Treatments and costs for recurrent and/or metastatic squamous cell carcinoma of the head and neck in the Netherlands

__Abstract__ For patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN), chemotherapy can prolong life and alleviate symptoms. However, expected gains may be small, not necessarily outweighing considerable toxicity and high costs. Treatment choice is to a large extent dependent on preferences of doctors and patients and data on these choices are scarce. The purpose of this study is to obtain real-world information on palliative systemic treatment and costs of R/M SCCHN in the Netherlands. In six Dutch head and neck treatment centers, data were collected on patient and tumor characteristics, treatment patterns, disease progression, survival, adverse events, and resource use for R/M SCCHN, between 2006 and 2013. 125 (14 %) out of 893 R/M SCCHN patients received palliative, non-trial first-line systemic treatment, mainly platinum + 5FU + cetuximab (32 %), other platinum-based combination therapy (13 %), methotrexate monotherapy (27 %) and capecitabine monotherapy (14 %). Median progression-free survival and overall survival were 3.4 and 6.0 months, respectively. 34 (27 %) patients experienced severe adverse events. Mean total hospital costs ranged from €10,075 (±€9,891) (methotrexate monotherapy) to €39,459 (±€21,149) (platinum + 5FU + cetuximab). Primary cost drivers were hospital stays and anticancer drug treatments. Major health care utilization and costs are involved in systemically treating R/M SCCHN patients with a limited survival

Continuously improving the practice of cardiology

Guidelines for the management of patients with cardiovascular disease are designed to assist cardiologists and other physicans in their practice. Surveys are conducted to assess whether guidelines are followed in practice. The results of surveys on acute coronary syndromes, coronary revascularisation, secondary prevention, valvular heart disease and heart failure are presented. Comparing surveys conducted between 1995 and 2002, a gradual improvement in use ofsecondary preventive therapy is observed. Nevertheless, important deviations from established guidelines are noted, with a significant variation among different hospitals in the Netherlands and in other European countries. Measures for fiuther improvement of clinical practice indude more rapid treatment of patients with evolving myocardial infarction, more frequent use of clopidogrel and glycoprotein IIb/IIIa receptor blockers in patients with acute coronary syndromes, more frequent use of 5-blockers in patients with heart failure and more intense measures to encourage patients to stop smoking. Targets for the proportion ofpatients who might receive specific therapies are presented

Recurrent differentiated thyroid cancer: Towards personalized treatment based on evaluation of tumor characteristics with PET (THYROPET Study): Study protocol of a multicenter observational cohort study

Background: After initial treatment of differentiated thyroid carcinoma (DTC) patients are followed with thyroglobulin (Tg) measurements to detect recurrences. In case of elevated levels of Tg and negative neck ultrasonography, patients are treated 'blindly' with Iodine-131 (131I). However, in up to 50% of patients, the post-therapy scan reveals no 131I-targeting of tumor lesions. Such patients derive no benefit from the blind therapy but are exposed to its toxicity. Alternatively, iodine-124 (124I) Positron Emission Tomography/Computed Tomography (PET/CT) has become available to visualize DTC lesions and without toxicity. In addition to this, 18F-fluorodeoxyglucose (18F-FDG) PET/CT detects the recurrent DTC phenotype, which lost the capacity to accumulate iodine. Taken together, the combination of 124I and 18F-FDG PET/CT has potential to stratify patients for treatment with 131I.Methods/Design: In a multicenter prospective observational cohort study the hypothesis that the combination of 124I and 18F-FDG PET/CT can avoid futile 131I treatments in patients planned for 'blind' therapy with 131I, is tested.One hundred patients planned for 131I undergo both 124I and 18F-FDG PET/CT after rhTSH stimulation. Independent of the outcome of the scans, all patients will subsequently receive, after thyroid hormone withdrawal, the 131I therapy. The post 131I therapeutic scintigraphy is compared with the outcome of the 124I and 18F-FDG PET/CT in order to evaluate the diagnostic value of the combined PET modalities.This study primary aims to reduce the number of futile 131I therapies. Secondary aims are the nationwide introduction of 124I PET/CT by a quality assurance and quality control (QA/QC) program, to correlate imaging outcome with histopathological features, to compare 124I PET/CT after rhTSH and after withdrawal of thyroid hormone, and to compare 124I and 131I dosimetry.Discussion: This study aims to evaluate the potential value of the combination of 124I and 18F-FDG PET/CT in the prevention of futile 131I therapies in patients with biochemically suspected recurrence of DTC. To our best knowledge no studies addressed this in a prospective cohort of patients. This is of great clinical importance as a futile 131I is a costly treatment associated with morbidity and therefore should be restricted to those likely to benefit from this treatment.Trial registration: Clinicaltrials.gov identifier: NCT01641679

Infradiaphragmatic irradiation and high procarbazine doses increase colorectal cancer risk in Hodgkin lymphoma survivors

Background:Hodgkin lymphoma (HL) survivors are at increased risk of second malignancies, but few studies have assessed colorectal cancer (CRC) risk after HL treatment. We assessed long-term, subsite-specific CRC risk associated with specific radiation fields and chemotherapy regimens.Methods:In a Dutch cohort of 3121 5-year HL survivors treated between 1965 and 1995, subsite-specific CRC incidence was compared with general population rates. Treatment effects were quantified by Cox regression analyses.Results:After a median follow-up of 2

Feedback preferences of patients, professionals and health insurers in integrated head and neck cancer care

Background: Audit and feedback on professional practice and health care outcomes are the most often used interventions to change behaviour of professionals and improve quality of health care. However, limited information is available regarding preferred feedback for patients, professionals and health insurers. Objective: Investigate the (differences in) preferences of receiving feedback between stakeholders, using the Dutch Head and Neck Audit as an example. Methods: A total of 37 patients, medical specialists, allied health professionals and health insurers were interviewed using semi-structured interviews. Questions focussed on: “Why,” “On what aspects” and “How” do you prefer to receive feedback on professional practice and health care outcomes?. Results: All stakeholders mentioned that feedback can improve health care by creating awareness, enabling self-reflection and reflection on peers or colleagues, and by benchmarking to others. Patients prefer feedback on the actual professional practice that matches the health care received, whereas medical specialists and health insurers are interested mainly in health care outcomes. All stakeholders largely prefer a bar graph. Patients prefer a pie chart for patient-reported outcomes and experiences, while Kaplan-Meier survival curves are preferred by medical specialists. Feedback should be simple with firstly an overview, and 1-4 times a year sent by e-mail. Finally, patients and health professionals are cautious with regard to transparency of audit data. Conclusions: This exploratory study shows how feedback preferences differ between stakeholders. Therefore, tailored reports are recommended. Using this information, effects of audit and feedback can be improved by adapting the feedback format and contents to the preferences of stakeholders

High prevalence of advanced colorectal neoplasia and serrated polyposis syndrome in Hodgkin lymphoma survivors

Background: Hodgkin lymphoma (HL) survivors treated with abdominal radiotherapy and/or alkylating chemotherapy have an increased risk of colorectal cancer (CRC). This study was aimed at evaluating the prevalence of colorectal neoplasia in HL survivors. Methods: This multicenter cohort study assessed the diagnostic yield of advanced colorectal neoplasia detected by a first surveillance colonoscopy among HL survivors treated with abdominal radiotherapy and/or procarbazine. Advanced colorectal neoplasia included advanced adenomas (high-grade dysplasia, ≥25% villous component, or ≥10-mm diameter), advanced serrated lesions (dysplasia or ≥10-mm diameter), and CRC. The results were compared with those for a Dutch general population cohort that underwent a primary screening colonoscopy (1426 asymptomatic individuals 50-75 years old). This study demonstrated the results of a predefined interim analysis. Results: A colonoscopy was performed in 101 HL survivors, who were significantly younger (median, 51 years; interquartile range [IQR], 45-57 years) than the general population controls (median, 60 years; IQR, 55-65 years; P <.001). The prevalence of advanced neoplasia was higher in HL survivors than controls (25 of 101 [25%] vs 171 of 1426 [12%]; P <.001). Advanced adenomas were detected in 14 of 101 HL survivors (14%) and in 124 of 1426 controls (9%; P =.08). The prevalence of advanced serrated lesions was higher in HL survivors than controls (12 of 101 [12%] vs 55 of 1426 [4%]; P <.001). Serrated polyposis syndrome was present in 6% of HL survivors and absent in controls (P <.001). Conclusions: HL survivors treated with abdominal radiotherapy and/or procarbazine have a high prevalence of advanced colorectal neoplasia. The implementation of a colonoscopy surveillance program should be considered

Search for Gravitational Waves Associated with Gamma-Ray Bursts Detected by Fermi and Swift during the LIGO-Virgo Run O3b

We search for gravitational-wave signals associated with gamma-ray bursts (GRBs) detected by the Fermi and Swift satellites during the second half of the third observing run of Advanced LIGO and Advanced Virgo (2019 November 1 15:00 UTC-2020 March 27 17:00 UTC). We conduct two independent searches: A generic gravitational-wave transients search to analyze 86 GRBs and an analysis to target binary mergers with at least one neutron star as short GRB progenitors for 17 events. We find no significant evidence for gravitational-wave signals associated with any of these GRBs. A weighted binomial test of the combined results finds no evidence for subthreshold gravitational-wave signals associated with this GRB ensemble either. We use several source types and signal morphologies during the searches, resulting in lower bounds on the estimated distance to each GRB. Finally, we constrain the population of low-luminosity short GRBs using results from the first to the third observing runs of Advanced LIGO and Advanced Virgo. The resulting population is in accordance with the local binary neutron star merger rate. © 2022. The Author(s). Published by the American Astronomical Society

Narrowband Searches for Continuous and Long-duration Transient Gravitational Waves from Known Pulsars in the LIGO-Virgo Third Observing Run

Isolated neutron stars that are asymmetric with respect to their spin axis are possible sources of detectable continuous gravitational waves. This paper presents a fully coherent search for such signals from eighteen pulsars in data from LIGO and Virgo's third observing run (O3). For known pulsars, efficient and sensitive matched-filter searches can be carried out if one assumes the gravitational radiation is phase-locked to the electromagnetic emission. In the search presented here, we relax this assumption and allow both the frequency and the time derivative of the frequency of the gravitational waves to vary in a small range around those inferred from electromagnetic observations. We find no evidence for continuous gravitational waves, and set upper limits on the strain amplitude for each target. These limits are more constraining for seven of the targets than the spin-down limit defined by ascribing all rotational energy loss to gravitational radiation. In an additional search, we look in O3 data for long-duration (hours-months) transient gravitational waves in the aftermath of pulsar glitches for six targets with a total of nine glitches. We report two marginal outliers from this search, but find no clear evidence for such emission either. The resulting duration-dependent strain upper limits do not surpass indirect energy constraints for any of these targets. © 2022. The Author(s). Published by the American Astronomical Society

Late cardiotoxicity after treatment for Hodgkin lymphoma

We assessed cardiovascular disease (CVD) incidence in 1474 survivors of Hodgkin lymphoma (HL) younger than 41 years at treatment (1965-1995). Multivariable Cox regression and competing risk analyses were used to quantify treatment effects on CVD risk. After a median follow-up of 18.7 years, risks of myocardial infarction (MI) and congestive heart failure (CHF) were strongly increased compared with the general population (standardized incidence ratios [SIRs] = 3.6 and 4.9, respectively), resulting in 35.7 excess cases of MI and 25.6 excess cases of CHF per 10 000 patients/year. SIRs of all CVDs combined remained increased for at least 25 years and were more strongly elevated in younger patients. Mediastinal radiotherapy significantly increased the risks of MI, angina pectoris, CHF, and valvular disorders (2- to 7-fold). Anthracyclines significantly added to the elevated risks of CHF and valvular disorders from mediastinal RT (hazard ratios [HRs] were 2.81 and 2.10, respectively). The 25-year cumulative incidence of CHF after mediastinal radiotherapy and anthracyclines in competing risk analyses was 7.9%. In conclusion, risks of several CVDs are 3- to 5-fold increased in survivors of HL compared with the general population, even after prolonged follow-up, leading to increasing absolute excess risks over time. Anthracyclines further increase the elevated risks of CHF and valvular disorders from mediastinal radiotherapy

Ventilation management and clinical outcomes in invasively ventilated patients with COVID-19 (PRoVENT-COVID): a national, multicentre, observational cohort study

Background: Little is known about the practice of ventilation management in patients with COVID-19. We aimed to describe the practice of ventilation management and to establish outcomes in invasively ventilated patients with COVID-19 in a single country during the first month of the outbreak. Methods: PRoVENT-COVID is a national, multicentre, retrospective observational study done at 18 intensive care units (ICUs) in the Netherlands. Consecutive patients aged at least 18 years were eligible for participation if they had received invasive ventilation for COVID-19 at a participating ICU during the first month of the national outbreak in the Netherlands. The primary outcome was a combination of ventilator variables and parameters over the first 4 calendar days of ventilation: tidal volume, positive end-expiratory pressure (PEEP), respiratory system compliance, and driving pressure. Secondary outcomes included the use of adjunctive treatments for refractory hypoxaemia and ICU complications. Patient-centred outcomes were ventilator-free days at day 28, duration of ventilation, duration of ICU and hospital stay, and mortality. PRoVENT-COVID is registered at ClinicalTrials.gov (NCT04346342). Findings: Between March 1 and April 1, 2020, 553 patients were included in the study. Median tidal volume was 6·3 mL/kg predicted bodyweight (IQR 5·7–7·1), PEEP was 14·0 cm H2O (IQR 11·0–15·0), and driving pressure was 14·0 cm H2O (11·2–16·0). Median respiratory system compliance was 31·9 mL/cm H2O (26·0–39·9). Of the adjunctive treatments for refractory hypoxaemia, prone positioning was most often used in the first 4 days of ventilation (283 [53%] of 530 patients). The median number of ventilator-free days at day 28 was 0 (IQR 0–15); 186 (35%) of 530 patients had died by day 28. Predictors of 28-day mortality were gender, age, tidal volume, respiratory system compliance, arterial pH, and heart rate on the first day of invasive ventilation. Interpretation: In patients with COVID-19 who were invasively ventilated during the first month of the outbreak in the Netherlands, lung-protective ventilation with low tidal volume and low driving pressure was broadly applied and prone positioning was often used. The applied PEEP varied widely, despite an invariably low respiratory system compliance. The findings of this national study provide a basis for new hypotheses and sample size calculations for future trials of invasive ventilation for COVID-19. These data could also help in the interpretation of findings from other studies of ventilation practice and outcomes in invasively ventilated patients with COVID-19. Funding: Amsterdam University Medical Centers, location Academic Medical Center