Page 59 - MemoriaEHD-Eng

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The activity in translational research has primed the establishment of a molecular clas-

sification of liver cancer and elucidated some of the most relevant signalling pathways

involved in tumour progression. In addition, studies have identified genomic signatures
associated with different outcome either due to tumor progression or to liver disease pro-

gression. As a whole, the combined clinical and translational research is paving the path
for stratified medicine.

The BCLC group work has resulted, along the years, in more than 600 publications, with an

Impact Factor higher than 3.000, and a total citations number higher than 36.000.

• s D, h y, v a, r s, F J, t B. Integrative molecular analy-
Most relevant iaoshiDaiLLaNuevaoayaieerreraBaK
sis of intrahepatic cholangiocarcinoma reveals 2 classes that have different outco-
scientific
mes.Gastroenterology. 2013 Apr;144(4):829-40.
articles
• reig M, riMoLa J, torres F, DarNeLL a, roDríguez-Lope C, ForNer a. Postprogression sur-
vival of patients with advanced hepatocellular carcinoma: rationale for second-line

trial design.Hepatology. 2013 Dec;58(6):2023-31.

• NauLt JC, De reyNiès a, viLLaNueva a, CaLDeraro J, reBouissou s, CouChy g et aL.. A he-
patocellular carcinoma 5-gene score associated with survival of patients after liver

resection.Gastroenterology. 2013 Jul;145(1):176-87.

• FiNN rs, pooN rt, yau t, KLüMpeN hJ, CheN Lt, KaNg yK. Phase I study investigating evero-
limus combined with sorafenib in patients with advanced hepatocellular carcinoma.J

Hepatol. 2013 Dec;59(6):1271-7.

The 2013 clinical highlights include the demonstration of the correlation between
Highlights
tumor progression and survival. This validates time to progression as a relevant
signal to detect treatment efficacy in phase 1-2 trials, but at the same time we

have exposed that the pattern of progression rather than all progression types is

key to predict the outcome of the patients. Design of future trials has to be modi-
fied according to our findings.

We have also shown that the development of adverse events to sorafenib are as-

sociated to a better outcome. Thus, there is need to identifying the profile of the

patients that is responsible for adverse events development. Adverse event ap-
pearance has to be incorporated also in trial design. Indeed, during 2013 we have

published the phase 2 of sorafenib in combination with everolimus as well as the
phase 3 trial in second line assessing brivanib vs placebo. Both studies were nega-

tive, but data have helped to optimise future therapeutic studies.

At the translational level, we have published major contributions to characterize

the genomic profile of hepatocellular carcinoma and cholangiocarcinoma. Our stu-
dies have allowed a consensus molecular classification of hepatocellular carcinoma
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with specific signatures that refine the current conventional evaluation of the pa- 20
T
tients. Similar effort has been done for the fibrolamellar variant of hepatocellular OR
carcinoma and for intrahepatic cholangiocarcinoma.
P
RE
New studies to evaluate imaging technology and novel therapeutic agents have L
A
been initiated in 2013. Also, further characterization of genetics and epigenetics in NU
human liver cancer are under way.
N
A
International leadership has been consolidated and this has resulted in the prepa- D /
H
ration of high impact reviews in high end journals as well as clinical practice and E
ER
research guidelines in the field of liver cancer.
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