IntroductionRadical chemoradiotherapy represents the gold standard for locally advanced cervical cancer. However, despite significant progress in improving local tumour control, distant relapse ...continues to impact overall survival. The development of predictive and prognostic biomarkers is consequently important to risk-stratify patients and identify populations at higher risk of poorer treatment response and survival outcomes. Exploratory study of using Magnetic resonance Prognostic Imaging markers for Radiotherapy In Cervix cancer (EMPIRIC) is a prospective exploratory cohort study, which aims to investigate the role of multiparametric functional MRI (fMRI) using diffusion-weighed imaging (DWI), dynamic contrast-enhanced (DCE) and blood oxygen level-dependent imaging (BOLD) MRI to assess treatment response and predict outcomes in patients undergoing radical chemoradiotherapy for cervical cancer.Methods and analysisThe study aims to recruit 40 patients across a single-centre over 2 years. Patients undergo multiparametric fMRI (DWI, DCE and BOLD-MRI) at three time points: before, during and at the completion of external beam radiotherapy. Tissue and liquid biopsies are collected at diagnosis and post-treatment to identify potential biomarker correlates against fMRI. The primary outcome is to evaluate sensitivity and specificity of quantitative parameters derived from fMRI as predictors of progression-free survival at 2 years following radical chemoradiotherapy for cervical cancer. The secondary outcome is to investigate the roles of fMRI as predictors of overall survival at 2 years and tumour volume reduction across treatment. Statistical analyses using regression models and survival analyses are employed to evaluate the relationships between the derived parameters, treatment response and clinical outcomes.Ethics and disseminationThe EMPIRIC study received ethical approval from the NHS Health Research Authority (HRA) on 14 February 2022 (protocol number RD2021-29). Confidentiality and data protection measures are strictly adhered to throughout the study. The findings of this study will be disseminated through peer-reviewed publications and scientific conferences, aiming to contribute to the growing body of evidence on the use of multiparametric MRI in cervical cancer management.Trial registration numberNCT05532930.
An increased mortality risk was observed in patients with cancer during the first wave of COVID-19. Here, we describe determinants of mortality in patients with solid cancer comparing the first and ...second waves of COVID-19. A retrospective analysis encompassing two waves of COVID-19 (March-May 2020; December 2020-February 2021) was performed. 207 patients with cancer were matched to 452 patients without cancer. Patient demographics and oncological variables such as cancer subtype, staging and anti-cancer treatment were evaluated for association with COVID-19 mortality. Overall mortality was lower in wave two compared to wave one, HR 0.41 (95% CI: 0.30-0.56). In patients with cancer, mortality was 43.6% in wave one and 15.9% in wave two. In hospitalized patients, after adjusting for age, ethnicity and co-morbidities, a history of cancer was associated with increased mortality in wave one but not wave two. In summary, the second UK wave of COVID-19 is associated with lower mortality in hospitalized patients. A history of solid cancer was not associated with increased mortality despite the dominance of the more transmissible B.1.1.7 SARS-CoV-2 variant. In both waves, metastatic disease and systemic anti-cancer treatment appeared to be independent risk factors for death within the combined cancer cohort.
The medium-term and long-term impact of COVID-19 in patients with cancer is not yet known. In this study, we aimed to describe the prevalence of COVID-19 sequelae and their impact on the survival of ...patients with cancer. We also aimed to describe patterns of resumption and modifications of systemic anti-cancer therapy following recovery from SARS-CoV-2 infection.
OnCovid is an active European registry study enrolling consecutive patients aged 18 years or older with a history of solid or haematological malignancy and who had a diagnosis of RT-PCR confirmed SARS-CoV-2 infection. For this retrospective study, patients were enrolled from 35 institutions across Belgium, France, Germany, Italy, Spain, and the UK. Patients who were diagnosed with SARS-CoV-2 infection between Feb 27, 2020, and Feb 14, 2021, and entered into the registry at the point of data lock (March 1, 2021), were eligible for analysis. The present analysis was focused on COVID-19 survivors who underwent clinical reassessment at each participating institution. We documented prevalence of COVID-19 sequelae and described factors associated with their development and their association with post-COVID-19 survival, which was defined as the interval from post-COVID-19 reassessment to the patients’ death or last follow-up. We also evaluated resumption of systemic anti-cancer therapy in patients treated within 4 weeks of COVID-19 diagnosis. The OnCovid study is registered in ClinicalTrials.gov, NCT04393974.
2795 patients diagnosed with SARS-CoV-2 infection between Feb 27, 2020, and Feb 14, 2021, were entered into the study by the time of the data lock on March 1, 2021. After the exclusion of ineligible patients, the final study population consisted of 2634 patients. 1557 COVID-19 survivors underwent a formal clinical reassessment after a median of 22·1 months (IQR 8·4–57·8) from cancer diagnosis and 44 days (28–329) from COVID-19 diagnosis. 234 (15·0%) patients reported COVID-19 sequelae, including respiratory symptoms (116 49·6%) and residual fatigue (96 41·0%). Sequelae were more common in men (vs women; p=0·041), patients aged 65 years or older (vs other age groups; p=0·048), patients with two or more comorbidities (vs one or none; p=0·0006), and patients with a history of smoking (vs no smoking history; p=0·0004). Sequelae were associated with hospitalisation for COVID-19 (p<0·0001), complicated COVID-19 (p<0·0001), and COVID-19 therapy (p=0·0002). With a median post-COVID-19 follow-up of 128 days (95% CI 113–148), COVID-19 sequelae were associated with an increased risk of death (hazard ratio HR 1·80 95% CI 1·18–2·75) after adjusting for time to post-COVID-19 reassessment, sex, age, comorbidity burden, tumour characteristics, anticancer therapy, and COVID-19 severity. Among 466 patients on systemic anti-cancer therapy, 70 (15·0%) permanently discontinued therapy, and 178 (38·2%) resumed treatment with a dose or regimen adjustment. Permanent treatment discontinuations were independently associated with an increased risk of death (HR 3·53 95% CI 1·45–8·59), but dose or regimen adjustments were not (0·84 0·35–2·02).
Sequelae post-COVID-19 affect up to 15% of patients with cancer and adversely affect survival and oncological outcomes after recovery. Adjustments to systemic anti-cancer therapy can be safely pursued in treatment-eligible patients.
National Institute for Health Research Imperial Biomedical Research Centre and the Cancer Treatment and Research Trust.
The omicron (B.1.1.529) variant of SARS-CoV-2 is highly transmissible and escapes vaccine-induced immunity. We aimed to describe outcomes due to COVID-19 during the omicron outbreak compared with the ...prevaccination period and alpha (B.1.1.7) and delta (B.1.617.2) waves in patients with cancer in Europe.
In this retrospective analysis of the multicentre OnCovid Registry study, we recruited patients aged 18 years or older with laboratory-confirmed diagnosis of SARS-CoV-2, who had a history of solid or haematological malignancy that was either active or in remission. Patient were recruited from 37 oncology centres from UK, Italy, Spain, France, Belgium, and Germany. Participants were followed up from COVID-19 diagnosis until death or loss to follow-up, while being treated as per standard of care. For this analysis, we excluded data from centres that did not actively enter new data after March 1, 2021 (in France, Germany, and Belgium). We compared measures of COVID-19 morbidity, which were complications from COVID-19, hospitalisation due to COVID-19, and requirement of supplemental oxygen and COVID-19-specific therapies, and COVID-19 mortality across three time periods designated as the prevaccination (Feb 27 to Nov 30, 2020), alpha-delta (Dec 1, 2020, to Dec 14, 2021), and omicron (Dec 15, 2021, to Jan 31, 2022) phases. We assessed all-cause case-fatality rates at 14 days and 28 days after diagnosis of COVID-19 overall and in unvaccinated and fully vaccinated patients and in those who received a booster dose, after adjusting for country of origin, sex, age, comorbidities, tumour type, stage, and status, and receipt of systemic anti-cancer therapy. This study is registered with ClinicalTrials.gov, NCT04393974, and is ongoing.
As of Feb 4, 2022 (database lock), the registry included 3820 patients who had been diagnosed with COVID-19 between Feb 27, 2020, and Jan 31, 2022. 3473 patients were eligible for inclusion (1640 47·4% were women and 1822 52·6% were men, with a median age of 68 years IQR 57–77). 2033 (58·5%) of 3473 were diagnosed during the prevaccination phase, 1075 (31·0%) during the alpha-delta phase, and 365 (10·5%) during the omicron phase. Among patients diagnosed during the omicron phase, 113 (33·3%) of 339 were fully vaccinated and 165 (48·7%) were boosted, whereas among those diagnosed during the alpha-delta phase, 152 (16·6%) of 915 were fully vaccinated and 21 (2·3%) were boosted. Compared with patients diagnosed during the prevaccination period, those who were diagnosed during the omicron phase had lower case-fatality rates at 14 days (adjusted odds ratio OR 0·32 95% CI 0·19–0·61) and 28 days (0·34 0·16–0·79), complications due to COVID-19 (0·26 0·17–0·46), and hospitalisation due to COVID-19 (0·17 0·09–0·32), and had less requirements for COVID-19-specific therapy (0·22 0·15–0·34) and oxygen therapy (0·24 0·14–0·43) than did those diagnosed during the alpha-delta phase. Unvaccinated patients diagnosed during the omicron phase had similar crude case-fatality rates at 14 days (ten 25% of 40 patients vs 114 17% of 656) and at 28 days (11 27% of 40 vs 184 28% of 656) and similar rates of hospitalisation due to COVID-19 (18 43% of 42 vs 266 41% of 652) and complications from COVID-19 (13 31% of 42 vs 237 36% of 659) as those diagnosed during the alpha-delta phase.
Despite time-dependent improvements in outcomes reported in the omicron phase compared with the earlier phases of the pandemic, patients with cancer remain highly susceptible to SARS-CoV-2 if they are not vaccinated against SARS-CoV-2. Our findings support universal vaccination of patients with cancer as a protective measure against morbidity and mortality from COVID-19.
National Institute for Health and Care Research Imperial Biomedical Research Centre and the Cancer Treatment and Research Trust.
Radical chemoradiotherapy represents the gold standard for locally advanced cervical cancer. However, despite significant progress in improving local tumour control, distant relapse continues to ...impact overall survival. The development of predictive and prognostic biomarkers is consequently important to risk-stratify patients and identify populations at higher risk of poorer treatment response and survival outcomes. Exploratory study of using Magnetic resonance Prognostic Imaging markers for Radiotherapy In Cervix cancer (EMPIRIC) is a prospective exploratory cohort study, which aims to investigate the role of multiparametric functional MRI (fMRI) using diffusion-weighed imaging (DWI), dynamic contrast-enhanced (DCE) and blood oxygen level-dependent imaging (BOLD) MRI to assess treatment response and predict outcomes in patients undergoing radical chemoradiotherapy for cervical cancer.
The study aims to recruit 40 patients across a single-centre over 2 years. Patients undergo multiparametric fMRI (DWI, DCE and BOLD-MRI) at three time points: before, during and at the completion of external beam radiotherapy. Tissue and liquid biopsies are collected at diagnosis and post-treatment to identify potential biomarker correlates against fMRI. The primary outcome is to evaluate sensitivity and specificity of quantitative parameters derived from fMRI as predictors of progression-free survival at 2 years following radical chemoradiotherapy for cervical cancer. The secondary outcome is to investigate the roles of fMRI as predictors of overall survival at 2 years and tumour volume reduction across treatment. Statistical analyses using regression models and survival analyses are employed to evaluate the relationships between the derived parameters, treatment response and clinical outcomes.
The EMPIRIC study received ethical approval from the NHS Health Research Authority (HRA) on 14 February 2022 (protocol number RD2021-29). Confidentiality and data protection measures are strictly adhered to throughout the study. The findings of this study will be disseminated through peer-reviewed publications and scientific conferences, aiming to contribute to the growing body of evidence on the use of multiparametric MRI in cervical cancer management.
NCT05532930.
Although SARS-CoV-2 vaccines immunogenicity in patients with cancer has been investigated, whether they can significantly improve the severity of COVID-19 in this specific population is undefined.
...Capitalizing on OnCovid (NCT04393974) registry data we reported COVID-19 mortality and proxies of COVID-19 morbidity, including post-COVID-19 outcomes, according to the vaccination status of the included patients.
2090 eligible patients diagnosed with COVID-19 between 02/2020 and 11/2021 were included, of whom 1930 (92.3%) unvaccinated, 91 (4.4%) fully vaccinated and 69 (3.3%) partially vaccinated. With the exception of a higher prevalence of patients from the UK (p = 0.0003) and receiving systemic anticancer therapy at COVID-19 diagnosis (p = 0.0082) among fully vaccinated patients, no demographics/oncological features were associated with vaccination status. The 14-days case fatality rate (CFR) (5.5% vs 20.7%, p = 0.0004) and the 28-days CFR (13.2% vs 27.4%, p = 0.0028) demonstrated a significant improvement for fully vaccinated patients in comparison with unvaccinated patients. The receipt of prior full vaccination was also associated with reduced symptomatic COVID-19 (79.1% vs 88.5%, p = 0.0070), need of COVID-19 oriented therapy (34.9% vs 63.2%, p < 0.0001), complications from COVID-19 (28.6% vs 39.4%, p = 0.0379), hospitalizations due to COVID-19 (42.2% vs 52.5%, p = 0.0007) and oxygen therapy requirement (35.7% vs 52%, p = 0.0036). Following Inverse Probability Treatment Weighting (IPTW) procedure no statistically significant difference according to the vaccination status was confirmed; however, all COVID-19 related outcomes were concordantly in favour of full vaccination. Among the 1228 (58.8%) patients who underwent a formal reassessment at participating centres after COVID-19 resolution, fully vaccinated patients experienced less sequelae than unvaccinated patients (6.7% vs 17.2%, p = 0.0320).
This analysis provides initial evidence in support of the beneficial effect of SARS-CoV-2 vaccines against morbidity and mortality from COVID-19 in patients with cancer.
•Immunogenicity of SARS-CoV-2 vaccines in patients with cancer has been investigated.•There is a need for evidence of SARS-CoV-2 vaccines’ efficacy from large populations.•In this analysis, vaccinated patients experienced improved COVID-19 outcomes.•SARS-CoV-2 vaccines are effective in reducing severe COVID-19 in patients with cancer.
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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 (CFR
14
) 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 CFR
14
(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.Table: see text
Treatment of metastatic hormone‐sensitive prostate cancer Rane, Jayant K; Chowdhury, Amani; Kinnaird, William ...
Trends in urology & men's health,
November/December 2021, 2021-11-00, 20211101, Letnik:
12, Številka:
6
Journal Article
Recenzirano
Odprti dostop
Men with metastatic prostate cancer have a significantly reduced median five‐year survival compared with that associated with the cancer overall. Clinical trials are exploring the most effective ...treatment strategies for metastatic hormone‐sensitive prostate cancer to intervene before transformation to castration‐resistant prostate cancers when options are limited.
Radio fingerprinting uniquely identifies wireless devices by leveraging tiny hardware-level imperfections inevitably present in off-the-shelf radio circuitry. This way, devices can be directly ...identified at the physical layer by analyzing the unprocessed received waveform - thus avoiding energy-expensive upper-layer cryptography that resource-challenged embedded devices may not be able to afford. Recent advances have proven that convolutional neural networks (CNNs) - thanks to their multidimensional mappings - can achieve fingerprinting accuracy levels impossible to achieve by traditional low-dimensional algorithms. The same research, however, has also suggested that the wireless channel may negatively impact the accuracy of CNN-based radio fingerprinting algorithms by making device-unique hardware imperfections much harder to recognize.In spite of the growing interest in radio fingerprinting research by academia and DARPA, the wireless research community still lacks (i) a large-scale open dataset for radio fingerprinting collected in diverse environments and rich, diverse, channel conditions; and (ii) a full-fledged, systematic, quantitative investigation of the impact of the wireless channel on the accuracy of CNN-based radio fingerprinting algorithms. The key contribution of this paper is to bridge this gap by (i) collecting and sharing with the community more than 7TB of wireless data obtained from 20 wireless devices with identical RF circuitry (and thus, worst-case scenario for fingerprinting) over the course of several days in (a) an anechoic chamber, (b) in-the-wild testbed, and (c) with cable connections; and (ii) providing a first-of-its-kind evaluation of the impact of the wireless channel on CNN-based fingerprinting algorithms through (a) the 7TB experimental dataset and (b) a 400GB dataset provided by DARPA containing hundreds of thousands of transmissions from thousands of WiFi and ADS-B devices with different SNR conditions. Experimental results conclude that (i) the wireless channel impacts the classification accuracy significantly, i.e., from 85% to 9% and from 30% to 17% in the experimental and DARPA dataset, respectively; and that (ii) equalizing I/Q data can increase the accuracy to a significant extent (i.e., by up to 23%) when the number of devices increases significantly.
The effects of process conditions on Fischer–Tropsch Synthesis (FTS) product distributions were studied using a fixed-bed microreactor and a Co–Mn/CNT catalyst. Cobalt and Manganese, supported on ...Carbon Nanotubes (CNT) catalyst were prepared by a Strong Electrostatic Adsorption (SEA) method. CNT supports were initially acid and thermally treated in order to functionalize support to uptake more Co clusters. Catalyst samples were characterized by Transmitted Electron Microscope (TEM), particle size analyzer, and Thermal Gravimetric Analysis (TGA). TEM images showed catalyst metal particle intake on CNT support with different Co and Mn loading percentage. Performance test of Co–Mn/CNT in Fischer–Tropsch synthesis (FTS) was carried out in a fixed-bed micro-reactor at different pressures (from 1 atm to 25 atm), H2/CO ratio (0.5–2.5), and reduction temperature and duration. The reactor was connected to the online Gas Chromatograph (GC) for product analysis. It was found that the reaction conditions have the dominant effect on product selectivity. Cobalt catalyst supported on acid and thermal pre-treated CNT at optimum reaction condition resulted in CO conversion of 58.7% and C5+ selectivity of 59.1%.
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