Dynamic contrast-enhanced computed tomography as a potential biomarker in patients with metastatic colorectal cancer treated with regorafenib

Iben R Andersen*, Rene Olesen, Anders K Boysen, Lars H Jensen, Frank V Mortensen, Dennis T Nielsen, Finn Rasmussen

*Kontaktforfatter for dette arbejde

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

Background: RECIST 1.1 presents challenges when evaluating treatment response to angiogenesis inhibitors. The objective response rate, when evaluating the treatment effect of regorafenib, using RECIST 1.1, is < 2% and beneficial treatment could erroneously be terminated. Dynamic contrast-enhanced computed tomography (DCE-CT) has potential as a non-invasive functional imaging biomarker, by quantifying the treatment effect of this targeted therapy. Purpose: To evaluate three-dimensional (3D) tumor dynamic parameters representing tumor microcirculation assessed by DCE-CT during the treatment with regorafenib in a cohort of patients with treatment-refractory metastatic colorectal cancer. Material and Methods: Thirty-three patients with colorectal metastases (27 liver lesions, three abdominal lesions, and three pulmonary lesions) were treated with regorafenib and evaluated using DCE-CT. A total of 112 DCE-CT scans were analyzed using Advanced Perfusion and Permeability Application and correlated to standard contrast-enhanced computed tomography (CE-CT) evaluated using RECIST 1.1. Results: A significant decrease in most DCE-CT parameters, a simultaneous decrease in tumor attenuation and an increase in tumor volume were detected during treatment. However, no associations were found between the DCE-CT parameters and PFS or OS using simple COX proportional hazards regression. Conclusion: In this exploratory study, a significant decrease in most dynamic parameters suggests an overall treatment effect of regorafenib in tumor vasculature. DCE-CT may assist in an objective evaluation of these responses compared to RECIST. The anti-angiogenic changes could not be associated with treatment outcome in terms of PFS and OS, which might be due to the small cohort or a rather limited survival benefit in this pre-medicated treatment-refractory group of patients.

OriginalsprogEngelsk
TidsskriftActa Radiologica
Vol/bind60
Udgave nummer7
Sider (fra-til)836-845
ISSN0284-1851
DOI
StatusUdgivet - 1. jul. 2019

Fingeraftryk

Colorectal Neoplasms
Neoplasms
Angiogenesis Inhibitors
Microcirculation
Tumor Burden
Perfusion
Lung
Response Evaluation Criteria in Solid Tumors
Liver

Citer dette

Andersen, Iben R ; Olesen, Rene ; Boysen, Anders K ; Jensen, Lars H ; Mortensen, Frank V ; Nielsen, Dennis T ; Rasmussen, Finn. / Dynamic contrast-enhanced computed tomography as a potential biomarker in patients with metastatic colorectal cancer treated with regorafenib. I: Acta Radiologica. 2019 ; Bind 60, Nr. 7. s. 836-845.
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abstract = "Background: RECIST 1.1 presents challenges when evaluating treatment response to angiogenesis inhibitors. The objective response rate, when evaluating the treatment effect of regorafenib, using RECIST 1.1, is < 2{\%} and beneficial treatment could erroneously be terminated. Dynamic contrast-enhanced computed tomography (DCE-CT) has potential as a non-invasive functional imaging biomarker, by quantifying the treatment effect of this targeted therapy. Purpose: To evaluate three-dimensional (3D) tumor dynamic parameters representing tumor microcirculation assessed by DCE-CT during the treatment with regorafenib in a cohort of patients with treatment-refractory metastatic colorectal cancer. Material and Methods: Thirty-three patients with colorectal metastases (27 liver lesions, three abdominal lesions, and three pulmonary lesions) were treated with regorafenib and evaluated using DCE-CT. A total of 112 DCE-CT scans were analyzed using Advanced Perfusion and Permeability Application and correlated to standard contrast-enhanced computed tomography (CE-CT) evaluated using RECIST 1.1. Results: A significant decrease in most DCE-CT parameters, a simultaneous decrease in tumor attenuation and an increase in tumor volume were detected during treatment. However, no associations were found between the DCE-CT parameters and PFS or OS using simple COX proportional hazards regression. Conclusion: In this exploratory study, a significant decrease in most dynamic parameters suggests an overall treatment effect of regorafenib in tumor vasculature. DCE-CT may assist in an objective evaluation of these responses compared to RECIST. The anti-angiogenic changes could not be associated with treatment outcome in terms of PFS and OS, which might be due to the small cohort or a rather limited survival benefit in this pre-medicated treatment-refractory group of patients.",
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author = "Andersen, {Iben R} and Rene Olesen and Boysen, {Anders K} and Jensen, {Lars H} and Mortensen, {Frank V} and Nielsen, {Dennis T} and Finn Rasmussen",
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Dynamic contrast-enhanced computed tomography as a potential biomarker in patients with metastatic colorectal cancer treated with regorafenib. / Andersen, Iben R; Olesen, Rene; Boysen, Anders K; Jensen, Lars H; Mortensen, Frank V; Nielsen, Dennis T; Rasmussen, Finn.

I: Acta Radiologica, Bind 60, Nr. 7, 01.07.2019, s. 836-845.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Dynamic contrast-enhanced computed tomography as a potential biomarker in patients with metastatic colorectal cancer treated with regorafenib

AU - Andersen, Iben R

AU - Olesen, Rene

AU - Boysen, Anders K

AU - Jensen, Lars H

AU - Mortensen, Frank V

AU - Nielsen, Dennis T

AU - Rasmussen, Finn

PY - 2019/7/1

Y1 - 2019/7/1

N2 - Background: RECIST 1.1 presents challenges when evaluating treatment response to angiogenesis inhibitors. The objective response rate, when evaluating the treatment effect of regorafenib, using RECIST 1.1, is < 2% and beneficial treatment could erroneously be terminated. Dynamic contrast-enhanced computed tomography (DCE-CT) has potential as a non-invasive functional imaging biomarker, by quantifying the treatment effect of this targeted therapy. Purpose: To evaluate three-dimensional (3D) tumor dynamic parameters representing tumor microcirculation assessed by DCE-CT during the treatment with regorafenib in a cohort of patients with treatment-refractory metastatic colorectal cancer. Material and Methods: Thirty-three patients with colorectal metastases (27 liver lesions, three abdominal lesions, and three pulmonary lesions) were treated with regorafenib and evaluated using DCE-CT. A total of 112 DCE-CT scans were analyzed using Advanced Perfusion and Permeability Application and correlated to standard contrast-enhanced computed tomography (CE-CT) evaluated using RECIST 1.1. Results: A significant decrease in most DCE-CT parameters, a simultaneous decrease in tumor attenuation and an increase in tumor volume were detected during treatment. However, no associations were found between the DCE-CT parameters and PFS or OS using simple COX proportional hazards regression. Conclusion: In this exploratory study, a significant decrease in most dynamic parameters suggests an overall treatment effect of regorafenib in tumor vasculature. DCE-CT may assist in an objective evaluation of these responses compared to RECIST. The anti-angiogenic changes could not be associated with treatment outcome in terms of PFS and OS, which might be due to the small cohort or a rather limited survival benefit in this pre-medicated treatment-refractory group of patients.

AB - Background: RECIST 1.1 presents challenges when evaluating treatment response to angiogenesis inhibitors. The objective response rate, when evaluating the treatment effect of regorafenib, using RECIST 1.1, is < 2% and beneficial treatment could erroneously be terminated. Dynamic contrast-enhanced computed tomography (DCE-CT) has potential as a non-invasive functional imaging biomarker, by quantifying the treatment effect of this targeted therapy. Purpose: To evaluate three-dimensional (3D) tumor dynamic parameters representing tumor microcirculation assessed by DCE-CT during the treatment with regorafenib in a cohort of patients with treatment-refractory metastatic colorectal cancer. Material and Methods: Thirty-three patients with colorectal metastases (27 liver lesions, three abdominal lesions, and three pulmonary lesions) were treated with regorafenib and evaluated using DCE-CT. A total of 112 DCE-CT scans were analyzed using Advanced Perfusion and Permeability Application and correlated to standard contrast-enhanced computed tomography (CE-CT) evaluated using RECIST 1.1. Results: A significant decrease in most DCE-CT parameters, a simultaneous decrease in tumor attenuation and an increase in tumor volume were detected during treatment. However, no associations were found between the DCE-CT parameters and PFS or OS using simple COX proportional hazards regression. Conclusion: In this exploratory study, a significant decrease in most dynamic parameters suggests an overall treatment effect of regorafenib in tumor vasculature. DCE-CT may assist in an objective evaluation of these responses compared to RECIST. The anti-angiogenic changes could not be associated with treatment outcome in terms of PFS and OS, which might be due to the small cohort or a rather limited survival benefit in this pre-medicated treatment-refractory group of patients.

KW - CT quantitative

KW - angiogenesis inhibitors

KW - dynamic contrast-enhanced computed tomography

KW - metastatic colorectal cancer

KW - patient outcome

KW - Liver Neoplasms/diagnostic imaging

KW - Colorectal Neoplasms/pathology

KW - Humans

KW - Middle Aged

KW - Four-Dimensional Computed Tomography/methods

KW - Male

KW - Response Evaluation Criteria in Solid Tumors

KW - Treatment Outcome

KW - Phenylurea Compounds/therapeutic use

KW - Lung Neoplasms/diagnostic imaging

KW - Contrast Media

KW - Pyridines/therapeutic use

KW - Radiographic Image Enhancement/methods

KW - Abdominal Neoplasms/diagnostic imaging

KW - Biomarkers

KW - Triiodobenzoic Acids

KW - Female

KW - Aged

U2 - 10.1177/0284185118806652

DO - 10.1177/0284185118806652

M3 - Journal article

C2 - 30348001

VL - 60

SP - 836

EP - 845

JO - Acta Radiologica

JF - Acta Radiologica

SN - 0284-1851

IS - 7

ER -