Subtype-guided 18F-FDG PET/CT in tailoring axillary surgery among node-positive breast cancer patients treated with neoadjuvant chemotherapy: A feasibility study

Abstract

Background: With the increased use of neoadjuvant chemotherapy (NAC), as well as increasing efficacy of systemic therapy, a substantial proportion of clinically nodepositive patients may achieve a nodal pathologic complete response (pCR) with chemotherapy. Instead of axillary lymph node dissection (ALND), a novel surgical technique called targeted axillary dissection (TAD) including removal of sentinel lymph nodes (SLNs) and clip-marked node has been gaining acceptance in recent years. Logically, preoperative identification of patients with pCR or residual disease would allow for the optimization of axillary surgery for performing a TAD or proceeding to a ALND after NAC, thus sparing patients unnecessary procedures or expense. The aim of this study was to investigate the value of 18F-FDG PET/CT in tailoring axillary surgery by predicting nodal response among node-positive breast cancer patients after NAC. Methods: Breast cancer patients with biopsy-confirmed nodal metastasis were prospectively enrolled. At least one 18F-FDG PET/CT scan was performed before NAC (a second one after two cycles with baseline SUVmax in axillary lymph nodes ≥ 2.5), among whom a subset of patients had underwent TAD. All the patients ultimately underwent ALND. The accuracy was calculated by a comparison with the final pathologic results. Results: Table. Accuracy of 18F-FDG PET/CT to Predict Ax-pCR in Overall Population and Different Subtypes Overall population ER-HER2+ subtype The rest subtypes No. of patients 111 31 80 Ax-pCR rate (%) 55.9 74.2 48.8 AUC (95%CI) 0.75 (0.65-0.84) 0.55 (0.31-0.79) 0.80 (0.70-0.91) P value <0.05 0.69 <0.05 Optimum cut-off (%) 78.4 79.9 76.2 Accuracy (%) 75.7 54.8 77.5 Sensitivity (%) 79.0 56.5 84.6 Specificity (%) 71.4 50.0 70.7 PPV (%) 77.8 76.5 73.3 NPV (%) 72.9 28.6 82.9 In this study, 133 patients were enrolled. With the optimum cut-off value of ≥2.5 for the baseline SUVmax and≥ 78.4% for the ΔSUVmax, 18F-FDG PET/CT scans showed a moderate predictive value of axillary (Ax-pCR) with an area under the curve (AUC) of 0.75 (95% CI: 0.65-0.84) (Table). Explorative subgroup analyses indicated little predictive value for estrogen receptor (ER)-negative, human epidermal factor receptor 2 (HER2)-positive (HER2- enriched) patients (AUC=0.55). And the application of 18F-FDG PET/CT could spare 22 patients from unnecessary TADs or supplementary ALNDs and reduce 1 of 3 falsenegative cases occurring in TAD among the non-HER2-enriched patients. Conclusions: Application of the subtype-guided 18F-FDG PET/CT could accurately predict nodal response and aid in tailoring axillary surgery among node-positive breast cancer patients after NAC, which included identifying candidates appropriate for TAD or directly proceeding to ALND. This approach might help to avoid false-negative events occurring in TAD.