Emerging role of 18F-fluorodeoxyglucose positron emission tomography for guiding management of hepatocellular carcinoma

Table 1 Current literature evaluating the role of ¹⁸F-fluorodexoyglucose positron emission tomography in staging hepatocellular carcinoma

First author	Year	No. of patients	Study design	Staging system	No. of patient with a change of stage by FDG PET	No. of patients with a change of treatment by FDG PET
Yoon et al[34]	2007	87	Not specified	TNM	4 patients (4.6%), 3 patients TNM IVa to IVb, 1 patient TNM III to IVa	Not specified
Kawamura et al[26]	2014	64	Retrospective	BCLC	16 patients (25%), 6 patients BCLC 0 to C, 7 patients BCLC A to C, 3 patients BCLC B to C	16 patients (25%)
Cho et al[35]	2014	457	Retrospective	BCLC and TNM	7 patients (1.5%), 6 patients BCLC A to C, 1 patient BCLC B to C	7 patients (1.5%)

FDG: ¹⁸F-fluorodexoyglucose; PET: Positron emission tomography; HCC: Hepatocellular carcinoma; BCLC: Barcelona Clinic Liver Cancer.

Table 2 Current literature evaluating the prognostic value of ¹⁸F-fluorodexoyglucose positron emission tomography in hepatocellular carcinoma patients with surgical resection

First author	Year	No. of patients	Study design	PET parameter	Cut-off values of PET parameter	Findings
Hatano et al[41]	2006	31	Retrospective	TLR	2.0	TLR showed significant positive association with overall survival
Ahn et al[47]	2011	93	Retrospective	SUV, TLR	4.0, 2.0	High SUV and TLR were predictors for early recurrence, but showed no statistical significance on multivariate analysis
Kitamura et al[42]	2012	63	Retrospective	TLR	2.0	TLR was an independent predictor for early recurrence
Han et al[43]	2014	298	Retrospective	SUV	3.5	SUV was an independent predictor for recurrence-free survival and overall survival
Baek et al[48]	2015	54	Retrospective	Tumor-to-muscle ratio	6.36	Tumor-to-muscle ratio was associated with recurrence-free survival, but, no statistical significance on multivariate analysis
Cho et al[44]	2017	56	Retrospective	SUV	4.9	Recurrence rate was higher in patients with high SUV, but, no significant difference of disease-free survival and overall survival according to SUV
Hwang et al[50]	2018	526	Retrospective	Visual analysis	-	Combination of ADV score and PET finding can predict risk of early recurrence and survival
Kim et al[49]	2018	226 HBV-related HCC	Retrospective	Visual analysis	-	Positive PET finding was associated with overall survival, but, not a predisposing factor for disease-free survival in HBV-related HCC patients
Lim et al[45]	2018	78	Prospective	Visual analysis	-	Positive PET finding was an independent predictor for early recurrence
Yoh et al[46]	2018	207	Retrospective	TLR	2.0	Prognostic model incorporating ALBI grade and PET finding can predict the disease-free survival and overall survival

FDG: ¹⁸F-fluorodexoyglucose; PET: Positron emission tomography; HCC: Hepatocellular carcinoma; HBV: Hepatitis B virus; TLR: Tumor-to-non-tumor liver uptake ratio; SUV: Standardized uptake value; ADV: Alpha-fetoprotein-Des-gamma-carboxy prothrombin-tumor volume; ALBI: Albumin-bilirubin.

Table 3 Current literature evaluating the prognostic value of ¹⁸F-fluorodexoyglucose positron emission tomography in hepatocellular carcinoma patients with liver transplantation

First author	Year	No. of patients	Study design	PET parameter	Cut-off values of PET parameter	Findings
Yang et al[51]	2006	38	Retrospective	Visual analysis	-	Patients with negative PET findings had significantly higher recurrence-free survival than those with positive findings
Kornberg et al[52]	2009	42	Retrospective	Visual analysis	-	Patients with positive PET findings had significantly higher recurrence rate with lower recurrence-free survival than those with negative findings
Lee et al[39]	2009	59	Retrospective	Tmax/Lmax	1.15	Tmax/Lmax was an independent predictor for recurrence-free survival
Kornberg et al[53]	2012	91	Retrospective	Visual analysis	-	PET finding was an independent prognostic variable for recurrence-free survival, and positive PET status was the independent predictor of patient dropout from the waiting list of liver transplantation
Lee et al[54]	2013	191	Retrospective	Visual analysis	-	Positive PET status was an independent prognostic factor for disease-free survival influencing early recurrence
Detry et al[55]	2015	27	Retrospective	Tmax/Lmax	1.15	Tmax/Lmax independently predicted recurrence-free survival
Hong et al[56]	2016	123	Retrospective	TLR	1.10	Combination of serum AFP and PET finding predicted better disease-free survival than using the Milan criteria
Hsu et al[57]	2016	147	Retrospective	SUV, TLR	4.8, 2.0	Combination of UCSF criteria and PET finding can predict the risk of recurrence
Lee et al[58]	2016	280	Retrospective	Visual analysis	-	The criteria combined of FDG PET and total tumor size can predict disease-free survival and overall survival, and showed similar area under the ROC curve of the Milan and UCSF criteria
Kornberg et al[59]	2017	116	Retrospective	Visual analysis	-	Combining radiographic criteria with FDG PET finding can predict recurrence-free survival
Takada et al[60]	2017	182	Retrospective	Visual analysis	-	PET positive status was an independent risk factor for recurrence-free survival
Ye et al[61]	2017	103	Retrospective	Visual analysis	-	Patients beyond the Milan criteria with a negative PET finding had comparable recurrence-free survival in comparison with those within the Milan criteria

FDG: ¹⁸F-fluorodexoyglucose; PET: Positron emission tomography; HCC: Hepatocellular carcinoma; Tmax/Lmax: Maximum FDG uptake of tumor-to-maximum FDG uptake of the normal liver ratio; TLR: Tumor-to-non-tumor liver uptake ratio; SUV: Standardized uptake value; AFP: Alpha-fetoprotein; UCSF: University of California San Francisco; ROC: Receiver operating characteristic.

Table 4 Current literature evaluating the prognostic value of ¹⁸F-fluorodexoyglucose positron emission tomography in hepatocellular carcinoma patients with treatments other than surgical resection and liver transplantation

First author	Year	No. of patients	Study design	PET parameter	Cut-off values of PET parameter	Treatment	Findings
Song et al[64]	2012	83	Retrospective	TLR	1.90	TACE	Patients with low TLR ratios had significantly longer overall survival than those with high ratios, but, no significant difference of time-to-progression was shown between them
Song et al[65]	2013	58	Retrospective	TLR	1.70	TACE	FDG PET can predict response to TACE and tumor progression
Ma et al[66]	2014	27	Retrospective	ΔTSUVmax%	0.1	TACE	ΔTSUVmax% can predict response to TACE and overall survival
Kim et al[67]	2015	77	Retrospective	TLR	1.83	TACE	TLR was an independent predictor of overall survival and tumor progression
Kim et al[68]	2011	107	Retrospective	SUV	6.1	CCRT	SUV was significantly associated with progression-free survival and overall survival, and patients with high SUV was more likely to have extrahepatic metastasis
Huang et al[69]	2013	31	Retrospective	SUV	3.2	SABR	SUV was the significant prognostic indicator of disease control rate
Rhee et al[70]	2017	228	Retrospective	SUV, TLR	4.825,2.355	Radiotherapy	Low FDG uptake group had better treatment response, longer median progression-free and overall survival
Kucuk et al[71]	2013	19	Retrospective	Visual analysis	-	Radioembolization	High FDG uptake lesions unexpectedly had better progression-free survival rates
Sabet et al[72]	2014	33	Retrospective	Visual analysis	-	Radioembolization	Findings on pre-therapeutic PET and relative changes of FDG uptake on post-therapeutic PET independently predict overall survival
Soydal et al[73]	2015	28	Retrospective	Visual analysis, SUV	Not specified	Radioembolization	Age, serum AFP level, and tumor size were significantly associated with survival, but, SUV showed no significant association
Abuodeh et al[74]	2016	34	Retrospective	Visual analysis	-	Radioembolization	FDG avidity independently predicts local liver control, distant liver control, and progression-free survival
Jreige et al[75]	2017	48	Prospective	SUV, TLR	5.0,2.0	Radioembolization	Both SUV and TLR were predictive markers of overall survival
Lee et al[76]	2011	29	Retrospective	SUV	5.0	Sorafenib	SUV was an independent prognostic factor for overall survival
Sung et al[40]	2018	35	Retrospective	TLR	2.9	Sorafenib	TLR was significant predictor for progression-free survival and overall survival

FDG: ¹⁸F-fluorodexoyglucose; PET: Positron emission tomography; HCC: Hepatocellular carcinoma; TLR: Tumor-to-non-tumor liver uptake ratio; ΔTSUVmax%: Relative changes of maximum FDG uptake of tumor between pre-therapeutic and post-therapeutic FDG PET scans; SUV: Standardized uptake value; TACE: Transarterial chemoembolization; CCRT: Concurrent chemoradiotherapy; SABR: Streotactic ablative radiotherapy; AFP: Alpha-fetoprotein.