- MeSH
- farmakoterapie * trendy MeSH
- lidé MeSH
- melanom * farmakoterapie MeSH
- metastázy nádorů farmakoterapie MeSH
- Check Tag
- lidé 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
- MeSH
- glukokortikoidy aplikace a dávkování MeSH
- lidé středního věku MeSH
- lidé MeSH
- melanom * chirurgie diagnóza farmakoterapie patologie MeSH
- mitomycin aplikace a dávkování MeSH
- nádory spojivky * chirurgie diagnóza farmakoterapie patologie MeSH
- poruchy pigmentace etiologie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
Uveální melanom je vzácnou malignitou, nicméně nejčastější nitrooční malignitou u dospělých. Má velmi vysoké riziko metastazování, především do jater, dále do plic, skeletu a kůže a podkoží, s rizikem rozvoje metastazujícího onemocnění u 25 % pacientů do 5 let a u 50 % pacientů do 15 let od diagnózy onemocnění. Biologické charakteristiky a mutační nálož uveálního melanomu jsou odlišné od standardního kožního melanomu s důsledkem omezeného využití imunoterapie checkpoint inhibitory u metastazujícího onemocnění. Jako zásadní molekula v léčbě pro vybrané pacienty s metastazujícím onemocněním se jeví tebentafusp.
Uveal melanoma is a rare malignancy, but the most common intraocular malignancy in adults. It has a very high risk of metastasis, mainly to the liver, lung, skeleton and skin and subcutaneous tissue, with a risk of metastatic disease in 25% of patients within 5 years and in 50% of patients within 15 years of diagnosis. The biological characteristics and mutational load of uveal melanoma are different from standard cutaneous melanoma, with the consequence of limited use of checkpoint inhibitor immunotherapy in metastatic disease. Tebentafusp appears to be an essential molecule in the treatment for selected patients with metastatic disease.
- Klíčová slova
- tebentafusp,
- MeSH
- inhibitory kontrolních bodů farmakologie terapeutické užití MeSH
- lidé MeSH
- melanom * diagnóza farmakoterapie genetika klasifikace MeSH
- metastázy nádorů diagnóza farmakoterapie MeSH
- nádory uvey * diagnóza farmakoterapie genetika klasifikace MeSH
- prognóza MeSH
- protilátky bispecifické farmakologie klasifikace terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Terapie maligního melanomu zaznamenala v poslední dekádě výrazné změny. Důvodem bylo pochopení molekulárních pochodů v patogenezi maligního melanomu a identifikace klíčových struktur kontrolujících průběh imunitní reakce. Standardem léčby pokročilého maligního melanomu u nemocných nesoucích mutaci genu BRAF je v současné době cílená léčba. Kazuistika popisuje účinnost enkorafenibu s binimetinibem po selhání adjuvantní imunoterapie.
The therapy for malignant melanoma has undergone significant changes in the past decade. This progress is attributed to the understanding of molecular processes in the pathogenesis of malignant melanoma and the identification of key structures controlling the immune response. Currently, the standard treatment for advanced malignant melanoma in patients with a BRAF gene mutation is targeted therapy. This case study describes the effectiveness of encorafenib with binimetinib following the failure of adjuvant immunotherapy.
- Klíčová slova
- enkorafenib, biminetinib,
- MeSH
- cílená molekulární terapie * klasifikace metody MeSH
- dospělí MeSH
- imunoterapie klasifikace metody MeSH
- lidé MeSH
- melanom * diagnostické zobrazování diagnóza farmakoterapie MeSH
- protoonkogenní proteiny B-Raf analýza genetika MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
BACKGROUND: Vitamin D deficiency associates with the risk of developing many diseases, including cancer. At the molecular level, vitamin D appears to have an antineoplastic effect. However, the role of vitamin D deficiency in cancer pathogenesis remains unelucidated and numerous studies have resulted in discordant results. This study aimed to determine whether vitamin D deficiency during melanoma diagnosis increases the risk of developing non-cutaneous second primary cancers (SPC). MATERIALS AND METHODS: A retrospective study on 663 patients diagnosed with melanoma between 1 January 2011 and 31 October 2022. The effect of each variable on the development of a subsequent non-cutaneous cancer was performed using Kaplan-Meier curves and differences were assessed by log-rank tests. Cox proportional hazard univariate and multivariate models were used to quantify the effect of each variable in the time to develop a non-cutaneous neoplasia. RESULTS: Out of 663 patients, 34 developed a non-cutaneous SPC. There was no statistically significant association between vitamin D levels and non-cutaneous SPC development (log-rank, p=0.761). Age>60 years, stage III/IV, and nodular melanoma subtype were significantly associated with the development of a SPC. After multivariate analysis, only age>60 years (HR 3.4; HR CI 95%: 1.5-7.6) and nodular melanoma subtype (HR 2.2; HR CI 95%: 1.0-4.8) were included in the final model. CONCLUSIONS: Our results suggest that vitamin D deficiency is not associated with an increased risk of developing non-cutaneous SPC in melanoma patients. However, age over 60 years and nodular melanoma subtype increase the risk for non-cutaneous SPC development.
- MeSH
- lidé středního věku MeSH
- lidé MeSH
- melanom * epidemiologie etiologie diagnóza MeSH
- nádory kůže * etiologie komplikace MeSH
- nedostatek vitaminu D * komplikace epidemiologie MeSH
- retrospektivní studie MeSH
- sekundární malignity * epidemiologie etiologie MeSH
- vitamin D škodlivé účinky MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
Complex injuries to the posterior trunk can still pose a significant challenge to the reconstructive surgeon. Due to the lack of skin laxity, dependent anatomical location and the importance of the deeper structures, a systematic approach tailored to the individual defect should be considered for these types of reconstructions. In our case report, we present a reconstructive solution of a chronic defect of the back caused by resection of an ulceration. What was previously considered to be a relapse of a malignant melanoma turned out to be a chronic osteomyelitis of the spinous processes of the thoracic vertebrae. The defect after the resection of the ulceration and infected spinous processes of the thoracic vertebrae with exposed dorsal lamina was covered with pedicled myocutaneous flap. Reconstruction yielded well-vascularized tissue that provided sufficient volume and tissue quality. Even in the light of modern perforator flaps, local or locoregional muscle and myocutaneous flaps remain the first choice for the treatment of deep back defects. Considering all the factors in the given case, plastic surgeons are able to tailor the reconstructive technique to every individual case to match the desired reconstruction goal.
- MeSH
- chirurgické laloky * chirurgie MeSH
- dermatochirurgické výkony metody MeSH
- hrudní obratle chirurgie patologie MeSH
- lidé MeSH
- maligní melanom kůže komplikace MeSH
- osteomyelitida * chirurgie MeSH
- pooperační péče metody MeSH
- senioři MeSH
- stafylokokové infekce komplikace MeSH
- vřed chirurgie komplikace patologie MeSH
- záda chirurgie patologie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- kazuistiky MeSH