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      Identification of risk factors for venous thromboembolism and validation of the Khorana score in patients with advanced lung cancer: based on the multicenter, prospective Rising-VTE/NEJ037 study data

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          Abstract

          Background

          Management of cancer-associated venous thromboembolism (VTE) is essential in cancer treatment selection and prognosis. However, currently, no method exists for assessing VTE risk associated with advanced lung cancer. Therefore, we assessed VTE risk, including driver gene mutation, in advanced lung cancer and performed a Khorana score validation.

          Methods

          The Rising-VTE/NEJ037 study was a multicenter prospective observational study that included patients with advanced lung cancer. In the Rising-VTE/NEJ037 study, the Khorana score was calculated for enrolled patients with available data on all Khorana score components. The modified Khorana score was based on the body mass index of ≥ 25 kg/m 2, according to the Japanese obesity standard. A multivariate logistic regression analysis, including patient background characteristics, was performed to evaluate the presence of VTE 2 years after the lung cancer diagnosis.

          Results

          This study included 1008 patients with lung cancer, of whom 100 (9.9%) developed VTE. From the receiver operating characteristic curve analysis, VTE risk could not be determined because both the Khorana score (0.518) and modified Khorana score (0.516) showed very low areas under the curve. The risk factors for VTE in the multivariate analysis included female sex, adenocarcinoma, performance status, N factor, lymphocyte count, platelet count, prothrombin fragment 1 + 2 and diastolic blood pressure.

          Conclusion

          The Khorana score, which is widely used in cancer-VTE risk assessment, was less useful for Japanese patients with advanced lung cancer. Prothrombin fragment 1 + 2, a serum marker involved in coagulation, was more suitable for risk identification.

          Clinical trial information

          jRCTs061180025.

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          Most cited references30

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          Venous Thromboembolism Prophylaxis and Treatment in Patients With Cancer: ASCO Clinical Practice Guideline Update

          PURPOSE To provide updated recommendations about prophylaxis and treatment of venous thromboembolism (VTE) in patients with cancer. METHODS PubMed and the Cochrane Library were searched for randomized controlled trials (RCTs) and meta-analyses of RCTs published from August 1, 2014, through December 4, 2018. ASCO convened an Expert Panel to review the evidence and revise previous recommendations as needed. RESULTS The systematic review included 35 publications on VTE prophylaxis and treatment and 18 publications on VTE risk assessment. Two RCTs of direct oral anticoagulants (DOACs) for the treatment of VTE in patients with cancer reported that edoxaban and rivaroxaban are effective but are linked with a higher risk of bleeding compared with low-molecular-weight heparin (LMWH) in patients with GI and potentially genitourinary cancers. Two additional RCTs reported on DOACs for thromboprophylaxis in ambulatory patients with cancer at increased risk of VTE. RECOMMENDATIONS Changes to previous recommendations: Clinicians may offer thromboprophylaxis with apixaban, rivaroxaban, or LMWH to selected high-risk outpatients with cancer; rivaroxaban and edoxaban have been added as options for VTE treatment; patients with brain metastases are now addressed in the VTE treatment section; and the recommendation regarding long-term postoperative LMWH has been expanded. Re-affirmed recommendations: Most hospitalized patients with cancer and an acute medical condition require thromboprophylaxis throughout hospitalization. Thromboprophylaxis is not routinely recommended for all outpatients with cancer. Patients undergoing major cancer surgery should receive prophylaxis starting before surgery and continuing for at least 7 to 10 days. Patients with cancer should be periodically assessed for VTE risk, and oncology professionals should provide patient education about the signs and symptoms of VTE. Additional information is available at www.asco.org/supportive-care-guidelines .
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            Development and validation of a predictive model for chemotherapy-associated thrombosis.

            Risk of venous thromboembolism (VTE) is elevated in cancer, but individual risk factors cannot identify a sufficiently high-risk group of outpatients for thromboprophylaxis. We developed a simple model for predicting chemotherapy-associated VTE using baseline clinical and laboratory variables. The association of VTE with multiple variables was characterized in a derivation cohort of 2701 cancer outpatients from a prospective observational study. A risk model was derived and validated in an independent cohort of 1365 patients from the same study. Five predictive variables were identified in a multivariate model: site of cancer (2 points for very high-risk site, 1 point for high-risk site), platelet count of 350 x 10(9)/L or more, hemoglobin less than 100 g/L (10 g/dL) and/or use of erythropoiesis-stimulating agents, leukocyte count more than 11 x 10(9)/L, and body mass index of 35 kg/m(2) or more (1 point each). Rates of VTE in the derivation and validation cohorts, respectively, were 0.8% and 0.3% in low-risk (score = 0), 1.8% and 2% in intermediate-risk (score = 1-2), and 7.1% and 6.7% in high-risk (score >/= 3) category over a median of 2.5 months (C-statistic = 0.7 for both cohorts). This model can identify patients with a nearly 7% short-term risk of symptomatic VTE and may be used to select cancer outpatients for studies of thromboprophylaxis.
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              The IASLC Lung Cancer Staging Project: proposals for the revision of the TNM stage groupings in the forthcoming (seventh) edition of the TNM Classification of malignant tumours.

              The seventh edition of the TNM Classification of Malignant Tumors is due to be published early in 2009. In preparation for this, the International Association for the Study of Lung Cancer established its Lung Cancer Staging Project in 1998. The recommendations of this committee for changes to the T, N, and M descriptors have been published. This report contains the proposals for the new stage groupings. Data were contributed from 46 sources in more than 19 countries. Adequate data were available on 67,725 cases of non-small cell lung cancer treated by all modalities of care between 1990 and 2000. The recommendations for changes to the T, N, and M descriptors were incorporated into TNM subsets. Candidate stage groupings were developed on a training subset and tested in a validation subset. The suggestions include additional cutoffs for tumor size, with tumors >7 cm moving from T2 to T3; reassigning the category given to additional pulmonary nodules in some locations; and reclassifying pleural effusion as an M descriptor. In addition, it is suggested that T2b N0 M0 cases be moved from stage IB to stage IIA, T2a N1 M0 cases from stage IIB to stage IIA, and T4 N0-1 M0 cases from stage IIIB to stage IIIA. Such changes, if accepted, will involve a reassessment of existing treatment algorithms. However, they are based on an intensive and validated analysis of the largest database to date. The proposed changes would improve the alignment of TNM stage with prognosis and, in certain subsets, with treatment.
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                Author and article information

                Contributors
                ytsubata@med.shimane-u.ac.jp
                Journal
                Int J Clin Oncol
                Int J Clin Oncol
                International Journal of Clinical Oncology
                Springer Nature Singapore (Singapore )
                1341-9625
                1437-7772
                10 November 2022
                10 November 2022
                2023
                : 28
                : 1
                : 69-78
                Affiliations
                [1 ]GRID grid.411621.1, ISNI 0000 0000 8661 1590, Division of Medical Oncology and Respiratory Medicine, Department of Internal Medicine, , Shimane University Faculty of Medicine, ; 89-1 Enya-Cho, Izumo, Shimane 693-8501 Japan
                [2 ]GRID grid.414173.4, ISNI 0000 0000 9368 0105, Department of Respiratory Medicine, , Hiroshima Prefectural Hospital, ; 1-5-54 Ujina-Kanda, Minami-ku, Hiroshima, 734-8530 Japan
                [3 ]GRID grid.412764.2, ISNI 0000 0004 0372 3116, Division of Respiratory Medicine, Department of Internal Medicine, , St. Marianna University School of Medicine, ; 2-16-1 Sugao, Miyamae-ku, Kawasaki, Kanagawa 216-8511 Japan
                [4 ]GRID grid.415565.6, ISNI 0000 0001 0688 6269, Department of Respiratory Medicine, , Kurashiki Central Hospital, ; 1-1-1, Miwa, Kurashiki, Okayama 710-8602 Japan
                [5 ]GRID grid.69566.3a, ISNI 0000 0001 2248 6943, Department of Respiratory Medicine, , Tohoku University, ; 1-1 Seiryo-Machi, Aoba-ku, Sendai, Miyagi 980-8574 Japan
                [6 ]GRID grid.415501.4, Department of Pulmonary Medicine, , Sendai Kousei Hospital, ; 4-15 Hirose-Machi, Aoba-ku, Sendai, Miyagi 980-0873 Japan
                [7 ]GRID grid.470097.d, ISNI 0000 0004 0618 7953, Department of Respiratory Medicine, , Hiroshima University Hospital, ; 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8553 Japan
                [8 ]Department of Respiratory Medicine, Iwakuni Clinical Center, 1-1-1 Atago-Machi, Iwakuni, Yamaguchi 740-8510 Japan
                [9 ]GRID grid.413946.d, Department of Respiratory Medicine, , Asahi General Hospital, ; I-1326 Asahi, Chiba, 289-2511 Japan
                [10 ]GRID grid.440118.8, ISNI 0000 0004 0569 3483, Department of Respiratory Medicine, , National Hospital Organization, Kure Medical Center, ; 3-1 Aoyamacho, Kure, Hiroshima 737-0023 Japan
                [11 ]Department of Medical Oncology, Yamaguchi-Ube Medical Center, 685 Higashikawa, Ube, Yamaguchi 755-0241 Japan
                [12 ]GRID grid.414175.2, ISNI 0000 0004 1774 3177, Department of Respiratory Disease, , Hiroshima Red Cross Hospital and Atomic-Bomb Survivors Hospital, ; 1-9-6, Senda-Machi, Naka-ku, Hiroshima, 730-8619 Japan
                [13 ]GRID grid.278276.e, ISNI 0000 0001 0659 9825, Department of Respiratory Medicine and Allergology, , Kochi University Hospital, ; 185-1 Kohasu, Oko-Cho, Nankoku, Kochi 783-8505 Japan
                [14 ]GRID grid.412377.4, ISNI 0000 0004 0372 168X, Department of Pulmonary Medicine, , Saitama Medical University International Medical Center, ; 1397-1 Yamane, Hidaka, Saitama 350-1298 Japan
                Author information
                http://orcid.org/0000-0002-4260-2849
                Article
                2257
                10.1007/s10147-022-02257-y
                9823025
                36357710
                1815d7f1-921b-4a21-bdd5-f71092d230d1
                © The Author(s) 2022

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 15 May 2022
                : 16 October 2022
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100002336, Daiichi Sankyo Company;
                Award ID: LIX-MD-15003
                Award Recipient :
                Categories
                Original Article
                Custom metadata
                © The Author(s) under exclusive licence to Japan Society of Clinical Oncology 2023

                deep vein thrombosis,pulmonary thromboembolism,lung cancer,khorana score,prothrombin fragment 1 + 2

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