Circulating Tumor DNA as a Marker for Treatment Response in Metastatic Melanoma Patients Using Next-Generation Sequencing-A Prospective Feasibility Study.

We prospectively performed a longitudinal analysis of circulating tumor DNA (ctDNA) from 149 plasma samples and CT scans in Stage III and IV metastatic melanoma patients (n = 20) treated with targeted agents or immunotherapy using two custom next-generation sequencing (NGS) Ion AmpliSeq™ HD panels including 60 and 81 amplicons in 18 genes, respectively. Concordance of matching cancer-associated mutations in tissue and plasma was 73.3%. Mutant allele frequency (MAF) levels showed a range from 0.04% to 28.7%, well detectable with NGS technologies utilizing single molecule tagging like the AmpliSeq™ HD workflow. Median followup time of the tissue and/or plasma positive cohort (n = 15) was 24.6 months and median progression-free survival (PFS) was 7.8 months. Higher MAF ≥ 1% at baseline was not significantly associated with a risk of progression (Odds Ratio = 0.15; p = 0.155). Although a trend could be seen, MAF levels did not differ significantly over time between patients with and without a PFS event (p = 0.745). Depending on the cell-free DNA amount, NGS achieved a sensitivity down to 0.1% MAF and allowed for parallel analysis of multiple mutations and previously unknown mutations. Our study indicates that NGS gene panels could be useful for monitoring disease burden during therapy with ctDNA in melanoma patients.

Assessing the Impact of Atopic Dermatitis on the Patients' Parents with the Visual Instrument 'Caregiver-PRISM'.

BACKGROUND: There is a need to improve the quality of communication between clinicians and parents of young patients with atopic eczema (AE). OBJECTIVE: To create a tool to measure the suffering that caregivers experience in association with their child's AE (Caregiver Pictorial Representation of Illness and Self-Measure, Caregiver-PRISM), assess the validity and reliability, and identify factors associated with caregiver suffering. METHODS: Caregiver-PRISM was administered to 45 parents of patients from an AE outpatient service (Padua, Italy). RESULTS: Caregiver-PRISM had a good test-retest reliability (r = 0.85; t7 = 4.13; p < 0.05), content validity and construct validity when used in parents of AE children. Parents with a less positive family affective climate, higher education, or with children following a diet experienced higher suffering associated with their child's AE, demonstrated by lower Caregiver-PRISM scores (p < 0.05). CONCLUSION: Our results support the use of Caregiver-PRISM in parents of AE patients to assess suffering associated with patients' illness.

Association of Stress Coping Strategies with Immunological Parameters in Melanoma Patients.

In this exploratory case control study the association between stress coping strategies and lymphocyte subpopulations was calculated in 18 non-metastatic melanoma patients and 18 controls with benign skin diseases. Coping strategies were assessed using the German version of the stress-coping questionnaire (SVF 120). While in the control group patients showed significant negative correlations of lymphocyte subpopulations (CD3+, CD4+, CD8+, CD19+, CD45+ cells) with coping strategies that refer to defence, in melanoma patients significant positive correlations between lymphocyte subpopulations (CD3+, CD4+, CD19+, CD45+ cells) were found with regard to coping strategies that are characterized by diversion from stress and focusing on stress-compensating situations. The present data, in melanoma patients and controls, show contrary correlations between stress coping strategies and lymphocyte subpopulations. The interconnection between stress coping and immunologic alterations in malignant melanoma is a field deserving further multiprofessional investigation in order to provide new therapeutical approaches in the treatment and understanding of melanoma patients.

Psychological Stress and Immunological Modulations in Early-stage Melanoma Patients.

Mental stress may have a negative impact on the immune state of cancer patients, in whom immunologic surveillance is essential for survival. This study investigated the immunological response of 19 patients with early-stage melanoma and a matched control group undergoing the Determination Stress Test before surgery. Cytokine and chemokine levels and lymphocyte subpopulations were measured at baseline and post-stress test time-points. Following the stress test lower levels of interleukin (IL)-6 were observed in the melanoma group compared with healthy volunteers (p = 0.044). IL-10 increased significantly in the control group 30 min after the stress test (p = 0.002) in comparison with the melanoma group (p = 0.407). CCL5/Rantes decreased significantly in the melanoma group, whereas CD16/CD56+ natural killer cells increased in both groups, with a sharp decrease below baseline after stress in the melanoma group (p = 0.001). This pilot study shows an altered immunological response to stressors in melanoma patients.

Higher psychological and psychovegetative strain in adolescents with atypical pigment naevi.

An observational, exploratory, cross-sectional study was performed to assess whether the presence of atypical naevi (AN) in adolescents is associated with psychological and psychovegetative stress parameters. Fifty-one students of a secondary school in Graz, Austria, completed a defined test procedure consisting of an initial period of rest, a standardised mental stress task, another period rest and a questionnaire, the change-sensitive symptom list (ASS-SYM). Electrocardiogram and blood pressure were recorded continuously. The study population was divided in two groups: probands without AN (NAN, n = 33), and probands with at least one AN (n = 18). We found higher values for the AN group in all scales of ASS-SYM, reaching statistical significance in the dimensions "nervousness and mental tension" (p = 0.025), "psychophysiological dysregulation" (p = 0.020), burden of pain" (p = 0.023) and "general symptoms and problems" (p = 0.031). Regarding physiological parameters, the AN group showed higher vegetative strain reflected in heart rate and heart rate varibility during the periods of rest as well as a reduced baroreceptor sensitivity. On the basis of our results, the presence of AN in adolescents seems to be associated with a higher vegetative arousal. Additionally, participants with AN complained significantly more often about stress-associated general psychological symptoms and problems.

Autonomic nervous tone in vitiligo patients--a case-control study.

In this cross-sectional, exploratory case-control study the vegetative arousal in vitiligo patients compared to an age and gender matched healthy control group was assessed. Forty-eight participants (24 outpatients with generalised vitiligo and 24 healthy controls) completed a test procedure consisting of an initial period of rest (R1), a defined mental stress task (the d2 test of attention), a second period of rest (R2) followed by an individually, age adapted physical stress task (bicycle ergometry) and a final period of rest (R3). Based on a continuously recorded electrocardiogram, heart rate variability, in particular high frequency (HF) and low frequency (LF) components were determined. Within the 3 periods of rest, vitiligo patients showed a higher vegetative arousal than controls, represented by the ratio of LF/HF which mirrors the sympatho-vagal balance (R1: p = 0.027; R2: p = 0.003; R3: p = 0.029). No differences between the 2 groups were found during the mental (p = 0.187) and the physical stress task (p = 0.773). The results suggest a higher vegetative arousal in vitiligo patients.

Coping strategies in melanoma patients.

An observational, questionnaire-based, cross-sectional study was performed to assess whether differences in coping behaviour (positive and negative strategies) between patients with either a recent diagnosis of malignant melanoma (MM) or with benign dermatological disease, were predictive of the diagnosis. Coping strategies were assessed with the German version of the stress-coping questionnaire (SVF 120) in 46 inpatients for whom surgery was planned at the Department of Dermatology, Medical University of Graz, Austria. Subjects were divided into two groups: patients with non-metastatic MM, and patients with benign dermatological diseases (controls). The risk for the diagnosis "melanoma" decreased with higher values of "situation control" (p = 0.007) and increased with higher values of resignation (p = 0.035) and trivialisation (p = 0.039). More-over, the risk for having a MM with thickness > 1 mm decreased in patients with higher values in positive coping strategies (p < 0.34). These results suggest differences in coping behaviour between patients with MM and those with benign skin diseases and, amidst patients with MM, between patients with different MM thickness; the results may hence lead to earlier, more specific and more effective psychological interventions to improve coping in patients with MM, as differences in coping behaviour seem to appear even in the non-metastatic stage of the disease.