William Alago

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.

Treatment of pulmonary colorectal metastases by radiofrequency ablation.

UNLABELLED We evaluated the local tumor control and the survival benefit achieved with radiofrequency ablation (RFA) for nonoperable lung metastases in 45 patients with colorectal cancer. Median survival from the time of RFA was 46 months. One-, 2- and 3-year local tumor progression (LTP)-free survival rates were 92%, 77%, and 77%, respectively. RFA offers very good local control in patients with pulmonary metastases from colorectal cancer. BACKGROUND Radiofrequency ablation has emerged as a potential, lung function-preserving treatment of colorectal lung metastases. PATIENTS AND METHODS Forty-five patients with colorectal pulmonary metastases underwent computed tomography-guided RFA from December 2004 to June 2010. A baseline posttreatment scan was obtained 4-6 weeks after RFA and follow-up imaging studies every 3 months thereafter were obtained and compared to evaluate the tumor progression at site of ablation or elsewhere. The primary end points were LTP-free survival and overall survival from RFA procedure. The Kaplan-Meier method was used to analyze the end points. A Cox proportional hazard model with robust inference was used to estimate the associations between baseline factors and survival end points. RESULTS Sixty-nine metastases were ablated in 45 patients. Tumor size ranged from 0.4 to 3.5 cm. The median number of metastases ablated per patient was 1 (range, 1-3). Median follow-up after RFA was 18 months. Median survival from the time of RFA was 46 months (95% confidence interval [CI], 27.8-47.3). One-, 2- and 3-year overall survival rates from the time of RFA were 95% (95% CI, 82%-99%), 72% (95% CI, 52%-85%), and 50% (95% CI, 26%-71%), respectively. Nine of 69 lesions (13%) progressed and 4 were retreated with no progression after second RFA. Median time to progression was not reached. LTP-free survival from RFA was 92% (95% CI, 82%-97%) at 1 year, 77% (95% CI, 58%-88%) at 2 years, and 77% (95% CI, 58%-88%) at 3 years. CONCLUSION Radiofrequency ablation of lung metastases is an effective minimally invasive, parenchymal-sparing technique that has very good local control rates in patients with pulmonary metastases from colorectal cancer, with LTP-free survival of 77% at 3 years.

CT-guided Radiofrequency Ablation as a Salvage Treatment of Colorectal Cancer Hepatic Metastases Developing after Hepatectomy

PURPOSE To evaluate the clinical outcomes of percutaneous radiofrequency (RF) ablation of colorectal cancer liver metastases (CLMs) that recur after hepatectomy. MATERIALS AND METHODS From December 2002 to December 2008, 71 CLMs that developed after hepatectomy were ablated in 56 patients. Medical records and imaging were reviewed to determine technique effectiveness/complete ablation (ie, ablation defect covering the entire tumor on 4-6-week postablation computed tomography [CT]), complications, and local tumor progression (LTP) at the site of ablation. LTP-free and overall survival were calculated by using Kaplan-Meier methodology. A modified clinical risk score (CRS) including nodal status of the primary tumor, time interval between diagnoses of the primary tumor and liver metastases, number of tumors, and size of the largest tumor was assessed for its effect on overall survival and LTP. RESULTS Tumor size ranged between 0.5 and 5.7 cm. Complete ablation was documented in 67 of 71 cases (94%). Complications included liver abscess (n = 1) and pleural effusion (n = 1). Median overall survival time was 31 months. One-, 2- and 3-year overall survival rates were 91%, 66%, and 41%, respectively. CRS was an independent factor for overall survival (74% for CRS of 0-2 vs 42% for CRS of 3-4 at 2 y; P = .03) and for LTP-free survival (66% for CRS of 0-2 vs 22% for CRS of 3-4 at 1 y after a single ablation; P <.01). CONCLUSIONS CT-guided RF ablation can be used to treat recurrent CLM after hepatectomy. A low CRS is associated with better clinical outcomes.

Image-guided Thermal Ablation of Tumors Increases the Plasma Level of Interleukin-6 and Interleukin-10

PURPOSE To identify changes in plasma cytokine levels after image-guided thermal ablation of human tumors and to identify the factors that independently predict changes in plasma cytokine levels. MATERIALS AND METHODS Whole-blood samples were collected from 36 patients at three time points: before ablation, after ablation (within 48 hours), and at follow-up (1-5 weeks after ablation). Plasma levels of interleukin (IL)-1α, IL-2, IL-6, IL-10, and tumor necrosis factor (TNF)-α were measured using a multiplex immunoassay. Univariate and multivariate analyses were performed using cytokine level as the dependent variable and sample collection, time, age, sex, primary diagnosis, metastatic status, ablation site, and ablation type as the independent variables. RESULTS There was a significant increase in the plasma level of IL-6 after ablation compared with before ablation (9.6-fold ± 31-fold, P<.002). IL-10 also showed a significant increase after ablation (1.9-fold ± 2.8-fold, P<.02). Plasma levels of IL-1α, IL-2, and TNF-α were not significantly changed after ablation. Cryoablation resulted in the largest change in IL-6 level (>54-fold), whereas radiofrequency ablation and microwave ablation showed 3.6-fold and 3.4-fold changes, respectively. Ablation of melanomas showed the largest change in IL-6 48 hours after ablation (92×), followed by ablation of kidney (26×), liver (8×), and lung (6×) cancers. Multivariate analysis revealed that ablation type (P<.0003) and primary diagnosis (P<.03) were independent predictors of changes to IL-6 after ablation. Age was the only independent predictor of IL-10 levels after ablation (P< .019). CONCLUSIONS Image-guided thermal ablation of tumors increases plasma levels of IL-6 and IL-10, without increasing plasma levels of IL-1α, IL-2, or TNF-α.

Frequency of Use and Predictors of Cancer-Directed Surgery in the Management of Malignant Pleural Mesothelioma in a Community-Based (Surveillance, Epidemiology, and End Results [SEER]) Population

Introduction: Surgical intervention rates for mesothelioma patients treated at specialized tertiary hospitals are well more than 42%. Mesothelioma surgical strategies in the community are less well defined. This study evaluates the frequency of use and predictors of cancer-directed surgical intervention in a nontertiary-based population and the predictors for surgical intervention. Methods: The Surveillance, Epidemiology, and End Results database was searched from 1990 to 2004. Variables analyzed included age, sex, race, year of diagnosis, region, vital status, stage, surgery, and reasons for no surgery. The association of patient variables on receipt of cancer-directed surgery was evaluated using &khgr;2 tests and logistic regression. The incidence of mesothelioma was also evaluated over this period of time. Results: Pathologically proven malignant pleural mesothelioma was identified in 1166 women and 4771 men. The rate of cancer-directed surgery was 22% (n = 1317). Significant predictors of receiving cancer-directed surgery included race, age, and stage (all p < 0.0001). A landmark analysis on the effect of cancer-directed surgery on survival after adjusting for patient and disease characteristics demonstrated a hazard ratio of 0.68 (p < 0.0001). The incidence rate of malignant pleural mesothelioma has remained constant. Conclusions: The rate of surgical intervention in the community is lower compared with tertiary referral centers. Age, stage, and race predict the likelihood of receiving cancer-directed surgery. A lower rate of cancer-directed surgery and worse overall outcome were observed in black patients. As part of quality assurance, referral of patients to centers with multidisciplinary programs that include thoracic surgical expertise should be considered.

Pulmonary Thermal Ablation in Patients With Prior Pneumonectomy

OBJECTIVE The purpose of this article is to review the safety and efficacy of thermal ablation of lung malignancies after pneumonectomy. MATERIALS AND METHODS We reviewed patients who underwent thermal ablation for malignant lung tumors after pneumonectomy between 1999 and 2009. Patient demographics, complications, procedural success, and oncologic outcomes were recorded. Technique effectiveness was evaluated at imaging 4-6 weeks after ablation. The Kaplan-Meier method was used to evaluate overall survival. A cumulative incidence and competing risk method was used to account for progression-free tumors at the time of patient death. RESULTS Of 619 lung ablations, 17 were performed to treat 13 tumors (nine primary and four metastatic) in 12 patients with a single lung. The median tumor size was 2 cm (range, 1.2-4 cm). Technical success was documented in all 17 cases. Technical effectiveness was documented in 10 of 12 patients. Local tumor progression occurred in five lesions within a median of 12 months (range, 10-22 months) after ablation and was treated with repeat ablation in four lesions. Complications included six (35%) of 17 pneumothoraces requiring thoracostomy. Deaths occurred within 2-12 days after three (19%) of 16 ablation sessions. The median time to primary local tumor progression was 18 months (95% CI, 12 months through not reached), and the median time to assisted (after repeat ablation) local tumor progression was 33 months (95% CI, not reached). Median overall survival was 21 months (95% CI, 18-53 months). After excluding the two early deaths complicating the initial ablation procedure, median overall survival was 37 months. CONCLUSION Thermal ablation can offer local tumor control after pneumonectomy, despite a relatively high postprocedure clinical risk.

Factors Affecting Periprocedural Morbidity and Mortality and Long-term Patient Survival after Arterial Embolization of Hepatic Neuroendocrine Metastases

PURPOSE To identify factors affecting periprocedural morbidity and mortality and long-term survival following hepatic artery embolization (HAE) of hepatic neuroendocrine tumor (NET) metastases. MATERIALS AND METHODS This single-center, institutional review board-approved retrospective review included 320 consecutive HAEs for NET metastases performed in 137 patients between September 1996 and September 2007. Forty-seven HAEs (15%) were performed urgently to manage refractory symptoms in inpatients (urgent group), and 273 HAEs (85%) were elective (elective group). Overall survival (OS) was estimated by Kaplan-Meier methodology. Complications were categorized per Common Terminology Criteria for Adverse Events, version 4.0. Univariate and multivariate analyses were performed to determine independent predictors for OS, complications, and 30-day mortality. The independent factors were combined to develop clinical risk score groups. RESULTS Urgent HAE (P = .007), greater than 50% liver replacement by tumor (P < .0001), and extrahepatic metastasis (P = .007) were independent predictors for shorter OS. Patients with all three risk factors had decreased OS versus those with none (median, 8.5 vs 86 mo; P < .001). Thirty-day mortality was significantly lower in the elective (1%) versus the urgent group (8.5%; P = .0009). There were eight complications (3%) in the elective group and five (10.6%) in the urgent group (P = .03). Male sex and urgent group were independent factors for higher 30-day mortality rate (P = .023 and P =.016, respectively) and complications (P = .012 and P =.001, respectively). CONCLUSIONS Urgent HAE, replacement of more than 50% of liver by tumor, and extrahepatic metastasis are strong independent predictors of shorter OS. Male sex and urgent HAE carry higher 30-day mortality and periprocedural morbidity risks.

Colorectal Cancer Liver Metastases: Biopsy of the Ablation Zone and Margins Can Be Used to Predict Oncologic Outcome

Purpose To establish the prognostic value of biopsy of the central and marginal ablation zones for time to local tumor progression (LTP) after radiofrequency (RF) ablation of colorectal cancer liver metastasis (CLM). Materials and Methods A total of 47 patients with 67 CLMs were enrolled in this prospective institutional review board-approved and HIPAA-compliant study between November 2009 and August 2012. Mean tumor size was 2.1 cm (range, 0.6-4.3 cm). Biopsy of the center and margin of the ablation zone was performed immediately after RF ablation (mean number of biopsy samples per ablation zone, 1.9) and was evaluated for the presence of viable tumor cells. Samples containing tumor cells at morphologic evaluation were further interrogated with immunohistochemistry and were classified as either positive, viable tumor (V) or negative, necrotic (N). Minimal ablation margin size was evaluated in the first postablation CT study performed 4-8 weeks after ablation. Variables were evaluated as predictors of time to LTP with the competing-risks model (uni- and multivariate analyses). Results Technical effectiveness was evident in 66 of 67 (98%) ablated lesions on the first contrast material-enhanced CT images at 4-8-week follow-up. The cumulative incidence of LTP at 12-month follow-up was 22% (95% confidence interval [CI]: 12, 32). Samples from 16 (24%) of 67 ablation zones were classified as viable tumor. At univariate analysis, tumor size, minimal margin size, and biopsy results were significant in predicting LTP. When these variables were subsequently entered in a multivariate model, margin size of less than 5 mm (P < .001; hazard ratio [HR], 6.7) and positive biopsy results (P = .008; HR, 3.4) were significant. LTP within 12 months after RF ablation was noted in 3% (95% CI: 0, 9) of necrotic CLMs with margins of at least 5 mm. Conclusion Biopsy proof of complete tumor ablation and minimal ablation margins of at least 5 mm are independent predictors of LTP and yield the best oncologic outcomes. (©) RSNA, 2016.

Recurrent non-small cell lung cancer: evaluation of CT-guided radiofrequency ablation as salvage therapy.

Background Radiofrequency ablation (RFA) is a potential application as a salvage tool after failure of surgery, chemotherapy, or radiotherapy of non-small cell lung cancer (NSCLC). Although several studies have evaluated the use of RFA in primary NSCLC, there is little literature on its potential application as a salvage tool. Purpose To evaluate CT-guided RFA employed as a salvage therapy for pulmonary recurrences of NSCLC after prior treatment with chemotherapy, radiation therapy, and/or surgery. Material and Methods A retrospective computer database search yielded 33 patients with biopsy proven primary NSCLC who underwent CT-guided RFA of 39 recurrent tumors following surgery, chemotherapy, and/or radiotherapy. Follow-up imaging was performed with CT and PET-CT. The endpoints of interest were progression-free survival (PFS) and time to local progression (TTLP). PFS and TTLP were compared by lesion size (<3 cm, ≥3 cm). Results The median PFS was 8 months. For patients with a tumor size <3 cm median PFS was 11 months, whereas the median PFS of patients with a tumor size ≥3 cm was 5 months. The difference did not reach statistical significance (P = 0.09). The median TTLP of all tumors was 14 months. TTLP of ablated tumors <3 cm in size was 24 months, compared to 8 months for ablated tumors ≥3 cm in size. The difference did not reach statistical significance (P = 0.07). Conclusion RFA of recurrent NSCLC may be a valuable salvage tool to achieve local tumor control, especially in tumors measuring <3 cm in size.

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.