BackgroundMyelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are myeloid neoplasms in which outgrowth of neoplastic clones disrupts normal hematopoiesis. Some patients with unexplained persistent cytopenias may not meet minimal diagnostic criteria for MDS but an alternate diagnosis is not apparent; the term idiopathic cytopenia of undetermined significance (ICUS) has been used to describe this state. MDS and AML occur primarily in older patients who are often treated outside the clinical trial setting. Consequently, our understanding of the patterns of diagnostic evaluation, management, and outcomes of these patients is limited. Furthermore, there are few natural history studies of ICUS. To better understand how patients who have MDS, ICUS, or AML are managed in the routine clinical setting, the Connect MDS/AML Disease Registry, a multicenter, prospective, observational cohort study of patients newly diagnosed with these conditions has been initiated.Methods/DesignThe Connect MDS/AML Disease Registry will capture diagnosis, risk assessment, treatment, and outcomes data for approximately 1500 newly diagnosed patients from approximately 150 community and academic sites in the United States in 4 cohorts: (1) lower-risk MDS (International Prognostic Scoring System [IPSS] low and intermediate-1 risk), with and without del(5q); (2) higher-risk MDS (IPSS intermediate-2 and high risk); (3) ICUS; and (4) AML in patients aged ≥ 55 years (excluding acute promyelocytic leukemia). Diagnosis will be confirmed by central review. Baseline patient characteristics, diagnostic patterns, treatment patterns, clinical outcomes, health economics outcomes, and patient-reported health-related quality of life will be entered into an electronic data capture system at enrollment and quarterly for 8 years. A tissue substudy to explore the relationship between karyotypes, molecular markers, and clinical outcomes will be conducted, and is optional for patients.DiscussionThe Connect MDS/AML Disease Registry will be the first prospective, observational, non-interventional study in the United States to collect clinical information, patient-reported outcomes, and tissue samples from patients with MDS, ICUS, or AML receiving multiple therapies. Results from this registry may provide new insights into the relationship between diagnostic practices, treatment regimens, and outcomes in patients with these diseases and identify areas for future investigation.Trial registrationConnect MDS/AML Disease Registry (NCT01688011). Registered 14 September 2012.

BackgroundProstate cancer is the most common non-cutaneous malignancy in men. Today most patients may expect to live years following the diagnosis and may thus experience significant morbidity due to disease progression and treatment toxicity. In order to address some of these problems exercise has been suggested and previously studies have shown improvements of disease specific quality of life and a reduction in treatment-related toxicity. Cohort studies with long term follow up have suggested that physical activity is associated with improved survival in prostate cancer patients. Previously one randomised controlled trial has examined the efficacy of football in prostate cancer patients undergoing androgen deprivation therapy to usual care and reported positive effects on lean body mass and bone markers. Against this background, we wish to examine the effectiveness of community-based football for men diagnosed with prostate cancer.MethodsUsing a randomised controlled parallel group, multicenter, superiority trial design, two hundred prostate cancer patients will be recruited and randomised (1:1) to either community-based football one hour twice weekly or to a control group. The intervention period will be six months. The primary outcome is quality of life assessed after 12 weeks based on the change from baseline in the Functional Assessment of Cancer Therapy–Prostate questionnaire. Secondary outcomes are change from baseline to six months in quality of life, lean body mass, fat mass, whole body and regional bone markers, as well as physical activity and functional capacity at 12 weeks and six months. Safety outcome variables will be falls resulting in seeking medical assessment and fractures during the six-month period.DiscussionFootball is viewed as a case for non-professional, supervised community-based team sport for promoting long-term physical activity in men diagnosed with prostate cancer. This randomised trial will provide data on effectiveness and safety for men with prostate cancer when football training is delivered in local football clubs.Trial registrationClinicaltrials.gov identifier: NCT02430792

BackgroundGlobally, cancer rates are increasing. In Scotland, it is estimated that 2 in 5 people will develop cancer in their lifetime. Therefore, this is crucial time to provide personalised care and support to individuals affected by cancer. In response to this a community based supportive cancer service was launched in Glasgow, Scotland. The aim of this service is to proactively provide those affected by cancer with an assessment of their needs and personalised support where needed. To our knowledge, there is no other service like this in the United Kingdom.MethodsThe aim of this study is to understand if and how the service impacts upon the experiences and outcomes of people living with and affected by cancer. The study uses a sequential mixed methods design across a 5 year time point. Data gathering includes questionnaires, interviews, observations and reflective diaries. Participants include people affected by cancer who have used the service, a comparative sample who have not used the service, individuals who deliver the service and wider stakeholders. Outcomes include measures of patient activation, quality of life, health status, and social support. Data collection occurs at baseline, 2.5 years and 4 years with data from observations and reflective diaries supplemented throughout.DiscussionThis study evaluates an innovative community based cancer service. It focuses on impact and process issues relevant to a) the individuals in receipt of the service, b) the service providers, and c) the wider culture. As the programme evolves overtime, the research has been designed to draw out learning from the programme in order to support future commissioning both within Scotland and across the UK.

BackgroundStereotactic ablative body radiotherapy (SABR) is emerging as a non-invasive method for precision irradiation of lung tumours. However, the ideal dose/fractionation schedule is not yet known. The primary purpose of this study is to assess safety and efficacy profile of single and multi-fraction SABR in the context of pulmonary oligometastases.Methods/DesignThe TROG 13.01/ALTG 13.001 clinical trial is a multicentre unblinded randomised phase II study. Eligible patients have up to three metastases to the lung from any non-haematological malignancy, each < 5 cm in size, non-central targets, and have all primary and extrathoracic disease controlled with local therapies. Patients are randomised 1:1 to a single fraction of 28Gy versus 48Gy in four fractions of SABR. The primary objective is to assess the safety of each treatment arm, with secondary objectives including assessment of quality of life, local efficacy, resource use and costs, overall and disease free survival and time to distant failure. Outcomes will be stratified by number of metastases and origin of the primary disease (colorectal versus non-colorectal primary). Planned substudies include an assessment of the impact of online e-Learning platforms for lung SABR and assessment of the effect of SABR fractionation on the immune responses. A total of 84 patients are required to complete the study.DiscussionFractionation schedules have not yet been investigated in a randomised fashion in the setting of oligometastatic disease. Assuming the likelihood of similar clinical efficacy in both arms, the present study design allows for exploration of the hypothesis that cost implications of managing potentially increased toxicities from single fraction SABR will be outweighed by costs associated with delivering multiple-fraction SABR.Trials registrationACTRN12613001157763, registered 17th October 2013

BackgroundPrimary central nervous system lymphoma (PCNSL) is a highly aggressive Non-Hodgkin lymphoma (NHL) with rising incidence over the past 30 years in immunocompetent patients. Although outcomes have improved, PCNSL is still associated with inferior prognosis compared to systemic NHL. Many questions regarding the optimal therapeutic approach remain unanswered.Methods/DesignThis is a randomized, open-label, international phase III trial with two parallel arms. We will recruit 250 patients with newly diagnosed PCNSL from approximately 35 centers within the networks of the German Cooperative PCNSL study group and the International Extranodal Lymphoma Study Group. All enrolled patients will undergo induction chemotherapy consisting of 4 cycles of rituximab 375 mg/m2/d (days 0 & 5), methotrexate 3.5 g/m2 (d1), cytarabine 2 × 2 g/m2/d (d2-3), and thiotepa 30 mg/m2 (d4) every 21 days. All patients will undergo stem-cell harvest after the second cycle. After 4 cycles of induction chemotherapy, patients achieving partial or complete response will be centrally randomized to 2 different consolidation treatments: (A) conventional-dose immuno chemotherapy with rituximab 375 mg/m2 (d0), dexamethasone 40 mg/d (d1-3), etoposide 100 mg/m2/d (d1-3), ifosfamide 1500 mg/m2/d (d1-3) and carboplatin 300 mg/m2 (d1) (R-DeVIC) or (B) high-dose chemotherapy with BCNU (or busulfan) and thiotepa followed by autologous stem cell transplantation (HCT-ASCT). The objective is to demonstrate superiority of HCT-ASCT compared to R-DeVIC with respect to progression-free survival (PFS, primary endpoint). Secondary endpoints include overall survival (OS), treatment response and treatment-related morbidities. Minimal follow-up after treatment completion is 24 months.DiscussionThe rationale for consolidation treatment in PCNSL is to eliminate residual lymphoma cells and to decrease the risk for relapse. This can be achieved by agents crossing the blood brain barrier either applied at conventional doses or at high doses requiring autologous stem cell support. HCT-ASCT has been shown to be feasible and highly effective in patients with newly-diagnosed PCNSL. However, it is unclear whether HCT-ASCT is really superior compared to conventional-dose chemotherapy after an intensified antimetabolites-based immunochemotherapy in patients with newly-diagnosed PCNSL. To answer this question, we designed this investigator initiated randomized phase III trial.Trial registrationGerman clinical trials registry DRKS00005503 registered 22 April 2014 and ClinicalTrials.gov NCT02531841 registered 24 August 2015.

BackgroundBladder cancer is a very heterogeneous disease as regards natural history. Environmental exposures, constitutional genetic and/or epigenetic background may affect not only the likelihood of bladder tumor occurrence, but also the histologic type of cancer and its outcome. Currently, only a few data are available to study the prognostic role of genetic and environmental factors. Likewise, data on the economic burden of bladder cancer and the longitudinal impact of the disease and the treatments on patient quality of life are scarce.MethodsCOBLAnCE is a large French-based clinical cohort study on bladder cancer. Newly diagnosed patients are enrolled prospectively in 12 public hospitals and 5 private for profits hospitals. The target sample size is 2,000 patients. All patients are to be followed for 6 years. Information on patient characteristics and lifestyle is collected during a face-to-face interview at enrollment. Clinical information on disease presentation, diagnosis, and treatment is extracted from medical records for the primary tumor and for all subsequent local and distant recurrences. Quality of life and resource use is collected at recruitment and during follow-up. In parallel, 4 types of biological samples (blood, tumor tissue, urine and nail) are collected, at baseline and during follow-up. DNA, RNA and PBMLs are extracted from blood samples, DNA and RNA from stabilized urine, proteins from frozen urine, DNA, RNA and proteins from frozen tumor tissues, and DNA and RNA from formalin-fixed paraffin-embedded tumor tissues. All derived products are stored at −80 °C or in liquid nitrogen. Main endpoints are gene-environment interactions, molecular classification, biomarker discovery, therapeutic innovation, treatment patterns, healthcare resource use, bladder cancer outcomes and quality of life.DiscussionThe COBLAnCE cohort will provide considerable insight into the biology of bladder cancer and the mechanisms through which genetic and environmental factors may influence the prognosis. It may allow the discovery of emerging biomarkers. Finally, economic data will be useful for future cost-effectiveness studies of immunotherapy drugs or other therapeutics in bladder cancer.