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'-F-18-fluorothymidine (F-18-FLT) using PET with CT could predict pathologic complete response (pCR) of primary breast cancer to neoadjuvant chemotherapy (NAG). The key secondary objective was to correlate SUV with the proliferation marker Ki-67 at baseline and after NAG. Methods: This prospective, multicenter phase II study did not specify the therapeutic regimen, thus, NAG varied among centers. All evaluable patients underwent F-18-FLT PET/CT at baseline (FLT1) and after 1 cycle of NAG (FLT2); 43 patients were imaged at FLT1, FLT2, and after NAG completion (FLT3). The percentage change in maximum SUV (%Delta SUVmax) between FLT1 and FLT2 and FLT3 was calculated for the primary tumors. The predictive value of Delta SUVmax for pCR was determined using receiver-operating-characteristic curve analysis. The correlation between SUVmax 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. NAG resulted in a significant reduction in %SUVmax (mean A, 39%; 95% confidence interval, 31-46). There was a marginal difference in %Delta SUVmax_FLT1-FLT2 between pCR and no-pCR patient groups (Wil-coxon 1-sided P = 0.050). The area under the curve for Delta SUVmax 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 SUVmax and Ki-67 (r = 0.29, P = 0.04), but the correlation between SUVmax and Ki-67 after completion of NAG was stronger (r = 0.68, P < 0.0001). Conclusion: F-18-FLT PET imaging of breast cancer after 1 cycle of NAG weakly predicted pCR in the setting of variable NAG regimens. Posttherapy (18)FZ-FLT uptake correlated with Ki-67 on surgical specimens. These results suggest some efficacy of F-18-FLT as an indicator of early therapeutic response of breast cancer to NAG and support future multicenter studies to test F-18-FLT PET in a more uniformly treated patient population.