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asn AUTORITÉ DE SÛRETÉ NUCLÉAIRE RÉPUBLIQUE FRANÇAISE DIVISION DE BORDEAUX Docteur Igor LATORZEFF Hôpital de RANGUEIL 1 avenue Jean-Poulhès - TSA 50032 31059 TOULOUSE Cedex 9 Bordeaux, le 2 9 MAI 2007 Subject: Inspection INS-2007-ENTBOR-082 of 3 May 2007 further to incident report 20 April 2007 Authorisation DEP-DSNR Bordeaux-0494-2006 7 Apri1 2006 Ref : [1] - Letter DEP-Bordeaux-0460-2007 dated 27 April 2007 [2] - Letter DGSNR/SD7/n 1027/2006 dated 19 April 2006 relating to the prevention of serious radiotherapy risks via an approach based on organisational and human factors. Dear Dr Latorzeff, As was announced in the letter whose reference is given above, Officers from the Nuclear Safety Authority (ASN) carried out on 3 May 2007 a reactive inspection in accordance with protection against ionizing radiation after a notification of an incident involving the stereotactic radiosurgery accelerator. I am writing to provide you with a summary of the visit, as well as to inform you of the main requests and comments resulting from the observations made on this occasion. Summary of the inspection The inspection followed a notification of an incident concerning the calibration of the Novalis stereotactic radiosurgery facility, which led to a large number of patients receiving higher doses than those prescribed. The information obtained between the time of the notification and the inspection was clarified and explanations were given regarding the detection and causes of the event. The use of an ionisation chamber of inappropriate dimensions for the size of the microbeams produced for most treatment led to a calibration error from the moment the facility began operation in April 2006. The error came to light during an intercomparison with other similar facilities used throughout the world carried out in April 2007 by the BrainLAB company, the provider of the facility. Once the correction of the calibration had been carried out by the CHU working with the manufacturer, the dosimetric data were recalculated for all 172 patients treated since the facility began operation. Taking into account the type of beams affected by the error, the team in charge of treatment identified 145 patients who had been subject to an overexposure the size and length of which depended on the size of the fields, the location of the lesion and the type of pathology. The patients treated by stereotactic radiosurgery at the Toulouse CHU are undergoing a quarterly medical checkup and the ASN inspectors have taken note of the fact that until now no functional clinical event has been reported for the 145 patients. /

A summary report presenting the recalculated dosimetric parameters for the 145 patients was handed over to the inspectors by the CHU during the meeting. It was agreed that resumption of operation of the accelerator was possible, after implementation of the acceptance procedure for the dosimetry software. A comparison of the isodoses of patients medical records with another Novalis centre would also provide a further guarantee for ensuring the safety of treatment. Finally, the issue of patient information linked to that of information about the incident was examined. The information should be made public within a reasonable time limit, while leaving the hospital enough time to inform and accompany the patients when the incident is announced. The communications strategy will be defined following consultation of the decision-making bodies of the Ministry of Health and ASN. A. Requests for corrective action Comparison before resumption of operation Given the specific methodology required in order to calibrate the microbeams, as well as the errors which led to the problems that caused the incident, it is clear that a new intercomparison with other hospitals using the same equipment would appear to be a useful safety measure for the validation of the configuration of the accelerator. Request A.1: I ask you to undertake a comparison of the estimated dosimetry of the patients concerned by the incident with another Novalis centre in order to confirm the correct configuration of your device. The incident demonstrates, similarly to other incidents recently reported in France, sometimes with more serious consequences, the importance which should be granted to ensuring the safety of radiotherapy treatment, since such malfunctions can lead to situations which have a major impact on health. In the circular whose reference is given above [2], following the initial reports of incidents in Lyon and Grenoble, ASN alerted beam therapy departments to the importance of the role of people and of organisations in making treatment safer. To this end, in the appendix to the letter it was proposed to set up a risk management procedure comprising phases of risk identification, analysis and treatment. The need to analyse risks is in fact more necessary than ever, and should lead to the following topics in particular being covered: patient program: reception and first consultation, acquisition of morphological data, utilisation of images in order to determine volumes of concern, calculation of the dose distribution and MUs, definition of ballistics, treatment. materials: TPS, "record and verify", materials for immobilisation and marking, masks, portal imaging, treatment equipment, metrology. In this respect, the impact of computerization on changes in staff activity should be analysed; organization of the department. Finally, I would like to point out that risk analysis should be open-ended in nature in order to take into account, on the one hand, changes in the department (materials, staff, organization, etc) and, on the other, both internal and external feedback. To this end, regarding the latter point, you might want to take into consideration any events (near-incidents and incidents) identified within your department. I would therefore ask you to set up a system for the reporting of such events (logbook). Request A.2: I ask you to initiate an analysis of the risks within your department in order to formalize your work procedures, identify critical operations and on that basis take steps to set up the appropriate structural and organizational measures. Page 2 /4

Request A.3: I ask you to set up a system for identifying and reporting any event which may be considered as a discrepancy which might possibly lead to an incident. Patient follow-up You should ensure that patients are systematically and regularly monitored following their treatment. Following the detection of the dose anomaly, an exceptional consultation should be proposed to all the patients, while the medical follow-up should be extended to several years, given the delay before the appearance of side effects potentially linked to the treatment. Request A.4: I ask you to keep me informed of the results of the clinical follow-up of the patients following the exceptional post-incident consultation, and then on an annual basis or in the event of clinical signs which suggest the recent appearance of a radiation-induced complication. B. Additional information: Analysis of the incident Request B.1: I ask you to draw up and send to me a report on the incident. It should present an analysis of the causes of the incident, the lessons that have been learnt from the event by the department and the CHU, and should lay out the corrective action taken to ensure such a situation does not happen again. The analysis of the causes should in particular examine human and organizational factors (workload, skills, training, etc). The report should also detail: The precise experimental conditions under which the erroneous measurements leading to the calibration errors were carried out; The precise experimental conditions under which the measurements were corrected after the discovery of the incident; The results of measurements of scatter factor, before and after correction, for all the beams affected by the error. Dosimetric data for patients Request B.3: I ask you to add to the final summary table of the anonymous dosimetric data for the 145 patients an additional column which mentions, for each patient, the dose initially prescribed on the PTV envelope and the corresponding isodose. Medical records IRSN observed that, in the final summary table of dosimetric data, there are 6 patients for whom the dose restrictions for organs at risk that you selected were exceeded for significant volumes of the organ. Request B.4: I ask you to send, in confidence, the complete records for these 6 patients containing the dose-volume histograms, the isodose curves, the treatment plan and the clinical records, to an IRSN doctor (Pr. Gourmelon). C. Remarks. None. Page 3 /4

I would be grateful if you sent me your comments and responses regarding these points within a time limit not exceeding 3 months. With regard to any commitments you may make, I would ask you to identify them clearly and specify, for each one, the target date for its completion. Yours sincerely, For the President of ASN and acting on the authority of the head of the Bordeaux division Julien COLLET Page 4 /4