Cancer risk after iodine-131 therapy for hyperthyroidism.

Cancer incidence was studied in 10,552 patients (mean age, 57 years) who received 131I therapy (mean dose, 506 MBq) for hyperthyroidism between 1950 and 1975. Follow-up on these patients was continued for an average of 15 years. Record linkage with the Swedish Cancer Register for the period 1958-1985 identified 1543 cancers occurring 1 year or more after 131I treatment, and the standardized incidence ratio (SIR) was 1.06 (95% confidence interval = 1.01-1.11). Significantly increased SIRs were observed for cancers of the lung (SIR = 1.32; n = 105) and kidney (SIR = 1.39; n = 66). Among 10-year survivors, significantly elevated risks were seen for cancers of the stomach (SIR = 1.33; n = 58), kidney (SIR = 1.51; n = 37), and brain (SIR = 1.63; n = 30). Only the risk for stomach cancer, however, increased over time (P less than .05) and with increasing activity administered (P = not significant). The risk for malignant lymphoma was significantly below expectation (SIR = 0.53; n = 11). Overall cancer risk did not increase with administered 131I dose or with time since exposure. The absence of any increase in leukemia adds further support to the view that a radiation dose delivered gradually over time is less carcinogenic than the same total dose received over a short time. Only for stomach cancer was a possible radiogenic excess suggested.

Cancer risk in population examined with diagnostic doses of 131I.

Previously, we conducted a study of 35,074 patients receiving diagnostic doses of 131I for suspected thyroid disorders between 1951 and 1969. We reported that, between 1958 and 1984, the incidence of thyroid cancers in these patients was insignificantly greater than the incidence expected in the general population. This increase was attributed to the underlying condition that prompted the examination and not to the administration of 131I. The purpose of the present study was to analyze the total cancer risk in the same cohort of patients examined with diagnostic doses of 131I. To further evaluate the underlying risk of disease in these patients, we compared the incidence of all cancers with that expected in the general population. The average radiation dose was approximately 500 mGy to the thyroid and less than 10 mGy to other organs. In the 35,074 patients, 3,746 cancers occurred following the first 5 years after examination, and the resulting standardized incidence rate (SIR) was 1.01 (95% confidence interval = 0.98-1.04). SIRs were significantly increased for endocrine tumors other than thyroid cancer (1.93) and for lymphomas (1.24), leukemias (1.34), and nervous system tumors (1.19). The risk of leukemia was similar for chronic lymphocytic leukemia (CLL) (SIR = 1.30) and non-CLL (SIR = 1.34). SIR was significantly decreased for cancers of the female genital organs (0.86). The risk for cancer of all sites and types combined was highest 5-9 years after examination (SIR = 1.07) and did not differ from unity thereafter. With greater than or equal to 10 years of follow-up, risk was not statistically associated with the dose of 131I. Overall, the data exclude cancer risk increments greater than 5% (SIR = 1.05) with 95% confidence. The significant increase in the risk of non-CLL, a prominent radiogenic malignancy, however, warrants special attention. We are continuing our study to determine the possible factors involved in the significant increase in the risk of leukemia.

Thyroid cancer after diagnostic doses of iodine-131: a retrospective cohort study.

The incidence of thyroid cancer was evaluated in 35,074 patients examined for suspected thyroid disorders between 1951 and 1969 with an average of 1.92 megabecquerel [(MBq) 52 microCi] of 131I. The radiation dose to the thyroid gland was, on the average, approximately 0.5 Gy. The mean age at the time of examination was 44 years; 5% were under age 20. Patients were followed for an average of 20 years. Record linkage with the Swedish Cancer Register identified 50 thyroid cancers occurring 5 years or more after the initial 131I examination, in contrast to 39.4 expected based on general population rates [standardized incidence ratio (SIR) = 1.27, 95% confidence interval = 0.94-1.67]. Risk was highest among males (SIR = 2.70, n = 10), patients followed 5-9 years (SIR = 2.22, n = 23), and patients receiving more than 74 microCi or 2.74 MBq of 131I (SIR = 2.04, n = 17). However, these observations were confounded by the fact that patients examined for a suspected thyroid tumor received the highest 131I exposures and were at highest overall risk (SIR = 2.77, n = 34). Patients given 131I for reasons other than a suspected tumor were not at increased risk (SIR = 0.62, n = 16). Patients anticipated to be at highest risk, i.e., women (SIR = 1.12, n = 40) and those observed for 10 years or more (SIR = 0.93, n = 27), showed no evidence of a dose response. Overall, these data provide little proof that 131I is carcinogenic in humans and support the notion that the carcinogenic potential of internal 131I beta particles might be as low as four times less than external x rays or gamma rays.

Value of liver scintigraphy in pretreatment staging and in follow-up of patients with malignant melanoma.

Liver scintigraphy (99Tcm sulphur colloid) was performed in 118 patients with malignant melanoma. In 73 patients diagnosed as stage I, the pretreatment evaluation showed one false-negative and one false-positive examination. During follow-up there were ten abnormal liver scintigraphies; one was later correlated to liver metastases. In 46 patients diagnosed as stage II-IV, the pretreatment liver scintigraphy yielded false-negative results in 36% and false-positive results in 15%. The predictive values of positive and negative tests were 44% and 81%, respectively. The yields of liver tests (S-alkaline phosphatase, S-gamma-glutamyl-transferase) in patients with liver metastases were low. This study demonstrated the limitations of liver scintigraphy for diagnosis of liver metastases in patients with malignant melanoma.

Clinical comparison of bone scintigraphy with 99Tcm-DPD, 99Tcm-HDP and 99Tcm-MDP.

The bone-imaging agents MDP, DPD and HDP were compared radiochemically (only minor differences were found) in 12 patients with prostatic and 12 patients with breast carcinoma. Each patient received both MDP and either DPD or HDP. The scintigraphic examinations were compared visually and quantitatively. The uptake ratio normal bone/soft tissue was higher for DPD and HDP than for MDP. The ratio pathologic bone/normal bone was highest for MDP, particularly for prostatic carcinoma. The differences in this ratio for breast carcinoma were in general non-significant. The observed differences were minor and of little practical importance.

Preoperative scintigraphy with correlation to cytology and histopathology in carcinoma of the thyroid.

At preoperative scintigraphy of 83 consecutive histopathologically confirmed thyroid carcinomas a solitary reduced uptake was observed in 70 per cent. The minimum detectable size was 10 mm for differential carcinomas showing this image, but in the 'screening group' of hereditary medullary carcinoma several scintigrams were considered normal despite a tumour size of 10 to 15 mm. In the imaging of the undifferentiated carcinoma a solitary reduced uptake with disappearance of the entire affected lobe was often demonstrated. Multifocal areas in the dot scintigram representing tumours were often missed at fine needle aspiration biopsy. Computer-processed scintigrams were superior in showing multifocal lesions.

Surgical treatment of metastatic disease in the thyroid gland.

Metastatic disease in the thyroid gland is uncommon in clinical practice. Preoperative investigation with thyroid scan and fine-needle aspiration biopsy verified or strongly suggested metastatic disease in seven out of nine patients. All patients were treated by thyroid surgery. Three patients died within 4 months in disseminated disease. The remaining seven patients had a survival rate of between 1 and 5 years. Three patients are still alive 12, 29, and 48 months after thyroid surgery. Surgical treatment for metastatic disease in the thyroid, especially due to metastatic renal carcinoma and melanoma, is recommended.

Scintigraphic evaluation and dynamic studies with thallium-201 in thyroid lesions with suspected cancer.

Scintigraphic studies of the thyroid with thallium-201 chloride were performed in 46 patients in whom the final diagnosis was established by histology. In dynamic studies of 36 patients, sequential imaging was performed the first 40 min after injection. A single exponential, Cexp(-lambda t), was fitted to each of the curves generated from apparently pathological and from normal regions in each patient, as determined by earlier conventional scintigrams. To minimize the effects of normal individual variations, the relation between pathological (p) and normal (n) regions in the same patient was emphasized and quantified by two parameters, namely the extrapolated zero-time intercept (Cp/Cn) and the time development (lambda p-lambda n) of the ratio of counting rates/unit area in the two regions. The turnover appears to be somewhat slower for pathological tissue than for normal tissue. Although this difference was significant on the 5% level for both cancer and adenoma as a group, only the relative disappearance rate (lambda p-lambda n) resolved cancer frm adenoma and from goiter on the same level. All but one of the differentiated cancers had an increased uptake.

An evaluation of angiography, 75Se-methionine scintigraphy and the Lundh test in the diagnosis of pancreatic disease.

In order to asses accuracy and consistency of diagnostic opinion in suspected pancreatic disease, using available diagnostic procedures 74 patients, subjected to selective angiography, pancreatic function test (Lundh test), and scintigraphy, were studied retrospectively. The patients were divided into four diagnostic subgroups, three of which represented defined pancreatic disease, the fourth serving as a control group since such disease could be excluded. The primary diagnostic results were compared. After a stipulated minimum of six months the angiographic films and scintigraphic recordings were re-appraised in a randomized manner without access to clinical data. The evaluations thus achieved were compared to those delivered primarily. The results of the present study seem to indicate that the Lundh test and pancreatic scintigraphy are screening tests with a high level of diagnostic reliability and consistency; when normal, practically ruling out pancreatic disease. Angiography is recommendable only if one or both of the above mentioned screening methods yield pathologic results, supported by clinical evidence. The principal aims of selective angiography in suscepted pancreatic disease, are to map vascular anatomy, to differentiate non-neoplastic disease from cancer and to assist estimation of operability. The results of the reappraisal indicate that the diagnostic accuracy of angiography, more than that of scintigraphy, is dependent on the experience of the examiner.