During the last decade completion axillary lymph node dissection (cALND) was gradually omitted in sentinel lymph node positive (SLN+) breast cancer patients. However, adoption varies among hospitals. ...We analyzed factors associated with the omission of cALND in all Dutch SLN+ patients. As one of the focus hospital‐related factors we defined “innovative” as the percentage of gene‐expression profile (GEP) deployment within the indicated group of patients per hospital as a proxy for early adoption of innovations. cT1‐2N0M0 SLN+ patients treated between 2011 and 2018 were selected from the Netherlands Cancer Registry. Hospitals were defined to be innovative based on their GEP use. Multivariable logistic regression (MLR) was performed to assess the relationship between innovative capacity, patient‐, treatment‐ and hospital‐related characteristics and cALND performance. 14 317 patients were included. Treatment in a hospital with high innovative capacity was associated with a lower probability of receiving cALND (OR 0.69, OR 0.46 and OR 0.35 in modestly, fairly and very innovative, respectively). Other factors associated with a lower probability of receiving a cALND were age 70 and 79 years and ≥79 years (ORs 0.59 95% CI: 0.50‐0.68 and 0.21 95% CI: 0.17‐0.26) and treatment in an academic hospital (OR 0.41 95% CI: 0.33‐0.51). Factors associated with an increased probability of undergoing cALND were HR−/HER2− tumors (OR 1.46 95% CI: 1.19‐1.80), macrometastatic lymph node involvement (OR 6.37 95% CI: 5.70‐7.13) and mastectomy (OR 4.57 95% CI: 4.09‐5.10). Patients treated in a hospital that early adopted innovations were less likely to receive cALND. Our findings endorse the need for studies on barriers and facilitators of implementing innovations.
What's new?
Novel treatment insights and adjusted guidelines have propagated a de‐escalating treatment approach in breast cancer. However, little is known about the factors associated with early or late adoption of less aggressive strategies. This nationwide prospective study assesses inequalities in the omission of completion axillary lymph node dissection (cALND) in sentinel lymph node‐positive breast cancer patients. Besides known patient and tumor characteristics, treatment in an academic or highly innovative hospital lowers the chance of receiving cALND. The findings call for further research on the implementation of innovation in clinical practice to help reduce national inequalities in breast cancer care.
Hydrogels of amyloid fibrils are a versatile biomaterial for tissue engineering and other biomedical applications. Their suitability for these applications has been partly ascribed to their excellent ...and potentially engineerable rheological properties. However, while in biomedical applications the gels have to function in compositionally complex physiological solutions, their rheological behavior is typically only characterized in simple buffers. Here we show that the viscoelastic response of networks of amyloid fibrils of the protein lysozyme in biologically relevant solutions substantially differs from the response in simple buffers. We observe enhanced energy dissipation in both cell culture medium and synovial fluid. We attribute this energy dissipation to interactions of the amyloid fibrils with other molecules in these solutions and especially to the adsorption of the abundantly present protein serum albumin. This finding provides the basis for a better understanding of the performance of amyloid hydrogels in biomedical applications.
Background The aim of this systematic review was to summarise and appraise the published evidence with regard to the frequency and risk factors of subclinical cardiotoxicity in apparently healthy ...survivors of childhood cancer after anthracycline therapy. Patients and methods A search was made in Medline for studies published between 1966 and May 2001 that included >50 children and reported on the frequency of measures of subclinical cardiotoxicity. Information about the studies was abstracted by two reviewers and a validity score was calculated for each study. Results The reported frequency of subclinical cardiotoxicity varied between 0% and 57% in the 25 studies included. Differences in outcome definitions of subclinical cardiotoxicity and differences in study patients with respect to the dose of anthracycline seemed to explain part of the wide variance of the frequency of subclinical cardiotoxicity. Fourteen of the 25 studies showed serious methodological limitations. Conclusions The reported frequency of subclinical cardiotoxicity shows a wide variation. Well designed studies with accurate and precise outcome measurements in well described groups of patients, after a sufficiently long follow-up period, are needed to obtain more insight into the frequency and importance of risk factors, and the clinical consequences of anthracycline-related subclinical cardiotoxicity.
Aims
Phosphohistone H3 (PhH3) has been proposed as a novel proliferation marker in breast cancer. This study compares the interobserver agreement for assessment of the mitotic activity index (MAI), ...Ki67 expression, and PhH3 in a cohort of oestrogen receptor (ER)‐positive breast cancer patients.
Methods and results
Tumour samples of 159 luminal breast cancer patients were collected. MAI and PhH3 scores were assessed by three breast cancer pathologists. Ki67 scores were assessed separately by two of the three pathologists. PhH3‐positive cells were counted in an area of 2 mm2, with a threshold of ≥13 positive cells being used to discriminate between low‐proliferative and high‐proliferative tumours. Ki67 expression was assessed with the global scoring method. Ki67 percentages of <20% were considered to be low. The intraclass correlation coefficient (ICC) and Cohen's κ statistics were used to evaluate interobserver agreement. The impact on histological grading of replacing the MAI with PhH3 was assessed. Counting PhH3‐positive cells was highly reproducible among all three observers (ICC of 0.86). The κ scores for the categorical PhH3 count (κ = 0.78, κ = 0.68, and κ = 0.80) reflected substantial agreement among all observers, whereas agreement for the MAI (κ = 0.38, κ = 0.52, and κ = 0.26) and Ki67 (κ = 0.55) was fair to moderate. When PhH3 was used to determine the histological grade, agreement in grading increased (PhH3, κ = 0.52, κ = 0.48, and κ = 0.52; MAI, κ = 0.43, κ = 0.35, and κ = 0.32), and the proportion of grade III tumours increased (14%, 18%, and 27%).
Conclusion
PhH3 seems to outperform Ki67 and the MAI as a reproducible means to measure tumour proliferation in luminal‐type breast cancer. Variation in the assessment of histological grade might be reduced by using PhH3, but would result in an increase in the proportion of high‐grade cancers.
Over the past decades, health care services for pancreatic surgery were reorganized. Volume norms were applied with the result that only a limited number of expert centers perform pancreatic surgery. ...As a result of this centralization of pancreatic surgery, the patient journey of patients with pancreatic tumors has become multi-institutional. To illustrate, patients are referred to a center of expertise for pancreatic surgery whereas other parts of pancreatic care, such as chemotherapy, take place in local hospitals. This fragmentation of health care services could affect continuity of care (COC). The aim of this study was to assess COC perceived by patients in a pancreatic care network and investigate correlations with patient-and care-related characteristics.
This is a pilot study in which patients with (pre) malignant pancreatic tumors discussed in a multidisciplinary tumor board in a Dutch tertiary hospital were asked to participate. Patients were asked to fill out the Nijmegen Continuity of Care-questionnaire (NCQ) (5-point Likert scale). Additionally, their patient-and care-related data were retrieved from medical records. Correlations of NCQ score and patient-and care-related characteristics were calculated with Spearman's correlation coefficient.
In total, 44 patients were included (92% response rate). Pancreatic cancer was the predominant diagnosis (32%). Forty percent received a repetition of diagnostic investigations in the tertiary hospital. Mean scores for personal continuity were 3.55 ± 0.74 for GP, 3.29 ± 0.91 for the specialist and 3.43 ± 0.65 for collaboration between GPs and specialists. Overall COC was scored with a mean 3.38 ± 0.72. No significant correlations were observed between NCQ score and certain patient-or care-related characteristics.
Continuity of care perceived by patients with pancreatic tumors was scored as moderate. This outcome supports the need to improve continuity of care within multi-institutional pancreatic care networks.
Celotno besedilo
Dostopno za:
CEKLJ, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Purpose
We assessed the recent trends in the administration of adjuvant chemotherapy thereby evaluating the role of the 70-gene signature (70-GS) testing in decision-making in the systemic treatment ...of patients with lymph node negative (N0) and lymph node positive (N+) breast cancer.
Methods
Patients with a national guideline directed indication for 70-GS use treated between 2013 and 2016 were selected from the Netherlands Cancer Registry. Time trends in the administration of adjuvant chemotherapy were evaluated within guideline- and age-delineated subgroups. The influence of the 70-GS on chemotherapy use was assessed with logistic regression.
Results
During the study period, the overall administration of adjuvant chemotherapy decreased from 49 to 23% and 70-GS use increased from 24 to 51%. The 70-GS was not associated with a decreased likelihood for N0 patients to receive chemotherapy (odds ratio OR 1.0; 95% confidence interval CI 0.86–1.17), as the proportion of N0 patients who received chemotherapy in the absence of 70-GS use decreased during the study period. In patients with N1a disease, 70-GS testing was associated with a decreased likelihood to receive chemotherapy (OR 0.21; 95% CI 0.15–0.29). In patients < 50 years and 50–59 years of age, 70-GS use was associated with a consistent lower proportion of patients receiving chemotherapy throughout the study period (OR 0.17; 95% CI 0.13–0.23 and OR 0.53; 95% CI 0.43–0.65, respectively).
Conclusions
In this population-based study, the administration of adjuvant chemotherapy in ER+ breast cancer strongly declined. For node-positive and younger patients, 70-GS use was associated with a decreased probability for patients to receive adjuvant chemotherapy.
The Late Effects of Childhood Cancer task force of the Dutch Childhood Oncology Group (DCOG LATER) developed a guideline for follow-up of asymptomatic cardiac dysfunction in childhood cancer ...survivors (CCS). In this paper, we present the methods, available evidence and final recommendations of our guideline.
A multidisciplinary working group specified clinical questions that should be answered to get to recommendations for the guideline. We carried out short or extensive evidence summaries and determined methodological quality of studies and levels of evidence in order to answer all clinical questions. When evidence was lacking for CCS, we carefully extrapolated evidence from other populations. Final recommendations were based on evidence and consensus.
There was high-level evidence for the increased risk of cardiac dysfunction in CCS and its main risk factors. Evidence was lacking regarding the prognosis, diagnosis and treatment of cardiac dysfunction in CCS. We recommended echocardiographic screening for asymptomatic cardiac dysfunction in CCS treated with cardiotoxic treatments and counseling about potential advantages and disadvantages of our screening recommendations.
The DCOG LATER guideline recommends risk-based screening for asymptomatic cardiac dysfunction in CCS, but it should be noted that recommendations are not completely supported by evidence in CCS.
Long-term childhood cancer survivors are at high risk of late adverse effects, including stroke. We aimed to determine the cumulative incidence of clinically validated symptomatic stroke (transient ...ischemic attack TIA, cerebral infarction, and intracerebral hemorrhage ICH) and to quantify dose-effect relationships for cranial radiation therapy (CRT) and supradiaphragmatic radiation therapy (SDRT).
Our single-center study cohort included 1362 survivors of childhood cancer that were diagnosed between 1966 and 1996. Prescribed CRT and SDRT doses were converted into the equivalent dose in 2-Gy fractions (EQD2). Multivariate Cox regression models were used to analyze the relationship between the EQD2 and stroke.
After a median latency time of 24.9 years and at a median age of 31.2 years, 28 survivors had experienced a first stroke: TIA (n=5), infarction (n=13), and ICH (n=10). At an attained age of 45 years, the estimated cumulative incidences, with death as competing risk, among survivors treated with CRT only, SDRT only, both CRT and SDRT, and neither CRT nor SDRT were, respectively, 10.0% (95% confidence interval CI, 2.5%-17.0%), 5.4% (95% CI, 0%-17.0%), 12.5% (95% CI, 5.5%-18.9%), and 0.1% (95% CI, 0%-0.4%). Radiation at both locations significantly increased the risk of stroke in a dose-dependent manner (hazard ratios: HRCRT 1.02 Gy(-1); 95% CI, 1.01-1.03, and HRSDRT 1.04 Gy(-1); 95% CI, 1.02-1.05).
Childhood cancer survivors treated with CRT, SDRT, or both have a high stroke risk. One in 8 survivors treated at both locations will have experienced a symptomatic stroke at an attained age of 45 years. Further research on the pathophysiologic processes involved in stroke in this specific group of patients is needed to enable the development of tailored secondary prevention strategies.
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