## 4 Discussions
Other issue refers to the gene copy number and structural variations, such as in KIT, which are much more numerous in MM than in CM. KIT inhibitors and tyrosine kinase inhibitors: TKIs important for the treatment of MM include Imatinib, Nilotinib, and Dasatinib [1]. In the last 4 years, many articles regarding the efficiency of immunotherapy with MM have been published, and we are mentioning here [PERSON] et al. [24] and [PERSON] et al. [25]. CheckMate 172 was a phase II, single-arm, open-label, multicenter study that evaluated nivolumab in melanoma patients with advanced disease who manifested relapsed disease during or after ipilimumab treatment. The authors report data on 1008 treated patients, 6.3% of cases with mucosal melanoma, non-acral cutaneous melanoma in 71.7% of cases and acral cutaneous melanoma in 5.5% of cases. The minimum monitoring period was 18 months and median OS was 25.8 months for acral cutaneous melanoma, 25.3 months for non-acral cutaneous melanoma and 18-month OS rates were less than 60% for both. Median OS for ocular and mucosal melanoma was under 13 months and OS rates were under 35% for both their localizations [26]. So, nivolumab treatment after ipilimumab therapy is similar for melanoma subtypes and has a safety profile. OS was similar for both non-acral cutaneous and acral cutaneous melanoma situations. On the other hand, ocular and mucosal melanoma had differing median OS [25]. A study by [PERSON] et al. [1] evaluated, in a retrospective study, five retrospective case series and nine case reports with gynecologic melanomas treated with immunotherapy (immune checkpoint inhibitor) and/or targeted therapy. This study is a comprehensive review of the literature data and randomized clinical trials regarding immunotherapy in mucosal melanoma. Among the articles reviewed by [PERSON] et al., the same author published a study in 2020 that drew attention [26]. [PERSON] et al. [27] published a study which described the management of one patient with gynecologic melanoma, originating in the vagina, regionally unresectable, with no primary treatment. The patient received nivolumab treatment, with complete response (CR), PFS of 8 months and OS of 8 months, being alive with no evidence of disease at the time of the article's publishing. [PERSON] et al. [28] also published a study which described the management of one patient with gynecologic melanoma, originating in the vagina, with distant disease (brain) without primary systemic treatment, performed immunotherapy with nivolumab, with confirmed progressive disease (CPD) and PFS for 2 months. The OS was not specified, but the patient was alive with disease at the time the article was published. Although for a long time, malignant melanoma was considered radioresistant, radiotherapy may play a role in vulvovaginal melanoma management, especially in the domain of symptom control. There are limited data to provide recommendations, but the use of hypoffractionated radiation therapy may be considered to possibly achieve a less radical local excision. Radiotherapy is applied using different advanced conformal techniques or radiousurgery (SRS) and it is part of the therapeutic arsenal of MM complications: spinal cord compression syndrome; brain secondary brain lesions; secondary bone lesions, in antalgic scope; an anti-hemorrhagic scope for obstruction management; metastases and extracranial disease. Radiotherapy is also used as a consolidation treatment for residual tumors. It was reported that control rates at one year range between 60 to 90% after SRS for melanoma brain metastases [29]. Regarding techniques, IMRT, IGRT or SRS are preferred due to the better sparing of organs that are at risk and fewer, later radiotherapy effects [5]. Vulvovaginal melanomas have an increased recurrence rate, higher than in other cutaneous/mucosal melanomas.