ABSTRACT
PURPOSE: Recent studies have suggested that machine learning (ML) could be used to predict venous thromboembolism (VTE) in cancer patients with high accuracy.
METHODS: We aimed to evaluate the performance of ML in predicting VTE events in patients with cancer. PubMed, Web of Science, and EMBASE to identify studies were searched.
RESULTS: Seven studies involving 12,249 patients with cancer were included. The combined results of the different ML models demonstrated good accuracy in the prediction of VTE. In the training set, the global pooled sensitivity was 0.87, the global pooled specificity was 0.87, and the AUC was 0.91, and in the test set 0.65, 0.84, and 0.80, respectively.
CONCLUSION: The prediction ML models showed good performance to predict VTE. External validation to determine the result's reproducibility is necessary.
PMID:37616550 | DOI:10.1200/CCI.23.00060
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PubMed articles on: Cancer & VTE/PE
No evidence for a genetic causal effect of breast cancer on venous thromboembolism: a mendelian randomization study
J Thromb Thrombolysis. 2023 Aug 24. doi: 10.1007/s11239-023-02871-1. Online ahead of print.
ABSTRACT
Active cancer is known to contribute to venous thromboembolism (VTE), but the cause-and-effect association of breast cancer on VTE is not yet clear. In order to investigate the possible causal relationships, we used a Mendelian randomization analysis. Data for generically predicted breast cancer were identified based on the BCAC consortium. A meta-analysis of genome-wide association study (GWAS) comprising 1,500,861 participants for VTE as well as data from the FinnGen study for VTE, DVT and PE was used for the causal-effect estimation. Our primary method was inverse-variance weighted (IVW), and our supplementary methods included weighted median and MR-Egger. We also carried out sensitivity analysis for the study. No evidence of causal-effect was detected of overall breast cancer on VTE in both the GWAS meta-analysis (OR=1.01, 95%CI:0.98-1.04, p = 0.495) and the FinnGen consortium (OR=1.00,95%CI:0.96-1.04, p = 0.945). In addition, the presence of ER-positive or ER-negative disease did not significantly influence the incidence of VTE and its subtypes. In conclusion, no genetic cause-and-effect of breast cancer on VTE risk was detected in the large MR analysis.
PMID:37615800 | DOI:10.1007/s11239-023-02871-1
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PubMed articles on: Cancer & VTE/PE
Updated meta-analysis of randomized controlled trials on primary outpatient thromboprophylaxis in patients with gastric and gastroesophageal junction cancers receiving chemotherapy
Proc (Bayl Univ Med Cent). 2023 Jul 3;36(5):635-640. doi: 10.1080/08998280.2023.2225913. eCollection 2023.
ABSTRACT
Advanced gastric cancer is a highly thrombogenic cancer per Khorana score. Recent clinical practice guidelines suggest primary outpatient thromboprophylaxis (POTP) for patients with a Khorana score ≥2. We performed an updated meta-analysis to evaluate the benefit of POTP in patients with gastric cancer and gastroesophageal junction cancers receiving chemotherapy. Randomized controlled trials with reduction in venous thromboembolism (VTE) as a primary or secondary endpoint were incorporated. A total of 631 patients from subgroups of three randomized controlled trials were included. The VTE incidence was 1.6% and 5.1% in POTP and control groups, respectively (risk ratio 0.31; confidence interval 0.11 to 0.83; P= 0.02), with a number needed to treat of 29 to prevent one VTE event. Even though the recent clinical practice guidelines suggest POTP in patients with gastric cancer and gastroesophageal junction cancers, our meta-analysis findings do not support the routine use of POTP in those patients.
PMID:37614866 | PMC:PMC10443955 | DOI:10.1080/08998280.2023.2225913
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PubMed articles on: Cancer & VTE/PE
Anticoagulation for the Prevention of Arterial Thrombosis in Ambulatory Cancer Patients: Systematic Review and Meta-Analysis
JACC CardioOncol. 2023 Jun 27;5(4):520-532. doi: 10.1016/j.jaccao.2023.04.003. eCollection 2023 Aug.
ABSTRACT
BACKGROUND: The risk of arterial thrombotic events (ATEs) is high among patients on systemic anticancer therapies. Despite the efficacy of anticoagulants in the prevention of cancer-associated venous thromboembolism, it is unknown whether anticoagulation is effective to prevent ATEs.
OBJECTIVES: This study sought to examine the efficacy and safety of anticoagulants in ATE prevention among ambulatory cancer patients.
METHODS: We performed a systematic review using Medline, Embase, Scopus, and Cochrane Central Register of Controlled Trials (CENTRAL) from inception to May 21, 2022, and included studies comparing oral or parenteral anticoagulation with no anticoagulation among ambulatory patients receiving systemic anticancer therapy with no other indication for anticoagulation. The primary outcome was ATE (myocardial infarction, ischemic stroke, intra-abdominal arterial embolism, or peripheral artery occlusion). The secondary outcomes were major and nonmajor bleeding and all-cause mortality.
RESULTS: Fourteen randomized trials involving low-molecular-weight heparins, direct oral anticoagulants, and warfarin were included. ATEs were captured as coefficacy endpoints or adverse events. Anticoagulant use was not associated with a reduction in ATEs compared with placebo or standard treatment (RR: 0.73, 95% CI: 0.50-1.04; P =0.08; I2 = 0%). RRs of major and minor bleeding were 1.56 (95% CI: 1.12-2.17) and 2.25 (95% CI: 1.45-3.48) with anticoagulant use. In 13 trials that reported all-cause mortality, risk of death was not reduced with anticoagulants (RR: 0.99; 95% CI: 0.95-1.02; P =0.38; I2 = 0%).
CONCLUSIONS: Anticoagulants did not reduce ATE risk among ambulatory patients on systemic anticancer therapy and were associated with increased bleeding. Based on the current data, anticoagulants have a limited role in ATE prevention in this population as a whole.
PMID:37614584 | PMC:PMC10443118 | DOI:10.1016/j.jaccao.2023.04.003
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PubMed articles on: Cancer & VTE/PE
Physicians' assessment of complications after gynecological surgery in Sweden: The GYNCOM survey
Acta Obstet Gynecol Scand. 2023 Aug 23. doi: 10.1111/aogs.14661. Online ahead of print.
ABSTRACT
INTRODUCTION: Complications after gynecological surgery in Sweden are registered in the well-established Swedish National Quality Register of Gynecological Surgery, GynOp. The aim of this study was to analyze interrater reliability in assessing complications according to the methods in GynOp, and to explore physicians' perceptions of registering complications.
MATERIAL AND METHODS: A digital survey was sent to gynecologists and residents in gynecology in Sweden. Participating clinics were recruited through the Swedish network for national clinical studies in Obstetrics and Gynecology, SNAKS. Twenty fictional cases, intended to represent normal postoperative course, failure to cure, and varying degrees of complications, were developed by the research group. The clinical scenarios included abdominal and laparoscopic surgery of the uterus and adnexa, vaginal hysterectomies, as well as hysteroscopy. The respondents graded each case on the presence of a complication (yes/no). Type of complication, severity, and what action the complication required according to Clavien-Dindo was registered if a complication was acknowledged, according to the method in GynOp. Interrater reliability and the opinions of the respondents were presented descriptively. More than 80% of respondents making the same assessment was considered as agreement.
RESULTS: The response rate was 41%, with 104 responding physicians from 16 gynecological clinics. Type and severity of complication was considered relevant to register by 88% and 89% of respondents, respectively. Agreement on whether the case described a complication was >80% in 85% (17/20) of cases and agreement using the Clavien-Dindo classification was >90% in 80% (16/20) of cases. There was high agreement in assessments of classically severe complications, such as pulmonary embolism and ureteral damage, in both presence of complication and severity, as well as Clavien-Dindo (>90% for all methods). Cases with agreement <80%
CONCLUSIONS: This study provides validation for the methods used to register complications after gynecological surgery according to the GynOp register, including the use of Clavien-Dindo in gynecology. However, the results indicate a need to define what should be considered symptoms inherent to each type of surgery.
PMID:37614120 | DOI:10.1111/aogs.14661
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PubMed articles on: Cancer & VTE/PE
Tumor-associated thrombosis
Dtsch Med Wochenschr. 2023 Sep;148(17):1070-1074. doi: 10.1055/a-1941-7132. Epub 2023 Aug 23.
ABSTRACT
The evidence available today from randomized controlled trials shows that for many patients with CAT, direct FXa-inhibitors are a safer and potentially more effective therapy than long-term treatment with Low Molecular Weight Heparin (LMWH), which has been the gold standard. Oral therapy should be used with caution, particularly in the case of gastrointestinal or urothelial tumors, especially if the tumor is still in situ. Even with LMWH there is an increased risk of bleeding. Although no randomized studies are available yet, for selected stable patients, a dose reduction for secondary prophylaxis after 6 months can represent an alternative with a relatively low risk of bleeding - an individual benefit-risk assessment is essential. Incidental VTE are anticoagulated according to the guidelines according to the standard. A less intensive AK may be justifiable in individual cases.
PMID:37611569 | DOI:10.1055/a-1941-7132
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PubMed articles on: Cardio-Oncology
Role of echocardiography in patients treated with immune checkpoints inhibitors
J Echocardiogr. 2023 Aug 30. doi: 10.1007/s12574-023-00621-z. Online ahead of print.
ABSTRACT
Immune-related adverse events occurring in the heart (cardiac immune-related adverse events; irAEs) by immune checkpoint inhibitors (ICIs) include myocarditis, arrhythmia, conduction disturbance, pericardial diseases, and takotsubo cardiomyopathy. Cardiac irAEs are rare but life-threatening. In cardio-oncology, the study of cardiac disorders caused by cancer treatment has recently attracted attention, and such studies may elucidate the pathophysiology of cardiac irAEs and contribute to management strategies. This review discusses the pathogenic mechanisms underlying cardiac irAEs and the role of echocardiography in patients treated with ICIs.
PMID:37644319 | DOI:10.1007/s12574-023-00621-z
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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
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PubMed articles on: Cardio-Oncology
Non-pegylated liposomal doxorubicin in older adjuvant early breast cancer patients: cardiac safety analysis and final results of the COLTONE study
11:49
PubMed articles on: Cardio-Oncology
Global Effect of Modifiable Risk Factors on Cardiovascular Disease and Mortality
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PubMed articles on: Cardio-Oncology
Nanobiotechnology-based strategies in alleviation of chemotherapy-mediated cardiotoxicity
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PubMed articles on: Cardio-Oncology
In Vitro Evaluation of Ferutinin Rich-Ferula communis L., ssp. glauca, Root Extract on Doxorubicin-Induced Cardiotoxicity: Antioxidant Properties and Cell Cycle Modulation
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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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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.
ABSTRACT
BACKGROUND: Twenty percent of colorectal cancer liver metastases (CLMs) are initially resectable with a 5-year survival rate of 25%-40%. Perioperative folinic acid, 5-fluorouracil, oxaliplatin (FOLFOX) increases progression-free survival (PFS). In advanced disease, the addition of targeting therapies results in an overall survival (OS) advantage. The aim of this study was to evaluate panitumumab and FOLFIRI as perioperative therapy in resectable CLM.
METHODS: Patients with previously untreated, wild-type Rat sarcoma virus (RAS), and resectable CLM were included. Preoperative four and postoperative eight cycles of panitumumab and folinic acid, 5-fluorouracil, irinotecan (FOLFIRI) were administered. Primary objectives were efficacy and safety. Secondary endpoints included PFS and OS.
RESULTS: We enrolled 36 patients in seven centers in Austria (intention-to-treat analyses, 35 patients). There were 28 men and seven women, and the median age was 66 years. About 91.4% completed preoperative therapy and 82.9% underwent liver resection. The R0 resection rate was 82.7%. Twenty patients started and 12 patients completed postoperative chemotherapy. The objective radiological response rate after preoperative therapy was 65.7%. About 20% and 5.7% of patients had stable disease and progressive disease, respectively. The most common grade 3 adverse events were diarrhea, rash, and leukopenia during preoperative therapy. One patient died because of sepsis, and one had a pulmonary embolism grade 4. After surgery, two patients died because of hepatic failure. Most common grade 3 adverse events during postoperative therapy were skin toxicities/rash and leukopenia/neutropenia, and the two grade 4 adverse events were stroke and intestinal obstruction. Median PFS was 13.2 months. The OS rate at 12 and 24 months were 85.6% and 73.3%, respectively.
CONCLUSIONS: Panitumumab and FOLFIRI as perioperative therapy for resectable CLM result in a radiological objective response rate in 65.7% of patients with a manageable grade 3 diarrhea rate of 14.3%. Median PFS was 13.2 months, and the 24-month OS rate was 73.3%. These data are insufficient to widen the indication of panitumumab from the unresectable setting to the setting of resectable CLM.
PMID:37621684 | PMC:PMC10446765 | DOI:10.3389/fonc.2023.1231600
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PubMed articles on: Cancer & VTE/PE
Prediction of Venous Thromboembolism in Patients With Cancer Using Machine Learning Approaches: A Systematic Review and Meta-Analysis
JCO Clin Cancer Inform. 2023 Aug;7:e2300060. doi: 10.1200/CCI.23.00060.
ABSTRACT
PURPOSE: Recent studies have suggested that machine learning (ML) could be used to predict venous thromboembolism (VTE) in cancer patients with high accuracy.
METHODS: We aimed to evaluate the performance of ML in predicting VTE events in patients with cancer. PubMed, Web of Science, and EMBASE to identify studies were searched.
RESULTS: Seven studies involving 12,249 patients with cancer were included. The combined results of the different ML models demonstrated good accuracy in the prediction of VTE. In the training set, the global pooled sensitivity was 0.87, the global pooled specificity was 0.87, and the AUC was 0.91, and in the test set 0.65, 0.84, and 0.80, respectively.
CONCLUSION: The prediction ML models showed good performance to predict VTE. External validation to determine the result's reproducibility is necessary.
PMID:37616550 | DOI:10.1200/CCI.23.00060
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PubMed articles on: Cancer & VTE/PE
No evidence for a genetic causal effect of breast cancer on venous thromboembolism: a mendelian randomization study
J Thromb Thrombolysis. 2023 Aug 24. doi: 10.1007/s11239-023-02871-1. Online ahead of print.
ABSTRACT
Active cancer is known to contribute to venous thromboembolism (VTE), but the cause-and-effect association of breast cancer on VTE is not yet clear. In order to investigate the possible causal relationships, we used a Mendelian randomization analysis. Data for generically predicted breast cancer were identified based on the BCAC consortium. A meta-analysis of genome-wide association study (GWAS) comprising 1,500,861 participants for VTE as well as data from the FinnGen study for VTE, DVT and PE was used for the causal-effect estimation. Our primary method was inverse-variance weighted (IVW), and our supplementary methods included weighted median and MR-Egger. We also carried out sensitivity analysis for the study. No evidence of causal-effect was detected of overall breast cancer on VTE in both the GWAS meta-analysis (OR=1.01, 95%CI:0.98-1.04, p = 0.495) and the FinnGen consortium (OR=1.00,95%CI:0.96-1.04, p = 0.945). In addition, the presence of ER-positive or ER-negative disease did not significantly influence the incidence of VTE and its subtypes. In conclusion, no genetic cause-and-effect of breast cancer on VTE risk was detected in the large MR analysis.
PMID:37615800 | DOI:10.1007/s11239-023-02871-1
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PubMed articles on: Cancer & VTE/PE
Updated meta-analysis of randomized controlled trials on primary outpatient thromboprophylaxis in patients with gastric and gastroesophageal junction cancers receiving chemotherapy
Proc (Bayl Univ Med Cent). 2023 Jul 3;36(5):635-640. doi: 10.1080/08998280.2023.2225913. eCollection 2023.
ABSTRACT
Advanced gastric cancer is a highly thrombogenic cancer per Khorana score. Recent clinical practice guidelines suggest primary outpatient thromboprophylaxis (POTP) for patients with a Khorana score ≥2. We performed an updated meta-analysis to evaluate the benefit of POTP in patients with gastric cancer and gastroesophageal junction cancers receiving chemotherapy. Randomized controlled trials with reduction in venous thromboembolism (VTE) as a primary or secondary endpoint were incorporated. A total of 631 patients from subgroups of three randomized controlled trials were included. The VTE incidence was 1.6% and 5.1% in POTP and control groups, respectively (risk ratio 0.31; confidence interval 0.11 to 0.83; P= 0.02), with a number needed to treat of 29 to prevent one VTE event. Even though the recent clinical practice guidelines suggest POTP in patients with gastric cancer and gastroesophageal junction cancers, our meta-analysis findings do not support the routine use of POTP in those patients.
PMID:37614866 | PMC:PMC10443955 | DOI:10.1080/08998280.2023.2225913
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PubMed articles on: Cancer & VTE/PE
Anticoagulation for the Prevention of Arterial Thrombosis in Ambulatory Cancer Patients: Systematic Review and Meta-Analysis
JACC CardioOncol. 2023 Jun 27;5(4):520-532. doi: 10.1016/j.jaccao.2023.04.003. eCollection 2023 Aug.
ABSTRACT
BACKGROUND: The risk of arterial thrombotic events (ATEs) is high among patients on systemic anticancer therapies. Despite the efficacy of anticoagulants in the prevention of cancer-associated venous thromboembolism, it is unknown whether anticoagulation is effective to prevent ATEs.
OBJECTIVES: This study sought to examine the efficacy and safety of anticoagulants in ATE prevention among ambulatory cancer patients.
METHODS: We performed a systematic review using Medline, Embase, Scopus, and Cochrane Central Register of Controlled Trials (CENTRAL) from inception to May 21, 2022, and included studies comparing oral or parenteral anticoagulation with no anticoagulation among ambulatory patients receiving systemic anticancer therapy with no other indication for anticoagulation. The primary outcome was ATE (myocardial infarction, ischemic stroke, intra-abdominal arterial embolism, or peripheral artery occlusion). The secondary outcomes were major and nonmajor bleeding and all-cause mortality.
RESULTS: Fourteen randomized trials involving low-molecular-weight heparins, direct oral anticoagulants, and warfarin were included. ATEs were captured as coefficacy endpoints or adverse events. Anticoagulant use was not associated with a reduction in ATEs compared with placebo or standard treatment (RR: 0.73, 95% CI: 0.50-1.04; P =0.08; I2 = 0%). RRs of major and minor bleeding were 1.56 (95% CI: 1.12-2.17) and 2.25 (95% CI: 1.45-3.48) with anticoagulant use. In 13 trials that reported all-cause mortality, risk of death was not reduced with anticoagulants (RR: 0.99; 95% CI: 0.95-1.02; P =0.38; I2 = 0%).
CONCLUSIONS: Anticoagulants did not reduce ATE risk among ambulatory patients on systemic anticancer therapy and were associated with increased bleeding. Based on the current data, anticoagulants have a limited role in ATE prevention in this population as a whole.
PMID:37614584 | PMC:PMC10443118 | DOI:10.1016/j.jaccao.2023.04.003
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PubMed articles on: Cancer & VTE/PE
Physicians' assessment of complications after gynecological surgery in Sweden: The GYNCOM survey
Acta Obstet Gynecol Scand. 2023 Aug 23. doi: 10.1111/aogs.14661. Online ahead of print.
ABSTRACT
INTRODUCTION: Complications after gynecological surgery in Sweden are registered in the well-established Swedish National Quality Register of Gynecological Surgery, GynOp. The aim of this study was to analyze interrater reliability in assessing complications according to the methods in GynOp, and to explore physicians' perceptions of registering complications.
MATERIAL AND METHODS: A digital survey was sent to gynecologists and residents in gynecology in Sweden. Participating clinics were recruited through the Swedish network for national clinical studies in Obstetrics and Gynecology, SNAKS. Twenty fictional cases, intended to represent normal postoperative course, failure to cure, and varying degrees of complications, were developed by the research group. The clinical scenarios included abdominal and laparoscopic surgery of the uterus and adnexa, vaginal hysterectomies, as well as hysteroscopy. The respondents graded each case on the presence of a complication (yes/no). Type of complication, severity, and what action the complication required according to Clavien-Dindo was registered if a complication was acknowledged, according to the method in GynOp. Interrater reliability and the opinions of the respondents were presented descriptively. More than 80% of respondents making the same assessment was considered as agreement.
RESULTS: The response rate was 41%, with 104 responding physicians from 16 gynecological clinics. Type and severity of complication was considered relevant to register by 88% and 89% of respondents, respectively. Agreement on whether the case described a complication was >80% in 85% (17/20) of cases and agreement using the Clavien-Dindo classification was >90% in 80% (16/20) of cases. There was high agreement in assessments of classically severe complications, such as pulmonary embolism and ureteral damage, in both presence of complication and severity, as well as Clavien-Dindo (>90% for all methods). Cases with agreement <80%
CONCLUSIONS: This study provides validation for the methods used to register complications after gynecological surgery according to the GynOp register, including the use of Clavien-Dindo in gynecology. However, the results indicate a need to define what should be considered symptoms inherent to each type of surgery.
PMID:37614120 | DOI:10.1111/aogs.14661
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PubMed articles on: Cancer & VTE/PE
Tumor-associated thrombosis
Dtsch Med Wochenschr. 2023 Sep;148(17):1070-1074. doi: 10.1055/a-1941-7132. Epub 2023 Aug 23.
ABSTRACT
The evidence available today from randomized controlled trials shows that for many patients with CAT, direct FXa-inhibitors are a safer and potentially more effective therapy than long-term treatment with Low Molecular Weight Heparin (LMWH), which has been the gold standard. Oral therapy should be used with caution, particularly in the case of gastrointestinal or urothelial tumors, especially if the tumor is still in situ. Even with LMWH there is an increased risk of bleeding. Although no randomized studies are available yet, for selected stable patients, a dose reduction for secondary prophylaxis after 6 months can represent an alternative with a relatively low risk of bleeding - an individual benefit-risk assessment is essential. Incidental VTE are anticoagulated according to the guidelines according to the standard. A less intensive AK may be justifiable in individual cases.
PMID:37611569 | DOI:10.1055/a-1941-7132
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PubMed articles on: Cancer & VTE/PE
Hormone Therapy: Menopausal Hormone Therapy
FP Essent. 2023 Aug;531:15-21.
ABSTRACT
The marked decrease in estrogen levels in menopausal women can cause bothersome symptoms that affect daily life. More than 75% of women experience menopausal symptoms, which can include vaginal dryness, itching, discharge, dyspareunia, mood changes, hot flushes, and night sweats. Menopausal hormone therapy (MHT) is the most effective treatment for vasomotor symptoms. Benefits include decreased risk of osteoporotic fractures and vaginal atrophy, improved glycemic control, and decreased vasomotor symptoms. However, recent research on risks associated with MHT has shown increased risk of venous thromboembolism and breast cancer. MHT typically is an option for patients younger than 60 years or within 10 years of menopause onset with bothersome vasomotor symptoms. The decision to start MHT should be made on an individual basis after a thorough evaluation and counseling. Oral, intramuscular, transdermal, and intravaginal formulations are available. The goal of therapy is use of the lowest dose for the shortest time that effectively manages symptoms. The patient and physician should regularly assess the risks and benefits associated with MHT and ensure that the benefits of its use continue to outweigh the risks.
PMID:37603881
C
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PubMed articles on: Cardio-Oncology
Role of echocardiography in patients treated with immune checkpoints inhibitors
J Echocardiogr. 2023 Aug 30. doi: 10.1007/s12574-023-00621-z. Online ahead of print.
ABSTRACT
Immune-related adverse events occurring in the heart (cardiac immune-related adverse events; irAEs) by immune checkpoint inhibitors (ICIs) include myocarditis, arrhythmia, conduction disturbance, pericardial diseases, and takotsubo cardiomyopathy. Cardiac irAEs are rare but life-threatening. In cardio-oncology, the study of cardiac disorders caused by cancer treatment has recently attracted attention, and such studies may elucidate the pathophysiology of cardiac irAEs and contribute to management strategies. This review discusses the pathogenic mechanisms underlying cardiac irAEs and the role of echocardiography in patients treated with ICIs.
PMID:37644319 | DOI:10.1007/s12574-023-00621-z
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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.
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