DAXX Mutation Status of Embolization-Treated Neuroendocrine Tumors Predicts Shorter Time to Hepatic Progression.

PURPOSE: To identify common gene mutations in patients with neuroendocrine liver metastases (NLM) undergoing transarterial embolization (TAE) and establish relationship between these mutations and response to TAE. MATERIALS AND METHODS: Patients (n = 51; mean age 61 y; 29 men, 22 women) with NLMs who underwent TAE and had available mutation analysis were identified. Mutation status and clinical variables were recorded and evaluated in relation to hepatic progression-free survival (HPFS) (Cox proportional hazards) and time to hepatic progression (TTHP) (competing risk proportional hazards). Subgroup analysis of patients with pancreatic NLM was performed using Fisher exact test to identify correlation between mutation and event (hepatic progression or death) by 6 months. Changes in mutation status over time and across specimens in a subset of patients were recorded. RESULTS: Technical success of TAE was 100%. Common mutations identified were MEN1 (16/51; 31%) and DAXX (13/51; 25%). Median overall survival was 48.7 months. DAXX mutation status (hazard ratio = 6.21; 95% confidence interval [CI], 2.67-14.48; P < .001) and tumor grade (hazard ratio = 3.05; 95% CI, 1.80-5.17; P < .001) were associated with shorter HPFS and TTHP on univariate and multivariate analysis. Median HPFS was 3.6 months (95% CI, 1.7-5.3) for patients with DAXX mutation compared with 8.9 months (95% CI, 6.6-11.4) for patients with DAXX wild-type status. In patients with pancreatic NLMs, DAXX mutation status was associated with hepatic progression or death by 6 months (P = .024). DAXX mutation status was concordant between primary and metastatic sites. CONCLUSIONS: DAXX mutation is common in patients with pancreatic NLMs. DAXX mutation status is associated with shorter HPFS and TTHP after TAE.

Gene Signature Associated with Upregulation of the Wnt/ß-Catenin Signaling Pathway Predicts Tumor Response to Transarterial Embolization.

PURPOSE: To identify gene mutations in tumors undergoing transarterial embolization and explore the relationship between gene mutations and tumor response to embolization. MATERIALS AND METHODS: This was a retrospective review that included 17 patients with primary or metastatic liver tumors treated with embolization and had specimens analyzed for a 341-gene panel next-generation sequence assay. Pathologic conditions included hepatocellular, carcinoid, pancreatic neuroendocrine, melanoma, medullary thyroid, and liver acinar-cell carcinoma. Disease, procedure data, and tumor response data were collected. Dimensionality reduction was performed by using principal component analysis. A linear support vector machine was used to learn a prediction rule and identify the genes most predictive of objective tumor response (partial or complete) per modified Response Evaluation Criteria In Solid Tumors. Cross-validation was used to test the prediction on the holdout set. Permutation testing was used to determine statistical significance of prediction accuracy. Recursive feature elimination was used to identify the most predictive genes. RESULTS: At 4 months after embolization, 9 tumors showed a response and 8 did not. Using the top two principal components, prediction accuracy of the gene mutation signature was 70% (±11%), which was statistically significant (P < .05). The most predictive genes were CTNNB1, MEN1, and NCOR1: three genes associated with the Wnt/ß-catenin and hypoxia signaling pathways. CONCLUSIONS: This study identifies gene mutations in tumors treated with transarterial embolization. A gene-mutation signature obtained from the mutation data suggests that upregulation of the Wnt/ß-catenin signaling pathway may be associated with sensitivity to embolization.

Utility of Core Biopsy Specimen to Identify Histologic Subtype and Predict Outcome for Lung Adenocarcinoma.

BACKGROUND: Lung adenocarcinoma histologic subtype is an important indicator of patient outcomes, so preoperative knowledge of subtype may be helpful to guide surgical planning. We evaluated the sensitivity and prognostic efficacy of specimens from computed tomography-guided core needle biopsies to predict histologic subtype and patient outcome after surgery. METHODS: We retrospectively identified 221 patients with lung adenocarcinoma who underwent computed tomography-guided lung biopsy and subsequent surgical resection. Concordance, accuracy, specificity, and sensitivity of histologic subtypes from core biopsy specimens were compared with surgically resected specimens. Tumor characteristics and biopsy procedural factors were analyzed to determine impact on diagnostic sensitivity. Histologic subtype based on biopsy specimen, clinical, tumor, and treatment variables were also examined in relation to time to progression. RESULTS: Overall concordance of biopsy samples with the predominant subtype from surgical specimens was 77%. Specificity (sensitivity) of detecting a nonaggressive and aggressive subtype were 86% (93%) and 95% (48%), respectively. Length of core specimen and percentage subtype composition in the surgically resected specimen were correlated with improved sensitivity but to a lesser extent with aggressive subtypes. Presence of an aggressive subtype in biopsy specimens was an independent predictor of progression after surgery (subdistribution hazard ratio, 2.51; 95% confidence interval, 1.28-4.94; p = 0.0075). CONCLUSIONS: Specimens from computed tomography-guided core biopsies can predict lung adenocarcinoma progression after surgical resection. Future prospective studies should address the role of core biopsy in preoperative planning.

Thermal Ablation in the Management of Colorectal Cancer Patients with Oligometastatic Liver Disease.

BACKGROUND: Surgical resection of limited colorectal liver disease improves long-term survival and can be curative in a subset of selected cases. Image-guided percutaneous ablation therapies have emerged as safe and effective alternative options for selected patients with unresectable colorectal liver metastases (CLM) that can be ablated with margins. Ablation causes focal destruction of tissue and has increasingly been shown to provide durable eradication of tumors. METHODS: A selective review of literature was conducted in PubMed, focusing on recent studies reporting on the safety, efficacy, and long-term outcomes of percutaneous ablation modalities in the treatment of CLM. The present work gives an overview of the different ablation techniques, their current clinical indications, and reported outcomes from most recently published studies. The 'test of time' concept for using ablation as a first local therapy is also described. RESULTS: There are several thermal ablative tools currently available, including radiofrequency ablation (RFA), microwave ablation, and cryoablation. Most data to date originated from the application of RFA. Adjuvant thermal ablation in the treatment of oligometastatic colon cancer liver disease offers improved oncologic outcomes. The ideal CLM amenable to percutaneous ablation is a solitary tumor with the largest diameter up to 3 cm that can be completely ablated with a sufficient margin. 5-year overall survival rates up to 70% after ablation of unresectable CLM have been reported. Pathologic confirmation of complete tumor necrosis with margins over 5 mm provides best long-term local tumor control by thermal ablation. CONCLUSION: Current evidence suggests that percutaneous ablation as adjuvant to chemotherapy improves oncologic outcomes of patients with CLM. For small tumors that can be ablated completely with clear margins, percutaneous ablation may offer outcomes similar to those of surgery.