A NTCP approach for estimating the outcome in radioiodine treatment of hyperthyroidism.

Radioiodine has been in use for over 60 years as a treatment for hyperthyroidism. Major changes in clinical practice have led to accurate dosimetry capable of avoiding the risks of adverse effects and the optimization of the treatment. The aim of this study was to test the capability of a radiobiological model, based on normal tissue complication probability (NTCP), to predict the outcome after oral therapeutic 131I administration. Following dosimetric study, 79 patients underwent treatment for hyperthyroidism using radioiodine and then 67 had at least a one-year follow up. The delivered dose was calculated using the MIRD formula, taking into account the measured maximum uptake of administered iodine transferred to the thyroid, U0, and the effective clearance rate, Teff and target mass. The dose was converted to normalized total dose delivered at 2 Gy per fraction (NTD2). Furthermore, the method to take into account the reduction of the mass of the gland during radioiodine therapy was also applied. The clinical outcome and dosimetric parameters were analyzed in order to study the dose-response relationship for hypothyroidism. The TD50 and m parameters of the NTCP model approach were then estimated using the likelihood method. The TD50, expressed as NTD2, resulted in 60 Gy (95% C.I.: 45-75 Gy) and 96 Gy (95% C.I.: 86-109 Gy) for patients affected by Graves or autonomous/multinodular disease, respectively. This supports the clinical evidence that Graves' disease should be characterized by more radiosensitive cells compared to autonomous nodules. The m parameter for all patients was 0.27 (95% C.I.: 0.22-0.36). These parameters were compared with those reported in the literature for hypothyroidism induced after external beam radiotherapy. The NTCP model correctly predicted the clinical outcome after the therapeutic administration of radioiodine in our series.

Radionuclide therapy with bone seeking radionuclides in palliation of painful bone metastases.

Radionuclide therapy with bone seeking radiopharmaceuticals is one of the oldest interventions in nuclear medicine and has been now in use for many years as an effective method of palliating painful bone metastases. Clinical indications have slowly but progressively increased starting from end-stage prostate cancer with diffuse painful bone metastases to earlier stages of several cancers with only microinvolvement of the skeleton. Several newer bone seeking agents for therapeutic applications have been developed during the last 10 years. A large body of specific literature is now available, but only a few well designed clinical trials can be selected to obtain evidence-based guidelines. This study summarizes the therapeutic effects of the three commercially available radiopharmaceuticals, the current indication for their use as supported by the most rigorous literature studies and the original contributions of the "Regina Elena" ten-year experience. Innovative strategies and future research questions are also breafly addressed.

Metastatic bone pain palliation with 89-Sr and 186-Re-HEDP in breast cancer patients.

AIM: The study evaluates the therapeutic efficacy of Strontium-89-chloride (89Sr) and 186Re-1,1-hydroxyethylidene diphosphonate (186Re-HEDP) in the palliation of painful bone metastases from breast cancer. PATIENTS AND METHODS: Fifty patients with painful multifocal bone metastases from breast cancer entered the study and were randomized into two groups according to the radiopharmaceutical used: 148 MBq 89Sr i.v. (Group A: 25 patients) and 1406 MBq 186Re-HEDP i.v. (Group B: 25 patients). Pain palliation was evaluated on the basis of the Wisconsin pain test improvement at two months and response was graded as complete, partial, minimal or absent. Hematological toxicity and side effects were reported according to WHO guidelines. RESULTS: The global response rate was 84% (21/25) for 89Sr and 92% (23/25) for 186Re-HEDP, respectively. The onset of pain palliation appeared significantly earlier in Group B (p < 0.0001). The duration of pain relief ranged from two months to 14 months (mean of 125 days with a median value of 120 days) in Group A and from one month to 12 months (mean of 107 days with a median value of 60 days) in Group B (p = 0.39). A moderate hematological toxicity was apparent in both groups. Platelet and white blood cell counts returned to baseline levels within 12 weeks after 89Sr administration and 6 weeks after 186Re-HEDP administration (p < 0.01). CONCLUSIONS: Both 89Sr and 186Re-HEDP are effective and safe in bone pain palliation in breast cancer with the latter showing a significantly faster onset of pain relief.

Ultrasound in the detection of breast cancer associated with isolated clustered microcalcifications, mammographically identified.

The purpose of this work was to evaluate the effectiveness of US scanning in detecting breast cancer associated with isolated clustered microcalcifications (MC) mammographically identified. 52 isolated clusters of MC mammographically detected underwent histological examination. In all cases, ultrasonographic of (US) and cytologic examinations were performed for the improved definition of the nature of the MC. Fine needle aspiration was performed under radiographical (Rx)-guidance, only in cases of US-negativity. Ultrasound detected a breast lesion in 31 cases, out of which 24 (77.4%) were found to be carcinomas (invasive in 87.5% of the cases). Out of the remaining 21 US-negative cases, 7 (33.3%) were malignant lesions (15% invasive). Statistical analysis demonstrated that US-positivity significantly correlated with the presence of malignant lesions (p < 0.001). US-examination should also be performed in cases of isolated clustered microcalcifications for a more accurate selection of cases requiring histological verification.

The integration of diagnostic tests and the role of outpatient surgery in the management of breast disease.

The aim of the earliest possible diagnosis of breast carcinoma achieved through the integration of clinical, mammographic, sonographic and cytologic data has determined an increased detection of breast lesions and a greater accuracy in their description. Nevertheless, the nature of some of these lesions cannot be well-defined because of their biological characteristics and their physical, radiological or cytological aspects. The need to obtain a definitive diagnosis in any case has given rise to a paradoxical increase in histologic examinations: in specific conditions and for certain kinds of lesions, outpatient surgery under local anesthesia could very well represent a supplementary tool in the diagnostic and therapeutic strategy for the management of breast lesions. The data here reported concern 397 breast lesions for which it was thought appropriate to complete the diagnostic procedure with the surgical excision on an outpatient basis under local anesthesia. Excluding the 3 breast lymphomas and the 19 loco-regional recurrences, for which the purpose of outpatient surgery was therapeutic, at the histologic examination 35% benign lesions, of which 91 associated with an increased risk of breast cancer, were found, as well as 11 in situ and 10 invasive carcinomas (false negatives), with a therapeutic option error of 2.5%. Now that one of the principal aims of public management is to put a check on health expenditures, outpatient surgery would contribute to obtaining the correct balance between proper management of breast lesions and low cost/effective ratio.

The role of cytology in differentiation of breast lesions.

The introduction of cytologic examination in to the diagnostic procedure has made it possible to define breast lesions better as early as the preoperative stage. However, there are interpretative problems depending on the nature of the lesions that make a histologic examination necessary. The cytology of nipple discharge or FNA of breast lesions would permit the best possible selection of the cases, indicating not only whether surgery is necessary, but also the basis on which it should be performed (outpatient under local anesthesia or inpatient under general anesthesia). The definitive histologic diagnosis of 447 cases submitted to surgery under general anesthesia and of 379 who were operated under local anesthesia has been correlated with the relative cytologic examination. The sensitivity and specificity of the cytologic examination are respectively 97.7% and 98.8%.

[Findings on an epidemic of human trichinelliasis verified in Italy]. / Indagini su un'epidemia di trichinellosi umana verificatasi in Italia.

The present article completes the information already given in previous papers (Mantovani et al., 1976; Bellani et al., 1977; Mantovani, 1978) and is connected with the research on the infection of horses by Pampiglione et al. (1978). In September 1975 an epidemic of Trichinellosis involving at least 89 people was reported at Bagnolo in Piano (Reggio Emilia). This present article describes the epidemiological investigations. In the introductory part, the Trichinellosis outbreaks are summarized which were reported in Italy during this century along with research on domestic and wild animals. The Bagnolo in Piano outbreak is described with special reference to: A) onset of the disease and symptoms; B) age and sex of the patients; C) serological tests; D) isolation of Trichinella and its classification as Trichinella nelsoni by S.N. Boev. In the epidemiological survey the following is reported: A) detection of the infection source, attributed to the meat from an imported horse; B) identification of the infection period; C) exclusion of possible adulterations; D) exclusion of possible infection sources, with the exception of horse meat; E) absence of Trichinella in domestic and synanthropic animals in the involved area. The Discussion and Conclusions stress that the outbreak presented some features in common with a similar outbreak in Paris. These features consisted of a series of conditions: 1) the exceptional infection of a horse, possibly by ingestion of an infected rodent; 2) the local habit of eating raw horse meat; 3) the occurrence of the outbreak in a Trichinella-free area, which required and permitted an accurate survey.