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Summary: Two early papers expressing conflicting views on the occurrence of effective immune attack against cancers stimulate an analysis of the gradual development of an understanding of tumour biology. This understanding has led to the development of the strikingly effective check point blocking and CART anti-cancer immunotherapies, and the promise of more widely applicable therapies based on T cell attracting genetically engineered monoclonal antibodies. [ABSTRACT FROM AUTHOR]

Background: Immune-related adverse events (irAE) induced by immune checkpoint inhibitors (ICI) are a treatment-limiting barrier. There are few large-scale studies that estimate irAE prevalence. This paper presents a systematic review that reports the prevalence of irAE by cancer type and ICI. Methods: A systematic review was undertaken in MEDLINE OVID, EMBASE and Web of Science databases from 2017–2021. A total of 293 studies were identified for analysis and, of these, event rate was calculated for 272 studies, which involved 58,291 patients with irAE among 305,879 total patients on ICI. Event rate was calculated by irAE and ICI type. Results: Mean event rate for general irAE occurrence across any grade was 40.0% (37.3–42.7%) and high grade was 19.7% (15.8–23.7%). Mean event rates for six specific types of irAE are reported. Mean event rate for ICI monotherapy was 30.5% (28.1–32.9%), 45.7% (29.6–61.7%) for ICI combination therapy, and 30.0% (25.3–34.6%) for both ICI monotherapy and combination therapy. Conclusion: This systematic review characterises irAE prevalence across current research that examines irAE risk factors across cancers and ICI. The findings confirms that irAE occurrence is very common in the real-world setting, both high grade and irAE across any grade. [ABSTRACT FROM AUTHOR]

This paper outlines the impact of the COVID-19 pandemic on cancer services in the UK including screening, symptomatic diagnosis, treatment pathways and projections on clinical outcomes as a result of these care disruptions. A restoration of cancer services to pre-pandemic levels is not likely to mitigate this adverse impact, particularly with an ageing population and increased cancer burden. New cancer cases are projected to rise to over 500,000 per year by 2035, with over 4 million people living with and beyond cancer. This paper calls for a strategic transformation to prioritise effort on the basis of available datasets and evidence—in particular, to prioritise cancers where an earlier diagnosis is feasible and clinically useful with a focus on mortality benefit by preventing emergency presentations by harnessing data and analytics. This could be delivered by a focus on underperforming groups/areas to try and reduce inequity, linking near real-time datasets with clinical decision support systems at the primary and secondary care levels, promoting the use of novel technologies to improve patient uptake of services, screening and diagnosis, and finally, upskilling and cross-skilling healthcare workers to expand supply of diagnostic and screening services. [ABSTRACT FROM AUTHOR]

This paper summarises the position of ESGO and EFC on cervical screening based on existing guidelines and opinions of a team of lead experts. HPV test is replacing cytology as this offers greater protection against cervical cancer and allows longer screening intervals. Only a dozen of HPV tests are considered as clinically validated for screening. The lower specificity of HPV test dictates the use of triage tests that can select women for colposcopy. Reflex cytology is currently the only well validated triage test; HPV genotyping and p16 immunostaining may be used in the future, although methylation assays and viral load also look promising. A summary of quality assurance benchmarks is provided, and the importance to audit the screening histories of women who developed cancer is noted as a key objective. HPV-based screening is more cost-effective than cytology or cotesting. HPV-based screening should continue in the post-vaccination era. Only a fraction of the female population is vaccinated, and this varies across countries. A major challenge will be to personalise screening frequency according to vaccination status. Still the most important factor for successful prevention by screening is high population coverage and organised screening. Screening with self-sampling to reach under-screened women is promising. [ABSTRACT FROM AUTHOR]

Background: We proposed the Physical Activity and Cancer Control (PACC) framework in 2007 to help organise, focus, and stimulate research on physical activity in eight cancer control categories: prevention, detection, treatment preparation/coping, treatment coping/effectiveness, recovery/rehabilitation, disease prevention/health promotion, palliation, and survival. Methods: This perspective paper provides a high-level overview of the scientific advances in physical activity research across cancer control categories, summarises current guidelines, updates the PACC framework, identifies remaining and emerging knowledge gaps, and provides future research directions. Results: Many scientific advances have been made that are reflected in updated physical activity guidelines for six of the cancer control categories apart from detection and palliation. Nevertheless, the minimal and optimal type, dose, and timing of physical activity across cancer control categories remain unknown, especially for the understudied population subgroups defined by cancer type, age, race/ethnicity, and resource level of regions/countries. Conclusion: To achieve the full benefit of physical activity in cancer control, future research should use innovative study designs that include diverse at-risk populations and understudied cancer sites. Additionally, effective behaviour change strategies are needed to increase physical activity levels across populations that use implementation science to accelerate the translation from evidence generation into practical, real-world interventions. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic brought unplanned service disruption for breast cancer diagnostic, treatment and support services. This scoping review describes these changes and their impact in the UK and the Republic of Ireland based on studies published between January 2020 and August 2023. Thirty-four of 569 papers were included. Data were extracted and results thematically organized. Findings include fewer new cases; stage shift (fewer early- and more late-stage disease); and changes to healthcare organization, breast screening and treatment. Examples are accepting fewer referrals, applying stricter referral criteria and relying more on virtual consultations and multi-disciplinary meetings. Screening service programs paused during the pandemic before enacting risk-based phased restarts with longer appointment times to accommodate reduced staffing numbers and enhanced infection-control regimes. Treatments shifted from predominantly conventional to hypofractionated radiotherapy, fewer surgical procedures and increased use of bridging endocrine therapy. The long-term impact of such changes are unknown so definitive guidelines for future emergencies are not yet available. Cancer registries, with their large sample sizes and population coverage, are well placed to monitor changes to stage and survival despite difficulties obtaining definitive staging during diagnosis because surgery and pathological assessments are delayed. Multisite longitudinal studies can also provide guidance for future disaster preparedness. [ABSTRACT FROM AUTHOR]

Immunotherapy with checkpoint inhibitors against programmed cell death receptor (PD-1) and programmed cell death ligand (PD-L1) has been implemented in the treatment pathway of patients with non-small cell lung cancer (NSCLC) from locally advanced disease to the metastatic setting. This approach has resulted in improved survival and a more favourable toxicity profile when compared with chemotherapy. Following the successful introduction of single-agent immunotherapy, current clinical trials are focusing on combination treatments with chemotherapy or radiotherapy or even other immunotherapeutic agents. However, most of the data available from these trials are derived from, and therefore might be more applicable to younger and fitter patients rather than older and often frail lung cancer real-world patients. This article provides a detailed review of these immunotherapy agents with a focus on the data available regarding older NSCLC patients and makes recommendations to fill evidence gaps in this patient population. [ABSTRACT FROM AUTHOR]

The article reports on several research papers related to cancer and its treatment. It informs that loss of the apoptotic response has been implicated in carcinogenesis as a consequence of increased survival of DNA-damage bearing cells. Many cancer cells have an inherent resistance to chemotherapy due to the abnormal expression of anti-apoptosis genes. The increased risk of cancer in immunosuppressed patients after organ transplantation, and in patients with inherited defects in immune function, such as severe combined immune deficiency, was thought to support the immune surveillance hypothesis.

Presents invited papers on cancer. 'Preliminary Results of a MRC Randomised Controlled Trial of Post-Operative Irrigation of Superficial Bladder Cancer,' by P. Whelan, G. Griffiths, M. Stower, D. Wallace, J. Hetherington, T. Hargreave, P. English, P. Weston, M. Parmar; 'New Ways to Exploit Tumour Hypoxia,' by M. Brown; 'Measuring Tumour Hypoxia in the Clinic,' by C. West.

In current clinical practice, radiotherapy (RT) is prescribed as a pre-determined total dose divided over daily doses (fractions) given over several weeks. The treatment response is typically assessed months after the end of RT. However, the conventional one-dose-fits-all strategy may not achieve the desired outcome, owing to patient and tumor heterogeneity. Therefore, a treatment strategy that allows for RT dose personalization based on each individual response is preferred. Multiple strategies have been adopted to address this challenge. As an alternative to current known strategies, artificial intelligence (AI)-derived mechanism-independent small data phenotypic medicine (PM) platforms may be utilized for N-of-1 RT personalization. Unlike existing big data approaches, PM does not engage in model refining, training, and validation, and guides treatment by utilizing prospectively collected patient's own small datasets. With PM, clinicians may guide patients' RT dose recommendations using their responses in real-time and potentially avoid over-treatment in good responders and under-treatment in poor responders. In this paper, we discuss the potential of engaging PM to guide clinicians on upfront dose selections and ongoing adaptations during RT, as well as considerations and limitations for implementation. For practicing oncologists, clinical trialists, and researchers, PM can either be implemented as a standalone strategy or in complement with other existing RT personalizations. In addition, PM can either be used for monotherapeutic RT personalization, or in combination with other therapeutics (e.g. chemotherapy, targeted therapy). The potential of N-of-1 RT personalization with drugs will also be presented. [ABSTRACT FROM AUTHOR]

The article presents several studies related to cancer research. Certain alkylating agents because of their toxic properties, are also used for cancer chemotherapy. These affect very different target cell populations. Results on its study demonstrate that global cellular responses to alkylation damage are far more complex than first thought. It also discusses about replicating adenoviruses that target colon cancer. Adenoviruses that were developed, selectively replicate in cells with activated Wnt signaling by inserting binding sites for the Tcf family of transcription factors in the early promoters of human adenovirus 5.

Detecting cancer early is essential to improving cancer outcomes. Minoritized groups remain underrepresented in early detection cancer research, which means that findings and interventions are not generalisable across the population, thus exacerbating disparities in cancer outcomes. In light of these challenges, this paper sets out twelve recommendations to build relations of trust and include minoritized groups in ED cancer research. The Recommendations were formulated by a range of stakeholders at the 2022 REPRESENT consensus-building workshop and are based on empirical data, including a systematic literature review and two ethnographic case studies in the US and the UK. The recommendations focus on: Long-term relationships that build trust; Sharing available resources; Inclusive and accessible communication; Harnessing community expertise; Unique risks and benefits; Compensation and support; Representative samples; Demographic data; Post-research support; Sharing results; Research training; Diversifying research teams. For each recommendation, the paper outlines the rationale, specifications for how different stakeholders may implement it, and advice for best practices. Instead of isolated recruitment, public involvement and engagement activities, the recommendations here aim to advance mutually beneficial and trusting relationships between researchers and research participants embedded in ED cancer research institutions. [ABSTRACT FROM AUTHOR]

Interest in understanding the relationship between body composition and cancer survival has remained strong for decades, with a number of recent systematic reviews on the topic. However, the current state of evidence is based on heterogeneous exposure definitions based on anthropometry, yielding inconsistent findings with regard to this association. Recently the field has taken an exciting direction with the application of radiological assessments to measure specific aspects of body composition, yet reconciliation of findings from these modern assessment tools with those from the historic use of anthropometric data proves challenging. In this paper, I briefly review the biological basis for a link between body composition and cancer survival and summarize the epidemiological evidence with consideration to specific exposure measures. As enthusiasm is building around novel assessments, I conclude with a discussion of issues that researchers should be aware of when interpreting results from these new modalities. [ABSTRACT FROM AUTHOR]

The article reports on several research papers related to cancer and its treatment. It states that intensive, high dose therapy with meiphalan yields high remission rates but evidence on survival benefits has been inconclusive. It also focuses on the roles of adjuvant chemoradiotherapy and adjuvant chemotherapy in pancreatic cancer remain uncertain. The article also reveals that removing the internal mammary nodes remains a difficult routine procedure. Due to the relatively small percentage of patients that have positive internal mammary nodes with negative axillary status. The roles of adjuvant chemoradiotherapy and adjuvant chemotherapy in pancreatic cancer remain uncertain.

Summarizes the proceedings of the UKCCCR Trials Committee related to management of elderly cancer patients and their entry into clinical trials. Terms of reference set by the working group of UKCCCR; Problems related to clinical trials of elderly cancer patients; Representation of elderly patients in trials; Reasons for poor entry of elderly in clinical trials; Problems related to toxicity of treatment.

Allowing selected patients with few distant metastases to undergo potentially curative local ablation, the designation "oligometastatic" has become a widely popular concept in oncology. However, accumulating evidence suggests that many of these patients harbour an unrecognised microscopic disease, leading either to the continuous development of new metastases or to an overt polymetastatic state and questioning thus an indiscriminate use of potentially harmful local ablation. In this paper, reviewing data on oligometastatic disease, we advocate the importance of identifying a true oligometastatic disease, characterised by a slow speed of development, instead of relying solely on a low number of lesions as the term "oligometastatic" implies. This is particularly relevant in clinical practice, where terminology has been shown to influence decision making. To define a true oligometastatic disease in the context of its still elusive biology and interaction with the immune system, we propose using clinical criteria. As discussed further in the paper, these criteria can be classified into three categories involving a low probability of occult metastases, low tumour growth rate and low tumour burden. Such cases with slow tumour-cell shedding and slow proliferation leave a sufficiently broad window-of-opportunity to detect and treat accessible lesions, increasing thus the odds of a cure. [ABSTRACT FROM AUTHOR]

Longitudinal models of biomarkers such as tumour size dynamics capture treatment efficacy and predict treatment outcome (overall survival) of a variety of anticancer therapies, including chemotherapies, targeted therapies, immunotherapies and their combinations. These pharmacological endpoints like tumour dynamic (tumour growth inhibition) metrics have been proposed as alternative endpoints to complement the classical RECIST endpoints (objective response rate, progression-free survival) to support early decisions both at the study level in drug development as well as at the patients level in personalised therapy with checkpoint inhibitors. This perspective paper presents recent developments and future directions to enable wider and robust use of model-based decision frameworks based on pharmacological endpoints. [ABSTRACT FROM AUTHOR]

Background: This systematic review and meta-analysis aimed to evaluate existing evidence on the relationship between diagnostic and treatment intervals and outcomes for colorectal cancer. Methods: Four databases were searched for English language articles assessing the role of time before initial treatment in colorectal cancer on any outcome, including stage and survival. Two reviewers independently screened articles for inclusion and data were synthesised narratively. A dose–response meta-analysis was performed to examine the association between treatment interval and survival. Results: One hundred and thirty papers were included in the systematic review, eight were included in the meta-analysis. Forty-five different intervals were considered in the time from first symptom to treatment. The most common finding was of no association between the length of intervals on any outcome. The dose–response meta-analysis showed a U-shaped association between the treatment interval and overall survival with the nadir at 45 days. Conclusion: The review found inconsistent, but mostly a lack of, association between interval length and colorectal cancer outcomes, but study design and quality were heterogeneous. Meta-analysis suggests survival becomes increasingly poorer for those commencing treatment more than 45 days after diagnosis. Registration: This review was registered, and the protocol is available, in PROSPERO, the international database of systematic reviews, with the registration ID CRD42021255864. [ABSTRACT FROM AUTHOR]

Background: Risk stratification as a routine part of the NHS Breast Screening Programme (NHSBSP) could provide a better balance of benefits and harms. We developed BC-Predict, to offer women when invited to the NHSBSP, which collects standard risk factor information; mammographic density; and in a sub-sample, a Polygenic Risk Score (PRS). Methods: Risk prediction was estimated primarily from self-reported questionnaires and mammographic density using the Tyrer–Cuzick risk model. Women eligible for NHSBSP were recruited. BC-Predict produced risk feedback letters, inviting women at high risk (≥8% 10-year) or moderate risk (≥5–<8% 10-year) to have appointments to discuss prevention and additional screening. Results: Overall uptake of BC-Predict in screening attendees was 16.9% with 2472 consenting to the study; 76.8% of those received risk feedback within the 8-week timeframe. Recruitment was 63.2% with an onsite recruiter and paper questionnaire compared to <10% with BC-Predict only (P < 0.0001). Risk appointment attendance was highest for those at high risk (40.6%); 77.5% of those opted for preventive medication. Discussion: We have shown that a real-time offer of breast cancer risk information (including both mammographic density and PRS) is feasible and can be delivered in reasonable time, although uptake requires personal contact. Preventive medication uptake in women newly identified at high risk is high and could improve the cost-effectiveness of risk stratification. Trial registration: Retrospectively registered with clinicaltrials.gov (NCT04359420). [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is a prevalent disease worldwide, with more than 50% of patients developing metastases to the liver. Five-year overall survival remains modest among patients with metastatic CRC (mCRC) treated with conventional therapies however, liver transplantation in a highly selected population can improve clinical outcomes with an impressive 5-year overall survival of 83%. Despite liver transplantation appearing to be a promising therapeutical option for well-selected patients with mCRC with the liver-limited disease, these data come from small monocentric trials which included a heterogeneous population. Currently, several clinical trials are evaluating liver transplantation in this scenario, aiming for a more accurate patient selection by integrating liquid biopsy, tissue profiling, and nuclear medicine to the already known clinical biomarkers that eventually may lead to a survival improvement. In this paper, the clinical outcomes and inclusion criteria from the most relevant clinical trials and clinical series involving liver transplantation in patients with liver-limited disease colorectal cancer are reviewed as well as the trials currently recruiting. [ABSTRACT FROM AUTHOR]

In our 2020 consensus paper, we devised ten recommendations for conducting Complex Innovative Design (CID) trials to evaluate cancer drugs. Within weeks of its publication, the UK was hit by the first wave of the SARS-CoV-2 pandemic. Large CID trials were prioritised to compare the efficacy of new and repurposed COVID-19 treatments and inform regulatory decisions. The unusual circumstances of the pandemic meant studies such as RECOVERY were opened almost immediately and recruited record numbers of participants. However, trial teams were required to make concessions and adaptations to these studies to ensure recruitment was rapid and broad. As these are relevant to cancer trials that enrol patients with similar risk factors, we have added three new recommendations to our original ten: employing pragmatism such as using focused information sheets and collection of only the most relevant data; minimising negative environmental impacts with paperless systems; and using direct-to-patient communication methods to improve uptake. These recommendations can be applied to all oncology CID trials to improve their inclusivity, uptake and efficiency. Above all, the success of CID studies during the COVID-19 pandemic underscores their efficacy as tools for rapid treatment evaluation. [ABSTRACT FROM AUTHOR]

Cell death is part of the lifecycle of every multicellular organism. Nineteenth-century pathologists already recognised that organised forms of cell death must exist to explain the demise and turnover of cells during metamorphosis (of insects), embryogenesis and normal tissue homoeostasis [1]. Nevertheless, Kerr, Wyllie and Currie in their seminal paper of 1972, were the first to collate and define the distinct morphological features of controlled cell death in different contexts [2]. To describe the processes of cell deletion observed under both physiological and pathological conditions, they coined the term 'Apoptosis' (derived from the Greek word 'ἀπόπτωσις', meaning 'dropping off or falling off' of petals from flowers). Kerr, Wyllie and Currie defined apoptosis as a mechanism 'complementary to mitosis in the regulation of animal cell populations'. In addition, they already recognised the potential to use this programmed form of cell death for cancer therapy, but they also emphasised the occurrence of apoptosis during cancer development. In this article, some 50 years after its initial publication in The British Journal of Cancer, we revaluate and put the authors initial assumptions and general concepts about apoptosis into the context of modern-day biology. [ABSTRACT FROM AUTHOR]

Delivering lung cancer care during the COVID-19 pandemic has posed significant and ongoing challenges. There is a lack of published COVID-19 and lung cancer evidence-based reviews, including for the whole patient pathway. We searched for COVID-19 and lung cancer publications and brought together a multidisciplinary group of stakeholders to review and comment on the evidence and challenges. A rapid review of the literature was undertaken up to 28 October 2020, producing 144 papers, with 113 full texts screened. We focused on new primary data collection (qualitative or quantitative evidence) and excluded case reports, editorials and commentaries. Following exclusions, 15 published papers were included in the review and are summarised. They included one qualitative paper and 14 quantitative studies (surveys or cohort studies), with a total of 2295 lung cancer patients data included (mean study size 153 patients; range 7-803). Review of current evidence and commentary included awareness and help-seeking; lung cancer screening; primary care assessment and referral; diagnosis and treatment in secondary care, including oncology and surgery; patient experience and palliative care. Cross-cutting themes and challenges were identified using qualitative methods for patients, healthcare professionals and service delivery, with a clear need for continued studies to guide evidence-based decision-making. [ABSTRACT FROM AUTHOR]

Immunotherapy deals with therapeutic interventions to arrest the progression of tumours using the immune system. These include checkpoint inhibitors, T-cell manipulation, cytokines, oncolytic viruses and tumour vaccines. In this paper, we present a survey of the latest developments on immunotherapy in colorectal cancer (CRC) and the role of artificial intelligence (AI) in this context. Among these, microsatellite instability (MSI) is perhaps the most popular IO biomarker globally. We first discuss the MSI status of tumours, its implications for patient management, and its relationship to immune response. In recent years, several aspiring studies have used AI to predict the MSI status of patients from digital whole-slide images (WSIs) of routine diagnostic slides. We present a survey of AI literature on the prediction of MSI and tumour mutation burden from digitised WSIs of haematoxylin and eosin-stained diagnostic slides. We discuss AI approaches in detail and elaborate their contributions, limitations and key takeaways to drive future research. We further expand this survey to other IO-related biomarkers like immune cell infiltrates and alternate data modalities like immunohistochemistry and gene expression. Finally, we underline possible future directions in immunotherapy for CRC and promise of AI to accelerate this exploration for patient benefits. [ABSTRACT FROM AUTHOR]

Background: Molecular Tumour Boards (MTBs) were created with the purpose of supporting clinical decision-making within precision medicine. Though in use globally, reporting on these meetings often focuses on the small percentages of patients that receive treatment via this process and are less likely to report on, and assess, patients who do not receive treatment.Methods: A literature review was performed to understand patient attrition within MTBs and barriers to patients receiving treatment. A total of 51 papers were reviewed spanning a 6-year period from 11 different countries.Results: In total, 20% of patients received treatment through the MTB process. Of those that did not receive treatment, the main reasons were no mutations identified (27%), no actionable mutations (22%) and clinical deterioration (15%). However, data were often incomplete due to inconsistent reporting of MTBs with only 55% reporting on patients having no mutations, 55% reporting on the presence of actionable mutations with no treatment options and 59% reporting on clinical deterioration.Discussion: As patient attrition in MTBs is an issue which is very rarely alluded to in reporting, more transparent reporting is needed to understand barriers to treatment and integration of new technologies is required to process increasing omic and treatment data. [ABSTRACT FROM AUTHOR]

Presents information on several research papers on cancer. Assessment of the roles of adjuvant chemotherapy and adjuvant chemoradiation in pancreatic cancer; Comparison of efficacy and toxicity of adriamycin and mitoxantrone in the treatment of lymphoma.

The article presents several studies related to cancer research. Firstly, it discusses the minimal initial chemotherapy plus involved field radiotherapy (RT) versus mantle field RT for clinical stage IA/IIA supra-diaphragmatic Hodgkin's disease. Results of the lymphoma group LY07 trial in Great Britain is stated. Also the ABC trial tested the added benefits of ovarian ablation and/or chemotherapy in women with early breast cancer prescribed tamoxifen 20mg daily for 5 years.

Cell-free DNA (cfDNA) analysis represents a promising method for the diagnosis, treatment selection and clinical follow-up of cancer patients. Although its general methodological feasibility and usefulness has been demonstrated, several issues related to standardisation and technical validation must be addressed for its routine clinical application in cancer. In this regard, most cfDNA clinical applications are still limited to clinical trials, proving its value in several settings. In this paper, we review the current clinical trials involving cfDNA/ctDNA analysis and highlight those where it has been useful for patient stratification, treatment follow-up or development of novel approaches for early diagnosis. Our query included clinical trials, including the terms 'cfDNA', 'ctDNA', 'liquid biopsy' AND 'cancer OR neoplasm' in the FDA and EMA public databases. We identified 1370 clinical trials (FDA = 1129, EMA = 241) involving liquid-biopsy analysis in cancer. These clinical trials show promising results for the early detection of cancer and confirm cfDNA as a tool for real-time monitoring of acquired therapy resistance, accurate disease-progression surveillance and improvement of treatment, situations that result in a better quality of life and extended overall survival for cancer patients. [ABSTRACT FROM AUTHOR]

Cell-free DNA (cfDNA) analysis represents a promising method for the diagnosis, treatment selection and clinical follow-up of cancer patients. Although its general methodological feasibility and usefulness has been demonstrated, several issues related to standardisation and technical validation must be addressed for its routine clinical application in cancer. In this regard, most cfDNA clinical applications are still limited to clinical trials, proving its value in several settings. In this paper, we review the current clinical trials involving cfDNA/ctDNA analysis and highlight those where it has been useful for patient stratification, treatment follow-up or development of novel approaches for early diagnosis. Our query included clinical trials, including the terms 'cfDNA', 'ctDNA', 'liquid biopsy' AND 'cancer OR neoplasm' in the FDA and EMA public databases. We identified 1370 clinical trials (FDA = 1129, EMA = 241) involving liquid-biopsy analysis in cancer. These clinical trials show promising results for the early detection of cancer and confirm cfDNA as a tool for real-time monitoring of acquired therapy resistance, accurate disease-progression surveillance and improvement of treatment, situations that result in a better quality of life and extended overall survival for cancer patients. [ABSTRACT FROM AUTHOR]

Background: This paper reviews recent literature employing Artificial Intelligence/Machine Learning (AI/ML) methods for diagnostic evaluation of head and neck cancers (HNC) using automated image analysis.Methods: Electronic database searches using MEDLINE via OVID, EMBASE and Google Scholar were conducted to retrieve articles using AI/ML for diagnostic evaluation of HNC (2009-2020). No restrictions were placed on the AI/ML method or imaging modality used.Results: In total, 32 articles were identified. HNC sites included oral cavity (n = 16), nasopharynx (n = 3), oropharynx (n = 3), larynx (n = 2), salivary glands (n = 2), sinonasal (n = 1) and in five studies multiple sites were studied. Imaging modalities included histological (n = 9), radiological (n = 8), hyperspectral (n = 6), endoscopic/clinical (n = 5), infrared thermal (n = 1) and optical (n = 1). Clinicopathologic/genomic data were used in two studies. Traditional ML methods were employed in 22 studies (69%), deep learning (DL) in eight studies (25%) and a combination of these methods in two studies (6%).Conclusions: There is an increasing volume of studies exploring the role of AI/ML to aid HNC detection using a range of imaging modalities. These methods can achieve high degrees of accuracy that can exceed the abilities of human judgement in making data predictions. Large-scale multi-centric prospective studies are required to aid deployment into clinical practice. [ABSTRACT FROM AUTHOR]

An amendment to this paper has been published and can be accessed via a link at the top of the paper. [ABSTRACT FROM AUTHOR]

Earlier diagnosis and more effective treatments mean that the estimated number of cancer survivors in the United Kingdom is expected to reach 4 million by 2030. However, there is an increasing realisation that excess body fatness (EBF) is likely to influence the quality of cancer survivorship and disease-free survival. For decades, the discussion of weight management in patients with cancer has been dominated by concerns about unintentional weight loss, low body weight and interventions to increase weight, often re-enforced by the existence of the obesity paradox, which indicates that high body weight is associated with survival benefits for some types of cancer. However, observational evidence provides strong grounds for testing the hypothesis that interventions for promoting intentional loss of body fat and maintaining skeletal muscle in overweight and obese cancer survivors would bring important health benefits in terms of survival outcomes and long-term impact on treatment-related side effects. In this paper, we outline the need for studies to improve our understanding of the health benefits of weight-loss interventions, such as hypocaloric healthy-eating plans combined with physical activity. In particular, complex intervention trials that are pragmatically designed are urgently needed to develop effective, clinically practical, evidence-based strategies for reducing EBF and optimising body composition in people living with and beyond common cancers. [ABSTRACT FROM AUTHOR]

Growing data from epidemiological studies highlight the association between excess body fat and cancer incidence, but good indicative evidence demonstrates that intentional weight loss, as well as increasing physical activity, offers much promise as a cost-effective approach for reducing the cancer burden. However, clear gaps remain in our understanding of how changes in body fat or levels of physical activity are mechanistically linked to cancer, and the magnitude of their impact on cancer risk. It is important to investigate the causal link between programmes that successfully achieve short-term modest weight loss followed by weight-loss maintenance and cancer incidence. The longer-term impact of weight loss and duration of overweight and obesity on risk reduction also need to be fully considered in trial design. These gaps in knowledge need to be urgently addressed to expedite the development and implementation of future cancer-control strategies. Comprehensive approaches to trial design, Mendelian randomisation studies and data-linkage opportunities offer real possibilities to tackle current research gaps. In this paper, we set out the case for why non-pharmacological weight-management trials are urgently needed to support cancer-risk reduction and help control the growing global burden of cancer. [ABSTRACT FROM AUTHOR]

Background: This paper investigates the difference in survival of melanoma patients across stage and sex by utilising net survival measures. Metrics are presented at both the individual and population level.Methods: Flexible parametric models were fitted to estimate life-expectancy metrics to be applied to a group of 104,938 subjects with a melanoma skin cancer diagnosis from 2000 to 2017. Period analysis was used for better predictions for newly diagnosed patients, and missing-stage information was imputed for 9918 patients. Female relative survival was assigned to male subjects to demonstrate the survival discrepancies experienced between sexes.Results: At the age of 60, males diagnosed at the regional stage lose an average of 4.99 years of life compared to the general population, and females lose 4.79 years, demonstrating the sex variation in expected mortality. In 2017, males contributed 3545 more life years lost than females, and a potential 1931 life years could be preserved if sex differences in survival were eliminated.Conclusions: This study demonstrates the survival differences across population subgroups as a result of a melanoma cancer diagnosis. Females experience better prognosis across age and stage at diagnosis; however, further investigation is necessary to better understand the mechanisms behind this difference. [ABSTRACT FROM AUTHOR]

Background: There is a great interest in developing biomarkers to enhance early detection and clinical management of tongue squamous cell carcinoma (TSCC). However, the developmental path towards a clinically valid biomarker remains extremely challenging. Ideally, the initial key step in moving a newly discovered biomarker towards clinical implementation is independent replication. Therefore, the focus of this review is on biomarkers that consistently showed clinical relevance in two or more publications.Methods: We searched PubMed database for relevant papers across different TSCC sample sources, i.e., body fluids (saliva, serum/plasma) and tissues. No restriction regarding the date of publication was applied except for immunohistochemistry (IHC); only studies published between 2010 and June 2017 were included.Results: The search strategy identified 1429 abstracts, of which 96 papers, examining 150 biomarkers, were eventually included. Of these papers, 66% were exploratory studies evaluating single or a panel of biomarkers in one publication. Ultimately, based on studies that had undergone validation for their clinical relevance in at least two independent studies, we identified 10 promising candidates, consisting of different types of molecules (IL-6, IL-8, and Prolactin in liquid samples; HIF-1α, SOX2, E-cadherin, vimentin, MALAT1, TP53, and NOTCH1 in tissue biopsies) CONCLUSIONS: Although more exploratory research is needed with newer methods to identify biomarkers for TSCC, rigorous validation of biomarkers that have already shown unbiased assessment in at least two publications should be considered a high priority. Further research on these promising biomarkers or their combination in multi-institutional studies, could provide new possibilities to develop a specific panel for early diagnosis, prognosis, and individualized treatments. [ABSTRACT FROM AUTHOR]

Background: High doses of ionising radiation are a known cause of childhood cancer and great public and professional interest attaches to possible links between childhood cancer and lower doses, particularly of man-made radiation. This paper describes work done by the Childhood Cancer Research Group (CCRG) on this topic METHODS: Most UK investigations have made use of the National Registry of Childhood Tumours and associated controls. Epidemiological investigations have included national incidence and mortality analyses, geographical investigations, record linkage and case-control studies. Dosimetric studies use biokinetic and dosimetric modelling.Results: This paper reviews the work of the CCRG on the association between exposure to ionising radiation and childhood cancer, 1975-2014.Conclusion: The work of CCRG has been influential in developing understanding of the causes of 'clusters' of childhood cancer and the risks arising from exposure to ionising radiation both natural and man-made. Some clusters around nuclear installations have certainly been observed, but ionising radiation does not seem to be a plausible cause. The group's work has also been instrumental in discounting the hypothesis that paternal preconception irradiation was a cause of childhood cancers and has demonstrated an increased leukaemia risk for children exposed to higher levels of natural gamma-ray radiation. [ABSTRACT FROM AUTHOR]

Background: Significant research on the epidemiology and natural history of childhood cancer took place in the Universities of Oxford and Birmingham over sixty years. This is the first of three papers recording this work and describes the Oxford Survey of Childhood Cancers (OSCC), the largest case-control survey of childhood cancer ever undertaken.Methods: The OSCC studied deaths in Britain from 1953 to 1981. Parents were interviewed and medical records from ante-natal clinics and treatment centres were followed up and abstracted. The survey left Oxford in 1975 and was run subsequently from Birmingham. The data are now being documented and archived to make them available for future study.Results: Many papers have resulted from this survey, most notably those relating to the association first reported therein between childhood cancer and ante-natal X-raying. This paper is a historical review of the OSCC.Conclusions: In spite of many analyses of the study, this historic data set has continuing value because of the large number of examples of some very rare tumours and the detailed clinical and family history data that are available; and also because of the possibility of carrying out new analyses to investigate emerging research issues. [ABSTRACT FROM AUTHOR]

Brain metastases from breast cancer (BCBM) constitute the second most common cause of brain metastasis (BM), and the incidence of these frequently lethal lesions is currently increasing, following better systemic treatment. Patients with ER-negative and HER2-positive metastatic breast cancer (BC) are the most likely to develop BM, but if this diagnosis remains associated with a worse prognosis, long survival is now common for patients with HER2-positive BC. BCBM represents a therapeutic challenge that needs a coordinated treatment strategy along international guidelines. Surgery has always to be considered when feasible. It is now well established that stereotaxic radiosurgery allows for equivalent control and less-cognitive toxicities than whole-brain radiation therapy, which should be delayed as much as possible. Medical treatment for BCBM is currently a rapidly evolving field. It has been shown that the blood-brain barrier (BBB) is often impaired in macroscopic BM, and several chemotherapy regimens, antibody-drug conjugates and tyrosine-kinase inhibitors have been shown to be active on BCBM and can be part of the global treatment strategy. This paper provides an overview of the therapeutic option for BCBM that is currently available and outlines potential new approaches for tackling these deadly secondary tumours. [ABSTRACT FROM AUTHOR]

The type of patients with stage III non-small-cell lung cancer (NSCLC) selected for concurrent chemoradiotherapy (cCRT) varies between and within countries, with higher-volume centres treating patients with more co-morbidities and higher-stage disease. However, in spite of these disease characteristics, these patients have improved overall survival, suggesting that there are additional approaches that should be optimised and potentially standardised. This paper aims to review the current knowledge and best practices surrounding treatment for patients eligible for cCRT. Initially, this includes timely acquisition of the full diagnostic workup for the multidisciplinary team to comprehensively assess a patient for treatment, as well as imaging scans, patient history, lung function and genetic tests. Such information can provide prognostic information on how a patient will tolerate their cCRT regimen, and to perhaps limit the use of additional supportive care, such as steroids, which could impact on further treatments, such as immunotherapy. Furthermore, knowledge of the safety profile of individual double-platinum chemotherapy regimens and the technological advances in radiotherapy could aid in optimising patients for cCRT treatment, improving its efficacy whilst minimising its toxicities. Finally, providing patients with preparatory and ongoing support with input from dieticians, palliative care professionals, respiratory and care-of-the-elderly physicians during treatment may also help in more effective treatment delivery, allowing patients to achieve the maximum potential from their treatments. [ABSTRACT FROM AUTHOR]

When treating patients with unresectable stage III non-small-cell lung cancer (NSCLC), those with a good performance status and disease measured within a radical treatment volume should be considered for definitive concurrent chemoradiotherapy (cCRT). This guidance is based on key scientific rationale from two large Phase 3 randomised studies and meta-analyses demonstrating the superiority of cCRT over sequential (sCRT). However, the efficacy of cCRT comes at the cost of increased acute toxicity versus sequential treatment. Currently, there are several documented approaches that are addressing this drawback, which this paper outlines. At the point of diagnosis, a multidisciplinary team (MDT) approach can enable accurate assessment of patients, to determine the optimal treatment strategy to minimise risks. In addition, reviewing the Advisory Committee on Radiation Oncology Practice (ACROP) guidelines can provide clinical oncologists with additional recommendations for outlining target volume and organ-at-risk delineation for standard clinical scenarios in definitive cCRT (and adjuvant radiotherapy). Furthermore, modern advances in radiotherapy treatment planning software and treatment delivery mean that radiation oncologists can safely treat substantially larger lung tumours with higher radiotherapy doses, with greater accuracy, whilst minimising the radiotherapy dose to the surrounding healthy tissues. The combination of these advances in cCRT may assist in creating comprehensive strategies to allow patients to receive potentially curative benefits from treatments such as immunotherapy, as well as minimising treatment-related risks. [ABSTRACT FROM AUTHOR]

Background: Patients with non-specific symptoms often experience longer times to diagnosis and poorer clinical outcomes than those with site-specific symptoms. This paper reports initial results from five multidisciplinary diagnostic centre (MDC) projects in England, piloting rapid referral for patients with non-specific symptoms.Methods: The evaluation covered MDC activity from 1st December 2016 to 31st July 2018, with projects using a common dataset. Logistical regression analyses were conducted, with a diagnosis of any cancer as the dependent variable. Exploratory analysis was conducted on presenting symptoms and diagnoses of cancer, and on comparisons within these groupings.Results: In total, 2961 patients were referred into the MDCs and 241 cancers were diagnosed. The pathway detected cancers across a broad range of tumour sites, including several rare and less common cancers. An association between patient age and cancer was identified (p < 0.001). GP 'clinical suspicion' was identified as a strong predictor of cancer (p = 0.006), with a reduced association with cancer observed in patients with higher numbers of GP consultation before referral (p = 0.008).Conclusions: The MDC model diagnoses cancer in patients with non-specific symptoms, with a conversion rate of 8%, demonstrating the diagnostic potential of a non-site-specific symptomatic referral pathway. [ABSTRACT FROM AUTHOR]

Background: This is the first review to identify, appraise and synthesise women's experiences of having a false-positive breast screening test result. Methods: We systematically searched eight databases for qualitative research reporting women's experiences of receiving a false-positive screening test result. Two reviewers independently screened articles. Eight papers reporting seven studies were included. Study quality was appraised. Data were thematically synthesised. Results: Women passively attended screening in order to prove their perceived good health. Consequently, being recalled was unexpected, shocking and disempowering: women felt without options. They endured great uncertainty and stress and sought clarity about their health (e.g. by scrutinising the wording of recall letters and conversations with healthcare professionals). Their result was accompanied by relief and welcome feelings of certainty about their health, but some received unclear explanations of their result, contributing to lasting breast cancer-related worry and an ongoing need for further reassurance. Conclusion: The organisation of breast screening programmes may constrain choice for women: they became passive recipients. The way healthcare professionals verbally communicate results to women may contribute to lasting breast cancer-related worry. Women need more reassurance, emotional support and answers to their questions before and during screening assessment, and after receiving their result. [ABSTRACT FROM AUTHOR]

Background: This is the first review to identify, appraise and synthesise women's experiences of having a false-positive breast screening test result.Methods: We systematically searched eight databases for qualitative research reporting women's experiences of receiving a false-positive screening test result. Two reviewers independently screened articles. Eight papers reporting seven studies were included. Study quality was appraised. Data were thematically synthesised.Results: Women passively attended screening in order to prove their perceived good health. Consequently, being recalled was unexpected, shocking and disempowering: women felt without options. They endured great uncertainty and stress and sought clarity about their health (e.g. by scrutinising the wording of recall letters and conversations with healthcare professionals). Their result was accompanied by relief and welcome feelings of certainty about their health, but some received unclear explanations of their result, contributing to lasting breast cancer-related worry and an ongoing need for further reassurance.Conclusion: The organisation of breast screening programmes may constrain choice for women: they became passive recipients. The way healthcare professionals verbally communicate results to women may contribute to lasting breast cancer-related worry. Women need more reassurance, emotional support and answers to their questions before and during screening assessment, and after receiving their result. [ABSTRACT FROM AUTHOR]

Background: Tumour budding is a histological finding in epithelial cancers indicating an unfavourable phenotype. Previous studies have demonstrated that it is a negative prognostic indicator in colorectal cancer (CRC), and has been proposed as an additional factor to incorporate into staging protocols.Methods: A systematic review of papers until March 2016 published on Embase, Medline, PubMed, PubMed Central and Cochrane databases pertaining to tumour budding in CRC was performed. Study end points were the presence of lymph node metastases, recurrence (local and distal) and 5-year cancer-related death.Results: A total of 7821 patients from 34 papers were included, with a mean rate of tumour budding of 36.8±16.5%. Pooled analysis suggested that specimens exhibiting tumour budding were significantly associated with lymph node positivity (OR 4.94, 95% CI 3.96-6.17, P<0.00001), more likely to develop disease recurrence over the time period (OR 5.50, 95% CI 3.64-8.29, P<0.00001) and more likely to lead to cancer-related death at 5 years (OR 4.51, 95% CI 2.55-7.99, P<0.00001).Conclusions: Tumour budding in CRC is strongly predictive of lymph node metastases, recurrence and cancer-related death at 5 years, and its incorporation into the CRC staging algorithm will contribute to more effective risk stratification. [ABSTRACT FROM AUTHOR]

Summary: We discuss Pyrhönen's paper as a catalyst for defining systemic therapy approaches in gastric cancer and how the field has evolved in the last two decades in sequential, targeted and more recently immune-directed therapies and how it may develop to transform survival in this cancer of high unmet need. [ABSTRACT FROM AUTHOR]

Background:A recent Monographs Working Group of the International Agency for Research on Cancer concluded that there is limited evidence for a causal association between exposure to asbestos and stomach cancer.Methods:We performed a meta-analysis to quantitatively evaluate this association. Random effects models were used to summarise the relative risks across studies. Sources of heterogeneity were explored through subgroup analyses and meta-regression.Results:We identified 40 mortality cohort studies from 37 separate papers, and cancer incidence data were extracted for 15 separate cohorts from 14 papers. The overall meta-SMR for stomach cancer for total cohort was 1.15 (95% confidence interval 1.03-1.27), with heterogeneous results across studies. Statistically significant excesses were observed in North America and Australia but not in Europe, and for generic asbestos workers and insulators. Meta-SMRs were larger for cohorts reporting a SMR for lung cancer above 2 and cohort sizes below 1000.Conclusions:Our results support the conclusion by IARC that exposure to asbestos is associated with a moderate increased risk of stomach cancer. [ABSTRACT FROM AUTHOR]

Background: The European NCI compounds programme, a joint initiative of the EORTC Research Branch, Cancer Research Campaign and the US National Cancer Institute, was initiated in 1993. The objective was to help the NCI in reducing the backlog of in vivo testing of potential anticancer compounds, synthesised in Europe that emerged from the NCI in vitro 60-cell screen.Methods: Over a period of more than twenty years the EORTC-Cancer Research Campaign panel reviewed ∼2000 compounds of which 95 were selected for further evaluation. Selected compounds were stepwise developed with clear go/no go decision points using a pharmacologically directed programme.Results: This approach eliminated quickly compounds with unsuitable pharmacological properties. A few compounds went into Phase I clinical evaluation. The lessons learned and many of the principles outlined in the paper can easily be applied to current and future drug discovery and development programmes.Conclusions: Changes in the review panel, restrictions regarding numbers and types of compounds tested in the NCI in vitro screen and the appearance of targeted agents led to the discontinuation of the European NCI programme in 2017 and its transformation into an academic platform of excellence for anticancer drug discovery and development within the EORTC-PAMM group. This group remains open for advice and collaboration with interested parties in the field of cancer pharmacology. [ABSTRACT FROM AUTHOR]

Background: Vitamin D has been linked with improved cancer outcome. This systematic review and meta-analysis investigates the relationship between cancer outcomes and both vitamin D-related genetic variation and circulating 25-hydroxyvitamin D (25OHD) concentration.Methods: A systematic review and meta-analysis of papers until November 2016 on PubMed, EMBASE and Web of Science pertaining to association between circulating vitamin D level, functionally relevant vitamin D receptor genetic variants and variants within vitamin D pathway genes and cancer survival or disease progression was performed.Results: A total of 44 165 cases from 64 studies were included in meta-analyses. Higher 25OHD was associated with better overall survival (hazard ratio (HR=0.74, 95% CI: 0.66-0.82) and progression-free survival (HR=0.84, 95% CI: 0.77-0.91). The rs1544410 (BsmI) variant was associated with overall survival (HR=1.40, 95% CI: 1.05-1.75) and rs7975232 (ApaI) with progression-free survival (HR=1.29, 95% CI: 1.02-1.56). The rs2228570 (FokI) variant was associated with overall survival in lung cancer patients (HR=1.29, 95% CI: 1.0-1.57), with a suggestive association across all cancers (HR=1.26, 95% CI: 0.96-1.56).Conclusions: Higher 25OHD concentration is associated with better cancer outcome, and the observed association of functional variants in vitamin D pathway genes with outcome supports a causal link. This analysis provides powerful background rationale to instigate clinical trials to investigate the potential beneficial effect of vitamin D in the context of stratification by genotype. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC) is common and associated with significant mortality. Current screening methods for CRC lack patient compliance. microRNAs (miRNAs), identified in body fluids, are negative regulators of gene expression and are dysregulated in many cancers, including CRC. This paper summarises studies identifying blood-based miRNAs dysregulated in CRC compared with healthy controls in an attempt to evaluate their use as a screening tool for the diagnosis of CRC.Methods: A search of electronic databases (PubMed and EMBASE) and grey literature was performed between January 2002 and April 2016. Studies reporting plasma or serum miRNAs in the diagnosis of CRC compared with healthy controls were selected. Patient demographics, type of patient sample (serum or plasma), method of miRNA detection, type of normalisation, and the number of significantly dysregulated miRNAs identified were recorded. Statistical evaluation of dysregulated miRNAs using sensitivity, specificity, and area under the curve (AUC) was performed.Results: Thirty-four studies investigating plasma or serum miRNAs in the diagnosis of CRC were included. A total of 31 miRNAs were found to be either upregulated (n=17) or downregulated (n=14) in CRC cases as compared with controls. Fourteen studies identified panels of ⩾2 dysregulated miRNAs. The highest AUC, 0.943, was identified using a panel of 4 miRNAs with 83.3% sensitivity and 93.1% specificity. Meta-analysis of studies identifying a single dysregulated miRNA in CRC cases compared with controls was performed. Overall sensitivity and specificity of 28 individual miRNAs in the diagnosis of CRC were 76% (95% CI 72%-80%) and 76% (95% CI 72%-80%), respectively, indicating good discriminative ability of miRNAs as biomarkers for CRC. These data did not change with sensitivity analyses.Conclusions: Blood-based miRNAs distinguish patients with CRC from healthy controls with high sensitivity and specificity comparable to other common and invasive currently used screening methods for CRC. In future, miRNAs may be used as a relatively non-invasive blood-based marker for detection of CRC. [ABSTRACT FROM AUTHOR]

In evidence-based medicine (EBM), systematic reviews and meta-analyses have been widely applied in biological and medical research. Moreover, the most popular application of meta-analyses in this field may be to examine diagnostic (sensitivity and specificity) and prognostic (hazard ratio (HR) and its variance, standard error (SE) or confidence interval (CI)) test accuracy. However, conducting such analyses requires not only a great deal of time but also an advanced professional knowledge of mathematics, statistics and computer science. Regarding the practical application of meta-analyses for diagnostic and prognostic markers, the majority of users are clinicians and biologists, most of whom are not skilled at mathematics and computer science in particular. Hence, it is necessary for these users to have a simplified version of a protocol to help them to quickly conduct meta-analyses of the accuracy of diagnostic and prognostic tests. The aim of this paper is to enable individuals who have never performed a meta-analysis to do so from scratch. The paper does not attempt to serve as a comprehensive theoretical guide but instead describes one rigorous way of conducting a meta-analysis for diagnostic and prognostic markers. Investigators who follow the outlined methods should be able to understand the basic ideas behind the steps taken, the meaning of the meta-analysis results obtained for diagnostic and prognostic markers and the scope of questions that can be answered with Systematic Reviews and Meta-Analyses (SRMA). The presented protocols have been successfully tested by clinicians without meta-analysis experience. [ABSTRACT FROM AUTHOR]