The Value of a New Diagnostic Test for Prostate Cancer: A Cost-Utility Analysis in Early Stage of Development.

BACKGROUND: Standard biopsy for prostate cancer diagnosis is an unpleasant and sometimes painful procedure with a detection rate as low as around 50%. Consequently, an accurate blood-based test would be highly desirable to improve the predictive accuracy. However, the clinical value of a new blood test for diagnosing prostate cancer depends on its sensitivity and specificity, in relation to the selected target population. OBJECTIVE: The aim of this analysis was to investigate the health-economic value of introducing a new and more accurate diagnostic blood-based test to identify men in need of a biopsy to diagnose prostate cancer. METHOD: We developed a Discrete Event Simulation Model with outputs including number of biopsies, cancer diagnosis, treatments and prostate cancer deaths. The analysis was performed from a health care perspective. It used epidemiologic data, treatment patterns, and health care costs from the Swedish region Skåne (population of 1.3 million). A 90% sensitivity and specificity of the new test was assumed. RESULTS: Among 31,250 men, age 50-69 years, 16.4% had a PSA between 3.0 and 9.9 µg/L and 28.9% a PSA of 2.0-9.9 µg/L. Testing men with PSA 3.0-9.9 µg/L, as in current clinical practice, decreased the number of biopsies by 3595, detected 61 more cancers, resulting in and two more fatalities and subsequently a loss of 14 QALYs. Cost offsets could justify a test value of SEK 4996. Testing a larger population, PSA 2.0-9.9 µg/L prevented 6 deaths, added 50 QALYs, and could justify a value of the test of SEK 5165, given a value of health of SEK 500,000 per QALY. CONCLUSION: A new blood-based test for prostate cancer has a significant potential to reduce the number of biopsies needed, resulting in reduced health care costs and improve patient care.

Multiplex profiling of serum proteins in solution using barcoded antibody fragments and next generation sequencing.

The composition of serum proteins is reflecting the current health status and can, with the right tools, be used to detect early signs of disease, such as an emerging cancer. An earlier diagnosis of cancer would greatly increase the chance of an improved outcome for the patients. However, there is still an unmet need for proficient tools to decipher the information in the blood proteome, which calls for further technological development. Here, we present a proof-of-concept study that demonstrates an alternative approach for multiplexed protein profiling of serum samples in solution, using DNA barcoded scFv antibody fragments and next generation sequencing. The outcome shows high accuracy when discriminating samples derived from pancreatic cancer patients and healthy controls and represents a scalable alternative for serum analysis.

A multicenter study investigating the molecular fingerprint of psychological resilience in breast cancer patients: study protocol of the SCAN-B resilience study.

BACKGROUND: Individual patients differ in their psychological response when receiving a cancer diagnosis, in this case breast cancer. Given the same disease burden, some patients master the situation well, while others experience a great deal of stress, depression and lowered quality of life. Patients with high psychological resilience are likely to experience fewer stress reactions and better adapt to and manage the life threat and the demanding treatment that follows the diagnosis. If this phenomenon of mastering difficult situations is reflected also in biomolecular processes is not much studied, nor has its capacity for impacting the cancer prognosis been addressed. This project specifically aims, for the first time, to investigate how a breast cancer patient's psychological resilience is coupled to biomolecular parameters using advanced "omics" and, as a secondary aim, whether it relates to prognosis and quality of life one year after diagnosis. METHOD: The study population consists of newly diagnosed breast cancer patients enrolled in the Sweden Cancerome Analysis Network - Breast (SCAN-B) at four hospitals in Sweden. At the time of cancer diagnosis, the patient fills out the standardized method to measure psychological resilience, the "Connor-Davidson Resilience scale" (CD-RISC), the quality of life measure SF-36, as well as providing social and socioeconomic variables. In addition, one blood sample is collected. At the one-year follow-up, the patient will be subjected to the same assessments, and we also collect information regarding smoking, exercise habits, and BMI, as well as patients' trust in the treatment and their satisfaction with the care and treatment. DISCUSSION: This explorative hypothesis-generating project will pave the way for larger validation studies, potentially leading to a standardized method of measuring psychological resilience as an important parameter in cancer care. Revealing the body-mind interaction, in terms of psychological resilience and quality of life, will herald the development of truly personalized psychosocial care and cancer intervention treatment strategies. TRIAL REGISTRATION: This is a retrospectively registered trial at ClinicalTrials.gov, ID: NCT03430492 on February 6, 2018.

Modelling the benefits of early diagnosis of pancreatic cancer using a biomarker signature.

Pancreatic cancer (PC) has a poor prognosis, with a 5-year survival of 3-4%. This is mainly due to late diagnosis because of diffuse symptoms, where 80-85% of the patients are inoperable. Consequently, early diagnosis would be of significant benefit, resulting in a potential 5-year survival of 30-40%. However, new technologies must be carefully evaluated concerning effectiveness and healthcare costs. We have developed a framework for modelling cost and health effects from early detection of PC, which for the first time allowed us to analyse its cost-effectiveness. A probabilistic cohort model for estimating costs and quality adjusted life-years (QALY) arising from screening for PC, compared to a "wait-and-see"-approach, was designed. The test accuracy, Swedish survival and costs by tumour stage, expected life gain from early detection and pretest probabilities in risk groups, were retrieved from previous investigations. In a cohort of newly diagnosed diabetic patient (incidence 0.71%) the incremental cost per QALY gained (ICER) was €13,500, which is considered cost-effective in Europe. Results were mainly sensitive to the incidence with the ICER ranging from €315 to €204,000 (familial PC 35% and general population 0.046%, respectively). This is the first study focusing on clinical implementation of advanced testing and what is required for novel technologies in cancer care to be cost-effective. The model clearly demonstrated the potential of multiplexed proteomic-testing of PC and also identified the requirements for test accuracy. Consequently, it can serve as a model for assessing the possibilities to introduce advanced test platforms also for other cancer indications.

The GARD assay for assessment of chemical skin sensitizers.

Allergic contact dermatitis is a skin disease caused by an immunologic reaction to low molecular weight compounds, so called haptens. These substances are commonly present in products used by humans in daily life, such as in cosmetics and fragrances, as well as within chemical industry and in pharmaceuticals. The frequent usage of these compounds in different applications has led to increasing incidences of allergic contact dermatitis, which has become a substantial economic burden for society. As a consequence, chemicals are routinely tested for their ability to induce skin sensitization, using animal models such as the murine Local Lymph Node Assay. However, recent legislations regulate the use of animal models within chemical testing. Thus, there is an urgent need for in vitro alternatives to replace these assays for safety assessment of chemicals. Recently, we identified a signature of predictive genes, which are differentially regulated in the human myeloid cell-line MUTZ-3 when stimulated with sensitizing compounds compared to non-sensitizing compounds. Based on these findings, we have formulated a test strategy for assessment of sensitizing compounds, called Genomic Allergen Rapid Detection, GARD. In this paper, we present a detailed method description of how the assay should be performed.

Transcriptional profiling and assessment of cell lines as in vitro models for mantle cell lymphoma.

Mantle cell lymphoma (MCL) is an aggressive malignancy and new treatment modalities must be established to increase patient survival time. In the search for new therapeutic targets, reliable and well-characterised in vitro models are essential. In this study, we have characterised three MCL cell lines (SP53, Granta 519 and NCEB1) in comparison with primary tumours from MCL, follicular lymphomas (FL), a FL cell line (RL), a Burkitt lymphoma cell line (RAJI) and five different B cell populations from healthy individuals. Expression profiling was used to determine the relative expression of >12000 transcripts in these samples, and flow cytometry analysis was performed to establish a phenotypic signature for each of the cell lines. In addition, the cell lines were sequenced, and the frequency of somatic mutations and immunoglobulin (Ig) variable heavy chain (VH) usage were determined. We show by hierarchical clustering that the cell lines retain a genetic signature similar to primary MCL, which readily separated the MCL samples from the other lymphoma cell lines and the FL tumours. Furthermore, the MCL cell lines showed differences in the frequency of VH somatic mutations (0-2.1%). The increased number of mutations in NCEB1, compared to the other MCL cell lines, was in agreement with a decreased expression of CD31, CD44, CXCR5, CCR7 and CCR6. Taken together, our data show that the cell lines are clearly derived from MCL tumours and expressed similar genetic and phenotypic signatures compared to primary tumours, which confirmed their usefulness as in vitro models.