Hormonal crises following receptor radionuclide therapy with the radiolabeled somatostatin analogue [177Lu-DOTA0,Tyr 3]octreotate

Introduction: Receptor radionuclide therapy is a promising treatment modality for patients with neuroendocrine tumors for whom alternative treatments are limited. The aim of this study was to investigate the incidence of hormonal crises after therapy with the radiolabeled somatostatin analogue [177Lu-DOTA0,Tyr3]octreotate (177Lu-octreotate). Materials and methods: All177Lu- octreotate treatments between January 2000 and January 2007 were investigated. Four hundred seventy-six patients with gastroenteropancreatic neuroendocrine tumors and three patients with metastatic pheochromocytoma were included fo

Response assessment after induction chemotherapy for head and neck squamous cell carcinoma: From physical examination to modern imaging techniques and beyond

Significant correlations between the response to induction chemotherapy and success of subsequent radiotherapy have been reported and suggest that the response to induction chemotherapy is able to predict a response to radiotherapy. Therefore, induction chemotherapy may be used to tailor the treatment plan to the individual patient with head and neck cancer: following the planned subsequent (chemo)radiation schedule, planning a radiation dose boost, or reassessing the modality of treatment (eg, upfront surgery). Findings from reported trials suggest room for improvement in clinical response assessment after induction chemotherapy, but an optimal method has yet to be identified. Historically, indices of treatment efficacy in solid tumors have been based solely on systematic assessment of tumor size. However, functional imaging (eg, fluorodeoxyglucose‐positron emission tomography (FDG‐PET) potentially provides an earlier indication of response to treatment than conventional imaging techniques. More advanced imaging techniques are still in an exploratory phase and are not ready for use in clinical practice.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138890/1/hed24883_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138890/2/hed24883.pd

Screening rules for growth to detect celiac disease: A case-control simulation study

Background: It is generally assumed that most patients with celiac disease (CD) have a slowed growth in terms of length (or height) and weight. However, the effectiveness of slowed growth as a tool for identifying children with CD is unknown. Our aim is to study the diagnostic efficiency of several growth criteria used to detect CD children. Methods: A case-control simulation study was carried out. Longitudinal length and weight measurements from birth to 2.5 years of age were used from three groups of CD patients (n = 134) (one group diagnosed by screening, two groups with clinical manifestations), and a reference group obtained from the Social Medical Survey of Children Attending Child Health Clinics (SMOCC) cohort (n = 2,151) in The Netherlands. The main outcome measures were sensitivity, specificity and positive predictive value (PPV) for each criterion. Results: Body mass index (BMI) performed best for the groups with clinical manifestations. Thirty percent of the CD children with clinical manifestations and two percent of the reference children had a BMI Standard Deviation Score (SDS) less than -1.5 and a decrease in BMI SDS of at least -2.5 (PPV = 0.85%). The growth criteria did not discriminate between the screened CD group and the reference group. Conclusion: For the CD children with clinical manifestations, the most sensitive growth parameter is a decrease in BMI SDS. BMI is a better predictor than weight, and much better than length or height. Toddlers with CD detected by screening grow normally at this stage of the disease

Neuroblastoma stage 4S: Tumor regression rate and risk factors of progressive disease

Background: The clinical course of neuroblastoma stage 4S or MS is characterized by a high rate of spontaneous tumor regression and favorable outcome. However, the clinical course and rate of the regression are poorly understood. Methods: A retrospective cohort study was performed, including all patients with stage 4S neuroblastoma without MYCN amplification, from two Dutch centers between 1972 and 2012. We investigated the clinical characteristics, the biochemical activity reflected in urinary catecholamine excretion, and radiological imaging to describe the kinetics of tumor regression, therapy response and outcome. Results: The cohort of 31 patients reached a 10-year overall survival of 84% ± 7% (median follow-up 16 years; range, 3.3-39). During the regressive phase, liver size normalized in 91% of the patients and catecholamine excretion in 83%, both after a median of two months (liver size: range, 0-131; catecholamines: range, 0-158). The primary tumors completely regressed in 69% after 13 months (range, 6-73), and the liver architecture normaliz

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

Observer variability of absolute and relative thrombus density measurements in patients with acute ischemic stroke

Introduction: Thrombus density may be a predictor for acute ischemic stroke treatment success. However, only limited data on observer variability for thrombus density measurements exist. This study assesses the variability and bias of four common thrombus density measurement methods by expert and non-expert observers. Methods: For 132 consecutive patients with acute ischemic stroke, three experts and two trained observers determined thrombus density by placing three standardized regions of interest (ROIs) in the thrombus and corresponding contralateral arterial segment. Subsequently, absolute and relative thrombus densities were determined using either one or three ROIs. Intraclass correlation coefficient (ICC) was determined, and Bland–Altman analysis was performed to evaluate interobserver and intermethod agreement. Accuracy of the trained observer was evaluated with a reference expert observer using the same statistical analysis. Results: The highest interobserver agreement was obtained for absolute thrombus measurements using three ROIs (ICCs ranging from 0.54 to 0.91). In general, interobserver agreement was lower for relative measurements, and for using one instead of three ROIs. Interobserver agreement of trained non-experts and experts was similar. Accuracy of the trained observer measurements was comparable to the expert interobserver agreement and was better for absolute measurements and with three ROIs. The agreement between the one ROI and three ROI methods was good. Conclusion: Absolute thrombus density measurement has superior interobserver agreement compared to relative density measurement. Interobserver variation is smaller when multiple ROIs are used. Trained non-expert observers can accurately and reproducibly assess absolute thrombus densities using three ROIs

Neuroblastoma between 1990 and 2014 in the Netherlands: Increased incidence and improved survival of high-risk neuroblastoma

Purpose: Long-term trends in neuroblastoma incidence and survival in unscreened populations are unknown. We explored trends in incidence, stage at diagnosis, treatment and survival of neuroblastoma in the Netherlands from 1990 to 2014. Methods: The Netherlands Cancer Registry provided data on all patients aged <18 years diagnosed with a neuroblastoma. Trends in incidence and stage were evaluated by calculating the average annual percentage change (AAPC). Univariate and multivariable survival analyses were performed for stage 4 disease to test whether changes in treatment are associated with survival. Results: Of the 593 newly diagnosed neuroblastoma cases, 45% was <18 months of age at diagnosis and 52% had stage 4 disease. The age-standardized incidence rate for stage 4 disease increased at all ages from 3.2 to 5.3 per million children per year (AAPC + 2.9%, p <. 01). This increase was solely for patients ≥18 months old (3.0–5.4; AAPC +3.3%, p =. 01). Five-year OS of all patients increased from 44 ± 5% to 61 ± 4% from 1990 to 2014 (p <. 01) and from 19 ± 6% to 44 ± 6% (p <. 01) for patients with stage 4 disease. Multivariable analysis revealed that high-dose chemotherapy followed by autologous stem cell rescue and anti-GD2-based immunotherapy were associated with this survival increase (HR 0.46, p <. 01 and HR 0.37, p <. 01, respectively). Conclusion: Incidence of stage 4 neuroblastoma increased exclusively in patients aged ≥18 months since 1990, whereas the incidence of other stages remained stable. The 5-year OS of stage 4 patients improved, mostly due to the introduction of high-dose chemotherapy followed by stem cell rescue and immunotherapy

PET Molecular Targets and Near-Infrared Fluorescence Imaging of Atherosclerosis

PURPOSE OF REVIEW: With this review, we aim to summarize the role of positron emission tomography (PET) and near-infrared fluorescence imaging (NIRF) in the detection of atherosclerosis. RECENT FINDINGS: (18)F-FDG is an established measure of increased macrophage activity. However, due to its low specificity, new radiotracers have emerged for more specific detection of vascular inflammation and other high-risk plaque features such as microcalcification and neovascularization. Novel NIRF probes are engineered to sense endothelial damage as an early sign of plaque erosion as well as oxidized low-density lipoprotein (oxLDL) as a prime target for atherosclerosis. Integrated NIRF/OCT (optical coherence tomography) catheters enable to detect stent-associated microthrombi. Novel radiotracers can improve specificity of PET for imaging atherosclerosis. Advanced NIRF probes show promise for future application in human. Intravascular NIRF might play a prominent role in the detection of stent-induced vascular injury

Two-year clinical follow-up of the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in The Netherlands (MR CLEAN): Design and statistical analysis plan of the extended follow-up study

Background: MR CLEAN was the first randomized trial to demonstrate the short-term clinical effectiveness of endovascular treatment in patients with acute ischemic stroke caused by large vessel occlusion in the anterior circulation. Several other trials confirmed that endovascular treatment improves clinical outcome at three months. However, limited data are available on long-term clinical outcome. We aimed to estimate the effect of endovascular treatment on functional outcome at two-year follow-up in patients with acute ischemic stroke. Secondly, we aimed to assess the effect of endovascular treatment on major vascular events and mortality during two years of follow-up. Methods: MR CLEAN is a multicenter clinical trial with randomized treatment allocation, open-label treatment, and blinded endpoint evaluation. Patients included were 18 years or older with acute ischemic stroke caused by a proven anterior proximal artery occlusion who could be treated within six hours after stroke onset. The intervention contrast was endovascular treatment and usual care versus no endovascular treatment and usual care. The current study extended the follow-up duration from three months to two years. The primary outcome is the score on the modified Rankin scale at two years. Secondary outcomes include all-cause mortality and the occurrence of major vascular events within two years of follow-up. Discussion: The results of our study provide information on the long-term clinical effectiveness of endovascular treatment, which may have implications for individual treatment decisions and estimates of cost-effectiveness. Trial registration:NTR1804. Registered on 7 May 2009; ISRCTN10888758. Registered on 24 July 2012 (main MR CLEAN trial); NTR5073. Registered on 26 February 2015 (extended follow-up study)