Research ArticleClinical Investigation
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68Ga-Labeled Fibroblast Activation Protein Inhibitor PET/CT for the Early and Late Prediction of Pathologic Response to Neoadjuvant Chemotherapy in Breast Cancer Patients: A Prospective Study

Ling Chen, Shan Zheng, Linying Chen, Sunwang Xu, Kunlin Wu, Lingjun Kong, Jiajie Xue, Xiangjin Chen, Weibing Miao and Youzhi Zhu
Journal of Nuclear Medicine December 2023, 64 (12) 1899-1905; DOI: https://doi.org/10.2967/jnumed.123.266079

Article Figures & Data

Figures

  • Figure
  • FIGURE 1.
    FIGURE 1.

    Correlation between relative ΔSUVmax of primary tumor (A) and metastatic lymph node (B) at PET2 and PET3.

  • FIGURE 2.
    FIGURE 2.

    Box plots of ΔSUVmax and pathologic response (pCR vs. non-pCR) at PET2 and PET3. *P < 0.05. **P < 0.01. ***P < 0.001.

  • FIGURE 3.
    FIGURE 3.

    Changes in SUVmax of primary tumor (A) and metastatic lymph node (B) according to pathologic response (pCR vs. non-pCR) at PET1, PET2, and PET3.

  • FIGURE 4.
    FIGURE 4.

    Changes in SUVmax of primary tumor according to pathologic response (concentric withdrawal vs. diffuse withdrawal) at PET1, PET2, and PET3.

  • FIGURE 5.
    FIGURE 5.

    Representative 68Ga-FAPI PET/CT images of 48-y-old woman who had left invasive ductal carcinoma and who achieved pCR. (A) Baseline 68Ga-FAPI PET/CT maximum-intensity-projection (MIP) image demonstrated primary lesion (red arrowhead; SUVmax, 26.72) and 68Ga-FAPI–avid lymph node in left axilla (red arrows). (B) 68Ga-FAPI PET/CT MIP image after 2 cycles of NAC showed that primary lesion (red arrowhead; SUVmax, 8.87) and axillary lymph nodes (red arrow) were reduced in size and radioactivity uptake. (C and D) Representative images of immunohistochemical staining for FAP before NAC showed strong FAP-positive staining in stromal cells (C), which was significantly decreased on tumor bed after 6 cycles of NAC (D).

  • FIGURE 6.
    FIGURE 6.

    Representative 68Ga-FAPI PET/CT images of 46-y-old woman who had left invasive ductal carcinoma and who did not achieve pCR. (A) Baseline 68Ga-FAPI PET/CT maximum-intensity-projection (MIP) image demonstrated primary lesion (red arrowhead; SUVmax, 11.62). (B) 68Ga-FAPI PET/CT MIP image after 2 cycles of NAC showed that primary lesion (red arrowhead; SUVmax, 10.59) was smaller and that radioactivity uptake was slightly lower than before. (C and D) Representative images of immunohistochemical staining for FAP before NAC showed strong FAP-positive staining in stromal cells (C), but no obvious change was observed on tumor bed after 6 cycles of NAC (D).

Tables

  • TABLE 1.

    Overall Characteristics of Breast Cancer Patients

    CharacteristicNo. of patients*
    Menstrual state
     Premenopausal12 (54.5)
     Postmenopausal10 (45.5)
    Tumor classification
     T220 (91.0)
     T31 (4.5)
     T41 (4.5)
    Lymph node classification
     N02 (9.1)
     N116 (72.7)
     N22 (9.1)
     N32 (9.1)
    AJCC clinical stage
     IIA2 (9.1)
     IIB14 (63.6)
     IIIA3 (13.6)
     IIIB2 (9.1)
     IIIC1 (4.5)
    Tumor type
     Invasive ductal carcinoma21 (95.5)
     Invasive lobular carcinoma1 (4.5)
    Grade
     G28 (36.4)
     G314 (63.6)
    Molecular subtype
     Luminal B/HER2 negative9 (40.9)
     Luminal B/HER2 positive7 (31.8)
     HER2 positive4 (18.2)
     Triple-negative–like2 (9.1)
    Surgery
     BCR6 (27.3)†
     Mastectomy16 (72.7)
    Pathologic response
     pCR7 (31.8)
     Non-pCR15 (68.2)

    • ↵* Values in parentheses are percentages.

    • ↵† Of the 6 BCR patients, 2 underwent extensive resection of incisal margin because of diffuse withdrawal in postoperative pathologic evaluation.

    • AJCC = American Joint Commission on Cancer.

  • TABLE 2.

    Correlations Between 68Ga-FAPI PET/CT Parameters and Pathologic Response

    ParameterpCRNon-pCRPConcentric withdrawalDiffuse withdrawalP
    Primary tumor
     SUVmax118.1 ± 6.414.9 ± 5.20.22415.8 ± 6.116.1 ± 5.30.92
     SUVmax24.7 ± 2.912.7 ± 8.40.0246.3 ± 3.715.8 ± 9.40.017
     SUVmax31.1 ± 0.35.2 ± 3.90.0012.2 ± 1.86.4 ± 4.50.024
     ΔSUVmax1 (%)−70.5 ± 25.6−14.6 ± 46.20.008−53.8 ± 31.1−1.5 ± 53.00.008
     ΔSUVmax2 (%)−93.5 ± 2.0−64.8 ± 18.80.001−83.1 ± 15.1−60.7 ± 20.90.008
     TBR114.7 ± 3.115.7 ± 7.90.66215.4 ± 7.015.3 ± 7.00.974
     TBR24.8 ± 4.011.9 ± 7.40.0276.3 ± 3.814.6 ± 8.40.02
     TBR31.0 ± 0.34.7 ± 3.60.0011.9 ± 1.35.9 ± 4.20.022
    Metastatic lymph node
     SUVmax111.7 ± 8.110.5 ± 6.20.7239.2 ± 6.614.2 ± 6.00.113
     SUVmax22.1 ± 1.06.6 ± 7.40.0542.7 ± 1.99.3 ± 9.20.111
     SUVmax30.2 ± 0.62.2 ± 1.50.0010.9 ± 1.32.7 ± 1.40.014
     ΔSUVmax1 (%)−76.7 ± 10.0−41.7 ± 43.60.053−64.0 ± 19.4−36.3 ± 58.70.25
     ΔSUVmax2 (%)−98.8 ± 3.1−77.5 ± 13.10.001−88.3 ± 15.1−78.7 ± 13.20.171

    • TBR1 = TBR at baseline.

  • TABLE 3.

    Diagnostic Agreement of 68Ga-FAPI Uptake Cutoff Values with Favorable Pathologic Response of Primary Tumor

    VariablepCRConcentric withdrawal
    Sensitivity (%)Specificity (%)PPV (%)NPV (%)κ-indexSensitivity (%)Specificity (%)PPV (%)NPV (%)κ-index
    ΔSUVmax17592.985.786.70.69783.37076.977.80.538
    SUVmax210088.271.41000.77376.510010055.60.596
    ΔSUVmax287.510010093.30.89910064.361.51000.567
    SUVmax387.510010093.30.89991.78084.688.90.723
    TBR285.78066.792.30.61176.977.883.3700.538
    TBR310093.385.71000.89976.988.990.972.70.636

    • PPV = positive predictive value; NPV = negative predictive value.

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