Overall survival in the OlympiA phase III trial of adjuvant olaparib in patients with germline pathogenic variants in BRCA1/2 and high-risk, early breast cancer

Adjuvant therapy; Breast cancer; OlaparibTerapia adyuvante; Cáncer de mama; OlaparibTeràpia adjuvant; Càncer de mama; OlaparibBackground The randomized, double-blind OlympiA trial compared 1 year of the oral poly(adenosine diphosphate-ribose) polymerase inhibitor, olaparib, to matching placebo as adjuvant therapy for patients with pathogenic or likely pathogenic variants in germline BRCA1 or BRCA2 (gBRCA1/2pv) and high-risk, human epidermal growth factor receptor 2-negative, early breast cancer (EBC). The first pre-specified interim analysis (IA) previously demonstrated statistically significant improvement in invasive disease-free survival (IDFS) and distant disease-free survival (DDFS). The olaparib group had fewer deaths than the placebo group, but the difference did not reach statistical significance for overall survival (OS). We now report the pre-specified second IA of OS with updates of IDFS, DDFS, and safety. Patients and methods One thousand eight hundred and thirty-six patients were randomly assigned to olaparib or placebo following (neo)adjuvant chemotherapy, surgery, and radiation therapy if indicated. Endocrine therapy was given concurrently with study medication for hormone receptor-positive cancers. Statistical significance for OS at this IA required P < 0.015. Results With a median follow-up of 3.5 years, the second IA of OS demonstrated significant improvement in the olaparib group relative to the placebo group [hazard ratio 0.68; 98.5% confidence interval (CI) 0.47-0.97; P = 0.009]. Four-year OS was 89.8% in the olaparib group and 86.4% in the placebo group (Δ 3.4%, 95% CI −0.1% to 6.8%). Four-year IDFS for the olaparib group versus placebo group was 82.7% versus 75.4% (Δ 7.3%, 95% CI 3.0% to 11.5%) and 4-year DDFS was 86.5% versus 79.1% (Δ 7.4%, 95% CI 3.6% to 11.3%), respectively. Subset analyses for OS, IDFS, and DDFS demonstrated benefit across major subgroups. No new safety signals were identified including no new cases of acute myeloid leukemia or myelodysplastic syndrome. Conclusion With 3.5 years of median follow-up, OlympiA demonstrates statistically significant improvement in OS with adjuvant olaparib compared with placebo for gBRCA1/2pv-associated EBC and maintained improvements in the previously reported, statistically significant endpoints of IDFS and DDFS with no new safety signals.Funding for this work, which was conducted as a collaborative partnership among the Breast International Group, NRG Oncology, Frontier Science, AstraZeneca, and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, U.S.A. (MSD), was provided by the National Institutes of Health (grant numbers: U10CA 180868, UG1CA 189867, and U10CA 180822) and by AstraZeneca as part of an alliance between AstraZeneca and MSD. Provision of olaparib and placebo was from AstraZeneca

Future Design of Accessibility in Games : A Design Vocabulary

Games represent one of the most significant cultural artefacts of this century. They are a massive force in economies around the world and are enjoyed by millions of players worldwide. With their cultural significance firmly in place, it is important to ensure that all people can participate in and play games in order to feel included in our wider society. For people with disabilities, games in particular provide a cultural outlet where they can be included with everyone else, and enabled to do things on an even footing with their non-disabled peers. However, this only happens if we create the necessary design environments that provide inclusive opportunities to game alongside the rest of the player base. Guidelines have been successful in raising awareness of accessibility in games and still function well for evaluating finished games. However, they are not the generative design thinking tools that developers need. Further in being divided to address specific disabilities, they are not capturing the diversity of needs of players with disabilities and the personalised and idiosyncratic adaptations that they make in order to play. We therefore propose developing a vocabulary and language of game accessibility which is no longer about whether someone can perceive or operate an interactive technology, but instead as to whether they can have the experience they want to have. We propose the structure for such a vocabulary showing that it needs to distinguish between access to controls, enablement to meet the challenges of the game and the player experience itself. We show how the intermediate-level knowledge embodied in guidelines can be reformulated in this way to be more generative and so support designers to develop games that deliver accessible player experiences

Biomarkers to identify and isolate senescent cells

This paper was accepted for publication in the journal Ageing Research Reviews and the definitive published version is available at http://dx.doi.org/10.1016/j.arr.2016.05.003.Aging is the main risk factor for many degenerative diseases and declining health. Senescent cells are part of the underlying mechanism for time-dependent tissue dysfunction. These cells can negatively affect neighbouring cells through an altered secretory phenotype: the senescence-associated secretory phenotype (SASP). The SASP induces senescence in healthy cells, promotes tumour formation and progression, and contributes to other age-related diseases such as atherosclerosis, immune-senescence and neurodegeneration. Removal of senescent cells was recently demonstrated to delay age-related degeneration and extend lifespan. To better understand cell aging and to reap the benefits of senescent cell removal, it is necessary to have a reliable biomarker to identify these cells. Following an introduction to cellular senescence, we discuss several classes of biomarkers in the context of their utility in identifying and/or removing senescent cells from tissues. Although senescence can be induced by a variety of stimuli, senescent cells share some characteristics that enable their identification both in vitro and in vivo. Nevertheless, it may prove difficult to identify a single biomarker capable of distinguishing senescence in all cell types. Therefore, this will not be a comprehensive review of all senescence biomarkers but rather an outlook on technologies and markers that are most suitable to identify and isolate senescent cells

Solar Sail Propulsion by 2050: an Enabling Capability for Heliophysics Missions

No abstract available

18th Annual Pancreatic Cancer and Related Diseases Patient Symposium

On November 11, 2023, Charles J. Yeo, MD, FACS, and the multidisciplinary team of clinicians and scientists hosted the 18th Annual Pancreatic Cancer & Related Diseases Patient Symposium. View the Event Photo Gallery View our Pancreatic Cancer Program 2023 Update to learn more about Dr. Yeo and the team’s great work! PROGRAM Welcome and Program OverviewCharles J. Yeo, MD, FACSSamuel D. Gross Professor and Chair of Surgery, Co-Director, Jefferson Pancreas, Biliary, and Related Cancer Center The Jefferson Pancreas Tumor Registry: 2022-2023 Annual UpdateEika Barriera-Justiniano, CRNPDepartment of Surgery Nicole Pocetti, CRNPDepartment of Surgery Patient Support and Programming at SKCCGreg Garber, MSW, LCSWAdministrative Director, Division of Supportive Oncology, Sidney Kimmel Cancer Center Katie Lundy, MSW, LSWOncology Social Worker, Division of Supportive Oncology, Jefferson Health-Asplundh Cancer Pavilion Targeting BARD1 in Pancreatic Cancer: “Expanding BRCAness”Aditi Jain, PhDResearch Assistant Professor, Department of Surgery Advanced Endoscopy: Leaping ForwardDavid Kastenberg, MDJ. Edward Berk Professor of Medicine and Chief, Division of Gastroenterology and Hepatology Clinical Trials Update: Antibiotics in Pancreatic SurgeryHarish Lavu, MD, FACSProfessor of Surgery and Section Chief, Hepatopancreatobiliary Surgery and Director, Jefferson Pancreas Tumor Registry What About My Gut...?James A. Posey, III, MDProfessor of Medicine and Director, Gastrointestinal Program of Medical Oncology and Co-Director, Jefferson Pancreas, Biliary, and Related Cancer Center A Patient’s StoryShawn Johnson Survivor Tribute Phot