Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 149
Filtrar
1.
Sci Rep ; 10(1): 15745, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32978468

RESUMO

Detection of BRAFV600E within cell free tumor DNA (ctDNA) is emerging as a promising means to improve patients' stratification or enable BRAF inhibitor (BRAFi) therapeutic monitoring in a minimally invasive manner. Here, we investigated whether extracellular vesicle-(EV)-associated-DNA (EV-DNA) has value as an alternative source of circulating BRAFV600E. To do so, we identified a clinical practice-compatible protocol for the isolation of EV-DNA and assessed BRAF gene status on plasma samples from metastatic melanoma patients at the beginning and during BRAFi therapy. This protocol uses a peptide with high affinity for EVs and it has been found to recover more mutant DNA from plasma than standard ultracentrifugation. Molecular analyses revealed that mutant DNA is largely unprotected from nuclease digestion, interacting with the outer side of the EV membrane or directly with the peptide. When used on clinical samples, we found that the protocol improves the detection of BRAFV600E gene copies in comparison to the reference protocol for ctDNA isolation. Taken together, these findings indicate that EVs are a promising source of mutant DNA and should be considered for the development of next-generation liquid biopsy approaches.

2.
Semin Oncol ; 2020 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-32883537

RESUMO

BACKGROUND: Patients with cancer are presumed to have a higher risk to contract SARS-CoV-2 infection, because of their immunosuppressed status. The impact and course of COVID-19 infection in cancer patients receiving immunotherapy remains unknown. OBJECTIVES: To evaluate the safety of the management of patients with advanced melanoma treated with immunotherapy in 2 Cancer Centers located in areas of Italy with a high incidence of COVID-19 infections. METHODS: We retrospectively analyzed data from January 1 to April 30, 2020 on patients with locally advanced and metastatic melanoma receiving immunotherapy at either Istituto Europeo di Oncologia or Città della Salute e della Scienza University Hospital. RESULTS: One-hundred and sixty-nine patients with stage III and IV melanoma were treated with an immunotherapy regimen at either Istituto Europeo di Oncologia or Città della Salute e della Scienza University Hospital. One-hundred and four patients continued treatment without interruption or delay, while 49 patients had a treatment delay. The main reasons for treatment delay were older age (median age of the group of patients with or without treatment-delay, respectively 60 and 69 years, P value <0.001) and/or presence of comorbidities (percentage of patients with at least one comorbidity respectively 81% and 62%, in patients with or without treatment delay, P value = 0.001). One-hundred and twelve patients had at least 1 thoracic CT scan performed and radiological findings suspicious for COVID-19 were observed in only 7 cases (4%). Fifteen patients (9%) developed symptoms potentially related to COVID-19; nasopharyngeal swabs were collected in 9 patients and only 1 was positive for SARS-CoV-2. CONCLUSIONS: The incidence of symptomatic COVID-19 infection observed in our cohort of patients with advanced malignant melanoma treated with immunotherapy appears meaningfully lower as compared with that reported in the overall population in Italy as well as in patients affected by solid tumors. We conclude that in patients with locally advanced and metastatic melanoma, immunotherapy can be safely continued without delay in the majority of cases, reserving precautionary delay only for the most frail patients.

3.
Eur J Cancer ; 137: 30-39, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32739767

RESUMO

BACKGROUND: Sentinel lymph node biopsy (SNB) still remains a key procedure to appropriately stage melanoma patients and to select those who are candidate to novel treatments with immunotherapy and targeted therapy in the adjuvant setting. The impact of timing of SNB on disease-free survival (DFS) and overall survival (OS) is still unclear. MATERIAL AND METHODS: The study was conducted at 6 Italian Melanoma Intergroup (IMI) centres and included 8953 consecutive clinical stage I-II melanoma patients who were diagnosed, treated, and followed up between November 1997 and March 2018. All patients were prospectively included in dedicated IMI database. Multivariable Cox regression analyses were performed to investigate how baseline characteristics and time interval until SNB are related to DFS and OS. RESULTS: Considering the whole population, at multivariable analysis, after adjusting for age, gender, Breslow thickness, site, ulceration, and the SNB status, a delay in the timing of SNB was associated with a better DFS (adjusted hazard ratio [aHR, delayed versus early SNB] 0.98, 95% confidence interval [CI] 0.97-0.99, p < 0.001) and OS (aHR 0.98, 95% CI 0.97-0.99, p = 0.001). Specifically, in patients with a negative SNB status, a beneficial impact of delayed SNB (i.e. at least 32 days after primary excision) was confirmed for DFS (aHR 0.70, 95%CI 0.63-0.79, p < 0.001) and OS (aHR 0.69, 95%CI 0.61-0.78, p < 0.001), whereas in those with a positive SNB status, DFS (aHR 0.96, 95%CI 0.84-1.09, p = 0.534) and OS (aHR 0.94 95%CI 0.81-1.08, p = 0.374) were not significantly different in patients with early or delayed SNB. CONCLUSIONS: Our study does not support a strict time interval for SNB. These results may be useful for national guidelines, for counselling patients and reducing the number of high urgency referrals.

4.
Emerg Infect Dis ; 26(8): 1904-1905, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32687051

RESUMO

Trombiculosis is a skin infestation by larvae of mites of the Trombiculidae family. We used fluorescence-advanced videodermatoscopy to diagnose trombiculosis in a woman in Italy with targetoid patches. This method might be useful for identifying atypical manifestations of trombiculosis.

5.
Dermatol Ther ; : e13992, 2020 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-32648324

RESUMO

Two round tables involving experts were organized in order to reach a consensus on the management of patients with actinic keratosis (AK). In the first, seven clinical questions were selected and analyzed by a systematic literature review, using a Population, Intervention, Control, and Outcomes framework; in the second, the experts discussed relevant evidences and a consensus statement for each question was developed. Consensus was reached among experts on how to best treat AK patients with respect to different clinical scenarios and special populations. Lesion-directed treatments are preferred in patients with few AKs. Patients with multiple AKs are challenging, with more than one treatment usually needed to achieve complete lesion clearance or a high lesion response rate, therapy should be personalized, based on previous treatments, patient, and lesion characteristics. Methyl aminolevulinate-PDT, DL (day light) PDT, and imiquimod cream were demonstrated to have the lowest percentage of new AKs after post treatment follow-up. For IMQ 5% and 3.75%, a higher intensity of skin reactions is associated with higher efficacy. Photodynamic therapy (PDT) is the most studied treatment for AKs on the arms. Regular sunscreen use helps preventing new AKs. Oral nicotinamide 500 mg twice daily, systemic retinoids and regular sunscreen use were demonstrated to reduce the number of new squamous cell carcinomas in patients with AKs. Limited evidence is available for the treatment of AKs in organ transplant recipients. There is no evidence in favor or against the use of any of the available treatments in patients suffering from hematological cancer.

7.
Eur J Cancer ; 133: 120-130, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32502876

RESUMO

BACKGROUND: Brentuximab vedotin was approved for adult patients with CD30-expressing cutaneous T-cell lymphoma treated with prior systemic therapy based on improved response rates and progression-free survival with brentuximab vedotin (1.8 mg/kg once every 3 weeks; ≤16 cycles) versus physician's choice (methotrexate/bexarotene; ≤48 weeks) in the phase III ALCANZA study. Quality of life (QoL) in ALCANZA patients was also examined. METHODS: QoL measures in ALCANZA were based on the Skindex-29, Functional Assessment of Cancer Therapy-General (FACT-G) and European QoL 5-dimension (EQ-5D) questionnaires. RESULTS: Mean maximum reduction from the baseline Skindex-29 symptom domain score (key secondary end-point) was greater with brentuximab vedotin than physician's choice (-27.96 versus -8.62); the difference, -18.9 (95% confidence interval -26.6, -11.2; adjusted p < 0.001), exceeded the study-defined minimally important difference (9.0-12.3). Mean changes from baseline to end-of-treatment visit total FACT-G scores were similar with brentuximab vedotin and physician's choice (0.15 versus -2.29). EQ-5D changes were also comparable between arms. Among brentuximab vedotin-treated patients with peripheral neuropathy (PN), mean maximum reduction in Skindex-29 symptom domain was -35.54 versus -11.11 in patients without PN. PN had no meaningful effect on FACT-G and EQ-5D QoL scores. CONCLUSIONS: In summary, brentuximab vedotin produced superior reductions in symptom burden compared with physician's choice, without adversely impacting QoL. QoL was unaffected by the presence of PN in brentuximab vedotin-treated patients. CLINICAL TRIAL REGISTRATION: NCT01578499.

12.
J Clin Oncol ; 38(14): 1591-1601, 2020 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-32167862

RESUMO

PURPOSE: Thin melanomas (T1; ≤ 1 mm) constitute 70% of newly diagnosed cutaneous melanomas. Regional node metastasis determined by sentinel node biopsy (SNB) is an important prognostic factor for T1 melanoma. However, current melanoma guidelines do not provide clear indications on when to perform SNB in T1 disease and stress an individualized approach to SNB that considers all clinicopathologic risk factors. We aimed to identify determinants of sentinel node (SN) status for incorporation into an externally validated nomogram to better select patients with T1 disease for SNB. PATIENTS AND METHODS: The development cohort comprised 3,666 patients with T1 disease consecutively treated at the Istituto Nazionale Tumori (Milan, Italy) between 2001 and 2018; 4,227 patients with T1 disease treated at 13 other European centers over the same period formed the validation cohort. A random forest procedure was applied to the development data set to select characteristics associated with SN status for inclusion in a multiple binary logistic model from which a nomogram was elaborated. Decision curve analyses assessed the clinical utility of the nomogram. RESULTS: Of patients in the development cohort, 1,635 underwent SNB; 108 patients (6.6%) were SN positive. By univariable analysis, age, growth phase, Breslow thickness, ulceration, mitotic rate, regression, and lymphovascular invasion were significantly associated with SN status. The random forest procedure selected 6 variables (not growth phase) for inclusion in the logistic model and nomogram. The nomogram proved well calibrated and had good discriminative ability in both cohorts. Decision curve analyses revealed the superior net benefit of the nomogram compared with each individual variable included in it as well as with variables suggested by current guidelines. CONCLUSION: We propose the nomogram as a decision aid in all patients with T1 melanoma being considered for SNB.

16.
Oncologist ; 25(6): e946-e954, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32181960

RESUMO

The safety and activity of immune checkpoint inhibitors have been characterized in interventional and observational studies. However, only small studies have specifically investigated these agents in patients who are excluded or underrepresented in clinical trials, frequently referred to as "special populations" or "underrepresented populations." These include older adults, those with dysregulated immune activation, patients with a compromised immune function, and those carrying major viral infections, lymphoproliferative diseases, and major organ dysfunctions. Therefore, there remains substantial uncertainty regarding the use of immune checkpoint inhibitors in these specific settings. The Network of Italian Supportive Care in Oncology has carried out a multidisciplinary project, with the contribution of oncologists and other specialists, to retrieve the existing evidence on the use of immunotherapy in patients with solid and hematological cancers with the final aim to provide an expert guidance. The results of this effort are presented in this article, which is focused on patients with major viral infections or those with immune dysregulation/autoimmune diseases, and could be useful to guide decisions in clinical practice and to design prospective clinical trials focusing on the use of immunotherapy in these populations. IMPLICATIONS FOR PRACTICE: Substantial uncertainty remains regarding the use of immune checkpoint inhibitors in "underrepresented" patients, such as older adults, those with dysregulated immune activation, and patients with a compromised immune function, major viral infections, lymphoproliferative diseases or major organ dysfunctions. The Network of Italian Supportive Care in Oncology has carried out a multidisciplinary project to retrieve the existing evidence on the use of immunotherapy in underrepresented patients with cancer in order provide an expert guidance. The results of this effort, with a focus on patients with major viral infections or those with immune dysregulation/autoimmune diseases, are presented in this article and could be useful to guide decisions both in clinical practice and to design clinical trials.

17.
Medicine (Baltimore) ; 99(1): e18078, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31895765

RESUMO

Sun protection early in life is an essential issue for primary prevention of skin cancers. The Il Sole per Amico was an educational campaign among 66 Italian primary schools. A total of 12,188 questionnaires were completed at baseline. Overall, 9.4% children reported >1 sunburn during the last year and 44.7% parents a use of sunlamps. Independent factors associated with sunburns were: age, lower level of parents' education, light eye and skin color, freckles, nevi on arms, intense sun exposure during the last year, sporadic use of sunscreens, and parental use of sunlamps. A total of 7280 (59.7%) questionnaires were completed at the end of the educational intervention. No significant difference was documented about behavior between the pre- and post-intervention periods. A significant reduction was instead found in both prevalence of recent sunburns and total number of sunburn episodes after comparison with the data obtained by identical questionnaire in the same geographic areas in the "Sole Si Sole No" project in 2001.


Assuntos
Queimadura Solar/epidemiologia , Protetores Solares/administração & dosagem , Criança , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Itália , Masculino , Pais/psicologia , Avaliação de Programas e Projetos de Saúde , Neoplasias Cutâneas/prevenção & controle , Estudantes/estatística & dados numéricos , Queimadura Solar/prevenção & controle , Inquéritos e Questionários
18.
Acta Derm Venereol ; 100(1): adv00001, 2020 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-31532537

RESUMO

Current therapies for metastatic melanoma (anti-PD1 and BRAF/MEK inhibitors) can cause drug-induced vitiligo. The aim of this study is to dermatologically define and histologically characterize this new type of vitiligo, and assess the clinical course of the disease. Fourteen patients with metastatic melanoma treated with immune or targeted therapy were included in a dataset evaluating clinical data, vitiligo description and histopathological features. Vitiligo-like lesions occurred after a mean of 7.5 months from the start of the therapies (range 1-42 months), with a prevalence of the non-segmental variant (71.4%). Fifty percent of patients showed a clinical response (4 complete response and 3 partial response), 35.7% had stable disease, and one patient died after disease progression. Median survival from the start of the therapies was 32.5 months. Drug-induced vitiligo can be related to both immune and targeted therapies, is associated with a favourable prognosis, and has clinical characteristics different from the classical form.


Assuntos
Imunoterapia/métodos , Melanoma/complicações , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Neoplasias Cutâneas/complicações , Vitiligo/induzido quimicamente , Adulto , Feminino , Humanos , Masculino , Melanoma/mortalidade , Melanoma/patologia , Pessoa de Meia-Idade , Inibidores de Proteínas Quinases/farmacologia , Estudos Retrospectivos , Taxa de Sobrevida , Vitiligo/patologia
19.
Melanoma Res ; 30(3): 286-296, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30371537

RESUMO

Industrial workers are exposed to occupational pollutants, which may cause diseases such as cancer, but links to melanoma are not established. The identification of industry-related risk factors for melanoma incidence and mortality might be of importance for workers, health providers, and insurance companies. To assess melanoma incidence and mortality among oil/petroleum, chemical, and electrical industry workers. All studies reporting standardized mortality ratios (SMR) and/or standardized incidence ratios (SIR) of melanoma in workers employed in oil/petroleum, chemical, and electrical industries were included. Random-effect meta-analyses were carried out to summarize SIR and SMR for melanoma among oil/petroleum, chemical, and electrical industry workers. Heterogeneity was assessed using χ and I statistics. Possible source bias and quality were assessed using the Strengthening the Reporting of Observational Studies in Epidemiology checklist and a modified version of the Newcastle-Ottawa scale. Of 1878 citations retrieved, we meta-analyzed 21, 6, and 9 studies for the oil/petroleum, electrical, and chemical industry, respectively. Oil/petroleum industry: summary standardized incidence ratio (SSIR) = 1.23 [95% confidence interval (CI): 1.11-1.36, I = 45%]; summary standardized mortality ratio (SSMR) = 1.02 (95% CI: 0.81-1.28, I = 48%); subgroups: SSIR = 1.16 (95% CI: 1.01-1.32, I = 15%), SSMR = 1.19 (95% CI: 1.00-1.42, I = 20%). Electrical industry: SSIR = 1.00 (95% CI: 0.93-1.11, I = 72%); SSMR = 1.16 (95% CI: 0.74-1.81, I = 11%). Chemical industry: SSIR = 2.08 (95% CI: 0.47-9.24, I = 73%); SSMR = 2.01 (95% CI: 1.09-3.72, I = 33%). Our meta-analysis suggests a slightly increased risk of developing melanoma among oil/petroleum industry workers and an increased melanoma mortality among oil/petroleum and chemical industry workers. No increased risks were found among electrical industry workers.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA