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1 Estimation of the Radiation Dose from Thoracic CT Scans in a Cystic Fibrosis Population Journal: Manuscript ID: Manuscript Type: Date Submitted by the Author: -0-0.R Manuscript 0-Jun-0 Complete List of Authors: Donadieu, jean; Institut de veille sanitaire, Santé et Environnement ROUDIER, candice; Institut de veille sanitaire, Santé et environnement Saguintaah, Magali; CHU de Montpellier, Pediatric radiology Maccia, carlo; Centre dassurance de qualité des Applications Technologiques dans le domaine de la Santé (CAATS), Chiron, raphaël; CHU de Montpellier, Centre de Ressources et de Compétences pour la Mucoviscidose (CRCM) Keywords: CAT SCAN PULMONARY, CYSTIC FIBROSIS, RADIOLOGY - THORACIC

2 Page of Radiation dose from CT scans in CF patients date : 0/0/0 - - Estimation of the Radiation Dose from Thoracic CT Scans in a Cystic Fibrosis Population Jean Donadieu, Candice Roudier, Magali Saguintaah, Carlo Maccia and Raphaël Chiron Département Santé et Environnement, Institut de Veille Sanitaire, St Maurice, France. Service de radiologie pédiatrique, CHU Montpellier, France Centre d Assurance de qualité des Applications Technologiques dans le domaine de la Santé (CAATS), Bd Maréchal Joffre Bourg la Reine France, Centre de Ressources et de Compétences pour la Mucoviscidose (CRCM), CHU Montpellier, Hôpital Arnaud de Villeneuve, F-0 France Corresponding author Jean Donadieu j.donadieu@invs.sante.fr Fax: Phone: Number of words: abstract: Text: 0 Running title: Radiation dose from CT scans in CF patients Key words: Radiation; CT scan; Cystic Fibrosis Conflicts of interest: None of the authors have any conflicts of interest

3 Page of Radiation dose from CT scans in CF patients date : 0/0/0 - - Objective: To determine the radiation exposure associated with computed tomography (CT) scans in a population of patients with cystic fibrosis (CF). Methods: We reviewed the medical charts of patients with typical CF who received regular medical management in a reference center from birth to March 0. Results: Among 0 patients with a total follow-up of person-years, patients received a total of CT scans, including thoracic CT scans. The full parameters of the examination were available for thoracic CT scans, allowing the ED and organ doses to be calculated. The ED was determined by the number of slices and the type of tomographs. The ED per thoracic CT scan was asymmetrically distributed (mean. msv, range.-.). The mean dose delivered to the four most strongly exposed organs (lungs, breasts, bone marrow and thyroid) was respectively.,.,. and. mgy. The mean lifetime number of CT scans per patient was. (range 0-) and the average lifetime ED was. msv per patient (range. -. msv). Age at the first CT scan fell over the years, from years for patients born before 0 to. years for patients born after. Conclusion: The mean effective dose per CT scan in CF patients is about. msv. Age at the first CT scan is lower in the most recent generation of patients. The lifetime effective dose of radiation received by CF patients, especially in the most recent generation, warrants long term follow-up.

4 Page of Radiation dose from CT scans in CF patients date : 0/0/0 - - Introduction Cystic fibrosis (CF) is a common genetic disease in which death is generally due to pulmonary damage by chronic inflammation and infections. Disease progression is mainly monitored by means of pulmonary function tests. Thoracic computed tomography (CT) can detect early lung changes, offering detailed views of lesions that are not visible on standard chest roentograms. The first study in this setting was done in by Jacobsen, and the utility of CT was subsequently confirmed by many other authors -. Anatomical abnormalities are visible on CT scans before they become apparent in pulmonary function tests ;. Recent clinical trials used thoracic CT features as surrogate endpoints. The place of pulmonary CT in the routine management of CF remains controversial, however, both because the individual benefits of CT-based monitoring have not been proven, and because the financial cost is far from negligible. Moreover, CT delivers a far higher X-ray dose than standard roentograms, and the latter thus remain the radiological examination of first choice. With respect to radioprotection, regular CT monitoring of patients with cystic fibrosis raises two main issues. First, CF patients life expectancy has gradually risen over the last three decades, and is now between and years ;. Second, thoracic CT tends to be performed increasingly early in these patient s lives. The lifetime X-ray dose received by CF patients undergoing repeated CT has only been the subject of theoretical studies. We therefore studied patients with cystic fibrosis in order to determine the precise number and type of CT scans received, and the dosimetric parameters of thoracic CT in this setting. Materials and Methods Inclusion criteria and recruitment The Montpellier cystic fibrosis regional reference center (Centre de Ressource et de Compétence pour la Mucoviscidose) is a medical group created in 0 in order to organize the management of both children and adults with cystic fibrosis in the Languedoc Roussillon region. It is located in Montpellier University Hospital. This center took over from a group of medical practitioners that had specialized in CF for more than years, but that had no relevant administrative status. All the charts of patients with cystic fibrosis who were managed by this group over the past years were examined. We excluded patients with atypical CF (n=), i.e. those diagnosed after years of age and who had no gastrointestinal or pulmonary involvement. We also excluded patients who had moved out of the region (n = 0). Finally, only 0 patients for whom the entire medical records from birth to the cutoff date ( March 0) were

5 Page of Radiation dose from CT scans in CF patients date : 0/0/0 - - available were included in this study. None of these 0 patients had received CT scans related to participation in a clinical trial. CT was always part of standard patient management, and no specific recommendations on its use were made. All the data analyzed here were collected during the course of standard patient management, and the center s database was declared to the French computer watchdog commission (Commission Nationale Informatique et Liberté). Assessment of the number of CT scans and resulting X-ray doses The patient charts and radiology unit registers were systematically examined to identify all CT scans done up to the cutoff date. Pulmonary CT films were read to determine the following technical parameters of the procedure: the date of the examination and the device used; and, for each sequence, the anatomical zone examined, the displayed kilovoltage value (kv), the anodic current (mas), the slice thickness and interslice distance, the number of slices, and the exposure times. From these parameters, and for each sequence, the effective dose (ED) received and the organ doses were calculated with Impactscan software version 0.W ( Extrapolation to patients with missing dosimetric data: To calculate the dosimetric exposure of the entire cohort, the thoracic CT scans for which we did not have all the parameters of the examination were attributed the mean dosimetric parameters (effective dose, organ doses) of the examinations for which full dosimetric data were available. These values are shown in table. For other CT locations, the effective dose per examination was assumed to be the mean dose recorded by the NRPB survey, i.e.. msv for sinus CT, msv for abdominal CT and. msv for cranial CT. Statistical methods In addition to standard descriptive statistics, a generalized linear model (GLM) was used to identify determinants of the ED per CT scan, i.e. continuous variables (age at CT scan, number of slices) and categorical variables (year of CT scan, CT device). To normalize the distribution of the residuals, the ED was first log-transformed. All analyses were done with Stata software version. Results Patient characteristics The cohort consisted of female patients and male patients born between and 0. Three patients died before the cutoff date, at the ages of.,. and. years. At age years the survival rate was.% (% CI.-.). At the cutoff

6 Page of Radiation dose from CT scans in CF patients date : 0/0/0 - - date the patients median age was. years overall (range 0.. years), and did not differ between male and female patients (p=0.). Only one subject, a child aged. years at the cutoff date, received no CT scans. The length of follow-up after the first CT scan ranged from 0. to. years (median. years). Among the patients who had at least one CT scan, median age at the first CT scan was. years (range 0.- years). Technical characteristics of thoracic CT One hundred eighty-five thoracic CT scans, in patients, were evaluated. These examinations were done in two radiology departments (a pediatric unit and an adult unit) with five different model of CT camera, during precise time periods: General Electric EC 0000 between and (n=), General Electric Prospeed between and 0 (n=), General Electric Highspeed ADV between and (n=), General Electric Light Speed in 0 (n=), General Electric Light Speed Ultra between 0 and 0 (n=) and Siemens Somatom Plus between and 0 (n=). A given examination comprised between and distinct sequences (mean.), and each sequence had its own basic characteristics (number of slices, exposure time, kv, masas, anatomical limits, etc.). The mean number of slices per sequence was, and the exposure time was. s per slice. The technical parameters are shown in table. Dosimetric characteristics of thoracic CT The dosimetric parameters were calculated from each examination protocol and the anatomical characteristics of the field of interest (table ). The mean effective dose per examination was. msv, and the range was. msv to. msv (figure ). Organ doses reflect the heterogeneous distribution of the dose within the body: by definition, only organs included in the CT field of view receive a strong dose. Thus, the maximal dose is delivered to the lungs and the breasts (respectively. mgy and. mgy) and, to a lesser extent, to the bone marrow, thyroid and liver (respectively.,. and. mgy). Note the wide range of values, the dose to the lungs and breasts exceeding mgy in % of examinations (table ). We then analyzed the following determinants of the effective dose of thoracic CT: age at the time of the examination, year of the examination, camera models, and total number of slices. In univariate analysis, age at CT did not significantly influence the dose delivered to the patient per examination. In contrast, camera models used (GE EC 000 median dose., GE Hispeed., GE Light Speed Ultra., and Siemens Somato Plus,.) significantly influenced the dose, as did the number of slices per examination and the year of the examination (the dose tended to increase between and 0). To analyze the respective roles of each dose determinant, we constructed a generalized linear model. This showed that, when all these factors were simultaneously taken into

7 Page of Radiation dose from CT scans in CF patients date : 0/0/0 - - account, only two factors significantly influenced the dose delivered to the patient, namely the type of machine and the number of slices (table ). Distribution of the number of CT scans per patient and estimation of the cumulative dose received In the patients who had at least one CT scan, the lifetime cumulative effective dose was. msv on average, with an asymmetrical distribution (range.-. msv). The mean cumulative dose delivered to the lungs was msv (.-.), to the breasts. msv (0.-.), to the thyroid 0. msv (0.-.) and to the bone marrow. msv (.-0.). The lifetime cumulative X-ray dose depends on the number of CT scans and the dose per CT scan. In total, CT scans were performed in patients. Only one subject had no CT scans. The vast majority of CT examinations were thoracic scans (, %), while the other focused on the sinuses (n=), head (n=) or abdomen (n=). The mean number of CT scans per patient was., with a maximum of. The number of scans depended on medical practices, which evolved over the -year study period. This is illustrated by dividing the study population into four generations (those born before 0, between 0 and 0, between 0 and, and after ). During the study period, age at the first CT scan fell markedly, from about years to years, while the interval between scans was similar in the different generations (table ). Discussion We report the doses of ionizing radiation received during CT scans by a cohort of 0 patients with cystic fibrosis managed in a French regional reference center, with a total follow-up of patient-years. Despite the large numbers of studies focusing on thoracic CT in CF patients -;, no precise estimate of the effective dose received in this setting has been published. The dosimetry of thoracic CT examinations in patients with cystic fibrosis is important, because general studies show that it is highly dependent on the technical protocol, which varies with the indication. In addition to the average effective dose delivered by thoracic CT (estimated here at. msv per examination), it is important to take into account the very heterogeneous anatomical distribution of X-rays during thoracic CT, as the effective dose alone is not entirely representative of a patient s exposure. The highest doses are delivered to the organs, and particularly to the lungs, breasts, bone marrow and thyroid. The value obtained here differs from that obtained in the only other study that mentions a dosimetric value in patients with cystic fibrosis, i.e. msv per examination. However, it is noteworthy that this dose of msv/ct was not obtained from the technical protocols of real examinations but from a theoretical technical protocol. Two studies involving and patients described a light CT

8 Page of Radiation dose from CT scans in CF patients date : 0/0/0 - - technical protocol ;, without calculating the dose received during a standard protocol. One of these studies concluded that the light protocol did not yield satisfactory diagnostic information. However, recent CT devices minimize the dose by optimizing exposure parameters, and the radiological community is more aware of the ALARA concept, which advocates keeping the radiation dose "As Low As Reasonably Achievable". Our study shows that the CT dose varies little with age, probably because the technical protocol is adapted to bodyweight and age. In contrast, it varies not only with the number of slices, but also, significantly, according to the radiological equipment used. It is known that, for a given number of slices, recent cameras irradiate the patient more strongly than older cameras. Our study extends this observation to cystic fibrosis patients. The second original and important result of this study is the patients lifetime CT exposure. This is crucial for calculating dosimetric parameters but raises a number of methodological issues. In particular, the use of thoracic CT has evolved markedly in the last years. Indeed, our study shows that age at the first CT scan has fallen drastically in the last years, while the frequency of scans after the first scan has remained relatively stable. This is more important for predicting the dosimetric consequences of CT in this setting than is the cumulative ED or the cumulative organ doses. Indeed, numerically, the figures obtained are, on average, fairly moderate (. msv per patient) but these data combine treatments of older patients with a cumulative follow-up of more than years who had their first CT late in life, and patients less than 0 years old at initial management and who have relatively short follow-up. However, if the frequency of CT scans remains the same throughout their lives, these younger patients will be exposed more than older patients, owing also to their longer life expectancy. When the first thoracic CT is done at. years of age, for example, followed by a scan every two years delivering an effective dose of msv, with mgy to the lungs and mgy to the breasts, at the age of years the cumulative effective dose would be. msv, with mgy to the lungs, 0 mgy to the breasts, and mgy to the thyroid. These extrapolated doses are not particularly dangerous according to the literature (BEIR VII) and to recent epidemiological data, but they are far from negligible. It should also be underlined that, in practice, recent CT devices do not deliver a smaller dose per examination. In addition, protocols comprising a smaller number of slices per examination, intended to reduce the dose per examination, do not always provide satisfactory results. This further stresses the importance of determining the long term individual health benefits of CT monitoring for the patient with cystic fibrosis. The use of CT to provide surrogate endpoints in clinical trials is not intended to yield an individual benefit, and some authors have expressed their reservations regarding this use. The existence of

9 Page of Radiation dose from CT scans in CF patients date : 0/0/0 - - even a small risk associated with long-term use of CT means that the health benefit for the individual patient should be carefully assessed. The potential benefits of repeated CT remain to be demonstrated in this setting, and the use of thoracic CT in patients with cystic fibrosis should probably be limited to the management of acute infections. Finally, bystander tissues (thyroid, gonads, etc.) should be protected with appropriate lead screens during all CT examinations.

10 Page of Radiation dose from CT scans in CF patients date : 0/0/0 - - References () Davis PB. Cystic fibrosis since. Am J Respir Crit Care Med 0; ():-. () Jacobsen LE, Houston CS, Habbick BF et al. Cystic fibrosis: a comparison of computed tomography and plain chest radiographs. Can Assoc Radiol J ; ():-. () Brody AS, Molina PL, Klein JS et al. High-resolution computed tomography of the chest in children with cystic fibrosis: support for use as an outcome surrogate. Pediatr Radiol ; (0):-. () Brody AS. Scoring systems for CT in cystic fibrosis: who cares? Radiology 0; ():-. () Brody AS, Tiddens HA, Castile RG et al. Computed tomography in the evaluation of cystic fibrosis lung disease. Am J Respir Crit Care Med 0; (0):-. () Brody AS, Kosorok MR, Li Z et al. Reproducibility of a scoring system for computed tomography scanning in cystic fibrosis. J Thorac Imaging 0; ():-. () de Jong PA, Nakano Y, Lequin MH et al. Progressive damage on high resolution computed tomography despite stable lung function in cystic fibrosis. Eur Respir J 0; ():-. () de Jong PA, Ottink MD, Robben SG et al. Pulmonary disease assessment in cystic fibrosis: comparison of CT scoring systems and value of bronchial and arterial dimension measurements. Radiology 0; ():-. () Donnelly LF, Gelfand MJ, Brody AS et al. Comparison between morphologic changes seen on high-resolution CT and regional pulmonary perfusion seen on SPECT in patients with cystic fibrosis. Pediatr Radiol ; ():-. (0) Dorlochter L, Nes H, Fluge G et al. High resolution CT in cystic fibrosis--the contribution of expiratory scans. Eur J Radiol 0; ():-. () Helbich TH, Heinz-Peer G, Fleischmann D et al. Evolution of CT findings in patients with cystic fibrosis. AJR Am J Roentgenol ; ():-.

11 Page 0 of Radiation dose from CT scans in CF patients date : 0/0/0-0 - () Demirkazik FB, Ariyurek OM, Ozcelik U et al. High resolution CT in children with cystic fibrosis: correlation with pulmonary functions and radiographic scores. Eur J Radiol 0; ():-. () Judge EP, Dodd JD, Masterson JB et al. Pulmonary abnormalities on highresolution CT demonstrate more rapid decline than FEV in adults with cystic fibrosis. Chest 0; 0():-. () Robinson TE, Goris ML, Zhu HJ et al. Dornase alfa reduces air trapping in children with mild cystic fibrosis lung disease: a quantitative analysis. Chest 0; ():-. () Langton Hewer SC. Is limited computed tomography the future for imaging the lungs of children with cystic fibrosis? Arch Dis Child 0; ():-. () Cystic Fibrosis Foundation guidelines for patient services, evaluation, and monitoring in cystic fibrosis centers. The Cystic Fibrosis Foundation Center Committee and Guidelines Subcommittee. Am J Dis Child 0; ():-. () Assael BM, Castellani C, Ocampo MB et al. Epidemiology and survival analysis of cystic fibrosis in an area of intense neonatal screening over years. Am J Epidemiol 0; ():-. () Dodge JA, Morison S, Lewis PA et al. Incidence, population, and survival of cystic fibrosis in the UK, -. UK Cystic Fibrosis Survey Management Committee. Arch Dis Child ; ():-. () de Jong PA, Mayo JR, Golmohammadi K et al. Estimation of cancer mortality associated with repetitive computed tomography scanning. Am J Respir Crit Care Med 0; ():-. () Wall BF, Hart D. Revised radiation doses for typical X-ray examinations. Report on a recent review of doses to patients from medical X-ray examinations in the UK by NRPB. National Radiological Protection Board. Br J Radiol ; 0():-. () de Jong PA, Nakano Y, Lequin MH et al. Dose reduction for CT in children with cystic fibrosis: is it feasible to reduce the number of images per scan? Pediatr Radiol 0; ():0-.

12 Page of Radiation dose from CT scans in CF patients date : 0/0/0 - - () Jimenez S, Jimenez JR, Crespo M et al. Computed tomography in children with cystic fibrosis: a new way to reduce radiation dose. Arch Dis Child 0; ():-0. () Brody AS. CT scanner design and patient radiation exposure. Pediatr Radiol 0; ():-. () Committee to Assess Health Risks from Exposure to Low Levels of Ionizing Radiation NRC. Health Risks from Exposure to Low Levels of Ionizing Radiation: BEIR VII Phase. National academic press ed. Washington DC: 0 () Cardis E, Vrijheid M, Blettner M et al. Risk of cancer after low doses of ionising radiation: retrospective cohort study in countries. BMJ 0; (0):.

13 Page of Radiation dose from CT scans in CF patients date : 0/0/0 - - Figure : Distribution of the effective doses delivered by a given thoracic CT scan in CF patients. % of CT scan 0 0 Figure 0 0 Effective Dose per Thoracic CT in msv

14 Page of Radiation dose from CT scans in CF patients date : 0/0/0 - - Table : Technical characteristics of thoracic CT scans (n =) done in CF patients Median Mean Range Number of sequences per examination. - Number of slices/sequence - Milliamps/sequence -0 Kv/sequence 00 : n= : n= 0 : n= 0 : n= Exposure time (s)/sequence

15 Page of Radiation dose from CT scans in CF patients date : 0/0/0 - - Table : Dosimetric values of the examinations analyzed. The doses were calculated from the technical parameters of each examination by using Impactscan software. Median Mean Range Total effective dose (msv)...-. Thyroid (msv) Breast (msv) Lung (msv)...-. Liver (msv). 0.- Bone marrow (msv)...-. Kidney (msv) Brain (msv) Gonads (msv)

16 Page of Radiation dose from CT scans in CF patients date : 0/0/0 - - Table : Determinants of the effective dose (ED) per CT scan (n = ) expressed in msv. The following generalized linear model was used: log(ed ) = Constant + (Nb of Slices)+ ( GE LIGHT SPEED ULTRA)+ ( SOMATOM PLUS ). This final model included only significant variables in a model also including age at CT scan, year of CT scan, and the CT device. Coefficient in the general linear model % CI lower limit % CI upper limit P value Constant..0. <0.00 Binary variables Multiplication factor of ED for each variable GE LIGHT SPEED ULTRA / yes SOMATOM PLUS / yes < 0.00 Continuous variables Multiplication factor of ED per slice Nb of slices < 0.00

17 Page of 0 Radiation dose from CT scans in CF patients date : 0/0/0 - - Table : Distribution of thoracic CT scans and doses received, according to the length of follow-up, in the overall population and in the different birth generations. Population N Total nb of Total nb Mean age Mean followup Situation one year after the first CT scan Situation five years after the first CT scan personyears of CT at st CT after st scans scan (years) CT scan (years) Nb of evaluable pts Mean Nb of CT scans perform Mean Cumulative effective dose (msv) received at Nb of evaluable pts Mean Nb of CT scans performed at one year Mean Cumulative effective dose (msv) received at one year ed at one year one year Whole population Born before 0 Born 0-0 Born 0- Born after