Abstract P4-01-05: 3’-deoxy-3’-[18F]fluoro-thymidine (18F-FLT) positron emission tomography (PET): An accurate and effective tool for assessing tumor response in breast cancer

Abstract

Objectives : A French multicenter study was promoted by the national French cancer federation (Unicancer R&D) to assess the potential of [18F]FLT (positron emission tomography (PET) biomarker of proliferation)to manage breast cancer neoadjuvant chemotherapy (NAC). The main objective was to compare changes in tumor [18F]FLT uptake to histopathological changes induced by NAC, assuming an arrest of tumor growth related to the effectiveness of NAC. Methods : 97 patients (age 48.6 +/- 10.2 y.) were included in 13 nuclear medicine centers. All patients were eligible to anthracycline-based NAC for a de novo unifocal breast cancer (ductal n = 84, lobular = 11, other type = 2; stage II n = 75, stage III n = 21 et stage IV n = 1). 90 patients underwent a baseline PET before the onset of NAC (PET1) and a final PET after the end of NAC and before surgery (PET3). PET acquisitions were performed 60±7min after FLT injection. SUVmax (maximum standardized uptake value), SUVpeak (1 cm3 ROI including pixel max) and SUV41 (isocontour 41% of pixel max) were computed. Changes in SUV on PET3 vs PET1 were analyzed in relation to histopathological findings at the end of NAC (Sataloff criteria). Results : Tumor FLT uptake decreased markedly between TEP1 and TEP3 (SUVmax = 6.2±4.8 vs 1.3±1.2 respectively; SUVpeak = 4.6±3.2 vs 0.9±0.9; SUV41 = 3.6±2.8 vs 0.8±0.7). Total or near-total therapeutic effect (grade A) were obtained in 20 patients, more than 50% therapeutic effect but less than total or near-total effect (grade B) in 37 patients, less than 50% therapeutic effect but visible effect (grade C) in 22 patients, or no therapeutic effect (grade D) in 11 patients. SUVmax decreased dramatically (87.5%) to background levels in all patients with a complete response (grade A). Overall, changes in SUV differed depending on the type of histological response (p<0.01) i.e. SUVmax changes were more pronounced as pathological responses were good: 61% for grade D; 65.7% grade C and 69.8% grade B. The same results were obtained with the two other SUV types. Conclusions : Pathologic response to NAC in breast cancer can be assessed accurately by FLT. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P4-01-05.

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

“…Small, single-center preliminary studies indicated good predictive value for response (11–14), whereas others did not (12,15–17). Our multicenter study suggested some utility for 18 F-FLT as an early predictor of response, but preliminary reports of other multicenter trials did not find a predictive value for 18 F-FLT (25).…”

“…18 F-FLT is a substrate for thymidine kinase-1, and the accumulation of 18 F-FLT in tumors provides a quantitative measure of cell proliferation through the relationship between thymidine kinase-1 expression and cell cycle regulation (6–9). Several prior single-center studies have demonstrated that changes in breast cancer tumor proliferation assessed by 18 F-FLT PET/CT early after initiating chemotherapy predict tumor response with good sensitivity; however, the results of these studies were variable and none of the prior studies investigated the potential for predicting pCR to NAC (10–17). In the present multicenter study, our objective was to correlate changes measured by 18 F-FLT in the primary tumor early during NAC with pCR in locally advanced breast cancer patients.…”