Carlos Bekerman

The role of gallium-67 in the clinical evaluation of cancer.

This review is based primarily on historic data, and it examines the indications for and limitations of gallium-67 scanning in the evaluation of patients with neoplasms. The use of gallium-67 scans is discussed according to tumor type, and data from the most representative and comprehensive studies are included. The results described, some of which were obtained primarily with older imaging techniques, should be regarded as representing the minimum that can be expected from application of this imaging procedure.

Radiation-induced tumors of the head and neck following childhood irradiation. Prospective studies

Nodules were found in 1108 subjects who received childhood radiation for benign conditions of the cervical area at our institution. This is 37.5% of 2958 subjects, out of a total of 5379, for whom there is follow-up information. Of the 848 subjects who have had thyroidectomies, 297 (35.0%) had thyroid cancer. In addition to thyroid tumors, salivary, neural, and probably parathyroid tumors also occurred as a late consequence of childhood radiation. Prospective studies of the subjects indicate that thyroid nodules are continuing to occur at a constant rate. The measurement of serum thyroglobulin is helpful in identifying individuals for whom the risk of developing a nodule is increased. Follow-up of patients with nonsurgically-treated nodules indicates that some of their nodules are progressive. At the present time there is no indication that radiation-induced cancers behave differently than ones in other settings. However, some of their characteristics, especially their multicentricity and occurrence in younger individuals, indicate that continued follow-up is necessary. On the basis of the data generated by the follow-up program at our institution and programs elsewhere, recommendations for screening, treatment, and follow-up are made. The recommendations stress the importance of estimating risk based on radiation dose, previous tumors, and serum thyroglobulin, in arriving at clinical decisions for these subjects.

Recurrence of Thyroid Nodules after Surgical Removal in Patients Irradiated in Childhood for Benign Conditions

To determine the incidence of benign thyroid nodules and the risk factors for their recurrence after surgical removal, we followed 511 patients for 1 to 40.6 years (median, 11.2) after surgery for benign thyroid nodules arising after local irradiation for unrelated benign diseases in childhood. Recurrent thyroid nodules developed in 100 patients (19.5 percent). The risk of recurrence correlated inversely with the amount of thyroid tissue removed. Women had a higher recurrence rate than men (28.4 percent vs. 10.3 percent; P less than 0.05). Among the 299 patients who had been treated with thyroid hormone at the discretion of their physicians to suppress thyroid-stimulating hormone, 25 had recurrences (8.4 percent), as compared with 72 of 201 patients who did not receive thyroid hormone (35.8 percent) (hazard ratio taking into account the extent of surgery and the patients sex, 2.5; 95 percent confidence interval, 1.5 to 4.1). Histologic analysis of the 73 tissue samples from patients with recurrences showed that 14 samples (19.2 percent) were malignant. Thyroid hormone treatment had no effect on the rate of thyroid cancer. We conclude that radiation-associated benign thyroid nodules have a high recurrence rate, similar to that reported among nonirradiated patients with benign thyroid nodules. We also conclude that treatment with thyroid hormone decreases the risk of benign recurrences, particularly in women, but not the risk of cancer.

Radiation-induced thyroid carcinoma. Clinical course and results of therapy in 296 patients.

Of 5379 patients who had received radiation treatment at our institution for benign conditions of the head and neck, 318 developed thyroid cancer 3 to 42 years later. We report follow-up observations (median interval from diagnosis to recurrence or last contact, 10 years; longest interval, 31) for 296 of these patients. Three patients died of thyroid cancer and 40 had recurrences. The rate of recurrence during the 10 years after the detection of thyroid cancer, determined by life-table analysis, was 1.1%/yr. Factors that correlated with the risk of recurrence were tumor size, histologic type, number of lobes involved, vessel invasion, and lymph node metastases. The time from radiation exposure to the discovery of thyroid cancer (latency) and the age at diagnosis both inversely correlated with recurrence. The administration of thyroid hormones reduced the number of recurrences in patients with combined papillary and follicular cancer, but no reductions could be associated with the extent of surgery done or the prophylactic use of radioactive iodine ablation. We conclude that the course of radiation-induced thyroid cancer is the same as that of thyroid cancer found in other settings. We advocate a conservative approach to the treatment of small tumors that have no associated risk for thyroid cancer other than that they developed many years after the patient had been exposed to radiation.

Characteristics of 108 thyroid cancers detected by screening in a population with a history of head and neck irradiation

One hundred and eight cases of thyroid cancer have been discovered as a result of screening 1712 individuals from a well defined population known to be at high risk because of prior head or neck irradiation for benign conditions. Of these 108 cancers, 43 (39.8%) were palpable, 27 (25.0%) were detectable by means of thyroid scintigraphy alone, and 38 (35.2%), referred to as incidental carcinomas, were found when the patients were operated on for lesions which proved to be benign. The most striking feature of these cancers was the high frequency of multicentricity (55%) and bilaterality (36%). This high frequency was found in clinically apparent as well as incidental cancers, and could not be accounted for by the operative pathologic techniques of investigation. Of 42 subjects reevaluated at our institution after a mean time of 38 months, 2 had definite and 2 had probable recurrent or residual thyroid disease. The postoperative thyroglobulin levels in subjects with thyroid cancer were proportional to the amount of thyroid tissue remaining. Follow‐up evaluation of the entire group did not disclose any differences in the behavior of these thyroid cancers compared to those not associated with radiation.

Gallium-67 citrate imaging studies of the lung

In spite of localization of gallium in the lungs in a large variety of inflammatory pulmonary diseases, the chest radiograph is and will continue to be the principal diagnostic tool for evaluation of pulmonary inflammatory disease. The 67Ga-citrate scan, however, serves as a study complementary to chest radiography because it indicates the extent, localization, and degree of activity of the inflammatory disease with greater accuracy than do the radiographic studies. It also permits the physician to follow progression of the disease or response to treatment and possible to detect disseminated interstitial disease not visualized on radiographs. Gallium-67 scanning may be used in the evaluation of patients with lymphorecticular neoplasms (Hodgkins disease and malignant lymphomas) both during initial staging and in evaluation of the response to therapy. The 67Ga-citrate scan is useful in the evaluation of patients with lung cancer provided its limitations are kept in mind. It cannot and should not replace the pathologists microscope. The scan is useful as a screening test only in patients who have radiographic lesions not consistent with inflammatory disease and in whom invasive diagnostic procedures or exploratory surgery are contraindicated unless the probability of detecting a resectable tumor is high. However, the limited resolution of the scanning system restricts the possibility of detecting lesions before they become radiographically visible. The histologic type of the lesion appears to have no effect on the probability of detection. As a noninvasive procedure, the 67Ga-citrate scan complements mediastinoscopy by indicating which lymph nodes should be biopsied. It is also useful in evaluation of the controlateral hilar node region. The scan frequently detects clinically unsuspected extrathoracic lesions. It may therefore be a useful initial procedure in guiding the work-up of the patient with a known or strongly suspected tumor. The combination of the 67Ga scan with the chest radiograph could provide the information necessary for presurgical clinical staging in patients who have no symptoms that suggest distant metastases. Gallium-67 scans may be useful in indicating the effectiveness of treatment and the sensitivity of a tumor to radiation.

Scintigraphic evaluation of sarcomata in children and adults by Ga67 citrate

Gallium‐67 scans were performed on 32 patients with adult and childhood sarcomata as part of clinical staging studies. Gallium‐67 scans proved to be highly accurate in assessing sites of disease in patients with malignant schwannoma, Ewings sarcoma, and rhabdomyosarcoma. Gallium‐67 scans were inaccurate in determining sites of disease in patients with other types of sarcomata. It is concluded that Gallium‐67 scanning is a useful adjunct to clinical staging in selected patients with sarcomata. Cancer 42:1760–1765, 1978.

Gallium-67 scanning in the clinical evaluation of human immunodeficiency virus infection: Indications and limitations

This review, examines the indications for and limitations of gallium-67 (67Ga) scanning in the evaluation of patients infected with human immunodeficiency virus (HIV). The imaging protocol, as well as the normal biodistribution of 67Ga and its normal variants are discussed. The diagnostic significance of the different scintigraphic patterns that are found in acquired immune deficiency syndrome (AIDS) or AIDS-related complex (ARC) patients is reviewed. The use of 67Ga scintigraphy for measurement of the effectiveness of treatment in this patient population is also discussed, as is the likelihood that this examination could be used as a prognostic indicator in the future.

Scintigraphic Thyroid Abnormalities after Radiation: A Controlled Study with 99mTc Pertechnetate Scanning

We did 99mTc-pertechnetate thyroid scintigraphy on 99 subjects with no history of therapeutic irradiation to the head or neck. They were compared with 198 irradiated patients selected from a group of over 1700 who were evaluated because of radiation treatment for benign head and neck conditions during childhood. The two groups were similar with respect to age and sex distribution. There were significantly more abnormal scintigrams in the irradiated group (55 of 198 patients versus one of 99 controls). Even after patients and controls with palpable nodules were excluded from the analysis there were still more abnormal scintigrams in the irradiated group (16 of 150 irradiated versus one of 97 control subjects). We conclude that thyroid nodules, including the smaller, nonpalpable nodules discovered by scintigraphy, are related to previous radiation therapy. For persons at substantial risk, such as those who received high-dose treatment (greater than 700 R) during childhood, the data support the use of screening scintigraphy, even with normal findings on palpation.

Enhanced sensitivity and specificity of thallium-201 imaging for the detection of regional ischemic coronary disease by combining SPECT with "bull's eye" analysis.

Previous studies have indicated that the combination of single photon emission computed tomography (SPECT) and quantitative “bulls eye” analysis (QBA) TI–201 cardiac stress imaging may improve the detection of myocardial ischemia over that achieved with planar (PLN) imaging. This study will evaluate the sensitivity and specificity of SPECT and QBA in the detection of disease in the left anterior descending (LAD), left circumflex (LCX), and right coronary artery. Ninety–nine patients who underwent both TI–201 stress imaging and coronary arteriography were evaluated retrospectively. Of the 99, 62 had PLN imaging and 37 were evaluated with SPECT; 23 of these 37 had QBA. The overall sensitivity and specificity were as follows: PLN, 94% and 50%; SPECT, 90% and 67%; QBA, 100% and 20%; and SPECT with QBA, 92% and 72%, respectively. The regional sensitivity and specificity of PLN for individual coronary arteries were as follows: RCA, 78% and 74%; LAD, 89% and 60%; LCX, 50% and 89%, respectively. For SPECT, the results were: RCA, 86% and 93%; LAD, 85% and 88%; and LCX, 60% and 88%. For QBA alone, the results were: RCA, 100% and 75%; LAD, 88% and 53%; and LCX, 100% and 89%. The results for QBA with SPECT were: RCA, 100% and 94%; LAD, 88% and 80%; and LCX, 67% and 95%. Thus, SPECT interpreted on conjunction with QBA showed higher sensitivity for evaluation of ischemia in the RCA and LCX arteries and higher specificity in the detection of LAD and RCA disease than did PLN TI–201 imaging. Because of the low specificity of QBA (20%), caution is advised in the interpretation of QBA alone without reviewing SPECT images.