Neoadjuvant Chemotherapy for Breast Cancer: Functional Tumor Volume by MR Imaging Predicts Recurrence-free Survival—Results from the ACRIN 6657/CALGB 150007 I-SPY 1 TRIAL

Hylton NM, Gatsonis CA, Rosen MA, Lehman CD, Newitt DC, Partridge SC, Bernreuter WK, Pisano ED, Morris EA, Weatherall PT, Polin SM, Newstead GM, Marques HS, Esserman LJ, Schnall MD, For the ACRIN 6657 Trial Team and I-SPY 1 TRIAL Investigators

Background: The hypothesis of this study was that MRI-based radiomics has the ability to predict recurrence-free survival “early on” in breast cancer neoadjuvant chemotherapy.

Methods: A subset, based on availability, of the ACRIN 6657 dynamic contrast-enhanced MR images was used in which we analyzed images of all women imaged at pre-treatment baseline (141 women: 40 with a recurrence, 101 without) and all those imaged after completion of the first cycle of chemotherapy, i.e., at early treatment (143 women: 37 with a recurrence vs. 105 without). Our method was completely automated apart from manual localization of the approximate tumor center. The most enhancing tumor volume (METV) was automatically calculated for the pre-treatment and early treatment exams. Performance of METV in the task of predicting a recurrence was evaluated using ROC analysis. The association of recurrence-free survival with METV was assessed using a Cox regression model controlling for patient age, race, and hormone receptor status and evaluated by C-statistics. Kaplan-Meier analysis was used to estimate survival functions.

Results: The C-statistics for the association of METV with recurrence-free survival were 0.69 with 95% confidence interval of [0.58; 0.80] at pre-treatment and 0.72 [0.60; 0.84] at early treatment. The hazard ratios calculated from Kaplan-Meier curves were 2.28 [1.08; 4.61], 3.43 [1.83; 6.75], and 4.81 [2.16; 10.72] for the lowest quartile, median quartile, and upper quartile cut-points for METV at early treatment, respectively.

Conclusion: The performance of the automatically-calculated METV rivaled that of a semi-manual model described for the ACRIN 6657 study (published C-statistic 0.72 [0.60; 0.84]), which involved the same dataset but required semi-manual delineation of the functional tumor volume (FTV) and knowledge of the pre-surgical residual cancer burden.

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