tbuckley/cabot-search huggingface dataset:
Feasibility of a physical activity intervention for ethnically diverse endometrial cancer survivors.
Authors: Amerigo Rossi, Carol Garber, Monica Ortiz, Alyson Moadel-Robblee, Gurpreet Kaur, Shankar Viswanathan, Mark H. Einstein, Gary L. Goldberg, Nicole Nevadunsky
Journal: Journal of Clinical Oncology (2015)

5598 Background: To determine the feasibility of a 12-week physical activity (PA) intervention guided by social cognitive theory for ethnically diverse endometrial cancer (EC) survivors and to evaluate whether such an intervention might improve PA behavior, physical function, waist circumference, and quality of life. Methods: Out of 119 potential participants contacted via telephone, 54 did not respond, 29 declined, and 6 expressed interest but did not complete baseline testing. 30 obese EC survivors (40% non-Hispanic black, 33% Hispanic, 17% non-Hispanic white) were placed into a PA intervention (INT, n = 15) or wait-list control (CON, n = 15). Group classes consisted of 30 min of behavioral counseling and a 60 min exercise program. CON was assigned to usual care. Participants attended classes 1-2x/week and were provided with a 90 min/week at-home exercise program. The intervention data from each group were pooled and the change scores were compared to CON using independent samples t-tests. Data are presented as mean ± sd. Statistical significance was p ≤ 0.05. Results: Mean age was 64 ± 8 years and Body Mass Index was 36.5 ± 6.9 kg·m-2. Three control participants did not attend follow-up. For the INT groups (n = 27), 16 attended 75-100% of the weeks, 4 attended 50-67%, 4 never attended, and 3 dropped out due to unrelated illness/injury. Additionally, 13 participants regularly attended twice per week with 85% attendance. Participants reported walking 117 ± 77 minutes per week at home. There were no reported differences in PA (Yale Physical Activity Survey). However, waist circumference (-5.1 cm vs: 2.6 cm, p < 0.001), 6-min walk test (22m vs. 0.3m, p = 0.007) and quality of life (FACT-En: 7.9 vs. -0.5, p = 0.048) all improved significantly following the intervention compared to the control. Conclusions: About 25% of potential participants entered into the study, demonstrating the challenges of working with this population. However, once enrolled, the drop out rate was modest and adherence was high, demonstrating the acceptability and feasibility of this PA intervention in a diverse urban population of EC survivors. Furthermore, the results show promising effects that will need to be confirmed in a larger randomized control trial.
Abstract P019: Albuminuria in Mid-Life and Older-Age and Risk of Dementia: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Johannes B Scheppach, Aozhou Wu, Rebecca F Gottesman, David S Knopman, Silvia Koton, Thomas H Mosley, Morgan E Grams, Richey Sharrett, Josef Coresh
Journal: Circulation (2019)

Background: Dementia is increasingly appreciated to have important vascular disease contributions. Albuminuria and decreased estimated glomerular filtration rate (eGFR) define chronic kidney disease (CKD) and are related to the risk of its consequences as well as microvascular disease and endothelial damage across multiple vascular beds. We extend previous studies by examining albuminuria and eGFR measured at both mid-life and older age as risk factors for dementia. Methods: We studied 10,876 adult participants in the Atherosclerosis Risk in Communities (ARIC) Study excluding participants with end-stage renal disease, stroke and incident dementia at baseline. We analyzed the adjusted relative hazard of incident dementia as a function of eGFR (linear spine with a knot at 60 ml/min per 1.73m 2 ) and log urinary albumin-creatinine-ratio (UACR) adjusting for age, sex, race, education level, Apolipoprotein E4 level, smoking, alcohol consumption, body mass index, diabetes and hypertension. We used two different baseline visits: (1) Starting in 1996-1999 (Visit 4, age 54-74 years); (2) Starting 2011-2013 (Visit 5, age 70-90 years) with follow-up to 2017. Results: We observed 2,001 dementia cases over 16 years of follow-up (446 after Visit 5). Risk of dementia increased with higher levels of albuminuria with a stronger magnitude at older-age than in midlife ( see table ). Estimated GFR was more weakly associated with dementia (p&gt;0.05 at both baselines). The albuminuria association was consistent across sex and race (p-interaction&gt;0.05). Conclusion: Albuminuria, a marker of kidney disease and endothelial damage, is strongly related to dementia incidence. Albuminuria’s association with dementia is stronger in late-life unlike other vascular risk factors, where the association is weaker at older age.
Studies in Peripheral Arterial Occlusive Disease
Authors: STANFORD WESSLER, SHELDON G. SHEPS, MARVIN GILBERT, MINDEL C. SHEPS, Carol Ho, Helen Silver, Kathleen Ward
Journal: Circulation (1958)

Material for an analysis of the pathogenesis and course of acute peripheral arterial occlusion was provided by patients with acute arterial occlusion in a lower extremity, special arterial injection studies of amputated limbs, arteriograms performed on cadavers, and data from an experimental investigation of acute femoral artery embolism in dogs. This correlative study offers a basis for the evaluation of procedures recommended for the prophylaxis and treatment of acute ischemia.
Hydroxyurea reduces cerebral metabolic stress in patients with sickle cell anemia
Authors: Melanie E. Fields, Kristin P. Guilliams, Dustin Ragan, Michael M. Binkley, Amy Mirro, Slim Fellah, Monica L. Hulbert, Morey Blinder, Cihat Eldeniz, Katie Vo, Joshua S. Shimony, Yasheng Chen, Robert C. McKinstry, Hongyu An, Jin-Moo Lee, Andria L. Ford
Journal: Blood (2019)
A retrospective analysis on the effect of time to adjuvant chemotherapy (TTAC) from surgery in stage III colon cancer.
Authors: Sunil Parimi, Aalok Kumar, Eugene Batuyong, Jacob C. Easaw
Journal: Journal of Clinical Oncology (2015)

e17562 Background: A narrow therapeutic window exists within which to initiate adjuvant chemotherapy (AC) post surgery and delays may impact disease free (DFS) and overall survival (OS). In a publically funded health care system, determining TTAC can have significant implications for resource allocation and funding. We evaluated the impact of delayed treatment using modern AC regimens on DFS and OS. Methods: A retrospective analysis was performed on patients receiving AC for stage III colon cancer at the Tom Baker Cancer Centre between 2007 and 2012. Kaplan-Meier methods and Cox regression were used to evaluate the impact of TTAC on DFS and OS. TTAC was categorized into > 8 vs < 8 weeks and > 12 vs < 12 weeks. Results: Three hundred forty-one patients were included. Median age was 62 years old. 52.5% tumors were left sided, compared to 40.2% right sided, and 7.3% transverse colon tumors. T3 was the predominant T stage (63.0%), followed by T4 (28.2%), T2 (6.2%), and T1 (2.6%). Predominant N stage was N1 (55.7%), followed by N2 (31.1%), and N0 (13.2%). Regarding AC usage, capecitabine was most frequent (48.4%), followed by FOLFOX (39.9%), CAPOX (8.2%), and 5FU (3.5%). 66.9% of patients started AC within 8 weeks and 80.9% started within 12 weeks. Univariate analysis did not show a significant difference in DFS or OS regardless of whether chemotherapy was initiated before or after 8 weeks. The same held true for TTAC at the 12-week cutoff. Multivariate analyses, controlling for gender, age, tumor location, T stage, N stage, and chemotherapy regimen, showed that TTAC had no significant impact on DFS or OS at the 8-week cutoff point (DFS HR1.08,95%CI 0.69-1.68,p = 0.74; OS HR1.07,95%CI 0.60-1.90,p = 0.82), nor at the 12-week cutoff (DFS HR1.01,95%CI 0.60-1.70,p = 0.96; OS HR1.31,95%CI 0.69-2.47,p = 0.41). Conclusions: Delays in modern AC for stage III colon cancer patients beyond 8 and 12 weeks did not impact DFS or OS. If these findings are reproducible, resource management and access to care should be re-evaluated for the care of this patient population in the Canadian health care system.
Abstract P402: Association Between Post-stroke Disability and 5-year Hip-fracture Risk: the Women’s Health Initiative
Authors: Carin Northuis, Carolyn J Crandall, Karen L Margolis, Susan J Diem, Kristine E Ensrud, Jean Wactawski-Wende, Kamakshi Lakshminarayan
Journal: Circulation (2019)

Background: Hip fractures are a significant post-stroke complication. While studies have shown an increased incidence of hip fractures post-stroke, the relationship between stroke-related disability and hip fracture rates are not well characterized. Herein, we examine factors associated with hip fracture risk after stroke using the Women’s Health Initiative (WHI) data. Methods: The WHI is a prospective study of 161,808 postmenopausal women aged 50-79 years. In the WHI, stroke cases were initially self-reported and then confirmed by a neurologist adjudication using medical records and a manual. Hip fracture cases were self-reported and then radiologically confirmed by physician adjudication. We included stroke survivors from the observational and clinical trial arms who had a Glasgow Outcome Score (GOS) of 1-3 (good recovery, moderately disabled, severely disabled) and survived at least one week after stroke (n=4,640). Survival free from any radiologically-confirmed hip fracture post-stroke was estimated and compared by GOS status. Secondary analysis examined the post-stroke hip fracture risk while accounting for the competing risk of death. Results: There were 124 hip fractures. Average age of stroke was 74.6 ± 7.2 years. Mean follow-up time was 3.1±1.8 years. Hip fractures by GOS status represented 2.4% (45/1872), 2.5% (34/1366), and 3.5% (45/1278) among good recovery, moderately disabled, and severely disabled. In the competing risk model, 23.3% (1079/4640) of the participants died before the end of follow-up or the occurrence of a hip fracture. Severely disabled (HR: 2.1 (95% CI: 1.3, 3.2), p=0.001) status, but not moderately disabled (HR: 1.1 (95% CI: 0.7, 1.7) p=0.8), was significantly associated with an increase in risk of hip fracture compared to good recovery status. This association was attenuated and not significant for moderately disabled (HR: 1.1 (95%CI: 0.7, 1.7), p=0.8) and severely disabled (HR 1.5 (95%CI: 1.0, 2.3), p=0.06) status when accounting for mortality after stroke. High Hip Fracture Risk Assessment Tool (FRAX) risk (without bone density information), being Caucasian, and increasing age were associated with an increased post stroke hip fracture risk. When accounting for mortality after stroke, higher FRAX-predicted hip fracture risk and race/ethnicity remained significant. The association between age and hip fracture was attenuated and not significant after accounting for post-stroke mortality. Conclusion: Among stroke survivors, severely disabled status and FRAX-predicted hip fracture risk were associated with a higher risk of subsequent radiologically confirmed hip fracture, but only the FRAX-predicted hip fracture risk association remained significant when considering the competing risk of mortality after stroke. Interventions to reduce fracture risk after stroke should be evaluated in clinical trials.
A phase I study of temsirolimus plus erlotinib in patients with refractory solid tumors.
Authors: Andrea Wang-Gillam, Benjamin R. Tan, Saiama Naheed Waqar, Rama Suresh, Daniel Morgensztern, Brian Andrew Van Tine, Rebecca Nieman, Ramaswamy Govindan, Albert C. Lockhart
Journal: Journal of Clinical Oncology (2015)

2600 Background: Resistance to treatment with inhibitors of mammalian Target of Rapamycin (mTOR) is partially mediated by activation of epidermal growth factor receptor (EGFR). Based on pre-clinical evidence of synergy, we conducted a phase I study to determine the recommended phase II dose (RP2D) and dose-limiting toxicities (DLT) of temsirolimus (mTOR inhibitor) combined with erlotinib (EGFR inhibitor) in patients with refractory solid tumors. Methods: A classic 3+3 design was used for the dose escalation portion of the study. An expansion cohort at RP2D included only those with mutations that may contribute to PI3K or EGFR pathway activation or squamous histology. A cycle was defined as 28 days. Patients started daily erlotinib 7 days prior to starting temsirolimus on cycle 1. Intravenous temsirolimus was administered weekly. Starting dose levels were 15 mg temsirolimus and 100 mg erlotinib. Results: Forty-six patients were enrolled in this study (29 in dose escalation and 17 in the expansion cohort). Two patients experienced (DLTs) (grade 3 dehydration and grade 4 renal failure). The most common drug-related adverse events of all grades were rash, mucositis/stomatitis, diarrhea, nausea and fatigue. The RP2D is temsirolimus at a 25 mg weekly dose and 100 mg of daily erlotinib. No complete or partial responses were observed in the study. The median duration on this study was 77 days (range 15-770 days). Among 12 evaluable patients in the expansion cohort, 9 (75%) had stable disease and 3(25%) had progressive disease. The median duration on the study was 98 days (range 25- 243 days) for the expansion cohort. Clinical benefits were seen in patients with squamous cell histology; for example, a patient with refractory squamous cell cancer of the head and neck had durable disease control lasting 770 days. Stable disease was also observed in patients with specific genetic alternations; for example, a patient with refractory sarcoma with PTEN loss achieved stable disease of 194 days. Conclusions: The combination of temsirolimus and erlotinib at the RP2D is well tolerated, and the regimen resulted in prolonged disease stabilization in selected patients. Clinical trial information: NCT00770263.
Contemporary analysis of ureteroenteric strictures after open and robot-assisted radical cystectomy: A population-based study.
Authors: Neal Patel, Mark Alshak, Alvin Goh, Art Sedrakyan, Andre Belarmino, Tianyi Sun, Bernard H. Bochner, Jim C. Hu
Journal: Journal of Clinical Oncology (2019)

484 Background: Robot-assisted radical cystectomy (RARC) has been shown to have comparable oncologic efficacy compared to open radical cystectomy (ORC). We sought to compare the rates of benign strictures after RARC and ORC using a population-based data. Methods: From Surveillance, Epidemiology, and End Results (SEER)-Medicare, we identified 332 RARC and 1449 ORC performed during 2009 and 2014, using International Classification of Diseases-9th edition and Current Procedural Terminology 4 th edition to compare the development of ureteroenteric strictures at 6 months, 1 year and 2 years following radical cystectomy. We defined ureteroenteric stricture as the need for procedural intervention, consistent with prior studies. Additionally, we compared the incidence of stricture diagnosis. Multivariable proportional hazards regression was performed to determine factors associated with stricture development. Results: The incidence of ureteroenteric stricture at 6 months and 12 was higher for RARC vs. ORC at 12.1% vs. 7.0% (p&lt;0.01) and 15.0% vs. 9.5% (p=0.01), respectively. However, the RARC vs. ORC stricture incidence at 2 years did not differ significantly at 14.6% vs. 11.4% (p=0.29). Similarly, the stricture diagnosis rates were significantly lower following ORC at 6, 12, and 24 months (p&lt;0.05). In adjusted analysis, RARC (HR 1.70, 95% CI 1.28-2.26) and pre-operative hydronephrosis (HR 1.48, 95% CI 1.15-1.91) were associated with the development of stricture. Conversely, higher hospital volume was associated with a lower risk of stricture (HR 0.43, 95% CI 0.29-0.63). Conclusions: RARC is associated with a higher rate of post-radical cystectomy stricture complication diagnosis and intervention on a population-based level that is mitigated by higher hospital volume. Technical factors are likely responsible and prospective studies are needed to assess the influence of ureteral dissection, tissue handling and perfusion, redundancy, and/or tension on the anastomosis. A significant study limitation is the inability to differentiate extracorporeal versus intracorporeal diversion with our use of administrative data.
Relative risk of adverse events with lanreotide depot/autogel (LAN) vs. placebo (PBO) in patients with intestinal and pancreatic neuroendocrine tumors (NETs).
Authors: Alexandria T. Phan, Martyn E. Caplin, Marianne E. Pavel, Jaroslaw B Cwikla, Markus Raderer, Eva Sedlackova, Guillaume Cadiot, Edward M. Wolin, Jaume Capdevila, Lucy Wall, Guido Rindi, Alison Langley, Edda Gomez-Panzani, Philippe B. Ruszniewski
Journal: Journal of Clinical Oncology (2015)

e15181 Background: CLARINET was a large 96-week phase 3 study showing that LAN 120 mg significantly improved progression-free survival vs PBO in patients with intestinal and pancreatic NETs. Here, we analyze the safety/tolerability data in greater detail, quantifying the relative risk (RR) of adverse events (AEs). Methods: Patients withmetastatic grade 1/2 (Ki-67 <10%) non-functioning intestinal and pancreatic NETs received LAN 120 mg (n=101) or PBO (n=103) for 96 weeks or until death/disease progression (NCT00353496). TheRR (LAN vs PBO) and 95% CIs were calculated post hoc for any AE occurring in ≥5% of patients in either group. Results: The incidence of AEs overall was similar for LAN and PBO (88% vs 90%). Gastrointestinal disorders were the most common AE class (67% vs 63%; RR 1.1 [0.9, 1.3]) and diarrhea the most common individual AE (35% vs 35%; RR 1.0 [0.7, 1.4]); based on RR, these incidences were not significantly different for LAN vs PBO (lower CIs were ≤1). Furthermore, there were no significant differences for any AE occurring in ≥5% in either group (see Table for the subset occurring in ≥10% in either group), although CIs for RRs were wide in a number of cases. Conclusions: There were no significant safety signals for LAN in the CLARINET study, highlighting its favorable benefit–risk profile in patients with intestinal and pancreatic NETs. For significant difference between treatment groups, lower CIs would need to be >1. Clinical trial information: NCT00353496.RRs for AEs occurring in ≥10% in either group. LAN, n (%) (n=101) PBO, n (%) (n=103) RR (95% CI) GI Diarrhea 35 (34.7) 36 (35.0) 1.0 (0.7, 1.4) Abdominal pain 24 (23.8) 17 (16.5) 1.4 (0.8, 2.5) Vomiting 19 (18.8) 9 (8.7) 2.2 (1.0, 4.5) Nausea 14 (13.9) 14 (13.6) 1.0 (0.5, 2.0) Constipation 12 (11.9) 13 (12.6) 0.9 (0.5, 2.0) Flatulence 12 (11.9) 9 (8.7) 1.4 (0.6, 3.1) Musculoskeletal Headache 16 (15.8) 11 (10.7) 1.5 (0.7, 3.0) Back pain 12 (11.9) 11 (10.7) 1.1 (0.5, 2.4) Hepatobiliary Cholelithiasis 14 (13.9) 7 (6.8) 2.0 (0.9, 4.8) Vascular Hypertension 13 (12.9) 5 (4.9) 2.7 (1.0, 7.2) General and administration site Fatigue 10 (9.9) 15 (14.6) 0.7 (0.3, 1.4) Infections and infestations Nasopharyngitis 9 (8.9) 16 (15.5) 0.6 (0.3, 1.2)
Sixty seconds on . . . democracy
Authors: Nigel Hawkes
Journal: BMJ (2019)

On the contrary, it’s democracy in action and that’s good for your health.

The authors of a paper in the Lancet 1 which looks at countries that have embraced democracy since 1980 and concludes that their health outcomes are significantly better than they would otherwise have been. Over 20 years, democratic experience cut heart mortality, for …
Improving the value of PSA prostate cancer screening with “smarter” strategies and increased use of active surveillance.
Authors: Joshua A. Roth, Roman Gulati, John L. Gore, Matthew R. Cooperberg, Ruth Douglas Etzioni
Journal: Journal of Clinical Oncology (2015)

6616 Background: Prostate-specific antigen (PSA) screening for prostate cancer is controversial. Epidemiological researchers and guideline groups have suggested many personalized and conservative strategies to improve benefit-risk tradeoffs.The goal of this study is to identify strategies most likely to be cost-effective, and to examine the added value of increased active surveillance (AS) for low-risk cases. Methods: We extended an established CISNET microsimulation model to project life years (LY), quality-adjusted life years (QALYs), and costs for cohorts of U.S. men from age 40 to death in 15 screening strategies with fixed or personalized screening ages, intervals, and PSA biopsy thresholds. We calculated the incremental cost-effectiveness ratio (ICER) for each vs. no screening under “contemporary” or “increased AS” treatment practices. “Contemporary” practices were based on age, stage, and grade-specific initial treatments in the SEER program. “Increased AS” practices immediately treated cases if Gleason sum ≥ 7 or clinical T-stage ≥ T2a and monitored all others. Analyses used a 3% annual discount rate and a willingness to pay of $150,000/QALY. Results: All PSA screening strategies increased LYs (range = 0.014-0.021) and costs (range = $100-900) vs. no screening and were highly cost-effective (ICER range = $25,000-43,000/LY). With “contemporary” treatments, only strategies with biopsy threshold at PSA ≥ 10 mg/L increased QALYs (range = 0.001-0.002), and only quadrennial screening of ages 50-74 was cost-effective ($150,000/QALY). With “increased AS,” all strategies with biopsy threshold at PSA ≥ 10 mg/L increased QALYs (range = 0.003-0.005) and were cost-effective (ICER range = $45,000-95,000/QALY), as was quadrennial screening of ages 55-69 with biopsy threshold at PSA ≥ 3 mg/L (Inc QALYs = 0.002, Inc Cost = $130, ICER = $65,000/QALY). Conclusions: Personalized PSA screening strategies with conservative screening frequency and/or PSA biopsy threshold appear to be cost-effective vs. no screening, particularly when combined with increased AS for low-risk cases.
A phase II study of axitinib in advanced carcinoid tumors: Preliminary results.
Authors: Mauro Cives, Jonathan R. Strosberg, Tiffany Campos, Thomas Weber, McKinley Nickerson, Chloe Evelyn Atreya, Alan P. Venook, Robin Kate Kelley, Tiffany Valone, Domenico Coppola, Emily K. Bergsland
Journal: Journal of Clinical Oncology (2015)

4100 Background: Neuroendocrine tumors (NETs) are highly vascular neoplasms overexpressing VEGF as well as VEGFR. Axitinib is an inhibitor of receptor tyrosine kinases with picomolar potency against VEGFR-1, -2 and -3 and nanomolar potency against PDGFR-β. Methods: We performed a phase II trial of axitinib 5 mg twice daily in patients with unresectable or metastatic low to intermediate grade carcinoid tumors. Prior antiangiogenic therapy with a dedicated VEGF pathway inhibitor was not permitted. The primary endpoints were PFS and 12-month PFS rate. H0= 12 mo PFS rate of 36% (corresponding to median PFS of 8.1 months); Ha= 12 mo PFS rate of 56.5% (corresponding to median PFS of 14.6 months). Preliminary findings are reported. Results: 30 patients were enrolled and assessable for toxicity; 22 were assessable for response. Primary sites included small intestine (19 patients), lung (3), unknown (3), colon (2), rectum (2), and thymus (1). 21 patients had low-grade and 9 patients had intermediate-grade tumors. Carcinoid syndrome was diagnosed in 16/30 patients. Median TTF was 8.99 months (SD ±7.18) and the 12 mo PFS rate was 65% (SD ±13%). Median PFS not yet determined due to small number of events. The 1-year OS rate was 93% (SD±4.9%). Best radiographic response was PR in 1/30 (3.3%) and stable disease in 21/30 (70%); 8/30 patients (27%) unevaluable due to toxicity (4/30) and consent withdrawn (4/30). Among 25 patients with baseline elevated chromogranin A levels, 4 (16%) experienced major reductions ( > 50%) of the tumor marker. 90% of patients experienced hypertension (any grade). Grade 3 and 4 hypertension were seen in 18 (60%) and 2 (7%) patients respectively. Hypertension led to treatment discontinuation in two cases, however, axitinib interruption prompted a fast recovery without sequelae. Conclusions: The 12 mo PFS rate associated with axitinib in advanced carcinoid tumors appears promising when compared to results observed in phase II studies of other antiangiogenic TKIs such as sunitinib or pazopanib. Although associated hypertension is common, axitinib treatment was overall well tolerated. Clinical trial information: NCT01435122.