Broad use of germline testing has identified an increasing number of women at risk for breast cancer with a need for effective chemoprevention. We report a novel method to selectively deliver various anti-estrogens at high drug levels to the breast tissue by implanting a device comprised of silastic tubing. Optimized tubing properties allow elution of otherwise poorly bioavailable anti-estrogens, such as fulvestrant, into mammary tissue in vitro and in vivo with levels sufficient to inhibit estrogen receptor activation and tumor cell proliferation. Implantable silastic tubing delivers fulvestrant selectively to mouse mammary fat tissue for one year with anti-tumor effects similar to those achieved with systemic fulvestrant exposure. Furthermore, local delivery of fulvestrant significantly decreases cell proliferation, as assessed by Ki67 expression, most effectively in tumor sections adjacent to tubing. This approach may thereby introduce a potential paradigm shift and offer a promising alternative to systemic therapy for prevention and early interception of breast cancer.
Purpose: Multiparametric MRI (mpMRI) improves detection of clinically significant prostate cancer (csPCa), but the qualitative PI-RADS system and quantitative apparent diffusion coefficient (ADC) yield inconsistent results. An advanced Restrictrion Spectrum Imaging (RSI) model may yield a better quantitative marker for csPCa, the RSI restriction score (RSIrs). We evaluated RSIrs for patient-level detection of csPCa.
Materials and Methods: Retrospective analysis of men who underwent mpMRI with RSI and prostate biopsy for suspected prostate cancer from 2017-2019. Maximum RSIrs within the prostate was assessed by area under the receiver operating characteristic curve (AUC) for discriminating csPCa (grade group ≥2) from benign or grade group 1 biopsies. Performance of RSIrs was compared to minimum ADC and PI-RADS v2-2.1via bootstrap confidence intervals and bootstrap difference (two-tailed α=0.05). We also tested whether the combination of PI-RADS and RSIrs (PI-RADS+RSIrs) was superior to PI-RADS, alone.
Results: 151 patients met criteria for inclusion. AUC values for ADC, RSIrs, and PI-RADS were 0.50 [95% confidence interval: 0.41, 0.60], 0.76 [0.68, 0.84], and 0.78 [0.71, 0.85], respectively. RSIrs (p=0.0002) and PI-RADS (p<0.0001) were superior to ADC for patient-level detection of csPCa. The performance of RSIrs was comparable to that of PI-RADS (p=0.6). AUC for PI-RADS+RSIrs was 0.84 [0.77, 0.90], superior to PI-RADS or RSIrs, alone (p=0.008, p=0.009).
Conclusions: RSIrs was superior to conventional ADC and comparable to (routine, clinical) PI-RADS for patient-level detection of csPCa. The combination of PI-RADS and RSIrs was superior to either alone. RSIrs is a promising quantitative marker worthy of prospective study in the setting of csPCa detection.
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