Natural History of Incidental Enhancing Nodules on Cone-Beam Computer Tomography during Transarterial Therapy of Hepatocellular carcinoma

Clinical question
To characterize incidental enhancing nodules (IENs) seen on contrast-enhanced cone beam CT during transarterial HCC treatment.

Take away point
The majority of incidental enhancing nodules (IENs) ≥ 3 mm in patients with segmental sublobar HCC do not progress to HCC. Risk factors for progression of IENs to HCC include ≥ 4 nodules, hepatitis C, and elevated pretreatment AFP.

Reference
Elboraey M, Devcic Z, Montazeri S, Paz-Fumagalli R, McKinney J, Toskich B, et al. Natural History of Incidental Enhancing Nodules on Cone-Beam Computer Tomography during Transarterial Therapy of Hepatocellular Carcinoma. J Vasc Interv Radiol. 2021 Aug; 1(8): 1186-1192.

Click here for abstract

Study design
Single-center retrospective analysis with 100 patients with segmental sublobar HCC with contrast-enhanced CT prior to transarterial treatment.

Funding Source
No reported funding

Setting
Academic setting. Mayo Clinic Florida, Jacksonville, Florida.

Figure

Figure: Contrast enhanced MRI and CT demonstrating IENs that progressed to HCC in 6 months. (a) Contrast-enhanced magnetic resonance (MR) image demonstrated a questionable focus of enhancement in segment 5 within 30 days of cone-beam computed tomography (CT) acquisition during the transarterial treatment of hepatocellular carcinoma (HCC). (b) Contrast-enhanced cone-beam CT clearly demonstrated an incidental enhancing nodule (IEN) of ≥3 mm in segment 5. (c, d) Contrast-enhanced MR image 6 months after cone-beam CT demonstrated arterial enhancement, washout, and pseudocapsule of the progressed IEN consistent with HCC.

Summary

Hepatocellular carcinoma is diagnosed based on characteristic imaging features including arterial enhancement, delayed washout, and pseudocapsule formation on contrast-enhanced CT or MRI. Other benign and premalignant conditions such as regenerative nodules, dysplastic nodules, confluent fibrosis, and vascular shunts may also demonstrate arterial hyperenhancement, posing a diagnostic dilemma. Contrast-enhanced cone-beam CT is useful tool for detecting small hypervascular liver tumors and used during transarterial HCC therapy to identify parasitized arteries feeding the tumor. Occult enhancing lesions seen on contrast-enhanced cone beam CT may represent regenerative nodules, dysplastic nodules, or HCC and are of indeterminate significance. The authors followed incidental enhancing nodules (IENs) on contrast-enhanced CT after treatment and compared characteristics of patient with progression of IENs with those of patients without progression to HCC. Statistical analysis including the Mann-Whitney U test, chi-square test with a significance level of p <0.05, and receiver operating characteristic (ROC) curve analysis using SPSS.

One hundred-eighty patients met the study inclusion criteria of having segmental distribution sub-lobar HCC, contrast-enhanced cone-beam CT, and follow-up cross sectional imaging at least one month after the procedure. Eighty patients were excluded due to having multifocal disease, cone-beam CT not inclusive of nontarget parenchyma, lack of follow-up imaging, biphenotypic tumors, and IEN in treated territory. Of the remaining one-hundred patients, fifty-six patients had IENs on cone-beam imaging, while forty-four patients did not have IENs. One hundred fifty-four IENs were followed over a median follow-up time of two hundred eighty-two days at intervals of one, three, six, nine, and twelve months after treatment. Thirteen IENs progressed to HCC in ten patients, while one hundred forty-one IENs did not transform to HCC.

• Patients with four or more IENs had an odds ratio (OR) of 5.9 of progression to HCC compared to patients with one to three IENs (p = 0.020).
• Patients with increased baseline AFP had an increased risk of progression of IENs to HCC (p = 0.035, median 61.5 vs 8.6 ng/mL). Recommended cutoff of 15.5 ng/mL with AUC of 0.71, sensitivity of 80% and specificity of 67%. 
• Patients with hepatitis C virus (HCV) infection had increased risk of progression of IENs to HCC (p = 0.015)

Characteristics of IENs that were not associated with increased risk of progression to HCC include neutrophil count (p = 0.719), lymphocyte count (p = 0.432), neutrophil-to-lymphocyte ratio (p = 0.383), and IEN size (p = 0.458).

While HCC macrovascular invasion is associated with poor prognosis, it was not associated with increased risk for IEN progression (p > 0.99). Additional characteristics of HCC that were not associated with IEN progression include HCC infiltrative patter, (p = 0.143), presence of satellites (p = 0.143), and typical HCC features (p = 0.40).

Commentary

The authors attempted to address a diagnostic dilemma encountered during the transarterial treatment of hepatocellular carcinoma: incidental enhancing nodules (IENs). The most recent guidance regarding incidental hepatic nodules is addressed in the ACR White Paper published in 2017, which recommends follow-up MRI of incidental liver masses < 1 cm in size in high-risk patients. This study provides an update to these recommendations with new data regarding the potential for IENs to progress to HCC. A prior study on IEN progression by Lucatelli et al. has reported a significantly higher rate of progression of IENs to HCC, however this is likely due to difference in study design and progression criteria. Limitations of this study include the retrospective nature, small sample size, and single institution study, which limits drawing conclusions from the data. Inherent biases of this study include a lead time bias due to a significant difference in follow-up between patients with and without progression. Further prospective studies are necessary to further evaluate the significance of incidental enhancing nodules (IENs) in the setting of hepatocellular carcinoma. The study may provide guidance in designing a prospective study to evaluate how to manage IENs in a similar patient population. Furthermore, this study suggests wider application of enhanced cone beam CT. The factors associated with increased risk of progression of IENs to HCC identified in this study (hepatitis C, IEN number >4, and elevated AFP above 15.5 ng/mL) may help guide future prospective studies and recommendations regarding this diagnostic dilemma.

Post Author
Brian Stephen Wong, MD MPH
PGY-3 Diagnostic Radiology Resident
University of Texas Medical Branch

Edited and formatted by @NingchengLi

Interventional Radiology Resident

Dotter Institute, Oregon Health and Science University