ALK/ROS1 rearrangements: A real hallmark for thromboembolic events in cancer patients?

Nichetti, Federico; Russo, Giuseppe Lo; Prelaj, Arsela; Provenzano, Leonardo; Braud, Filippo de; Cabiddu, Mary; Garassino, Marina Chiara; Petrelli, Fausto

doi:10.1016/j.thromres.2020.06.041

Cited by 7 publications

(4 citation statements)

References 6 publications

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“…Given our data, we hypothesize that low albumin and high LDH and CRP serve as markers of cancer-related systemic inflammation and cachexia, resulting also in a greater hypercoagulable state in these patients. In this light, TEs occur as manifestations of disease progression in patients with advanced and uncontrolled tumors 27 . This hypothesis is further supported by the evidence that patients experiencing TEs had significantly poorer survival.…”

Section: Discussionmentioning

confidence: 99%

Risk assessment of thromboembolic events in hospitalized cancer patients

Nichetti

Ligorio

Montelatici

et al. 2021

Sci Rep

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Hospitalized cancer patients are at increased risk for Thromboembolic Events (TEs). As untailored thromboprophylaxis is associated with hemorrhagic complications, the definition of a risk-assessment model (RAM) in this population is needed. INDICATE was a prospective observational study enrolling hospitalized cancer patients, with the primary objective of assessing the Negative Predictive Value (NPV) for TEs during hospitalization and within 45 days from discharge of low-grade Khorana Score (KS = 0). Secondary objectives were to assess KS Positive Predictive Value (PPV), the impact of TEs on survival and the development of a new RAM. Assuming 7% of TEs in KS = 0 patients as unsatisfactory percentage and 3% of as satisfactory, 149 patients were needed to detect the favorable NPV with one-sided α = 0.10 and power = 0.80. Stepwise logistic regression was adopted to identify variables included in a new RAM. Among 535 enrolled patients, 153 (28.6%) had a KS = 0. The primary study objective was met: 29 (5.4%) TEs were diagnosed, with 7 (4.6%) cases in the KS = 0 group (NPV = 95.4%, 95% CI 90.8–98.1%; one-sided p = 0.084). However, the PPV was low (5.7%, 95% CI 1.9–12.8%); a new RAM based on albumin (OR 0.34, p = 0.003), log(LDH) (OR 1.89, p = 0.023) and presence of vascular compression (OR 5.32, p < 0.001) was developed and internally validated. Also, TEs were associated with poorer OS (median, 5.7 vs 24.8 months, p < 0.001). INDICATE showed that the KS has a good NPV but poor PPV for TEs in hospitalized cancer patients. A new RAM was developed, and deserves further assessment in external cohorts.

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Section: Discussionmentioning

confidence: 99%

Risk assessment of thromboembolic events in hospitalized cancer patients

Nichetti

Ligorio

Montelatici

et al. 2021

Sci Rep

Self Cite

View full text Add to dashboard Cite

show abstract

“…Given our data, we hypothesize that low albumin and high LDH and CRP serve as markers of cancer-related systemic in ammation and cachexia, resulting also in a greater hypercoagulable state in these patients. In this light, TEs occur as a manifestation of disease progression in patients with advanced and uncontrolled tumors [27]. This hypothesis is further supported by the evidence that patients experiencing TEs had signi cantly poorer survival.…”

Section: Discussionmentioning

confidence: 78%

Finding a rIsk assessmeNt moDel for thromboembolic events in hospItalized Cancer pATiEnts: the INDICATE study running title: thromboembolism in hospitalized cancer patients

Nichetti

Ligorio

Montelatici

et al. 2021

Preprint

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Background: Hospitalized cancer patients are at increased risk for Thromboembolic Events (TEs). As untailored thromboprophylaxis is associated with hemorrhagic complications, the definition of a risk-assessment model (RAM) in this population is needed. Objectives: INDICATE was an observational study enrolling hospitalized cancer patients, with the primary objective of assessing the Negative Predictive Value (NPV) for TEs during hospitalization and within 45 days from discharge of low-grade Khorana Score (KS=0). Secondary objectives were to assess KS Positive Predictive Value (PPV), the impact of TEs on survival and the development of a new RAM. Materials and Methods: Assuming 7% of TEs in KS=0 patients as unsatisfactory percentage and 3% of as satisfactory, 149 patients were needed to detect the favorable NPV with one-sided a= 0.10 and power=0.80. Stepwise logistic regression was adopted to identify variables included in a new RAM.Results: Among 535 enrolled patients, 153 (28.6%) had a KS=0. The primary study objective was met: 29 (5.4%) TEs were diagnosed, with 7 (4.6%) cases in the KS=0 group (NPV=95.4%, 95%CI: 90.8-98.1%; one-sided p=0.084). However, the PPV was low (5.7%, 95%CI: 1.9-12.8%); a new RAM based on albumin (OR 0.34, p=0.003), log(LDH) (OR 1.89, p=0.023) and presence of vascular compression (OR 5.32, p<.001) was developed and internally validated. Also, TEs were associated with poorer OS (median, 5.7 vs 24.8 months, p <.001).Conclusion: INDICATE showed that the KS has a good NPV but poor PPV for TEs in hospitalized cancer patients. A new RAM was developed, and deserves further assessment in external cohorts.

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“…This result suggests that the thrombotic predisposition of ALK rearrangement may be related to the gene alteration and derived kinase activity ( 32 ). In addition, a recent meta-analysis indicated that TKIs treating NSCLC with ALK/ROS1 rearrangements did not significantly increase the VTE risk compared with platinum-based chemotherapy by analyzing 6 randomized control studies ( 44 ). All the evidence supports that ALK/ROS1 rearrangements are associated with increased TE risks.…”

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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ALK/ROS1 rearrangements: A real hallmark for thromboembolic events in cancer patients?

Cited by 7 publications

References 6 publications

Risk assessment of thromboembolic events in hospitalized cancer patients

Risk assessment of thromboembolic events in hospitalized cancer patients

Finding a rIsk assessmeNt moDel for thromboembolic events in hospItalized Cancer pATiEnts: the INDICATE study running title: thromboembolism in hospitalized cancer patients

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

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