Assessment of response to therapy in hepatocellular carcinoma

Figures & data

Table I. Overview of current therapeutic modalities for HCC. Surgery offers the potential for cure. Local therapies may result in cure for very small lesions that are completely ablated, whereas other modalities result in reduction of tumor burden or delay in tumor progression.

Surgery	• Transplantation • Resection
Local therapy	• Radiofrequency ablation • Microwave ablation • Cryotherapy • Ethanol or acetic acid ablation
Regional therapy	• Trans-arterial chemotherapy • Trans-arterial radiation therapy • External beam radiation • Stereotactic body radiation therapy
Systemic therapy	• Doxorubicin • Sorafenib

Table II. Comparison of anatomical and morphological imaging-based criteria.

	WHO (1)	RECIST 1.0 (2)	RECIST 1.1 (3)	EASL (20)	AASLD/JNCI mRECIST (18,19)
Size of lesion	+	+	+	+	+
Vascularity—contrast enhancement	−	−	−	+	+
Dimensions	2	1	1	2	1
Number of lesions		5 target; 5 non-target	2 target; 5 non-target

Figure 1. MR imaging of HCC. A: Pre-treatment. A solitary enhancing HCC is present in the right lobe. B: Post-transarterial chemoembolization. The HCC has been successfully treated, and there is an absence of viable tumor despite an increase in size of lesion.

Table III. Measures of response to therapy.

	Criterion	Description	Limitations
Clinical	Symptomatic relief or progression	Reduction or progression of symptoms, change in QOL measures, transfusion requirements or other parameters	Lack of validated tools to measure QOL, or symptom response
			Lack of defining symptoms
	Tumor recurrence		Lack of standardized time to assess response based on size or tumor necrosis
	New lesions and tumor progression		Challenging to document new tumors in cirrhotic livers and distinguish from cirrhotic nodules
			Progression of underlying liver disease can mask tumor progression
	Survival	Time from treatment initiation to death	Confounded by competing causes of mortality from liver disease or therapy
Biochemical (tumor markers)	AFP	Serum tumor marker	AFP is not elevated in up to 50% patients with HCC
			AFP levels may not normalize even with complete tumor response in patients with underlying chronic hepatitis
Structural imaging (anatomical-morphological)	RECIST	Tumor size, largest diameter	Size measurements
			Observer variations
	RECIST 1.1	Unidimensional measurement of tumor size	Irregular or infiltrative lesions difficult to quantitate
	WHO	Cross-product of tumor size in two directions	Changes may lag behind biochemical or molecular changes
	EASL	Contrast enhanced lesion ( = viable tumor )	Contrast-enhanced region
	mRECIST	Unidimensional? assessment of viable tumor
	Volumetry	Assessment of viable tumor volume based on contrast enhancement
Functional imaging (cellular-molecular-biological)	18F FDG-PET	Metabolic/proliferative activity within tumors	Not widely available
	DW-MRI	Water motion and tumor cellularity	Not standardized, other than for PET imaging
	DCE-MRI	Contrast biodistribution within tumors	Not yet validated as markers of outcomes, or viable tumor
	MRS	Relative amounts of biochemical components within tumors

Modalities in italics are currently under investigation.

18F FDG-PET = 18F fluorodeoxyglucose positron emission tomography; AFP = alpha-fetoprotein; DCE-MRI = diffusion contrast-enhanced MRI; DW-MRI = diffusion-weighted MRI; EASL = European Association for Study of Liver Disease; MRS = magnetic resonance spectroscopy; RECIST = Response Evaluation Criteria in Solid Tumors; WHO = World Health Organization.

Figure 2. Criteria used for the classification of response to therapy for hepatocellular cancer. Disease control is defined as stable disease or objective response, whereas progressive disease is defined by change in selected imaging or biochemical parameters. AFP = alpha-fetoprotein; mRECIST = modified Response Evaluation Criteria in Solid Tumors; RECIST = Response Evaluation Criteria in Solid Tumors; WHO = World Health Organization.

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