Nab-paclitaxel in pretreated metastatic breast cancer: evaluation of activity, safety, and quality of life

Objective: Metastatic breast cancer (MBC) is an incurable disease; the treatment of this disease prolongs survival, improving the quality of life (QoL) with a balance between efficacy and toxicity of the treatment. In recent years, treatment with nab-paclitaxel has improved the already known antitumor activity of conventional paclitaxel, in terms of increased efficacy and better tolerability. The aim of this study was to evaluate nab-paclitaxel in Italian patients with MBC. Methods: We conducted a retrospective analysis of 90 patients with histologically confirmed diagnosis of MBC. To evaluate the efficacy of nab-paclitaxel, overall survival (OS), progression-free survival (PFS), and overall response rate were the primary endpoints, whereas carbohydrate antigen 15.3 (Ca15.3) reduction, QoL, and tolerability were secondary endpoints. Results: The median OS was 10.4 months, the median PFS was 6.8 months. A considerable difference Ca15.3 before and after treatment was observed. Descriptive and regression analyses were done to examine the associations between Ca15.3 response and OS, demonstrating good correlation, revealing that Ca15.3 reduction is an important predictor of OS. Conclusion: Nab-paclitaxel is an effective and well-tolerated treatment of patients affected by MBC. The drug showed an improved tolerability profile. With all the limitations of the observational nature of our results, nab-paclitaxel has proven to be an effective and safe therapeutic option in patients with MBC

Progression-free survival as a surrogate endpoint of overall survival in patients with metastatic colorectal cancer

Background: In many clinical trials designed to assess the efficacy of anticancer treatments, overall survival (OS) is often used as a primary endpoint despite its several points of weakness. Methods: This study evaluated the role of progression-free survival (PFS) in the first three lines of treatment as a potential surrogate endpoint of OS in patients with metastatic colorectal cancer (MCRC). One hundred and twenty patients with MCRC were enrolled in this study. The median PFS of the first-, second-, and third-lines of treatment and the OS were evaluated. The correlation between the time to progression and the OS was analyzed. The median PFS of the three lines of treatment were 8.5, 5, and 3 months, respectively. Results: The median OS was 32.4 months. A modest correlation was found between the PFS to the first-line treatment with Folfox\u2013avastin and OS. Similar data were obtained with the second-line treatment. However, no correlation was found between the PFS and OS during the third-line treatment. The regression analysis revealed that PFS is predictive of OS. Conclusion: In brief, the PFS of the first- and second-lines of treatment could be a good candidate as a surrogate endpoint of OS in patients with MCRC

Mild behavioral impairment in Parkinson's disease: Data from the Parkinson's disease cognitive impairment study (PACOS)

Neuropsychiatric symptoms (NPS) have been frequently described in Parkinson's disease (PD), even in the earliest stages of the disease. Recently the construct of mild behavioral impairment (MBI) has been proposed as an at-risk state for incident cognitive decline and dementia. The aim of the present study is to evaluate the prevalence and associated factors of MBI in PD. Cross-sectional data from 429 consecutive PD patients enrolled in the PArkinson's disease COgnitive impairment Study (PACOS) were included in the study. All subjects underwent neuropsychological assessment, according to the MDS Level II criteria. NPS were evaluated with the Neuropsychiatric Inventory. Multivariate logistic regression models were used to evaluate clinical and behavioral characteristics, which are associated with PD-MBI. The latter was ascertained in 361 (84.1%) subjects of whom 155 (36.1%) were newly diagnosed patients (disease duration ≥1 year) and 206 (48.0%) had a disease duration <1 year. Furthermore, 68 (15.9%) out of 429 subjects were PDw (without MBI). Across the MBI domains, Impulse Dyscontrol was significantly more prevalent among PD-MBI with disease duration <1 year than newly diagnosed patients. The frequency of Social Inappropriateness and Abnormal Perception significantly increased throughout the entire PD-MBI sample with increasing Hoehn andYahr (H&Y) stages. PD-MBI in newly diagnosed PDwas significantly associated with H&Y stage (OR 2.35, 95% CI 1.05-5.24) and marginally with antidepressant drug use (OR 2.94, 95% CI 0.91-9.47), while in patients with a disease duration >1 year was associated with UPDRS-ME (OR 3.37, 95% CI 1.41-8.00). The overall MBI frequency in the PACOS sample was 84% and 36% among newly diagnosed patients. The presence of MBI mainly related to motor impairment and disability

Incidence of mild cognitive impairment and dementia in Parkinson's disease: The Parkinson's disease cognitive impairment study

Background: Cognitive impairment in Parkinson's disease (PD) includes a spectrum varying from Mild Cognitive Impairment (PD-MCI) to PD Dementia (PDD). The main aim of the present study is to evaluate the incidence of PD-MCI, its rate of progression to dementia, and to identify demographic and clinical characteristics which predict cognitive impairment in PD patients. Methods: PD patients from a large hospital-based cohort who underwent at least two comprehensive neuropsychological evaluations were retrospectively enrolled in the study. PD-MCI and PDD were diagnosed according to the Movement Disorder Society criteria. Incidence rates of PD-MCI and PDD were estimated. Clinical and demographic factors predicting PD-MCI and dementia were evaluated using Cox proportional hazard model. Results: Out of 139 enrolled PD patients, 84 were classified with normal cognition (PD-NC), while 55 (39.6%) fulfilled the diagnosis of PD-MCI at baseline. At follow-up (mean follow-up 23.5 ± 10.3 months) 28 (33.3%) of the 84 PD-NC at baseline developed MCI and 4 (4.8%) converted to PDD. The incidence rate of PD-MCI was 184.0/1000 pyar (95% CI 124.7-262.3). At multivariate analysis a negative association between education and MCI development at follow-up was observed (HR 0.37, 95% CI 0.15-0.89; p = 0.03). The incidence rate of dementia was 24.3/1000 pyar (95% CI 7.7-58.5). Out of 55 PD-MCI patients at baseline, 14 (25.4%) converted to PDD, giving an incidence rate of 123.5/1000 pyar (95% CI 70.3-202.2). A five time increased risk of PDD was found in PD patients with MCI at baseline (RR 5.09, 95% CI 1.60-21.4). Conclusion: Our study supports the relevant role of PD-MCI in predicting PDD and underlines the importance of education in reducing the risk of cognitive impairment

Use of Eribulin mesylate as second-line therapy in elderly patients with HER/2 negative metastatic breast cancer (MBC): Efficacy, tolerability and Quality of Life

OBJECTIVE: Eribulin mesylate (Halaven®) is a non-taxane inhibitor of microtubule indicated as monotherapy in patients with metastatic breast cancer (MBC), which progresses after anthracycline and taxanes therapy. In this retrospective observational study, we want to evaluate the efficacy of Eribulin in elderly women with MBC pretreated with anthracyclines and taxanes. PATIENTS AND METHODS: 40 elderly patients > 70 years of age were enrolled, and the median age was 76 years (range 70-82). Overall survival (OS), Progression Free Survival (PFS), Objective Response Rate (ORR) were primary endpoints, tolerability, carcinoembryonic antigen levels 15.3 (Ca 15.3), before and after treatment, and Quality of Life (QoL) were secondary endpoints. RESULTS: Eribulin treatment was well tolerated, produced a good level of disease control, a manageable toxicity profile and a significant impact on QoL. Median OS was 12.8 months and median PFS was 3.2 months. A significant correlation was observed between reduction of Ca 15.3 and PFS with a value of 0.59 (p = 0.002). CONCLUSIONS: Despite a limited number of patients and a modest manageable toxicity, Eribulin is a chemotherapy treatment that has showed to be an effective and well-tolerated therapeutic option in elderly patients with MBC. Further analysis should focus on the elderly patients in our setting of study

Clinical efficacy of nab-paclitaxel in patients with metastatic pancreatic cancer

Purpose: Pancreatic carcinoma is the neoplasia with the major mortality, and main standard treatments in this cancer increase survival but do not lead to complete recovery of the patient. The aim of this study was to evaluate the efficacy of Abraxane® (nab-paclitaxel) in Italian patients with metastatic pancreatic cancer (MPC). Patients and methods: We conducted a retrospective analysis of 80 patients. Overall survival (OS) was the primary end point for evaluating the efficacy of nab-paclitaxel in combination with gemcitabine treatment, while carbohydrate antigen 19-9 (CA 19-9) reduction, safety, progression-free survival (PFS), overall response rate and reduction in pain were secondary end points. Results: The median OS was 8 months, and the median PFS was 5 months. A considerable difference in CA 19-9 before and after treatment was observed. Descriptive and correlation analyses were done to examine the relationship between CA 19-9 response and OS. Linear regression analysis between OS and CA 19-9 response revealed that CA 19-9 is an important predictor of OS, showing a positive correlation. Conclusion: Nab-paclitaxel is a well-tolerated and effective treatment for patients affected by MPC. The drug showed an improved tolerability profile, significant pain relief and an increase in survival rate

The patient-physician relationship in the face of oncological disease: A review of literature on the emotional and psychological reactions of patients and physician

The physician-patient relationship is daily destabilized by emotional reactions and psychic defenses that cancer arises in the two partners. Continued scientific and technological progresses which were reached by medicine in recent years, and particularly oncologic clinical discoveries, increased the chance of not only survival but also healing. Nevertheless, cancer diagnosis is still a hard existential text that destabilizes everyday life, all the psychic and relational balance, inevitably causing a psychological and social change not only in the patient who is affected but also into the wide social network around him (family, friends, doctors, healthcare team). The aim of this review is to understand how problems, feelings, emotions, distresses or defense mechanisms could garble the relation and the communication dynamics between physician and patients and then prejudicing the efficacy of oncologic therapeutic compliance. Pubmed and Scopus were searched, using strings related to "cancer", "physician-patient relations", burn-out", "compliance", and "communication", identifying literature published from 2000 to January 2015. Extracted papers were assessed for their relevance (10 of 412 papers initially reviewed). Results indicate that a good and empathetic relationship between physician and patient were related to good therapeutic adherence. In particular, a good physician-patient relation maximizes the impact of clinical therapies and reduces psychophysical implications

Impact of combination chemotherapy on toxicity in ovarian cancer: Systematic revision of literature and meta-analysis

The purpose of this statistical analysis is to demonstrate the real advantages in terms of cost-benefit of combination chemotherapy compared with single-agent chemotherapy. The trials, which are used in this meta-analysis, have been searched on PubMed database and they are phase II or randomized phase III studies with only chemotherapy regimens. In this meta-analysis were evaluated adverse effects with odds ratio (OR), which is expressed in 95% confidence intervals (95% CI). Only 4 studies contained all the set selection criteria and they were selected. The data, which were obtained, were analyzed using MedCalc Application. The combination therapy was more strongly linked to certain adverse events than to chemotherapy with a single agent: thrombocytopenia, anemia, neutropenia and nausea. The data obtained for leukopenia, for vomiting and for stomatitis are not statistically significant, as well as those of antitumor activity. Obtained data allow us to state that the overall combination therapy is more closely related to adverse effects such as thrombocytopenia, anemia, neutropenia and nausea compared tosingle-agent chemotherapy

Cardiovascular autonomic function and MCI in Parkinson's disease

Introduction: dysautonomic dysfunction and cognitive impairment represent the most disabling non-motor features of Parkinson's Disease (PD). Recent evidences suggest the association between Orthostatic Hypotension (OH) and PD-Dementia. However, little is known on the interactions between cardiovascular dysautonomia and Mild Cognitive Impairment (MCI). We aimed to evaluate the association between cardiovascular dysautonomia and MCI in patients with PD. Methods: non-demented PD patients belonging to the PACOS cohort underwent a comprehensive instrumental neurovegetative assessment including the study of both parasympathetic and sympathetic function (30:15 ratio, Expiratory-Inspiratory ratio [E-I] and presence of Orthostatic Hypotension [OH]). Diagnosis of MCI was made according to the MDS criteria level II. Results: we enrolled 185 PD patients of whom 102 (55.1%) were men, mean age was 64.6 ± 9.7 years, mean disease duration of 5.6 ± 5.5 years with a mean UPDRS-ME score of 31.7 ± 10.9. MCI was diagnosed in 79 (42.7%) patients. OH was recorded in 52 (28.1%) patients, altered 30:15 ratio was recorded in 39 (24.1%) patients and an altered E-I ratio was found in 24 (19.1%) patients. Presence of MCI was associated with an altered 30:15 ratio (adjOR 2.83; 95%CI 1.25–6.40) but not with an altered E-I ratio, while OH was associated only with the amnestic MCI subgroup (OR 2.43; 95% CI 1.05–5.06). Conclusion: in our study sample, MCI was mainly associated with parasympathetic dysfunction in PD

The Brain on Low Power Architectures - Efficient Simulation of Cortical Slow Waves and Asynchronous States

Efficient brain simulation is a scientific grand challenge, a parallel/distributed coding challenge and a source of requirements and suggestions for future computing architectures. Indeed, the human brain includes about 10^15 synapses and 10^11 neurons activated at a mean rate of several Hz. Full brain simulation poses Exascale challenges even if simulated at the highest abstraction level. The WaveScalES experiment in the Human Brain Project (HBP) has the goal of matching experimental measures and simulations of slow waves during deep-sleep and anesthesia and the transition to other brain states. The focus is the development of dedicated large-scale parallel/distributed simulation technologies. The ExaNeSt project designs an ARM-based, low-power HPC architecture scalable to million of cores, developing a dedicated scalable interconnect system, and SWA/AW simulations are included among the driving benchmarks. At the joint between both projects is the INFN proprietary Distributed and Plastic Spiking Neural Networks (DPSNN) simulation engine. DPSNN can be configured to stress either the networking or the computation features available on the execution platforms. The simulation stresses the networking component when the neural net - composed by a relatively low number of neurons, each one projecting thousands of synapses - is distributed over a large number of hardware cores. When growing the number of neurons per core, the computation starts to be the dominating component for short range connections. This paper reports about preliminary performance results obtained on an ARM-based HPC prototype developed in the framework of the ExaNeSt project. Furthermore, a comparison is given of instantaneous power, total energy consumption, execution time and energetic cost per synaptic event of SWA/AW DPSNN simulations when executed on either ARM- or Intel-based server platforms