Coastal zone management in the fisheries sector program

International audienceThis paper presents an analysis of censored survival data for breast cancer specific mortality and disease-free survival. There are three stages to the process, namely time-to-event modelling, risk stratification by predicted outcome and model interpretation using rule extraction. Model selection was carried out using the benchmark linear model, Cox regression but risk staging was derived with Cox regression and with Partial Logistic Regression Artificial Neural Networks regularised with Automatic Relevance Determination (PLANN-ARD). This analysis compares the two approaches showing the benefit of using the neural network framework especially for patients at high risk. The neural network model also has results in a smooth model of the hazard without the need for limiting assumptions of proportionality. The model predictions were verified using out-of-sample testing with the mortality model also compared with two other prognostic models called TNG and the NPI rule model. Further verification was carried out by comparing marginal estimates of the predicted and actual cumulative hazards. It was also observed that doctors seem to treat mortality and disease-free models as equivalent, so a further analysis was performed to observe if this was the case. The analysis was extended with automatic rule generation using Orthogonal Search Rule Extraction (OSRE). This methodology translates analytical risk scores into the language of the clinical domain, enabling direct validation of the operation of the Cox or neural network model. This paper extends the existing OSRE methodology to data sets that include continuous-valued variables

Maintenance therapy in NSCLC: why? To whom? Which agent?

Maintenance therapy is emerging as a treatment strategy in the management of advanced non small cell lung cancer (NSCLC). Initial trials addressing the question of duration of combination chemotherapy failed to show any overall survival benefit for the prolonged administration over a fixed number of cycles with an increased risk for cumulative toxicity. Nowadays several agents with different ways of administration and a different pattern of toxicity have been formally investigated in the maintenance setting. Maintenance strategies include continuing with an agent already present in the induction regimen or switching to a different one. Taking into consideration that no comparative trials of maintenance with different chemotherapy drugs or targeted agents have been conducted, the choice and the duration of maintenance agents is largely empirical. Furthermore, it is still unknown and it remains an open question if this approach needs to be proposed to every patient in the case of partial/complete response or stable disease after the induction therapy. Here, we critically review available data on maintenance treatment, discussing the possibility to tailor the right treatment to the right patient, in an attempt to optimize costs and benefits of an ever-growing panel of different treatment options

Alectinib versus crizotinib in untreated ALK-positive non–small-cell lung cancer

Alectinib, a highly selective inhibitor of anaplastic lymphoma kinase (ALK), has shown systemic and central nervous system (CNS) efficacy in the treatment of ALK-positive non-small-cell lung cancer (NSCLC). We investigated alectinib as compared with crizotinib in patients with previously untreated, advanced ALK-positive NSCLC, including those with asymptomatic CNS disease. In a randomized, open-label, phase 3 trial, we randomly assigned 303 patients with previously untreated, advanced ALK-positive NSCLC to receive either alectinib (600 mg twice daily) or crizotinib (250 mg twice daily). The primary end point was investigator-assessed progression-free survival. Secondary end points were independent review committee-assessed progression-free survival, time to CNS progression, objective response rate, and overall survival. During a median follow-up of 17.6 months (crizotinib) and 18.6 months (alectinib), an event of disease progression or death occurred in 62 of 152 patients (41%) in the alectinib group and 102 of 151 patients (68%) in the crizotinib group. The rate of investigator-assessed progression-free survival was significantly higher with alectinib than with crizotinib (12-month event-free survival rate, 68.4% [95% confidence interval (CI), 61.0 to 75.9] with alectinib vs. 48.7% [95% CI, 40.4 to 56.9] with crizotinib; hazard ratio for disease progression or death, 0.47 [95% CI, 0.34 to 0.65]; P<0.001); the median progression-free survival with alectinib was not reached. The results for independent review committee-assessed progression-free survival were consistent with those for the primary end point. A total of 18 patients (12%) in the alectinib group had an event of CNS progression, as compared with 68 patients (45%) in the crizotinib group (cause-specific hazard ratio, 0.16; 95% CI, 0.10 to 0.28; P<0.001). A response occurred in 126 patients in the alectinib group (response rate, 82.9%; 95% CI, 76.0 to 88.5) and in 114 patients in the crizotinib group (response rate, 75.5%; 95% CI, 67.8 to 82.1) (P=0.09). Grade 3 to 5 adverse events were less frequent with alectinib (41% vs. 50% with crizotinib). As compared with crizotinib, alectinib showed superior efficacy and lower toxicity in primary treatment of ALK-positive NSCLC. (Funded by F. Hoffmann-La Roche; ALEX ClinicalTrials.gov number, NCT02075840 .)

First step in management of weight gain induced by chemotherapy for early breast cancer.

Abstract Abstract #6139 Adjuvant therapies for breast cancer are often associated with weight gain (WG). Overweight, obesity and WG have deleterious consequences for quality of life and probably for breast cancer evolution.&amp;#x2028; This french monocentric prospective study aimed to determine the incidence of overweight, obesity and WG during and one year after adjuvant chemotherapy (CT) for early breast cancer. Secondary goals were to examine the observance of national nutritional recommendations for healthy living, to observe their effects on WG prevention and to estimate patients needs for dietetic management.&amp;#x2028; Method : Patients younger than 66 years candidates for adjuvant CT for early breast cancer underwent dietary evaluation at the beginning of CT and were informed of the benefits of WG prevention, healthy diet and living habits. Written recommendations are given. A dietetic follow-up was systematically proposed. Weight, Body Mass Index (BMI) and nutritional habits over the last year before diagnosis, and at 6 and 12 months after chemotherapy were recorded. Statistical analysis is performed to test the association between WG and initial parameters (alpha level 5%).&amp;#x2028; Results: Of 272 consecutive patients recruited from Oct 2004 to Oct 2006, 242 are evaluated at 6 months and 233 after 1 year. The mean age was 51 years ; 44.1% were not menopausal before chemotherapy. TNM classification was as follows: T0: 15%, T1: 41%, T2: 32%, T3: 9%, T4: 3% and N+: 68%. Chemotherapy regimes were based on doxorubicin for 40% of cases, on taxanes for 1.5% and both for 58.5% . Hormonal therapy was provided to 74.85% of the patients. The average weight before chemotherapy was 65.9 kg (44-117); 25.7% of patients were overweight (25&amp;lt;BMI&amp;lt;30) and 15.1% obese (BMI&amp;gt;30). A third experienced WG during the year before diagnosis. Six months after CT, 52.1% patients had gained weight (&amp;lt;5% body weight for 59%, but &amp;gt;10% for 7.1%) and 29.8 % had lost weight. At one year, WG affected 59.7% of the patients. The average of WG is 5.88% of body weight and 14.4% of the patients gained more than 10%. WG before diagnosis seems to be the only factor associated with post CT absence of weight gain (OR 0.542, IC 95% [0.308-0.954], p= 0.0338). Only 43 women (16%) asked for dietetic follow-up, which induced weight loss for 57%. Health recommendations of the national program of nutrition and health (PNNS in France) were observed by 36.1% of the patients at the beginning of treatment, versus 43.5% at 6 months and 52.1% at one year.&amp;#x2028; Discussion and conclusions :&amp;#x2028; This study confirms the high rate of patients gaining weight after chemotherapy. Nutritional information alone is not sufficient, and appropriate healthy program (nutritional follow up and physical activities) must be proposed to limit weight gain and avoid possible consequences on disease free survival and further co morbidities. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6139.</jats:p