RESUMEN
Tumor mutational burden (TMB) has recently been identified as a biomarker of response to immune checkpoint inhibitors in many cancers, including melanoma. Co-assessment of TMB with inflammatory markers and genetic mutations may better predict disease outcomes. The goal of this study was to evaluate the potential for TMB and somatic mutations in combination to predict the recurrence of disease in advanced melanoma. A retrospective review of 85 patients with stage III or IV melanoma whose tumors were analyzed by next-generation sequencing was conducted. Fisher's exact test was used to assess differences in TMB category by somatic mutation status as well as recurrence locations. Kaplan-Meier estimates and Cox-proportional regression model were used for survival analyses. The most frequently detected mutations were TERT (32.9%), CDKN2A (28.2%), KMT2 (25.9%), BRAF V600E (24.7%), and NRAS (24.7%). Patients with TMB-L + BRAFWT status were more likely to have a recurrence [hazard ratio (HR), 3.43; confidence interval (CI), 1.29-9.15; P = 0.01] compared to TMB-H + BRAF WT. Patients with TMB-L + NRASmut were more likely to have a recurrence (HR, 5.29; 95% CI, 1.44-19.45; P = 0.01) compared to TMB-H + NRAS WT. TMB-L tumors were associated with local (P = 0.029) and in-transit (P = 0.004) recurrences. Analysis of TMB alone may be insufficient in understanding the relationship between melanoma's molecular profile and the body's immune system. Classification into BRAFmut, NRASmut, and tumor mutational load groups may aid in identifying patients who are more likely to have disease recurrence in advanced melanoma.
Asunto(s)
Melanoma , Neoplasias Cutáneas , Biomarcadores de Tumor/genética , Humanos , Melanoma/patología , Mutación , Recurrencia Local de Neoplasia/genética , Proteínas Proto-Oncogénicas B-raf/genética , Neoplasias Cutáneas/patologíaRESUMEN
Issue addressed: Unwanted sexual attention and unhealthy intimate relationships have the potential to have serious negative health consequences. To date, there has been scant focus on these issues among university students in Australia. The aim of the current study was to describe the extent of unwanted sexual attention and unhealthy intimate relationships experienced in their lifetime by female university students aged 18-25 years.Methods: A cross-sectional study was undertaken involving 465 female students aged 18-25 years. Students were recruited through one faculty within a Victorian university and invited to complete an anonymous online questionnaire.Results: Sixty-seven per cent (n = 312) of female students reported experiencing unwanted sexual attention in their lifetime. The most common form of unwanted sexual attention was kissing or touching over clothes (98%; n = 306). Over 43% (n = 124) of the female students reported that the experience of unwanted sexual experience occurred after their protests were ignored. Thirty per cent (n = 135) of the female students reported experiencing at least one element of an unhealthy intimate relationship.Conclusions: The high rates of unwanted sexual attention and unhealthy intimate relationships among female university students is of concern given the negative impact such events can have on individual's physical, emotional and social well being.So what?: Public health and health promotion action is required to prevent female students from experiencing unwanted sexual attention and unhealthy intimate relationships, and to address the negative health and well being consequences.