ABSTRACT

AIMS: With improving cancer survivorship, cardiovascular disease (CVD) has become a leading cause of death in breast cancer (BC) survivors. At present, there is no prospectively validated, contemporary risk assessment tool specific to this patient cohort. Accordingly, we sought to investigate long-term cardiovascular outcomes in early-stage BC patients utilising a well characterised database at a quaternary referral centre. With the assembly of this cohort, we have derived a BC cardiovascular risk index titled the 'CRIB (Cardiovascular Risk Index in Breast Cancer)' to estimate the risk of a major adverse cardiovascular event (MACE) in women undergoing treatment for BC.

METHODS: A retrospective cohort study was conducted examining all female patients aged ≥18 years of age who underwent treatment for early-stage BC at a cancer centre in Melbourne, Australia, between 2009 and 2019. The primary aim of this study was to assess causes and predictors of MACE.

RESULTS: A total of 1,173 women with early-stage BC were included. During a median follow-up of 4.4 (1.8-6.7) years, 80 (6.8%) women experienced a MACE. These women were more likely to be older, with a high burden of cardiovascular risk factors and were more likely to have a history of established coronary artery disease (CAD) (p≤0.001 for all). A CRIB ≥3 (2 points: renal impairment, 1 point: age ≥65 years, body mass index [BMI]>27, diabetes, hypertension, history of smoking) demonstrated moderate discrimination (c-statistic 0.75) with appropriate calibration. A CRIB ≥3, which represented 23.9% of our cohort, was associated with a high risk of MACE (odds ratio [OR] 17.85, 95% confidence interval [CI] 6.36-50.05; p<0.001).

CONCLUSION: Cardiovascular risk stratification at the time of BC diagnosis using the novel CRIB may help guide surveillance and the use of cardioprotective therapies as well as identify those who require long-term cardiac follow-up.

PMID:37574416 | DOI:10.1016/j.hlc.2023.05.021

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PubMed articles on: Cardio-Oncology

Incident Atrial Fibrillation and Survival Outcomes in Esophageal Cancer following Radiotherapy

Int J Radiat Oncol Biol Phys. 2023 Aug 11:S0360-3016(23)07748-9. doi: 10.1016/j.ijrobp.2023.08.011. Online ahead of print.

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: 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

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PubMed articles on: Cancer & VTE/PE

Giant breast phyllodes tumor with silent thromboembolism: A case report

Cancer Rep (Hoboken). 2023 Aug 14:e1865. doi: 10.1002/cnr2.1865. Online ahead of print.

ABSTRACT

BACKGROUND: Phyllodes tumor (PT) is a solid fibroepithelial breast lesion with proliferation of stromal and epithelial elements, usually presents with a rapidly expanding feature. Venous thromboembolism (VTE) have been reported to increase the burden in terms of mortality and morbidity of malignant tumor, and associate with worsened survival. However, benign PTs with silent thromboembolism that have not yet been reported, we report an unusual case of massive benign PT that grew on the left side of the breast in a cauliflower-shaped form and presented severe chronic blood loss and deep VTE.

CASE: A 37-year-old woman with uncontrolled pain presented a rapidly enlarging left breast mass, measuring approximately 30 × 20 × 15 cm3 that first started 25 years ago. color Doppler ultrasound showed a large mass lesion on the left breast and deep VTE, several enlarged lymph nodes in the left axilla and mediastinum, which presented a malignant character. However, the biopsies of the mass did not show evidence of malignancy and the pathology result was considered to be benign PT. The patient was treated with an inferior vena cava and anticoagulation, the operation was arranged according to the surgical procedure, the patient recovered very well after mastectomy.

CONCLUSION: This case is unique in that the giant breast mass presented with malignant character, was eventually pathologically confirmed to be benign PT, and it's rare that the benign tumor accompanied with silent thromboembolism. This finding describes the atypia features of giant benign PT and reminds the surgeon to consider the factor of VTE and risk when encountering ulcerative benign breast tumor and avoid excessive treatment.

PMID:37580942 | DOI:10.1002/cnr2.1865

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PubMed articles on: Cancer & VTE/PE

Venous thromboembolism and acute myeloid leukemia: risk factors and mortality in elderly white, black and Asian patients

Blood Coagul Fibrinolysis. 2023 Jul 7. doi: 10.1097/MBC.0000000000001226. Online ahead of print.