Targeted systemic therapies for hepatocellular carcinoma: Clinical perspectives, challenges and implications

Table 1 Response assessment by modified World Health Organization criteria and modified Response Evaluation Criteria in Solid Tumors

Parameter	Modified WHO	Modified RECIST
Type of assessment	Spiral CT	Spiral CT or dynamic MRI
Frequency of assessment	≥ 4 wk	6-8 wk
Measurement of tumor volume	Bidimensional measurement	Unidimensional measurement
Tumor necrosis measurement	Reduction in viable tumor area using contrast-enhanced radiological imaging	Reduction in viable tumor area using contrast-enhanced radiological imaging
Viable tumor definition	Enhanced areas inside treatment lesions	Uptake of contrast agent in the arterial phase
Complete response	Complete disappearance of tumor enhancement determined by 2 observations ≥ 4 wk apart	Disappearance of any intratumoral arterial enhancement in all target lesions
Partial response	> 50% reduction in total area of tumor enhancement determined by 2 observations ≥ 4 wk apart	≥ 30% decrease in the sum of diameters of viable target lesions, taking as reference the baseline sum of the diameters of target lesions
Stable disease	Insufficient shrinkage to qualify for partial response and insufficient increase to qualify for progressive disease	Any cases that do not qualify for either partial response or progressive disease
Progressive disease	> 25% increase in total area of tumor enhancement or the appearance of new lesions	≥ 20% increase in the sum of the diameters of viable target lesions, taking as reference the smallest sum of the diameters of viable target lesions recorded since the treatment started or the appearance of 1 or more new lesions

CT: Computed tomography; MRI: Magnetic resonance imaging; RECIST: Response Evaluation Criteria in Solid Tumors; WHO: World Health Organization.

Table 2 Agents with antiangiogenic properties in development for the treatment of hepatocellular carcinoma

Agent	Therapeutic target	Phase of study
Brivanib	VEGFR, FGFR	III
Bevacizumab	VEGF	II
Ramucirumab	VEGFR-2	III
ABT-869	VEGFR-1, VEGFR-2, PDGFR-β, c-KIT, Flt-3	III
Everolimus	mTOR	III
ARQ 197	c-MET	II