Abstract PD4-03: MRI detection of residual disease following neoadjuvant chemotherapy (NAC) in the I-SPY 2 TRIAL
Authors: Li W , Newitt D , Yun BL , Kornak J , Joe B , Yau C , Abe H , Wolverton D , Crane E , Ward K , Nelson M , Niell B , Drukteinis J , Oh K , Brandt K , Bang DH , Ojeda H , Eghtedari M , Sheth P , Bernreuter W , Umphrey H , Rosen M , Dogan B , Yang W , Esserman L , Hylton N 
Published: May 2019

Background: Detecting residual disease accurately using MRI after NAC to identify both responders and non-responders is essential for de-escalating therapy or redirecting patients to more effective treatment. The purpose of this study is to determine if the combination of longest diameter (LD) and functional tumor volume (FTV) from dynamic contrast enhanced (DCE-) MRI is superior to FTV alone or LD alone for assessing treatment response after neoadjuvant therapy in breast cancer patients.

Methods: Data from patients in the graduated drug arms of the I-SPY 2 trial were included in the analysis. Both LD and FTV were assessed using DCE-MRI after neoadjuvant therapy. LD was measured by the site radiologist as the longest dimension of the enhanced area on early post-contrast images. Functional tumor volume (FTV) was assessed as the sum of voxels with enhancement above specific thresholds within the pre-defined region-of-interest (ROI). A linearized variable was derived to represent the combination of FTV and LD. The area under the receiver operating characteristic curve (AUC) was used to evaluate the assessment of treatment response, pathologic complete response (pCR), defined as no invasive disease in the breast and lymph nodes, and in-breast pCR, defined as no invasive disease in the breast only. The analysis was performed in the full cohort and in breast cancer subtype defined by hormone receptor status and HER2 status.

Results: Among the patient cohort of N=675 with FTV and LD, 247 (37%) did and 428 (41%) did not achieve pCR after neoadjuvant therapy. pCR rates varied among HR/HER2 subtypes (HR+/HER2-: 19%; HR+/HER2+: 38%; HR-/HER2+: 71%; HR-/HER2- (triple negative, TN): 43%). In-breast pathologic complete response rates were slightly higher in each group (full: 41%; HR+/HER2-: 23%; HR+/HER2+: 43%; HR-/HER2+: 72%; HR-/HER2-: 49%). Table 1 shows AUCs for assessing pCR using FTV alone, LD alone, and the variable combining FTV and LD. Higher AUCs were observed in all patient groups using the combined variable. AUC of 0.79 (95% CI: 0.77, 0.81) was observed for the combined variable to assess pCR in the full cohort. AUCs varied from 0.69 to 0.86 among HR/HER2 subgroups (HR+/HER2-: 0.69; HR+/HER2+: 0.74; HR-/HER2+: 0.86; HR-/HER2-: 0.80), with no difference in assessing pCR or in-breast pCR. The performance is best for the HR- subtypes.

Conclusions: Both FTV and LD can be used in the assessment of invasive disease residual after neoadjuvant therapy. The combined variable of FTV and LD achieved highest AUCs, compared to using individual variable alone. Tools to improve performance in the HR+ subsets are underway.

AUCs of MR measurements for identifying pCR  FTV alone (95% CI)LD alone (95% CI)Combined (95% CI)FullWith subtype adj.0.73 (0.71, 0.75)0.77 (0.74, 0.79)0.79 (0.77, 0.81)FullWithout subtype adj0.69 (0.65, 0.73)0.72 (0.68, 0.76)0.75 (0.71, 0.79)HR+/HER2- 0.68 (0.60, 0.77)0.68 (0.59, 0.77)0.69 (0.61, 0.77)HR+/HER2+ 0.65 (0.56, 0.75)0.72 (0.64, 0.80)0.74 (0.66, 0.82)HR-/HER2+ 0.69 (0.55, 0.83)0.82 (0.71, 0.92)0.86 (0.77, 0.95)HR-/HER2- (TN) 0.72 (0.66, 0.79)0.73 (0.67, 0.80)0.80 (0.74, 0.85)

Citation Format: Li W, Newitt D, Yun BL, Kornak J, Joe B, Yau C, Abe H, Wolverton D, Crane E, Ward K, Nelson M, Niell B, Drukteinis J, Oh K, Brandt K, Bang DH, Ojeda H, Eghtedari M, Sheth P, Bernreuter W, Umphrey H, Rosen M, Dogan B, Yang W, Esserman L, Hylton N. MRI detection of residual disease following neoadjuvant chemotherapy (NAC) in the I-SPY 2 TRIAL [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr PD4-03.