Metasztatikus progresszió kezelése primer cutan és ocularis melanoma szinkrón előfordulását követően = Treatment of metastatic progression following the synchronous occurrence of cutaneous and ocular primary melanomas

Absztrakt: A melanoma előfordulási gyakorisága az életkorral nő, legnagyobb arányban a nem hispániai fehérekben fordul elő. Bár az ocularis melanoma gyakorisága a töredéke a cutan melanomáénak – az összes melanomás eset mintegy 4%-a, éves incidenciája 0,6 : 100 000 –, a szemtumorok között a leggyakrabban előforduló malignitás. Az ocularis és a cutan melanoma együttes előfordulása irodalmi ritkaságnak számít. Közleményünkben egy 80 éves férfi esetét prezentáljuk, akinél 2008-ban cutan nodularis melanomát excindáltak. Szemészeten 2013-ban fokozódó visuscsökkenés miatt uvealis melanomát diagnosztizáltak, amelyet brachytherapiával kezeltek. Képalkotó vizsgálatokkal és biopsziával 2015-ben melanoma hepaticus propagatiója igazolódott. A primer cutan laesio mutációanalízise BRAF V600 K típusú funkciónyerő mutációt igazolt, míg az áttétben a vad típusú gén jelenlétét mutattuk ki. Onkoteam javaslata alapján 2015 augusztusában intraarterialis májkemoterápia kezdődött, melyből 11 ciklust kapott meg, 21 napos időintervallumokkal. A beteg a kezelést jól tolerálta, mellékhatás nem jelentkezett. A 2016. februári CT a májban lévő laesio parciális regresszióját igazolta; a tizenegyedik ciklus intraarterialis májkemoterápiáját követően a beteg komplett remisszióba került, amely több mint egy évig tartott. Az ocularis és a cutan melanoma szinkrón előfordulása igen ritka, metasztatikus progresszió esetén ugyanakkor az optimális onkoterápia kiválasztása komoly kihívást jelent. A két melanomatípus molekuláris patológiai háttere eltérő, amely segítheti a metasztatikus laesiók eredetének azonosítását és az optimális, személyre szabott kezelés megválasztását. Orv Hetil. 2018; 159(16): 642–647. | Abstract: 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

Biomarkers Associated with Clinical Outcome of Advanced Melanoma Patients Treated with Ipilimumab

Ipilimumab was the first immunotherapy approved for metastatic melanoma in decades and is currently registered as a second-line treatment. However, new immunotherapies, in combination with ipilimumab, offer even better clinical outcomes for patients compared with single-agent treatments, at the expense of improved toxicity. The aim of this study was to evaluate the feasibility of ipilimumab outside the clinical trials and to identify survival predictors for treatment benefit. Data were collected on 47 advanced melanoma patients treated with ipilimumab between 2010 and 2015 at a single center. Association of clinical characteristics (including primary tumor characteristics), serum lactate dehydrogenase (LDH), erythrocyte sedimentation rate, absolute eosinophil, lymphocyte, and neutrophil count, neutrophil/lymphocyte and eosinophil/lymphocyte ratio with toxicity and clinical outcome were assessed using univariate and multivariate analysis. Median progression-free survival at a median follow-up of 10 months was 2.7 months and median overall survival was 9.8 months. Objective response was observed in 17% of patients and the disease control rate at week 24 was 40%. The 1- and 2-year survival rates documented were 40 and 28%, respectively. Significant association between high LDH level (>1.5x upper limit of normal) and decreased overall survival was demonstrated in uni- and multivariate analysis (hazard ratio [HR]: 3.554, 95% CI: 1.225-10.306, p = 0.019). Neither biomarkers nor clinical outcome were associated with toxicity. Using baseline serum LDH to identify patients most likely to benefit from ipilimumab therapy could serve as a simple and inexpensive biomarker of clinical outcome