Metastatic Melanoma of the Heart: A Case Series
As it progresses into stage IV, cancer spreads via metastasis to other parts of the body. Melanoma is a highly invasive cancer by nature that can spread throughout the body hematologically (through the blood), lymphatically, and transvenously. This tendency to metastasize results in cardiac metastasis in 50% of melanoma cases, yet discovery of said cases rarely occurs antemortem (before mortality).
This proposal is focused on understanding the rare diagnosis of antemortem cardiac metastatic melanoma. By studying risk factors, modalities of image screening and treatment, and clinical outcomes, we strive to expedite diagnosis of cardiac metastatic melanoma and lower the burden of mortality for future patients.
We are utilizing a retrospective chart review for patients diagnosed with stage IV melanoma and histologically confirmed findings of cardiac metastasis. From these charts, we will compare and contrast trends related to comorbidities, symptomatology, imaging findings, interventions, and outcomes to understand the associated mortality risk factors and outcomes for cardiac metastatic melanoma.
Cardiovascular Predictors of Bone Marrow Transplantation Outcomes
Hematopoietic stem cell transplantation (HSCT), also known as bone marrow transplantation, is a potentially curative therapy for many life-threatening cancers, non-malignant marrow disorders, and in-borne errors of metabolism. Hematopoietic progenitor cells are collected from a human donor from multiple possible sources (bone marrow, peripheral blood, umbilical cord blood) and administered to the patient to reconstitute their bone marrow after suppression by chemotherapeutic treatments. Over 20,000 bone marrow transplants are performed annually in the United States.
Unfortunately, patients undergoing HSCT are subjected to challenges to nearly all organ system, including various cardiovascular complications. Early cardiovascular complications include arrhythmias, congestive heart failure, and acute thrombosis. HSCT survivors beyond the first 100 days remain at a higher risk of complications including death from cardiac causes, hypertension, diabetes mellitus, hyperlipidemia, and heart failure at an incidence of 10% at 15 years, a rate that is close to 5-fold higher than the general population, and with the increasing use of HSCT as the field grows, the incidence of cardiovascular complications is only expected to increase.
We aim to establish evidence-based strategies to identify cancer patients undergoing HSCT at high risk of cardiovascular complications and optimize their cardiovascular health prior to, and following, transplantation.
Also, find our recent publication on the clinical and research tools used to study cardiovascular effects of cancer therapy.
Cardiovascular Predictors of CAR-T Outcomes
The use of chimeric antigen receptor T-cell (CAR-T) therapy has rapidly grown since FDA approval in 2017 of Yescarta for Diffus Large B-cell Lymphoma (DLBCL) and Kymriah for Acute B Lymphoblastic Leukemia (B-ALL). While a promising and lifesaving therapy for patients with refractory hematologic malignancies, CAR-T therapy has a series of unique toxicities that create management challenges.
The cytokine release syndrome (CRS) and CAR-T related neurotoxicity are well described, however the incidence of therapy related onset of cardiac dysfunction, the risk factors for the onset, and the implications of patients with new dysfunction is still unclear.
We plan to describe the incidence of CAR-T therapy related cardiac dysfunction, and to delineate risk factors or protective factors that will help us to guide the use of this therapy and potential treatments for short-term and long-term survivors.
Immune Checkpoint Inhibitors and Myocarditis
Immune checkpoints are a natural part of our body's immune system that limit the response, preventing autoimmunity. Lymphocytes expressing checkpoint protein receptors can bind their partner ligand on neighboring cells, sending a signal to dampen the immune response.
Some tumor cells express checkpoint proteins as a means to evade the immune system, decreasing the immune response that would otherwise kill the tumor cells, and preventing the immune system from destroying the cancer. Using immunotherapy drugs known as immune checkpoint inhibitors to block the checkpoint proteins from binding partner proteins, the "off" signal is no longer transmitted and cytotoxic T-cells can decrease tumor size.
We are studying adverse drug reactions in cancer patients at risk of developing cardiovascular and metabolic toxicities. Using large databases including the FDA's adverse event reporting system (FAERS), the European Union Drug Regulating Authorities Pharmacovigilance (EudraVigilance), the World Health Organizations global individual case safety reports database (VigiBase), and published case reports we are able to evaluate adverse effects of cancer therapeutics, including immune checkpoint inhibitors, in a real world population.
Cardiac biomarkers may represent a cost-effective approach for the risk-stratification, screening and monitoring of patients receiving immune checkpoint inhibitor treatment (ICI). Numerous non-cardiac biomarkers reflecting processes contributing to cardiac injury such as inflammation. Blood-based biomarkers of myocardial injury and inflammation have the potential to guide the treatment of ICI through pre-treatment risk stratification and early diagnosis of cardiovascular immune-related adverse events (irAEs).
This project utilizes samples from a biorepository for the Southwest Oncology Group (SWOG) clinical trials. Specimen will be measured for Hs-TnT, NT-proBNP, hs-CRP, and GDF-15 in serial samples collected from patients prior to and during ICI treatment. These samples will be assessed for patient variability according to treatment and measured levels may be associated with patient's determined adverse outcomes. The overall goal of this proposal is to assess the clinical utility of cardiac and inflammatory blood-based biomarker measurements in the management of patients receiving ICI treatment.