Two Components of Long-Distance Extraction: Successive Cyclicity in Dinka

This article presents novel data from the Nilotic language Dinka, in which the syntax of successive-cyclic movement is remarkably transparent. We show that Dinka provides strong support for the view that long-distance extraction proceeds through the edge of every verb phrase and every clause on the path of movement (Chomsky 1986, 2000, 2001, 2008). In addition, long-distance dependencies in Dinka offer evidence that extraction from a CP requires agreement between v and the CP that is extracted from (Rackowski and Richards 2005, Den Dikken 2009b, 2012a,b). The claim that both of these components constrain long-distance movement is important, as much contemporary work on extraction incorporates only one of them. To accommodate this conclusion, we propose a modification of Rackowski and Richards 2005, in which both intermediate movement and Agree relations between phase heads are necessary steps in establishing a long-distance dependency

PREDICT underestimates survival of patients with HER2-positive early-stage breast cancer

The prognostic performance of PREDICT in patients with HER2-positive early breast cancer (EBC) treated in the modern era with effective chemotherapy and anti-HER2 targeted therapies is unclear. Therefore, we investigated its prognostic performance using data extracted from ALTTO, a phase III trial evaluating adjuvant lapatinib +/- trastuzumab vs. trastuzumab alone in patients with HER2-positive EBC. Our analysis included 2794 patients. After a median follow-up of 6.0 years (IQR, 5.8-6.7), 182 deaths were observed. Overall, PREDICT underestimated 5-year OS by 6.7% (95% CI, 5.8-7.6): observed 5-year OS was 94.7% vs. predicted 88.0%. The underestimation was consistent across all subgroups, including those according to the type of anti HER2-therapy. The highest absolute differences were observed for patients with hormone receptor negative-disease, nodal involvement, and large tumor size (13.0%, 15.8%, and 15.3%, respectively). AUC under the ROC curve was 73.7% (95% CI 69.7-77.8) in the overall population, ranging between 61.7% and 77.7% across the analyzed subgroups. In conclusion, our analysis showed that PREDICT highly underestimated OS in HER2-positive EBC. Hence, it should be used with caution to give prognostic estimation to HER2-positive EBC patients treated in the modern era with effective chemotherapy and anti-HER2 targeted therapies

The effect of body mass index on overall and disease-free survival in node-positive breast cancer patients treated with docetaxel and doxorubicin-containing adjuvant chemotherapy: the experience of the BIG 02-98 trial.

BACKGROUND: Obesity has been shown to be an indicator of poor prognosis for patients with primary breast cancer (BC) regardless of the use of adjuvant systemic therapy. PATIENTS AND METHODS: This is a retrospective analysis of 2,887 node-positive BC patients enrolled in the BIG 02-98 adjuvant study, a randomised phase III trial whose primary objective was to evaluate disease-free survival (DFS) by adding docetaxel to doxorubicin-based chemotherapy. In the current analysis, the effect of body mass index (BMI) on DFS and overall survival (OS) was assessed. BMI was obtained before the first cycle of chemotherapy. Obesity was defined as a BMI >or= 30 kg/m2. RESULTS: In total, 547 (19%) patients were obese at baseline, while 2,340 (81%) patients were non-obese. Estimated 5-year OS was 87.5% for non-obese and 82.9% for obese patients (HR 1.34; P = 0.013). Estimated 5-years DFS was 75.9% for nonobese and 70.0% for obese patients (HR 1.20; P = 0.041). Ina multivariate model, obesity remained an independent prognostic factor for OS and DFS. CONCLUSIONS: In this study,obesity was associated with poorer outcome in node-positive BC patients. Given the increasing prevalence of obesity worldwide, more research on improving the treatment of obese BC patients is needed.Clinical Trial, Phase IIIJournal ArticleRandomized Controlled TrialResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe

Lucitanib for the treatment of HR+/ HER2- metastatic breast cancer: results from the multicohort phase II FINESSE study

reserved23siFGFR1 gene is amplified in 14% of HR+/ HER2- breast cancer patients. Efficacy and safety of lucitanib, an inhibitor of VEGFR1-3, FGFR1-3 and PDGFRα/β, were assessed.mixedHui, Rina; Pearson, Alex; Cortés, Javier; Campbell, Christine; Poirot, Camille; Azim, Hatem A; Fumagalli, Debora; Lambertini, Matteo; Daly, Fergus; Arahmani, Amal; Pérez-Garcia, José; Aftimos, Philippe; Bedard, Phillipe L; Xuereb, Laura; Scheepers, Elsemieke D; Vicente, Malou; Goulioti, Theodora; Loibl, Sibylle; Loi, Sherene; Pierrat, Marie-Jeanne; Turner, Nicholas C; Andre, Fabrice; Curigliano, GiuseppeHui, Rina; Pearson, Alex; Cortés, Javier; Campbell, Christine; Poirot, Camille; Azim, Hatem A; Fumagalli, Debora; Lambertini, Matteo; Daly, Fergus; Arahmani, Amal; Pérez-Garcia, José; Aftimos, Philippe; Bedard, Phillipe L; Xuereb, Laura; Scheepers, Elsemieke D; Vicente, Malou; Goulioti, Theodora; Loibl, Sibylle; Loi, Sherene; Pierrat, Marie-Jeanne; Turner, Nicholas C; Andre, Fabrice; Curigliano, Giusepp

Lucitanib for the treatment of HR+/HER2- metastatic breast cancer:results from the multicohort phase II FINESSE study

Purpose: The FGFR1 gene is amplified in 14% of patients with HR+/HER2− breast cancer. Efficacy and safety of lucitanib, an inhibitor of VEGFR1-3, FGFR1-3, and PDGFRα/β, were assessed.Patients and Methods: Patients with HR+/HER2− metastatic breast cancer (MBC) received oral lucitanib in three centrally confirmed cohorts: (i) FGFR1 amplified, (ii) FGFR1 nonamplified, 11q13 amplified, and (iii) FGFR1 and 11q13 nonamplified. Key inclusion criteria included Eastern Cooperative Oncology Group Performance Status ≤2, ≥1 line of anticancer therapy, but ≤2 lines of chemotherapy. Primary endpoint was overall response rates (ORR) by RECIST1.1. Simon's two-stage design was used: If ≥2 patients responded among 21 patients, 20 additional patients could be enrolled in each cohort. FGFR1 copy-number variation (CNV) was determined by FISH and droplet digital PCR, whereas FGFR1 expression was determined by IHC.Results: Seventy-six patients (32/18/26 in cohorts 1/2/3) from nine countries were enrolled. The prespecified primary endpoint was met in cohort 1 with ORR of 19% [95% confidence interval (CI), 9%–35%], but not in cohorts 2 and 3 with ORR of 0% (95% CI, 0%–18%) and 15% (95% CI, 6%–34%), respectively. Frequent adverse events included hypertension (87%), hypothyroidism (45%), nausea (33%), and proteinuria (32%). Exploratory biomarker analyses suggested higher ORR in patients with high FGFR1 amplification (≥4 CNV) than those without high amplification (22% vs. 9%). ORR in patients with FGFR1-high tumors (IHC, H-score ≥50) was 25% versus 8% in FGFR1-low cancers.Conclusions: Lucitanib had modest antitumor activity and significant hypertension-related toxicity in patients with HR+/HER2− MBC. Although based on small sample sizes, exploratory biomarker analyses suggested that patients with high FGFR1 amplification or expression might derive greater benefit.</p