Mark Clements

Cancer is a leading cause of death globally. Precision medicine, offering novel (targeted) therapies, has the potential to substantially improve cancer patient outcomes. However, to be effective, precision diagnostic solutions for patient stratification (prognostic and predictive) are required. To improve outcomes for broad groups of patients, fast, reliable and cost-effective precision diagnostic solutions are needed. Current routine diagnosis of cancer is based on manual histopathological assessment, which is imprecise. Molecular diagnostics offers improved patient stratification, but at a high price, limiting patient access and imposing a high economic burden on healthcare systems. CHIME develops, validates and contributes to translation of AI-based image analysis solutions (computational pathology) for cancer diagnosis and patient stratification that meet current and future needs in clinical cancer precision medicine, trials and cancer research. Clinical pathology is undergoing a digital transition that enables translation of AI-based decision support tools for precision diagnostics at a fraction of the cost of molecular diagnostics. CHIME will leverage large and unique study materials (&gt

400,000 histopathology images and clinical data with outcomes) for the development and validation of clinically relevant models for patient stratification in multiple cancer diseases. CHIME will contribute toward increased access to precision diagnostic and equality in cancer care.

Our general aim is to use modelling to reduce the burden due to prostate and cervical cancer through cost-effective screening. For prostate cancer, new tests, magnetic resonance imaging (MRI) and artificial intelligence (AI) assisted pathology are expected to reduce harms while maintaining the mortality benefits from early detection. For cervical cancer, human papillomavirus (HPV) vaccinations are expected to substantially reduce HPV incidence and eventually lead to the eradication of cervical cancer. With changes to HPV transmission, cervical cancer screening may require extended genotyping, self-sampling and renewed guidelines to be cost-effective.We will evaluate the cost-effectiveness of: (i) organised prostate cancer testing (OPT) in Sweden, including MRI and the Stockholm3 test

(ii) prostate cancer testing using a genetic risk score

(iii) prostate cancer diagnostics using AI-assisted pathology

and (iv) primary HPV testing with extended genotyping in vaccinated cohorts with clinic-based testing or self-sampling. These results will inform policy for (a) the development and planning of a national OPT program, (b) the use of AI-assisted histopathology, and (c) the development of national cervical cancer screening guidelines for vaccinated cohorts.

Prostate cancer is the most common cancer among men in Sweden. Screening using a prostate-specific antigen (PSA) test may lead to fewer deaths from prostate cancer, but also to more men being diagnosed with prostate cancer that may not be life-threatening. Cervical cancer is the fourth most common cancer among women globally. The cervical cancer screening program has reduced the number of cases of cervical cancer in Sweden. In addition, school-based vaccinations are expected to further reduce the number of cancer cases. Our overall goal is to use health economic models to reduce the impact on society and the individual due to cancer through cost-effective cancer screening. For prostate cancer, new and more accurate tests are expected to reduce harm while maintaining the benefits of early detection. For cervical cancer, more accurate testing and screening-based vaccination would further reduce the incidence of cervical cancer. The fundamental question is: How should a cancer screening program be planned? We will tackle these questions by developing evidence-based simulation models that can help policy makers make policy decisions. To show how harm from prostate cancer testing can be reduced and to achieve the goal of eradicating cervical cancer through screening based on risk selection and screening-based vaccination. For Sweden, our research can be used for evaluation of ongoing pilot tests of systematic prostate cancer screening and contribute to the development of guidelines for cervical cancer screening. Policy reforms and increasing health care costs are driving the demands for efficient allocation of cancer care resources through evidence-based decision making. We propose that interdisciplinary tools and concepts be used to improve existing cancer care.

Prostate cancer is the most common form of cancer and the leading cause of cancer mortality among men in Sweden. A recent review of the new prostate cancer tests by SBU not convincingly the National Board of Health and Welfare which concluded that sufficient evidence is lacking for the cost-effectiveness of the new test and further research is needed.   Cervical cancer is the fourth most common cancer among women globally. Cytology-based screening programs have markedly reduced the incidence and mortality of cervical cancer in industrialized countries. There is uncertainty about the question of how best to plan the screening for both younger and older women. How should we plan for cancer screening? The purpose is to use epidemiological models and simulations to reduce the burden due to cancer by means of cost-effective screening. New prostate cancer tests and MRI-guided biopsies should reduce the damage but retain the benefits of early detection. For cervical cancer, high participation in vaccination and testing for HPV by younger and older women can further reduce incidence and mortality.   We do this by using evidence-based models to answer practical research issues, including evaluating costs and assessing cost-effectiveness in both test programs. Experience from cervical cancer screening should help control the prostate cancer test so that it has a more functional organization with better tests, better compliance and reduced costs through risk-based screening. Political reforms and increased costs for health and medical care are a driving force so that demands for efficient allocation of resources within cancer care are taken on the basis of evidence-based research. Health economics, biostatistics and epidemiology together provide an interdisciplinary set of tools and concepts to be able to assess the value of the decisions taken to improve existing cancer care.

Prostate cancer is the most common form of cancer among men and one of the highest mortality forms. Although there is information indicating that screening with a prostate-specific antigen (PSA) may cause fewer deaths, it is unclear whether the benefits outweigh the disadvantages. There are other biomarkers that can be combined into a better test. A large study (Stockholm-3) is underway to assess whether these can maintain the safety of detection of advanced prostate cancer, while being able to work more specifically so that fewer men without cancer are referred to biopsy (tissue sampling). The project aims to use the results from Stockholm-3 and model the advantages and disadvantages of screening for prostate cancer. In the project, an existing model for prostate cancer will be expanded with these biomarkers and methods developed to analyze Stockholm-3 data to assess the effectiveness of the biomarkers. The model should be adjusted to reproduce cancer incidence and deaths in cancer for Stockholm. The adjusted model will then be used to assess long-term disadvantages and benefits with respect to different types of prostate cancer screening. The project is of importance to be able to determine how best (most efficiently) to screen for the emergence of prostate cancer, both in Sweden and internationally.