Efficacy of Vemurafenib Treatment in 43 Metastatic Melanoma Patients with BRAF Mutation. Single-Institute Retrospective Analysis, Early Real-Life Survival Data.

BRAF inhibitor vemurafenib achieved improved overall survival over chemotherapy and have been approved by the FDA and EMA for the treatment of BRAF-mutated metastatic melanoma. The aim of our retrospective analysis was to determine the efficacy and safety of vemurafenib therapy for BRAF mutated metastatic melanoma and subsequently to prove the clinical benefit for the studied 43 patients, based on real-life data. From November 2012 to October 2015 we have selected 43 BRAF mutated, metastatic melanoma patients, treated with vemurafenib. The median follow-up time was 15.9 months. We evaluated progression free survival (PFS), overall survival (OS) and toxicities. According to the AJCC staging system 70% of the patients had stage M1c metastasis, including 6 with stable brain metastasis. Objective responses were noted in 51.1%, the disease control rate was achieved in 79% of the patients. Complete responses were attained by 5 patients (11.6%). Median PFS was 6.48 (95% CI:4.8-15.0) months, median OS was 11.47 (95% CI:8.08-NA) months. We found significant association between LDH level and OS in univariate (p = 0.000613) and multivariate analysis (p = 0.0168). The most common adverse events (AEs) included follicular hyperkeratosis, rash, arthralgia and photosensitivity. Grade 3 AEs, such as cutaneous squamous-cell carcinoma, QTcB interval prolongation, rash, arthralgia were reported in 7 patients (17%). We had no Grade 4 side effects. Similar to the previously published data our analysis confirms the improved survival with vemurafenib treatment (11.47 months) in patients with BRAF V600 mutation. Vemurafenib therapy was well tolerated, the AE profile was almost consistent with the previously reported data of randomised clinical trials.

[Treatment of metastatic progression following the synchronous occurrence of cutaneous and ocular primary melanomas]. / Metasztatikus progresszió kezelése primer cutan és ocularis melanoma szinkrón elofordulását követoen.

The incidence rates of cutaneous melanoma in non-Hispanic whites show an increasing tendency with age. While uveal melanoma in general is a rare disease, representing only 4% of all melanomas with an incidence rate of 0.6 per 100 000, it is still the most frequent malignancy of the eye. Synchronous occurrence of ocular and cutaneous melanoma is an exceptional rarity, due to the distinct genetic background of the diseases. We report the case of a 80-year-old man who underwent total excision of a cutaneous melanoma in 2008. In 2013, he was diagnosed with uveal melanoma as part of a routine work-up for reduced vision. The uveal melanoma was treated by brachytherapy. In 2015, liver metastases were suspected by routine ultrasonography. Core biopsy was carried out, and the histology confirmed melanoma metastases. The molecular analysis of the cutaneous lesion showed gain of function mutation of the BRAF V600 K gene, while we found a wild-type BRAF gene in the metastatic lesion. Based on the recommendation of the oncoteam, hepatic intra-arterial Epirubicin-Platidiam therapy was introduced. He received 11 doses of intra-arterial chemotherapy (IAC), in 21 cycles. IAC was well tolerated without any catheter-related complications or toxicities. Partial regression of the hepatic metastases were documented in February 2016. After completing the eleventh cycle of intrahepatic chemotherapy, the disease remained in complete remission for over a year. The parallel occurrence of cutaneous and ocular melanoma is rare, however, the metastatic progression in such cases make the selection of optimal medical therapy challenging. The distinct genetic background of two melanoma types may help the identification of the source of the metastatic lesions, in order to guide the treatment decisions. Orv Hetil. 2018; 159(16): 642-647.

[Psychological aspects of immunotherapies in the treatment of malignant melanoma]. / Immunterápiák pszichológiai vonatkozásai a melanoma komplex és multidiszciplináris kezelésében.

Psychological problems may arise in connection with oncomedical treatments in three ways: 1. acute and/or 2. chronic ways, as well as 3. co-morbid psychiatric diseases that already exist must also be taken into account. Immunotherapies have the most common and also clinically relevant psychological side effects. Fatigue, anhedonia, social isolation, psychomotor slowness is reported during treatment. Anti-CTLA-4 antibody (ipilimumab) immunotherapy can present one of the most modern opportunities for adequate treatment for patients having distant metastasis or unresectable tumour. In relation to immunotherapies, acute psychological side effects (acute stress) emerging during treatments develop in a way that can mostly be linked to environmental factors, e.g. notification of diagnosis, hospitalisation, progression, deterioration in quality of life, imminent dates of control. Crisis is a temporary and threatening condition that endangers psychological balance. In such conditions, enhanced psychological vulnerability must be taken into account and doctors play a key role in the rapid recognition of the condition. Chronic psychological problems, which may arise from the depressogenic effect of the applied treatment or originated from a pre-melanoma psychiatric condition, may exceed the diagnostic and psychotherapeutic competences of a clinical psychologist. Even in case of a well-defined depressogenic biological mechanism such as the activation of the pro-inflammatory cytokine pathway, positive environmental effects can reduce symptoms and thus increase compliance. Side effects can be treated successfully using psychotherapeutic methods and/or psychiatric medicines. The application of routinely used complex psychosocial screening packages can provide the easiest method to identify worsening psychological condition during immunotherapy and give rapid feedback to the oncologist and the patient. Team work is of particular importance in a situation like this as it requires complex, interdisciplinary and high-level professional collaboration. Multidisciplinarity is the basic framework for modern tumour therapy where, under the guidance of oncologists, the work of specialist nurses, social workers, physiotherapists, dieticians and last but not least psychiatrists/psychologists are indispensable and play a significant role.