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Apparent diffusion coefficient and kurtosis parameters show early response to anti-angiogenic therapy in patients
Mihaela Rata1,2, Khurum Khan3,4, David J Collins5,6
1MRI Unit, Department of Radiology, The Royal Marsden NHS Foundation Trust, Downs Road, London, SM2 5PT, UK. Mihaela.Rata@icr.ac.uk.
Background:
To investigate whether the diffusion kurtosis imaging (DKI) technique can identify tumour response to an anti-angiogenic therapy in a pilot study of patients with RAS-mutant colorectal liver metastases.
Methods:
This prospective imaging study enrolled 20 participants receiving Regorafenib treatment. A target metastasis > 2 cm in each patient was imaged before and at 15 days after treatment on a 1.5T MR scanner using a coronal, free-breathing DKI protocol. Data were motion-corrected and modelled using both the mono-exponential and DKI models. Median values derived from voxel-wise analysis of the whole delineated tumour were reported for three parameters [apparent diffusion coefficient (ADC, 10- 3 mm2/s), apparent kurtosis (K, a.u.) and kurtosis-corrected apparent diffusion (D, 10- 3 mm2/s)] before and after treatment. A 5-patient supplementary cohort was used to assess the repeatability of DKI parameters using the Bland-Altman analysis. Changes in pre- and post-treatment measurements of the three parameters were assessed using Wilcoxon signed-rank tests (P < 0.05 was considered significant). Diffusion weighted imaging (DWI) and DKI parameter correlations were evaluated with Spearman tests. Functional MR parameters were also compared against Response Evaluation Criteria In Solid Tumours v.1.1 (RECIST) evaluations.
Results:
Significant treatment-induced changes across the cohort were observed for all parameters: K decrease (0.907 vs. 0.786, P < 0.01; 13.3%), D increase (1.256 vs. 1.386 × 10- 3 mm2/s, P < 0.001; 10.4%) and ADC increase (0.910 vs. 1.035 × 10- 3 mm2/s, P < 0.001; 13.7%). For both visits, Spearman correlation tests found a moderate negative correlation between K and D, (r=-0.70; P < 0.001 and r=-0.58; P < 0.01) and a strong positive correlation (r = 0.84 and 0.88; P < < 0.001) between ADC and D. The repeatability R was lowest for K (51%), followed by D (12%), and ADC (9.4%). When compared to RECIST v.1.1 evaluations, K identified no clinical responders, whilst D and ADC identified 7/12 and 11/12 responders.
Conclusions:
Both ADC and DKI parameters showed a significant early cohort change to the anti-angiogenic effects of Regorafenib treatment in RAS-mutant colorectal liver metastases. The ADC parameter performed better than the K parameter in identifying patients benefitting from the treatment.
Trial Registration:
NCT03010722 clinicaltrials.gov; registration date 6th January 2015.
Insights
Diffusion kurtosis imaging (DKI) and apparent diffusion coefficient (ADC) show early response to Regorafenib in colorectal liver metastases. ADC performed better than DKI's K parameter in identifying treatment benefits.
Area of Science:
- Radiology
- Oncology
- Medical Imaging
Background:
- Investigating Diffusion Kurtosis Imaging (DKI) for tumour response assessment.
- Focus on RAS-mutant colorectal liver metastases treated with anti-angiogenic therapy.
Purpose of the Study:
- To evaluate DKI's ability to detect early treatment response.
- Assessing Regorafenib's anti-angiogenic effects on liver metastases.
Main Methods:
- Prospective study of 20 patients receiving Regorafenib.
- 1.5T MRI with DKI protocol before and 15 days after treatment.
- Analysis of apparent diffusion coefficient (ADC), kurtosis (K), and diffusion (D) parameters.
Main Results:
- Significant changes observed in K, D, and ADC post-treatment.
- ADC and D showed strong correlations; K showed moderate correlation with D.
- ADC identified more responders (11/12) compared to K (0/12) and D (7/12).
Conclusions:
- Both ADC and DKI parameters indicate early anti-angiogenic effects.
- ADC is more effective than K in identifying patients benefiting from Regorafenib treatment.
