Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 132
Filter
1.
Lancet ; 399(10336): 1718-1729, 2022 04 30.
Article in English | MEDLINE | ID: covidwho-1882652

ABSTRACT

BACKGROUND: Pembrolizumab prolongs progression-free and overall survival among patients with advanced melanoma and recurrence-free survival in resected stage III disease. KEYNOTE-716 assessed pembrolizumab as adjuvant therapy in patients with completely resected, high-risk, stage II melanoma. We report results from the planned first and second interim analyses for recurrence-free survival. METHODS: In this double-blind, randomised, placebo-controlled phase 3 study, involving 160 academic medical centres and hospitals in 16 countries (Australia, Belgium, Brazil, Canada, Chile, France, Germany, Israel, Italy, Japan, Poland, South Africa, Spain, Switzerland, the UK, and the USA), patients aged 12 years or older with newly diagnosed, completely resected stage IIB or IIC melanoma (TNM stage T3b or T4 with a negative sentinel lymph node biopsy) were recruited. Eligible patients were randomly assigned (1:1), in blocks of four and stratified by T-category (3b, 4a, and 4b) and paediatric status (age 12-17 years vs ≥18 years), using an interactive response technology system to intravenous pembrolizumab 200 mg (2 mg/kg in paediatric patients) or placebo every 3 weeks for 17 cycles or until disease recurrence or unacceptable toxicity. All patients, clinical investigators, and analysts were masked to treatment assignment. The primary endpoint was investigator-assessed recurrence-free survival (defined as time from randomisation to recurrence or death) in the intention-to-treat (ITT) population (ie, all patients randomly assigned to treatment). The primary endpoint was met if recurrence-free survival was significantly improved for pembrolizumab versus placebo at either the first interim analysis (after approximately 128 patients had events) or second interim analysis (after 179 patients had events) under multiplicity control. Safety was assessed in all patients randomly assigned to treatment who received at least one dose of study treatment. This study is registered with ClinicalTrials.gov, NCT03553836, and is closed to accrual. FINDINGS: Between Sept 23, 2018, and Nov 4, 2020, 1182 patients were screened, of whom 976 were randomly assigned to pembrolizumab (n=487) or placebo (n=489; ITT population). The median age was 61 years (IQR 52-69) and 387 (40%) patients were female and 589 (60%) were male. 874 (90%) of 976 patients were White and 799 (82%) were not Hispanic or Latino. 483 (99%) of 487 patients in the pembrolizumab group and 486 (99%) of 489 in the placebo group received assigned treatment. At the first interim analysis (data cutoff on Dec 4, 2020; median follow-up of 14·4 months [IQR 10·2-18·7] in the pembrolizumab group and 14·3 months [10·1-18·7] in the placebo group), 54 (11%) of 487 patients in the pembrolizumab group and 82 (17%) of 489 in the placebo group had a first recurrence of disease or died (hazard ratio [HR] 0·65 [95% CI 0·46-0·92]; p=0·0066). At the second interim analysis (data cutoff on June 21, 2021; median follow-up of 20·9 months [16·7-25·3] in the pembrolizumab group and 20·9 months [16·6-25·3] in the placebo group), 72 (15%) patients in the pembrolizumab group and 115 (24%) in the placebo group had a first recurrence or died (HR 0·61 [95% CI 0·45-0·82]). Median recurrence-free survival was not reached in either group at either assessment timepoint. At the first interim analysis, grade 3-4 treatment-related adverse events occurred in 78 (16%) of 483 patients in the pembrolizumab groups versus 21 (4%) of 486 in the placebo group. At the first interim analysis, four patients died from an adverse event, all in the placebo group (one each due to pneumonia, COVID-19-related pneumonia, suicide, and recurrent cancer), and at the second interim analysis, one additional patient, who was in the pembrolizumab group, died from an adverse event (COVID-19-related pneumonia). No deaths due to study treatment occurred. INTERPRETATION: Pembrolizumab as adjuvant therapy for up to approximately 1 year for stage IIB or IIC melanoma resulted in a significant reduction in the risk of disease recurrence or death versus placebo, with a manageable safety profile. FUNDING: Merck Sharp & Dohme, a subsidiary of Merck & Co, Kenilworth, NJ, USA.


Subject(s)
COVID-19 , Melanoma , Testicular Neoplasms , Antibodies, Monoclonal, Humanized/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Child , Double-Blind Method , Female , Humans , Male , Melanoma/drug therapy , Melanoma/surgery , Middle Aged , Neoplasm Recurrence, Local/drug therapy
2.
Molecules ; 27(10)2022 May 21.
Article in English | MEDLINE | ID: covidwho-1875716

ABSTRACT

Nowadays, many individuals, whether healthy or diagnosed with disease, tend to expose themselves to various easily accessible natural products in hopes of benefiting their health and well-being. Mediterranean populations have traditionally used olive oil not only in nutrition but also in cosmetics, including skincare. In this study, the phenolic profile-composed of twelve compounds altogether, including the secoiridoids oleocanthal (OCAL) and oleacein (OCEIN)-of extra virgin olive oil (EVOO) from autochthonous cultivars from Croatia was determined using 1H qNMR spectroscopy and HPLC-DAD analysis, and its biological activity was investigated in melanoma cell lines. The EVOO with the highest OCEIN content had the strongest anti-cancer activity in A375 melanoma cells and the least toxic effect on the non-cancerous keratocyte cell line (HaCaT). On the other hand, pure OCAL was shown to be more effective and safer than pure OCEIN. Post-treatment with any of the EVOO phenolic extracts (EVOO-PEs) enhanced the anti-cancer effect of the anti-cancerous drug dacarbazine (DTIC) applied in pre-treatment, while they did not compromise the viability of non-cancerous cells. The metastatic melanoma A375M cell line was almost unresponsive to the EVOO-PEs themselves, as well as to pure OCEIN and OCAL. Our results demonstrate that olive oils and/or their compounds may have a potentially beneficial effect on melanoma treatment. However, their usage can be detrimental or futile, especially in healthy cells, due to inadequately applied concentrations/combinations or the presence of resistant cells.


Subject(s)
Iridoids , Melanoma , Dacarbazine , Humans , Iridoids/pharmacology , Melanoma/drug therapy , Olive Oil/chemistry , Plant Oils/chemistry , Plant Oils/pharmacology
4.
Indian J Ophthalmol ; 70(5): 1837-1840, 2022 05.
Article in English | MEDLINE | ID: covidwho-1835160

ABSTRACT

A 49-year-old Indian male presented with rapidly progressive vision loss 1 day after receiving the second dose of BNT162b2 mRNA coronavirus disease 2019 (COVID-19) vaccine (Pfizer-BioNTech, NY, USA). The eye had secondary angle closure glaucoma, bullous retinal detachment, and massive intraocular hemorrhage. Ultrasound showed an ill-defined subretinal mass with moderate internal reflectivity. Magnetic resonance imaging (MRI) confirmed an enhancing heterogeneous subretinal mass. Histopathology showed a necrotic melanocytic lesion arising from the posterior edge of the ciliary body and choroid. Necrotic uveal melanoma was confirmed after expert histopathology opinion. Uveal melanomas can rarely present with tumor necrosis following mRNA COVID-19 vaccination.


Subject(s)
COVID-19 , Melanoma , COVID-19 Vaccines/adverse effects , Humans , Male , Melanoma/diagnosis , Melanoma/pathology , Middle Aged , Necrosis , RNA, Messenger , Uveal Neoplasms , Vaccination
5.
Pathol Res Pract ; 233: 153805, 2022 May.
Article in English | MEDLINE | ID: covidwho-1829375

ABSTRACT

BACKGROUND: The diagnosis of nodal nevi (NN) is challenging as they mimic melanoma metastases (MM), with a detection rate mostly ranging between 1% and 11% in sentinel lymph node biopsy (SLNB). Herein, we assessed the incidence of NN and the association with the clinical-pathological features of primary melanoma, adopting the updated European Organisation for Research and Treatment of Cancer (EORTC) protocol for SLNB. METHODS: All cases of paired melanoma and SLNB were retrospectively evaluated (April 2019-May 2020). Appropriate statistical tests were adopted, with significant variables included in the logistic regression model. RESULTS: 81 patients and a total of 186 lymph nodes (LNs) were included. Eleven patients had only NN and 4 had both NN and MM (18.5%); 29 LNs (15.6%) showed at least one NN and 12 (6.5%) showed more than one NN (a total amount of 43 NN was detected). All NN and none MM stained for p16. NN were associated with age < 60 years (p: 0.042), no ulceration (p: 0.025) and nevus-associated melanoma (NAM) (p: 0.018), with this latter being the only predictor at the logistic regression model (p: 0.022). CONCLUSIONS: The updated EORTC protocol shows a high number of NN and highlights a strong association with NAM.


Subject(s)
Melanoma , Nevus , Skin Neoplasms , Humans , Lymph Nodes/pathology , Melanoma/pathology , Middle Aged , Nevus/diagnosis , Retrospective Studies , Sentinel Lymph Node Biopsy , Skin Neoplasms/pathology
6.
Medicina (Kaunas) ; 58(4)2022 Apr 03.
Article in English | MEDLINE | ID: covidwho-1810018

ABSTRACT

Dabrafenib and trametinib are two available molecules that have been approved for the treatment of metastatic melanoma with BRAF-V600E or V600K mutations. Their combined therapy has led to long-lasting survival benefits and substantially improved outcomes. Until now, only a few cases of severe hypersensitivity reactions to dabrafenib and vemurafenib have been reported, and even fewer desensitization protocols to these molecules have been documented. We report the case of a 71-year-old female patient with metastatic melanoma harboring a BRAF-V600E mutation undergoing targeted therapy with dabrafenib and trametinib. Two weeks after the initiation of the combined treatment, she developed a hypersensitivity reaction. The cause-effect relationship between dabrafenib and the hypersensitivity reaction was demonstrated twice, when symptoms recurred upon dabrafenib reintroduction. We started a rapid 3-day dabrafenib desensitization protocol, which was well tolerated. When the patient discontinued the drug administration, we decided on a longer protocol that included more steps and more days in order to prevent the occurrence of other hypersensitivity reactions. Our patient tolerated both rapid and slow-going schedules, the first one reaching the final dose within 3 days and the second one reaching the total daily dose within 14 days. Depending on the patient's needs, the severity of the hypersensitivity reaction and the hospital's availability, the doctor may choose either the rapid or slow-going desensitization protocol.


Subject(s)
Melanoma , Neoplasms, Second Primary , Skin Neoplasms , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Female , Humans , Imidazoles , Melanoma/drug therapy , Melanoma/genetics , Mutation , Neoplasm Recurrence, Local/drug therapy , Neoplasms, Second Primary/etiology , Oximes , Proto-Oncogene Proteins B-raf/genetics , Skin Neoplasms/pathology
8.
Front Public Health ; 9: 743368, 2021.
Article in English | MEDLINE | ID: covidwho-1775905

ABSTRACT

Objectives: To investigate the association of gender, ethnicity, living region, and socioeconomic status (SES) with health literacy and attitudes toward nevi and melanoma in Chinese adolescents and to examine whether health literacy mediates the association of SES with attitudes. Study Design: A multicenter cross-sectional study was conducted among newly enrolled college students. First-year students were recruited from five universities in different regions of China in 2018 using the cluster sampling method. The observers were blinded to the participants. Methods: Health literacy and attitudes were measured using a previously validated tool (Nevus and Melanoma Health Literacy and attitudes Test). SES was measured by annual family income and parental highest educational level. Nonparametric test was used to examine the association of participants' characteristics with health literacy and attitudes. Two-level generalized linear model with logarithm link function and Gamma distribution was used individually for SES. The mediation effect model was used to examine the mediation effect of health literacy. Results: A total of 21,086 questionnaires were completed by college students with a mean age of 18.0 ± 0.8 years. The mean scores of health literacy and attitudes were 9.83 ± 7.46 (maximum score: 28) and 16.98 ± 2.92 (maximum score: 20), respectively. Female, Han nationality, annual family income, and parental educational levels were positively associated with health literacy and attitudes. Regional differences showed different effects on health literacy and attitudes. A mediation model showed that literacy mediated the association of SES with attitudes toward nevi and melanoma. Health literacy mediated ~30-50% of the association of SES with attitudes. Conclusions: Melanoma-related health literacy among Chinese college students is generally insufficient and needs to be improved. Targeted and personalized health education for improving health literacy related to nevi and melanoma may improve the general population's attitudes and further promote health-related behavior to prevent and identify early-stage melanoma.


Subject(s)
Health Literacy , Melanoma , Students , Adolescent , Attitude , China/epidemiology , Cross-Sectional Studies , Female , Health Promotion , Humans , Socioeconomic Factors
9.
Cells ; 11(6)2022 03 17.
Article in English | MEDLINE | ID: covidwho-1760409

ABSTRACT

Cancer therapy is an emergent application for mRNA therapeutics. While in tumor immunotherapy, mRNA encoding for tumor-associated antigens is delivered to antigen-presenting cells in spleen and lymph nodes, other therapeutic options benefit from immediate delivery of mRNA nanomedicines directly to the tumor. However, tumor targeting of mRNA therapeutics is still a challenge, since, in addition to delivery of the cargo to the tumor, specifics of the targeted cell type as well as its interplay with the tumor microenvironment are crucial for successful intervention. This study investigated lipoplex nanoparticle-mediated mRNA delivery to spheroid cell culture models of melanoma. Insights into cell-type specific targeting, non-cell-autonomous effects, and penetration capacity in tumor and stroma cells of the mRNA lipoplex nanoparticles were obtained. It was shown that both coculture of different cell types as well as three-dimensional cell growth characteristics can modulate distribution and transfection efficiency of mRNA lipoplex formulations. The results demonstrate that three-dimensional coculture spheroids can provide a valuable surplus of information in comparison to adherent cells. Thus, they may represent in vitro models with enhanced predictivity for the in vivo activity of cancer nanotherapeutics.


Subject(s)
Melanoma , Nanoparticles , Coculture Techniques , Humans , Melanoma/therapy , Nanoparticles/therapeutic use , RNA , RNA, Messenger/genetics , Tumor Microenvironment
10.
Medicina (Kaunas) ; 58(2)2022 Jan 30.
Article in English | MEDLINE | ID: covidwho-1715541

ABSTRACT

Immunotherapy with immune checkpoint inhibitors represents nowadays a marked improvement in cancer treatment. Nevertheless, they can cause severe toxicities that put the patient at high risk, often requiring aggressive treatment. We present the case of a female patient who developed a severe immune-related adverse reaction to Pembrolizumab prescribed for melanoma treatment. Her array of symptoms, which presented a few days after last drug administration, consisted of severe neurological deficit, severe renal failure, polymyositis, and hyperthyroidism. Treatment required the immediate interruption of the trigger drug, infusion of high dose steroids, renal replacement therapy, plasmapheresis, and methimazole, as will be further discussed.


Subject(s)
Acute Kidney Injury , Antibodies, Monoclonal, Humanized/adverse effects , Melanoma , Acute Kidney Injury/chemically induced , Acute Kidney Injury/therapy , Female , Humans , Immunotherapy , Melanoma/drug therapy
11.
Clin Imaging ; 85: 78-82, 2022 May.
Article in English | MEDLINE | ID: covidwho-1708841

ABSTRACT

Metastatic melanoma of the breast is rare, and demonstrates nonspecific imaging findings which may overlap with both benign and malignant pathology.1-3 Immunohistochemical stains are important to confirm the diagnosis, particularly combining S100, a sensitive marker for melanoma, with more specific tumor markers such as Melan-A and HMB-45, and lack of cytokeratin staining.4-7 We present a case of a 64-year-old female who presented for diagnostic imaging of a palpable abnormality in her right breast, with medical history notable for previously excised cutaneous melanoma, recent COVID-19 vaccination, and significant family history of breast cancer. Diagnostic mammogram of the right breast demonstrated a circumscribed mass in the lower inner quadrant corresponding to the area of palpable concern, as well as an additional non-palpable circumscribed mass in the lower inner quadrant. Targeted right breast ultrasound demonstrated corresponding circumscribed cystic versus solid masses as well as a morphologically abnormal right axillary lymph node. Pathologic results after tissue sampling of the two right breast masses and right axillary lymph node all yielded metastatic melanoma.


Subject(s)
Breast Neoplasms , COVID-19 , Melanoma , Skin Neoplasms , Axilla/pathology , Breast Neoplasms/pathology , COVID-19 Vaccines , Female , Humans , Lymph Nodes/pathology , Lymphatic Metastasis/pathology , Melanoma/diagnostic imaging , Melanoma/pathology , Middle Aged , Skin Neoplasms/diagnostic imaging , Skin Neoplasms/pathology
12.
Rev Med Suisse ; 18(767): 182-186, 2022 Feb 02.
Article in French | MEDLINE | ID: covidwho-1675730

ABSTRACT

Despite COVID-19 pandemic, which is still deeply affecting world economy and global health, medical oncology specialists keep pursuing their effort for the identification of new therapeutic options to improve patients' life expectancy and quality of life. 2021 confirms the immunotherapy efficacy, alone or in combination with other modalities, across several indications. This year, we are summarizing the new approaches in the following sectors: lung, breast, melanoma, gynecological, digestive, urological and ENT areas.


En dépit de la pandémie de Covid-19 qui continue à grandement impacter l'économie mondiale et la santé, l'oncologie médicale poursuit sa quête d'identification de nouvelles options thérapeutiques ayant pour buts la prolongation de l'espérance de vie et l'amélioration de la qualité de vie de ses patients, en nombre croissant. L'année 2021 confirme également l'efficacité de l'immunothérapie, seule ou en combinaison à d'autres modalités, dans de nombreuses indications. Cette année, nous vous résumons les nouvelles approches dans les domaines suivants: poumon, sein, mélanome, sphères gynécologique, digestive, urologique et ORL.


Subject(s)
COVID-19 , Melanoma , Humans , Medical Oncology , Pandemics , Quality of Life , SARS-CoV-2
13.
Cancer Imaging ; 22(1): 3, 2022 Jan 04.
Article in English | MEDLINE | ID: covidwho-1603334

ABSTRACT

18F-FDG PET/CT plays an increasingly pivotal role in the staging and post-treatment monitoring of high-risk melanoma patients, augmented by the introduction of therapies, including tyrosine kinase inhibitors (TKI) and immune checkpoint inhibitors (ICIs), that have novel modes of action that challenge conventional response assessment. Simultaneously, technological advances have been regularly released, including advanced reconstruction algorithms, digital PET and motion correction, which have allowed the PET community to detect ever-smaller cancer lesions, improving diagnostic performance in the context of indications previously viewed as limitations, such as detection of in-transit disease and confirmation of the nature of small pulmonary metastases apparent on CT.This review will provide advice regarding melanoma-related PET protocols and will focus on variants encountered during the imaging of melanoma patients. Emphasis will be made on pitfalls related to non-malignant diseases and treatment-related findings that may confound accurate interpretation unless recognized. The latter include signs of immune activation and immune-related adverse events (irAEs). Technology-related pitfalls are also discussed, since while new PET technologies improve detection of small lesions, these may also induce false-positive cases and require a learning curve to be observed. In these times of the COVID 19 pandemic, cases illustrating lessons learned from COVID 19 or vaccination-related pitfalls will also be described.


Subject(s)
COVID-19 , Melanoma , Skin Neoplasms , Fluorodeoxyglucose F18 , Humans , Melanoma/diagnostic imaging , Positron Emission Tomography Computed Tomography , Positron-Emission Tomography , Radiopharmaceuticals , SARS-CoV-2 , Skin Neoplasms/diagnostic imaging
16.
Int J Environ Res Public Health ; 18(24)2021 12 16.
Article in English | MEDLINE | ID: covidwho-1580736

ABSTRACT

INTRODUCTION: The recent COVID-19 pandemic has compromised socio-health care, with consequences for the diagnosis and follow-up of other pathologies. The aim of this study was to evaluate the impact of COVID-19 on cancer diagnosis in Girona, Spain. METHODOLOGY: Observational study of samples received in two pathology laboratories during 2019-2020 (tertiary hospital in Girona and county hospital in Figueres). Date, sample type, and location and morphology were available. Samples were recoded to determine malignancy and grouped by location. Comparisons were made by calendar year and period of exposure to COVID-19. RESULTS: 102,360 samples were included: 80,517 from Girona and 21,843 from Figueres. The reduction in activity in the pathology laboratories in 2020 compared to the previous year was 25.4% in Girona and 27.5% in Figueres. The reduction in cancer diagnoses in 2020 compared to 2019 was 6.8% in Girona and 21% in Figueres. In both laboratories, a decrease was observed in the diagnoses of neoplasms of the lip, oral cavity and pharynx, larynx, colon, rectum and anus, kidney and urinary system, melanoma, and central nervous system. A statistically significant higher probability of a sample received in the pathology laboratory displaying malignancy during COVID-19 was found (Girona: OR = 1.28, 95% CI: 1.23-1.34; Figueres: OR = 1.10, 95% CI: 1.01-1.20) with respect to the COVID-19-free period. CONCLUSIONS: The COVID-19 pandemic has resulted in a reduction in cancer diagnoses by pathology departments that varies according to tumor location and type of hospital. Despite this, the optimization of care resources and the recovery effort have partially reduced the impact of the pandemic in certain neoplasms.


Subject(s)
COVID-19 , Melanoma , Humans , Laboratories , Pandemics , SARS-CoV-2
17.
J Drugs Dermatol ; 20(12): 1343-1345, 2021 Dec 01.
Article in English | MEDLINE | ID: covidwho-1573164

ABSTRACT

Patients with polypoid (pedunculated) melanoma have the poorest 5-year survival rate compared with all other variants of nodular melanoma, presenting with increased thickness, incidence of metastasis, and rates of ulceration. There are few published reports regarding the pathogenesis and treatment of polypoid melanomas. We report the successful treatment of a rapidly developing red nodular polypoid melanoma with metastasis using surgery followed by anti-PD-1 antibody nivolumab in a SARS-CoV-2-positive patient who delayed seeking care due to the COVID-19 pandemic. J Drugs Dermatol. 2021;20(12):1343-1345. doi:10.36849/JDD.6071.


Subject(s)
COVID-19 , Melanoma , Skin Neoplasms , Humans , Melanoma/diagnosis , Melanoma/drug therapy , Melanoma/epidemiology , Nivolumab , Pandemics , SARS-CoV-2 , Skin Neoplasms/diagnosis , Skin Neoplasms/drug therapy , Skin Neoplasms/epidemiology
20.
Ann Surg Oncol ; 29(3): 1629-1635, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1526674

ABSTRACT

BACKGROUND: Covid-19 significantly affected healthcare delivery over the past year, with a shift in focus away from nonurgent care. Emerging data are showing that screening for breast and colon cancer has dramatically decreased. It is unknown whether the same trend has affected patients with melanoma. METHODS: This is a retrospective cohort study of melanoma patients at two large-volume cancer centers. Patients were compared for 8 months before and after the lockdown. Outcomes focused on delay in treatment and possible resultant upstaging of melanoma. RESULTS: A total of 375 patients were treated pre-lockdown and 313 patients were treated post-lockdown (17% decrease). Fewer patients presented with in situ disease post-lockdown (15.3% vs. 17.9%), and a higher proportion presented with stage III-IV melanoma (11.2% vs. 9.9%). Comparing patients presenting 2 months before versus 2 months after the lockdown, there was an even more significant increase in Stage III-IV melanoma from 7.1% to 27.5% (p < 0.0001). Finally, in Stage IIIB-IIID patients, there was a decrease in patients receiving adjuvant therapy in the post lockdown period (20.0% vs. 15.2%). CONCLUSIONS: As a result of the recent pandemic, it appears there has been a shift away from melanoma in situ and toward more advanced disease, which may have significant downstream effects on prognosis and could be due to a delay in screening. Significantly patients have presented after the lockdown, and fewer patients are undergoing the recommended adjuvant therapies. Patient outreach efforts are essential to ensure that patients continue to receive preventative medical care and screening as the pandemic continues.


Subject(s)
COVID-19 , Melanoma , Communicable Disease Control , Humans , Melanoma/diagnosis , Melanoma/epidemiology , Melanoma/therapy , Retrospective Studies , SARS-CoV-2
SELECTION OF CITATIONS
SEARCH DETAIL