Association between Radiotherapy and Risk of Cancer Associated Venous Thromboembolism: A Sub-Analysis of the COMPASS—CAT Study

Abstract

Background: The role and effect of radiotherapy in the development of VTE has not been extensively explored; Methods: This is a post-hoc analysis from the COMPASS-CAT trial. Patients with breast, lung, colon or ovarian cancer, with early, locally advanced or metastatic disease and receiving chemotherapy were included. Primary endpoint was documented symptomatic VTE; Results: A total of 1355 patients were enrolled between November 2013 and November 2015. Of those, 194 patients were excluded because of missing data or the use of anticoagulation. Of the evaluable patients, 361 patients received radiotherapy (33.6%) At a median follow up of 6 months, 9.1% (n = 33) of patients receiving radiotherapy developed a VTE event (excluding those with missing data on follow up). After applying the competing risk model, radiotherapy remained significantly associated with increased risk for VTE (HR 2.47, 95% CI: 1.47–4.12, p = 0.001). Stratification analysis for the cohort that received radiotherapy revealed an increased risk of VTE in women compared to men (10.8% vs. 2.7%; p = 0.03), in those older than 50 (12.2% vs. 3.7%; p = 0.011); for patients receiving anthracycline chemotherapy (14.4% vs. 2.9%; p < 0.001) and hormonal therapy (12.9% vs. 3.9%; p < 0.001); Conclusions: Analysis from the COMPASS-CAT revealed a significant correlation between radiotherapy and VTE in patients with cancer. Further studies are needed to better understand the potential cellular toxicity associated with radiotherapy.

Venous thromboembolism and radiation therapy: The final radiation‐induced thrombosis study analysis

“…In the retrospective analysis that assessed VTE incidence in RT‐treated patients versus chemotherapy‐treated patients, four cases were reported in the RT group for body tumors, out of 158 patients, thus suggesting a comparable VTE incidence to our study 26 . By contrast, in the post‐hoc analysis of the COMPASS‐CAT trial, the authors reported a higher VTE incidence of about 9.1%, with 33 events in 336 evaluable patients, considering that all patients were treated by chemotherapy and that 25% of patients were metastatic 27,30 . In this context, it is therefore tempting to speculate that the inclusion of advanced stage of cancers may bias this incidence, given that the presence of distant metastases increases the risk of VTE.…”

“…Moreover, in a retrospective analysis that stratified patients in three groups (i.e., RT for brain tumors, RT for body tumors, chemotherapy‐treated brain and body tumors), external beam RT was identified as an independent risk factor for VTE development in outpatient setting, with a risk difference of 5% ( p 0.018 ) in comparison to chemotherapy 26 . Similarly, in a recent sub‐analysis of the COMPASS‐CAT study, a significant correlation between RT and VTE was described in patients with breast, lung, ovarian or colon cancer (HR 2.47, 95% CI 1.47–4.12, p 0.011 ) 27 . Yet, other studies did not find any specific association between RT and cancer‐associated thrombosis.…”

“… 26 Similarly, in a recent sub‐analysis of the COMPASS‐CAT study, a significant correlation between RT and VTE was described in patients with breast, lung, ovarian or colon cancer (HR 2.47, 95% CI 1.47–4.12, p 0.011 ). 27 Yet, other studies did not find any specific association between RT and cancer‐associated thrombosis. For example, in a large cohort of patients with prostate cancer, no link was established between curative RT and an increased risk of thromboembolic disease.…”

Venous thromboembolism and radiation therapy: The final radiation‐induced thrombosis study analysis

“…In the retrospective analysis that assessed VTE incidence in RT‐treated patients versus chemotherapy‐treated patients, four cases were reported in the RT group for body tumors, out of 158 patients, thus suggesting a comparable VTE incidence to our study 26 . By contrast, in the post‐hoc analysis of the COMPASS‐CAT trial, the authors reported a higher VTE incidence of about 9.1%, with 33 events in 336 evaluable patients, considering that all patients were treated by chemotherapy and that 25% of patients were metastatic 27,30 . In this context, it is therefore tempting to speculate that the inclusion of advanced stage of cancers may bias this incidence, given that the presence of distant metastases increases the risk of VTE.…”

“…Moreover, in a retrospective analysis that stratified patients in three groups (i.e., RT for brain tumors, RT for body tumors, chemotherapy‐treated brain and body tumors), external beam RT was identified as an independent risk factor for VTE development in outpatient setting, with a risk difference of 5% ( p 0.018 ) in comparison to chemotherapy 26 . Similarly, in a recent sub‐analysis of the COMPASS‐CAT study, a significant correlation between RT and VTE was described in patients with breast, lung, ovarian or colon cancer (HR 2.47, 95% CI 1.47–4.12, p 0.011 ) 27 . Yet, other studies did not find any specific association between RT and cancer‐associated thrombosis.…”

“… 26 Similarly, in a recent sub‐analysis of the COMPASS‐CAT study, a significant correlation between RT and VTE was described in patients with breast, lung, ovarian or colon cancer (HR 2.47, 95% CI 1.47–4.12, p 0.011 ). 27 Yet, other studies did not find any specific association between RT and cancer‐associated thrombosis. For example, in a large cohort of patients with prostate cancer, no link was established between curative RT and an increased risk of thromboembolic disease.…”

The factors affecting the survivability of malignant cancer patients with deep vein thrombosis among subjects with gynecologic and non-gynecologic cancer: An ambispective cohort study

“…Thus, additional studies with longer time periods are warranted to fully comprehend the clinical significance of the prospective cellular toxicity related to radiotherapy. 61,62 As can be observed in Figure 1F, the survival time was significantly higher in subjects who received high-risk systemic therapy compared to those who received low-risk systemic therapy (p-value 0.048). According to recent research, the administration of tamoxifen, aromatase inhibitors, thalidomide, lenalidomide, bevacizumab, cisplatin, nitrogen mustard, or anthracycline has been linked to a higher incidence of DVT.…”

Association of Gonadotropin-Releasing Hormone Therapies With Venous Thromboembolic Events in Patients With Prostate Cancer: A National Cohort Study

“…In contrast, although radiotherapies did not represent a significant correlation with VTEs after being adjusted with age and comorbidities, in this cohort, there were still more GnRH users who have received radiotherapies. Previous studies have observed a significant correlation between radiotherapy and VTE in patients with cancer ( 34 , 35 ). Analysis from the Registro Informatizado de Enfermedad TromboEmbólica (RIETE) registry revealed that 13% of patients with cancer-associated thrombosis received radiotherapy treatments ( 34 ).…”

Venous thromboembolism and radiation therapy: The final radiation‐induced thrombosis study analysis

“…In the retrospective analysis that assessed VTE incidence in RT‐treated patients versus chemotherapy‐treated patients, four cases were reported in the RT group for body tumors, out of 158 patients, thus suggesting a comparable VTE incidence to our study 26 . By contrast, in the post‐hoc analysis of the COMPASS‐CAT trial, the authors reported a higher VTE incidence of about 9.1%, with 33 events in 336 evaluable patients, considering that all patients were treated by chemotherapy and that 25% of patients were metastatic 27,30 . In this context, it is therefore tempting to speculate that the inclusion of advanced stage of cancers may bias this incidence, given that the presence of distant metastases increases the risk of VTE.…”

“…Moreover, in a retrospective analysis that stratified patients in three groups (i.e., RT for brain tumors, RT for body tumors, chemotherapy‐treated brain and body tumors), external beam RT was identified as an independent risk factor for VTE development in outpatient setting, with a risk difference of 5% ( p 0.018 ) in comparison to chemotherapy 26 . Similarly, in a recent sub‐analysis of the COMPASS‐CAT study, a significant correlation between RT and VTE was described in patients with breast, lung, ovarian or colon cancer (HR 2.47, 95% CI 1.47–4.12, p 0.011 ) 27 . Yet, other studies did not find any specific association between RT and cancer‐associated thrombosis.…”

“… 26 Similarly, in a recent sub‐analysis of the COMPASS‐CAT study, a significant correlation between RT and VTE was described in patients with breast, lung, ovarian or colon cancer (HR 2.47, 95% CI 1.47–4.12, p 0.011 ). 27 Yet, other studies did not find any specific association between RT and cancer‐associated thrombosis. For example, in a large cohort of patients with prostate cancer, no link was established between curative RT and an increased risk of thromboembolic disease.…”

The factors affecting the survivability of malignant cancer patients with deep vein thrombosis among subjects with gynecologic and non-gynecologic cancer: An ambispective cohort study

“…Thus, additional studies with longer time periods are warranted to fully comprehend the clinical significance of the prospective cellular toxicity related to radiotherapy. 61,62 As can be observed in Figure 1F, the survival time was significantly higher in subjects who received high-risk systemic therapy compared to those who received low-risk systemic therapy (p-value 0.048). According to recent research, the administration of tamoxifen, aromatase inhibitors, thalidomide, lenalidomide, bevacizumab, cisplatin, nitrogen mustard, or anthracycline has been linked to a higher incidence of DVT.…”

Association of Gonadotropin-Releasing Hormone Therapies With Venous Thromboembolic Events in Patients With Prostate Cancer: A National Cohort Study

“…In contrast, although radiotherapies did not represent a significant correlation with VTEs after being adjusted with age and comorbidities, in this cohort, there were still more GnRH users who have received radiotherapies. Previous studies have observed a significant correlation between radiotherapy and VTE in patients with cancer ( 34 , 35 ). Analysis from the Registro Informatizado de Enfermedad TromboEmbólica (RIETE) registry revealed that 13% of patients with cancer-associated thrombosis received radiotherapy treatments ( 34 ).…”

Venous thromboembolism and radiation therapy: The final radiation‐induced thrombosis study analysis

“…In the retrospective analysis that assessed VTE incidence in RT‐treated patients versus chemotherapy‐treated patients, four cases were reported in the RT group for body tumors, out of 158 patients, thus suggesting a comparable VTE incidence to our study 26 . By contrast, in the post‐hoc analysis of the COMPASS‐CAT trial, the authors reported a higher VTE incidence of about 9.1%, with 33 events in 336 evaluable patients, considering that all patients were treated by chemotherapy and that 25% of patients were metastatic 27,30 . In this context, it is therefore tempting to speculate that the inclusion of advanced stage of cancers may bias this incidence, given that the presence of distant metastases increases the risk of VTE.…”

“…Moreover, in a retrospective analysis that stratified patients in three groups (i.e., RT for brain tumors, RT for body tumors, chemotherapy‐treated brain and body tumors), external beam RT was identified as an independent risk factor for VTE development in outpatient setting, with a risk difference of 5% ( p 0.018 ) in comparison to chemotherapy 26 . Similarly, in a recent sub‐analysis of the COMPASS‐CAT study, a significant correlation between RT and VTE was described in patients with breast, lung, ovarian or colon cancer (HR 2.47, 95% CI 1.47–4.12, p 0.011 ) 27 . Yet, other studies did not find any specific association between RT and cancer‐associated thrombosis.…”

“… 26 Similarly, in a recent sub‐analysis of the COMPASS‐CAT study, a significant correlation between RT and VTE was described in patients with breast, lung, ovarian or colon cancer (HR 2.47, 95% CI 1.47–4.12, p 0.011 ). 27 Yet, other studies did not find any specific association between RT and cancer‐associated thrombosis. For example, in a large cohort of patients with prostate cancer, no link was established between curative RT and an increased risk of thromboembolic disease.…”

The factors affecting the survivability of malignant cancer patients with deep vein thrombosis among subjects with gynecologic and non-gynecologic cancer: An ambispective cohort study

“…Thus, additional studies with longer time periods are warranted to fully comprehend the clinical significance of the prospective cellular toxicity related to radiotherapy. 61,62 As can be observed in Figure 1F, the survival time was significantly higher in subjects who received high-risk systemic therapy compared to those who received low-risk systemic therapy (p-value 0.048). According to recent research, the administration of tamoxifen, aromatase inhibitors, thalidomide, lenalidomide, bevacizumab, cisplatin, nitrogen mustard, or anthracycline has been linked to a higher incidence of DVT.…”

Association of Gonadotropin-Releasing Hormone Therapies With Venous Thromboembolic Events in Patients With Prostate Cancer: A National Cohort Study

“…In contrast, although radiotherapies did not represent a significant correlation with VTEs after being adjusted with age and comorbidities, in this cohort, there were still more GnRH users who have received radiotherapies. Previous studies have observed a significant correlation between radiotherapy and VTE in patients with cancer ( 34 , 35 ). Analysis from the Registro Informatizado de Enfermedad TromboEmbólica (RIETE) registry revealed that 13% of patients with cancer-associated thrombosis received radiotherapy treatments ( 34 ).…”