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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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]