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

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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PubMed articles on: Cancer & VTE/PE

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: Cardio-Oncology

Baseline Troponin Level and Cardiac Toxicity in HER2-positive Early Breast Cancer Patients Receiving Trastuzumab

In Vivo. 2023 Sep-Oct;37(5):2139-2146. doi: 10.21873/invivo.13311.

ABSTRACT

BACKGROUND/AIM: There is controversy around the use of high-sensitive troponin T (hs-TnT) as an early biomarker of cardiac toxicity in patients with breast cancer on trastuzumab (T).

PATIENTS AND METHODS: Patients receiving adjuvant or neo-adjuvant T for early HER2-positive breast cancer were prospectively included. Transthoracic echocardiograms and matched hs-TnT before T and at 3, 6, and 9 months were performed on all patients. Congestive heart failure, cardiac death, a decline in left ventricular ejection fraction (LVEF) of more than 10% from baseline even if it is still within the normal range, or a drop in LVEF below 55% were all considered signs of cardiac toxicity.

RESULTS: In total, 24 patients (median age: 57; range=39-79 years) were enrolled. Anthracyclines were administered to all patients but three as part of neo/adjuvant treatment before T. Cardiovascular toxicity was observed in 3 out of 24 (12.5%) patients: two non-symptomatic LVEF declines (8.3%) and one heart failure episode (4.2%). In the entire population, the mean baseline hs-TnT level was 10.1±8.8 pg/ml, and after 3, 6, and 12 months, no appreciable change was observed. Patients with cardiac toxicity had mean hs-TnT levels higher than those without (18.3±12.3 vs. 8.2±7.2 pg/ml; p=0.049). A definite trend was evident in the chi-square test (chi2=3.52; p=0.06).

CONCLUSION: In anthracycline-exposed patients with early breast cancer, hs-TnT may be able to identify those at risk of developing cardiac toxicity during neo/adjuvant T treatment.

PMID:37652487 | DOI:10.21873/invivo.13311

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PubMed articles on: Cardio-Oncology

A framework for assessing the impact of cardiac and respiratory motion for STereotactic Arrhythmia Radioablation (STAR) using a digital phantom with a 17-segment model - A STOPSTORM.eu consortium study

Int J Radiat Oncol Biol Phys. 2023 Aug 29:S0360-3016(23)07853-7. doi: 10.1016/j.ijrobp.2023.08.059. Online ahead of print.

ABSTRACT

The optimal motion management strategy for patients receiving stereotactic arrhythmia radioablation (STAR) for the treatment of ventricular tachycardia (VT) is not fully known. We developed a framework using a digital phantom to simulate cardiorespiratory motion in combination with different motion management strategies to gain insight into the impact of cardiorespiratory motion on STAR. The 4D XCAT phantom was expanded with the 17-segment left ventricular (LV) model which allowed placement of STAR targets in standardized ventricular regions. Cardiac- and respiratory-binned 4D-CT scans were simulated for free-breathing, reduced free-breathing, respiratory-gating, and breath-hold scenarios. Respiratory motion of the heart was set to population-averaged values of VT patients: 6, 2, and 1 mm in the Superior-Inferior, Posterior-Anterior, and Left-Right direction, respectively. Cardiac contraction was adjusted by reducing LV ejection fraction to 35%. Target displacement was evaluated for all segments using envelopes encompassing the cardiorespiratory motion. Envelopes incorporating only the diastole plus respiratory motion were created to simulate the scenario where cardiac motion is not fully captured on 4D-respiratory CT scans used for radiotherapy planning. The average volume of the 17 segments was 6 cm3 (1-9 cm3). Cardiac contraction-relaxation resulted in maximum segment (centroid) motion of 4, 6, and 3.5 mm in Superior-Inferior, Posterior-Anterior, and Left-Right direction, respectively. Cardiac contraction-relaxation resulted in a motion envelope increase of 49% (24-79%) compared to individual segment volumes, whereas envelopes increased by 126% (79-167%) if also respiratory motion was considered. Envelopes incorporating only the diastole and respiration motion covered on average 68-75% of the motion envelope. The developed LV-segmental XCAT framework showed that free-wall regions display the most cardiorespiratory displacement. Our framework supports the optimization of STAR by evaluating the impact of (cardio)respiratory motion and motion management strategies for VT patients.

PMID:37652302 | DOI:10.1016/j.ijrobp.2023.08.059

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PubMed articles on: Cardio-Oncology

Circulating microRNAs and cytokines as prognostic biomarkers for doxorubicin-induced cardiac injury and for evaluating the effectiveness of an exercise intervention

Clin Cancer Res. 2023 Aug 31. doi: 10.1158/1078-0432.CCR-23-1055. Online ahead of print.

ABSTRACT

PURPOSE: To define a set of biomarkers that can be used to identify patients at high risk of developing late DOX-induced cardiac morbidity with the goal of focused monitoring and early interventions.

EXPERIMENTAL DESIGN: Mice received phosphate buffered saline or DOX 2.5 mg/kg 2x/week for 2 weeks. Blood samples were obtained before and after therapy for quantification of miRNAs (6 and 24 h), cytokines (24 h), and troponin (24 h, 4 and 6weeks). Cardiac function was evaluated using echocardiography before and 24 h after therapy. To assess the effectiveness of exercise intervention in preventing DOX-induced cardiotoxicity blood samples were collected from mice treated with DOX or DOX + exercise. Plasma samples from 13 DOX-treated sarcoma patients were also evaluated before and 24 h after therapy.

RESULTS: Elevations in in plasma miRNA-1, miRNA-499 and IL-1α, IL-1β, and IL-6 were seen in DOX-treated in mice with decreased ejection fraction and fractional shortening 24 h after DOX therapy. Troponin levels were not elevated until 4 weeks after therapy. In mice treated with exercise during Dox there was no elevation in these biomarkers and no change in cardiac function. Elevations in these biomarkers were seen in 12 of 13 sarcoma patients treated with Dox.

CONCLUSIONS: These findings define a potential set of biomarkers to identify and predict patients at risk for developing acute and late cardiovascular diseases with the goal of focused monitoring and early intervention. Further studies are needed to confirm the predictive value of these biomarkers in late cardiotoxicity.

PMID:37651264 | DOI:10.1158/1078-0432.CCR-23-1055

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PubMed articles on: Cardio-Oncology

Case Report: Replacement of PD-1 inhibitors with PD-L1 inhibitors in the treatment of squamous non-small-cell lung carcinoma

Front Immunol. 2023 Aug 15;14:1243980. doi: 10.3389/fimmu.2023.1243980. eCollection 2023.

ABSTRACT

BACKGROUND: Immune checkpoint inhibitor (ICI)-associated cardiotoxicity is a relatively uncommon immune-related adverse effects (irAEs) with a high mortality rate. There are few recommendations for the replacement of different immune checkpoint inhibitors in domestic and international reports.

CASE PRESENTATION: We report a case of a patient with squamous non-small cell lung carcinoma (squamous NSCLC) who developed cardiotoxicity after being treated with a programmed death-1 (PD-1) inhibitor and then changed to a PD-L1 inhibitor to continue the treatment. A significant benefit was observed after four cycles of immunotherapy, and no further cardiotoxicity occurred after the treatment was started.

CONCLUSION: This case demonstrates that myocardial damage induced by tislelizumab (PD-1 inhibitor) can be improved after switching to sugemalimab (PD-L1 inhibitor) and that antitumor immunotherapy is effective. This result may have important implications for optimizing immunotherapy management regimens in cancer patients.

PMID:37649479 | PMC:PMC10465174 | DOI:10.3389/fimmu.2023.1243980

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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

Anti-breast cancer-induced cardiomyopathy: Mechanisms and future directions

Biomed Pharmacother. 2023 Aug 28;166:115373. doi: 10.1016/j.biopha.2023.115373. Online ahead of print.