Neoadjuvant therapy bridging patients with hepatocellular cancer waiting for liver transplant
A. A. Pitkevich,
V. Yu. Kosyrev,
I. A. Dzhanyan,
M. S. Novruzbekov,
A. R. Monakhov,
S. I. Zubenko,
S. E. Voskanyan,
V. S. Rudakov,
E. A. Moroz,
V. V. Breder https://doi.org/10.21518/2079-701X-2021-20-110-116
Abstract
Introduction. Liver transplant (LT) is a widely accepted treatment for hepatocellular carcinoma (HCC). The role of neoadjuvant (NAT) is still under debate.
The aim of the work is to assess the effect of NAT on relapse-free survival (RFS) and overall survival (OS) in patients with HCC who underwent LT.
Methods and materials. 63 patients diagnosed with HCC were observed at Blokhin National Medical Research Center of Oncology from October 2010 to January 2020. Of these, 28 patients did not receive any type of treatment before transplantation, 35 patients received various types of NAT. Two groups had similar patient and tumour characteristics at baseline. A significant number of patients with decompensated cirrhosis were observed in the non-NAT group (n = 14; 50%), while no patients with CP-C liver cirrhosis were observed in the NAT group (n = 0; 0%; p = 0.000). The average wait for a liver transplant was 10.3 months in the NAT group and 6.8 months in the NAT-free group (p = 0.561).
Results. In the bridging subgroup, the tumour progression was detected in 29% of patients, stable disease in 47% of patients, partial response was achieved in 14% of patients, complete tumour response was observed in 5%. For 5% of patients, it was not possible to estimate the effect of the therapy due to the lack of appropriate data archives. In the subgroup of downstaging therapy, the tumour progression was detected in 23% of patients, stable disease in 41% of patients, a partial response was achieved in 12% of patients, a complete tumour response was observed in 6%. The treatment allowed the Milan criteria to be fulfilled in 18% of patients.
Conclusion. There was no difference in overall survival (OS) or disease-free survival (DFS) between the NAT and control groups.
About the Authors
A. A. Pitkevich
Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University)
Russian Federation
Russian Federation
Postgraduate Student,
8, Bldg. 2, Trubetskaya St., Moscow, 119991
V. Yu. Kosyrev
Blokhin National Medical Research Center of Oncology;
Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University)
Russian Federation
Russian Federation
Dr. Sci. (Med.), Lead Reasearch Associate, X-ray Surgical Diagnostics and Treatment Department, Lead Reasearch Associate, Department of Interventional Radiology, 24, Kashirskoye Shosse, Moscow, 115478;
Associate Professor of Oncology Department, 8, Bldg. 2, Trubetskaya St., Moscow, 119991
I. A. Dzhanyan
Blokhin National Medical Research Center of Oncology
Russian Federation
Russian Federation
Surgeon of Chemotherapy Department No.17,
24, Kashirskoye Shosse, Moscow, 115478
M. S. Novruzbekov
Research Institute of Emergency Medical Care named after N.V. Sklifosovsky
Russian Federation
Russian Federation
Dr. Sci. (Med.), Head of Liver Transplant Research Department,
3, Bldg. 21, B. Sukharevskaya Square, Moscow, 129090
A. R. Monakhov
Federal Scientific Center for Transplantology and Artificial Organs named after Academician V.I. Shumakov
Russian Federation
Russian Federation
Cand. Sci. (Med.), Head of Surgical Department No.2 (liver transplant), Associate Professor of Department of Transplantology and Artificial Organs,
1, Shchukinskaya St., Moscow, 123182
S. I. Zubenko
Federal Scientific Center for Transplantology and Artificial Organs named after Academician V.I. Shumakov
Russian Federation
Russian Federation
Surgeon of Surgical Department No.2,
1, Shchukinskaya St., Moscow, 123182
S. E. Voskanyan
Burnazyan Federal Medical Biophysical Center;
Clinical Transplantology and Organ Donation, Burnazyan Federal Medical Biophysical Center
Russian Federation
Russian Federation
Dr. Sci. (Med.), Corr. Member of RAS, Professor, Deputy Chief Physician for Surgical Care - Head, 23, Marshal Novikov St., Moscow, 123098;
Head of Department of Surgery with Courses in Oncosurgery, Endoscopy, Surgical Pathology, 46, Bldg. 8, Zhivopisnaya St.,
Moscow, 123098
V. S. Rudakov
Center for Surgery and Transplantology, Burnazyan Federal Medical Biophysical Center
Russian Federation
Russian Federation
Cand. Sci. (Med.), Surgeon of Surgical Department for Coordination of Human Organs and (or) Tissues Procurement,
23, Marshal Novikov St., Moscow, 123098
E. A. Moroz
Blokhin National Medical Research Center of Oncology
Russian Federation
Russian Federation
Cand. Sci. (Med.), Senior Research Associate, Division of Pathological Anatomy of Human Tumours,
24, Kashirskoye Shosse, Moscow, 115478
V. V. Breder
Blokhin National Medical Research Center of Oncology
Russian Federation
Russian Federation
Dr. Sci. (Med.), Lead Research Associate, Chemotherapy Department No.17,
24, Kashirskoye Shosse, Moscow, 115478
References
1. Bray F., Ferlay J., Soerjomataram I., Siegel R.L., Torre L.A., Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 2018;68(6):394–424. https://doi.org/10.3322/caac.21492.
2. Marengo A., Rosso C,. Bugianesi E. Liver cancer: connections with obesity, fatty liver, and cirrhosis. Annu Rev Med. 2016;67:103–117. https://doi.org/10.1146/annurev-med-090514-013832.
3. Chang M.-H., Chen C.-J., Lai M.-S., Hsu H.-M., Wu T.-C., Kong M.-Sh. et al. Universal hepatitis B vaccination in Taiwan and the incidence of hepatocellular carcinoma in children. N Engl J Med. 1997;336(26):1855–1859. https://doi.org/10.1056/nejm199706263362602.
4. Thursz M., Fontanet A. HCV transmission in industrialized countries and resource-constrained areas. Nat Rev Gastroenterol Hepatol. 2014;11(1):28–35. https://doi.org/10.1038/nrgastro.2013.179.
5. European Association for the Study of the Liver, European Organisation for Research and Treatment of Cancer. EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol. 2012;48(5):599–641. https://doi.org/10.1016/j.ejca.2011.12.021.
6. Lang H., Sotiropoulos G.C., Dömland M., Frühauf N.R., Paul A., Hüsing J. et al. Liver resection for hepatocellular carcinoma in non-cirrhotic liver without underlying viral hepatitis. Brit J Surg. 2005;92(2):198–202. https://doi.org/10.1002/bjs.4763.
7. Santambrogio R., Kluger M.D., Costa M., Belli A., Barabino M., Laurentet A. et al. Hepatic resection for hepatocellular carcinoma in patients with Child-Pugh’s A cirrhosis: is clinical evidence of portal hypertension a contraindication? HPB. 2013;15(1):78–84. https://doi.org/10.1111/j.1477-2574.2012.00594.x.
8. Ercolani G., Grazi G.L., Ravaioli M., Gaudio M.D., Gardini A., Cescon M. et al. Liver resection for hepatocellular carcinoma on cirrhosis: univariate and multivariate analysis of risk factors for intrahepatic recurrence. Ann Surg. 2003;237(4):536–543. https://doi.org/10.1097/01.sla.0000059988.22416.f2.
9. Wayne J.D., Gregory Y.L., Ikai I., Dorota A.D., Belghiti J., Yamaoka Y. et al. Preoperative predictors of survival after resectionn of small hepatocellular carcinomas. Ann Surg. 2002;235(5):722–730. https://doi.org/10.1097/00000658-200205000-00015.
10. Zheng Z., Liang W., Milgrom D.P., Zheng Z., Schroder P.M., Kong N.S. et al. Liver transplantation versus liver resection in the treatment of hepatocellular carcinoma: a meta-analysis of observational studies. Transplantation. 2014;97(2):227–234. https://doi.org/10.1097/tp.0b013e3182a89383.
11. Tanaka S., Iimuro Yu., Hirano T., Hai S., Suzumura K., Nakamura I. et al. Safety of hepatic resection for hepatocellular carcinoma in obese patients with cirrhosis. Surg Today. 2013;43(11):1290–1297. https://doi.org/10.1007/s00595-013-0706-2.
12. Kornberg A. Liver transplantation for hepatocellular carcinoma beyond Milan criteria: multidisciplinary approach to improve outcome. ISRN Hepatology. 2014;2014:706945. https://doi.org/10.1155/2014/706945.
13. Lee Y.Ch., Chow P. Liver transplantation for hepatocellular carcinoma: an appraisal of current controversies. Liver Cancer. 2012;1(3–4):183–189. https://doi.org/10.1159/000343832. 14. Bruix J., Sherman M. Management of Hepatocellular Carcinoma: An update. Hepatology. 2011;53(3):1020–1022. https://doi.org/10.1002/hep.24199.
14. Alba E., Valls C., Dominguez J., Martinez L., Escalante E., Lladó L. et al. Transcatheter arterial chemoembolization in patients with hepatocellular carcinoma on the waiting list for orthotopic liver transplantation. AJR Am J Roentgenol. 2008;190(5):1341–1348. https://doi.org/10.2214/AJR.07.2972.
15. Mazzaferro V., Battiston C., Perrone S., Pulvirenti A., Regalia E., Romito R. et al. Radiofrequency ablation of small hepatocellular carcinoma in cirrhotic patients awaiting liver transplantation: a prospective study. Ann Surg. 2004;240(5):900–909. https://doi.org/10.1097/01.sla.0000143301.56154.95.
16. Lu D.S., Yu N.C., Raman S.S., Lassman C., Tong M.J., Britten C. et al. Percutaneous radiofrequency ablation of hepatocellular carcinoma as a bridge to liver transplantation. Hepatology. 2005;41(5):1130–1137. https://doi.org/10.1002/hep.20688.
17. Tsochatzis E., Garcovich M., Marelli L., Papastergiou V., Fatourou E., Rodriguez-Peralvarez M.L. et al. Transarterial embolization as neo-adjuvant therapy pretransplantation in patients with hepatocellular carcinoma. Liver Int. 2013;33(6):944–949. https://doi.org/10.1111/liv.12144.
18. Freeman R.B., Steffick D.E., Guidinger M.K., Farmer D.G., Berg C.L., Merion R.M. Liver and intestine transplantation in the United States, 1997-2006. Am J Transplant. 2008;8(4 Pt 2):958–976. https://doi.org/10.1111/j.1600-6143.2008.02174.x.
19. Lai Q., Avolio A.W., Graziadei I., Otto G., Rossi M., Tisone G. et al. Alphafetoprotein and modified response evaluation criteria in solid tumors progression after locoregional therapy as predictors of hepatocellular cancer recurrence and death after transplantation. Liver Transpl. 2013;19(10):1108–1118. https://doi.org/10.1002/lt.23706.
20. Yao F.Y., Kerlan R.K., Hirose R., Davern T.J., Bass N.M., Feng S et al. Excellent outcome following down-staging of hepatocellular carcinoma prior to liver transplantation: an intention-to-treat analysis. Hepatology. 2008;48(3):819–827. https://doi.org/10.1002/hep.22412.
21. De Carlis L., Di Sandro S., Giacomoni A., Slim A., Lauterio A., Mangoni I. et al. Beyond the Milan criteria: what risks for patients with hepatocellular carcinoma progression before liver transplantation? J Clin Gastroenterol. 2012;46(1):78–86. https://doi.org/10.1097/mcg.0b013e31822b36f6.
22. Gautier S.V., Monakhov A.R., Tsirulnikova O.M., Zubenko S.I., Sitnikova E.V., Umrik D.V. et al. Outcomes of liver transplantation in hepatocellular carcinoma: a single-center experience. Annaly khirurgicheskoy gepatologii = Annals of HPB Surgery. 2020;25(2):67–76. (In Russ.) https://doi.org/10.16931/1995-5464.2020267-76.
23. Otto G., Herber S., Heise M., Lohse A.W., Mönch C., Bittinger F. et al. Response to transarterial chemoembolization as a biological selection criterion for liver transplantation in hepatocellular carcinoma. Liver Transpl. 2006;12(8):1260–1267. https://doi.org/10.1002/lt.20837 .
24. Graziadei I.W., Sandmueller H., Waldenberger P., Koenigsrainer A., Nachbaur K., Jaschke W. et al. Chemoembolization followed by liver transplantation for hepatocellular carcinoma impedes tumor progression while on the waiting list and leads to excellent outcome. Liver Transpl. 2003;9(6):557–563. https://doi.org/10.1053/jlts.2003.50106.
25. Decaens T., Roudot-Thoraval F., Bresson-Hadni S., Meyer C., Gugenheim J., Durand F. et al. Impact of pretransplantation transarterial chemoembolization on survival and recurrence after liver transplantation for hepatocellular carcinoma. Liver Transpl. 2005;11(7):767–775. https://doi.org/10.1002/lt.20418.
26. Agopian V.G., Morshedi M.M., McWilliams J., Harlander-Locke M.P., Markovic D., Zarrinpar A. et al. Complete pathologic response to pretransplant locoregional therapy for hepatocellular carcinoma defines cancer cure after liver transplantation: analysis of 501 consecutively treated patients. Ann Surg. 2015;262(3):536–545. https://doi.org/10.1097/sla.0000000000001384.
27. Cescon M., Cucchetti A., Ravaioli M., Pinna AD. Hepatocellular carcinoma locoregional therapies for patients in the waiting list. Impact on transplantability and recurrence rate. J Hepatol. 2013;58(3):609–618. https://doi.org/10.1016/j.jhep.2012.09.021.
28. Garwood E.R., Fidelman N., Hoch S.E., Kerlan R.K., Yao F.Y. Morbidity and mortality following transarterial liver chemoembolization in patients with hepatocellular carcinoma and synthetic hepatic dysfunction. Liver Transpl. 2013;19(2):164–173. https://doi.org/10.1016/j.jhep.2012.09.021.
29. Hsin I.F., Hsu C.Y., Huang H.C., Huang Y.H., Lin H.C., Lee R.C. et al. Liver failure after transarterial chemoembolization for patients with hepatocellular carcinoma and ascites: incidence, risk factors, and prognostic prediction. J Clin Gastroenterol. 2011;45(6):556–562. https://doi.org/10.1097/mcg.0b013e318210ff17.
30. Kothary N., Weintraub J.L., Susman J., Rundback J.H. Transarterial chemoembolization for primary hepatocellular carcinoma in patients at high risk. J Vasc Interv Radiol. 2007;18(12):1517–1526. https://doi.org/10.1016/j. jvir.2007.07.035.
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For citations:
Pitkevich AA, Kosyrev VY, Dzhanyan IA, Novruzbekov MS, Monakhov AR, Zubenko SI, Voskanyan SE, Rudakov VS, Moroz EA, Breder VV. Neoadjuvant therapy bridging patients with hepatocellular cancer waiting for liver transplant. Meditsinskiy sovet = Medical Council. 2021;(20):110-116. (In Russ.) https://doi.org/10.21518/2079-701X-2021-20-110-116
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