ABSTRACT

With the progression of tumor treatment, the 5-year survival rate of breast cancer is close to 90%. Cardiovascular toxicity caused by chemotherapy has become a vital factor affecting the survival of patients with breast cancer. Anthracyclines, such as doxorubicin, are still some of the most effective chemotherapeutic agents, but their resulting cardiotoxicity is generally considered to be progressive and irreversible. In addition to anthracyclines, platinum- and alkyl-based antitumor drugs also demonstrate certain cardiotoxic effects. Targeted drugs have always been considered a relatively safe option. However, in recent years, some random clinical trials have observed the occurrence of subclinical cardiotoxicity in targeted antitumor drug users, which may be related to the effects of targeted drugs on the angiotensin converting enzyme, angiotensin receptor and β receptor. The use of angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers and beta-blockers may prevent clinical cardiotoxicity. This article reviews the toxicity and mechanisms of current clinical anti-breast cancer drugs and proposes strategies for preventing cardiovascular toxicity to provide recommendations for the clinical prevention and treatment of chemotherapy-related cardiomyopathy.

PMID:37647693 | DOI:10.1016/j.biopha.2023.115373

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PubMed articles on: Cardio-Oncology

Challenges in Cardiovascular Imaging in Women with Breast Cancer

Curr Cardiol Rep. 2023 Aug 29. doi: 10.1007/s11886-023-01941-3. Online ahead of print.

ABSTRACT

Cardiovascular imaging in breast cancer patients is paramount for the surveillance of cancer therapy-related cardiac dysfunction (CTRCD); however, it comes with specific limitations. PURPOSE OF REVIEW: This review aims to describe the unique challenges faced in cardiovascular imaging of breast cancer patients, discuss evidence to support the utility of various imaging modalities, and provide solutions for improvement in imaging this unique population. RECENT FINDINGS: Updated clinical society guidelines have introduced more unifying surveillance of CTRCD, although there remains a lack of a universally accepted definition. Traditional and novel multi-modality imaging can be used to detect CTRCD and myocarditis in breast cancer patients. Cardiovascular imaging in breast cancer patients is difficult due to reconstructive surgery. Although echocardiography with myocardial strain is the cornerstone, multi-modality imaging can be used to evaluate for CTRCD and myocarditis. Novel imaging techniques to improve the diagnosis of cardiotoxicities in breast cancer patients are needed.

PMID:37642930 | DOI:10.1007/s11886-023-01941-3

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PubMed articles on: Cardio-Oncology

Pharmacotherapy for Cancer Treatment-Related Cardiac Dysfunction and Heart Failure in Childhood Cancer Survivors

Paediatr Drugs. 2023 Aug 28. doi: 10.1007/s40272-023-00585-8. Online ahead of print.

ABSTRACT

The number of childhood cancer survivors is increasing rapidly. According to American Association for Cancer Research, there are more than 750,000 childhood cancer survivors in the United States and Europe. As the number of childhood cancer survivors increases, so does cancer treatment-related cardiac dysfunction (CTRCD), leading to heart failure (HF). It has been reported that childhood cancer survivors who received anthracyclines are 15 times more likely to have late cancer treatment-related HF and have a 5-fold higher risk of death from cardiovascular (CV) disease than the general population. CV disease is the leading cause of death in childhood cancer survivors. The increasing need to manage cancer survivor patients has led to the rapid creation and adaptation of cardio-oncology. Cardio-oncology is a multidisciplinary science that monitors, treats, and prevents CTRCD. Many guidelines and position statements have been published to help diagnose and manage CTRCD, including those from the American Society of Clinical Oncology, the European Society of Cardiology, the Canadian Cardiovascular Society, the European Society of Medical Oncology, the International Late Effects of Childhood Cancer Guideline Harmonization Group, and many others. However, there remains a gap in identifying high-risk patients likely to develop cardiomyopathy and HF in later life, thus reducing primary and secondary measures being instituted, and when to start treatment when there is echocardiographic evidence of left ventricular (LV) dysfunctions without symptoms of HF. There are no randomized controlled clinical trials for treatment for CTRCD leading to HF in childhood cancer survivors. The treatment of HF due to cancer treatment is similar to the guidelines for general HF. This review describes the latest pharmacologic therapy for preventing and treating LV dysfunction and HF in childhood cancer survivors based on expert consensus guidelines and extrapolating data from adult HF trials.

PMID:37639193 | DOI:10.1007/s40272-023-00585-8

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PubMed articles on: Cardio-Oncology

Trastuzumab and ECG Changes Dilemma

Int J Hematol Oncol Stem Cell Res. 2023 Apr 1;17(2):63-64. doi: 10.18502/ijhoscr.v17i2.12641.

NO ABSTRACT

PMID:37637771 | PMC:PMC10452953 | DOI:10.18502/ijhoscr.v17i2.12641

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PubMed articles on: Cardio-Oncology

Chemotherapy-Related Cardiac Dysfunction: Quantitative Cardiac Magnetic Resonance Image Parameters and Their Prognostic Implications

Korean J Radiol. 2023 Sep;24(9):838-848. doi: 10.3348/kjr.2023.0095.

ABSTRACT

OBJECTIVE: To quantitatively analyze the cardiac magnetic resonance imaging (CMR) characteristics of chemotherapy-related cardiac dysfunction (CTRCD) and explore their prognostic value for major adverse cardiovascular events (MACE).

MATERIALS AND METHODS: A total of 145 patients (male:female = 76:69, mean age = 63.0 years) with cancer and heart failure who underwent CMR between January 2015 and January 2021 were included. CMR was performed using a 3T scanner (Siemens). Biventricular functions, native T1 T2, extracellular volume fraction (ECV) values, and late gadolinium enhancement (LGE) of the left ventricle (LV) were compared between those with and without CTRCD. These were compared between patients with mild-to-moderate CTRCD and those with severe CTRCD. Cox proportional hazard regression analysis was used to evaluate the association between the CMR parameters and MACE occurrence during follow-up in the CTRCD patients.

RESULTS: Among 145 patients, 61 had CTRCD and 84 did not have CTRCD. Native T1, ECV, and T2 were significantly higher in the CTRCD group (1336.9 ms, 32.5%, and 44.7 ms, respectively) than those in the non-CTRCD group (1303.4 ms, 30.5%, and 42.0 ms, respectively; P= 0.013, 0.010, and < 0.001, respectively). They were not significantly different between patients with mild-to-moderate and severe CTRCD. Indexed LV mass was significantly smaller in the CTRCD group (65.0 g/m² vs. 78.9 g/m²; P< 0.001). According to the multivariable Cox regression analysis, T2 (hazard ratio [HR]: 1.14, 95% confidence interval [CI]: 1.01-1.27; P= 0.028) and quantified LGE (HR: 1.07, 95% CI: 1.01-1.13; P= 0.021) were independently associated with MACE in the CTRCD patients.

CONCLUSION: Quantitative parameters from CMR have the potential to evaluate myocardial changes in CTRCD. Increased T2 with reduced LV mass was demonstrated in CTRCD patients even before the development of severe cardiac dysfunction. T2 and quantified LGE may be independent prognostic factors for MACE in patients with CTRCD.

PMID:37634639 | PMC:PMC10462900 | DOI:10.3348/kjr.2023.0095

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PubMed articles on: Cancer & VTE/PE

The unfolded protein response links ER stress to cancer-associated thrombosis

JCI Insight. 2023 Aug 31:e170148. doi: 10.1172/jci.insight.170148. Online ahead of print.

ABSTRACT

Thrombosis is a common complication of advanced cancer. Yet the cellular mechanisms linking malignancy to thrombosis are poorly understood. The unfolded protein response (UPR) is an ER stress response associated with advanced cancers. A proteomic evaluation of plasmas from gastric and non-small cell lung cancer patients who were monitored prospectively for venous thromboembolism demonstrated increased levels of UPR-related markers in plasmas of patients who developed clots compared to those who did not. Release of procoagulant activity into supernatants of gastric, lung, and pancreatic cancer cells was enhanced by UPR induction and blocked by antagonists of the UPR receptors IRE1α or PERK. Release of extracellular vesicles bearing tissue factor (EVTF) from pancreatic cancer cells was inhibited by siRNA-mediated knockdown of IRE1α/XBP1 or PERK pathways. Induction of UPR did not increase TF synthesis, but rather stimulated localization of TF to the cell surface. UPR-induced TF delivery to EVTFs was inhibited by Arf1 knockdown or GBF1 antagonism, confirming the role of vesicular trafficking. Our findings show that UPR activation results in increased vesicular trafficking leading to release of prothrombotic EVTFs, thus providing a mechanistic link between ER stress and cancer-associated thrombosis.

PMID:37651191 | DOI:10.1172/jci.insight.170148

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PubMed articles on: Cancer & VTE/PE

Association of type of oral anticoagulation with risk of bleeding in 45,114 patients with venous thromboembolism during initial and extended treatment-A nationwide register-based study

J Intern Med. 2023 Aug 28. doi: 10.1111/joim.13712. Online ahead of print.

ABSTRACT

BACKGROUND: Safety data for different anticoagulant medications in venous thromboembolism (VTE) are scarce, in particular for extended treatment.

OBJECTIVES: To compare major bleeding rates depending on the choice of anticoagulation during initial (first 6 months) and extended treatment (6 months up to 5 years).

METHODS: A nationwide register-based study including cancer-free patients with a first-time VTE between 2014 and 2020. Cox proportional hazards models were used to compare bleeding rates.

RESULTS: We included 6558 patients on warfarin, 18,196 on rivaroxaban, and 19,498 on apixaban. At 6 months, 4750 (72.4%) remained on warfarin, 11,366 (62.5%) on rivaroxaban, and 11,940 (61.2%) on apixaban. During initial treatment, major bleeding rates were 3.86 (95% CI 3.14-4.58), 2.93 (2.55-3.31), and 1.95 (1.65-2.25) per 100 patient-years for warfarin, rivaroxaban, and apixaban, respectively, yielding adjusted hazard ratios (aHRs) of 0.89 (95% CI 0.71-1.12) for rivaroxaban versus warfarin, 0.55 (0.43-0.71) for apixaban versus warfarin, and 0.62 (0.50-0.76) for apixaban versus rivaroxaban. During extended treatment, major bleeding rates were 1.55 (1.19-1.91), 1.05 (0.85-1.26), and 0.96 (0.78-1.15) per 100 patient-years for warfarin, rivaroxaban, and apixaban, respectively, with aHRs of 0.72 (0.53-0.99) for rivaroxaban versus warfarin, 0.60 (0.44-0.82) for apixaban versus warfarin, and 0.85 (0.64-1.12) for apixaban versus rivaroxaban. Previous bleeding and increasing age were risk factors for bleeding both during initial and extended treatment.

CONCLUSION: Apixaban had a lower bleeding risk than warfarin or rivaroxaban during initial treatment. During extended treatment, bleeding risk was similar for apixaban and rivaroxaban, and higher with warfarin.

PMID:37641391 | DOI:10.1111/joim.13712

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PubMed articles on: Cancer & VTE/PE

Edoxaban for 12 Months Versus 3 Months in Cancer Patients With Isolated Distal Deep Vein Thrombosis (ONCO DVT study): An Open-label, Multicenter, Randomized Clinical Trial

Circulation. 2023 Aug 28. doi: 10.1161/CIRCULATIONAHA.123.066360. Online ahead of print.

ABSTRACT

Background:The optimal duration of anticoagulation therapy for isolated distal deep vein thrombosis (DVT) in patients with cancer is clinically relevant, but the evidence is lacking. The prolonged anticoagulation therapy could have a potential benefit for prevention of thrombotic events, however, it could also increase the risk of bleeding. Methods:In a multicenter, open-label, adjudicator-blinded, randomized clinical trial at 60 institutions in Japan, we randomly assigned cancer patients with isolated distal DVT, in a 1-to-1 ratio, to receive either a 12-month or 3-month edoxaban treatment. The primary endpoint was a composite of a symptomatic recurrent venous thromboembolism (VTE) or VTE-related death at 12 months. The major secondary endpoint was major bleeding at 12 months, according to the criteria of the International Society on Thrombosis and Hemostasis. The primary hypothesis was that a 12-month edoxaban treatment was superior to a 3-month edoxaban treatment with respect to the primary endpoint. Results:From April 2019 through June 2022, 604 patients were randomized, and after excluding 3 patients who withdrew consent, 601 patients were included in the intention-to-treat population: 296 patients in the 12-month edoxaban group and 305 patients in the 3-month edoxaban group. The mean age was 70.8 years, 28% of the patients were men, and 20% of the patients had symptoms of DVT at baseline. The primary endpoint of a symptomatic recurrent VTE event or VTE-related death occurred in 3 of the 296 patients (1.0%) in the 12-month edoxaban group and in 22 of the 305 (7.2%) in the 3-month edoxaban group (odds ratio, 0.13; 95% CI, 0.03 to 0.44). The major secondary endpoint of major bleeding occurred in 28 of the 296 patients (9.5%) in the 12-month edoxaban group and in 22 of the 305 (7.2%) in the 3-month edoxaban group (odds ratio, 1.34; 95% CI, 0.75 to 2.41). The prespecified subgroups did not affect the estimates on the primary endpoint. Conclusions:In cancer patients with isolated distal DVT, 12 months was superior to 3 months for an edoxaban treatment with respect to the composite outcome of a symptomatic recurrent VTE or VTE-related death.

PMID:37638968 | DOI:10.1161/CIRCULATIONAHA.123.066360

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PubMed articles on: Cancer & VTE/PE

Sternum Metastases: From Case-Identifying Strategy to Multidisciplinary Management

Diagnostics (Basel). 2023 Aug 17;13(16):2698. doi: 10.3390/diagnostics13162698. ABSTRACTWe aimed to overview the most recent data on sternal metastases from a multidisciplinary approach (diagnosis strategies, outcome, and histological reports). This narrative review based on a PubMed search (between January 2020 and 22 July 2023) using key words such as "sternal", "manubrium", and "metastasis" within the title and/or abstract only included original papers that specifically addressed secondary sternal spreading of cancer in adults, for a total of 48 original articles (14 studies and 34 single case reports). A prior unpublished case in point is also introduced (percutaneous incisional biopsy was used to address a 10 cm sternal tumour upon first admission on an apparently healthy male). The studies (n = 14) may be classified into one of three groups: studies addressing the incidence of bone metastases (including sternum) amid different primary cancers, such as prostate cancer (N = 122 with bone metastases, 83% of them with chest wall metastases), head and neck cancers (N = 3620, 0.8% with bone metastases, and 10.34% of this subgroup with sternum involvement); and glioblastoma (N = 92 with bone metastases, 37% of them with non-vertebral metastases, including the sternum); assessment cohorts, including breast cancer (N = 410; accuracy and sensitivity of PET/CT vs. bone scintigraphy is superior with concern to sternum spreading) and bone metastases of unknown origin (N = 83, including a subgroup with sternum metastases; some features of PET/CT help the differentiation with multiple myeloma); and cohorts with various therapeutic approaches, such as palliative arterial embolization (N = 10), thymic neuroendocrine neoplasia (1/5 detected with sternum metastases), survival rates for sternum metastases vs. non-sternum chest wall involvement (N = 87), oligo-metastatic (sternal) breast cancer (3 studies, N = 16 for all of them), oligo-metastatic head and neck cancer (N = 81), conformal radiotherapy (N = 24,215, including an analysis on sternum spreading), and EBRT followed by MR-HIFU (N = 6). Core data coming from the isolated case reports (N = 34) showed a female to male ratio of 1.6; the females' ages were between 34 and 80 (mean of 57.28) and the males' ages varied between 33 and 79 (average of 58.78) years. The originating tumour profile revealed that the most frequent types were mammary (N = 8, all females) and thyroid (N = 9, both women and men), followed by bladder (N = 3), lung (N = 2), and kidney (N = 2). There was also one case for each of the following: adenoid cystic carcinoma of the jaw, malignant melanoma, caecum MiNEN, a brain and an extracranial meningioma, tongue carcinoma, cholangiocarcinoma, osteosarcoma, and hepatocellular carcinoma. To our knowledge, this is the most complex and the largest analysis of prior published data within the time frame of our methods. These data open up new perspectives of this intricate, dynamic, and challenging domain of sternum metastases. Awareness is a mandatory factor since the patients may have a complex multidisciplinary medical and/or surgical background or they are admitted for the first time with this condition; thus, the convolute puzzle will start from this newly detected sternal lump. Abbreviations: N = number of patients; n = number of studies; PET/CT = positron emission tomography/computed tomography; EVRT = external beam radiotherapy; MR-HIFU = magnetic resonance-guided high-intensity focused ultrasound; MiNEN = mixed neuroendocrine-non-neuroendocrine tumour.

PMID:37627957 | PMC:PMC10453928 | DOI:10.3390/diagnostics13162698

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PubMed articles on: Cancer & VTE/PE

Venous thrombotic events and impact on outcomes in patients treated with first-line single-agent pembrolizumab in PD-L1 ≥ 50% advanced non small cell lung cancer

J Cancer Res Clin Oncol. 2023 Aug 25. doi: 10.1007/s00432-023-05321-w. Online ahead of print.

ABSTRACT

BACKGROUND: Few data are available on the impact of venous thrombotic events (VTE) in patients with metastatic non-small cell lung cancer (mNSCLC) treated with immunotherapy.

METHODS: This is a secondary analysis of the ESKEYP study, a national, retrospective, multicenter study that consecutively included all PD-L1 ≥ 50% mNSCLC patients who initiated first-line treatment with pembrolizumab monotherapy. From May 2017 to November 2019, 845 patients were included (from availability of pembrolizumab in this indication in France to the authorization of the combination with chemotherapy). Impact of VTE and patient characteristics were analyzed.

RESULTS: Of the 748 patients (88.5%) with available data, the incidence of VTE was 14.8% (111/748). At pembrolizumab initiation, Khorana score was ≥ 2 for 55.0% (61/111) of them. Recurrence of VTE was reported for 4 of the 111 patients and 5 had bleeding complications. Patients with VTE were significantly younger, had more frequently long-term corticosteroids treatment and more often liver metastases. Progression-free survival (PFS) was significantly shorter in patients with VTE compared to patients without VTE: 6.1 (95% CI 4.1-9.0) months vs. 8.3 (6.9-10.3) months (p = 0.03). VTE did not significantly impact overall survival (OS): 15.2 (10.0-24.7) months with VTE and 22.6 (18.4-29.8) months without VTE (p = 0.07). In multivariate analysis for PFS and OS, HRs for VTE were 1.3 (0.99-1.71), p = 0.06 and 1.32 (0.99-1.76), p = 0.05.

CONCLUSION: The incidence of VTE appears to be as high with in first-line immunotherapy as with chemotherapy in patients with mNSCLC, with in patient with VTE, a no significant trend for lower PFS and OS in multivariate analysis. more marked impact on PFS than on OS.

PMID:37626173 | DOI:10.1007/s00432-023-05321-w

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LM02 trial Perioperative treatment with panitumumab and FOLFIRI in patients with wild-type RAS, potentially resectable colorectal cancer liver metastases-a phase II study

Front Oncol. 2023 Aug 9;13:1231600. doi: 10.3389/fonc.2023.1231600. eCollection 2023.