Targeted Alpha Therapy with Thorium-227.

Targeted alpha therapy (TAT) can deliver high localized burden of radiation selectively to cancer cells as well as the tumor microenvironment, while minimizing toxicity to normal surrounding cell. Radium-223 (223Ra), the first-in-class α-emitter approved for bone metastatic castration-resistant prostate cancer has shown the ability to prolong patient survival. Targeted Thorium-227 (227Th) conjugates represent a new class of therapeutic radiopharmaceuticals for TAT. They are comprised of the α-emitter 227Th complexed to a chelator conjugated to a tumor-targeting monoclonal antibody. In this review, the authors will focus out interest on this therapeutic agent. In recent studies 227Th-labeled radioimmunoconjugates showed a relevant stability both in serum and vivo conditions with a significant antigen-dependent inhibition of cell growth. Unlike 223Ra, the parent radionuclide 227Th can form highly stable chelator complexes and is therefore amenable to targeted radioimmunotherapy. The authors discuss the future potential role of 227Th TAT in the treatment of several solid as well as hematologic malignancies.

Radium-223 in patients with metastatic castration-resistant prostate cancer: Efficacy and safety in clinical practice.

Radium-223 has improved overall survival (OS) and reduced symptomatic skeletal events (SSE) in patients with metastatic castration-resistant prostate cancer (mCRPC) and bone metastases (ALSYMPCA trial). Our aim was to assess clinical and biochemical factors related to survival, safety and survival outcomes of Radium-223 in a clinical practice setting. We retrospectively analysed 32 mCRPC patients treated with Radium-223, assessing bone scan, pain reduction, alkaline phosphatase (ALP) and prostate-specific antigen (PSA) response (≥30% reduction). At scintigraphic assessment, 41% had partial response with a disease control rate of 91%; 56% had ALP response and 25% had PSA response; 41% had pain reduction with pain control of 72%. Scintigraphic response and stability were correlated with longer median progression-free survival (mPFS) (13 and 12 vs. 6 months; P=0.002) and mOS (16 and 12 vs. 6 months; P=0.003). ALP response was associated with longer mPFS (13 vs. 12 months; P=0.2) and mOS (16 vs. 12 months; P=0.2). PSA response was associated with longer mPFS (13 vs. 12 months; P=0.02), whereas mOS could not be computed. Pain response and stability were associated with survival benefit according to mPFS (13 and 12 vs. 9 months) and mOS (both 16 vs. 12 months) without statistical significance. Baseline ALP <220 UI/l, Eastern Cooperative Oncology Group (ECOG) performance status 0 and absence of previous chemotherapy correlated with statistically significantly longer survival outcomes. Skeletal-related events (SRE) occurred in three patients and median time to first SRE was 9.5 months, mPFS was 12 months and mOS 14 months. G3-G4 toxicities developed in 16% of patients. Our results are in line with those reported in the pivotal trial and in other retrospective studies. In conclusion, Radium-223 was associated with high scintigraphic, biochemical and pain response rates and was tolerated well by most patients. Response to Radium-223 and better baseline factors correlated to longer survival in clinical practice experience as in the clinical trial setting.

An unusual orbital metastasis of breast cancer.

In this paper we report the clinical case of a 84 year old female patient with a history of breast cancer diagnosed 14 years before, treated only with hormone therapy for 10 years and with subsequent follow-up oncology which always demonstrated negative results. 14 years after the first diagnosis, the patient presented with an increase in mass markers (CEA), and progressive symptoms of the right eye (diplopia). A CT scan and an MRI of the orbits confirmed the presence of an expansive neoplastic formation of the right orbit of 16 × 9 mm. The orbital metastases are rare locations of metastatic breast cancer which pose problems of differential diagnosis and require prompt and multimodal treatment (chemotherapy, hormone therapy, radiation therapy) aimed at improving the quality of life of the patient.

Urokinase expression in course of benign and malignant mammary lesions: comparison between nodular and healthy tissues.

PURPOSE: Increased expression of urokinase (uPA), a member of the serine protease family, is an effector of metastatic cascade and has been reported in various malignancies, including breast cancer. uPA overexpression in cancer tissues was correlated with a more aggressive phenotype and it is considered a strong and independent unfavorable prognostic factor in breast cancer. METHODS: Using real-time PCR assay, we analyzed uPA expression of malignant and benign breast nodular lesions versus healthy tissues (normal breast and lymphocytes). RESULTS: We found that besides breast cancer nodule, normal mammary gland and lymphocytes overexpressed uPA too. Tissues obtained from women with benign lesions expressed homogeneous and lower uPA. CONCLUSIONS: In conclusion, although uPA overexpression is typical of cancer tissues, it could be considered as a feature of the whole organism affected by cancer. On the basis of these first results, uPA could be considered for further studies as a possible useful therapeutic target in breast cancer.

[Quadrantectomy and removal of the sentinel lymph node under local anaesthesia in the day hospital setting]. / Quadrantectomia e asportazione del linfonodo sentinella in anestesia locale in day hospital.

In recent years, breast carcinoma diagnostics and therapy have evolved very considerably, allowing conservative surgery in most cases. These kinds of major operations have been greatly simplified since the introduction of the sentinel lymph node approach, with the possibility of a day surgery operation under local anaesthesia. The aim of this study, after thorough analysis of the axillary lymph nodes with ultrasound and cytological examinations, was to assess whether it would be possible to distinguish between negative and metastatic lymph nodes and whether the operation could be performed under local anaesthesia without hospitalisation. From January 2005 to January 2007, 54 breast carcinoma patients with negative axillary lymph nodes (after ultrasound examination) had a quadrantectomy and sentinel lymph node removal under local anaesthesia together with sedation where appropriate. Eight patients who presented micrometastases or isolated tumour cells in the sentinel lymph node underwent a subsequent lymphadenectomy. Our data show that, thanks to thorough analysis of the axillary cavity, it may be possible to use the sentinel lymph node approach with a good chance of the patient remaining free of distant metastases and of operating under local anaesthesia.

[Diagnosis and treatment of fibroadenoma of the breast: 20 years' experience]. / Diagnosi e trattamento del fibroadenoma della mammella: 20 anni di esperienza.

The diagnostic differentiation of breast lesions is very important because of the frequency with which they occur. Though fibroadenoma is easy to diagnose, some cases prove really hard to distinguish. Therefore, various methods have been suggested both for diagnosis and therapy, but no common approach has been achieved to date. We report our experience with 1350 cases diagnosed over a twenty-year period. The diagnosis was made on the basis of a diagnostic protocol drawn up over the years where cytology is of primary importance. With regard to therapy, we decide to operate when the cytological findings prompt the need for a histological examination of the lesion. Moreover, we operate on those cases where either an increase in size or a morphological change of the lesion has taken place. Histological examinations were carried out in 420 cases out of 1350 and only one of these cases turned out to be a carcinoma. As a result, the 0.24% error in the diagnosis can be considered irrelevant. In spite of the different therapies suggested (cryoablation, laser hyperthermia, i.a.), we believe that surgical treatment with local anaesthetic is the most suitable solution in those cases requiring treatment. Obviously, the diagnosis has to be accurate and made by surgeons with appropriate expertise. When the diagnosis is certain and the conditions of the lesion are stable, the best policy seems to be periodic follow-up.

One-day surgery in a series of 150 breast cancer patients: efficacy and cost-benefit analysis.

Financing health-care expenditure has become increasingly more difficult. Considering the high frequency of breast cancer, which affects one million women in the world each year, the reductions of medical expenditure for the treatment of this disease is highly desirable within the limits of medical efficiency and safety. One hundred and fifty patients with carcinoma of the breast underwent surgery in our department with one-day hospitalization. Patients were discharged with the drainage tube still in place and later treated in the out-patient setting, for dressing and checking the wound, and removing the stitches and drainage tube. Four cases of seroma were registered, all resolved by aspiration of the fluid in a single visit, 1 case of haematoma and 1 case of infection. Patients who underwent this short-stay treatment were amply satisfied. Our experience demonstrates that this type of treatment is both safe and effective. Moreover, it provides considerable benefits in terms of national health-care costs as well as being psychologically better for the patients.

[Day surgery in a multidisciplinary breast unit]. / Day surgery nell'unità multidisciplinare di senologia.

The most recent studies on breast surgery have led us to radio-guided surgery which enables us to identify the sentinel lymph node and thus to remove just a single lymph node. As a result, we are moving in the direction of an increasingly conservative surgical technique which may be carried out in the day surgery setting. This kind of surgery requires both an extremely accurate and prompt diagnosis and a multidisciplinary breast unit, inasmuch as only the collaboration and teamwork of highly qualified staff are capable of furnishing a rapid, accurate diagnosis; in addition, during the operation it may be necessary to perform x-rays or ultrasonography on the surgical specimen. Obviously, nuclear medicine is essential for radio-guided surgery. We report here on our experience with 36,000 women with 1,147 carcinomas whose diameters were less than or equal to 2 cm in 78.64% of the cases, with the possibility of performing conservative surgery in such cases. Moreover, by way of confirmation of the good diagnostic accuracy, we report our findings in 954 lesions operated on under local anaesthesia, because they were presumed to be most probably or definitely benign, but which tended to increase in volume. During the final histological examination only 10 of these 954 lesions turned out to be malignant, with only a 1.05% incidence of diagnostic error.