Leukaemias and cancers following iodine-131 administration for thyroid cancer.

We studied 1771 patients treated for a thyroid cancer in two institutions. None of these patients had been treated with external radiotherapy and 1497 had received (131)I. The average (131)I cumulative activity administered was 7.2 GBq, and the estimated average dose was 0.34 Sv to the bone marrow and 0.80 Sv to the whole body. After a mean follow-up of 10 years, no case of leukaemia was observed, compared with 2.5 expected according to the coefficients derived from Japanese atomic bomb survivors (P = 0.1). A total of 80 patients developed a solid second malignant neoplasm (SMN), among whom 13 developed a colorectal cancer. The risk of colorectal cancer was found to be related to the total activity of (131)I administered 5 years or more before its diagnosis (excess relative risk = 0.5 per GBq, P = 0.02). These findings were probably caused by the accumulation of (131)I in the colon lumen. Hence, in the absence of laxative treatment, the dose to the colon as a result of (131)I administered for the treatment of thyroid cancer could be higher than expected from calculation of the International Commission on Radiological Protection (ICRP). When digestive tract cancers were excluded, the overall excess relative risk of second cancer per estimated effective sievert received to the whole body was -0.2 (P = 0.6).

Characterization and radiosensitivity at high or low dose rate of four cell lines derived from human thyroid tumors.

PURPOSE: This study attempted to establish cell lines derived from human differentiated thyroid tumors, and to characterize and evaluate the radiation dose-rate effect. METHODS AND MATERIALS: Two cell lines (K1 and K2) were derived from papillary carcinomas, one (K7) from a follicular less-differentiated carcinoma and one (A14) from a follicular adenoma. Cell-survival curves after irradiation were established by the in vitro colony method. Radiation doses were delivered either at a high (45.9 Gy/h) or low dose rate (0.6 Gy/h) by a 60Co source. The data were analyzed according to the linear quadratic and multitarget model of radiation action. RESULTS: Doubling times were around 24 h. All cell lines were positive for intracellular thyroglobulin. Cyclic adenosine monophosphate (cAMP) response to thyrotropin (TSH) was significant for the cell lines derived from the follicular adenoma and follicular carcinoma. The two cell lines derived from papillary carcinomas were tumorigenic after inoculation into nude mice. After high-dose-rate irradiation, the surviving fraction at 2 Gy (SF2) was not significantly different for the three malignant cell lines K1, K2, and K7, and ranged from 0.39 to 0.42. For the adenoma cell line A14, we found a higher radiosensitivity with a lower SF2 value and a higher alpha parameter. After low-dose-rate irradiation, only one cell line (K2) showed a significant low-dose-rate sparing with a dose reduction factor of 1.35. CONCLUSION: The major result of our study is the weak effect of the dose rate on the survival of thyroid cell lines.

Radioactive iodine treatment and external radiotherapy for lung and bone metastases from thyroid carcinoma.

UNLABELLED: We assessed the therapeutic benefits of 131I treatment in patients with distant metastases of differentiated thyroid carcinoma. METHODS: Of 2200 patients treated for differentiated thyroid carcinoma at our institution, 394 had lung and/or bone metastases. RESULTS: Two-thirds of the patients had 131I uptake in their metastases, but only 46% achieved a complete response. Prognostic factors for complete response were: younger age, presence of 131I uptake in the metastases and small extent of disease. The survival rate was 33% at 15 yr. As shown by multivariate analysis, favorable prognostic factors for survival were: younger age and time of metastases detection, well-differentiated histologic type of the thyroid tumor, presence of 131I type uptake in the metastases, small extent of the disease and year of discovery of metastases. CONCLUSION: In terms of survival, the benefits of 131I therapy cannot be demonstrated by prospective controlled studies. The present study clearly demonstrates, however, that treatment with 131I is one of the factors which accounts for survival; patients whose metastases concentrated 131I and who could be treated with radioiodine had higher survival rates. Patients who achieved complete response following treatment of distant metastases had a 15-yr survival rate of 89%, while those who did not achieve complete response had a survival rate of only 8%. The survival rate improved with the year of discovery of distant metastases, after 131I total-body imaging and serum thyroglobulin measurements were routinely used.

Pattern of ras and gsp oncogene mutations in radiation-associated human thyroid tumors.

The preferential activation of the Ki-ras oncogene in follicular radiation-associated human thyroid carcinomas, has been suggested by Wright et al. (1991). However, only 12 thyroid tumors were analysed in this study. In order to confirm if radiation favours, in human thyroid tumorigenesis, the appearance of a particular molecular lesion, we studied 33 benign and malignant human radiation-associated thyroid tumors. We used polymerase chain reaction (PCR) amplification and allele-specific hybridization with mutant-specific probes for the three ras genes and the gsp oncogene. Compared to 85 'spontaneous' human thyroid tumors, the radiation-associated cases: (1) show a similar overall frequency of ras and gsp mutations (about 30% and 6% respectively); (2) present a similar frequency of mutation of the three ras genes without any predominance in adenomas and papillary carcinomas and (3) all Ki-ras mutations were found in papillary carcinomas (4/15). ras and gsp genes were never found mutated simultaneously, suggesting an alternative role for both oncogenes in the thyroid tumorigenic radiation-associated process.

TRIAC (3,5,3'-triiodothyroacetic acid) has parallel effects at the pituitary and peripheral tissue levels in thyroid cancer patients treated with L-thyroxine.

OBJECTIVE: To investigate whether the addition of 3,5,3'-triiodothyroacetic acid (TRIAC) to thyroxine (T4) treatment can suppress TSH secretion without inducing thyrotoxicosis at the periphery. DESIGN: Thyroid cancer patients were studied with different treatment modalities: T4 at supraphysiologic dose (2.5 +/- 0.3 micrograms/kg/day) and after reduction to a physiologic dose (1.8 +/- 0.3 micrograms/kg/day); then with the addition of TRIAC 500 or 1000 micrograms/day to the physiologic T4 treatment dose. PATIENTS: Twenty-two patients who had total thyroid ablation for differentiated thyroid carcinoma. MEASUREMENTS: Clinical and biological parameters of thyroid hormone action studied included heart rate, serum creatine phosphokinase, testosterone-oestradiol binding globulin, procollagen III and osteocalcin levels. RESULTS: The addition of TRIAC induced a significant and dose-dependent decrease in serum TSH levels and parallel effects on peripheral tissues. Compared to the suppressive T4 treatment dose, the addition of TRIAC to the physiologic T4 dose resulted in greater inhibition of TSH secretion in only 50% of the patients. The effects at the periphery of both treatment modalities were similar for a comparable level of TSH suppression. CONCLUSIONS: Even at low dose and when combined with T4, TRIAC has parallel effects on the pituitary and peripheral tissues. There is no justification for the use of TRIAC as suppressive treatment in thyroid cancer patients.