Research ArticleClinical Investigation

Quantitative 68Ga-DOTATATE PET/CT Parameters for the Prediction of Therapy Response in Patients with Progressive Metastatic Neuroendocrine Tumors Treated with 177Lu-DOTATATE

Claudia Ortega, Rebecca K.S. Wong, Josh Schaefferkoetter, Patrick Veit-Haibach, Sten Myrehaug, Rosalyn Juergens, David Laidley, Reut Anconina, Amy Liu and Ur Metser
Journal of Nuclear Medicine October 2021, 62 (10) 1406-1414; DOI: https://doi.org/10.2967/jnumed.120.256727

Article Figures & Data

Figures

  • Figure
  • FIGURE 1.
    FIGURE 1.

    60-y-old woman with metastases of well-differentiated small bowel NET to liver and retroperitoneal lymph nodes (G1; Ki-67 index, 6%). Lesion-based assessment was done with bPET and iPET before cycle 2 of 177Lu-DOTATATE therapy. (A) Metastatic nodal mass chosen as marker lesion at bPET (SUVmax, 38.7) (outlined in red). (B) Same lesion before cycle 2 of therapy (SUVmax, 49.2) (outlined in red).

  • FIGURE 2.
    FIGURE 2.

    68Ga-DOTATATE tumor volume analysis using in-house automated segmentation software. (A) Multiplanar segmentation tool (to identify and confirm tumor sites). (B) Mask generated using tracer uptake in spleen as threshold (tumor lesions with SUVmax above that of spleen are outlined in green).

  • FIGURE 3.
    FIGURE 3.

    Lesion-based measures. Distributions of median SUVmax (P = 0.018) (A) and SUVmax T/L (P = 0.024) (B) are shown. Box plots represent median and upper and lower quartiles of each distribution, with whiskers showing limits of distribution (1.5 times interquartile range). NR = nonresponders; R = responders.

  • FIGURE 4.
    FIGURE 4.

    DTTV parameters. Distributions of mean DTTV SUVmax (P = 0.025) (A) and SUVmean obtained with liver as threshold (SUVmean Liver) (P = 0.0055) (B) are shown. Box plots represent median and upper and lower quartiles of each distribution, with whiskers showing limits of distribution (1.5 times interquartile range). NR = nonresponders; R = responders.

  • FIGURE 5.
    FIGURE 5.

    Kurtosis on baseline 68Ga-DOTATATE PET/CT. Distribution of kurtosis was estimated from 68Ga-DOTATATE tumor volumes (P = 0.031). Box plot represents median and upper and lower quartiles of each distribution, with whiskers showing limits of distribution (1.5 times interquartile range). NR = nonresponders; R = responders.

Tables

  • TABLE 1

    Patient Characteristics for Entire Cohort and Subgroup with iPET

    CharacteristicEntire cohortiPET cohort
    No. of patients9136
    Sex (M:F)53:3820:16
    Mean age (y)62.5 (SD = 12.9)59.7 (SD = 14.2)
    Primary site (No. of patients)
      Gastrointestinal tract4819
      Pancreas198
      Unknown primary92
      Bronchopulmonary63
      Adrenal42
      Other52
    Mean tumor Ki-67 index (%)8.3 (SD = 7.8)10.5 (SD = 8.3)
    Response status
      Nonresponders206
      Other7130
    Mean follow-up (mo)12.2 (SD = 7.2)20.1 (SD = 9.7)
  • TABLE 2

    bPET Reference Parameters, Lesion-Based Parameters, DTTV Parameters, and First-Order Heterogeneity Parameters

    bPET ParameterAll Patients (n = 91)Responders (n = 71)Nonresponders (n = 20)P*
    Reference tissue
     SUVmax liver0.49
      Mean (SD)5.7 (2.1)5.8 (2.3)5.3 (1.6)
      Minimum–maximum2–13.13.2–8.22–13.1
     SUVmax spleen0.30
      Mean (SD)13.8 (6.9)14.1 (6.9)12.6 (6.7)
      Minimum–maximum4.4–45.84.4–26.75–45.8
    Lesion based
     Mean SUVmax0.018
      Mean (SD)38.7 (25.1)41.7 (26.8)28.2 (14.2)
      Minimum–maximum11–137.713.4–77.411–137.7
     Mean SUVmax T/L0.024
      Mean (SD)8.3 (6.4)9 (7)5.8 (2.9)
      Minimum–maximum1.4–40.51.4–40.52.9–14.6
     Mean SUVmax T/S0.13
      Mean (SD)3.5 (2.7)3.7 (2.9)2.8 (1.8)
      Minimum–maximum0.2–14.60.2–14.61–8.3
    DTTV
     DTTV liver†0.12
      Mean (SD)554.1 (853.8)611.5 (921.7)350.4 (516.8)
      Minimum–maximum4.7–4,891.84.7–4,891.88.1–2,200.9
    DTTV spleen†0.06
      Mean (SD)317.1 (616.3)363.9 (677.6)150.9 (265.4)
      Minimum–maximum0–3,825.30–3,825.30–1,049.6
     DTTV SUVmax0.025
      Mean (SD)62.8 (46.4)66.8 (48.4)48.4 (36.2)
      Minimum–maximum15.6–307)17.1–30715.6–186.6
     DTTV SUVmean liver0.0055
      Mean (SD)15.6 (7.3)16.7 (7.7)11.6 (3.6)
      Minimum–maximum5.1–41.45.8–41.45.1–19.4
     DTTV SUVmean spleen0.06
      Mean (SD)23.5 (10.3)24.5 (10.4)20 (9.3)
      Minimum–maximum0–50.40–50.47.7–45.3
    Heterogeneity
     CoV0.17
      Mean (SD)0.6 (0.2)0.6 (0.2)0.6 (0.3)
      Minimum–maximum0.2–1.60.3–1.50.2–1.6
     Skewness0.055
      Mean (SD)1.5 (0.8)1.4 (0.8)1.9 (1.0)
      Minimum–maximum0.1–40.1–40.6–4
     Kurtosis0.031
      Mean (SD)6.4 (4.8)5.8 (4.1)8.6 (6.4)
      Minimum–maximum1.7–26.71.7–25.82.8–26.7

    • * P value.

    • ↵† Measured in cubic centimeters.

    • DTTV SUVmean liver = SUVmean in segmented volume obtained with liver as threshold; DTTV SUVmean spleen = SUVmean in segmented volume obtained with spleen as threshold; DTTV liver = DTTV obtained with liver as threshold; DTTV spleen = DTTV obtained with spleen as threshold; DTTV SUVmean liver = DTTV SUVmean obtained with liver as threshold; DTTV SUVmean spleen = DTTV SUVmean obtained with spleen as threshold; CoV = coefficient of variation.

    • Wilcoxon rank sum test P values are shown.

  • TABLE 3

    iPET Reference Parameters, Lesion-Based Parameters, DTTV Parameters, and First-Order Heterogeneity Measures, Part 1

    iPETAll patients (n = 36)Responders (n = 30)Nonresponders (n = 6)P*
    Reference tissue
     SUVmax liver0.011
      Mean (SD)5.8 (1.8)6.1 (1.8)4.2 (1.2)
      Minimum–maximum2.8–11.23.6–11.22.8–6.4
     SUVmax spleen0.0085
      Mean (SD)19.4 (10.6)21.2 (10.7)10.6 (3.8)
      Minimum–maximum4.3–49.17.3–49.14.3–14.6
    Lesion based
     Mean SUVmax0.048
      Mean (SD)34.3 (19.4)37 (20.2)21.2 (6)
      Minimum–maximum6.8–93.16.8–93.112.4–29.9
     Mean SUVmax T/L0.57
      Mean (SD)6.1 (3.2)6.3 (3.5)5.2 (1.4)
      Minimum–maximum0.9–17.40.9–17.42.9–6.8
     Mean SUVmax T/S0.92
      Mean (SD)2.1 (1.2)2.1 (1.3)2.2 (0.9)
      Minimum–maximum0.1–6.10.1–6.11.5–3.9

    • * P value.

    • † Measured in cubic centimeters.

    • DTTV SUVmean liver = SUVmean in segmented volume obtained with liver as threshold; DTTV SUVmean spleen = SUVmean in segmented volume obtained with spleen as threshold; DTTV liver = DTTV obtained with liver as threshold; DTTV spleen = DTTV obtained with spleen as threshold; DTTV SUVmean liver = DTTV SUVmean obtained with liver as threshold; DTTV SUVmean spleen = DTTV SUVmean obtained with spleen as threshold; CoV = coefficient of variation.

    • Wilcoxon rank sum test P values are shown.

  • TABLE 4

    Univariable (UVA) and Multivariable (MVA) Analyses of Lesion-Based, Tumor Volume–Based, and Heterogeneity Parameters as Predictors of PFS

    UVAMVA
    bPET covariateHR (95% CI)PHR (95% CI)P
    Lesion based
      Mean SUVmax0.98 (0.97–1)0.0230.98 (0.96–1)0.019
      SUVmax T/L0.92 (0.85–0.99)0.0280.89 (0.8–0.98)0.018
      SUVmax T/S0.86 (0.75–1)0.0470.83 (0.69–0.99)0.041
    Tumor volume
      DTTV SUVmean liver0.92 (0.87–0.98)0.00530.9 (0.83–0.97)0.0052
    Heterogeneity
      Skewness1.49 (1.07–2.07)0.0171.48 (1–2.18)0.048

    • DTTV SUVmean liver = SUVmean from tumor volume obtained with liver or spleen as threshold.

    • Cox proportional hazards model P values are shown.

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