Subsets of cancer survivors who have been subjected to thoracic irradiation face the prospect of developing pulmonary injury. Radiation-induced pulmonary fibrosis is an insidious injury that presents 6 to 24 months after irradiation and continues to progress over a period of years. TGF-β and reactive oxygen species contribute significantly to the pathogenesis of this injury. The transcription factor NRF2 controls antioxidant gene expression and therefore regulates the cellular oxidant burden. This work demonstrates an additional paradigm for NRF2: suppression of TGF-β-mediated signaling, assessed by measuring expression of a surrogate TGF-β1 target gene (PAI-1) in lung fibroblasts. Thoracic irradiation of Nfe2l2 (−/−) mice resulted in rapid expression of PAI-1 and FSP-1 compare to irradiated wild type mice. Examination of lung tissue 16 weeks after thoracic irradiation of Nfe2l2 (−/−) mice revealed the presence of distended alveoli and decreased numbers of alveoli compared to wild type mice. Suppression of NRF2 expression shortened life span in mice administered 16 Gy to the thorax. Nfe2l2 (+/−) and (−/−) mice exhibited a mean life span of 176 days compared to wild type mice that lived an average of 212 days. These novel results identify NRF2 as a susceptibility factor for development of late tissue injury.

PURPOSE Although mammography is the standard of care for breast cancer screening, dense breast tissue decreases mammographic sensitivity. We report the prevalent cancer detection rate (CDR) from the first clinical implementation of abbreviated breast magnetic resonance imaging (AB-MR) as a supplemental screening test in women with dense breasts. METHODS The study was approved by the institutional review board and is Health Insurance Portability and Accountability Act complaint. This retrospective review includes women who were imaged between January 1, 2016 and February 28, 2019. On a 1.5 Tesla magnet, the imaging protocol consisted of three sequences: Short-TI Inversion Recovery (STIR), precontrast, and postcontrast. A subtraction sequence and a maximum intensity projection were generated. We report the patient-level CDR and the positive predictive value of AB-MR examinations after negative/benign digital breast tomosynthesis (DBT). RESULTS Out of 511 prevalent rounds of AB-MR examinations, 36 women were excluded. The remaining 475 asymptomatic women with dense breasts had negative/benign DBT examinations before the AB-MR. There were 420 of 475 (88.4%) benign/negative examinations, 13 of 475 (2.7%) follow-up recommendations, and 42 biopsy recommendations. Thirty-nine biopsies were completed, resulting in 12/39 (30.8%) malignancies in 12 women: seven invasive carcinomas and five ductal carcinoma in situ. One additional patient was diagnosed with invasive ductal carcinoma at the time of 6-month follow-up. The CDR was 27.4 per 1,000 (13 of 475; 95% CI, 16.1 to 46.3). The size of invasive carcinomas ranged from 0.6-1.0 cm (mean, 0.5 cm). Of the seven women who underwent surgical evaluation of the axilla, zero of seven patients had positive nodes. There were no interval cancers at 1-year follow-up. CONCLUSION Preliminary results from clinical implementation of screening AB-MR resulted in a CDR of 27.4/1,000 at the patient level after DBT in women with dense breasts. Additional evaluation is warranted.

Background: Digital breast tomosynthesis (DBT) has been shown to improve screening outcomes compared with digital mammography (DM) alone. However, little is known about differences in breast cancer conspicuity between DM and DBT or by mammographic view. Purpose: To compare conspicuity of breast cancers at DM versus DBT and by mammographic view, craniocaudal (CC) versus mediolateral oblique (MLO). Materials and Methods: Lesion conspicuity was graded by three readers by using a 0-5 numerical scale on both DM and DBT images from combined DM and DBT studies for 197 consecutive screening-detected cancers in women (mean age, 60.4 years 6 11.1 [standard deviation]) from October 1, 2011, through December 31, 2014. Intermodality (ie, DM vs DBT) and intramodality (ie, CC vs MLO) analyses were performed. For intramodality analyses, conspicuity was analyzed by view, CC versus MLO, within the same modality. Conspicuity grades were dichotomized into low (scores 0-3) and high (scores 4 and 5) conspicuity. This binary result was assessed by using a generalized linear mixed-effects model with logit link function, random-effect intercept for reader, and compound symmetry covariance structure for lesion.

We conclude that PI is a common complication associated with treatment of GVHD after HSCT, and patients who develop PI experience higher TRM. Patients who develop PI should be managed medically.

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