safety and effectiveness of regorafenib in patients with metastatic colorectal cancer in routine clinical practice in the prospective observational correlate study

Abstract Background Regorafenib prolonged overall survival (OS) versus placebo in patients with treatment-refractory metastatic colorectal cancer (mCRC) in phase III trials. We conducted an observational study of regorafenib for patients with mCRC in real-world clinical practice. Methods The international, prospective, CORRELATE study recruited patients with mCRC previously treated with approved therapies, for whom the decision to treat with regorafenib was made by the treating physician according to the local health authority approved label. The primary objective was safety, assessed by treatment-emergent adverse events (TEAEs; National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03). Results A total of 1037 patients were treated. The median age was 65 years (range: 24–93); 87% of patients had Eastern Cooperative Oncology Group performance status 0–1, 56% of patients had KRAS, 7% had NRAS and 4% had BRAF mutations. The initial regorafenib dose was 160 mg/day in 57% of patients. The most common grade III or IV drug-related TEAEs were fatigue (9%), hand–foot skin reaction (7%) and hypertension (6%). Drug-related grade V (fatal) TEAEs occurred in 1% of patients. Dose reductions for drug-related TEAEs occurred in 24% of patients. Median OS was 7.7 months (95% confidence interval [CI]: 7.2–8.3), and median progression-free survival (PFS) was 2.9 months (95% CI: 2.8–3.0). Conclusions In this real-world, observational study of patients with mCRC, the regorafenib toxicity profile was similar to that reported in phase III trials. The starting dose for almost half of patients was less than the approved 160-mg dose, and the median OS and PFS were in the range observed in phase III trials. Trial registration: NCT02042144

Vascular Endothelial Growth Factor (VEGF) et carcinome épidermoïde de l'oesophage

BREST-BU Médecine-Odontologie (290192102) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Anticorps anti-p53 et carcinome épidermoïde de l'oesophage (résultats préliminaires)

BREST-BU Médecine-Odontologie (290192102) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Retrospective study of 19 patients with intramedullary spinal cord metastasis

International audienc

External validation of the modified Ottawa score for risk stratification of recurrent cancer-associated thrombosis.

International audienc

La levure modèle et outil… aussi pour la recherche thérapeutique

International audienceGastric cancer (GC), which includes cancer of the esophagus, the oesophagogastric junction, and the stomach fundus, is highly deadly with strong regional influence, Asia being the most affected. GC is often detected at late stages, with 30% of metastatic cases at diagnosis. Many authors have devised models to both unravel the mechanisms of GC development and to evaluate candidate therapeutics. Among these models, 2D-cell cultures are progressively replaced by 3D-cell cultures that recapitulate, much more comprehensively, tumor cellular and genetic heterogeneity, as well as responsiveness to environmental changes, such as exposure to drugs or irradiation. With respect to the specifics of GC, there are high hopes from such model systems, especially with the aim of identifying prognostic markers and novel drug targets.La levure a été utilisée de façon empirique pendant des millénaires pour la panification et la fermentation des sucres en alcool. C’est seulement à partir de 1857 que Louis Pasteur décrit le microorganisme à l’origine de ces deux activités agroalimentaires majeures. Dès lors, les souches de levure ont pu être sélectionnées et modifiées sur une base rationnelle pour optimiser leurs usages agroalimentaires, permettant ainsi l’essor de la levure comme modèle biologique eucaryote. Cette utilisation a conduit à de très nombreuses découvertes de biologie cellulaire fondamentale. Depuis une vingtaine d’années, la levure est également utilisée comme modèle et outil pour la santé humaine. Ces approches s’étendent de la production de molécules thérapeutiques à la recherche de candidats-médicaments et de sondes chimiques, en passant par la mise au point de tests diagnostiques et la découverte de nouvelles cibles thérapeutiques. Cette utilisation de la levure en chémobiologie fait l’objet de la présente revue

Occupational Exposures and Esophageal Cancer: Prog Study

Esophageal cancer is the sixth most common cause of cancer death worldwide. In France, Brittany is one of the regions most seriously affected. This increased incidence is usually linked to high rates of alcohol overconsumption and smoking, established risk factors for esophageal cancer, but the region has special occupational exposures. We aim to describe the occupational exposures of patients with esophageal cancer. Between June and October 2020, we conducted a monocentric descriptive study in a French Teaching Hospital and identified 37 eligible patients. We gathered data through a systematic individual interview for each participant and by an analysis of their medical file. We were able to include 36 patients; most were men (n = 27, 75.0%) and smokers (n = 25, 69.4%), 21 (58.3%) presented an adenocarcinoma esophageal cancer, 13 (36.1%) a squamous cell cancer, and 2 other types. On occupational exposure, patients declared respectively high exposure by manipulating asbestos materials for 11 (30.6%) patients, regularly in contact with benzene by handling fuel in 7 cases (19.4%), chlorinated solvents in 4 cases (11.1%), pesticides in 4 cases, and ionizing radiation exposure in 3 patients (8.3%). Our findings support the creation of a large-scale study to explore the impact of occupational exposures, particularly exposure to asbestos and hydrocarbons

Radiomics Approaches for the Prediction of Pathological Complete Response after Neoadjuvant Treatment in Locally Advanced Rectal Cancer: Ready for Prime Time?

In recent years, neoadjuvant therapy of locally advanced rectal cancer has seen tremendous modifications. Adding neoadjuvant chemotherapy before or after chemoradiotherapy significantly increases loco-regional disease-free survival, negative surgical margin rates, and complete response rates. The higher complete rate is particularly clinically meaningful given the possibility of organ preservation in this specific sub-population, without compromising overall survival. However, all locally advanced rectal cancer most likely does not benefit from total neoadjuvant therapy (TNT), but experiences higher toxicity rates. Diagnosis of complete response after neoadjuvant therapy is a real challenge, with a risk of false negatives and possible under-treatment. These new therapeutic approaches thus raise the need for better selection tools, enabling a personalized therapeutic approach for each patient. These tools mostly focus on the prediction of the pathological complete response given the clinical impact. In this article, we review the place of different biomarkers (clinical, biological, genomics, transcriptomics, proteomics, and radiomics) as well as their clinical implementation and discuss the most recent trends for future steps in prediction modeling in patients with locally advanced rectal cancer