University of Oulu

Uutela, A., Ovissi, A., Hakkarainen, A., Ristimäki, A., Lundbom, N., Kallio, R., Soveri, L. M., Salminen, T., Ålgars, A., Halonen, P., Ristamäki, R., Nordin, A., Blanco Sequeiros, R., Rinta-Kiikka, I., Lantto, E., Virtanen, J., Pääkkö, E., Liukkonen, E., Saunavaara, J., … Poussa, T. (2021). Treatment response of colorectal cancer liver metastases to neoadjuvant or conversion therapy: A prospective multicentre follow-up study using MRI, diffusion-weighted imaging and 1H-MR spectroscopy compared with histology (Subgroup in the raxo trial). ESMO Open, 6(4), 100208. https://doi.org/10.1016/j.esmoop.2021.100208

Treatment response of colorectal cancer liver metastases to neoadjuvant or conversion therapy : a prospective multicentre follow-up study using MRI, diffusion-weighted imaging and 1H-MR spectroscopy compared with histology (subgroup in the RAXO trial)

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Author: Uutela, A.1; Ovissi, A.2; Hakkarainen, A.2,3;
Organizations: 1Department of Transplantation and Liver Surgery, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
2Department of Radiology, HUS Medical Imaging Centre, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
3Department of Neuroscience and Biomedical Engineering, Aalto University School of Science, Helsinki, Finland
4Department of Pathology, HUS Diagnostic Centre and Applied Tumour Genomics, Research Programs Unit, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
5Department of Oncology, Oulu University Hospital, Oulu, Finland
6Joint Municipal Authority for Health Care and Social Services in Keski-Uusimaa, Home Care Geriatric Clinic and Palliative Care, Hyvinkää, Finland
7Department of Oncology, Tampere University Hospital and University of Tampere, Tampere, Finland
8Department of Oncology, Turku University Hospital and University of Turku, Turku, Finland
9Department of Oncology, Helsinki University Hospital Comprehensive Cancer Center and University of Helsinki, Helsinki, Finland
10Department of Radiology, Turku University Hospital and University of Turku, Turku, Finland
11Department of Radiology, Oulu University Hospital, Oulu, Finland
12Department of Radiology, Medical Imaging Centre Tampere University Hospital and University of Tampere, Tampere, Finland
13Department of Medical Physics, Medical Imaging Centre Tampere University Hospital and University of Tampere, Tampere, Finland
14Department of Radiology, Päijät-Häme Central Hospital, Lahti, Finland
15Department of Pathology/Oncology, Karolinska Institutet and Karolinska sjukhuset - Tema Cancer, Stockholm, Sweden
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1.6 MB)
Persistent link: http://urn.fi/urn:nbn:fi-fe2022030221470
Language: English
Published: BMJ, 2021
Publish Date: 2022-03-02
Description:

Abstract

Background: Colorectal cancer liver metastases respond to chemotherapy and targeted agents not only by shrinking, but also by morphologic and metabolic changes. The aim of this study was to evaluate the value of advanced magnetic resonance imaging (MRI) methods in predicting treatment response and survival.

Patients and methods: We investigated contrast-enhanced MRI, apparent diffusion coefficient (ADC) in diffusion-weighted imaging and 1H-magnetic resonance spectroscopy (1H-MRS) in detecting early morphologic and metabolic changes in borderline or resectable liver metastases, as a response to first-line neoadjuvant or conversion therapy in a prospective substudy of the RAXO trial (NCT01531621, EudraCT2011–003158–24). MRI findings were compared with histology of resected liver metastases and Kaplan–Meier estimates of overall survival (OS).

Results: In 2012–2018, 52 patients at four Finnish university hospitals were recruited. Forty-seven patients received neoadjuvant or conversion chemotherapy and 40 liver resections were carried out. Low ADC values (below median) of the representative liver metastases, at baseline and after systemic therapy, were associated with partial response according to RECIST criteria, but not with morphologic MRI changes or histology. Decreasing ADC values following systemic therapy were associated with improved OS compared to unchanged or increasing ADC, both in the liver resected subgroup (5-year OS rate 100% and 34%, respectively, P = 0.022) and systemic therapy subgroup (5-year OS rate 62% and 23%, P = 0.049). 1H-MRS revealed steatohepatosis induced by systemic therapy.

Conclusions: Low ADC values at baseline or during systemic therapy were associated with treatment response by RECIST but not with histology, morphologic or detectable metabolic changes. A decreasing ADC during systemic therapy is associated with improved OS both in all patients receiving systemic therapy and in the resected subgroup.

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The RAXO Study Group Collaborators: Heikki Mäkisalo, Riikka Huuhtanen, Juhani Kosunen, Sirpa Leppä, Petri Bono, Johanna Mattson, Emerik Österlund, Heidi Penttinen, Siru Mäkelä, Olli Carpén, Marjut Timonen, Kaisa Lehtomäki, Veera Salminen, Niina Paunu, Martine Vornanen, Nieminen Lasse, Eetu Heervä, Eija Korkeila, Eija Sutinen, Maija Lavonius, Jari Sundström, Markus Mäkinen, Tuija Poussa.
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Series: ESMO open
ISSN: 2059-7029
ISSN-E: 2059-7029
ISSN-L: 2059-7029
Volume: 6
Issue: 4
Article number: 100280
DOI: 10.1016/j.esmoop.2021.100208
OADOI: https://oadoi.org/10.1016/j.esmoop.2021.100208
Type of Publication: A1 Journal article – refereed
Field of Science: 3122 Cancers
3126 Surgery, anesthesiology, intensive care, radiology
Subjects:
Funding: This investigator-initiated RAXO study was supported by Finska Läkaresällskapet (2015, 2016, 2017, 2018, 2019, 2020, 2021); Cancer Foundation Finland (2018-2019, 2020); Relander's Foundation (2020-2022); the Competitive State Research Financing of the Expert Responsibility Area of Tampere, Helsinki and Turku (2016, 2017, 2018, 2019, 2020, 2021); Tampere University Hospital Funds (Tukisäätiö 2019, 2020; OOO 2020); and the Research Fund of Helsinki University Hospital (2019, 2020). The infrastructure with database and study nurses were partly supported by pharmaceutical companies (Amgen—unrestricted grant 2012-2020, Lilly 2012-2017, Merck KGaA 2012-2020, Roche Finland 2012-2020, Sanofi 2012-2017 and Servier—unrestricted grant 2016-2020). The funders had no role in the study design, analysis, interpretation of the data, decision to publish or writing of this report. All authors had full access to the data and had final responsibility for the decision to submit for publication.
Copyright information: © 2021 The Authors. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
  https://creativecommons.org/licenses/by/4.0/