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The COVID-19 pandemic has led to a range of novel and adaptive research designs. In this perspective, we use our experience coordinating the National COVID Cancer Antibody Survey to demonstrate how a balance between speed and integrity can be achieved within a hyper-accelerated study design. Using the COVID-19 pandemic as an example, we show this approach is necessary in the face of uncertain and evolving situations wherein reliable information is needed in a timely fashion to guide policy. We identify streamlined participant involvement, healthcare systems integration, data architecture and real-world real-time analytics as key areas that differentiate this design from traditional cancer trials, and enable rapid results. Caution needs to be taken to avoid the exclusion of patient subgroups without digital access or literacy. We summarise the merits and defining features of hyper-accelerated cancer studies.
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COVID-19 , Neoplasias , Humanos , Pandemias , Imunoglobulinas , Atenção à SaúdeRESUMO
BACKGROUND: People with cancer are at increased risk of hospitalisation and death following infection with SARS-CoV-2. Therefore, we aimed to conduct one of the first evaluations of vaccine effectiveness against breakthrough SARS-CoV-2 infections in patients with cancer at a population level. METHODS: In this population-based test-negative case-control study of the UK Coronavirus Cancer Evaluation Project (UKCCEP), we extracted data from the UKCCEP registry on all SARS-CoV-2 PCR test results (from the Second Generation Surveillance System), vaccination records (from the National Immunisation Management Service), patient demographics, and cancer records from England, UK, from Dec 8, 2020, to Oct 15, 2021. Adults (aged ≥18 years) with cancer in the UKCCEP registry were identified via Public Health England's Rapid Cancer Registration Dataset between Jan 1, 2018, and April 30, 2021, and comprised the cancer cohort. We constructed a control population cohort from adults with PCR tests in the UKCCEP registry who were not contained within the Rapid Cancer Registration Dataset. The coprimary endpoints were overall vaccine effectiveness against breakthrough infections after the second dose (positive PCR COVID-19 test) and vaccine effectiveness against breakthrough infections at 3-6 months after the second dose in the cancer cohort and control population. FINDINGS: The cancer cohort comprised 377 194 individuals, of whom 42 882 had breakthrough SARS-CoV-2 infections. The control population consisted of 28 010 955 individuals, of whom 5 748 708 had SARS-CoV-2 breakthrough infections. Overall vaccine effectiveness was 69·8% (95% CI 69·8-69·9) in the control population and 65·5% (65·1-65·9) in the cancer cohort. Vaccine effectiveness at 3-6 months was lower in the cancer cohort (47·0%, 46·3-47·6) than in the control population (61·4%, 61·4-61·5). INTERPRETATION: COVID-19 vaccination is effective for individuals with cancer, conferring varying levels of protection against breakthrough infections. However, vaccine effectiveness is lower in patients with cancer than in the general population. COVID-19 vaccination for patients with cancer should be used in conjunction with non-pharmacological strategies and community-based antiviral treatment programmes to reduce the risk that COVID-19 poses to patients with cancer. FUNDING: University of Oxford, University of Southampton, University of Birmingham, Department of Health and Social Care, and Blood Cancer UK.
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COVID-19 , Neoplasias , Vacinas Virais , Adolescente , Adulto , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Estudos de Casos e Controles , Humanos , Neoplasias/epidemiologia , SARS-CoV-2 , Eficácia de VacinasRESUMO
Importance: Accurate identification of patient groups with the lowest level of protection following COVID-19 vaccination is important to better target resources and interventions for the most vulnerable populations. It is not known whether SARS-CoV-2 antibody testing has clinical utility for high-risk groups, such as people with cancer. Objective: To evaluate whether spike protein antibody vaccine response (COV-S) following COVID-19 vaccination is associated with the risk of SARS-CoV-2 breakthrough infection or hospitalization among patients with cancer. Design, Setting, and Participants: This was a population-based cross-sectional study of patients with cancer from the UK as part of the National COVID Cancer Antibody Survey. Adults with a known or reported cancer diagnosis who had completed their primary SARS-CoV-2 vaccination schedule were included. This analysis ran from September 1, 2021, to March 4, 2022, a period covering the expansion of the UK's third-dose vaccination booster program. Interventions: Anti-SARS-CoV-2 COV-S antibody test (Elecsys; Roche). Main Outcomes and Measures: Odds of SARS-CoV-2 breakthrough infection and COVID-19 hospitalization. Results: The evaluation comprised 4249 antibody test results from 3555 patients with cancer and 294â¯230 test results from 225â¯272 individuals in the noncancer population. The overall cohort of 228â¯827 individuals (patients with cancer and the noncancer population) comprised 298â¯479 antibody tests. The median age of the cohort was in the age band of 40 and 49 years and included 182â¯741 test results (61.22%) from women and 115â¯737 (38.78%) from men. There were 279â¯721 tests (93.72%) taken by individuals identifying as White or White British. Patients with cancer were more likely to have undetectable anti-S antibody responses than the general population (199 of 4249 test results [4.68%] vs 376 of 294â¯230 [0.13%]; P < .001). Patients with leukemia or lymphoma had the lowest antibody titers. In the cancer cohort, following multivariable correction, patients who had an undetectable antibody response were at much greater risk for SARS-CoV-2 breakthrough infection (odds ratio [OR], 3.05; 95% CI, 1.96-4.72; P < .001) and SARS-CoV-2-related hospitalization (OR, 6.48; 95% CI, 3.31-12.67; P < .001) than individuals who had a positive antibody response. Conclusions and Relevance: The findings of this cross-sectional study suggest that COV-S antibody testing allows the identification of patients with cancer who have the lowest level of antibody-derived protection from COVID-19. This study supports larger evaluations of SARS-CoV-2 antibody testing. Prevention of SARS-CoV-2 transmission to patients with cancer should be prioritized to minimize impact on cancer treatments and maximize quality of life for individuals with cancer during the ongoing pandemic.
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COVID-19 , Neoplasias , Vacinas , Feminino , Adulto , Masculino , Humanos , Pessoa de Meia-Idade , Vacinas contra COVID-19 , Glicoproteína da Espícula de Coronavírus , Estudos Transversais , Formação de Anticorpos , Qualidade de Vida , COVID-19/epidemiologia , COVID-19/prevenção & controle , SARS-CoV-2 , Neoplasias/epidemiologia , Anticorpos Antivirais , Atenção à SaúdeRESUMO
Patients with cancer are at increased risk of hospitalisation and mortality following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, the SARS-CoV-2 phenotype evolution in patients with cancer since 2020 has not previously been described. We therefore evaluated SARS-CoV-2 on a UK populationscale from 01/11/2020-31/08/2022, assessing case-outcome rates of hospital assessment(s), intensive care admission and mortality. We observed that the SARS-CoV-2 disease phenotype has become less severe in patients with cancer and the non-cancer population. Case-hospitalisation rates for patients with cancer dropped from 30.58% in early 2021 to 7.45% in 2022 while case-mortality rates decreased from 20.53% to 3.25%. However, the risk of hospitalisation and mortality remains 2.10x and 2.54x higher in patients with cancer, respectively. Overall, the SARS-CoV-2 disease phenotype is less severe in 2022 compared to 2020 but patients with cancer remain at higher risk than the non-cancer population. Patients with cancer must therefore be empowered to live more normal lives, to see loved ones and families, while also being safeguarded with expanded measures to reduce the risk of transmission.
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COVID-19 , Neoplasias , Humanos , Masculino , Feminino , Estudos de Casos e Controles , Resultado do Tratamento , Neoplasias/complicações , Neoplasias/epidemiologia , COVID-19/complicações , COVID-19/epidemiologia , Inglaterra/epidemiologia , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou maisRESUMO
PURPOSE: People living with cancer and haematological malignancies are at an increased risk of hospitalisation and death following infection with acute respiratory syndrome coronavirus 2. Coronavirus third dose vaccine boosters are proposed to boost waning immune responses in immunocompromised individuals and increase coronavirus protection; however, their effectiveness has not yet been systematically evaluated. METHODS: This study is a population-scale real-world evaluation of the United Kingdom's third dose vaccine booster programme for cancer patients from 8th December 2020 to 7th December 2021. The cancer cohort comprises individuals from Public Health England's national cancer dataset, excluding individuals less than 18 years. A test-negative case-control design was used to assess the third dose booster vaccine effectiveness. Multivariable logistic regression models were fitted to compare risk in the cancer cohort relative to the general population. RESULTS: The cancer cohort comprised of 2,258,553 tests from 361,098 individuals. Third dose boosters were evaluated by reference to 87,039,743 polymerase chain reaction coronavirus tests. Vaccine effectiveness against breakthrough infections, symptomatic infections, coronavirus hospitalisation and death in cancer patients were 59.1%, 62.8%, 80.5% and 94.5%, respectively. Lower vaccine effectiveness was associated with a cancer diagnosis within 12 months, lymphoma, recent systemic anti-cancer therapy (SACT) or radiotherapy. Patients with lymphoma had low levels of protection from symptomatic disease. In spite of third dose boosters, following multivariable adjustment, individuals with cancer remain at an increased risk of coronavirus hospitalisation and death compared to the population control (OR 3.38, 3.01, respectively. p < 0.001 for both). CONCLUSIONS: Third dose boosters are effective for most individuals with cancer, increasing protection from coronavirus. However, their effectiveness is heterogenous and lower than the general population. Many patients with cancer will remain at the increased risk of coronavirus infections even after 3 doses. In the case of patients with lymphoma, there is a particularly strong disparity of vaccine effectiveness against breakthrough infection and severe disease. Breakthrough infections will disrupt cancer care and treatment with potentially adverse consequences on survival outcomes. The data support the role of vaccine boosters in preventing severe disease, and further pharmacological intervention to prevent transmission and aid viral clearance to limit the disruption of cancer care as the delivery of care continues to evolve during the coronavirus pandemic.
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COVID-19 , Neoplasias , COVID-19/epidemiologia , COVID-19/prevenção & controle , Hospitalização , Humanos , Pandemias , Vacinação , Eficácia de VacinasRESUMO
The COVID-19 pandemic is an era-defining, international emergency impacting the global economy, politics and countless individual lives. People living with cancer have increased risk of hospitalisation and mortality from COVID-19. There are limited data regarding vaccine efficacy in people with cancer, with lack of empirical evidence to guide vaccine strategy in cancer patients fostering uncertainty. Vulnerable groups, for whom vaccination protection may be attenuated, now carry the greatest burden of risk amongst the population. The cancer community needs to reconsider the potential on-going impact of COVID-19 and develop and plan new programs of work to mitigate it. Multiple potential future scenarios now exist, ranging from full protection from COVID-19 for cancer patients via herd immunity to viral evolution for vaccine resistance and increased virulence. Defining those most vulnerable to COVID-19 post-vaccination will require large-scale data and evidence to comprehensively identify factors that reduce vaccine efficacy. Once identified, protecting these groups through transmission and mortality risk reduction will become paramount. As the pandemic progresses, "protecting the vulnerable" may enable a return to normal for the majority, whilst still protecting individuals living with and beyond cancer who already live with the challenges of having a cancer diagnosis.
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A 56-year-old man undergoing immunotherapy treatment for metastatic melanoma presented with sudden onset testicular pain radiating into his abdomen. On examination, the abdomen was generally tender with associated guarding. Imaging revealed a perforation of the small bowel at the site of a metastatic lesion. Histology revealed that this process was non-inflammatory in nature. A diagnosis of small bowel perforation secondary to immunotherapy driven rapid tumour regression was made. The patient was treated with a small bowel resection plus anastomosis and made a full recovery. This case highlights the rare potential side effect of immunotherapy in causing non-inflammatory bowel perforations secondary to rapid tumour regression.