QUALITY OF LIFE CHANGES IN PATIENTS WITH THYROID CANCER AFTER WITHDRAWAL OF THYROID HORMONE THERAPY Maria Belgun, L.Dumitriu, A.Goldstein, Mariana Purice, F.Alexiu Institute of Endocrinology “C.I. Parhon”, Bucharest

Introduction

High dose 131I therapy ( RAI), after surgery, has been used for over 50 years in metastatic thyroïde carcinome. RAI efficiency is related to the amount of absorbed doses of radiation () in the lesions. The use of high doses even from the begining of RAI, has the best therapeutic effect, subsequent oncobiological alterations (decrease of the 131I uptake) could be minimized. Commonly, differentiated thyroid carcinoma derived from follicular cells (DTC) has a slow growth rate and subletaly doses allow surviving cells to recover their lesions. After many years of the apparent clinical remission of the disease, one can find recurrences of it. THE QUESTION IS : Does high doses of 131I efficient in the treatment of wildly metastatic thyroid carcinoma, increase the incidence of a second malignancy ???

Later potential complications of 131I therapy include damages of the gonads, bone marrow, lungs and induction of other malignancies. 1. Long term studies of fertility and birth histories suggest that gonads failure is seldom permanent. The incidence of infertility, miscarriage, prematurity, major congenital anomalies are not significantly different from that in the general population. 2. Bone marrow damages and production of other tumours are potentially more serious problems. Were reported some few deaths from leukaemia, bladder and stomach cancer.  From these reasons, bone marrow radiotoxicity is the dose - limiting factor for radiopharmaceutical administration in most cases. However 131I therapy, even in high doses: 1. Is well tolerated. 2. Sever bone marrow toxicity seldom occurs. 3. Bone marrow absorbed dose of 2 Gy (200 rad) is considered to be limiting dose ( in the majority of the cases, below this threshold does not lead to severe mielotoxicity).

Method

Groups Group 1 Group 2 27 patients with a second malignancy From 4200 patients with DTC treated with 131I in the Departament of Nuclear Medicine of the Institute of Endocrinology, Bucharest (1964-2003), were selected: Group 1 114 patients with DTC receiving total activities between 37-110 GBq (1000-2950 mCi) age: 14-64 years old Group 2 27 patients with a second malignancy age: 20-62 years old 2 patients with other two malignancies age : 32, 47 years old It has been reviewed: their medical charts hematological data incidence of the second malignancy in relation with 131I therapy

Results

Group 1 (n=114)

111 of patients (97.4%) did not have another malignancy after 131 I therapy. 3 of patients (2.6%) had a second malignancy after cumulative 131 I activities between 36-46 GBq (980-1250 mCi)

Case nr. 1 MR, 20/F : Dg: papillary carcinoma, follicular variant, lymph nodes and lung metastases (near- total thyroidectomy + lymph adenectomy) Period of RAI: 1980-1985 (5 years) Total 131 I activity: 44 GBq (1200 mCi) Haematological data: normal EVOLUTION 1986 : HGB = 11.6 g/dl, HCT =38%,WBC= 4300 /ul, PLT=151.000/ul, VSH =24/56 mm 1987 : HGB = 9.4 g/dl, HCT =33% 24 %, WBC= 27.800 /ul, with Lymphoblast 64%, PLT=149.000/ul, VSH =74/84 mm). Diagnosis : lymphocitic leukaemia 1989: died

Case nr. 2 PE, 32/F Dg: papillary carcinoma, follicular variant, lymph nodes metastases (near- total thyroidectomy + lymph adenectomy); local recurrences operated Period of RAI : 1980-1986 (6 years) Total 131 I activity : 49 GBq (1050 mCi) Haematological data : normal. EVOLUTION 1988: breast cancer (surgery + chemotherapy + external beam radiotherapy) 2001: Non-Hodgkin’s lymphoma 2003: died (after 17 years of thyroid cancer remission and 15 years after external beam radiotherapy)

Case nr. 3 MO, 33/F Dg: papillary carcinoma , follicular variant, lymph nodes metastases (near- total thyroidectomy + lymph adenectomy); local recurrences operated Period of RAI : 1979-1981 (2years) Total 131 I activity : 37 GBq (1000 mCi) Haematological data : normal. EVOLUTION : After 20 years of “free disease”: 2002 : bladder cancer 2003: lymph nodes+lung+ liver metastases

Group 2 (n=27)

15 patients with another cancer before RAI :

12 cases the second malignancy diagnosed during RAI

Case nr. 4 VS, 42/F 1982 : breast cancer (sectorial resection) 1982: papillary carcinoma , follicular variant, lymph nodes (near- total thyroidectomy + lymph adenectomy) 1982-1983: two doses 131 I (RAI )= 7.4 GBq (200 mCi) 1984: recurrence breast cancer (surgery+chemo therapy+external beam radiotherapy) 1990: diagnosis leukaemia 1996: died

Conclusions

1. The presence of the other malignancies in patients with DTC is not uncommon. 2. The incidence of a second malignancy after a high cumulated dose of 131I therapy in our casuistry, is not significant. 3. As of now, it appears that repeated administration of 131I is reasonably safe, well tolerated and necessary as long as there is evidence of continued tumor response. 4. Periodic monitoring of marrow status in all patients treated with high dose 131I therapy, could prevent sever damages 5. Rigorously respecting 131I administration’s conditions may reduce radiation exposure of the whole body. 6. Exposure to external radiation, can increase the incidence of the other malignancies by summation effects.