Cutaneous melanoma remains the most lethal of the primary cutaneous neoplasms, and although the incidence of primary melanoma continues to rise, the mortality from metastatic disease remains unchanged, in part through advances in treatment. Major developments in immunomodulatory and targeted therapies have provided robust improvements in response and survival trends that have transformed the clinical management of patients with metastatic melanoma. Additional advances in immunologic and cancer cell biology have contributed to further optimization in (1) risk stratification, (2) prognostication, (3) treatment, (4) toxicity management, and (5) surveillance approaches for patients with an advanced melanoma diagnosis. In this review, we provide a comprehensive overview of the historical and future advances regarding the translational and clinical implications of advanced melanoma and share multidisciplinary recommendations to aid clinicians in the navigation of current treatment approaches for a variety of patient cohorts.
BackgroundImmune checkpoint inhibitors (ICI) have emerged as a front-line therapy for a variety of solid tumors. With the widespread use of these agents, immune-associated toxicities are increasingly being recognized, including fatal myocarditis. There are limited data on the outcomes and prognostic utility of biomarkers associated with ICI-associated myocarditis. Our objective was to examine the associations between clinical biomarkers of cardiomyocyte damage and mortality in patients with cancer treated with ICIs.MethodsWe retrospectively studied 23 patients who developed symptomatic and asymptomatic troponin elevations while receiving ICI therapy at a National Cancer Institute-designated comprehensive cancer center. We obtained serial ECGs, troponin I, and creatine kinase-MD (CK-MB), in addition to other conventional clinical biomarkers, and compared covariates between survivors and non-survivors.ResultsAmong patients with myocarditis, higher troponin I (p=0.037) and CK-MB (p=0.034) levels on presentation correlated with progression to severe myocarditis. Higher troponin I (p=0.016), CK (p=0.013), and CK-MB (p=0.034) levels were associated with increased mortality, while the presence of advanced atrioventricular block on presentation (p=0.088) trended toward increased mortality. Weekly troponin monitoring lead to earlier hospitalization for potential myocarditis (p=0.022) and was associated with decreased time to steroid initiation (p=0.053) and improved outcomes.ConclusionsRoutine troponin surveillance may be helpful in predicting mortality in ICI-treated patients with cancer in the early phase of ICI therapy initiation. Early detection of troponin elevation is associated with earlier intervention and improved outcomes in ICI-associated myocarditis. The recommended assessment and diagnostic studies guiding treatment decisions are presented.
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.
Background
Venous thromboembolism (
VTE
) is a major cause of morbidity, mortality, and hospitalization in cancer patients.
Objectives
To evaluate the feasibility of an electronic alert to identify and screen at‐risk individuals and gather rates of early detection of deep vein thrombosis (
DVT
).
Patients/Methods
An alert was built into the electronic medical record based on a validated risk tool (Khorana Score [
KS
]) and outcomes evaluated in an initial silent phase. The alert functioned in real time to warn physicians of high‐risk patients (
KS
≥ 3) and suggested lower extremity screening ultrasonography in a subsequent active phase.
Results
Of 194 consecutive patients identified as high risk in the silent phase, 14 (7.2%) developed subsequent
DVT
or pulmonary embolism (
PE
) over 90‐day follow‐up, with a median of 27 days. Mean 90‐day emergency room (
ER
) visits, all‐cause admissions, and length of stay (days) for patients with
DVT
were 1.2, 1.6, and 9.1 compared to 0.89, 0.93, and 5.1 for all patients, respectively. In the active phase, 197 consecutive alerts met inclusion criteria, and 40 patients (20.3%) received a screening ultrasound. Five (12.5%) had a
DVT
and were started on therapeutic anticoagulation. Of patients with alerts who had screening deferred, 13 (8.3%) were later diagnosed with
DVT
(median 50.5 days) and 7 (4.5%) with
PE
.
Conclusion
An automated alert may have value in early detection of
DVT
in high‐risk cancer patients leading to earlier intervention, and could potentially prevent
VTE
‐related morbidity.
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