Metabolic Diversity in Human Non-Small Cell Lung Cancer Cells.

Intermediary metabolism in cancer cells is regulated by diverse cell-autonomous processes, including signal transduction and gene expression patterns, arising from specific oncogenotypes and cell lineages. Although it is well established that metabolic reprogramming is a hallmark of cancer, we lack a full view of the diversity of metabolic programs in cancer cells and an unbiased assessment of the associations between metabolic pathway preferences and other cell-autonomous processes. Here, we quantified metabolic features, mostly from the 13C enrichment of molecules from central carbon metabolism, in over 80 non-small cell lung cancer (NSCLC) cell lines cultured under identical conditions. Because these cell lines were extensively annotated for oncogenotype, gene expression, protein expression, and therapeutic sensitivity, the resulting database enables the user to uncover new relationships between metabolism and these orthogonal processes.

Pharmacokinetic study of erlotinib in a pregnant woman with advanced non-small cell lung cancer and observation of the effects on the child growth.

AIMS: The aim of the study is to report the clinical and pharmacological observations from a pregnant patient treated with erlotinib in the second and third trimesters of pregnancy. METHODS: Maternal and neonatal blood levels and safety of erlotinib and its metabolites were evaluated. Child development was monitored for 6 years. RESULTS: A 31-year-old woman with stage IV lung adenocarcinoma with EGFR exon19 deletion began treatment with erlotinib 150 mg/day at 17 weeks of gestation. Although foetal growth retardation and oligohydramnios were observed at several times during the pregnancy, treatment was continued due to the severity of the maternal presentation, with ongoing foetal monitoring. The foetus seemed to tolerate and recover well without specific interventions. A healthy baby boy was delivered at 37 weeks gestation. The child grew and developed without any obvious issues. At last follow-up, at age 6 years, he was attending school at a grade appropriate for his age without health or developmental problems. Blood levels of erlotinib were 397-856 ng/mL at 18-37 weeks of gestation and 1190 ng/mL at 8 weeks postpartum. The blood concentration ratios of OSI-413-to-erlotinib ranged from 0.167 to 0.253 at 18-37 weeks of gestation, excluding 24 weeks, and 0.131 at 8 weeks postpartum. The maternal-to-foetal transfer rate of erlotinib, OSI-420 and OSI-413 were 24.5, 34.8 and 20.3%, respectively. CONCLUSION: Erlotinib use during the second and third trimester of pregnancy did not seem to cause any untoward effects on the developing foetus, or any long-lasting effects that could be detected during 6 years of follow-up of the child.

Early Detection and Prediction of Anthracycline-Induced Cardiotoxicity　- A Prospective Cohort Study.

BACKGROUND: In the present study, we aimed to investigate whether early cardiac biomarker alterations and echocardiographic parameters, including left atrial (LA) strain, can predict anthracycline-induced cardiotoxicity (AIC) and thus develop a predictive risk score.Methods and Results: The AIC registry is a prospective, observational cohort study designed to gather serial echocardiographic and biomarker data before and after anthracycline chemotherapy. Cardiotoxicity was defined as a reduction in left ventricular ejection fraction (LVEF) ≥10 percentage points from baseline and <55%. In total, 383 patients (93% women; median age, 57 [46-66] years) completed the 2-year follow-up; 42 (11.0%) patients developed cardiotoxicity (median time to onset, 292 [175-440] days). Increases in cardiac troponin T (TnT) and B-type natriuretic peptide (BNP) and relative reductions in the left ventricular global longitudinal strain (LV GLS) and LA reservoir strain [LASr] at 3 months after anthracycline administration were independently associated with subsequent cardiotoxicity. A risk score containing 2 clinical variables (smoking and prior cardiovascular disease), 2 cardiac biomarkers at 3 months (TnT ≥0.019 ng/mL and BNP ≥31.1 pg/mL), 2 echocardiographic variables at 3 months (relative declines in LV GLS [≥6.5%], and LASr [≥7.5%]) was generated. CONCLUSIONS: Early decline in LASr was independently associated with subsequent cardiotoxicity. The AIC risk score may provide useful prognostication in patients receiving anthracyclines.

Impact of Hepatitis B Surface and Core Antibody Levels on Hepatitis B Virus Reactivation.

Hepatitis B virus reactivation (HBV-R) is a serious complication that can occur in patients with resolved HBV infection during cancer chemotherapy. We examined the levels of HBV surface antibody (HBsAb) and HBV core antibody (HBcAb) to assess the incidence of HBV-R in cancer patients including hematopoietic stem cell transplantation (HSCT) and rituximab administration. This retrospective cohort study included 590 patients with resolved HBV infection. The incidence of HBV-R was evaluated 761.5 (range, 90-3898) days after the inititiation of chemotherapy. Of the patients, 13 (2.2%) developed HBV-R after the start of chemotherapy. All 13 patients exhibited lower HBsAb (<100 mIU/mL) levels at baseline. A higher level of HBcAb (≥100 cut off index (C.O.I.)) was a possible risk factor for HBV-R as well as HSCT and rituximab administration. The simultaneous presence of HBsAb <100 mIU/mL and HBcAb ≥100 C.O.I. increased the risk of HBV-R by 18.5%. Patients treated with rituximab were at a higher risk of HBV-R (18.4%) despite having HBcAb <100 C.O.I. Our results suggest that assessment of HBsAb and HBcAb levels prior to the chemotherapy is important for identifying patients at high risk of HBV-R, especially in solid cancers without HSCT and rituximab administration.

Clonal heamatopoiesis and associated cardiovascular diseases.

Cancer and cardiovascular disease share several risk factors. Clonal heamatopoiesis, a novel risk factor associated with both diseases, has received increasing attention in the fields of cardiology, heamatology and oncology. Clonal heamatopoiesis of indeterminate potential refers to the presence of at least one driver mutation in the heamatopoietic cells of peripheral blood without heamatological malignancy. Clonal heamatopoiesis of indeterminate potential is a common age-related condition that affects up to 60% of individuals aged > 80 years. Importantly, clonal heamatopoiesis of indeterminate potential carriers have a 2- to 4-fold higher risk of developing cardiovascular disease than non-carriers. Therefore, we performed an up-to-date review of clonal heamatopoiesis and its association with various forms of cardiovascular disease, including atherosclerotic disease, heart failure, aortic stenosis and pulmonary hypertension. In addition, we reviewed experimental studies that examined the causality and directionality between clonal heamatopoiesis and cardiovascular disease. Lastly, we discussed future research directions that will aid in the design of personalized therapies and preventive strategies for individuals with clonal heamatopoiesis. This review showed that clonal heamatopoiesis of indeterminate potential is a common condition, especially in older patients, and is associated with an increased risk of cardiovascular disease and worse prognosis. However, further research is needed to determine whether anti-inflammatory therapies or therapies that can reduce or eliminate clone size are effective in preventing cardiovascular disease in patients with clonal heamatopoiesis of indeterminate potential.

Japanese Society of Medical Oncology/Japan Society of Clinical Oncology/Japanese Society of Pediatric Hematology/Oncology-led clinical recommendations on the diagnosis and use of immunotherapy in patients with DNA mismatch repair deficient (dMMR) tumors, third edition.

BACKGROUND: Clinical trials have reported the efficacy of immune checkpoint inhibitors in the treatment of mismatch repair-deficient (dMMR) advanced solid tumors. The accumulated evidence of tumor agnostic agent has been made since PD-1 inhibitor was approved and used in clinical practice. Therefore, we have revised the guideline "Japan Society of Clinical Oncology provisional clinical opinion for the diagnosis and use of immunotherapy in patients with deficient DNA mismatch repair tumors, cooperated by Japanese Society of Medical Oncology, First Edition". METHODS: Clinical questions regarding medical care were formulated for patients with dMMR advanced solid tumors. Relevant publications were searched by PubMed and Cochrane Database. Critical publications and conference reports were added manually. Systematic reviews were performed for each clinical question for the purpose of developing clinical recommendations. The committee members identified by Japan Society of Clinical Oncology (JSCO), Japanese Society of Medical Oncology (JSMO), and Japanese society of pediatric hematology/oncology (JSPHO) voted to determine the level of each recommendation considering the strength of evidence, expected risks and benefits to patients, and other related factors. Thereafter, a peer review by experts nominated from JSCO, JSMO, and JSPHO and the public comments among all societies' members were done. RESULTS: The current guideline describes two clinical questions and eight recommendations for whom, when, and how MMR status should be tested. CONCLUSION: In this guideline, the committee proposed eight recommendations for performing MMR testing properly to select patients who are likely to benefit from immunotherapy.

Japanese Society of Medical Oncology/Japan Society of Clinical Oncology/Japanese Society of Pediatric Hematology/Oncology-led clinical recommendations on the diagnosis and use of immunotherapy in patients with high tumor mutational burden tumors.

The development of novel antitumor agents and accompanying biomarkers has improved survival across several tumor types. Previously, we developed recommendations for tumor-agnostic treatments in patients with solid tumors with DNA mismatch repair deficient or neurotrophic receptor tyrosine kinase fusions. Recently, immune checkpoint inhibitors have shown efficacy in patient with tumor mutation burden-high (TMB-H) solid tumors and have been established as a third tumor-agnostic agent, making it necessary to develop the guideline prioritized for these patients. Clinical questions regarding medical care were formulated for patients with TMB-H advanced solid tumors. Relevant publications were searched by PubMed and Cochrane Database. Critical publications and conference reports were added manually. Systematic reviews were performed for each clinical question for the purpose of developing clinical recommendations. The committee members identified by Japan Society of Clinical Oncology (JSCO), Japanese Society of Medical Oncology (JSMO), and Japanese society of pediatric hematology/oncology (JSPHO) voted to determine the level of each recommendation considering the strength of evidence, expected risks and benefits to patients, and other related factors. Thereafter, a peer review by experts nominated from JSCO, JSMO, and JSPHO, and the public comments among all societies' members was done. The current guideline describes three clinical questions and seven recommendations for whom, when, and how TMB should be tested, and what is recommended for patients with TMB-H advanced solid tumors. In this guideline, the committee proposed seven recommendations for performing TMB testing properly to select patients who are likely to benefit from immunotherapy.

Japanese Society of Medical Oncology/Japan Society of Clinical Oncology/Japanese Society of Pediatric Hematology/Oncology-led clinical recommendations on the diagnosis and use of tropomyosin receptor kinase inhibitors in adult and pediatric patients with neurotrophic receptor tyrosine kinase fusion-positive advanced solid tumors.

BACKGROUND: Clinical trials have reported the efficacy of tropomyosin receptor kinase (TRK) inhibitors against neurotrophic receptor tyrosine kinase (NTRK) fusion gene-positive advanced solid tumors. The accumulated evidence of tumor-agnostic agent has made since TRK inhibitors were approved and used in clinical practice. Therefore, we have revised the 'Japan Society of Clinical Oncology (JSCO)/Japanese Society of Medical Oncology (JSMO)-led clinical recommendations on the diagnosis and use of tropomyosin receptor kinase inhibitors in adult and pediatric patients with neurotrophic receptor tyrosine kinase fusion-positive advanced solid tumors, cooperated by the Japanese Society of Pediatric Hematology/Oncology (JSPHO)'. METHODS: Clinical questions regarding medical care were formulated for patients with NTRK fusion-positive advanced solid tumors. Relevant publications were searched by PubMed and Cochrane Database. Critical publications and conference reports were added manually. Systematic reviews were performed for each clinical question for the purpose of developing clinical recommendations. The committee members identified by JSCO, JSMO, and JSPHO voted to determine the level of each recommendation considering the strength of evidence, expected risks and benefits to patients, and other related factors. Thereafter, a peer review by experts nominated from JSCO, JSMO, and JSPHO, and the public comments among all societies' members was done. RESULTS: The current guideline describes 3 clinical questions and 14 recommendations for whom, when, and how NTRK fusion should be tested, and what is recommended for patients with NTRK fusion-positive advanced solid tumors. CONCLUSION: The committee proposed 14 recommendations for performing NTRK testing properly to select patients who are likely to benefit from TRK inhibitors.

[Pharmacologic Therapy for Bone Metastases-Current Strategies and Future Directions].

Bisphosphonates were introduced in the late 1990s to reduce the frequency of skeletal-related events(SREs)in patients with metastatic bone disease. In the 2010s, anti-RANKL antibodies were launched as another type of bone modifying agents(BMA). Both induce osteoclast apoptosis and have been used in Japan for solid tumors with bone metastases and multiple myeloma. In addition to osteoclasts, bone microenvironment includes a wide variety of cells such as osteoblasts, vascular endothelial cells, and immune cells, which spatiotemporally interact with cancer cells, resulting in the colonization of dissociated tumor cells(DTCs). Understanding the pathways and microenvironmental factors through which cancer evolves to promote bone colony formation will lead to better planning of the therapeutic strategies in individual cases and to further elucidation of molecular drivers.

Characteristics of Cancers in Adolescents and Young Adults Compared with Those in Adults in Their 60s: A Single-Center Experience.

INTRODUCTION: Cancer is one of the main causes of death among adolescents and young adults (AYAs) aged 15-39 years. The improvement in overall 5-year survival in AYA cancer patients was far below than that of adult cancer patients. The purpose of this study was to clarify the features of cancer in AYAs by comparing them with those of controls. METHODS: Patients in the cancer registry of the University of Tsukuba Hospital between 2007 and 2017 (median age, 65 years) were included in this study. We used patients between the ages of 64 and 66 years as controls. We then obtained the age at diagnosis, sex, primary site, and pathological type. RESULTS: Among 27,281 cancer patients in the registry between 2007 and 2017, 1,947 (7.1%) patients were categorized into the AYA group, and 2,354 into the control group. Among men in the AYA group, central nervous system (CNS) tumors accounted for 22.7% of all cancers, followed by germ cell tumors, 22.5%, and hematopoietic malignancies, 12.5%. Among women in the AYA group, cervical cancer accounted for 35.9% of all cancers, followed by breast cancer, 14.6%, and CNS tumors, 11.6%. The proportion of specific cancer types relative to all cancers in the CNS, thyroid, adrenal glands, germ cells, cervix uteri, hematopoietic tissues, and sarcomas was higher in the AYA group than that in the control group. CONCLUSION: The present results for AYAs were in sharp contrast to those for adult cancers and may be related to different modes of pathogenesis in AYAs. The identification of high-risk groups of these tumors in the AYA generation is crucial for prevention and early detection and will be a major topic for future research. While most of adult cancers are treated independently by each medical department, AYA cancers need to be treated in collaboration with experts from several departments. It is desirable to address the issues involved in applying treatments established for adult cancers to AYA cancers on a cancer-by-cancer basis.

Efficacy of platinum agents for stage III non-small-cell lung cancer following platinum-based chemoradiotherapy: a retrospective study.

BACKGROUND: Platinum-based chemoradiotherapy is the standard treatment for unresectable stage III non-small-cell lung cancer (NSCLC). However, few studies have evaluated the efficacy of subsequent chemotherapy for relapsed NSCLC following platinum-based chemoradiotherapy. This study aimed to evaluate the efficacy of platinum-doublet chemotherapy as a second-line treatment for patients with unresectable stage III NSCLC. METHODS: We retrospectively evaluated patients with unresectable stage III NSCLC treated with cytotoxic chemotherapy following platinum-based chemoradiotherapy who were registered in a nationwide registry NSCLC database. Patients were divided into the platinum-doublet chemotherapy (platinum) group and single-agent chemotherapy (non-platinum) group based on the type of second-line chemotherapy. RESULTS: The platinum group (n = 119) showed significantly better overall survival (OS) than the non-platinum group (n = 201) (median OS: 21.5 vs. 10.5 months, hazard ratio [HR]: 0.54, 95% confidence interval [CI]: 0.40-0.73, p < 0.001). OS from the beginning of chemoradiotherapy was also significantly better in the platinum group than in the non-platinum group (median OS: 34.9 vs. 21.8 months, HR: 0.58, 95% CI: 0.43-0.79, p = 0.001). In the multivariate analysis, platinum-doublet chemotherapy as second-line therapy, female sex, clinical stage IIIA, and duration of ≥ 8.6 months from the beginning of first-line therapy to the beginning of second-line therapy were associated with significantly better OS. CONCLUSION: Platinum-doublet chemotherapy as a second-line therapy may prolong survival in unresectable stage III NSCLC patients following platinum-based chemoradiotherapy. Thus, re-administration of platinum agents may be a promising treatment for unresectable stage III NSCLC treated with platinum-based chemoradiotherapy.

Atherosclerotic cardiovascular events associated with immune checkpoint inhibitors in cancer patients.

Immune checkpoint inhibitors have demonstrated significant clinical benefits in many cancers, and the use of these drugs is rapidly expanding. Unfortunately, these agents can induce a wide range of immune-related adverse events through the activation of immune responses in non-target organs, including the cardiovascular system. Among cardiovascular immune-related adverse events, myocarditis is the most established and biologically plausible cardiac complication of immune checkpoint inhibitors therapy with immune-related pathophysiology. In contrast, atherosclerotic cardiovascular diseases, such as myocardial infarction and ischemic stroke, were not previously recognized as a part of the immune-related adverse event spectrum. However, there is now increasing preclinical and clinical evidence that suggests a possible correlation between immune checkpoint inhibitors therapy and atherosclerotic cardiovascular events, and cardiovascular disease is increasingly recognized as a toxicity of ICIs. Results from animal studies suggest that the blockade of the cytotoxic T-lymphocyte antigen 4 or programmed cell death protein 1 pathway plays a relevant role in promoting the progression of atherosclerotic lesions. Several clinical studies have reported an increased incidence of atherosclerotic vascular events after immune checkpoint inhibitor administration. Our findings suggest that clinicians should (i) recognize that immune checkpoint inhibitors can exacerbate atherosclerosis, (ii) consider the management of cardiovascular risk factors and (iii) perform periodic screening in patients receiving immune checkpoint inhibitors.

[Maturation and Development of the"All Japan E-Learning Cloud of the Training Program for Oncology Professionals].

This paper reports the 5-year operational status of the third phase of the"All Japan E-Learning Cloud of the Training Program for Oncology Professionals"by tabulating the viewing trends of available lecture contents. In this phase, the goal was to train cancer genome medical professionals in this new, advanced medical technology field as well as train personnel to treat rarely encountered pediatric, adolescent/young adult, and other life stage cancers. Additionally, new lecture items have been added to the e-learning cloud in collaboration with 7 oncology specialist centers, contributing to the development of human capital in cancer care(including graduate student education)and faculty development for local medical professionals.

A Japanese lung cancer registry study on demographics and treatment modalities in medically treated patients.

This study provides the benchmark statistics on medically treated patients with non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) in Japan. Demographic background, treatment, and prognosis were obtained from patients with lung cancer pathologically diagnosed in 2012, who received nonsurgical treatment. Descriptive statistics and their associations with survival were analyzed. In total, 12 320 patients were registered from 314 institutions in Japan. The median age was 70 years, and 73% of the patients were male. The number (%) of stages I, II, III, and IV diseases were 468 (3.8%), 421 (3.4%), 3260 (26.5%), and 8171 (66.3%), respectively. NSCLC and SCLC accounted for 9872 (80.1%) and 2353 (19.1%) patients, respectively. Thoracic radiotherapy-based therapy, chemotherapy, and palliative care alone were administered to 2572 (20.9%), 7790 (63.2%), and 1952 (15.8%) patients, respectively. Clinical TNM stage was one of the strongest prognostic factors with the 3-year survival rates of 62.9%, 47.3%, 40.0%, 27.8%, 37.5%, 26.5%, and 18.2% for stages IA, IB, IIA, IIB, IIIA, IIIB, and IV, respectively. Among 6158 patients with NSCLC treated with chemotherapy, the 3-year survival rate was 33.4% in patients receiving epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) at some point in their clinical course, whereas it was 17.4% in patients who did not. The 3-year survival rate of SCLC was only 15.9%. In conclusion, approximately two-thirds of the patients were diagnosed as stage IV at the initial diagnosis. Use of EGFR-TKIs significantly improved the survival of patients with NSCLC.

High-Performance Liquid Chromatography for Therapeutic Drug Monitoring of Serum Lenvatinib.

BACKGROUND: Therapeutic drug monitoring (TDM) and dose adjustment of lenvatinib may be beneficial in the treatment of radioiodine-refractory thyroid cancer, by maximizing antitumor effects and minimizing adverse drug reactions. The aim of this study was, therefore, to develop and validate a high-performance liquid chromatography method using an ultraviolet detection system for routine serum lenvatinib detection in patients with thyroid cancer. METHODS: Serum specimens, spiked with an internal standard, were treated by a solid-phase extraction through an octadecylsilyl silica cartridge. Lenvatinib and internal standard were concomitantly separated from serum using a conventional octadecylsilyl silica column through isocratic elution, using a mobile phase consisting of 0.02 mol/L sodium phosphate (pH 6.7) and acetonitrile (50/50, vol/vol) at a flow rate of 1.0 mL/min. The detection wavelength was set at 244 nm. Serum samples from 5 patients were used for clinical validation of the method. RESULTS: The calibration curve for lenvatinib was linear (Pearson correlation coefficient, r = 0.9998) over the concentration range of 6.25-400 ng/mL, with a lower limit of quantification of 6.25 ng/mL. Extraction recoveries for lenvatinib were 97% or more, with coefficients of variation less than 2.2%. The coefficients of variation for intraday and interday assays were less than 4.7% and 6.0%, respectively. CONCLUSIONS: This sensitive high-performance liquid chromatography method can be used for lenvatinib therapeutic drug monitoring when liquid chromatography-tandem mass spectrometry facilities are unavailable.

Cardiology consultation in oncology practice: a 5-year survey.

OBJECTIVE: Onco-cardiology services are expanding rapidly in Japan. To provide a better service, it is important to consider the needs of oncologists. However, little is known regarding specific needs for which oncologists should consult cardiologists to manage cardiovascular problems of their patients. We analysed cardiology consultations sought by oncologists to evaluate the role of cardiologists in cancer treatment. METHOD: We retrospectively investigated consecutive 2064 cardiology consultations of cancer patients in the University of Tsukuba Hospital, Tsukuba, Japan, between January 2014 and December 2018. RESULTS: The most common timing of cardiology consultation was before the commencement of cancer treatment (n = 1355; 65.7%), followed by after the commencement of cancer treatment (n = 686; 33.2%). Among the 361 consultations before the administration of anticancer drugs, 235 (65.1%) were for anthracycline-based regimens. There were 506 (24.5%) consultations for the management of cardiovascular emergencies developing after the commencement of cancer treatment; venous thromboembolism was the most frequent (n = 125; 24.7%), followed by atrial fibrillation (n = 110; 21.7%) and heart failure (n = 74; 14.6%). There were marked differences in the types of cardiovascular emergencies depending on the type of cancer. CONCLUSIONS: This survey revealed the various cardiovascular problems for which oncologists sought interventions by cardiologists. A multidisciplinary approach in an onco-cardiology service is essential to achieve optimal long-term outcomes.

[Cardiac Tamponade as Cardio-Oncologic Emergency Disease].

The causes of cardiac tamponade include neoplastic pericarditis as well as radiation-induced, drug-induced, purulent and iatrogenic pericarditis. Since we can get access to the advanced cancer therapy these days, some of the cardiac tamponade patients can survive longer if we can manage their pericardial effusion well. Here, we will summarize the clinical evidence in cardiac tamponade in patients with malignant tumor, and will discuss about its presentation, diagnosis and management.

Immune checkpoint inhibitor-related myocarditis.

Immune checkpoint inhibitors have demonstrated significant clinical benefit in many cancers. The clinical benefit afforded by these treatments can be accompanied by a unique and distinct spectrum of adverse events. Recently, several fatal cases of immune checkpoint inhibitor-related myocarditis were reported. Although its frequency is comparatively lower than that of other immune-related adverse events, myocarditis can lead to circulatory collapse and lethal ventricular arrhythmia. Immune checkpoints, cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1), play important roles in establishing peripheral tolerance to the heart. Evidence from studies using genetically engineered mouse models suggests that CTLA-4 signaling terminates proliferation and promotes anergy during the primary response to cardiac self-peptide recognition. PD-1 signaling restrains autoreactive T cells that enter the peripheral tissues and recognize cardiac-peptide, maintaining them in an anergic state. Patients affected by immune checkpoint inhibitor-related myocarditis often experience rapid onset of profound hemodynamic compromise progressing to cardiogenic shock. Early diagnosis is mandatory to address specific therapy and correct the timing of circulatory support. However, the diagnosis of myocarditis is challenging due to the heterogeneity of clinical presentations. Owing to its early onset, nonspecific symptomatology and fulminant progression, especially when these drugs are used in combination, oncologists should be vigilant for immune checkpoint inhibitor-related myocarditis. With many questions yet to be answered, from basic immune biology to clinical management, future research should aim to optimize the use of these drugs by identifying predictive biomarkers of either a response to therapy or the risks of myocarditis development.