M e d i c a l P hy s i c s a n d I n f o r m a t i c s • O r i g i n a l R e s e a r c h Hoang et al. Radiation-Associated Cancer Risks of 4D CT and Parathyroid Scintigraphy
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Medical Physics and Informatics Original Research
Lifetime Attributable Risk of Cancer From Radiation Exposure During Parathyroid Imaging: Comparison of 4D CT and Parathyroid Scintigraphy Jenny K. Hoang1,2 Robert E. Reiman1 Giao B. Nguyen1 Natalie Januzis 3 Bennett B. Chin1 Carolyn Lowry 1 Terry T. Yoshizumi1 Hoang JK, Reiman RE, Nguyen GB, et al.
Keywords: 4D CT, parathyroid, radiation dose, scintigraphy, stochastic effect DOI:10.2214/AJR.14.13278 Received June 10, 2014; accepted after revision August 21, 2014. 1 Department of Radiology, Duke University Medical Center, DUMC Box 3808, Durham, NC 27710. Address correspondence to J. K. Hoang ([email protected]). 2 Department of Radiation Oncology, Duke University Medical Center, Durham, NC. 3
Medical Physics Graduate Program, Duke University, Durham, NC.
WEB This is a web exclusive article. AJR 2015; 204:W579–W585 0361–803X/15/2045–W579 © American Roentgen Ray Society
OBJECTIVE. The purpose of this study is to measure the organ doses and effective dose (ED) for parathyroid 4D CT and scintigraphy and to estimate the lifetime attributable risk of cancer incidence associated with imaging. MATERIALS AND METHODS. Organ radiation doses for 4D CT and scintigraphy were measured on the basis of imaging with our institution’s protocols. An anthropomorphic phantom with metal oxide semiconductor field effect transistor detectors was scanned to measure CT organ dose. Organ doses from the radionuclide were based on International Commission for Radiological Protection report 80. ED was calculated for 4D CT and scintigraphy and was used to estimate the lifetime attributable risk of cancer incidence for patients differing in age and sex with the approach established by the Biologic Effects of Ionizing Radiation VII report. A 55-year-old woman was selected as the standard patient according to the demographics of patients with primary hyperparathyroidism. RESULTS. Organs receiving the highest radiation dose from 4D CT were the thyroid (150.6 mGy) and salivary glands (137.8 mGy). For scintigraphy, the highest organ doses were to the colon (41.5 mGy), gallbladder (39.8 mGy), and kidneys (32.3 mGy). The ED was 28 mSv for 4D CT, compared with 12 mSv for scintigraphy. In the exposed standard patient, the lifetime attributable risk for cancer incidence was 193 cancers/100,000 patients for 4D CT and 68 cancers/100,000 patients for scintigraphy. Given a baseline lifetime incidence of cancer of 46,300 cancers/100,000 patients, imaging results in an increase in lifetime incidence of cancer over baseline of 0.52% for 4D CT and 0.19% for scintigraphy. CONCLUSION. The ED of 4D CT is more than double that of scintigraphy, but both studies cause negligible increases in lifetime risk of cancer. Clinicians should not allow concern for radiation-induced cancer to influence decisions regarding workup in older patients.
P
reoperative imaging in a patient with primary hyperparathyroidism aims to localize one or more parathyroid adenomas and may involve imaging with a combination of ultrasound, parathyroid scintigraphy, and 4D CT. Recently, parathyroid 4D CT has gained popularity at multiple centers for second-line imaging investigation and even as an alternative primary investigation [1]. Four-dimensional CT has higher sensitivity than scintigraphy and ultrasound [2–4] and also provides anatomic detail and reformatted images that allow surgical planning. One of the main arguments against the use of 4D CT for first-line imaging is that it may result in greater radiation exposure to the patient compared with parathyroid scintigraphy scans; the 4D CT protocol involves multiple imaging phases (two to four) through the neck and up-
per chest [2, 5–7]. Thus, the advantages of 4D CT should be carefully weighed against potential hazards associated with higher radiation exposure. Previous studies report that the effective dose (ED) of 4D CT is higher than that of parathyroid scintigraphy [8, 9]. However, to our knowledge, no studies have directly measured organ dose from 4D CT protocols to obtain ED. In addition, the ED has different implications depending on the exposed patient’s age and sex. Because the mean age of a patient with primary hyperparathyroidism is 56–64 years [10, 11], the lifetime attributable risk of cancer may be low. This information would be valuable in counseling clinicians and patients about the radiation dose from parathyroid imaging. The aim of this study was to measure the organ doses and ED for 4D CT and parathyroid scintigraphy and to estimate the lifetime attributable risk of cancer incidence according
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Hoang et al. to the measured radiation doses. Our hypothesis was that the EDs for 4D CT would be higher than those for scintigraphy, but the increase in lifetime risk of cancer over baseline would be small in the patient age group that typically develops primary hyperparathyroidism. Materials and Methods
phic phantom (model 701-D, CIRS) loaded with 20 electronic dosimeters (Fig. 1). The mean absorbed radiation dose to organs exposed to CT were obtained for the organs listed in Table 1. The phantom was scanned three times with the 4D CT protocol and CT component of the scintigraphy SPECT protocol to obtain the mean organ doses.
The anthropomorphic phantom was equivalent to a human weighing 73 kg, with a height of 173 cm and thorax dimensions of 23 × 32 cm (Fig. 1). We chose the larger of two adult phantoms because it more realistically reflects the body size of our patient population. The phantom had breast attachments to permit estimation of breast doses in female patients.
Organ radiation doses for 4D CT and parathyroid scintigraphy were measured according to imaging with our institution’s protocols.
Parathyroid 4D CT Protocol The protocol consists of three imaging phases (Fig. 1) performed on a 64-MDCT scanner (750 HD, GE Healthcare). The first phase is an unenhanced CT to cover the thyroid gland; the z-axis is from the hyoid bone to the clavicular head. The next two phases are contrast-enhanced phases from the angle of the mandible to the carina and are performed after IV administration of 75 mL of iopamidol (Isovue-300, Bristol-Myers Squibb) via a 20-gauge cannula in a right antecubital vein at a rate of 4 mL/s, followed by a 25-mL saline bolus. Arterial phase images are acquired 25 seconds after the start of the injection, and the delayed (venous) phase is acquired 80 seconds from the start of the injection. The parameters for all three phases are as follows: 0.625-mm section thickness; tube rotation time, 0.4 second; pitch factor, 0.516:1, FOV, 20 cm; 120 kVp; and automatic tube current modulation (using mA Modulation, GE Healthcare, with a noise index of 8, a minimum of 100 mA and a maximum of 500 mA for unenhanced and delayed phases, and a maximum of 700 mA for the arterial phase).
Parathyroid Scintigraphy Protocol Parathyroid scintigraphy is performed with planar imaging and SPECT after an IV adult dose of 925 MBq (25 mCi) 99mTc-sestamibi. At 10 minutes and 2 hours after injection, anterior and 35° anterior oblique (left and right) planar images are acquired on a SPECT scanner (Discovery 670, GE Healthcare) with a 1.5 zoom on a 512 × 512 matrix, with a 20% window centered around the 140-keV photopeak using a low-energy high-resolution parallel collimator. SPECT images with a 128 × 128 matrix were acquired after planar imaging with a step-and-shoot protocol of 30 s/3° for a total of 60 views per camera head. Immediately after SPECT acquisition, CT was performed with the following parameters: 3.75mm section thickness; tube rotation time, 0.8 second; pitch factor, 1.375:1; FOV, 50 cm; 120 kVp; and fixed tube current of 80 mA.
Measuring Organ Dose for CT Organ doses from CT were measured directly using a commercially available anthropomor-
W580
Fig. 1—Photograph of anthropomorphic phantom (model 701-D, CIRS) with leads attached to metal oxide semiconductor field effect transistor dosimeters.
TABLE 1: Location of Metal Oxide Semiconductor Field Effect Transistor (MOSFET) Detectors MOSFET Detector No.
Organ
Slicea
Locationb
1
Skin
10
Anterior midline
2
Breast
Attachment
Center
3
Breast
Attachment
Center
4
Brain
4
10
5
Lens of the eye
5
15
6
Bone marrow mandible
9
24
7
Bone marrow cervical spine
10
27
8
Thyroid
11
29 30
9
Thyroid
12
10
Esophagus
12
32
11
Upper lung
12
34
12
Bone marrow sternum
13
39
13
Thymus
13
41
14
Bone marrow thoracolumbar spine
13
48
15
Lung
14
50
16
Esophagus and heart
15
68
17
Lung
16
77
18
Lung
18
97
19
Lung
20
113
20
Liver
20
126
aThe slice number is the axial location on the phantom.
bThe location number is the manufacturer’s assigned position for the MOSFET detectors.
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Estimates of Organ Doses for Parathyroid Scintigraphy The guidelines of the Society of Nuclear Medicine recommended a dose range of 740–1110 MBq (20–30 mCi) of 99mTc-sestamibi for parathyroid scintigraphy [13]. The radionuclide dose in this study was 925 MBq (25 mCi). The organ radiation doses for this radionuclide dose were estimated from values published in International Commission on Radiological Protection report 80 [14]. The publication contains tables of radiation dose estimates for a number of radiopharmaceuticals commonly used in nuclear medicine calculated using the Medical Internal Radiation Dose technique. With this method, the kinetics of the radiopharmaceutical are used in conjunction with radionuclide data and decay schemes to produce estimates of radiation doses to organs of a mathematic phantom. The radiation dose from low-dose CT obtained during the parathyroid scintigraphy study with SPECT was added to the radionuclide dose.
Effective Dose Calculation and Estimation of Cancer Risk The EDs from 4D CT and parathyroid scintigraphy were calculated from the measured organ doses (D) by applying tissue-weighting factors (W T) 450
using International Commission on Radiological Protection publication 103 [15] and by assuming a radiation-weighting factor (WR) of 1.0 for x-rays. The ED was computed by the following equation: ED = ∑WT × Hi = WR × ∑WT × Di, i
where Hi is the equivalent dose for organ i. Noncompact organs, such as the bone marrow, bone surface, skin, and muscle, were only partially irradiated, so the average organ dose was obtained by multiplying the measured dose by the fraction of the organ irradiated. This is most important for bone marrow, which has the higher tissue-weighting factor and contributes more to the ED than the other noncompact organs. The bone marrow distribution fractions for the measurements obtained in the mandible and skull, upper spine, sternum, and lower spine were 0.08, 0.17, 0.19, and 0.10, respectively. The bone surface dose was obtained from multiplying the measured dose to bony structures by the dry bone fraction, the cortical bone fraction, and the f-factor for bone. The f-factor is a conversion factor between exposure, or the amount of ionization in air, to absorbed dose in tissue. Since the MOSFETs used in this study were calibrated specifically for soft tissue dose, the f-factor for bone was applied when calculating bone surface dose because it accounts for differences in radiation interactions between bone and soft tissue. The fraction of skin and muscle irradiated was protocol dependent because of the different scan lengths and was approximately 7.5% for the unenhanced scan and 11% for both phases of the contrast-enhanced scans. We used the rule of the nines to determine the distribution of skin surface area in the upper body (≈ 45%) and then estimated the fraction of that which was irradiated in the unenhanced and contrast-enhanced scans. We use the same fractions for muscle because the mus-
4D CT Women 4D CT Men Parathyroid Scintigraphy Women Parathyroid Scintigraphy Men
400 350 300 250 200 150 100 50 0
25
35
45 55 Age at Exposure (y)
Fig. 2—Lifetime risk of cancer from parathyroid imaging.
i
65
75
cle distribution in the upper body (≈ 40%) was about equal to the skin surface area distribution (45%) [16]. The risk of cancer, based on the measured ED from the phantom, was calculated for patients undergoing 4D CT and parathyroid scintigraphy scans. The risk was expressed as the lifetime attributable risk of cancer for men and women of different ages. The relative increased risk of cancer resulting from radiation exposure was calculated as lifetime attributable risk divided by baseline risk of cancer. The lifetime attributable risk was calculated with the National Research Council Biologic Effects of Ionizing Radiation (BEIR) VII report formulas, which incorporate the magnitude of radiation exposure, sex, and patient age at the time of exposure [17]. Cancer types considered in calculation of lifetime attributable risk include the thyroid, breast, lung, colon, hematologic, and other malignancies. The BEIR VII report uses data collected from observational studies of Japanese atomic bomb survivors, populations near nuclear facilities during accidental releases of radioactive materials, workers with occupational exposures, and populations who receive exposure from diagnostic and therapeutic medical studies adjusted for the United States population demographics. The BEIR VII report ascribes greater cancer risk to exposed women and inverse risk based on age at time of exposure. Sex- and tissue-specific lifetime attributable risk values at ages 25, 35, 45, 55, 65, and 75 years, normalized to 100 mGy, were obtained from the BEIR VII tables by linear interpolation between tabulated age groups. The 4D CT and scintigraphy organ doses were divided by 100 mGy and multiplied by the normalized lifetime attributable risks to obtain the final tissuespecific lifetime attributable risk values for the 4D CT and scintigraphy protocols. “All cancers” risk was calculated in a similar fashion
1.20 Increase in Lifetime Risk of Cancer From Imaging (%)
The dosimeters were metal oxide semiconductor field effect transistor (MOSFET) dosimeters (model 1002RD, Best Medical) with active detector areas of 200 × 200 µm (total dimensions, 2.5 mm width × 1.3 mm thickness × 8 mm length). Each MOSFET detector was calibrated for the appropriate beam energy, and individual calibration factors for all 20 detectors were stored in a laptop. Detailed calibration methods and validation of MOSFET methods have been described previously by Yoshizumi et al. [12]. The lower limit of detection of absorbed dose for the MOSFETs with AutoSense Patient Dose Verification system (TN-RD-60, Best Medical) was 1.50 mGy.
Lifetime Attributable Risk of Cancer From Imaging (per 100,000 Patients)
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Radiation-Associated Cancer Risks of 4D CT and Parathyroid Scintigraphy
4D CT Women 4D CT Men Parathyroid Scintigraphy Women Parathyroid Scintigraphy Men
1.00 0.80 0.60 0.40 0.20 0
25
35
45 55 Age at Exposure (y)
65
75
Fig. 3—Increase in lifetime risk of cancer incidence from imaging over baseline cancer incidence.
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Hoang et al.
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TABLE 2: Radiation Dose From Parathyroid Imaging With 4D CT and Parathyroid Scintigraphy With SPECT 4D CT Organ Dose × Tissue-Weighting Factors (mSv)
Organs
4D CT Organ Dose (mGy)
Men
Women
Scintigraphy Organ Scintigraphy Organ Dose × TissueDose × TissueScintigraphy Weighting Factors Scintigraphy Weighting Factors Organ Dose (mGy) (mSv) Organ Dose (mGy) (mSv)
Male
Female
0.00
0.00
6.58
6.58
6.2
0.74
6.2
0.74
0.00
0.00
41.5
4.98
41.5
4.98
6.41
6.41
8.1
0.97
8.1
0.97
Stomach
0.00
0.00
4.6
0.55
4.6
0.55
Bladder
0.00
0.00
9.7
0.39
9.7
0.39
Gonads Red bone marrow
54.8
Colon Lung
53.4
0
0
7.8
0.61
Breast
2.8
0.00
0.34
1.8
0.21
7.0
0.84
Liver
5.5
0.22
0.22
15.1
0.61
15.1
0.61
Esophagus
87.3
3.49
3.49
5.1
0.20
5.1
0.20
Thyroid
150.6
6.02
6.02
11.3
0.45
11.3
0.45
Skin
24.8
0.25
0.25
12.0
0.12
12.0
0.12
Bone surface
37.1
0.37
0.37
22.0
0.22
22.0
0.22
Salivary glands
137.8
1.38
1.38
7.8
0.08
7.8
0.08
7.2
0.07
0.07
2.4
0.02
2.4
0.02
0.00
0.00
5.54
0.05
5.5
0.05
Brain Adrenal glands Extrathoracic tissue
150.6
1.29
1.29
6.4
0.05
6.4
0.05
Gallbladder
5.5
0.05
0.05
39.8
0.34
39.8
0.34
Heart wall
16.7
Kidneys
0.14
0.14
10.5
0.09
10.5
0.09
0.00
0.00
32.3
0.28
32.3
0.28
Muscle
24.8
0.21
0.21
13.4
0.12
13.4
0.12
Oral mucosa
137.8
1.18
1.18
39.0
0.34
39.0
0.34 0.05
Pancreas
0.00
0.00
5.7
0.05
5.7
Small intestine
0.00
0.00
14.1
0.12
14.1
0.12
Spleen
0.00
0.00
4.5
0.04
4.5
0.04
0.64
0.64
8.4
0.07
8.4
0.07
0.00
0.00
0.00
6.4
0.05
11.10
Thymus
74.8
Uterus and cervix Effective dose (mSv)
28.3
28.7
Dose-length product
1929.0
1929.0
Conversion factor for CT
0.015
0.015
12.4
Note—The radiation doses for scintigraphy include CT organ doses from SPECT (also measured with the phantom) added to the organ doses from 99mTc-sestamibi.
using the tabulated “all cancers” normalized lifetime attributable risk and the EDs. The final lifetime attributable risks were expressed as expected radiation-induced cancer per 100,000 exposed individuals.
Statistical Analysis Data entry and statistical analyses were performed using Excel (version 2010, Microsoft). Radiation organ doses were expressed as mean values. EDs were calculated for men and women. A
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55-year-old woman was selected as the standard patient on the basis of demographics of patients with primary hyperparathyroidism obtained from large population data [10, 11].
Results Organ and Effective Doses The organs that received the highest radiation dose for 4D CT were the thyroid (150.6 mGy), salivary glands (137.8 mGy), and the esophagus (87.3 mGy) (Table 2). For para-
thyroid scintigraphy, the highest organ doses were to the colon (41.5 mGy), gallbladder (39.8 mGy), and kidneys (32.3 mGy). The ED for women and men from scintigraphy was 12.4 and 11.1 mSv, respectively (mean, 11.8 mSv). The ED for women and men from 4D CT was 28.7 and 28.3 mSv, respectively (mean, 28.5 mSv). The CT dose indexes for the unenhanced, arterial, and delayed phases of 4D CT were 10, 42, and 30 mGy, respectively. The dose-length products for the
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Radiation-Associated Cancer Risks of 4D CT and Parathyroid Scintigraphy
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TABLE 3: Lifetime Attributable Risk of All Cancer, Lung Cancer, and Breast Cancer Associated With Parathyroid Imaging With 4D CT and Parathyroid Scintigraphy With SPECT Type of Cancer, Age at Exposure (y)
Baseline Lifetime Risk of Cancera
4D CT Lifetime Attributable Riska
Scintigraphy Lifetime Attributable Riska
4D CT Increase Risk Over Baseline (%)
Scintigraphy Increase Risk Over Baseline (%)
Men
Women
Men
Women
Men
Women
Men
Women
Men
Women
25
46,300
37,500
239
393
93
138
0.51
1.05
0.20
0.37
35
46,300
37,500
192
283
74
100
0.41
0.75
0.16
0.27
45
46,300
37,500
178
236
69
83
0.38
0.63
0.14
0.23
55
46,300
37,500
155
193
60
68
0.34
0.52
0.13
0.19
All Cancers
65
46,300
37,500
119
145
46
50
0.26
0.38
0.10
0.13
75
46,300
37,500
74
91
29
32
0.16
0.25
0.06
0.08
25
7700
5400
68
134
10
70
0.88
2.48
1.30
0.13
35
7700
5400
56
110
9
57
0.73
2.04
1.06
0.11
45
7700
5400
55
107
8
56
0.71
1.98
1.04
0.11
55
7700
5400
51
98
8
51
0.66
1.82
0.95
0.10
65
7700
5400
41
79
6
41
0.53
1.47
0.77
0.08
75
7700
5400
27
51
4
27
0.35
0.95
0.49
0.05
Lung
Breast 25
12,000
9
24
0.08
0.20
35
12,000
5
14
0.04
0.11
45
12,000
3
7
0.02
0.06
55
12,000
1
4
0.01
0.03
65
12,000
1
2
0.00
0.01
75
12000
0
1
0.00
0.00
Leukemia 25
830
590
49
32
6
9
5.95
5.47
0.67
35
830
590
46
30
5
9
5.56
5.15
0.62
1.60 1.51
45
830
590
46
30
5
9
5.56
5.07
0.62
1.48
55
830
590
46
29
5
8
5.49
4.90
0.62
1.43
65
830
590
43
26
5
8
5.16
4.41
0.58
1.29
75
830
590
33
21
4
6
4.03
3.59
0.45
1.05
25
230
550
23
92
2
23
9.85
16.66
0.73
4.25
35
230
550
9
33
1
8
3.94
5.95
0.29
1.52
45
230
550
3
11
0
3
1.31
1.95
0.10
0.50
55
230
550
2
3
0
1
0.66
0.54
0.05
0.14
65
230
550
0
1
0
0
0.13
0.14
0.01
0.04
75
230
550
0
0
0
0
0.07
0.03
0.00
0.01
Thyroid
Colon 25
4200
4200
62
41
1.48
0.98
35
4200
4200
51
33
1.21
0.79
45
4200
4200
49
32
1.17
0.76
55
4200
4200
43
28
1.02
0.67
65
4200
4200
33
22
0.79
0.52
75
4200
4200
20
14
0.48
0.33
aRisk of cancer is expressed as number of cases of cancer/100,000 patients.
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Hoang et al. unenhanced, arterial, and delayed phases of 4D CT were 89, 1073, and 767 mGy × cm, respectively. The maximum tube current for the unenhanced, arterial, and delayed phases was 246, 699, and 499 mA, respectively. Estimation of Cancer Risk All cancers—In the exposed 55-year-old female (standard) patient, lifetime attributable risk for cancer incidence was 193 cancers/100,000 patients for 4D CT and 68 cancers/100,000 patients for scintigraphy (Fig. 2 and Table 3). Given a baseline lifetime incidence of cancer of 46,300 cancers/100,000 people, imaging results in an increase in lifetime incidence of cancer over baseline of 0.52% for 4D CT and 0.19% for scintigraphy (Fig. 3 and Table 3). Men had a lower lifetime attributable risk of cancer from imaging than did women at all ages. The lifetime incidence of cancer from both imaging modalities increased with younger age at exposure (Fig. 2 and Table 3). This represented a greater difference for young women than young men. For a 25-year-old woman, the increase in the lifetime incidence of cancer over baseline risk was 1.05% for 4D CT and 0.37% for parathyroid scintigraphy. Cancer types—In the standard patient, the cancer type with the highest lifetime attributable risk for both imaging modalities was lung cancer, at 98 cancers/100,000 patients for 4D CT and 51 cancers/100,000 patients for scintigraphy (Table 3). The cancer type with second highest lifetime attributable risk differed between 4D CT and scintigraphy, leukemia for 4D CT and colon cancer for scintigraphy. Despite the high thyroid organ dose for 4D CT, the lifetime attributable risk for thyroid cancer in the standard patient was very low, at 3 cancers/100,000 patients. In female patients exposed at 35 years or younger, lung cancer still had the highest lifetime attributable risk for both 4D CT and scintigraphy. In men exposed at 35 years or younger, lung cancer had the highest lifetime attributable risk for 4D CT, but the colon had the highest lifetime attributable risk for scintigraphy. Discussion Preoperative parathyroid imaging requires one or more imaging modalities, including 4D CT and parathyroid scintigraphy. This study calculated the radiation dose by direct scanning with an anthropomorphic phantom and estimated the risk of cancer associated with imaging. We found that the ED of 4D CT is more than double that of para-
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thyroid scintigraphy, but the risk of developing a radiation-induced cancer is negligible compared with the baseline cancer risk in an unexposed patient. Two previous studies in the surgical literature also found that radiation exposure to patients resulting from 4D CT is higher than that associated with parathyroid scintigraphy [8, 9]. Madorin et al. [9] reported a mean radiation dose obtained from the radiology reports, but it is unclear what method was used to derive the dose in the reports, and the dose seemed too low to represent the ED. The study by M ahajan et al. [8] used the conventional measure of ED and found that the ED from 4D CT was 10.4 mSv compared with 7.8 mSv for parathyroid scintigraphy. In our study, the EDs were higher for both modalities than in prior studies, and the differences between the two modalities was greater: the ED from 4D CT was more than double that of scintigraphy. The two main reasons for the much higher ED for 4D CT in our study are differing protocols between our institutions and differences in technique of measuring the radiation exposure. Protocols for 4D CT differ across institutions with regard to CT scanner settings and number of imaging phases. The number of phases of scanning through the neck and upper chest in the literature ranges from two to four phases [2, 5–7]. The protocol of Mahajan et al. [8] and the protocol in our study used the same number of imaging phases, but the main difference was in the CT scanner settings. The protocol of Mahajan et al. used 120 kVp and 160 mA. Our protocol had the same tube voltage, but we used tube current modulation ranging from 100 to 700 mA for the arterial phase and from 100 to 400 mA for the other two phases. Our pitch factor was also low, which increases radiation dose and improves image noise. The pitch factor was not described by Mahajan et al. The CT dose settings for 4D CT at our institution are similar to those used at other institutions that have published their protocols. Beland et al. [18] used 120 kVp and tube current modulation between 100 and 750 mA. Rodgers et al. [2], Kelly et al. [19], and Lubitz et al. [20] used a higher tube voltage of 140 kVp and tube current modulation ranging from 180 to 300 mA. Other published protocols [21, 22] used lower tube currents of up to 300–320 mA, which were still higher than those in the study by Mahajan et al. These differences in protocols across institutions may be the result of different scanner types and CT settings for existing CT neck protocols, but they may also be related to regional differences in patients’ body habitus. Notably, we used low-
er tube current in our earlier 4D CT protocol, but this was modified because it did not provide sufficient diagnostic-quality images to detect subcentimeter lesions for most patients who had large body habitus. There are multiple methods for estimating radiation dose from CT. A common method is to convert dose-length product to ED with a body region–specific conversion factor. The problem with this method is that using the neck conversion factor (0.0054 mSv × mGy−1 × cm−1) underestimates ED because it does not account for scanning through the upper half of the thorax, but using the higher chest conversion factor (0.017 mSv × mGy−1 × cm−1) could overestimate the radiation exposure [14]. Mahajan et al. [8] calculated ED with the ImPACT CT Patient Dosimetry calculator [23], which is a spreadsheet tool for calculating patient organ dose and ED from CT scans with specified CT scan settings. The limitations of ImPACT are that it allows radiation dose calculation for only one adult patient size and only certain scanner types because it has not been updated since 2011. In fact, one of the scanners used in the institution of Mahajan et al. was not available for estimation with ImPACT. Our method of calculating the ED directly from organ doses and weighting factors can provide EDs specific to patient sex and phantom size and is not affected by scanner type. The fact that the ED is higher for one modality compared with another is only significant for its biologic effect: the potential risk from imaging with ionizing radiation is radiation-induced cancer. It has been shown that the risk of cancer is dependent on sex, age at the time of radiation exposure, type of radiation, and total absorbed radiation to the body. Primary hyperparathyroidism is nearly four times more common among women than men, which poses a higher risk of cancer, but the mean age of disease onset is in the fifth and sixth decades of life, which reduces the risk [10, 11]. This study found that when accounting for the baseline lifetime risk of developing cancer, the increase in risk of developing any cancer over baseline from imaging is no more than 0.5% in patients 55 years and older, and no more than 1% for both 4D CT and scintigraphy for all ages. The benefits of 4D CT over scintigraphy should be considered if the radiation dose and risks of future cancers are higher. The main advantage of 4D CT is the higher diagnostic accuracy compared with scintigraphy and ultrasound, which may ultimately reduce health care costs and radiation dose by preventing additional imaging with a second study. Rodgers
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Radiation-Associated Cancer Risks of 4D CT and Parathyroid Scintigraphy et al. [2] reported the sensitivity of 4D CT to be 70%, compared with 30% for scintigraphy and 29% for ultrasound, in localizing the lesion to the correct quadrant. Eichhorn-Wharry et al. [3] reported superior sensitivity of 4D CT compared with scintigraphy (73% vs 62%), particularly in patients with small lesions as defined by a gland weight of less than 500 mg (69% vs 45%). In our institution, the sensitivity of 4D CT in all lesions was 76% compared with 43% for scintigraphy [4]. The higher sensitivity of 4D CT can be attributed to the high spatial resolution of CT compared with scintigraphy and diagnostic confidence derived from imaging in multiple contrast-enhanced phases [24]. An additional advantage of 4D CT is that it provides anatomic detail and reformatted images that allow surgical planning for minimally invasive surgery, which has resulted in its popularity among surgeons. There are several limitations of our study. First, it is important to recognize that cancer risks are only estimates that may be used to guide clinicians and patients on the selection of imaging modality, but they do not apply directly to individuals. Second, the study evaluated a single protocol on one scanner type in one institution and for one phantom size, which will affect generalizability. We chose the larger phantom to provide the highest estimate of radiation dose. However, the data are still valuable because they provide an estimate for institutions that can compare their protocols and average patient sizes to our stated parameters. Third, there is controversy regarding the validity of extrapolating the BEIR VII risk estimates to doses under 100 mSv. Although the BEIR VII report uses the best available consensus models of radiation risk, the model parameters are heavily weighted toward data obtained at higher doses. Finally, the use of MOSFET technology yields dose values that are point location specific and that do not represent the overall absorbed dose for the entire organ. Although attention was made to place multiple detectors in the lung and thyroid to provide a better estimate of average dose, as well as scanning three times to reduce random error, the point-specific nature of the data does not account for tissue inhomogeneity and could introduce error into the organ dose estimates. Conclusion On the basis of phantom measures of radiation exposure, the ED from 4D CT is 28 mSv and more than double the ED from parathyroid sestamibi scintigraphy. However, both studies cause extremely small increases in lifetime risk
of cancer compared with baseline cancer incidence. Clinicians should not allow concern for radiation-induced cancer to influence decisions regarding workup in older patients. References 1. Hoang JK, Sung WK, Bahl M, Phillips CD. How to perform parathyroid 4D CT: tips and traps for technique and interpretation. Radiology 2014; 270:15–24 2. Rodgers SE, Hunter GJ, Hamberg LM, et al. Improved preoperative planning for directed parathyroidectomy with 4-dimensional computed tomography. Surgery 2006; 140:932–940; discussion, 940–941 3. Eichhorn-Wharry LI, Carlin AM, Talpos GB. Mild hypercalcemia: an indication to select 4-dimensional computed tomography scan for preoperative localization of parathyroid adenomas. Am J Surg 2011; 201:334–338; discussion, 338 4. Galvin P, Oldan J, Bahl M, Sosa JA, Hoang JK. Discordant parathyroid 4DCT and scintigraphy results: what factors contribute to missed parathyroid lesions? In: Galvin P, ed. Proceedings of the 52nd annual meeting of the American Society of Neuroradiology. Oak Brook, IL: American Society of Neuroradiology, 2014: www.asnr.org/ meeting-proceedings 5. Welling RD, Olson JA Jr, Kranz PG, Eastwood JD, Hoang JK. Bilateral retropharyngeal parathyroid hyperplasia detected with 4D multidetector row CT. AJNR 2011; 32:E80–E82 6. Gafton AR, Glastonbury CM, Eastwood JD, Hoang JK. Parathyroid lesions: characterization with dual-phase arterial and venous enhanced CT of the neck. AJNR 2012; 33:949–952 7. Starker LF, Mahajan A, Bjorklund P, Sze G, Udelsman R, Carling T. 4D parathyroid CT as the initial localization study for patients with de novo primary hyperparathyroidism. Ann Surg Oncol 2011; 18:1723–1728 8. Mahajan A, Starker LF, Ghita M, Udelsman R, Brink JA, Carling T. Parathyroid four-dimensional computed tomography: evaluation of radiation dose exposure during preoperative localization of parathyroid tumors in primary hyperparathyroidism. World J Surg 2012; 36:1335–1339 9. Madorin CA, Owen R, Coakley B, et al. Comparison of radiation exposure and cost between dynamic computed tomography and sestamibi scintigraphy for preoperative localization of parathyroid lesions. JAMA Surg 2013; 148:500–503 10. Yeh MW, Ituarte PH, Zhou HC, et al. Incidence and prevalence of primary hyperparathyroidism in a racially mixed population. J Clin Endocrinol Metab 2013; 98:1122–1129 11. Wermers RA, Khosla S, Atkinson EJ, et al. Incidence of primary hyperparathyroidism in Rochester, Minnesota, 1993-2001: an update on the
changing epidemiology of the disease. J Bone Miner Res 2006; 21:171–177 12. Yoshizumi TT, Goodman PC, Frush DP, et al. Validation of metal oxide semiconductor field effect transistor technology for organ dose assessment during CT: comparison with thermoluminescent dosimetry. AJR 2007; 188:1332–1336 13. Greenspan BS, Dillehay G, Intenzo C, et al. SNM practice guideline for parathyroid scintigraphy 4.0. J Nucl Med Technol 2012; 40:111–118 14. International Commission on Radiological Protection. Radiation dose to patients from radiopharmaceuticals (addendum to ICRP publication 53): ICRP publication 80. Ann ICRP 1998; 28(3) 15. International Commission on Radiological Protection. The 2007 recommendations of the International Commission on Radiological Protection: ICRP publication 103. Ann ICRP 2007; 37(2–5) 16. Janssen I, Heymsfield SB, Wang ZM, Ross R. Skeletal muscle mass and distribution in 468 men and women aged 18-88 yr. J Appl Physiol (1985) 2000; 89:81–88 17. U.S. National Research Council, Committee to Assess Health Risks from Exposure to Low Level of Ionizing Radiation. Health risks from exposure to low levels of ionizing radiation: BEIR VII phase 2. Washington, DC: National Academies Press, 2006:xvi 18. Beland MD, Mayo-Smith WW, Grand DJ, Machan JT, Monchik JM. Dynamic MDCT for localization of occult parathyroid adenomas in 26 patients with primary hyperparathyroidism. AJR 2011; 196:61–65 19. Kelly HR, Hamberg LM, Hunter GJ. 4D-CT for preoperative localization of abnormal parathyroid glands in patients with hyperparathyroidism: accuracy and ability to stratify patients by unilateral versus bilateral disease in surgery-naive and reexploration patients. AJNR 2014; 35:176–181 20. Lubitz CC, Stephen AE, Hodin RA, Pandharipande P. Preoperative localization strategies for primary hyperparathyroidism: an economic analysis. Ann Surg Oncol 2012; 19:4202–4209 21. Chazen JL, Gupta A, Dunning A, Phillips CD. Diagnostic accuracy of 4D-CT for parathyroid adenomas and hyperplasia. AJNR 2012; 33:429–433 22. Kutler DI, Moquete R, Kazam E, Kuhel WI. Parathyroid localization with modified 4D-computed tomography and ultrasonography for patients with primary hyperparathyroidism. Laryngoscope 2011; 121:1219–1224 23. ImPACT. ImPACT’s CT dosimetry tool: CT dosimetry version 1.0.4. ImPACT website. www. impactscan.org/ctdosimetry.htm. Published 2011. Accessed April 29, 2014 24. Bahl M, Sepahdari A, Sosa JA, Hoang JK. Parathyroid adenomas and hyperplasia on 4DCT: three patterns of enhancement relative to the thyroid gland justify a three-phase protocol.
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Medical Physics and Informatics Original Research
Lifetime Attributable Risk of Cancer From Radiation Exposure During Parathyroid Imaging: Comparison of 4D CT and Parathyroid Scintigraphy Jenny K. Hoang1,2 Robert E. Reiman1 Giao B. Nguyen1 Natalie Januzis 3 Bennett B. Chin1 Carolyn Lowry 1 Terry T. Yoshizumi1 Hoang JK, Reiman RE, Nguyen GB, et al.
Keywords: 4D CT, parathyroid, radiation dose, scintigraphy, stochastic effect DOI:10.2214/AJR.14.13278 Received June 10, 2014; accepted after revision August 21, 2014. 1 Department of Radiology, Duke University Medical Center, DUMC Box 3808, Durham, NC 27710. Address correspondence to J. K. Hoang ([email protected]). 2 Department of Radiation Oncology, Duke University Medical Center, Durham, NC. 3
Medical Physics Graduate Program, Duke University, Durham, NC.
WEB This is a web exclusive article. AJR 2015; 204:W579–W585 0361–803X/15/2045–W579 © American Roentgen Ray Society
OBJECTIVE. The purpose of this study is to measure the organ doses and effective dose (ED) for parathyroid 4D CT and scintigraphy and to estimate the lifetime attributable risk of cancer incidence associated with imaging. MATERIALS AND METHODS. Organ radiation doses for 4D CT and scintigraphy were measured on the basis of imaging with our institution’s protocols. An anthropomorphic phantom with metal oxide semiconductor field effect transistor detectors was scanned to measure CT organ dose. Organ doses from the radionuclide were based on International Commission for Radiological Protection report 80. ED was calculated for 4D CT and scintigraphy and was used to estimate the lifetime attributable risk of cancer incidence for patients differing in age and sex with the approach established by the Biologic Effects of Ionizing Radiation VII report. A 55-year-old woman was selected as the standard patient according to the demographics of patients with primary hyperparathyroidism. RESULTS. Organs receiving the highest radiation dose from 4D CT were the thyroid (150.6 mGy) and salivary glands (137.8 mGy). For scintigraphy, the highest organ doses were to the colon (41.5 mGy), gallbladder (39.8 mGy), and kidneys (32.3 mGy). The ED was 28 mSv for 4D CT, compared with 12 mSv for scintigraphy. In the exposed standard patient, the lifetime attributable risk for cancer incidence was 193 cancers/100,000 patients for 4D CT and 68 cancers/100,000 patients for scintigraphy. Given a baseline lifetime incidence of cancer of 46,300 cancers/100,000 patients, imaging results in an increase in lifetime incidence of cancer over baseline of 0.52% for 4D CT and 0.19% for scintigraphy. CONCLUSION. The ED of 4D CT is more than double that of scintigraphy, but both studies cause negligible increases in lifetime risk of cancer. Clinicians should not allow concern for radiation-induced cancer to influence decisions regarding workup in older patients.
P
reoperative imaging in a patient with primary hyperparathyroidism aims to localize one or more parathyroid adenomas and may involve imaging with a combination of ultrasound, parathyroid scintigraphy, and 4D CT. Recently, parathyroid 4D CT has gained popularity at multiple centers for second-line imaging investigation and even as an alternative primary investigation [1]. Four-dimensional CT has higher sensitivity than scintigraphy and ultrasound [2–4] and also provides anatomic detail and reformatted images that allow surgical planning. One of the main arguments against the use of 4D CT for first-line imaging is that it may result in greater radiation exposure to the patient compared with parathyroid scintigraphy scans; the 4D CT protocol involves multiple imaging phases (two to four) through the neck and up-
per chest [2, 5–7]. Thus, the advantages of 4D CT should be carefully weighed against potential hazards associated with higher radiation exposure. Previous studies report that the effective dose (ED) of 4D CT is higher than that of parathyroid scintigraphy [8, 9]. However, to our knowledge, no studies have directly measured organ dose from 4D CT protocols to obtain ED. In addition, the ED has different implications depending on the exposed patient’s age and sex. Because the mean age of a patient with primary hyperparathyroidism is 56–64 years [10, 11], the lifetime attributable risk of cancer may be low. This information would be valuable in counseling clinicians and patients about the radiation dose from parathyroid imaging. The aim of this study was to measure the organ doses and ED for 4D CT and parathyroid scintigraphy and to estimate the lifetime attributable risk of cancer incidence according
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Hoang et al. to the measured radiation doses. Our hypothesis was that the EDs for 4D CT would be higher than those for scintigraphy, but the increase in lifetime risk of cancer over baseline would be small in the patient age group that typically develops primary hyperparathyroidism. Materials and Methods
phic phantom (model 701-D, CIRS) loaded with 20 electronic dosimeters (Fig. 1). The mean absorbed radiation dose to organs exposed to CT were obtained for the organs listed in Table 1. The phantom was scanned three times with the 4D CT protocol and CT component of the scintigraphy SPECT protocol to obtain the mean organ doses.
The anthropomorphic phantom was equivalent to a human weighing 73 kg, with a height of 173 cm and thorax dimensions of 23 × 32 cm (Fig. 1). We chose the larger of two adult phantoms because it more realistically reflects the body size of our patient population. The phantom had breast attachments to permit estimation of breast doses in female patients.
Organ radiation doses for 4D CT and parathyroid scintigraphy were measured according to imaging with our institution’s protocols.
Parathyroid 4D CT Protocol The protocol consists of three imaging phases (Fig. 1) performed on a 64-MDCT scanner (750 HD, GE Healthcare). The first phase is an unenhanced CT to cover the thyroid gland; the z-axis is from the hyoid bone to the clavicular head. The next two phases are contrast-enhanced phases from the angle of the mandible to the carina and are performed after IV administration of 75 mL of iopamidol (Isovue-300, Bristol-Myers Squibb) via a 20-gauge cannula in a right antecubital vein at a rate of 4 mL/s, followed by a 25-mL saline bolus. Arterial phase images are acquired 25 seconds after the start of the injection, and the delayed (venous) phase is acquired 80 seconds from the start of the injection. The parameters for all three phases are as follows: 0.625-mm section thickness; tube rotation time, 0.4 second; pitch factor, 0.516:1, FOV, 20 cm; 120 kVp; and automatic tube current modulation (using mA Modulation, GE Healthcare, with a noise index of 8, a minimum of 100 mA and a maximum of 500 mA for unenhanced and delayed phases, and a maximum of 700 mA for the arterial phase).
Parathyroid Scintigraphy Protocol Parathyroid scintigraphy is performed with planar imaging and SPECT after an IV adult dose of 925 MBq (25 mCi) 99mTc-sestamibi. At 10 minutes and 2 hours after injection, anterior and 35° anterior oblique (left and right) planar images are acquired on a SPECT scanner (Discovery 670, GE Healthcare) with a 1.5 zoom on a 512 × 512 matrix, with a 20% window centered around the 140-keV photopeak using a low-energy high-resolution parallel collimator. SPECT images with a 128 × 128 matrix were acquired after planar imaging with a step-and-shoot protocol of 30 s/3° for a total of 60 views per camera head. Immediately after SPECT acquisition, CT was performed with the following parameters: 3.75mm section thickness; tube rotation time, 0.8 second; pitch factor, 1.375:1; FOV, 50 cm; 120 kVp; and fixed tube current of 80 mA.
Measuring Organ Dose for CT Organ doses from CT were measured directly using a commercially available anthropomor-
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Fig. 1—Photograph of anthropomorphic phantom (model 701-D, CIRS) with leads attached to metal oxide semiconductor field effect transistor dosimeters.
TABLE 1: Location of Metal Oxide Semiconductor Field Effect Transistor (MOSFET) Detectors MOSFET Detector No.
Organ
Slicea
Locationb
1
Skin
10
Anterior midline
2
Breast
Attachment
Center
3
Breast
Attachment
Center
4
Brain
4
10
5
Lens of the eye
5
15
6
Bone marrow mandible
9
24
7
Bone marrow cervical spine
10
27
8
Thyroid
11
29 30
9
Thyroid
12
10
Esophagus
12
32
11
Upper lung
12
34
12
Bone marrow sternum
13
39
13
Thymus
13
41
14
Bone marrow thoracolumbar spine
13
48
15
Lung
14
50
16
Esophagus and heart
15
68
17
Lung
16
77
18
Lung
18
97
19
Lung
20
113
20
Liver
20
126
aThe slice number is the axial location on the phantom.
bThe location number is the manufacturer’s assigned position for the MOSFET detectors.
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Estimates of Organ Doses for Parathyroid Scintigraphy The guidelines of the Society of Nuclear Medicine recommended a dose range of 740–1110 MBq (20–30 mCi) of 99mTc-sestamibi for parathyroid scintigraphy [13]. The radionuclide dose in this study was 925 MBq (25 mCi). The organ radiation doses for this radionuclide dose were estimated from values published in International Commission on Radiological Protection report 80 [14]. The publication contains tables of radiation dose estimates for a number of radiopharmaceuticals commonly used in nuclear medicine calculated using the Medical Internal Radiation Dose technique. With this method, the kinetics of the radiopharmaceutical are used in conjunction with radionuclide data and decay schemes to produce estimates of radiation doses to organs of a mathematic phantom. The radiation dose from low-dose CT obtained during the parathyroid scintigraphy study with SPECT was added to the radionuclide dose.
Effective Dose Calculation and Estimation of Cancer Risk The EDs from 4D CT and parathyroid scintigraphy were calculated from the measured organ doses (D) by applying tissue-weighting factors (W T) 450
using International Commission on Radiological Protection publication 103 [15] and by assuming a radiation-weighting factor (WR) of 1.0 for x-rays. The ED was computed by the following equation: ED = ∑WT × Hi = WR × ∑WT × Di, i
where Hi is the equivalent dose for organ i. Noncompact organs, such as the bone marrow, bone surface, skin, and muscle, were only partially irradiated, so the average organ dose was obtained by multiplying the measured dose by the fraction of the organ irradiated. This is most important for bone marrow, which has the higher tissue-weighting factor and contributes more to the ED than the other noncompact organs. The bone marrow distribution fractions for the measurements obtained in the mandible and skull, upper spine, sternum, and lower spine were 0.08, 0.17, 0.19, and 0.10, respectively. The bone surface dose was obtained from multiplying the measured dose to bony structures by the dry bone fraction, the cortical bone fraction, and the f-factor for bone. The f-factor is a conversion factor between exposure, or the amount of ionization in air, to absorbed dose in tissue. Since the MOSFETs used in this study were calibrated specifically for soft tissue dose, the f-factor for bone was applied when calculating bone surface dose because it accounts for differences in radiation interactions between bone and soft tissue. The fraction of skin and muscle irradiated was protocol dependent because of the different scan lengths and was approximately 7.5% for the unenhanced scan and 11% for both phases of the contrast-enhanced scans. We used the rule of the nines to determine the distribution of skin surface area in the upper body (≈ 45%) and then estimated the fraction of that which was irradiated in the unenhanced and contrast-enhanced scans. We use the same fractions for muscle because the mus-
4D CT Women 4D CT Men Parathyroid Scintigraphy Women Parathyroid Scintigraphy Men
400 350 300 250 200 150 100 50 0
25
35
45 55 Age at Exposure (y)
Fig. 2—Lifetime risk of cancer from parathyroid imaging.
i
65
75
cle distribution in the upper body (≈ 40%) was about equal to the skin surface area distribution (45%) [16]. The risk of cancer, based on the measured ED from the phantom, was calculated for patients undergoing 4D CT and parathyroid scintigraphy scans. The risk was expressed as the lifetime attributable risk of cancer for men and women of different ages. The relative increased risk of cancer resulting from radiation exposure was calculated as lifetime attributable risk divided by baseline risk of cancer. The lifetime attributable risk was calculated with the National Research Council Biologic Effects of Ionizing Radiation (BEIR) VII report formulas, which incorporate the magnitude of radiation exposure, sex, and patient age at the time of exposure [17]. Cancer types considered in calculation of lifetime attributable risk include the thyroid, breast, lung, colon, hematologic, and other malignancies. The BEIR VII report uses data collected from observational studies of Japanese atomic bomb survivors, populations near nuclear facilities during accidental releases of radioactive materials, workers with occupational exposures, and populations who receive exposure from diagnostic and therapeutic medical studies adjusted for the United States population demographics. The BEIR VII report ascribes greater cancer risk to exposed women and inverse risk based on age at time of exposure. Sex- and tissue-specific lifetime attributable risk values at ages 25, 35, 45, 55, 65, and 75 years, normalized to 100 mGy, were obtained from the BEIR VII tables by linear interpolation between tabulated age groups. The 4D CT and scintigraphy organ doses were divided by 100 mGy and multiplied by the normalized lifetime attributable risks to obtain the final tissuespecific lifetime attributable risk values for the 4D CT and scintigraphy protocols. “All cancers” risk was calculated in a similar fashion
1.20 Increase in Lifetime Risk of Cancer From Imaging (%)
The dosimeters were metal oxide semiconductor field effect transistor (MOSFET) dosimeters (model 1002RD, Best Medical) with active detector areas of 200 × 200 µm (total dimensions, 2.5 mm width × 1.3 mm thickness × 8 mm length). Each MOSFET detector was calibrated for the appropriate beam energy, and individual calibration factors for all 20 detectors were stored in a laptop. Detailed calibration methods and validation of MOSFET methods have been described previously by Yoshizumi et al. [12]. The lower limit of detection of absorbed dose for the MOSFETs with AutoSense Patient Dose Verification system (TN-RD-60, Best Medical) was 1.50 mGy.
Lifetime Attributable Risk of Cancer From Imaging (per 100,000 Patients)
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Radiation-Associated Cancer Risks of 4D CT and Parathyroid Scintigraphy
4D CT Women 4D CT Men Parathyroid Scintigraphy Women Parathyroid Scintigraphy Men
1.00 0.80 0.60 0.40 0.20 0
25
35
45 55 Age at Exposure (y)
65
75
Fig. 3—Increase in lifetime risk of cancer incidence from imaging over baseline cancer incidence.
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Hoang et al.
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TABLE 2: Radiation Dose From Parathyroid Imaging With 4D CT and Parathyroid Scintigraphy With SPECT 4D CT Organ Dose × Tissue-Weighting Factors (mSv)
Organs
4D CT Organ Dose (mGy)
Men
Women
Scintigraphy Organ Scintigraphy Organ Dose × TissueDose × TissueScintigraphy Weighting Factors Scintigraphy Weighting Factors Organ Dose (mGy) (mSv) Organ Dose (mGy) (mSv)
Male
Female
0.00
0.00
6.58
6.58
6.2
0.74
6.2
0.74
0.00
0.00
41.5
4.98
41.5
4.98
6.41
6.41
8.1
0.97
8.1
0.97
Stomach
0.00
0.00
4.6
0.55
4.6
0.55
Bladder
0.00
0.00
9.7
0.39
9.7
0.39
Gonads Red bone marrow
54.8
Colon Lung
53.4
0
0
7.8
0.61
Breast
2.8
0.00
0.34
1.8
0.21
7.0
0.84
Liver
5.5
0.22
0.22
15.1
0.61
15.1
0.61
Esophagus
87.3
3.49
3.49
5.1
0.20
5.1
0.20
Thyroid
150.6
6.02
6.02
11.3
0.45
11.3
0.45
Skin
24.8
0.25
0.25
12.0
0.12
12.0
0.12
Bone surface
37.1
0.37
0.37
22.0
0.22
22.0
0.22
Salivary glands
137.8
1.38
1.38
7.8
0.08
7.8
0.08
7.2
0.07
0.07
2.4
0.02
2.4
0.02
0.00
0.00
5.54
0.05
5.5
0.05
Brain Adrenal glands Extrathoracic tissue
150.6
1.29
1.29
6.4
0.05
6.4
0.05
Gallbladder
5.5
0.05
0.05
39.8
0.34
39.8
0.34
Heart wall
16.7
Kidneys
0.14
0.14
10.5
0.09
10.5
0.09
0.00
0.00
32.3
0.28
32.3
0.28
Muscle
24.8
0.21
0.21
13.4
0.12
13.4
0.12
Oral mucosa
137.8
1.18
1.18
39.0
0.34
39.0
0.34 0.05
Pancreas
0.00
0.00
5.7
0.05
5.7
Small intestine
0.00
0.00
14.1
0.12
14.1
0.12
Spleen
0.00
0.00
4.5
0.04
4.5
0.04
0.64
0.64
8.4
0.07
8.4
0.07
0.00
0.00
0.00
6.4
0.05
11.10
Thymus
74.8
Uterus and cervix Effective dose (mSv)
28.3
28.7
Dose-length product
1929.0
1929.0
Conversion factor for CT
0.015
0.015
12.4
Note—The radiation doses for scintigraphy include CT organ doses from SPECT (also measured with the phantom) added to the organ doses from 99mTc-sestamibi.
using the tabulated “all cancers” normalized lifetime attributable risk and the EDs. The final lifetime attributable risks were expressed as expected radiation-induced cancer per 100,000 exposed individuals.
Statistical Analysis Data entry and statistical analyses were performed using Excel (version 2010, Microsoft). Radiation organ doses were expressed as mean values. EDs were calculated for men and women. A
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55-year-old woman was selected as the standard patient on the basis of demographics of patients with primary hyperparathyroidism obtained from large population data [10, 11].
Results Organ and Effective Doses The organs that received the highest radiation dose for 4D CT were the thyroid (150.6 mGy), salivary glands (137.8 mGy), and the esophagus (87.3 mGy) (Table 2). For para-
thyroid scintigraphy, the highest organ doses were to the colon (41.5 mGy), gallbladder (39.8 mGy), and kidneys (32.3 mGy). The ED for women and men from scintigraphy was 12.4 and 11.1 mSv, respectively (mean, 11.8 mSv). The ED for women and men from 4D CT was 28.7 and 28.3 mSv, respectively (mean, 28.5 mSv). The CT dose indexes for the unenhanced, arterial, and delayed phases of 4D CT were 10, 42, and 30 mGy, respectively. The dose-length products for the
AJR:204, May 2015
Radiation-Associated Cancer Risks of 4D CT and Parathyroid Scintigraphy
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TABLE 3: Lifetime Attributable Risk of All Cancer, Lung Cancer, and Breast Cancer Associated With Parathyroid Imaging With 4D CT and Parathyroid Scintigraphy With SPECT Type of Cancer, Age at Exposure (y)
Baseline Lifetime Risk of Cancera
4D CT Lifetime Attributable Riska
Scintigraphy Lifetime Attributable Riska
4D CT Increase Risk Over Baseline (%)
Scintigraphy Increase Risk Over Baseline (%)
Men
Women
Men
Women
Men
Women
Men
Women
Men
Women
25
46,300
37,500
239
393
93
138
0.51
1.05
0.20
0.37
35
46,300
37,500
192
283
74
100
0.41
0.75
0.16
0.27
45
46,300
37,500
178
236
69
83
0.38
0.63
0.14
0.23
55
46,300
37,500
155
193
60
68
0.34
0.52
0.13
0.19
All Cancers
65
46,300
37,500
119
145
46
50
0.26
0.38
0.10
0.13
75
46,300
37,500
74
91
29
32
0.16
0.25
0.06
0.08
25
7700
5400
68
134
10
70
0.88
2.48
1.30
0.13
35
7700
5400
56
110
9
57
0.73
2.04
1.06
0.11
45
7700
5400
55
107
8
56
0.71
1.98
1.04
0.11
55
7700
5400
51
98
8
51
0.66
1.82
0.95
0.10
65
7700
5400
41
79
6
41
0.53
1.47
0.77
0.08
75
7700
5400
27
51
4
27
0.35
0.95
0.49
0.05
Lung
Breast 25
12,000
9
24
0.08
0.20
35
12,000
5
14
0.04
0.11
45
12,000
3
7
0.02
0.06
55
12,000
1
4
0.01
0.03
65
12,000
1
2
0.00
0.01
75
12000
0
1
0.00
0.00
Leukemia 25
830
590
49
32
6
9
5.95
5.47
0.67
35
830
590
46
30
5
9
5.56
5.15
0.62
1.60 1.51
45
830
590
46
30
5
9
5.56
5.07
0.62
1.48
55
830
590
46
29
5
8
5.49
4.90
0.62
1.43
65
830
590
43
26
5
8
5.16
4.41
0.58
1.29
75
830
590
33
21
4
6
4.03
3.59
0.45
1.05
25
230
550
23
92
2
23
9.85
16.66
0.73
4.25
35
230
550
9
33
1
8
3.94
5.95
0.29
1.52
45
230
550
3
11
0
3
1.31
1.95
0.10
0.50
55
230
550
2
3
0
1
0.66
0.54
0.05
0.14
65
230
550
0
1
0
0
0.13
0.14
0.01
0.04
75
230
550
0
0
0
0
0.07
0.03
0.00
0.01
Thyroid
Colon 25
4200
4200
62
41
1.48
0.98
35
4200
4200
51
33
1.21
0.79
45
4200
4200
49
32
1.17
0.76
55
4200
4200
43
28
1.02
0.67
65
4200
4200
33
22
0.79
0.52
75
4200
4200
20
14
0.48
0.33
aRisk of cancer is expressed as number of cases of cancer/100,000 patients.
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Hoang et al. unenhanced, arterial, and delayed phases of 4D CT were 89, 1073, and 767 mGy × cm, respectively. The maximum tube current for the unenhanced, arterial, and delayed phases was 246, 699, and 499 mA, respectively. Estimation of Cancer Risk All cancers—In the exposed 55-year-old female (standard) patient, lifetime attributable risk for cancer incidence was 193 cancers/100,000 patients for 4D CT and 68 cancers/100,000 patients for scintigraphy (Fig. 2 and Table 3). Given a baseline lifetime incidence of cancer of 46,300 cancers/100,000 people, imaging results in an increase in lifetime incidence of cancer over baseline of 0.52% for 4D CT and 0.19% for scintigraphy (Fig. 3 and Table 3). Men had a lower lifetime attributable risk of cancer from imaging than did women at all ages. The lifetime incidence of cancer from both imaging modalities increased with younger age at exposure (Fig. 2 and Table 3). This represented a greater difference for young women than young men. For a 25-year-old woman, the increase in the lifetime incidence of cancer over baseline risk was 1.05% for 4D CT and 0.37% for parathyroid scintigraphy. Cancer types—In the standard patient, the cancer type with the highest lifetime attributable risk for both imaging modalities was lung cancer, at 98 cancers/100,000 patients for 4D CT and 51 cancers/100,000 patients for scintigraphy (Table 3). The cancer type with second highest lifetime attributable risk differed between 4D CT and scintigraphy, leukemia for 4D CT and colon cancer for scintigraphy. Despite the high thyroid organ dose for 4D CT, the lifetime attributable risk for thyroid cancer in the standard patient was very low, at 3 cancers/100,000 patients. In female patients exposed at 35 years or younger, lung cancer still had the highest lifetime attributable risk for both 4D CT and scintigraphy. In men exposed at 35 years or younger, lung cancer had the highest lifetime attributable risk for 4D CT, but the colon had the highest lifetime attributable risk for scintigraphy. Discussion Preoperative parathyroid imaging requires one or more imaging modalities, including 4D CT and parathyroid scintigraphy. This study calculated the radiation dose by direct scanning with an anthropomorphic phantom and estimated the risk of cancer associated with imaging. We found that the ED of 4D CT is more than double that of para-
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thyroid scintigraphy, but the risk of developing a radiation-induced cancer is negligible compared with the baseline cancer risk in an unexposed patient. Two previous studies in the surgical literature also found that radiation exposure to patients resulting from 4D CT is higher than that associated with parathyroid scintigraphy [8, 9]. Madorin et al. [9] reported a mean radiation dose obtained from the radiology reports, but it is unclear what method was used to derive the dose in the reports, and the dose seemed too low to represent the ED. The study by M ahajan et al. [8] used the conventional measure of ED and found that the ED from 4D CT was 10.4 mSv compared with 7.8 mSv for parathyroid scintigraphy. In our study, the EDs were higher for both modalities than in prior studies, and the differences between the two modalities was greater: the ED from 4D CT was more than double that of scintigraphy. The two main reasons for the much higher ED for 4D CT in our study are differing protocols between our institutions and differences in technique of measuring the radiation exposure. Protocols for 4D CT differ across institutions with regard to CT scanner settings and number of imaging phases. The number of phases of scanning through the neck and upper chest in the literature ranges from two to four phases [2, 5–7]. The protocol of Mahajan et al. [8] and the protocol in our study used the same number of imaging phases, but the main difference was in the CT scanner settings. The protocol of Mahajan et al. used 120 kVp and 160 mA. Our protocol had the same tube voltage, but we used tube current modulation ranging from 100 to 700 mA for the arterial phase and from 100 to 400 mA for the other two phases. Our pitch factor was also low, which increases radiation dose and improves image noise. The pitch factor was not described by Mahajan et al. The CT dose settings for 4D CT at our institution are similar to those used at other institutions that have published their protocols. Beland et al. [18] used 120 kVp and tube current modulation between 100 and 750 mA. Rodgers et al. [2], Kelly et al. [19], and Lubitz et al. [20] used a higher tube voltage of 140 kVp and tube current modulation ranging from 180 to 300 mA. Other published protocols [21, 22] used lower tube currents of up to 300–320 mA, which were still higher than those in the study by Mahajan et al. These differences in protocols across institutions may be the result of different scanner types and CT settings for existing CT neck protocols, but they may also be related to regional differences in patients’ body habitus. Notably, we used low-
er tube current in our earlier 4D CT protocol, but this was modified because it did not provide sufficient diagnostic-quality images to detect subcentimeter lesions for most patients who had large body habitus. There are multiple methods for estimating radiation dose from CT. A common method is to convert dose-length product to ED with a body region–specific conversion factor. The problem with this method is that using the neck conversion factor (0.0054 mSv × mGy−1 × cm−1) underestimates ED because it does not account for scanning through the upper half of the thorax, but using the higher chest conversion factor (0.017 mSv × mGy−1 × cm−1) could overestimate the radiation exposure [14]. Mahajan et al. [8] calculated ED with the ImPACT CT Patient Dosimetry calculator [23], which is a spreadsheet tool for calculating patient organ dose and ED from CT scans with specified CT scan settings. The limitations of ImPACT are that it allows radiation dose calculation for only one adult patient size and only certain scanner types because it has not been updated since 2011. In fact, one of the scanners used in the institution of Mahajan et al. was not available for estimation with ImPACT. Our method of calculating the ED directly from organ doses and weighting factors can provide EDs specific to patient sex and phantom size and is not affected by scanner type. The fact that the ED is higher for one modality compared with another is only significant for its biologic effect: the potential risk from imaging with ionizing radiation is radiation-induced cancer. It has been shown that the risk of cancer is dependent on sex, age at the time of radiation exposure, type of radiation, and total absorbed radiation to the body. Primary hyperparathyroidism is nearly four times more common among women than men, which poses a higher risk of cancer, but the mean age of disease onset is in the fifth and sixth decades of life, which reduces the risk [10, 11]. This study found that when accounting for the baseline lifetime risk of developing cancer, the increase in risk of developing any cancer over baseline from imaging is no more than 0.5% in patients 55 years and older, and no more than 1% for both 4D CT and scintigraphy for all ages. The benefits of 4D CT over scintigraphy should be considered if the radiation dose and risks of future cancers are higher. The main advantage of 4D CT is the higher diagnostic accuracy compared with scintigraphy and ultrasound, which may ultimately reduce health care costs and radiation dose by preventing additional imaging with a second study. Rodgers
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Radiation-Associated Cancer Risks of 4D CT and Parathyroid Scintigraphy et al. [2] reported the sensitivity of 4D CT to be 70%, compared with 30% for scintigraphy and 29% for ultrasound, in localizing the lesion to the correct quadrant. Eichhorn-Wharry et al. [3] reported superior sensitivity of 4D CT compared with scintigraphy (73% vs 62%), particularly in patients with small lesions as defined by a gland weight of less than 500 mg (69% vs 45%). In our institution, the sensitivity of 4D CT in all lesions was 76% compared with 43% for scintigraphy [4]. The higher sensitivity of 4D CT can be attributed to the high spatial resolution of CT compared with scintigraphy and diagnostic confidence derived from imaging in multiple contrast-enhanced phases [24]. An additional advantage of 4D CT is that it provides anatomic detail and reformatted images that allow surgical planning for minimally invasive surgery, which has resulted in its popularity among surgeons. There are several limitations of our study. First, it is important to recognize that cancer risks are only estimates that may be used to guide clinicians and patients on the selection of imaging modality, but they do not apply directly to individuals. Second, the study evaluated a single protocol on one scanner type in one institution and for one phantom size, which will affect generalizability. We chose the larger phantom to provide the highest estimate of radiation dose. However, the data are still valuable because they provide an estimate for institutions that can compare their protocols and average patient sizes to our stated parameters. Third, there is controversy regarding the validity of extrapolating the BEIR VII risk estimates to doses under 100 mSv. Although the BEIR VII report uses the best available consensus models of radiation risk, the model parameters are heavily weighted toward data obtained at higher doses. Finally, the use of MOSFET technology yields dose values that are point location specific and that do not represent the overall absorbed dose for the entire organ. Although attention was made to place multiple detectors in the lung and thyroid to provide a better estimate of average dose, as well as scanning three times to reduce random error, the point-specific nature of the data does not account for tissue inhomogeneity and could introduce error into the organ dose estimates. Conclusion On the basis of phantom measures of radiation exposure, the ED from 4D CT is 28 mSv and more than double the ED from parathyroid sestamibi scintigraphy. However, both studies cause extremely small increases in lifetime risk
of cancer compared with baseline cancer incidence. Clinicians should not allow concern for radiation-induced cancer to influence decisions regarding workup in older patients. References 1. Hoang JK, Sung WK, Bahl M, Phillips CD. How to perform parathyroid 4D CT: tips and traps for technique and interpretation. Radiology 2014; 270:15–24 2. Rodgers SE, Hunter GJ, Hamberg LM, et al. Improved preoperative planning for directed parathyroidectomy with 4-dimensional computed tomography. Surgery 2006; 140:932–940; discussion, 940–941 3. Eichhorn-Wharry LI, Carlin AM, Talpos GB. Mild hypercalcemia: an indication to select 4-dimensional computed tomography scan for preoperative localization of parathyroid adenomas. Am J Surg 2011; 201:334–338; discussion, 338 4. Galvin P, Oldan J, Bahl M, Sosa JA, Hoang JK. Discordant parathyroid 4DCT and scintigraphy results: what factors contribute to missed parathyroid lesions? In: Galvin P, ed. Proceedings of the 52nd annual meeting of the American Society of Neuroradiology. Oak Brook, IL: American Society of Neuroradiology, 2014: www.asnr.org/ meeting-proceedings 5. Welling RD, Olson JA Jr, Kranz PG, Eastwood JD, Hoang JK. Bilateral retropharyngeal parathyroid hyperplasia detected with 4D multidetector row CT. AJNR 2011; 32:E80–E82 6. Gafton AR, Glastonbury CM, Eastwood JD, Hoang JK. Parathyroid lesions: characterization with dual-phase arterial and venous enhanced CT of the neck. AJNR 2012; 33:949–952 7. Starker LF, Mahajan A, Bjorklund P, Sze G, Udelsman R, Carling T. 4D parathyroid CT as the initial localization study for patients with de novo primary hyperparathyroidism. Ann Surg Oncol 2011; 18:1723–1728 8. Mahajan A, Starker LF, Ghita M, Udelsman R, Brink JA, Carling T. Parathyroid four-dimensional computed tomography: evaluation of radiation dose exposure during preoperative localization of parathyroid tumors in primary hyperparathyroidism. World J Surg 2012; 36:1335–1339 9. Madorin CA, Owen R, Coakley B, et al. Comparison of radiation exposure and cost between dynamic computed tomography and sestamibi scintigraphy for preoperative localization of parathyroid lesions. JAMA Surg 2013; 148:500–503 10. Yeh MW, Ituarte PH, Zhou HC, et al. Incidence and prevalence of primary hyperparathyroidism in a racially mixed population. J Clin Endocrinol Metab 2013; 98:1122–1129 11. Wermers RA, Khosla S, Atkinson EJ, et al. Incidence of primary hyperparathyroidism in Rochester, Minnesota, 1993-2001: an update on the
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