St.Jans Gasthuis Weert

BackgroundWe aimed to describe real-world complete response (CR) rates, predictors of CR, and survival outcomes in patients treated with first-line pertuzumab, trastuzumab, and chemotherapy for HER2-positive (HER2+) metastatic breast cancer (MBC).MethodsPatients with HER2+ MBC who started first-line pertuzumab, trastuzumab, and chemotherapy in 2013–2021 were selected from the SONABRE Registry (NCT-03577197), involving eleven Dutch hospitals. CR was defined as no evidence of disease on imaging during first-line systemic therapy with or without local therapy (surgery and/or radiotherapy). Multivariable logistic regression was used to identify predictors for CR. Progression-free survival (PFS) and overall survival (OS) from the start of first-line pertuzumab, trastuzumab, and chemotherapy were computed with the Kaplan-Meier method.ResultsWe included 244 patients treated with first-line pertuzumab, trastuzumab, and chemotherapy, with a median follow-up duration of 71 months (interquartile range: 60–82 months). A CR during first-line systemic therapy was reached in 63 patients (26 %). Patients younger than 65 years (odds ratio (OR) = 5.24, 95 %CI:1.49–18.44, p = 0.01), those with de Novo MBC (OR = 2.48, 95 %CI:1.24–4.93, p = 0.01), or those with a single metastatic site (OR = 3.81, 95 %CI:1.83–7.96, p < 0.001) were more likely to reach CR than their counterparts. The 5-year PFS and OS rates were, respectively, 63 % (95 %CI:48 %–75 %) and 85 % (95 %CI:72 %–92 %) in patients with a CR and 10 % (95 %CI:6 %–16 %) and 36 % (95 %CI:28 %–44 %) in patients without a CR.ConclusionsIn the real world, one in four patients treated with first-line pertuzumab, trastuzumab, chemotherapy, with or without local therapy, reached CR. Two third of patients with a CR were still free of progression after five years.

Comprehensive insights are lacking into why patients with hematological malignancies (HMs) receive no cancer-directed treatment. We evaluated socio-demographic and cancer-related characteristics, decision-making rationales, and overall survival in patients with three common HMs-diffuse large B-cell lymphoma (DLBCL), symptomatic multiple myeloma (MM), and acute myeloid leukemia (AML)-who do not receive cancer-directed treatment, using the nationwide Netherlands Cancer Registry. A total of 26 945 patients diagnosed with DLBCL (47%), symptomatic MM (29%), or AML (25%) between 2014 and 2021 were included. About 16% of the patients did not receive cancer-directed treatment, ranging from 26% in AML to 15% in DLBCL and 10% in MM. The primary reason for not receiving cancer-directed treatment in all three HMs was related to physical condition. The second main reason was patient/family choice in DLBCL and MM, whereas in AML it was rapid disease progression. In female patients, patient/family choice was a more prevalent reason for not receiving cancer-directed treatment than in male patients. Patients with a lower socio-economic position more often did not receive cancer-directed treatment. Median OS varied by reason for not receiving cancer-directed treatment, with the shortest OS in patients experiencing rapid disease progression or death before treatment initiation (0·4 to 0·6 months).

The emergency department (ED) is a hectic place, where many critically ill patients are treated. For residents working in the ED, this environment may be demanding. The aim of this study was to investigate the [1] cognitive load experienced by residents working in the ED, and [2] differences in cognitive load during the day. In this multicentre, prospective study in three EDs in the Netherlands, the experienced cognitive load was graded by residents on three scales, agreed upon during Delphi meetings: the complexity (low-high: 1-3), mental effort (low-high: 1-9) and comfortability scale (low-high: 0-100%). We applied the scores per decision, 1-hour and 2-hour intervals, patient and shift. We observed 14 residents and analysed 74 1-hour and 45 2-hour intervals, 79 patients, 24 shifts and 592 separate decisions. The experienced cognitive load per decision was low. In contrast, the cognitive load was higher per 2-hour interval (mental effort: median 4.0 (IQR 4.0) and comfortability 80% (IQR 20)) and per shift (mental effort: median 5.5 (IQR 4.0) and comfortability 80% (IQR 20). Complexity was low for all measurements. Mental effort rose from 17h onwards higher values, whereas a decrease in comfortability was seen from 21h onwards. From 17h onwards, residents working in the ED experienced rather high mental effort and reported feeling not optimally comfortable when making decisions. The mental effort was highest between 21-23h. This was found when cognitive load was measured per 2-hour interval and per shift, but not per decision. This study may provide an insights to optimise cognitive load by reorganisation of the ED.

Increasing numbers of people with multiple sclerosis (MS) use disease-modifying therapy (DMT). Long-term stable disease while taking such medications provides a rationale for considering DMT discontinuation given patient burden, costs, and potential adverse effects of immunomodulating therapy. To investigate whether first-line DMT can be safely discontinued in patients with long-term stable MS. This multicenter, rater-blinded, noninferiority randomized clinical trial was conducted between July 1, 2020, and March 20, 2023, at 14 Dutch centers. Data analysis was performed between July 2023 and January 2024. Key inclusion criteria were relapse-onset MS, aged 18 years or older, without relapses, and without substantial magnetic resonance imaging (MRI) activity in the previous 5 years under first-line DMT. Participants were randomized 1:1 to discontinue or continue first-line DMT. Discontinuation of first-line DMT. The primary outcome was significant inflammatory disease activity, defined as relapse and/or 3 or more new T2 lesions or 2 or more contrast-enhancing lesions on brain MRI. Of 163 potentially eligible participants, 89 participants were included in the trial at the moment of early termination. Forty-four participants (49.4%) were assigned to the continue group and 45 participants (50.6%) were assigned to the discontinue group. Median (IQR) age was 54.0 (49.0-59.0) years, and 60 participants (67.4%) were female. Two participants in the continue group were lost to follow-up. After a median (IQR) follow-up time of 15.3 (11.4-23.9) months, the trial was prematurely terminated because of inflammatory disease activity recurrence above the predefined limit. In total, 8 of 45 participants in the discontinue group (17.8%) vs 0 of 44 participants in the continue group reached the primary end point and had recurrent, mostly radiological inflammation. Two of these 8 participants had a clinical relapse. Median (IQR) time to disease activity was 12.0 (6.0-12.0) months. In this randomized clinical trial, even in patients with long-term MS stable for over 5 years, first-line DMT discontinuation can lead to recurrence of inflammatory disease activity. Although this study cohort was relatively small, the recurrence of inflammation in the discontinue group was significantly higher than in the continue group and also higher than in the previously published DISCOMS trial, which only included individuals aged 55 years or older. This study provides additional data, especially in a younger population and including longitudinal biomarker measurements, for informed decision-making in cases when treatment discontinuation is considered. ClinicalTrials.gov Identifier: NCT04260711.

PurposeThis study determines the prognostic impact of body mass index (BMI) in patients with hormone receptor-positive/human epidermal growth factor receptor-2-negative (HR+/HER2−) advanced (i.e., metastatic) breast cancer (ABC).MethodsAll patients with HR+/HER2− ABC who received endocrine therapy +—a cyclin-dependent kinase 4/6 inhibitor as first-given systemic therapy in 2007–2020 in the Netherlands were identified from the Southeast Netherlands Advanced Breast Cancer (SONABRE) registry (NCT03577197). Patients were categorised as underweight (BMI: < 18.5 kg/m2), normal weight (18.5–24.9 kg/m2), overweight (25.0–29.9 kg/m2), or obese (≥ 30.0 kg/m2). Overall survival (OS) and progression-free survival (PFS) were compared between BMI classes using multivariable Cox regression analyses.ResultsThis study included 1456 patients, of whom 35 (2%) were underweight, 580 (40%) normal weight, 479 (33%) overweight, and 362 (25%) obese. No differences in OS were observed between normal weight patients and respectively overweight (HR 0.99; 95% CI 0.85–1.16; p = 0.93) and obese patients (HR 1.04; 95% CI 0.88–1.24; p = 0.62). However, the OS of underweight patients (HR 1.45; 95% CI 0.97–2.15; p = 0.07) tended to be worse than the OS of normal weight patients. When compared with normal weight patients, the PFS was similar in underweight (HR 1.05; 95% CI 0.73–1.51; p = 0.81), overweight (HR 0.90; 95% CI 0.79–1.03; p = 0.14), and obese patients (HR 0.88; 95% CI 0.76–1.02; p = 0.10).ConclusionIn this study among 1456 patients with HR+/HER2− ABC, overweight and obesity were prevalent, whereas underweight was uncommon. When compared with normal weight, overweight and obesity were not associated with either OS or PFS. However, underweight seemed to be an adverse prognostic factor for OS.

BackgroundKnee osteoarthritis (KOA) is a heterogenous disease, meaning individuals can present with various signs and symptoms related to different biopsychosocial (BPS) factors [1,2]. Several phenotypes can as such be expected. Phenotyping KOA patients, specifically those awaiting total knee arthroplasty (TKA), could be relevant, because a substantial part of patients (20%) reports chronic post-TKA pain [3]. Various preoperative phenotypic factors related to domains of the BPS model have been described, but consensus and a classification of patients based on these factors is still lacking [4–7].ObjectivesThe aim of this exploratory study is to identify phenotypes based on BPS related factors in KOA patients awaiting TKA.MethodsParticipants were included if they were diagnosed with KOA and waiting for TKA surgery in one of the four participating hospitals in Belgium and the Netherlands. A cross-sectional latent profile analysis was conducted in MPlus [8] containing the grade of KOA before TKA surgery (structural variable); body mass index and glycated hemoglobin value (metabolic variables); isometric strength of m. Quadriceps and m. Hamstrings of the affected leg, proprioceptive accuracy of the affected leg, and physical function (functional variables); pain intensity scores and symptoms related to altered somatosensory processing (pain-related variables); pain catastrophizing, depression, anxiety symptoms, expectations and satisfaction (psychological variables); and work and education level (social variables). Data were checked for multicollinearity and multivariate outliers. The ideal model was chosen based on qualitative evaluation, goodness of fit and classification uncertainty.Results224 participants were included of which 109 women (65.19 +/- 8.18 years old) and 108 men (66.92 +/- 7.18 years old). A model with 2 phenotypes was found to be most appropriate. Both phenotypes differed in 13 out of 19 continuous variables. Phenotype 1 (72% of all participants) was characterized by scoring better on at least one of all metabolic, functional, psychological and pain-related continuous variables compared to phenotype 2 (28% of all participants), except for glycated hemoglobin value, proprioception, expectations, and widespread temporal summation and conditioned pain modulation (part of somatosensory processing variables). Concerning categorical variables, phenotype 1 (72%) was characterized by having a lower probability to have a Kellgren & Lawrence (K&L) scale 2 compared with patients in phenotype 2 (28%). The probabilities of the other categorical variables did not differ between the two phenotypes.ConclusionA model with 2 phenotypes in KOA patients awaiting TKA appeared the most appropriate, which confirmed the existence of a group that experiences disturbed somatosensory processing signs in combination with worse results on psychological (pain catastrophizing, fear and depression), functional (strength and physical function), structural (higher possibility to have a K&L grade 2 compared to the other phenotype) and metabolic factors (body mass index), and a group that does not present this disruption in combination with better results on the aforementioned BPS factors. Further research is necessary and should also investigate if different phenotypes react differently regarding treatment outcome after TKA.

Stroke may be a first manifestation of an occult cancer or may be an indicator of an increased cancer risk in later life. However, data, especially for younger adults, are limited. To assess the association of stroke with new cancer diagnoses after a first stroke, stratified by stroke subtype, age, and sex, and to compare this association with that in the general population. This registry- and population-based study included 390 398 patients in the Netherlands aged 15 years or older without a history of cancer and with a first-ever ischemic stroke or intracerebral hemorrhage (ICH) between January 1, 1998, and January 1, 2019. Patients and outcomes were identified through linkage of the Dutch Population Register, the Dutch National Hospital Discharge Register, and National Cause of Death Register. Reference data were gathered from the Dutch Cancer Registry. Statistical analysis was performed from January 6, 2021, to January 2, 2022. First-ever ischemic stroke or ICH. Patients were identified by administrative codes from the International Classification of Diseases, Ninth Revision, and the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision. The primary outcome was the cumulative incidence of first-ever cancer after index stroke, stratified by stroke subtype, age, and sex, compared with age-, sex- and calendar year-matched peers from the general population. The study included 27 616 patients aged 15 to 49 years (median age, 44.5 years [IQR, 39.1-47.6 years]; 13 916 women [50.4%]; 22 622 [81.9%] with ischemic stroke) and 362 782 patients aged 50 years or older (median age, 75.8 years [IQR, 66.9-82.9 years]; 181 847 women [50.1%]; 307 739 [84.8%] with ischemic stroke). The cumulative incidence of new cancer at 10 years was 3.7% (95% CI, 3.4%-4.0%) among patients aged 15 to 49 years and 8.5% (95% CI, 8.4%-8.6%) among patients aged 50 years or older. The cumulative incidence of new cancer after any stroke among patients aged 15 to 49 years was higher among women than men (Gray test statistic, 22.2; P < .001), whereas among those aged 50 years or older, the cumulative incidence of new cancer after any stroke was higher among men (Gray test statistic, 943.1; P < .001). In the first year after stroke, compared with peers from the general population, patients aged 15 to 49 years were more likely to receive a diagnosis of a new cancer after ischemic stroke (standardized incidence ratio [SIR], 2.6 [95% CI, 2.2-3.1]) and ICH (SIR, 5.4 [95% CI, 3.8-7.3]). For patients aged 50 years or older, the SIR was 1.2 (95% CI, 1.2-1.2) after ischemic stroke and 1.2 (95% CI, 1.1-1.2) after ICH. This study suggests that, compared with the general population, patients aged 15 to 49 years who have had a stroke may have a 3- to 5-fold increased risk of cancer in the first year after stroke, whereas this risk is only slightly elevated for patients aged 50 years or older. Whether this finding has implications for screening remains to be investigated.

To assess perception of prognosis in patients with advanced cancer, its association with patient's characteristics and health-related quality of life (HRQoL). In a multicentre observational cohort study (eQuiPe), conducted on patients with advanced cancer, perceived prognosis, coping strategies, and HRQoL were assessed. Clinical data were obtained from the Netherlands Cancer Registry. Patients with vs. without a perception of prognosis, patients who perceived their prognosis as limited (< 1year) vs. longer (> 1year), and patients who did not want to know their prognosis vs. those who did not know for other reasons were compared. Of 1000 patients with advanced cancer, 29% perceived their prognosis as > 1year, 13% < 1year, and 4% non-life threatening. Thirty-six percent did not know their prognosis and another 15% did not want to know. Patients without a perception were older, lower educated, coped differently (less accepting, planning, active; more denial), and received treatment more often (p < 0.05). Global QoL was lower in patients with vs. without a perceived prognosis (66 (SD21) vs. 69 (SD19), p = 0.01), specifically in patients who perceived a limited rather than a longer prognosis (57 (SD22) vs. 70 (SD19), p < 0.01). Global QoL of patients who did not want to know their prognosis was comparable to patients who did not know for other reasons (71 (SD19) vs. 69 (SD19), p = 0.22). More than half of the patients with advanced cancer have no perception of their prognosis. Patients with a perceived prognosis have lower HRQoL, but only in patients who perceived their prognosis as limited (< 1year) and were probably closer to the end of life, which more likely determines their poorer HRQoL, rather than prognostic perception. Ignorance of prognosis is not associated with lower HRQoL, however, should not hamper appropriate palliative care.

PurposeWe assessed the systemic treatment choices and outcomes in patients diagnosed with human epidermal growth factor receptor-2-positive (HER2 +) advanced breast cancer (ABC), for the first four lines of systemic therapy and by hormone receptor (HR) status.MethodsWe identified 330 patients diagnosed with HER2 + ABC in 2013–2018 in the Southeast of The Netherlands, of whom 64% with HR + /HER2 + and 36% with HR-/HER2 + disease. Overall survival (OS) from start of therapy was calculated using the Kaplan–Meier method.ResultsIn real world, 95% of patients with HR + /HER2 + and 74% of patients with HR-/HER2 + disease received systemic therapy. In HR + /HER2 + disease, use of endocrine, chemo- and HER2-targeted therapy was , respectively, 64%, 46% and 60% in first line, and 39%, 64% and 75% in fourth line. In HR-/HER2 + disease, 91–96% of patients received chemotherapy and 77–91% HER2-targeted therapy, irrespective of line of therapy. In patients with HR + /HER2 + disease, median OS was 34.9 months (95%CI:25.8–44.0) for the first line and 12.8 months (95%CI:10.7–14.9) for the fourth line. In HR-/HER2 + disease, median OS was 39.9 months (95%CI:23.9–55.8) for the first line and 15.2 months (95%CI:10.9–19.5) for the fourth line. For patients treated with first-line pertuzumab, trastuzumab plus chemotherapy, median OS was not reached at 56.0 months in HR + /HER2 + disease and 48.4 months (95%CI:32.6–64.3) in HR-/HER2 + disease.ConclusionSurvival times for later lines of therapy are surprisingly long and justify the use of multiple lines of systemic therapy in well-selected patients with HER2 + ABC. Our real-world evidence adds valuable observations to the accumulating evidence that within HER2 + ABC, the HR status defines two distinct disease subtypes.