The aetiology and burden of myeloproliferative neoplasms in the United Kingdom: the MyelOproliferative neoplasmS: an In-depth case-control (MOSAICC) study protocol.

BACKGROUND: Myeloproliferative neoplasms (MPNs) are a group of haematological malignancies that affect approximately 8 people in every 100,000 individuals in the UK. Little is known about the aetiology of MPNs, as previous studies have been hampered by small sample sizes, thus it is important to understand the cause of MPNs in a larger study to identify prevention strategies and improve treatment strategies. This study aims to determine environmental, lifestyle, genetic and medical causes of MPNs and to assess the relevance of occupational carcinogen exposures and quality of life impacts. METHODS: A UK-wide case-control study of 610 recently diagnosed MPN patients (within 24 months) receiving clinical care at 21 NHS study sites in Scotland, England, Wales and Northern Ireland and 610 non-blood relative/friend controls is underway. Data on occupational and residential history, medical and environmental factors, and quality of life are being collected from the participants via a structured interview and self-complete questionnaires. Clinical data is being provided by the clinical team. Blood, saliva and toenail samples are also being collected for genetic and elemental analysis. Adjusted odds ratios (ORs) and 95% confidence intervals (95%CI) will be calculated using a p < 0.05 to investigate potential risk factors for the MPN clinical and genetic subtypes, and further analyses will be conducted based on the type of data and outcome of interest at a later stage. DISCUSSION: The study design is most effective for investigating the aetiology of rare diseases. The study will enable identification of potential causes of MPNs through in-depth assessment of potential risk factors with potential for longer follow-up of a number of outcomes.

The impact of rurality on patient experience and diagnostic pathway intervals in Scotland's cancer patients: Further results from a national cancer diagnosis audit.

BACKGROUND: In Scotland 17 % of the population reside rurally and previous research has demonstrated worse cancer outcomes in this group. The underlying reason for this is unclear. This study aims to determine whether patient presenting factors, GP consultation factors or the diagnostic pathways differ between urban and rural patients within Scotland. METHODS: This study combined two Scottish National Cancer Diagnosis Audits. Participating GPs collected data on the diagnostic pathway from primary to secondary care for cancer patients diagnosed during the audit period. Using the Scottish Government Urban Rural Classification, patients were designated as rural or urban dwellers and compared in descriptive analyses. Key cancer intervals (primary, diagnostic, secondary and treatment interval) were compared between urban and rural dwellers with an additional adjusted analysis for the main cancer sites. RESULTS: A total of 4309 cancer diagnoses were included in the study; 22 % were in patients from rural locations. Rural patients had significantly more consultations and investigations prior to referral than their urban counterparts. There was no difference in prolonged cancer pathways between the two groups except in lung cancer patients where rural patients had a significantly increased odds of a diagnostic interval of >90 days. CONCLUSION: Our findings suggest differences in the interaction between patients and GPs prior to referral in urban and rural settings. However, this does not appear to lead to prolonged patient pathways, except in lung cancer. Further research is needed to determine whether this delay is clinically significant and contributing to poorer outcomes in Scottish rural dwellers with lung cancer.

Not all small HER2 positive breast cancers have the same clinical outcome in the North-East of Scotland.

HER2-positive breast cancers, representing up to 20% of all breast cancers, are more aggressive and have poorer outcomes. Systemic therapy has been proven to prevent disease recurrence and improve survival. Existing literature provides only limited evidence to support this in smaller HER2-positive tumors. The study aimed to evaluate HER-2 positive breast cancer management and treatment of all T1N0 tumors in the North of Scotland, diagnosed 2012-2019. Clinical-pathological details, comorbidities, treatments and clinical events were retrieved from the Scottish North Cancer Alliance audit database and analyzed using univariate and multivariate analysis including cox-regression and log-rank testing (SPSSv23).Overall, 299 patients (41% screen detected/ 56.9% symptomatic /2.1% other), median age 63 years and median tumor size 13 mm, were included. Most cancers were grade 2/3 (43.1%/ 55.5%). Most patients (59.5%) received treatment with trastuzumab (tT); 40.8% concurrent with chemotherapy and endocrine therapy. 7.7% of patients received neo adjuvant chemotherapy. Median follow-up time was 2.6 years, with recurrence on average occurring 2.9 years after diagnosis. Patients receiving trastuzumab were younger, had a higher grade and larger size tumor. 78.5% of patients in the untreated group (non-tT) were ER positive compared to 65.2% in the treated group (tT). Trastuzumab significantly lowered breast cancer recurrence (Tt=3.4% versus non-Tt=8.3%, p = 0.022 HR= 0.096, 95% CI 0.025-0.361). In conclusion, receiving anti-HER2 treatment significantly improved clinical outcome in this T1N0 patient group. Consideration, at the very least informed discussions with patients, should be undertaken to treat these early stage HER2-positive breast cancers.

A National Network of Safe Havens: Scottish Perspective.

For over a decade, Scotland has implemented and operationalized a system of Safe Havens, which provides secure analytics platforms for researchers to access linked, deidentified electronic health records (EHRs) while managing the risk of unauthorized reidentification. In this paper, a perspective is provided on the state-of-the-art Scottish Safe Haven network, including its evolution, to define the key activities required to scale the Scottish Safe Haven network's capability to facilitate research and health care improvement initiatives. A set of processes related to EHR data and their delivery in Scotland have been discussed. An interview with each Safe Haven was conducted to understand their services in detail, as well as their commonalities. The results show how Safe Havens in Scotland have protected privacy while facilitating the reuse of the EHR data. This study provides a common definition of a Safe Haven and promotes a consistent understanding among the Scottish Safe Haven network and the clinical and academic research community. We conclude by identifying areas where efficiencies across the network can be made to meet the needs of population-level studies at scale.

Spatial disparities in the reported incidence and survival of myeloproliferative neoplasms in Australia.

Myeloproliferative neoplasms (MPNs) are an uncommon group of blood cancers that, if untreated, result in an increased risk of haemorrhagic event or thrombosis. Unlike other cancer types, diagnosis of MPNs requires a combination of microscopic, clinical and genetic evidence, which provide unique challenges given the typical notification processes of cancer registries. This, and the relatively recent advances in diagnosis and revision of the World Health Organization diagnostic criteria, may result in under-diagnosis or under-reporting of MPNs. We used population-based cancer registry data from the Australian Cancer Database and modelled the incidence and survival of MPNs between 2007 and 2016 using generalised linear models and Bayesian spatial Leroux models. Substantial evidence was found of spatial heterogeneity in the incidence of MPNs and significant differences in incidence and survival by state or territory. States with lower incidence tended to have poorer survival, suggesting that some less severe cases may not be diagnosed or notified to the registries in those states. Population rates of genetic testing and percentages of records diagnosed using bone marrow biopsies did not explain the differences in incidence by state and territory. It is important to determine the key drivers of these geographical patterns, including the need to standardise diagnosis and reporting of MPNs.

Changes in the Demographic and Clinicopathological Characteristics of Thyroid Cancer: A Population-Based Investigation in Algeria, 1993-2013.

Over the last three decades, the incidence of thyroid cancer has increased worldwide. The reasons for this increase remain controversial. In Algeria, however, to date, information on thyroid cancer has been limited to a hospital-based case series. We analyzed data from a population-based cohort study in Oran District, Algeria, to describe demographic and clinicopathological characteristics of patients diagnosed with thyroid cancer between 1993 and 2013. Medical records and pathology reports of thyroid cancer patients who had surgery were reviewed. Changes in demographic and clinicopathological features over the 21-year period are described. During the study period, thyroid cancer was diagnosed in 1248 women (86.5%, mean age 43.7 ± 15.2 years) and 195 men (23.4%, mean age 48.1 ± 15.9 years). Most cases (83.1% for women and 69.8% for men) sought a diagnosis following a self-neck check. The most common histologic types were papillary (58.3%), follicular (29.7%), anaplastic (4.1%), and medullary (0.8%) carcinomas. The incidence of papillary carcinomas significantly increased (p < 0.001) while the incidence of other histologic types significantly decreased over time. Tumor size overall significantly decreased (p < 0.001) while the frequency of small (≤20 mm) and larger (>20 mm) carcinomas significantly increased (p < 0.05). The frequency of thyroid cancers with capsular effractions and angioinvasions also decreased over time. Thyroid cancer incidence in Algeria has increased substantially in line with international trends with changes in clinical practice being a possible contributing factor. However, the increasing papillary-to-follicular cancer ratio may be due to changes in iodine nutrition status in Algeria. Further research, including exploration of biological and molecular features of thyroid cancer, will enable a better understanding of risk factors and etiopathogenetic mechanisms.

Aetiology of Myeloproliferative Neoplasms.

Myeloproliferative neoplasms (MPNs) have estimated annual incidence rates for polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis of 0.84, 1.03, and 0.47 per 100,000. Prevalence is much higher, particularly for PV and ET, as mortality rates are relatively low. Patients are often concerned about why they developed an MPN and epidemiological studies enable the identification of potential causative factors. Previous work in small heterogeneous studies has identified a variety of risk factors associated with MPNs including family history of MPN, autoimmune conditions, some occupational exposures, and blood donation. At a population level, germline predisposition factors in various populations have been associated with MPNs. The pilot MOSAICC (Myeloproliferative Neoplasm: An In-depth Case-Control) study is one of the largest epidemiological studies in MPN ever carried out to date. It demonstrated the most effective methods for carrying out a significant epidemiological study in this patient group including the best way of recruiting controls, as well as how to evaluate occupational and lifestyle exposures, evaluate symptoms, and collect biological samples. Significant results linked to MPNs in the pilot study of 106 patients included smoking, obesity, and childhood socioeconomic status. The methodology is now in place for a much larger ongoing MOSAICC study which should provide further insight into the potential causes of MPNs.

Rare thyroid malignancies in Europe: Data from the information network on rare cancers in Europe (RARECAREnet).

OBJECTIVE: Limited information is available on the incidence of rare thyroid cancer (TC) subtypes: anaplastic (ATC) and medullary (MTC). The aim of this study was to describe incidence variations and trends across European countries of all TC subtypes. MATERIALS AND METHODS: We used the RARECAREnet database including 80721 TC incident cases in the period 2000-2007 from 77 population-based cancer registries (CRs) in Europe. In the trend analyses, we included 68890 TC cases from 53 CRs with at least 6 years of incidence data in the years 2000-2007. RESULTS: In Europe age-standardised incidence rates (ASR) in women were <0.3/100,000 for MTC and ATC whereas ASR were 5.3/100,000 for papillary thyroid cancer (PTC) and 1.1/100,000 for follicular TC (FTC). Corresponding ASRs in men were <0.2/100,000 for MTC and ATC, 1.5 for PTC and 0.4 for FTC. Across countries and in both sexes the incidence of FTC and MTC was moderately correlated (r ~ 0.5) with that of PTC, while a less marked correlation (r < 0.4) emerged for ATC ASRs. The changes of the PTC ASRs across countries and time were weakly (r < 0.3) or moderately (r ~ 0.5) correlated to the changes of the other subtypes for both sexes. CONCLUSION: The huge increase and heterogeneity between countries of PTC incidence has a small influence on the trends and variations of MTC and ATC in Europe. Large-scale epidemiological and clinical registry-based studies are warranted to increase knowledge about the rarest TC subtypes. This information would be fundamental for the design of new clinical trials and for inference.

Prognoses and improvement for head and neck cancers diagnosed in Europe in early 2000s: The EUROCARE-5 population-based study.

BACKGROUND: Head and neck (H&N) cancers are a heterogeneous group of malignancies, affecting various sites, with different prognoses. The aims of this study are to analyse survival for patients with H&N cancers in relation to tumour location, to assess the change in survival between European countries, and to investigate whether survival improved over time. METHODS: We analysed about 250,000 H&N cancer cases from 86 cancer registries (CRs). Relative survival (RS) was estimated by sex, age, country and stage. We described survival time trends over 1999-2007, using the period approach. Model based survival estimates of relative excess risks (RERs) of death were also provided by country, after adjusting for sex, age and sub-site. RESULTS: Five-year RS was the poorest for hypopharynx (25%) and the highest for larynx (59%). Outcome was significantly better in female than in male patients. In Europe, age-standardised 5-year survival remained stable from 1999-2001 to 2005-2007 for laryngeal cancer, while it increased for all the other H&N cancers. Five-year age-standardised RS was low in Eastern countries, 47% for larynx and 28% for all the other H&N cancers combined, and high in Ireland and the United Kingdom (UK), and Northern Europe (62% and 46%). Adjustment for sub-site narrowed the difference between countries. Fifty-four percent of patients was diagnosed at advanced stage (regional or metastatic). Five-year RS for localised cases ranged between 42% (hypopharynx) and 74% (larynx). CONCLUSIONS: This study shows survival progresses during the study period. However, slightly more than half of patients were diagnosed with regional or metastatic disease at diagnosis. Early diagnosis and timely start of treatment are crucial to reduce the European gap to further improve H&N cancers outcome.