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

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

Cardiovascular Complications of ChimericAntigen Receptor T-Cell Therapy: The CytokineRelease Syndrome and Associated Arrhythmias

In recent years, cancer treatment has evolved, and new therapies have been introduced with significant improvement in prognosis. The immunotherapies stand out owing to their efficacy and remission rate. Chimeric antigen receptor (CAR) T-cell therapy is a part of this new era of therapies. Chimeric antigen receptor T-cell therapy is a form of adoptive cellular therapy that uses a genetically encoded CAR in modified human T cells to target specific tumor antigens in a nonconventional, non-major histocompatibility complex (MHC) protein presentation. Chimeric antigen receptor T-cell therapy successfully identifies tumor antigens and through activation of T cells destroys tumoral cells. It has been found to efficiently induce remission in patients who have been previously treated for B-cell malignancies and have persistent disease. As the use of this novel therapy increases, its potential side effects also have become more evident, including major complications like cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Cytokine release syndrome is a major systemic inflammatory process as a result of massive cytokine production by the proliferating and activated CAR T cells in which multiple interleukins and immune cells contribute to the inflammatory response. Cytokine release syndrome has been associated with cardiovascular life-threatening complications including hypotension, shock, tachycardia, arrhythmias, left ventricular dysfunction, heart failure, and cardiovascular death. Arrhythmias, among its major complications, vary from asymptomatic prolonged corrected QT interval (QTc) to supraventricular tachycardia, atrial fibrillation, flutter, and ventricular arrhythmias like Torsade de pointes. This article focuses on the cardiovascular complications and arrhythmias associated with CRS and CAR T-cell therapy