Citations

Abstract Background: Approximately 1% of all new cases of breast cancer (BC) occur in men. Care of male BC is largely based on extrapolation from treatment strategies and management of symptoms in women. The impact of BC diagnosis and therapy on Quality of Life (QoL) in women with BC is well documented. Comprehensive, prospective data about QoL in men treated for BC are sparse. Due to the lack of a validated male BC QoL questionnaire, we previously evaluated the QoL of the male BC using the original EORTC QLQ-C30 and breast module QLQ BR23 with “female” items replaced by male-specific items from the EORTC QoL prostate module (EORTC QLQ-PR25). The development of a validated worldwide questionnaire for male BC is sponsored by EORTC QoL Group and will be completed in cooperation with EORTC Breast Group and the International Male BC Program (a cooperation between EORTC-BCG, TBCRC, within the BIG and NABCG networks) Trial design: The evaluation of the QoL issues relevant for male BC, as well as the translation of issues into items to build the tool for QoL assessment in male BC will be carried out through four phases: 1. A systematic Literature review 2. Interviews with patients 3. Interviews with Health Care Professionals (HCP) 4. Consultation of experts in Oncology and QoL Inclusion criteria: • Histologically proven early BC or metastatic BC in male patients • Age ≥ 18 years • Ability to understand and fill out questionnaires • Written informed consent Exclusion criteria: • Other cancer in the past 5 years except non-melanotic skin cancer • Patients participating in interventional clinical studies with QoL as primary endpoint • Any condition potentially hampering compliance with the study protocol Aims: The study proposes to carry out an evaluation of the QoL issues relevant for male patients with BC, and translating the issues into questions to build the tool for an adequate QoL assessment in these patients. The specific aims are: 1) To carry out an evaluation of the existing EORTC QLQ-BR 45 (adapting for male BC) and for suitability of use in male BC patients 2) To carry out an evaluation of the EORTC QLQ-PR25 (adapting for male BC) for suitability of use in male BC patients 3) To provide recommendations to the EORTC on a suitable assessment approach to assess QOL in male BC Statistical methods: A systematic literature review to assess what factors are unique to male BC patients in influencing their QoL and what QoL measures exist for them will be performed. This will be conducted by reviewing all studies with male BC participants and including investigator brochures describing side effects in male BC patients, as well as by evaluating issues captured by other existing EORTC modules. The final list of potential QoL issues relevant to the male BC will be tested for relevance and importance in semi-structured qualitative interviews with patients and HCP. A total of 2-5 patients per year will be recruited from collaborating hospitals/countries. At least 40 in total will be interviewed before, during, or after treatment for male BC. At least 2 experts/country from the all collaborating centres will be included in the interview to discuss and consider the potential issues. Finally, the issue list will be translated into questions to build the tool for a QoL assessment in male BC patients. Present accrual and target accrual This study started in October 2019. A systematic literature review has been completed. Seventeen centres from worldwide are participating in the study. New centers may still join. Contact information for people with a specific interest in the trial Vesna Bjelic-Radisic E-Mail: Vesna.Bjelic-Radisic@helios-gesundheit.de Fatima Cardoso e-mail: fatimacardoso@fundacaochampalimaud.pt Citation Format: Vesna Bjelic-Radisic, Fatima Cardoso, Joachim Weis, Eveline Bleiker, David Cameron, Galina Velikova, Karatzyna Pogoda, Samantha Serpentini, Kevin Punie, Rinat Yerushalmi, Erika Matos, Birgit Carly, Ivana Bozovic-Spasojevic, Markus Fleisch, Zoe Luisa Probst, Sina Maria Schafer, Nicola Russell, Sofie Tombeur, Joanna Vermeij, Heidi Roelstraete, Kathryn Ruddy, Juan I Arraras, Andrew Bottomley. Adaption of the EORTC quality of life breast cancer module for male breast cancer - phase I [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr OT-14-01.

Abstract Age-related chronic inflammation promotes cellular senescence, chronic disease, cancer, and reduced lifespan. In this study, we wanted to explore the effects of a moderate exercise regimen on inflammatory liver disease and tumorigenesis. We used an established model of spontaneous inflammaging, steatosis, and cancer (nfkb1−/− mouse) to demonstrate whether 3 mo of moderate aerobic exercise was sufficient to suppress liver disease and cancer development. Interventional exercise when applied at a relatively late disease stage was effective at reducing tissue inflammation (liver, lung, and stomach), oxidative damage, and cellular senescence, and it reversed hepatic steatosis and prevented tumor development. Underlying these benefits were transcriptional changes in enzymes driving the conversion of tryptophan to NAD+, this leading to increased hepatic NAD+ and elevated activity of the NAD+-dependent deacetylase sirtuin. Increased SIRT activity was correlated with enhanced deacetylation of key transcriptional regulators of inflammation and metabolism, NF-κB (p65), and PGC-1α. We propose that moderate exercise can effectively reprogram pre-established inflammatory and metabolic pathologies in aging with the benefit of prevention of disease.

Germ line mutations in H3F3A and H3F3B cause a previously unidentified neurodevelopmental syndrome.

Abstract Background Face-to-face tobacco cessation has had limited reach and efficacy in Alaska Native (AN) communities. We describe our two-phased approach to develop content for Connecting Alaska Native People to Quit Smoking, a Facebook group intervention to reduce barriers to evidence-based smoking cessation treatment for AN people in Alaska. Methods Phase 1 included semi-structured telephone interviews with 30 AN people who smoke and ten stakeholders. They provided feedback on existing content from the Centers for Disease Control and Prevention Tips campaign and AN digital stories. Phase 2 included an online survey with a new group of 40 AN smokers who provided feedback on existing content via a measure of perceived effectiveness and cultural relevance. Results Phase I results revealed participants evaluated content based upon story strength, relevance to AN culture, emotional appeal, relatability to AN people, and favorite video. No single posting was rated highly across all themes. All perceived effectiveness (PE) and cultural relevance median scores fell between 3.5 and 4.4 (range 1–5). PE scores varied across participant demographic groups. Conclusions Content embodying characteristics perceived to be most appealing, effective, and culturally relevant were selected for the private Facebook group content library with refinements made to incorporate images of AN people engaged in AN activities. PE scores indicate a need for a wide variety of content that moderators could pull from when conducting the intervention. Implications Social media content targeting specific population sectors, such as American Indian/AN people for tobacco cessation needs to be culturally tailored. Our approach provides a model others can follow to determine what is appealing, relevant, and effective messaging. Clinical Trial Registration NCT 03645941.

Background and Purpose: Periventricular white matter hyperintensities (WMH; PVWMH) and deep WMH (DWMH) are regional classifications of WMH and reflect proposed differences in cause. In the first study, to date, we undertook genome-wide association analyses of DWMH and PVWMH to show that these phenotypes have different genetic underpinnings. Methods: Participants were aged 45 years and older, free of stroke and dementia. We conducted genome-wide association analyses of PVWMH and DWMH in 26,654 participants from CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology), ENIGMA (Enhancing Neuro-Imaging Genetics Through Meta-Analysis), and the UKB (UK Biobank). Regional correlations were investigated using the genome-wide association analyses -pairwise method. Cross-trait genetic correlations between PVWMH, DWMH, stroke, and dementia were estimated using LDSC. Results: In the discovery and replication analysis, for PVWMH only, we found associations on chromosomes 2 ( NBEAL ), 10q23.1 ( TSPAN14/FAM231A ), and 10q24.33 ( SH3PXD2A). In the much larger combined meta-analysis of all cohorts, we identified ten significant regions for PVWMH: chromosomes 2 (3 regions), 6, 7, 10 (2 regions), 13, 16, and 17q23.1. New loci of interest include 7q36.1 ( NOS3 ) and 16q24.2. In both the discovery/replication and combined analysis, we found genome-wide significant associations for the 17q25.1 locus for both DWMH and PVWMH. Using gene-based association analysis, 19 genes across all regions were identified for PVWMH only, including the new genes: CALCRL (2q32.1), KLHL24 (3q27.1), VCAN (5q27.1), and POLR2F (22q13.1). Thirteen genes in the 17q25.1 locus were significant for both phenotypes. More extensive genetic correlations were observed for PVWMH with small vessel ischemic stroke. There were no associations with dementia for either phenotype. Conclusions: Our study confirms these phenotypes have distinct and also shared genetic architectures. Genetic analyses indicated PVWMH was more associated with ischemic stroke whilst DWMH loci were implicated in vascular, astrocyte, and neuronal function. Our study confirms these phenotypes are distinct neuroimaging classifications and identifies new candidate genes associated with PVWMH only.

Abstract This is a protocol for a co‐registered Cochrane and Campbell Review (Methodology). The objectives are as follows: To identify, describe and assess methods for: when to replicate a systematic review; how to replicate a systematic review.

Significance Statement Kidney toxicity from use of immune checkpoint inhibitors is being recognized as an increasingly frequent complication of treatment. However, existing data on immune checkpoint inhibitor–associated AKI have been limited to small, mostly single-center studies. In this multicenter study of 138 patients with immune checkpoint inhibitor–associated AKI and 276 controls, the authors characterize the clinical features of this complication and identify risk factors associated with its development, clinicopathologic features, and determinants of kidney recovery after an episode. Failure to achieve kidney recovery was associated with worse overall survival, and a minority (23%) of patients who were retreated with immune checkpoint inhibitors had a recurrence of AKI. The study provides insights into immune checkpoint inhibitor–associated AKI, although further study is needed to inform the care of affected patients. Background Despite increasing recognition of the importance of immune checkpoint inhibitor–associated AKI, data on this complication of immunotherapy are sparse. Methods We conducted a multicenter study of 138 patients with immune checkpoint inhibitor–associated AKI, defined as a ≥2-fold increase in serum creatinine or new dialysis requirement directly attributed to an immune checkpoint inhibitor. We also collected data on 276 control patients who received these drugs but did not develop AKI. Results Lower baseline eGFR, proton pump inhibitor use, and combination immune checkpoint inhibitor therapy were each independently associated with an increased risk of immune checkpoint inhibitor–associated AKI. Median (interquartile range) time from immune checkpoint inhibitor initiation to AKI was 14 (6–37) weeks. Most patients had subnephrotic proteinuria, and approximately half had pyuria. Extrarenal immune-related adverse events occurred in 43% of patients; 69% were concurrently receiving a potential tubulointerstitial nephritis–causing medication. Tubulointerstitial nephritis was the dominant lesion in 93% of the 60 patients biopsied. Most patients (86%) were treated with steroids. Complete, partial, or no kidney recovery occurred in 40%, 45%, and 15% of patients, respectively. Concomitant extrarenal immune-related adverse events were associated with worse renal prognosis, whereas concomitant tubulointerstitial nephritis–causing medications and treatment with steroids were each associated with improved renal prognosis. Failure to achieve kidney recovery after immune checkpoint inhibitor–associated AKI was independently associated with higher mortality. Immune checkpoint inhibitor rechallenge occurred in 22% of patients, of whom 23% developed recurrent associated AKI. Conclusions This multicenter study identifies insights into the risk factors, clinical features, histopathologic findings, and renal and overall outcomes in patients with immune checkpoint inhibitor–associated AKI.

Abstract Background Pharyngeal and rectal Neisseria gonorrhoeae and Chlamydia trachomatis play important roles in infection and antibacterial resistance transmission, but no US Food and Drug Administration (FDA)–cleared assays for detection at these sites existed prior to this study. The objective was to estimate performance of assays to detect those infections in pharyngeal and rectal specimens to support regulatory submission. Methods We performed a cross-sectional, single-visit study of adults seeking sexually transmitted infection testing at 9 clinics in 7 states. We collected pharyngeal and rectal swabs from participants. The primary outcome was positive and negative percent agreement for detection of N. gonorrhoeae and C. trachomatis for 3 investigational assays compared to a composite reference. Secondary outcomes included positivity as well as positive and negative predictive values and likelihood ratios. Subgroup analyses included outcomes by symptom status and sex. Results A total of 2598 participants (79% male) underwent testing. We observed N. gonorrhoeae positivity of 8.1% in the pharynx and 7.9% in the rectum and C. trachomatis positivity of 2.0% in the pharynx and 8.7% in the rectum. Positive percent agreement ranged from 84.8% to 96.5% for different anatomic site infection combinations, whereas negative percent agreement was 98.8% to 99.6%. Conclusions This study utilized a Master Protocol to generate diagnostic performance data for multiple assays from different manufacturers in a single study population, which ultimately supported first-in-class FDA clearance for extragenital assays. We observed very good positive percent agreement when compared to a composite reference method for the detection of both pharyngeal and rectal N. gonorrhoeae and C. trachomatis. Clinical Trials Registration NCT02870101.

Abstract The objective of the study was to assess racial disparities in the treatment and outcomes among white, African American, and Hispanic patients with multiple myeloma (MM). Patients with an MM diagnosis from the Surveillance Epidemiology and End Results (SEER)–Medicare (2007-2013) database were included. Continuous Medicare enrollment for 6 months before (baseline) and after MM diagnosis was required unless death occurred. Time from MM diagnosis to novel therapy initiation and autologous stem cell transplant (ASCT), overall survival (OS), and MM-specific survival (MSS) was evaluated. Unadjusted and multivariable regressions compared African Americans and Hispanics vs whites. Trends of novel therapy and ASCT use across MM diagnosis years were assessed using linear regression models. The study included 3504 whites, 858 African Americans, and 468 Hispanics. African Americans and Hispanics had a longer time from MM diagnosis to novel therapy initiation vs whites (median: 5.2 and 4.6 vs 2.7 months, respectively). All cohorts had an increasing trend of novel therapy initiation within 6 months of MM diagnosis, particularly whites (all P < .05). Median MSS was significantly longer for African Americans (5.4 years) than whites (4.5 years; P < .05), and was comparable for Hispanics and whites. Median OS was similar overall (2.6-2.8 years). ASCT rate within 1 year of MM diagnosis rose among whites and African Americans (P < .05), but not Hispanics, who were less likely to receive ASCT vs whites. Significant variations in novel therapy and ASCT use were observed among different racial/ethnic groups with MM. Although OS was similar, both African Americans and Hispanics may not be fully benefitting from the introduction of novel therapies, as they receive them later than whites.