External validation of a lung cancer-based prediction model for two-year mortality in esophageal cancer patient cohorts.

PURPOSE/OBJECTIVE: Chemo-radiotherapy can improve the oncological outcome of esophageal cancer (EC) patients, but may cause long term radiation-induced toxicity, including an increased risk of non-cancer related death. For lung cancer patients, a model to predict 2-year total mortality using mean heart dose (MHD) and gross tumor volume (GTV) has previously been developed and validated. This project aimed to externally validate this model in EC patients. METHODS: Five EC patient cohorts from 3 different Dutch centres were used for model validation. External validity of the model was assessed separately in definitive (n = 170) and neo-adjuvant (n = 568) chemoradiotherapy (dCRT and nCRT) patients. External validity was assessed in terms of calibration by calibration plots, calibration-in-the-large (CITL) and calibration slope (CS), and discrimination by assessment of the c-statistic. If suboptimal model performance was observed, the model was further updated accordingly. RESULTS: For the dCRT patients, good calibration was found after adjustment of the intercept (CITL 0.00; CS 1.08). The c-statistic of the adjusted model was 0.67 (95%CI: 0.58 to 0.75). For nCRT patients the model needed adjustment of both the slope and the intercept because of initial miscalibration in the validation population (CITL 0.00; CS 1.72). After recalibration, the model showed perfect calibration (i.e., CITL 0, CS 1), as is common after recalibration. The c-statistic of the recalibrated model equaled 0.62 (95%CI: 0.57 to 0.67). CONCLUSION: The existing model for 2-year mortality prediction in lung cancer patients, based on the predictive factors MHD and GTV, showed good performance in EC patients after updating the intercept and/or slope of the original model.

Model-Based Selection for Proton Therapy in Breast Cancer: Development of the National Indication Protocol for Proton Therapy and First Clinical Experiences.

AIMS: Proton therapy is a radiation technique that yields less dose in normal tissues than photon therapy. In the Netherlands, proton therapy is reimbursed if the reduced dose to normal tissues is predicted to translate into a prespecified reduction in toxicity, based on nationally approved validated models. The aim of this paper is to present the development of a national indication protocol for proton therapy (NIPP) for model-based selection of breast cancer patients and to report on first clinical experiences. MATERIALS AND METHODS: A national proton therapy working group for breast cancer (PWG-BC) screened the literature for prognostic models able to estimate the individual risk of specific radiation-induced side-effects. After critical appraisal and selection of suitable models, a NIPP for breast cancer was written and subjected to comments by all stakeholders. The approved NIPP was subsequently introduced to select breast cancer patients who would benefit most from proton therapy. RESULTS: The model of Darby et al. (N Engl J Med 2013; 368:987-82) was the only model fulfilling the criteria prespecified by the PWG-BC. The model estimates the relative risk of an acute coronary event (ACE) based on the mean heart dose. The absolute lifetime risk of ACE <80 years was calculated by applying this model to the Dutch absolute incidence of ACE for female and male patients, between 40 and 70 years at breast cancer radiotherapy, with/without cardiovascular risk factors. The NIPP was approved for reimbursement in January 2019. Based on a threshold value of a 2% absolute lower risk on ACE for proton therapy compared with photons, 268 breast cancer patients have been treated in the Netherlands with proton therapy between February 2019 and January 2021. CONCLUSION: The NIPP includes a model that allows the estimation of the absolute risk on ACE <80 years based on mean heart dose. In the first 2 years, 268 breast cancer patients have been treated with proton therapy in The Netherlands.

An automated, quantitative, and case-specific evaluation of deformable image registration in computed tomography images.

A prerequisite for adaptive dose-tracking in radiotherapy is the assessment of the deformable image registration (DIR) quality. In this work, various metrics that quantify DIR uncertainties are investigated using realistic deformation fields of 26 head and neck and 12 lung cancer patients. Metrics related to the physiologically feasibility (the Jacobian determinant, harmonic energy (HE), and octahedral shear strain (OSS)) and numerically robustness of the deformation (the inverse consistency error (ICE), transitivity error (TE), and distance discordance metric (DDM)) were investigated. The deformable registrations were performed using a B-spline transformation model. The DIR error metrics were log-transformed and correlated (Pearson) against the log-transformed ground-truth error on a voxel level. Correlations of r ⩾ 0.5 were found for the DDM and HE. Given a DIR tolerance threshold of 2.0 mm and a negative predictive value of 0.90, the DDM and HE thresholds were 0.49 mm and 0.014, respectively. In conclusion, the log-transformed DDM and HE can be used to identify voxels at risk for large DIR errors with a large negative predictive value. The HE and/or DDM can therefore be used to perform automated quality assurance of each CT-based DIR for head and neck and lung cancer patients.

Radiation-induced fibrosis in the boost area after three-dimensional conformal radiotherapy with a simultaneous integrated boost technique for early-stage breast cancer: A multivariable prediction model.

BACKGROUND AND PURPOSE: To develop a multivariable prediction model for the risk of grade⩾2 fibrosis in the boost area after breast conserving surgery (BCS) followed by three-dimensional conformal radiotherapy (RT) with a simultaneous integrated photon boost (3D-CRT-SIB), five years after RT. MATERIAL AND METHODS: This prospective cohort study included 1,030 patients treated with RT for breast cancer (stage 0-III), after BCS. Data regarding physician-rated fibrosis and dose-volume parameters were available in 546 patients. A multivariable logistic regression model for grade⩾2 fibrosis was generated. RESULTS: At 5years, grade⩾2 fibrosis was observed in 13.4% of the patients. The multivariable analysis resulted in a prediction model for grade⩾2 fibrosis in the boost area including three independent variables: patient age, breast volume receiving⩾55Gy (V55 CTV breast) and the maximum radiation dose in the breast (Dmax). CONCLUSIONS: A multivariable prediction model was developed including age, V55 CTV breast and Dmax for grade⩾2 fibrosis in the boost area after breast cancer RT using a 3D-CRT-SIB technique. This model can be used to estimate the risk of fibrosis and to optimize dose distributions aiming at reducing this risk.

New precise measurement of the pion weak form factors in pi+-->e+ nugamma decay.

We have measured the pi+-->e+ nugamma branching ratio over a wide region of phase space, based on a total of 65 460 events acquired using the PIBETA detector. Minimum-chi2 fits to the measured (E(e+), E(gamma) energy distributions result in the weak form factor value of F(A)=0.0119(1) with a fixed value of F(V)=0.0259. An unconstrained fit yields F(V)=0.0258(17) and F(A)=0.0117(17). In addition, we have measured a=0.10(6) for the dependence of F(V) on q2, the e+ nu pair invariant mass squared, parametrized as F(V)(q2)=F(V)(0)(1+aq(2)). The branching ratio for the kinematic region E(gamma)>10 MeV and theta(e(+)gamma)>40 degrees is measured to be B(expt)=73.86(54)x10(-8). Earlier deviations we reported in the high-E(gamma)-low-E(e+) kinematic region are resolved without a tensor term. We also derive new values for the pion polarizability alpha(E)=2.78(10)x10(-4) fm3 and neutral pion lifetime tau(pi0)=(8.5+/-1.1)x10(-17) s.

[Mastitis caused by Yersinia pseudotuberculosis in a cow]. / Mastitis bij het rund door Yersinia pseudotuberculosis.

Subclinical mastitis with a raised somatic cell count was diagnosed in a cow in her fifth lactation. It was caused by Yersinia pseudotuberculosis, which can also infect humans. This is the first time that Yersinia pseudotuberculosis has been isolated from a mastitis sample in The Netherlands. Despite treatment with antibiotics in the dry period, Yersinia pseudotuberculosis was still present in the same quarter in the subsequent lactation. The somatic cell count was still high and milk production was much lower than in previous lactation. The pathogen did not spread to other quarters of the same cow or to herd mates on the farm over a 1-year period.

Diagnosis of pulmonary embolism: ventilation perfusion scintigraphy versus helical computed tomography pulmonary angiography.

The present study compared the accuracy of ventilation perfusion scintigraphy (VQS) and CT pulmonary angiography (CTPA) for the diagnosis of pulmonary embolism. This was a prospective observational study of 112 patients with suspected pulmonary embolism (PE) who could be studied with both investigations within 24 h. Results were compared to final diagnosis at completion of 6-month follow up, using receiver operating characteristic (ROC) analysis. Pulmonary embolism was diagnosed in 27 referred patients (24%). The sensitivity and specificity of VQS and CTPA were similar to that reported from the literature. A normal VQ scan had the highest negative predictive value (100%), while a high-probability VQ scan had the highest positive predictive value (92%). There was no overall difference (area under the ROC curve (AUC)) between VQS (AUC (95% CI) = 0.82 (0.75,0.89)) and CTPA (AUC = 0.88 (0.81,0.94)) for the diagnosis of PE. Among patients with abnormal chest X-rays, CTPA (AUC 0.90 (0.83,0.97)) appeared somewhat better than VQS (AUC 0.78 (0.68,0.88)) but this difference did not reach statistical significance. In this instance, CTPA is at least as accurate as VQS and may provide an opportunity to make alternative diagnoses.

Elective awake intubation in a patient with massive multinodular goitre presenting for radioiodine treatment.

We present the management of the potential airway complications in a case of massive multinodular goitre treated with radioactive iodine. The patient's trachea was prophylactically intubated, using a fibreoptic technique, to prevent further airway compromise due to thyroid oedema following radioactive iodine treatment. He remained awake and intubated for five days and was extubated when there was no clinical evidence of thyroid oedema as a consequence of his treatment. This approach avoided the considerable risk of thyroidectomy in a morbidly obese patient with airway obstruction. To the authors' knowledge this approach has not been previously described.

Independent component filters of natural images compared with simple cells in primary visual cortex.

Properties of the receptive fields of simple cells in macaque cortex were compared with properties of independent component filters generated by independent component analysis (ICA) on a large set of natural images. Histograms of spatial frequency bandwidth, orientation tuning bandwidth, aspect ratio and length of the receptive fields match well. This indicates that simple cells are well tuned to the expected statistics of natural stimuli. There is no match, however, in calculated and measured distributions for the peak of the spatial frequency response: the filters produced by ICA do not vary their spatial scale as much as simple cells do, but are fixed to scales close to the finest ones allowed by the sampling lattice. Possible ways to resolve this discrepancy are discussed.

Dipyridamole thallium-201 scintigraphy for early risk stratification of patients after uncomplicated myocardial infarction.

OBJECTIVE: To determine the safety and prognostic value of dipyridamole thallium-201 scintigraphy performed in patients within three to five days of acute myocardial infarction, including those receiving thrombolytic treatment. DESIGN: A prospective study of dipyridamole thallium-201 scintigraphy in patients early after acute myocardial infarction. SETTING: University hospital. PATIENTS: 200 patients who were clinically uncomplicated at day 3 after infarction, 92 (46%) of whom had received thrombolysis. MAIN OUTCOME MEASURES: Incidence of cardiac death, non-fatal reinfarction, readmission to hospital for unstable angina, or non-elective revascularisation procedure within six months' follow up. RESULTS: No patient had a serious complication from the dipyridamole study. At six month follow up, 55 patients (28%) had suffered a defined cardiac event. Patients who received thrombolysis had the same extent of thallium-201 redistribution and the same occurrence of subsequent cardiac events as those not receiving thrombolysis. Patients who subsequently had an event had more myocardial segments showing thallium-201 redistribution than event free patients: 2.7 (SD 1.9) v 1.2 (1.4), respectively (p < 0.001). Among all clinical and scintigraphic variables, multivariate analysis identified the extent of thallium-201 redistribution as the only independent predictor of outcome (p < 0.001). Among 63 patients (32%) of the study cohort who showed more than two myocardial segments with thallium-201 redistribution, the adjusted risk ratio for a cardiac event was 7.5 (95% confidence interval 2.9 to 19.1) compared with patients without any redistribution. CONCLUSIONS: Dipyridamole thallium-201 scintigraphy can be performed safely within a few days of the event in patients with uncomplicated myocardial infarction, including those who received thrombolysis, and can identify a subgroup of patients at high risk of future ischaemic events.

Modelling the power spectra of natural images: statistics and information.

Power spectra of an extensive set of natural images were analysed. Both the total power in a spectrum (corresponding to image contrast) and its dependence on spatial frequency vary considerably between images, and also within images when considered as functions of orientation. A series of probabilistic models for power spectra enabled calculating the information obtained from prior knowledge of parameters describing spectra. Most information is gained from contrast, 1/f2 spatial frequency behaviour, and contrast as a function of orientation. Variations in spatial frequency behaviour are relatively unimportant. For oriented contrast, a bandwidth of 10-30 deg is sufficient to obtain most information.

Surgery for severe constipation: the use of radioisotope transit scan and barium evacuation proctography in patient selection.

Nineteen women aged 19-64 years (median 38) with intractable constipation were assessed by Indium-111 DTPA colonic transit scan and barium evacuation proctogram. Patients were classified as having an isolated (I) or predominant disorder of colonic transit (II), a mixed disorder of colonic transit and rectal evacuation (III), a predominant disorder of rectal evacuation (IV) or normal colorectal emptying (V). Twelve patients fell into categories I and II and were considered suitable for surgery. Three responded to further vigorous aperient therapy and nine (32-55 years, median 38) underwent subtotal colectomy with ileorectal anastomosis at the level of the sacral promontory. Two patients required re-operation for suspected anastomotic leak. One patient required readmission on two occasions for small bowel obstruction. Follow up has been 2-21 months (median 16). Eight of the nine patients no longer take oral aperients. Eight patients have a satisfactory stool frequency of 2-8 per 24 h; the other patient has an ileostomy and incapacitating postprandial abdominal pain. Abdominal pain is troublesome in two other patients. Two patients require antidiarrhoeal therapy but none experience faecal incontinence. In severely constipated patients with a proven disorder of colonic transit but normal or near normal rectal evacuation subtotal colectomy provides excellent symptomatic relief.