Abstract P5-01-02: Multimodality molecular imaging with dynamic 18F-fluorodeoxyglucose positron emission tomography (FDG PET) and MRI to evaluate response and resistance to neoadjuvant chemotherapy (NAC)
Authors: Specht JM , Partridge S , Chai X , Novakova A , Peterson L , Shields A , Guenthoer J , Linden HM , Gralow JR , Gadi V , Korde L , Hills D , Hsu L , Hockenbery DM , Kinahan P , Mankoff DA , Porter PL 
Published: May 2016

Abstract
Background: Using quantitative FDG PET to measure glucose metabolism and perfusion, and dynamic contrast-enhanced (DCE) MRI to measure perfusion, we previously identified a metabolic signature for breast cancer resistant to NAC. This imaging signature is (1) persistent or increased tumor perfusion despite treatment, (2) an altered pattern of glucose kinetics in response to therapy, and (3) pre-therapy mismatch between tumor metabolism (MRFDG) and glucose delivery (K1) (high ratio of MRFDG/K1). These patterns predict poor response, early relapse and death independent of established prognostic factors, including pathologic response. Identification of factors associated with resistance or response to therapy is the translational goal of "Quantitative Dynamic PET and MRI in Breast Cancer Therapy," part of the Seattle Breast SPORE (1P50CA138293).
Methods: Patients (Pts) undergoing NAC for histologically confirmed breast cancer (stage II-III) were approached for this trial (CCIRB# 7587). FDG PET and DCE-MRI were obtained pre-therapy, 2-12 weeks after start of NAC (mid-therapy) and after completion of NAC. Breast biopsies were obtained pre-therapy and post-NAC. FDG PET included a dynamic scan with kinetic analysis. PET measures included SUVmax, MRFDG, K1, Ki, and Patlak. 3T DCE-MRI measurements included semi-quantitative vascular parameters of peak enhancement (PE), signal enhancement ratio (SER), washout fraction, functional tumor volume, and apparent diffusion coefficient (ADC) from diffusion-weighted MRI (DWI). Breast biopsies were assayed by immunohistochemistry and gene expression profiling. NAC was per physician's choice with most pts receiving weekly paclitaxel (with trastuzumab if HER2+) followed by doxorubicin/cyclophosphamide.
Results: 32 pts have completed the study. Pathologic complete response (pCR), defined as absence of invasive cancer in the breast, was observed in 9 (28%); near pCR defined as only microscopic residual invasive cancer in 3 (9%) more pts. Mid-therapy decline in SUVmax and K1 was associated with near pCR; (p-value 0.06, 0.04, respectively). Pre-therapy PET measures of MRFDG and K1 were not predictive of pCR. On MRI, pre-therapy PE (p=0.009), SER (p=0.01), washout fraction (p=0.02), ADC (p=0.08, trend) and mid-therapy change in volume (p=0.05) were each predictive of pCR. Gene profiling of pre-therapy biopsies showed correlation between high MRFDG/K1 ratio in basal and luminal B tumors.
Conclusions: Assessment of serial changes in tumor metabolism and perfusion by FDG PET and DCE-MRI is feasible in the clinic. Mid-therapy decline in metabolism and glucose delivery was predictive of pCR; consistent with prior retrospective series. Baseline DCE-MRI and DWI measures show promise to predict response, and associations of mid-therapy change in MR functional tumor volume with pCR agree with findings of another multisite clinical trial (ISPY). These imaging parameters may serve as useful biomarkers to inform future neoadjuvant trials. Integration of imaging data with gene expression profiling revealed that the pattern of metabolism in luminal B tumors was closer to that of the basal subtype compared to other ER-positive tumors.
Citation Format: Specht JM, Partridge S, Chai X, Novakova A, Peterson L, Shields A, Guenthoer J, Linden HM, Gralow JR, Gadi V, Korde L, Hills D, Hsu L, Hockenbery DM, Kinahan P, Mankoff DA, Porter PL. Multimodality molecular imaging with dynamic 18F-fluorodeoxyglucose positron emission tomography (FDG PET) and MRI to evaluate response and resistance to neoadjuvant chemotherapy (NAC). [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-01-02.