ABSTRACT
Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters into target cells by exploiting the cellular transmembrane protease serine 2 (TMPRSS2) for spike protein cleavage. Male gender, age, obesity, diabetes, hypertension are some of the factors related to coronavirus disease 2019 (COVID-19) severity and mortality. Prostate cancer (PCa) patients (pts) are expected to be at higher risk for COVID-19 due to age and disease related comorbidities. TMPRSS2 transcription depends on androgens and androgen receptor and it is significantly downregulated by hormone therapies commonly used to treat PCa in different settings. Supposing that in PCa pts androgen deprivation therapy (ADT) could hamper SARS-CoV-2 cell entry, we aim to evaluate if the presence of single nucleotide polymorphisms (SNPs) in the androgen responsive elements (AREs) in the TMPRSS2 promoter is associated to COVID-19 outcomes. Trial design: The present exploratory biological study is part of an ongoing retrospective-prospective multicenter cohort trial designed to verify whether PCa pts on ADT develop milder clinical presentation of COVID-19 than the general male population. The cohort trial collects real world data since February 2020 through regional databases that identified 200,000 potential pts to be enrolled to compare the clinical outcome of COVID-19 between PCa pts on active therapy (Study Group) and non-PCa pts (Control Group). Within the Study Group, we will compare the COVID-19 outcome between treatment subgroups: ADT alone, ADT plus antiandrogens, CYP17 inhibitors or chemotherapy. To identify SNPs in AREs of the TMPRSS2 gene and to describe possible associations with COVID-19 outcome, blood samples will be collected from 50 PCa pts treated at selected centers. Pts will participate voluntarily and sign an informed consent approved by local ethical committees. We will centrally perform PBMCs isolation and DNA extraction by using quiagen QIAamp DNA Mini Kit. SNPs will be evaluated with the Axiom™ Human Genotyping SARS-CoV-2 array. The effect of ADT will be corrected depending on identified SNPs and associated to COVID-19 outcome. The study is ongoing: we processed blood samples from 21 pts. Final results are awaited by the end of 2021. Legal entity responsible for the study: The authors. Funding: Fondazione IRCCS Istituto Nazionale Tumori di Milano. Disclosure: All authors have declared no conflicts of interest.
ABSTRACT
Background: In the midst of COVID-19 pandemic, cancer patients (pts) are regarded as a highly vulnerable population. Pts requiring hospital admission for treatment (Tx) administration are potentially exposed to a higher risk of infection and worse outcome given the multiple in-hospital exposures and the Tx immunosuppressive effects. Methods: COVINT is an observational study assessing COVID-19 incidence among pts receiving anticancer Tx in the outpatient clinic of the Istituto Nazionale dei Tumori di Milano. All consecutive pts with non-hematologic malignancies treated with intravenous or subcutaneous/intramuscular Tx in the outpatient clinic were enrolled. Pts were admitted to the clinic wearing surgical masks and only if asymptomatic and afebrile. The primary endpoint is the rate of occurrence of COVID-19. Secondary endpoints include the rate of COVID-19 related deaths and Tx interruptions. The association between clinical and biological characteristics and COVID-19 occurrence is also evaluated using nonparametric tests. COVID-19 diagnosis is defined as: a) certain if confirmed by RT-PCR assay of nasopharyngeal swabs (NFS);b) suspected in case of new symptoms and/or CT scan evidence of interstitial pneumonia with negative/not performed NFS;c) negative in case of neither symptoms nor radiological evidence. Results: In the first two months (16th February-10th April 2020) of observation, 1083 pts were included. Of these, 11 (1%) were confirmed and 73 (6.7%) suspected for COVID-19. No significant differences in terms of cancer and Tx type emerged between the three subgroups. Prophylactic use of myeloid growth factors was adopted in 5.3%, 2.7% and 0% of COVID-19-free, -suspected and -confirmed pts (p=0.003). Overall, 96 (8.9%) pts delayed Tx as a precaution for the pandemic. Among the 11 confirmed cases, 6 (55%) died of COVID-19 complications, and anticancer Tx was restarted in only one. Conclusions: During the pandemic peak, accurate protective measures successfully resulted in low rates of COVID-19 diagnosis, though with high lethality. Within the COVINT study, prospective pts surveillance will continue with NFS swabs and IgG/IgM serology performed before each Tx cycle until pandemic resolution. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: F.G.M. De Braud: Advisory/Consultancy: Tiziana Life Sciences;Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: BMS;Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Celgene;Advisory/Consultancy, Research grant/Funding (institution): Novartis;Advisory/Consultancy: Servier;Advisory/Consultancy: Pharm Research Associated;Advisory/Consultancy: Daiichi Sankyo;Advisory/Consultancy, Speaker Bureau/Expert testimony: Ignyta;Advisory/Consultancy, Travel/Accommodation/Expenses: Amgen;Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Pfizer;Advisory/Consultancy: Octimet Oncology;Advisory/Consultancy, Research grant/Funding (institution): Incyte;Advisory/Consultancy: Pierre Fabre;Advisory/Consultancy: Eli Lilly;Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche;Advisory/Consultancy: Astra Zeneca;Advisory/Consultancy: Gentili;Advisory/Consultancy, Speaker Bureau/Expert testimony: Dephaforum;Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): MSD;Advisory/Consultancy, Speaker Bureau/Expert testimony: Bayer;Advisory/Consultancy: Fondazione Menarini;Research grant/Funding (self): NMS;Research grant/Funding (institution): Merck KGAA;Research grant/Funding (institution): Kymab;Research grant/Funding (institution): Tesaro;Speaker Bureau/Expert testimony: Biotechespert Ltd;Speaker Bureau/Expert testimony: Prime Oncology. All other authors have declared no conflicts of interest.