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)

Aki Uutela ,Juhani Kosunen,Tuija Poussa,Siru Mäkelä,Maija Lavonius,Riikka Huuhtanen,Johanna Mattson,Eija Korkeila,Martine Vornanen,Marjut Timonen,Emerik Österlund,Niina Paunu,Veera Salminen,Olli Carpén,Jari Sundström,Sirpa Leppä,Petri Bono,Heikki Mäkisalo,Eija Sutinen,Nieminen Lasse,Eetu Heervä,Kaisa Lehtomäki,Heidi Penttinen,Eila Lantto ,Antti Hakkarainen ,Raija Kallio ,Johanna Virtanen ,Helena Isoniemi ,Tapio Salminen ,Pertti Ryymin ,Eveliina Lammentausta ,Ari Ristimäki ,Jani Saunavaara ,Arno Nordin ,Päivi Halonen ,Annika Ålgars ,Raija Ristamäki ,Pia Österlund ,Leena‐Maija Soveri ,Irina Rinta-Kiikka ,Elina Liukkonen ,Nina Lundbom ,Markus J Mäkinen ,Ali Ovissi ,Roberto Blanco Sequeiros ,Eija Pääkkö

doi:10.1016/j.esmoop.2021.100208

Abstract

BackgroundColorectal 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 methodsWe 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).ResultsIn 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.ConclusionsLow 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.

Highlights

Liver is the most common metastatic location in metastatic colorectal cancer, seen in 68%-71% when metastatic disease is diagnosed.[1,2] Without metastasectomy, the prognosis of mCRC is poor
Reverse median KaplaneMeier follow-up was 65 months
Partial response on neoadjuvant or conversion chemotherapy (NAC) according to RECIST was seen in 51% and stable disease in 49% (Table 2)

Summary

Introduction

Liver is the most common metastatic location in metastatic colorectal cancer (mCRC), seen in 68%-71% when metastatic disease is diagnosed.[1,2] Without metastasectomy, the prognosis of mCRC is poor. Colorectal cancer liver metastases respond to chemotherapy and targeted agents by shrinking, and by morphologic and metabolic changes. Patients and methods: We investigated contrast-enhanced MRI, apparent diffusion coefficient (ADC) in diffusionweighted 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). 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. 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.

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