Noninvasive, longitudinal imaging-based analysis of body adipose tissue and water composition in a melanoma mouse model and in immune checkpoint inhibitor-treated metastatic melanoma patients.

Background As cancer cachexia (CC) is associated with cancer progression, early identification would be beneficial. The aim of this study was to establish a workflow for automated MRI-based segmentation of visceral (VAT) and subcutaneous adipose tissue (SCAT) and lean tissue water (LTW) in a B16 melanoma animal model, monitor diseases progression and transfer the protocol to human melanoma patients for therapy assessment. Methods For in vivo monitoring of CC B16 melanoma-bearing and healthy mice underwent longitudinal three-point DIXON MRI (days 3, 12, 17 after subcutaneous tumor inoculation). In a prospective clinical study, 18 metastatic melanoma patients underwent MRI before, 2 and 12 weeks after onset of checkpoint inhibitor therapy (CIT; n = 16). We employed an in-house MATLAB script for automated whole-body segmentation for detection of VAT, SCAT and LTW. Results B16 mice exhibited a CC phenotype and developed a reduced VAT volume compared to baseline (B16 - 249.8 mu l, - 25%; controls + 85.3 mu l, + 10%, p = 0.003) and to healthy controls. LTW was increased in controls compared to melanoma mice. Five melanoma patients responded to CIT, 7 progressed, and 6 displayed a mixed response. Responding patients exhibited a very limited variability in VAT and SCAT in contrast to others. Interestingly, the LTW was decreased in CIT responding patients (- 3.02% +/- 2.67%; p = 0.0034) but increased in patients with progressive disease (+ 1.97% +/- 2.19%) and mixed response (+ 4.59% +/- 3.71%). Conclusion MRI-based segmentation of fat and water contents adds essential additional information for monitoring the development of CC in mice and metastatic melanoma patients during CIT or other treatment approaches

Lack of activity of betulin-based Oleogel-S10 in the treatment of actinic keratoses: A randomized, multicentre, placebo-controlled double-blind phase II trial

Background Betulinic acid and other triterpenes have shown strong antitumour activity in vitro and in vivo. A triterpene extract of birch bark formed the base of Oleogel-S10 and allowed topical application. Two previous trials have shown efficacy and tolerability in the treatment of actinic keratoses (AKs) with betulin-based Oleogel-S10. Objectives To confirm the efficacy and tolerability/safety of Oleogel-S10 in the treatment of AKs in a multicentre placebo-controlled study. Methods Patients (n = 165) were treated topically for 3 months in a four-arm parallel study design, randomly allocated to A (n = 53) Oleogel-S10 once daily, B (n = 51) Oleogel-S10 twice daily, or C (n = 25) or D (n = 28) placebo (petroleum jelly) once or twice daily, respectively. Clinical efficacy in this double-blind study was assessed by the investigators. Final and baseline biopsies were evaluated by central histopathology. Results Complete clearance of the target lesions was seen in 4% of patients in group A and 7% in group B, but not in the placebo groups. A clearance rate of > 75% was seen for 15% and 18% of patients in groups A and B, respectively, and for 13% in the placebo groups. These differences were not statistically significant. Histopathologically, 43·9% of patients showed a downgrading or clearance of the marker AK with no significant differences between the groups. Treatment with Oleogel-S10 was well tolerated. The tolerability as assessed by the investigator was mostly 'very good' (78·8%), followed by 'good' (18·2%) and only 1·2% assessed it as 'intolerable'. Patient-assessed tolerability was graded mostly 'very good' (56·4%) or 'good' (34·5%). Conclusions Treatment with Oleogel-S10 was well tolerated during a treatment period of 3 months, yet was no better than placebo in terms of efficacy in the treatment of AKs. What's already known about this topic? Previous single open-label trials have shown activity for Oleogel-S10 in actinic keratoses, with a clearance of > 75% of the lesions in 79% and 86% of patients. What does this study add? In this multicentre randomized double-blind trial Oleogel-S10 was highly tolerable but could not demonstrate superiority over placebo treatment. © 2014 British Association of Dermatologists

Circulating CD4+ T-cells that produce IL-4 or IL-17 when stimulated by Melan-A but not by NY-ESO-1 have negative impacts on survival of stage IV melanoma patients

Item does not contain fulltextPurpose: We initially observed that the presence of circulating NY-ESO-1- and/or Melan-A-specific T-cells in stage IV melanoma patients was significantly associated with prolonged survival. Here we report on how the phenotypes and functions of these T-cells differentially impact survival in patients pre-selected for NY-ESO-1 and/or Melan-A reactivity. Experimental Design: We assayed functional antigen-reactive T-cells recognizing NY-ESO-1 and/or Melan-A after in vitro stimulation using overlapping peptide pools. After restimulation, we assayed six cytokines simultaneously by intracellular cytokine staining. This allowed us to analyze the functional antigen-response of both CD4+ and CD8+ T-cells at the single-cell level. Results: We observed that NY-ESO-1 stimulated mainly CD4+ T-cells, whereas Melan-A more often stimulated CD8+ T-cells. NY-ESO-1-reactivity was not associated with an additional impact on survival whether CD4+ or CD8+ T-cells or both were responding. In contrast, recognition of Melan-A by CD4+ T-cells was associated with reduced survival in our cohort of patients pre-selected for NY-ESO-1 and/or Melan-A reactivity i.e. in patients with exceptionally long survival. We further observed a negative effect on survival in patients with CD4+ T-cells producing IL-4 and IL-17 upon Melan-A stimulation. Their prognosis was comparable to patients without any Melan-A reactivity. Conclusions: The nature and prognostic impact of specific T cell responses is different according to targeted antigen. Independent from phenotype and functional aspects, NY-ESO-1-reactivity is associated with good prognosis. For Melan-A, antigen-specific CD8+, but not CD4+ responses are associated with prolonged survival

The evolving field of Dermato‐oncology and the role of dermatologists: Position Paper of the EADO, EADV and Task Forces, EDF, IDS, EBDV–UEMS and EORTC Cutaneous Lymphoma Task Force

BACKGROUND The incidence of skin cancers has been increasing steadily over the last decades. Although there have been significant breakthroughs in the management of skin cancers with the introduction of novel diagnostic tools and innovative therapies, skin cancer mortality, morbidity and costs heavily burden the society. OBJECTIVE Members of the European Association of Dermato-Oncology, European Academy of Dermatology and Venereology, International Dermoscopy Society, European Dermatology Forum, European Board of Dermatovenereology of the European Union of Medical Specialists and EORTC Cutaneous Lymphoma Task Force have joined this effort to emphasize the fundamental role that the specialist in Dermatology-Venereology has in the diagnosis and management of different types of skin cancer. We review the role of dermatologists in the prevention, diagnosis, treatment and follow-up of patients with melanoma, non-melanoma skin cancers and cutaneous lymphomas, and discuss approaches to optimize their involvement in effectively addressing the current needs and priorities of dermato-oncology. DISCUSSION Dermatologists play a crucial role in virtually all aspects of skin cancer management including the implementation of primary and secondary prevention, the formation of standardized pathways of care for patients, the establishment of specialized skin cancer treatment centres, the coordination of an efficient multidisciplinary team and the setting up of specific follow-up plans for patients. CONCLUSION Skin cancers represent an important health issue for modern societies. The role of dermatologists is central to improving patient care and outcomes. In view of the emerging diagnostic methods and treatments for early and advanced skin cancer, and considering the increasingly diverse skills, knowledge and expertise needed for managing this heterogeneous group of diseases, dermato-oncology should be considered as a specific subspecialty of Dermatology-Venereology