Time trends in treatment patterns and survival of older patients with synchronous metastatic colorectal cancer in the Netherlands: A population-based study.

New treatment strategies have improved survival of metastatic colorectal cancer in trials. However, it is not clear whether older patients benefit from these novel therapies, as they are often not included in pivotal trials. Therefore, we investigated treatment patterns and overall survival over time in older patients with metastatic colorectal cancer in a population-based study. We identified 22.192 Dutch patients aged ≥70 years diagnosed with synchronous metastatic colorectal cancer between 2005 and 2020 from the Netherlands Cancer Registry. Changes in treatment over time were assessed with logistic regression models. Survival was assessed by Cox proportional hazard ratios (HR). Results showed that chemotherapy use increased between 2005 and 2015, but declined from 2015 onwards, while more patients received best supportive care. Over time, fewer patients underwent primary tumor resection alone. Although survival of both metastatic colon and rectal cancer improved until 2014, survival of colon cancer decreased from 2014 onwards (HR 1.04, 95% confidence interval [CI] 1.01-1.05), which was seen in all age groups. Survival of metastatic rectal cancer patients remained unchanged from 2014 onwards (HR 1.00, 95% CI 0.98-1.03) in all age groups. In conclusion, treatment patterns of Dutch older patients with synchronous metastatic colorectal cancer rapidly changed from 2005 to 2020, with increasing percentages of patients receiving best supportive care. Survival of metastatic colon cancer decreased from 2014 onwards. The implementation of a colorectal cancer screening program and patient selection might explain why only a subset of older patients seem to benefit from the availability of novel treatment options.

Risk of venous thromboembolism and major bleeding in the clinical course of osteosarcoma and Ewing sarcoma.

BACKGROUND: Patients with osteosarcoma (OS) and Ewing sarcoma (ES) are considered to have a high venous thromboembolism (VTE) risk, although the exact incidence and prognostic impact are under-researched in general as well as in relevant age groups. AIMS: To study the impact of VTE and major bleeding (MB) in OS and ES patients, subdivided in children, Adolescents Young Adults (AYAs; aged 18-39) and older adults. METHODS: Retrospective single-center chart review in 519 OS and 165 ES patients treated between 1980 and 2018. Patients were followed from sarcoma diagnosis until an outcome of interest (VTE, MB) or death occurred. Cumulative incidences were estimated with death as competing risk. Cox models were used to determine prognostic impact. RESULTS: Five-year cumulative incidences of VTE were 12 % (95%CI 9.1-15) for OS and 6.7 % (95%CI 3.5-11) for ES patients, mostly happening in patients ≥18 years; the most frequent VTE presentation was catheter-related upper-extremity thrombosis (OS: 18/65, ES: 7/11). Five-year cumulative incidences for MB were 5.8 % (95%CI 4.0-8.1) in OS and 5.4 % (95%CI 2.5-9.8) in ES patients. 192 OS and 77 ES AYAs were included, who faced similar VTE and MB incidences as older adults. In OS, VTE and MB were both associated with mortality (adjusted HRs 2.0 [95%CI 1.4-2.9] and 2.4 [95%CI 1.4-4.0], respectively), whereas in ES this association was only present for MB (aHR 3.4 [95%CI 1.2-9.6]). CONCLUSIONS: VTE is a frequent complication in adult OS and to a lesser extent in ES patients, while the rate of MB was comparably high in both sarcoma types.

Combining service design and discrete choice experiments for intervention design: An application to weather index insurance.

In this paper we provide a detailed description of the methodological steps involved in conducting a Service Design study in combination with Discrete Choice Experiments (DCEs). It complements the conceptual and epistemological argument developed for this methodological combination in Osborne et al. (2021, World Development, in review WD-19535). Service Design for the co-creative development of policy interventions in complex adaptive systems involves an iterative process of moving between the six methodological stages of (1) problem co-definition, (2) actor-centred mapping, (3) experience-based problem diagnosis, (4) rapid prototyping, (5) design and testing and (6) upscaling. We suggest using DCEs as a quantitative method that is contextually adaptable and comparatively fast and cheap to implement, as part of stage (6) design and testing. Whilst both methods can operate independently with their own strengths and limitations, we find their combination to add value to the processes and outcomes of each. We illustrate the general methodological approach with a step-by-step description of its application to Weather Index Insurance in eastern Uganda. Bullet points: • Service Design co-creatively develops well-targeted solutions in complex adaptive systems. • Discrete Choice Experiments quantitatively elicit actors' preferences over the design of goods or services. • Their combination can bring deeply contextualised, user-centred, operational and experimentally verified ideas for development interventions prior to their implementation.

Higher incidence rates than previously known in tenosynovial giant cell tumors.

Background and purpose - Tenosynovial giant cell tumors (TGCT) are rare, benign tumors, arising in synovial lining of joints, tendon sheaths, or bursae. 2 types are distinguished: localized, either digits or extremity, and diffuse lesions. Current TGCT incidence is based on 1 single US-county study in 1980, with an incidence of 9 and 2 per million person-years in localized (including digits) and diffuse TGCT, respectively. We aim to determine nationwide and worldwide incidence rates (IR) in TGCT affecting digits, localized-extremity TGCT and diffuse-type TGCT. Material and methods - Over a 5-year period, the Dutch Pathology Registry (PALGA) identified 4,503 pathology reports on TGCT. Reports affecting digits were solely used for IR calculations. Reports affecting extremities were clinically evaluated. Dutch IRs were converted to world population IRs. Results - 2,815 (68%) digits, 933 (23%) localized-extremity and 390 (9%) diffuse-type TGCT were identified. Dutch IR in digits, localized-extremity, and diffuse-type TGCT was 34, 11 and 5 per million person-years, respectively. All 3 groups showed a female predilection and highest number of new cases in age category 40-59 years. The knee joint was most often affected: localized-extremity (46%) and diffuse-type (64%) TGCT, mostly treated with open resection: localized (65%) and diffuse (49%). Reoperation rate due to local recurrence for localized-extremity was 9%, and diffuse TGCT 23%. Interpretation - This first nationwide study and detailed analyses of IRs in TGCT estimated a worldwide IR in digits, localized-extremity and diffuse TGCT of 29, 10, and 4 per million person-years, respectively. Recurrence rate in diffuse type is 2.6 times higher, compared with localized extremity. TGCT is still considered a rare disease; however, it is more common than previously understood.

Imatinib-induced agranulocytosis in patients with gastrointestinal stromal tumors.

Agranulocytosis is a rare but serious side effect of imatinib in gastrointestinal stromal tumor (GIST) patients. Imatinib is an inhibitor of the proto-oncogene tyrosine kinase (c-kit) and the first-line agent in patients with locally advanced and metastatic GIST. Little evidence is available on the management of this adverse event, and consensus-based guidelines are lacking. In this article, we describe 4 patients with agranulocytosis after starting imatinib. In addition, an overview of the available literature concerning the underlying mechanisms is given, and therapeutic strategies for overcoming this adverse event are discussed. In our experience it appears safe to restart imatinib after normalization of neutrophil count. In case of relapse of agranulocytosis, reintroduction combined with prednisolone, with treatment with granulocyte colony-stimulating factor or dose reduction can be considered.

Vesiculopustular dermatosis: an uncommon side-effect of liraglutide?

Liraglutide is a GLP-1 receptor agonist, a novel medication for type 2 diabetes. We describe a case of pustules in a patient recently started on liraglutide. Common side effects of liraglutide are gastrointestinal disorders. Skin and tissue reactions are less well-known side effects. Liraglutide could be the cause of skin eruptions in this patient, possibly by immunogenicity.