Dataset Information

Targeted exome-based predictors of patterns of progression of colorectal liver metastasis after percutaneous thermal ablation.

ABSTRACT:

Background

Percutaneous thermal ablation is a curative-intent locoregional therapy (LRT) for selected patients with unresectable colorectal liver metastasis (CLM). Several factors have been identified that contribute to local tumour control after ablation. However, factors contributing to disease progression outside the ablation zone after ablation are poorly understood.

Methods

In this retrospective study, using next-generation sequencing, we identified genetic biomarkers associated with different patterns of progression following thermal ablation of CLM.

Results

A total of 191 ablation naïve patients between January 2011 and March 2020 were included in the analysis, and 101 had genomic profiling available. Alterations in the TGFβ pathway were associated with increased risk of development of new intrahepatic tumours (hazard ratio [HR], 2.75, 95% confidence interval [95% CI] 1.39-5.45, P = 0.004); and alterations in the Wnt pathway were associated with increased probability of receiving salvage LRT for any intrahepatic progression (HR, 5.8, 95% CI 1.94-19.5, P = 0.003).

Conclusions

Our findings indicate that genomic alterations in cancer-related signalling pathways can predict different progression patterns and the likelihood of receiving salvage LRT following percutaneous thermal ablation of CLM.

SUBMITTER: Paolucci I

PROVIDER: S-EPMC9814547 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Publications

Targeted exome-based predictors of patterns of progression of colorectal liver metastasis after percutaneous thermal ablation.

Paolucci Iwan I Lin Yuan-Mao YM Kawaguchi Yoshikuni Y Maki Harufumi H Jones A Kyle AK Calandri Marco M Kopetz Scott S Newhook Timothy E TE Brock Kristy K KK Vauthey Jean-Nicolas JN Odisio Bruno C BC

British journal of cancer 20221101 1

<h4>Background</h4>Percutaneous thermal ablation is a curative-intent locoregional therapy (LRT) for selected patients with unresectable colorectal liver metastasis (CLM). Several factors have been identified that contribute to local tumour control after ablation. However, factors contributing to disease progression outside the ablation zone after ablation are poorly understood.<h4>Methods</h4>In this retrospective study, using next-generation sequencing, we identified genetic biomarkers associa ...[more]

PMID: 36319850

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Project description:Percutaneous thermal ablation (PTA), resection, and liver transplantation are the standard curative options for hepatocellular carcinoma (HCC). Liver transplantation yields the best long-term outcomes but is limited by graft shortage. Thus, patients with ≤3-cm HCC are primarily treated by PTA even though recurrence is frequent and may occur outside transplant criteria. Data on non-transplantable recurrence (NTR) following PTA are lacking, however. We therefore investigated the incidence and predictors of NTR among 213 potentially transplantable patients (cirrhosis, 93%; Child-Pugh A, 98.6%; alcohol-related disease, 62%) with ≤3-cm HCC(s) treated by PTA, to stratify them according to their NTR risk and to improve treatment allocation. During follow-up (median: 41.2 months), NTR occurred in 18.3% (alpha-fetoprotein [AFP] model) and 23% (Milan) patients. NTR prediction with competing-risk analysis and internal validation revealed AFP > 100 ng/ml (subdistribution hazard ratio: 7.28; p < 0.001) and prior HCC (subdistribution hazard ratio: 3.77; p = 0.002) as independent predictors (Harrell's C: 0.76). Based on this model using the AFP score (equally predictive within Milan criteria), patients were stratified into three NTR risk categories: HCC-naïve with AFP < 100 ng/ml (low risk, n = 108 of 213), non-HCC naïve with AFP < 100 ng/ml (intermediate risk, n = 92 of 213), AFP ≥ 100 ng/ml (high risk, n = 13 of 213), among whom 9.3% (3.7% [Milan]), 22.8% (25% [Milan]), and 61.5% (38/5% [Milan]) presented NTR (p < 0.001). Median recurrence-free survival was 4.6, 14.5, and 43.4 months, respectively, in high-risk, intermediate-risk, and low-risk categories (p < 0.001). Median overall survival, which was 19.1 months in high-risk patients, was not reached otherwise (p < 0.001). Conclusion: Overall, PTA of ≤3-cm HCC incurs a low NTR risk. Simple and noninvasive predictors (HCC naivety, AFP) accurately stratified patients' risk of NTR, and should help to improve treatment allocation. Patients with AFP ≥ 100 ng/ml have a high risk of NTR, poor recurrence-free survival, and overall survival. Further studies evaluating preemptive transplantation or adjuvant/neoadjuvant strategies are highly needed in this small patient subset.

Project description:PurposeThe goal of this study was to develop and evaluate a volumetric three-dimensional (3D) approach to improve the accuracy of ablation margin assessment following thermal ablation of hepatic tumors.MethodsThe 3D margin assessment technique was developed to generate the new 3D assessment metrics: volumes of insufficient coverage (VICs) measuring volume of tissue at risk post-ablation. VICs were computed for the tumor and tumor plus theoretical 5- and 10-mm margins. The diagnostic accuracy of the 3D assessment to predict 2-year local tumor progression (LTP) was compared to that of manual 2D assessment using retrospective analysis of a patient cohort that has previously been reported as a part of an outcome-centered study. Eighty-six consecutive patients with 108 colorectal cancer liver metastases treated with radiofrequency ablation (2002-2012) were used for evaluation. The 2-year LTP discrimination power was assessed using receiver operating characteristic area under the curve (AUC) analysis.ResultsA 3D assessment of margins was successfully completed for 93 out of 108 tumors. The minimum margin size measured using the 3D method had higher discrimination power compared with the 2D method, with an AUC value of 0.893 vs. 0.790 (p = 0.01). The new 5-mm VIC metric had the highest 2-year LTP discrimination power with an AUC value of 0.923 (p = 0.004).ConclusionsVolumetric semi-automated 3D assessment of the ablation zone in the liver is feasible and can improve accuracy of 2-year LTP prediction following thermal ablation of hepatic tumors.Key points• More accurate prediction of local tumor progression risk using volumetric 3D ablation zone assessment can help improve the efficacy of image-guided percutaneous thermal ablation of hepatic tumors. • The accuracy of evaluation of ablation zone margins after thermal ablation of colorectal liver metastases can be improved using a volumetric 3D semi-automated assessment approach and the volume of insufficient coverage assessment metric. • The new 5-mm volume-of-insufficient-coverage metric, indicating the volume of tumor plus 5-mm margin that remained untreated, had the highest 2-year local tumor progression discrimination power.

Project description:PurposeTo investigate the correlation of minimal ablative margin (MAM) quantification using biomechanical deformable (DIR) versus intensity-based rigid image registration (RIR) with local outcomes following colorectal liver metastasis (CLM) thermal ablation.MethodsThis retrospective single-institution study included consecutive patients undergoing thermal ablation between May 2016 and October 2021. Patients who did not have intraprocedural pre- and post-ablation contrast-enhanced CT images for MAM quantification or follow-up period less than 1 year without residual tumor or local tumor progression (LTP) were excluded. DIR and RIR methods were used to quantify the MAM. The registration accuracy was compared using Dice similarity coefficient (DSC). Area under the receiver operating characteristic curve (AUC) was used to test MAM in predicting local tumor outcomes.ResultsA total of 72 patients (mean age 57; 44 men) with 139 tumors (mean diameter 1.5 cm ± 0.8 (SD)) were included. During a median follow-up of 29.4 months, there was one residual unablated tumor and the LTP rate was 17% (24/138). The ranges of DSC were 0.96-0.98 and 0.67-0.98 for DIR and RIR, respectively (p < 0.001). When using DIR, 27 (19%) tumors were partially or totally registered outside the liver, compared to 46 (33%) with RIR. Using DIR versus RIR, the corresponding median MAM was 4.7 mm versus 4.0 mm, respectively (p = 0.5). The AUC in predicting residual tumor and 1-year LTP for DIR versus RIR was 0.89 versus 0.72, respectively (p < 0.001).ConclusionAblative margin quantified on intra-procedural CT imaging using DIR method outperformed RIR for predicting local outcomes of CLM thermal ablation.Clinical relevance statementThe study supports the role of biomechanical deformable image registration as the preferred image registration method over rigid image registration for quantifying minimal ablative margins using intraprocedural contrast-enhanced CT images.Key points• Accurate and reproducible image registration is a prerequisite for clinical application of image-based ablation confirmation methods. • When compared to intensity-based rigid image registration, biomechanical deformable image registration for minimal ablative margin quantification was more accurate for liver registration using intraprocedural contrast-enhanced CT images. • Biomechanical deformable image registration outperformed intensity-based rigid image registration for predicting local tumor outcomes following colorectal liver metastasis thermal ablation.

Dataset Information

Targeted exome-based predictors of patterns of progression of colorectal liver metastasis after percutaneous thermal ablation.

Background

Methods

Results

Conclusions

Publications

Targeted exome-based predictors of patterns of progression of colorectal liver metastasis after percutaneous thermal ablation.

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