Introduction

Examinations are performed only when the physician judges that the benefits of the examination are greater than the disadvantages. Conventional imaging (CI) must be performed with sufficient care because these types of examinations are accompanied by radiation exposure, whether the imaging technique used is chest and abdomen X-ray, computed tomography (CT), bone scintigraphy, or tumor scintigraphy. Particularly for children, who are more vulnerable to radiation than adults, unnecessary examinations should be avoided. The effects of medical radiation exposure on the body are a focus of investigation around the world, and various findings have been obtained [1–4]. Recently, positron emission tomography (PET)/CT with 18F-fluoro-2-deoxy-d-glucose (18FDG) has been reported to be useful for assessment of pediatric cancers, including both staging and treatment evaluation [5–8]. This technology has the potential to replace the multiple examination modalities currently used. If 18FDG PET/CT integrated plans can successfully replace CI plans, this may lead to a reduction in radiation exposure to the patient and an improvement in the patient’s quality of life (QOL).

In this study, we calculated the patient’s radiation doses in both CI plans and 18FDG PET/CT integrated plans for patients with pediatric cancers. We compared the current and new plans in the effect of radiation using the shortening of average life expectancy as an index. We further discuss the related findings and the different effects of radiation exposure.

Method

Patient model

In this study, we used a patient model of a 10-year-old child of 140 cm in height and 35 kg in weight, which are the national average in Japan. Ten major pediatric cancers were evaluated: brain tumor, soft tissue sarcoma, osteosarcoma, germ cell tumor, hepatoblastoma, neuroblastoma, retinoblastoma, Wilms’ tumor, leukemia, and malignant lymphoma.

Current CI plans

The CI study was comprised diagnostic CT (chest and abdomen, brain, or liver dynamic scans), 99mTc-hydroxymethylene diphosphonate bone scintigraphy (20 mCi), 67 Ga citrate scintigraphy (3 mCi), 201Tl chloride scintigraphy (2 mCi), and/or 123I metaiodobenzylguanidine (MIBG) scintigraphy (3 mCi). Chest and abdomen X-ray examinations were performed, but radiation exposure doses from these examinations were lower than 0.1 mSv, which was far smaller than those of other CIs. Therefore, they were excluded from this study. Diagnostic CT was performed separately from PET/CT using a multidetector scanner (Aquilion 16; Toshiba Medical Systems) with the following settings: axial collimation 4.0 mm × 4 modes; 120 kVp, automated electric current (SD 8); tube rotation 0.5/s; and pitch factor 1.25.

New 18FDG PET/CT integrated plans

The new 18FDG PET/CT plans, which are as beneficial as the current CI plans, were designed by a radiologist in the National Cancer Center (NCC). PET/CT was performed with a PET/CT device (Aquiduo; Toshiba Medical Systems, Tokyo, Japan), which consisted of a PET scanner (ECAT HR+; CTI, Knoxville, TN) and a 16-section CT scanner (Aquilion V-detector; Toshiba Medical Systems) with whole-body mode implemented as standard. The CT scan was performed from the skull vertex through the pelvis using the standardized protocol with the following settings: axial 2.0-mm collimation × 16 modes; 120 kVp; automated electric current (SD 30); tube rotation 0.5/s; and pitch factor 0.94. Emission scans from the skull vertex to the pelvis began approximately 60 min following intravenous administration of 5 mCi of 18FDG.

Data collection and analysis

The plans were divided into five phases (before treatment, during treatment, after treatment, follow-up, and recurrence) for each cancer (Tables 1, 2, 3, 4, 5, 6, 7, 8).

Table 1 Current CT plan protocols
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Table 2 Current FDG PET/CT plan protocols
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Table 3 Current 99mTc-hydroxymethylene diphosphonate bone scintigraphy, 67Ga citrate scintigraphy, 123I-MIBG scintigraphy and 201Tl chloride scintigraphy plan protocols
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Table 4 New CT plan protocols
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Table 5 New FDG PET/CT plan protocols
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Table 6 New 99mTc-hydroxymethylene diphosphonate bone scintigraphy and new 123I-MIBG scintigraphy plan protocols
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Table 7 Effective doses of current CI plans for the five phases (mSv)
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Table 8 Effective doses of new CI plans for the five phases (mSv)
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Effective doses from CT were calculated from the simulation spreadsheet software ImPACT [9]. The scanner type and protocol parameters were entered in the spreadsheet [10]. Because CT tube current was automatically controlled using the CT auto exposure control (CT-AEC) system, the radiation doses were different depending upon the body region. Therefore, we calculated the effective doses for the head, chest, and abdominal regions separately using ImPACT and added these values to obtain the effective dose for the whole body. Absorbed dose and effective dose in each organ and tissue from radiopharmaceuticals were obtained from the International Commission on Radiological Protection (ICRP) publication 80 [11].

The effect of radiation exposure caused by CI was expressed as a shortening of the average life expectancy. This value was calculated using a software program in which the linear non-threshold model (LNT) by the ICRP was adopted [12]. The individual shortening Si(u 0) of the average life expectancy due to exposure to equivalent dose D H at age u 0 was used to calculate total shortening S(u 0 ) of the average life expectancy by summing Si(u 0) values for all organs and tissues exposed to the radiation as follows:

$$ \left( {{\frac{{{\text{d}}p}}{{{\text{d}}u}}}} \right)_{\text{rad,i}} = P \cdot W(u) \cdot B_{i} (u) \cdot {\text{rmi(}}u )\cdot D_{H} /d $$
(1)
$$ {\text{Si(}}u_{0} )= \int\limits_{{u_{0} + 10}}^{\infty } {\left( {{\frac{{{\text{d}}p}}{{{\text{d}}u}}}} \right)_{\text{rad,i}} } \cdot T(u){\text{d}}u $$
(2)
$$ S (u_{ 0} )= \sum\limits_{i} {{\text{Si}}(u_{0} )} $$
(3)

where \( ( {{\frac{{{\text{d}}p}}{{{\text{d}}u}}}})_{\text{rad,i}} \) was defined to be the excess mortality of cancer in organ or tissue I due to radiation exposure per age group (per 100 thousands of individuals): P was defined to be the population size per age group (in 100 thousands of individuals); W(u) was defined to be the survival rate at age u (per 100 thousands of individuals); Bi(u) was defined to be the mortality of cancer in organ or tissue i at age u (per 100 thousands of individuals); rmi(u) was defined to be the excess relative risk factor of annual cancer deaths per age group in organ or tissue i (per mSv); D H was defined to be the equivalent dose (mSv); d was defined to be the dose and dose rate effectiveness factor (=2); T(u) was defined to be the average life expectancy at age u (years); and Si(u 0 ) was defined to be the shortening of the average life expectancy due to cancer in organ or tissue i at age at exposure u 0 (year/100 thousands of individuals).

W(u) was obtained from the 20th complete life tables (2005) [13], Bi(u) from Cancer Statistics [14], and rmi(u) from Pierce et al. [15].

Statistical analysis

All data were stored in a database (Excel2003, Microsoft™). The Wilcoxon-Signed-Rank Test was used to compare the effective dose and shortening of the average life expectancy between CI plans and 18FDG PET/CT plans. p values less than 0.01 were considered to be statistically significant.

Results

Tables 1, 2, and 3 show current CI plan protocols. Tables 4, 5, and 6 show 18FDG PET/CT plan protocols that have equivalent benefits to CI plans. Some chest and abdomen CT examinations were eliminated with 18FDG PET/CT. 99mTc-hydroxymethylene diphosphonate bone scintigraphy was performed only before treatment of Wilms’ tumor and was eliminated for the other cancers. 67 Ga citrate scintigraphy and 201Tl chloride scintigraphy were eliminated for all cancers.

Tables 7 and 8 show effective doses in CI plans and 18FDG PET/CT plans for different pediatric cancers. In CI plans, mean effective doses were 168.6 mSv (range 50.5–513.4 mSv) for males, and 127 mSv (range 54–239.7 mSv) for females. The largest effective doses were 513.4 and 239.7 mSv, respectively, for males and females with osteosarcoma, followed by soft tissue sarcoma and malignant lymphoma. In 18FDG PET/CT plans, mean effective doses were 64.1 mSv (range 54.1–84.5 mSv) for males and 68.2 mSv (range 58.1–88.0 mSv) for females. The largest effective doses were 84.5 and 88.0 mSv, respectively, for males and females with hepatoblastoma, followed by malignant lymphoma and neuroblastoma. Effective doses of 18FDG PET/CT plans were significantly lower than those of CI plans (p = 0.0051 for males, p = 0.0051 for females).

Table 9 shows the shortening Si(u 0 ) of the average life expectancy caused by CI plans and 18FDG PET/CT plans. In CI plans, mean Si(u 0 ) values were 177 days (range 53.3–542 days) for males and 185 days (range 80.4–371 days) for females. The largest Si(u 0 ) values were 542 and 371 days, respectively, for males and females with osteosarcoma, followed by soft tissue sarcoma and malignant lymphoma. In 18FDG PET/CT plans, mean Si(u 0 ) values were 67.6 days (range 57.1–89.2 days) for males and 102.5 days (range 86.8–132.6 days) for females. The largest Si(u 0 ) values were 89.2 and 132.6 days, respectively, for males and females with hepatoblastoma, followed by malignant lymphoma and neuroblastoma. The values for shortening of the average life expectancy caused by 18FDG PET/CT plans were significantly lower than those caused by CI plans (p = 0.0077 for males, p = 0.0077 for females).

Table 9 Value of lifetime loss caused by pediatric cancers (days)
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Discussion

We obtained significant differences in effective radiation dose and shortening of the average life expectancy when comparing current CI plans to new 18FDG PET/CT integrated plans for patients with pediatric cancers. The reduction in effective dose and shortening of the average life expectancy contributes to an improvement in the patient’s QOL.

In both the current and new plans, radiation dose in CT is optimized to avoid excessive exposure with CT-AEC. However, in current CI plans, effective doses are large for osteosarcoma and soft tissue sarcoma because either 201Tl chloride scintigraphy or 67 Ga citrate scintigraphy is performed. 201Tl chloride accumulates in the sex gland and 67 Ga citrate in the red marrow, colon, and sex gland. Total effective doses in CI plans for the some of the other cancers are greater than 100 mSv due to repeated examinations.

In 18FDG PET/CT plans, the number of examinations performed was decreased. 201Tl chloride scintigraphy and 67 Ga citrate scintigraphy were eliminated by 18FDG PET/CT, decreasing the total effective doses to less than 100 mSv for all cancers. Both the patient’s physical burden and medical expenses are thus expected to be reduced, improving QOL.

Regarding the shortening of the average life expectancy due to radiation exposure, gender-related differences were observed, even under the same examination conditions. Pierce et al. [15] reported that the risk of radiation exposure was dependent upon the organ or tissue exposed, and was higher in women than in men for the same organ or tissue. Therefore, the effective dose is considered to be different between men and women undergoing the same examination, and the average life expectancy becomes shorter in women than in men with the same effective dose.

The effects of radiation exposure are classified into deterministic effects, including erythema of skin and sterility, and stochastic effects, including radiation-induced cancer. Generally, deterministic effects occur with exposure to radiation greater than 150 mSv at a single dose [12]. In the CI plans assessed in this study, the largest total effective dose was 542 mSv for osteosarcoma. However, deterministic effects were considered to be avoided because these CI plans are generally performed at an interval of approximately 1 month, and the exposure is not of an acute nature. Some symptoms, including a decrease in sperm count, may appear if the patient is exposed to a radiation dose of 542 mSv at one time.

Stochastic effects are known to occur in patients exposed to radiation greater than 200 mSv [15]. Effective doses of current CI plans can be greater than 200 mSv, which may induce cancer. Children, who are more vulnerable to radiation than adults, are considered to be more prone to radiation-induced cancers.

The greatest limitation of this study lies in our hypothesis that the 10-year-old patient model will live until the average age of death. The shortening of the average life expectancy was calculated on the basis of this hypothesis. However, the subjects in this study were pediatric cancer patients, who may have a decreased possibility of reaching the average life expectancy. Considering this fact, the results may be slightly skewed toward greater life expectancy.

Conclusion

In this study, we evaluated the risk of radiation exposure of current CI plans and the new 18FDG PET/CT integrated plans for patients with pediatric cancers using the shortening of the average life expectancy as index. We concluded that the effective dose and shortening of average life expectancy in 18FDG PET/CT plans were significantly lower than in CI plans. With respect to the effects of radiation exposure, deterministic effects may not occur, but stochastic effects may occur as a result of CI plans.