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Background: The GOG240 trial established bevacizumab with chemotherapy as standard first-line therapy for metastatic or recurrent cervical cancer. In the BEATcc trial (ENGOT-Cx10–GEICO 68-C–JGOG1084–GOG-3030), we aimed to evaluate the addition of an immune checkpoint inhibitor to this standard backbone. Methods: In this investigator-initiated, randomised, open-label, phase 3 trial, patients from 92 sites in Europe, Japan, and the USA with metastatic (stage IVB), persistent, or recurrent cervical cancer that was measurable, previously untreated, and not amenable to curative surgery or radiation were randomly assigned 1:1 to receive standard therapy (cisplatin 50 mg/m2 or carboplatin area under the curve of 5, paclitaxel 175 mg/m2, and bevacizumab 15 mg/kg, all on day 1 of every 3-week cycle) with or without atezolizumab 1200 mg. Treatment was continued until disease progression, unacceptable toxicity, patient withdrawal, or death. Stratification factors were previous concomitant chemoradiation (yes vs no), histology (squamous cell carcinoma vs adenocarcinoma including adenosquamous carcinoma), and platinum backbone (cisplatin vs carboplatin). Dual primary endpoints were investigator-assessed progression-free survival according to Response Evaluation Criteria in Solid Tumours version 1.1 and overall survival analysed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT03556839, and is ongoing. Findings: Between Oct 8, 2018, and Aug 20, 2021, 410 of 519 patients assessed for eligibility were enrolled. Median progression-free survival was 13·7 months (95% CI 12·3–16·6) with atezolizumab and 10·4 months (9·7–11·7) with standard therapy (hazard ratio [HR]=0·62 [95% CI 0·49–0·78]; p<0·0001); at the interim overall survival analysis, median overall survival was 32·1 months (95% CI 25·3–36·8) versus 22·8 months (20·3–28·0), respectively (HR 0·68 [95% CI 0·52–0·88]; p=0·0046). Grade 3 or worse adverse events occurred in 79% of patient

Background: Limited evidence exists to support CA-125 as a valid surrogate biomarker for progression in patients with ovarian cancer on maintenance PARP inhibitor (PARPi) therapy. We aimed to assess the concordance between CA-125 and Response Evaluation Criteria in Solid Tumours (RECIST) criteria for progression in patients with BRCA mutations on maintenance PARPi or placebo. Methods: We extracted data on progression as defined by Gynecologic Cancer InterGroup CA-125, investigator- and independent central-assessed RECIST from the SOLO2/ENGOT-ov21(NCT01874353) trial. We excluded those with progression other than by RECIST, progression on date of randomisation, and no repeat CA-125 beyond baseline. We evaluated the concordance between CA-125 progression and RECIST progression, and assessed the negative (NPV) and positive predictive value (PPV). Results: Of 295 randomised patients, 275 (184 olaparib, 91 placebo) were included. 171 patients had investigator-assessed RECIST progression. Of 80 patients with CA-125 progression, 77 had concordant RECIST progression (PPV 96%, 95% confidence interval 90–99%). Of 195 patients without CA-125 progression, 94 had RECIST progression (NPV 52%, 45–59%). Within treatment arms, PPV was similar (olaparib: 95% [84–99%], placebo: 97% [87–100%]) but NPV was lower in patients on placebo (olaparib: 60% [52–68%], placebo: 30% [20–44%]). Of 94 patients with RECIST but without CA-125 progression, 64 (68%) had CA-125 that remained within normal range. We observed similar findings using independent-assessed RECIST. Conclusions: Almost half the patients without CA-125 progression had RECIST progression, and most of these had CA-125 within the normal range. Regular computed tomography imaging should be considered as part of surveillance in patients treated with or without maintenance olaparib rather than relying on CA-125 alone.

Despite the strong prognostic stratification of circulating tumor cells (CTCs) enumeration in metastatic breast cancer (MBC), current clinical trials usually do not include a baseline CTCs in their design. This study aimed to generate a classifier for CTCs prognostic simulation in existing datasets for hypothesis generation in patients with MBC. A K-nearest neighbor machine learning algorithm was trained on a pooled dataset comprising 2436 individual MBC patients from the European Pooled Analysis Consortium and the MD Anderson Cancer Center to identify patients likely to have CTCs ≥ 5/7 mL blood (StageIVaggressive vs StageIVindolent). The model had a 65.1% accuracy and its prognostic impact resulted in a hazard ratio (HR) of 1.89 (Simulatedaggressive vs SimulatedindolentP < .001), similar to patients with actual CTCs enumeration (HR 2.76; P < .001). The classifier's performance was then tested on an independent retrospective database comprising 446 consecutive hormone receptor (HR)-positive HER2-negative MBC patients. The model further stratified clinical subgroups usually considered prognostically homogeneous such as patients with bone-only or liver metastases. Bone-only disease classified as Simulatedaggressive had a significantly worse overall survival (OS; P < .0001), while patients with liver metastases classified as Simulatedindolent had a significantly better prognosis (P < .0001). Consistent results were observed for patients who had undergone CTCs enumeration in the pooled population. The differential prognostic impact of endocrine- (ET) and chemotherapy (CT) was explored across the simulated subgroups. No significant differences were observed between ET and CT in the overall population, both in terms of progression-free survival (PFS) and OS. In contrast, a statistically significant difference, favoring CT over ET was observed among Simulatedaggressive patients (HR: 0.62; P = .030 and HR: 0.60; P = .037, respectively, for PFS and OS).

Con la presente investigación se analiza el lenguaje no verbal que utilizan los dos protagonistas de la película Un cuento chino para comunicarse entre ellos. El chino Jun y el bonaerense Roberto no hablan el mismo idioma y, por esto, a la hora de cohabitar tienen que buscar maneras para entenderse mutuamente mediante, entre otros, varios gestos. Para llevar a cabo el trabajo, se ha realizado un análisis pragmático sociocultural con el que se han analizado unas secuencias relevantes, que ha permitido la individuación del proceso del choque cultural en Jun. De hecho, la principal pregunta de investigación a la que se ha intentado contestar es averiguar en qué medida contribuye la comunicación no verbal a mitigar el choque cultural de Jun en su vida en Buenos Aires. La hipótesis es que si existen unos gestos compartidos a la vez por la cultura china y la argentina el choque cultural podría ser evitado o, mejor dicho, limitado. Por lo que concierne a los resultados, estos demuestran que lo que vive Jun es un choque único en su género, pues resulta muy singular.

Investigaciones recientes demuestran que los alumnos neerlandeses son los menos motivados y los peores lectores del mundo y que el currículo neerlandés de L2 necesita un enfoque intercultural. Por lo tanto, este estudio investiga cómo una lista de lecturas en español centrada en el alumno (A1/A2) del tercer año del Spinoza20first puede contribuir al desarrollo literario e intercultural. La investigación cualitativa y cuantitativa se llevó a cabo mediante una encuesta rellenada por alumnos de 14 a 16 años (n = 16) sobre su mundo de percepción y preferencias de lectura. A partir de los aspectos teóricos de las competencias literarias e interculturales y de los resultados de la encuesta, se ha elaborado una lista de lecturas que corresponde en la medida de lo posible con la vida diaria de los alumnos y sus preferencias de lectura. El análisis ha mostrado que especialmente la familia, la amistad, las redes sociales, la música, la guerra, los viajes y las vacaciones, los deportes, la escuela y los videojuegos forman parte de su vida cotidiana. En cuanto a la temática, los alumnos tienen un abanico muy amplio de gustos (30 de 31 temas fueron elegidos por al menos un alumno) y en cuanto a los protagonistas, prefieren a alguien de aproximadamente su misma edad (56%) y que la perspectiva narrativa se sitúe también en el protagonista (44%). El análisis también ha mostrado que los participantes están más motivados para leer en español cuando con ello pueden aprender sobre la cultura de habla hispana (6% frente al 25%). Con el objetivo de fomentar las competencias literarias de los alumnos, la lista de lecturas debe ajustarse a su percepción del mundo y, para las competencias interculturales, la lectura también debe permitirles aprender sobre las culturas hispanohablantes. Si en ello se tienen en cuenta las preferencias de lectura, aumentará también la motivación por la lectura y así también se estimulará el desarrollo literario e intercultural.