PRIZER study using RenzanTM stent for endovascular interventions in femoropopliteal area: primary safety endpoint at 30- days

Purpose: to report 30-day safety outcomes in PRIZER study. Material(s) and Method(s): PRIZER is a prospective single-arm multicentre study aiming to assess the safety and effectiveness of percutaneous treatment of femoropopliteal lesions with the RenzanTM stent in 135 patients. RenzanTM is an innovative self-expandable interwoven nitinol dual-layer micromesh stent. Result(s): 39 patients with Rutherford class 2 to 5 are included in this analysis, age 71.6 +/-10.16, male 27 (69%), BMI 26.9 +/- 4.62. Of these, 15 (38%) have diabetes, 25 (64%) hypertension, 8 (21%) coronary revascularization, 4 (10%) low limb amputation, 5 (13%) TIA/stroke in anamnesis. ABI and Rutherford score at baseline was 0.58 +/- 0.13, 3.28 +/- 0.79 and 0.98 +/-0.09, 0.27+/- 0.96 at 30 days, respectively. The mean lesion length is 66.5 mm +/- 20.65, diameter stenosis is 89.8% +/- 9.89, calcified lesions are observed in 34 (87%) patients. Prior to implantation the permitted level of stenosis <=20% was achieved in all patients, using POBA only. Dissections happened in 15 (33%) cases, distal embolization in one case. Mean stent length is 84.1 mm +/-16.66. Safety endpoint defined as absence of death, TLR, index limb amputation achieved in 38 (97%) patients. One death was not study related (COVID). One patient had hematoma at the access site. Conclusion(s): preliminary results show a promising safety profile with RenzanTM stent. Results on 30-days safety in complete sample size of 135 patients are expected in August 2022.

Clinical assessment of the Omicron outbreak in Europe and trends in morbidity and mortality from COVID-19 and cancer

Background: Whilst patients (pts) with cancer are at increased risk of adverse outcome from Coronavirus disease 2019 (COVID-19), no evidence exists as to the natural history of the SARS-CoV-2 B.1.1.529 (Omicron) variant in this population. Methods: Capitalizing on OnCovid study data (NCT04393974), a European registry that collects data on consecutive patients with cancer and COVID-19, we analysed COVID-19 morbidity and case fatality rates at 14 days (CFR14) across 3 phases defined following the evolution of the pandemic in Europe, according to date of COVID-19 diagnosis: “Pre-vaccination” phase (27/02/2020-30/ 11/2020), “Alpha-Delta variant” phase (01/12/2020-14/12/2021), “Omicron variant” phase (15/12/2020-31/01/2022). Results: By the data lock of 04/02/2022, 3820 consecutive pts were enrolled, 3473 of whom were eligible for this analysis. Among them, 2033 (58.6%), 1075 (30.9%) and 365 (10.5%) were diagnosed during the Pre-vaccination, Alpha-Delta and Omicron phases. Pts diagnosed in the Omicron phase were more likely aged < 65 years (48.6% vs 42.5%, 39.4% p = 0.01), had < 2 comorbidities (61.9% vs 55.6%, 52.1% p = 0.01). They had more advanced-stage tumours (62.1% vs 53.3%, 49.0%, p < 0.01) and were more likely receiving systemic anticancer therapy (SACT) at COVID-19 diagnosis (54.9% vs 43.9%, 39.6%, p < 0.01). Proportions of fully vaccinated/boosted pts were higher in the Omicron phase (33.9%-48.1%) compared to the Alpha-Delta phase (16.6%-2.3%, p < 0.01). Pts diagnosed in the Omicron phase had improved CFR14 (9.0% vs 13.9%, 23.1%, p < 0.01) lower hospitalization rates due to COVID-19 (24.4% vs 41.4%, 56.6%, p < 0.01), lower complications rates (15.3% vs 33.6%, 39.4%, p < 0.01) and reduced need for COVID-19 specific therapy (22.4% vs 43.0%, 65.7% p < 0.01) compared to the Alpha-Delta and pre-vaccinal phase. After adjusting for country of origin, sex, age, comorbidities, tumour stage, status and receipt of SACT at COVID-19, patients diagnosed in the Omicron phase displayed the lowest risk of death at 14 days compared to earlier phases. Similarly, rates of hospitalization and complicated COVID-19 were lowest for Omicron phase. Conclusions: This is the first study to portray the evolution of the SARS-CoV-2 Omicron outbreak in Europe, documenting an improvement in all COVID-19 outcomes compared to earlier phases of the pandemic. Enhanced healthcare capacity, improved disease management, immunization campaigns alongside differential virulence of viral strains are likely contributing to improved outcomes across phases.

The acute phase response identifies cancer patients with adverse outcomes from SARS-CoV-2 infection as quantified by the OnCovid Inflammatory Score

We sought to determine parameters of the acute phase response, a feature of innate immunity activated by infectious noxae and cancer, deranged by Covid-19 and establish oncological indices' prognostic potential for patients with concomitant cancer and Covid-19. Between 27/02 and 23/06/2020, OnCovid retrospectively accrued 1,318 consecutive referrals of patients with cancer and Covid-19 aged 18 from the U.K., Spain, Italy, Belgium, and Germany. Patients with myeloma, leukemia, or insufficient data were excluded. The neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), prognostic nutritional index (PNI), modified Glasgow prognostic score (mGPS), and prognostic index (PI) were evaluated for their prognostic potential, with the NLR, PLR, and PNI risk stratifications dichotomized around median values and the pre-established risk categorizations from literature utilized for the mGPS and PI. 1,071 eligible patients were randomly assorted into a training set (TS, n=529) and validation set (VS, n=542) matched for age (67.9±13.3 TS, 68.5±13.5 VS), presence of 1 comorbidity (52.1% TS, 49.8% VS), development of 1 Covid-19 complication (27% TS, 25.9% VS), and active malignancy at Covid-19 diagnosis (66.7% TS, 61.6% VS). Among all 1,071 patients, deceased patients tended to categorize into poor risk groups for the NLR, PNI, mGPS, and PI (P<0.0001) with a return to pre-Covid-19 diagnosis NLR, PNI, and mGPS categorizations following recovery (P<0.01). In the TS, higher mortality rates were associated with NLR>6 (44.6% vs 28%, P<0.0001), PNI<40 (46.6% vs 20.9%, P<0.0001), mGPS (50.6% for mGPS2 vs 30.4% and 11.4% for mGPS1 and 0, P<0.0001), and PI (50% for PI2 vs 40% for PI1 and 9.1% for PI0, P<0.0001). Findings were confirmed in the VS (P<0.001 for all comparisons). Patients in poor risk categories had shorter median overall survival [OS], (NLR>6 30 days 95%CI 1-63, PNI<40 23 days 95%CI 10-35, mGPS2 20 days 95%CI 8-32, PI2 23 days 95%CI 1-56) compared to patients in good risk categories, for whom median OS was not reached (P<0.001 for all comparisons). The PLR was not associated with survival. Analyses of survival in the VS confirmed the NLR (P<0.0001), PNI (P<0.0001), PI (P<0.01), and mGPS (P<0.001) as predictors of survival. In a multivariable Cox regression model including all inflammatory indices and pre-established prognostic factors for severe Covid-19 including sex, age, comorbid burden, malignancy status, and receipt of anti-cancer therapy at Covid-19 diagnosis, the PNI was the only factor to emerge with a significant hazard ratio [HR] in both TS and VS analysis (TS HR 1.97, 95%CI 1.19-3.26, P=0.008;VS HR 2.48, 95%CI 1.47- 4.20, P=0.001). We conclude that systemic inflammation drives mortality from Covid-19 through hypoalbuminemia and lymphocytopenia as measured by the PNI and propose the PNI as the OnCovid Inflammatory Score (OIS) in this context.

SARS-CoV-2 antibody seroprevalence and safety of vaccines in cancer patients who recovered from COVID-19

Background: Little is known about natural anti-SARS-CoV-2 antibody seroprevalence post COVID-19 and safety of vaccines in COVID-19 survivors with cancer. Methods: Among 2795 consecutive patients (pts) with COVID-19 and cancer registered to OnCovid between 01/2020 and 02/2021, we examined natural seroprevalence of anti-SARS-CoV-2 Antibodies (SC2Ab, IgM or IgG) in pts tested post-infection. We analysed prevalence and safety of SARS-Cov-2 vaccine administration in pts who underwent clinical re-assessment at participating institutions. Results: Out of 350 pts tested for SC2Ab, 318 (90.9%) had a positive SC2Ab titre post-convalescence. Neither baseline features (sex, age, comorbidities, smoking history, tumour stage/status, anticancer-therapy and primary tumour) nor COVID-19-specific features (complications, hospitalization, sequelae) were significantly associated SC2Ab status. Receipt of COVID-19 specific therapy was higher among SC2Ab+ pts (62.6% vs 40.6%, p=0.0156). Out of 593 pts with known vaccination status, 178 (30%) had received 1 dose, whilst 38 pts (6.4%) received 2 doses of mRNA based (70.2%) or viral vector vaccine (17.4%). Vaccinated pts were more likely aged ≥65 years (59% vs 48.3%, p=0.0172), with loco-regional tumour stage (56% vs 40.8%, p=0.0014), on anti-cancer therapy at COVID-19 (49.1% vs 38.2%, p=0.0168) and history of prior hospitalisation due to COVID-19 (61.8% vs 48.3%, p=0.0029). Vaccine-related adverse events were reported for 18/56 evaluable pts (32.1%) and included injection site reactions (50%), fever (44.4%), arthralgias (33.3%), fatigue (33.3%) and allergy (5.5%). No long-term vaccine-related morbidity was reported. Conclusions: We report high seroprevalence (>90%) of SC2Ab in convalescent cancer pts who survived COVID-19 irrespective of baseline demographics, oncological characteristics and COVID-19 severity. COVID-19 vaccines appear to be safe in cancer pts with history of prior infection. Clinical trial identification: NCT04393974. Legal entity responsible for the study: Imperial College London. Funding: Has not received any funding. Disclosure: D.J. Pinato: Financial Interests, Personal, Invited Speaker: ViiV Healthcare;Financial Interests, Personal, Invited Speaker: Bayer;Financial Interests, Personal, Advisory Board: Eisai;Financial Interests, Personal, Advisory Board: Amgen;Financial Interests, Personal, Advisory Board: BMS;Financial Interests, Personal, Advisory Board: Pfizer;Financial Interests, Personal, Advisory Board: Nanostring tech. A. Cortellini: Financial Interests, Personal, Advisory Board: MSD;Financial Interests, Personal, Advisory Board: BMS;Financial Interests, Personal, Advisory Board: Roche;Financial Interests, Personal, Invited Speaker: Novartis;Financial Interests, Personal, Advisory Board: SunPharma;Financial Interests, Personal, Invited Speaker: AstraZeneca;Financial Interests, Personal, Invited Speaker: Astellas. All other authors have declared no conflicts of interest.

Determinants of enhanced vulnerability to Covid-19 in U.K. cancer patients: Results from the OnCovid study

Background: Despite high contagiousness and rapid spread, SARS-Cov-2 has led to heterogeneous outcomes across affected nations. Within Europe, the United Kingdom is the most severely affected country, with a death toll in excess of 100.000 as of February 2021. We aimed to compare the national impact of Covid19 on the risk of death in UK cancer patients versus those in continental Europe (EU). Methods: We performed a retrospective analysis of the OnCovid study database, a European registry of cancer patients consecutively diagnosed with Covid-19 in 27 centres from February 27 to September 10, 2020. We analysed case fatality rates and risk of death at 30 days and 6 months stratified by region of origin (UK versus EU). We compared patient characteristics at baseline, oncological and Covid-19 specific therapy across cohorts and tested these in multivariable Cox regression models to identify predictors of adverse outcome in UK versus EU patients. Results: Compared to EU patients (n = 924), UK patients (n = 468) were characterised by higher case fatality rates (40.38% versus 26.5%, p < 0.0001), higher risk of death at 30 days (hazard ratio, HR 1.64 [95%CI 1.36-1.99]) and 6 months after Covid-19 diagnosis (47.64% versus 33.33%, p < 0.0001, HR 1.59 [95%CI 1.33-1.88]). UK patients were more often males, of older age and more co-morbid than EU counterparts (p < 0.01). Receipt of anti-cancer therapy was lower in UK versus EU patients (p < 0.001). Despite equal proportions of complicated Covid-19, rates of intensive care admission and use of mechanical ventilation, UK cancer patients were less likely to receive anti-Covid-19 therapies including corticosteroids, anti-virals and interleukin-6 antagonists (p < 0.0001). Multivariable analyses adjusted for imbalanced prognostic factors confirmed the UK cohort to be characterised by worse risk of death at 30 days and 6 months, independent of patient's age, gender, tumour stage and status, number of co-morbidities, Covid-19 severity, receipt of anti-cancer and anti-Covid-19 therapy. Rates of permanent cessation of anti-cancer therapy post Covid-19 were similar in UK versus EU. Conclusions: UK cancer patients have been more severely impacted by the unfolding of the Covid-19 pandemic despite societal risk mitigation factors and rapid deferral of anti-cancer therapy. The increased frailty of UK cancer patients highlights high-risk groups that should be prioritised for anti-SARS-Cov-2 vaccination. Continued evaluation of long-term outcomes is warranted.

Context of health care workers contamination during the first SARS-CoV-2 epidemic wave in France

Two thousand three hundred and twenty nine health care professionals infected by the SARS-CoV-2 during the first wave of the epidemic in France, working in public/private hospitals and clinics, foster care homes and private practices, provided information on the potential circumstances of their contamination through an online questionnaire. The analysis of the collected data points to possible links of these differences with the availability of the type of masks and the recommendation and protocols used in the different types of facilities/activity sectors during February-April 2020, the period where 96% of the reported contaminations occurred. The study is still ongoing and will continue up to April 2021.

Determinants of mortality from SARS-CoV-2 infection in European cancer patients

Background: The severity of SARS-CoV-2 infection (COVID-19) is predicted by advancing age and co-morbidities. The relative contribution of cancer in influencing the course of COVID-19 is poorly understood. We designed the OnCOVID study to investigate natural history of COVID-19 disease in cancer patients. Methods: This retrospective, multi-center observational study conducted across 8 tertiary centers in Europe recruited cancer patients aged >/= 18 and diagnosed with COVID-19 between February 26th and April 1st, 2020. Descriptive statistics, univariable and multivariable Cox regression models were used to assess patient’s main characteristics and to evaluate the factors associated to COVID-19 related mortality. Results: We identified 204 patients from United Kingdom (n=97, 48%), Italy (n=56, 27%) and Spain (n=51, 25%). Most patients were male (n=127, 62%) had a diagnosis of solid malignancy (n=184, 91%) and 103 (51%) had non-metastatic disease. Mean (±SD) patient age was 69±13 years, and 161 (79%) had >/= 1 co-morbidity, most commonly hypertension (n=88, 43%) and diabetes (n=46, 23%). Commonest presenting symptoms were fever (n=136, 67%) and cough (n=119, 58%), beginning 3.8 (±4.5 SD) days before diagnosis. Most patients (n=141, 69%) had >/= 1 complication from COVID-19, including respiratory failure (n=128, 63%) and acute respiratory distress syndrome (n=49, 24%). In total, 36 patients (19%) patients were escalated to high-dependency or intensive care. At time of analysis, 59 patients had died (29%), 53 were discharged from hospital (26%) and 92 (45%) were in-hospital survivors. Mortality was higher in patients aged >/= 65 (36% versus 16%), in those with >/= 2 co-morbidities (40% versus 18%) and developing >/= 1 complication from COVID-19 (38% versus 4%, p=0.004). Multi-variable analyses confirmed age >/= 65 and >/= 2 co-morbidities to predict for patient mortality independent of tumor stage, active malignancy or anti-cancer therapy. Conclusions: In the early outbreak of SARS-CoV-2 infection in Europe co-morbid burden and advancing age predicted for adverse disease course in cancer patients. Risk stratification based on these factors should inform personalized oncological decision making during the COVID-19 pandemic. Legal entity responsible for the study: Imperial College London. Funding: Has not received any funding. Disclosure: D.J. Pinato: Speaker Bureau/Expert testimony, received lecture fees : ViiV Healthcare;Speaker Bureau/Expert testimony, received lecture fees : Bayer Healthcare;Travel/Accommodation/Expenses: BMS;Advisory/Consultancy: Mina Therapeutics;EISAI;Roche;Astra Zeneca;Research grant/Funding (institution): MSD;BMS. A. Patriarca: Advisory/Consultancy: Takeda;Sanofi. G. Gaidano: Advisory/Consultancy, Speaker Bureau/Expert testimony: Janssen;Abbvie;Advisory/Consultancy: AstraZeneca;Sunesys. J. Brunet: Advisory/Consultancy: MSD;AstraZeneca. J. Tabernero: Advisory/Consultancy: Array Biopharma;Astra Zeneca;Bayer;Beigene;Boehringer Ingelheim;Chugai;Genentech;GenMab;Halozyme;Inflection Biosciences Limited;Ipsen;Kura;Lilly;MSD;Menarini;Merck Serono;Merrimack;Merus;Molecular Partners;Novartis;Peptomics;Pfizer;Pharmacyclics;Rafael Pharmaceuticals;ProteoDesign SL;F. Hoffmann-La Roche Ltd;Sanofi;Servier;Seagen;Symphogen, Taiho, VCN Biosciences, Biocartis, Foundation Medicine, HalioDX SAS and Roche Diagnostics. A. Prat:Honoraria (self), Advisory/Consultancy: Pfeizer;Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Novartis;Roche;Honoraria (self): MSD Oncology;Lilly;Honoraria (self), Travel/Accommodation/Expenses: Daiichi Sankyo;Advisory/Consultancy: BMS;Amgen;NanoString Technologies. A. Gennari: Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): Roche;Eli Lilly;EISAI;Advisory/Consultancy: Pierre Fabre;MSD;Novartis;Advisory/Consultancy, Speaker Bureau/Expert testimony: Daiichi Sankyo;Speaker Bureau/Expert testimony: Teva;Gentili;Pfizer;AstraZeneca;Celgene. All other authors have declared no onflicts of interest.