Entity

Time filter

Source Type

Cittadella, Italy

Casaluce F.,The Second University of Naples | Sgambato A.,The Second University of Naples | Maione P.,S.G. Moscati Hospital | Rossi A.,S.G. Moscati Hospital | And 5 more authors.
Targeted Oncology | Year: 2013

The anaplastic lymphoma kinase (ALK) fusion gene is a key oncogenic driver in a subset of patients with advanced non-small cell lung cancer (NSCLC). Oncogenic fusion genes, including echinoderm microtubule-associated protein-like 4 (EML4) and ALK, have been detected in approximately 2-7 % of NSCLC patients. Fluorescence in situ hybridization (FISH) is the recommended method for detecting ALK gene rearrangement. EML4-ALK fusion genes define a molecular subset of NSCLC with distinct clinical characteristic (lung adenocarcinoma, never or former smoker, usually mutually exclusive with EGFR mutations). Crizotinib (PF-02341066) is an orally bioavailable, ATP-competitive, small molecule inhibitor of both the receptor tyrosine kinases ALK and c-MET (hepatocyte growth factor receptor). Crizotinib has been shown to yield important clinical benefit such as objective response rate, progression-free survival (PFS), and anticipated improvements in quality of life when used in pretreated patients with advanced NSCLC harboring EML4-ALK gene rearrangement. Preliminary phase II data suggested that crizotinib is safe and well tolerated with rapid and robust antitumor activity. A phase III randomized trial in a second-line setting showed response rate and PFS (primary study endpoint) advantage for crizotinib as compared to second-line chemotherapy. Treatment-related adverse events, predominantly restricted to the gastrointestinal and visual systems, are generally self-limiting or easily managed. Crizotinib is a new standard of care for patients with advanced, ALK-positive, NSCLC. In this review, we will discuss the discovery of ALK rearrangements, the clinical epidemiology of lung cancer driven by ALK, the clinical data for ALK-targeted therapy in NSCLC, and ongoing ALK inhibitor-based clinical trials. © 2013 Springer-Verlag France. Source


Amadori D.,IRCCS Scientific Institute of Romagna for the Study and Treatment of Cancer IRST IRCCS | Aglietta M.,Institute for Cancer Research and Treatment | Alessi B.,University of Udine | Gianni L.,Infermi Hospital | And 8 more authors.
The Lancet Oncology | Year: 2013

Background: Zoledronic acid reduces skeletal-related events in patients with breast cancer, but concerns have been raised about prolonged monthly administration. We assessed the efficacy and safety of a reduced dosing frequency of zoledronic acid in women treated previously with monthly zoledronic acid. Methods: We did this non-inferiority, phase 3 trial in 62 centres in Italy. We enrolled patients with breast cancer who had one or more bone metastases and had completed 12-15 months of monthly treatment with zoledronic acid. Patients were randomly assigned with a permutated block (size four to eight) random list stratified by centre in a 1:1 ratio to zoledronic acid 4 mg once every 12 weeks or once every 4 weeks, and followed up for at least 1 year. Neither patients nor investigators were masked to treatment allocation. The primary outcome was skeletal morbidity rate (skeletal-related events per patient per year) in the intention-to-treat population. We used a non-inferiority margin of 0·19. The trial is registered with EudraCT, number 2005-004942-15. Findings: We screened 430 patients and enrolled 425, of whom 209 were assigned to the 12-week group and 216 to the 4-week group. The skeletal morbidity rate was 0·26 (95% CI 0·15-0·37) in the 12-week group versus 0·22 (0·14-0·29) in the 4-week group. The between-group difference was 0·04 and the upper limit of one-tailed 97·5% CI was 0·17, which is lower than the non-inferiority margin. The most common grade 3-4 adverse events were bone pain (56 [27%] patients in the 12-week group vs 65 [30%] in the 4-week group), nausea (24 [11%] vs 33 [15%]), and asthenia (18 [9%] vs 33 [15%]). Renal adverse events occurred in one patient (<1%) in the 12-week group versus two (1%) in the 4-week group. One patient (<1%) in the 4-week group had grade 1 acute renal failure. Osteonecrosis of the jaw occurred in four patients in the 12-week group versus three in the 4-week group. No treatment-related deaths were reported. Median N-terminal telopeptide concentration changed from baseline more in the 12-week group than in the 4-week group after 12 months (12·2% vs 0·0%; p=0·011). Interpretation: Our results raise the possibility of decreasing administration of zoledronic acid to a 12-weekly regimen to reduce exposure during the second year, while maintaining its therapeutic effects. However, the effects on N-terminal telopeptide should be investigated further before changing current practice. Funding: Novartis Farma. © 2013 Elsevier Ltd. Source


Scocco P.,ULSS | Castriotta C.,Soproxi Project | Toffol E.,Soproxi Project | Toffol E.,University of Helsinki | And 2 more authors.
Psychiatry Research | Year: 2012

This study aimed at validating two new assessment tools, the Stigma of Suicide Attempt (STOSA) scale and the Stigma of Suicide and Suicide Survivor (STOSASS) scale. The Devaluation-Discrimination scale of Link et al. was translated into Italian and adapted to measure stigma towards suicidal behavior. Both scales were administered to a mixed sample including members of the general population (n=282), patients with a mental disorder (n=113), suicide attempters (n=57) and people who had lost a significant other to suicide (n=75). Reliability of the scales was good in terms of both internal coherence and test-retest stability. Factor analysis produced an acceptable solution for the STOSA-scale. Items were distributed into two factors, one grouping items to measure supportive, respectful and caring attitudes, the other factor grouping items oriented towards stigmatizing attitudes and beliefs. The clinical populations were more inclined towards stigmatization of suicide than were people from the general population, who might be less aware of the stigma attached to suicide.The two scales may be helpful to quantify stigma at individual level in order to provide targeted supportive interventions, and at population level to measure changes in the beliefs and attitudes of the general population. © 2012 Elsevier Ireland Ltd. Source


Masi L.,Casa di Cura S. Chiara | Casamassima F.,Casa di Cura S. Chiara | Doro R.,Casa di Cura S. Chiara | Francescon P.,ULSS
Medical Physics | Year: 2011

Purpose: To compare and evaluate different dosimetric techniques and devices for the QA of VMAT plans created by two treatment planning systems (TPSs). Methods: A total of 50 VMAT plans were optimized for treatment of anatomical sites of various complexities by two TPSs which use rather different approaches to VMAT optimization. Dosimetric plan verifications were performed both as part of commissioning and as patient specific QA of clinical treatments. Absolute point doses were measured for all plans by a micro ion chamber inserted in a dedicated water-filled cylindrical phantom. Delivered dose distributions were verified by four techniques based on different detectors: radiographic and gafchromic films, two systems based on 2D diode arrays and an ion chamber array. Gamma index analysis with various tolerance levels (3%, 3 mm and 3%, 2 mm) was used to analyze differences between calculated and delivered doses. Sensitivity to possible delivery errors was also evaluated for three of the considered devices introducing ±3 mm shifts along the three directions and a 3° gantry offset. Results: Ion chamber measured point doses were within 3% of calculated ones for 48 out of 50 values. For delivered dose distribution, the average fraction of passed gamma values using 3% and 3 mm criteria was above 95% for both TPSs and all detectors except gafchromic film which yielded on average of 91.4%. For 49 out of 50 plans, a pass-rate above 94% was obtained by at least one of the four techniques. Shrinking the tolerance to 3% and 2 mm, the average pass-rate by all detectors (except film) was still above 95% for one of the two TPSs, but lower for the other one. The detector sensitivity to 3 mm shifts and to gantry angle offset was strongly plan and partially detector dependent: the obtained pass-rate reduction ranged from 2% to 30%. Conclusions: The presented results for VMAT plans QA assess the reliability of the delivered doses for both TPSs. The slightly lower pass-rate obtained for one of the considered TPS can be attributed to a higher level of complexity of the optimized plans. The results by different dosimetric techniques are coherent, apart from a few measurements by gafchromic films. The detector sensitivity to delivery errors, being strongly plan dependent, is not easy to evaluate. © 2011 American Association of Physicists in Medicine. Source


Rubini A.,University of Padua | Del Monte D.,ULSS | Catena V.,ULSS
Annals of Thoracic Medicine | Year: 2012

Purpose: To describe the consequences of the cranial displacement of the diaphgram occurring during pneumoperitoneum (Pnp) and/or Trendelenburg (Tnd) position on respiratory mechanics. Possible addictive effects and the changes of the viscoelastic respiratory system resistance were studied, which were not extensively described before. Methods: The end-inflation occlusion method was applied on eight rats. It allows us to determine mechanical parameters such as respiratory system static elastance, the ohmic resistance due to frictional forces in the airways, and the additional viscoelastic impedance due to tissues deformation. Measurements during mechanical ventilation were taken in controls (supine position), after 20-25° head-down tilting (Tnd), after abdominal air insufflation up to 12 mmHg abdominal pressure in the supine position (Pnp), and combining Tnd + Pnp. Tnd and Pnp modalities were similar to those commonly applied during surgical procedures in humans. Results: We confirmed the previously described detrimental effects on respiratory mechanics due to the diaphgram displacement during both Pnp and Tnd. The increment in the total resistive pressure dissipation was found to depend primarily on the effects on the viscoelastic characteristics of the respiratory system. Data suggesting greater effects of Pnp compared to those of Tnd were obtained. Conclusion: The cranial displacement of the diaphgram occurring as a consequence of Pnp and/or Tnd, for example during laparoscopic surgical procedures, causes an increment of respiratory system elastance and viscoelastic resistance. The analysis of addictive effects show that these are more likely to occur when Pnp + Tnd are compared to isolated Tnd rather than to isolated Pnp. Source

Discover hidden collaborations