Biomarkers Predictive of Distant Disease-free Survival Derived from Diffusion-weighted Imaging of Breast Cancer

Purpose: To investigate whether intravoxel incoherent motion (IVIM) and/or non-Gaussian diffusion parameters are associated with distant disease-free survival (DDFS) in patients with invasive breast cancer. Methods: From May 2013 to March 2015, 101 patients (mean age 60.0, range 28–88) with invasive breast cancer were evaluated prospectively. IVIM parameters (flowing blood volume fraction [f(IVIM)] and pseudodiffusion coefficient [D*]) and non-Gaussian diffusion parameters (theoretical apparent diffusion coefficient [ADC] at a b value of 0 s/mm(2) [ADC(0)] and kurtosis [K]) were estimated using a diffusion-weighted imaging series of 16 b values up to 2500 s/mm(2). Shifted ADC values (sADC(200–1500)) and standard ADC values (ADC(0–800)) were also calculated. The Kaplan–Meier method was used to generate survival analyses for DDFS, which were compared using the log-rank test. Univariable Cox proportional hazards models were used to assess any associations between each parameter and distant metastasis-free survival. Results: The median observation period was 80 months (range, 35–92 months). Among the 101 patients, 12 (11.9%) developed distant metastasis, with a median time to metastasis of 79 months (range, 10–92 months). Kaplan–Meier analysis showed that DDFS was significantly shorter in patients with K > 0.98 than in those with K ≤ 0.98 (P = 0.04). Cox regression analysis showed a marginal statistical association between K and distant metastasis-free survival (P = 0.05). Conclusion: Non-Gaussian diffusion may be associated with prognosis in invasive breast cancer. A higher K may be a marker to help identify patients at an elevated risk of distant metastasis, which could guide subsequent treatment.