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Background: Nonmass enhancement (NME) on breast MRI impacts surgical planning. Purpose: To evaluate positive predictive values (PPVs) and identify malignancy discriminators of NME ipsilateral to breast cancer on initial staging MRI. Study Type: Retrospective. Subjects: Eighty‐six women (median age, 48 years; range, 26–75 years) with 101 NME lesions (BI‐RADS 4 and 5) ipsilateral to known cancers and confirmed histopathology. Field Strength/Sequence: 1.5 T and 3.0 T dynamic contrast‐enhanced fat‐suppressed T1‐weighted fast spoiled gradient‐echo. Assessment: Three radiologists blinded to pathology independently reviewed MRI features (distribution, internal enhancement pattern, and enhancement kinetics) of NME, locations relative to index cancers (contiguous, non‐contiguous, and different quadrants), associated mammographic calcifications, lymphovascular invasion (LVI), axillary node metastasis, and radiology‐pathology correlations. Clinical factors, NME features, and cancer characteristics were analyzed for associations with NME malignancy. Statistical Tests: Fisher's exact, Chi‐square, Wilcoxon rank sum tests, and mixed‐effect multivariable logistic regression were used. Significance threshold was set at P < 0.05. Results: Overall NME malignancy rate was 48.5% (49/101). Contiguous NME had a significantly higher malignancy rate (86.7%) than non‐contiguous NME (25.0%) and NME in different quadrants (10.7%), but no significant difference was observed by distance from cancer for non‐contiguous NME, P = 0.68. All calcified NME lesions contiguous to the calcified index cancer were malignant. NME was significantly more likely malignant when index cancers were masses compared to NME (52.9% vs. 21.4%), had mammographic calcifications (63.2% vs. 39.7%), LVI (81.8% vs. 44.4%), and axillary node metastasis (70.8% vs. 41.6%). NME features with highest PPVs were segmental distribution (85.7%), clumped enhancement (66.7%), and nonpersistent kinetics (77.1%). On multivariable analysis, contiguous NME, segmental distribution, and nonpersistent kinetics were associated with malignancy. Data Conclusion: Malignancy discriminators of ipsilateral NME on staging MRI included contiguous location to index cancers, segmental distribution, and nonpersistent kinetics. Evidence Level: 3 Technical Efficacy: Stage 2 [ABSTRACT FROM AUTHOR]

Background: We evaluated whether patients' initial screening symptoms were related to subsequent utilization of supportive care services and hospitalizations, and whether patient‐level demographics, symptoms, hospitalizations, and supportive care service utilization were associated with mortality in primarily low‐income, older, Black Veterans with cancer. Methods: This quality improvement project created collaborative clinics to conduct cancer distress screenings and refer to supportive care services at an urban, VA medical center. All patients completed a distress screen with follow‐up screening every 3 months. Supportive care utilization, hospitalization rates, and mortality were abstracted through medical records. Poisson regression models and cox proportional hazard models were utilized. Results: Five hundred and eighty five screened patients were older (m = 72), mostly Black 70% (n = 412), and had advanced cancer 54%. Fifty‐eight percent (n = 340) were screened only once with 81% (n = 470) receiving ≥1 supportive care service and 51.5% (n = 297) being hospitalized ≥1 time 18 months following initial screen. Symptom severity was significantly related to number of hospitalizations. Low mood was significantly related to higher supportive services (p < 0.001), but not hospitalizations (p ≥ 0.52). Pain, fatigue, physical function, nutrition, and physical symptoms were significantly associated with more supportive services and hospitalizations (p < 0.01). Twenty percent (n = 168) died; Veterans who were Black, had lower stage cancers, better physical health, and utilized less supportive care services had lower odds of mortality (p ≤ 0.01). Conclusion: Individuals with elevated distress needs and those reporting lower physical function utilized more supportive care services and had higher hospitalization rates. Lower physical function, greater supportive care use, higher stage cancer, and being non‐Black were associated with higher odds of death. [ABSTRACT FROM AUTHOR]

Background: In this multicenter, single‐arm, multicohort, phase 2 trial, the efficacy of nivolumab and ipilimumab was evaluated in patients with advanced rare genitourinary cancers, including bladder and upper tract carcinoma of variant histology (BUTCVH), adrenal tumors, platinum‐refractory germ cell tumors, penile carcinoma, and prostate cancer of variant histology (NCT03333616). Methods: Patients with rare genitourinary malignancies and no prior immune checkpoint inhibitor exposure were enrolled. Patients received nivolumab at 3 mg/kg and ipilimumab at 1 mg/kg intravenously every 3 weeks for 4 doses, and this was followed by 480 mg of nivolumab intravenously every 4 weeks. The primary endpoint was the objective response rate (ORR) by the Response Evaluation Criteria in Solid Tumors (version 1.1). Results: Fifty‐five patients were enrolled at 6 institutions between April 2018 and July 2019 in 3 cohorts: BUTCVH (n = 19), adrenal tumors (n = 18), and other tumors (n = 18). The median follow‐up was 9.9 months (range, 1 to 21 months). Twenty‐eight patients (51%) received 4 doses of nivolumab and ipilimumab; 25 patients received nivolumab maintenance for a median of 4 cycles (range, 1‐18 cycles). The ORR for the entire study was 16% (80% confidence interval, 10%‐25%); the ORR in the BUTCVH cohort, including 2 complete responses, was 37%, and it was 6% in the other 2 cohorts. Twenty‐two patients (40%) developed treatment‐related grade 3 or higher toxicities; 24% (n = 13) required high‐dose steroids (≥40 mg of prednisone or the equivalent). Grade 5 events occurred in 3 patients; 1 death was treatment related. Conclusions: Nivolumab and ipilimumab resulted in objective responses in a subset of patients with rare genitourinary malignancies, especially those with BUTCVH. An additional cohort exploring their activity in genitourinary tumors with neuroendocrine differentiation is ongoing. Lay Summary: Patients with rare cancers are often excluded from studies and have limited treatment options.Fifty‐five patients with rare tumors of the genitourinary system were enrolled from multiple sites and were treated with nivolumab and ipilimumab, a regimen used for kidney cancer.The regimen showed activity in some patients, particularly those with bladder or upper tract cancers of unusual or variant histology; 37% of those patients responded to therapy.Additional studies are ongoing to better determine who benefits the most from this combination. Patients with rare genitourinary malignancies have limited treatment options and are underrepresented in clinical trials. In this phase 2 trial, which has accrued 55 patients in less than 18 months, the combination of nivolumab and ipilimumab is active in a subset of patients with rare genitourinary malignancies, particularly those with bladder or upper tract carcinoma of variant histology (objective response rate 37%). [ABSTRACT FROM AUTHOR]

Objectives:  To assess primary care physicians' (PCPs) perception of the need for serious illness conversations (SIC) or other palliative care interventions in patients flagged by a machine learning tool for high 1-year mortality risk., Methods:  We surveyed PCPs from four Brigham and Women's Hospital primary care practice sites. Multiple mortality prediction algorithms were ensembled to assess adult patients of these PCPs who were either enrolled in the hospital's integrated care management program or had one of several chronic conditions. The patients were classified as high or low risk of 1-year mortality. A blinded survey had PCPs evaluate these patients for palliative care needs. We measured PCP and machine learning tool agreement regarding patients' need for an SIC/elevated risk of mortality., Results:  Of 66 PCPs, 20 (30.3%) participated in the survey. Out of 312 patients evaluated, 60.6% were female, with a mean (standard deviation [SD]) age of 69.3 (17.5) years, and a mean (SD) Charlson Comorbidity Index of 2.80 (2.89). The machine learning tool identified 162 (51.9%) patients as high risk. Excluding deceased or unfamiliar patients, PCPs felt that an SIC was appropriate for 179 patients; the machine learning tool flagged 123 of these patients as high risk (68.7% concordance). For 105 patients whom PCPs deemed SIC unnecessary, the tool classified 83 as low risk (79.1% concordance). There was substantial agreement between PCPs and the tool (Gwet's agreement coefficient of 0.640)., Conclusions:  A machine learning mortality prediction tool offers promise as a clinical decision aid, helping clinicians pinpoint patients needing palliative care interventions., Competing Interests: L.R. reports serving on the AI Advisory Board for Augmedix Inc, receiving grants from the Agency for Healthcare Research and Quality (AHRQ), the American Medical Association, and FeelBetter Inc, outside the submitted work. D.W.B. reports receiving grants and personal fees from EarlySense, personal fees from CDI Negev, equity from ValeraHealth, equity from Clew, equity from MDClone, personal fees and equity from AESOP, personal fees and equity from FeelBetter, personal fees and equity from Guided Clinical Solutions and grants from IBM Watson Health, outside the submitted work. L.Z. reported receiving grants from the AHRQ, CRICO, IBM Watson Health, and the National Institutes of Health (NIH)., (Thieme. All rights reserved.)

BACKGROUND. CT-based body composition (BC) measurements have historically been too resource intensive to analyze for widespread use and have lacked robust comparison with traditional weight metrics for predicting cardiovascular risk. OBJECTIVE. The aim of this study was to determine whether BC measurements obtained from routine CT scans by use of a fully automated deep learning algorithm could predict subsequent cardiovascular events independently from weight, BMI, and additional cardiovascular risk factors. METHODS. This retrospective study included 9752 outpatients (5519 women and 4233 men; mean age, 53.2 years; 890 patients self-reported their race as Black and 8862 self-reported their race as White) who underwent routine abdominal CT at a single health system from January 2012 through December 2012 and who were given no major cardiovascular or oncologic diagnosis within 3 months of undergoing CT. Using publicly available code, fully automated deep learning BC analysis was performed at the L3 vertebral body level to determine three BC areas (skeletal muscle area [SMA], visceral fat area [VFA], and subcutaneous fat area [SFA]). Age-, sex-, and race-normalized reference curves were used to generate z scores for the three BC areas. Subsequent myocardial infarction (MI) or stroke was determined from the electronic medical record. Multivariable-adjusted Cox proportional hazards models were used to determine hazard ratios (HRs) for MI or stroke within 5 years after CT for the three BC area z scores, with adjustment for normalized weight, normalized BMI, and additional cardiovascular risk factors (smoking status, diabetes diagnosis, and systolic blood pressure). RESULTS. In multivariable models, age-, race-, and sex-normalized VFA was associated with subsequent MI risk (HR of highest quartile compared with lowest quartile, 1.31 [95% CI, 1.03-1.67], p = .04 for overall effect) and stroke risk (HR of highest compared with lowest quartile, 1.46 [95% CI, 1.07-2.00], p = .04 for overall effect). In multivariable models, normalized SMA, SFA, weight, and BMI were not associated with subsequent MI or stroke risk. CONCLUSION. VFA derived from fully automated and normalized analysis of abdominal CT examinations predicts subsequent MI or stroke in Black and White patients, independent of traditional weight metrics, and should be considered an adjunct to BMI in risk models. CLINICAL IMPACT. Fully automated and normalized BC analysis of abdominal CT has promise to augment traditional cardiovascular risk prediction models.

Purpose: Antiangiogenic VEGF receptor (VEGFR) inhibitors are approved for metastatic clear cell renal cell carcinoma (mccRCC) and their efficacy is higher in high angiogenic tumors. As cabozantinib inhibits multiple tyrosine kinase receptors, including VEGFRs, we tested whether markers of angiogenesis, including microvascular density (MVD) and mast cell density (MCD), could predict benefit from cabozantinib versus everolimus, using RCC samples from the METEOR (NCT01865747) trial., Experimental Design: MVD and MCD were studied in 430 patients (cabozantinib = 216, everolimus = 214) by double immunohistochemistry for CD31 (vascular marker) and tryptase (mast cell marker) coupled with automated image analysis. Results from evaluable cases (MVD = 360, MCD = 325) were correlated with progression-free survival (PFS), overall survival (OS), and objective response rate (ORR)., Results: MVD was positively correlated with MCD. In the whole cohort, high MVD and high MCD were associated with longer PFS; improved PFS was most evident in patients with high levels of both MCD and MVD. Cabozantinib was associated with improved PFS, OS, and ORR compared with everolimus, irrespective of MVD levels. Cabozantinib was also associated with improved ORR compared with everolimus, irrespective of MCD levels. For PFS and OS, the treatment effect for cabozantinib versus everolimus tended to be greater in tumors with low MCD., Conclusions: High MVD and high MCD are associated with improved outcome in mccRCC but do not predict efficacy to cabozantinib versus everolimus. The high efficacy of cabozantinib in low angiogenic tumors allows us to speculate that its antitumor activity is not exclusively mediated by VEGFR inhibition., (©2021 American Association for Cancer Research.)