Giulia Anna Follacchio

Prostate-Specific Antigen Flare Phenomenon During 223Ra-Dichloride Treatment for Bone Metastatic Castration-Resistant Prostate Cancer: A Case Report

Clinical Practice Points Ra-dichloride is an alpha-emitting radionuclide recently approved for treatment of castration-resistant prostate cancer (CRPC) patients with symptomatic bone metastases. In this specific therapeutic setting, prostate-specific antigen (PSA) is not an objective biomarker in assessing Ra efficacy. We present a 79-year-old patient who was affected by CRPC and symptomatic bone metastases enrolled in the Ra-dichloride Early Access Program who presented a relevant rise in PSA levels after the fifth Ra administration. No radiological signs of disease progression were found, so this event was recognized as a PSA flare phenomenon and the last Ra infusion was administered. In clinical practice, PSA flare in the course of Ra treatment can be misinterpreted as a therapeutic failure with early withdrawal from a potentially effective therapy. During Ra treatment, PSA flare can be explained as a direct consequence of Ra cytotoxic effect on cancer cells. Further analysis should be conducted on large cohort to evaluate the clinical significance of PSA flare phenomenon during Ra treatment.

A modified sentinel node and occult lesion localization (SNOLL) technique in non-palpable breast cancer: a pilot study.

BackgroundThe spread of mammographic screening programs has allowed an increasing amount of early breast cancer diagnosis. A modern approach to non-palpable breast lesions requires an accurate intraoperative localization, in order to achieve a complete surgical resection. In addiction, the assessment of lymph node status is mandatory as it represents a major prognostic factor in these patients. The aim of this study is to evaluate the reliability of a modified technical approach using a single nanocolloidal radiotracer to localize both sentinel node and breast occult lesion.MethodsTwenty-five patients with a single non-palpable breast lesions and clinically negative axilla were enrolled. In the same day of surgery, patients underwent intratumoral and peritumoral administration of 99mTc-labeled nanocolloid tracer under sonographic guidance. A lymphoscintigraphy was performed to localize the sentinel lymph node and its cutaneous projection was marked on the skin in order to guide the surgeon to an optimal incision. During surgery an hand-held gamma-detection probe was used to select the best surgical access route and to guide localization of both occult breast lesion and sentinel lymph node. After specimen excision, the surgical field was checked with the gamma-probe to verify the absence of residual sources of significant radioactivity, thereby ensuring a radical treatment in a single surgical session and minimizing normal tissue excision.ResultsBoth targeted breast lesion and sentinel lymph node were localized and removed at the first attempt in every patients and histopathological diagnosis of malignancy was confirmed in 25/26 samples. Non-palpable lesions were included within the surgical margins in all patients and in all samples surgical margins were free from neoplastic infiltration thus avoiding any further reintervention. Only two patients showed metastatic involvement of sentinel lymph node.ConclusionsThe modified sentinel node and occult lesion localization (SNOLL) technique performed with a single injection of nanocolloidal radiotracer has shown an excellent intraoperative identification rate of both non-palpable lesion and sentinel lymph node. This procedure offers, as opposed to standard techniques, an accurate, simple and reliable approach to the management of non-palpable breast cancer.

99mTc-labeled White Blood Cell Scan as a Guide to Open Biopsy in the Management of Hip and Knee Prosthesis Infection: Preliminary Results

OBJECTIVE The aim of the present prospective study was to evaluate the usefulness of labeled leukocyte scan as a guide to open biopsy for the management of hip and knee prosthesis infection in patients without loosening of orthopedic device. METHODS Twenty-six patients with suspected hip (24) and knee (2) prosthesis infection underwent routine analysis of blood, plain radiography and 99mTc-HMPAO labelled leukocyte scan (WBCS). On these basis, patients were subdivided in the following groups: bone infection without loosening (n°=14), septic loosening (n°=8), superficial infection (n°=2), no infection (n°=2). Patients with septic loosening underwent empirical antibiotic therapy in order to avoid two-stage reimplantation. When the medical treatment was effective patients were submitted to one-stage operation. Patients without loosening of prosthesis but positive WBCS results underwent open biopsy: bone samples and periprosthetic tissues were taken from the regions showing pathological leukocyte uptake at the scan. Samples were submitted to microbiological examination and antibiotic treatments were undertaken in cases of bacterial growth. A 24-months clinical and instrumental follow-up was carried out in all patients. RESULTS WBCS showed 22 patients affected by bone infection, 2 by superficial infection and 2 not infected. Height out of the 22 patients affected by deep infection had a septic loosening. In these cases, the medical treatment was inadequate in 6 patients and effective in 2. Fourteen patients with bone infection without loosening were submitted to open biopsy: in 9 cases a complete remission of the disease was found. Two patients, without infection, underwent single-stage surgery for mechanical problems. Superficial infection was assessed and successfully treated in 2 patients. CONCLUSION The obtained results indicate that a multidisciplinary approach to infection of orthopedic prostheses, characterized by the combined use of open biopsy, WBC, and microbiological examination, produced positive outcome in 9 out of 14 patients.

223 Ra-dichloride therapy in an elderly bone metastatic castration-resistant prostate cancer patient: a case report presentation and comparison with existing literature

disability, leading to a reduced quality of life. Moreover, bone metastases in patients with CRPC are independently associated with increased mortality. In consideration of the needs of older patient population, the optimal approach of elderly PC patients poses a particular clinical challenge. Over last years, several novel drugs for CRPC have been introduced, such as the new taxan agent cabazitaxel, immunotherapy (sipuleucel-T), RANK-L inhibitor denosumab, androgen biosynthesis inhibitors (abiraterone acetate), and androgen receptor antagonists (enzalutamide). These antitumoral agents have changed therapeutic management of CRPC patients, although there is still the need to define an appropriate sequencing for their application to maximize patient benefit and minimize costs. In this evolving scenario, a first-in-class alpha-emitting radionuclide, 223Radichloride, has been recently approved for the treatment of CRPC patients with symptomatic bone metastases and no known visceral disease. FDA approval of 223Ra came in May 2013 as a result of the findings of the international, randomized, double-blind alpharadin in symptomatic prostate cancer (ALSYMPCA) Phase III trial that evaluated efficacy on overall survival of 223Ra treatment versus placebo in patients with mCRPC [2]. Thanks to its analogy to calcium, 223Ra targets areas of high osteoblastic activity such as sites of bone metastases, delivering high-energy short-range alpha particle radiation. Alpha particles are characterized by a high-linear energy transfer (LET) to surrounding tissues delivered in a short path (<100 μm), inducing double-stranded breaks in DNA with a local cytotoxic effect that is, notably, independent from dose rate, oxygen level, and cell cycle status [3]. The short penetration range of alpha particles (approximately corresponding to 2–10 cell diameters) determines a low dose of radiation delivered to normal bone-marrow cell population, with minimal hematological adverse effects. Results

Ra-223 dichloride management in a Nuclear Medicine Unit: experience of a referral institution

Prostate cancer is the most common male cancer and one of the leading causes of cancer-related morbidity and death [1]. In prostate cancer natural history, approximately 10% of patients will develop a castration-resistant disease, with a median survival of 2 years [2]. The majority of patients with metastatic CastrationResistant Prostate Cancer (mCRPC) has a radiological evidence of bone metastases, which are the main cause of pain and disability, leading to a reduced quality of life. Moreover, in patients with mCRPC bone metastases are independently associated to mortality [3].