Whole lesion histogram analysis of apparent diffusion coefficient predicts therapy response in locally advanced rectal cancer

Abstract

BACKGROUND

Whole-tumor apparent diffusion coefficient (ADC) histogram analysis is relevant to predicting the neoadjuvant chemoradiation therapy (nCRT) response in patients with locally advanced rectal cancer (LARC).

AIM

To evaluate the performance of ADC histogram-derived parameters for predicting the outcomes of patients with LARC.

METHODS

This is a single-center, retrospective study, which included 48 patients with LARC. All patients underwent a pre-treatment magnetic resonance imaging (MRI) scan for primary tumor staging and a second restaging MRI for response evaluation. The sample was distributed as follows: 18 responder patients (R) and 30 non-responders (non-R). Eight parameters derived from the whole-lesion histogram analysis (ADCmean, skewness, kurtosis, and ADC10^th, 25^th, 50^th, 75^th, 90^th percentiles), as well as the ADCmean from the hot spot region of interest (ROI), were calculated for each patient before and after treatment. Then all data were compared between R and non-R using the Mann-Whitney U test. Two measures of diagnostic accuracy were applied: the receiver operating characteristic curve and the diagnostic odds ratio (DOR). We also reported intra- and interobserver variability by calculating the intraclass correlation coefficient (ICC).

RESULTS

Post-nCRT kurtosis, as well as post-nCRT skewness, were significantly lower in R than in non-R (both P < 0.001, respectively). We also found that, after treatment, R had a larger loss of both kurtosis and skewness than non-R (∆%kurtosis and ∆skewness, P < 0.001). Other parameters that demonstrated changes between groups were post-nCRT ADC10^th, ∆%ADC10^th, ∆%ADCmean, and ROI ∆%ADCmean. However, the best diagnostic performance was achieved by ∆%kurtosis at a threshold of 11.85% (Area under the receiver operating characteristic curve [AUC] = 0.991, DOR = 376), followed by post-nCRT kurtosis = 0.78 × 10^-3 mm²/s (AUC = 0.985, DOR = 375.3), ∆skewness = 0.16 (AUC = 0.885, DOR = 192.2) and post-nCRT skewness = 1.59 × 10^-3 mm²/s (AUC = 0.815, DOR = 168.6). Finally, intraclass correlation coefficient analysis showed excellent intraobserver and interobserver agreement, ensuring the implementation of histogram analysis into routine clinical practice.

CONCLUSION

Whole-tumor ADC histogram parameters, particularly kurtosis and skewness, are relevant biomarkers for predicting the nCRT response in LARC. Both parameters appear to be more reliable than ADCmean from one-slice ROI.

Keywords: Apparent diffusion coefficient, Diffusion-weighted imaging, Histogram analysis, Magnetic resonance imaging, Locally advanced rectal cancer

Core Tip: Whole-tumor apparent diffusion coefficient (ADC) histogram analysis is an emergent imaging analysis in which every voxel is used to obtain a histogram; it thus provides statistical information about tumors. Our study revealed that ADC histogram profiling is a valuable approach that can help differentiate treatment response in locally advanced rectal cancer. When determining tailored treatments that are associated with minimal morbidities, such as the watch and wait method, an accurate treatment response prediction is critical. Given the limitations of this study, more research is needed to establish the clinical utility of our findings.