Uveal Melanoma: A European Network to Face the Many Challenges of a Rare Cancer

Uveal melanoma (UM) is the most frequent primary ocular cancer in adults, accounting for 5% of all melanomas. Despite effective treatments for the primary tumour, up to 50% of UM patients will develop metastasis, leading to a very poor prognosis and a median overall survival of 6 to 12 months, with no major improvements in the last 30 years. There is no standard oncological treatment available for metastatic UM patients, and BRAF/MEK and immune checkpoint inhibitors show disappointing results when compared to cutaneous melanoma (CM). Recent advances in biology, however, identified specific gene and chromosome alterations, potentially permitting an actively tailored surveillance strategy, and dedicated clinical studies. Being a rare cancer, UM patients have to overcome issues such as identifying referral centres, having access to information, and partnering with oncologists for specific management strategies and research priorities. Here, we describe how the EUropean Rare Adult solid CAacer Network (EURACAN) will help in addressing these challenges and accelerating international collaborations to enhance the development of innovative treatments in UM

Off-label use of targeted therapies in osteosarcomas: data from the French registry OUTC'S (Observatoire de l'Utilisation des Thérapies Ciblées dans les Sarcomes):

BACKGROUND: The objective of this study is to explore the off-label use of targeted therapies (TTs) for patients with osteosarcoma registered within the French Sarcoma Group--Bone Tumor Study Group (GSF-GETO) national registry. METHODS: All patients with an osteosarcoma, registered between January 1, 2009 and July 15, 2013 were analyzed. RESULTS: Twenty-nine patients with refractory relapsed osteosarcomas received 33 treatment lines of TTs. The median age at the beginning of treatment was 19 years (range 9-72). The median number of previous lines of chemotherapy was 3 (range 1-8). Before inclusion, 3 patients were in second complete remission, 26 were in progression for metastatic relapse. Twenty-three patients received sirolimus (in combination with cyclophosphamide for 18); 5, sunitinib; 4, sorafenib; and one, pazopanib. Stable disease was observed for 45.5% of patients (95% Confidence Interval (CI) [20-52.8]). The median Progression-Free Survival (PFS) was 3 months (95% CI [2-5.4]) for patients treated by sirolimus and 1.8 months (95% CI [1.3-2.8]) for patients receiving multi-targeted tyrosine kinase inhibitors; 6-month PFS 15%. The median Overall Survival (OS) was 6.8 months (95% CI [4.7-12.1]), and one-year OS was 24%. In a multivariate analysis, PFS was superior for patients receiving sirolimus compared to other TTs (Hazard Ratio (HR) = 2.7, 95% CI [1.05-7.1]). No toxic death was reported. Grade 3 and 4 toxicities were observed in 27 and 6% of cases respectively. CONCLUSION: Off-label TTs, especially sirolimus, reported benefit in the treatment of refractory osteosarcomas with an acceptable toxicity profile, including in pediatric population

Autologous chondrocyte implantation for traumatic full-thickness cartilage defects of the knee in 14 patients: 6-year functional outcomes

Background: Autologous chondrocyte implantation (ACI) was introduced in 1987 in Sweden by Brittberg and Peterson for the treatment of severe chondral defects of the knee. Here, our objective was to evaluate mid-term outcomes of ACI in young athletic patients with deep chondral defects of the knee after trauma. Hypothesis: ACI is effective in filling full-thickness chondral defects of the knee. Patients and methods: We prospectively monitored 14 patients, with International Cartilage Repair Society grade III or IV lesions, who underwent ACI between 2001 and 2006. Standard evaluation measurements were used. Mean age at surgery was 37.7 years (range, 30—45). A history of surgery on the same knee was noted in ten (67%) patients. The defect was on the medial femoral condyle in 11 patients, lateral femoral condyle in two patients, and both femoral condyles in one patient. Mean defect surface area after debridement was 2.1 cm2 (1—6.3). Results: After a mean follow-up of six years, improvements were noted in 12 (86%) patients, with an International Knee Documentation Committee (IKDC) score increase from 40 (27.6—65.5) to 60.2 (35.6—89.6) (P = 0.003) and a Brittberg-Perterson score decrease from 54.4 (11.8—98.2) to 32.9 (0—83.9) (P = 0.02), between the preoperative assessment and last follow-up. The visual analogic scale pain score decreased from 66.3 (44—89) to 23.2 (0—77) (P = 0.0006). In two (14%) patients, no improvements were detectable at last follow-up. The remaining 12 patients were satisfied and able to resume sporting activities, albeit at a less strenuous level. Two ACIspecific complications occurred, namely, periosteal hypertrophy treated with debridement in one patient and transplant delamination in another

Osteoarthritic cartilage fibrillation is associated with a decrease in chondrocyte adhesion to fibronectin.

International audienceObjective: Cartilage destruction in osteoarthritis (OA) is generally accepted as a failed repair process. Cell adhesion is implicated in tissue repair. Therefore, adhesion of OA chondrocytes to extracellular matrix proteins was investigated.Design: Using chondrocytes from human OA femoral head cartilage, adhesion to fibronectin and type II collagen of cells from distinct areas showing an intact cartilage surface or a fibrillated cartilage surface was studied. Modulation of chondrocyte adhesion by both protein kinase C (PKC) inhibitors and glucosamine sulfate (GS) was also investigated.Results: A significant (P<0.05) decrease in adhesion to fibronectin of chondrocytes from fibrillated cartilage, relative to those from grossly normal OA cartilage, was demonstrated. Adhesion to type II collagen was not modified by the chondrocyte origins (either from normal or fibrillated OA cartilage) Adhesion to fibronectin of cells from grossly intact cartilage was decreased by the addition of PKC and calmodulin-dependent kinase inhibitors, W7 and sphingosine, to the cell culture. Adhesion to fibronectin of chondrocytes from fibrillated cartilage was significantly (P<0.05) increased after glucosamine sulfate treatment.Conclusion: Fibrillation of cartilage from OA femoral head is associated with a defective adhesion of chondrocytes to fibronectin. The process is suggested to be dependent of PKC and/or calmodulin-dependent kinases and potentially reversible. Conceivably, it could play a role in OA cartilage destruction

Cartilage-Characteristic Matrix Reconstruction by Sequential Addition of Soluble Factors During Expansion of Human Articular Chondrocytes and Their Cultivation in Collagen Sponges

International audienc

Development and Validation of a Self-Administered Questionnaire Measuring Essential Knowledge in Patients with Rheumatoid Arthritis

Abstract To develop and validate a questionnaire assessing patient knowledge in rheumatoid arthritis (RA). Knowledge considered essential for patients with RA was identified through a series of Delphi rounds among rheumatologists, health professionals (HPs), patients, and then reformulated to construct the knowledge questionnaire. Cross-sectional multicenter validation was performed in 12 rheumatology departments to assess internal validity (Kuder\textendash Richardson coefficient), external validity, acceptability, reproducibility (Lin's concordance correlation coefficient) and sensitivity to change (difference in total score before and after patient education sessions). Associations between patient variables and knowledge levels were evaluated. RAKE (RA Knowledge questionnairE) is a self-administered 45-item questionnaire scored 0\textendash 100, with a 32-item short-form survey assessing knowledge of disease, comorbidity, pharmacological treatments, non-pharmacological treatments, self-care and adaptative skills. Of 130 patients included in the validation study, 108 were women. Acceptability was good with\,<\,5% missing data. Internal validity coefficient was 0.90. Mean (standard deviation) long-form score was 72.8\,±\,17.8, with lower scores in comorbidity and self-care and higher scores in adaptive skills. Reproducibility was good (0.86 [0.80; 0.92]). RAKE score was positively correlated with the patients' level of education and the HPs' opinion on the patients' knowledge. RAKE score showed good sensitivity to change: 66.8\,±\,16.4 then 83.8\,±\,12.7, representing a hedges effect size of 1.14 [95% CI 0.73; 1.55]. RAKE is an updated questionnaire assessing essential knowledge for patients with RA to enhance self-management according to current guidelines and the patients' perspective. RAKE can usefully inform patient education interventions, routine care and research