MRI Apparent Diffusion Coefficient (ADC) as a Biomarker of Tumour Response: Imaging-Pathology Correlation in Patients with Hepatic Metastases from Colorectal Cancer (EORTC 1423)
by
, , , ,
Alan Jackson
1, 
Ryan Pathak
1,
Nandita M. deSouza
2,
Yan Liu
3,
Bart K. M. Jacobs
3,
Saskia Litiere
3,
Maria Urbanowicz-Nijaki
3,
Catherine Julie
4,5,
Arturo Chiti
6,7,
Jens Theysohn
8,
Juan R. Ayuso
9,
Sigrid Stroobants
10 and
John C. Waterton
1,*
1
Centre for Imaging Sciences, University of Manchester, Manchester M20 4GJ, UK
2
CRUK Cancer Imaging Centre, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Downs Road, London SW7 3RP, UK
3
European Organisation for Research and Treatment of Cancer, 1200 Brussels, Belgium
4
EA 4340 BECCOH, UVSQ, Universite Paris-Saclay, 92104 Boulogne-Billancourt, France
5
Department of Pathology, APHP-Hopital Ambroise Pare, 92100 Boulogne-Billancourt, France
6
Nuclear Medicine Unit, IRCCS Humanitas Research Hospital, 20089 Rozzano, Italy
7
Department of Bio-Medical Sciences, Humanitas University, 20072 Milan, Italy
8
Institute of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen, University Duisburg-Essen, 45122 Essen, Germany
9
Radiology Department—CDI, Hospital Clinic Universitari de Barcelona, 08036 Barcelona, Spain
10
Molecular Imaging and Radiology, University of Antwerp, 2000 Antwerp, Belgium
*
Author to whom correspondence should be addressed.
Cancers 2023, 15(14), 3580; https://doi.org/10.3390/cancers15143580
Submission received: 13 May 2023
/
Revised: 29 June 2023
/
Accepted: 30 June 2023
/
Published: 12 July 2023
(This article belongs to the Special Issue Quantitative Imaging and Digital Pathology in Clinical Cancer Research)
Simple Summary
We hypothesised that change in a magnetic resonance imaging (MRI) biomarker, the apparent diffusion coefficient (ADC) after 14 days of treatment could be a proxy for tumour regression grade (TRG) on pathology. Measurement of the imaging biomarker was standardised across centres. We restricted measurements to liver metastases from colorectal cancer and ensured a standardised chemotherapy approach. We identified and eliminated significant measurement error due to MRI scanner performance. We excluded studies that failed to conform to the imaging protocol or where images contained movement artefact. We ensured stability of the scanners by periodic quality control testing and used a standard, widely used data analysis technique to derive the ADC. Despite these measures, our results showed no significant correlation between ADC and TRG or between ADC and percentage of viable tumour, percentage necrosis, percentage fibrosis or a tumour proliferation index. This may reflect the complex cellular architecture of tumours after treatment.
Abstract
Background: Tumour apparent diffusion coefficient (ADC) from diffusion-weighted magnetic resonance imaging (MRI) is a putative pharmacodynamic/response biomarker but the relationship between drug-induced effects on the ADC and on the underlying pathology has not been adequately defined. Hypothesis: Changes in ADC during early chemotherapy reflect underlying histological markers of tumour response as measured by tumour regression grade (TRG). Methods: Twenty-six patients were enrolled in the study. Baseline, 14 days, and pre-surgery MRI were performed per study protocol. Surgical resection was performed in 23 of the enrolled patients; imaging-pathological correlation was obtained from 39 lesions from 21 patients. Results: There was no evidence of correlation between TRG and ADC changes at day 14 (study primary endpoint), and no significant correlation with other ADC metrics. In scans acquired one week prior to surgery, there was no significant correlation between ADC metrics and percentage of viable tumour, percentage necrosis, percentage fibrosis, or Ki67 index. Conclusions: Our hypothesis was not supported by the data. The lack of meaningful correlation between change in ADC and TRG is a robust finding which is not explained by variability or small sample size. Change in ADC is not a proxy for TRG in metastatic colorectal cancer.
