Current and future perspectives in diagnostic imaging as a guide to targeted/local therapies in breast cancer recurrence.

In recent years, a multidisciplinary approach for breast cancer patient management has been adopted to provide an accurate evaluation of primary/recurrent tumor and to guiding appropriate treatment. The introduction of positron emission tomography (PET) and PET/computed tomography (CT) with 18F-fluorodeoxyglucose and other radiolabelled molecules for the early detection of breast cancer recurrence has important consequences both for staging and treatment planning. In particular, in the last few years, research efforts have been made to guide targeted or local therapies directing against the cancer outgrowth. Based on the available data in the literature, in the present review, we will discuss 1) the role of PET and PET/CT in guiding local therapies for breast cancer recurrences, (both loco-regional and distant sites); and 2) its current status in clinical practice and its possible future role.

Comparison of 18F-FDG positron emission tomography/computed tomography and computed tomography in patients with already-treated breast cancer: diagnostic and prognostic implications.

AIM: The purpose of the study was to assess the comparison of 18F-FDG PET/CT and CT in patients with breast cancer (BC) already treated with primary therapy, in evaluating the diagnostic and prognostic values. METHODS: We retrospectively studied 190 patients (187 women and 3 men, mean age 61±11 years) with previous BC (all stages) after surgery and other primary treatments. They underwent within three months CT and 18F-FDG PET/CT examinations for the evaluation of disease status. Disease relapse was confirmed by clinical evaluation and/or radiological findings. Survival curves of disease-free survival (DFS) and overall survival (OS) were computed using Kaplan-Meier method. Cox analysis regression was used to determine predictive factors of DFS and OS. RESULTS: Of the overall 190 patients, 82 (43%) had evidence of clinical and/or imaging disease relapse, while 108 (57%) did not. Sensitivity, specificity, negative predictive and positive predictive values for disease relapse or progression were of 89% vs. 77%, 73% vs. 53%, 90% vs. 75% and 72% vs. 55%, respectively for PET/CT and CT. DFS curves were significantly different in patients with both negative and positive PET/CT and CT (log-rank test 33.6; P<0.0001 and 12.7; P=0.003, respectively). OS curves were similar in patients with positive/negative PET/CT and CT (P=NS). By both univariate and multivariate Cox regression analysis positive PET/CT was found to be related to the disease recurrence (HR 0.18 and 0.20, both P<0.0001, respectively). CONCLUSION: PET/CT is more accurate than CT in identification of disease relapse in a large population of BC patients. In women at high-risk of recurrence, PET/CT imaging can provide the early detection of BC metastases, tailoring a proper treatment.

Clinical outcome of low-risk differentiated thyroid cancer patients after radioiodine remnant ablation and recombinant human thyroid-stimulating hormone preparation.

AIM: Recombinant human thyroid-stimulating hormone (rhTSH) has been approved in Europe as a preparation tool for radioiodine ablation of post-surgical thyroid remnants in patients with low-risk differentiated thyroid cancer (DTC). Published studies report that, both thyroid hormone withdrawal and rhTSH preparation result in similar rates of successful remnant ablation, but few studies have determined the effectiveness of rhTSH preparation on disease recurrence. We sought to determine the clinical outcome, considering both ablation success and disease recurrence, of low-risk DTC patients who underwent (131)I ablation. MATERIALS AND METHODS: This retrospective study describes the clinical outcome of 100 patients treated with (131)I remnant ablation after preparation with rhTSH. After ablation, patients were classified as in complete remission, as having no evidence of persistent disease, or as having clinical recurrence on the basis of a subsequent diagnostic whole body scan with (131)I, stimulated thyroglobulin and cross-sectional imaging studies. RESULTS: Overall assessment of ablation success was verified and obtained in 75% of patients (75/100). Considering only patients who underwent a diagnostic whole body scan and stimulated thyroglobulin without interfering anti-thyroglobulin antibody, complete ablation was obtained in 96% of patients (75/78). After a follow-up of about 4 years, 78 patients are in complete remission: 75 with initial ablation success and three who achieved a complete remission during subsequent follow-up. Among the remaining 22 patients, 21 have no clinical evidence of disease (NCED), indicating the inability to verify the complete remission or to detect residual disease, as in patients with positive thyroglobulin antibody, whereas one has persistent disease demonstrated only by stimulated thyroglobulin. No recurrences were observed. Of four patients initially classified as having persistent disease, one obtained a complete remission and two are now considered NCED. CONCLUSION: Our data confirm the favourable outcome, with low rates of recurrence and persistent disease, of patients with low-risk DTC who underwent (131)I ablation after rhTSH. Moreover, our results compare favourably with those reported in the literature in patients prepared with rhTSH, but also in patients prepared with hormone withdrawal.

99mTc-MIBI radio-guided surgery in primary hyperparathyroidism: a prospective study of 128 patients.

UNLABELLED: AIMS AND STUDY DESIGN: We investigated the role of an intraoperative gamma probe (IGP) technique in 128 patients with primary hyperparathyroidism (HPT). The patients were evaluated before surgery by 99mTc04/MIBI scintigraphy and neck ultrasound and then operated on by the same surgical team. The IGP technique consisted of the injection of a low dose (37 MBq) of 99mTc-MIBI in the operating room shortly before the start of surgery. Quick parathyroid hormone (QPTH) was routinely measured during the operation. RESULTS: In 94/97 patients (96.9%) with a preoperative diagnosis of solitary parathyroid adenoma (PA) minimally invasive radioguided surgery (MIRS) was successfully performed; in the other 3/97 patients (3.1%) conversion to bilateral neck exploration (BNE) was required because of the intraoperative diagnosis of parathyroid carcinoma in two cases and multiglandular disease (MGD) in one. MIRS was successfully performed also in 23 patients who had undergone previous thyroid or parathyroid surgery. In 31 patients with a preoperative diagnosis of MGD (n = 5) or concomitant nodular goiter (n = 26) the IGP technique was used during a bilateral neck exploration. Among these patients IGP was useful in localizing an ectopic parathyroid gland in the thymus in one case of MGD and a PA located deep in the neck (n = 2) or ectopic at the carotid bifurcation (n = 1) in three cases with nodular goiter. However, in several other patients with nodular goiter it was difficult for the probe to distinguish intraoperatively between thyroid nodules and PA located close to the thyroid gland. CONCLUSIONS: It can be concluded that a) in primary HPT patients with a high likelihood (according to scintigraphic and ultrasound findings) of being affected by a single PA and with a normal thyroid gland, the IGP technique appears useful in MIRS; b) a 99mTc-MIBI dose as low as 37 MBq appears to be adequate to perform MIRS; c) the measurement of QPTH is strongly recommended in HPT patients selected for MIRS to confirm the radicality of parathyroidectomy; d) MIRS can be useful also in HPT patients who underwent previous parathyroid or thyroid surgery to limit the surgical trauma of reoperation and minimize complications; e) with the exception of PAs located at ectopic sites or deep in the neck, the IGP technique does not seem to be recommendable in HPT patients with concomitant nodular goiter.

Renal involvement in subjects with peripheral atherosclerosis.

BACKGROUND: Ischemic nephropathy is an important cause of renal failure in western countries. Subclinical renal function abnormalities may exist in patients with extrarenal atherosclerosis, and may precede the onset of overt ischemic nephropathy. METHODS: To assess the impact of extrarenal atherosclerosis on the kidney, we evaluated renal function in 89 subjects with differing degrees of peripheral atherosclerosis, without manifest clinical or laboratory signs of ischemic nephropathy and renovascular hypertension. All laboratory testing, ultrasonography with Doppler analysis for the localization of peripheral vascular disease (carotid and lower limb arteries), and non-invasive evaluation of renal function by radionuclide studies of renal plasma flow (MAG3 clearance) and glomerular filtration (DTPA clearance), as well as total, LDL and HDL cholesterol, and triglycerides were determined; smoking habit was recorded. By combining sonographic data on arterial tree stenosis (ATS), the subjects were grouped according to the atherosclerotic vascular damage (ATS involvement). RESULTS: Despite no change in plasma creatinine and DTPA clearance (from 91.58+/-26.53 mL/min/1.73 m2 to 93.47+/-24.82), MAG3 clearance progressively declined with the severity of vascular damage (from 244.86+/-60.60 mL/min/1.73 m2 to 173.59+/-58.74). Stepwise multiple regression analysis indicated that MAG3 clearance was best explained by ATS involvement (standardized beta coefficient -0.40; p<0.001), smoking habit (-0.34; p= 0.004), and serum LDL-cholesterol (-0.24; p<0.035). CONCLUSIONS: The renal hemodynamic profile in atherosclerotic patients might constitute functional evidence of the silent phase of ischemic renal disease. The findings suggest that renal function should be carefully assessed in patients with extrarenal atherosclerosis, particularly in those with classic cardiovascular risk factors.

[The role of scintigraphy with dual tracer and potassium perchlorate (99mTcO4 & KClO4/ MIBI) in primary hyperparathyroidism]. / Ruolo della scintigrafia con doppio indicatore e perclorato di potassion (99mTc04 & KCl04/MIBI) nell'iperparatiroidismo.

BACKGROUND: The diagnostic value of scintigraphy using a dual tracer and high-resolution neck ecotomography in the preoperative localisation of parathyroid enlargements was evaluated in a group of consecutive patients suffering from primary hyperparathyroidism (HPT) who were uniformly studied and subsequently operated by the same surgical team. METHODS: Scintigraphic imaging and high-resolution neck ecotomography were carried out in a single session on 143 patients. Scintigraphic imaging was performed using a dual tracer, 99mTc-pertechnetate/99mTc-MIBI), modified by the addition of potassium perchlorate (KCL04) to achieve a rapid washout of 99mTc04 from the thyroid and, consequently, to achieve good quality and rapid MIBI images. In a limited number of patients (21 cases) SPECT was also performed. Limited surgery was planned in patients with evidence of single parathyroid lesions and with normal thyroid parameters, in the form of either unilateral or with mini-invasive surgery (91 cases). Patients with eco-scintigraphic evidence of multiglandular parathyroid pathology or the coexistence of a nodular thyroid goitre, or in patients suffering from MEN or familial HPT, or lastly those with negative eco-scintigraphic results under-went more extensive surgery with bilateral exploration of the neck (52 cases). A single parathyroid lesion was diagnosed during surgery in 90 out of 91 patients undergoing planned unilateral or mini-invasive exploration of the neck. Therefore, in our experience, the predictive value of preoperative imaging as a mean of identifying single parathyroid lesions was 98.9% with a clear impact on the choice of conservative surgery. After the removal of the parathyroid to which preoperative imaging referred, it was only necessary in one patient to extend surgical exploration to the other side of the neck to remove another enlarged parathyroid owing to persistent high PTH. RESULTS: The sensitivity of scintigraphy and high-resolution neck ecotomography in pa-tients with a single adenoma was 94% and 83.7% respectively, whereas it was 76.9% and 64.5% respectively in the group of patients with multiglandular pathology. It is worth underlining that in all 31 patients with associated nodular thyroid pathology, the evaluation of thyroid scintigraphic imaging using 99mTc04 and high-resolution neck ecotomography enabled the preoperative diagnosis of thyroid pathology, therefore guiding the surgeon towards more extensive surgery. SPECT enabled the parathyroid adenoma to be correctly localised in a deep site in 5 patients, in the neck in 3 cases and at the mediastinum in 2 patients, providing additional data that helped the surgeon to plan surgery. CONCLUSIONS: In conclusion, in our experience: a) an integrated diagnostic approach based on scintigraphy 99mTc04 & KCLO4/MIBI and high-resolution neck ecotomography was an extremely accurate mean of identifying patients with single parathyroid lesions before surgery, enabling them to undergo limited surgery, b) scintigraphy with a dual tracer might be the elective methods for studying patients with HPT because it allows the contemporary diagnosis of possible thyroid diseases. This aspect is extremely important in geographical areas with a high predominance of nodular thyroid pathology, c) SPECT scintigraphic analysis may be useful in some patients with suspected parathyroid adenoma localised in a deep seat, allowing a more precise identification of the latter and better surgical planning.

Role of scintigraphy with tumor-seeking agents in the diagnosis and preoperative staging of malignant thyroid nodules.

The commonly used procedure for the diagnosis of thyroid nodule malignancy is based on high resolution thyroid ultrasonography (US) combined with US-guided fine needle aspiration cytology (FNAC). The other imaging procedures have a limited role in malignancy diagnosis. However, nuclear medicine procedures, particularly scintigraphy with tumor-seeking agents such as 201-thallium (201-TI), 99mTc-methoxy-isobutyl-isonitrile (99mTc-MIBI) and 99mTc-tetrofosmin may play an important role in the differential diagnosis between benign and malignant thyroid nodules in cases of non-diagnostic or inadequate FNAC. This type of scintigraphy can also be used in the follow-up of patients with cytologically 'high'-risk thyroid nodules such as Hurtle cell adenomas and follicular adenomas. Furthermore, scans with tumor-seeking agents can be helpful in determining the preoperative staging of thyroid carcinoma patients with locally advanced disease, and in accurately evaluating the extent, and consequently, the surgical management of the disease.

Nuclear medicine imaging procedures in differentiated thyroid carcinoma patients with negative iodine scan.

Radioiodine treatment following surgery is an effective therapy in differentiated thyroid carcinoma (DTC) patients. However, in DTC patients with metastases characterized by very low or absent iodine uptake, total thyroidectomy and radical loco-regional lymphoadenectomy is the only effective therapeutic approach. In the present article, we have discussed the most recently available nuclear medicine techniques utilized for the detection of DTC metastases that have lost the capacity to trap radioiodine. A review of the data published in the literature has been presented, and a comparative analysis made of the results obtained by other imaging modalities such as high resolution neck ultrasonography (US), computed tomography (CT) and magnetic resonance imaging (MRI). In our experience, the most sensitive and accurate imaging procedure is represented by the combination of neck US and whole body 99mTc-methoxy-isobutylisonitrile (99mTc-MIBI) scintigraphy; this combination might be proposed as a first-line diagnostic approach in DTC patients with increased serum thyroglobulin (Tg) levels and negative high dose 131I scans.

Parathyroid imaging with pertechnetate plus perchlorate/MIBI subtraction scintigraphy: a fast and effective technique.

We set up a modified technetium-99m (Tc-99m) pertechnetate/Tc-99m MIBI (Tc-MIBI) subtraction scintigraphy for parathyroid imaging by introducing the use of potassium perchlorate (KCLO4). Initially, the effect of KCLO4 on technetium thyroid wash-out was evaluated in five healthy volunteers: 40-minute dynamic studies of the thyroid were obtained 20 minutes after the injection of technetium 150 MBq (4 mCi), both in baseline conditions and after the oral administration of 400 mg KCLO4. After an average latency time of 10.5 minutes, KCLO4 administration resulted in fast and relevant technetium thyroid wash-out with a mean half-time of 16.2 minutes (the half-time was 142.8 minutes in baseline conditions), and a 40-minute reduction of thyroid activity of 78% (it was 14% in baseline conditions). Based on these findings, a new Tc-MIBI subtraction procedure was established as follows: 1) 150 MBq technetium (4 mCi) injection; 2) 400 mg KCLO4 administered orally; 3) patient neck immobilization; 4) acquisition of a 5-minute technetium thyroid scan; 5) 500 MBq MIBI (13.5 mCi) injection; 6) acquisition of a sequence of seven MIBI images, each lasting 5 minutes; and 7) processing (image realignment when necessary, background subtraction, normalization of MIBI images to the maximum pixel count of the technetium image, and subtraction of the technetium image from the MIBI images). In addition, high-resolution neck ultrasound (US) was performed in all cases on the same day as the scintigraphic evaluation. Eighteen consecutive patients with primary hyperparathyroidism were enrolled in the study. Tc-MIBI scintigraphy revealed a single adenoma in all cases and US showed this finding in 15 of 18 cases (83.3%). Furthermore, in three patients, a thyroid nodule associated with hyperparathyroidism was detected by technetium thyroid scans and neck US. In all patients, the parathyroid adenoma was easily identified on both the 20- to 40-minute MIBI and subtracted (MIBI-Tc) images. Regarding the scintigraphic parameters, no difference was found between parathyroid adenomas located in the region of the thyroid bed or in ectopic sites and in parathyroid adenomas with a retrothyroid location. Surgical findings confirmed the presence of a single parathyroid adenoma in all cases. In the three patients with a concomitant thyroid nodule, thyroid lobectomy was performed. These preliminary data suggest that 1) double-tracer subtraction scintigraphy, combined with neck US, appears to be the preferable preoperative imaging procedure in hyperparathyroidism patients with concomitant thyroid nodular disease, 2) in the Tc-MIBI parathyroid scan, the use of KCLO4 results in a rapid and relevant technetium thyroid clearance, improving the quality of MIBI images and making the visualization of parathyroid adenomas, particularly those located behind the thyroid gland, easier.

Clinical approach in patients with metastatic differentiated thyroid carcinoma and negative 131I whole body scintigraphy: importance of 99mTc MIBI scan combined with high resolution neck ultrasonography.

AIMS AND BACKGROUND: The aim of this study was to define the clinical impact of MIBI scan combined with neck ultrasonography on the detection of metastates in differentiated thyroid carcinoma (DTC) patients with elevated serum Tg levels but negative 131I scan (non-functioning DTC). METHODS AND STUDY DESIGN: Eighty-two patients with non-functioning DTC, 19 patients with 131I-positive metastases (functioning DTC), and 24 DTC patients who were disease free after therapy (no cancer patients) were enrolled. 131I scan was performed after administration of low diagnostic and high therapeutic tracer doses. Early and delayed images were obtained after MIBI injection. Neck-chest CT scan and/or MRI were also performed in patients with non-functioning DTC. RESULTS: In the group of non-functioning DTC patients, metastatic foci were detected in 71/82 cases: in the cervical lymph nodes in 51 cases (sensitivity 94.1% with MIBI, 90.2% with US, 35.3% with CT/MRI), mediastinal lymph nodes in 31 cases (sensitivity 100% with MIBI, 58% with CT/MRI), lungs in 8 cases (sensitivity 100% with both MIBI and CT/MRI), and bone in 2 cases (sensitivity 50% with MIBI, 100% with MDP bone scan). Among the 19 patients with functioning DTC a close relationship between MIBI and 131I findings was observed. As regards the 24 tumor-free patients, MIBI was correctly negative in all cases, while US visualized enlarged cervical lymph nodes that were suspected to be neoplastic but proved to be inflammatory lesions at cytology in three patients. CONCLUSIONS: On the basis of these data, MIBI scan combined with neck US could be proposed as a first-line diagnostic imaging modality in the follow-up of DTC patients with elevated serum Tg levels and negative 131I scan.

Renal impairment in chronic cigarette smokers.

To determine the effect of chronic cigarette smoking on renal function, a cross-sectional study was carried out with 30 subjects who had no known vascular disease risk factor other than cigarette smoking, and 24 age- and sex-matched controls without any vascular risk factor including cigarette smoking. Renal function by radionuclide studies of renal plasma flow, GFR, and plasma endothelin-1 concentration was determined. Compared with nonsmokers, smokers had a renal function impairment characterized by a normal GFR and a significant reduction in renal plasma flow as reflected by MAG3 clearance (199.20 +/- 58.85 ml/min per 1.73 m2 versus 256.54 +/- 60.14 ml/min per 1.73 m2; t = 3.52, P < 0.001). MAG3 clearance was significantly correlated with age and smoking. The renal dysfunction was associated with an increase in plasma endothelin-1 concentration (21.56 +/- 1.15 pmol/L versus 25.01 +/- 3.21 pmol/L; t = 5.00, P < 0.001). Former smokers as well had similar, although milder, abnormalities. In conclusion, cigarette smokers manifest an impairment of renal function, suggesting that smoke may have a detrimental effect on renal function.

Ultrarapid high-dose course of prophylactic cranial irradiation in small-cell lung cancer: evaluation of late neurologic morbidity in 16 long-term survivors.

Despite the reduction in the incidence of brain metastases following prophylactic cranial irradiation (PCI) in patients with small-cell lung cancer (SCLC), the use of this modality is still controversial due to the lack of improvement in survival and the appearance of neurotoxicity in long-term survivors. Moreover, the optimum dose, fraction size, and timing are not known. From 1980 to 1988, 70 patients with limited stage SCLC underwent PCI after or during multimodality treatment of their primary tumor. Most of these patients (75.7%) received an unconventional ultrarapid high-dose course of 17 Gy in two fractions over 3 days. Long-term (range 60-138 months) survivors (n = 16) were invited to have a complete neurological evaluation including computed cranial tomography (CCT), 99mTc-HMPAO single photon emission computerized tomography (SPECT) scan, electroencephalography (EEG), magnetic resonance imaging (MRI), and neuropsychometry. Delayed neurologic complications or psychometric impairment was observed in 46% of patients. One or more abnormalities were detected by CCT in all patients, and the presence of neurologic complications seemed to correlate with periventricular and subcortical white matter changes. A strong correlation was found between CCT and SPECT periventricular white matter changes. Although the incidence of late neurologic toxicity following this rapid course of irradiation was high, clinical findings were less severe than expected, and all the patients were capable of self-care.

Different features of pulmonary metastases in differentiated thyroid cancer: natural history and multivariate statistical analysis of prognostic variables.

We studied 134 patients with differentiated thyroid cancer and pulmonary metastases. All were treated with total or near total thyroidectomy, radioiodine and L-thyroxine. The prognostic value of the following variables in three groups of patients were evaluated by univariate and multivariate analysis: age at diagnosis, sex, histologic type, tumor extension, cervical lymph node metastases, mediastinic metastases, presence of metastases in distant sites other than lungs (multiple distant metastases) and morphological (chest x-rays) and functional (131I uptake) features of lung metastases. Univariate analysis identified patient age (p < 0.0001), morphological and functional features of lung metastases (p < 0.0001), presence of multiple distant metastases (p < 0.0001) and histologic type (p = 0.04) as significant prognostic factors. Multivariate analysis showed only morphological (p = 0.0014) and functional (p < 0.0001) features of lung metastases and the presence of multiple distant metastases (p = 0.01) as significant and independent variables. The data show that early (pre-radiological) scintigraphic diagnosis and 131I therapy of lung metastases appear to be the most important elements in obtaining both a significant improvement in survival rate and a prolonged disease-free time interval in these patients.

Pregnancy after high therapeutic doses of iodine-131 in differentiated thyroid cancer: potential risks and recommendations.

Seventy female patients who had been treated with high doses of iodine-131 for differentiated thyroid cancer (DTC) and who had a subsequent pregnancy were evaluated. The total 131I dose ranged from 1.85 to 16.55 GBq (mean +/- SD = 4.39 +/- 25.20 GBq). Age at first therapy ranged from 15 to 36 years (mean +/- SD = 24.3 +/- 5.0 years) and the interval from 131I therapy to pregnancy varied from 2 to 10 years (mean +/- SD = 5.3 +/- 2.8 years). The estimated radiation dose to the gonads ranged from 10 to 63 cGy (mean +/- SD = 24.0 +/- 13.5 cGy). All patients were treated with L-thyroxine at doses capable of suppressing thyroid-stimulating hormone. Seventy-three children were followed-up and seven pregnancies are still in progress. One child was affected by Fallot's trilogy and three had a low birth weight through with subsequent normal growth; the others were healthy with subsequent normal growth. No newborn with clinical or biochemical thyroid dysfunctions was found. Two spontaneous abortions during the second month of pregnancy were recorded. One of two patients in question subsequently had two healthy children. On the basis of these data, previous administration of high 131I doses does not appear to be a valid reason for dissuading young female DTC patients from considering pregnancy. However, patients should be advised to avoid pregnancy after 131I administration for a period sufficient to ensure complete elimination of the radionuclide and to permit confirmation of complete disease remission, i.e. at least 1 year in our opinion.

Differentiated thyroid carcinoma in the elderly.

Prognostic factors and therapeutic results in a group of 268 patients with differentiated thyroid cancer (DTC) aged over 60 years are reported. These cases were selected from a total of 1457 DTC-patients seen at our Center from 1967 to 1987. All elderly patients underwent total thyroidectomy, and were treated with 131I therapy and suppressive hormonal therapy. Moreover, external radiotherapy was performed in 20% and chemotherapy in 3.8% of all cases. Follow-up included periodical clinical examination, serum Thyroglobulin (Tg) determination, 131I total body scan (TBS), and echographic and radiologic survey. Several unfavorable prognostic factors were identified in elderly patients with DTC. In comparison with data obtained in a group of patients under 60 years of age, 1) the follicular histologic type was increased, papillary/follicular ratio was 1.1 vs 2.6; 2) the F/M ratio was decreased, 1.5 vs 2.8 for papillary tumors, and 1.7 vs 3.6 for follicular tumors; 3) the rate of cases with local extrathyroid tumor growth and distant metastases was higher, and 4) rates of metastases to bone and metastases with low 131I uptake were increased. Moreover, the 10-year survival rate in elderly patients with lymph node and distant metastases was significantly reduced compared to younger patients, both for papillary and follicular cancer. The finding of detectable serum Tg levels was well correlated with the presence of metastatic disease. Moreover, Tg sensitivity was higher than TBS in showing the presence of metastatic foci. DTC in elderly people must be considered an aggressive tumor both for follicular and papillary histologic types. A radical approach is recommended: total thyroidectomy, 131I administration, and suppressive hormonal therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Distant metastases in differentiated thyroid cancer: long-term results of radioiodine treatment and statistical analysis of prognostic factors in 214 patients.

Long-term results and statistical analysis of prognostic factors in a series of 214 patients with distant metastases from differentiated thyroid cancer (DTC) are reported here. These 214 were part of a total series of 1457 patients with DTC referred to our center from 1967 to 1987. All patients underwent surgery and 131-I therapy and were treated with TSH suppressive doses of thyroid hormones. After a mean follow-up of 7.3 years including clinical, scintigraphic, radiological and laboratory investigations, 24.4% of patients were alive without disease, 36.5% alive with disease, 1.8% dead without disease and 37.3% dead with disease. One of the main factors influencing the survival in our series was 131-I uptake (RIU) by metastatic tissue. No case of complete remission of disease was observed among patients with nonfunctioning metastases. Another important factor was the site of metastases, patients with bone metastases having the worst prognosis. The patient's age at diagnosis represented another important factor for survival; patients over 40 years, particularly those over 60 years had a bad prognosis. A clear interrelation was found among the factors advanced age, nonfunctioning metastases and bone metastases. Patients with these last clinical features were considered to be at high risk and generally had a fatal outcome. Another significant prognostic factor revealed by univariate analysis was the histologic type. Patients with follicular tumor showed a poorer prognosis in comparison to papillary tumor. When multivariate analysis was applied, the factors age at diagnosis, site of metastases and RIU proved to have a significant influence on survival, but not the histologic type. Lastly, the relative rate of males was higher in the group of patients with metastases in comparison to the whole series of DTC patients. Despite this, the factor sex did not influence survival.

[Natural history of cancer of the breast. Probability of developing bone metastases]. / Storia naturale del cancro della mammella. Probabilità di sviluppo di metastasi ossee.

The incidence of bone metastases in 448 patients with breast cancer was evaluated. 374 out of 448 cases showed negative bone scan at initial clinical staging and were followed up during a period of at least 5 years with serial bone scans. The results of bone scans were compared on the basis of clinical stage (according to the International UICC classification), of lymph node involvement (groups N0, N + ) and of complementary therapy after surgery (radiotherapy v/s hormone-chemotherapy). Cumulative probability of bone metastases in breast cancer showed a linear trend with annual mean rate of 5% (1st yr 2%; 2nd yr 8%; 3rd yr 15%; 4th yr 22%; 5th yr 29%; 10th yr 59%). Statistical analysis in different clinical stages showed mild difference not statistically significant, neither in lymph node involvement (NO v/s N + ) nor in complementary therapy (radiotherapy v/s hormone-chemotherapy).