Bloom Syndrome (BSyn) is an autosomal recessive disorder that causes growth deficiency, endocrine abnormalities, photosensitive skin rash, immune abnormalities, and predisposition to early-onset cancer. The available treatments for BSyn are symptomatic, and early identification of complications has the potential to improve outcomes. To accomplish this, standardized recommendations for health supervision are needed for early diagnosis and treatment. The purpose of this report is to use information from the BSyn Registry, published literature, and expertise from clinicians and researchers with experience in BSyn to develop recommendations for diagnosis, screening, and treatment of the clinical manifestations in people with BSyn. These health supervision recommendations can be incorporated into the routine clinical care of people with BSyn and can be revised as more knowledge is gained regarding their clinical utility.
Immuno-oncology is a rapidly evolving field with growing relevance in the treatment of numerous malignancies. The prior study of immunotherapy in dermatologic oncology has largely focused on cutaneous melanoma. However, recent focus has shifted to the use of immunotherapy to treat non-melanoma skin cancers (NMSCs), such as basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (cSCC), and Merkel cell carcinoma (MCC). NMSCs represent the most ubiquitous cancers globally and, while they have a lower propensity to develop into advanced disease than cutaneous melanoma, their absolute mortality burden has recently surpassed that of melanoma. Patients with advanced NMSC are now benefiting from the successes of immunotherapy, including checkpoint inhibition with anti-CTLA-4 and anti-PD-1 monoclonal antibodies. In this review, we discuss the existing clinical evidence for immunotherapy in the treatment of NMSCs, with an emphasis on checkpoint inhibitor therapies. We highlight key studies in the field and provide up-to-date clinical evidence regarding ongoing clinical trials, as well as future study directions. Our review demonstrates that checkpoint inhibitors are positioned to provide unparalleled results in the previously challenging landscape of advanced NMSC treatment.
(1) Melanoma is the most aggressive dermatologic malignancy, with an estimated 106,110 new cases to be diagnosed in 2021. The annual incidence rates continue to climb, which underscores the critical importance of improving the methods to prevent this disease. The interventions to assist with melanoma prevention vary and typically include measures such as UV avoidance and the use of protective clothing, sunscreen, and other chemopreventive agents. However, the evidence is mixed surrounding the use of these and other interventions. This review discusses the heritable etiologies underlying melanoma development before delving into the data surrounding the preventive methods highlighted above. (2) A comprehensive literature review was performed to identify the clinical trials, observational studies, and meta-analyses pertinent to melanoma prevention and incidence. Online resources were queried to identify epidemiologic and clinical trial information. (3) Evidence exists to support population-wide screening programs, the proper use of sunscreen, and community-targeted measures in the prevention of melanoma. Clinical evidence for the majority of the proposed preventive chemotherapeutics is presently minimal but continues to evolve. (4) Further study of these chemotherapeutics, as well as improvement of techniques in artificial intelligence and imaging techniques for melanoma screening, is warranted for continued improvement of melanoma prevention.
e21595 Background: Cutaneous melanoma is an aggressive dermatologic malignancy with stage II-III recurrence rates ranging from 27-46%. Analysis of the tumor microenvironment (TME) is a promising mechanism to identify the patients who would benefit most from adjuvant immunotherapy given the risk for potential immune-related adverse events. Previous research by our group established the potential of utilizing CD3+CD8+ cytotoxic lymphocyte (CTL) and CD68+ macrophage densities, as well as the CTL/macrophage ratio in the TME, as prognostic biomarkers for metastatic progression and disease-specific survival (DSS). We sought to test the prognostic accuracy of the CTL/macrophage ratio in a second cohort of stage II-III melanoma patients from the Geisinger Health System. Methods: We utilized quantitative multiplex immunofluorescence (qmIF) to analyze 43 patient samples with stage II-III melanoma to validate the prospective biomarkers established in our previous CUIMC cohort. TME cell phenotype and cell density data were acquired for both the stroma as well as the combined tumor + stroma (“total TME”) via utilization of a trainable machine learning program. Cell densities and ratios were subsequently analyzed to determine associations with clinical outcomes including both disease recurrence and DSS. Results: In patients without distant metastatic recurrence (DMR), the density of CTLs and activated HLA-DR+ CTLs was higher in both the stroma ( p= 0.0003, p= 0.0152, respectively), as well as total TME ( p< 0.0001, p= 0.0165, respectively), when compared to those with DMR. The CTL/macrophage ratio in the total TME was greater in those without recurrence ( p= 0.0031). The ratio of CTLs to MPO+ neutrophils was higher in both the stroma ( p= 0.0015) and the total TME ( p= 0.0016) in those without recurrence. Survival analysis of 38 patients with known cause of death indicated a higher CTL/macrophage ratio in the total TME was associated with improved survival ( p= 0.0005). Improved survival was also associated with high CTL/neutrophil ratios in both the stroma ( p< 0.0001) and the total TME ( p< 0.0001). Cox regression analysis demonstrated a strong association between low CTL/macrophage and CTL/neutrophil ratios in the total TME and an increased risk of death ( p= 0.003, HR: 7.24, CI: 1.99-26.31; p= 0.003, HR: 22.35, CI: 2.87-173.97, respectively). Conclusions: Patients without disease recurrence display an increased infiltration of CTLs and activated HLA-DR+ CTLs, in addition to higher ratios of CTLs to macrophages and neutrophils, in the TME. High CTL/macrophage and CTL/neutrophil ratios in the total TME were also independently associated with improved DSS. Validation is underway with an additional cohort to further explore the use of these prospective biomarkers as clinical decision-making support tools to help guide the determination of patient risk and the use of adjuvant immunotherapy in melanoma.
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