ABSTRACT
OBJECTIVES: In patients with epithelial ovarian cancer (EOC), the clinical efficacy of monotherapy with immune checkpoint inhibitors (ICIs) against PD-1/PD-L1 is modest. To enhance response rates to these immunotherapeutic agents and broaden the indications for their use, new approaches involving combinational therapy are needed. The immune regulator CD73 is a potential target, as it promotes tumor escape by producing immunosuppressive extracellular adenosine in the tumor microenvironment. Here, we present the results from the NSGO-OV-UMB1/ENGOT-OV-30 trial evaluating the activity of combining the anti-CD73 antibody oleclumab with the anti-PD-L1 checkpoint inhibitor durvalumab in patients with recurrent EOC. METHODS: In this phase II open-label non-randomized study, patients with CD73-positive relapsed EOC were intravenously administered oleclumab (3000 mg, Q2W) and durvalumab (1500 mg, Q4W). The primary endpoint was disease control rate (DCR) at 16 weeks. The expression of PD-L1 and CD8 was assessed by immunohistochemistry of archival tumors. RESULTS: This trial included 25 patients with a median age of 66 years (47-77 years). Twenty-two patients were evaluable for treatment activity analysis. The DCR was 27%, the median progression-free survival was 2.7 months (95% CI: 2.2-4.2) and the median overall survival was 8.4 months (95% CI: 5.0-13.4). Infiltration of CD8+ cells and PD-L1 expression on tumor cells were observed in partially overlapping sets of 74% of the tumor samples. Neither CD8- nor PD-L1-positivity were significantly associated with better DCR. CONCLUSIONS: Combined treatment with oleclumab and durvalumab was safe and demonstrated limited anti-tumor activity in patients with recurrent EOC.
ABSTRACT
OBJECTIVE: This study aimed to explore whether phenotypic characteristics of patients with chronic widespread pain (CWP) and fibromyalgia (FM) can be aggregated into definable clusters that may help to tailor treatments. METHOD: Baseline variables (sex, age, education, marital/employment status, pain duration, prior CWP/FM diagnosis, concomitant rheumatic disease, analgesics, tender point count, and disease variables derived from standardized questionnaires) collected from 1099 patients (93.4% females, mean age 44.6 years) with a confirmed CWP or FM diagnosis were evaluated by hierarchical cluster analysis. The number of clusters was based on coefficients in the agglomeration schedule, supported by dendrograms and silhouette plots. Simple and multiple regression analyses using all variables as independent predictors were used to assess the likelihood of cluster assignment, reported as odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: Only one cluster emerged (Cluster 1: 455 patients). Participants in this cluster were characterized as working (OR 66.67, 95% CI 7.14 to 500.00), with a medium-term/higher education (OR 16.80, 95% CI 1.94 to 145.41), married/cohabiting (OR 14.29, 95% CI 1.26 to 166.67), and using mild analgesics (OR 25.64, 95% CI 0.58 to > 999.99). The odds of being an individual in Cluster 1 were lower when having a worse score on the PDQ (score ≥ 18) (OR < 0.001, 95% CI < 0.001 to 0.02). CONCLUSION: We identified one cluster, where participants were characterized by a potentially favourable clinical profile. More studies are needed to evaluate whether these characteristics could be used to guide the management of patients with CWP and FM.
ABSTRACT
A fin de evaluar los criterios quirúrgicos en la coledocolitiasis asintomática, se aplicó un protocolo prospectivo a 134 pacientes, todos portadores de colecistitis crónica litiásica sin evidencia de coledocolitiasis preoperatoria. A todos los pacientes se les practicó colangiografía intraoperatoria, pero antes de efectuarla el cirujano era consultado si de no disponer de colangiografía, el paciente sería tributario de exploración de colédoco, por sospecha de coledocolitiasis y en qué basaba su opción. Tras efectuada la colangiografía se correlacionaron los hallazgos con la decisión del cirujano. Se establecieron 4 grupos: a) colédoco explorable y CIO normal=15 casos (11%); b) colédoco no explorable y CIO normal=106 casos (79,1%); c) colédoco explorable y CIO con litiasis=11 casos (8,2%) y d) colédoco no explorable y CIO con litiasis=2 casos (1,5%). Se concluye que en un grupo seleccionado de pacientes el cirujano es capaz de discernir correctamente en el 87,3% de los casos. La posibilidad de coledocolitiasis inadvertida es baja (1,5%). Las razones para explorar o no el colédoco son fundamentalmente: el diámetro del cístico y de la vía biliar, la presencia de cálculos pequeños en vesícula o en el cístico. La experiencia del equipo quirúrgico no se correlacionó con ninguno de los grupos en particular