ABSTRACT
Background: Studies evaluating COVID-19 in cancer patients beyond the effects of the infection itself are generally from single institutions, voluntary surveillance registries, or surveys. To extend the limited evidence available, we analyzed both the incidence and one-year mortality of breast cancer (BC) female patients at a population level in Lombardy, the first Italian region affected by the pandemic and the most populous one. Method(s): The regional COVID-19 database, including all SARS-CoV2 cases based on a positive swab result, was integrated with the Regional Health Information System, collecting data from 10 million habitants on primary medical care;hospitalization;pharmaceuticals;and survival status. From the database, we extracted data of newly-diagnosed not previously treated BC patients, including patient characteristics and comorbidities (respiratory insufficiency, diabetes, chronic kidney disease, cerebral vasculopathy, hypertension and cardiovascular disease), BC stage, and treatment. Result(s): The study population consisted of 12912 newlydiagnosed/ not previously treated BC patients, 7349 in 2019 and 5563 in 2020. There were two drops of newly diagnosed cases, one in the first wave (March-May 2020;-37.2%), the other in the second wave (October-December 2020;-15.8%). No major differences were found between characteristics of cases occurring in 2019 and 2020;with the exception of a reduced use of both chemotherapy (86.2% vs 53.4%) and radiotherapy (65.7% vs 42.1%) in 2020. One-year overall survival was 97.6% in 2020 vs 98.3% in 2019, Hazard Ratio [HR] (95% Confidence Interval [95%CI]): 1.51 (1.18-1.93);p=0.0010 at univariate analysis;HR 0.91 (0.71-1.17), p= 0.47, after adjusting for age, stage, BC treatment and comorbidities at multivariable analysis. COVID-19 occurred in 250 of 5563 (4.5%) newly-diagnosed BC cases in 2020. Notably, the time-dependent COVID-19 effect was significantly associated with mortality (multivariable Cox analysis HR 2.25 (1.35-3.74);p=0.0018) even after adjusting for age, stage, treatment and comorbidities. Conclusion(s): Breast cancer incidence and survival were both reduced in 2020, and COVID-19 was an independent predictor of death in BC patients. While follow-up is ongoing to assess long sequelae of COVID-19, these results encourage prevention of infection regardless of BC stage;and at the same time warn against suboptimal treatment and overlooking new diagnoses to ensure a favourable prognostic outcome.
ABSTRACT
Background-Physical distancing for COVID-19 led to decreased in-person patient follow up assessments and delayed imaging appointments. Herein we describe for the first time the impact of delays in diagnostic investigations of patients with an history of early-stage breast cancer (BC) in the largest public cancer center of Lombardy, the Italian region most affected by the pandemic. Methods-This single-institution retrospective study included three observational periods. The first pandemic peak period (March-April 2020) corresponding to the interruption of follow up imaging;the post-peak period (May-December 2020);the pre-pandemic period represented by the five previous years (January 2015-December 2019) as control. The flow of diagnostic activities was compared among the different years. Moreover, the number and characteristics of recurrent BC cases (rBC) diagnosed in the post-peak period were compared to the figures observed in pre-pandemic years, when imaging was regularly carried out, using descriptive statistics. A further comparison was performed between the characteristics of scheduled and delayed rBC diagnosed after the first peak. Results-During the first pandemic peak, diagnostic investigations declined by 81.2% (from 1032 in January-February to 194 in March-April), a drop which was not identified in the same period of the pre-pandemic years, before rebounding to 1065 in May-June, 832 July-August (reflecting the Ssummer physiological drop), 1334 September-October, and 879 November-December. The average number of rBC cases of 16 (range 12-25) in March-April of the pre-pandemic period declined to a value as low as 4 during the first pandemic peak. Thereafter, the number of rBC cases began a steady increase, until reaching a total of 27 in September-October 2020, almost doubling the mean of 14.8 (range 11-21) achieved in the corresponding months of 2015-2019. As a result, the absolute number of rBC cases was 76 in 2020 and on average 78.4 (range 70-95) in pre-pandemic years, and the rBC proportion of 1.42% (76/5336;95% exact confidence interval, CI: 1.12-1.78%) in 2020 was slightly higher than the average proportion of 1.26% of the five previous years, though the latter being well included in the CI of the 2020 proportion. No difference in primary tumor presentation and age at initial diagnosis was found among recurrent patients before and after the pandemic. Of the rBC cases reported during 2020, 10 were from 513 patients with postponed follow up who were finally diagnosed between September-December. As compared to patients on schedule, delayed rBC cases did not present with ductal carcinoma in situ, and reported a median tumor size of 18 mm (range 4.3-90 mm), which was 20% higher than the median of 15 mm (3.1-34) observed for scheduled patients. Distribution of luminal-like, triple negative and HER2-overexpressing BC subtypes among evaluable rBC cases was 75%, 12.5%, 12.5% in scheduled and 66%, 11% and 22% in delayed cases, respectively. Conclusions-Our data showed a slight decrease in the absolute number of rBC during 2020 despite a rebound of examinations, and an increased size of invasive recurrence following the 2-month stop of the first pandemic peak. The full impact of the COVID-19 pandemic on recurrent cancer diagnosis will be known when national population-based data become available in the coming years.
ABSTRACT
Background: End of life medical treatment is an issue widely discussed in Oncology. There is little data about the indications for decision making between active treatment versus best supportive care. In this report we present our experience in patients (pts) who received oncologic treatment within the last 30 days of life. Material and methods: We retrospectively collected data of pts who have been hospitalized in the Medical Oncology Department of Istituto Nazionale Tumori of Milan receiving oncologic treatment from the 15th of November 2020 to the 15th of May 2021. We considered this period to mitigate the confusing effect of the SARS-Cov2 pandemic on the increase of mortality. We selected pts affected by any stage of cancer, who received any line of active cancer therapy within 30 days from death. We collected: age, sex, Performance Status according to the Eastern Cooperative Oncology Group (PS), type of cancer, line and type of treatment, Hemoglobin (Hb), White Blood Cells (WBC), Neutrophils (N), Platelets (PLT), Lactate Dehydrogenase (LDH), modified Glasgow Prognostic Score (mGPS) calculated with Albumine and C Reactive Protein, and cause of death. Results: In total 263 pts were hospitalized. Of these, 166 have received oncologic treatment. Of them, 9 pts (5.4%) died within 30 days of treatment. Among them, the mean age was 64 years, 4 pts were women (44%) while 5 were men (56%). Three pts were PS 1 (33%), 3 pts were PS 2 (33%) and 3 pts were PS 3 (33%). All pts were affected by advanced cancer;7 pts had lung cancer (78%), 1 gastric cancer (11%) and 1 breast cancer (11%). Four pts (44%) received first line therapy and 5 pts (56%) further line therapy. Five pts were treated with chemotherapy (56%), 3 pts with immunotherapy (33%), 1 with chemo-immunotherapy (11%). Considering the blood tests, median WBC count was 9680/μL (1080 - 33820), median N levels were 8860/μL (3780 - 31520), median Hb was 11.2 g/dL (9-15), median PLT count was 314 000/μL (196 000 - 413 000) and median LDH was 216 U/L (150 - 1372). mGPS were 2 in 5 pts (56%), 1 in 2 pts (22%) and 0 in 2 pts (22%). Causes of death were progression (78%), toxicity (11%) and other causes (infection, 11%). Conclusions: Our study is consistent with available literature about end of life oncologic treatment. Based on our data, pts' selection according to PS and mGPS should not be the only parameter to consider for treatment decisions. A comprehensive characterization of the pts treatment must be studied.
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.