Research ArticleClinical Investigation

Comparison of Baseline 68Ga-FAPI and 18F-FDG PET/CT for Prediction of Response and Clinical Outcome in Patients with Unresectable Hepatocellular Carcinoma Treated with PD-1 Inhibitor and Lenvatinib

Meiqi Wu, Yanyu Wang, Qiao Yang, Xuezhu Wang, Xu Yang, Haiqun Xing, Xinting Sang, Xiang Li, Haitao Zhao and Li Huo
Journal of Nuclear Medicine October 2023, 64 (10) 1532-1539; DOI: https://doi.org/10.2967/jnumed.123.265712

Article Figures & Data

Figures

  • Figure
  • FIGURE 1.
    FIGURE 1.

    Flowchart of patients’ enrollment, treatment, and follow-up. BOR = Best objective response.

  • FIGURE 2.
    FIGURE 2.

    Comparison of 18F-FDG SUVmax, MTV, and TLG and of 68Ga-FAPI SUVmax, FTV, and TLF between DCB and NDB patients.

  • FIGURE 3.
    FIGURE 3.

    Representative baseline 68Ga-FAPI and 18F-FDG PET/CT images of patients with DCB. (A) A 63-y-old woman with multiple hepatic HCC, portal vein invasion, and lung metastases showing low 68Ga-FAPI avidity and high metabolic tumor burden. (B) A 47-y-old woman with right-lobe HCC, portal vein invasion, and lymph node metastases showing low 68Ga-FAPI avidity and metabolic tumor burden. Patients in A and B reached partial response and underwent conversion surgery. (C) A 40-y-old man with multiple intrahepatic lesions, portal vein invasion, lymph node metastases, and bone metastases. (D) A 50-y-old man with right-lobe HCC and portal vein invasion. Patients in C and D had low 68Ga-FAPI avididy and metabolic tumor burden, with stable disease for >6 mo. All 4 patients had OS > 12 mo. wb = whole body.

  • FIGURE 4.
    FIGURE 4.

    Representative baseline 68Ga-FAPI and 18F-FDG PET/CT images of patients with NDB. (A) A 63-y-old man with diffuse HCC. (B) A 69-y-old man with multiple intrahepatic HCC, portal vein invasion, and lung and bone metastases. (C) A 69-y-old man with diffuse right-lobe HCC, portal vein invasion, and lymph node metastases. Patients in A–C showed high 68Ga-FAPI avidity and low metabolic tumor burden. (D) A 71-y-old man with diffuse right-lobe HCC and portal vein invasion showing high 68Ga-FAPI avidity and metabolic tumor burden. All 4 patients progressed on first evaluation after 2–3 cycles of PD-1 inhibitor and had OS of <6 mo. wb = whole body.

  • FIGURE 5.
    FIGURE 5.

    Axial PET, CT, and PET/CT images of patients in Figures 3A (left) and 4A (right).

  • FIGURE 6.
    FIGURE 6.

    Receiver-operating-characteristic analysis curve for 18F-FDG SUVmax, TLG, and MTV and for 68Ga-FAPI SUVmax, TLF, and FTV for predicting NDB.

  • FIGURE 7.
    FIGURE 7.

    Kaplan–Meier curves for PFS (A) and OS (B) in uHCC patients stratified by optimal cutoffs for 18F-FDG SUVmax, MTV/TLG, 68Ga-FAPI SUVmax, and FTV/TLF.

Tables

  • TABLE 1.

    Baseline Characteristics of uHCC Patients (n = 22)

    CharacteristicData
    Median age (y)62.0 (range, 35–76)
    Age > 65 y7 (32%)
    Sex
     Female3 (14%)
     Male19 (86%)
    Hepatitis B surface antigen A–positive18 (82%)
    Ascites6 (27%)
    Cirrhosis13 (59%)
    ECOG PS
     0 or 119 (87%)
     23 (14%)
    Child–Pugh class
     A15 (68%)
     B7 (32%)
    α-fetoprotein > 200 ng/mL9 (41%)
    Macrovascular invasion16 (73%)
    Extrahepatic spread12 (53%)
    Metastases to distant organs7 (32%)
    Bone metastases3 (14%)
    Barcelona Clinic Liver Cancer stage for HCC
     B3 (14%)
     C19 (86%)
    Prior regional treatment10 (45%)
     Partial resection3 (14%)
     Transarterial chemoembolization/ radioembolization8 (36%)
     Radiofrequency ablation2 (9%)
     Radiotherapy for bone metastasis1 (5%)
    Prior targeted therapy5 (23%)
    Median 18F-FDG SUVmax6.7 (IQR, 4.5–10.9)
    Median MTV (cm3)157.4 (IQR, 18.3–365.3)
    Median TLG (SUVbw⋅cm3)534.8 (IQR, 58.9–1599.5)
    Median 68Ga-FAPI SUVmax8.9 (IQR, 6.7–10.9)
    Median FTV (cm3)312.6 (IQR, 106.4–525.4)
    Median TLF (SUVbw⋅cm3)1,274.8 (IQR, 323.8–1,840.1)

    • ECOG PS = Eastern Cooperative Oncology Group performance status; IQR = interquartile range.

    • Data are number followed by percentage in parentheses, unless indicated otherwise.

  • TABLE 2.

    Comparison of Potential Predictors Between Patients with DCB and NDB

    CharacteristicDCB (n = 11)NDB (n = 11)P
    Age > 65 y3 (27%)4 (36%)1.000
    Male8 (73%)11 (100%)0.214
    Hepatitis B surface antigen A–positive8 (73%)10 (91%)0.586
    Ascites1 (9%)5 (45%)0.149
    Cirrhosis4 (36%)9 (82%)0.080
    ECOG PS0.214
     07 (64%)4 (36%)
     14 (36%)3 (27%)
     20 (0%)3 (27%)
    Child–Pugh class B1 (9%)6 (55%)0.063
    α-fetoprotein > 200 ng/mL5 (45%)4 (36%)1.000
    Macrovascular invasion7 (64%)9 (82%)0.635
    Extrahepatic spread6 (55%)6 (55%)1.000
    Metastases to distant organs3 (27%)4 (36%)1.000
    Bone metastases1 (9%)2 (18%)1.000
    Barcelona Clinic Liver Cancer stage C9 (82%)10 (91%)1.000
    Prior regional treatment7 (64%)3 (27%)0.198
    Prior targeted therapy4 (36%)1 (9%)0.311
    Median 18F-FDG SUVmax5.7 (IQR, 5.0–10.2)6.9 (IQR, 3.3–13.0)1.000
    Median MTV (cm3)154.2 (IQR, 16.1–200.7)212.9 (IQR, 21.6–463.5)0.438
    Median TLG (SUVbw⋅cm3)492.2 (IQR, 57.2–693.5)693.5 (IQR, 62.3–3701.0)0.365
    Median 68Ga-FAPI SUVmax8.8 (IQR, 6.0–10.7)8.9 (IQR, 8.3–11.5)0.401
    Median FTV (cm3)121.3 (IQR, 35.6–337.0)436.1 (IQR, 289.1–838.9)0.003
    Median TLF (SUVbw⋅cm3)359.2 (IQR, 120.0–1,344.5)1,514.3 (IQR, 1,266.8–4,150.3)0.004

    • ECOG PS = Eastern Cooperative Oncology Group performance status; IQR = interquartile range.

    • Data are number followed by percentage in parentheses, unless indicated otherwise.

  • TABLE 3.

    Cox Proportional-Hazards Regression Analysis for PFS and OS

    PFSOS
    UnivariableMultivariableUnivariableMultivariable
    PredictorHRPHRPHRPHRP
    Age > 65 y1.01 (0.35–2.91)0.991.85 (0.54–6.41)0.33
    Male2.24 (0.50–9.96)0.296.42 (0.23–30.40)0.36
    HBsAg (+)1.90 (0.54–6.74)0.322.64 (0.34–20.80)0.36
    Ascites1.66 (0.58–4.79)0.352.66 (0.76–9.24)0.12
    Cirrhosis2.96 (1.03–8.49)0.0382.27 (0.62–8.28)0.221.66 (0.48–5.69)0.42
    ECOG PS 24.34 (1.01–18.6)0.0462.83 (0.66–12.21)0.162.91 (0.57–14.72)0.20
    Child–Pugh class B1.98 (0.71–5.51)0.193.45 (1.02–11.66)0.0541.43 (0.35–5.79)0.62
    AFP > 200 ng/mL1.46 (0.56–3.74)0.431.27 (0.39–4.19)0.69
    Macrovascular invasion3.60 (1.01–12.85)0.0484.00 (1.06–15.14)0.0392.17 (0.46–10.16)0.33
    Extrahepatic spread0.71 (0.27–1.86)0.491.22 (0.37–4.02)0.75
    Distant-organ metastases0.93 (0.32–2.66)0.892.07 (0.63–6.83)0.23
    Bone metastases2.21 (0.60–8.21)0.244.27 (1.05–17.25)0.0375.88 (1.33–25.93)0.022
    BCLC stage C1.48 (0.34–6.49)0.611.63 (0.21–12.78)0.64
    Prior regional treatment0.58 (0.23–1.50)0.260.74 (0.22–2.42)0.61
    Prior targeted therapy0.39 (0.11–1.37)0.140.25 (0.03–1.96)0.19
    18F-FDG SUVmax > 6.691.39 (0.55–3.52)0.491.94 (0.57–6.66)0.29
    MTV > 206.80 cm3 or TLG > 693.53 SUVbw⋅cm31.81 (0.69–4.76)0.232.74 (0.83–9.07)0.102.80 (0.83–9.42)0.10
    68Ga-FAPI SUVmax > 7.041.36 (0.53–3.45)0.521.55 (0.45–5.30)0.49
    FTV > 230.46 cm3 or TLF > 961.74 SUVbw⋅cm33.54 (1.20–10.45)0.0153.88 (1.26–12.01)0.0204.83 (1.02–22.88)0.0485.92 (1.19–29.42)0.035

    • HBsAg (+) = hepatitis B surface antigen A–positive; ECOG PS = Eastern Cooperative Oncology Group performance status; AFP = α-fetoprotein; BCLC = Barcelona Clinic Liver Cancer.

    • Data in parentheses are 95% CIs.

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