Uveal melanoma is the most prevalent and aggressive intraocular malignancy affecting adults. Compared with cutaneous melanoma, uveal melanoma has distinct pathogenesis and molecular characteristics. Not surprisingly, it derives limited benefits from checkpoint inhibitors. Until recently, no systemic therapy had impacted survival outcomes for this patient population. Tebentafusp, a T-cell receptor-based molecule, is the first US Food and Drug Administration/European Medicines Agency-approved systemic therapy to improve the survival outcomes for uveal melanoma patients expressing HLA-A∗02:01. Only 45%-50% of this patient population will express the HLA-A∗02:01, however, and therefore are eligible to receive this novel treatment. Moreover, global access to tebentafusp is limited, and there are no guidelines to aid clinicians in decision-making regarding treatment. In this review, we outline our experience as Canada's largest tertiary referral centre in managing metastatic uveal melanoma patients and provide a comprehensive overview of the currently available treatment options, challenging scenarios, and ongoing clinical trials for patients with metastatic uveal melanoma.
Immune checkpoint inhibitors (ICI) cemiplimab and pembrolizumab have revolutionized the treatment of advanced cutaneous squamous cell carcinoma (cSCC). We aimed to evaluate the effectiveness and safety of ICI in a real-world cSCC population, including patients with conditions that would exclude clinical trial participation. In this single-center, retrospective cohort study, we included all non-trial patients with advanced cSCC treated with ICI between 2017 and 2022. We evaluated investigator-assessed best overall response (BOR) and immune-related adverse events (irAEs). We correlated survival outcomes with age, performance status, immune status and irAEs. Of the 36 patients identified, the best overall response (BOR) to ICI was a partial response (PR) in 41.7%, a complete response (CR) in 27.8%, and stable disease in (SD) 13.9%. The progression-free survival (PFS) rate for 1 year was 58.1%; the median PFS was 21.3 months (95% CI 6.4–NE). The 1-year overall survival (OS) was 76.7%, and the median OS was 38.6 months (95% CI 25.4–NE). Immune-compromised patients, ECOG performance 2–3, and age ≥ 75 years were not significantly associated with PFS or OS. IrAE grades 3–4 were seen in 13.9% of patients. In our Canadian experience with real-world patients, ICI was an effective and safe treatment for advanced cSCC patients. Patients achieved great benefits with ICI regardless of age, immune status or ECOG performance status. We acknowledge the small sample size and retrospective methodology as the main limitations of our study.
: Immune checkpoint inhibitors (ICI) cemiplimab and pembrolizumab have revolutionized the treatment of advanced cutaneous squamous cell carcinoma (cSCC). We aimed to evaluate the effectiveness and safety of ICI in a real-world cSCC population, including patients with conditions which would exclude clinical trial participation. In this single-center, retrospective cohort study, we included all non-trial patients with advanced cSCC treated with ICI between 2017 and 2022. We evaluated investigator-assessed best overall response (BOR) and immune-related adverse events (irAEs). We correlated survival outcomes with age, performance status, immune status and irAEs. For the 36 patients identified, best overall response (BOR) to ICI was partial response (PR) in 41.7%, complete response (CR) in 27.8%, and stable disease in (SD) 13.9% of patients. The PFS rate at 1 year was 63%; median PFS was not reached (NR). The median OS was 38.6 months (95% CI 25.4-NR). Immune compromised patients, ECOG performance 2-3, and age ≥75 years were not significantly associated with PFS or OS. IrAE grade 3-4 were seen in 13.9% of patients. In our Canadian experience with real-world patients, ICI was an effective and safe treatment for advanced cSCC patients. Patients achieved great benefit with ICI regardless of age, immune status or ECOG performance status.
El cáncer de ovario ocupa el quinto lugar en frecuencia y es la cuarta causa de muerte por cáncer en las mujeres. Según la clasificación de la Organización Mundial de la Salud (OMS), existen diferentes tipos basados en sus características histopatológicas. El más frecuente es el epitelial (90%) que se subdivide en: seroso, mucinoso, seromucinosos, endometroide, de células claras, carcinosarcoma, mixtos y de células transicionales. Dentro de estos últimos tenemos que distinguir a los tumores de Brenner (benigno, borderline, malignos) de los carcinomas de células transicionales, menos frecuentes y con distinto valor pronóstico, lo que motiva su estudio e investigación dada la escasa evidencia científica disponible. Presentamos el caso clínico de una mujer de 50 años de edad con diagnóstico de carcinoma de células transicionales de ovario con mutación en el gen BRCA1 con la finalidad de caracterizar los rasgos clínicos, patológicos y moleculares de esta neoplasia poco habitual que abra paso a nuevos caminos de investigación en su terapéutica y formas de prevención.
1 January 2021 in Cancer Treatment and Research Communications
Breast cancer is the tumor with highest incidence in women worldwide and adjuvant treatment is extremely important to achieve disease control. Given the relevance of systematic reviews, their rigor should be warranted to avoid biased conclusions. Our objective was to investigate the methodological quality of meta-analysis of early breast cancer adjuvant treatment. Comprehensive searches were performed using electronic databases from 1/1/2007 to 11/12/2018. All studies identified as a systematic review with meta-analysis investigating the efficacy of breast cancer adjuvant treatments were included. Two reviewers independently assessed titles and abstracts, then full-texts for eligibility. Quality was assessed using the Assessing the Methodological Quality of Systematic Reviews (AMSTAR) version 2 tool. Of 950 citations retrieved, 66 studies (7.0%) were deemed eligible. Methodological quality was highly variable, median AMSTAR score 8.5 (IQR 7-9.5) and range 0-16. There was a weak positive correlation between journal impact factor and AMSTAR score (r = 0.17) and citation rate and AMSTAR score (r = 0.16). Cochrane Systematic Reviews were of higher quality than reviews from other journals. Overall confidence was critically low for 61 (92.4%) studies, and the least well-reported domains were the statement of conflict of interest and funding source for the included studies (4.6%), the report of a pre-defined study protocol (15.2%), and the description of details of excluded studies (6.1%). Our findings reinforce concerns about the design, conduction and interpretation of meta-analysis in current literature. Methodological quality should be carefully considered and journal editors, decision makers and readers in general, must follow a critical approach to this studies.