Citations

Abstract Background: Breast cancer (BC) treatment, including surgery, can impact not only short-term health outcomes but may also affect longer term health-related and psychosocial quality of life (QOL). We sought to describe the impact of BC surgery on QOL among breast cancer survivors followed in a large randomized trial. Methods: The ECOG-ACRIN protocol E5103 was a phase III trial that randomized BC patients (pts) who had undergone definitive BC surgery to receive adjuvant doxorubicin, cyclophosphamide, and paclitaxel with either bevacizumab (bev) or placebo. Telephone based surveys were administered to all pts enrolled between 01/Jan/10 and 08/Jun/10 as part of a Decision-Making/QOL component until 18 mos post enrollment. Functional/psychosocial QOL domains were assessed by the EQ-5D-3L and the FACT B+G. Fisher's exact test compared categorical and Wilcoxon rank sum test compared continuous variables between subgroups. Multivariable regression was used to evaluate factors in addition to primary surgery at enrollment (age, race, ER/PgR status, tumor size, nodal status) associated with overall FACT score at 18 mos. Results: Patient reported outcomes at 18 mos were available from 89.6% (465/519) pts. At enrollment, 57% (266/465) had a mastectomy; 43% (199/465) breast conserving surgery (BCS). Median age at enrollment was 52 (range: 25-76) years. There were no differences in QOL between bev vs placebo treatment arms (EQ-5D-3L Index Score p=0.65; FACT B+G Score p=0.23) at 18 mos so groups were combined. Using EQ-5D-3L, over half of the pts (58%) reported at least some pain/discomfort; 38% symptoms of anxiety/depression. A higher proportion of mastectomy pts reported problems with usual activities compared to BCS pts (Table). Compared to BCS pts, mastectomy pts had lower average EQ5D-3L scores 0.80 vs. 0.84, p=0.04 and FACT B+G scores 109 vs. 114, p=0.01, indicating worse QOL. In univariate analyses, non-white race (p=0.03), ER/PgR+ status (p=0.04) and mastectomy as primary surgery (p=0.01) were significantly associated with worse QOL (lower FACT B+G scores). In multivariable analyses, non-white race (p=0.02) and ER/PgR+ status (p=0.05) remained associated with worse QOL; mastectomy was borderline significant (p=0.06). Conclusions: Among women participating in a contemporary adjuvant BC chemotherapy trial, a substantial proportion of survivors experience symptoms that may be amenable to intervention, including referral to physical rehabilitation, especially among pts undergoing more extensive surgery. Attention to psychosocial health is also essential both during and after completion of active treatment to optimize QOL outcomes. N(%) reporting problems* 5 DimensionsBCSMastectomyOverallp**Mobility44(23)59(23)103(23)1.00Self-care11(6)23(9)34(7)0.21Usual activities49(25)90(34)139(30)0.04Pain/discomfort104(53)161(61)265(58)0.08Anxiety/depression70(36)105(40)175(38)0.44*3L: 3 possible answers: 1) no problems 2) some/moderate problems 3) problems; responses then collapsed into no problems vs. any problems' (=some/moderate problems and problems). ** Fisher's exact test p-value. Citation Format: Rosenberg SM, O'Neill A, Sepucha K, Miller KD, Dang CT, Northfelt DW, Sledge GW, Schneider BP, Partridge AH. The impact of breast cancer surgery on quality of life: Long term results from E5103 [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr GS6-05.

AbstractIntroductionPlatelet function disorders (PFD) are an important group of bleeding disorders that require validated and practical laboratory strategies for diagnosis.MethodsThis review summarizes the authors’ experiences, current literature, and an international survey to evaluate the practices of diagnostic laboratories that offer tests for PFD.ResultsBlood counts, blood film review, and aggregation tests are the most commonly performed investigations for PFD and help determine whether there is thrombocytopenia and/or defective platelet function due to a variety of causes. The performance characteristics of tests for PFD, and the level of evidence that these tests detect bleeding problems, are important issues to determine where tests are useful for diagnostic or correlative purposes, or research only uses. Platelet aggregation assays, and quantitative analysis of platelet dense granule numbers, are tests with good performance characteristics that detect abnormalities associated with increased bleeding in a significant proportion of individuals referred for PFD investigations. Lumiaggregometry estimates of platelet adenosine triphosphate release show greater variability which limits the diagnostic usefulness. Diagnostic laboratories report that fiscal and other constraints, including a lack of high‐quality evidence, limit their ability to offer an expanded test menu for PFD.ConclusionPFD are clinically important bleeding disorders that remain challenging for diagnostic laboratories to investigate. While some PFD tests are well validated for diagnostic purposes, gaps in scientific evidence and resource limitations influence diagnostic laboratory decisions on which PFD tests to offer.

Abstract Background Vedolizumab effectiveness estimates immediately after Food and Drug Administration (FDA) approval for ulcerative colitis (UC) and Crohn’s disease (CD) are limited by use in refractory populations. We aimed to compare treatment patterns and outcomes of vedolizumab in 2 time frames after FDA approval. Methods We used 2 data sets for time trend analysis, an academic multicenter vedolizumab consortium (VICTORY) and the Truven MarketScan database, and 2 time periods, May 2014–June 2015 (Era 1) and July 2015–June 2017 (Era 2). VICTORY cumulative 12-month clinical remission, corticosteroid-free remission, and mucosal healing rates, and Truven 12-month hospitalization and surgery rates, were compared between Eras 1 and 2 using time-to-event analyses. Results A total of 3661 vedolizumab-treated patients were included (n = 1087 VICTORY, n = 2574 Truven). In both cohorts, CD and UC patients treated during Era 2 were more likely to be biologic naïve. Compared with Era 1, Era 2 CD patients in the VICTORY consortium had higher rates of clinical remission (31% vs 40%, P = 0.03) and mucosal healing (42% vs 58%, P < 0.01). These trends were not observed for UC. In the Truven database, UC patients treated during Era 2 had lower rates of inflammatory bowel disease–related hospitalization (22.4% vs 9.6%, P < 0.001) and surgery (17.2% vs 9.4%, P = 0.008), which was not observed for CD. Conclusion Since FDA approval, remission and mucosal healing rates have increased for vedolizumab-treated CD patients, and vedolizumab-treated UC patients have had fewer hospitalizations and surgeries. This is likely due to differences between patient populations treated immediately after drug approval and those treated later.

Background PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors effectively lower LDL (low‐density lipoprotein) cholesterol and have been shown to reduce cardiovascular outcomes in high‐risk patients. We used real‐world electronic health record data to characterize use of PCSK9 inhibitors, in addition to standard therapies, according to cardiovascular risk status. Methods and Results Data were obtained from 18 health systems with data marts within the National Patient‐Centered Clinical Research Network (PCORnet) using a common data model. Participating sites identified >17.5 million adults, of whom 3.6 million met study criteria. Patients were categorized into 3 groups: (1) dyslipidemia, (2) untreated LDL ≥130 mg/dL, and (3) coronary artery disease or coronary heart disease. Demographics, comorbidities, estimated 10‐year atherosclerotic cardiovascular disease risk, and lipid‐lowering pharmacotherapies were summarized for each group. Participants’ average age was 62 years, 50% were female, and 11% were black. LDL cholesterol ranged from 85 to 151 mg/dL. Among patients in groups 1 and 3, 54% received standard lipid‐lowering therapies and a PCSK9 inhibitor was prescribed in <1%. PCSK9 inhibitor prescribing was greatest for patients with coronary artery disease or coronary heart disease and, although prescribing increased during the study period, overall PCSK9 inhibitor prescribing was low. Conclusions We successfully used electronic health record data from 18 PCORnet data marts to identify >3.6 million patients meeting criteria for 3 patient groups. Approximately half of patients had been prescribed lipid‐lowering medication, but <1% were prescribed PCSK9 inhibitors. PCSK9 inhibitor prescribing increased over time for patients with coronary artery disease or coronary heart disease but not for those with dyslipidemia.

Aquifer Geriatrics, formerly web‐based Geriatrics Education Modules, was initially developed through Donald W. Reynolds Foundation funding, and is now the national curriculum of the American Geriatrics Society and the Association of Directors of Geriatric Academic Programs. Aquifer Geriatrics consists of 26 evidence‐based, peer‐reviewed, online case‐based modules based on the Association of American Medical Colleges/John A. Hartford Foundation Minimum Geriatrics Competencies for Medical Students and is available by subscription at www.aquifer.org/courses . This curriculum aims to help address the national shortage of geriatrics educators, complement current teaching, bridge content gaps in geriatrics education, and standardize geriatrics‐focused educational content. This report will describe the development of Aquifer Geriatrics, highlight best practices to incorporate cases in a variety of teaching settings, describe teaching methods that utilize the curriculum to create a robust experience for learners, and address the cost of obtaining the curriculum. J Am Geriatr Soc 67:811–817, 2019.

Background Bacteria and bacterial components have been associated with the activation of coagulation factors and initiating the blood clot formation. The aim of this study was to investigate whether bacterial populations are present in clots retrieved from patients that have suffered a large vessel occlusion acute ischemic stroke (AIS). Materials and methods Clot samples were collected from 20 AIS patients who underwent clot retrieval with mechanical thrombectomy. Patient clinical demographic details were noted. Expression of bacterial 16S rDNA was analyzed by standard and real-time polymerase chain reaction (PCR). Gram staining was performed to identify Gram-positive and Gram-negative bacteria. Results Both the real-time and standard PCR demonstrated no expression of 16S rDNA in any of the 20 clots samples from AIS patients. Gram staining results showed no expression of Gram-positive or Gram-negative bacteria present in the clot samples. Conclusion Our current study found no bacteria populations in the clots of AIS patients.

Abstract Antitumor T-cell responses raised by first-line therapies such as chemotherapy, radiation, tumor cell vaccines, and viroimmunotherapy tend to be weak, both quantitatively (low frequency) and qualitatively (low affinity). We show here that T cells that recognize tumor-associated antigens can directly kill tumor cells if used at high effector-to-target ratios. However, when these tumor-reactive T cells were present at suboptimal ratios, direct T-cell–mediated tumor cell killing was reduced and the ability of tumor cells to evolve away from a coapplied therapy (oncolytic or suicide gene therapy) was promoted. This T-cell–mediated increase in therapeutic resistance was associated with C to T transition mutations that are characteristic of APOBEC3 cytosine deaminase activity and was induced through a TNFα and protein kinase C–dependent pathway. Short hairpin RNA inhibition of endogenous APOBEC3 reduced rates of tumor escape from oncolytic virus or suicide gene therapy to those seen in the absence of antitumor T-cell coculture. Conversely, overexpression of human APOBEC3B in tumor cells enhanced escape from suicide gene therapy and oncolytic virus therapy both in vitro and in vivo. Our data suggest that weak affinity or low frequency T-cell responses against tumor antigens may contribute to the ability of tumor cells to evolve away from first-line therapies. We conclude that immunotherapies need to be optimized as early as possible so that, if they do not kill the tumor completely, they do not promote treatment resistance.