Immune Checkpoint Inhibitor Myocarditis: Concomitant Coronary Artery Disease and Heart Failure

https://openworks.mdanderson.org/sumexp21/1209/thumbnail.jp

Prospective Study Evaluating Management of Hypertension Induced by anti-VEGF Therapy in Patients with Active Cancer: VEGFHTN Trial

https://openworks.mdanderson.org/sumexp23/1027/thumbnail.jp

The Impact of Radiation Dose to Heart Substructures on Major Coronary Events and Patient Survival after Chemoradiation Therapy for Esophageal Cancer

Background: There is a paucity of data regarding the association between radiation exposure of heart substructures and the incidence of major coronary events (MCEs) in patients with esophageal cancer (ESOC) undergoing chemoradiation therapy. We studied radiation dosimetric determinants of MCE risk and measured their impact on patient prognosis using a cohort of ESOC patients treated at a single institution. Methods: Between March 2005 and October 2015, 355 ESOC patients treated with concurrent chemoradiotherapy were identified from a prospectively maintained and institutional-regulatory-board-approved clinical database. Dose-distribution parameters of the whole heart, the atria, the ventricles, the left main coronary artery, and three main coronary arteries were extracted for analysis. Results: Within a median follow-up time of 67 months, 14 patients experienced MCEs at a median of 16 months. The incidence of MCEs was significantly associated with the left anterior descending coronary artery (LAD) receiving ≥30 Gy (V30Gy) (p = 0.048). Patients receiving LAD V30Gy ≥ 10% of volume experienced a higher incidence of MCEs versus the LAD V30Gy p = 0.044). The relative rate of death increased with the left main coronary artery (LMA) mean dose (Gy) (p = 0.002). Furthermore, a mutual promotion effect of hyperlipidemia and RT on MCEs was observed. Conclusion: Radiation dose to coronary substructures is associated with MCEs and overall survival in patients with ESOC. In this study, the doses to these substructures appeared to be better predictors of toxicity outcomes than mean heart dose (MHD) or whole-heart V30Gy. These findings have implications for reducing coronary events through radiation therapy planning

Inflammatory Myositis in Cancer Patients Receiving Immune Checkpoint Inhibitors

Objective To estimate the incidence of immune checkpoint inhibitor-related myositis (ICI-myositis) in cancer patients receiving ICIs, and to report associated clinical manifestations, patterns of care, and outcomes. Methods We identified a retrospective cohort of patients receiving ICIs between 2016 and 2019 seen at the University of Texas MD Anderson Cancer Center. Cases of ICI-myositis were identified using International Classification of Disease codes and confirmed by reviewing medical records and pathology, as available. Results A total of 9,088 patients received an ICI. Thirty-six patients (0.40%) were identified as having ICI-myositis: 17 patients (47%) with ICI-myositis alone and 19 (53%) with overlap manifestations (5 patients with myocarditis, 5 with myasthenia gravis, and 9 with both). The incidence of ICI-myositis was 0.31% in those receiving ICI monotherapy and 0.94% in those receiving combination ICI therapy (relative risk 3.1 [95% confidence interval 1.5-6.1]). Twenty-five patients (69%) received >= 1 treatment in addition to glucocorticoids: plasmapheresis in 17 patients (47%), intravenous immunoglobulin in 12 (33%), and biologics in 11 (31%). Patients with overlap conditions had worse outcomes than those with myositis alone, and 79% of them developed respiratory failure. Eight patients died as a result of ICI-myositis, and all had overlap syndrome with myasthenia gravis or myocarditis (P < 0.05); 75% of these patients had a concomitant infection. Conclusion ICI-myositis is a rare but severe adverse event. More than half of the patients presented with overlap manifestations and had deleterious outcomes, including respiratory failure and death. None of the patients with ICI-myositis alone died as a result of adverse events. Optimal treatment strategies have yet to be determined

Cardiotoxicity of FDA-approved immune checkpoint inhibitors: A rare but serious adverse event

Refractory cancer represents a challenge for oncologists in providing treatment options without excessive toxicity and has led to the investigation of immune mechanisms. Immune checkpoint inhibitors (ICIs) directly interfere with the tumor cells' ability to evade the innate and adaptive immune system by targeting specific proteins such as cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), programmed cell death protein-1 (PD-1), and programmed cell death protein-ligand 1 (PD-L1), which are involved as negative regulators of T-cell function. Their growing success has led to the investigation for frontline treatment in several types of cancers. Even though these ICIs have demonstrated efficacy in the treatment of a variety of cancers, their use has been associated with the development of rare but severe adverse events. These events are the result of targeting specific checkpoint proteins on normal cells of the body as well as secondary downstream off-target effects on normal tissue. Similar to combined conventional cancer treatment, treating with combined ICIs are also associated with a higher risk of adverse events. Although cardiotoxicities related to immunotherapy are reportedly rare, they can be severe and associated with life-threatening conditions such as fulminant heart failure, hemodynamic instability, and cardiac arrest. Oncologists must carefully weigh the risk versus the therapeutic benefit of these agents in determining the best option for improving overall survival and minimizing morbidity and mortality of their patients. Our review focuses on the approved ICIs, their mechanism of action, their oncologic efficacy, and the associated potential for cardiovascular toxicity