Improved survival in myeloma patients-a nationwide registry study of 4,647 patients ≥75 years treated in Denmark and Sweden.

The prevalence of multiple myeloma (MM) is increasing in Nordic countries and the rest of the western world. Patients aged ≥75 years at diagnosis constitute an increasing proportion of all MM patients, but are underrepresented in randomized clinical trials. There is an urgent need for studies of the characteristics, treatment and outcome in this cohort. We present data from two nationwide population-based registries of all MM patients diagnosed in Denmark from January 1, 2005 until February 18, 2020, and in Sweden from January 1, 2008 until December 31, 2019, including treatment data for patients diagnosed until 2018 (Denmark) and 2019 (Sweden). In total 4,647 patients were ≥75 years at diagnosis, compared to 7,378 younger patients. Patients ≥75 years, accounting for approximately 40% of all MM patients, are a distinct cohort with more advanced disease at diagnosis, reflected by higher International Staging System (ISS) stage, and a higher proportion have renal failure and anemia. We found a more gradual introduction of modern medications in the older cohort than in the younger, despite simultaneous changes in guidelines. Compared to the cohorts in randomized controlled trials that guide the treatment of non-transplant eligible patients, we found a higher proportion of patients ≥75 years and presenting with ISS III in the real-world populations. Nevertheless, response rates and survival are increasing, indicating that modern treatment regimens are effective and well tolerated also in elderly MM patients in real-world populations.

Regional differences in treatment and outcome for myeloma patients in Sweden: A population based Swedish myeloma register study.

BACKGROUND: We wanted to evaluate if health care for multiple myeloma (MM) patients is equal in different regions of Sweden. AIM: To study differences in survival for MM depending on health care region and early use of modern treatment. METHODS AND RESULTS: Data from the Swedish Myeloma Register from patients diagnosed between 2008 and 2017 was used. Cohorts were defined by the six healthcare regions (labeled A-F) in Sweden and modern initial treatment was defined as including certain drug combinations. To adjust for time to treatment bias, survival analyses were performed also for patients alive 6 months after diagnosis. In all treated MM patients (n = 5326), we observed a superior overall survival (OS) for region A compared to all other regions (p < .01 for all respectively). After adjusting for time to treatment there was also a superior survival in the region with highest use of modern initial treatment (region A) compared to the regions defined in the study as having intermediate and low use (p < .01 for both). In patients receiving autologous stem cell transplantation (ASCT) a superior survival was observed for region A compared to all regions besides region B. Similar results were seen when adjusting for a time to treatment bias. In patients not receiving ASCT, 75 years or older and adjusted for time to treatment bias, a difference was noted only between region A and E (log rank p = .04, HR 1.2, CI 1.00-1.44, p = .06). In multivariate analyses including age, international staging system stage and time period of diagnosis, differences in survival remained for patients receiving ASCT between region A versus C, D, E and F (p = .01, p < .01, p < .01, p = .03). CONCLUSION: We observed a superior survival in region A for patients receiving ASCT. Explanations may be higher usage of modern initial treatment or regional residual confounding. For patients not receiving ASCT, 75 years or older, differences in survival could be adjusted for.

Exploring the meaning, role and experiences of a patient-led social innovation for people affected by cancer: a new collaborative care model complementing traditional cancer rehabilitation in Sweden.

OBJECTIVE: Kraftens Hus is the first support centre in Sweden designed by and for people affected by cancer, including patients, family, friends, staff members and local community representatives (collectively 'stakeholders'). The purpose of this study was to explore the meaning, role and experiences of Kraftens Hus stakeholders using a patient and public involved methodology. METHODS: To understand and map the experiences of visitors to Kraftens Hus, we applied concept mapping (CM), a mixed methods approach where data are collected and analysed in four structured steps designed to capture the diverse perspectives of multiple stakeholders. Qualitative interviews with relevant stakeholders supplemented the CM findings. RESULTS: The final concept map contained six clusters of ideas. Within the clusters, there was a recurring theme that cancer-affected people value accessible and long-term psychosocial support (PSS). The intended emotional, social and practical needs identified in a previous design process seem to have been addressed and appreciated by Kraftens Hus visitors. CONCLUSION: Kraftens Hus is an example of a new patient-led social innovation based on a life-event perspective and integration of resources from different sectors in society. By focusing on life, not the disease, the care continuum expands, and long-term PSS is provided alongside cancer treatment. The evaluation confirms that PSS should focus on health and well-being in the broadest sense.

Evaluating the implementation and use of the regional cancer plan in Western Sweden through concept mapping.

QUALITY PROBLEM OR ISSUE: Within healthcare, policy documents are often used to strategically standardize, streamline or change how general health issues are managed for a specific patient group or treatment. Despite significant effort in developing policy and strategic planning documents, these may not have the intended impact and their value has long been questioned by practitioners. CHOICE OF SOLUTION: To identify barriers and affordances for the implementation and use of a strategic plan for cancer care in the Western Sweden Healthcare Region, we used Concept Mapping; a participatory mixed method approach to inquiry consisting of both qualitative and quantitative tasks intended to elicit and integrate the diverse perspectives of multiple stakeholders. IMPLEMENTATION: The study was carried out between April and October 2017 and consisted of several sequential data collection steps: idea generation, sorting and rating ideas for importance and feasibility. Stakeholders from different levels and professions in cancercare participated, but the number varied in the separate steps of data collection: idea generation (n = 112), sorting (n = 16) and rating (n = 38). EVALUATION: A concept map visualized seven areas that stakeholders throughout the cancer-care process considered necessary to address in order to enable the implementation of the plan. Skills provision was considered the most important cluster but also rated as least feasible. A consistent theme emerged that information, or lack thereof, might be a barrier for the plan being put into action to a greater extent in the cancer-care units. Nine actionable ideas rated highly on both importance and feasibility were presented as a go-zone. LESSONS LEARNED: Our results suggest that efforts might be better spent on ensuring information about and accessibility to strategic documents throughout the organization, rather than frequently updating them or producing new ones. Having sufficient skills provision seems to be the prerequisite for successful implementation.

Outcome and survival of myeloma patients diagnosed 2008-2015. Real-world data on 4904 patients from the Swedish Myeloma Registry.

Epidemiology and outcome of myeloma are mainly reported from large university centers and collaborative groups, and do not represent 'real-world' patients. The Swedish Myeloma Registry is a prospective population-based registry documenting characteristics, treatment and outcome in newly diagnosed myeloma, including asymptomatic and localized forms, with the purpose of improving disease management and outcome. This report presents information on patients diagnosed between 2008 and 2015, including data on first-line treatment in patients diagnosed up to 2014, with a follow up until December 2016. We present age-adjusted incidence, patients' characteristics at baseline, treatment, response, and survival. Baseline data were available with a 97% coverage in 4904 patients (median age 71 years, males 70 years, females 73 years; 72% were 65 years or older), and at 1-year follow up in 3558 patients with symptomatic disease (92% of patients initially reported). The age-adjusted incidence was 6.8 myeloma cases per 100,000 inhabitants per year. Among initially symptomatic patients (n=3988), 77% had osteolytic lesions or compression fractures, 49% had anemia, 18% impaired kidney function, and 13% hypercalcemia. High-dose therapy with autologous stem cell transplantation was given to 77% of patients aged up to 66 years, and to 22% of patients aged 66-70 years. In the study period, 68% received bortezomib, thalidomide, and/or lenalidomide as part of the first-line treatment, rising from 31% in 2008 to 81% in 2014. In active myeloma, the median relative survival of patients aged 65 years or under was 7.7 years, and 3.4 years in patients aged 66 years and over. Patients diagnosed with myeloma in more recent years were associated with significantly higher rates of complete or very good partial remission (P<0.05), and with a significantly higher survival, with a Hazard Ratio (HR) of 0.84 (95%CI: 0.77-0.92; P<0.05). There was a small, but significant survival benefit in patients treated at university hospitals (HR 0.93; 95%CI: 0.87-0.99; P<0.05). We report here on a near complete 'real-world' population of myeloma patients during an 8-year period; a period in which newer drugs were implemented into standard practice. The overall incidence and median age were both higher than in most previous studies, indicating a more complete coverage of older patients. Myeloma survival in Sweden is comparable to other large registry studies, and responses and survival improved during the study period.

Incidence, characteristics, and outcome of solitary plasmacytoma and plasma cell leukemia. Population-based data from the Swedish Myeloma Register.

Solitary plasmacytoma (SP) and plasma cell leukemia (PCL) are uncommon (3-6%) types of plasma cell disease. The risk of progression to symptomatic multiple myeloma (MM) is probably important for the outcome of SP. PCL is rare and has a dismal outcome. In this study, we report on incidence and survival in PCL/SP, and progression to MM in SP, using the prospective observational Swedish Multiple Myeloma Register designed to document all newly diagnosed plasma cell diseases in Sweden since 2008. Both solitary bone plasmacytoma (SBP) (n=124) and extramedullary plasmacytoma (EMP) (n=67) have better overall survival (OS) than MM (n=3549). Progression to MM was higher in SBP than in EMP (35% and 7% at 2 years, respectively), but this did not translate into better survival in EMP. In spite of treatment developments, the OS of primary PCL is still dismal (median of 11 months, 0% at 5 years). Hence, there is a great need for diagnostic and treatment guidelines as well as prospective studies addressing the role for alternative treatment options, such as allogeneic stem cell transplantation and monoclonal antibodies in the treatment of PCL.

Model selection in medical research: a simulation study comparing Bayesian model averaging and stepwise regression.

BACKGROUND: Automatic variable selection methods are usually discouraged in medical research although we believe they might be valuable for studies where subject matter knowledge is limited. Bayesian model averaging may be useful for model selection but only limited attempts to compare it to stepwise regression have been published. We therefore performed a simulation study to compare stepwise regression with Bayesian model averaging. METHODS: We simulated data corresponding to five different data generating processes and thirty different values of the effect size (the parameter estimate divided by its standard error). Each data generating process contained twenty explanatory variables in total and had between zero and two true predictors. Three data generating processes were built of uncorrelated predictor variables while two had a mixture of correlated and uncorrelated variables. We fitted linear regression models to the simulated data. We used Bayesian model averaging and stepwise regression respectively as model selection procedures and compared the estimated selection probabilities. RESULTS: The estimated probability of not selecting a redundant variable was between 0.99 and 1 for Bayesian model averaging while approximately 0.95 for stepwise regression when the redundant variable was not correlated with a true predictor. These probabilities did not depend on the effect size of the true predictor. In the case of correlation between a redundant variable and a true predictor, the probability of not selecting a redundant variable was 0.95 to 1 for Bayesian model averaging while for stepwise regression it was between 0.7 and 0.9, depending on the effect size of the true predictor. The probability of selecting a true predictor increased as the effect size of the true predictor increased and leveled out at between 0.9 and 1 for stepwise regression, while it leveled out at 1 for Bayesian model averaging. CONCLUSIONS: Our simulation study showed that under the given conditions, Bayesian model averaging had a higher probability of not selecting a redundant variable than stepwise regression and had a similar probability of selecting a true predictor. Medical researchers building regression models with limited subject matter knowledge could thus benefit from using Bayesian model averaging.

Bias in odds ratios by logistic regression modelling and sample size.

BACKGROUND: In epidemiological studies researchers use logistic regression as an analytical tool to study the association of a binary outcome to a set of possible exposures. METHODS: Using a simulation study we illustrate how the analytically derived bias of odds ratios modelling in logistic regression varies as a function of the sample size. RESULTS: Logistic regression overestimates odds ratios in studies with small to moderate samples size. The small sample size induced bias is a systematic one, bias away from null. Regression coefficient estimates shifts away from zero, odds ratios from one. CONCLUSION: If several small studies are pooled without consideration of the bias introduced by the inherent mathematical properties of the logistic regression model, researchers may be mislead to erroneous interpretation of the results.

Usefulness of current risk groups in the treatment of surgically staged endometrial carcinomas; a population-based study from Western Sweden.

BACKGROUND: Endometrial carcinoma is the most common malignancy of the female genital tract and its incidence is increasing. However, treatment results have not improved during the last decades. PATIENTS AND METHODS: Our regional quality register was used to evaluate treatment results for the period between January 1995 and December 2003. This study includes 2211 consecutive patients, of which 1993 surgically staged patients were evaluated in detail. Of these, 831 (53%) were at low risk and were given no further treatment after primary surgery. Patients with moderate- and high-risk tumors were postoperatively treated according to the respective protocols of one Swedish and one international study. Postoperative vaginal brachytherapy +/- external radiation was given to 486 (31%) patients at moderate risk, while 234 (15%) had high-risk disease and were randomized to external radiation + brachytherapy or external radiation + brachyterapy + chemotherapy. RESULTS: Overall cause-specific 5- and 10-year survival was 83.9% and 81.3%, respectively, for all included patients. The corresponding figures for surgically staged patients were 87.4% and 84.9%, respectively. One important observation was that there was no significant difference in survival between patients at low and moderate risk. CONCLUSION: The results strongly suggest that the risk groups used during this study period were not optimal. It is recommended to use smaller, better specified groups defined by more prognostic factors for enhanced individualization of treatment.