Venous thromboembolism during preoperative chemotherapy in the CRITICS gastric cancer trial

Astrid E Slagter, Karolina Sikorska, Cecile Grootscholten, Hanneke W M van Laarhoven, Pehr Lind, Marianne Nordsmark, Elma Meershoek-Klein Kranenbarg, Cornelis J H van de Velde, Nicole C T van Grieken, Johanna W van Sandick, Edwin P M Jansen, Marcel Verheij, Annemieke Cats, Astrid E Slagter, Karolina Sikorska, Cecile Grootscholten, Hanneke W M van Laarhoven, Pehr Lind, Marianne Nordsmark, Elma Meershoek-Klein Kranenbarg, Cornelis J H van de Velde, Nicole C T van Grieken, Johanna W van Sandick, Edwin P M Jansen, Marcel Verheij, Annemieke Cats

Abstract

Background: The occurrence of a venous thromboembolism (VTE) is common in patients with cancer. Gastric cancer has been associated with one of the highest risks for VTE. Chemotherapy, especially cisplatin has been associated with a high VTE risk. In this study, risk factors for VTE occurrence and their potential impact on subsequent therapeutic interventions were investigated in patients who underwent preoperative chemotherapy, in the CRITICS gastric cancer trial.

Patients and methods: Patients with resectable gastric cancer were preoperatively treated with three cycles of 3-weekly epirubicin, cisplatin or oxaliplatin, and capecitabine (ECC/EOC). VTE was defined as any thrombus in the venous system, excluding superficial and/or device related VTEs. Potential risk factors were analyzed in a multivariable regression model with age, gender, Body Mass Index (BMI), tumor localization, Lauren classification, type of chemotherapy (ECC/EOC), (cardiovascular) comorbidity, and previous VTE as independent risk factors. The impact of VTE on completion rate of preoperative chemotherapy, surgical resection rate, postoperative complications, and start of postoperative therapy were investigated.

Results: Of 781 patients, 78 (10%) of 781 patients developed a VTE during preoperative chemotherapy. On multivariable analysis, BMI ≥ 30 kg/m2 and previous VTE were associated with VTE occurrence (reference BMI < 25 kg/m2 ; OR 2.190; 95% CI 1.152-4.164; P = .017/previous VTE; OR 3.617; 95% CI 1.201-10.890; P = .022). Treatment with cisplatin was, compared to oxaliplatin, not significantly associated with VTE occurrence (OR 1.535; 95% CI 0.761-3.094; P = .231). VTE occurrence did not affect completion of preoperative chemotherapy, surgical resection rate, postoperative complications, or start of postoperative therapy.

Conclusion: High BMI and previous VTE were independent risk factors for VTE occurrence during preoperative chemotherapy in patients with resectable gastric cancer. VTE occurrence in the preoperative setting did not affect receipt of further treatment.

Trial registration: ClinicalTrials.gov NCT00407186.

Keywords: cancer-associated thrombosis; gastrectomy; gastric cancer; preoperative chemotherapy; venous thromboembolism.

Conflict of interest statement

HWM van Laarhoven reported receiving grants/medication support from Bayer, BMS, Celgene, Janssen, Lilly, Nordic Pharma, Philips, Roche, Servier, and serving on an advisory board for BMS, Lilly, MSD, Nordic Pharma, Novartis, Servier. NCT van Grieken reported receiving grants from the Dutch Cancer Society and The Netherlands Organization for Health Research and Development, and serving on an advisory board for Bristol‐Myers Squibb and Merck Sharp & Dohme. EPM Jansen, A. Cats and M. Verheij reported receiving grants from the Dutch Cancer Society, the Dutch Colorectal Cancer Group and Hoffmann La Roche. All remaining authors have declared no conflict of interest.

© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

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