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 Uutela; A Ovissi; A Hakkarainen; A Ristimäki; N Lundbom; R Kallio; L M Soveri; T Salminen; A Ålgars; P Halonen; R Ristamäki; A Nordin; R Blanco Sequeiros; I Rinta-Kiikka; E Lantto; J Virtanen; E Pääkkö; E Liukkonen; J Saunavaara; P Ryymin; E Lammentausta; P Osterlund; H Isoniemi; RAXO Study Group

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)

ESMO Open. 2021 Aug;6(4):100208. doi: 10.1016/j.esmoop.2021.100208. Epub 2021 Jul 26.

Authors

A Uutela¹, A Ovissi², A Hakkarainen³, A Ristimäki⁴, N Lundbom², R Kallio⁵, L M Soveri⁶, T Salminen⁷, A Ålgars⁸, P Halonen⁹, R Ristamäki⁸, A Nordin¹, R Blanco Sequeiros¹⁰, I Rinta-Kiikka¹¹, E Lantto¹², J Virtanen¹³, E Pääkkö¹⁴, E Liukkonen¹⁴, J Saunavaara¹³, P Ryymin¹¹, E Lammentausta¹⁴, P Osterlund¹⁵, H Isoniemi¹; RAXO Study Group

Collaborators

Affiliations

¹ Department of Transplantation and Liver Surgery, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
² Department of Radiology, HUS Medical Imaging Centre, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
³ Department of Radiology, HUS Medical Imaging Centre, Helsinki University Hospital and University of Helsinki, Helsinki, Finland; Department of Neuroscience and Biomedical Engineering, Aalto University School of Science, Helsinki, Finland.
⁴ Department of Pathology, HUS Diagnostic Centre and Applied Tumour Genomics, Research Programs Unit, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
⁵ Department of Oncology, Oulu University Hospital, Oulu, Finland.
⁶ Joint Municipal Authority for Health Care and Social Services in Keski-Uusimaa, Home Care Geriatric Clinic and Palliative Care, Hyvinkää, Finland.
⁷ Department of Oncology, Tampere University Hospital and University of Tampere, Tampere, Finland.
⁸ Department of Oncology, Turku University Hospital and University of Turku, Turku, Finland.
⁹ Department of Oncology, Helsinki University Hospital Comprehensive Cancer Center and University of Helsinki, Helsinki, Finland.
¹⁰ Department of Radiology, Turku University Hospital and University of Turku, Turku, Finland; Department of Radiology, Oulu University Hospital, Oulu, Finland.
¹¹ Department of Radiology, Medical Imaging Centre Tampere University Hospital and University of Tampere, Tampere, Finland; Department of Medical Physics, Medical Imaging Centre Tampere University Hospital and University of Tampere, Tampere, Finland.
¹² Department of Radiology, Päijät-Häme Central Hospital, Lahti, Finland.
¹³ Department of Radiology, Turku University Hospital and University of Turku, Turku, Finland.
¹⁴ Department of Radiology, Oulu University Hospital, Oulu, Finland.
¹⁵ Department of Oncology, Tampere University Hospital and University of Tampere, Tampere, Finland; Department of Oncology, Helsinki University Hospital Comprehensive Cancer Center and University of Helsinki, Helsinki, Finland; Department of Pathology/Oncology, Karolinska Institutet and Karolinska sjukhuset - Tema Cancer, Stockholm, Sweden. Electronic address: pia.osterlund@helsinki.fi.

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; diffusion-weighted imaging; liver metastasis; liver surgery; magnetic resonance spectroscopy; neoadjuvant chemotherapy.

Publication types

Multicenter Study
Research Support, Non-U.S. Gov't

MeSH terms

Colorectal Neoplasms* / diagnostic imaging
Colorectal Neoplasms* / drug therapy
Diffusion Magnetic Resonance Imaging
Follow-Up Studies
Humans
Liver Neoplasms* / diagnostic imaging
Liver Neoplasms* / drug therapy
Magnetic Resonance Spectroscopy
Neoadjuvant Therapy
Prospective Studies

Associated data

ClinicalTrials.gov/NCT01531621
EudraCT/2011-003158-24