Second primary cancer risk - the impact of applying different definitions of multiple primaries: results from a retrospective population-based cancer registry study

Background: There is evidence that cancer survivors are at increased risk of second primary cancers. Changes in the prevalence of risk factors and diagnostic techniques may have affected more recent risks.<p></p> Methods: We examined the incidence of second primary cancer among adults in the West of Scotland, UK, diagnosed with cancer between 2000 and 2004 (n = 57,393). We used National Cancer Institute Surveillance Epidemiology and End Results and International Agency for Research on Cancer definitions of multiple primary cancers and estimated indirectly standardised incidence ratios (SIR) with 95% confidence intervals (CI).<p></p> Results: There was a high incidence of cancer during the first 60 days following diagnosis (SIR = 2.36, 95% CI = 2.12 to 2.63). When this period was excluded the risk was not raised, but it was high for some patient groups; in particular women aged <50 years with breast cancer (SIR = 2.13, 95% CI = 1.58 to 2.78), patients with bladder (SIR = 1.41, 95% CI = 1.19 to 1.67) and head & neck (SIR = 1.93, 95% CI = 1.67 to 2.21) cancer. Head & neck cancer patients had increased risks of lung cancer (SIR = 3.75, 95% CI = 3.01 to 4.62), oesophageal (SIR = 4.62, 95% CI = 2.73 to 7.29) and other head & neck tumours (SIR = 6.10, 95% CI = 4.17 to 8.61). Patients with bladder cancer had raised risks of lung (SIR = 2.18, 95% CI = 1.62 to 2.88) and prostate (SIR = 2.41, 95% CI = 1.72 to 3.30) cancer.<p></p> Conclusions: Relative risks of second primary cancers may be smaller than previously reported. Premenopausal women with breast cancer and patients with malignant melanomas, bladder and head & neck cancers may benefit from increased surveillance and advice to avoid known risk factors

Family history of cancer as a risk factor for second malignancies after Hodgkin's lymphoma

This study estimated the risk of second primary malignancies after Hodgkin's lymphoma (HL) in relation to family history of cancer, age at diagnosis and latency, among 6946 patients treated for HL in Sweden in 1965–1995 identified through the Swedish Cancer Register (SCR). First-degree relatives (FDRs) to the HL patients and their malignancies were then ascertained together with their malignancies through the Multi-Generation Registry and SCR. The HL patient cohort was stratified on the number of FDRs with cancer, and standardised incidence ratios (SIRs) of developing SM were analysed. In the HL cohort, 781 SM were observed 1 year or longer after HL diagnosis. The risk for developing SM increased with the number of FDRs with cancer, SIRs being 2.26, 3.01, and 3.45 with 0, 1, or ⩾2 FDRs with cancer, respectively. Hodgkin's lymphoma long-term survivors treated at a young age with a family history of cancer carry an increased risk for developing SM and may represent a subgroup where standardised screening for the most common cancer sites could be offered in a stringent surveillance programme

COVIDENZA - A prospective, multicenter, randomized PHASE II clinical trial of enzalutamide treatment to decrease the morbidity in patients with Corona virus disease 2019 (COVID-19): a structured summary of a study protocol for a randomised controlled trial

Objectives: The main goal of the COVIDENZA trial is to evaluate if inhibition of testosterone signalling by enzalutamide can improve the outcome of patients hospitalised for COVID-19. The hypothesis is based on the observation that the majority of patients in need of intensive care are male, and the connection between androgen receptor signalling and expression of TMPRSS2, an enzyme important for SARS-CoV-2 host cell internalization. Trial design: Hospitalised COVID-19 patients will be randomised (2:1) to enzalutamide plus standard of care vs. standard of care designed to identify superiority. Participants: Included participants, men or women above 50 years of age, must be hospitalised for PCR confirmed COVID-19 symptoms and not in need of immediate mechanical ventilation. Major exclusion criteria are breast-feeding or pregnant women, hormonal treatment for prostate or breast cancer, treatment with immunosuppressive drugs, current symptomatic unstable cardiovascular disease (see Additional file 1 for further details). The trial is registered at Umeå University Hospital, Region Västerbotten, Sweden and 8 hospitals are approved for inclusion in Sweden. Intervention and comparator: Patients randomised to the treatment arm will be treated orally with 160 mg (4x40 mg) enzalutamide (Xtandi®) daily, for five consecutive days. The study is not placebo controlled. The comparator is standard of care treatment for patients hospitalised with COVID-19. Main outcomes: The primary endpoints of the study are (time to) need of mechanical ventilation or discharge from hospital as assessed by a clinical 7-point ordinal scale (up to 30 days after inclusion). Randomisation: Randomisation was stratified by center and sex. Each strata was randomized separately with block size six with a 2:1 allocation ratio (enzalutamide + “standard of care”: “standard of care”). The randomisation list, with consecutive subject numbers, was generated by an independent statistician using the PROC PLAN procedure of SAS version 9.4 software (SAS Institute, Inc, Cary, North Carolina) Blinding (masking): This is an open-label trial. Numbers to be randomised (sample size): The trial is designed to have three phases. The first, an exploration phase of 45 participants (30 treatment and 15 control) will focus on safety and includes a more extensive laboratory assessment as well as more frequent safety evaluation. The second prolongation phase, includes the first 100 participants followed by an interim analysis to define the power of the study. The third phase is the continuation of the study up to maximum 600 participants included in total. Trial Status: The current protocol version is COVIDENZA v2.0 as of September 10, 2020. Recruitment started July 29, 2020 and is presently in safety pause after the first exploration phase. Recruitment is anticipated to be complete by 31 December 2021. Trial registrationEudract number 2020-002027-10 ClinicalTrials.gov Identifier: NCT04475601, registered June 8, 2020 Full protoco: lThe full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol

A Phase 2 Trial of the Effect of Antiandrogen Therapy on COVID-19 Outcome : No Evidence of Benefit, Supported by Epidemiology and In Vitro Data

Background: Men are more severely affected by COVID-19. Testosterone may influence SARS-CoV-2 infection and the immune response. Objective: To clinically, epidemiologically, and experimentally evaluate the effect of antiandrogens on SARS-CoV-2 infection. Designs, settings, and participants: A randomized phase 2 clinical trial (COVIDENZA) enrolled 42 hospitalized COVID-19 patients before safety evaluation. We also conducted a population-based retrospective study of 7894 SARS-CoV-2–positive prostate cancer patients and an experimental study using an air-liquid interface three-dimensional culture model of primary lung cells. Intervention: In COVIDENZA, patients were randomized 2:1 to 5 d of enzalutamide or standard of care. Outcome measurements: The primary outcomes in COVIDENZA were the time to mechanical ventilation or discharge from hospital. The population-based study investigated risk of hospitalization, intensive care, and death from COVID-19 after androgen inhibition. Results and limitations: Enzalutamide-treated patients required longer hospitalization (hazard ratio [HR] for discharge from hospital 0.43, 95% confidence interval [CI] 0.20–0.93) and the trial was terminated early. In the epidemiological study, no preventive effects were observed. The frail population of patients treated with androgen deprivation therapy (ADT) in combination with abiraterone acetate or enzalutamide had a higher risk of dying from COVID-19 (HR 2.51, 95% CI 1.52–4.16). In vitro data showed no effect of enzalutamide on virus replication. The epidemiological study has limitations that include residual confounders. Conclusions: The results do not support a therapeutic effect of enzalutamide or preventive effects of bicalutamide or ADT in COVID-19. Thus, these antiandrogens should not be used for hospitalized COVID-19 patients or as prevention for COVID-19. Further research on these therapeutics in this setting are not warranted. Patient summary: We studied whether inhibition of testosterone could diminish COVID-19 symptoms. We found no evidence of an effect in a clinical study or in epidemiological or experimental investigations. We conclude that androgen inhibition should not be used for prevention or treatment of COVID-19