Pediatr Blood Cancer 2014;61:1152–1153
HIGHLIGHT
by Monica L. Hulbert,
MD
*
Children With Sickle Cell Disease Need More Effective Therapies, Not More X-rays (Commentary on Vetter et al., page 1322)
I
n this issue of Pediatric Blood and Cancer, Vetter et al. [1] report that children with sickle cell disease (SCD) are frequently exposed to ionizing radiation in the form of plain radiographs, fluoroscopy, computed tomography (CT) scans, bone scans, and other tests when cared for at a large academic medical center. In their cohort of 938 children with SCD, the first report of diagnostic radiation exposure in this population, 76% of children had at least one radiograph, and 19% had at least one CT. Furthermore, the number of imaging exams per year and the number of exams per patient both increased steadily during the 13-year study period. Based on trends in multiple pediatric populationbased studies, these findings are not surprising. For example, in a large insurance claims-based study encompassing 355,088 children between 2005 and 2008, over 40% had at least one diagnostic radiation exposure, and almost 8% had at least one CT scan [2]. The risks of ionizing radiation have gained attention in the lay press, as demonstrated by a recent New York Times op/ed, provocatively titled “We Are Giving Ourselves Cancer” [3]. As Vetter et al. discuss, exposure to ionizing radiation during childhood carries a risk of developing cancer that is directly related to the total radiation dose. Epidemiological data from the United States [4], the United Kingdom [5], and Australia [6] have demonstrated an increase both in diagnostic radiation and in actual or predicted resultant cancer diagnoses. Children are particularly vulnerable to radiation-induced cancer because their bones, soft tissues, and organs are still actively growing and thus are at greater risk of acquiring an oncogenic mutation in an actively dividing cell. Due to these concerns, the Image Gently Campaign, an effort by the Alliance for Radiation Safety in Pediatric Imaging, has encouraged limiting the radiation dose of CT scans to the lowest level appropriate for the child’s age and weight and choosing the best imaging modality for the clinical concern [7]. As Vetter et al. discuss, the diagnostic radiation exposure in many children with SCD is probably even higher than described not only because of inability to capture imaging studies performed at other hospitals [1], but also because non-pediatric hospitals may be less likely to use “child-sized” CT protocols [7]. One cannot deny that the overall care of children with SCD has improved in the past decades. Data from the Dallas Newborn Cohort indicate that 94% of children with SCD now survive to adulthood [8]. Certainly, timely identification and treatment of serious complications of SCD may rely on diagnostic radiation. In some cases, diagnostic radiation is truly necessary because highquality images cannot be obtained any other way, such as a carotid angiogram in a patient whose brain magnetic resonance imaging (MRI) reveals an aneurysm. A brain- and life-saving intervention
C
2014 Wiley Periodicals, Inc. DOI 10.1002/pbc.25016 Published online 18 March 2014 in Wiley Online Library (wileyonlinelibrary.com).
may result from the test, thus tipping the risk/benefit analysis in favor of the radiation exposure. However, in other situations, especially plain radiographs of painful bony sites and CT scans for abdominal pain, the benefits do not appear to outweigh the risks. Furthermore, radiation exposure is not the only risk of frequent imaging. The benefits versus costs of repeated CT scans have been explored in lymphoma survivors. In pediatric and adult survivors of Hodgkin lymphoma and Burkitt or diffuse large B cell lymphoma, surveillance CT or positron emission tomography (PET)/CT scans fail to detect relapse more effectively than history and physical exam, carry significant radiation exposure, and cost $10,000 or more per patient [9,10]. Even more concerning, the false-positive rate of routine post-remission PET/CT scans in lymphoma survivors is higher than their true-positive rate [11], subjecting patients to unnecessary invasive biopsies, even more imaging, and emotional distress. Similarly, it is not clear that frequent diagnostic X-rays add value to pediatric SCD care. Pain due to vaso-occlusion in bones and bone marrow is the most common manifestation of SCD. Vetter et al. note that their institution’s clinical practice discourages obtaining plain radiographs of painful bony sites in SCD patients, yet they found that 21% of radiographs of bony sites were ordered due to pain [1]. Presumably, the institutional practice was developed because the results of these radiographs have not typically been helpful in directing patients’ clinical care. Although no data have been published regarding the outcomes of diagnostic imaging in children with SCD, it is easy to draw parallels with the postremission lymphoma population. In clinical practice, X-rays of painful extremities in SCD may lead to invasive procedures, such as arthrocentesis of a small, reactive joint effusion adjacent to a bone infarct, analogous to the lymph node biopsy in an asymptomatic lymphoma survivor following an abnormal PET/CT. Hopefully, future work will clarify the utility of both the imaging studies and any subsequent invasive procedures in children with SCD. As the pediatric oncology community reduces post-remission surveillance scanning in cancer survivors, hematologists should focus on the same principles of diagnostic utility, radiation exposure, and cost for children with SCD and other non-malignant disorders.
Affiliation: Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri
Correspondence to: Monica L. Hulbert, Washington University School of Medicine, Campus Box 8116, One Children’s Place, St. Louis, MO 63110. E-mail: [email protected] Received 8 February 2014; Accepted 10 February 2014
Better Therapies, not More X-Rays, for SCD Hospital-based care algorithms can help guide appropriate imaging. At our institution, a rapid evaluation process was developed for children with SCD and neurological symptoms. Children with suspected strokes have a bedside evaluation by a pediatric neurologist and pediatric hematologist and proceed to brain MRI if indicated by the history and physical exam. This guideline was motivated in part by the recognition that children presenting with neurological symptoms often underwent brain CT scans that provided insufficient clinical benefit to justify the radiation dose. Finally, we must remember that the number of radiographic studies to which these children are exposed reflects the severity of their disease. SCD pain is complex and often challenging to treat effectively. Individuals without frequent SCD pain can present with unexpected, catastrophic complications. Reducing exposure to ionizing radiation and the other avoidable risks of frequent diagnostic imaging is an important goal. Ultimately, though, patients will benefit most from effective disease-modifying therapies to prevent pain and other SCD manifestations. Then we will reduce imaging risks by reducing the need for imaging in the first place.
Pediatr Blood Cancer DOI 10.1002/pbc
1153
REFERENCES 1. Vetter CL, Buchanan G, Quinn CT. Burden of diagnostic radiation exposure in children with sickle cell disease. Pediatr Blood Cancer 2014; doi: 10.1002/pbc.24956 2. Dorfman AL, Fazel M, Einstein AJ, et al. Use of medical imaging procedures with ionizing radiation in children. Arch Pediatr Adolesc Med 2011;165:458–464. 3. Redberg RF, Smith-Bindman R. “We are giving ourselves cancer”. New York Times 2014;CLXIII: A27. 4. Miglioretti DL, Johnson E, Williams A, et al. The use of computed tomography in pediatrics and the associated radiation exposure and estimated cancer risk. JAMA Pediatr 2013;167:700–707. 5. Pearce MS, Salotti JA, Little MP, et al. Radiation exposure from CT scans in childhood and subsequent risk of leukaemia and brain tumours: A retrospective cohort study. Lancet 2012;380:499–505. 6. Mathews JD, Forsythe AV, Brady Z, et al. Cancer risk in 680,000 people exposed to computed tomography scans in childhood or adolescence: Data linkage study of 11 million Australians. BMJ 2013;348:f2360. 7. Goske MJ, Applegate KE, Bulas D, et al. Image Gently: Progress and challenges in CT education and advocacy. Pediatr Radiol 2011;41:S461–S466. 8. Quinn CT, Rogers ZR, McCavit TL, et al. Improved survival of children and adolescents with sickle cell disease. Blood 2010;115:3447–3452. 9. Patel V, Buckstein M, Perini R, et al. Computed tomography and positron emission tomography/ computed tomography surveillance after combined modality treatment of supradiaphragmatic Hodgkin lymphoma: A clinical and economic perspective. Leuk Lymphoma 2013;54:2168– 2176. 10. Voss SD, Chen L, Constine LS, et al. Surveillance computed tomography imaging and detection of relapse in intermediate- and advanced-stage pediatric Hodgkin’s lymphoma: A report from the Children’s Oncology Group. J Clin Oncol 2012;30:2635–2640. 11. El-Galaly TC, Mylam KJ, Brown P, et al. Positron emission tomography/computed tomography surveillance in patients with Hodgkin lymphoma in first remission has a low positive predictive value and high costs. Haematologica 2012;97:931–936.
HIGHLIGHT
by Monica L. Hulbert,
MD
*
Children With Sickle Cell Disease Need More Effective Therapies, Not More X-rays (Commentary on Vetter et al., page 1322)
I
n this issue of Pediatric Blood and Cancer, Vetter et al. [1] report that children with sickle cell disease (SCD) are frequently exposed to ionizing radiation in the form of plain radiographs, fluoroscopy, computed tomography (CT) scans, bone scans, and other tests when cared for at a large academic medical center. In their cohort of 938 children with SCD, the first report of diagnostic radiation exposure in this population, 76% of children had at least one radiograph, and 19% had at least one CT. Furthermore, the number of imaging exams per year and the number of exams per patient both increased steadily during the 13-year study period. Based on trends in multiple pediatric populationbased studies, these findings are not surprising. For example, in a large insurance claims-based study encompassing 355,088 children between 2005 and 2008, over 40% had at least one diagnostic radiation exposure, and almost 8% had at least one CT scan [2]. The risks of ionizing radiation have gained attention in the lay press, as demonstrated by a recent New York Times op/ed, provocatively titled “We Are Giving Ourselves Cancer” [3]. As Vetter et al. discuss, exposure to ionizing radiation during childhood carries a risk of developing cancer that is directly related to the total radiation dose. Epidemiological data from the United States [4], the United Kingdom [5], and Australia [6] have demonstrated an increase both in diagnostic radiation and in actual or predicted resultant cancer diagnoses. Children are particularly vulnerable to radiation-induced cancer because their bones, soft tissues, and organs are still actively growing and thus are at greater risk of acquiring an oncogenic mutation in an actively dividing cell. Due to these concerns, the Image Gently Campaign, an effort by the Alliance for Radiation Safety in Pediatric Imaging, has encouraged limiting the radiation dose of CT scans to the lowest level appropriate for the child’s age and weight and choosing the best imaging modality for the clinical concern [7]. As Vetter et al. discuss, the diagnostic radiation exposure in many children with SCD is probably even higher than described not only because of inability to capture imaging studies performed at other hospitals [1], but also because non-pediatric hospitals may be less likely to use “child-sized” CT protocols [7]. One cannot deny that the overall care of children with SCD has improved in the past decades. Data from the Dallas Newborn Cohort indicate that 94% of children with SCD now survive to adulthood [8]. Certainly, timely identification and treatment of serious complications of SCD may rely on diagnostic radiation. In some cases, diagnostic radiation is truly necessary because highquality images cannot be obtained any other way, such as a carotid angiogram in a patient whose brain magnetic resonance imaging (MRI) reveals an aneurysm. A brain- and life-saving intervention
C
2014 Wiley Periodicals, Inc. DOI 10.1002/pbc.25016 Published online 18 March 2014 in Wiley Online Library (wileyonlinelibrary.com).
may result from the test, thus tipping the risk/benefit analysis in favor of the radiation exposure. However, in other situations, especially plain radiographs of painful bony sites and CT scans for abdominal pain, the benefits do not appear to outweigh the risks. Furthermore, radiation exposure is not the only risk of frequent imaging. The benefits versus costs of repeated CT scans have been explored in lymphoma survivors. In pediatric and adult survivors of Hodgkin lymphoma and Burkitt or diffuse large B cell lymphoma, surveillance CT or positron emission tomography (PET)/CT scans fail to detect relapse more effectively than history and physical exam, carry significant radiation exposure, and cost $10,000 or more per patient [9,10]. Even more concerning, the false-positive rate of routine post-remission PET/CT scans in lymphoma survivors is higher than their true-positive rate [11], subjecting patients to unnecessary invasive biopsies, even more imaging, and emotional distress. Similarly, it is not clear that frequent diagnostic X-rays add value to pediatric SCD care. Pain due to vaso-occlusion in bones and bone marrow is the most common manifestation of SCD. Vetter et al. note that their institution’s clinical practice discourages obtaining plain radiographs of painful bony sites in SCD patients, yet they found that 21% of radiographs of bony sites were ordered due to pain [1]. Presumably, the institutional practice was developed because the results of these radiographs have not typically been helpful in directing patients’ clinical care. Although no data have been published regarding the outcomes of diagnostic imaging in children with SCD, it is easy to draw parallels with the postremission lymphoma population. In clinical practice, X-rays of painful extremities in SCD may lead to invasive procedures, such as arthrocentesis of a small, reactive joint effusion adjacent to a bone infarct, analogous to the lymph node biopsy in an asymptomatic lymphoma survivor following an abnormal PET/CT. Hopefully, future work will clarify the utility of both the imaging studies and any subsequent invasive procedures in children with SCD. As the pediatric oncology community reduces post-remission surveillance scanning in cancer survivors, hematologists should focus on the same principles of diagnostic utility, radiation exposure, and cost for children with SCD and other non-malignant disorders.
Affiliation: Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri
Correspondence to: Monica L. Hulbert, Washington University School of Medicine, Campus Box 8116, One Children’s Place, St. Louis, MO 63110. E-mail: [email protected] Received 8 February 2014; Accepted 10 February 2014
Better Therapies, not More X-Rays, for SCD Hospital-based care algorithms can help guide appropriate imaging. At our institution, a rapid evaluation process was developed for children with SCD and neurological symptoms. Children with suspected strokes have a bedside evaluation by a pediatric neurologist and pediatric hematologist and proceed to brain MRI if indicated by the history and physical exam. This guideline was motivated in part by the recognition that children presenting with neurological symptoms often underwent brain CT scans that provided insufficient clinical benefit to justify the radiation dose. Finally, we must remember that the number of radiographic studies to which these children are exposed reflects the severity of their disease. SCD pain is complex and often challenging to treat effectively. Individuals without frequent SCD pain can present with unexpected, catastrophic complications. Reducing exposure to ionizing radiation and the other avoidable risks of frequent diagnostic imaging is an important goal. Ultimately, though, patients will benefit most from effective disease-modifying therapies to prevent pain and other SCD manifestations. Then we will reduce imaging risks by reducing the need for imaging in the first place.
Pediatr Blood Cancer DOI 10.1002/pbc
1153
REFERENCES 1. Vetter CL, Buchanan G, Quinn CT. Burden of diagnostic radiation exposure in children with sickle cell disease. Pediatr Blood Cancer 2014; doi: 10.1002/pbc.24956 2. Dorfman AL, Fazel M, Einstein AJ, et al. Use of medical imaging procedures with ionizing radiation in children. Arch Pediatr Adolesc Med 2011;165:458–464. 3. Redberg RF, Smith-Bindman R. “We are giving ourselves cancer”. New York Times 2014;CLXIII: A27. 4. Miglioretti DL, Johnson E, Williams A, et al. The use of computed tomography in pediatrics and the associated radiation exposure and estimated cancer risk. JAMA Pediatr 2013;167:700–707. 5. Pearce MS, Salotti JA, Little MP, et al. Radiation exposure from CT scans in childhood and subsequent risk of leukaemia and brain tumours: A retrospective cohort study. Lancet 2012;380:499–505. 6. Mathews JD, Forsythe AV, Brady Z, et al. Cancer risk in 680,000 people exposed to computed tomography scans in childhood or adolescence: Data linkage study of 11 million Australians. BMJ 2013;348:f2360. 7. Goske MJ, Applegate KE, Bulas D, et al. Image Gently: Progress and challenges in CT education and advocacy. Pediatr Radiol 2011;41:S461–S466. 8. Quinn CT, Rogers ZR, McCavit TL, et al. Improved survival of children and adolescents with sickle cell disease. Blood 2010;115:3447–3452. 9. Patel V, Buckstein M, Perini R, et al. Computed tomography and positron emission tomography/ computed tomography surveillance after combined modality treatment of supradiaphragmatic Hodgkin lymphoma: A clinical and economic perspective. Leuk Lymphoma 2013;54:2168– 2176. 10. Voss SD, Chen L, Constine LS, et al. Surveillance computed tomography imaging and detection of relapse in intermediate- and advanced-stage pediatric Hodgkin’s lymphoma: A report from the Children’s Oncology Group. J Clin Oncol 2012;30:2635–2640. 11. El-Galaly TC, Mylam KJ, Brown P, et al. Positron emission tomography/computed tomography surveillance in patients with Hodgkin lymphoma in first remission has a low positive predictive value and high costs. Haematologica 2012;97:931–936.
