Risk Stratification of 18F-Fluorodeoxyglucose-Avid Thyroid Nodules Based on ACR Thyroid Imaging Reporting and Data System.

OBJECTIVE: Fine needle aspiration (FNA) of thyroid nodules is often requested based on 18F-fluorodeoxyglucose (FDG) uptake regardless of sonographic features. The purpose of this study is to determine the risk of malignancy in FDG-avid thyroid nodules when stratified according to the ACR Thyroid Imaging Reporting and Data System (TI-RADS). METHODS: This retrospective study included patients who underwent ultrasound-guided FNA between January 1, 2010, and November 19, 2018, and PET/CT within 1 year before the FNA. In all, 170 nodules in 166 patients (65 men, 101 women, age 60.2 ± 14.3 years) were eligible for inclusion, of which 151 had a clearly benign or malignant histology. PET images were reviewed for maximum standardized uptake value and nodule location. Sonographic features and TI-RADS category were determined by three radiologists. Patient charts were reviewed for histology. Statistical analyses included risk of malignancy in FDG-avid nodules within each TI-RADS category. RESULTS: Of the 151 nodules, 52 were malignant (34.4%). Malignancy risk was 0% in 1 TR1 nodule (compared with 0.3% in the published TI-RADS study), 16.7% in 6 TR2 nodules (compared with 1.5%), 13.2% in 38 TR3 nodules (compared with 4.8%), 23.7% in 59 TR4 nodules (compared with 9.1%), and 68.1% in 47 TR5 nodules (compared with 35.0%). DISCUSSION: The majority (71%, 121 of 170) of FDG-avid thyroid nodules are TR4 and TR5, with rates of malignancy greater than those in the general TI-RADS population. ACR TI-RADS is helpful in stratification of FDG-avid nodules; the risk of malignancy in sonographically low-suspicion nodules (13.3%, 6 of 45) is significantly lower than high-suspicion nodules (43.4%, 46 of 106, P < .001).

Volumetric 3D assessment of ablation zones after thermal ablation of colorectal liver metastases to improve prediction of local tumor progression.

PURPOSE: The 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. METHODS: The 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. RESULTS: A 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). CONCLUSIONS: Volumetric 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.

Micropapillary and/or Solid Histologic Subtype Based on Pre-Treatment Biopsy Predicts Local Recurrence After Thermal Ablation of Lung Adenocarcinoma.

BACKGROUND: To investigate whether histologic subtyping from biopsies can predict local recurrence after thermal ablation for lung adenocarcinoma. METHODS: Patients treated with CT-guided thermal ablation for lung adenocarcinoma that had pre-ablation needle biopsy with analysis of histologic components were identified. Age, gender, smoking status, treatment indication (primary stage 1 tumor versus salvage), histologic subtype, ground-glass radiographic appearance, tumor size, ablation modality, and ablation margin were evaluated in relation to time to local recurrence (TTLR). Cumulative incidence of recurrence (CIR) was calculated using competing risks analysis and compared across groups using Fine and Grey method with clustering. Multivariate analysis was conducted with stepwise regression. RESULTS: There were 53 patients with 57 tumors diagnosed as adenocarcinoma on pre-ablation biopsy and with histologic subtype analysis. Of these, 19% (11) had micropapillary components, 14% (8) had solid components, and 26% (15) had micropapillary and/or solid components. In the univariate analysis, solid (subdistribution hazard ratio [SHR] = 4.04, p = 0.0051, 95% confidence interval [CI] = 1.52-10.7), micropapillary (SHR = 3.36, p = 0.01, CI = 1.33-8.47), and micropapillary and/or solid components (SHR = 5.85, p = 0.00038, CI = 2.21-15.5) were significantly correlated with shorter TTLR. On multivariate analysis, the presence of micropapillary and/or solid component (SHR = 11.4, p = 0.00021, CI: 3.14-41.3) was the only independent predictor of TTLR. The 1-, 2-, and 3-year CIR in patients with micropapillary and/or solid components was 33, 49, and 66% compared to 5, 14, and 18% in patients with no micropapillary or solid components on biopsy specimens. CONCLUSION: Micropapillary and/or solid histologic components identified in pre-ablation biopsy are associated with shorter TTLR after thermal ablation of lung adenocarcinoma.

Percutaneous Microwave versus Radiofrequency Ablation of Colorectal Liver Metastases: Ablation with Clear Margins (A0) Provides the Best Local Tumor Control.

PURPOSE: To identify and compare predictors of local tumor progression (LTP)-free survival (LTPFS) after radiofrequency (RF) ablation and microwave (MW) ablation of colorectal liver metastases (CLMs). MATERIALS AND METHODS: This is a retrospective review of CLMs ablated from November 2009 to April 2015 (110 patients). Margins were measured on contrast-enhanced computed tomography (CT) 6 weeks after ablation. Clinical and technical predictors of LTPFS were assessed using a competing risk model adjusted for clustering. RESULTS: Technique effectiveness (complete ablation) was 93% (79/85) for RF ablation and 97% (58/60) for MW ablation (P = .47). The median follow-up period was significantly longer for RF ablation than for MW ablation (56 months vs. 29 months) (P < .001). There was no difference in the local tumor progression (LTP) rates between RF ablation and MW ablation (P = 0.84). Significant predictors of shorter LTPFS for RF ablation on univariate analysis were ablation margins 5 mm or smaller (P < .001) (hazard ratio [HR]: 14.6; 95% confidence interval [CI]: 5.2-40.9) and perivascular tumors (P = .021) (HR: 2.2; 95% CI: 1.1-4.3); both retained significance on multivariate analysis. Significant predictors of shorter LTPFS on univariate analysis for MW ablation were ablation margins 5 mm or smaller (P < .001) (subhazard ratio: 11.6; 95% CI: 3.1-42.7) and no history of prior liver resection (P < .013) (HR: 3.2; 95%: 1.3-7.8); both retained significance on multivariate analysis. There was no LTP for tumors ablated with margins over 10 mm (median LTPFS: not reached). Perivascular tumors were not predictive for MW ablation (P = .43). CONCLUSIONS: Regardless of the thermal ablation modality used, margins larger than 5 mm are critical for local tumor control, with no LTP noted for margins over 10 mm. Unlike RF ablation, the efficiency of MW ablation was not affected for perivascular tumors.

Kras mutation is a marker of worse oncologic outcomes after percutaneous radiofrequency ablation of colorectal liver metastases.

BACKGROUND: Kras mutation has been associated with shorter overall survival and time to disease recurrence after resection of colorectal liver metastases (CLM). This study evaluated the prognostic value of Kras mutation in patients with CLM treated by percutaneous radiofrequency ablation (RFA). METHODS: This is an IRB waived retrospective analysis of the impact of KRAS mutation status on oncologic outcomes after CLM RFA. The endpoints were overall survival (OS), local tumor progression (LTP) rates, and incidence of new liver, lung, and peritoneal metastases. Survival times were calculated using Kaplan-Meier methodology from the time of RFA. RESULTS: The study enrolled 97 patients. Kras exon 2 mutation was detected in 39% (38/97) of patients. On univariate analysis, Kras mutation (P=0.016) (HR: 1.8; 95% CI: 1.1 - 2.9) was a significant predictor of OS and retained significance on multivariate analysis. Kras mutation was a significant predictor of new liver metastases (P=0.037) (SHR: 2.0; CI: 1.0-3.7) and peritoneal metastases (P=0.015) (sHR: 3.0; 95% CI: 1.2-7.2) on multivariate analysis. Kras mutation was a significant predictor of LTP after RFA of CLM ablated with margins of 1-5 mm (P=0.018) (SHR: 3.0; 95% CI: 1.2-7.7) with an LTP rate of 80% (12/15) versus 41% (11/27) for wild type. CONCLUSION: Kras mutation is a significant predictor of overall survival, new liver, and peritoneal metastases after RFA of CLM. A minimal radiographic ablation margin ≥ 6 mm is essential for local tumor control especially for mutant CLM.

Lung Adenocarcinoma: Predictive Value of KRAS Mutation Status in Assessing Local Recurrence in Patients Undergoing Image-guided Ablation.

Purpose To establish the relationship between KRAS mutation status and local recurrence after image-guided ablation of lung adenocarcinoma. Materials and Methods This study consisted of a HIPAA-compliant institutional review board-approved retrospective review of 56 primary lung adenocarcinomas in 54 patients (24 men, 30 women; median age, 72 years; range, 54-87 years) treated with percutaneous image-guided ablation and with available genetic mutational analysis. KRAS mutation status and additional clinical and technical variables-Eastern Cooperative Oncology Group (ECOG) status, smoking history, stage at diagnosis, status (new primary or not), history of radiation, history of surgery, prior systemic treatment, modality of ablation, size of nodule, ablation margin, and presence of ground-glass appearance-were recorded and evaluated in relation to time to local recurrence, which was calculated from the time of ablation to the first radiographic evidence of recurrence. Predictors of outcome were identified by using a proportional hazards model for both univariate and multivariate analysis, with death as a competing risk. Results Technical success was 100%. Of the 56 ablated tumors, 37 (66%) were wild type for KRAS and 19 (34%) were KRAS mutants. The 1-year and 3-year cumulative incidences of recurrence were 20% and 35% for wild-type KRAS compared with 40% and 63% for KRAS mutant tumors. KRAS mutation status was a significant predictor of local recurrence at both univariate (P = .05; subdistribution hazard ratio [sHR], 2.32) and multivariate (P = .006; sHR, 3.75) analysis. At multivariate analysis, size (P = .026; sHR, 2.54) and ECOG status (P = .012; sHR, 2.23) were also independent significant predictors, whereas minimum margin (P = .066) was not. Conclusion The results of this study show that there is a relationship between KRAS mutation status and local recurrence after image-guided ablation of lung adenocarcinoma. Specifically, KRAS mutation status of the ablated lesion is a significant predictor of time to local recurrence, independent of size and margin. © RSNA, 2016.

Surrogate Imaging Biomarkers of Response of Colorectal Liver Metastases After Salvage Radioembolization Using 90Y-Loaded Resin Microspheres.

OBJECTIVE: The purpose of the present study is to evaluate Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, tumor attenuation criteria, Choi criteria, and European Organization for Research and Treatment of Cancer (EORTC) PET criteria as measures of response and subsequent predictors of liver progression-free survival (PFS) after radioembolization (RE) of colorectal liver metastases (CLM). The study also assesses interobserver variability for measuring tumor attenuation using a single 2D ROI on a simple PACS workstation. MATERIALS AND METHODS: We performed a retrospective review of the clinical RE database at our institution, to identify patients treated in the salvage setting for CLM between December 2009 and March 2013. Response was evaluated on FDG PET scans, with the use of EORTC PET criteria, and on portal venous phase CT scans, with the use of RECIST 1.1, tumor attenuation criteria, and Choi criteria. Two independent blinded observers measured tumor attenuation using a single 2D ROI. The intraclass correlation coefficient (ICC) for interobserver variability was assessed. Kaplan-Meier methodology was used to calculate liver PFS, and the log-rank test was used to assess the response criteria as predictors of liver PFS. RESULTS: A total of 25 patients with 46 target tumors were enrolled in the study. The ICC was 0.95 at baseline and 0.98 at response evaluation. Among the 25 patients, more responders (i.e., partial response) were identified on the basis of EORTC PET criteria (n = 14), Choi criteria (n = 15), and tumor attenuation criteria (n = 13) than on the basis of RECIST 1.1 (n = 2). The median liver PFS was 3.0 months (95% CI, 2.1-4.0 months). Response identified on the basis of EORTC PET criteria (p < 0.001), Choi criteria (p < 0.001), or tumor attenuation criteria (p = 0.01) predicted liver PFS; however, response identified by RECIST 1.1 did not (p = 0.1). CONCLUSION: RECIST 1.1 has poor sensitivity for detecting metabolic responses classified by EORTC PET criteria. EORTC PET criteria, Choi criteria, and tumor attenuation criteria appear to be equally reliable surrogate imaging biomarkers of liver PFS after RE in patients with CLM.

Quantitative Measurements of Enhancement on Preprocedure Triphasic CT Can Predict Response of Colorectal Liver Metastases to Radioembolization.

OBJECTIVE: Colorectal liver metastases (CLM) have a variable response to radioembolization. This may be due at least partly to differences in tumor arterial perfusion. The present study examines whether quantitative measurements of enhancement on preprocedure triphasic CT can be used to predict the response of CLM to radioembolization. MATERIALS AND METHODS: We retrospectively reviewed patients with CLM treated with radioembolization who underwent pretreatment PET/CT and triphasic CT examinations and posttreatment PET/CT examinations. A total of 31 consecutive patients with 60 target tumors were included in the present study. For each tumor, we calculated the hepatic artery coefficient (HAC), portal vein coefficient (PVC), and arterial enhancement fraction (AEF) based on enhancement measurements on pretreatment triphasic CT. HAC and PVC are estimates of the hepatic artery and portal vein blood supply. AEF, which is the arterial phase enhancement divided by the portal phase enhancement, provides an estimate of the hepatic artery blood supply as a fraction of the total blood supply. For each tumor, the metabolic response to radioembolization was based on findings from the initial follow-up PET/CT scan obtained at 4-8 weeks after treatment. RESULTS: A total of 55% of CLM had a complete or partial metabolic response. Arterial phase enhancement, the HAC, and the PVC did not predict which tumors responded to radioembolization. However, the AEF was statistically significantly greater in tumors with a complete or partial metabolic response than in tumors with no metabolic response (i.e., those with stable disease or disease progression) (p = 0.038). An AEF of less than 0.4 was associated with a 40% response rate, whereas an AEF greater than 0.75 was associated with a 78% response rate. CONCLUSION: Response to radioembolization can be predicted using the AEF calculated from the preprocedure triphasic CT.

Metabolic tumor volume and total lesion glycolysis on FDG-PET/CT can predict overall survival after (90)Y radioembolization of colorectal liver metastases: A comparison with SUVmax, SUVpeak, and RECIST 1.0.

PURPOSE: To compare the performance of 4 metrics of metabolic response on FDG-PET/CT against RECIST 1.0 for determining response and predicting overall survival (OS) following (90)Y resin microspheres radioembolization of colorectal liver metastases (CLM). METHODS: We conducted an IRB-waived retrospective review of our radioembolization database to identify patients with unresectable CLM treated between December 2009 and December 2013. We included patients who had both PET/CT and contrast enhanced CT (CECT) available at baseline and on the first follow-up post-radioembolization. On baseline CECT up to five target tumors were chosen per patient according to RECIST 1.0. Four metrics of FDG-avidity (SUVmax, SUVpeak, metabolic tumor volume (MTV), and total lesion glycolysis (TLG)) on PET/CT were measured for the same target tumors. Using RECIST 1.0, patients were classified as no progression (partial response or stable disease) and progression. For each PET metric, a cut-off point of ≥30% decrease was chosen to define response. OS was calculated from the time of radioembolization using Kaplan-Meier methodology. The log-rank test was used for univariate analysis to identify predictors of OS. RESULTS: The study enrolled 49 patients with 119 target tumors; a median of 2 (range: 1-5) tumors were selected per patient. Median OS was 12.7 months (95%CI: 7.2-16.7). Response by MTV (P=0.035) and TLG (P=0.044) reached statistical significance in predicting OS. Response by SUVmax (P=0.21), SUVpeak (P=0.20) or no progression by RECIST 1.0 (P=0.44) did not predict OS. CONCLUSION: Metabolic response based on changes in MTV and TLG can predict OS post-radioembolization of CLM.

Percutaneous Radiofrequency Ablation of Colorectal Cancer Liver Metastases: Factors Affecting Outcomes--A 10-year Experience at a Single Center.

PURPOSE: To identify predictors of oncologic outcomes after percutaneous radiofrequency ablation (RFA) of colorectal cancer liver metastases (CLMs) and to describe and evaluate a modified clinical risk score (CRS) adapted for ablation as a patient stratification and prognostic tool. MATERIALS AND METHODS: This study consisted of a HIPAA-compliant institutional review board-approved retrospective review of data in 162 patients with 233 CLMs treated with percutaneous RFA between December 2002 and December 2012. Contrast material-enhanced CT was used to assess technique effectiveness 4-8 weeks after RFA. Patients were followed up with contrast-enhanced CT every 2-4 months. Overall survival (OS) and local tumor progression-free survival (LTPFS) were calculated from the time of RFA by using the Kaplan-Meier method. Log-rank tests and Cox regression models were used for univariate and multivariate analysis to identify predictors of outcomes. RESULTS: Technique effectiveness was 94% (218 of 233). Median LTPFS was 26 months. At univariate analysis, predictors of shorter LTPFS were tumor size greater than 3 cm (P < .001), ablation margin size of 5 mm or less (P < .001), high modified CRS (P = .009), male sex (P = .03), and no history of prior hepatectomy (P = .04) or hepatic arterial infusion chemotherapy (P = .01). At multivariate analysis, only tumor size greater than 3 cm (P = .01) and margin size of 5 mm or less (P < .001) were independent predictors of shorter LTPFS. Median and 5-year OS were 36 months and 31%. At univariate analysis, predictors of shorter OS were tumor size larger than 3 cm (P = .005), carcinoembryonic antigen level greater than 30 ng/mL (P = .003), high modified CRS (P = .02), and extrahepatic disease (EHD) (P < .001). At multivariate analysis, tumor size greater than 3 cm (P = .006) and more than one site of EHD (P < .001) were independent predictors of shorter OS. CONCLUSION: Tumor size of less than 3 cm and ablation margins greater than 5 mm are essential for satisfactory local tumor control. Tumor size of more than 3 cm and the presence of more than one site of EHD are associated with shorter OS.

Radioembolization as a Salvage Therapy for Heavily Pretreated Patients With Colorectal Cancer Liver Metastases: Factors That Affect Outcomes.

BACKGROUND: In this study we assessed the efficacy and factors that affect outcomes of radioembolization (RE) using yttrium-90 resin microspheres in patients with unresectable and chemorefractory colorectal cancer liver metastases (CLM). PATIENTS AND METHODS: After an institutional review board waiver of approval, a review of a Health Insurance Portability and Accountability Act-registered, prospectively created and maintained database was performed. Data on patient demographic and disease characteristics, RE treatment parameters, and additional treatments were evaluated for significance in predicting overall survival (OS) and liver progression-free survival (LPFS). Complications were evaluated according to the National Cancer Institute Common Terminology Criteria for adverse events. RESULTS: From September 2009 to September 2013, 53 patients underwent RE at a median of 35 months after CLM diagnosis. Median OS was 12.7 months. Multivariate analysis showed that carcinoembryonic antigen levels at the time of RE ≥ 90 ng/mL (P = .004) and microscopic lymphovascular invasion of the primary (P = .002) were independent predictors of decreased OS. Median LPFS was 4.7 months. At 4 to 8 and 12 to 16 weeks after RE, most patients (80% and 61%, respectively) according to Response Evaluation Criteria in Solid Tumors (RECIST) had stable disease; additional evaluation using PET Response Criteria in Solid Tumors (PERCIST) led to reclassification in 77% of these cases (response or progression). No deaths were noted within the first 30 days. Within the first 90 days after RE, 4 patients (8%) developed liver failure and 5 patients (9%) died, all with evidence of disease progression. CONCLUSION: RE in the salvage setting was well-tolerated, and permitted the administration of additional therapies and led to a median OS of 12.7 months. Evaluation using PERCIST was more likely than RECIST to document response or progression compared with the baseline assessment before RE.