RESUMO
BACKGROUND: Uveal melanoma (UM) has a poor prognosis once liver metastases occur. The melphalan/Hepatic Delivery System (melphalan/HDS) is a drug/device combination used for liver-directed treatment of metastatic UM (mUM) patients. The purpose of the FOCUS study was to assess the efficacy and safety of melphalan/HDS in patients with unresectable mUM. METHODS: Eligible patients with mUM received treatment with melphalan (3.0 mg/kg ideal body weight) once every 6 to 8 weeks for a maximum of six cycles. The primary end point was the objective response rate (ORR). The secondary end points included duration of response (DOR), overall survival (OS), and progression-free survival (PFS). RESULTS: The study enrolled 102 patients with mUM. Treatment was attempted in 95 patients, and 91 patients received treatment. In the treated population (n = 91), the ORR was 36.3 % (95 % confidence interval [CI], 26.44-47.01), including 7.7 % of patients with a complete response. Thus, the study met its primary end point because the lower bound of the 95 % CI for ORR exceeded the upper bound (8.3 %) from the benchmark meta-analysis. The median DOR was 14 months, and the median OS was 20.5 months, with an OS of 80 % at 1 year. The median PFS was 9 months, with a PFS of 65 % at 6 months. The most common serious treatment-emergent adverse events were thrombocytopenia (15.8 %) and neutropenia (10.5 %), treated mostly on an outpatient basis with observation. No treatment-related deaths were observed. CONCLUSION: Treatment with melphalan/HDS provides a clinically meaningful response rate and demonstrates a favorable benefit-risk profile in patients with unresectable mUM (study funded by Delcath; ClinicalTrials.gov identifier: NCT02678572; EudraCT no. 2015-000417-44).
Assuntos
Antineoplásicos Alquilantes , Neoplasias Hepáticas , Melanoma , Melfalan , Neoplasias Uveais , Humanos , Melanoma/tratamento farmacológico , Melanoma/patologia , Melanoma/secundário , Melanoma/mortalidade , Melfalan/administração & dosagem , Masculino , Feminino , Pessoa de Meia-Idade , Neoplasias Uveais/tratamento farmacológico , Neoplasias Uveais/patologia , Neoplasias Uveais/mortalidade , Idoso , Adulto , Taxa de Sobrevida , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/tratamento farmacológico , Seguimentos , Antineoplásicos Alquilantes/administração & dosagem , Antineoplásicos Alquilantes/uso terapêutico , Prognóstico , Idoso de 80 Anos ou mais , Sistemas de Liberação de MedicamentosRESUMO
BACKGROUND: Cutaneous T-cell lymphomas (CTCL) are rare types of non-Hodgkin lymphoma, which present in skin. Mycosis fungoides (MF) and Sézary syndrome (SS) are subtypes which make up two-thirds of all CTCL cases. The phase 3 MAVORIC study (NCT01728805) compared mogamulizumab to vorinostat in MF and SS patients, with post hoc data showing a trend for higher efficacy in mogamulizumab-treated patients as baseline blood tumour burden increases. OBJECTIVES: The aim of this study was to use updated post hoc analyses in order to examine the efficacy of mogamulizumab and vorinostat in MF patients when stratified by baseline blood involvement and to determine what factors affect time-to-global and time-to-skin response to inform clinical follow-up. METHODS: Post hoc analyses were carried out using data from MAVORIC. Overall response rate (ORR), progression-free survival (PFS) and time-to-next-treatment (TTNT) data were used to assess efficacy in patients with MF. Time-to-global response (TTR) was examined by disease subtype, by blood involvement in MF patients, and time-to-skin response was examined by blood involvement in MF patients. RESULTS: Numerically superior results were seen for ORR, PFS and TTNT in mogamulizumab-treated patients with MF compared with vorinostat, with a trend for outcomes improving with increasing baseline blood class. Statistically significant results for mogamulizumab compared with vorinostat were seen for MF B1 pts for PFS (8.43 vs. 2.83 months, p = 0.003) and TTNT (11.9 vs. 3.13 months, p = 0.002), and for MF B2 pts for ORR (46.2 vs. 9.1 months, p = 0.033). CONCLUSIONS: In mogamulizumab-treated MF patients, ORR and PFS were seen to improve with increasing blood involvement, which led to improved TTNT. TTR was more predictable for mogamulizumab-treated MF patients with blood involvement, and skin response may take longer than previously reported in some patients.
Assuntos
Linfoma Cutâneo de Células T , Micose Fungoide , Síndrome de Sézary , Neoplasias Cutâneas , Humanos , Linfoma Cutâneo de Células T/patologia , Micose Fungoide/tratamento farmacológico , Micose Fungoide/patologia , Síndrome de Sézary/tratamento farmacológico , Síndrome de Sézary/patologia , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologia , Vorinostat/uso terapêuticoRESUMO
BACKGROUND: Programmed death-1 (PD-1) antibodies and BRAF + MEK inhibitors are widely used for adjuvant therapy of fully resected high-risk melanoma. Little is known about treatment efficacy outside of phase III trials. This real-world study reports on clinical outcomes of modern adjuvant melanoma treatment in specialized skin cancer centers in Germany, Austria and Switzerland. METHODS: Multicenter, retrospective study investigating stage III-IV melanoma patients receiving adjuvant nivolumab (NIV), pembrolizumab (PEM) or dabrafenib + trametinib (D + T) between 1/2017 and 10/2021. The primary endpoint was 12-month recurrence-free survival (RFS). Further analyses included descriptive and correlative statistics, and a multivariate linear-regression machine learning model to assess the risk of early melanoma recurrence. RESULTS: In total, 1198 patients from 39 skin cancer centers from Germany, Austria and Switzerland were analysed. The vast majority received anti PD-1 therapies (n = 1003). Twelve-month RFS for anti PD-1 and BRAF + MEK inhibitor-treated patients were 78.1% and 86.5%, respectively (hazard ratio [HR] 1.998 [95% CI 1.335-2.991]; p = 0.001). There was no statistically significant difference in overall survival (OS) in anti PD-1 (95.8%) and BRAF + MEK inhibitor (96.9%) treated patients (p > 0.05) during the median follow-up of 17 months. Data indicates that anti PD-1 treated patients who develop immune-related adverse events (irAEs) have lower recurrence rates compared to patients with no irAEs (HR 0.578 [95% CI 0.443-0.754], p = 0.001). BRAF mutation status did not affect overall efficacy of anti PD-1 treatment (p > 0.05). In both, anti PD-1 and BRAF + MEK inhibitor treated cohorts, data did not show any difference in 12-month RFS and 12-month OS comparing patients receiving total lymph node dissection (TLND) versus sentinel lymph node biopsy only (p > 0.05). The recurrence prediction model reached high specificity but only low sensitivity with an AUC = 0.65. No new safety signals were detected. Overall, recorded numbers and severity of adverse events were lower than reported in pivotal phase III trials. CONCLUSIONS: Despite recent advances in adjuvant melanoma treatment, early recurrence remains a significant clinical challenge. This study shows that TLND does not reduce the risk of early melanoma recurrence and should only be considered in selected patients. Data further highlight that variables collected during clinical routine are unlikely to allow for a clinically relevant prediction of individual recurrence risk.
Assuntos
Melanoma , Neoplasias Cutâneas , Humanos , Proteínas Proto-Oncogênicas B-raf/genética , Áustria , Suíça , Estudos Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Melanoma/patologia , Neoplasias Cutâneas/patologia , Adjuvantes Imunológicos/uso terapêutico , Quinases de Proteína Quinase Ativadas por Mitógeno/uso terapêutico , Melanoma Maligno CutâneoRESUMO
Superficial leiomyosarcomas (LMS) are rare skin cancers (2-3% of cutaneous sarcomas) that originate from dermally located hair follicle muscles, dartos or areolar muscles (cutaneous/dermal LMS), or from vascular muscle cells of the subcutaneous adipose tissue (subcutaneous LMS). These superficial LMS are distinct from LMS of the deep soft tissues. Leiomyosarcomas are typically localized at the lower extremities, trunk or capillitium, and present as painful, erythematous to brownish nodules. Diagnosis is made by histopathology. The treatment of choice for primary LMS is complete (R0) microscopically controlled excision, with safety margins of 1 cm in dermal LMS, and 2 cm in subcutaneous LMS, if possible. Non-resectable or metastatic LMS require individual treatment decisions. After R0 resection with 1 cm safety margins, the local recurrence rate of dermal LMS is very low, and metastasis is very rare. Subcutaneous LMS, very large, or incompletely excised LMS recur and metastasize more frequently. For this reason, clinical follow-up examinations are recommended every six months for cutaneous LMS, and every three months for subcutaneous LMS within the first two years (in subcutaneous LMS including locoregional lymph node sonography). Imaging such as CT/MRI is indicated only in primary tumors with special features, recurrences, or already metastasized tumors.
Assuntos
Leiomiossarcoma , Neoplasias Cutâneas , Humanos , Leiomiossarcoma/diagnóstico , Leiomiossarcoma/cirurgia , Leiomiossarcoma/patologia , Pele/patologia , Neoplasias Cutâneas/patologia , Tela Subcutânea/patologia , Gordura SubcutâneaRESUMO
BACKGROUND: Total skin electron beam therapy (TSEBT) combined with systemic therapy or maintenance treatment is a reasonable approach to enhance the remission rate and duration in mycosis fungoides (MF) and Sézary syndrome (SS). This study assesses the efficacy of oral bexarotene therapy after low-dose TSEBT for patients with MF and SS. METHODS: In this prospective observational study, we recruited MF/SS patients for treatment with low-dose total skin electron beam therapy (TSEBT) with or without bexarotene therapy to describe outcomes and toxicities. RESULTS: Forty-six subjects with MF or SS underwent TSEBT between 2016 and 2021 at our institute. Following TSEBT, 27 patients (59 %) received oral bexarotene treatment. The median follow-up was 13 months. The overall response rate (ORR) for the cohort was 85 %. The response rate was significantly higher with combined modality (CM) than TSEBT alone (96 % vs. 68 %, p = 0.03). Median progression-free survival (PFS) for the CM was 17 months versus five months following TSEBT alone (p = 0.001). One patient (4 %) in the retinoid group discontinued the bexarotene therapy because of adverse events. The administration of bexarotene therapy did not increase radiation-related toxicities. CONCLUSIONS: Response rate and progression-free survival might be improved with TSEBT in combination with oral bexarotene compared to TSEBT alone.
Assuntos
Linfoma Cutâneo de Células T , Micose Fungoide , Neoplasias Cutâneas , Bexaroteno/uso terapêutico , Elétrons , Humanos , Linfoma Cutâneo de Células T/patologia , Micose Fungoide/tratamento farmacológico , Micose Fungoide/radioterapia , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologia , Resultado do TratamentoRESUMO
Atypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS) are rare cutaneous neoplasms representing histomorphological, genetic as well as epigenetic variants of a disease spectrum. Both tumors typically manifest as nonspecific, often ulcerated, skin- to flesh-colored nodules in chronically sun-damaged skin of elderly male patients. AFX is a rather well demarcated, often rapidly growing tumor. PDS tumors are poorly circumscribed and are characterized by aggressive infiltrative growth. Fast as well as slow growth behavior has been reported for both tumors. Histologically, both are composed of spindle-shaped and epithelioid tumor cells with pleomorphic nuclei as well as atypical multinucleated giant cells. Atypical mitoses are common. In contrast to AFX, PDS involves relevant parts of the subcutis and shows areas of tumor necrosis and/or perineural infiltration. Due to the poorly differentiated nature of AFX/PDS (Grade 3), histopathologically similar cutaneous sarcomas, undifferentiated carcinomas, melanomas and other diseases have to be excluded by immunohistochemical analysis. The treatment of choice is micrographically controlled surgery. In cases of AFX, a cure can be assumed after complete excision. Local recurrence rates are low as long as PDS tumors are surgically removed with a safety margin of 2 cm. Metastasis is rare and mostly associated with very thick or incompletely excised tumors; it mainly affects the skin and lymph nodes. Distant metastasis is even more rare. No approved and effective systemic therapy has been established.
Assuntos
Histiocitoma Fibroso Maligno , Sarcoma , Neoplasias Cutâneas , Idoso , Biomarcadores Tumorais , Diagnóstico Diferencial , Humanos , Masculino , Sarcoma/diagnóstico , Sarcoma/patologia , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/cirurgiaRESUMO
OBJECTIVE: Radiotherapy (RT) has an established role in the curative treatment of indolent primary cutaneous Bcell lymphoma (PCBCL). With the role of low-dose regimens such as 2 × 2 Gy being uncertain, we compared conventional-dose RT to a low-dose approach and investigated outcome and toxicities. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 26 patients with 44 cutaneous lesions treated at our institution between 2007 and 2017, comprising 22 marginal zone lymphoma (PCMZL) lesions and 22 follicle center lymphoma (PCFCL) lesions. Seven lesions (16%) were treated with low-dose RT (LDRT) (4â¯Gy) and 37 (84%) with conventional-dose RT (≥24â¯Gy, median 40â¯Gy). Median follow-up duration was 76 months. RESULTS: The overall response rate (ORR) was 91% (complete response rate [CRR]: 75%). The 5year local control rate (LCR) was 88% and the 10-year LCR was 84%. The response rates were significantly higher following conventional-dose RT (ORR: 92% vs. 86%; CRR: 84% vs. 29%; Pâ¯= 0.007). In terms of radiation dose, the rate of infield relapses (14% vs. 11%, Pâ¯= 0.4) and the 5year LCR (86% vs. 90%, Pâ¯= 0.4) were comparable in the LDRT and conventional-dose RT groups. During RT courses, about two-thirds of patients experienced mild toxicities, with grade I and II acute toxicity rates of 61% and 9%, respectively, with lower incidences of grade I (14% vs. 70%) and grade II (0% vs. 8%, Pâ¯= 0.004) toxicities following LDRT. CONCLUSION: This long-term analysis confirms the excellent outcome of RT in the management of PCBCL. The LDRT concept with 4â¯Gy was associated with a comparable LCR and reduced rates of acute toxicity. However, the response rates were significantly lower for this group and LDRT may therefore not be recommended as standard treatment.
Assuntos
Linfoma de Zona Marginal Tipo Células B/radioterapia , Linfoma Folicular/radioterapia , Neoplasias Cutâneas/radioterapia , Adulto , Idoso , Intervalo Livre de Doença , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
PURPOSE: Total skin electron beam therapy (TSEBT) has proved to be a safe and effective treatment for cutaneous Tcell lymphomas. Here, we examined the impact of this treatment on patient quality of life and outcome. PATIENTS AND METHODS: Forty-four patients with mycosis fungoides (MF) or Sezary syndrome (SS) received 48 TSEBT courses with a median dose of 12â¯Gy within the past 8 years at our institute. Patient and treatment characteristics for these cases as well as the impact of TSEBT on quality of life and duration of response were retrospectively analyzed and compared. RESULTS: The median modified Severity-Weighted Assessment Tool score before the start of TSEBT was 44. The overall response rate was 88%, with a complete response (CR) rate of 33%. The median follow-up period was 13 months. The median duration of response (DOR) and progression-free survival (PFS) for the entire cohort were 10 months and 9 months, respectively. Patient-reported symptom burden was measured with the Dermatological Life Quality Index and Skindex-29 questionnaires. The mean symptom reductions were 6⯱ 8 (Pâ¯= 0.005) and 21⯱ 24 (Pâ¯= 0.002), respectively. In the Functional Assessment of Cancer Therapy-General Assessment, significant improvements in the emotional (Pâ¯= 0.03) domains were observed after TSEBT. Patients who received maintenance or adjuvant treatments had a longer PFS (Pâ¯= 0.01). CONCLUSION: TSEBT improved disease symptoms and significantly improved emotional domains of patients' quality of life in patients with MF or SS. In addition, our results indicate that maintenance or adjuvant therapy after TSEBT may improve the PFS.
Assuntos
Elétrons/uso terapêutico , Micose Fungoide/radioterapia , Síndrome de Sézary/radioterapia , Neoplasias Cutâneas/radioterapia , Pele/efeitos da radiação , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Micose Fungoide/psicologia , Qualidade de Vida/psicologia , Dosagem Radioterapêutica , Radioterapia Adjuvante , Estudos Retrospectivos , Síndrome de Sézary/prevenção & controle , Neoplasias Cutâneas/psicologiaRESUMO
OBJECTIVE: To evaluate clinical, histopathologic, and radiation (RT) dose parameters in patients with extranodal low-grade (ENLG) non-Hodgkin lymphoma (NHL) and their possible impact on local control (LC) and survival. MATERIALS AND METHODS: The medical records of 159 patients with 181 histologically confirmed ENLG-NHL lesions treated at our institution were reviewed retrospectively. RESULTS: The predominant histological subtype (73%) was marginal zone lymphoma (MZL). Common lesion sites were the gastrointestinal tract (GIT; 33%), skin (26%), and orbit (21%). The majority of patients (88%) presented with stage I/II disease. Thirty-three (20%) lesions were treated with reduced-dose RT (≤30.6â¯Gy) and 148 lesions (80%) with conventional-dose RT (>30.6â¯Gy), with an overall median dose of 39.6â¯Gy (range 4-63). The median follow-up period was 72 months. The 10-year local control (LC), Progression-free survival (PFS), and overall survival (OS) rates were 96, 65, and 82%, respectively. Higher overall response rate (ORR; 98% vs. 94%, pâ¯= 0.001) and complete response rate (CRR; 95% vs. 73%, pâ¯= 0.001) were observed in patients treated with conventional-dose regimens than in those treated with reduced-dose regimens. Ten-year PFS (pâ¯= 0.90) and OS (pâ¯= 0.40) was similar between the two dose groups. RT was well tolerated in both dose groups, with no grade 4/5 toxicities. In the multivariate analysis, RT dose and timing (upfront or salvage) were related to LC, whereas age, histology, and complete response (CR) to RT were associated with PFS. Patient age and radiation field size impacted OS. CONCLUSION: RT is an effective and curative local treatment for early-stage FL and MZL at conventional and reduced radiation doses. Conventional-doses seems to be associated with local response improvement, without significant differences in PFS rates. Age, histology, and response to RT may influence the PFS.
Assuntos
Extensão Extranodal/radioterapia , Linfoma de Zona Marginal Tipo Células B/radioterapia , Linfoma Folicular/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Extensão Extranodal/patologia , Feminino , Seguimentos , Humanos , Linfoma de Zona Marginal Tipo Células B/patologia , Linfoma Folicular/patologia , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Dosagem Radioterapêutica , Resultado do Tratamento , Adulto JovemRESUMO
Metastatic melanoma is a devastating disease with a marginal-albeit increasing-hope for cure. Melanoma has a high mutation rate which correlates to the expression of numerous neo-antigens and thus is associated with the potential to induce and strengthen effective antitumoral immunity. However, the incomplete and potentially insufficient response to established immunotherapies (response rates usually do not markedly exceed 60%) already points to the need of further studies to improve treatment strategies. Multiple tumor escape mechanisms that allow melanoma to evade from antitumoral immune responses have been characterized and must be overcome to achieve a better clinical efficacy of immunotherapies. Recently, promising progress has been made in targeting tumor vasculature to control and increase the infiltration of tumors with effector lymphocytes. It has been hypothesized that amplified lymphocytic infiltrates in melanoma metastases result in a switch of the tumor microenvironment from a non-inflammatory to an inflammatory state. In this view point essay, we discuss the requirements for successful homing of lymphocytes to melanoma tissue and we present a mouse melanoma xenograft model that allows the investigation of human tumor vessels in vivo. Furthermore, current clinical studies dealing with the activation of melanoma vasculature for enhanced effectiveness of immunotherapy protocols are presented and open questions for routine clinical application are addressed.
Assuntos
Endotélio/imunologia , Imunoterapia , Linfócitos/imunologia , Melanoma/terapia , Neoplasias Cutâneas/terapia , Animais , Vasos Sanguíneos/imunologia , Movimento Celular , Modelos Animais de Doenças , Humanos , Melanoma/irrigação sanguínea , Melanoma/imunologia , Melanoma/secundário , Camundongos , Receptores de Retorno de Linfócitos , Neoplasias Cutâneas/irrigação sanguínea , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/patologia , Evasão Tumoral/imunologiaRESUMO
Although recent therapeutic developments raise hope, melanoma remains a devastating disease with a need for new treatment targets. In other tumours prohormone convertases have been shown to be pro-tumourigenic as they are involved in processing preforms of matrix-metalloproteinases, growth factors and adhesion molecules. The aim of this study was to look for new treatment options for melanoma, by investigating the role of the prohormone convertase Paired basic Amino acid-Cleaving Enzyme 4 (PACE4/PCSK6) in melanoma cell lines and human melanoma tissue. PACE4-transfected A375 melanoma cells displayed significantly increased proliferation, MMP-2 production, gelatinase activity and migratory capacity in vitro compared with sham-transfected cells. In vivo, elevated PACE4 expression resulted in significantly increased tumour growth on immunodeficient mice. In the majority of 45 human primary melanomas and melanoma metastases ex vivo PACE4 immunoreactivity was detectable, while it was absent in in situ melanomas. These results indicate PACE4 as a regulator of melanoma cell aggressiveness.
Assuntos
Melanoma/enzimologia , Pró-Proteína Convertases/metabolismo , Serina Endopeptidases/metabolismo , Neoplasias Cutâneas/enzimologia , Animais , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , Melanoma/tratamento farmacológico , Melanoma/genética , Melanoma/patologia , Camundongos Pelados , Camundongos SCID , Terapia de Alvo Molecular , Invasividade Neoplásica , Pró-Proteína Convertases/antagonistas & inibidores , Pró-Proteína Convertases/genética , Serina Endopeptidases/genética , Inibidores de Serina Proteinase/uso terapêutico , Transdução de Sinais , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Carga TumoralRESUMO
BACKGROUND: PD-1 inhibition (PD-1i) is the standard of care in melanoma and other malignancies. In patients with bone metastases of solid tumors, the monoclonal antibody denosumab directed against RANKL is approved for the prevention of skeletal-related events. However, RANKL is not only relevant in osteoclastogenesis, but also has immunological effects. Hence, we aimed at investigating, whether the combination of PD-1i and denosumab produces synergistic effects in metastatic melanoma treatment. METHODS: We retrospectively collected and analyzed clinical data of metastatic melanoma patients with bone metastases, who received PD-1i and denosumab therapy. RESULTS: 29 patients were identified with a median age of 60.7 years: 20 were male and 9 were female. 20 patients (69%) were in stage IV M1c and 9 (31%) in stage IV M1d; 52% had an increased serum LDH. 24 patients (83%) received PD-1i as first-line therapy and five patients (17%) as second- or third-line therapy. 13 patients received the triple combination nivolumab, ipilimumab and denosumab (N + I+D), 16 patients received PD-1i and denosumab (PD-1i + D). Within a median follow-up time of 19.8 months, 17 patients progressed with a median time to progression of 6 months. The objective response rate was 54% in the N + I + D group and 50% in the PD-1i + D group. Recalcification of bone metastases was radiologically observed in 18 (62%) patients. No unexpected treatment-related adverse events emerged. CONCLUSIONS: The combination therapy of metastatic melanoma with PD-1i and denosumab was feasible without unexpected safety issues and showed a promising efficacy signal. Further investigation in prospective studies is needed.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Denosumab/uso terapêutico , Melanoma/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Neoplasias Ósseas/imunologia , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/secundário , Denosumab/farmacologia , Feminino , Humanos , Ipilimumab/farmacologia , Ipilimumab/uso terapêutico , Estimativa de Kaplan-Meier , Masculino , Melanoma/imunologia , Melanoma/mortalidade , Melanoma/secundário , Pessoa de Meia-Idade , Nivolumabe/farmacologia , Nivolumabe/uso terapêutico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia , Intervalo Livre de Progressão , Ligante RANK/antagonistas & inibidores , Ligante RANK/imunologia , Estudos Retrospectivos , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologiaAssuntos
Antineoplásicos Alquilantes , Melanoma , Melfalan , Neoplasias Uveais , Humanos , Melanoma/tratamento farmacológico , Melanoma/patologia , Melanoma/secundário , Melfalan/administração & dosagem , Neoplasias Uveais/tratamento farmacológico , Neoplasias Uveais/patologia , Antineoplásicos Alquilantes/administração & dosagem , Taxa de Sobrevida , Prognóstico , Seguimentos , Sistemas de Liberação de Medicamentos , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/tratamento farmacológicoRESUMO
Lymphocytic infiltration into melanoma tissue is an important prerequisite for effective antitumoral immunity. However, analysis of human metastatic melanoma has shown that leucocyte adhesion receptor expression on melanoma blood vessels is very low or absent, thereby impairing the entry of cytotoxic lymphocytes into tumor tissue. We hypothesized that adhesion molecules can be induced on melanoma vasculature allowing better infiltration of cytotoxic lymphocytes. Quantitative real-time PCR and immunofluorescence staining indicated that the adhesion molecules ICAM-1 (CD54) and E-selectin (CD62E) can be significantly induced by intralesional application of TNF alpha in tissue from human melanoma metastases either in vitro or in vivo when grafted onto immunodeficient NSG (NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ) mice that preserved human vessels. Furthermore, activated human autologous CD3+ lymphocytes were injected intravenously into mice bearing melanoma xenografts treated with TNF-α or PBS in addition to the leucocyte chemoattractant TARC (CCL17). Significantly increased numbers of CD8+ cells were detected in TNF-α-treated melanoma metastases compared with PBS-treated controls. In addition, tumor cell apoptosis was enhanced and melanoma cell proliferation reduced as shown by TUNEL assay and KI-67 staining. We conclude that adhesion molecules can be induced on human melanoma vasculature resulting in significantly improved homing of activated autologous cytotoxic T cells to melanoma tissue and inhibition of melanoma cell proliferation. These observations should be considered when designing protocols for immunotherapy of malignant melanoma.
Assuntos
Selectina E/metabolismo , Endotélio Vascular/metabolismo , Molécula 1 de Adesão Intercelular/metabolismo , Melanoma Experimental/metabolismo , Linfócitos T/fisiologia , Animais , Feminino , Humanos , Masculino , Camundongos Endogâmicos NOD , Camundongos SCID , Transplante de NeoplasiasRESUMO
BACKGROUND AND OBJECTIVES: The aim of the present study was to determine the prevalence and incidence of skin cancer. PATIENTS AND METHODS: We calculated prevalence and incidence for cutaneous melanoma (CM) and non-melanoma skin cancer (NMSC) in 2012 in Germany, using claims data of 2.1 million insured persons. In order to allow statements concerning differences between subgroups, we calculated 95 % confidence intervals. Finally, we standardized prevalence and incidence with regard to the German population. RESULTS: The prevalence and incidence of CM amounted to 0.12 % and 0.04 % and increased with age. For NMSC these measures were 0.65 % and 0.15 %. Of the prevalent and incident patients, 88.9 % and 87.4 % (CM) and 99.4 % and 98.8 % (NMSC) respectively were at early stages. A projection on the whole population resulted in 75,419 persons affected by CM and 376,004 persons affected by NMSC, including 24,075 (CM) and 84,618 (NMSC) incident patients. CONCLUSIONS: In this study, we defined epidemiological measures according to the number of patients affected by skin cancer and having a medical consultation indicating a need for treatment. These results can serve in future research as a data basis for analysis of health service demand in skin cancer patients and the associated costs.
Assuntos
Melanoma/epidemiologia , Neoplasias Cutâneas/epidemiologia , Feminino , Alemanha/epidemiologia , Humanos , Incidência , Masculino , Prevalência , Distribuição por Sexo , Melanoma Maligno CutâneoRESUMO
This corrects the article DOI: 10.1038/bjc.2017.85.