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Oligometastatic prostate cancer is an intermediate state between localized disease and widespread metastasis. Its biological and clinical peculiarities are still to be elucidated. New imaging techniques contribute to the detection of patients with oligometastatic disease. PET/CT scanning with prostate-specific membrane antigen can improve the selection of men with true early, low-volume oligometastatic disease, who are candidates for metastasis-directed therapy. Clinical studies demonstrated that androgen deprivation therapy can be delayed in oligometastatic patients with a low tumor burden, although no survival benefit has been demonstrated at present. This article presents available evidence on the treatment strategies for oligometastatic prostate cancer.

Background The use of intra-fractional monitoring and correction of prostate position with the Image Guided Radio Therapy (IGRT) system can increase the spatial accuracy of dose delivery. Clarity is a system used for intrafraction prostate-motion management, it provides a real-time visualization of prostate with a transperineal ultrasound. The aim of this study was to evaluate the use of Clarity-IGRT on proper intrafraction alignment and monitoring, its impact on Planning Tumor Volume margin and on urinary and rectal toxicity in elderly patients not eligible for surgery. Patients and methods Twenty-five elderly prostate cancer patients, median age=75 years (range=75-90 years) were treated with Volumetric Radiotherapy and Clarity-IGRT using 3 different schemes: A) 64.5/72 Gray (Gy) in 30 fractions on prostate and seminal vesicles (6 patients); B) 35 Gy in 5 fractions on prostate and seminal vesicles (12 patients); C): 35 Gy in 5 fractions on prostate (7 patients). Ultrasound identification of the overlapped structures to the detected ones during simulation has been used in each session. A specific software calculates direction and entity of necessary shift to obtain the perfect match. The average misalignment in the three-dimensional space has been determined and shown in a box-plot. Results All patients completed treatment with mild-moderate toxicity. During treatment, genitourinary toxicity was 32% Grade 1; 4% Grade 2, rectal was 4% Grade 1. At follow-up of 3 months, genitourinary toxicity was 20% Grade 1; 4% Grade 2, rectal toxicity was 4% Grade 2. At follow-up of 6 months, genitourinary toxicity was 4% Grade 1; 4% Grade 2. Rectal toxicity was 4% Grade 2. Conclusion Radiotherapy with the Clarity System allows a reduction of PTV margins, the amount of fractions can be reduced increasing the total dose, not exacerbating urinary and rectal toxicity with greater patient's compliance.

In the pre-chemotherapy (CT) and post-CT settings of metastatic castration-resistant prostate cancer (mCRPC), abiraterone acetate plus prednisone (AAP) significantly extended median overall survival and radiographic progression-free survival (PFS) compared with prednisone alone. Yet, few data are available on therapy efficacy in the subgroup with visceral metastases, who represent a small population with poor prognosis. The aim of this study was to describe the clinical experience of AAP in patients with mCRPC with liver and/or lung metastases in real-world setting. We retrospectively reviewed the clinical records of patients with mCRPC with liver and/or lung metastases treated at the National Cancer Institute 'Fondazione G. Pascale' from September 2011 to May 2017. Co-primary end points were overall survival and radiographic PFS. Survival estimates were computed using Kaplan-Meier method. Secondary end points were response rate and safety. Of 143 patients with mCRPC treated, 18.9% (N=27) had visceral metastases: 85.2% (N=23) of the lung, 11.1% (N=3) of the liver and 3.7% (N=1) of both. Median PFS was 13.1 months [95% confidence interval (CI): 4.8-NA] in the pre-CT setting (N=11, median follow-up: 12.9 months), and 10.5 months (95% CI: 4.4-16.6) in the post-CT setting (N=16, median follow-up: 17.2 months). Pre-CT and post-CT patients with lung metastases had a median PFS of 16.5 months (95% CI: 4.3-NA) and 11.4 months (95% CI: 4.2-17.0), respectively. AAP tolerability was consistent with that previously reported in patients with mCRPC, without new safety concerns. Our finding provides preliminary evidence that AAP in real-world setting is a potential effective and safe therapeutic option for patients with mCRPC with a more advanced disease associated with the presence of visceral metastases, in both the pre-CT and post-CT settings.

Testicular germ cell tumors (TGCTs) represent the most common solid tumors affecting young men. They constitute a distinct entity because of their embryonic origin and their unique biological behavior. Recent preclinical data regarding biological signaling machinery as well as genetic and epigenetic mechanisms associated with molecular patterns of tumors have contribute to explain the pathogenesis and the differentiation of TGCTs and to understand the mechanisms responsible for the development of resistance to treatment. In this review, we discuss the main genetic and epigenetic events associated with TGCTs development in order to better define their role in the pathogenesis of these tumors and in cisplatin-acquired resistance.

Renal cell carcinoma (RCC) is a chemoresistant tumor, characterized by a poor response and lack of survival benefit with conventional cytotoxic agents. Furthermore, the complexity and heterogeneity of RCC limit the biologic targets for novel agents to manage RCC. Expression of the multiple drug resistance (MDR) protein (ATP-binding cassette P-glycoprotein) is increased in RCC, while the Von Hippel Lindau protein is mutated or silenced in approximately half of sporadic RCC, resulting in high levels of hypoxia inhibiting factor (HIF) and the activation of several genes codifying growth factors and growth factors receptors, such as vascular endothelial growth factor (VEGF), platelet-derived growth factor B (PDGF-B), and transforming growth factor alpha (TGFα). Consequently, immunodrugs targeting pathways related to these proteins have been evaluated for the management of metastatic RCC (mRCC). This review provides an overview of drugs that have been evaluated or are under investigation for the treatment of mRCC, including the multi-tyrosine kinase inhibitors (TKIs) sunitinib, pazopanib, axitinib, the mammalian target of rapamycin (mTOR) inhibitors everolimus and temsirolimus, and nivolumab, which targets the programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) pathway. Promising results have been obtained with nivolumab, alone or in combination with TKIs such as sunitinib and pazopanib, and with ipilimumab, an immune checkpoint inhibitor which acts on the CTLA-4 pathway. Although much progress has been made, research with these and other agents is ongoing, and there is a need to identify makers of response to “tailor” the most suitable therapy, or sequence of therapies, to the individual patient, with the aim of improving outcomes and reducing unneeded toxicity.

// Daniela Vanacore 1, 2, * , Mariarosaria Boccellino 2, * , Sabrina Rossetti 1, 3 , Carla Cavaliere 1, 4 , Carmine D’Aniello 1, 5 , Rossella Di Franco 1, 6 , Francesco Jacopo Romano 1 , Micaela Montanari 1, 7 , Elvira La Mantia 1, 8 , Raffaele Piscitelli 1, 9 , Flavia Nocerino 1, 10 , Francesca Cappuccio 1, 11 , Giovanni Grimaldi 1, 12 , Alessandro Izzo 1, 12 , Luigi Castaldo 1, 12 , Maria Filomena Pepe 1, 8 , Maria Gabriella Malzone 1, 8 , Gelsomina Iovane 3 , Gianluca Ametrano 1, 6 , Paola Stiuso 2 , Lucio Quagliuolo 2 , Daniela Barberio 1, 11 , Sisto Perdona 12 , Paolo Muto 6 , Maurizio Montella 10 , Piera Maiolino 9 , Bianca Maria Veneziani 7 , Gerardo Botti 8, 13 , Michele Caraglia 2 and Gaetano Facchini 1, 3 1 Progetto ONCONET2.0, Linea progettuale 14 per l’implementazione della Prevenzione e Diagnosi Precoce del Tumore alla Prostata e Testicolo, Regione Campania, Italy 2 Department of Biochemistry, Biophysics and General Pathology, University of Campania “L. Vanvitelli” Naples, Naples, Italy 3 Division of Medical Oncology, Department of Uro-Gynaecological Oncology, Istituto Nazionale Tumori ‘Fondazione G. Pascale’, IRCCS, Naples, Italy 4 Department of Onco-Ematology Medical Oncology, S.G. Moscati Hospital of Taranto, Taranto, Italy 5 Division of Medical Oncology, A.O.R.N. dei COLLI “Ospedali Monaldi-Cotugno-CTO”, Napoli, Italy 6 Radiation Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori ‘Fondazione Giovanni Pascale’, IRCCS, Napoli, Italy 7 Department of Molecular Medicine and Medical Biotechnologies, University of Naples “Federico II”, Naples, Italy 8 Pathology Unit, Istituto Nazionale Tumori “Fondazione G. Pascale”, IRCCS, Naples, Italy 9 Pharmacy Unit, Istituto Nazionale Tumori, Istituto Nazionale Tumori-Fondazione G. Pascale, Naples, Italy 10 Epidemiology Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori ‘Fondazione Giovanni Pascale’, IRCCS, Napoli, Italy 11 Psicology Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori ‘Fondazione Giovanni Pascale’, IRCCS, Napoli, Italy 12 Division of Urology, Department of Uro-Gynaecological Oncology, Istituto Nazionale Tumori ‘Fondazione G. Pascale’, IRCCS, Naples, Italy 13 Scientific Directorate, Istituto Nazionale Tumori ‘Fondazione G. Pascale’, IRCCS, Naples, Italy * These authors have contributed equally to this work Correspondence to: Michele Caraglia, email: michele.caraglia@unina2.it , michele.caraglia@alice.it Keywords: microRNAs, prostate cancer, biomarkers, oncogenic miRNAs, tumor suppressor miRNAs Received: February 06, 2017 Accepted: March 25, 2017 Published: April 07, 2017 ABSTRACT Prostate cancer is the second highest cause of cancer mortality after lung tumours. In USA it affects about 2.8 million men and the incidence increases with age in many countries. Therefore, early diagnosis is a very important step for patient clinical evaluation and for a selective and efficient therapy. The study of miRNAs’ functions and molecular mechanisms has brought new knowledge in biological processes of cancer. In prostate cancer there is a deregulation of several miRNAs that may function as tumour suppressors or oncogenes. The aim of this review is to analyze the progress made to our understanding of the role of miRNA dysregulation in prostate cancer tumourigenesis.

// Vincenzo Quagliariello 1,2,3,16 , Sabrina Rossetti 1,2 , Carla Cavaliere 1,4 , Rossella Di Palo 1,5 , Elvira Lamantia 1,6 , Luigi Castaldo 1,7 , Flavia Nocerino 8 , Gianluca Ametrano 1,5 , Francesca Cappuccio 1,9 , Gabriella Malzone 1,6 , Micaela Montanari 1,10 , Daniela Vanacore 1 , Francesco Jacopo Romano 1 , Raffaele Piscitelli 1,11 , Gelsomina Iovane 2 , Maria Filomena Pepe 1,6 , Massimiliano Berretta 12,16 , Carmine D’Aniello 1,13 , Sisto Perdona 7 , Paolo Muto 5 , Gerardo Botti 6 , Gennaro Ciliberto 14,17 , Bianca Maria Veneziani 10 , Francesco De Falco 9 , Piera Maiolino 11 , Michele Caraglia 15 , Maurizio Montella 8 , Rosario Vincenzo Iaffaioli 3,16 and Gaetano Facchini 1,2,16 1 Progetto ONCONET2.0 - Linea progettuale 14 per l’implementazione della prevenzione e diagnosi precoce del tumore alla prostata e testicolo, Regione Campania, Italy 2 Division of Medical Oncology, Department of Uro-Gynaecological Oncology , Istituto Nazionale Tumori ‘Fondazione G. Pascale’ - IRCCS, Naples, Italy 3 Medical Oncology, Abdominal Department, National Cancer Institute G. Pascale Foundation, Napoli, Italy 4 Department of Onco-Ematology Medical Oncology, S.G. Moscati Hospital of Taranto, Taranto, Italy 5 Radiation Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori ‘Fondazione Giovanni Pascale’ - IRCCS, Napoli, Italy 6 Pathology Unit, Istituto Nazionale Tumori “Fondazione G. Pascale”-IRCCS, Naples, Italy 7 Division of Urology, Department of Uro-Gynaecological Oncology , Istituto Nazionale Tumori ‘Fondazione G. Pascale’ - IRCCS, Naples, Italy 8 Epidemiology Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori ‘Fondazione Giovanni Pascale’ - IRCCS, Napoli, Italy 9 Psicology Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori ‘Fondazione Giovanni Pascale’ - IRCCS, Napoli, Italy 10 Department of Molecular Medicine and Medical Biotechnologies, University of Naples “Federico II”, Naples, Italy 11 Pharmacy Unit, Istituto Nazionale Tumori, Istituto Nazionale Tumori-Fondazione G. Pascale, Naples, Italy 12 Department of Medical Oncology, CRO Aviano, National Cancer Institute, Aviano, Italy 13 Division of Medical Oncology, A.O.R.N. dei COLLI “Ospedali Monaldi-Cotugno-CTO”, Napoli, Italy 14 Scientific Directorate, Istituto Nazionale per lo Studio e la Cura dei Tumori ‘Fondazione Giovanni Pascale’ - IRCCS, Napoli, Italy 15 Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, Naples, Italy 16 Association for Multidisciplinary Studies in Oncology and Mediterranean Diet, Piazza Nicola Amore, Naples, Italy 17 Scientific Directorate, Istituto Nazionale per lo Studio e la Cura dei Tumori ‘Regina Elena’ - IRCCS, Roma, Italy Correspondence to: Vincenzo Quagliariello, email: // Keywords : metabolic syndrome, endocrine disruptors, prostate, cancer, nutrition Received : October 28, 2016 Accepted : February 06, 2017 Published : March 30, 2017 Abstract This review summarizes the main pathophysiological basis of the relationship between metabolic syndrome, endocrine disruptor exposure and prostate cancer that is the most common cancer among men in industrialized countries. Metabolic syndrome is a cluster of metabolic and hormonal factors having a central role in the initiation and recurrence of many western chronic diseases including hormonal-related cancers and it is considered as the world’s leading health problem in the coming years. Many biological factors correlate metabolic syndrome to prostate cancer and this review is aimed to focus, principally, on growth factors, cytokines, adipokines, central obesity, endocrine abnormalities and exposure to specific endocrine disruptors, a cluster of chemicals, to which we are daily exposed, with a hormone-like structure influencing oncogenes, tumor suppressors and proteins with a key role in metabolism, cell survival and chemo-resistance of prostate cancer cells. Finally, this review will analyze, from a molecular point of view, how specific foods could reduce the relative risk of incidence and recurrence of prostate cancer or inhibit the biological effects of endocrine disruptors on prostate cancer cells. On the basis of these considerations, prostate cancer remains a great health problem in terms of incidence and prevalence and interventional studies based on the treatment of metabolic syndrome in cancer patients, minimizing exposure to endocrine disruptors, could be a key point in the overall management of this disease.

Objective The aim of this work was to evaluate the impact of stereotactic radiosurgery/fractionated stereotactic radiotherapy with the Cyberknife system on local disease control, clinical outcome and toxicity in patients with meningioma, according to the site and histological grade of lesion. From January 2013 to April 2017, 52 patients with intracranial meningiomas were treated with the Cyberknife system. Twenty-four patients had undergone previous surgery: 38% gross total resection, 10% subtotal resection; 27 patients underwent no surgery; 22 patients had a recurrence of meningioma. Methods Radiosurgery was used for lesions smaller than 2 cm, stereotactic radiotherapy for lesions larger than 2 cm, or smaller but close to a critical site such as the optical chiasm, optic pathway or brainstem. Results Local control and clinical outcomes were analysed. Median follow-up was 20 months: six patients died, one after re-surgery died from post-surgical sepsis, three from heart disease. Progression-free survival had a mean value of 38.3 months and overall survival of 41.6 months. We evaluated at 12 months 28 patients (100% local control); at 24 months 19 patients (89% local control); at 36 months nine patients (89% local control). At baseline, 44/52 patients (85%) were symptomatic: 19 visual disorders, 17 motor disorders, six hearing disorders, 10 headache and six epilepsy. Visual symptoms remained unchanged in 52%, improved in 32%, resolved in 16%. Headache was improved in 40%, resolved in 10%, unchanged in 50%. Epilepsy was resolved in 17%, unchanged in 33%, worsened in 33%. Conclusions Stereotactic radiosurgery/fractionated stereotactic radiotherapy with Cyberknife provides a good local disease control, improving visual, hearing and motor symptoms.

This review summarizes the main pathophysiological basis of the relationship between metabolic syndrome, endocrine disruptor exposure and prostate cancer that is the most common cancer among men in industrialized countries. Metabolic syndrome is a cluster of metabolic and hormonal factors having a central role in the initiation and recurrence of many western chronic diseases including hormonal-related cancers and it is considered as the worlds leading health problem in the coming years. Many biological factors correlate metabolic syndrome to prostate cancer and this review is aimed to focus, principally, on growth factors, cytokines, adipokines, central obesity, endocrine abnormalities and exposure to specific endocrine disruptors, a cluster of chemicals, to which we are daily exposed, with a hormone-like structure influencing oncogenes, tumor suppressors and proteins with a key role in metabolism, cell survival and chemo-resistance of prostate cancer cells. Finally, this review will analyze, from a molecular point of view, how specific foods could reduce the relative risk of incidence and recurrence of prostate cancer or inhibit the biological effects of endocrine disruptors on prostate cancer cells. On the basis of these considerations, prostate cancer remains a great health problem in terms of incidence and prevalence and interventional studies based on the treatment of metabolic syndrome in cancer patients, minimizing exposure to endocrine disruptors, could be a key point in the overall management of this disease.

Testicular cancer (TC) is one of the most common neoplasms that occurs in male and includes germ cell tumors (GCT), sex cord-gonadal stromal tumors and secondary testicular tumors. Diagnosis of TC involves the evaluation of serum tumor markers alpha-fetoprotein, human chorionic gonadotropin and lactate dehydrogenase, but clinically several types of immunohistochemical markers are more useful and more sensitive in GCT, but not in teratoma. These new biomarkers are genes expressed in primordial germ cells/gonocytes and embryonic pluripotency-related cells but not in normal adult germ cells and they include PLAP, OCT3/4 (POU5F1), NANOG, SOX2, REX1, AP-2γ (TFAP2C) and LIN28. Gene expression in GCT is regulated, at least in part, by DNA and histone modifications, and the epigenetic profile of these tumours is characterised by genome-wide demethylation. There are different epigenetic modifications in TG-subtypes that reflect the normal developmental switch in primordial germ cells from an under- to normally methylated genome. The main purpose of this review is to illustrate the findings of recent investigations in the classification of male genital organs, the discoveries in the use of prognostic and diagnostic markers and the epigenetic aberrations mainly affecting the patterns of DNA methylation/histone modifications of genes (especially tumor suppressors) and microRNAs (miRNAs).

In metastatic renal cell carcinoma, complete response to first-line antiangiogenic agents is rare and resistance to therapy often develops. Protocols for sequential treatment with angiogenesis and mTOR inhibitors are under evaluation to improve outcomes. In this observational, real-world study, patients received a first-line therapy with pazopanib until discontinuation for disease progression or toxicity, then a second-line with everolimus. Primary endpoints were overall survival (OS) for sequence, progression free survival (PFS) for each agent, and safety. Thirty-one patients were included in the analysis: 73.3% of patients underwent nephrectomy before treatment, 25.8% had at least three comorbidities. At the beginning of therapy, the median age was 68 years, with more than 60% of patients older than 65 years. The median OS for sequence was 26.5 months (95% CI 17.4-nc); median PFS was 10.6 months (95% CI 6.3-12.1) with pazopanib and 5.3 months (95% CI 3.8-6.7) with everolimus. The median persistence in pazopanib therapy was 8.1 months (Interquartile Range IQR 5.3-12.7), with 31% of patients who required dose reduction, while persistence in everolimus was 4.4 months (IQR 3.4-6.5). Sequence was well tolerated with a different profile of adverse events for each agent. These data confirmed that pazopanib was effective, even in reduced dosing, and well tolerated and suggested that everolimus may represent an opportunity to continue a therapy when patients cannot further tolerate angiogenesis inhibitors or develop a resistance.

// Micaela Montanari 1,2 , Sabrina Rossetti 1 , Carla Cavaliere 1,3 , Carmine D’Aniello 1,4 , Maria Gabriella Malzone 1,5 , Daniela Vanacore 1 , Rossella Di Franco 1,6 , Elvira La Mantia 1,5 , Gelsomina Iovane 1,7 , Raffaele Piscitelli 1 , Raffaele Muscariello 8 , Massimiliano Berretta 9 , Sisto Perdona 8 , Paolo Muto 6 , Gerardo Botti 5,10 , Attilio Antonio Montano Bianchi 11 , Bianca Maria Veneziani 2 and Gaetano Facchini 1,7 1 Progetto ONCONET2.0, Linea Progettuale 14 per L’implementazione della Prevenzione e Diagnosi Precoce del Tumore alla Prostata e Testicolo, Regione Campania, Italy 2 Department of Molecular Medicine and Medical Biotechnologies, University of Naples “Federico II”, Naples, Italy 3 Department of Onco-Ematology Medical Oncology, S.G. Moscati Hospital of Taranto, Taranto, Italy 4 Division of Medical Oncology, A.O.R.N. dei COLLI “Ospedali Monaldi-Cotugno-CTO”, Naples, Italy 5 Pathology Unit, Istituto Nazionale Tumori “Fondazione G. Pascale”, IRCCS, Naples, Italy 6 Radiation Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori ‘Fondazione Giovanni Pascale’, IRCCS, Naples, Italy 7 Department of Uro-Gynaecological Oncology, Division of Medical Oncology, Istituto Nazionale Tumori ‘Fondazione G. Pascale’, IRCCS, Naples, Italy 8 Department of Uro-Gynaecological Oncology, Division of Urology, Istituto Nazionale Tumori ‘Fondazione G. Pascale’, IRCCS, Naples, Italy 9 Department of Medical Oncology, CRO Aviano, National Cancer Institute, Aviano, Italy 10 Scientific Directorate, Istituto Nazionale Tumori ‘Fondazione G. Pascale’, IRCCS, Naples, Italy 11 Directorate-General for Management, Istituto Nazionale Tumori ‘Fondazione G. Pascale’, IRCCS, Naples, Italy Correspondence to: Micaela Montanari, email: // Keywords : prostate cancer; epithelial-mesenchymal transition; androgen receptor; TGF-β signaling; EGF/EGFR Received : November 10, 2016 Accepted : February 15, 2017 Published : February 25, 2017 Abstract Prostate cancer is a main urological disease associated with significant morbidity and mortality. Radical prostatectomy and radiotherapy are potentially curative for localized prostate cancer, while androgen deprivation therapy is the initial systemic therapy for metastatic prostate disease. However, despite temporary response, most patients relapse and evolve into castration resistant cancer. Epithelial-mesenchymal transition (EMT) is a complex gradual process that occurs during embryonic development and/or tumor progression. During this process, cells lose their epithelial characteristics and acquire mesenchymal features. Increasing evidences indicate that EMT promotes prostate cancer metastatic progression and it is closely correlated with increased stemness and drug resistance. In this review, we discuss the main molecular events that directly or indirectly govern the EMT program in prostate cancer, in order to better define the role and the mechanisms underlying this process in prostate cancer progression and therapeutic resistance.

// Rossella Di Franco 1,2 , Valentina Borzillo 2 , Vincenzo Ravo 2 , Gianluca Ametrano 1,2 , Sara Falivene 2 , Fabrizio Cammarota 2 , Sabrina Rossetti 1 , Francesco Jacopo Romano 1 , Carmine D’Aniello 1,3 , Carla Cavaliere 1,4 , Gelsomina Iovane 1,5 , Raffaele Piscitelli 1 , Massimiliano Berretta 6 , Paolo Muto 2 and Gaetano Facchini 1,5 1 Progetto ONCONET2.0 – Linea progettuale 14 per l’implementazione della prevenzione e diagnosi precoce del tumore alla prostata e testicolo – Regione Campania, Italy 2 Radiation Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori ‘Fondazione Giovanni Pascale’ – IRCCS, Napoli, Italy 3 Division of Medical Oncology, A.O.R.N. dei COLLI “Ospedali Monaldi-Cotugno-CTO”, Napoli 4 Department of Onco-Ematology Medical Oncology, S.G. Moscati Hospital of Taranto, Taranto, Italy 5 Division of Medical Oncology, Department of Uro-Gynaecological Oncology, Istituto Nazionale Tumori ‘Fondazione G. Pascale’ - IRCCS , Naples , Italy 6 Department of Medical Oncology, CRO Aviano, National Cancer Institute, Aviano, Italy Correspondence to: Rossella Di Franco, email: // Keywords : prostate cancer; radiotherapy; toxicity; meta-analysis; review Received : October 12, 2016 Accepted : December 07, 2016 Published : January 22, 2017 Abstract Purpose: The aim of this review was to compare radiation toxicity in Localized Prostate Cancer (LPC) patients who underwent conventional fractionation (CV), hypofractionated (HYPO) or extreme hypofractionated (eHYPO) radiotherapy. We analyzed the impact of technological innovation on the management of prostate cancer, attempting to make a meta-analysis of randomized trials. Methods: PubMed database has been explored for studies concerning acute and late urinary/gastrointestinal toxicity in low/intermediate risk LPC patients after receiving radiotherapy. Studies were then gathered into 5 groups: detected acute and chronic toxicity data from phase II non randomized trials were analyzed and Odds Ratio (OR) was calculated by comparing the number of patients with G0-1 toxicity and those with toxicity > G2 in the studied groups. A meta-analysis of prospective randomized trials was also carried out. Results: The initial search yielded 575 results, but only 32 manuscripts met all eligibility requirements: in terms of radiation-induced side effects, such as gastrointestinal and genitourinary acute and late toxicity, hypofractionated 3DCRT seemed to be more advantageous than 3DCRT with conventional fractionation as well as IMRT with conventional fractionation compared to 3DCRT with conventional fractionation; furthermore, IMRT hypofractionated technique appeared more advantageous than IMRT with conventional fractionation in late toxicities. Randomized trials meta-analysis disclosed an advantage in terms of acute gastrointestinal and late genitourinary toxicity for Hypofractionated schemes. Conclusions: Although our analysis pointed out a more favorable toxicity profile in terms of gastrointestinal acute side effects of conventional radiotherapy schemes compared to hypofractionated ones, prospective randomized trials are needed to better understand the real incidence of rectal and urinary toxicity in patients receiving radiotherapy for localized prostate cancer.

BACKGROUND Abiraterone Acetate (AA) is approved for the treatment of mCRPC after failure of androgen deprivation therapy in whom chemotherapy is not yet clinically indicated and for treatment of mCRPC progressed during or after docetaxel-based chemotherapy regimen. The aim of this study is to evaluate the role of early PSA decline for detection of therapy success or failure in mCRPC patients treated with AA in post chemotherapy setting. PATIENTS AND METHODS We retrospectively evaluated 87 patients with mCRPC treated with AA. Serum PSA levels were evaluated after 15, 90 days and then monthly. The PSA flare phenomenon was evaluated, according to a confirmation value at least one week apart. The primary endpoint was to demonstrate that an early PSA decline correlates with a longer progression free survival (PFS) and overall survival (OS). The secondary endpoind was to demonstrate a correlation between better outcome and demographic and clinical patient characteristics. RESULTS We have collected data of 87 patients between Sep 2011 and Sep 2014. Early PSA response (≥ 50% from baseline at 15 days) was found in 56% evaluated patients and confirmed in 29 patients after 90 days. The median progression free survival (PFS) was 5,5 months (4,6-6,5) and the median overall survival (OS) was 17,1 months (8,8-25,2). In early responders patients (PSA RR ≥ 50% at 15 days), we found a significant statistical advantage in terms of PFS at 1 year, HR 0.28, 95%CI 0.12-0.65, p=0.003, and OS, HR 0.21 95% CI 0.06-0.72, p=0.01. The results in PFS at 1 years and OS reached statistical significance also in the evaluation at 90 days. CONCLUSION A significant proportion (78.6%) of patients achieved a rapid response in terms of PSA decline. Early PSA RR (≥ 50% at 15 days after start of AA) can provide clinically meaningful information and can be considered a surrogate of longer PFS and OS.

The percentages of dry matter (DM), protein, casein, fat, lactose, solids-not-fat and ash of milk and the characteristics of the curd (31 components and/or characteristics) were evaluated on 326 milk samples collected from 60 buffaloes every 50 days. The animals were half sib (same father or same mother ascertained by DNA test) and were bred in two farms. Relationships between the values of components and/or characteristics were also calculated. Significant relationships were found among DM percentage of milk and its components, cheese yield, curd characteristics, ratio between the studied cheese yields and protein percentage. Protein, casein and fat showed positive relationships, whereas lactose presented negative relationships. The association among proteins and real cheese yield or the dry matter of the curd that derived from 1 litre of milk (CDM), was lower than that with calculated cheese yield. This difference strongly decreased if proteins percentage, corrected for urea value, was utilized in cheese yield calculation. No relationship was found between proteins and urea in milk, but a direct relation was present between proteins and proteins adjusted for urea. This relation affects a correct estimation of cheese yield, because the percentage of true proteins in milk, corrected per urea was 4.52 vs. 4.64.

Here reported are data relative to the chemical composition/characteristics of the milk, of milk samples collected every 50 days from 60 buffaloes (326 samples) that were half-sibs (through paternal or maternal lineage, ascertained by DNA test), bred in two farms (S.A. and M respectively n. = 27 and n = 33). The subjects were divided in relation to the productive level (> vs. < 2601 kg/lactation). The production level did not influence the theoretical yield (ThCY), the yield at 4 h (FCY) and at 28 h (28CY), the curd dry matter (CDM) and the ratios between ThCY and real yields (FCY, 28CY and CDM). Compared to the less productive subjects, despite similar percentage of proteins, the more productive subjects had a higher percentage of casein (3.73 vs. 3.64; P < 0.05), a greater incidence of the latter on total protein (80.52 vs. 79.60; P < 0.05), higher content in lactose (4.88 vs. 4.81; P < 0.01) and urea (42.44 vs. 40.48; P < 0.05) and a lower BCS value (6.79 vs. 7.25; P < 0.05). These differences are not always confirmed in both farms. Regardless of the production level, subjects of farm S.A. had a lower production/lactation (2524 vs. 2817 kg; P < 0.01), higher values of R and k20 (P < 0.01), lower value of a30, a higher SH value and lower contents in urea and solid not fat. They also showed a lower ThCY yield and a lower ratio between ThCY and 28CY when proteins were corrected for the urea content, and a higher ratio between 28CY and the percentage of proteins, both when corrected or not for the urea content. It is difficult to explain the influence of the production level on the casein content whereas the greater lactose content in more productive buffaloes may be accounted for by the greater persistence of lactation curve. The higher urea content found in buffaloes with a greater galactopoietic attitude may be due to a greater DM intake caused by the inadequacy of the diet, hypothesis confirmed by the lower BCS observed in the more productive subjects.

The aim of this study was to screen for Brucella spp. buffalo embryos produced in- vitro, by using cumulus oocytes complexes (COCs) recovered from ovaries of slaughtered buffaloes naturally infected with Brucella spp. Ovaries were collected from 5 female pluriparous buffaloes slaughtered in a local abattoir. EDTA-blood samples and nasal swabs collected from each animal were used for Brucella spp. DNA detection by real-time PCR. Buffalo ovaries (n = 10) were transported to the laboratory and maintained strictly separated throughout laboratory processing. Recovered COCs were matured, fertilized and cultured in vitro until day 7. Some immature COCs, all uncleaved COCs, all blocked cleaved embryos (2 to 16 cells) and all transferable embryos (tight morulae and blastocysts) were separately analysed by real-time PCR assay. Brucella spp. DNA was detected in both blood and nasal mucus of all subjects, whereas no trace of DNA of Brucella spp. was found on either COCs or embryos. Currently, the infected or seropositive buffaloes have to be slaughtered for sanitary reasons. Interestingly, the results of this preliminary trial suggest a possible utilization of the COCs from the infected subjects of high genetic value to obtain safe embryos.

e16054 Background: Axitinib, a selective tyrosine kinase inhibitor (TKI), is currently approved for the treatment of mRCC after failure of prior treatment with sunitinib or cytokine, according to AXIS trial results. The best sequence hasn’t been established: both axitinib and everolimus (a mTOR inhibitor) are viable therapeutic options, although recently immunotherapy agents entered this setting. This Italian multi-institutional retrospective analysis evaluated outcomes of Axitinib in exclusive sequence after sunitinib in second line treatment of mRCC Methods: Medical records of 148 patients treated with Axitinib from 21 Italian Oncology Centers were retrospectively assessed: PFS, OS, ORR DCR, and safety profile of axitinib were primary endpoints. Results: Median PFS and OS were 7.14 and 15.5 months, respectively. Overall, axitinib at standard schedule of 5 mg bid, was well tolerated, with no grade 4 toxicity event. Most common adverse events were hypertension (26% of the cases), fatigue (50 %), hypothyroidism (18%). At univariate analysis, when patients were stratified by Heng score, mPFS was 5.8, 7.0 and 9.0 months according to poor, intermediate and favourable risk group, respectively. When stratified by median duration of prior sunitinib therapy (≥ 13,1 mo vs < 13,1 mo), there was a statistically significant difference in PFS with 8.8 vs 6.3 months, respectively. Disease control rate (DCR) to previous sunitinib treatment was associated to longer PFS with axitinib ( 8.0 months vs4.0 months). The sequence sunitinib-axitinib was well tolerated, with a mOS of 41 months. At multivariate analysis, prognostic factors for progression were gender (p-value = 0,006), DCR to axitinib (p < 0,0001) and to previous sunitinib (p = 0,041); DCR to axitinib (p = < 0,0001), nephrectomy (p = 0,002) and Heng score (p = 0,025) independently affected overall survival. Conclusions: The preliminary SAX results in the real world population are consistent with available literature. The study confirms that Axitinib is effective and safe in routine clinical practice, and its efficacy seems to be greater in patients who most benefited from first-line sunitinib.

e16569Background: Although several new agents changed the therapeutic landscape of mCRPC, it remains a lethal disease. Among the new available agents, AA demonstrated a survival improvement in pts ...

219 Background: In the last years the therapeutic scenario of mCRPC has undergone a radical change with the approval of new drugs. AA is approved for the treatment of mCRPC after failure of ADT in whom chemotherapy (CT) is not yet clinically indicated and for treatment of mCRPC progressed on or after docetaxel (DTX) based chemotherapy. The aim of this study is to evaluate the role of early PSA decline as a marker of response for an early detection of therapy success in mCRPC patients treated with AA. Methods: We retrospectively evaluated 87 pts with mCRPC treated with AA in compassionate use in Napoli, Trento, and Candiolo, Italy. Serum PSA levels were performed after 15, 90 days and then monthly, a time course of serum PSA was obtained. The PSA flare phenomenon was evaluated, according to a confirmation value at least one week apart. The Cox proportional hazards model was used to test the effect of several variables on survival outcomes in multivariate analyses. Results: We have collected data of 87 patients between Sep 2011 and Sep 2014; 75/87 were eligible for correlation analysis. PSA decline was observed in 78.6 % (59/75) of pts. Early PSA response ( ≥ 50% from baseline at 15 days) was found in 56%(42/75) evaluated patients and confirmed in 29 of them after 90 days. In early responders patients (PSA RR ≥ 50% at 15 days), we found a significant statistical advantage in terms of PFS at 1 year, HR 0.28,95% CI 0.12-0.65, p = 0.003, and OS, HR 0.21 95% CI 0.06-0.72, p = 0.01. The median OS was 17,1 months(8,8-25,2). PFS at 1 year and OS reached statistical significance also in the evaluation at 90 days, HR: 0.23 95% CI 0.07-0.77, p = 0.02 and HR: 0.14 95% CI 0.03-0.70, p = 0.02 respectively. Our analysis showed a positive correlation between OS and duration of AA treatment, previous chemotherapy treatment, cumulative dose of docetaxel ≤ 675 mg/m² and previous hormonal therapy duration ( ≥ 2.5 months) for metastatic setting in early responders group. Conclusions: A significant proportion (78.6%) of patients achieved a rapid response in terms of decline of PSA. Early PSA RR ( ≥ 50% at 15 days after start of AA) can provide clinically meaningful information and could be considered a surrogate of longer PFS and OS.

The Comprehensive Geriatric Assessment (CGA) represents the future of the geriatric oncology to reduce toxicities and treatment-related hospitalization in the elderly. Most patients receiving docetaxel for metastatic castration-resistant prostate cancer are in their seventies or older. We explored the efficacy of the CGA in predicting chemotherapy feasibility and response to docetaxel in a cohort of 24 patients aged at least 70. This was an observational, prospective study involving 24 patients who were 70 years of age or older and about to start chemotherapy with docetaxel for metastatic castration-resistant prostate cancer; we performed a CGA including five domains and divided our patients into 'healthy' and 'frail'; the relations between general condition and (i) early chemotherapy discontinuation and (ii) response to docetaxel were explored. We found a statistically significant relationship between frailty assessed by CGA and early docetaxel discontinuation; we also found an association between frailty and response to chemotherapy, but this did not reach statistical significance. A geriatric assessment before starting chemotherapy may help clinicians to recognize frail patients, and hence to reduce toxicities and early treatment discontinuation. Further analyses are required to simplify the CGA tools and to facilitate its incorporation into routine clinical practice.