Treatment Of Neuroendocrine Liver Metastases Research Articles

Liver metastases of neuroendocrine tumors: Conventional transarterial chemoembolization and thermal ablation.

To identify prognostic factors for patients with neuroendocrine liver metastases (NELM) undergoing conventional transarterial chemoembolization (c-TACE), microwave ablation (MWA), or laser interstitial thermotherapy (LITT) and to determine the most effective therapy regarding volume reduction of NELM and survival. Between 1996 and 2020, 130 patients (82 men, 48 women) were treated with c-TACE, and 40 patients were additionally treated with thermal ablation. Survival was retrospectively analyzed using the Kaplan-Meier-method. Additional analyses were performed depending on the therapeutic intention (curative, palliative, symptomatic). Prognostic factors were derived using Cox regression. To find predictive factors for volume reduction in response to c-TACE, a mixed-effects model was used. With c-TACE, an overall median volume reduction of 23.5 % was achieved. An average decrease in tumor volume was shown until the 6th c-TACE treatment, then the effect stopped. C-TACE interventions were most effective at the beginning of c-TACE therapy, and treatment breaks longer than 90 days negatively influenced the outcome. Significant prognostic factors for survival were number of liver lesions (p = 0.0001) and type of therapeutic intention (p < 0.0001). Minor complications and one major complication occurred in 20.3 % of LITT and only in 8.6 % of MWA interventions. Complete ablation was observed in 95.7 % (LITT) and 93.1 % (MWA) of interventions. New prognostic factors were found for survival and volume reduction. Efficacy of c-TACE decreases after the 6th intervention and treatment breaks longer than 90 days should be avoided. With thermal ablation, a high rate of complete ablation was achieved, and survival improved. · Number of liver lesions and therapeutic intention are prognostic factors for survival.. · Regarding volume reduction, C-TACE is most effective at the beginning of treatment and longer treatment breaks should be avoided.. · With MWA and LITT, a high rate of complete ablation was achieved. MWA trends toward fewer complications than LITT in the treatment of NELM (p = 0.07)..

A Comparison of the Outcomes of Transarterial Chemoembolization and Transarterial Radioembolization in the Management of Neuroendocrine Liver Metastases in Adults: A Systematic Review.

The purpose of this article is to review the existing English scientific literature and determine the superior modality between transarterial chemoembolization (TACE) and radioembolization (TARE) in the treatment of neuroendocrine liver metastases (NELMs). To that end, we followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to search PubMed, the Cochrane Library, and Google Scholar. We identified 14 observational studies and no randomized controlled trials (RCTs) investigating the use of TACE or TARE to treat NELM. We used the Newcastle-Ottawa Scale to assess the risk of bias in these studies. We concluded that TACE and TARE appeared to have similar outcomes when comparing overall survival, progression-free survival, radiological response, symptomatic response, and the incidence of severe adverse events. Further large-scale RCTs are needed to identify the superior modality conclusively. We also identified several unique prognostic factors for overall survival, such as the neutrophil-lymphocyte ratio, volumetric multiparametric magnetic resonance imaging, serum albumin, alkaline phosphatase, and pancreastatin.

Local Treatment of Neuroendocrine Liver Metastases: How Effective and Safe is Stereotactic Microwave Ablation?

Abstract Background The less invasiveness of local ablation techniques such as stereotactic microwave ablation (SMWA) for the treatment of malignant hepatic lesions has made it an attractive alternative to conventional surgical resection. Aims The aim of this retrospective study was to assess the successful ablation rate of neuroendocrine tumor liver metastases (NETLM) 3 months after SMWA, the recurrence-free survival time, as well as the rate of peri- and early post interventional complications. Methods Retrospective analysis including all patients treated with SMWA for NETLM in our institution between 03/2015 and 07/2022. SMWA was performed as per the decision of the interdisciplinary tumorboard. Patients were included independent of location of primary tumors, disease stage, prior treatments. Patients underwent follow-up imaging (FU) every 1-6 months. Results 41 metastases were ablated in 21 interventions in 17 patients with a mean age of 63.6±9.7 years. A median of two lesions (range 1-4) were ablated per intervention. Mean time until first FU was 2.8±1.5 months. 39 of 41 (95.1%) lesions were fully ablated at the first FU. The two incompletely ablated lesions were treated using re-ablation and systemic treatment, respectively. A local recurrence occurred in further two ablation zones (4.9%) after 3.6 years in a patient with a progressive disease. Remaining 37 (90.2%) patients had no tumor recurrence in the ablation zone at the latest available FU (mean 24.3±17.3 months). Postinterventional length of hospital stay was a median of 1 [IQR 1;1.5]. No complications higher than Clavien Dindo Grade II occurred. Conclusions SMWA is a good minimal invasive intervention for the treatment of NETLM with low morbidity and high local efficacy.

The Evolving Role of Radioembolization in the Treatment of Neuroendocrine Liver Metastases.

Simple SummaryThis review provides basic insights into radioembolization, also known as selective internal radiation therapy, in patients suffering from neuroendocrine liver metastases. Radioembolization is a treatment that uses radioactive beads that are implanted intra-arterially to locally irradiate liver tumors. The available literature on radioembolization in neuroendocrine liver metastases show promising results in terms of efficacy and toxicity and will be discussed in more detail. However, data in the field of NELM need clarification, and this review also discusses the caveats, challenges and new insights when considering radioembolization in neuroendocrine liver metastases.At diagnosis, 21–50% of neuroendocrine tumors already have distant metastases, of which the liver is most commonly affected. Unfortunately, the presence of neuroendocrine liver metastases (NELM) is the most incriminating factor for survival. At NELM diagnosis, 60–70% of patients suffer from bilobar multifocal disease, making them ineligible for surgical resection. With limited systemic options, a clinical need for liver-directed treatments exists. Trans-arterial (bland) embolization, chemoembolization and radioembolization have been increasingly used in the treatment of NELM. In recent years, radioembolization (also known as selective internal radiation therapy) has gained attention due to promising tumor reductive results, limited toxicities and increasing scientific evidence. This review provides basic insights into radioembolization as a technique, a summary of available literature on radioembolization in NELM, and discusses caveats, challenges and new insights when considering radioembolization in NELM.

Long-term outcomes following 90Y Radioembolization of neuroendocrine liver metastases: evaluation of the radiation-emitting SIR-spheres in non-resectable liver tumor (RESiN) registry

BackgroundThe goal of this study was to evaluate efficacy and safety of 90Y radioembolization for neuroendocrine liver metastases (NELM) in a multicenter registry.MethodsOne hundred-seventy patients with NELM were enrolled in the registry (NCT 02685631). Prior treatments included hepatic resection (n = 23, 14%), arterial therapy (n = 62, 36%), octreotide (n = 119, 83%), cytotoxic chemotherapy (n = 58, 41%), biologic therapy (n = 49, 33%) and immunotherapy (n = 10, 6%). Seventy-seven (45%) patients had extrahepatic disease. Seventy-eight (48%), 61 (37%), and 25 (15%) patients were Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or ≥ 2. Tumor grade was known in 81 (48%) patients: 57 (70%) were well-, 12 (15%) moderate-, and 12 (15%) poorly-differentiated. Kaplan-Meier analysis and log rank tests were performed to compare overall and progression-free survival (OS/PFS) by tumor location and grade. Toxicities were reported using Common Terminology Criteria for Adverse Events v.5. Cox Proportional Hazards were calculated for pancreatic primary, performance status, extrahepatic disease at treatment, unilobar treatment, baseline ascites, and > 25% tumor burden.ResultsOne, 2, and 3-year OS rates were 75, 62 and 46%, respectively. Median OS was 33 months [(95% CI: 25-not reached (NR)]. The longest median OS was in patients with pancreatic (42 months, 95% CI: 33-NR) and hindgut 41 months, 95% CI: 12-NR) primaries. The shortest OS was in foregut primaries (26 months; 95% CI: 23-NR; X2 = 7, p = 0.1). Median OS of well-differentiated tumors was 36 months (95% CI: 10-NR), compared to 44 (95% CI: 7-NR) and 25 (95% CI: 3-NR) months for moderate and poorly differentiated tumors. Median progression-free survival (PFS) was 25 months with 1, 2, and 3-year PFS rates of 70, 54, and 35%, respectively. Thirteen patients (7.6%) developed grade 3 hepatic toxicity, most commonly new ascites (n = 8, 5%) at a median of 5.5 months. Performance status of ≥2 (HR 2.7, p = 0.01) and baseline ascites (HR 2.8, P = 0.049) predicted shorter OS.DiscussionIn a population with a high incidence of extrahepatic disease, 90Y was effective and safe in treatment of NELM, with median OS of 41 months for well differentiated tumors. Grade 3 or greater hepatic toxicity was developed in 7.6% of patients.Trial registrationNCT 02685631.

Efficacy and safety of Yttrium-90 radioembolization in the treatment of neuroendocrine liver metastases. Long-term monitoring and impact on survival

Introduction and objectiveNeuroendocrine tumors (NETs) debut in 75% of cases with liver metastases (LMNETs), whose therapeutic approach includes surgical resection and liver transplantation, while liver radioembolization with 90Y-microspheres (TARE) is reserved for non-operable patients usually due to high tumor burden.We present the accumulated experience of 10 years inTARE treatment of LMNETs in order to describe the safety and the effectiveness of the oncological response in terms of survival, as well as to detect the prognostic factors involved. Material and methodsOf 136 TARE procedures, performed between January 2006 and December 2016, 30 LMNETs (11.1%) were retrospectively analyzed. The study measures were: Tumor response, time to liver progression, survival at 3 and 5 years, overall mortality and mortality associated with TARE. The radiological response assessment was assessed using RECIST 1.1 and mRECIST criteria. ResultsAn average activity of 2.4 ± 1.3 GBq of 90Y was administered. No patient presented postembolization syndrome or carcinoid syndrome. There were also no vascular complications associated with the procedure. According to RECIST 1.1 criteria at 6 months, 78.6% presented partial response and 21.4% stable disease, there was no progression or complete response (1 by mRECIST). Survival at 3 and 5 years was 73% in both cases. ConclusionTARE treatment with 90Y-microspheres in LMNETs, applied within a multidisciplinary approach, is a safe procedure, with low morbidity, capable of achieving a high rate of radiological response and achieving lasting tumor responses.

Chemoembolization Versus Radioembolization for Neuroendocrine Liver Metastases: A Meta-analysis Comparing Clinical Outcomes.

Studies have shown intra-arterial therapies to be effective in controlling neuroendocrine liver metastases (NELMs), but the evidence supporting the selection of specific methods is limited. This meta-analysis is the first to compare survival outcomes between transarterial chemoembolization (TACE) and transarterial radioembolization (TARE) in the treatment of NELM. A systematic search according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines in PubMed and Embase databases was conducted in February 2020 for published studies comparing survival outcomes between TACE and TARE in the treatment of NELM. Six eligible cohort studies with a total of 643 patients were identified. The TACE and TARE groups were similar in terms of age, sex, hepatic tumor burden, tumor grade, and Eastern Cooperative Oncology Group (ECOG) score. The patients treated with TACE had significantly better overall survival (odds ratio [OR], 1.92; 95% confidence interval [CI] 1.14-3.22, p=0.014) than those treated with TARE. Overall survival ranged from 16.8 to 81.9 months with TACE and from 14.5 to 66.8months with TARE. No significant differences in hepatic progression-free survival (OR, 1.01; 95% CI 0.75-1.35; p=0.96) or tumor response were observed within the first 3 months (OR, 2.87; 95% CI 0.81-10.21; p=0.10) or thereafter (OR, 0.98; 95% CI 0.12-7.86; p=0.99). The complication rates were similar between the two groups, with 6.9% of the TACE patients versus 8.5% of TARE patients reporting major complications (OR, 1.16; 95% CI 0.54-2.48; p=0.71) and respectively 44.6% and 58.8% of the TACE and TARE patients reporting minor adverse events (OR, 1.08; 95% CI 0.39-2.99; p=0.88). Despite similar tumor responses, an overall survival benefit was associated with TACE treatment of NELM compared with TARE treatment. Randomized controlled trials are warranted to confirm this finding and clarify whether certain subpopulations benefit from different transarterial methods.

Operative Microwave Ablation for the Multimodal Treatment of Neuroendocrine Liver Metastases

Background and Purpose: Operative microwave ablation (MWA) is a safe modality for treating hepatic tumors. The aim of this study is to present our 10-year, single-center experience of operative MWA for neuroendocrine liver metastases (NLM). Methods: A single-institution retrospective review of patients who underwent operative MWA for NLM was performed (2008-2018). Demographics, primary tumor site, operative approach, combined surgical operations, and carcinoid symptoms were recorded. Clinical outcomes for major complications, readmission, and mortality were analyzed 30 days postoperatively. Postablation imaging was evaluated for incomplete ablation/missed lesions, and surveillance imaging reviewed for local, regional, and metastatic recurrence. Results: Of the 50 patients (166 targeted lesions) who received MWA for NLM, 41 (82%) were treated with a minimally invasive approach, and 22 (44%) underwent MWA concomitant with hepatectomy and/or primary tumor resection. Within the study cohort 70% of patients were treated with curative intent with a 77% (27/35) success rate. Carcinoid symptoms were reported in 40% (20/50) of patients preoperatively, and MWA treatment improved symptoms in 19/20 patients. Incomplete ablation occurred in 1/166 treated lesions. Recurrence-free survival at 1 and 5 years was 86% and 28%, respectively. Overall survival at 1 and 5 years was 94% and 70%, respectively (median follow-up 32 months, range 0-116 months). Conclusion: Operative MWA is a versatile modality, which can be safe and effectively performed alone or combined with hepatectomy for NLM, preferably using a minimally invasive approach, to achieve symptom control and possibly improve survival.

Radioembolization for neuroendocrine liver metastases is safe and effective prior to major hepatic resection.

Radioembolization (RE) is well established in the treatment of neuroendocrine liver metastases. However surgery is rarely performed after RE, although liver resection is the gold standard in the treatment of localized neuroendocrine liver metastases. Therefore, aim of the present study was to evaluate the safety and feasibility of liver resection after RE in a homogenous cohort. From a prospective surgical (n=494) and nuclear medical (n=138) database patients with NELM who underwent liver resection and/or RE were evaluated. Between September 2011 and December 2017 eight patients could be identified who underwent liver resection after RE (mean therapeutic activity of 1,746 Mbq). Overall and progression free survival were evaluated as well as epidemiological and perioperative factors. The surgical specimens were analyzed for necrosis, fibrosis, inflammation, and steatosis. The mean hepatic tumor load of patients, who had liver surgery after RE, was 31.4% with a mean Ki-67 proliferation index of 5.9%. The majority of these patients (7/8) received whole liver RE prior to liver resection, which did not increase morbidity and mortality compared to a surgical collective. Indications for RE were oncological (6/8) or carcinoid syndrome associated reasons (2/8). Mean overall survival was 25.1 months after RE and subsequent surgery. Tumor necrosis in radioembolized lesions was 29.4% without evidence of fibrosis and inflammation in hepatic tissue. This is the first study analyzing the multimodal therapeutic approach of liver resection following whole liver RE. This treatment algorithm is safe, does not lead to an increased morbidity and is associated with a favorable oncological outcome. Nonetheless, patient selection remains a key issue.

Can Microwave Ablation be an Alternative to Resection for the Treatment of Neuroendocrine Liver Metastases?

Objective: Surgical resection of neuroendocrine tumor liver metastases has been proven to improve survival, but the benefit of microwave ablation as an alternative or adjunct to surgery has yet to be assessed. Our hypothesis is that ablation is equal to surgery in terms of local recurrence and survival. Methods: We conducted a retrospective analysis including all patients treated with microwave ablation and/or surgical resection for neuroendocrine liver metastases in our institution between 2008 and 2017. Results: A total of 47 patients and 68 treatments were analyzed, including 34 liver resections, 20 ablations, and 14 combined procedures. A total of 130 individual metastases were treated with ablation, representing a median of 4 per session (range 1-30). While no major complications occurred after ablation, we observed 11 minor and 3 major complications after open surgical resection (P = .0135). Length of stay was significantly shorter after ablation (P = .0008). The majority of patients (33/47, 70.2%) underwent curative procedures, 14 patients underwent (29.8%) debulking procedures. There was no difference in local recurrence rate between tumors treated with ablation or resection. Liver-only disease progression was detected in 29% of the patients and overall progression was detected in 66% of the patients. The mean survival was not significantly different between patients treated with ablation only versus resection with or without ablation (P = .1570). Overall survival was mean 75.3 months (6 to 374 months). Conclusion: Depending on the extent of the liver metastases, microwave ablation might be a safe alternative or addition to resection for neuroendocrine tumor liver metastases with low morbidity and high local efficiency. Abbreviations: CT = computed tomography; MWA = microwave ablation; NET = neuroendocrine tumor; PET = positron emission tomography; RFA = radiofrequency ablation; RFS = recurrence-free survival; SMWA = stereotactic microwave ablation.

Abstract No. 566 Yttrium-90 radioembolization for unresectable neuroendocrine liver metastases: report in an Asian population

Yttrium-90 radioembolization is one of the intra-arterial therapies for unresectable neuroendocrine liver metastases (NELM). However, the data regarding Asian population is lacking. The aim of this study is to present the efficacy of Yttrium-90 radioembolization (Y90-RE) in the treatment of NELM and identify prognostic factors for survival in pure Asian population. This retrospective study was approved by the institutional review board and requirement for informed consent was waived. Between May 2008 and December 2016, twenty-three patients (13 men, 10 women; age range, 33 – 77 years) with NELM treated with Y90-RE at our institute were enrolled. Response to therapy was assessed by RECIST criteria by using periprocedural MR imaging. Posttreatment three-month radiologic response and survival were measured as the clinical end points. Of the 23 patients, 31 Y90-RE sessions were performed with a mean delivered dose 1.5 ± 0.6 GBq (range, 0.5 – 3.0 GBq) of first treatment and 2.6 ± 1.6 GBq (range, 0.7 – 5.0 GBq) of second treatment. In 3 and 6 months imaging follow-up, 8 (34.8%) and 8 (34.8%) patients had radiographic partial response to treatment, 9 (39.1%) and 12 (52.2%) had stable disease, 3 (13.0%) and 1 (4.3%) developed progressive disease. Median survival was 37.4 months, with 1-, 2-, and 3-year overall survival rates of 78.3%, 56.5%, and 30.4%, respectively. In univariate analysis, resection of primary tumor (P = 0.023), post Y90 local regional treat (LRT) (P = 0.019) and 3 months disease control (P = 0.0) were associated with good survival. On the contrary, high-grade (grade 3) histopathology of tumor (P = 0.008), tumor burden > 50% (P = 0.013), estimated absorbed tumor dose 103Gy (P = 0.030) and progressive radiographic response at 3 months (P = 0.005) were related to worse survival. Multivariate analysis revealed that disease control at 3 months (HR 0.002, P = 0.031), primary tumor resection (HR 0.035, P = 0.023), Post Y90 LRTs(HR 0.031, P = 0.001)were a predictor for better survival outcome. In Asian NELM population who underwent Y90-RE, primary tumor resection, 3 month tumor response, and post Y90 LRTs can predict survival outcome.

ALPPS in neuroendocrine liver metastases not amenable for conventional resection – lessons learned from an interim analysis of the International ALPPS Registry

BackgroundSurgery is the most effective treatment option for neuroendocrine liver metastases (NELM). This study investigated the role of associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) as a novel strategy in treatment of NELM. MethodsThe International ALPPS Registry was reviewed to study patients who underwent ALPPS for NELM. ResultsFrom 2010 to 2017, 954 ALPPS procedures from 135 international centers were recorded in the International ALPPS Registry. Of them, 24 (2.5%) were performed for NELM. Twenty-one patients entered the final analysis. Overall grade ≥3b morbidity was 9% after stage 1 and 27% after stage 2. Ninety-day mortality was 5%. R0 resection was achieved in 19 cases (90%) at stage 2. Median follow-up was 28 (19–48) months. Median disease free survival (DFS) was 17.3 (95% CI: 7.1–27.4) months, 1-year and 2-year DFS was 73.2% and 41.8%, respectively. Median overall survival (OS) was not reached. One-year and 2-year OS was 95.2% and 95.2%, respectively. ConclusionsALPPS appears to be a suitable strategy for inclusion in the multimodal armamentarium of well-selected patients with neuroendocrine liver metastases. In light of the morbidity in this initial series and a high rate of disease-recurrence, the procedure should be taken with caution.

Long-term outcomes of liver transplantation (LT) for the treatment of neuroendocrine liver metastases (NELM): The Mayo Clinic experience.

355 Background: In this study, we sought to determine the prognostic factors impacting survival of patients with NELM who underwent LT at Mayo Clinic. Methods: We performed a three-site retrospective analysis of patients with unresectable NELM treated with LT from 1990 -2017. Cases were identified from clinical databases at Mayo Clinic. Data on demographics, timing of diagnosis and transplant, extent of liver involvement, and tumor grade, were extracted. Extent of liver involvement was calculated using previously validated standardized volumetry with high defined as &gt; 25% increase in the weight of the extracted liver at the time of the transplant as compared to the standard liver volume. Survival was calculated using the Kaplan–Meier method. Results: We identified 37 patients. Median age at LT was 47 (range 17.0-64.0), male: female (73% vs. 27%, respectively). Primary tumor site was in the pancreas in 51.3% and in the small bowels in 43.2%; 78.4% had NELM at presentation. While primary tumor resection was done at the time of LT in 5 (13.9%) cases, most patients (80.6%) had ˃6-months interval between primary tumor resection and LT surgery. Prior to LT, 25 (74.3%) patients received somatostatin analogues and 18 (61.3%) had liver-directed therapy. Median time from diagnosis to transplant was 33.6 months (0-246). High extent of liver involvement was identified in 12 patients (33.3%). Disease-Free Survival (DFS) at 3, 5, and 10 years was 56.8%, 43.1%, and 22.4% respectively. Overall-survival (OS) at 3, 5, and 10 years was 86.9%, 79.6%, and 52.6% respectively. High extent of liver involvement at the time of transplantation was associated with inferior DFS and OS and patients˃45 years-old at the time of transplantation had worse DFS. Patients whose disease met the OPTN (Organ Procurement and Transplantation Network) criteria for NELM transplantation had significantly better DFS and OS with median 10-year OS of 80.7 % vs. 17%. Conclusions: LT is a reasonable therapeutic option for selected patients with unresectable NELM with 10-year OS of 52.6%. High extent of liver involvement was associated with worse long-term outcomes while meeting OPTN criteria resulted in best outcomes.

Therapeutic strategies for neuroendocrine liver metastases.

Patients who have neuroendocrine tumors frequently present with liver metastases. A wide panel of treatment options exists for these patients. Liver resection with curative intent achieves the best long-term results. Highly selected patients may be considered for liver transplantation. Substantial recurrence rates reported after surgical approaches call for neoadjuvant and adjuvant concepts. Liver-directed, locally ablative procedures are recommended for patients with limited, nonresectable tumor burden. Angiographic liver-directed techniques, such as transarterial embolization, transarterial chemoembolization, and selective internal radiotherapy, offer excellent palliation for patients with liver-predominant disease. Peptide receptor radionuclide therapy is a promising palliative procedure for patients with hepatic and/or extrahepatic metastases. The efficacy of these treatment options needs to be evaluated in randomized trials. Somatostatin analogues have demonstrated effectiveness not only for symptomatic relief in patients with secreting tumors but also for the control of proliferation in small intestinal neuroendocrine tumors and most recently also in those originating from the pancreas. Chemotherapy is an option mainly for those with pancreatic neuroendocrine tumors and high-grade tumors irrespective of the origin. Novel drugs targeting specific pathways within the tumor cell have produced improved progression-free survival compared with placebo in patients with pancreatic neuroendocrine tumors. Despite such a diverse armamentarium, there is uncertainty with regard to the optimal treatment regimens. Newly introduced molecular-based markers, along with the conduction of clinical trials comparing the efficacy of treatment modalities, offer a chance to move the treatment of neuroendocrine tumor disease toward personalized patient care. In this report, the authors review the approaches for treatment of neuroendocrine liver metastases, identify shortcomings, and anticipate future perspectives. Furthermore, clinical practice recommendations are provided for currently available treatment options. Although multiple modalities are available for the treatment of neuroendocrine liver metastases, optimal management is unclear. The current knowledge pertaining to these treatment options is analyzed.

31p Mr Spectroscopy to Evaluate the Efficacy of Hepatic Artery Embolization in the Treatment of Neuroendocrine Liver Metastases

It is common to treat patients with metastatic disease from gastrointestinal neuroendocrine (NE) tumors with surgical reduction to prolong survival. This can be combined with hepatic arterial embolization (HAE) and medical treatment to reduce hormonal symptoms. Today there are no rapid and reliable methods to evaluate the efficacy of HAE in the treatment of neuroendocrine liver metastasis. To investigate metabolic changes in hepatic metastases of NE tumors following HAE, and to establish if there are any early spectral patterns that might indicate therapeutic efficacy based on in vivo (31)P MRS data. Volume selective (31)P MRS was used to study 11 patients with disseminated NE tumors with regional lymph nodes and bilobar liver metastases. Measurements were performed before and 1 and 3 days after HAE. Non-responders had significantly higher PME/Pi and αNTP/ΣNTP ratios than the responders before HAE (P < 0.05). Three days after HAE, non-responders still had significantly higher αNTP/ΣNTP than the responders did (P < 0.05). We also observed trends for increased PME ratios 3 days after HAE, decreased ATP-levels, and liberated Pi in responders. This (31)P-MRS study showed significant differences in PME/Pi and αNTP/ΣP ratios between responders and non-responders on the day before HAE, which is an interesting finding that may reflect intrinsic properties of the tumor tissue. We also observed trends for cell membrane renewal and increased energy consumption in responders after HAE. These results demonstrate potentials for (31)P-MRS to predict individual responsiveness prior to HAE.

Surgical treatment of neuroendocrine liver metastases.

Management of Neuroendocrine liver metastases (NELM) is challenging. The presence of NELM worsens survival outcome and almost 10% of all liver metastases are neuroendocrine in origin. There is no firm consensus on the optimal treatment strategy for NELM. A systematic search of the PubMed database was performed from 1995–2010, to collate the current evidence and formulate a sound management algorithm. There are 22 case series with a total of 793 patients who had undergone surgery for NELM. The overall survival ranges from 46–86% at 5 years, 35–79% at 10 years, and the median survival ranges from 52–123 months. After successful cytoreductive surgery, the mean duration of symptom reduction is between 16–26 months, and the 5-year recurrence/progression rate ranges from 59–76%. Five studies evaluated the efficacy of a combination cytoreductive strategy reporting survival rate of ranging from 83% at 3 years to 50% at 10 years. To date, there is no level 1 evidence comparing surgery versus other liver-directed treatment options for NELM. An aggressive surgical approach, including combination with additional liver-directed procedures is recommended as it leads to long-term survival, significant long-term palliation, and a good quality of life. A multidisciplinary approach should be established as the platform for decision making.

Multimodality treatment of neuroendocrine liver metastases

Neuroendocrine liver metastases have a distinct tumor biology and symptomatology that render their management challenging. This difficulty is reflected in the literature, which lacks consensus on a treatment algorithm. The aim of this study is to propose a treatment algorithm based on patient morbidity and the efficacy of different treatment options. The medical records of 127 patients with neuroendocrine liver metastases were reviewed. As first-line treatment, 69 of these patients underwent radiofrequency ablation (RFA), 29 patients were treated by liver resection, and 29 underwent embolization. Clinical characteristics and surgical parameters were analyzed with the chi-square test, and cumulative survival was analyzed with the Kaplan-Meier method. All data are expressed as mean ± standard error of the mean. Of the 3 treatment modalities, RFA was the most commonly used initial treatment for patients with up to approximately 16 discrete lesions. Resection was used to debulk large tumors of limited number. Embolization was the first-line treatment for more extensive disease not amenable to RFA or resection. RFA provided effective cytoreduction while affording patients a shorter duration of stay and lower complication rates. On univariate analysis, the size of dominant metastases, extrahepatic disease, resection of primary tumor, and treatment modality affected survival. On multivariate analysis, sex, the size of dominant metastases, and extrahepatic disease were independent predictors of survival. To our knowledge, this study is the largest report on a multimodality approach to the treatment of neuroendocrine liver metastases yet published in the literature. Because of the patient selection criteria used in our study, a direct comparison of the treatment arms is not strictly possible. We used an initial treatment algorithm based on the presentation of the patient. Because this disease has a multifocal nature and accompanying elevated recurrence rate, careful follow-up of patients and subsequent treatments are often needed to minimize disease burden.

The role of liver transplantation in treatment of neuroendocrine liver metastases

The role of liver transplantation in treatment of neuroendocrine liver metastases

Abstract No. 33: Treatment of Neuroendocrine Liver Metastases with 90Y Radioembolization

Abstract No. 33: Treatment of Neuroendocrine Liver Metastases with 90Y Radioembolization

Cryoablation, percutaneous alcohol injection, and radiofrequency ablation for treatment of neuroendocrine liver metastases.

Neuroendocrine liver metastases are associated with slow clinical progression, prolonged patient survival, and symptoms of hormone oversecretion. Although surgical resection is the gold standard of treatment, most of the patients are not candidates for resection, and the 5-year survival of patients with neuroendocrine liver metastases is 11% to 40%. Cryotherapy, percutaneous alcohol injection, and radiofrequency thermal ablation are among the alternative regional treatment options available for these patients. The current role of these treatment options for neuroendocrine liver tumors are discussed in this review. Cryosurgery is the classic technique for local tumor destruction, mostly performed with open surgery. There has been limited experience with percutaneous alcohol injection for neuroendocrine liver metastasis. Radiofrequency thermal ablation is a relatively new modality that can be performed percutaneously or laparoscopically, and encouraging results have been obtained with it for treatment of neuroendocrine liver metastases.