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1.
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
2.
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
3.
Future Oncol ; 17(28): 3705-3716, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1458407

ABSTRACT

Advances in research have transformed the management of melanoma in the past decade. In parallel, patient advocacy has gained traction, and funders are increasingly prioritizing patient and public involvement. Here we discuss the ways in which patients and the public can be engaged in different stages of the research process, from developing, prioritizing and refining the research question to preclinical studies and clinical trials, then finally to ongoing research in the clinic. We discuss the challenges and opportunities that exist at each stage in order to ensure that a representative population of patients and the public contribute to melanoma research both now and in the future.


Subject(s)
Biomedical Research , Melanoma/therapy , Patient Participation , Clinical Trials as Topic , Humans , Information Dissemination , Informed Consent , Patient Advocacy , Patient Selection , Research Design
4.
Melanoma Res ; 31(4): 389-392, 2021 08 01.
Article in English | MEDLINE | ID: covidwho-1434530

ABSTRACT

The Novel Coronavirus disease (COVID-19) first emerged in Wuhan province, China, in late November 2019 and changed public healthcare perception. It has caused a significant decline in attendance to outpatient clinics. However, other diseases have not stopped, including malignant melanoma. Survey of the number of visits to plastic surgery outpatient clinic during the first lockdown in Israel concerning malignant melanoma was compared to the same months in the previous years. We assessed the number of visits to the oncology department during 2020 compared to the number of visits and treatment protocols for malignant melanoma. During the first lockdown, the attendance at the plastic surgery outpatient clinic and ambulatory surgery decreased significantly (P = 0.002), both in excisions of suspected malignant melanoma and malignant melanoma follow-ups (P = 0.019 and P = 0.035, respectively). The last third of 2020 (from September to December) had shown a significant rise in new protocols commenced (P < 0.001). This rise in the final third of the year was not noted in 2018 or 2019. These data clearly show the rise in advanced and metastatic malignant melanoma cases due to refraining from medical follow-ups and treatments during the COVID-19 pandemic. Diseases other than COVID-19 have not vanished, and continue to treat those diseases. Ignoring malignant melanoma treatment because of COVID-19 and vice-versa will not benefit our patients.


Subject(s)
Appointments and Schedules , COVID-19/prevention & control , Melanoma/epidemiology , Patient Acceptance of Health Care , Skin Neoplasms/epidemiology , COVID-19/epidemiology , COVID-19/transmission , Humans , Israel/epidemiology , Melanoma/diagnosis , Melanoma/therapy , Skin Neoplasms/diagnosis , Skin Neoplasms/therapy , Time Factors , Workload
5.
Am Soc Clin Oncol Educ Book ; 41: e295-e303, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1416833

ABSTRACT

A diagnosis of melanoma requires multidisciplinary specialized care across all stages of disease. Although many important advances have been made for the treatment of melanoma for local and advanced disease, barriers to optimal care remain for many patients who live in areas without ready access to the expertise of a specialized melanoma center. In this article, we review some of the recent advances in the treatment of melanoma and the persistent challenges around the world that prevent the delivery of the best standard of care to patients living in the community. With the therapeutic landscape continuing to evolve and newer more complex drug therapies soon to be approved, it is important to recognize the many challenges that patients face and attempt to identify tools and policies that will help to improve treatment outcomes for their melanoma.


Subject(s)
Melanoma , Humans , Melanoma/diagnosis , Melanoma/epidemiology , Melanoma/therapy , Treatment Outcome
7.
Nat Commun ; 12(1): 1087, 2021 02 17.
Article in English | MEDLINE | ID: covidwho-1333934

ABSTRACT

The introduction of immune checkpoint inhibitors has demonstrated significant improvements in survival for subsets of cancer patients. However, they carry significant and sometimes life-threatening toxicities. Prompt prediction and monitoring of immune toxicities have the potential to maximise the benefits of immune checkpoint therapy. Herein, we develop a digital nanopillar SERS platform that achieves real-time single cytokine counting and enables dynamic tracking of immune toxicities in cancer patients receiving immune checkpoint inhibitor treatment - broader applications are anticipated in other disease indications. By analysing four prospective cytokine biomarkers that initiate inflammatory responses, the digital nanopillar SERS assay achieves both highly specific and highly sensitive cytokine detection down to attomolar level. Significantly, we report the capability of the assay to longitudinally monitor 10 melanoma patients during immune inhibitor blockade treatment. Here, we show that elevated cytokine concentrations predict for higher risk of developing severe immune toxicities in our pilot cohort of patients.


Subject(s)
Immunotherapy/methods , Melanoma/therapy , Monitoring, Immunologic/methods , Spectrum Analysis, Raman/methods , Chemokine CX3CL1/immunology , Chemokine CX3CL1/metabolism , Cohort Studies , Cytokines/immunology , Cytokines/metabolism , Granulocyte Colony-Stimulating Factor/immunology , Granulocyte Colony-Stimulating Factor/metabolism , Granulocyte-Macrophage Colony-Stimulating Factor/immunology , Granulocyte-Macrophage Colony-Stimulating Factor/metabolism , Humans , Immune Checkpoint Inhibitors/adverse effects , Immune Checkpoint Inhibitors/immunology , Immune Checkpoint Inhibitors/therapeutic use , Ipilimumab/adverse effects , Ipilimumab/immunology , Ipilimumab/therapeutic use , Melanoma/immunology , Melanoma/metabolism , Microscopy, Confocal/methods , Pilot Projects , Reproducibility of Results
8.
J Immunother Cancer ; 9(7)2021 07.
Article in English | MEDLINE | ID: covidwho-1317020

ABSTRACT

The clinical and immunologic implications of the SARS-CoV-2 pandemic for patients with cancer receiving systemic anticancer therapy have introduced a multitude of clinical challenges and academic controversies. This review summarizes the current evidence, discussion points, and recommendations regarding the use of immune checkpoint inhibitors (ICIs) in patients with cancer during the SARS-CoV-2 pandemic, with a focus on patients with melanoma and renal cell carcinoma (RCC). More specifically, we summarize the theoretical concepts and available objective data regarding the relationships between ICIs and the antiviral immune response, along with recommended clinical approaches to the management of melanoma and RCC patient cohorts receiving ICIs throughout the course of the COVID-19 pandemic. Additional insights regarding the use of ICIs in the setting of current and upcoming COVID-19 vaccines and broader implications toward future pandemics are also discussed.


Subject(s)
COVID-19/immunology , Carcinoma, Renal Cell/immunology , Immune Checkpoint Inhibitors/immunology , Kidney Neoplasms/immunology , Melanoma/immunology , SARS-CoV-2/immunology , COVID-19/drug therapy , COVID-19/epidemiology , COVID-19 Vaccines/immunology , COVID-19 Vaccines/therapeutic use , Carcinoma, Renal Cell/therapy , Humans , Immune Checkpoint Inhibitors/therapeutic use , Immunotherapy/methods , Kidney Neoplasms/therapy , Melanoma/therapy , Pandemics/prevention & control , SARS-CoV-2/drug effects
9.
Clin Exp Dermatol ; 47(1): 114-116, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1301463

ABSTRACT

The impact of the COVID-19 pandemic upon care of malignant melanoma (MM) remains as yet poorly understood. We undertook a UK-wide national survey, in conjunction with a patient support group (Melanoma UK), to explore patient perceptions of the impact of the pandemic upon treatment and outpatient care of their MM. Our findings suggest that following the onset of COVID-19, a significant minority of treatments and appointments have been delayed, there has been a shift from face-to-face to virtual outpatient consultations and there may be a rise in psychological comorbidities in patients with MM. We would urge clinicians to consider mental health interventions as part of a holistic care package.


Subject(s)
Anxiety/etiology , COVID-19/prevention & control , Melanoma/therapy , Skin Neoplasms/therapy , Stress, Psychological/etiology , Adult , Aged , Aged, 80 and over , Ambulatory Care , Appointments and Schedules , Communicable Disease Control/methods , Cross-Sectional Studies , Female , Health Care Surveys , Health Services Accessibility , Humans , Male , Melanoma/psychology , Middle Aged , SARS-CoV-2 , Skin Neoplasms/psychology , Telemedicine , United Kingdom , Young Adult
12.
Br J Cancer ; 124(8): 1357-1360, 2021 04.
Article in English | MEDLINE | ID: covidwho-1072146

ABSTRACT

The COVID-19 pandemic has had an unprecedented impact on the National Health Service in United Kingdom. The UK Ocular Oncology Services evaluated the impact on the adult eye cancer care in the UK. All four adult Ocular Oncology centres participated in a multicentre retrospective review comparing uveal melanoma referral patterns and treatments in a 4-month period during the national lockdown and first wave of the COVID-19 pandemic in 2020 with corresponding periods in previous 2 years. During the national lockdown, referral numbers and confirmed uveal melanoma cases reduced considerably, equalling to ~120 fewer diagnosed uveal melanoma cases compared to previous 2 years. Contrary to the recent trend, increased caseloads of enucleation and stereotactic radiosurgery (p > 0.05), in comparison to fewer proton beam therapy (p < 0.05), were performed. In the 4-month period following lockdown, there was a surge in clinical activities with more advanced diseases (p < 0.05) presenting to the services. As the COVID-19 pandemic continues to mount pressure and reveal its hidden impact on the eye cancer care, it is imperative for the Ocular Oncology Services to plan recovery strategies and innovative ways of working.


Subject(s)
COVID-19/epidemiology , Eye Neoplasms/epidemiology , Melanoma/epidemiology , Pandemics , Uveal Neoplasms/epidemiology , COVID-19/complications , COVID-19/therapy , COVID-19/virology , Communicable Disease Control/methods , Eye Neoplasms/complications , Eye Neoplasms/therapy , Eye Neoplasms/virology , Humans , Melanoma/complications , Melanoma/therapy , Melanoma/virology , Proton Therapy/methods , SARS-CoV-2/pathogenicity , State Medicine , United Kingdom/epidemiology , Uveal Neoplasms/complications , Uveal Neoplasms/therapy , Uveal Neoplasms/virology
15.
J Biol Regul Homeost Agents ; 34(6): 1977-1982, 2020.
Article in English | MEDLINE | ID: covidwho-1027415

ABSTRACT

COVID-19 pandemic emerged as a condition that changed our entire life and led us to develop new perspectives on diseases. Cancers are generally additional risk factors for COVID-19, and this has implications also for skin cancer patients. Those patients require special attention, due to situations such as an increased risk of infection as a result of visiting the hospital for treatment. It is imperative that the diagnosis and treatment of patients who have a cancer that progresses rapidly, such as malignant melanoma, high-risk squamous cell carcinoma and a high risk of metastasis, are delayed. Due to the relatively long-lasting nature of basal cell carcinoma and, as almost no metastasis would be expected, its treatment may be postponed, except for those that occur in areas such as the eyes and mouth. Diagnosis and treatment of skin cancers is a process that requires many procedures. Throughout this process, physicians should take appropriate precautions that are sufficient to protect both the patient and themselves in the best way without leading to any delay in the procedures.


Subject(s)
COVID-19 , Melanoma , Skin Neoplasms , Humans , Melanoma/diagnosis , Melanoma/epidemiology , Melanoma/therapy , Pandemics , Skin Neoplasms/diagnosis , Skin Neoplasms/epidemiology , Skin Neoplasms/therapy
16.
Clin Cancer Res ; 27(10): 2678-2697, 2021 05 15.
Article in English | MEDLINE | ID: covidwho-1015729

ABSTRACT

Five years ago, the Melanoma Research Foundation (MRF) conducted an assessment of the challenges and opportunities facing the melanoma research community and patients with melanoma. Since then, remarkable progress has been made on both the basic and clinical research fronts. However, the incidence, recurrence, and death rates for melanoma remain unacceptably high and significant challenges remain. Hence, the MRF Scientific Advisory Council and Breakthrough Consortium, a group that includes clinicians and scientists, reconvened to facilitate intensive discussions on thematic areas essential to melanoma researchers and patients alike, prevention, detection, diagnosis, metastatic dormancy and progression, response and resistance to targeted and immune-based therapy, and the clinical consequences of COVID-19 for patients with melanoma and providers. These extensive discussions helped to crystalize our understanding of the challenges and opportunities facing the broader melanoma community today. In this report, we discuss the progress made since the last MRF assessment, comment on what remains to be overcome, and offer recommendations for the best path forward.


Subject(s)
COVID-19/prevention & control , Medical Oncology/methods , Melanoma/therapy , Practice Guidelines as Topic , SARS-CoV-2/isolation & purification , Skin Neoplasms/therapy , Biomedical Research/methods , Biomedical Research/trends , COVID-19/epidemiology , COVID-19/virology , Humans , Medical Oncology/organization & administration , Medical Oncology/trends , Melanoma/diagnosis , SARS-CoV-2/physiology , Skin Neoplasms/diagnosis
17.
ESMO Open ; 5(4)2020 07.
Article in English | MEDLINE | ID: covidwho-668037

ABSTRACT

Click here to listen to the Podcast.


Subject(s)
Melanoma , Neoadjuvant Therapy , Humans , Melanoma/therapy
18.
Semin Oncol ; 47(5): 302-304, 2020 10.
Article in English | MEDLINE | ID: covidwho-696421

ABSTRACT

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.


Subject(s)
COVID-19/diagnosis , Immunotherapy/methods , Melanoma/therapy , Adult , Aged , Aged, 80 and over , COVID-19/epidemiology , COVID-19/virology , Comorbidity , Female , Humans , Incidence , Italy/epidemiology , Male , Melanoma/epidemiology , Melanoma/immunology , Middle Aged , Pandemics , Retrospective Studies , SARS-CoV-2/physiology , Young Adult
19.
Dermatol Ther ; 33(6): e14101, 2020 11.
Article in English | MEDLINE | ID: covidwho-690449

ABSTRACT

Melanoma is the most severe form of skin cancer and its incidence has increased over the past few decades. COVID-19 pandemic affected the diagnosis and management of many diseases including melanoma. In this study, we aimed to provide a review focused on the diagnosis and management of melanoma in the era of COVID-19. A comprehensive search was conducted on PubMed, Web of Science, and Google Scholar databases using the keywords "melanoma," "coronavirus," "COVID 19," and "SARS-CoV-2." The relevant guidelines published by the European Society for Medical Oncology and the National Comprehensive Cancer Network were also included. The current guidelines recommend that surgical interventions for new diagnosis of invasive primary melanoma, patients with postoperative complications, wide resection and sentinel lymph node biopsy for newly diagnosed T3-T4 melanoma, and planned surgical procedures for patients in neo-adjuvant trials should be prioritized. Surgical treatment of T3/T4 melanomas should be prioritized over T1/T2 melanomas except for any melanoma in which large clinical residual lesion is visible. Adjuvant therapies can be postponed for up to 12 weeks depending on the local center circumstances. PD-1 inhibitor monotherapy is recommended for patients starting immunologic therapy. Combination immunotherapy is still considered suitable for patients with higher-risk disease. Encorafenib and binimetinib should be prioritized for patients requiring BRAF-targeted therapy due to the lower chance of symptoms mimicking COVID-19 infection.


Subject(s)
COVID-19 , Melanoma/therapy , Skin Neoplasms/therapy , Combined Modality Therapy , Humans , Immunotherapy , Melanoma/diagnosis , Melanoma/pathology , Molecular Targeted Therapy , Practice Guidelines as Topic , Skin Neoplasms/diagnosis , Skin Neoplasms/pathology
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