Assessment of treatment response during chemoradiation therapy for pancreatic cancer based on quantitative radiomic analysis of daily CTs: An exploratory study

Abstract

Purpose: In an effort for early assessment of treatment response, we investigate radiation induced changes in quantitative CT features of tumor during the delivery of chemoradiation therapy (CRT) for pancreatic cancer.

Methods: Diagnostic-quality CT data acquired daily during routine CT-guided CRT using a CT-on-rails for 20 pancreatic head cancer patients were analyzed. On each daily CT, the pancreatic head, the spinal cord and the aorta were delineated and the histograms of CT number (CTN) in these contours were extracted. Eight histogram-based radiomic metrics including the mean CTN (MCTN), peak position, volume, standard deviation (SD), skewness, kurtosis, energy and entropy were calculated for each fraction. Paired t-test was used to check the significance of the change of specific metric at specific time. GEE model was used to test the association between changes of metrics over time for different pathology responses.

Results: In general, CTN histogram in the pancreatic head (but not in spinal cord) changed during the CRT delivery. Changes from the 1st to the 26th fraction in MCTN ranged from -15.8 to 3.9 HU with an average of -4.7 HU (p<0.001). Meanwhile the volume decreased, the skewness increased (less skewed), and the kurtosis decreased (less peaked). The changes of MCTN, volume, skewness, and kurtosis became significant after two weeks of treatment. Patient pathological response is associated with the changes of MCTN, SD, and skewness. In cases of good response, patients tend to have large reductions in MCTN and skewness, and large increases in SD and kurtosis.

Conclusions: Significant changes in CT radiomic features, such as the MCTN, skewness, and kurtosis in tumor were observed during the course of CRT for pancreas cancer based on quantitative analysis of daily CTs. These changes may be potentially used for early assessment of treatment response and stratification for therapeutic intensification.

Fig 1. An example case.

(a) a comparison of axial CT slice with contour of the GTV (pancreas head) from the daily CTs for the 1^st and 26^th fractions, (b) HU histograms of the GTVs for the 1^st and 26^th fraction (the histograms were normalized and the actual ratio of volumes was 1.73:1), and (c) the change of mean CTN in GTV with elapsed time through the course of treatment.

Fig 2. Changes in MCTN and other metrics with treatment.

(a) The MCTN (solid red) and relative volume (dashed blue) changes from the 1^st fraction to the 26^th fraction for the 20 patients; (b) the average MCTN changes over all patients with respect to the elapsed time of treatment for the GTV, spinal cord, and blood in aorta. The uncertainty region (shaded) of the machine measurement was defined with the 95% confidence interval within the ±2σ dash lines determined from phantom measurement over 40 months; (c) the average changes in PP, volume, skewness, and kurtosis over all patients with respect to the elapsed time of treatment for the GTV.

Fig 3. The changes in CTN histograms and metrics for three typical patients.

The CTN histograms of the GTVs for the first day of each week along with the changes of the eight metrics with respect to the elapsed treatment time for two good pathologic response patients: (a) Patient 9 and (b) Patient 20, and for one with poor response (c) Patient 3.

Fig 4. Comparisons of the average changes of for the good- and poor-response groups.

(a) moments of histogram including MCTN, SD, skewness, kurtosis, and (b) volume in GTV from the first RT fraction during the course of CRT. The error bar is the standard error of the values of the cohort.

Fig 5. The correlation of the change and initial value of MCTN.

The straight line is the best linear fit.