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)

A. Hakkarainen; Eila Lantto; RAXO Study Grp

doi: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)

A. Hakkarainen
, Eila Lantto
, RAXO Study Grp

Department of Neuroscience and Biomedical Engineering

University of Helsinki
Tampere University Hospital
University Hospital of Oulu
University of Oulu
Tampere University
Päijät-Häme Central Hospital
University of Turku
Karolinska Sjukhuset
Helsinki University Central Hospital
Turku PET Centre
Turku University Hospital

Research output: Contribution to journal › Article › Scientific › peer-review

14 Citations (Web of Science)

94 Downloads (Pure)

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.

Original language	English
Article number	100208
Pages (from-to)	100208
Number of pages	11
Journal	ESMO Open
Volume	6
Issue number	4
DOIs	https://doi.org/10.1016/j.esmoop.2021.100208
Publication status	Published - 1 Aug 2021
MoE publication type	A1 Journal article-refereed

Funding

This investigator-initiated RAXO study was supported by Finska Lakaresallskapet (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 (Tukisaatio 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 (Amgendunrestricted grant 2012-2020, Lilly 2012-2017, Merck KGaA 2012-2020, Roche Finland 2012-2020, Sanofi 2012-2017 and Servierd 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.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

colorectal cancer
liver metastasis
neoadjuvant chemotherapy
liver surgery
diffusion-weighted imaging
magnetic resonance spectroscopy
PATHOLOGICAL RESPONSE
CHEMOTHERAPY
PREDICTION
TUMOR
BEVACIZUMAB
SURVIVAL
CRITERIA
OUTCOMES
SURGERY
FAT

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Hakkarainen, A., Lantto, E., & RAXO Study Grp (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. Article 100208. https://doi.org/10.1016/j.esmoop.2021.100208

@article{11205ae230b647afba4dd4a68faab48a,

title = "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)",

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.",

keywords = "colorectal cancer, liver metastasis, neoadjuvant chemotherapy, liver surgery, diffusion-weighted imaging, magnetic resonance spectroscopy, PATHOLOGICAL RESPONSE, CHEMOTHERAPY, PREDICTION, TUMOR, BEVACIZUMAB, SURVIVAL, CRITERIA, OUTCOMES, SURGERY, FAT",

author = "A. Uutela and A. Ovissi and A. Hakkarainen and A. Ristimaki and N. Lundbom and R. Kallio and Soveri, \{L. M.\} and T. Salminen and A. Algars and P. Halonen and R. Ristamaki and A. Nordin and \{Blanco Sequeiros\}, Roberto and I. Rinta-Kiikka and Eila Lantto and J. Virtanen and E. Paakko and E. Liukkonen and J. Saunavaara and P. Ryymin and E. Lammentausta and P. Osterlund and H. Isoniemi and \{RAXO Study Grp\}",

year = "2021",

month = aug,

day = "1",

doi = "10.1016/j.esmoop.2021.100208",

language = "English",

volume = "6",

pages = "100208",

journal = "ESMO Open ",

issn = "2059-7029",

publisher = "Elsevier",

number = "4",

}

Hakkarainen, A, Lantto, E & RAXO Study Grp 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 , vol. 6, no. 4, 100208, pp. 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). / Hakkarainen, A.; Lantto, Eila; RAXO Study Grp.
In: ESMO Open , Vol. 6, No. 4, 100208, 01.08.2021, p. 100208.

Research output: Contribution to journal › Article › Scientific › peer-review

TY - JOUR

T1 - Treatment response of colorectal cancer liver metastases to neoadjuvant or conversion therapy

T2 - a prospective multicentre follow-up study using MRI, diffusion-weighted imaging and 1H-MR spectroscopy compared with histology (subgroup in the RAXO trial)

AU - Uutela, A.

AU - Ovissi, A.

AU - Hakkarainen, A.

AU - Ristimaki, A.

AU - Lundbom, N.

AU - Kallio, R.

AU - Soveri, L. M.

AU - Salminen, T.

AU - Algars, A.

AU - Halonen, P.

AU - Ristamaki, R.

AU - Nordin, A.

AU - Blanco Sequeiros, Roberto

AU - Rinta-Kiikka, I.

AU - Lantto, Eila

AU - Virtanen, J.

AU - Paakko, E.

AU - Liukkonen, E.

AU - Saunavaara, J.

AU - Ryymin, P.

AU - Lammentausta, E.

AU - Osterlund, P.

AU - Isoniemi, H.

AU - RAXO Study Grp

PY - 2021/8/1

Y1 - 2021/8/1

N2 - 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.

AB - 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.

KW - colorectal cancer

KW - liver metastasis

KW - neoadjuvant chemotherapy

KW - liver surgery

KW - diffusion-weighted imaging

KW - magnetic resonance spectroscopy

KW - PATHOLOGICAL RESPONSE

KW - CHEMOTHERAPY

KW - PREDICTION

KW - TUMOR

KW - BEVACIZUMAB

KW - SURVIVAL

KW - CRITERIA

KW - OUTCOMES

KW - SURGERY

KW - FAT

UR - https://www.scopus.com/pages/publications/85117623550

U2 - 10.1016/j.esmoop.2021.100208

DO - 10.1016/j.esmoop.2021.100208

M3 - Article

C2 - 34325107

SN - 2059-7029

VL - 6

SP - 100208

JO - ESMO Open

JF - ESMO Open

IS - 4

M1 - 100208

ER -

Hakkarainen A, Lantto E, RAXO Study Grp. 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 . 2021 Aug 1;6(4):100208. 100208. doi: 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)