Treatment of BRAF+ melanoma in light of current drug programs

The past decade has seen significant advances in the understanding of molecular pathogenesis of cutaneous melanoma. Currently, mutations of BRAF oncogene have been a well established and powerful predictive role as validated target in recently developed molecular targeted therapy for melanoma. It has been proven in a number of studies that the effective treatment for this group of patients consists of the combination of a BRAF inhibitor and MEK inhibitor, two such combinations are currently registered and reimbursed in Poland — vemurafenib and cobimetinib, dabrafenib and trametinib. Median progression-free survival (PFS) exceeds one year for BRAF and MEK combined therapy, and overall survival (OS) reaches approximately 2 years. Currently, the first line therapeutic option for BRAF-mutated advanced melanoma include also immunotherapy with anti-PD-1 antibodies (combination of PD-1/CTLA-4 blockers can be an option in a specific group of patients, although not reimbursed in Poland).The past decade has seen significant advances in the understanding of molecular pathogenesis of cutaneous melanoma. Currently, mutations of BRAF oncogene have been a well established and powerful predictive role as validated target in recently developed molecular targeted therapy for melanoma. It has been proven in a number of studies that the effective treatment for this group of patients consists of the combination of a BRAF inhibitor and MEK inhibitor, two such combinations are currently registered and reimbursed in Poland — vemurafenib and cobimetinib, dabrafenib and trametinib. Median progression-free survival (PFS) exceeds one year for BRAF and MEK combined therapy, and overall survival (OS) reaches approximately 2 years. Currently, the first line therapeutic option for BRAF-mutated advanced melanoma include also immunotherapy with anti-PD-1 antibodies (combination of PD-1/CTLA-4 blockers can be an option in a specific group of patients, although not reimbursed in Poland)

Leczenie czerniaków BRAF+ w świetle obowiązujących programów lekowych

W ciągu ostatniej dekady poczyniono znaczące postępy w poznaniu patogenezy molekularnej czerniaków skóry. Obecnie wiadomo, że mutacje w onkogenie BRAF odgrywają podstawową rolę jako zwalidowany cel molekularny dla leczenia ukierunkowanego tego nowotworu. Na podstawie kilku badań potwierdzono, że skuteczne leczenie w grupie chorych na zaawansowane czerniaki z obecnością mutacji BRAF obejmuje zastosowanie inhibitora BRAF i MEK, a obecnie zarejestrowane i refundowane w Polsce są dwie takie terapie skojarzone: wemurafenib z kobimetynibem i dabrafenib z trametynibem. Mediana przeżycia wolnego od progresji choroby (PFS) przekracza rok, a przeżycia całkowitego (OS) wynosi około 2 lat. Obecnie opcję terapeutyczną w pierwszej linii leczenia czerniaka BRAF-dodatniego stanowi również immunoterapia za pomocą przeciwciał anty-PD-1 (leczenie skojarzone inhibitorami PD-1/CTLA-4 również może stanowić opcję terapii w specyficznych grupach chorych, choć nierefundowaną w Polsce)

Factors Predicting Response to the Recovery-Oriented Cognitive Behavioural Workshop for Persons Diagnosed with Schizophrenia

A recovery-oriented, cognitive behavioural workshop for service users diagnosed with schizophrenia was developed, implemented and evaluated in a pilot study. Further analysis is required regarding factors which contribute to better treatment response, as this will provide useful information for workshop adaptation. Secondary multilevel model analyses were performed to determine whether workshop and booster session attendance, as well as sociodemographic variables such as gender, age, education, and duration of illness, predicted workshop responsiveness. Results showed that completers had lower responsiveness to the workshop in terms of confidence and hope, whereas those who attended an online booster session demonstrated better responsiveness as to psychosocial functioning. Longer duration of illness and older age generally predicted lower intervention responsiveness. In conclusion, adaptations utilising more booster sessions and accommodating older participants with longer duration of illness are required, as is further workshop evaluation in a randomised controlled study

Peer network status and depressive symptoms among early adolescents : testing the mediating effects of metaperception and loneliness

Previous research shows that deficits in social relationships increase the risk of depression. This study tests the hypothesis that among early adolescents, their status in their peer network (likeability/dislikeability) will be associated with depressive symptoms but only indirectly, through the subjective perception of this status (positive/negative metaperception) and loneliness (feeling of social isolation). Data were collected using sociometric methods and self-report scales from 388 students aged 12-13. Path analysis was applied to verify the hypothesized relationships between the study variables. The findings indicate that: (1) status in the peer network and its perception affect depressive symptoms only indirectly, through loneliness; (2) depressive symptoms depend directly on loneliness alone; (3) status in the peer network does not directly translate into loneliness - its effect is mediated by metaperception; (4) the negative dimension of the peer network status indirectly affects both loneliness and depressive symptoms more strongly than the positive one. The main limitation of the research is its cross-sectional design, which precludes definite conclusions about the direction of the relationships observed. The results obtained help to clarify the complex mechanisms through which objective status in the peer network, its subjective perception and feelings of loneliness contribute to the severity of depressive symptoms among early adolescents. On the practical side, the findings highlight the importance of developing and implementing interventions targeting both the objective and subjective aspects of social relations for the prevention of depression in this age group

Disability and recovery in schizophrenia: a systematic review of cognitive behavioral therapy interventions

Background: Schizophrenia is a disabling disease that impacts all major life areas. There is a growing need for meeting the challenge of disability from a perspective that extends symptomatic reduction. Therefore, this study aimed to systematically review the extent to which traditional and “third wave” cognitive – behavioral (CBT) interventions address the whole scope of disabilities experienced by people with lived experience of schizophrenia using the WHO’s International Classification of Functioning, Disability and Health (ICF) as a frame of reference. It also explores if current CBT interventions focus on recovery and what is their impact on disability domains.Methods: Medline and PsycINFO databases were searched for studies published in English between January 2009 and December 2015. Abstracts and full papers were screened against pre-defined selection criteria by two reviewers. Methodological quality of included studies was assessed by two independent raters using the Effective Public Health Practice Project Quality assessment tool for quantitative studies (EPHPP) guidelines.Results: A total of 50 studies were included, 35 studies evaluating traditional CBT interventions and 15 evaluating “third wave” approaches. Overall, traditional CBT interventions addressed more disability domains than “third wave” approaches and mostly focused on mental functions reflecting schizophrenia psychopathology. Seven studies met the inclusion criteria of recovery-oriented interventions. The majority of studies evaluating these interventions had however a high risk of bias, therefore evidence on their effectiveness is inconclusive.Conclusions: Traditional CBT interventions address more disability domains than “third wave” therapies, however both approaches focus mostly on mental functions that reflect schizophrenia psychopathology. There are also few interventions that focus on recovery. These results indicate that CBT interventions going beyond symptom reduction are still needed. Recovery-focused CBT interventions seem to be a promising treatment approach as they target disability from a broader perspective including activity and participation domains. Although their effectiveness is inconclusive, they reflect users’ views of recovery and trends towards improvement of mood, negative symptoms and functioning are shown

New developments in the perioperative treatment of melanomas with locoregional advancement

Surgical intervention is the treatment of choice for patients with melanomas. However, the prognoses of the patients with melanomas at the IIC–IV stage, even after a complete resection of the lesions, is very diverse and, to a great degree, connected with a high risk of disease recurrence. The positive results of the studies in this area have resulted in systemic adjuvant therapy becoming the standard for patients in this group. New methods of systemic treatment – both the mo­lecularly targeted treatment with BRAF and MEK inhibitors (dabrafenib with trametinib) and anti-PD-1 immunotherapy (nivolumab or pembrolizumab) – are already registered in the United States and the European Union. Also the results of the studies concerning the use of preoperative systemic treatment in patients with loco-regionally advanced melanomas seem to be very promising

Progress in adjuvant treatment of melanoma patients

Surgery is therapy of choice in melanoma patients. However, prognosis of patients at stage IIC–IV even after radical resection is very heterogenous and related to high risk of disease relapse. Positive results of clinical trials indicate that in the nearest future systemic adjuvant therapy in high risk melanomas will become the standard of care. New treatment modalities, both molecular targeted therapy with BRAF+MEK inhibitors dabrafenib with trametinib and immunotherapy anti-PD-1 with nivolumab or pembrolizumab have been approved in US and EU