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Radiofrequency ablation is beneficial in simultaneous treatment of synchronous liver metastases and primary colorectal cancer.

ABSTRACT: In patients with resectable synchronous colorectal liver metastases (CRLM), either two-staged or simultaneous resections of the primary tumor and liver metastases are performed. Data on radiofrequency ablation (RFA) for the treatment of CRLM during a simultaneous procedure is lacking. The primary aim was to analyze short-term and long-term outcome of RFA in simultaneous treatment. A secondary aim was to compare simultaneous resection with the colorectal-first approach.Retrospective analysis of 241 patients with colorectal cancer and synchronous CRLM between 2000-2016. Median follow-up was 36.1 months (IQR 18.2-58.8 months). A multivariable analysis was performed to analyze the postoperative morbidity, using the comprehensive complication index. A propensity matched analysis was performed to compare survival rates.In multivariable analysis, the best predictor of lower complication severity was treatment with RFA (p = 0.040). Higher complication rates were encountered in patients who underwent an abdominoperineal resection (p = 0.027) or age > 60 years (p = 0.022). The matched analysis showed comparable overall survival in RFA treated patients versus patients undergoing a liver resection with a five year overall survival of 39.4% and 37.5%, respectively (p = 0.782). In a second matched analysis, 5-year overall survival rates in simultaneously treated patients (43.8%) was comparable to patients undergoing the colorectal first approach (43.0%, p = 0.223).RFA treatment of CRLM in simultaneous procedures is associated with a lower complication severity and non-inferior oncological outcome as compared to partial liver resection. RFA should be considered a useful alternative to liver resection.

SUBMITTER: Hof J

PROVIDER: S-EPMC5854258 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Radiofrequency ablation is beneficial in simultaneous treatment of synchronous liver metastases and primary colorectal cancer.

Hof Joost J Joosten Hanneke J HJ Havenga Klaas K de Jong Koert P KP

PloS one 20180315 3

<h4>Background</h4>In patients with resectable synchronous colorectal liver metastases (CRLM), either two-staged or simultaneous resections of the primary tumor and liver metastases are performed. Data on radiofrequency ablation (RFA) for the treatment of CRLM during a simultaneous procedure is lacking. The primary aim was to analyze short-term and long-term outcome of RFA in simultaneous treatment. A secondary aim was to compare simultaneous resection with the colorectal-first approach.<h4>Meth ...[more]

PMID: 29543821

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Project description:Background: Radiofrequency ablation (RFA) is an established treatment option for malignancies located in the liver. RFA-induced irreversible coagulation necrosis leads to the release of danger signals and cellular content. Hence, RFA may constitute an endogenous in situ tumor vaccination, stimulating innate and adaptive immune responses, including tumor-antigen specific T cells. This may explain a phenomenon termed abscopal effect, namely tumor regression in untreated lesions evidenced after distant thermal ablation or irradiation. In this study, we therefore assessed systemic and local immune responses in individual patients treated with RFA. Methods: For this prospective clinical trial, patients with liver metastasis from colorectal carcinoma (mCRC) receiving RFA and undergoing metachronous liver surgery for another lesion were recruited (n = 9) during a 5-year period. Tumor and non-malignant liver tissue samples from six patients were investigated by whole transcriptome sequencing and tandem-mass spectrometry, characterizing naturally presented HLA ligands. Tumor antigen-derived HLA-restricted peptides were selected by different predefined approaches. Further, candidate HLA ligands were manually curated. Peripheral blood mononuclear cells were stimulated in vitro with epitope candidate peptides, and functional T cell responses were assessed by intracellular cytokine staining. Immunohistochemical markers were additionally investigated in surgically resected mCRC from patients treated with (n = 9) or without RFA (n = 7). Results: In all six investigated patients, either induced immune responses and/or pre-existing T cell immunity against the selected targets were observed. Multi-cytokine responses were inter alia directed against known tumor antigens such as cyclin D1 but also against a (predicted) mutation contained in ERBB3. Immunohistochemistry did not show a relevant influx of immune cells into distant malignant lesions after RFA treatment (n = 9) as compared to the surgery only mCRC group (n = 7). Conclusions: Using an individualized approach for target selection, RFA induced and/or boosted T cell responses specific for individual tumor antigens were more frequently detectable as compared to previously published observations with well-characterized tumor antigens. However, the witnessed modest RFA-induced immunological effects alone may not be sufficient for the rejection of established tumors. Therefore, these findings warrant further clinical investigation including the assessment of RFA combination therapies e.g., with immune stimulatory agents, cancer vaccination, and/or immune checkpoint inhibitors.

Project description:Thermal ablation of colorectal liver metastases (CRLM) may result in local progression, which generally appear within a year of treatment. As the timely diagnosis of this progression allows potentially curative local treatment, an optimal follow-up imaging strategy is essential. PET-MRI is a one potential imaging modality, combining the advantages of PET and MRI. The aim of this study is evaluate fluorine-18 deoxyglucose positron emission tomography (FDG) PET-MRI as a modality for detection of local tumor progression during the first year following thermal ablation, as compared to the current standard, FDG PET-CT. The ability of FDG PET-MRI to detect new intrahepatic lesions, and the extent to which FDG PET-MRI alters clinical management, inter-observer variability and patient preference will also be included as secondary outcomes.Twenty patients undergoing treatment with radiofrequency or microwave ablation for (recurrent) CRLM will be included in this prospective trial. During the first year of follow-up, patients will be scanned at the VU University Medical Center at 3-monthly intervals using a 4-phase liver CT, FDG PET-CT and FDG PET-MRI. Patients treated with chemotherapy <6 weeks prior to scanning or with a contra-indication for MRI will be excluded. MRI will be performed using both whole body imaging (mDixon) and dedicated liver sequences, including diffusion-weighted imaging, T1 in-phase and opposed-phase, T2 and dynamic contrast-enhanced imaging. The results of all modalities will be scored by 4 individual reviewers and inter-observer agreement will be determined. The reference standard will be histology or clinical follow-up. A questionnaire regarding patients' experience with both modalities will also be completed at the end of the follow-up year.Improved treatment options for local site recurrences following CRLM ablation mean that accurate post-ablation staging is becoming increasingly important. The combination of the sensitivity of MRI as a detection method for small intrahepatic lesions with the ability of FDG PET to visualize enhanced metabolism at the ablation site suggests that FDG PET-MRI could potentially improve the accuracy of (early) detection of progressive disease, and thus allow swifter and more effective decision-making regarding appropriate treatment.NCT01895673.

Project description:BackgroundThe optimal timing of resection for synchronous colorectal liver metastases is still controversial. Retrospective cohort studies always had baseline imbalances in comparing simultaneous resection with staged strategy. Significantly more patients with mild conditions received simultaneous resections. Previous published meta-analyses based on these studies did not correct these biases, resulting in low reliability. Our meta-analysis was conducted to compensate for this deficiency and find candidates for each surgical strategy.MethodsA systemic search for major databases and relevant journals from January 2000 to April 2013 was performed. The primary outcomes were postoperative mortality, morbidity, overall survival and disease-free survival. Other outcomes such as number of patients need blood transfusion and length of hospital stay were also assessed. Baseline analyses were conducted to find and correct potential confounding factors.Results22 studies with a total of 4494 patients were finally included. After correction of baseline imbalance, simultaneous and staged resections were similar in postoperative mortality (RR = 1.14, P = 0.52), morbidity (RR = 1.02, P = 0.85), overall survival (HR = 0.96, P = 0.50) and disease-free survival (HR = 0.97, P = 0.87). Only in pulmonary complications, simultaneous resection took a significant advantage (RR = 0.23, P = 0.003). The number of liver metastases was the major factor interfering with selecting surgical strategies. With >3 metastases, simultaneous and staged strategies were almost the same in morbidity (49.4% vs. 50.9%). With ≤3 metastases, staged resection caused lower morbidity (13.8% vs. 17.2%), not statistically significant.ConclusionsThe number of liver metastases was the major confounding factor for postoperative morbidity, especially in staged resections. Without baseline imbalances, simultaneous took no statistical significant advantage in safety and efficacy. Considering the inherent limitations of this meta-analysis, the results should be interpret and applied prudently.

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Radiofrequency ablation is beneficial in simultaneous treatment of synchronous liver metastases and primary colorectal cancer.

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Radiofrequency ablation is beneficial in simultaneous treatment of synchronous liver metastases and primary colorectal cancer.

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