John Simpson

Investigation of a real-time EPID-based patient dose monitoring safety system using site-specific control limits

PurposeThe aim of this study is to investigate the performance and limitations of a real-time transit electronic portal imaging device (EPID) dosimetry system for error detection during dynamic intensity modulated radiation therapy (IMRT) treatment delivery. Sites studied are prostate, head and neck (HN), and rectal cancer treatments.MethodsThe system compares measured cumulative transit EPID image frames with predicted cumulative image frames in real-time during treatment using a χ comparison with 4xa0%, 4xa0mm criteria. The treatment site-specific thresholds (prostate, HN and rectum IMRT) were determined using initial data collected from 137 patients (274 measured treatment fractions) and a statistical process control methodology. These thresholds were then applied to data from 15 selected patients including 5 prostate, 5 HN, and 5 rectum IMRT treatments for system evaluation and classification of error sources.ResultsClinical demonstration of real-time transit EPID dosimetry in IMRT was presented. For error simulation, the system could detect gross errors (i.e. wrong patient, wrong plan, wrong gantry angle) immediately after EPID stabilisation; 2xa0seconds after the start of treatment. The average rate of error detection was 7.0xa0% (prostateu2009=u20095.6xa0%, HN=u20098.7xa0% and rectumu2009=u20096.7xa0%). The detected errors were classified as either clinical in origin (e.g. patient anatomical changes), or non-clinical in origin (e.g. detection system errors). Classified errors were 3.2xa0% clinical and 3.9xa0% non-clinical.ConclusionAn EPID-based real-time error detection method for treatment verification during dynamic IMRT has been developed and tested for its performance and limitations. The system is able to detect gross errors in real-time, however improvement in system robustness is required to reduce the non-clinical sources of errorxa0detection.

Clinical performance evaluation of the Idylla NRAS-BRAF mutation test on retrospectively collected formalin-fixed paraffin-embedded colorectal cancer tissue

Aims Understanding the molecular mechanisms of underlying disease has led to a movement away from the one-drug-fits-all paradigm towards treatment tailored to the genetic profile of the patient. The Biocartis Idylla platform is a novel fully automated, real-time PCR–based in vitro diagnostic system. The Idylla NRAS-BRAF mutation test has been developed for the qualitative detection of mutations in NRAS and BRAF oncogenes, facilitating genetic profiling of patients with cancer. The aim of this study was to carry out a formal clinical performance evaluation. Methods Two-hundred and forty-two formalin-fixed paraffin-embedded (FFPE) human malignant colorectal cancer (CRC) tissue samples were identified in departmental archives and tested with both the Idylla NRAS-BRAF mutation test and the Agena Bioscience MassARRAY test. Results The overall concordance between the Idylla NRAS-BRAF mutation test and the MassARRAY comparator reference test result was 241/242 (99.59%, lower bound of one-sided 95%u2009CI=98.1%) for NRAS and 242/242 (lower bound of 95% one-sided 95%u2009CI=98.89%) for BRAF. The Idylla NRAS-BRAF test detected one NRAS mutation that had not been reported by the MassARRAY comparator reference test. Reanalysis of this sample by droplet digital PCR confirmed that the mutation was present, but at an allelic frequency below the stated sensitivity level of the MassARRAY system. Conclusion These results confirm that the Idylla NRAS-BRAF mutation test has high concordance with a widely used NRAS-BRAF test, and is therefore suitable for use as an in vitro diagnostic device for this application.

A method for evaluating treatment quality using in vivo EPID dosimetry and statistical process control in radiation therapy

Purpose Due to increasing complexity, modern radiotherapy techniques require comprehensive quality assurance (QA) programmes, that to date generally focus on the pre-treatment stage. The purpose of this paper is to provide a method for an individual patient treatment QA evaluation and identification of a quality gap for continuous quality improvement. Design/methodology/approach A statistical process control (SPC) was applied to evaluate treatment delivery using in vivo electronic portal imaging device (EPID) dosimetry. A moving range control chart was constructed to monitor the individual patient treatment performance based on a control limit generated from initial data of 90 intensity-modulated radiotherapy (IMRT) and ten volumetric-modulated arc therapy (VMAT) patient deliveries. A process capability index was used to evaluate the continuing treatment quality based on three quality classes: treatment type-specific, treatment linac-specific, and body site-specific. Findings The determined control limits were 62.5 and 70.0 per cent of the χ pass-rate for IMRT and VMAT deliveries, respectively. In total, 14 patients were selected for a pilot study the results of which showed that about 1 per cent of all treatments contained errors relating to unexpected anatomical changes between treatment fractions. Both rectum and pelvis cancer treatments demonstrated process capability indices were less than 1, indicating the potential for quality improvement and hence may benefit from further assessment. Research limitations/implications The study relied on the application of in vivo EPID dosimetry for patients treated at the specific centre. Sampling patients for generating the control limits were limited to 100 patients. Whilst the quantitative results are specific to the clinical techniques and equipment used, the described method is generally applicable to IMRT and VMAT treatment QA. Whilst more work is required to determine the level of clinical significance, the authors have demonstrated the capability of the method for both treatment specific QA and continuing quality improvement. Practical implications The proposed method is a valuable tool for assessing the accuracy of treatment delivery whilst also improving treatment quality and patient safety. Originality/value Assessing in vivo EPID dosimetry with SPC can be used to improve the quality of radiation treatment for cancer patients.

Mitochondrial DNA depletion induces innate immune dysfunction rescued by IFN-γ

County Council (ALF), the ChAMP Consortium, the Swedish Strategical Research Foundation (SSF), the V ardal Foundation, and Karolinska Institutet. Disclosure of potential conflict of interest: S. E. Dalhen has received grants from the Swedish Science Foundation, the Swedish Research Council, and the Swedish Heart-Lung Foundation; has a board membership with RSPR Pharma; and has consultant arrangements with AstraZeneca, GlaxoSmithKline, and Regeneron. B. Dahlen has received grants from the Swedish Medical Research Council and the Swedish Heart-Lung Foundation. M. van Hage has consultant arrangements with Biomay AG and Hycor Biomedical LLC and has received payment for lectures from Thermo Fisher Scientific. S. Gabrielsson has received grants from the Swedish Research Council, the Swedish Heart-Lung Foundation, the Hesselman’s Foundation, the Cancer and Allergy Research Foundation, the Stockholm County Council (ALF), the ChAMP Consortium, and Karolinska Institutet. The rest of the authors declare that they have no relevant conflicts of interest.

Interactive visualisation for interpreting diagnostic test accuracy study results

Information about the performance of diagnostic tests is typically presented in the form of measures of test accuracy such as sensitivity and specificity. These measures may be difficult to translate directly into decisions about patient treatment, for which information presented in the form of probabilities of disease after a positive or a negative test result may be more useful. These probabilities depend on the prevalence of the disease, which is likely to vary between populations. This article aims to clarify the relationship between pre-test (prevalence) and post-test probabilities of disease, and presents two free, online interactive tools to illustrate this relationship. These tools allow probabilities of disease to be compared with decision thresholds above and below which different treatment decisions may be indicated. They are intended to help those involved in communicating information about diagnostic test performance and are likely to be of benefit when teaching these concepts. A substantive example is presented using C reactive protein as a diagnostic marker for bacterial infection in the older adult population. The tools may also be useful for manufacturers of clinical tests in planning product development, for authors of test evaluation studies to improve reporting and for users of test evaluations to facilitate interpretation and application of the results.

TH-CD-207A-11: Sensitivity Analysis of Action Limits for Real-Time EPID-Based Delivery Verification System Using Artificial Clinical Relevant Error Simulations

PURPOSEnA real-time patient treatment delivery verification system using EPID (Watchdog) has been developed as an advanced patient safety tool. In a pilot study data was acquired for 119 prostate and head and neck (HN) IMRT patient deliveries to generate body-site specific action limits using statistical process control. The purpose of this study is to determine the sensitivity of Watchdog to detect clinically significant errors during treatment delivery.nnnMETHODSnWatchdog utilizes a physics-based model to generate a series of predicted transit cine EPID images as a reference data set, and compares these in real-time to measured transit cine-EPID images acquired during treatment using chi comparison (4%, 4mm criteria) after the initial 2s of treatment to allow for dose ramp-up. Four study cases were used; dosimetric (monitor unit) errors in prostate (7 fields) and HN (9 fields) IMRT treatments of (5%, 7%, 10%) and positioning (systematic displacement) errors in the same treatments of (5mm, 7mm, 10mm). These errors were introduced by modifying the patient CT scan and re-calculating the predicted EPID data set. The error embedded predicted EPID data sets were compared to the measured EPID data acquired during patient treatment. The treatment delivery percentage (measured from 2s) where Watchdog detected the error was determined.nnnRESULTSnWatchdog detected all simulated errors for all fields during delivery. The dosimetric errors were detected at average treatment delivery percentage of (4%, 0%, 0%) and (7%, 0%, 0%) for prostate and HN respectively. For patient positional errors, the average treatment delivery percentage was (52%, 43%, 25%) and (39%, 16%, 6%).nnnCONCLUSIONnThese results suggest that Watchdog can detect significant dosimetric and positioning errors in prostate and HN IMRT treatments in real-time allowing for treatment interruption. Displacements of the patient require longer to detect however incorrect body site or very large geographic misses will be detected rapidly.