ABSTRACT

Background Surgery is a major transient risk factor for venous thromboembolism (VTE). However, the impact of major surgery as a VTE trigger has been scarcely investigated using a case-crossover design. Aim To investigate the role of major surgery as a trigger for incident VTE in a population-based case-crossover study while adjusting for other concomitant VTE triggers. Methods We conducted a case-crossover study with 531 cancer-free VTE cases derived from the Tromsø Study cohort. Triggers were registered during the 90 days before a VTE event (hazard period) and in four preceding 90-day control periods. Conditional logistic regression was used to estimate odds ratios (ORs) with 95% confidence intervals (CIs) for VTE according to major surgery and after adjustment for other VTE triggers. Results Surgery was registered in 85 of the 531 (16.0%) hazard periods and in 38 of the 2,124 (1.8%) control periods, yielding an OR for VTE of 11.40 (95% CI: 7.42-17.51). The OR decreased to 4.10 (95% CI: 2.40-6.94) after adjustment for immobilization and infection and was further attenuated to 3.31 (95% CI: 1.83-5.96) when additionally adjusted for trauma, blood transfusion, and central venous catheter. In a mediation analysis, 51.4% (95% CI: 35.5-79.7%) of the effect of surgery on VTE risk could be mediated through immobilization and infection. Conclusions Major surgery was a trigger for VTE, but the association between surgery and VTE risk was in part explained by other VTE triggers often coexisting with surgery, particularly immobilization and infection.

PMID:37736074 | PMC:PMC10511275 | DOI:10.1055/a-2159-9957

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PubMed articles on: Cancer & VTE/PE

Trimodality therapy versus perioperative chemotherapy in the management of locally advanced adenocarcinoma of the oesophagus and oesophagogastric junction (Neo-AEGIS): an open-label, randomised, phase 3 trial

Lancet Gastroenterol Hepatol. 2023 Sep 18:S2468-1253(23)00243-1. doi: 10.1016/S2468-1253(23)00243-1. Online ahead of print. ABSTRACT

BACKGROUND: The optimum curative approach to adenocarcinoma of the oesophagus and oesophagogastric junction is unknown. We aimed to compare trimodality therapy (preoperative radiotherapy with carboplatin plus paclitaxel [CROSS regimen]) with optimum contemporaneous perioperative chemotherapy regimens (epirubicin plus cisplatin or oxaliplatin plus fluorouracil or capecitabine [a modified MAGIC regimen] before 2018 and fluorouracil, leucovorin, oxaliplatin, and docetaxel [FLOT] subsequently).

METHODS: Neo-AEGIS (CTRIAL-IE 10-14) was an open-label, randomised, phase 3 trial done at 24 centres in Europe. Patients aged 18 years or older with clinical tumour stage T2-3, nodal stage N0-3, and M0 adenocarcinoma of the oesophagus and oesophagogastric junction were randomly assigned to perioperative chemotherapy (three preoperative and three postoperative 3-week cycles of intravenous 50 mg/m2 epirubicin on day 1 plus intravenous 60 mg/m2 cisplatin or intravenous 130 mg/m2 oxaliplatin on day 1 plus continuous infusion of 200 mg/m2 fluorouracil daily or oral 625 mg/m2 capecitabine twice daily up to 2018, with four preoperative and four postoperative 2-week cycles of 2600 mg/m2 fluorouracil, 85 mg/m2 oxaliplatin, 200 mg/m2 leucovorin, and 50 mg/m2 docetaxel intravenously on day 1 as an option from 2018) or trimodality therapy (41·4 Gy in 23 fractions on days 1-5, 8-12, 15-19, 22-26, and 29-31 with intravenous area under the curve 2 mg/mL per min carboplatin plus intravenous 50 mg/m2 paclitaxel on days 1, 8, 15, 22, and 29). The primary endpoint was overall survival, assessed in all randomly assigned patients who received at least one dose of study drug, regardless of which study drug they received, by intention to treat. Secondary endpoints were disease-free survival, site of treatment failure, operative complications, toxicity, pathological response (complete [ypT0N0] and major [tumour regression grade 1 and 2]), margin-free resection (R0), and health-related quality of life. Toxicity and safety data were analysed in the safety population, defined as patients who took at least one dose of study drug, according to treatment actually received. The initial power calculation was based on superiority of trimodality therapy (n=366 patients); it was adjusted after FLOT became an option to a non-inferiority design with a margin of 5% for perioperative chemotherapy (n=540). This study is registered with ClinicalTrials.gov, NCT01726452.

FINDINGS: Between Jan 24, 2013, and Dec 23, 2020, 377 patients were randomly assigned, of whom 362 were included in the intention-to treat population (327 [90%] male and 360 [99%] White): 184 in the perioperative chemotherapy group and 178 in the trimodality therapy group. The trial closed prematurely in December, 2020, after the second interim futility analysis (143 deaths), on the basis of similar survival metrics and the impact of the COVID-19 pandemic. At a median follow-up of 38·8 months (IQR 16·3-55·1), median overall survival was 48·0 months (95% CI 33·6-64·8) in the perioperative chemotherapy group and 49·2 months (34·8-74·4) in the trimodality therapy group (3-year overall survival 55% [95% CI 47-62] vs 57% [49-64]; hazard ratio 1·03 [95% CI 0·77-1·38]; log-rank p=0·82). Median disease-free survival was 32·4 months (95% CI 22·8-64·8) in the perioperative chemotherapy group and 24·0 months (18·0-40·8) in the trimodality therapy group[...]

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PubMed articles on: Cancer & VTE/PE

The risk of recurrent venous thromboembolism after discontinuation of anticoagulant therapy in patients with cancer-associated thrombosis: a systematic review and meta-analysis

EClinicalMedicine. 2023 Sep 8;64:102194. doi: 10.1016/j.eclinm.2023.102194. eCollection 2023 Oct.

ABSTRACT

BACKGROUND: The optimal duration of anticoagulation in patients with active cancer and venous thromboembolism (VTE) is unknown. Current clinical guidelines advocate anticoagulant therapy for 3-6 months and to continue anticoagulant therapy for as long as the cancer is active. However, an adequate systematic review on the rate of recurrent VTE after discontinuation of anticoagulant therapy has not been performed.

METHODS: For this systemic review and meta-analysis, we searched Embase.com, Medline (Ovid), Web of Science, Cochrane Library, and Google Scholar, from database inception to February 16, 2023, for studies on anticoagulant therapy in patients with cancer and the recurrence of venous thromboembolism after discontinuation of this therapy. We included randomised controlled trials and cohort studies published in English that reported on patients who met the following: cancer and a first VTE, completed at least 3 months of anticoagulant therapy, were followed after discontinuation of anticoagulant therapy, and with symptomatic recurrent VTE as an outcome during follow-up. Study-level data were requested from study authors. The primary outcome was the rate of recurrent VTE after discontinuation of anticoagulant therapy. A Bayesian random-effects meta-analysis was used to estimate the rate of recurrent VTE per 100 person-years for the pooled studies at different time intervals after discontinuation of anticoagulation therapy. We also calculated the cumulative VTE recurrence rate at different time intervals. Forest plots were mapped and the results were summarized by the median and 95% credible interval (CIs). This study was registered with PROSPERO, CRD42021249060.

FINDINGS: Of 3856 studies identified in our search, 33 studies were identified for inclusion. After requesting study-level data, 14 studies involving 1922 patients with cancer-associated thrombosis were included. The pooled rate of recurrent VTE per 100 person-years after discontinuation of anticoagulant therapy was 14.6 events (95% credible interval 6.5-22.8) in the first three months, decreasing to 1.1 events (95% CI 0.3-2.1) in year 2-3, and 2.2 events (95% CI 0.0-4.4) in year 3-5 after discontinuation of anticoagulant therapy. The cumulative VTE recurrence rate was 28.3% (95% CI 15.6-39.6%) at 1 year; 31.1% (95% CI 16.5-43.8%) at 2 years; 31.9% (95% CI 16.8-45.0%) at 3 years; and 35.0% (95% CI 16.8-47.4%) at 5 years after discontinuation of anticoagulant therapy.

INTERPRETATION: This meta-analysis demonstrates a high rate of recurrent VTE over time after discontinuation of anticoagulant therapy in patients with cancer-associated thrombosis. Our results support the current clinical guidelines to continue anticoagulant therapy in patients with active cancer.

FUNDING: Erasmus MC.

PMID:37731937 | PMC:PMC10507196 | DOI:10.1016/j.eclinm.2023.102194

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[hazard ratio 0·89 [95% CI 0·68-1·17]; log-rank p=0·41). The pattern of recurrence, locoregional or systemic, was not significantly different (odds ratio 1·35 [95% CI 0·63-2·91], p=0·44). Pathological complete response (odds ratio 0·33 [95% CI 0·14-0·81], p=0·012), major pathological response (0·21 [0·12-0·38], p<0·0001),

INTERPRETATION: Although underpowered and incomplete, Neo-AEGIS provides the largest comprehensive randomised dataset for patients with adenocarcinoma of the oesophagus and oesophagogastric junction treated with perioperative chemotherapy (predominantly the modified MAGIC regimen), and CROSS trimodality therapy, and reports similar 3-year survival and no major differences in operative and health-related quality of life outcomes. We suggest that these data support continued clinical equipoise.

FUNDING: Health Research Board, Cancer Research UK, Irish Cancer Society, Oesophageal Cancer Fund, and French National Cancer Institute.

PMID:37734399 | DOI:10.1016/S2468-1253(23)00243-1

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PubMed articles on: Cardio-Oncology

Papillary Adenocarcinoma: A Rare Subtype of Lung Adenocarcinoma

Cureus. 2023 Sep 7;15(9):e44838. doi: 10.7759/cureus.44838. eCollection 2023 Sep.