Imaging the tumour microenvironment in rectal cancer: Decline in tumour blood flow during radiotherapy predicts good outcome
Background and purpose: Measuring rectal tumour response to radiation is pivotal to restaging patients and for possibly stratification to a watch-and-wait strategy. Recognizing the importance of the tumour microenvironment, we investigated a less explored quantitative imaging marker assessing tumour...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-01-01
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| Series: | Physics and Imaging in Radiation Oncology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405631623000088 |
| _version_ | 1797870539638833152 |
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| author | Kine Mari Bakke Sebastian Meltzer Endre Grøvik Anne Negård Stein Harald Holmedal Lars Tore Gyland Mikalsen Arne Engebret Færden Lars Gustav Lyckander Frida Marie Ihle Julbø Atle Bjørnerud Kjell-Inge Gjesdal Anne Hansen Ree Kathrine Røe Redalen |
| author_facet | Kine Mari Bakke Sebastian Meltzer Endre Grøvik Anne Negård Stein Harald Holmedal Lars Tore Gyland Mikalsen Arne Engebret Færden Lars Gustav Lyckander Frida Marie Ihle Julbø Atle Bjørnerud Kjell-Inge Gjesdal Anne Hansen Ree Kathrine Røe Redalen |
| author_sort | Kine Mari Bakke |
| collection | DOAJ |
| description | Background and purpose: Measuring rectal tumour response to radiation is pivotal to restaging patients and for possibly stratification to a watch-and-wait strategy. Recognizing the importance of the tumour microenvironment, we investigated a less explored quantitative imaging marker assessing tumour blood flow (BF) for its potential to predict overall survival (OS). Materials and methods: 24 rectal cancer patients given curative-intent neoadjuvant radiotherapy underwent a multi-echo dynamic magnetic resonance imaging (MRI) sequence with gadolinium contrast for quantification of tumour BF before either 25x2 Gy (n = 18) with concomitant chemotherapy or 5x5 Gy (n = 6). CD34 staining of excised tumour tissue was performed and baseline blood samples were analysed for lactate dehydrogenase (LDH) and angiopoietin-2 (ANGPT-2). Tumour volumes were measured before and after treatment. After subsequent surgery, ypTN scoring assessed tumour response. Cox regression for 5-year OS analysis and t-test for group comparisons were performed. Results: The change in tumour BF (ΔBF) during neoadjuvant radiotherapy was a significant marker of OS, whereas tumour stage and volume were not related to OS. All patients with >20 % decline in BF were long-term survivors. Separating cases in two groups based on ΔBF revealed that patients with increase or a low decrease had higher baseline LDH (p = 0.032) and ANGPT-2 (p = 0.028) levels. Conclusion: MRI-assessed tumour ΔBF during neoadjuvant treatment is a significant predictor of OS in rectal cancer patients, making ΔBF a potential quantitative imaging biomarker for treatment stratification. Blood LDH and ANGPT-2 indicate that non-responding tumours may have a hypoxic microenvironment resistant to radiotherapy. |
| first_indexed | 2024-04-10T00:30:08Z |
| format | Article |
| id | doaj.art-aeac339ff24f413f90e40f15fbad1f67 |
| institution | Directory Open Access Journal |
| issn | 2405-6316 |
| language | English |
| last_indexed | 2024-04-10T00:30:08Z |
| publishDate | 2023-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Physics and Imaging in Radiation Oncology |
| spelling | doaj.art-aeac339ff24f413f90e40f15fbad1f672023-03-15T04:28:41ZengElsevierPhysics and Imaging in Radiation Oncology2405-63162023-01-0125100417Imaging the tumour microenvironment in rectal cancer: Decline in tumour blood flow during radiotherapy predicts good outcomeKine Mari Bakke0Sebastian Meltzer1Endre Grøvik2Anne Negård3Stein Harald Holmedal4Lars Tore Gyland Mikalsen5Arne Engebret Færden6Lars Gustav Lyckander7Frida Marie Ihle Julbø8Atle Bjørnerud9Kjell-Inge Gjesdal10Anne Hansen Ree11Kathrine Røe Redalen12Department of Oncology, Akershus University Hospital, Lørenskog, Norway; Corresponding author at: Skremmaveien 40, 1425 Ski, Norway.Department of Oncology, Akershus University Hospital, Lørenskog, NorwayMøre and Romsdal Hospital Trust, Ålesund; Department of Physics, Norwegian University of Science and Technology, Trondheim, NorwayDepartment of Radiology, Akershus University Hospital, Lørenskog, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, NorwayDepartment of Radiology, Akershus University Hospital, Lørenskog, NorwayDepartment of Diagnostic Physics, Division of Radiology and Nuclear Medicine, Oslo University Hospital, Oslo, Norway; Department of Life Sciences and Health, Oslo Metropolitan University, Oslo, NorwayDepartment of Digestive Surgery, Akershus University Hospital, Lørenskog, NorwayDepartment of Pathology, Akershus University Hospital, Lørenskog, NorwayDepartment of Oncology, Akershus University Hospital, Lørenskog, Norway; Institute for Cancer Genetics and Informatics, Oslo University Hospital, NorwayDepartment of Diagnostic Physics, Division of Radiology and Nuclear Medicine, Oslo University Hospital, Oslo, Norway; Department of Physics, University of Oslo, Oslo, NorwayDepartment of Radiology, Akershus University Hospital, Lørenskog, Norway; Sunnmøre MR-klinikk, Ålesund, NorwayDepartment of Oncology, Akershus University Hospital, Lørenskog, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, NorwayDepartment of Physics, Norwegian University of Science and Technology, Trondheim, NorwayBackground and purpose: Measuring rectal tumour response to radiation is pivotal to restaging patients and for possibly stratification to a watch-and-wait strategy. Recognizing the importance of the tumour microenvironment, we investigated a less explored quantitative imaging marker assessing tumour blood flow (BF) for its potential to predict overall survival (OS). Materials and methods: 24 rectal cancer patients given curative-intent neoadjuvant radiotherapy underwent a multi-echo dynamic magnetic resonance imaging (MRI) sequence with gadolinium contrast for quantification of tumour BF before either 25x2 Gy (n = 18) with concomitant chemotherapy or 5x5 Gy (n = 6). CD34 staining of excised tumour tissue was performed and baseline blood samples were analysed for lactate dehydrogenase (LDH) and angiopoietin-2 (ANGPT-2). Tumour volumes were measured before and after treatment. After subsequent surgery, ypTN scoring assessed tumour response. Cox regression for 5-year OS analysis and t-test for group comparisons were performed. Results: The change in tumour BF (ΔBF) during neoadjuvant radiotherapy was a significant marker of OS, whereas tumour stage and volume were not related to OS. All patients with >20 % decline in BF were long-term survivors. Separating cases in two groups based on ΔBF revealed that patients with increase or a low decrease had higher baseline LDH (p = 0.032) and ANGPT-2 (p = 0.028) levels. Conclusion: MRI-assessed tumour ΔBF during neoadjuvant treatment is a significant predictor of OS in rectal cancer patients, making ΔBF a potential quantitative imaging biomarker for treatment stratification. Blood LDH and ANGPT-2 indicate that non-responding tumours may have a hypoxic microenvironment resistant to radiotherapy.http://www.sciencedirect.com/science/article/pii/S2405631623000088PerfusionBlood flowMRIRectal cancerResponse assessment |
| spellingShingle | Kine Mari Bakke Sebastian Meltzer Endre Grøvik Anne Negård Stein Harald Holmedal Lars Tore Gyland Mikalsen Arne Engebret Færden Lars Gustav Lyckander Frida Marie Ihle Julbø Atle Bjørnerud Kjell-Inge Gjesdal Anne Hansen Ree Kathrine Røe Redalen Imaging the tumour microenvironment in rectal cancer: Decline in tumour blood flow during radiotherapy predicts good outcome Physics and Imaging in Radiation Oncology Perfusion Blood flow MRI Rectal cancer Response assessment |
| title | Imaging the tumour microenvironment in rectal cancer: Decline in tumour blood flow during radiotherapy predicts good outcome |
| title_full | Imaging the tumour microenvironment in rectal cancer: Decline in tumour blood flow during radiotherapy predicts good outcome |
| title_fullStr | Imaging the tumour microenvironment in rectal cancer: Decline in tumour blood flow during radiotherapy predicts good outcome |
| title_full_unstemmed | Imaging the tumour microenvironment in rectal cancer: Decline in tumour blood flow during radiotherapy predicts good outcome |
| title_short | Imaging the tumour microenvironment in rectal cancer: Decline in tumour blood flow during radiotherapy predicts good outcome |
| title_sort | imaging the tumour microenvironment in rectal cancer decline in tumour blood flow during radiotherapy predicts good outcome |
| topic | Perfusion Blood flow MRI Rectal cancer Response assessment |
| url | http://www.sciencedirect.com/science/article/pii/S2405631623000088 |
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