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medicinska revija medical review UDK: 616.441-085.849.2.035.2 ; 615.849.2.035.2:546.15 ID BROJ: 205590796 Zdraveska Kochovska M. and Majstorov V. MD-Medical Data 2014;6(1): 023-027 Originalni ~lanci/ Original articles Correspondence to: Marina Zdraveska Kochovska Institute of pathophysiology and nuclear medicine / Medical faculty Skopje Vodnjanska 17 1000 Skopje Mob: 00 389 78 517 171 E mail: mzk2003@hotmail.com DOSIMETRY TO FAMILY MEMBERS OF PATIENTS TREATED WITH 131I PROCENA DOZE KOJU PRIME ^LANOVI PORODICE PACIJENATA TRETIRANIH 131I Marina Zdraveska Kochovska 1, Venjamin Majstorov 1 1 Institute of pathophysiology and nuclear medicine Akad.Isak S.Tadzer, Medical faculty, University of Ss. Cyril and Methodius, Skopje, Republic of Macedonia Abstract Key words radioiodine, dosimetry, effective dose Klju~ne re~i radioaktivni jod, dozimetrija, efektivna doza The purpose of this study was to evaluate the effective dose to family members of thyroid cancer and hyperthyroid patients treated with radioiodine 131; also to compare the results with dose constraints proposed by the International Commission of Radiological Protection (ICRP) and the Basic Safety Standards (BSS) of the International Atomic Energy Agency (IAEA). For the estimation of the effective doses sixty family members of sixty patients treated with radioiodine 131, thermoluminiscent dosimeters, Model TLD 100, were used. Thyroid cancer patients were hospitalized for three days, while hyperthyroid patients were treated on out-patient basis. The family members wore TLD in front of the torso for seven days. The radiation doses to family members of thyroid cancer patients were well below the recommended dose constraint of 1 msv. The mean value of effective dose was 0.21 msv (min 0.02 - max 0.51 msv). Effective doses, higher than 1 msv, were detected for 11 family members of hyperthyroid patients. The mean value of effective dose of family members of hyperthyroid patients was 0.87 msv (min 0.12 - max 6.79). The estimated effective doses of hyperthyroid patients were higher than the effective doses of family members of thyroid carcinoma patients. These findings may be considered when establishing new national guidelines concerning radiation protection and release of patients after a treatment with radioiodine therapy. 1. INTRODUCTION Many types of cancer and some other non-malignant diseases can be treated with radiations emitted by radionuclides. The unsealed radionuclides, that are injected, ingested, or inhaled, and which move through the body, are referring to as radiopharmaceuticals. These can localize in body tissues until they decay or they can be eliminated through various pathways, such as sweat and saliva and excreted into urine and feces. The radionuclides used for radiopharmaceutical therapy are usually relatively short-lived beta emitters. Most of these radionuclides also emit photons, which usually contribute minimally to the treatment dose, but produce an undesirable radiation field emanating from the patient. The most frequently used radiopharmaceutical for the treatment of thyroid diseases, such as Thyroid Cancer and Hyperthyroidism, is radioactive iodine 131. It has very high success rate in the treatment of patients with thyroid diseases and it has also proven to be safe and a relatively inexpensive treatment modality. The treatment renders the patient radioactive. The patients, treated with radioactive iodine 131 present a radiation hazard to other individuals such as hospital staff, the patient s family and members of the public with whom a treated patient may come in close contact. This situation can be overcome by imposing restriction on the behavior of the patient, to minimize the dose to close relatives and other individuals. In 1991, the International Commission of Radiological Protection (ICRP) [1] has recommended a radiation constraint of 1 msv/year to the general population. According to the Basic Safety Standards Directive [2], the dose limits to the general public are not valid for exposure of individuals, who are knowingly and willingly helping, other than as part of their occupation, in the support and comfort of in-patient and out-patients undergoing medical diagnosis or treatment. Proposed dose constraint from the BSS is: 0.3 msv per episode for public, 1 msv for children, for adults up to sixty years of age the dose constraint is 3 msv and for adults more than 60 years old it is 15 msv. The implementation of this guideline differs Lalo{evi} D. Med Data Rev 2013;5(1): 000-000 Zdraveska Kochovska M. and Majstorov V. MD-Medical Data 2014;6(1): 023-027

24 MD MEDICAL DATA / Vol.6 N O 1 / Mart/March 2014. between countries. In the Institute of pathophysiology and nuclear medicine, Skopje about 50 thyroid cancer patients are treated on in-patient basis and approximately the same number of hyperthyroid patients is treated ambulatory on out-patient basis. According to the local hospital rule and the old guidelines, the maximum given activity to hyperthyroid patients, treated on out-patients basis, is 1110 MBq. The new, not yet established guidelines, proposed to reduce the maximum given activity to hyperthyroid patients, treated on out-patient basis, to 555 MBq. This group of patients presents great radiation hazard to their family members. Upon discharge from hospital, the patients as well as their family members are given brief radiation safety instructions. The aim is to minimize the transfer of radioactive material to persons coming in close contact with the patient. There are several papers in the literature concerning the subject of doses received by family members of thyroid cancer and hyperthyroid patients [3-8]. Most of the published studies agree that doses to the family members are bellow the proposed dose constraint of 1 msv. But there are also several papers [5, 9] that present cases where children or other persons have received higher radiation doses than the proposed dose limit and usually this is the case with hyperthyroid patients and their relatives. 2. AIM The main purpose of this study was to estimate the radiation exposure to family members of patients treated with radioiodine 131 either for thyroid carcinoma or hyperthyroidism at our nuclear medicine centre. The other purpose was to use the results to identify necessary restrictions to ensure that the recommended dose constraint proposed by ICRP and the BSS of IAEA are met. 3. MATERIALS AND METHODS The study population comprised thirty family members of the same number of thyroid cancer patients and thirty family members of thirty hyperthyroid patients. The total number of people included in the study was one hundred and twenty. The administered dose for the treatment of Thyroid cancer patients ranged from 3700 MBq to 5550 MBq of 131I. Mean administered dose was 3539 MBq. Twenty six patients received 3700 MBq, two patients received 4440 MBq and two patients received 5550 MBq. They were hospitalized for three days after administration and their dose rate was measured every day at a distance of 0.25 m, 0.5 m, 1.0 m and 2.0 m by a medical physicist. The dose rate measurements were performed with a calibrated survey meter mini-rad series 1000, Morgan. When the level of 8 µsv/h at 2m was reached the patients were released from hospital. Upon discharge, the patients were given radiation safety instructions for their further behavior, in order to minimize the transfer of radiation to persons coming in close contact with them, especially children and pregnant women. Their relatives wore the TLD for one week and they were informed not to stay very close to the patient; and if so, to reduce the time of staying. It was suggested to maintain the distance between them and patient more than 2.0 m and to reduce time of staying to less than 10 minutes up to one hour. Hyperthyroid patients were treated with 185 MBq to 1295 MBq of radioiodine 131. Mean administered dose activity was 683 MBq. External dose rate measurements were performed at the same distance as Thyroid cancer patients fifteen minute after administration of therapy. Afterwards they were released from hospital. All the patients were interviewed and were informed about the research aims by a medical physicist and a physician. They signed an agreement for participating in the study. Family members groups consisted of 12 females and 18 males in the hyperthyroid group and 24 males and 6 females in the thyroid cancer group. Their age varied from 15 up to 80 years. The effective dose measurements were carried out with thermoluminiscent dosimeters, model TLD 100, which contain 3 mm 2 hot pressed chips of lithium fluoride (LiF:Mg,Ti), encapsulated between two sheets of Teflon 10 mg/cm2 thick and mounted on an aluminium substrate with-bar code and within shielded filter holders (type 8814 Harshaw). The detection threshold of the dosimetry system is 0.0054 msv. TLD s were most appropriate to estimate radiation because the amount of ionizing radiation is directly proportional to the effective dose [10]. Actually the depth dose Hp (10) was estimated. These types of dosimeters have photon energy response for gamma rays that ranges from (15 kev- 3MeV) (IEC 1066). The TLD Reader and Cards are calibrating on regular basis. The combined standard uncertainty of a dosimetry system is less than 15%. Control TLDs were kept separately to measure the background. The background readings were subtracted from the dose readings of the relatives. 4. RESULTS AND DISCUSSION 4.1 Thyroid cancer patients Table 1 presents the effective dose to relatives of the thyroid cancer patients treated with radioiodine 131, measured with TLD dosimeters. The TLDs were worn by the relatives for one week. The range of the effective dose varied from 0.02 msv to 0.51 msv. For three family members the TLD showed a value of 0 msv and the explanation was that patients continue to be isolated from others after they had left the hospital for one week period of time The mean value of the effective dose to relatives of thyroid cancer patients is 0.21 msv. Standard deviation was 0.15 and variance (SD) 0.02. Figure 1 presents the effective doses to relatives of thyroid cancer patients versus proposed dose constraint for adults of 3 msv and 15 msv for older than 60 years of age according to the BSS. The family members age varied from 28 years up to 73 years. Mean value was 46.7. The results show that the effective doses to all family members were well below the recommended dose constraints of 1 msv (recommended dose for children by the BSS). The results agreed with the previously published paper by Buchan et al. and proved that the protocol used for performing radioiodine therapy for thyroid cancer patient is sufficiently safe. Three days of hospitalization and dose rate measurements should be continued. Originalni ~lanci/ Original articles

Medicinska revija Medical review 25 will improve the process of optimization in radiation protection to family members, public and environment. Mathieu et al. reported the dose to family members and children of thyroid cancer patients, and in all cases the measured doses were lower than 0.5 msv [6]. Grigsby et al. [13] reported radiation dose to 65 family members ranged from 0.01 msv to 1.09 msv from patients received iodine 131 doses ranging from 2.8 to 5.6 GBq. These patients were treated on outpatient basis. Figure 1. Effective doses vs. dose constraint Table 1.Effective doses to family members of thyroid cancer patients It is recommended to suggest an additional seven days of No msv sex Age(y) 1 0.05 m 28 2 0.00 m 35 3 0.00 m 26 4 0.27 f 38 5 0.00 m 46 6 0.16 m 35 7 0.02 f 50 8 0.43 m 35 9 0.32 f 33 10 0.23 f 73 11 0.31 m 32 12 0.25 m 70 13 0.17 f 60 14 0.20 m 44 15 0.15 m 40 16 0.40 m 40 17 0.51 m 70 18 0.08 m 40 19 0.43 m 40 20 0.06 m 41 21 0.33 f 60 22 0.02 m 41 23 0.15 m 61 24 0.20 m 65 25 0.41 m 40 26 0.17 m 38 27 0.23 m 56 28 0.37 m 60 29 0.02 m 58 30 0.35 m 48 mean 0.21 46,7 SD 0.15 SEM 0.02 sleeping separately and avoiding close contact with other people, children and pregnant women [11]. Giving written instructions on the further behaviour of the patients at home 4.2 Hyperthyroid patients Table 2 presents the effective doses to relatives of the hyperthyroid patients treated with Iodine 131 as measured with TLD dosimeters. Patient s relatives wore the TLDs for a period of one week. The mean value of the effective dose for the relatives of the hyperthyroid patients was 0.87 msv. Standard deviation is 1.24 and variance (SD) 1.55. The range of the effective dose varied from 0.12 msv to 6.79 msv. For three patient spouses the measured value was 0 msv, and the explanation was that the patients stayed in different rooms and most of the times were away from home. The spouse of patient number 18 received the highest dose (6.79 msv). The explanation was that the woman did not follow the given recommendation. She stayed very close to her husband all the time after he received his treatment. On further analysis, it was found that the woman 69 years old and according to the BSS for adults aged more than 60 years old, the allowed dose constraint is 15 msv. Eleven family members received effective doses higher than 1mSv but less than 3 msv. Figure 2 presents the values of effective doses of the hyperthyroid patients vs. the Dose Figure 2. Effective doses vs dose constraint Constraint of the BSS. All values, except one, are below 3 msv. The statistical analysis was done using SPSS 6.0 software for Windows. Mann Whitney non parametric test allows two groups to be compared without making assumption that values are normally distributed. Statistical significance was set at p<0.05. Comparison between two groups Lalo{evi} Zdraveska D. Kochovska Med Data Rev M. 2013;5(1): and Majstorov 000-000 V. MD-Medical Data 2014;6(1): 023-027

26 MD MEDICAL DATA / Vol.6 N O 1 / Mart/March 2014. showed significant difference (Mann-Whitney U-Test p<0,001). The results presented in this study confirm the results of the study by Culver et al. [12], stating that the doses for relatives of hyperthyroid patients are higher than the doses for relatives of thyroid cancer patients. This observation is due to the lower retention and the faster wash out of the iodine 131 activity from the body of the thyroid carcinoma patients, in spite of the higher administered activity. Furthermore the thyroid cancer patients after the administration of the radioiodine were hospitalized for three days in an isolation room. Another reason is that thyroid cancer patients retain less iodine as a result of the minimal thyroid tissue left after surgery. On the other hand, hyperthyroid patients were administered with fewer doses but were treated on an outpatient basis. Table 2.Effective doses to family members of Hyperthyroid patients No msv sex Age(y) 1 1.25 m 63 2 0.00 m 40 3 0.00 m 29 4 0.78 f 44 5 0.23 m 45 6 0.52 m 41 7 0.23 m 52 8 0.12 m 39 9 1.2 f 44 10 1.14 m 58 11 0.52 m 80 12 0.54 m 40 13 0.17 m 32 14 0.16 m 56 15 0.48 m 70 16 1.90 m 55 17 0.33 f 52 18 6.79 f 69 19 0.21 m 56 20 1.23 m 66 21 0.38 f 33 22 0.40 f 44 23 0.21 m 57 24 0.00 m 40 25 0.51 f 43 26 1.25 f 57 27 1.48 f 50 28 1.32 f 42 29 1.70 f 47 30 1.17 f 60 mean 0.87 50.1 SD 1.24 SEM 0.22 The given oral and written instructions were same, for both hyperthyroid and thyroid cancer patients. The restriction time is different (seven days for thyroid cancer patients and three days for hyperthyroid patients) and this information is usually given verbally by the physicians. Although the radiation doses to hyperthyroid family members are within the recommended limits, the values are higher in comparison with the doses of the family members of thyroid cancer patients. The higher doses of the relatives of the hyperthyroid patients are also due to the higher radioiodine retention of the thyroid gland and thus higher doses to the patients [6]. 3. CONCLUSION The radiation doses to family members of patients treated with radioiodine 131 for Thyroid cancer were found to be well below the proposed dose limit of 1 msv. Thyroid cancer patients should continue to be treated as in patients to ensure that after three days of hospitalization they do not present a radiation hazard to their family members. The effective doses of eleven family members of hyperthyroid patients were higher than 1 msv. One person received 6.79 msv. It is necessary to formulate new instructions for outpatients after treatment with radioiodine 131 to comply with the requirements of the revised ICRP limits. This study has provided useful information on radiation protection and exposure to family members of patients with Thyroid carcinoma and hyperthyroid patients treated with radioiodine 131. Originalni ~lanci/ Original articles

Medicinska revija Medical review 27 Sa`etak Cilj ove studije je bio da se proceni efektivna doza bliskih ~lanova porodice pacijenata obolelih od karcinoma {titne `lezde kao i od hipertiroidizma. Rezultati su uporedjeni sa granicama doze koje propisuje Komisija za radiolo{ku za{titu i osnovni standard radijacione sigurnosti Medjunarodne agencije za atomsku energiju. Procena efektivne doze izvedena je kod {ezdeset ~lanova porodice za isti broj pacijenata tretirani sa radioaktivnim jodom 131 kori{}enjem termoluminescentnih dozimetara, model TLD 100. Pacijenti sa dijagnozom tiroidnog karcinoma {titne `lezde bili su hospitalizovani tri dana dok su hipertiroidni pacijenti tretirani samo ambulantno. ^lanovi porodice nosili su TLD u periodu od sedam dana. Rezultati su pokazali da su doze ~lanova porodice pacijenata sa tiroidnim karcinomom ispod preporu~ene vrednosti granice doze od 1mSv. Srednja vrednost efektivne doze je 0.21 msv (min 0.02 max 0.51) msv. Kod jedanaest ~lanova porodice hipertiroidnih pacijenta detektovane su ve}e vrednosti od 1 msv. Srednja vrednost efektivne doze je bila 0.87 msv (min 0.12 max 6.79) msv. Vrednosti efektivne doze kod ~lanova porodice pacijenta sa tiroidnim karcinomom bile su ve}e od vrednosti efektivnih doza kod ~lanova porodice hipertiroidnih pacijenta. Ovi rezultati su zna~ajni i treba ih analizirati prilikom uspostavljanja novih nacionalnih smernica u vezi zastite od zracenja i pu{tanja pacijenta posle tretmana radiojodnom terapijom. REFERENCES [1] International Commission of Radiological Protection 1991 Recommendations of the International Commission on Radiological Protection, Ann ICRP 1991;21:1-3. [2] Council of the European Union 1996 Guideline 96/29/EURATOM to determine basic directions for health protection of public and workers against radiation related dangers, Leafl Eur Commun 1996; L159/1. [3] Monsieurs M et al 1998 Real-life burden to relatives of patients treated with iodine- 131: a study in eight centers in Flanders (Belgium) Eur J Nucl Med 25 1368-76 [4] Barrington S F et al 1999 Radiation exposure of the families of outpatients treated with radioiodine (iodine 131) for hyperthyroidism Eur J Nucl Med 26 686-92 [5] Barrington S F et al 1995 Radiation exposures of patient s children at home post I- 131 administration Eur J Nucl Med 22 798 [6] Mathieu I et al 1997 Doses in family members after 131I treatment Lancet 350 1074-5 [7] O Doherty M J et al 1993 Radiation dose rates from adult patients receiving 131I therapy for thyrotoxicosis Nucl Med Commun 13 160-8 [8] Cappelen T, Unhjem J F 2004 Patients with hyperthyroidism treated with radioactive iodine and exposures to family members Eur J Nucl Med Mol Imaging 31 P828 S457 [9] Athanasopoulou E M et al 2007 Unexpected dose to the daughter of a patient treated with iodine-131 for hyperthyroidism Hell J Nucl Med, Vol 10 175-6. [10] Jacobsen A P, Plato P A and Toeroek D 1978 Contamination of the home environment by patients treated with iodine-131: initial result Am J Public Health 68 225-30 [11] Buchan R C T, Brindle J M 1971 Radioiodine therapy to out-patient-the radiation hazard British Journal of radiology 44 973-5 [12] Culver, C. and Dworkin, H. (1991), Radiation safety consideration for post-iodine- 131 hyperthyroid therapy, J Nucl Med; Vol 32:69-173,1991. [13] Grigsby PW, et al., Radiation exposure from outpatient radioactive iodine therapy for thyroid carcinoma, J Am Med Assoc 2000;283: 2274-2274. The paper was received on 25.01.2014., Accepted on 31.01.2014. Lalo{evi} Zdraveska D. Kochovska Med Data Rev M. 2013;5(1): and Majstorov 000-000 V. MD-Medical Data 2014;6(1): 023-027