A phase II study of 3′-Deoxy-3′-¹⁸F-fluorothymidine PET in the assessment of early response of breast cancer to neoadjuvant chemotherapy: Results from ACRIN 6688

Our objective was to determine whether early change in standardized uptake values (SUVs) of 3′deoxy-3′-¹⁸F-fluorothymidine (¹⁸F-FLT) using PET with CT could predict pathologic complete response (pCR) of primary breast cancer to neoadjuvant chemotherapy (NAC). The key secondary objective was to correlate SUV with the proliferation marker Ki-67 at baseline and after NAC Methods: This prospective, multicenter phase II study did not specify the therapeutic regimen, thus, NAC varied among centers. Al evaluable patients underwent ¹⁸F-FLT PET/CT at baseline (FLT1) and after 1 cycle of NAC (FLT2); 43 patients were imaged at FLT1, FLT2, and after NAC completion (FLT3). The percentage change in maximum SUV (%DSUV_max) between FLT1 and FLT2 and FLT3 was calculated for the primary tumors. The predictive value of DSUVmax for pCR was determined using receiver-operating-characteristic curve analysis. The correlation between SUV_max and Ki-67 was also assessed. Results: Fifty-one of 90 recruited patients (median age, 54 y; stage IIA-IIIC) met the eligibility criteria for the primary objective analysis, with an additional 22 patients totaling 73 patients for secondary analyses. A pCR in the primary breast cancer was achieved in 9 of 51 patients. NAC resulted in a significant reduction in %SUV_max (mean D, 39%; 95% confidence interval, 31-46). There was a marginal difference in %DSUV_max-FLT1-FLT2 between pCR and no-pCR patient groups (Wilcoxon 1 -sided P = 0.050). The area under the curve for DSUV_max in the prediction of pCR was 0.68 (90% confidence interval, 0.50-0.83; Delong 1-sided P = 0.05), with slightly better predictive value for percentage mean SUV (P = 0.02) and similar prediction for peak SUV (P = 0.04). There was a weak correlation with pretherapy SUV_max and Ki-67 (r = 0.29, P = 0.04), but the correlation between SUV_max and Ki-67 after completion of NAC was stronger (r = 0.68, P < 0.0001). Conclusion: ¹⁸F-FLT PET imaging of breast cancer after 1 cycle of NAC weakly predicted pCR in the setting of variable NAC regimens. Posttherapy ¹⁸F-FLT uptake correlated with Ki-67 on surgical specimens. These results suggest some efficacy of ¹⁸F-FLT as an indicator of early therapeutic response of breast cancer to NAC and support future multicenter studies to test ¹⁸F-FLT PET in a more uniformly treated patient population.