Frank, Ryan D.

Purpose Women with atypical hyperplasia (AH) on breast biopsy have an aggregate increased risk of breast cancer (BC), but existing risk prediction models do not provide accurate individualized estimates of risk in this subset of high-risk women. Here, we used the Mayo benign breast disease cohort to develop and validate a model of BC risk prediction that is specifically for women with AH, which we have designated as AH-BC. Patients and Methods Retrospective cohorts of women age 18 to 85 years with pathologically confirmed benign AH from Rochester, MN, and Nashville, TN, were used for model development and external validation, respectively. Clinical risk factors and histologic features of the tissue biopsy were selected using L1-penalized Cox proportional hazards regression. Identified features were included in a Fine and Gray regression model to estimate BC risk, with death as a competing risk. Model discrimination and calibration were assessed in the model-building set and an external validation set. Results The model-building set consisted of 699 women with AH, 142 of whom developed BC (median follow-up, 8.1 years), and the external validation set consisted of 461 women with 114 later BC events (median follow-up, 11.4 years). The final AH-BC model included three covariates: age at biopsy, age at biopsy squared, and number of foci of AH. At 10 years, the AH-BC model demonstrated good discrimination (0.63 [95% CI, 0.57 to 0.70]) and calibration (0.87 [95% CI, 0.66 to 1.24]). In the external validation set, the model showed acceptable discrimination (0.59 [95% CI, 0.51 to 0.67]) and calibration (0.91 [95% CI, 0.65 to 1.42]). Conclusion We have created a new model with which to refine BC risk prediction for women with AH. The AH-BC model demonstrates good discrimination and calibration, and it validates in an external data set.

Background: Palliative care is associated with improved survival and quality of life, but its use among patients with colorectal cancer varies nationwide and the determinants of those variations are not clear. Objective: To determine the factors associated with palliative care use among patients who died of colorectal cancer. Methods: Deceased patients treated for colorectal cancer (2004-2013) were identified within the National Cancer Database. Multivariable logistic regression was used to evaluate patient and institutional characteristics associated with palliative care use. Patients were classified based on their length of survival (<6 months, 6-24 months, and 24+ months) to provide timing context. Results: A total of 287 923 patients were analyzed. Overall, 4.3% of the patients received palliative care. Patients who received palliative care were more likely to be younger, recently diagnosed, treated at academic hospitals, and have stage IV disease. Patients living in Mountain and Pacific regions had higher odds of palliative care receipt than those in the East Coast. Patients without insurance had higher odds of palliative care if they survived <24 months. Insurance coverage through Medicaid was associated with increased palliative care use among patients who survived 6 to 24 months. Patients who survived <6 months and lived >9 miles from the institution received more palliative care. Conclusion: Palliative care use among patients with colorectal cancer is associated with a younger age, a more recent year of diagnosis, insurance status, academic hospitals, and living in Mountain and Pacific regions.

BACKGROUNDOutcomes have improved significantly in multiple myeloma (MM), but racial disparities in health care access and survival exist. A comprehensive analysis exploring MM care and racial disparities is warranted.METHODSPatients with MM from 1991 to 2010 in the Surveillance, Epidemiology, and End Results‐Medicare database were evaluated for racial trends in clinical myeloma‐defining events (MDEs), the receipt of treatment (drugs and stem cell transplantation; [SCT]), the cost of care, and overall survival (OS).RESULTSAmong 35,842 patients, the frequency of all MDEs at diagnosis increased over time; whereas, in recent years (2006‐2010), all MDEs with the exception of renal dialysis decreased. Blacks had highest rates for all MDEs except bone fractures, which were highest in whites. Over time, the proportion of patients who received any treatment, multiple agents, and SCT increased significantly, and the largest increase was observed in the receipt of immunomodulatory drugs and steroids. There was greater receipt of bortezomib and SCT among whites and blacks and higher receipt of immunomodulatory drugs among Hispanics and Asians (P < .001). Medicare claims were highest during first 6 months after MM diagnosis for blacks and at any time after MM diagnosis for Hispanics. Over time, Medicare claims increased most steadily for Hispanics (P < .001). Hypercalcemia, renal dysfunction, and bone fractures were associated with inferior OS. Blacks and Asians had superior OS compared with whites, but racial differences in OS became less pronounced during 2006 through 2010 (P = .182) compared with prior years (P < .01). Better OS was noted among patients who had higher median incomes.CONCLUSIONSThe current results indicate that there have been significant changes in the management of patients with MM over time and provide an in‐depth understanding of the factors that may help explain racial disparities. Cancer 2018;124:1710‐21. © 2018 American Cancer Society

BACKGROUND: Thrombocytopenia is frequently encountered in critically ill patients, often resulting in prophylactic transfusion of platelets for the prevention of bleeding complications. However, the efficacy of this practice remains unclear. The objective of this study was to determine the relationship between prophylactic platelet transfusion and bleeding complications in critically ill patients. METHODS: This is a retrospective cohort study of adults admitted to surgical, medical, or combined medical-surgical intensive care units (ICUs) at a single academic institution between January 1, 2009, and December 31, 2013. Inclusion criteria included age ≥18 years and a platelet count measured during ICU admission. Propensity-matched analyses were used to evaluate associations between prophylactic platelet transfusions and the outcomes of interest with a primary outcome of red blood cell transfusion in the ensuing 24 hours and secondary outcomes of ICU and hospital-free days and changes in sequential organ failure assessment scores. RESULTS: A total of 40,693 patients were included in the investigation with 3227 (7.9%) receiving a platelet transfusion and 1065 (33.0%) for which platelet transfusion was prophylactic in nature. In propensity-matched analyses, 994 patients with prophylactic platelet transfusion were matched to those without a transfusion. Patients receiving prophylactic platelets had significantly higher red blood cell transfusion rates (odds ratio 7.5 [5.9–9.5]; P < .001), fewer ICU-free days (mean [standard deviation] 20.8 [9.1] vs 22.7 [8.3] days; P = .004), fewer hospital-free days (13.0 [9.7] vs 15.8 [9.4] days; P < .001), and less improvement in sequential organ failure assessment scores (mean decrease of 0.2 [3.6] vs 1.8 [3.3]; P < .001) in the subsequent 24 hours. These findings appeared robust, persisting in multiple predefined sensitivity analyses. CONCLUSIONS: Prophylactic administration of platelets in the critically ill was not associated with improved clinical outcomes, though residual confounding may exist. Further investigation of platelet transfusion strategies in this population is warranted.

AbstractWe conducted a surveillance epidemiology and end results (SEER)‐based analysis to describe the incidence and characteristics of second primary acute lymphoblastic leukemia (sALL) among adults (≥18 years) with a history of primary malignancies (1M). Standardized incidence ratios (SIRs) of sALL cases were calculated by site and 1M stage. We also evaluated the differences in 5‐year sALL survival by age, site, and extent of 1M, latency of sALL after 1M, and evidence of underlying racial/ethnic disparity. We identified 10,956 patients with de‐novo/primary acute lymphoblastic leukemia (1ALL) and 772 with sALL. Women (49.1% vs. 42.9%), white patients (72.0% vs. 59.5%), older patients (58.8% vs. 25.2%; age ≥65 years), and patients diagnosed between 2003 and 2012 (66.8% vs. 53.9%) had a higher proportion of sALL compared with 1ALL. There was a significantly inferior median 5‐year survival for sALL patients compared to 1ALL (6 vs. 15 months; HR 1.20, 95% CI 1.10–1.31, P < 0.001). The median latency period was 60.0 months; the most common 1M among sALL patients were breast (17.9%) and prostate (17.4%). Patients with any 1M were at increased risk of developing sALL (SIR 1.76, 95% CI 1.58–1.95, P < 0.001). Hematological‐1M sites had significantly higher SIRs (hematological‐SIR 7.35; solid‐SIR 1.33; P < 0.001). We observed a significant increase in sALL incidence after a 1M and a significantly worse 5‐year survival with different demographic characteristics from 1ALL. There is a need to define appropriate screening methods for patients surviving their primary cancer.

69 Background: Due to improved survival, an increasing number of patients with advanced cancer are eligible for aggressive ICU care, including intubation. The American Society of Clinical Oncology recommends early integration of palliative care in patients with advanced cancer. We analyzed 10-year trends in the utilization of palliative care, and predictors of palliative care use in patients with metastatic cancer undergoing intubation using the National Hospital Discharge Survey database from 2001-2010. Methods: Diagnosis and procedure codes were utilized to identify adult patients with metastatic cancer who underwent intubation, and received palliative care. Demographics, diagnoses, length of stay (LOS), and discharge information were extracted. T-tests and χ^2 tests were used to compare medians and proportions respectively in patients that did or did not receive palliative care. Multivariate regression models with weighted analysis were conducted to study predictors of palliative care use. Results: Over the 10-year study period, 200,350 patients with metastatic cancer and intubation were identified, mean age 65.3 years, 46.2% male. Of these, 6690 (3.3%) received palliative care. There was a significant increase in the use of palliative care from 2001 (0%) to 2010 (17.4%), p for trend < 0.001. In multivariate analysis, patients who received palliative care were more likely to have age > 65 years, be white vs non-white, be hospitalized in 2009-2010 vs 2000-2001, and be admitted to hospitals in the Western part of the US. The overall inpatient mortality rate was 57.3%, discharge to a care facility (DTCF) rate was 15.2%, and mean LOS was 11.1 days. The LOS and DTCF rates were similar in patients with and without palliative care. Patients with palliative care had higher rates of inpatient mortality (adjusted OR 9.6, 95% CI 2.2- 42.0). Conclusions: There was a dramatic increase in the use of palliative care in intubated patients with metastatic cancer. Studies to address the racial and geographic discrepancies in palliative care use are warranted. The higher mortality in palliative care group suggests it is being used for the sickest patients. Early (vs end of life) palliative care may be more beneficial.

AbstractOutcomes have improved considerably in multiple myeloma (MM), but disparities among racial‐ethnic groups exist. Differences in utilization of novel therapeutics are likely contributing factors. We explored such differences from the SEER‐Medicare database. A utilization analysis of lenalidomide, thalidomide, bortezomib, and stem cell transplant (SCT) was performed for patients diagnosed with MM between 2007 and 2009, including use over time, use by race, time‐dependent trends for each racial subgroup, and survival analysis. A total of 5338 MM patients were included with median 2.4‐year follow‐up. Within the first year of MM diagnosis, utilization of lenalidomide, bortezomib, SCT, and more than one novel agent increased over time while utilization of thalidomide decreased. There was significantly lower utilization of lenalidomide among African‐Americans (P < 0.01), higher thalidomide use among Hispanics and Asians (P < 0.01), and lower bortezomib use among Asians (P < 0.01). Hispanics had the highest median number of days to first dose of bortezomib (P = 0.02) and the lowest utilization of SCT (P < 0.01). Hispanics and Asians were the only groups without notable increases in lenalidomide and bortezomib use, respectively. SCT utilization increased over time for all except African‐Americans. SCT use within the first year after diagnosis was associated with better overall survival (HR 0.52; 95% CI: 0.4–0.68), while bortezomib use was associated with inferior survival (HR 1.14; 95% CI 1.02–1.28). We noted considerable variability in MM therapeutics utilization with seeming inequity for racial‐ethnic minorities. These trends should be considered to eliminate drug access and utilization disparities and achieve equitable benefit of therapeutic advances across all races.

Abstract Background: The Breast Cancer Surveillance Consortium (BCSC) model predicts invasive breast cancer risk in women with Benign Breast Disease (BBD), and recently incorporated BBD histology into the model. The BCSC has been validated in the Mayo Mammography Health Study, but has yet to be examined in Mayo Clinic’s BBD cohort. The Benign Breast Disease to Breast Cancer (BBD-BC) model predicts risk of both invasive and in situ breast cancer. Here we compare the performance of the BCSC and BBD-BC in Mayo Clinic’s BBD cohort. Methods: Eligible women underwent a breast biopsy with benign findings at the Mayo Clinic between years 1997-2001 and had a 4-view screening mammogram within six months of biopsy. Clinical BI-RADS density assessments using the 4th edition American College of Radiology were available on all mammograms, and were coded as almost entirely fat, scattered fibroglandular densities, heterogeneously dense, and extremely dense. Risk at 5 and 10 years of invasive cancer only (BCSC model) or both invasive and in situ cancer (BBD-BC model) were estimated. In situ cancers were censored at time of diagnosis for both models. Concordance statistics, i.e. model discrimination (higher is better), for each model were calculated using a Cox proportional hazards model with predicted risk as the sole predictor, and were compared using permutation tests. The ratio of total predicted (sum of predicted risk) to observed number of invasive breast cancers was used to assess model calibration. Calibration was not formally compared across models due to differences in how DCIS was treated in the development of each (BCSC censored; BBD-BC event). Results: 999 women met inclusion criteria. BI-RADS density was categorized as fatty in 46 (4.6%), scattered densities in 372 (37.2%), heterogeneously dense in 423 (42.3%), and extremely dense in 158 (15.8%). 62 invasive cancers occurred over a median 13.3yrs of follow-up, with 16 (25.8%) and 48 (77.4%) of the cancers occurring with-in 5 and 10 years. The concordance of the BCSC at 5 years was 0.550 (95% CI 0.409—0.691), compared to 0.719 (95% CI 0.578—0.860) for the BBD-BC (p-value=0.005). At 10 years the BCSC concordance was not significantly different from the BBD-BC, at 0.624 (95% CI 0.542—0.706) and 0.662 (95% CI 0.580—0.744), respectively (p-value=0.306). The BCSC over predicted the number invasive cancers in the BBD cohort at 5 years (predicted-to-observed=1.54; 95% CI 1.01—2.70), but was well calibrated at 10 years (1.06; 95% CI 0.83, 1.47). Conclusions: The BCSC model performed reasonably well in the BBD Cohort 10 years post-biopsy, but overestimated risk at 5 years. Additional study is needed to improve models for prediction of breast cancer risk among women with BBD. Citation Format: Ryan D. Frank, Celine M. Vachon, Stacey J. Winham, Robert A. Vierkant, Marlene H. Frost, Derek C. Radisky, Daniel W. Visscher, Amy C. Degnim. Validation of the BCSC model within the Mayo Benign Breast Disease Cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5299. doi:10.1158/1538-7445.AM2017-5299

704 Background: Inpatients with gastrointestinal (GI) malignancies are at a high risk for Clostridium difficile infection (CDI) but the impact of CDI on outcomes in these patients needs elucidation. We analyzed the incidence of CDI and its impact on outcomes in GI cancer patients using the National Hospital Discharge Survey (NHDS) database from 2001 - 2010. Methods: NHDS collects clinical information on patients dismissed from non-Federal short-stay United States hospitals. Demographics, diagnoses (GI malignancies, CDI and comorbidities), length of stay (LOS), and dismissal information were abstracted using ICD-9 diagnosis and procedure codes. Weighted analyses were performed using SAS version 9.4. Results: Of an estimated 317.9 million unique hospitalizations; 4.6 million had a diagnosis of a GI malignancy (1.4%); median age 68 years, 46.1% female. CDI was more common in patients with GI malignancies compared to patients with no GI malignancy (1.05% vs 0.69%, aOR 1.16, 95% CI 1.15- 1.17, p < 0.0001). There was a significant increase in CDI incidence in GI cancer patients over the 10-year study period (72.7 in 2001-2002 to 109.1 in 2009-2010, per 10,000 discharges, p < 0001). In multivariable analysis, compared to GI cancer patients without CDI, GI cancer patients with CDI had a longer mean LOS (3.94 more days, 95% CI 3.31-4.56) and dismissal to a care facility (adjusted OR, 1.75; 95% CI, 1.71-1.79), but lower all-cause in-hospital mortality (adjusted OR, 0.76; 95% CI, 0.74-0.79), all p < 0.0001 Conclusions: In this national database of hospitalized patients, an increasing incidence of CDI in patients with GI malignancies was noted over the study period. CDI prolonged hospitalization, and was associated with increased dismissal to a care-facility. Lower rates of in-hospital mortality may represent early diagnosis due to vigilance or a milder form of CDI. Despite increased attention over the last few decades, CDI remained a serious infection in GI cancer patients, and merits appropriate prevention, management and follow-up.

Objectives: Effective pharmacologic treatments directly targeting lung injury in patients with the acute respiratory distress syndrome are lacking. Early treatment with inhaled corticosteroids and beta agonists may reduce progression to acute respiratory distress syndrome by reducing lung inflammation and enhancing alveolar fluid clearance. Design: Double-blind, randomized clinical trial (ClinicalTrials.gov: NCT01783821). The primary outcome was longitudinal change in oxygen saturation divided by the F io 2 (S/F) through day 5. We also analyzed categorical change in S/F by greater than 20%. Other outcomes included need for mechanical ventilation and development of acute respiratory distress syndrome. Setting: Five academic centers in the United States. Patients: Adult patients admitted through the emergency department at risk for acute respiratory distress syndrome. Interventions: Aerosolized budesonide/formoterol versus placebo bid for up to 5 days. Measurements and Main Results: Sixty-one patients were enrolled from September 3, 2013, to June 9, 2015. Median time from presentation to first study drug was less than 9 hours. More patients in the control group had shock at enrollment (14 vs 3 patients). The longitudinal increase in S/F was greater in the treatment group ( p = 0.02) and independent of shock ( p = 0.04). Categorical change in S/F improved ( p = 0.01) but not after adjustment for shock ( p = 0.15). More patients in the placebo group developed acute respiratory distress syndrome (7 vs 0) and required mechanical ventilation (53% vs 21%). Conclusions: Early treatment with inhaled budesonide/formoterol in patients at risk for acute respiratory distress syndrome is feasible and improved oxygenation as assessed by S/F. These results support further study to test the efficacy of inhaled corticosteroids and beta agonists for prevention of acute respiratory distress syndrome.