Releasing thyroid cancer patients from the hospital based on dose rate measurement after 131 I activity administration

*Corresponding author (hewamanna_r@yahoo.com) Abstract: The treatment of thyroid cancer generally comprises total thyroidectomy and oral administration of radioiodine (I). One consideration in this therapy is the radiation exposure risks, which have led the Sri Lankan Regulatory Authority to lay down criteria on releasing patients from hospitals when the therapy procedure involves I activities greater than 1.85 GBq (50 mCi). This study was carried out to assess the time dependent dose rate following the administration of I activities and estimate the radioiodine effective half-life (T eff ) inside the patient’s body, which would be useful for releasing patients from hospitals and guide radiation protection recommendations as well. External whole body dose rates at 1.0 m from 60 patients were measured immediately after I administration and at 24 hour intervals up to 5 days. These dose rates were used to estimate the T eff . The results demonstrated a bi-exponential radioiodine clearance pattern up to 5 days with T eff values of 15.9 and 25.3 hours in the first and second phase, respectively. Also, majority of the patients could be released from the hospital after 72 hours post-therapy administration as they reach the permissible dose rate limit recommended by the regulatory authority of Sri Lanka by this time.


INTRODUCTION
Although medical procedures using radionuclides have increased worldwide, they represent an important source of radiation exposure to the population.One example of this procedure is administering radioactive iodine ( 131 I) to treat patients with thyroid disorders such as hyperthyroidism and thyroid cancer (Maxon & Smith, 1990;Schlumberger, 1998). 131I is administered to thyroid cancer patients with the aim of ablating thyroid remnant tissues after total thyroidectomy or to treat metastatic disease.The efficiency of such treatment is generally related to the radiation dose absorbed by the thyroid tissue and tumors (Hanscheid et al., 2006).After therapeutic administration, 131 I activities enter the blood circulation, being partially retained by the patient's body and is excreted mainly by the kidneys.
The therapeutic 131 I activities applied to treat thyroid cancer commonly range from 3.7 to 7.4 GBq, with the larger activities employed in metastatic disease.Because of the relatively high ionizing radiation field that exists near a patient's body after therapy administration, regulations are required that such patients remain hospitalized until the radiation protective measures are satisfied.Atomic Energy Authority (AEA), the regulatory body in Sri Lanka, states that radioactive patients may be released from hospitals provided that the potential of effective dose to others is not likely to exceed 5 mSv (Atomic Energy Authority, 1999).However, the suitability of dose based, rather than activity based release criteria for radionuclide therapy patients remain controversial (Grigsby et al., 2000;Venencia et al., 2002;ICRP, 2004).
The current regulations in Sri Lanka state the need for interning patients when the administered 131 I activity is greater than 1.85 GBq (50 mCi) or alternatively, when the dose rate is greater than 30 μSv h -1 at 1.0 m from the patient's body.In some countries including Sri Lanka, patient's dose rate measured at a fixed distance has been used as a criterion for releasing patients from hospitals (Zanzonico et al., 2000;de Carvalho et al., 2009).Assessing this radiation exposure or the dose rate permits estimation of radioactive iodine inside a patient's body as a function of time post-therapy administration (Thomas et al., 1980).This helps the licensee to calculate the potential of radiation dose to others by means of 131 I effective half-time (T eff ) inside a patient's whole body.
The objective of the present study was to assess the time dependent dose rate following 131 I administration in thyroid cancer treatment to estimate the T eff and establish recommendations regarding the time necessary for the patients to be hospitalized in isolated wards at the National Cancer Institute, Maharagama (NCI).

METHODS AND MATERIALS
The study population comprised 60 patients (40 women and 20 men) who required hospitalization to treat thyroid cancer with 131 I.All the patients had previously submitted to total or near-total thyroidectomy before receiving 131 I therapy to ablate residual thyroid tissues or to treat metastatic disease.The patients were without any documented renal insufficiency or other medical conditions, which could alter the iodine excretion from their bodies.Thyroid hormone replacement therapy had been discontinued for an appropriate period (4 − 6 weeks) to assure adequate hypothyroidism state when 131 I activity was administered.All the patients were furnished with a written instruction guide to follow during the inpatient therapy and advised to hydrate themselves with copious fluid intake.The fluid intake and urine output volumes were not measured as the goal of this study did not address these points.
Immediately after 131 I administration, dose rates from the patients were measured using a radiation detector (Mini Rad Series 1000, C0002723), which was previously calibrated in µSv h -1 .In each measurement, the dose rates at 1.0 m from the neck area (anterior, posterior, left and right directions) were recorded while the patient was in a seated position.Subsequent similar sets of dose rates were recorded after 1, 24, 48, 72 and 120 h post-therapy administration.All the measurements were taken after emptying the bladder and background radiation was subtracted from the data.The average value for each dataset (dose rates from all directions) was used in T eff and 131 I activity calculation as this methodology seems less sensitive to iodine distribution inside a patient's body.The routine procedure adopted by the hospital for these patients were strictly followed and no change was made to accommodate the present study.

RESULTS
The mean 131 I activity administered to the patients was 4.9 GBq.Table 1 shows the mean dose rates measured at 1.0 m from the patients and at different times of post-131 I administration.All the patients were released from the hospital on the 5 th day.One example of the variation of the dose rate with time is given in Figure 1.This figure indicates that the dose rate decays in a bi-exponential manner where a fast clearance phase is followed by a slower one.The mean T eff to all patients obtained by means of MATLAB software were 15.8 (± 3.1) and 25.5 (± 5.8) hours for the initial fast and the second slower clearance phase, respectively.The T eff values calculated for each patient are given in Figure 2. It is possible to extract from this figure, that for the initial phase 58 % of the patients had a T eff value between 11 and 15 hours, and 32 % between 16 and 20 hours.For the slower phase these values are 43 % between 21 and 25 hours and 42 % between 16 and 20 hours, respectively.A comparison between the mean T eff for all the patients and previously reported values are given in Table 2.However, the external dose rate method is operationally relevant since it is based on measurements of a quantity of interest in radiation protection.The principal source of error in the exposure rate measurement was probably the inaccuracy in the distance between the patient's body axis and the radiation detector.
In this study the mean dose rate measured at 1.0 m from the patients is presented with a range of values (Table 1) as a consequence of many variables involved such as the administered 131 I activity, different patients' gender, age and body weight.However, these dose rates constitute an important information for radiation protection purposes because they are directly linked to the risk involved in the management of thyroid cancer patients after receiving 131 I therapy.
In the current study the dose rate from patients decreased in a bi-exponential pattern, where there is a fast clearance of radioiodine in the first day post-131 I administration and a slower clearance after this time.The fast clearance could be partially explained by the biokinetic of 131 I inside the patient's body once the maximum dose rate is measured immediately after the ingestion of 131 I capsule by the patient and, after dissolved, the 131 I activity is diluted throughout the body, in this way changing the geometry of the source, and being partially shielded by the patient's body.Also,

DISCUSSION AND CONCLUSION
Surgical resection of the thyroid gland followed by 131 I therapy has long been the standard treatment for differentiated thyroid cancer.The 131 I T eff in total body of the patients with intact thyroid gland is generally estimated as 5.5 d (132 h), but in thyroidectomized patients this value is much shorter (Ravichandran et al., 2010).
The method used in this study to estimate the T eff was based on dose rate measurements performed during actual treatments of thyroid cancer patients.This method is somewhat crude compared to biokinetic studies where the metabolized and eliminated iodine is accounted.T eff (2) T eff (h) the rapid clearance in the first phase corresponds to the urinary excretion of inorganic radioiodine, whereas the second phase corresponds to the organified 131 I with a slow excretion, although organification of 131 I is minimal in thyroidectomized patients (Shahhosseini et al., 2004).In a similar study by Barrington et al. (1996) with 86 patients, a bi-exponential pattern was found and the correspondent values for T eff in the first and second phase were 0.50 (± 0.09) and 4.28 (± 1.55) days, respectively.In the study by Ravichandran et al. (2010), the reported values were 14.4 and 22.0 hours, respectively.The results from the present work, i.e. 15.9 and 25.3 hours, respectively (Table 2), are in agreement with both these studies.
Some researchers have revealed a tri-exponential clearance pattern on differentiated thyroid cancer patients (Castronovo et al., 1983;Sasikala et al., 1996), but such a difference in the clearance model may be related to the datasets used for T eff calculation, the methodology applied for dose rate measurement, population size, patients' characteristics and other factors.Furthermore, it is possible that the T eff value decreases in both phases according to the 131 I activity administered to patients as reported by Tabei et al. (2012) in a study with 562 patients and dosages of 131 I ranging from 3.7 GBq (100 mCi) to 9.25 GBq (250 mCi).It was not possible to show this difference in our study due to the small sample size.
According to Pacilio et al. (2005), about 80 % of the administered 131 I activity is eliminated from a patient's body within 48 hours, while Thompson (2001) reported that between 35 % and 75 % is eliminated within the first 24 hours after administration in a majority of patients.
At the National Cancer Institute (NCI) of Sri Lanka, all the patients are discharged from the hospital only when the dose rate measured at 1.0 m from their bodies is less than 30 μSv h -1 .Our experiment has demonstrated that the isolation time depends on the T eff value instead of the administered 131 I activity.The results of this study have indicated that in 48 hours post-131 I therapy the remaining radioiodine activity in a patient's body is almost always less than 1.85 GBq (50 mCi); only four patients presented a dose rate greater than 30 μSv h -1 at this time.This suggests that a majority of the patients could be discharged from the hospital on the third day of the post-therapy administration, without a significant radiation risk to the public or family members.If the logistic of interning patients is optimized, several advantages may appear such as reducing therapy costs and increasing psychological benefits for the patients and their families.The current practice at the NCI is to discharge all patients after the fifth day post-therapy, but releasing the patients based on dose rate measurement would help to optimize this procedure while complying with the AEA regulations.

Figure 1 :
Figure 1: Pattern of clearance of body burden with administered 131 I Post administration time (h)

Figure 2 :
Figure 2: Distribution of effective half-time (T eff ) for the two phases

Table 1 :
Dose rate [µSv h -1 ] measured at 1.0 m from patients (n = 60) as a function of time of post-131 I activity administration

Table 2 :
Comparison of T eff from this study and from current literature