, Karamanakos G, Arizumi T, Adjogatse D, Kim YW, Stebbing J, Kudo M, Jang JW, Sharma R (2014) Dynamic changes of the inflammation-based index predict mortality following chemoembolisation for hepatocellular carcinoma: a prospective study. Aliment Pharmacol Ther 40(11):1270–1281. https://doi.org/10.1111/apt.12992 CrossRefPubMed

11.

Mendez Romero A, de Man RA (2016) Stereotactic body radiation therapy for primary and metastatic liver tumors: from technological evolution to improved patient care. Best Pract Res Clin Gastroenterol 30(4):603–616. https://doi.org/10.1016/j.bpg.2016.06.003 CrossRefPubMed

12.

Bujold A, Massey CA, Kim JJ, Brierley J, Cho C, Wong RK, Dinniwell RE, Kassam Z, Ringash J, Cummings B, Sykes J, Sherman M, Knox JJ, Dawson LA (2013) Sequential phase I and II trials of stereotactic body radiotherapy for locally advanced hepatocellular carcinoma. J Clin Oncol 31(13):1631–1639. https://doi.org/10.1200/JCO.2012.44.1659 CrossRefPubMed

13.

Pan CC, Kavanagh BD, Dawson LA, Li XA, Das SK, Miften M, Ten Haken RK (2010) Radiation-associated liver injury. Int J Radiat Oncol Biol Phys 76(3 Suppl):S94–S100. https://doi.org/10.1016/j.ijrobp.2009.06.092 CrossRefPubMedPubMedCentral

14.

Bruix J, Sherman M, American Association for the Study of Liver Diseases (2011) Management of hepatocellular carcinoma: an update. Hepatology 53(3):1020–1022. https://doi.org/10.1002/hep.24199 CrossRefPubMedPubMedCentral

15.

Pinato DJ, Stebbing J, Ishizuka M, Khan SA, Wasan HS, North BV, Kubota K, Sharma R (2012) A novel and validated prognostic index in hepatocellular carcinoma: the inflammation based index (IBI). J Hepatol 57(5):1013–1020. https://doi.org/10.1016/j.jhep.2012.06.022 CrossRefPubMed

16.

Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45(2):228–247. https://doi.org/10.1016/j.ejca.2008.10.026 CrossRefPubMed

17.

Gkika E, Adebahr S, Kirste S, Schimek-Jasch T, Wiehle R, Claus R, Wittel U, Nestle U, Baltas D, Grosu AL, Brunner TB (2017) Stereotactic body radiotherapy (SBRT) in recurrent or oligometastatic pancreatic cancer. Strahlenther Onkol 193(6):433–443. https://doi.org/10.1007/s00066-017-1099-8 CrossRefPubMed

18.

Timmerman RD (2008) An overview of hypofractionation and introduction to this issue of seminars in radiation oncology. Semin Radiat Oncol 18(4):215–222. https://doi.org/10.1016/j.semradonc.2008.04.001 CrossRefPubMed

19.

Brunner TB, Nestle U, Adebahr S, Gkika E, Wiehle R, Baltas D, Grosu AL (2016) Simultaneous integrated protection: a new concept for high-precision radiation therapy. Strahlenther Onkol. https://doi.org/10.1007/s00066-016-1057-x PubMedCentral

20.

Fowler JF, Tome WA, Fenwick JD, Mehta MP (2004) A challenge to traditional radiation oncology. Int J Radiat Oncol Biol Phys 60(4):1241–1256. https://doi.org/10.1016/j.ijrobp.2004.07.691 CrossRefPubMed

21.

Toyoda H, Lai PB, O’Beirne J, Chong CC, Berhane S, Reeves H, Manas D, Fox RP, Yeo W, Mo F, Chan AW, Tada T, Inarrairaegui M, Vogel A, Schweitzer N, Chan SL, Sangro B, Kumada T, Johnson PJ (2016) Long-term impact of liver function on curative therapy for hepatocellular carcinoma: application of the ALBI grade. Br J Cancer 114(7):744–750. https://doi.org/10.1038/bjc.2016.33 CrossRefPubMedPubMedCentral

22.

Hickey R, Mouli S, Kulik L, Desai K, Thornburg B, Ganger D, Baker T, Abecassis M, Kallini RJ, Gabr A, Gates VL, Benson Iii AB, Lewandowski RJ, Salem R (2016) Independent analysis of albumin-bilirubin grade in a 765-patient cohort treated with transarterial locoregional therapy for hepatocellular carcinoma. J Vasc Interv Radiol 27(6):795–802. https://doi.org/10.1016/j.jvir.2016.03.005 CrossRefPubMed

23.

Culleton S, Jiang H, Haddad CR, Kim J, Brierley J, Brade A, Ringash J, Dawson LA (2014) Outcomes following definitive stereotactic body radiotherapy for patients with child-pugh B or C hepatocellular carcinoma. Radiother Oncol 111(3):412–417. https://doi.org/10.1016/j.radonc.2014.05.002 CrossRefPubMed

24.

Velec M, Haddad CR, Craig T, Wang L, Lindsay P, Brierley J, Brade A, Ringash J, Wong R, Kim J, Dawson LA (2017) Predictors of liver toxicity following stereotactic body radiation therapy for hepatocellular carcinoma. Int J Radiat Oncol Biol Phys 97(5):939–946. https://doi.org/10.1016/j.ijrobp.2017.01.221 CrossRefPubMed

25.

Mantovani A, Allavena P, Sica A, Balkwill F (2008) Cancer-related inflammation. Nature 454(7203):436–444. https://doi.org/10.1038/nature07205 CrossRefPubMed

26.

Hoshida Y, Moeini A, Alsinet C, Kojima K, Villanueva A (2012) Gene signatures in the management of hepatocellular carcinoma. Semin Oncol 39(4):473–485. https://doi.org/10.1053/j.seminoncol.2012.05.003 CrossRefPubMed

27.

Budhu A, Forgues M, Ye QH, Jia HL, He P, Zanetti KA, Kammula US, Chen Y, Qin LX, Tang ZY, Wang XW (2006) Prediction of venous metastases, recurrence, and prognosis in hepatocellular carcinoma based on a unique immune response signature of the liver microenvironment. Cancer Cell 10(2):99–111. https://doi.org/10.1016/j.ccr.2006.06.016 CrossRefPubMed

Title: The role of albumin–bilirubin grade and inflammation-based index in patients with hepatocellular carcinoma treated with stereotactic body radiotherapy
Authors: Eleni Gkika
Dominik Bettinger
Leo Krafft
Michael Schultheiss
Hannes Philipp Neeff
Lars Maruschke
Michaela Schulenburg
Sonja Adebahr
Simon Kirste
Ursula Nestle
Robert Thimme
Anca-Ligia Grosu
Thomas Baptist Brunner
Publication date: 01-05-2018
Publisher: Springer Berlin Heidelberg
Published in: Strahlentherapie und Onkologie / Issue 5/2018
Print ISSN: 0179-7158
Electronic ISSN: 1439-099X
DOI: https://doi.org/10.1007/s00066-017-1256-0

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

The role of albumin–bilirubin grade and inflammation-based index in patients with hepatocellular carcinoma treated with stereotactic body radiotherapy

Abstract

Purpose

Materials and methods

Results

Conclusions

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Purpose

Materials and methods

Results

Conclusions

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