HCC is one of the most common primary hepatic tumors worldwide [1, 2]. The first line of HCC treatment is surgical resection and liver transplantation, yet few patients can be treated surgically, at the time of diagnosis. TACE is considered a palliative treatment for HCC and partial response after TACE therapy occurs in 15–55% of the patients, so early assessment of the response to therapy is important for guiding further treatment [19].
CT was considered the first imaging tool for follow up the patient after TACE yet beam hardening artefact that occurs after TACE may hinder the proper evaluation of the residual/viable enhancing tumor by CT scans [4]. In contrast to CT scan, MRI signals are not degraded by lipiodol droplets; so, a residual or newly developed lesion are better to be detected by MRI study [3].
Dynamic contrast-enhanced cross-section images detect the change in the size of the residual tumor and the enhancement pattern of the lesion [1] while FDG PET/CT is a functional biomarker that detects mainly the metabolism of the lesion which reflects the presence of underlying viable tumoral tissue [20, 21], DWI gives information about the degree of tumor viability, whereas the necrotic tumors have increased water diffusibility and increased ADC values due to cell membrane damage, while the viable tumoral tissue shows diffusion restriction of the water and relatively low ADC values [22].
In this study, the well-embolized HCC lesion appeared visually as photopenic area in the FDG PET/CT images while the residual viable tumoral tissue showed variable FDG uptake in the fused images, the sensitivity, specificity, and accuracy of qualitative FDG PET/CT for detection of residual viable tumoral tissue were 81.5%, 75%, and 80% respectively, similar results were also noted by and Kim et al. [11] and Song et al. [23], who reported sensitivity of 87.5% and 89.3%, specificity of 71.4% and 65.7% and accuracy of 80% and 80.2% respectively. The well-differentiated HCC didn`t retain much glucose and appear in FDG PET/CT as the normal hepatocytes while the poorly differentiated HCCs tend to show a high activity of the glycolytic enzyme and hence in the detectability by FDG PET/CT [23].
The mean values of the residual SUVmax and the SUV ratio (residual tumor SUVmax/liver SUVmean ratio) were higher than the values seen in the well-ablated lesion. The FDG uptake is affected by underlying liver cirrhosis which is noted in many of HCC patients and many studies have revealed that the SUV ratio is a more important parameter than the tumor SUV [10, 24], as it reflects the variation in glucose metabolism in both the tumor and the liver than the tumor's SUV does alone [24].
The quantitative assessment of SUV ratio revealed that the optimal cut off value for discrimination between the residual HCC and the well ablated HCC was 1.09 with sensitivity and specificity of 88.9% and 87.5% respectively, near similar cut off value was noted in Hetta et al. [14], who revealed that the optimal cut off value was 1, another study was done by Song et al. [24], revealed a higher cut off value of 1.65, the more aggressive residual tumor growth in their study may explain the higher ratio of this study. The SUV ratio was considered as an independent predictor for HCC response after TACE [24]. An advantage of the FDG PET/CT is the detection of extrahepatic metastases, in the current study, extrahepatic metastases were detected by FDG PET/CT in three patients, one was in the abdominal LNs which was also seen in the dynamic cross-section imaging, and the other two metastatic lesions were seen in chest and brain which were missed by the dynamic cross-section imaging.
In the current study, the sensitivity and specificity of the qualitative DWI for the detection of residual viable HCC after TACE were 77.8% and 75% respectively, a similar result was also noted in Ebeed et al. [3] study who revealed 82.3% sensitivity and 73.9% specificity. Saleh et al. [1] revealed different diagnostic values with a lower sensitivity of 52.6% and higher specificity of 90.5%, their study incorporated LR-TR non-evaluable HCC which was excluded in this study.
The sensitivity of quantitative ADC value was higher than the DWI for the detection of residual HCC, with a sensitivity and specificity of 81.5% and 75% respectively at ADC cut off value of 1.32 × 10−3 mm2/s, a higher cut off value was reported by Ebeed et al. [3] who revealed a sensitivity of 76.5% and specificity of 65.2% at a cut off value of 1.38 × 10−3 mm2/s.
According to logistic regression analysis, the current study revealed that the ADC value was the most significant functional imaging variable for predicting viable HCC, with the optimal ADC value for predicting viable HCC being 1.35 × 10−3 mm2/s with 88.6% accuracy. A similar result was reported by Saleh et al. [1], who revealed an accuracy of 82.5% at a cut off value of 1.35 × 10−3 mm2/s.
The LI-RAS v2018 has involved major and minor criteria for categorization of the non-treated hepatic focal lesion, and the DWI was considered one of its minor features, yet LI-RADS treatment response depends only upon the enhancement pattern of the treated HCC, and it didn’t incorporate the DWI, ADC or the FDG PET/CT. In our study the accuracy of ADC and SUV ratio were comparable, and further studies may reveal the added value of ADC and PET/CT for the detection of the residual HCC after TACE. The standardized reporting method must be a dynamic process, subjected to clinical and radiological feedback and data validation, for further evaluation and development [25, 26], both DWI and FDG PET/CT gained the advantage of avoiding contrast administration, which may be a major problem in patients suffering from renal impairment.
To summarize the implication of various functional imaging modalities and based upon the logistic regression analysis, we proposed that if a local residual or recurrent tumoral tissue is suspected following TACE, the imaging modality of choice will be an MRI study with anatomical, functional images such as DWIs and ADC, and dynamic contrast study. PET/CT, on the other hand, will be the imaging modality of choice if alpha-fetoprotein is substantially increased with probable metastatic deposits since it can evaluate the hepatic focal lesion and precisely locate any distant metastatic deposits.