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4/12/26

ABSTRACT

BACKGROUND: Radiotherapy (RT) associates with long-term cardiotoxicity. In preclinical models, RT-exposure induces early cardiotoxic arrhythmias including atrial fibrillation (AF). Yet, whether this occurs in patients is unknown.

METHODS: Leveraging a large cohort of consecutive esophageal cancer patients treated with thoracic-RT from 2007-2019, we assessed incidence and outcomes of incident-AF. Secondary outcomes included major adverse cardiovascular events (MACE), defined as AF, heart failure, ventricular-arrhythmias and sudden-death, by cardiac RT-dose. We also assessed the relationship between AF-development and progression-free and overall-survival. Observed incident-AF rates were compared with Framingham predicted-rates, and absolute-excess-risks (AER) were estimated. Multivariate-regression was used to define the relationship between clinical and RT-measures, and outcomes. Differences in outcomes, by AF-status, were also evaluated via 30-day landmark-analysis. Furthermore, we assessed the effect of cardiac substructure RT-dose (ex. left atrium, LA) on the risk of post RT-related outcomes.

RESULTS: Overall, from 238 RT-treated esophageal cancer patients, 21.4% developed incident-AF, and 33% developed MACE, with the majority (84%) of events occurring ≤2 years of RT-initiation; median time-to-AF, 4.1 months. Cumulative incidence of AF and MACE at 1-year was 19.5%, and 25.7%, respectively; translating into an observed incident-AF rate of 824 per 10,000 person-years, compared to the Framingham predicted-rate of 92 (RR 8.96, P<0.001,

CONCLUSIONS: Among esophageal cancer patients, radiotherapy increases AF-risk, and associates with worse long-term outcomes.

PMID:37574171 | DOI:10.1016/j.ijrobp.2023.08.011

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PubMed articles on: Cardio-Oncology

Brigatinib Versus Alectinib in ALK-positive Non-small Cell Lung Cancer After Disease Progression on Crizotinib: Results of Phase 3 ALTA-3 Trial

J Thorac Oncol. 2023 Aug 11:S1556-0864(23)00730-X. doi: 10.1016/j.jtho.2023.08.010. Online ahead of print.

ABSTRACT

INTRODUCTION: This open-label, phase 3 trial (ALTA-3; NCT03596866) compared efficacy and safety of brigatinib versus alectinib for ALK+ NSCLC after disease progression on crizotinib.

METHODS: Patients with advanced ALK+ NSCLC that progressed on crizotinib were randomized 1:1 to brigatinib 180 mg once daily (7-day lead-in, 90 mg) or alectinib 600 mg twice daily, aiming to test superiority. The primary endpoint was blinded independent review committee (BIRC)-assessed progression-free survival (PFS). Interim analysis for efficacy and futility was planned at approximately 70% of 164 expected PFS events.

RESULTS: The population (N=248; brigatinib, n=125; alectinib, n=123) was notable for long median duration of prior crizotinib (16.0-16.8 months) and low rate of ALK fusion in baseline circulating tumor DNA (ctDNA; 78/232 [34%]). Median BIRC-assessed PFS was 19.3 months with brigatinib and 19.2 months with alectinib (hazard ratio: 0.97 [95% confidence interval [CI]: 0.66-1.42]; p=0.8672]). The study met futility criterion. Overall survival was immature (41 events [17%]). Exploratory analyses pooled across treatment groups demonstrated median PFS of 11.1 versus 22.5 months in patients with versus without ctDNA-detectable ALK fusion at baseline (hazard ratio: 0.48 [95% CI: 0.32-0.71]). Treatment-related adverse events in >30% of patients (brigatinib/alectinib) were elevated blood creatine phosphokinase (70%/29%), aspartate aminotransferase (53%/38%), and alanine aminotransferase (40%/36%).

CONCLUSION: Brigatinib was not superior to alectinib for PFS in crizotinib-pretreated ALK+ NSCLC. Safety was consistent with the well-established and unique profiles of each drug. The low proportion of patients with ctDNA-detectable ALK fusion may account for prolonged PFS with both drugs in ALTA-3.

PMID:37574132 | DOI:10.1016/j.jtho.2023.08.010

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PubMed articles on: Cardio-Oncology

Lethal ventricular arrhythmia due to entrectinib-induced Brugada syndrome: a case report and literature review

Int Cancer Conf J. 2023 Jun 26;12(4):299-304. doi: 10.1007/s13691-023-00620-y. eCollection 2023 Oct.

ABSTRACT

Entrectinib, a multikinase inhibitor of ROS1and tropomyosin receptor kinases, is recommended to treat ROS1-positive metastatic non-small cell lung cancer (NSCLC). In a previous study, entrectinib-related cardiotoxicity occurred in 2% of patients; however, lethal arrhythmias remain understudied. We encountered a case of fatal arrhythmia due to drug-induced Brugada syndrome caused by entrectinib. An 81-year-old Japanese male with lung adenocarcinoma harboring ROS1-fusion gene was treated with entrectinib. The patient developed lethal arrhythmias three days after drug initiation, including ventricular tachycardia with Brugada-like electrocardiogram changes. Echocardiography and coronary angiography revealed no evidence of acute coronary syndrome or myocarditis. Following the termination of entrectinib, the electrocardiogram abnormality improved within 12 days. Hence, paying special attention to and monitoring electrocardiogram changes is necessary. In addition, it is also necessary to consider early therapeutic interventions and discontinuation of the drug in cases of drug-induced Brugada syndrome.

PMID:37577345 | PMC:PMC10421830 | DOI:10.1007/s13691-023-00620-y

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PubMed articles on: Cardio-Oncology

Clinical score for colorectal cancer patients with lung-limited metastases undergoing surgical resection: Meta-Lung Score

Lung Cancer. 2023 Aug 9;184:107342. doi: 10.1016/j.lungcan.2023.107342. Online ahead of print.

ABSTRACT

BACKGROUND: Radical resection of isolated lung metastases (LM) from colorectal cancer (CRC) is debated. Like Fong's criteria in liver metastases, our study was meant to assign a clinical prognostic score in patients with LM from CRC, aiming for better surgery selection.

METHODS: We retrospectively analyzed data from 260 CRC patients who underwent curative LM resection from December 2002 to January 2022, verifying the impact of different clinicopathological features on the overall survival (OS).

RESULTS: At the univariate analysis: higher baseline CEA levels (p = 0.0001), disease-free survival less than or equal to 12 months (m) (p = 0.0043), LM size larger than 2 cm (p = 0.0187), multiple resectable nodules (p = 0.0083), and positive nodal status of the primary tumor (p = 0.0011) were associated with worse prognosis. In a Cox regression model, these characteristics retained their independent role for OS (p < 0.0001) and were chosen as criteria to be assigned one point each for clinical risk score. The 5-year survival rate in patients with 0 points was 88%, while no patients with a 5-point score survived at 2 years. Based on the 0-1 vs. 2-5 score range, we obtained a significant difference in median OS: not reached vs. 40.8 months (95 %CI 36 to 87.5), respectively (p < 0.0001) stratifying patients into good and poor prognosis. The prognostic role of the score was also confirmed in terms of median RFS: not reached in 0-1 scored patients vs. 30.5 months (95 %CI 19.4 to 42) in patients with 2-5 scores (p = 0.0006).

CONCLUSIONS: When LM from CRC is resectable, the Meta-Lung Score provides valuable prognostic information. Indeed, while upfront surgery should be considered in patients with scores of 0 to 1, it should be cautiously suggested in patients with scores of 2 to 5, for whom a prognosis comparison between preventive surgery and other treatments should be investigated in prospective randomized clinical trials.

PMID:37573705 | DOI:10.1016/j.lungcan.2023.107342

16 August 2023

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Cardiotoxicity News

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PubMed articles on: Cancer & VTE/PE

Commentary on the 2023 ASH guidelines for thrombophilia testing in VTE

Blood Adv. 2023 Aug 15:bloodadvances.2023011393. doi: 10.1182/bloodadvances.2023011393. Online ahead of print.

NO ABSTRACT

PMID:37581979 | DOI:10.1182/bloodadvances.2023011393

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PubMed articles on: Cancer & VTE/PE

Venous thromboembolism in multiple myeloma: Increasing evidence in support of direct oral anticoagulants

Br J Haematol. 2023 Aug 15. doi: 10.1111/bjh.19056. Online ahead of print.

ABSTRACT

Venous thromboembolism (VTE) continues to cause significant morbidity and excess mortality in patients with multiple myeloma. The report by Costa and colleagues demonstrates superiority of direct oral anticoagulants over aspirin in terms of VTE prevention, without increased bleeding complications seen. Commentary on: Costa et al. Direct oral anticoagulants versus aspirin for primary thromboprophylaxis in patients with multiple myeloma undergoing outpatient therapy: A systematic review and updated meta-analysis. Br J Haematol 2023 (Online ahead of print). doi: 10.1111/bjh.19017.

PMID:37581247 | DOI:10.1111/bjh.19056