ABSTRACT
Background: Multi-parameter tumor gene expression assays (MPAs) are used to estimate individual patient risk and guide chemotherapy use in hormone-sensitive, HER2-negative early breast cancer. The TAILORx trial supports MPA use in a node-negative population. Evidence for MPA use in postmenopausal node-positive breast cancer has been provided by the RxPONDER trial interim analysis but this relies on the absence of superiority in an analysis where >50% of events were unrelated to breast cancer. There is much uncertainty about MPA use for premenopausal patients. OPTIMA (Optimal Personalised Treatment of early breast cancer usIng Multi-parameter Analysis) (ISRCTN42400492) is a prospective international randomized controlled trial designed to validate MPAs as predictors of chemotherapy sensitivity in a largely node-positive breast cancer population. Method(s): OPTIMA is a partially blinded study with an adaptive two-stage design. The trial recruits women and men age 40 or older with resected ER-positive, HER2-negative invasive breast cancer and up to 9 involved axillary lymph nodes. Randomization is to standard management (chemotherapy and endocrine therapy) or to MPA-directed treatment using the Prosigna (PAM50) test. Those with a Prosigna tumor Score (ROR-PT) >60 receive standard management whilst those with a low score (<=60) tumor are treated with endocrine therapy alone. Endocrine therapy for premenopausal women includes ovarian suppression for all participants unless they experience a chemotherapy-induced menopause. Adjuvant abemaciclib is permitted. The trial will be analyzed for (1) non-inferiority of recurrence according to randomization and (2) cost-effectiveness. The key secondary outcome is non-inferiority of recurrence for patients with low ROR-PT score tumors. The efficacy analyses will be performed Per Protocol using Invasive Breast Cancer Free Survival (IBCFS) as the primary outcome measure to limit the risk of a false non-inferiority conclusion. Recruitment of 4500 patients over 8 years will permit demonstration of up to 3% non-inferiority of test-directed treatment with at least 83% power, assuming 5-year IBCFS is 87% with standard management. An integrated qualitative recruitment study addresses challenges to consent and recruitment, building on experience from the feasibility study which found that a multidisciplinary approach is important for recruitment success. OPTIMA is strongly supported by a patient group which has helped design all patient documents and which is represented on the TMG. Result(s): The OPTIMA main trial opened in January 2017 and has continued to recruit throughout the COVID-19 pandemic. Overall recruitment as of 1 July 2022 was 2814 (2593 from UK, 221 from Norway). Patient characteristics are well balanced between the trial arms. Currently 95% of randomized participants are eligible for inclusion in the PP analysis. 66% of the MPA-directed arm participants have been allocated to endocrine therapy only. The test failure rate is < 1%. Conclusion(s): OPTIMA will provide robust unbiased evidence on test-directed chemotherapy safety for both postmenopausal and premenopausal women with 1-3 involved nodes as well as for patients with 4-9 involved nodes and for patients treated with abemaciclib.
ABSTRACT
Background: The efficacy and safety of awake prone positioning (APP) in hypoxemic patients with coronavirus disease 2019 (COVID-19) is unclear. Aim(s): To evaluate the efficacy and safety of APP in non-intubated adults with COVID-19. Method(s): We performed a pragmatic, international, randomized trial at 21 centers in Canada, Saudi Arabia, Kuwait, and the United States between May 19, 2020, and May 18, 2021. Eligible patients were hospitalized adults with COVID-19 requiring >40% oxygen. Patients were randomized to APP (n=205) or usual care (n=195). The primary outcome was intubation by day 30. Secondary outcomes included mortality at 60 days, ventilation-free days at 30 days, intensive care unit (ICU) and hospital-free days at 60 days, adverse events, and serious adverse events. Result(s): Patients in the APP group proned for a median of 4.8 hours per day (IQR 1.8 to 8.0) in the first 4 days. By day 30, 70/205 patients (34.1%) in the APP group and 79/195 (40.5%) in the control group were intubated (hazard ratio [HR] 0.81;95% confidence interval [CI] 0.59 to 1.12). APP did not reduce mortality at 60 days (HR 0.93;95% CI 0.62 to 1.40) and had no effect on days alive invasively or noninvasively ventilated at 30 days, or days out of ICU or hospital at 60 days. There were no serious adverse events in either group. A prespecified subgroup analysis suggested that APP reduced intubation among patients with SpO2:FiO2 >150 (HR of 0.44, 95% CI 0.23 to 0.87) but not among patients with SpO2:FiO2 <150 (HR 1.02;95% CI 0.70 to 1.48;P-interaction= 0.03). Conclusion(s): APP did not significantly reduce intubation at 30 days or mortality at 60 days overall, but may be effective in patients with SpO2:FiO2 >150.
ABSTRACT
30 year GBMSM presented to our sexual health service requesting PrEP. He was taking PEP after a sexual exposure and was keen to transition straight to PrEP. Baseline testing including HIV were negative before PEP was initiated. He was given a supply of PrEP and returned for HIV testing post PEP as per BASHH guidelines. He reported a recent Covid infection confirmed by PCR testing. We carried out a rapid Abbott Determine Early Detect HIV test which was reactive. The assay is a 4th generation test that detects both HIV-1/2 antibodies and free HIV-1 p24 antigen. The patient was advised of this test result and a repeat rapid test the same day remained reactive. He was advised that this could be as a result of recent Covid infection resulting in a cross reaction and that we would await confirmatory testing. He was advised to discontinue PrEP until the result was clarified. Laboratory testing was requested expeditiously and the sample tested on 2 different immunoassay analyzers for the detection of HIV Ab/Ag. Both results were confirmed negative and he was advised to restart the PrEP. A literature search showed that cross reaction with the HIV rapid test had been reported after recent Covid 19 infection in other centres but not in the UK. He was seen 4 weeks later for further screening and rapid HIV testing on this occasion was negative together with the virology HIV immunoassay test. The patient was tested for COVID at the same time and was PCR negative at this stage.
ABSTRACT
BACKGROUND: European Society for Medical Oncology Women for Oncology (ESMO W4O) research has previously shown under-representation of female oncologists in leadership roles. As early reports suggested disproportionate effects of the COVID-19 pandemic on women, the ESMO W4O Committee initiated a study on the impact of the pandemic on the lives of female and male oncologists. METHODS: A questionnaire was sent to ESMO members and put on the ESMO website between 8 June 2020 and 2 July 2020. Questions focused on the working (hospital tasks, laboratory tasks, science) and home (household management, childcare, parent care, personal care) lives of oncologists during and after COVID-19-related lockdowns. RESULTS: Of 649 respondents, 541 completed the questionnaire. Of these, 58% reported that COVID-19 had affected their professional career, 83% of whom said this was in a negative way (85% of women versus 76% of men). Approximately 86% reported that COVID-19 had changed their personal life and 82% their family life. Women were again significantly more affected than men: personal life (89% versus 78%; P = 0.001); family life (84% versus 77%; P = 0.037). During lockdowns, women reported increased time spent on hospital and laboratory tasks compared with men (53% versus 46% and 33% versus 26%, respectively) and a significantly higher proportion of women than men spent less time on science (39% versus 25%) and personal care (58% versus 39%). After confinement, this trend remained for science (42% versus 23%) and personal care (55% versus 36%). CONCLUSIONS: The COVID-19 pandemic has adversely affected the professional and home lives of oncologists, especially women. Reduced research time for female oncologists may have long-lasting career consequences, especially for those at key stages in their career. The gender gap for promotion to leadership positions may widen further as a result of the pandemic.