Catheter-related thrombosis (CRT) is a serious complication in cancer patients undergoing chemotherapy, yet existing risk prediction models demonstrate limited accuracy. This study aimed to evaluate the clinical utility of machine learning (ML) and Bayesian-learning models for CRT prediction in a large cohort of breast cancer patients undergoing catheterization. A total of 3337 breast cancer patients with central venous catheters (Cohort 1) were included to develop and test ML models. Given the suboptimal clinical feasibility of ML models, the Bayesian-learning model was constructed using odds ratio analysis and Gaussian distribution. The hazard ratio for the high-risk and low-risk groups was calculated using Cox proportional hazards regression analysis, and the model was validated in an independent cohort of 1274 patients (Cohort 2). In Cohort 1, 246 patients (7.37

Background: Antibody–drug conjugates (ADCs) combine the targeted nature of monoclonal antibodies with the potent efficacy of small-molecule cytotoxic drugs. However, they also carry unique safety risks, including lung toxicity. Objective: To conduct a systematic review and analysis of ADC-related interstitial lung disease (ILD) incidence, characteristics, and risk factors to optimize safe and effective clinical use. Design: ADC-related ILD reports from the FDA Adverse Event Reporting System (FAERS) database between January 2014 and March 2023 were analyzed. Methods: ADC-related ILD reports were retrieved from the FAERS database. Statistical analyses were conducted using reporting odds ratio (ROR) and information components (ICs). The lower limit of the 95% confidence interval (CI) was set for ROR (ROR025) >1 or IC (IC025) >0, and statistical significance was determined based on a minimum of three reports. Results: The study analyzed the statistical data on ADC-induced ILDs (1277 cases). Trastuzumab deruxtecan was reported to be the most frequent (38.4%). Among the 33 preferred terms (PTs) in standardized MedDRA queries (SMQ) = “Interstitial lung disease,” the three most common were as follows: ILD (40.6%), pneumonitis (27.9%), and acute respiratory distress syndrome (ARDS) (7.6%). Trastuzumab deruxtecan showed the strongest association with ILD (PT) and pneumonitis, whereas ARDS was associated with four different drugs. The median time to onset of ADC-related ILDs was 51 days (interquartile range (IQR), 16–196), with ARDS having the earliest median time to onset at 15 days (IQR, 6–52). The onsets of pneumonitis, ILD, lung infiltration, and pulmonary toxicity were similar. More than 26% of ADC-related ILD cases result in death, with ARDS having the highest mortality rate of 65.0%. Conclusion: ADCs are associated with an increased risk of pulmonary adverse events, such as ILDs, with significant differences between drugs and varying mortality rates for different adverse events, necessitating distinct monitoring and appropriate management.

BackgroundThe combination of anti-PD-1 antibody serplulimab and chemotherapy is considered standard first-line therapy for advanced esophageal squamous cell carcinoma (ESCC), but few later-line treatments are available. Here we evaluated the therapeutic efficacy of the recombinant, humanized anti-EGFR antibody HLX07 when used alone or together with serplulimab and chemotherapy against advanced ESCC.MethodsThis open-label, non-randomized, two-cohort, phase 2 trial involved patients 18-75 years old with histologically or cytologically confirmed locally advanced, unresectable, or metastatic ESCC, and an Eastern Cooperative Oncology Group performance status of 0-1. Patients who had failed first-line immuno-chemotherapy or at least two lines of other systemic therapy received HLX07 monotherapy intravenously at a dose of 1,000 mg once every 2 weeks (Q2W). Patients with no prior systemic therapy received HLX07 (1,000 mg, day 1) and serplulimab (200 mg, day 1) intravenously Q2W for up to 2 years, concurrently with cisplatin (50 mg/m2, day 1) for up to 8 cycles and 5-fluorouracil (1,200 mg/m2, days 1-2) for up to 12 cycles intravenously Q2W. The primary endpoints were progression-free survival (PFS) and objective response rate (ORR).ResultsOverall, 50 patients were enrolled. In the HLX07 monotherapy group, ORR was 15.0% (3/20), and the median PFS was 1.5 months (95% confidence interval [CI], 1.3 to 3.7). The median duration of response was not reached, and the rate of patients showing an objective response lasting at least 6 months was 66.7% (95% CI, 5.4 to 94.5). Two (10.0%, 2/20) patients experienced grade 3-4 treatment-related adverse events (TRAEs), including hypomagnesemia, hypocalcemia, and fatigue. No patient experienced grade 5 TRAEs. In the HLX07 combination group, the ORR was 60.0% (18/30), and the median PFS was 7.8 months (95% CI, 3.3 to 9.1). Fourteen (46.7%, 14/30) patients experienced grade 3-4 TRAEs, and one (3.3%, 1/30) patient died due to serplulimab-related pneumonitis.ConclusionsHLX07 monotherapy and its combination with serplulimab and chemotherapy showed manageable toxicity and promising antitumor activity in patients with recurrent or metastatic ESCC. Randomized controlled trials are warranted to further establish the safety and efficacy of HLX07 against ESCC.Trial registrationThis trial was registered at Clinicaltrials.gov (NCT05221658).

Background: Current clinical trial data on PARP inhibitors (PARPis)-related acute renal failure (ARF) are not entirely representative of real-world situations. Therefore, in this study, the US Food and Drug Administration Adverse Event Reporting System (FAERS) was used to evaluate PARPis-related ARF. Research design and methods: Data were obtained from 1 January 2015, to 30 September 2023. ARF event reports were analyzed based on four algorithms. The time-to-onset (TTO) and clinical outcomes of PARPis-associated ARF were assessed. Results: The total included cases were 2726. Significant signals were observed for olaparib, niraparib, and rucaparib (reporting odds ratio (ROR): 1.62, 95% confidence interval (CI): 1.49-1.78, 1.25, 95% CI: 1.19-1.32 and 1.59, 95% CI: 1.47-1.72 respectively). The median TTO of ARF onset was 57, 36, and 85 days for olaparib, niraparib, and rucaparib, respectively. The proportion of deaths with olaparib (9.88%) was significantly higher than for niraparib (2.52%) and rucaparib (2.94%) (p < 0.005). The proportion of life-threatening adverse events associated with niraparib (4.89%) was significantly higher than for rucaparib (0.98%) (p < 0.005). Conclusions: ARF and PARPi were related, with the exception of talazoparib. More emphasis should be given to PARPis-related ARF due to the high proportion of serious AEs and delayed adverse reactions.

Abstract Background Nervous system toxicity (NST) is one of the most frequent and dangerous side effects of chimeric antigen receptor T-cell (CAR-T) therapy, which is an effective treatment for related tumors in most relapsed/refractory (r/r) hematologic malignancies. Current clinical trial data do not fully reflect the real-world situation. Therefore, this study evaluated the NST of CAR-T therapy using the FDA Adverse Event Reporting System (FAERS). Methods Data were retrieved from FAERS for the period from January 1, 2017 to March 31, 2023. Disproportionality analysis and Bayesian analysis were used for data mining. The reporting odds ratio (ROR) for NST with 95% confidence interval (CI) was calculated for each CAR-T product. The time to onset (TTO) and clinical outcomes due to CAR-T therapy-associated NST were assessed. Results Overall, 6946 cases of NST associated with CAR-T therapy were identified. The patients had a median age of 61 years (interquartile range [IQR]: 47–69 years). Significant signals were observed for all CAR-T products (ROR: 2.19, 95% CI: 2.13–2.44). Anti-CD19 CAR-T products showed a higher NST signal than anti-B cell maturation antigen (BCMA) CAR-T products (ROR025 2.13 vs. 1.98). Brexucabtagene autoleucel (ROR: 3.17, 95% CI: 2.90–3.47) and axicabtagene ciloleucel (ROR: 2.92, 95% CI: 2.81–3.03) had the two highest NST signals. For the preferred term “brain edema,” the highest signals were obtained for CD28 CAR-T products. The median TTO of NST for all CAR-T products was 7 days (IQR: 3–17 days). The proportion of death, life-threatening and hospitalization adverse events associated with NST was 20.06%, 7.21%, and 32.70%, respectively. The proportion of death outcomes was higher in patients treated with tisagenlecleucel (30.36%) than in those treated with other CAR-T products, except ciltacabtagene autoleucel (P < 0.001). The proportion of hospitalizations was significantly higher for lisocabtagene maraleucel-associated NST (53.85%) than for other drugs, except for ciltacabtagene autoleucel (P < 0.001). Conclusions NST is more closely associated with anti-CD19 CAR-Ts and CAR-Ts containing CD28. Serious NST (brain oedema) is likely to occur with CAR-Ts that contain CD28. CAR-T-related NST warrants greater attention owing to the high proportion of serious adverse events and delayed NST.

Cancer patients face a heightened risk of venous thromboembolism (VTE), emerging as the second most prevalent cause of death within this population. Central venous catheterization (CVC), a routine procedure in cancer care, amplifies the VTE risk, leading to catheter-related thrombosis (CRT). Although traditional risk-assessment models and certain AI methods exist for VTE prediction, their capability and application in CRT risk prediciton for cancer patients remains limited. This paper addresses the shortcomings of current models (RAMs) by crafting a dedicated AI model to predict CRT risks for cancer patients. Leveraging a dataset encompassing 10,512 cancer patients undergoing catheterization over a decade, we meticulously select nine specific features for model construction, resulting in an impressive 0.794 AUROC in prediction, 54.9% higher than baseline. Furthermore, we estimate CRT-free probability using the Kaplan-Meier method. We also develop a WeChat Mini Program designed for efficient data collection and risk prediction, enhancing the efficiency of CRT risk detection for both doctors and patients.

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BACKGROUND:The 5-year survival rate of oesophageal squamous cell carcinoma (ESCC) is approximately 20%. The prognosis and drug response exhibit substantial heterogeneity in ESCC, impeding progress in survival outcomes. Our goal is to identify a signature for tumour subtype classification, enabling precise clinical treatments. METHODS:Utilising pre-treatment multi-omics data from an ESCC dataset (n = 310), an enhancer methylation-eRNA-target gene regulation network was constructed and validated by in vitro experiments. Four machine learning methods collectively identified core target genes, establishing an Enhancer Demethylation-Regulated Gene Score (EDRGS) model for classification. The molecular function of EDRGS subtyping was explored in scRNA-seq (n = 60) and bulk-seq (n = 310), and the EDRGS's potential to predict treatment response was assessed in datasets of various cancer types. FINDINGS:EDRGS stratified ESCCs into EDRGS-high/low subtypes, with EDRGS-high signifying a less favourable prognosis in ESCC and nine additional cancer types. EDRGS-high exhibited an immune-hot but immune-suppressive phenotype with elevated immune checkpoint expression, increased T cell infiltration, and IFNγ signalling in ESCC, suggesting a better response to immunotherapy. Notably, EDRGS outperformed PD-L1 in predicting anti-PD-1/L1 therapy effectiveness in ESCC (n = 42), kidney renal clear cell carcinoma (KIRC, n = 181), and bladder urothelial carcinoma (BLCA, n = 348) cohorts. EDRGS-low showed a cell cycle-activated phenotype with higher CDK4 and/or CDK6 expression, demonstrating a superior response to the CDK4/6 inhibitor palbociclib, validated in ESCC (n = 26), melanoma (n = 18), prostate cancer (n = 15) cells, and PDX models derived from patients with pancreatic cancer (n = 30). INTERPRETATION:Identification of EDRGS subtypes enlightens ESCC categorisation, offering clinical insights for patient management in immunotherapy (anti-PD-1/L1) and CDK4/6 inhibitor therapy across cancer types. FUNDING:This study was supported by funding from the National Key R&D Program of China (2021YFC2501000, 2020YFA0803300), the National Natural Science Foundation of China (82030089, 82188102), the CAMS Innovation Fund for Medical Sciences (2021-I2M-1-018, 2022-I2M-2-001, 2021-I2M-1-067), the Fundamental Research Funds for the Central Universities (3332021091).

BackgroundLymphoma patients have a considerable risk of developing catheter-related thrombosis (CRT), which may affect their expected treatment and quality of life. The high occurrence of CRT events is a major unmet challenge in the clinical management of lymphoma. In this study, we aim to develop a clinically based risk model to estimate the risk of CRT in lymphoma patients.MethodsAll lymphoma inpatients undergoing catheterization between June 2012 and December 2022 at the National Cancer Center were retrospectively enrolled. Data including potential clinical predictors were obtained from hospital records. The lymphoma-specific CRT risk prediction model was generated based on a multivariate Cox regression analysis to identify potential predictors associated with CRT. The performance of the CRT risk prediction model was evaluated for discrimination, calibration, and decision curve analysis.ResultsWe analyzed the data of 537 lymphoma patients who underwent CVC insertion and developed a nomogram to predict their risk of CRT. A total of 41 patients underwent CRT. The risk factors for CRT in this cohort were BMI≥24 kg/m2 (3.79 [95% CI, 1.54-9.34]), VTE history (4.10 [95% CI, 2.09-8.03]), B symptoms (11.29 [95% CI, 5.07-25.13]), Hb<100 g/L (3.93 [95% CI, 1.69-9.07]) and PICC insertion (1.79 [95% CI, 0.78-4.16]). The model presented reliable calibration and discrimination, with a concordance index of 0.877 and a well-fitted calibration curve, indicating its clinical usefulness. A cutoff value of 11.14 was determined to predict CRT via the risk model.ConclusionsThe lymphoma-specific CRT risk prediction model is based on lymphoma clinical features and provides a more appropriate prediction model for assessing the risk of CRT in lymphoma patients.

Background: With the rapid development of the field of cardio-oncology, it has been recognized as an important medical area to improve the healthcare quality of cancer patients with cardiac complications. In this study, we investigated the knowledge level of cardio-oncology of oncologists and cardiologists in China. Methods: A structured questionnaire survey was conducted during 30th September, 2018 to 3rd December, 2019. Questionnaires were given to oncologists and cardiologists randomly selected. A general linear model was used to explore the significant factors associated with the knowledge level. Results: In total, 973 responses were finally solicited and included in the analysis. Only 3 respondents reached the full marks. Results of knowledge level of cardio-oncology in China were not found satisfactory. The knowledge level was better in respondents with a cardiology background (P-value =0.001), worked in the higher-level hospital (P-value =0.01), from the east or west region of mainland China (P-value <0.001), at a high position of doctor (Chief doctor, P-value =0.009), with full awareness of cardio-oncology (P-value <0.001) and favorable attitude toward cardio-oncology development (P-value <0.001). Conclusions: Our survey suggested that the demands of cardio-oncology service in China was huge but the low level of knowledge on cardio-oncology was alarming. Strong supports are needed to improve the dedicated education of cardio-oncology in China

目的 探讨食管癌放疗患者经外周静脉穿刺的中心静脉导管(PICC)相关静脉血栓形成的危险因素.方法 收集298例接受PICC置管的食管癌放疗患者的临床资料,根据静脉血栓的发生情况分为血栓组(108例)及无血栓组(190例).采用多因素Logistic回归模型分析PICC相关静脉血栓形成的独立影响因素.结果 298例患者中,同步放化疗患者180例(60.4％),单纯放疗患者118例(39.6％).发生PICC相关静脉血栓108例(36.2％),其中症状血栓26例(8.7％),无症状血栓82例(27.5％).单因素分析结果显示,血栓组中具有高脂血症史、置管长度﹤45 cm、同步放化疗、血管超声检查次数≥3次的患者比例均高于无血栓组,差异均有统计学意义(P﹤0.05).多因素Logistic回归分析结果显示,同步放化疗是食管癌放疗患者PICC相关静脉血栓形成的独立危险因素(P﹤0.01).结论 同步放化疗可能增加食管癌患者PICC相关静脉血栓的发生风险,加强血管超声检查有利于PICC相关静脉血栓的监测及诊断,有助于及时进行抗栓治疗和疗效评价.

目的 本研究探讨低剂量聚乙二醇化重组人粒细胞刺激因子(pegylated recombinant human granulocyte colony stimulating,PEG-rhG-CSF)对于预防肺癌化疗导致的中性粒细胞减少症的有效性及安全性.方法 2021年11月至2023年5月中国医学科学院肿瘤医院综合科收治的肺癌化疗患者40例作为一级预防组,在每周期化疗结束24h给予低剂量PEG-rhG-CSF 3mg进行预防性治疗;同时选择同期的肺癌化疗后前一周期出现中性粒细胞减少患者40例作为二级预防组,在第2个周期化疗后24h给予低剂量PEG-rhG-CSF 3mg进行预防性治疗,观察化疗后未发生中性粒细胞减少、发热及应用抗菌药物的比例及安全性评价.结果 一级预防组患者治疗后31例(77.5%)未出现中性粒细胞减少,9例(22.5%)出现中性粒细胞减少,其中3～4级中性粒细胞减少2例(5.0%),1例合并抗生素治疗,1例因出现4级血小板减少导致化疗药物减量并化疗延迟.二级预防组治疗前1～2级中性粒细胞减少22例(55%),3～4级中性粒细胞减少18例(45%),1例出现中性粒细胞减少性发热(febrile neutropenia,FN)合并抗生素治疗,发生率2.5%,化疗延迟10例(25.0%).在给予3mg PEG-rhG-CSF治疗后,32例(80.0%)未出现中性粒细胞减少,8例(20.0%)出现中性粒细胞减少,其中3～4级中性粒细胞减少者3例(7.5%),无化疗药物减量者,化疗延迟1例(2.5%),无发热及使用抗菌药物.两组不良反应主要为骨痛(15.0%比 12.5%)及乏力(7.5%比10%).结论 低剂量聚乙二醇化粒细胞刺激因子能够预防肺癌化疗后中性粒细胞减少,且安全性良好.

BACKGROUND:DTL has been found to be related with multiple cancers. However, comprehensive analyses, which identify the prediction value of DTL in diagnosis, prognosis, immune infiltration and treatment, have rarely been reported so far.METHODS:Combined with the data online databases, the gene expression, gene mutation, function enrichment and the correlations with the immunity status and clinical indexes of DTL were analyzed. Expression of DTL and the degree of immune cell infiltration were examined by immunofluorescence (IF) and immunohistochemistry (IHC) and analyzed by statistical analysis. Furthermore, the influences of DTL on the cell cycle, cell proliferation and apoptosis were detected by live cell imaging, IF and flow cytometric (FC) analysis. Genomic stability assays were conducted by chromosome slide preparation.RESULTS:DTL was widely expressed in various cells and tissues, while it was overexpressed in tumor tissues except acute myeloid leukemia (LAML). Pan-cancer bioinformatics analysis showed that the expression of DTL was correlated with the prognosis, immunotherapy, and clinical indexes in various cancers. In addition, gene set enrichment analysis (GSEA) uncovered that DTL was enriched in oocyte meiosis, pyrimidine metabolism, the cell cycle, the G2M checkpoint, mTORC1 signaling and E2F targets. Furthermore, the overexpression of DTL, and its association with immune cell infiltration and clinical indexes in liver hepatocellular carcinoma (LIHC), bladder urothelial carcinoma (BLCA) and stomach adenocarcinoma (STAD) were verified in our study. It was also verified that overexpression of DTL could regulate the cell cycle, promote cell proliferation and cause genomic instability in cultured cells, which may be the reason why DTL plays a role in the occurrence, progression and treatment of cancer.CONCLUSIONS:Collectively, this study suggested that DTL is of clinical value in the diagnosis, prognosis and treatment of various cancers, and may be a potential biomarker in certain cancers.

BackgroundImmune checkpoint inhibitors (ICIs) combined with angiogenesis inhibitors (AGIs) have become increasingly available for multiple types of cancers, although the cardiovascular safety profiles of this combination therapy in real-world settings have not been elucidated to date. Therefore, we aimed to comprehensively investigate the cardiovascular toxicity profiles of ICIs combined with AGIs in comparison with ICIs alone. MethodsThe Food and Drug Administration Adverse Event Reporting System (FAERS) database from the 1(st) quarter of 2014 to the 1(st) quarter of 2022 was retrospectively queried to extract reports of cardiovascular adverse events (AEs) associated with ICIs alone, AGIs alone and combination therapy. To perform disproportionality analysis, the reporting odds ratios (RORs) and information components (ICs) were calculated with statistical shrinkage transformation formulas and a lower limit of the 95% confidence interval (CI) for ROR (ROR025) > 1 or IC (IC025) > 0 with at least 3 reports was considered statistically significant. ResultsA total of 18 854 cardiovascular AE cases/26 059 reports for ICIs alone, 47 168 cases/67 595 reports for AGIs alone, and 3 978 cases/5 263 reports for combination therapy were extracted. Compared to the entire database of patients without AGIs or ICIs, cardiovascular AEs were overreported in patients with combination therapy (IC025/ROR025 = 0.559/1.478), showing stronger signal strength than those taking ICIs alone (IC025/ROR025 = 0.118/1.086) or AGIs alone (IC025/ROR025 = 0.323/1.252). Importantly, compared with ICIs alone, combination therapy showed a decrease in signal strength for noninfectious myocarditis/pericarditis (IC025/ROR025 = 1.142/2.216 vs. IC025/ROR025 = 0.673/1.614), while an increase in signal value for embolic and thrombotic events (IC025/ROR025 = 0.147/1.111 vs. IC025/ROR025 = 0.591/1.519). For outcomes of cardiovascular AEs, the frequency of death and life-threatening AEs was lower for combination therapy than ICIs alone in noninfectious myocarditis/pericarditis (37.7% vs. 49.2%) as well as in embolic and thrombotic events (29.9% vs. 39.6%). Analysis among indications of cancer showed similar findings. ConclusionOverall, ICIs combined with AGIs showed a greater risk of cardiovascular AEs than ICIs alone, mainly due to an increase in embolic and thrombotic events while a decrease in noninfectious myocarditis/pericarditis. In addition, compared with ICIs alone, combination therapy presented a lower frequency of death and life-threatening in noninfectious myocarditis/pericarditis and embolic and thrombotic events.

近些年,随着乳腺癌患者的5年生存率不断提高,抗肿瘤治疗相关的心血管疾病已成为乳腺癌患者最常见的非肿瘤死亡因素.早期识别抗肿瘤治疗相关的心脏毒性对提高患者生存质量和改善预后有重要意义.本文就乳腺癌治疗相关的心血管不良事件研究现状作一简要回顾和评述,旨在加强肿瘤科医师和心血管科医师的共同关注与协同合作,让更多的肿瘤患者获益.

To the Editor: Cancer and cardiovascular (CV) disease are associated with the largest morbidity and mortality in the world, and they are related to each other through some common risk factors.[1] The incidence of cardiac toxicity during anticancer treatment will continue to increase as the survival time of cancer patients is prolonged, the population ages, the incidence of chronic underlying diseases related to CV diseases increases, and a large number of new drugs are introduced.[1] Cardio-oncology is a new interdisciplinary research field focusing on the screening, prevention, detection, monitoring, and treatment of CV toxicity related to anticancer treatment, and the development of rational management strategies for cancer patients is within its research scope.[1] The incidence of CV injury induced by anticancer therapy varies widely and depends on the type of drug used, its duration of use, and underlying patient comorbidities.[2] Many kinds of CV drugs can cause one or more forms of cardiac toxicity, including most chemotherapy drugs, a large number of new targeted therapeutic drugs, immune checkpoint inhibitors (ICIs), and radiation.[1,3,4] Chemotherapeutic agents, represented by anthracyclines, mostly cause type I cardiotoxicity, and their pathophysiology is related to cell loss, which is irreversible. Most targeted drugs, represented by trastuzumab, cause type II cardiotoxicity, the pathophysiology of which is cellular dysfunction (mitochondrial and protein alterations). The manifestations of CV damage caused by chemotherapy or targeted therapy drugs include congestive heart failure (HF), cardiomyopathy, arrhythmia, QT interval prolongation, thrombosis, hypertension, etc. ICI-related cardiotoxicity is caused by non-specific activation of the immune system, and the symptoms vary slightly, with myocarditis being the most common symptom. Although the incidence is not high (approximately 0.09% for a single drug and 0.3% for a combined drug), the mortality rate is very high (approximately 50%),[5] and toxicity is followed by various arrhythmias, myocardial pericarditis, cardiomyopathy, acute coronary syndrome, and sudden cardiac death. Radiation exposure has potentially profound effects on vascular structures, valves, the pericardium/myocardium, the conduction system, and the autonomic nervous system, and symptoms are dominated by the clinical manifestations of these lesions.[1,6] However, although CV events among cancer patients are diverse, the long-term clinical consequences mainly include left ventricular dysfunction and HF.[3] At present, the most commonly used definition of chemotherapy-induced cardiotoxicity is a left ventricular ejection fractions (LVEF) decrease greater than 10% compared with the LVEF at baseline, and an absolute value below 50% or 53% (various among different guidelines).[3,6] In general, the initial stage of cardiotoxicity is more insidious and may be characterized by only subclinical symptoms or some very subtle signs, such as a decreased exercise ability and resting tachycardia.[6] However, cardiac function is often damaged continuously with treatment progression until symptomatic cardiac insufficiency occurs after a certain trigger.[2] The schematic diagram of disease progression for cardiotoxicity was shown in Supplementary Figure 1, https://links.lww.com/CM9/B28. Even if the symptoms are relieved after treatment, the LVEF cannot recover before the onset of toxicity, resulting in irreparable long-term heart damage.[2] Careful baseline assessment of patients' health status and CV risk factors is always the first step before any anticancer therapy.[3,4,7] For chemotherapy-associated cardiotoxicity, considering the many types of chemotherapy drugs and different mechanisms, the risk factors generally include the following: prior anthracycline-based treatment; combined treatment with trastuzumab and anthracycline or chest radiotherapy; elderly or very young age (>75 or <10 years old); hypertension or diabetes mellitus; smoking exposure; elevated cardiac biomarkers at baseline; and baseline abnormal systolic LV function with a LVEF <0.50.[2] If the most representative anthracycline is taken as an example, the 2016 European Society of Cardiology (ESC) guideline[3] and 2017 American Society of Clinical Oncology guideline[7] provide different recommendations. The risk factors were noted in the two guidelines as follows: (1) Female sex; (2) Young or elderly age; (3) Treatment factors, including high-dose anthracycline (doxorubicin >250 mg/m2 or epirubicin >600 mg/m2), lower dose anthracycline in combination with lower dose radiotherapy when the heart is in the treatment field, treatment with lower dose anthracycline followed by trastuzumab, concomitant chemotherapy with alkylating or antimicrotubule agents, and concomitant chemotherapy with immuno- and targeted therapies; (4) High-dose radiotherapy (>30 Gy) when the heart is in the treatment field; (5) Renal failure; (6) The presence of any of the following CV risk factors (>two risk factors): smoking, hypertension, diabetes, dyslipidemia, and obesity; (7) A compromised borderline LVEF at baseline, a history of myocardial infarction, >moderate valvular heart disease at any time during treatment; and (8) Genetic factors. Among targeted drugs, trastuzumab is the most representative drug with CV toxicity, and its risk factors include elderly age, previous exposure to anthracyclines, a short time between anthracycline and anti-HER2 treatment, preexisting arterial hypertension, a low LVEF, elevated baseline troponin, a previous radiotherapy history, a history of arterial hypertension, a low LVEF and obesity.[3] The risk factors for radiation-associated cardiotoxicity include a dose >30 to 35 Gy; a dose per fraction >2 Gy; a large volume of irradiated heart; younger age; concurrent radiation therapy and chemotherapy/endocrine therapy/trastuzumab; and the presence of other CV risk factors (hypertension, diabetes mellitus, dyslipidemia, smoking, etc).[6] The risk factors for ICI-related cardiotoxicity are not clear. The definite risk factors include previous CV diseases and the combined use of immunotherapeutic drugs.[5] Any anticancer therapy that impacts cardiac safety requires timely and adequate monitoring for the detection and identification of cardiotoxicity.[1,2] Oncologists should comprehensively evaluate CV risk factors before any treatment with potential CV toxicity; at least electrocardiogram (ECG), echocardiography, myocardial marker, and blood lipid spectrum results should be reviewed.[1,3,4,7] For immunotherapy patients, no authoritative guidelines are available for assessment items in baseline examinations, but in addition to the above examination items, total creatine kinase, C-reactive protein, virus titers, and cardiac magnetic resonance (MR) examination are also recommended items for patients who develop new CV symptoms[4,5] However, at present, no consistent detection frequency recommendation is available, and most existing monitoring programs are based on the methodology of clinical trials and expert opinions. For patients under treatment, continuous CV risk assessments including ultrasonic cardiogram (UCG) (LVEF and global longitudinal strain [GLS]), ECG, and myocardial enzymes must be carried out every 1 to 2 cycles of anthracycline use and at least every 3 months during trastuzumab treatment[1–3]; for survivors with normal cardiac function, screening with an LVEF assessment should be considered at 6 to 12 months and possibly 2 years post-treatment, and periodic reassessment can be considered thereafter.[1] Cardiotoxicity prevention can also be classified as tertiary prevention. Cardio-oncology focuses more on primary prevention and secondary prevention. Primary prevention includes lifestyle interventions and drug interventions. Positive health-promoting behaviors including a healthy diet, smoking cessation, regular aerobic exercise, and weight control should be the first forms of cardiotoxicity prevention and are strongly advised before or during antitumor treatment.[1,2] For drug interventions, dexrazoxane is currently the most convincing protective agent against anthracycline-induced cardiotoxicity. Dexrazoxane has been recommended as a cardioprotectant in patients who have already received more than 300 mg/m2 of doxorubicin.[2] Angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin II receptor blockers (ARBs) are also considered to have cardioprotective effects. For chemotherapy, candesartan and enalapril have demonstrated cardioprotective effects.[8,9] Although controversy remains regarding ACEI/ARB prevention of cardiotoxicity caused by trastuzumab, perindopril and lisinopril are believed to have cardioprotective effects based on clinical studies.[10,11] In most studies, β-blockers have been shown to promote ventricular recovery through inhibition of adverse remodeling and to preserve the LVEF through adrenergic and neuroendocrine dysregulation mechanisms.[12] β-blockers such as carvedilol[11] and bisoprolol[10] have been concluded to achieve cardioprotective effects on cancer patients during antitumor treatment. However, neither carvedilol[13,14] nor metoprolol[8] showed positive results. Prophylactic treatment with ACEIs/ARBs or β-blockers alone or in combination has shown equivocal results. Positive results were shown for enalapril combined with carvedilol therapy in the OVERCOME study,[15] while negative results were shown for candesartan combined with metoprolol therapy in the PRADA clinical study.[8] Combination therapy may be more appropriate for people at a high risk of cardiotoxicity.[12] Other drugs, such as statins, have been shown to reduce the decrease in the LVEF during antitumor treatment.[16] Some drugs originally considered to have potential cardioprotective effects, such as coenzyme Q10, L-carnitine, N-acetylcysteine, and antioxidants (vitamin C and vitamin E), were found to have no significant protective effects after meta-analysis. The detailed information of prospective clinical studies involved were shown in Supplementary Table 1, https://links.lww.com/CM9/B28. Studies have shown that implantable cardioverter defibrillators (ICDs) or cardiac resynchronization defibrillators are beneficial for the prevention of sudden cardiac death for patients with a life expectancy >1 year and a good general condition. Secondary prevention mainly includes early detection and diagnosis of cardiac toxicity in cancer patients and timely treatment. Some early signs of heart injury require our attention, such as an impaired exercise capacity, resting tachycardia, increased myocardial markers, and decreased GLS. For patients who already have cardiotoxicity, a clinical trial confirmed the efficacy of enalapril ± carvedilol treatment,[17] and this protocol is also recommended by several guidelines.[1,3] The ESC also recommends using ICDs to reduce the risk of sudden death in patients who have recovered from ventricular arrhythmia causing hemodynamic instability and who are expected to survive for >1 year with a good functional status. For the choice of treatment length, the ESC recommends that HF treatment should be continued indefinitely unless normal systolic blood pressure function remains stable after HF treatment cessation and no further anticancer treatment is planned. Since cardiac dysfunction caused by trastuzumab is usually reversible, these patients can consider discontinuing HF therapy after their LVEF returns to normal.[1,3] In summary, regarding preventive drugs for cardiotoxicity, the preventive effect of dexrazoxane is relatively clear. Although controversies remain, most studies still agree on the effects of β-blockers and ACEI/ARB drugs on preventing and treating cardiotoxicity.[1,2,4] The treatment strategies discussed in this article will be applicable to most patients. Nevertheless, in the era of individualized care, a doctor's clinical judgment is important.[1] In the future, cardio-oncology must be a patient-centered, multidisciplinary, collaborative, and innovative discipline. The cardio-oncology team can use existing risk prediction models to determine a patient's individual risk of CV events and use existing evidence to support anticancer treatment and CV drug selection to reduce the risk of CV disease. Prevention of antitumor drug cardiotoxicity, better identification of high-risk factors for cardiotoxicity, and optimization of the diagnosis and treatment processes in clinical practice are problems that must be solved. With close cooperation among experts in the field of cancer and CV disease, the individualized health management of cancer patients can be realized. Funding This work was supported by grants from Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences (CIFMS, 2021-I2M-1-014) and National Natural Science Foundation of China (No. 82172875).

Abstract Purpose This study further approaches immune-related interstitial lung disease adverse event (AE) in patients undergoing immune checkpoint inhibitor (ICI) monotherapy, ICI plus chemotherapy and ICI plus anti-VEGF therapy in the postmarketing period. Methods This study analysed reports for ICI-related interstitial lung disease AE from the FDA Adverse Event Reporting System (FAERS) database between 2014 and 2022. The reporting odds ratio (ROR) and Bayesian confidence propagation neural networks of information components (IC) were computed to identify disproportionate reporting of ICI-related interstitial lung disease. Results 44,964,609 records were extracted from the FAERS database, with 9150 records for interstitial lung disease after ICI treatment. Men had a slightly higher reporting frequency than women (63.07% vs. 25.69%). The morbidity rate (2.05%) of acute respiratory distress syndrome was low, the fatality rate (67.55%) was the highest, the time to onset was relatively short. Within 3 months, the cumulative proportion of ICI-related interstitial lung disease records was 75.03%. The ICI plus anti-VEGF therapy group had the lowest frequency of interstitial lung disease AEs compared to the ICI monotherapy group and the ICI plus chemotherapy group (IC025 = 1.72, IC025 = 3.21, IC025 = 3.22). Moreover, ICI plus anti-VEGF therapy group had the narrowest spectrum of interstitial lung disease among these three therapeutic regimens. Conclusion This study showed a high reporting frequency and substantial characteristics of a spectrum of interstitial lung disease AEs after different ICI regimens. Notably, ICI plus anti-VEGF therapy might be a treatment method that can to some extent control ICI-related interstitial lung disease. These data provide some important information for clinicians to weigh the risks and benefits of different ICI regimens.

Abstract Objective The aim of this study is to evaluate the prognostic value of the modified Glasgow prognostic score (mGPS) in advanced esophageal squamous cell carcinoma (SCC) patients. Methods The study enrolled 311 patients with advanced esophageal SCC from January 2012 to December 2018. Univariate and multivariate analyses were calculated by the Cox proportional hazards regression model in advanced esophageal SCC patients. The Kaplan–Meier method was used to evaluate the ability of the mGPS for survival rates. Propensity score‐matched (PSM) analysis was carried out to balance imbalanced variables. Results The Cox proportional hazards analysis showed that factors including M stage, ECOG, mGPS group, and sex were identified as independent predictors. The mGPS presented a good level of overall survival (OS) prediction with a risk‐adopted classification for advanced esophageal SCC patients. The survival rates in advanced esophageal SCC patients with mGPS 0, 1, and 2 were 18.8%, 8.4%, and 4.2%, respectively (p < 0.001). Moreover, before and after PSM, the mGPS was associated with 3‐year survival rates of advanced esophageal SCC patients in the Kaplan–Meier survival analysis. In addition, the mGPS for OS prediction demonstrated better performance than sex and ECOG score. The area under curve (AUC) of the mGPS combined with M stage for the prognosis of advanced esophageal SCC was 0.677 (0.592–0.763). Conclusion The mGPS is a cost‐effective, accessible tool capable of prognosticating in this cohort. It could be a useful surveillance system of prognosis in advanced esophageal SCC patients.

AbstractBackgroundCurrent predictive tools assess catheter‐related thrombosis (CRT) in patients with lung cancer in a static manner at a single time point of catheterization. The subsequent hazard changes over time are unknown. The conditional catheter‐related thrombosis‐free probability (CCFP) can provide dynamic information on continual CRT‐free expectations. This study aimed to assess the CCFP and hazard rates based on risk categories and various venous access devices (VADs).MethodsThis retrospective study reviewed 939 patients with lung cancer with peripherally inserted central venous catheters (PICCs) or central venous catheters (CVCs) identified at the National Clinical Research Center for Cancer between January 1, 2015 and December 31, 2018. The incidence of CRT has also been reported. Patients were stratified into low‐ and high‐risk groups according to multivariate Cox regression analyses. CCFP is defined as the CRT‐free probability given that patients have no CRT for a definite time.ResultsA total of 507 patients with PICCs and 432 patients with CVCs were included in this study. The 3‐month CCFP increased from 74.2% at catheter insertion to 93.6% at 3 months. The hazards of CRT in the first month were highest (16.4%) and slightly thereafter. The high‐risk group initially had a higher (21.4%) but significantly decreased CRT hazard after 2 months (8.3%), whereas the low‐risk group maintained a comparable lower risk hazard of less than 5% after 1 month. In the overall cohort, patients with CVCs had lower CRT probability than those with PICCs (HR, 1.76; 95% CI: 1.28–2.41; p < 0.01). Further analysis demonstrated that compared with PICCs, CVCs provided a CRT‐free benefit in low‐risk patients (p = 0.02) but not in high‐risk patients (p = 0.06).ConclusionsCCFP increased, and the hazards of CRT decreased over time in a risk‐dependent manner in patients with lung cancer. These valuable dynamic data may help optimize risk‐adjusted choices of VADs and risk‐adjusted prophylactic anticoagulation strategies for patients.

The Journal of the American College of Cardiology: CardioOncology (JACC: CardioOncology) has been published in its tenth issue since its inception in 2019. This issue is consistently presented in the form of original articles and reviews, and continues to be highly professional and brings together many hot-spot topics and the latest achievements in the field of CardioOncology, with some wonderful contents and clear and original opinions. This article gives a brief introduction to this issue.