Citations

BACKGROUNDTo evaluate the impact of depression before autologous and allogeneic hematopoietic cell transplantation (HCT) on clinical outcomes post‐transplantation.METHODSWe analyzed data from the Center for International Blood and Marrow Transplant Research to compare outcomes after autologous (n = 3786) or allogeneic (n = 7433) HCT for adult patients with hematologic malignancies with an existing diagnosis of pre‐HCT depression requiring treatment versus those without pre‐HCT depression. Using Cox regression models, we compared overall survival (OS) between patients with or without depression. We compared the number of days alive and out of the hospital in the first 100 days post‐HCT using Poisson models. We also compared the incidence of grade 2‐4 acute and chronic graft‐versus‐host disease (GVHD) in allogeneic HCT.RESULTSThe study included 1116 (15%) patients with pre‐transplant depression and 6317 (85%) without depression who underwent allogeneic HCT between 2008 and 2012. Pre‐transplant depression was associated with lower OS (hazard ratio [HR], 1.13; 95% confidence interval [CI], 1.04‐1.23; P = 0.004) and a higher incidence of grade 2‐4 acute GVHD (HR, 1.25; 95% CI, 1.14‐1.37; P < 0.0001), but similar incidence of chronic GVHD. Pre‐transplant depression was associated with fewer days‐alive‐and‐out‐of‐the hospital (means ratio [MR] = 0.97; 95% CI, 0.95‐0.99; P = 0.004). There were 512 (13.5%) patients with Pre‐transplant depression and 3274 (86.5%) without depression who underwent autologous HCT. Pre‐transplant depression in autologous HCT was not associated with OS (HR, 1.15; 95% CI, 0.98‐1.34; P = 0.096) but was associated with fewer days alive and out of the hospital (MR, 0.98; 95% CI, 0.97‐0.99; P = 0.002).CONCLUSIONPre‐transplant depression was associated with lower OS and higher risk of acute GVHD among allogeneic HCT recipients and fewer days alive and out of the hospital during the first 100 days after autologous and allogeneic HCT. Patients with pre‐transplant depression represent a population that is at risk for post‐transplant complications. Cancer 2017;123:1828–1838. © 2017 American Cancer Society.

BACKGROUND The Patient‐Reported Outcomes Measurement Information System (PROMIS) was a National Institutes of Health‐funded initiative to develop measures of symptoms and function. Responsiveness is the degree to which a measure can detect underlying changes over time. The objective of the current study was to document the responsiveness of 8 PROMIS measures in a large, population‐based cancer cohort. METHODS The Measuring Your Health study recruited 2968 patients who were diagnosed with 1 of 7 cancers between 2010 and 2012 through 4 Surveillance, Epidemiology, and End Results registries. Participants completed a baseline survey (6‐13 months after diagnosis) and a 6‐month follow‐up survey. Changes in 8 PROMIS scores were compared with global ratings of transition, changes in performance status, and clinical events. RESULTS Measures were responsive to 6‐month declines and improvements in performance status with small to large effect sizes (ES) (Cohen d = 0.34‐0.71; P < .01). Mean changes and effect sizes were larger for participants who reported declines compared with those who reported improvements. Small‐to‐medium ES were observed in patients who reported being “a little” worse (d = 0.31‐0.56), and medium‐to‐large ES were observed in those who reported being “a lot” worse (d = 0.53‐0.72). Hospitalized participants reported significant score increases, resulting in worsening of pain (d = 0.51), fatigue (d = 0.35), and depression (d = 0.57; all P < .01). Cancer recurrence and progression were associated with smaller increases in pain, fatigue, and sleep disturbance (d = 0.22‐0.27). CONCLUSIONS The current results indicated that all 8 PROMIS measures were sensitive to patient‐perceived worsening and improvement and to major clinical events. These findings will be able to inform the design and interpretation of future research studies and clinical initiatives administering PROMIS measures. Cancer 2017;123:327–335. © 2016 American Cancer Society .

Background: In the initial PARTNER trial (Placement of Aortic Transcatheter Valves) of transcatheter aortic valve replacement for high-risk (HR) and inoperable patients, mortality at 1 year was 24% in HR and 31% in inoperable patients. A recent report of the 30-day outcomes with the low-profile SAPIEN 3 transcatheter aortic valve replacement system demonstrated very low rates of adverse events, but little is known about the longer-term outcomes with this device. Methods: Between October 2013 and September 2014, 583 HR (65%) or inoperable (35%) patients were treated via the transfemoral (84%) or transapical/transaortic (16%) access route at 29 US sites. Major clinical events at 1 year were adjudicated by an independent clinical events committee, and echocardiographic results were analyzed by a core laboratory. Results: Baseline characteristics included age of 83 years, 42% female, and median Society of Thoracic Surgeons score of 8.4%. At the 1-year follow-up, survival (all-cause) was 85.6% for all patients, 87.3% in the HR subgroup, and 82.3% in the inoperable subgroup. Survival free of all-cause and cardiovascular mortality in the transfemoral patients from the HR cohort was 87.7% and 93.3%, respectively. There was no severe paravalvular leak. Moderate paravalvular leak (2.7%) was associated with an increase in mortality at 1 year, whereas mild paravalvular leak had no significant association with mortality. Symptomatic improvement as assessed by the percentage of patients in New York Heart Association class III and IV (90.1% to 7.7% at 1 year; P <0.0001) and by Kansas City Cardiomyopathy Questionnaire overall summary score (improved from 46.9 to 72.4; P <0.0001) was marked. Multivariable predictors of 1-year mortality included alternative access, Society of Thoracic Surgeons score, and disabling stroke. Conclusions: In this large, adjudicated registry of SAPIEN 3 HR and inoperable patients, the very low rates of important complications resulted in a strikingly low mortality rate at 1 year. Between 30 and 365 days, the incidence of moderate paravalvular aortic regurgitation did not increase, and no association between mild paravalvular leak and 1-year mortality was observed, although a small increase in disabling stroke occurred. These results, which likely reflect device iteration and procedural evolution, support the use of transcatheter aortic valve replacement as the preferred therapy in HR and inoperable patients with aortic stenosis. Clinical Trial Registration : URL: http://www.clinicaltrials.gov . Unique identifier: NCT01314313.

BACKGROUND: It is not clear if starting intravenous proton pump inhibitors (IV PPI) before endoscopic therapy provides additional benefit over starting it afterward in patients with high-risk ulcer stigmata of peptic ulcer disease.METHODS: All patients who received IV pantoprazole bolus and infusion and underwent endoscopy in six Canadian hospitals over 20 months were reviewed. Only patients with high-risk ulcer stigmata (arterial bleeding, oozing, nonbleeding visible vessel or adherent clot) were included. Patients receiving IV PPI before endoscopy (before group) were compared with those who received it after endoscopy (after group) with respect to endoscopic findings and, secondarily, to patient demographics and clinical outcomes.RESULTS: The demographics and baseline characteristics of the before group (n=57) and the after group (n=109) were similar. The before group was more likely to have had IV PPI started outside of daytime hours, and median time to endoscopy in patients admitted with upper gastrointestinal bleeding was 24 h (interquartile range 9.5 to 35) in the before group and 11.3 h (interquartile range 3.7 to 17.2) in the after group ( P<0.0001). At the time of endoscopy, 33% of patients in the before group had actively bleeding lesions (Forrest 1a or 1b) compared with 54% in the after group (P=0.01), but there were no significant differences in rebleeding, surgical rates, intensive care unit admission or death between the groups.CONCLUSION: IV PPI infusions before endoscopy may lower the proportion of actively bleeding peptic ulcer lesions at endoscopy, but this finding does not appear to affect rates of rebleeding, surgery or death.

Abstract Neoadjuvant endocrine therapy (ET) in patients (pts) with locally advanced estrogen receptor positive (ER+) breast cancer (BC) improves breast conservation rate, and importantly offers an opportunity for individualized assessment of tumor responsiveness to ET to guide subsequent treatment. Previous neoadjuvant ET trials demonstrated that pathologic tumor size (pT), axillary lymph node status (N), and tumor Ki67 value at surgery predicted risk of relapse. Preoperative endocrine prognostic index (PEPI) was therefore developed to assign risk scores based on these factors. Modified PEPI 0, defined by pT1-2 N0 Ki67&lt; 2.7%, was associated with extremely low risk of recurrence without adjuvant chemotherapy. In addition, high Ki67 post 2-4 weeks (wks) of neoadjuvant ET identified resistant tumors with poor outcome. ALTERNATE trial is a three-arm phase III neoadjuvant/adjuvant ET trial designed to achieve two primary objectives. The first is to prospectively validate that modified PEPI 0 predicts &gt; 95% relapse-free survival (RFS). The second is to determine whether fulvestrant (F), or fulvestrant (F) plus anastrozole (A), is superior to A in inducing a higher rate of modified PEPI 0. Secondary objectives include assessing RFS for pts with endocrine resistant tumor, defined by Ki67 &gt; 10% at 4 or 12 wk, disease progression, or modified PEPI non-0, and pathologic responses of resistant tumors to neoadjuvant chemotherapy. Correlative studies include degrees of Ki67 suppression and ER level post treatment. In addition, ongoing research sequencing studies of DNA and RNA will be performed to contrast sensitive vs resistant tumors. During the first phase of the trial, 1200 pts are randomized 1:1:1 to the F, A or F/A. This provides an 82% chance, 1-sided alpha 0.025 chi-square test to detect at least 10% difference in modified PEPI 0 rate comparing F or F/A with A. While waiting for result of analysis, the A arm will continue for the 2nd phase enrollment. Only the F-containing arm(s) superior over A will be continued to the 2nd phase. During the 2nd phase, an additional 540 pts in each arm is estimated to obtain 317 pts with PEPI score 0. This will have a 90% chance, with a one-sided alpha=0.025 nonparametric Brookmeyer-Crowley type one sample survival test, rejecting that 5 year RFS rate is 95%. The maximum sample size is 2820 pts. Eligible pts include postmenopausal women with newly diagnosed clinical stage II or III ER+ (Allred score 6-8) HER2- BC. Tumor biopsy is required at baseline, 4 wk, and surgery for central Ki67 analysis. Treatment decision is individualized based on 4 wk Ki67 and modified PEPI score. Pts with Ki67 &gt; 10% at 4 wk are switched to chemotherapy. Pts with a modified PEPI score of 0 are recommended not to receive chemotherapy, but continue the assigned ET for 1.5 years followed by 3 years of A. This trial is currently accruing pts through CTSU. This research is supported in part by NCI BIQSFP, and grants from Breast Cancer Research Foundation, Genentech, and the Investigator-Sponsored Study Program of AstraZeneca. The Clinical Trials.gov Identifier: NCT01953588. Citation Format: Cynthia X Ma, Vera Suman, A Marilyn Leitch, Souzan Sanati, Katherine DeSchryver, Gary W Unzeitig, Paul Haluska, Mark Watson, Olwen Hahn, Jo Anne Zujewski, Kelly Hunt, Eric P Winer, Cliff A Hudis, Matthew J Ellis. Alliance A011106: ALTernate approaches for clinical stage II or III Estrogen Receptor positive breast cancer NeoAdjuvant TrEatment (ALTERNATE) in postmenopausal women: A phase III study [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr OT2-1-04.