Neuroendocrine Liver Metastases Research Articles

Utility of clinical and MR imaging parameters for prediction and monitoring of response to capecitabine and temozolomide (CAPTEM) therapy in patients with liver metastases of neuroendocrine tumors.

This study explores the predictive and monitoring capabilities of clinical and multiparametric MR parameters in assessing capecitabine and temozolomide (CAPTEM) therapy response in patients with neuroendocrine tumors (NET). This retrospective study (n = 44) assessed CAPTEM therapy response in neuroendocrine liver metastases (NELM) patients. Among 33 monitored patients, as a subgroup of the overall study cohort, pretherapeutic and follow-up MRI data (size, apparent diffusion coefficient [ADC] values, and signal intensities), along with clinical parameters (chromogranin A [CgA] and Ki-67%), were analyzed. Progression-free survival (PFS) served as the reference. Responders were defined as those with PFS ≥ 6 months. Most patients were male (75%) and had G2 tumors (76%) with a pancreatic origin (84%). Median PFS was 5.7 months; Overall Survival (OS) was 25 months. Non-responders (NR) had higher Ki-67 in primary tumors (16.5 vs. 10%, p = 0.01) and increased hepatic burden (20% vs. 5%, p = 0.007). NR showed elevated CgA post-treatment, while responders (R) exhibited a mild decrease. ADC changes differed significantly between groups, with NR having decreased ADCmin (-23%) and liver-adjusted ADCmean/ADCmean liver (-16%), compared to R's increases of ADCmin (50%) and ADCmean/ADCmean liver (30%). Receiver operating characteristic (ROC) analysis identified the highest area under the curve (AUC) (0.76) for a single parameter for ∆ ADC mean/liver ADCmean, with a cut-off of < 6.9 (76% sensitivity, 75% specificity). Combining ∆ Size NELM and ∆ ADCmin achieved the best balance (88% sensitivity, 60% specificity) outperforming ∆ Size NELM alone (69% sensitivity, 65% specificity). Kaplan-Meier analysis indicated significantly longer PFS for ∆ ADCmean/ADCmean liver < 6.9 (p = 0.024) and ∆ Size NELM > 0% + ∆ ADCmin < -2.9% (p = 0.021). Survival analysis emphasizes the need for adapted response criteria, involving combined evaluation of CgA, ADC values, and tumor size for monitoring CAPTEM response in hepatic metastasized NETs.

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)..

Comparison of post-hepatectomy long-term survival outcome between non-colorectal non-neuroendocrine and colorectal liver metastases: A population-based propensity-score matching analysis

BackgroundHepatectomy is an established treatment for colorectal liver metastasis (CLM) or neuroendocrine liver metastasis. However, its role in non-colorectal non-neuroendocrine liver metastasis (NCNNLM) is controversial. This study aims to compare long-term survival outcomes after hepatectomy between NCNNLM and CLM in a population-based cohort. MethodsFrom 2009 to 2018, curative hepatectomy were performed in 964 patients with NCNNLM (n ​= ​133) or CLM (n ​= ​831). Propensity score (PS) matching was performed. Short-term and long-term outcomes were compared between PS-matched groups. Univariate and multivariate analyses were performed to identify prognostic factors affecting survival. ResultsThere were 133 patients in the NCNNLM group and 266 patients in the CLM group. The mortality (1.5 ​% vs 1.5 ​%) and morbidity (19.5 ​% vs 20.3 ​%) rates were comparable between the two groups. There was no statistically significant difference in 5-year overall (48.9 ​% vs 39.8 ​%) and recurrence-free (25.1 ​% vs 23.4 ​%) survival rates between NCNNLM and CLM groups. A high pre-operative serum bilirubin level, severe postoperative complications and multiple tumors were independent prognostic factors for poor survival. ConclusionHepatectomy for selected patients with NCNNLM can achieve similar long-term oncological outcomes as those with CLM. High serum bilirubin, severe postoperative complication and multiple tumors are poor prognostic factors for survival.

Quantitative SSTR-PET/CT for predicting response and survival outcomes in patients with pancreatic neuroendocrine tumors receiving CAPTEM.

This study aimed to evaluate the predictive and monitoring role of somatostatin receptor (SSTR) positron emission tomography-computed tomography (PET/CT) and clinical parameters in patients with neuroendocrine liver metastases (NELM) from pancreatic neuroendocrine tumors (pNET) receiving capecitabine and temozolomide (CAPTEM). This retrospective study included twenty-two patients with pNET and NELM receiving CAPTEM who underwent pre- and post-therapeutic 68Ga-DOTATATE/-TOC PET/CT. Imaging (including standardized uptake value [SUV] of target lesions [NELM and pNET], normal spleen and liver) and clinical (Chromogranin A [CgA], Ki-67) parameters were assessed. Treatment outcome was evaluated as response according to RECIST 1.1, progression free survival (PFS) and overall survival (OS). The median PFS (mPFS) was 7 months. Responders had a significantly longer mPFS compared to non-responders (10 vs. 4 months p = 0.022). Median OS (mOS) was 33 months (mOS: responders = 80 months, non-responders = 24 months p = 0.182). Baseline imaging showed higher SUV in responders, including absolute SUV, tumor-to-spleen (T/S), and tumor-to-liver (T/L) ratios (p < 0.02). All SUV parameters changed only in the responders during follow-up. Univariable Cox regression analysis identified baseline Tmax/Smean ratio and percentage change in size of pNETs as significant factors associated with PFS. A baseline Tmax/Smean ratio < 1.5 was associated with a shorter mPFS (10 vs. 4 months, (p < 0.05)). Prognostic factors for OS included age, percentage change in CgA and in T/S ratios in univariable Cox regression. SSTR-PET/CT can be useful for predicting response and survival outcomes in pNET patients receiving CAPTEM: Higher baseline SUV values, particularly Tmax/Smean ratios of liver metastases were associated with better response and prolonged PFS.

Defining MRI Superiority over CT for Colorectal and Neuroendocrine Liver Metastases.

We compared CT and MRI for staging metastatic colorectal or neuroendocrine liver metastases (CRLMs and NELMs, respectively) to assess their impact on tumor burden. A prospectively maintained database was queried for patients who underwent both imaging modalities within 3 months, with two blinded radiologists (R1 and R2) independently assessing the images for liver lesions. To minimize recall bias, studies were grouped by modality, and were randomized and evaluated separately. Our query yielded 76 patients (42 CRLMs; 34 NELMs) with low interrater variability (intraclass correlation coefficients: CT = 0.941, MRI = 0.975). For CRLMs, there were no significant differences in lesion number or size between CT and MRI. However, in NELMs, Eovist®-enhanced MRI detected more lesions (R1: 14.3 vs. 12.1, p = 0.02; R2: 14.4 vs. 12.4, p = 0.01) and smaller lesions (R1: 5.7 vs. 4.4, p = 0.03; R2: 4.8 vs. 2.9, p = 0.02) than CT. CT and MRI are equivalent for CRLMs, but for NELMs, MRI outperforms CT in detecting more and smaller lesions, potentially influencing treatment planning and surgery.

An attempt to establish and apply global benchmarks for liver resection of malignant hepatic tumors

BackgroundBenchmarking is a process of continuous self-evaluation and comparison with best-in-class hospitals to guide quality improvement initiatives. We sought to define global benchmarks relative to liver resection for malignancy and to assess their achievement in hospitals in the United States. MethodsPatients who underwent curative-intent liver resection for hepatocellular carcinoma, intrahepatic cholangiocarcinoma, or colorectal or neuroendocrine liver metastases between 2000 and 2019 were identified from an international multi-institutional database. Propensity score matching was conducted to balance baseline characteristics between open and minimally invasive approaches. Best-in-class hospitals were defined relative to the achievement rate of textbook oncologic outcomes and case volume. Benchmark values were established relative to best-in-class institutions. The achievement of benchmark values among hospitals in the National Cancer Database was then assessed. ResultsAmong 2,624 patients treated at 20 centers, a majority underwent liver resection for hepatocellular carcinoma (n = 1,609, 61.3%), followed by colorectal liver metastases (n = 650, 24.8%), intrahepatic cholangiocarcinoma (n = 299, 11.4%), and neuroendocrine liver metastases (n = 66, 2.5%). Notably, 1,947 (74.2%) patients achieved a textbook oncologic outcome. After propensity score matching, 6 best-in-class hospitals with the highest textbook oncologic outcome rates (≥75.0%) were identified. Benchmark values were calculated for margin positivity (≤11.7%), 30-day readmission (≤4.1%), 30-day mortality (≤1.6%), minor postoperative complications (≤24.7%), severe complications (≤12.4%), and failure to achieve the textbook oncologic outcome (≤22.8%). Among the National Cancer Database hospitals, global benchmarks for margin positivity, 30-day readmission, 30-day mortality, severe complications, and textbook oncologic outcome failure were achieved in 62.9%, 27.1%, 12.1%, 7.1%, and 29.3% of centers, respectively. ConclusionThese global benchmarks may help identify hospitals that may benefit from quality improvement initiatives, aiming to improve patient safety and surgical oncologic outcomes.

Neuroendocrine liver metastases treated using transarterial radioembolization: Identification of prognostic parameters at 68Ga-DOTATATE PET/CT

PurposeTo identify prognostic clinical and imaging parameters for patients with neuroendocrine liver metastases (NELMs) undergoing transarterial radioembolization (TARE). Materials and methodsForty-seven patients (27 men; mean age, 64 years) with NELMs who received TARE, along with pre-procedure liver MRI and 68Ga-DOTATATE positron emission tomography/computed tomography were included. Apparent diffusion coefficient and standardized uptake value (SUV) of three liver metastases, normal spleen and liver were measured. SUVmax or SUVmean were used for the calculation of tumor-to-organ ratios (tumor-to-spleen and tumor-to-liver ratios) using all possible combinations (including SUVmax/SUVmax, SUVmax/SUVmean, and SUVmean/SUVmean). Clinical parameters (hepatic tumor-burden, presence of extra-hepatic metastases, chromograninA, Ki-67 and bilirubin levels) were assessed. Overall survival, progression-free survival (PFS) and hepatic progression-free survival (HPFS) were calculated using Kaplan-Meier curves. ResultsMedian overall survival, PFS and HPFS were 49.6, 13.1 and 28.3 months, respectively. In multivariable Cox regression analysis, low Ki-67 (≤ 5%), low hepatic tumor-burden (< 10%), absence of extrahepatic metastases, and increased Tmean/Lmax ratio were significant prognostic factors of longer overall survival and HPFS. High baseline chromograninA (> 1330 ng/mL) was associated with shorter HPFS. Tmean/Lmax > 1.9 yielded a median overall survival of 69 vs. 33 months (P < 0.04), and a median HPFS of 30 vs. 19 months (P = 0.09). For PFS, high baseline SUVmax of NELMs was the single significant parameter in the multivariable model. SUVmax > 28 resulted in a median PFS of 16.9 vs. 6.5 months, respectively (P = 0.001). ConclusionHigh preinterventional Tmean/Lmax ratios, and high SUVmax on 68Ga-DOTATATE positron emission tomography/computed tomography seem to have prognostic value in patients with NELMs undergoing TARE, potentially aiding patient selection and management alongside conventional variables.

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.

Transarterial chemoembolization (TACE) for neuroendocrine liver metastasis (NELM): Predictive value of volumetric arterial enhancement (VAE) on baseline MRI

Neuroendocrine tumors (NETs) belong to a rare family of tumors whose incidence has increased significantly over the past 50 years. To evaluate the prognostic value of volumetric arterial enhancement (VAE) on baseline magnetic resonance imaging (MRI) for patients with neuroendocrine liver metastasis (NELM) treated using transarterial chemoembolization (TACE). Between October 2012 and December 2018, VAE in 37 patients was measured with a semi-automatic volume of Interest (VOI) on subtracted T1 sequence in the arterial phase. Patients underwent 1-3 sectoral lipiodol TACE. Radiologic response using modified Response Evaluation Criteria in Solid Tumors (mRECIST) at the treatment cycle end and progression free survival were determined. Median age was 68.0 (60.0; 73.0). Twenty-three patients (62%) had a partial response, 10 (27%) had stable disease, four (11%) had progressive disease. VAE was a significant (P<0.05) predictor of radiologic response. Median progression free survival was 13 months (IC 95: 8; 16). In univariate analysis, significant predictors of local progression were alkaline phosphatase (AP) (P=0.035), Ki-67 index (P=0.014), and VAE (P<0.01). VAE over 500ms and Ki-67 index over 3%were risk factors of progression (P=<0.01) in multivariate analysis. VAE before TACE could be predictive of radiologic response and could be related to oncologic outcomes in patients with NELM.

Therapie von Lebermetastasen

BackgroundThe liver is the main destination for distant metastases of gastrointestinal as well as other malignancies. Consequently, the therapy of liver metastases plays a key role in oncological treatment strategies.ObjectivesIn this review, the current treatment options and multimodal therapy strategies for liver metastases are presented.Materials and methodsCurrent literature and national/international consensus guidelines are reviewed and general treatment options for liver metastases are summarized and then presented for the respective malignancies.ResultsAccording to treatment strategy and prognosis, liver metastases are divided into three categories: colorectal liver metastases (CRLM), neuroendocrine liver metastases, and non-colorectal non-neuroendocrine liver metastases which include liver metastases of all other malignancies. Due to their highest incidence, CRLM are of major interest. The individual treatment is chosen according to patient’s oncological situation, liver function, and comorbidities.ConclusionsSurgery is the best curative treatment option. Thus, all patients should be evaluated for surgery in specialized oncological boards. Despite higher local recurrence, local ablation methods are good alternative options for small and limited metastases. Systemic treatments and radiation are implemented in palliative settings as well as multimodal treatment strategies with the goal of cure.

Volumetric Enhancing Tumor Burden at CT to Predict Survival Outcomes in Patients with Neuroendocrine Liver Metastases after Intra-arterial Treatment

Purpose To investigate whether liver enhancing tumor burden (LETB) assessed at contrast-enhanced CT indicates early response and helps predict survival outcomes in patients with multifocal neuroendocrine liver metastases (NELM) after intra-arterial treatment. Materials and Methods This retrospective study included patients with NELM who underwent intra-arterial treatment with transarterial embolization (TAE) or chemoembolization (TACE) between April 2006 and December 2018. Tumor response in treated NELM was evaluated by using the Response Evaluation Criteria in Solid Tumors (RECIST) and modified RECIST (mRECIST). LETB was measured as attenuation 2 SDs greater than that of a region of interest in the nontumoral liver parenchyma. Overall survival (OS); time to unTA(C)Eable progression, defined as the time from the initial treatment until the time when intra-arterial treatments were considered technically unfeasible, either not recommended by the multidisciplinary tumor board or until death; and hepatic and whole-body progression-free survival (PFS) were evaluated using multivariable Cox proportional hazards analyses, the Kaplan-Meier method, and log-rank test. Results The study included 119 patients (mean age, 60 years ± 11 [SD]; 61 men) who underwent 161 treatments. A median LETB change of -25.8% best discriminated OS (83 months in responders vs 51 months in nonresponders; P = .02) and whole-body PFS (18 vs 8 months, respectively; P < .001). A -10% LETB change best discriminated time to unTA(C)Eable progression (32 months in responders vs 12 months in nonresponders; P < .001) and hepatic PFS (18 vs 8 months, respectively; P < .001). LETB change remained independently associated with improved OS (hazard ratio [HR], 0.56), time to unTA(C)Eable progression (HR, 0.44), hepatic PFS (HR, 0.42), and whole-body PFS (HR, 0.47) on multivariable analysis. Neither RECIST nor mRECIST helped predict patient outcome. Conclusion Response according to LETB change helped predict survival outcomes in patients with NELM after intra-arterial treatments, with better discrimination than RECIST and mRECIST. Keywords: CT, Chemoembolization, Embolization, Abdomen/GI, Liver Supplemental material is available for this article. © RSNA, 2023.

Long-term outcomes of resection versus transplantation for neuroendocrine liver metastases meeting the Milan criteria

Liver resection (LR) is considered the treatment of choice for resectable neuroendocrine liver metastases (NELM), while liver transplantation (LT) is currently reserved for highly selected unresectable patients. We retrospectively analyzed data from consecutive patients undergoing either curative resection or transplantation for liver-only NELM meeting Milan criteria at a single center between 1984 and 2019. Patients who fit Milan criteria were 48 in the transplantation group and 56 in the resection group. After a median follow-up of 158 months for the transplantation group and 126 for the resection group, the 10-year survival rate was 93% for transplantation and 75% for resection (p= .007). The 10-year disease-free survival rate was 52% for transplantation and 18% for resection (p< .001). Transplantation was associated with improved survival at univariate analysis. The median disease-free interval between surgery and recurrence was 78 months for transplantation vs. 24 months for resection (p< .001). The transplantation group had more multisite recurrences (12/25, 48% vs. 5/42, 12% in the resection group, p= .001), while most recurrences in the resection group were intra-hepatic (37/42, 88%, versus 2/25, 8% in the transplantation group). In conclusion, LT was associated with improved survival outcomes in NELM meeting the Milan criteria compared with LR.

Role of Radioembolization in Metastatic Neuroendocrine Tumors.

The liver is the most common site of metastasis for neuroendocrine tumors originating from the gastrointestinal tract. Neuroendocrine liver metastases (NELMs) portend a worsening clinical course, making local management important. Local treatment options include surgery, thermal ablation, and trans-catheter intra-arterial therapies, such as radioembolization. Radioembolization is generally preferred over other embolotherapies in patients with colonized biliary systems. Current best practice involves personalized treatment planning, optimizing tumor radiation absorbed dose and minimizing radiation to the normal hepatic parenchyma. As part of a multidisciplinary approach, radioembolization is a versatile embolotherapy offering neoadjuvant, palliative, and ablative treatment options for patients with NELMs.

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.

Liver Transplant for Nonhepatocellular Malignancies: A Review for Radiologists.

Although liver transplant is traditionally only performed for hepatocellular carcinoma (HCC), the last decade has seen a resurgence in its use for non-HCC malignancies, likely due to improvements in neoadjuvant treatment regimens and the establishment of well-defined eligibility criteria. Given promising survival results, patients with perihilar cholangiocarcinoma, neuroendocrine liver metastases, and hepatic hemangioendothelioma are eligible to receive Model for End-Stage Liver Disease (MELD) exception points for tumors that meet well-defined criteria. Patients with additional tumors such as colorectal cancer liver metastases, intrahepatic cholangiocarcinoma, and hepatocellular cholangiocarcinoma may undergo transplant at specialized centers with well-defined protocols, although these patients are not yet eligible for MELD exception. Transplant eligibility criteria commonly incorporate imaging findings; however, because of the relatively novel and evolving nature of liver transplant for non-HCC malignancies, radiologists may be unaware of relevant criteria or the implications of their imaging interpretations. Knowledge of the allocation process, previous studies, and liver transplant selection criteria facilitates radiologists' active participation in multidisciplinary discussion, leading to better and more equitable care for transplant candidates with non-HCC malignancy. This review provides an overview of transplant allocation and selection criteria in patients with non-HCC malignancy, with an emphasis on imaging features and the role of the radiologist.

Human Immunocompetent Model of Neuroendocrine Liver Metastases Recapitulates Patient-Specific Tumour Microenvironment.

Neuroendocrine liver metastases (LM-NEN) develop in a considerable proportion of patients with gastroenteropancreatic neuroendocrine neoplasms. There is a paucity of experimental models that accurately recapitulate this complex metastatic human liver microenvironment precluding scientific and clinical advancements. Here, we describe the development of a novel personalised immunocompetent precision cut tumour slice (PCTS) model for LM-NEN using resected human liver tissue. The histological assessment throughout the culture demonstrated that slices maintain viability for at least 7 days and retain the cellular heterogeneity of the original tumour. Essential clinical features, such as patient-specific histoarchitecture, tumour grade, neuroendocrine differentiation and metabolic capacity, are preserved in the slices. The PCTS also replicate the tumor-specific immunological profile as shown by the innate and adaptive immunity markers analysis. Furthermore, the study of soluble immune checkpoint receptors in the culture supernatants proves that these immunomodulators are actively produced by LM-NEN and suggests that this process is epithelium-dependent. This model can be employed to investigate these pathways and provides a powerful platform for mechanistic, immunological and pre-clinical studies.

Dynamic Contrast-enhanced CT to Evaluate Early Response in Neuroendocrine Liver Metastases Treated With Everolimus and Radiation.

The optimal method to evaluate response of neuroendocrine liver metastases (NELM) to radiation treatment (RT) is unknown; tumor perfusion parameters were evaluated by using dynamic contrast-enhanced computed tomography (DCE-CT) to correlate with efficacy in a prospective pilot study utilizing everolimus with radiotherapy for NELM. Fourteen patients with progressive NELM received everolimus for 28 days prior to, concurrent with, and 14 days following radiation. Patients had a DCE-CT at baseline (t0), prior to radiation (t1) and 7 days after radiation (t2). Per lesion response was evaluated per standard response evaluation criteria (RECIST v1.1). Median statistics of the perfusion parameters were tabulated and included: blood flow (BF), blood volume (BV), and permeability (PS). Correlations between the parameters and the maximum percent change in size of the NELM at 12-months were explored. NELM not treated with radiation served as an internal control. Twenty-one treated NELM in 10 patients were evaluable. Compared to t0, BV increased at t1 (median 11%, range -15 to +37%, p=0.59), and then decreased significantly at t2 (median -8.4%, range -29 to +5.4%, p<0.03). A trend of increased BV in internal controls at each time point supports that the observed effect is due to radiation. Conventional objective response rate was 33%; no progression was seen within 12-months. Changes in DCE-CT were observed in patients receiving everolimus and radiation for NELM, with BV decreasing significantly following radiotherapy. Given the challenges in assessing response in NELM using traditional response evaluation criteria in any context, DCE-CT appears to be a promising modality.

Liver metastases-Non-colorectal, non-endocrine

In contrast to colorectal and neuroendocrine liver metastases, liver surgery has not yet gained the same status for non-colorectal non-endocrine (NCNE) liver metastases. The main explanation is adifferent tumor biology but is also due to the lack of effective systemic treatment options for some tumor entities in the past. Even selected chemotherapy-naive patients with NCNE liver metastases can benefit from liver resection. Due to the sometimes dramatic improvements in systemic treatment in recent years, multimodality treatment concepts should be increasingly considered for several diseases in which modern liver surgery will become an integral part.

CT-based radiomics to distinguish progressive from stable neuroendocrine liver metastases treated with somatostatin analogues: an explorative study.

Accurate response evaluation in patients with neuroendocrine liver metastases (NELM) remains a challenge. Radiomics has shown promising results regarding response assessment. To differentiate progressive (PD) from stable disease (SD) with radiomics in patients with NELM undergoing somatostatin analogue (SSA) treatment. A total of 46 patients with histologically confirmed gastroenteropancreatic neuroendocrine tumors (GEP-NET) with ≥1 NELM and ≥2 computed tomography (CT) scans were included. Response was assessed with Response Evaluation Criteria in Solid Tumors (RECIST1.1). Hepatic target lesions were manually delineated and analyzed with radiomics. Radiomics features were extracted from each NELM on both arterial-phase (AP) and portal-venous-phase (PVP) CT. Multiple instance learning with regularized logistic regression via LASSO penalization (with threefold cross-validation) was used to classify response. Three models were computed: (i) AP model; (ii) PVP model; and (iii) AP + PVP model for a lesion-based and patient-based outcome. Next, clinical features were added to each model. In total, 19 (40%) patients had PD. Median follow-up was 13 months (range 1-50 months). Radiomics models could not accurately classify response (area under the curve 0.44-0.60). Adding clinical variables to the radiomics models did not significantly improve the performance of any model. Radiomics features were not able to accurately classify response of NELM on surveillance CT scans during SSA treatment.

Current status of surgical treatment for neuroendocrine liver metastases

Surgical resection is the optimal choice to achieve a better long-term survival for patients with neuroendocrine liver metastases(NELM). With the deeper understanding of neuroendocrine neoplasms and the establishment of a comprehensive diagnosis and treatment system, the concept of surgery for NELM is continually being updated. This article shares our experience and clinical practice of surgical resection for patients with NELM, and makes a brief review about the current status and controversy of surgical resection with NELM.