HCC CONNECT review paper published in Liver Cancer

Dr Mohamed Bouattour is a physician in the Department of Digestive Oncology and Consultant in the Department of Hepatology at Beaujon University Hospital and has held this these positions since November 2007. He is board certified in Gastroenterology-Hepatology and Medical Oncology. He has expertise in the field of liver tumours, hepatocellular carcinoma, and pre-clinical and clinical research for liver disease. Dr Bouattour works in close collaboration with a multidisciplinary team including, liver surgeons, radiologists, oncologists, hepatologists and pathologists, to improve the management of patients with liver cancers. Dr Bouattour has been involved in presenting several collaborative works in national and international scientific meetings. He has authored and co-authored scientific papers in the field of liver and cancer diseases. He is investigator and sub investigator for several phase 1, 2 and 3 clinical trials. Dr Bouattour is member of several national and international societies such as the American Association for the Study of Liver Diseases (AASLD) and the European Association for the Study of the Liver (EASL), the International Liver Cancer Association (ILCA) and the American Society of Clinical Oncology (ASCO). Relevant Publications Coriat R, Faivre SJ, Mir O, Dreyer C, Ropert S, Bouattour M, Desjardins R, Goldwasser F, Raymond E. Pharmacokinetics and safety of DTS-108, a human oligopeptide bound to SN-38 with an esterase-sensitive cross-linker in patients with advanced malignancies: a Phase I study. Int J Nanomedicine 2016; 21; 11: 6207-6216. Bouattour M, Soubrane O, de Gramont A, Faivre S. Adjuvant therapies in advanced hepatocellular carcinoma: moving forward from the STORM. Trials 2016; 25; 17(1): 563. Bouattour M, Payancé A, Wassermann J. Evaluation of antiangiogenic efficacy in advanced hepatocellular carcinoma: Biomarkers and functional imaging. World J Hepatol 2015; 7(20):2245-63. Bouattour M, Rousseau B, Wassermann J, Payancé A, Huillard O. Negative Trials for Foreseeable Safety Reasons in Advanced Hepatocellular Carcinoma: How Long Are We Going to Take Lightly Pharmacokinetics of Tyrosine Kinase Inhibitors? J Clin Oncol 2015; 33(22): 2484-5. Dreyer C, Sablin MP, Bouattour M, Neuzillet C, Ronot M, Dokmak S, Belghiti J, Guedj N, Paradis V, Raymond E, Faivre S. Disease control with sunitinib in advanced intrahepatic cholangiocarcinoma resistant to gemcitabine-oxaliplatin chemotherapy. World J Hepatol 2015; 7(6): 910-5. Patrikidou A, Sinapi I, Regnault H, Fayard F, Bouattour M, Fartoux L, Faivre S, Malka D, Ducreux M, Boige V. Gemcitabine and oxaliplatin chemotherapy for advanced hepatocellular carcinoma after failure of anti-angiogenic therapies. Invest New Drugs 2014; 32(5): 1028-35. Ronot M, Bouattour M, Wassermann J, Bruno O, Dreyer C, Larroque B, Castera L, Vilgrain V, Belghiti J, Raymond E, Faivre S. Alternative Response Criteria (Choi, European association for the study of the liver, and modified Response Evaluation Criteria in Solid Tumors [RECIST]) Versus RECIST 1.1 in patients with advanced hepatocellular carcinoma treated with sorafenib. Oncologist 2014; (4): 394-402. Ozenne V, Bouattour M, Goutté N, Vullierme MP, Ripault MP, Castelnau C, Valla DC, Degos F, Farges O. Prospective evaluation of the management of hepatocellular carcinoma in the elderly. Dig Liver Dis 2011; 43(12):1001-5.

Dr Mohamed Bouattour has received financial support/sponsorship for research support, consultation, or speaker fees from the following companies:

AstraZeneca, Bayer, BMS, Eisai, MSD, Roche and Sirtex Medical. 

Dr Neil Mehta underwent medical training at the University of California, San Francisco (UCSF). He was an Intern then a Resident at the Hospital of the University of Pennsylvania before becoming a Fellow in Gastroenterology and Transplant Hepatology at UCSF. He is Associate Professor in Medicine at UCSF and has held this position since 2013. He is specifically interested in issues related to the diagnosis and management of patients with hepatocellular carcinoma (HCC) particularly with regards to outcomes in liver transplantation.

Assoc. Prof. Neil Mehta has received financial support/sponsorship for research support, consultation, or speaker fees from the following companies:

Fujifilm Wako

Aiwu Ruth He MD underwent medical training at Hunan Medical University in China. She then completed post graduate training at East Carolina University, USA. Dr He completed a Fellowship at Georgetown University School of Medicine in 2006 and is currently Assistant Professor in the Division of Hematology / Oncology.

Dr He has received awards from the National Institute of Health, the American Association for Cancer Research and Digestive Disease Week. She has been an invited reviewer on a number of international journals and holds membership of several professional societies. Dr He has been an investigator in various different research trials in the field of hepatocellular carcinoma.

Relevant publications:

Kim K, Jha R, Prins PA, Wang H, Chacha M, Hartley ML, He AR. Regorafenib in advanced hepatocellular carcinoma (HCC): considerations for treatment. Cancer Chemother Pharmacol 2017 Nov;80(5):945-954. doi: 10.1007/s00280-017-3431-5. Epub 2017 Sep 20.

Fu Y, Silverstein S, McCutcheon JN, Dyba M, Nath RG, Aggarwal M, Coia H, Bai A, Pan J, Jiang J, Kallakury B, Wang H, Zhang YW, Giaccone G, He AR, Chung FL. An endogenous DNA adduct as a prognostic biomarker for hepatocarcinogenesis and its prevention by Theaphenon E in mice. Hepatology 2018 Jan;67(1):159-170. doi: 10.1002/hep.29380. Epub 2017 Nov 13.

Shetty K, He AR. A STORM in a teacup?-the challenges of adjuvant therapy in hepatocellular carcinoma (HCC). Transl Gastroenterol Hepatol 2016 Mar 16;1:2. doi: 10.21037/tgh.2016.03.10. eCollection 2016.

Sarantopoulos J, Mita AC, He A, Wade JL, Hsueh CT, Morris JC, Lockhart AC, Quinn DI, Hwang J, Mier J, Zhang W, Wack C, Yin J, Clot PF, Rixe O. Safety and pharmacokinetics of cabazitaxel in patients with hepatic impairment: a phase I dose-escalation study. Cancer Chemother Pharmacol 2017 Feb;79(2):339-351. doi: 10.1007/s00280-016-3210-8.

Gabrielson A, Tesfaye A, Choradia N, Marshall J, Pishvaian M, Smaglo B, Dorsch-Vogel K, Wang H, He AR. Phase II study of temozolomide and veliparib combination therapy for sorafenib-refractory advanced hepatocellular carcinoma. Cancer Chemotherapy and Pharmacology 2015 Nov;76(5):1073-9. doi: 10.1007/s00280-015-2852-2. Epub 2015 Oct 8.

Gabrielson A, Wu Y, Wang H, Jiang J, Kallakury B, Gatalica Z, Reddy S, Kleiner D, Fishbein T, Johnson L, Island E, Satoskar R, Banovac F, Jha R, Kachhela J, Feng P, Zhang T, Tesfaye A, Prins P, Loffredo C, Marshall J, Weiner L, Atkins M, He AR. Intratumoral CD3 and CD8 T-cell Densities Associated with Relapse-Free Survival in HCC. Cancer Immunol Res 2016 May;4(5):419-30. doi: 10.1158/2326-6066.CIR-15-0110. Epub 2016 Mar 11.

Tian X, Shivapurkar N, Wu Z, Hwang J, Pishvaian MJ, Weiner LM, Ley L, Zhou D, Zhi X, Wellstein A, Marshall JL, He AR. Circulating microRNA profile predicts disease progression in patients receiving second-line treatment of lapatinib and capecitabine for metastatic pancreatic cancer. Oncol Lett 2016 Mar;11(3):1645-1650. Epub 2016 Jan 13.

Gabrielson A, Miller A, Banovac F, Kim A, He AR, Unger K. Outcomes and Predictors of Toxicity after Selective Internal Radiation Therapy Using Yttrium-90 Resin Microspheres for Unresectable Hepatocellular Carcinoma. Front Oncol 2015 Dec 23;5:292. doi: 10.3389/fonc.2015.00292.

Gabrielson A, Tesfaye AA, Marshall JL, Pishvaian MJ, Smaglo B, Jha R, Dorsch-Vogel K, Wang H, He AR. Phase II study of temozolomide and veliparib combination therapy for sorafenib-refractory advanced hepatocellular carcinoma. Cancer Chemother Pharmacol 2015 Nov;76(5):1073-9. doi: 10.1007/s00280-015-2852-2. Epub 2015 Oct 8.

Wu Z, Gabrielson A, Hwang JJ, Pishvaian MJ, Weiner LM, Zhuang T, Ley L, Marshall JL, He AR. Phase II study of lapatinib and capecitabine in second-line treatment for metastatic pancreatic cancer. Cancer Chemother Pharmacol 2015 Dec;76(6):1309-14. doi: 10.1007/s00280-015-2855-z. Epub 2015 Oct 27.

Deeken JF, Wang H, Subramaniam D, He AR, Hwang J, Marshall JL, Urso CE, Wang Y, Ramos C, Steadman K, Pishvaian MJ. A phase 1 study of cetuximab and lapatinib in patients with advanced solid tumor malignancies. Cancer 2015 May 15;121(10):1645-53. doi: 10.1002/cncr.29224. Epub 2015 Jan 29.

Subramaniam D, He AR, Hwang J, Deeken J, Pishvaian M, Hartley ML, Marshall JL. Irreversible Multitargeted ErbB Family Inhibitors for Therapy of Lung and Breast Cancer. Curr Cancer Drug Targets 2015;14(9):775-93.

Cheng AL, Kang YK, He AR, Lim HY, Ryoo BY, Hung CH, Sheen IS, Izumi N, Austin T, Wang Q, Greenberg J, Shiratori S, Beckman RA, Kudo M; Investigators’ Study Group..Safety and efficacy of tigatuzumab plus sorafenib as first-line therapy in subjects with advanced hepatocellular carcinoma: A phase 2 randomized study. J Hepatol 2015 Oct;63(4):896-904. doi: 10.1016/j.jhep.2015.06.001.

Zhi X, Lin L, Yang S, Bhuvaneshwar K, Wang H, Gusev Y, Lee M, Kallakury B, Shivapurkar N, Cahn K, Tian X, Marshall J, Byers S, He AR. βII-spectrin (SPTBN1) suppresses progression of hepatocellular carcinoma and Wnt signaling via regulation of Wnt inhibitor Kallistatin. Hepatology 2014 Oct 12. doi: 10.1002/hep.27558.

Lin L, Yao Z, Bhuvaneshwar K, Gusev Y, Kallakury K, Yang X, Shetty K, and He AR. Transcriptional Regulation of STAT3 by SPTBN1 and SMAD3 in Hepatocellular Carcinoma Through cAMP-Response Element–Binding Proteins ATF3 and CREB2. Carcinogenesis 2014 Aug 5. pii: bgu163.

Rimassa L, Porta C, Borbath I, Daniele B, Finn R, Raoul J, Schwartz L, He AR, Trojan J, Peck-Radosavljevic M, Abbadessa G, Goldberg T, Santoro A, Bruix J. Tivantinib in MET-high hepatocellular carcinoma patients and the ongoing Phase III clinical trial. Hepatic Oncol 2014, doi:10.2217/HEP.14.3

Rana N., Ju A.W, Bazylewicz M, Kallakury B, He AR, Unger K, Lee J. Yttrium-90 radioembolization in patients with hepatocellular carcinoma who have previously received sorafenib. Front Oncol 2013 Dec 12; 3(323): 1-10.

Weinberg B, Wang H, Yang X, Wu C, Pishvaian M, He AR, Marshall J, Hwang J. Maintenance therapy with capecitabine in patients with resected pancreatic adenocarcinoma after adjuvant therapy, a retrospective cohort study. Gastrointest Cancer Res 2014 May;7(3-4):91-7.

Forero-Torres A, Infante J, Waterhouse D, Wong L, Arrowsmith V, He AR, Hart L,Trent D, Wade J, Jin X, Wang Q, Austin T, Rosen M, Beckman R, von Roemeling R, Greenberg J, Saleh M. Phase 2, multicenter, open-label study of tigatuzumab (CS-1008), a humanized monoclonal antibody targeting death receptor 5, in combination with gemcitabine in chemotherapy-naive patients with unresectable or metastatic pancreatic cancer. Cancer Med 2013 Dec;2(6):925-32. doi: 10.1002/cam4.137. Epub 2013 Oct 25.

Shivapurkar N, Mikhail S, Navarro R, Bai W, Marshall J, Hwang J, Pishvaian M, Wellstein A, He AR. Decrease in blood miR-296 predicts chemotherapy resistance and poor clinical outcome in patients receiving systemic chemotherapy for metastatic colon cancer. Int J Colorectal Dis 2013 Jun;28(6):887. doi: 10.1007/s00384-012-1560-1. Epub 2012 Aug 15.

Zhang JX, Li DQ, He AR, Motwani M, Vasiliou V, Eswaran J, Mishra L, Kumar R . Synergistic inhibition of hepatocellular carcinoma growth by cotargeting chromatin modifying enzymes and poly (ADP-ribose) polymerases. Hepatology 2012 Jun;55(6):1840-51.

Pishvaian MJ, Marshall JL, Wagner AJ, Hwang JJ, Malik S, Cotarla I, Deeken JF, He AR, Daniel H, Halim AB, Zahir H, Copigneaux C, Liu K, Beckman RA, Demetri GD. A phase 1 study of efatutazone, an oral peroxisome proliferator-activated receptor gamma agonist, administered to patients with advanced malignancies. Cancer 2012 Nov 1;118(21):5403-13. doi: 10.1002/cncr.27526. Epub 2012 May 8.

Pishvaian MJ, Slack R, Koh EY, Beumer JH, Hartley ML, Cotarla I, Deeken J, He AR, Hwang J, Malik S, Firozvi K, Liu M, Elston B, Strychor S, Egorin MJ, Marshall JL. A Phase I clinical trial of the combination of imatinib and paclitaxel in patients with advanced or metastatic solid tumors refractory to standard therapy. Cancer Chemother Pharmacol 2012 Dec;70(6):843-53. doi: 10.1007/s00280-012-1969-9. Epub 2012 Sep 27.

Kunz PL, He AR, Colevas AD, Pishvaian MJ, Hwang JJ, Clemens PL, Messina M, Kaleta R, Abrahao F, Sikic BI, Marshall JL.2012. Phase I trial of ixabepilone administered as three oral doses each separated by 6 hours every 3 weeks in patients with advanced solid tumors. Invest New Drugs 2012 Dec; 30(6): 2364-2370.

Dr Aiwu Ruth He has received financial support/sponsorship for research support, consultation, or speaker fees from the following companies:

Genentech and MERCK 

Dr Emil Cohen completed medical training at George Washington University Medical School and then went on to an Internship at Washington Hospital Center. He completed residencies and fellowships in the Department of Radiology at the Mount Sinai Medical Center in New York. He is currently Assistant Professor in the Department of Radiology at Georgetown University Hospital in Washington DC. Dr Cohen has been an investigator and co-investigator on two international clinical trials for hepatocellular carcinoma and is a reviewer on the Journal of Vascular and Interventional Radiology and the American Journal of Roentgenology. Relevant publications Gaba RC, Lewandowski RJ, Hickey R, Baerlocher MO, Cohen EI, Dariushnia SR, d’Othée BJ, Padia SA, Salem R, Wang DS, Nikolic B. Transcatheter therapy for hepatic malignancy: standardization of terminology and reporting criteria. J Vasc Interv Radiol 2016 Apr; 27(4): 457-73. McWilliams JP, Kuo MD, Rose SC, Bagla S, Caplin DM, Cohen EI, Faintuch S, Spies JB, Saad WE, Nikolic B. Society of interventional radiology position statement: prostate artery embolization for treatment of benign disease of the prostate. J Vasc Interv Radiol 2014; 25: 1349–1351. Franklin BR, Patel KM, Nahabedian MY, Baldassari LE, Cohen EI, Bhanot P. Predicting abdominal closure after component separation for complex ventral hernias: maximizing the use of preoperative computed tomography. Ann Plast Surg 2013; 71: 261–265. Lee JS, Patel KM, Zou Z, Prince MR, Cohen EI. Computerized tomographic and magnetic resonance angiography for perforator-based free flaps: technical considerations. Clinics in Plastic Surgery 2011; 38: 219–228. Stanca CM, Fiel MI, Aledort L, Cohen E, del Rio Martin J, Schiano TD. Factors associated with persistent thrombocytopenia after liver transplantation. Transplant Proc 2010; 42: 1769–1773. Aidi HE, Mani V, Weinshelbaum KB, Aguiar SH, Taniguchi H, Postley JE, Samber DD, Cohen EI, Stern J, van der Geest RJ, Reiber JH, Woodward M, Fuster V, Gidding SS, Fayad ZA. Cross-sectional, prospective study of MRI reproducibility in the assessment of plaque burden of the carotid arteries and aorta. Nat Clin Pract Cardiovasc Med 2009 Mar; 6(3): 219-28. doi: 10.1038/ncpcardio1444. Epub 2009 Jan 27. Lim KH, Ward SC, Roayaie S, Cohen E, Schwartz M, Fiel MI, Thung SN. Multiple inflammatory and serum amyloid a positive telangiectatic hepatic adenomas with glycogenated nuclei arising in a background of nonalcoholic steatohepatitis. Semin Liver Dis 2008 Nov; 28(4): 434-439. Siegel AB, Cohen EI, Ocean A, Lehrer D, Goldenberg A, Knox JJ, Chen H, Clark-Garvey S, Weinberg A, Mandeli J, Christos P, Mazumdar M, Popa E, Brown RS Jr, Rafii S, Schwartz JD. Phase II trial evaluating the clinical and biologic effects of bevacizumab in unresectable hepatocellular carcinoma. J Clin Oncol 2008 Jun 20; 26(18): 2992-2998. Cohen EI, Kelly SA, Edye M, Mitty HA, Bromberg JS. MRI estimation of total renal volume demonstrates significant association with healthy donor weight. Eur J Radiol 2009 Aug; 71(2): 283-287. Cohen EI, Weinreb DB, Siegelbaum RH, Honig S, Marin M, Weintraub JL, Lookstein RA. Time resolved magnetic resonance angiography for the classification of endoleaks after endovascular aneurysm repair. J Magn Reson Imaging 2008 Mar; 27(3): 500-503. Emre S, Arnon R, Cohen E, Morotti RA, Vaysman D, Shneider BL. Resolution of hepatopulmonary syndrome after auxiliary partial orthotopic liver transplantation in abernethy malformation. A case report. Liver Transpl 2007; 13: 1662-1668. Talenfeld AD, Schwope RB, Alper HJ, Cohen EI, Lookstein RA. MDCT angiography of the renal arteries in patients with atherosclerotic renal artery stenosis: implications for renal artery stenting with distal protection. AJR Am J Roentgenol 2007; 188: 1652-1658. Schwope RB, Alper HJ, Talenfeld AD, Cohen EI, Lookstein RA. MR angiography for patient surveillance after endovascular repair of abdominal aortic aneurysms. AJR Am J Roentgenol 2007; 188(4): W334-340. Xu R, Bu-Ghanim M, Fiel M, Schiano T, Cohen E, Thung S. Hepatocellular carcinoma associated with an atypical presentation of Wilson's Disease. Semin Liver Dis 2007; 27(1): 124-127. Levi G, Moueen B, Xu R, Cohen E, Abittan C, Roayaie S. 48 year-old obese man with a 3 cm liver lesion and a history of hemochromatosis and lymphoma. Semin Liver Dis 2004; 24(3): 327-332. Cohen EI, Wilck E, Shapiro R. Hepatic imaging in the 21st Century. Semin Liver Dis 2006; 26: 363–372.

Jean-Charles Nault received his MD and PhD from Paris Descartes University. He is currently working in the liver unit of the Jean Verdier Hospital in Bondy, France with a high priority on early detection of primary liver tumors and on therapeutic innovation. He is also an active member of the Laboratory of Functional Genomics of Solid Tumours at the INSERM UMR 1162 headed by Professor Jessica-Zucman Rossi. His research is dedicated to translational research in particular the identification of new driver genes in hepatocellular adenoma and hepatocellular carcinoma, of new therapeutic targets and of the molecular determinants of hepatocellular carcinoma’s prognosis. Relevant publications Nault JC, Couchy G, Balabaud C, Morcrette G, Caruso S, Blanc JF, Bacq Y, Calderaro J, Paradis V, Ramos J, Scoazec JY, Gnemmi V, Sturm N, Guettier C, Fabre M, Savier E, Chiche L, Labrune P, Selves J, Wendum D, Pilati C, Laurent A, De Muret A, Le Bail B, Rebouissou S, Imbeaud S; GENTHEP investigators., Bioulac-Sage P, Letouzé E, Zucman-Rossi J. Molecular classification of hepatocellular adenoma associates with risk factors, bleeding, and malignant transformation. Gastroenterology 2016 Dec 7. Nault JC. The end of almost 10 years of negative RCTs in advanced hepatocellular carcinoma. Lancet 2017 Jan 7; 389(10064): 4-6. Nault JC, Datta S, Imbeaud S, Franconi A, Mallet M, Couchy G, Letouzé E, Pilati C, Verret B, Blanc JF, Balabaud C, Calderaro J, Laurent A, Letexier M, Bioulac-Sage P, Calvo F, Zucman-Rossi J. Recurrent AAV2-related insertional mutagenesis in human hepatocellular carcinomas. Nat Genet 2015 Oct; 47(10): 1187-93. Nault JC, Calderaro J, Di Tommaso L, Balabaud C, Zafrani ES, Bioulac-Sage P, Roncalli M, Zucman-Rossi J. Telomerase reverse transcriptase promoter mutation is an early somatic genetic alteration in the transformation of premalignant nodules in hepatocellular carcinoma on cirrhosis. Hepatology 2014 Dec; 60(6): 1983-92. Nault JC, Mallet M, Pilati C, Calderaro J, Bioulac-Sage P, Laurent C, Laurent A, Balabaud C, Zucman-Rossi J. High frequency of TERT promoter mutations in hepatocellular carcinoma and pre-neoplastic lesions. Nat Commun 2013; 4: 2218. doi: 10.1038/ncomms3218. Nault JC, de Reyniès A, Villanueva A, Calderaro J, Rebouissou S, Couchy G, Decaens T, Franco D, Imbeaud S, Rousseau F, Azoulay D, Saric J, Blanc JF, Balabaud C, Bioulac-Sage P, Laurent A, Laurent-Puig P, Llovet JM, Zucman-Rossi J. A hepatocellular carcinoma 5-gene score associated with survival of patients following liver resection. Gastroenterology 2013 Jul; 145(1): 176-87. doi: 10.1053/j.gastro.2013.03.051. Nault JC, Bioulac-Sage P, Zucman-Rossi J. Hepatocellular benign tumors-from molecular classification to personalized clinical care. Gastroenterology 2013 Feb; 144(5): 888-902. doi: 10.1053/j.gastro.2013.02.032. Nault JC, Fabre M, Couchy G, Pilati C, Jeannot E, Tran Van Nhieu J, Saint-Paul MC, De Muret A, Redon MJ, Buffet C, Salenave S, Balabaud C, Prevot S, Labrune P, Bioulac-Sage P, Scoazec JY, Chanson P, Zucman-Rossi J. GNAS-activating mutations define a rare subgroup of inflammatory liver tumors characterized by STAT3 activation. J Hepatol 2012 Jan; 56(1): 184-91.