Prediction Role of Baseline Digital Substraction Angiography in GEP Neuroendocrine Liver Metastases Treated with TAE/ TACE

Aim Transarterial embolization (TAE) or transarterial chemoembolization (TACE) is an important treatment approach for unresectable liver metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs). The prediction tool for therapeutic evaluation is still unclear. This study was performed to assess the prediction role of baseline digital substraction angiography (DSA) in synchronous liver metastatic GEP-NETs treated with TAE/ TACE. Methods Twenty-two patients with synchronous unresectable liver metastatic GEP-NETs (G1/2) and treated with TAE/ TACE were retrospectively enrolled. Clinical characteristics, baseline DSA and computed tomography (CT) information were collected. Results Totally, the overall response rate of TAE/ TACE on liver metastasis was 45.5%. The average baseline CT ratio (the density of the target lesion / the density of abdominal aorta during arterial phase) between responsive group and nonresponsive group were not statistically different (0.30±0.06 versus 0.36±0.11, P=0.149). Whereas, the average baseline DSA ratio (the density of target lesion / the density of liver background on DSA imaging before TAE/ TACE) of responsive group was significantly lower compared with that of nonresponsive group (0.57±0.13 versus 0.70±0.15, P=0.037). Patients with a DSA ratio ≤0.64 were more responsive to TAE/ TACE than those with a DSA ratio ༞0.64 (58.3% versus 30%). Univariate and multivariate analysis indicated that patients with lower hepatic tumor burden had longer PFS. Conclusions Baseline DSA ratio is a simple and potentially useful method to predict therapeutic effect of TAE/ TACE in liver metastases from GEP-NETs. And patients with lower hepatic tumor burden might indicate better prognosis. Prospective large-scale study is warranted.

Liver-First Approach for Synchronous Colorectal Metastases: Analysis of 7360 Patients from the LiverMetSurvey Registry

Background The liver-first approach in patients with synchronous colorectal liver metastases (CRLM) has gained wide consensus but its role is still to be clarified. We aimed to elucidate the outcome of the liver-first approach and to identify patients who benefit at most from this approach. Methods Patients with synchronous CRLM included in the LiverMetSurvey registry between 2000 and 2017 were considered. Three strategies were analyzed, i.e. liver-first approach, colorectal resection followed by liver resection (primary-first), and simultaneous resection, and three groups of patients were analyzed, i.e. solitary metastasis, multiple unilobar CRLM, and multiple bilobar CRLM. In each group, patients from the three strategy groups were matched by propensity score analysis. Results Overall, 7360 patients were analyzed: 4415 primary-first, 552 liver-first, and 2393 simultaneous resections. Compared with the other groups, the liver-first group had more rectal tumors (58.0% vs. 31.2%) and higher hepatic tumor burden (more than three CRLMs: 34.8% vs. 24.0%; size > 50 mm: 35.6% vs. 22.8%; p < 0.001). In patients with solitary and multiple unilobar CRLM, survival was similar regardless of treatment strategy, whereas in patients with multiple bilobar metastases, the liver-first approach was an independent positive prognostic factor, both in unmatched patients (3-year survival 65.9% vs. primary-first 60.4%: hazard ratio [HR] 1.321, p = 0.031; vs. simultaneous resections 54.4%: HR 1.624, p < 0.001) and after propensity score matching (vs. primary-first: HR 1.667, p = 0.017; vs. simultaneous resections: HR 2.278, p = 0.003). Conclusion In patients with synchronous CRLM, the surgical strategy should be decided according to the hepatic tumor burden. In the presence of multiple bilobar CRLM, the liver-first approach is associated with longer survival than the alternative approaches and should be evaluated as standard.

Image-Guided Peri-Tumoral Radiofrequency Hyperthermia-Enhanced Direct Chemo-Destruction of Hepatic Tumor Margins

PurposeTo validate the feasibility of using peri-tumoral radiofrequency hyperthermia (RFH)-enhanced chemotherapy to obliterate hepatic tumor margins.Method and MaterialsThis study included in vitro experiments with VX2 tumor cells and in vivo validation experiments using rabbit models of liver VX2 tumors. Both in vitro and in vivo experiments received different treatments in four groups (n=6/group): (i) RFH-enhanced chemotherapy consisting of peri-tumoral injection of doxorubicin plus RFH at 42°C; (ii) RFH alone; (iii) doxorubicin alone; and (iv) saline. Therapeutic effect on cells was evaluated using different laboratory examinations. For in vivo experiments, orthotopic hepatic VX2 tumors in 24 rabbits were treated by using a multipolar radiofrequency ablation electrode, enabling simultaneous delivery of both doxorubicin and RFH within the tumor margins. Ultrasound imaging was used to follow tumor growth overtime, correlated with subsequent histopathological analysis.ResultsIn in vitro experiments, MTS assay demonstrated the lowest cell proliferation, and apoptosis analysis showed the highest apoptotic index with RFH-enhanced chemotherapy, compared with the other three groups (p&lt;0.01). In in vivo experiments, ultrasound imaging detected the smallest relative tumor volume with RFH-enhanced chemotherapy (p&lt;0.01). The TUNEL assay further confirmed the significantly increased apoptotic index and decreased cell proliferation in the RFH-enhanced therapy group (p&lt;0.01).ConclusionThis study demonstrates that peri-tumoral RFH can specifically enhance the destruction of tumor margins in combination with peri-tumoral injection of a chemotherapeutic agent. This new interventional oncology technique may address the critical clinical problem of frequent marginal tumor recurrence/persistence following thermal ablation of large (&gt;3 cm) hepatic cancers.

Automatized Hepatic Tumor Volume Analysis of Neuroendocrine Liver Metastases by Gd-EOB MRI—A Deep-Learning Model to Support Multidisciplinary Cancer Conference Decision-Making

Background: Rapid quantification of liver metastasis for diagnosis and follow-up is an unmet medical need in patients with secondary liver malignancies. We present a 3D-quantification model of neuroendocrine liver metastases (NELM) using gadoxetic-acid (Gd-EOB)-enhanced MRI as a useful tool for multidisciplinary cancer conferences (MCC). Methods: Manual 3D-segmentations of NELM and livers (149 patients in 278 Gd-EOB MRI scans) were used to train a neural network (U-Net architecture). Clinical usefulness was evaluated in another 33 patients who were discussed in our MCC and received a Gd-EOB MRI both at baseline and follow-up examination (n = 66) over 12 months. Model measurements (NELM volume; hepatic tumor load (HTL)) with corresponding absolute (ΔabsNELM; ΔabsHTL) and relative changes (ΔrelNELM; ΔrelHTL) between baseline and follow-up were compared to MCC decisions (therapy success/failure). Results: Internal validation of the model’s accuracy showed a high overlap for NELM and livers (Matthew’s correlation coefficient (φ): 0.76/0.95, respectively) with higher φ in larger NELM volume (φ = 0.80 vs. 0.71; p = 0.003). External validation confirmed the high accuracy for NELM (φ = 0.86) and livers (φ = 0.96). MCC decisions were significantly differentiated by all response variables (ΔabsNELM; ΔabsHTL; ΔrelNELM; ΔrelHTL) (p < 0.001). ΔrelNELM and ΔrelHTL showed optimal discrimination between therapy success or failure (AUC: 1.000; p < 0.001). Conclusion: The model shows high accuracy in 3D-quantification of NELM and HTL in Gd-EOB-MRI. The model’s measurements correlated well with MCC’s evaluation of therapeutic response.