circulating tumor DNA • liquid biopsy • cell-free DNA • head and neck squamous cell carcinoma • head and neck neoplasms • genomic testing • next-generation sequencing • prognosis • overall survival • precision medicine

High tissue iron levels are a risk factor for multiple chronic diseases including type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD). To investigate causal relationships and underlying mechanisms, we used an established NAFLD model—mice fed a high fat diet with supplemental fructose in the water (“fast food”, FF). Iron did not affect excess hepatic triglyceride accumulation in the mice on FF, and FF did not affect iron accumulation compared to normal chow. Mice on low iron are protected from worsening of markers for non-alcoholic steatohepatitis (NASH), including serum transaminases and fibrotic gene transcript levels. These occurred prior to the onset of significant insulin resistance or changes in adipokines. Transcriptome sequencing revealed the major effects of iron to be on signaling by the transforming growth factor beta (TGF-β) pathway, a known mechanistic factor in NASH. High iron increased fibrotic gene expression in vitro, demonstrating that the effect of dietary iron on NASH is direct. Conclusion: A lower tissue iron level prevents accelerated progression of NAFLD to NASH, suggesting a possible therapeutic strategy in humans with the disease.

Objectives/Hypothesis: Neck Imaging Reporting and Data System (NI-RADS) is a radiology reporting system developed for head and neck cancer surveillance imaging, using standardized terminology, numeric levels of suspicion, and linked management recommendations. Through a multidisciplinary, interdepartmental quality improvement initiative, we implemented NI-RADS for the reporting of head and neck cancer surveillance CT. Our objective is to summarize our initial experience from the standpoints of head and neck cancer providers and radiologists.Study Design: Quality improvement study. Methods: Before and 3 months post-implementation, surveys were offered to referring physicians (n = 21 pre-adoption; 22 post-adoption) and radiologists (n = 17 pre-and post-adoption). NI-RADS utilization was assessed over time.Results: Survey response rates were 62% (13/21) and 73% (16/22) for referring physicians pre-and post-adoption, respectively, and 94% (16/17) for radiologists pre-and post-adoption. Among post-adoption provider respondents, 100% (16/16) strongly agreed or agreed with "I want our radiologists to continue using NI-RADS," "The NI-RADS numerical rating of radiologic suspicion is helpful," and "The language and style of NI-RADS neck CT reports are clear and understandable." Among radiologist respondents, 88% (14/16) strongly agreed or agreed with "NI-RADS improves consistency among our radiologists in the reporting of surveillance neck CTs." Radiologist NI-RADS utilization increased over time (46% month 1; 72% month 3).Conclusions: Most referring physicians and radiologists preferred NI-RADS. Head and neck cancer providers indicated that NI-RADS reports are clear, understandable, direct, and helpful in guiding clinical management. Radiologists indicated that NI-RADS improves radiologist consistency in the reporting of surveillance neck CT, and radiologists increasingly used NI-RADS over time.

Objectives: Neck Imaging Reporting and Data System (NI-RADS) is a radiology reporting system for head and neck cancer surveillance. Imaging findings of high suspicion for recurrence are assigned Category 3 and recommended for "Biopsy, if clinically indicated." After implementing NI-RADS for surveillance neck computed tomography (CT), our objectives are to determine the incidence of squamous cell carcinoma (SCC) Category 3 lesions in the year post-implementation, the associated biopsy rate, and the positive predictive value of NI-RADS 3 for SCC recurrence.Study Design: Retrospective cohort study. Methods: Neck CTs reported with NI-RADS between February 2020 and February 2021 were reviewed to identify patients undergoing surveillance for SCC assigned NI-RADS 3. Cancer recurrence, defined as positive biopsy result or treatment of clinically determined recurrence, was determined by electronic medical record review.Results: During the study period, 580 neck CTs were reported with NI-RADS, of which 39 (7%) CTs obtained in 37 unique patients (28 male, 9 female, mean age 66.6 years) formed the study cohort. Biopsies were obtained in 23 lesions (45%), of which 17 (74%) were positive for recurrent SCC. One nondiagnostic biopsy was clinically determined to represent recurrence. Of 28 (55%) lesions not biopsied, 18 (64%) were ultimately treated as clinically determined recurrence. Thus, among 51 individual NI-RADS 3 lesions (32 primary, 19 neck), 36 (71%) represented recurrence. Conclusion:The incidence of NI-RADS 3 lesions in our cohort was 7%. The biopsy rate was 45%, and the overall positive predictive value of NI-RADS 3 for recurrent SCC was 71%. Category 3 lesions are associated with substantial SCC recurrence risk and should be managed accordingly.