Článek obsahuje výsledky studií a přehled literatury týkající se výskytu melanomu u pacientů mladších 21 let. Jsou diskutovány charakteristické znaky melanomu u dětí, rizikové faktory, histologické a imuno-histochemické rysy a možnosti léčby. Ze studií vyplývá, že pečlivá analýza histologických a imuno-histochemických rysů by měla umožnit správnou diagnózu ve většině případů melanomů u dětí. Pacienti s melanomem v dětském věku mají sice vyšší pravděpodobnost přežití než dospělí, u řady dětí se ale vyvinou metastázy, zvláště když je melanom diagnostikován po pubertě. Melanom patří sice mezi vzácná onemocnění dětského věku, přesto je nejčastějším typem kožního zhoubného nádoru u mladých lidí. Se zvyšující incidencí je potřeba brát toto onemocnění do úvahy; na melanom u dětí se často nepomýšlí a diagnóza je opožděná.

Melanoma in children is relatively rare, making it difficult to determine prognostic factors, biological behavior, and efficacy of therapy in the pediatric population. The article presents the results of studies and a review of the literature regarding the incidence of melanoma in patients younger than 21 years. The characteristic features of melanoma in children, risk factors, histological and immunohistochemical features, and treatment options are discussed. Studies suggest that careful analysis of histologi­cal and immunohistochemical features should allow for the correct diagnosis in most cases of melanoma in children. Although patients with melanoma in childhood have a higher chance of survival than adults, many children develop metastases, especially when melanoma is diagnosed after puberty. Although melanoma is a rare childhood disease, it is the most common type of skin cancer in young people. With its increa­sing incidence, it is important to consider this disease; melanoma in children is often overlooked and diagnosis is delayed.

• MeSH
• diferenciální diagnóza MeSH
• dítě MeSH
• epiteloidní a vřetenobuněčný névus diagnóza   genetika   MeSH
• genetická onemocnění kůže diagnóza   genetika   klasifikace   MeSH
• inhibitory kontrolních bodů farmakologie   terapeutické užití   MeSH
• lidé MeSH
• melanom * diagnóza   genetika   klasifikace   MeSH
• mladiství MeSH
• nádory kůže diagnóza   genetika   klasifikace   MeSH
• névus diagnóza   genetika   klasifikace   komplikace   MeSH
• prognóza MeSH
• ultrafialové záření škodlivé účinky   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• Publikační typ
• přehledy MeSH

Předložená kazuistika popisuje případ pacientky s metastazujícím maligním melanomem anorekta. Vzhledem k synchronní generalizaci do lymfatických uzlin a plic, a tedy nemožnosti kurativního chirurgického či radioterapeutického řešení, byla pacientka léčena několika liniemi systémové léčby. V souladu s doporučenými postupy a též pro BRAF negativitu melanomu byla v 1. linii léčby indikována kombinovaná imunoterapie ipilimumabem a nivolumabem. Následně pro opakované progrese onemocnění absolvovala pacientka ještě dvě linie konvenční chemoterapie a poté s ohledem na metastatický rozsev do mozku ještě 3 cykly léčby temozolomidem. Mozkové metastázy byly ošetřeny Leksellovým gama nožem (LGN), později byla pro další progresi využita možnost paliativního celomozkového ozáření (WBRT - whole brain radiotherapy). V závěru života pacientka podstoupila paliativní radioterapii primárního ložiska anorekta s cílem ulevit od obtěžujících symptomů. Dále využívala ambulance hojení ran a podpůrnou péči paliativní kliniky, později domácího hospicu. Pacientka zemřela 33 měsíců od stanovení diagnózy metastazujícího melanomu a 12 měsíců od zjištění mozkových metastáz.

The presented case report describes the case of a patient with mucosal primary metastasizing malignant melanoma of the anorectum. Due to the synchronous generalization to the lymph nodes and lungs and therefore the impossibility of a curative surgical or radiotherapy solution, the patient was treated with several lines of systemic treatment. In accordance with guidelines and for BRAF negativity, combined immunotherapy with ipilimumab and nivolumab was indicated in the 1st line of treatment. Subsequently, due to repeated progression of the disease, the patient completed two more lines of conventional chemotherapy and then, regarding metastatic spread to the brain, three more cycles of temozolomide treatment. Brain metastases were treated with the Leksell Gamma Knife (LGN), later for further progression the palliative whole brain radiotherapy (WBRT) was used. At the end of her life, the patient underwent palliative radiotherapy of the primary anorectal lesion with the aim of relieving the bothersome symptoms, she used a wound healing clinic and supportive care through a palliative clinic, later a home hospice. The patient died 33 months after the diagnosis of metastatic melanoma and 12 months after the diagnosis of brain metastases.

• MeSH
• dakarbazin farmakologie   terapeutické užití   MeSH
• imunoterapie metody   MeSH
• ipilimumab farmakologie   terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• melanom chirurgie   farmakoterapie   radioterapie   MeSH
• metastázy nádorů MeSH
• nádory anu * chirurgie   farmakoterapie   radioterapie   MeSH
• nemoci mozku radioterapie   MeSH
• nivolumab farmakologie   terapeutické užití   MeSH
• paliativní péče metody   MeSH
• protokoly protinádorové léčby MeSH
• smrt MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

Tinostamustine is a first-in-class alkylating deacetylase inhibitor that facilitates access to cancer cell DNA, resulting in its damage and counteracting DNA repair systems. We hypothesize that the addition of tinostamustine to immune checkpoint inhibitors (ICIs) improves melanoma treatment. This open-label, nonrandomized phase IB study characterized dose-limiting toxicity (DLT) and the recommended dose (RD) of 2-weekly intravenous tinostamustine at escalating doses of 15 and 30 mg/m 2 when administered with 2-weekly nivolumab 3 mg/kg added in cycle 2 in patients with melanoma. We included 17 patients (four at 15 mg/m 2 and 13 at 30 mg/m 2 tinostamustine). A total of 13/17 (77%) patients were ICI-resistant, 7/17 (41%) had unfavorable melanoma subtypes. No DLT was identified. Tinostamustine RD was 30 mg/m 2 every 2 weeks. One patient experienced grade 2 nivolumab-associated immune-related pneumonitis. Tinostamustine-associated grade 3 leukocytopenia was documented in one patient, grade 2 leukocytopenia in five patients, and grade 1 thrombocytopenia in three patients. Treatment discontinuation occurred in one patient for nivolumab-associated immune-related pneumonitis and in another patient for tumor-related hemorrhage. A total of 7/13 (54%) evaluable patients had at least stable disease as best treatment response, including 3/13 (23%) patients with a confirmed partial response. Median progression-free survival was 8.3 weeks [95% confidence interval (CI): 2.4-15.4 weeks), median overall survival was 19.1 weeks (95% CI: 2.4-41 weeks). Two-weekly intravenous tinostamustine at an immune-modulatory dose of 30 mg/m 2 is safe when coadministered with nivolumab 3 mg/kg and resulted in 54% disease stabilization and 23% confirmed partial responses in patients with predominantly ICI-resistant, advanced melanoma.

• MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• melanom * farmakoterapie   patologie   MeSH
• nádory kůže * farmakoterapie   patologie   MeSH
• nivolumab * farmakologie   terapeutické užití   aplikace a dávkování   MeSH
• protokoly protinádorové kombinované chemoterapie * terapeutické užití   farmakologie   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze I MeSH

• MeSH
• farmakoterapie * trendy   MeSH
• lidé MeSH
• melanom * farmakoterapie   MeSH
• metastázy nádorů farmakoterapie   MeSH
• Check Tag
• lidé MeSH

PURPOSE: There are limited treatment options for advanced melanoma that have progressed during or after immune checkpoint inhibitor therapy. Intratumoral (IT) immunotherapy may improve tumor-specific immune activation by promoting local tumor antigen presentation while avoiding systemic toxicities. The phase 3 ILLUMINATE-301 study (ClinicalTrials.gov identifier: NCT03445533) evaluated tilsotolimod, a Toll-like receptor-9 agonist, with or without ipilimumab in patients with anti-PD-1 advanced refractory melanoma. METHODS: Patients with unresectable stage III-IV melanoma that progressed during or after anti-PD-1 therapy were randomly assigned 1:1 to receive 24 weeks of tilsotolimod plus ipilimumab or 10 weeks of ipilimumab alone. Nine IT injections of tilsotolimod were administered to a single designated lesion over 24 weeks. Intravenous ipilimumab 3 mg/kg was administered once every 3 weeks from week 2 in the tilsotolimod arm and week 1 in the ipilimumab arm. The primary end point was efficacy measured using objective response rate (ORR; independent review) and overall survival (OS). RESULTS: A total of 481 patients received tilsotolimod plus ipilimumab (n = 238) or ipilimumab alone (n = 243). ORRs were 8.8% in the tilsotolimod arm and 8.6% in the ipilimumab arm, with disease control rates of 34.5% and 27.2%, respectively. Median OS was 11.6 months in the tilsotolimod arm and 10 months in the ipilimumab arm (hazard ratio, 0.96 [95% CI, 0.77 to 1.19]; P = .7). Grade ≥3 treatment-emergent adverse events occurred in 61.1% and 55.5% of patients in the tilsotolimod and ipilimumab arms, respectively. CONCLUSION: Combining IT tilsotolimod with ipilimumab did not significantly improve the ORR or OS compared with ipilimumab alone in patients with anti-PD-1 advanced refractory melanoma.

• MeSH
• dospělí MeSH
• ipilimumab * aplikace a dávkování   škodlivé účinky   MeSH
• lidé středního věku MeSH
• lidé MeSH
• melanom * farmakoterapie   patologie   imunologie   mortalita   MeSH
• nádory kůže * farmakoterapie   patologie   imunologie   MeSH
• oligonukleotidy MeSH
• protokoly protinádorové kombinované chemoterapie * terapeutické užití   škodlivé účinky   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH

Neoadjuvant immunotherapy represents a pioneering approach in the preoperative treatment of cancer, providing new strategies for tumor reduction and improved patient outcomes by modulating the immune response. This study investigated neoadjuvant immunotherapy using intratumoral administration of mannan-BAM, Toll-like receptor ligands, and anti-CD40 antibody (MBTA therapy) followed by surgery in murine models of MTT pheochromocytoma, B16-F10 melanoma, and 4T1 and E0771.lmb mammary carcinomas. In the MTT pheochromocytoma model, it was found that neoadjuvant MBTA therapy followed by surgery could prevent the development of distant metastases in 100% of treated animals, compared to a 60% mortality rate in the control group due to metastatic disease after surgery. These outcomes were achieved even in tumors three times larger than those in the control group. In the aggressive 4T1 model, neoadjuvant MBTA therapy resulted in slower tumor progression and a significant prolongation of survival. In the B16-F10 and E0771.lmb models, neoadjuvant MBTA therapy also protected animals from metastases development and tumor recurrence upon rechallenge with tumor cells after surgery. Transcriptomic analysis revealed enhanced effector immune cell infiltration, cytotoxicity, and antigen presentation in retransplanted tumors from MBTA-treated mice, indicating robust immune memory. Notably, the exclusion of the anti-CD40 antibody from the neoadjuvant MBTA therapy (MBT therapy) yielded comparable outcomes in protection against metastases development. These findings advocate for further investigation of intratumoral neoadjuvant MBTA therapy for immunologically "cold" tumors, including those at high risk of metastases or recurrence.

• MeSH
• antigeny CD40 imunologie   antagonisté a inhibitory   MeSH
• imunoterapie * metody   MeSH
• lokální recidiva nádoru * prevence a kontrola   MeSH
• mannany farmakologie   MeSH
• melanom experimentální * imunologie   terapie   patologie   MeSH
• metastázy nádorů MeSH
• modely nemocí na zvířatech MeSH
• myši inbrední BALB C MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• neoadjuvantní terapie * metody   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• dexamethason aplikace a dávkování   MeSH
• diferenciální diagnóza MeSH
• dospělí MeSH
• fluoresceinová angiografie MeSH
• fluprednisolon aplikace a dávkování   MeSH
• imunohistochemie MeSH
• iridektomie metody   MeSH
• lidé MeSH
• melanom * diagnostické zobrazování   patologie   MeSH
• nádory duhovky * chirurgie   diagnostické zobrazování   farmakoterapie   patologie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

• MeSH
• brachyterapie metody   přístrojové vybavení   MeSH
• lidé středního věku MeSH
• lidé MeSH
• melanom * diagnostické zobrazování   patologie   radioterapie   MeSH
• nádory choroidey * diagnostické zobrazování   farmakoterapie   patologie   radioterapie   MeSH
• ultrasonografie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

BACKGROUND: Immune checkpoint inhibitors (ICIs), including those targeting PD-1, are currently used in a wide range of tumors, but only 20-40% of patients achieve clinical benefit. The objective of our study was to find predictive peripheral blood-based biomarkers for ICI treatment. METHODS: In 41 patients with advanced malignant melanoma (MM) and NSCLC treated with PD-1 inhibitors, we analyzed peripheral blood-based immune subsets by flow cytometry before treatment initialization and the second therapy dose. Specifically, we assessed basic blood differential count, overall T cells and their subgroups, B cells, and myeloid-derived suppressor cells (MDSC). In detail, CD4 + and CD8 + T cells were assessed according to their subtypes, such as central memory T cells (TCM), effector memory T cells (TEM), and naïve T cells (TN). Furthermore, we also evaluated the predictive value of CD28 and ICOS/CD278 co-expression on T cells. RESULTS: Patients who achieved disease control on ICIs had a significantly lower baseline proportion of CD4 + TEM (p = 0.013) and tended to have a higher baseline proportion of CD4 + TCM (p = 0.059). ICI therapy-induced increase in Treg count (p = 0.012) and the proportion of CD4 + TN (p = 0.008) and CD28 + ICOS- T cells (p = 0.012) was associated with disease control. Patients with a high baseline proportion of CD4 + TCM and a low baseline proportion of CD4 + TEM showed significantly longer PFS (p = 0.011, HR 2.6 and p ˂ 0.001, HR 0.23, respectively) and longer OS (p = 0.002, HR 3.75 and p ˂ 0.001, HR 0.15, respectively). Before the second dose, the high proportion of CD28 + ICOS- T cells after ICI therapy initiation was significantly associated with prolonged PFS (p = 0.017, HR 2.51) and OS (p = 0.030, HR 2.69). Also, a high Treg count after 2 weeks of ICI treatment was associated with significantly prolonged PFS (p = 0.016, HR 2.33). CONCLUSION: In summary, our findings suggest that CD4 + TEM and TCM baselines and an early increase in the Treg count induced by PD-1 inhibitors and the proportion of CD28 + ICOS- T cells may be useful in predicting the response in NSCLC and MM patients.

• MeSH
• antigeny CD278 metabolismus   MeSH
• antigeny CD279 antagonisté a inhibitory   MeSH
• antigeny CD28 MeSH
• CD8-pozitivní T-lymfocyty imunologie   účinky léků   metabolismus   MeSH
• dospělí MeSH
• inhibitory kontrolních bodů * terapeutické užití   farmakologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• melanom * farmakoterapie   imunologie   krev   patologie   MeSH
• nádory plic * farmakoterapie   imunologie   krev   patologie   MeSH
• nemalobuněčný karcinom plic * farmakoterapie   imunologie   krev   patologie   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Differences in survival according to the pTERT mutation subtypes (-124C > T, -146C > T, and tandem -138_139CC > TT) have been observed. The present study aimed to describe the clinical as the histopathological and molecular cutaneous melanoma features according to the presence of the three most prevalent pTERT mutation subtypes (-124C > T, -146C > T, and tandem -138_139CC > TT). A retrospective cross-sectional study including 684 patients was designed, and a Partial Least-Squares Discriminant Analysis (PLS-DA) was performed. After the PSL-DA, it was observed that the tandem -138_139CC > TT subtype differs from the other subtypes. The model demonstrated that the -124C > T and the -138_139 CC > TT subtypes were associated with fast-growing melanomas (OR 0.5, CI 0.29-0.86, p = .012) and with Breslow >2 mm (OR 0.6, CI 0.37-0.97, p = .037), compared to the -146C > T mutation. Finally, the -124C > T appeared to be more associated with the presence of TILs (non-brisk) than the -146C > T (OR 0.6, CI 0.40-1.01, p = .05). These findings confirmed that the -124C > T and the tandem -138_139 CC > TT subtypes are both highly associated with the presence of features of aggressiveness; however, only the -124C > T was highly associated with TILs. This difference could explain the worse survival rate associated with the tandem -138_139CC > TT mutations.

• MeSH
• lidé MeSH
• melanom * genetika   patologie   mortalita   MeSH
• mutace MeSH
• nádory kůže genetika   patologie   mortalita   MeSH
• promotorové oblasti (genetika) * genetika   MeSH
• průřezové studie MeSH
• retrospektivní studie MeSH
• telomerasa * genetika   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH