The SUV on 18F-FDG-PET/CT imaging as an independent predictor for overall survival and disease free survival after hepatectomy of Hepatocellular carcinoma(

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The SUV on 18F-FDG-PET/CT imaging as an independent predictor for overall survival and disease free survival after hepatectomy of Hepatocellular carcinoma( ≤5cm) Xu-Guang Hu, Sung yeon Hong,Ingyu Kim, Mao wei, Bong-Wan Kim, Hee-Jung Wang Department of Hepatobiliary Surgery and Liver Transplantation, Ajou University School of Medicine, Suwon, Korea

Background & AIM: 18F-Fluoro-deoxyglucose (FDG) PET/CT can be used to monitor the biological behavior and predicts clinical outcome in patients with HCC. To evaluate whether SUV could predict the risk of recurrence and death for patients with HCC (≤5) patients after hepatectomy. .

478 cases underwent surgical treatment 216 HCC cases with hepatectomy Methods and patients: Retrospective analysis was performed on a database of HCC patients who underwent hepatectomy between November 2008 and December 2014. 478 cases underwent surgical treatment 1. 100 cases Liver transplantation 262 2. 107 cases More than 5cm Exclusion 3. 55 cases without preoperative PET 216 HCC cases with hepatectomy

Methods and patients : Sensitivity:57.9% Specificty :86.8% Specificity:86.8% Area under the Curve : 0.701 Cutoff value:4.75 P value: 0.004 Area under the Curve : 0.757 Cutoff value:3.75 P value: 0.000

Median follow-up time:32.5 months (range,1-83) Results: Number at risk ( DFS) Year 1 3 5 216 169 66 20 % 81.6 64.4 56.3 Number at risk ( OS) Year 1 3 5 216 195 94 37 % 94.8 90.3 Median follow-up time:32.5 months (range,1-83)

Results: Comparison of clinical and pathological characteristics between the cutoff value of SUV Variables SUV<4.75 (n =179) SUV≥4.75 (n =37) P value Male sex 137/179 30/37 0.093 Age (years) 55.6 ± 9.40 55.8 ± 9.23 0.900 Etiology of cirrhosis HBV 138 29 1.000 HCV 12 4 0.486 Other 0.615 Albumin(g/L) 4.23 ± 0.34 4.19 ± 0.37 0.457 Tbilirubin(mg/dl) 0.80 ± 0.40 0.78 ± 0.35 0.747 AST(U/L) 41.4 ± 28.5 42.0 ± 19.8 0.903 ALT(U/L) 38.9 ± 30.9 37.0 ± 21.5 0.724 ICG R15 (%) 15.8 ± 7.92 15.0 ± 7.72 0.546 AFP (>400ng/ml) 29/179 (16.2%) 14/37 (37.8%) 0.008 Serum gloucose (mg/dl) 121.01 ± 35.6 123.89 ± 54.6 0.686 Tumor size(cm) 2.54 ± 0.96 3.51 ± 1.03 0.000 Tumor number (multi) 19/179 6/37 0.395 Vp present 28/178 18/36 Vv present 1/172 2/34 0.071 B present 6/172 5/36 0.025 IM present 17/177 10/36 0.006 McVI present 54/174 25/35 Microscopic resection Margin present 13/179 7/37 0.054 Cirrhosis (grade 4) 109//179 20/37 0.465 ES Grade ( grade 4) 34/168 20/32 0.002 Tumor recurrence 53/179 (29.6%) 19/37 (51.4%) 0.013

Results: Kaplan-Meier survival curve comparing the disease free survival time and overall survival between the cutoff value of SUV Normal SUV n=179 Normal SUV n=179 Elevated SUV n=37 Elevated SUV n=37 Log-rank test, P value=0.000 Log-rank test, P value=0.000 Number at risk ( DFS) Year 1 3 5 suv<4.75 179 151 58 17 % 87.0 68.0 59.9 Suv≥4.75 37 18 8 54.8 46.3 39.7 Number at risk ( OS) Year 1 3 5 suv<4.75) 179 169 82 31 % 98.3 94.4 Suv≥4.75) 37 27 12 6 77.5 69.0

Results: Cox proportional hazards model of risk factors for Disease free survival in 216 HCC patients after hepatectomy Prognostic variables Univariate Multivariate HR (95%CI) P value SUV(4.75) 2.569(1.514-4.358) 0.000 0.992(1.116-3.588) 0.020 Tumor size(3.75cm) 2.226(1.327-3.734) 0.002 1.752(0.986-3.113) 0.056 AFP (>400ng/ml) 1.190(0.688-2.056) 0.534 Vascular invasion 2.074(1.257-3.423) 0.004 1.510(0.823-2.773) 0.184 IM present 2.511(1.395-4.519) 1.659(0.856-3.217) 0.134 McVI present 2.102(1.309-3.375) 1.317(0.741-2.340) 0.384 Microscopic resection Margin present 1.875(0.931-3.778) 0.079 ES grade (4) 1.441(0.861-2.412) 0.165 Abbreviation: AFP; α- fetoprotein, CI: Confidence intervals, HR: hazard ratio, IM: introhepatic metastasis, McVI: microvascular invasion, SUV: standardized uptake value.

Results: Cox proportional hazards model of risk factors for Overall survival in 216 HCC patients after hepatectomy Prognostic variables Univariate Multivariate HR (95%CI) P value SUV(4.75) 8.369(3.350-20.91) 0.000 5.048(1.732-14.72) 0.003 Tumor size(3.75cm) 6.089(2.447-15.15) 4.101(1.415-11.88) 0.009 AFP (>400ng/ml) 1.025(0.340-3.094) 0.965 Vascular invasion 2.185(0.856-5.573) 0.102 IM present 3.273(1.170-9.159) 0.024 1.153(0.340-3.911) 0.820 McVI present 2.876(1.147-7.427) 0.029 1.003(0.339-2.968) 0.996 Microscopic resection Margin present 3.923(1.404-10.96) 2.875(0.879-9.404) 0.081 ES grade (4) 1.947(0.706-5.375) 0.198 Abbreviation: AFP; α- fetoprotein, CI: Confidence intervals, HR: hazard ratio, IM: introhepatic metastasis, McVI: microvascular invasion, SUV: standardized uptake value.

Results: Kaplan-Meier survival curve comparing the disease free survival time and overall survival between the low, moderate and high risk groups 1 1 2 2 Line 0 (low risk): suv<4.75 and tumor size <3.75 Line 1 (moderate risk): suv≥4.75 or tumor size ≥ 3.75 Line 2 (high risk): suv≥4.75 and tumor size ≥3.75

Conclusions: The elevated SUV (≥4.75) on 18F-FDG-PET/CT imaging was an independent and significant predictor for overall survival and disease free survival for the HCC patient (≤5 cm)after hepatectomy. SUV combined tumor size can be used for selecting patients who will be most benefit from hepatectomy. Otherwise , whether the patients with high risk factors (suv≥4.75 and tumor size ≥3.75) will be benefit from liver transplantation need further study.

Thanks for your kind attention!

Recurrence within 24 months Recurrence beyond 24 months Elevated SUV Value TACE (n=12) (N=19) RFA(n=4) RTx(n=2) Re-resection(n=1) Recurrent cases TACE(n=29) TACE(n=10) (N=72) Normal SUV Value RFA(n=2) (N=53) LT(n=2) RTx(n=4)