Investig Magn Reson Imaging.  2019 Dec;23(4):351-360. 10.13104/imri.2019.23.4.351.

Noninvasive Biomarker for Predicting Treatment Response to Concurrent Chemoradiotherapy in Patients with Hepatocellular Carcinoma

• Chung YE
• Park JY
• Choi JY
• Kim MJ
• Park MS
• Seong J

• KMID: 2468052
• DOI: http://doi.org/10.13104/imri.2019.23.4.351

Abstract

PURPOSE
To investigate noninvasive biomarkers for predicting treatment response in patients with locally advanced HCC who underwent concurrent chemoradiotherapy (CCRTx).
MATERIALS AND METHODS
Thirty patients (55.5 ± 10.2 years old, M:F = 24:6) who underwent CCRTx due to advanced HCC were enrolled. Contrast-enhanced US (CEUS) and dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) were obtained before and immediately after CCRTx. The third CEUS was obtained at one month after CCRTx was completed. Response was assessed at three months after CCRTx based on RECIST 1.1. Quantitative imaging biomarkers measured with CEUS and MRI were compared between groups. A cutoff value was calculated with ROC analysis. Overall survival (OS) was compared by the Breslow method.
RESULTS
Twenty-five patients were categorized into the non-progression group and five patients were categorized into the progression group. Peak enhancement of the first CEUS before CCRTx (PE1) was significantly lower in the non-progression group (median, 18.6%; IQR, 20.9%) than that in the progression group (median, 59.1%; IQR, 13.5%; P = 0.002). There was no significant difference in other quantitative biomarkers between the two groups. On ROC analysis, with a cutoff value of 42.6% in PE1, the non-progression group was diagnosed with a sensitivity of 90.9% and a specificity of 100%. OS was also significantly longer in patients with PE1 < 42.6% (P = 0.014).
CONCLUSION
Early treatment response and OS could be predicted by PE on CEUS before CCRTx in patients with HCC.

Keyword

Hepatocellular carcinoma; Ultrasonography; Perfusion imaging; Magnetic resonance imaging, Chemoradiotherapy, Biomarkers

MeSH Terms

Biomarkers
Carcinoma, Hepatocellular*
Chemoradiotherapy*
Humans
Magnetic Resonance Imaging
Methods
Perfusion Imaging
Response Evaluation Criteria in Solid Tumors
ROC Curve
Sensitivity and Specificity
Ultrasonography
Biomarkers

Figure

• 

  Fig. 1 Study protocol. DEC MRI and CEUS were performed before (MRI1 and CEUS1) and immediately after CCRTx (MRI2 and CEUS2). CEUS was also performed one month after CCRTx (CEUS3).

• 

  Fig. 2 Quantitative analysis of DCE MRI (a) and CEUS (b). (a) ROI was drawn with a dedicated program (Tissue 4D) as large as possible on the axial MR image to include the largest proportion of the tumor in DCE MRI. Ktrans, Kep and Ve values were calculated within the ROI. (b) In CEUS, the ROI was drawn as large as possible on the slice most similar to the MR image using dedicated software and PE, TTP and MTT were calculated.

• 

  Fig. 3 A 48-year-old male with locally advanced HCC. Huge hypervascular HCC with central necrosis was noted mainly in the left hepatic lobe in pretreatment (a–c), immediate (d–f) and 3 months after the end of CCRTx (g, h). PE was 40.8% in pretreatment CEUS, 47.8% immediately after CCRTx, and 10.2% at one month after CCRTx. (i) Three months after CCRTx was completed, both size and vascularity of the tumor decreased. The patient underwent left extended hemihepatectomy. On pathologic examination, there was 95% tumor necrosis. The patient was followed until the end of this study (December 31, 2016) without tumor recurrence (OS = 1943 days).

• 

  Fig. 4 Progression-free survival (a) and overall survival (b). Patients with PE < 42.6% showed better progression-free survival (P = 0.020) and overall survival (P = 0.032) than patients with PE ≥ 42.6%.

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  Fig. 5 DWI (a) DCE MRI (b–d) and CEUS (e–g) parameter changes. (a) ADC values (P < 0.001) and (d) Ve (P = 0.025) in DCE MRI significantly increased immediately after CCRTx, whereas the CEUS parameters showed no significant changes (P > 0.05).

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