ABSTRACT

IMPORTANCE: In patients with cancer who have venous thromboembolism (VTE) events, long-term anticoagulation with low-molecular-weight heparin (LMWH) is recommended to prevent recurrent VTE. The effectiveness of a direct oral anticoagulant (DOAC) compared with LMWH for preventing recurrent VTE in patients with cancer is uncertain.

OBJECTIVE: To evaluate DOACs, compared with LMWH, for preventing recurrent VTE and for rates of bleeding in patients with cancer following an initial VTE event.

DESIGN, SETTING, AND PARTICIPANTS: Unblinded, comparative effectiveness, noninferiority randomized clinical trial conducted at 67 oncology practices in the US that enrolled 671 patients with cancer (any invasive solid tumor, lymphoma, multiple myeloma, or chronic lymphocytic leukemia) who had a new clinical or radiological diagnosis of VTE. Enrollment occurred from December 2016 to April 2020. Final follow-up was in November 2020.

INTERVENTION: Participants were randomized in a 1:1 ratio to either a DOAC (n = 335) or LMWH (n = 336) and were followed up for 6 months or until death. Physicians and patients selected any DOAC or any LMWH (or fondaparinux) and physicians selected drug doses.

MAIN OUTCOMES AND MEASURES: The primary outcome was the recurrent VTE rate at 6 months. Noninferiority of anticoagulation with a DOAC vs LMWH was defined by the upper limit of the 1-sided 95% CI for the difference of a DOAC relative to LMWH of less than 3% in the randomized cohort that received at least 1 dose of assigned treatment. The 6 prespecified secondary outcomes included major bleeding, which was assessed using a 2.5% noninferiority margin.

RESULTS: Between December 2016 and April 2020, 671 participants were randomized and 638 (95%) completed the trial (median age, 64 years; 353 women [55%]). Among those randomized to a DOAC, 330 received at least 1 dose. Among those randomized to LMWH, 308 received at least 1 dose. Rates of recurrent VTE were 6.1% in the DOAC group and 8.8% in the LMWH group (difference, -2.7%; 1-sided 95% CI, -100% to 0.7%) consistent with the prespecified noninferiority criterion. Of 6 prespecified secondary outcomes, none were statistically significant. Major bleeding occurred in 5.2% of participants in the DOAC group and 5.6% in the LMWH group (difference, -0.4%; 1-sided 95% CI, -100% to 2.5%) and did not meet the noninferiority criterion. Severe adverse events occurred in 33.8% of participants in the DOAC group and 35.1% in the LMWH group. The most common serious adverse events were anemia and death.

CONCLUSIONS AND RELEVANCE: Among adults with cancer and VTE, DOACs were noninferior to LMWH for preventing recurrent VTE over 6-month follow-up. These findings support use of a DOAC to prevent recurrent VTE in patients with cancer.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02744092.

PMID:37266947 | DOI:10.1001/jama.2023.7843

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PubMed articles on: Cancer & VTE/PE

Role of 18F-FDG PET/CT in the diagnosis of benign vs. malignant tumor thrombus

Nucl Med Commun. 2023 Jun 5. doi: 10.1097/MNM.0000000000001708. Online ahead of print.

ABSTRACT

PURPOSE: Hypercoagulable state is a complication of various infections, and inflammatory processes and is a common scenario in cancer patients also. Timely diagnosis and treatment are essential to reduce further complications in such patients. The present study aimed to assess the role of FDG PET/CT in the diagnosis of benign vs. malignant tumor thrombus and to determine cut-off SUVmax to differentiate them.

PATIENTS AND METHODS: We retrospectively reviewed all FDG PET/CT scans of patients done in our department from January 2017 to March 2022. All scans were reviewed by two experienced nuclear medicine physicians. A total of 135 patients who had venous or arterial thrombus in FDG PET/CT scans were included. All the FDG PET/CT scans of 135 patients were analyzed for primary tumor site and/or site of thrombus. Additional clinical data were collected for patients with benign conditions in the form of ESR and CRP if available and doubtful cases were followed up by HPE reports and/or CEMRI. The SUV max of the primary tumor(in cancer patients), thrombus, and background (aorta) were calculated.

RESULTS: A total of 135 patients (108 cancer patients and 27 with benign thrombus) were included with an age range of 3 to 86 years (median 50 years). There were 91 males and 44 females. Of 108 cancer patients, the most common cancers were hepatocellular cancer - 38 (35.18%), renal cell cancer - 28(25.92%), and carcinoma of the thyroid - 6 (5.55%). Of 108 cancer patients, 36 (33.33%) had tumor thrombosis in inferior vena cava, 31 (28.70%) in the portal vein, and 41 (37.96%) in other vessels (renal vein, jugular vein, etc.). Of 27 patients with benign conditions,13 had venous thrombi, 11 had arterial thrombus and three had atrial thrombus and the most common thrombus sites were thoraco-abdominal aorta in seven (25.92%) and right atrium in three (11.11%) patients. In the subgroup of 108 oncological patients, the mean SUV max of the primary tumors was 17.67 (range 2.1-91.0; median 10.82), thrombi were 17.61 (range 2.14-90.11; median 14.56) and background was 5.29 (range 0.29-25.00; median 3.12). Of 27 patients with benign conditions, the mean SUV max of the thrombi was 11.09 (range 1.98-31; median 8.10) and the background was 9.80 (range 1.46-24.50; median 10.20) The ESR was raised in 13 of 26 patients (mean 35.84, range 10.98-62.00, median 35.00) and CRP was raised 22 of 26 patients (mean11.46, range 3.45-24.50, median 20.40). Upon plotting the receiver operating curve, a cutoff SUV max of 12.7 with a sensitivity of 62.96% and specificity of 77.77% was produced to demarcate tumor thrombus from benign thrombus.

CONCLUSION: FDG PET/CT plays a significant role in the detection of thrombo-embolic disease and can differentiate benign thrombus from tumor thrombus.

PMID:37272295 | DOI:10.1097/MNM.0000000000001708

11:16

PubMed articles on: Cancer & VTE/PE

Pulmonary vein stenosis with pulmonary infarction secondary to primary mediastinal seminoma: a case report

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PubMed articles on: Cardio-Oncology

Oxaliplatin-induced cardiotoxicity in mice is connected to the changes in energy metabolism in the heart tissue

bioRxiv. 2023 May 25:2023.05.24.542198. doi: 10.1101/2023.05.24.542198. Preprint.

ABSTRACT

Oxaliplatin is a platinum-based alkylating chemotherapeutic agent used for cancer treatment. At high cumulative dosage, the negative effect of oxaliplatin on the heart becomes evident and is linked to a growing number of clinical reports. The aim of this study was to determine how chronic oxaliplatin treatment causes the changes in energy-related metabolic activity in the heart that leads to cardiotoxicity and heart damage in mice. C57BL/6 male mice were treated with a human equivalent dosage of intraperitoneal oxaliplatin (0 and 10 mg/kg) once a week for eight weeks. During the treatment, mice were followed for physiological parameters, ECG, histology and RNA sequencing of the heart. We identified that oxaliplatin induces strong changes in the heart and affects the heart's energy-related metabolic profile. Histological post-mortem evaluation identified focal myocardial necrosis infiltrated with a small number of associated neutrophils. Accumulated doses of oxaliplatin led to significant changes in gene expression related to energy related metabolic pathways including fatty acid (FA) oxidation, amino acid metabolism, glycolysis, electron transport chain, and NAD synthesis pathway. At high accumulative doses of oxaliplatin, the heart shifts its metabolism from FAs to glycolysis and increases lactate production. It also leads to strong overexpression of genes in NAD synthesis pathways such as Nmrk2. Changes in gene expression associated with energy metabolic pathways can be used to develop diagnostic methods to detect oxaliplatin-induced cardiotoxicity early on as well as therapy to compensate for the energy deficit in the heart to prevent heart damage.

SIGNIFICANCE STATEMENT: This study uncovers the detrimental impact of chronic oxaliplatin treatment on heart metabolism in mice, linking high accumulative dosages to cardiotoxicity and heart damage. By identifying significant changes in gene expression related to energy metabolic pathways, the findings pave the way for the development of diagnostic methods to detect oxaliplatin-induced cardiotoxicity at an early stage. Furthermore, these insights may inform the creation of therapies that compensate for the energy deficit in the heart, ultimately preventing heart damage and improving patient outcomes in cancer treatment.

PMID:37292714 | PMC:PMC10245950 | DOI:10.1101/2023.05.24.542198

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PubMed articles on: Cardio-Oncology

Performance of non-invasive tests and histology for the prediction of clinical outcomes in patients with non-alcoholic fatty liver disease: an individual participant data meta-analysis

Lancet Gastroenterol Hepatol. 2023 Jun 5:S2468-1253(23)00141-3. doi: 10.1016/S2468-1253(23)00141-3. Online ahead of print.