Research ArticleOncology

18F-FDG PET/CT for Very Early Response Evaluation Predicts CT Response in Erlotinib-Treated Non–Small Cell Lung Cancer Patients: A Comparison of Assessment Methods

Joan Fledelius, Anne Winther-Larsen, Azza A. Khalil, Catharina M. Bylov, Karin Hjorthaug, Aksel Bertelsen, Jørgen Frøkiær and Peter Meldgaard
Journal of Nuclear Medicine December 2017, 58 (12) 1931-1937; DOI: https://doi.org/10.2967/jnumed.117.193003

Article Figures & Data

Figures

  • FIGURE 1.
    FIGURE 1.

    Patient selection.

  • FIGURE 2.
    FIGURE 2.

    Correlation between SULpeak (A), TLG (PERCIST) (B), and SULmax (C) at 7–10 d and SLD measured on CT scans performed after 9–11 wk.

  • FIGURE 3.
    FIGURE 3.

    ROC curves for SULpeak, SULmax, and various TLG variations. Curves illustrate parameters’ ability to predict PD on later CT scan obtained after 9–11 wk of treatment. Curves represent data from 43 patients who were analyzable by all methods.

  • FIGURE 4.
    FIGURE 4.

    Waterfall plots for SULpeak (A), TLG (PERCIST) (B), and SULmax (C) showing distribution of CT categories (light gray = PD, red = SD, and black = PR). Horizontal reference lines represent optimal cutoff for PMR and PMD. For SULmax, the horizontal reference lines represent 15% change suggested by European Organisation for Research and Treatment of Cancer criteria for early evaluation.

Tables

  • TABLE 1

    Time (Days) Between Scans and First Day of Treatment

    Imaging methodMedian baseline>4 wk (n)>2 wk (n)Median follow-upEarly CT (n)
    CT15 (range, 4–56)5 (10%)26 (52%)77 (range, 20–85)14 (28%)
    18F-FDG PET/CT1 (range, 0–21)8 (range, 2–23)

    • >4 and >2 wk = no. of patients with interval between baseline CT and first day of treatment above 4 (and 2) wk; early CT = no. of patients with a follow-up CT earlier than 9 wk.

  • TABLE 2

    Compliance with PERCIST 1.0 Standardization Criteria

    ParameterBaselineFollow-upNumeric differencePERCIST 1.0Adherence to PERCIST 1.0
    Injected activity (MBq)
     Mean ± SD340 ± 90335 ± 8718 ± 14Baseline ± 20%100% (50/50)
     Range197–609199–6180–54
    Glucose level (mmol/L)
     Mean ± SD6.3 ± 0.96.4 ± 0.90.4 ± 0.5<11 mM100% (50/50)
     Range4.6–8.84.7–9.00.0–1.6
    Uptake time (min)
     Mean ± SD58.7 ± 4.059.3 ± 4.95.1 ± 4.1960 ± 10 min98% (98/100*)
     Range51–6948–720–15Baseline ± 15 min100% (50/50)

    • ↵* Uptake time at both baseline and follow-up. Two patients with 48- and 72-min uptake time at follow-up were included because difference between scans in both cases was within ±15 min.

  • TABLE 3

    AUCs and Sensitivity and Specificity from ROC Analyses

    95% CISensitivity and specificity equally importantSpecificity as high as possible
    MethodAUCLowerUpperSensitivitySpecificityCutoffSensitivitySpecificityCutoff
    TLG (PERCIST)0.9230.8421.0000.890.88−6.6%0.501.009.2%
    SULpeak0.8870.7910.9830.770.82−6.9%0.581.002.1%
    SULmax0.8350.7150.9540.730.82−4.5%0.351.0013.2%
    TLG 500.8240.6980.9490.770.823.0%0.391.0030.0%
    TLG 400.8210.6960.9460.770.71−1.4%0.351.0024.6%
    TLG 300.7900.6450.9340.730.760.0%0.580.9411.9%

    • 95% CI = 95% confidence interval; cutoff = corresponding optimal cutoff value for percentage change.

    • AUCs optimized by identifying point on curve closest to upper left corner (considering sensitivity and specificity equally important [middle columns]) and considering specificity of major importance, thereby avoiding any false progressions [right columns]).

  • TABLE 4

    TLG (PERCIST [25%]), SULpeak (20%), and Visual Response Compared with RECIST 1.1

    TLG (PERCIST [25%])SULpeak (20%)Visual
    CTPMRSMDPMDTotalPMRSMDPMDTotalPMRSMDPMDTotal
    PR400432054105
    SD610016512017511117
    PD11511271198281171028
    Total125114793385010291150

    • SD = stable disease.

  • TABLE 5

    κ-Values for All Methods

    Methodκ (95% CI)
    Visual0.47 (0.24–0.70)*
    SULpeak 30%0.39 (0.19–0.59)
    SULpeak 25%0.41 (0.20–0.62)
    SULpeak 20%0.41 (0.20–0.62)
    SULpeak 20%0.42 (0.22–0.61)*
    TLG (PERCIST) 45%/75%0.25 (NC)
    TLG (PERCIST) 50%0.29 (0.20–0.39)
    TLG (PERCIST) 40%0.32 (0.16–0.47)
    TLG (PERCIST) 30%0.45 (0.24–0.67)
    TLG (PERCIST) 25%0.53 (0.31–0.75)*
    TLG (PERCIST) 20%0.49 (0.29–0.69)
    TLG 50, 45%/75%0.23 (NC)
    TLG 50, 50%0.27 (0.17–0.36)
    TLG 50, 40%0.25 (0.16–0.33)
    TLG 50, 30%0.35 (0.16–0.53)
    TLG 50, 25%0.33 (0.12–0.53)
    TLG 50, 20%0.38 (0.16–0.61)*
    TLG 40, 45%/75%0.27 (NC)
    TLG 40, 50%0.34 (0.16–0.52)
    TLG 40, 40%0.33 (0.16–0.50)
    TLG 40, 30%0.42 (0.18–0.66)
    TLG 40, 25%0.44 (0.20–0.69)*
    TLG 40, 20%0.43 (0.20–0.66)
    TLG 30, 45%/75%0.24 (NC)
    TLG 30, 50%0.33 (0.12–0.54)
    TLG 30, 40%0.38 (0.14–0.62)
    TLG 30, 30%0.32 (0.12–0.53)
    TLG 30, 25%0.38 (0.15–0.61)
    TLG 30, 20%0.41 (0.18–0.64)*

    • ↵* Highlight of cutoff resulting in highest κ values for each method.

    • 95% CI = 95% confidence interval; NC = not calculable by method used, described by Fleiss et al. (21).

    • Quadratic weighted κ-values (95% CIs) for all methods analyzed including various cutoffs for response and progression.

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