Over the past decade, various liquid biopsy techniques have emerged as viable alternatives to the analysis of traditional tissue biopsy samples. Such surrogate 'biopsies' offer numerous advantages, ...including the relative ease of obtaining serial samples and overcoming the issues of interpreting one or more small tissue samples that might not reflect the entire tumour burden. To date, the majority of research in the area of liquid biopsies has focused on blood-based biomarkers, predominantly using plasma-derived circulating tumour DNA (ctDNA). However, ctDNA can also be obtained from various non-blood sources and these might offer unique advantages over plasma ctDNA. In this Review, we discuss advances in the analysis of ctDNA from non-blood sources, focusing on urine, cerebrospinal fluid, and pleural or peritoneal fluid, but also consider other sources of ctDNA. We discuss how these alternative sources can have a distinct yet complementary role to that of blood ctDNA analysis and consider various technical aspects of non-blood ctDNA assay development. We also reflect on the settings in which non-blood ctDNA can offer distinct advantages over plasma ctDNA and explore some of the challenges associated with translating these alternative assays from academia into clinical use.
Patients with cancer are purported to have poor COVID-19 outcomes. However, cancer is a heterogeneous group of diseases, encompassing a spectrum of tumour subtypes. The aim of this study was to ...investigate COVID-19 risk according to tumour subtype and patient demographics in patients with cancer in the UK.
We compared adult patients with cancer enrolled in the UK Coronavirus Cancer Monitoring Project (UKCCMP) cohort between March 18 and May 8, 2020, with a parallel non-COVID-19 UK cancer control population from the UK Office for National Statistics (2017 data). The primary outcome of the study was the effect of primary tumour subtype, age, and sex and on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) prevalence and the case–fatality rate during hospital admission. We analysed the effect of tumour subtype and patient demographics (age and sex) on prevalence and mortality from COVID-19 using univariable and multivariable models.
319 (30·6%) of 1044 patients in the UKCCMP cohort died, 295 (92·5%) of whom had a cause of death recorded as due to COVID-19. The all-cause case–fatality rate in patients with cancer after SARS-CoV-2 infection was significantly associated with increasing age, rising from 0·10 in patients aged 40–49 years to 0·48 in those aged 80 years and older. Patients with haematological malignancies (leukaemia, lymphoma, and myeloma) had a more severe COVID-19 trajectory compared with patients with solid organ tumours (odds ratio OR 1·57, 95% CI 1·15–2·15; p<0·0043). Compared with the rest of the UKCCMP cohort, patients with leukaemia showed a significantly increased case–fatality rate (2·25, 1·13–4·57; p=0·023). After correction for age and sex, patients with haematological malignancies who had recent chemotherapy had an increased risk of death during COVID-19-associated hospital admission (OR 2·09, 95% CI 1·09–4·08; p=0·028).
Patients with cancer with different tumour types have differing susceptibility to SARS-CoV-2 infection and COVID-19 phenotypes. We generated individualised risk tables for patients with cancer, considering age, sex, and tumour subtype. Our results could be useful to assist physicians in informed risk–benefit discussions to explain COVID-19 risk and enable an evidenced-based approach to national social isolation policies.
University of Birmingham and University of Oxford.
Purpose of Review
Liquid biopsies, including circulating tumour DNA (ctDNA), can inform a variety of clinical questions. This review examines the potential role of ctDNA as a clinical tool to inform ...clinical decision-making from early to late stage cutaneous melanoma.
Recent Findings
In pre-clinical studies, ctDNA has been shown to detect minimal residual disease and molecular relapse; predict and monitor response to therapy; and identify key resistance mechanisms. Here, we examine the potential utility of ctDNA and discuss its limitations for use in patients with melanoma. We present novel clinical trials, which are testing its value as a tool to augment clinical decision-making. Finally, we discuss the steps that are needed to ensure that ctDNA is used optimally in order to improve outcomes for patients with melanoma.
Summary
Preclinical studies have shown that ctDNA has huge potential to provide real-time information about disease status in patients with melanoma. It is now time to test it rigorously within clinical trials to assess how it can be optimally used to benefit patients in the clinic.
Advances in research have transformed the management of melanoma in the past decade. In parallel, patient advocacy has gained traction, and funders are increasingly prioritizing patient and public ...involvement. Here we discuss the ways in which patients and the public can be engaged in different stages of the research process, from developing, prioritizing and refining the research question to preclinical studies and clinical trials, then finally to ongoing research in the clinic. We discuss the challenges and opportunities that exist at each stage in order to ensure that a representative population of patients and the public contribute to melanoma research both now and in the future.
The COVID-19 pandemic has been a disruptive event for cancer patients, especially those with haematological malignancies (HM). They may experience a more severe clinical course due to impaired immune ...responses. This multi-center retrospective UK audit identified cancer patients who had SARS-CoV-2 infection between 1 March and 10 June 2020 and collected data pertaining to cancer history, COVID-19 presentation and outcomes. In total, 179 patients were identified with a median age of 72 (IQR 61, 81) and follow-up of 44 days (IQR 42, 45). Forty-one percent were female and the overall mortality was 37%. Twenty-nine percent had HM and of these, those treated with chemotherapy in the preceding 28 days to COVID-19 diagnosis had worse outcome compared with solid malignancy (SM): 62% versus 19% died HR 8.33 (95% CI, 2.56-25), p < 0.001. Definite or probable nosocomial SARS-CoV-2 transmission accounted for 16% of cases and was associated with increased risk of death (HR 2.47, 95% CI 1.43-4.29, p = 0.001). Patients with haematological malignancies and those who acquire nosocomial transmission are at increased risk of death. Therefore, there is an urgent need to reassess shielding advice, reinforce stringent infection control, and ensure regular patient and staff testing to prevent nosocomial transmission.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
2522
Background: Pre-existing autoimmune disease (AID) potentially increases the propensity for the development of immune related adverse events (irAE) in response to oncological immune checkpoint ...inhibitors (ICIs) is biologically plausible and clinically observed. However, due to consistent clinical trial exclusion of those with pre-existing AID, the impact on the frequency and severity of irAEs is uncertain. Here we analyse this relationship in a large, real-world, UK multi-centre cohort. Methods: A retrospective analysis of 2049 patients treated with ICIs over a two year period was undertaken across 12 National Health Service centres by the UK National Oncology Trainees Collaborative for Healthcare Research (NOTCH). Patients received ICIs as standard of care for malignant melanoma, non-small cell lung cancer and renal cell carcinoma. The presence of pre-existing AIDs was assessed and classified as either autoantibody driven or autoinflammatory then correlated with clinically significant irAEs (i.e. ≥grade 2 or all-grade endocrinopathies). Statistical analyses included T-test, Mann-Whitney and Chi-squared. For overall survival (OS) Kaplan-Meier and log-rank tests were utilised. Results: Pre-existing AID were present in 13% (n = 257) of the overall cohort. Pre-existing endocrinopathies (30%; n = 76) were most common followed by rheumatological AIDs (18%; n = 46). In the pre-existing AID cohort there was a female predominance (48% vs 39%; p = 0.006) but no difference in smoking history (p = 0.074) or ethnicity (p = 0.12). There was no difference in ICI treatment between those with and without pre-existing AID (p = 0.2800). IrAEs occurred in 45% (n = 117) patients with pre-existing AID vs 33% (n = 583) without (p£0.001). The median time to onset of irAEs was similar. IrAEs with an increased incidence in the pre-existing AID cohort were colitis (p = < 0.001), arthralgia (p = 0.008) and dermatological irAEs (p = 0.014). There was no difference in the incidence of irAEs in patients with autoantibody driven vs autoinflammatory pre-existing AID (44.0 % vs 44.8%, p = 0.905). In the overall cohort, those with pre-existing AIDs had a median OS of 20.4 months (95% CI: 19.4-21.7) vs 14.1 months (95% CI: 12.8-16.3) in those without pre-existing AID (p = 0.004). Conclusions: This large multi-centre ICI-treated cohort demonstrates that pre-existing AID is a predisposing factor for the development of irAEs, however the incidence is lower than previously quoted. The pathological basis of pre-existing AID did not differentially affect irAE manifestation. Patients with pre-existing AID had improved OS compared to those without which has not been observed in previously reported studies. ICI treatment should be considered in those with pre-existing AID but further studies are needed to determine how best to optimise outcomes whilst mitigating the impact of irAEs.
Abstract only
12026
Background: Immune checkpoint inhibitor (ICI) therapy is now commonly used in a range of tumours and settings. Most data relating to outcomes and rates of immune-related adverse ...events (irAE) is derived from clinical trial or registry populations and small case series. Limited data exist for patients aged > 75 years. Here we present a multi-centre, real-world analysis of the outcomes and incidence of irAEs in older adults managed within a single comprehensive public health service. We also compare these outcomes to younger patients in the same cohort. Methods: A retrospective analysis of 2049 patients treated with ICIs was undertaken across 12 centres. All patients were managed within the UK National Health Service outside of a trial setting between June 2016 and September 2018. Patients received either ICI monotherapy (MT) or duel combination ICI therapy (CT) for malignant melanoma (MM), non-small cell lung cancer (NSCLC) or renal cell cancer (RCC). Data were collected using a standardised, collection tool. IrAEs ≥ grade 2 or all-grade endocrinopathies were recorded as per the Common Terminology Criteria for Adverse Events (V5) (CTCAE). Statistical analyses were performed using T-tests, Mann-Whitney and Chi-squared. Kaplan-Meier analysis and log-rank test were used for overall survival (OS) analysis. Results: 409 (20%) of patients were aged > 75 years(a), 1413 (69%) aged 50-75(b) and 227 (11.1%) aged < 50(c). There was no difference in sex, ethnicity or PD-L1 status (in the NSCLC cohort) between groups. Older patients were less likely to receive combination therapy (3%(a) v 13%(b) v 34%(c), p < 0.001). There was no difference in median OS across age groups in the cohort as a whole (p = 0.822) or for the individual tumour groups when treated with single agent ICI. Across the total cohort patients aged > 75 had no increased risk of any irAE (35%(a) v 33%(b) v 41%(c),p = 0.074). However there was an increase in irAEs in older patients treated with MT (36%(a) v 26(b) v 25%(c), p = 0.011) However there was no difference in the > 75s with regard to severe (G3/4) toxicity, toxicity type, admission or discontinuation due to toxicity in the aPD-1 group. In the overall cohort younger patients were more likely to develop irAEs and be admitted. Conclusions: Patients aged > 75 years treated with anti-PD1 therapy in the standard of care setting derive similar survival benefit to younger patients. There was no increase in ≥G3 toxicity. Our data support the safety of single agent aPD-1 ICI therapy in older adults and provide reassurance relating to the impact of toxicity.Table: see text
Highlights • A third of tuberculous spondylodiscitis patients had more than one region affected. • Age and ethnicity differs between tuberculous and pyogenic spondylodiscitis. • Thoracic then lumbar ...involvement were commonest in tuberculous spondylodiscitis. • Lumbar then thoracic involvement were commonest in pyogenic spondylodiscitis.
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