High risk of thrombosis in patients with advanced lung cancer harboring rearrangements in ROS1

Muñoz-Unceta, Nerea; Zugazagoitia, Jon; Manzano, Aránzazu; Jiménez-Aguilar, Elisabeth; Olmedo, María Eugenia; Cacho, Juan Diego; Oliveira, J.; Dómine, Manuel; Ortega-Morán, Laura; Aguado, Carlos; Luna, A.M. Castro; Fernández, Lourdes; Pérez, Javier Martínez; Font, Carme; Coloma, Carmen Salvador; Corral, J.; Benítez, Gretel; Ros, S.; Biosca, Mercedes; Calvo, Virginia; Martínez, J.; Sánchez-Cánovas, Manuel; López, Rafael García-Foncillas; Sereno, María; Mielgo, Xabier; Aparisi, Francisco; Carmona, M.F. Ropero; Carrión, Rafael; Soares, Marta; Martínez-Salas, I. Arcas; García-Morillo, Marcial; Juan-Vidal, O.; Blasco, Ana; Muñoz, Andrés; Paz‐Ares, Luis

doi:10.1016/j.ejca.2020.10.002

Cited by 16 publications

(12 citation statements)

References 14 publications

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“…What are the clinical implications of the observations in this report for the management of ALK+ and ROS1+ NSCLC especially regarding the role of prophylactic anti-coagulation? Notably, all four studies from Australia [15], Italy [14], Spain/Portugal [17], and USA/China [11] on ROS1+ NSCLC did not show any survival difference between ROS1+ NSCLC patients who developed TE and those who did not. Due to the Fig.…”

Section: Discussionmentioning

confidence: 91%

“…Surprisingly, hypertension was associated with decreased risk of TTE in one study (OR = 0.52, p = 0.017) [11]. Lymph node metastases (OR = 2.29, p = 0.004), but not brain metastases, was associated significantly with increased TTE [11,17]. Indeed the cumulative incidence of brain metastases detected in ROS1+ NSCLC was lowest when compared to RET+ and ALK+ NSCLC [26].…”

Section: Discussionmentioning

confidence: 93%

“…Risk factors associated with increased TTE in ROS1+ NSCLC are mostly patient-related factors including low albumin (P = 0.015) [17], increased age (4% increased risk per year increase in age, p < 0.001) [11], and current smoking status (OR = 2.19, p= 0.016) [11]. Surprisingly, hypertension was associated with decreased risk of TTE in one study (OR = 0.52, p = 0.017) [11].…”

Section: Discussionmentioning

confidence: 99%

“…Recently, a number of publications have reported an additional 3-to 5-fold increase in risk of TE among both anaplastic lymphoma kinase rearranged (ALK+) and c-ros oncogene 1 rearranged (ROS1+) NSCLC [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18]. Most of the studies however had limited number of ALK+ or ROS1+ patients, and did not include a paired NSCLC control group for the calculation of the odds ratio (OR) [3,4,[7][8][9][10]15,17]. We performed this systematic review with meta-analysis and time-to-event analysis to more precisely estimate the additional increased risk (reported as OR or hazard ratio [HR]) of total thromboembolism (TTE) (venous thromboembolism [VTE] and arterial thromboembolism [ATE]) in ALK+ and ROS1+ NSCLC patients, the incidence rate of TE among ALK+ and ROS1+ NSCLC patients, and to review the risk factors potentially associated with increased TE in these patients.…”

Section: Introductionmentioning

confidence: 99%

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Thromboembolism in ALK+ and ROS1+ NSCLC patients: A systematic review and meta-analysis

et al. 2021

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Increased thromboembolism (TE) has been reported in ALK+ and ROS1+ non-small cell lung cancer (NSCLC). Materials and Methods: Odds ratios (OR) and hazard ratios (HR) of TE were calculated from meta-analysis and time-to-event analysis respectively for either ALK+ or ROS1+ NSCLC patients. Results: We identified eight studies (766 ALK+, 143 ROS1+, 2314 non-ALK+ and non-ROS1+ NSCLC patients) for the meta-analysis. For ALK+ NSCLC, the pooled OR was 2.00 (95% CI: 1.60-2.50) for total TE (TTE) by random-effects model, 2.10 (95% CI: 1.70-2.60) for venous thromboembolism (VTE), and 1.24 (95% CI: 0.80-1.91) for arterial thromboembolism (ATE). For ROS1+ NSCLC, the pooled OR was 3.08 (95% CI: 1.95-4.86) for TTE, and 3.15 (95% CI: 1.83-5.43) for VTE. Six studies (739 ALK+, 137 ROS1+, 561 EGFR+, 714 "wildtype" NSCLC patients) were included in the time-to-event analysis. The TTE incidence rate was 17.4 (95% CI: 15.3-19.5) per 100 pateint-years for ALK+ NSCLC, and 32.1 (95% CI: 24.6-39.6) per 100 patient-years for ROS1+ NSCLC with a 50 % cumulative incidence rate at year 3 of diagnosis. HR for TTE was 2.35 (95% CI: 1.90-2.92, p < 0.001) and 3.23 (95% CI: 2.40-4.34, p < 0.001) for ALK+ and ROS1+ NSCLC, respectively. Comparing ROS1+ NSCLC to ALK+ NSCLC, HR for TTE was 1.37 (95% CI: 1.05-1.79, p = 0.020). Conclusions: ALK+ and ROS1+ NSCLC patients had an increased risk of TE. ROS1+ NSCLC had further increased risk of TE over ALK+ NSCLC.

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Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Thromboembolism in ALK+ and ROS1+ NSCLC patients: A systematic review and meta-analysis

et al. 2021

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“…However, detailed information from several studies included confirmed the relatively higher risks of TE in NSCLC with ALK/ROS1 rearrangements regardless of the effects caused by treatments. When the timing of TE events was analyzed, 50%~59% of TE in ROS1 rearranged patients happened with naïve treatments ( 23 , 31 ), while 37% of VTE in patients with ALK rearrangements occurred when patients received no treatments ( 38 ). In a study comparing the risk of TE between EGFR mutant and ALK rearranged patients, the incidence of TE before using TKI and the incidence of TE in patients who have never used TKI in patients with ALK rearrangements were significantly higher than those in patients with EGFR mutations (50% vs 17.2%; 90.9% vs 21.2%, respectively).…”

Section: Discussionmentioning

confidence: 99%

Driver Genes Associated With the Incidence of Venous Thromboembolism in Patients With Non-Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis

Qian

Zheng

et al. 2021

Front. Oncol.

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BackgroundThe association between driver genes and the incidence of thromboembolic events (TEs) in patients diagnosed with non-small-cell lung cancer (NSCLC) needs to be quantified to guide clinical management.MethodsWe interrogated PubMed, Embase, Web of Science and Cochrane library databases for terms related to venous thromboembolism (VTE) and arterial thromboembolism (ATE) in patients diagnosed with non-small-cell lung cancer harboring driver genes. This search was conducted for studies published between 1 January, 2000 and 31 December, 2020. A random-effects meta-analysis was performed to analyze the pooled incidence and odds ratios of VTE in patients with different driver genes.ResultsOf the 2,742 citations identified, a total of 25 studies that included 21,156 patients met eligibility criteria. The overall pooled incidence of VTE in patients with driver genes was 23% (95% CI 18-29). Patients with ROS1 rearrangements had the highest incidence of VTE (37%, 95%CI 23-52). ALK rearrangements were associated with increased VTE risks (OR=2.08,95% CI 1.69-2.55), with the second highest incidence of VTE (27%, 95%CI 20-35). Both groups of patients with EGFR and KRAS mutations did not show a significantly increased risk for VTE (OR=1.33, 95% CI 0.75-2.34; OR=1.31, 95% CI 0.40-4.28).ConclusionsALK rearrangements were shown to be associated with increased VTE risks in patients diagnosed with non-small lung cancer, while there was no significant relation observed between VTE risks and EGFR or KRAS mutations in lung cancer patients.

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Ambulatory cancer patients: who should definitely receive antithrombotic prophylaxis and who should never receive

2023

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High risk of thrombosis in patients with advanced lung cancer harboring rearrangements in ROS1

Cited by 16 publications

References 14 publications

Thromboembolism in ALK+ and ROS1+ NSCLC patients: A systematic review and meta-analysis

Thromboembolism in ALK+ and ROS1+ NSCLC patients: A systematic review and meta-analysis

Driver Genes Associated With the Incidence of Venous Thromboembolism in Patients With Non-Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis

Ambulatory cancer patients: who should definitely receive antithrombotic prophylaxis and who should never receive

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