Huang, Jeannie S.*; Tobin, Allison*; Harvey, Lee‡; Nelson, Thomas R.†
Diagnostic radiologic evaluation is a common modality used by clinicians to assess disease status in the management of inflammatory bowel disease (IBD). It is common for initial evaluation and disease management to involve imaging modalities such as computed tomography (CT) and/or fluoroscopic evaluation. Over time, these procedures have the potential to deliver significant radiation exposure (1) unless dose reduction strategies are used fully.
Recent evaluations of radiation exposure and potential future malignancy risk have brought into question the necessity of multiple radiation-intensive diagnostic procedures in this chronic disease population. Although any single diagnostic radiologic procedure carries a generally low risk for the development of malignancy, certain radiologic tests (including CT and fluoroscopic procedures) may increase the potential for malignancy with even single exposure as well as via cumulative dose from multiple procedures. The cumulative lifetime exposure from multiple low-risk radiation procedures such as routinely used in diagnostic radiology has been associated with cancer induction (2–6). A 2004 study suggested that 1% of all cancers in the United States resulted from medical radiation exposure (6). In addition, children have increased susceptibility to radiation effects in regard to the development of malignancy (4). Children and adolescents with IBD who routinely undergo diagnostic radiological procedures have an elevated risk for intestinal cancers that may be potentiated further by agents used for therapy (7–9).
A recent evaluation of diagnostic ionizing radiation exposure among a population-based sample of children with IBD demonstrated that 20% to 30% of cohort subjects were exposed to moderate diagnostic radiation doses during a 2-year period (defined as 1 abdominal or pelvic CT and/or 3 fluoroscopic procedures; equivalent estimated radiation exposure ≥6 mSv) (10). No data are available, however, regarding the cumulative lifetime exposure to radiation among children and adolescents with IBD resulting from diagnostic studies related to initial evaluation and chronic disease management. In the present study, the authors quantify the acute and cumulative effective dose (CED) of diagnostic radiation received by these patients; identify factors associated with exposure to high levels of diagnostic radiation; and review protocols that may be used to reduce the radiation doses in this patient population.
PATIENTS AND METHODS
Individuals with IBD were identified from the patient database of a tertiary pediatric referral center. Eligibility for inclusion in the study cohort was defined as having a diagnosis of IBD and having primary IBD disease management at our tertiary care center.
The study protocol was reviewed and approved by the institutional review boards at the University of California, San Diego and Rady Children's Hospital. Once cohort participants were identified, demographic and clinical data were obtained by chart review. The Pediatric Ulcerative Colitis Activity Index (PUCAI: range 0–85) and Abbreviated Pediatric Crohn's Disease Activity Index (CDAI: range 0–70) scores (11,12) were determined for disease activity with higher scores indicating greater disease severity; disease scores were normalized to a scale of 0 to 100 for inter-IBD–type comparison purposes.
Diagnostic Imaging and Dose Estimation Methodology
Details of all of the imaging studies performed on patients in the cohort from 1991 to 2010 were obtained from medical and radiology records and included studies performed in outpatient, inpatient, and emergency department settings. Only diagnostic imaging studies associated with radiation exposure were counted (ie, magnetic resonance imaging and ultrasound studies were not included).
Pediatric effective doses were estimated using the RADAR (Radiation Dose Assessment Resource) Medical Procedure Radiation Dose Calculator (http://www.doseinforadar.com/RADARDoseRiskCalc.html). A pediatric scaling factor (10 years) was used to convert the adult effective dose to the pediatric effective dose using data from Huda et al (13). Effective radiation doses are shown in Table 1. Finally, for each patient, the effective dose for each type of study was multiplied by the number of studies and summed to provide a CED (in millisieverts) for that particular patient. Radiation doses associated with endoscopic retrograde cholangiography and Meckel scan were assigned according to published reference standards (14,15).
Baseline statistics were calculated using distribution analyses. The main dependent variable for analyses was CED localized to the abdominopelvic region. Univariate analyses of abdominopelvic CED by various demographic and other factors were performed using van der Waerden test for categorical variables [prior surgery vs none, disease type (Crohn vs indeterminate and ulcerative colitis), disease location (small bowel involvement vs none and perianal disease vs none), racioethnic background, prior or current exposure to antitumor necrosis factor (anti-TNF) agents vs none, and prior immunomodulatory agent exposure vs none] and Spearman correlation analyses for continuous variables (age at diagnosis, years of follow-up, disease activity scores, and number of hospital admissions). Owing to demonstrated gross differences in data distribution, racioethnic background was recategorized into black descent versus not and disease type was recategorized into Crohn versus colitis (indeterminate or ulcerative colitis). Additional post hoc univariate analyses of disease factors according to black descent versus not also were performed to determine potential correlates given notable differences in abdominopelvic CED in patients of black descent as compared with patients of other backgrounds.
Multivariate analysis of abdominopelvic CED was performed, entering all of the variables (except for disease location) with potential associations (defined as univariate relations with P < 0.25). We did not enter disease location into the analysis owing to expected interclass correlation with disease type. Continuous variables with non-normal distribution were square-root transformed before entry because into model assumptions were better satisfied than when using untransformed variables. Statistical analyses were performed using JMP 5.0 statistical software (SAS Institute Inc, Cary, NC). Significance for all of the analyses was set at P < 0.05.
A total of 114 patients with a diagnosis of Crohn disease, indeterminate colitis, or ulcerative colitis were identified. Patients who were previously managed at other specialist centers were excluded (N = 7) because they were likely to undergo a significant proportion of imaging studies at initial diagnosis and dose information was not readily available. Similarly, patients with other chronic diseases that may have affected radiation exposure were excluded (N = 2, patients with VATER syndrome and nephrotic syndrome). Thus, a total of 105 patients were included (52 boys, age range 11 months–18 years at diagnosis) in the final study cohort. Patients were studied for an average of 5 (3) [mean (SD)] years. Table 2 shows baseline characteristics (sex, racioethnic background, age at diagnosis), disease category, disease activity scores, and the course of disease (medications required and surgical history) for the entire cohort.
The study cohort (N = 105) underwent a total of 632 diagnostic radiologic procedures and 394 were diagnostic radiologic procedures involving the abdominopelvic region. In general, patients underwent an average of 6 (6) [mean (SD)] diagnostic radiology procedures, with an average of 4 (4) procedures localized to the abdominopelvic region. CED resulting from abdominopelvic diagnostic radiology procedures among the 105 subjects was 15 (18) mSv [mean (SD) mSv] and 7 mSv (5,22) [median (interquartile range, IQR)], respectively. Six patients (6%) were exposed to CED ≥50 mSv from abdominopelvic diagnostic radiology procedures; these patients had undergone an average of 14 (4) [mean (SD)] diagnostic radiology procedures, including an average of 5 (3) plain abdominal films, 3 (1) abdominal CTs, 3 (1) pelvic CTs, and 2 (1) upper gastrointestinal (GI) small-bowel follow-through procedures.
Risk Factors for High CED at the Abdominopelvic Region
Increased CED was associated with a history of abdominal surgery for IBD (P = 0.008), disease type (Crohn vs indeterminate and ulcerative colitis, P = 0.08), disease location (small-bowel involvement vs not, P = 0.03), racioethnic background (black vs nonblack, P = 0.04), and prior or current exposure to anti-TNF agents (P = 0.003) (Fig. 1). In contrast, patients with prior or current exposure to immunomodulator agents such as 6-mercaptopurine and/or methotrexate (P = 0.66) and disease location (small bowel, P = 0.08; perianal, P = 0.54) did not demonstrate differences in regard to CED as compared to group counterparts. As expected, the higher a given patient's average disease score (greater disease activity), the higher the associated CED (ρ = 0.19, P = 0.05). Increased hospital admissions also were associated with higher CED (ρ = 0.49, P < 0.0001). Higher CED was not predicted by age at diagnosis (ρ = 0.09, P = 0.35), sex (P = 0.77), or years of follow-up (ρ = −0.02, P = 0.82).
Among black patients, abdominal CED was significantly higher as compared with patients of other racioethnic backgrounds. Black patients had more hospital admissions (1 (1–7) vs 1 (0–2), black versus nonblack, median (IQR), P = 0.01) and a higher prevalence of surgery (22% vs 1%, black vs nonblack, P = 0.02) as compared with nonblack patients. Black patients also demonstrated higher disease scores (P = 0.10), although this did not reach statistical significance.
In multiple regression modeling, history of surgery, number of hospital admissions, and disease type (ie, colitis [ulcerative or indeterminate] vs Crohn) had the greatest association with higher CED (Table 3; whole-model P < 0.0001).
The present study reviewed the diagnostic radiology radiation exposure of 105 pediatric subjects studied at our tertiary care center as a part of treatment for IBD. We also evaluated the clinical management risk factors for increased cumulative effective radiation dose among our patients.
Diagnostic radiology procedures are common among both adult and pediatric patients with IBD (1,10,16). Standard radiology procedures ordered during initial evaluation include an upper GI series and small bowel follow-through (with associated 5 mSv acute radiation dose) and/or abdominal and pelvic CT with contrast (with associated ∼17 mSv acute radiation doses). The only study of pediatric patients with IBD to date reports a 20% to 30% prevalence of moderate radiation-associated radiology procedures (defined as 1 CT and/or 3 fluoroscopic procedures; equivalent to ≥6 mSv) during a 2-year period (10). Similarly, in our cohort, 40% had undergone 1 CT and/or 3 fluoroscopic procedures.
Acute doses of 10 to 50 mSv radiation are associated with an increased risk for cancer development (3). In our cohort, 42% were exposed to acute levels of radiation at or above 10 mSv. Exposed patients met this criterion mainly via an abdominopelvic CT procedure.
Although the radiation exposure associated with routine diagnostic radiology procedures is typically considered to have minimal risk, increased CED from multiple procedures can increase cancer risk among otherwise healthy people, particularly among children. In particular, studies to date indicate that cumulative doses of 50 to 100 mSv can increase the risk for cancer (3). In our cohort, a minority (6%) of patients demonstrated CED ≥50 mSv. Although relatively few patients received these higher exposures in our cohort, particular attention must be given to these young patients with IBD because the potential to increase their cumulative doses over time is substantial given their chronic disease. Given an anticipated additional average radiation dose of 10 mSv (17) from diagnostic radiology procedures during the subsequent adult years of life, we can anticipate that 10% of our cohort will meet the threshold of 50 mSv for increased cancer risk based on radiation exposure alone. Further consideration must be given to the already documented additional malignancy risk associated with IBD itself and its associated medical therapies.
Factors associated with increased radiation exposure in our cohort included a diagnosis of Crohn disease versus indeterminate or ulcerative colitis. Similarly, other studies have demonstrated increased cumulative radiation exposure among adult patients with IBD with Crohn disease as compared with ulcerative colitis (16). The overall increased radiation dose among patients with Crohn disease may reflect the potential of Crohn disease inflammation to affect any and all areas of the GI tract. Thus, patients with Crohn disease may be more likely to require radiation-associated modalities such as upper GI series and/or abdominal CT to fully assess and manage the patient. Although prior adult studies demonstrate a reduced radiation exposure among adult patients receiving immunomodulators such as 6-mercaptopurine (16) perhaps because of improved disease control, we demonstrate significant increases in cumulative radiation dose among pediatric patients who have been exposed to anti-tumor necrosis factor (anti-TNF) agents. One potential explanation may be that the requirement for anti-TNF use among pediatric patients with IBD may be a marker of poor disease control or phenotype requiring increased evaluation via diagnostic radiology examinations. Our finding that frequent hospital admissions are associated with higher cumulative radiation dose further confirms that patients with IBD with poor disease control are more likely to undergo additional diagnostic radiology studies. Thus, particular attention should be paid to alternative imaging studies (eg, magnetic resonance imaging [MRI], ultrasound, endoscopy/capsule imaging) or more aggressive dose-reduction protocols when high radiation exposure procedures such as CT and fluoroscopy are essential in patient management.
We also demonstrated an increased risk for radiation exposure among black patients as compared with nonblack patients. This increased radiation exposure may have reflected increased disease severity as demonstrated by a greater number of hospital admissions and surgery prevalence among black versus nonblack patients in our cohort. Although increased disease severity has not been clearly demonstrated among black adults with IBD (18–20), prior evaluations among pediatric patients with IBD have documented greater prevalence of anemia, malnutrition, and stricturing disease among black children at diagnosis and during the first year of follow-up as compared with children with IBD from other racioethnic backgrounds (21,22). In addition, several studies have suggested that there may be differences in clinical management according to racioethnic background (22–24). Further studies are needed to determine whether radiology procedures are ordered based on clinical management bias versus disease severity.
Our study has several limitations. First, our data were based on a single institution's medical and radiologic records. It is therefore possible that patients in the studied cohort may have obtained radiology procedures at other locations such as private radiology suites or nearby adult hospitals and thus have further increased CED. Given the single center referral base for IBD at our geographic location, and thus sole management of IBD and ordering of IBD-related diagnostic radiology procedures by only physicians at our tertiary care site, the accounting of IBD-associated radiologic procedures is likely accurate. In addition, we have eliminated patients from the study who were previously managed at other locations to ensure full documentation of radiology orders.
Second, we used estimated radiation procedure doses to calculate the CEDs experienced by our patients because the specific exposure parameters were not recorded during the procedures, particularly fluoroscopy. Therefore, variation in the actual received dose of radiation for especially fluoroscopic procedures was not accounted for and we did not place monitors on our patients to document exact dose. Of note, our tertiary care center complies with the standards set by the Image Gently campaign (25) and exposes patients to reduced radiation doses for radiation-associated diagnostic procedures such as CT and fluoroscopy. In contrast, adolescents who may obtain similar procedures at adult institutions may be exposed to higher doses of radiation, thereby receiving even higher doses. Finally, although we are able to comment on radiation exposure for patients with IBD, we do not have a healthy control population for comparison.
In conclusion, we demonstrate that a majority of pediatric patients with IBD receive diagnostic radiology imaging procedures and have received acute radiation levels associated with potential increased risk for cancer. In addition, certain patient characteristics are associated with high cumulative radiation exposure. Although in the past, evaluation of the small bowel in particular was limited to imaging procedures involving radiation, currently available modalities such as capsule endoscopy and MRI offer the potential for reduced exposure to radiation and should be considered in this at-risk population. Such radiation-sparing procedures should be strongly considered in pediatric patients with IBD to reduce their risk for cancer given an already present increased lifetime malignancy potential. Furthermore, it is essential to establish particular pediatric imaging procedures that are age and weight appropriate for all diagnostic radiology imaging studies. Patients presenting with chronic management imaging requirements may benefit further from additional aggressive dose-reduction strategies, including alternative imaging studies or further reductions in dose to minimize cumulative radiation dose.
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