Aim: Little is known about the organisation of child maltreatment practice in Europe. We therefore explored medical child protection systems and training across Europe.Methods: An online survey was completed by physicians working in child maltreatment, identified through professional organisations in 28 member countries of the European Union, Iceland, Norway and Switzerland in 2012-2013. Respondents were questioned regarding management of suspected child maltreatment, mandatory reporting, professional training, patient referral and physician roles in multidisciplinary investigations. Responses underwent a narrative synthesis and descriptive enumerations.
Background. Immune checkpoint inhibitors (ICI) are effective in fractions of patients with disseminated melanoma. This study is the first to analyze the plasma activity of thymidine kinase (TK), an enzyme involved in DNA synthesis and repair, as a biomarker in melanoma patients. Methods. Plasma samples were collected prior to treatment start in patients with unresectable metastatic cutaneous melanoma, treated with ICI (anti-CTLA-4 and/or anti-PD-1). Plasma TK activity (TKa) levels were determined using the DiviTum TKa ELISA assay. TKa levels were correlated with patients’ baseline characteristics, response rate (RR), progression-free survival (PFS), and overall survival (OS). Results. In the 90 study patients, the median TKa level was 42 Du/L (range <20–1787 Du/L). A significantly higher plasma TKa was found in patients with ECOG performance status ≥1 (p = 0.003), M1c-d disease (p = 0.015), and elevated lactate dehydrogenase levels (p < 0.001). The RR was 63.2% and 30.3% in those with low or high TKa, respectively (p = 0.022). The median PFS was 19.9 and 12.6 months in patients with low or high TKa, respectively (hazard ratio (HR) 1.83 (95% CI, 1.08–3.08), p = 0.024). The median OS was >60 months and 18.5 months in patients with low or high TKa, respectively (HR: 2.25 (95% CI, 1.25–4.05), p = 0.011. Conclusions. High pretreatment plasma TKa levels were significantly associated with worse baseline characteristics and poor response and survival in ICI-treated melanoma patients. TKa is hence a novel and interesting plasma biomarker in melanoma and should be further studied to define its role as a prognostic and predictive marker in this disease.
9556 Background: In the recent decade, new effective immunotherapies and targeted therapies have emerged for the treatment of disseminated melanoma. However, a considerable fraction of patients does not respond or get lasting effects and the treatments also have significant side effects. Biomarkers can contribute with more knowledge on prognosis and the efficacy of these therapies in different patients. In other cancer types, the plasma activity of the enzyme thymidine kinase (TKa), has been demonstrated as a marker of tumor stage and prognosis. The TK enzyme is part of a reaction chain to introduce thymidine into the DNA strand. TK thereby has a key function in DNA-synthesis, -repair and cell division. Dividing cells release TK during mitotic exit and TK can thus be detected in the blood. This study is the first to investigate plasma TKa as a potential biomarker in melanoma patients. Methods: Plasma samples were collected within five days prior to treatment start in patients with unresectable metastatic cutaneous melanoma, treated with immunotherapy (anti-CTLA-4 and/or anti-PD-1) or targeted therapy (BRAF±MEK inhibitors). Plasma TKa levels were determined using the DiviTum TKa ELISA assay (Biovica, Sweden). TKa levels were correlated with the patients’ baseline criteria, response rate (RR), progression free survival (PFS) and overall survival (OS). Results: Among the 124 study patients, the median TKa was 50 Du/L (range < 20-3491 Du/L). Significantly higher plasma TKa levels were found in patients with ECOG performance status ≥1 vs. 0-1 ( P< 0.001), M1c-d vs. M1a-b disease ( P< 0.001), ≥3 vs. 1-2 affected organs ( P= 0.002) or elevated vs. non-elevated LDH ( P< 0.001). In the patients treated with immunotherapy (n = 86) the RR was 63.2% vs. 37.9% in those with low ( < 60 Du/L) vs. high TKa ( P= 0.024). The median PFS and OS was 19.9 and > 60 months in those with low TKa vs. 12.6 and 18.5 months in those with high TKa (HR for PFS: 1.73 (95% CI, 1.01-2.97), P= 0.044 and HR for OS: 2.16 (95% CI, 1.17-3.98), P= 0.011). In the patients treated with BRAF±MEK inhibitor (n = 38) a similar trend was observed, with shorter PFS and OS in those with high TKa, but the differences were not statistically significant. Conclusions: In this first study on plasma TKa in melanoma patients, high pretreatment TKa was significantly associated with poor baseline factors and poor response and survival in immunotherapy treated patients. Currently, plasma LDH is the only non-clinical factor that is routinely used as a prognostic marker in melanoma. Several other candidate markers have been described, such as PD-L1 tumor immunohistochemistry, tumor mutational burden, gut microbiome and circulating tumor DNA. Compared to these assays, TKa measured with DiviTum is a simpler, ELISA based test for a single plasma marker. TKa is hence a novel and interesting marker in melanoma and should be further studied to define its role as a prognostic and predictive marker in this disease.
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