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BACKGROUND: The present study aimed to validate the accuracy of a tumor-specific antibody to target liver metastases of colorectal cancer. METHODS: A humanized anti-CEA antibody conjugated to a fluorescent dye (M5A-IR800) was tested for targeting human colorectal cancer liver metastases (CRLMs) expressing luciferase in an orthotopic mouse model. Orthotopic mouse models of CRLMs were established by implanting fragments of a luciferase-expressing human colorectal cancer cell line, LS174T, in the liver of nude mice. Mice received 50 µg M5A-IR800 72 h prior to imaging. To test co-localization, bioluminescence imaging was performed using D-luciferin, which was given via intraperitoneal injection just prior to imaging. RESULTS: Tumors were able to be visualized non-invasively through the skin with the luciferase-luciferin signal. Intra-abdominal imaging showed accurate labeling of CRLMs with M5A-IR800, which co-localized with the luciferase-luciferin signal. CONCLUSIONS: The present results validate the accuracy of a tumor-specific anti-CEA antibody in targeting liver metastases of colorectal cancer.

Background: Colorectal neuroendocrine tumors with liver metastases (CRNELM) are associated with a poorer prognosis compared to their nonmetastatic counterparts. A comprehensive understanding of the tumor microenvironment (TME) heterogeneity between primary lesions (PL) and liver metastases (LM) could provide crucial insights for enhancing clinical management strategies for these patients. Methods: We utilized single-cell RNA sequencing to analyze fresh tissue samples from CRNELM patients, aiming to elucidate the variations in TME between PL and LM. Complementary multidimensional validation was achieved through spatial transcriptomics, bulk RNA sequencing, and multiplex immunohistochemistry/immunofluorescence. Results: Our single-cell RNA sequencing analysis revealed that LM harboured a higher proportion of CD8 + T cells, CD4 + T cells, NK cells, NKT cells, and B cells exhibiting a stress-like phenotype compared to PL. RGS5 + pericytes may play a role in the stress-like phenotype observed in immune cells within LM. MCs in PL (PL_MCs) and LM (LM_MCs) exhibit distinct activation of tumor-associated signaling pathways. Notably, COLEC11 + matrix cancer-associated fibroblasts (COLEC11_mCAFs) were found to be significantly associated with LM_MCs. Cell communication analysis unveiled potential targetable receptor-ligand interactions between COLEC11_mCAFs and LM_MCs. Multidimensional validation confirmed the prominence of the characteristic stress-like phenotypes, including HSPA6_CD8_Tstr, HSPA6_NK, and COLEC11_mCAFs in LM. Moreover, a higher abundance of COLEC11_mCAFs correlated with poorer survival rates in the neuroendocrine tumor patient cohort. Conclusion: Overall, our study provides the first single-cell analysis of the cellular and molecular differences between PL and LM in CRNELM patients. We identified distinct cell subsets and receptor-ligand interactions that may drive TME discrepancies and support metastatic tumor growth. These insights highlight potential therapeutic targets and inform strategies for better managing CRNELM patients. [ABSTRACT FROM AUTHOR]

Background: In recent years, the incidence of patients with colorectal neuroendocrine neoplasms (CRNENs) has been continuously increasing. When diagnosed, most patients have distant metastases. Liver metastasis (LM) is the most common type of distant metastasis, and the prognosis is poor once it occurs. However, there is still a lack of large studies on the risk and prognosis of LM in CRNENs. This study aims to identify factors related to LM and prognosis and to develop a predictive model accordingly. Methods: In this study, the Surveillance, Epidemiology, and End Results (SEER) database was used to collect clinical data from patients with CRNENs. The logistic regression analyses were conducted to identify factors associated with LM in patients with CRNENs. The patients with LM formed the prognostic cohort, and Cox regression analyses were performed to evaluate prognostic factors in patients with liver metastasis of colorectal neuroendocrine neoplasms (LM-CRNENs). Predictive and prognostic nomogram models were constructed based on the multivariate logistic and Cox analysis results. Finally, the capabilities of the nomogram models were verified through model assessment metrics, including the receiver operating characteristic (ROC) curves, calibration curve, and decision curve analysis (DCA) curve. Results: This study ultimately encompassed a total of 10,260 patients with CRNENs. Among these patients, 501 cases developed LM. The result of multivariate logistic regression analyses indicated that histologic type, tumor grade, T stage, N stage, lung metastasis, bone metastasis, and tumor size were independent predictive factors for LM in patients with CRNENs (p < 0.05). Multivariate Cox regression analyses indicated that age, primary tumor site, histologic type, tumor grade, N stage, tumor size, chemotherapy, and surgery were independent prognostic factors (p < 0.05) for patients with LM-CRNENs. The predictive and prognostic nomogram models were established based on the independent factors of logistic and Cox analyses. The nomogram models can provide higher accuracy and efficacy in predicting the probability of LM in patients with CRNENs and the prognosis of patients with LM. Conclusion: The factors associated with the occurrence of LM in CRNENs were identified. On the other hand, the relevant prognostic factors for patients with LM-CRNENs were also demonstrated. The nomogram models, based on independent factors, demonstrate greater efficiency and accuracy, promising to provide clinical interventions and decision-making support for patients. [ABSTRACT FROM AUTHOR]

Background: The survival benefit of adjuvant chemotherapy after curative hepatectomy for colorectal cancer (CRC) liver metastases remains controversial. This retrospective study aimed to evaluate the efficacy of adjuvant chemotherapy in improving recurrence-free survival (RFS) and overall survival (OS) in patients who underwent curative hepatectomy for CRC liver metastases at a tertiary medical center. Methods: We retrospectively analyzed clinicopathological factors in 89 patients (surgery alone, n = 63; adjuvant chemotherapy, n = 26) who underwent curative hepatectomy for CRC liver metastases from January 2010 to December 2022. Patients who received neoadjuvant therapy or prior hepatectomy were excluded to minimize patient heterogeneity. Multivariate analysis using Cox proportional hazards regression was conducted to assess the independent effect of adjuvant therapy on RFS and OS. Results: The 3-year RFS rates were 22.6% in the surgery alone group and 29.6% in the adjuvant chemotherapy group (hazard ratio, 0.71; 95% confidence interval, 0.43–1.21; p = 0.102). The 3-year OS rates were 72.3% in the surgery alone group and 88.5% in the adjuvant chemotherapy group (hazard ratio, 0.59; 95% confidence interval, 0.29–1.25; p = 0.17). Univariate analyses showed that the number of liver metastases (> 2) was significantly associated with poorer OS (hazard ratio, 2.44; 95% confidence interval, 1.11–5.37; p = 0.027). Additionally, multivariate analyses showed that the addition of adjuvant chemotherapy was significantly associated with improved OS (hazard ratio, 0.23; 95% confidence interval, 0.07–0.81; p = 0.021). Conclusions: Adjuvant chemotherapy may improve OS after curative hepatectomy for CRC liver metastases, though it did not significantly impact RFS. Larger-scale multicenter prospective studies with stratified analyses are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Objective: To explore the value of preoperative CT-based morphological heterogeneity (MH) for predicting local tumor disease-free survival (LTDFS) and progression-free survival (PFS) in patients with colorectal cancer liver metastases (CRLM). Methods: The latest CT data of 102 CRLM patients were retrospectively analyzed. The morphological score of each liver metastasis was obtained, and the morphological heterogeneity difference (MHD) was calculated. The receiver operating characteristic (ROC) curve was drawn, and the cutoff value was found. The Kaplan-Meier method was used to draw survival curves of patients with or without MH. The Cox regression analysis was used to build the model with MH and clinical characteristics for predicting PFS. Results: In 78 patients without MH, median PFS was 9.0 months (95% CI:6.5–11.5), while in 24 patients with MH, median PFS was 6.0 months (95% CI:4.0-8.1), indicating that MH significantly affected PFS (p = 0.001). MH affected PFS in both the chemotherapy group and the chemotherapy combined with targeted therapy group (p = 0.005, p = 0.043). MH, preoperative carcinoembryonic antigen (CEA) and chemotherapy after surgery were independent predictors for postoperative PFS in patients with CRLM. Conclusion: Preoperative CT-based MH had good efficacy for predicting LTDFS and PFS of CRLM patients after surgical resection, regardless of preoperative treatment. MH is one of the independent predictors of PFS. [ABSTRACT FROM AUTHOR]

Simple Summary: Percutaneous microwave ablation (MWA) is a key treatment for primary and secondary liver malignancies. The aim of this prospective study was to evaluate the efficacy and safety of the Surgnova Dophi™ M150E MWA system and to compare ablation defect characteristics with data from the manufacturer's ablation charts, as well as findings from the literature. In a cohort of 50 patients with 77 liver tumors, stereotactic CT-guided MWA was applied using this novel technology. A primary technique efficacy of 97.4% was achieved, with complete ablation in 75 out of 77 tumors. Complications occurred in 10% of patients, with only 4% classified as major. A comparison with previous in vivo data confirmed the reliability of the system in achieving reproducible and predictable ablation results. In conclusion, the Surgnova Dophi™ M150E system has an excellent efficacy and safety profile for percutaneous stereotactic liver tumor treatment, highlighting its potential in the growing field of interventional oncology. Purpose: To evaluate the efficacy and safety of the Surgnova Dophi™ M150E microwave ablation system in a prospective single-center observational study. Methods: A cohort of 50 patients with 77 primary or secondary liver tumors underwent CT-navigated stereotactic percutaneous microwave ablation with curative intention using the Surgnova Dophi™ M150E system. The endpoints were primary technique efficacy (PTE), number of complications, ablation defect dimensions, and sphericity index compared to previously reported findings. Results: The PTE was 97.4%, with complete ablation in 75 out of 77 tumors. Complications occurred in 10% of patients, with 4% classified as major. A comparison with previous in vivo data confirmed the reliability of the system in achieving reproducible and predictable ablation results. Conclusions: Stereotactic percutaneous microwave ablation with the Surgnova Dophi™ M150E system is safe and effective for liver tumor treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: In this work, we developed three neural networks based on the U-net architecture to automatically segment the healthy liver area, the metastatic liver area, and liver metastases in micro-CT images of mice with pancreatic ductal adenocarcinoma and liver metastases. The best network for each task was then identified by cross-validation. The results demonstrated the ability of the selected networks to segment the above areas in a manner comparable to manual segmentation, at the same time saving time and ensuring reproducibility. Therefore, despite the limited number of animals involved, our pilot study represents a first step toward the development of automated tools to support liver metastasis research in the preclinical setting. Background: The liver is one of the most common sites for the spread of pancreatic ductal adenocarcinoma (PDAC) cells, with metastases present in about 80% of patients. Clinical and preclinical studies of PDAC require quantification of the liver's metastatic burden from several acquired images, which can benefit from automatic image segmentation tools. Methods: We developed three neural networks based on U-net architecture to automatically segment the healthy liver area (HL), the metastatic liver area (MLA), and liver metastases (LM) in micro-CT images of a mouse model of PDAC with liver metastasis. Three alternative U-nets were trained for each structure to be segmented following appropriate image preprocessing and the one with the highest performance was then chosen and applied for each case. Results: Good performance was achieved, with accuracy of 92.6%, 88.6%, and 91.5%, specificity of 95.5%, 93.8%, and 99.9%, Dice of 71.6%, 74.4%, and 29.9%, and negative predicted value (NPV) of 97.9%, 91.5%, and 91.5% on the pilot validation set for the chosen HL, MLA, and LM networks, respectively. Conclusions: The networks provided good performance and advantages in terms of saving time and ensuring reproducibility. [ABSTRACT FROM AUTHOR]

Objectives: Treatment of metastatic colorectal cancer (mCRC) includes resection of liver metastases (LM), however, no validated biomarker identifies patients most likely to benefit from this procedure. This meta-analysis aimed to assess the impact of the most relevant molecular alterations in cancer-related genes of CRC (i.e., RAS, BRAF, SMAD4, PIK3CA) as prognostic markers of survival and disease recurrence in patients with mCRC surgically treated by LM resection. Methods: A systematic literature review was performed to identify studies reporting data regarding survival and/or recurrence in patients that underwent complete liver resection for CRC LM, stratified according to RAS, BRAF, PIK3CA, and SMAD4 mutational status. Hazard ratios (HRs) from multivariate analyses were pooled in the meta-analysis and various adjustment strategies for confounding factors were combined. The search was conducted in numerous databases, including MEDLINE (PubMed), Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL) (EBSCO host), and WHO Global Index Medicus, through March 18th, 2022. Meta-analyses, editorials, letters to the editor, case reports, studies on other primary cancers, studies with primary metastatic sites other than the liver, studies lacking specific oncological outcome variables or genetic data, non-English language studies, and studies omitting residual disease data from liver metastasectomy were excluded. The remaining 47 studies were summarized in a descriptive table which outlines the key characteristics of each study and final results were graphically presented. Results: RAS mutation status was negatively associated with overall survival (OS) (HR, 1.68; 95% CI, 1.54-1.84) and recurrence free survival (RFS) (HR, 1.46; 95% CI, 1.33-1.61). A negative association was also found for BRAF regarding OS (HR, 2.64; 95% CI, 2.15-3.24) and RFS (HR, 1.89; 95% CI, 1.32-2.73) and SMAD4 regarding OS (HR, 1.93; 95% CI, 1.56-2.38) and RFS (HR, 1.95; 95% CI, 1.31-2.91). For PIK3CA only three studies were eligible and no significant association with either OS or RFS could be highlighted. Conclusion: RAS, BRAF, and SMAD4 are negatively associated with OS and RFS in patients undergoing curative liver metastasectomy from colorectal cancer. No conclusion can be drawn for PIK3CA due to the limited literature availability. These data support the integration of RAS, BRAF, and SMAD4 mutational status in the surgical decision-making for colorectal liver metastasis. Nevertheless, we have to consider several limitations, the major ones being the pooling of results from studies that evaluated patient outcomes as either disease-free survival (DFS) or RFS; the inclusion of patients with minimal residual disease and unconsidered potential confounding factors, such as variability in resectability definitions, chemotherapy use, and a potential interaction between biological markers and pre- and post-resection pharmacological treatments. [ABSTRACT FROM AUTHOR]

Purpose: To develop and validate a nomogram for predicting the overall survival (OS) of ovarian cancer patients with liver metastases (OCLM). Methods: This study identified 821 patients in the Surveillance, Epidemiology, and End Results (SEER) database. All patients were randomly divided in a ratio of 7:3 into a training cohort (n = 574) and a validation cohort (n = 247). Clinical factors associated with OS were assessed using univariate and multivariate Cox regression analyses, and backward stepwise regression was applied using the Akaike information criterion (AIC) to select the optimal predictor variables. The nomogram for predicting the OS of the OCLM patients was constructed based on the identified prognostic factors. Their prediction ability was evaluated using the concordance index (C-index), receiver operating characteristic (ROC) curve, calibration curve, and decision curves analysis (DCA) in both the training and validation cohorts. Results: We identified factors that predict OS for OCLM patients and constructed a nomogram based on the data. The ROC, C-index, and calibration analyses indicated that the nomogram performed well over the 1, 2, and 3-year OS in both the training and validation cohorts. Additionally, in contrast to the External model from multiple perspectives, our model shows higher stability and accuracy in predictive power. DCA curves, NRI, and IDI index demonstrated that the nomogram was clinically valuable and superior to the External model. Conclusion: We established and validated a nomogram to predict 1,2- and 3-year OS of OCLM patients, and our results may also be helpful in clinical decision-making. [ABSTRACT FROM AUTHOR]

Objective To evaluate 2 years of clinical experience with markerless breath-hold liver stereotactic radiotherapy (SBRT) using noninvasive nasal high-flow therapy (NHFT) for breath-hold prolonging and surface guidance (SGRT) for monitoring. Methods Heated and humidified air was administered via a nasal cannula (40 L/min, 80% oxygen, 34 °C). Patients performed voluntary inspiration breath-holds with visual feedback. After a training session, 4-5 breath-hold CT scans were acquired to delineate an internal target volume (ITV) accounting for inter- and intra-breath-hold variations. Patients were treated in 3-8 fractions (7.5-20 Gy/fraction) using SGRT-controlled beam-hold. Patient setup was performed using SGRT and CBCT imaging. A posttreatment CBCT was acquired for evaluation purposes. Results Fifteen patients started the training session and received treatment, of whom 10 completed treatment in breath-hold. Half of all 60-second CBCT scans were acquired during a single breath-hold. The average maximum breath-hold duration during treatment ranged from 47 to 108 s. Breath-hold ITV was on average 6.5 cm³/30% larger (range: 1.1-23.9 cm³/5%-95%) than the largest GTV. Free-breathing ITV based on 4DCT scans was on average 16.9 cm³/47% larger (range: −2.3 to 58.7 cm3/−16% to 157%) than the breath-hold ITV. The average 3D displacement vector of the area around PTV for the posttreatment CBCT scans was 5.0 mm (range: 0.7-12.9 mm). Conclusions Liver SBRT in breath-hold using NHFT and SGRT is feasible for the majority of patients. An ITV reduction was observed compared to free-breathing treatments. To further decrease the PTV, internal anatomy-based breath-hold monitoring is desired. Advances in knowledge Noninvasive NHFT allows for prolonged breath-holding during surface-guided liver SBRT. [ABSTRACT FROM AUTHOR]

The role of immune checkpoint inhibitors for patients with gastroesophageal cancer with liver metastasis remains unclear. Our objective was to investigate whether immune checkpoint inhibitors are beneficial in patients with gastroesophageal cancer with liver metastasis. We searched PubMed, Embase, European Society for Medical Oncology, and American Society of Clinical Oncology meeting abstracts for phase 3 randomized clinical trials testing immune checkpoint inhibitors in metastatic/advanced gastroesophageal cancer from 2017 to 2023. Seven studies were included. Overall survival was similar among all patients (hazard ratio [HR] = 0.72 [95% confidence interval (CI) = 0.67 to 0.77], P  < .001), in patients without liver metastases (HR = 0.73 [95% CI = 0.67 to 0.81], P  < .001, I 2 = 0.0%), and in patients with liver metastases (HR = 0.74 [95% CI = 0.67 to 0.81], P  < .001, I 2 = 0.0%). Progression-free survival was also similar among all patients (HR = 0.63 [95% CI = 0.57 to 0.70], P  < .001), in patients without liver metastases (HR = 0.62 [95% CI = 0.51 to 0.76], P  < .001), and in patients with liver metastases (HR = 0.66 [95% CI = 0.57 to 0.76], P  < .001). Immune checkpoint inhibitors showed no difference in benefit in patients with gastroesophageal cancer, regardless of liver metastasis. Future studies could focus on deciphering the tumor microenvironment of liver metastasis as an area of translational research. [ABSTRACT FROM AUTHOR]

To explore the imaging manifestations and clinical application value of contrast-enhanced ultrasound (CEUS) in liver metastases of middle and low rectal cancer by performing CEUS in patients. Additionally, we compared the results of CEUS with those of abdominal contrast-enhanced computed tomography (CECT) to assess the reliability of diagnosing liver metastases in patients with middle and low rectal cancer. Methods: Hepatic CEUS was performed in 1095 patients with middle and low rectal cancer, and all patients underwent abdominal CECT examinations to determine the presence or absence of liver metastases. The results of both examinations were compared to evaluate the value of hepatic CEUS for detecting liver metastases in patients with middle and low rectal cancer. Results: Among 1095 patients with middle and low rectal cancer, 132 were diagnosed with liver metastases of middle and low rectal cancer. 130 cases of liver metastases of rectal cancer were identified using hepatic CEUS, whereas 126 cases were identified using abdominal CECT. The detection rates of hepatic CEUS and abdominal CECT for liver metastases of middle and low rectal cancer showed no statistically significant differences (P > 0.05). The Kappa value for the diagnosis of liver metastases of middle and low rectal cancer between hepatic CEUS and abdominal CECT was 0.974 (P < 0.001), indicating good consistency between the two imaging modalities in detecting liver metastases of middle and low rectal cancer. Conclusion: Hepatic CEUS can be used to diagnose liver metastases in middle and low rectal cancer, providing crucial imaging evidence for clinical treatment planning. It exhibited higher sensitivity than that of abdominal CECT in diagnosing liver metastases of middle and low rectal cancer, enabling the identification of higher number of liver metastases of middle and low rectal cancer cases. [ABSTRACT FROM AUTHOR]

Objectives: This study was designed to assess computed tomography (CT)-based radiomics of colorectal liver metastases (CRLM), extracted from posttreatment scans in estimating pathologic treatment response to neoadjuvant therapy, and to compare treatment response estimates between CT-based radiomics and radiological response assessment by using RECIST 1.1 and CT morphologic criteria. Methods: Patients who underwent resection for CRLM from January 2003–December 2012 at a single institution were included. Patients who did not receive preoperative systemic chemotherapy, or without adequate imaging, were excluded. Imaging characteristics were evaluated based on RECIST 1.1 and CT morphologic criteria. A machine-learning model was designed with radiomic features extracted from manually segmented posttreatment CT tumoral and peritumoral regions to identify pathologic responders (≥ 50% response) versus nonresponders. Statistical analysis was performed at the tumor level. Results: Eighty-five patients (median age, 62 years; 55 women) with 95 tumors were included. None of the subjectively evaluated imaging characteristics were associated with pathologic response (p > 0.05). Inter-reader agreement was substantial for RECIST categorical response assessment (K = 0.70) and moderate for CT morphological group response (K = 0.50). In the validation cohort, the machine learning model built with radiomic features obtained an area under the curve (AUC) of 0.87 and outperformed subjective RECIST assessment (AUC = 0.53, p = 0.01) and morphologic assessment (AUC = 0.56, p = 0.02). Conclusions: Radiologist assessment of oligometastatic CRLM after neoadjuvant therapy using RECIST 1.1 and CT morphologic criteria was not associated with pathologic response. In contrast, a machine-learning model based on radiomic features extracted from tumoral and peritumoral regions had high diagnostic performance in assessing responders versus nonresponders. [ABSTRACT FROM AUTHOR]

Background There have been conflicting reports on the predictive impact of metastatic disease sites on the response to checkpoint inhibitors (CPI) in microsatellite instability (MSI) metastatic colorectal cancers (mCRC). Recent studies have highlighted peritoneal metastases, ascites, and liver metastases as possible indicators of resistance to CPI. Methods We performed a detailed analysis of high microsatellite instability (MSI-H) mCRC treated with programmed cell death (PD-1) or PD-1/cytotoxic T-lymphocyte-associated protein 4 CPI in a single center. Overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and stable disease but with complete pathological response upon resection (SDcPR) were analyzed by the presence of liver metastases, peritoneal metastases, or absence of either. The impact of number and size of liver metastases on clinical outcomes were also interrogated. Results Thirty-five patients with MSI mCRC were included in the analysis. Patients with peritoneal metastatic disease had lower ORR and shorter PFS compared to patients without liver and peritoneal metastases. Contrary to recent reports, ORR and ORR + SDcPR rates were high in patients with liver metastases, at 58% and 66%, respectively. In the liver metastases category, a better response rate was noted for patients with<5 lesions compared to patients with more than 5 lesions. Patients who responded had a higher median tumor mutation burden than patients with progressive disease. Conclusions In MSI mCRC, no single clinical characteristic was sufficient to preclude CPI response. Peritoneal metastatic disease was associated with numerically lower ORR and shorter PFS. In contrast, liver metastases do not predict poor outcome. [ABSTRACT FROM AUTHOR]

Introduction: Surgical resection is gold standard for treatment of liver metastasis, locally ablative techniques including computer tomography (CT)-guided interstitial high-dose-rate (HDR) brachytherapy (CT-BRT) and stereotactic body radiotherapy (SBRT) have gained prominence as alternatives, offering comparable outcomes in selected patients. We aim to compare CT-BRT and SBRT - based on dosimetric analysis. Material and methods: Patients who underwent CT-BRT for oligometastatic, ≤4cm liver metastases between 2018 and 2024 were eligible. SBRT plans for Halcyon (SBRTh) and TrueBeam (SBRTtb) were prepared virtually. In the CT-BRT group CTV was equal to PTV, for SBRTh and SBRTtb planning, a 5 mm margin was applied to CTV to create PTV. Dose calculation was carried out with the TG-43 algorithm for CT-BRT and Anisotropic Analytical Algorithm for SBRTh and SBRTtb group. Descriptive statistics were used to compare the data. The Wilcoxon pairwise order test was utilized to compare dependent groups. Results: CT-BRT resulted in a more favorable dose distribution within PTVs for Dmean, D50, and D90, while SBRT showed better results for D98 and V27.5Gy. No significant differences were observed for V25Gy between CT-BRT and SBRTtb, but SBRTh favored over CT-BRT. For OARs, CT-BRT plans showed better values for V5, V10, and V11.6Gy in the uninvolved liver volume. There were no significant differences in dose distribution for the duodenum, bowel, and heart. SBRT modalities performed better in the kidney. CT-BRT had improved dose distribution in the esophagus, great vessels, ribs, skin, spinal cord, and stomach compared to SBRT. Conclusions: CT-BRT could be a viable alternative to SBRT for certain patients with liver malignancies. [ABSTRACT FROM AUTHOR]

Liver metastases are commonly detected in the advanced stages of various malignant tumors, representing a significant clinical challenge. Throughout the process of liver metastases formation, immune cells play a pivotal role, particularly in the pre-metastatic and metastatic niches within the liver. Immune cells establish extensive and intricate interactions with tumor cells and other components in the liver, collectively promoting and sustaining the growth of liver metastases. Despite the limited efficacy of existing therapeutic modalities against some advanced liver metastases, novel immune-based treatment approaches are continuously being explored and validated. Building on the systematic elucidation of the immunosuppressive characteristics of liver metastases, we explored the potential of novel immunotherapies applicable to patients with liver metastases from multiple dimensions. [ABSTRACT FROM AUTHOR]

Purpose: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRSH) or liver resection have led to increased survival in patients with peritoneal or liver metastases of colorectal cancer. Selected patients undergo concomitant CRSH and liver resection. Differences in survival and morbidity between patients who underwent concomitant surgery, CRSH or liver resection for peritoneal and/or liver metastases were compared. Methods: Patients who underwent liver resection and/or CRSH for colorectal liver and/or peritoneal metastases, 2006–2016, were included. Regression analysis was used to evaluate the associations between baseline characteristics and survival. Results: Overall, 634 patients were studied. Twenty-eight patients had peritoneal and liver metastases, 121 patients had peritoneal metastases only, and 485 patients had isolated liver metastases. Median survival after concomitant treatment was 23.8 months (95% CI 12.8–43.8), after CRSH 34.5 months (95% CI 27.1–41.9), and after liver resection 54.2 months (95% CI 47.4–61.0) (p < 0.001). Increased hepatic tumor burden (HR 3.2, 95% CI 1.8–5.8) and high-volume peritoneal disease (HR 6.0, 95% CI 3.7–9.8) were associated with decreased survival in multivariate analysis. Postoperative complications according to a Clavien–Dindo score > 3a were observed in 11% in the liver resection group, 15% in the CRSH group, and 11% in the concomitant treatment group (p = 0.945). Conclusions: Patients treated with concomitant surgery for liver and peritoneal metastases experienced a shorter median overall survival than patients treated for metastases at an isolated site but had a similar rate of severe postoperative complications. The extent of peritoneal spread seemed to impact survival more than the tumor burden in the liver. [ABSTRACT FROM AUTHOR]

Background: DNA methylation biomarkers are one of the most promising tools for the diagnosis and differentiation of adenocarcinomas of the liver, which are among the most common malignancies worldwide. Their differentiation is important because of the different prognoses and treatment options. This study aimed to validate previously identified DNA methylation biomarkers that successfully differentiate between liver adenocarcinomas, including the two most common primary liver cancers, hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), as well as two common metastatic liver cancers, colorectal liver metastases (CRLM) and pancreatic ductal adenocarcinoma liver metastases (PCLM), and translate them to the methylation-sensitive high-resolution melting (MS-HRM) and digital PCR (dPCR) platforms. Methods: Our study included a cohort of 149 formalin-fixed, paraffin-embedded tissue samples, including 19 CRLMs, 10 PCLMs, 15 HCCs, 15 CCAs, 15 colorectal adenocarcinomas (CRCs), 15 pancreatic ductal adenocarcinomas (PDACs) and their paired normal tissue samples. The methylation status of the samples was experimentally determined by MS-HRM and methylation-specific dPCR. Previously determined methylation threshold were adjusted according to dPCR data and applied to the same DNA methylation array datasets (provided by The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO)) used to originally identify the biomarkers for the included cancer types and additional CRLM projects. The sensitivities, specificities and diagnostic accuracies of the panels for individual cancer types were calculated. Results: In the dPCR experiment, the DNA methylation panels identified HCC, CCA, CRC, PDAC, CRLM and PCLM with sensitivities of 100%, 66.7%, 100%, 86.7%, 94.7% and 80%, respectively. The panels differentiate between HCC, CCA, CRLM, PCLM and healthy liver tissue with specificities of 100%, 100%, 97.1% and 94.9% and with diagnostic accuracies of 100%, 94%, 97% and 93%, respectively. Reevaluation of the same bioinformatic data with new additional CRLM projects demonstrated that the lower dPCR methylation threshold still effectively differentiates between the included cancer types. The bioinformatic data achieved sensitivities for HCC, CCA, CRC, PDAC, CRLM and PCLM of 88%, 64%, 97.4%, 75.5%, 80% and 84.6%, respectively. Specificities between HCC, CCA, CRLM, PCLM and healthy liver tissue were 98%, 93%, 86.6% and 98.2% and the diagnostic accuracies were 94%, 91%, 86% and 98%, respectively. Moreover, we confirmed that the methylation of the investigated promoters is preserved from primary CRC and PDAC to their liver metastases. Conclusions: The cancer-specific methylation biomarker panels exhibit high sensitivities, specificities and diagnostic accuracies and enable differentiation between primary and metastatic adenocarcinomas of the liver using methylation-specific dPCR. High concordance was achieved between MS-HRM, dPCR and bioinformatic data, demonstrating the successful translation of bioinformatically identified methylation biomarkers from the Illumina Infinium HumanMethylation450 BeadChip (HM450) and lllumina MethylationEPIC BeadChip (EPIC) platforms to the simpler MS-HRM and dPCR platforms. [ABSTRACT FROM AUTHOR]

In the era of minimally invasive surgery (MIS), parenchyma-preserving liver resections are gaining prominence with the potential to offer improved perioperative outcomes without compromising oncological safety. The surgeon learning curve remains challenging, and simulation plays a key role in surgical training. Existing simulation models can be limited by suboptimal fidelity and high cost. We describe a novel, reproducible, high-fidelity, low-cost liver metastases model using porcine livers from adult Landrace pigs, with porcine perinephric fat used to simulate subcapsular metastases. This model was then utilised in a training session for surgical trainees performing robotic parenchyma-preserving surgery (PPS) under the guidance of expert robotic surgeons, with feedback being recorded. Trainees rated the model highly on its fidelity to human liver simulation (median score 9), tissue handling (median score 8), and overall usefulness (median score 9). Tissue handling was felt to simulate in vivo liver resection closely, while suggestions for improvement included adding simulated blood flow. This is a novel, low-cost, high-fidelity simulation model of liver metastases with high acceptability to surgical trainees, which could be readily adopted by other training centres. [ABSTRACT FROM AUTHOR]

Background: The global incidence of secondary liver cancer is rising due to multiple risk factors, presenting significant challenges in public health. Similarly, colorectal cancer (CRC) remains a leading cause of cancer-related mortality with the development of frequent liver metastases. Surgical resection of CRC liver metastases is only suitable for a limited subset of patients, necessitating alternative nonsurgical treatments such as electrochemotherapy (ECT); Methods: This review adhered to the S.P.I.D.E.R. framework. Systematic searches of PubMed, Cochrane, and Scopus databases were conducted for studies published between 2003 and 2023, following PRISMA guidelines. Inclusion criteria were full-text clinical studies in English focusing on ECT-treated CRC liver metastases, excluding reviews, editorials, and non-clinical papers. The GRADE approach was utilized to assess evidence quality, considering study limitations, consistency, and other factors; Results: From 38 identified articles, 4 met the inclusion criteria, encompassing 78 patients and 128 treated lesions. The studies demonstrated variability in design and follow-up duration (3–11 months). Complete response (CR) rates ranged from 33.3% to 63.0%, while progression disease (PD) rates were high, ranging from 23.0% to 55.6%. Median overall survival (OS) spanned 11.3 to 29.0 months. No severe ECT-related complications were reported. Conclusions: ECT appears to be a safe and effective modality for the treatment of CRC liver metastases, especially for lesions unsuitable for other ablative techniques. Further prospective and randomized studies are essential to better define the role of ECT in managing CRC liver metastases and to compare its efficacy with other ablative methods. [ABSTRACT FROM AUTHOR]

Ablative therapies for primary and secondary liver malignancies are increasingly adopted in current guidelines. Nevertheless, surgical resection remains the gold standard in most curative therapy settings. Extensive studies on mortality and morbidity after ablative treatment of the liver are missing. We investigated complications and mortality after ablative treatment in a large, unselected study cohort. Standardized patient and treatment data in 4374 percutaneous and angiographic ablative procedures of the liver from the DRG-based hospital reimbursement system (diagnosis-related groups) of an academic hospital in Germany were retrospectively evaluated. We analyzed descriptive patient data, length of stay (LOS), pre-existing medical conditions, previous gastrointestinal surgeries, severe complications, and occurrence of death. Treatment of secondary liver malignancies constituted over two-thirds of all procedures (71%, n = 3053). The mean LOS was 4.1 ± 3.5 days. Severe complications were documented in 1.4% and in-house death in 0.2% of cases, significantly more often after treatment with chemoembolization of primary liver malignancies (p = 0.003; p = 0.0001). Previous partial liver resection, partial bowel resection, and chronic renal failure were independent risk factors for the occurrence of severe complications. Severe complications and in-hospital death are rare in the treatment of primary and secondary liver malignancies with percutaneous and angiographic procedures. They are a viable alternative or addition to a surgical approach in treating liver lesions. [ABSTRACT FROM AUTHOR]

In this review, we explore the role of stereotactic body radiotherapy (SBRT) and other advanced radiotherapy techniques in the treatment of gastrointestinal malignancies, which primarily involves primary and secondary liver cancers and pancreatic cancers. The review examines radiotherapy in both curative and palliative settings, emphasizing the evolution of SBRT and hypofractionation as alternatives to conventional radiotherapy. We review the recent literature evaluating radiotherapy in the management of unresectable, borderline resectable, and metastatic pancreatic cancer, highlighting recent advances in radiotherapy techniques that aim to improve local control, reduce toxicity, and increase resectability in appropriate patients. For primary liver cancers (hepatocellular carcinoma and cholangiocarcinoma), SBRT has emerged as a potential noninvasive alternative to surgery, particularly in patients with unresectable tumors or those awaiting liver transplantation. The review also provides insights into ongoing clinical trials, comparative studies between SBRT and other local therapies such as radiofrequency ablation, and the use of radiotherapy in managing liver metastases from various primary cancers. Throughout, we emphasize limitations in the available literature and highlight areas of ongoing and future investigation. [ABSTRACT FROM AUTHOR]

Objective: To study outcomes after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) in patients also treated for colorectal liver metastases (CLM). Background: Colorectal cancer (CRC) frequently metastasizes to the liver and peritoneum and is associated with a poor prognosis. In selected patients, a benefit in overall survival (OS) was shown for both peritoneal metastases (PM-CRC) offered CRS-HIPEC, and CLM treated with surgical resection. However, the presence of CLM was considered a relative contraindication to CRS-HIPEC, causing a paucity of outcome data in this patient group. Methods: Patients with PM-CRC having CRS-HIPEC at a single national center between 2007 and 2023, with additional intervention for CLM, were included (previous curative treatment for extraperitoneal and extrahepatic metastases was allowed). Three groups were defined: CLM before CRS-HIPEC (pre-CRS-HIPEC), CLM resected simultaneously with CRS-HIPEC (sim-CRS-HIPEC), and CLM after CRS-HIPEC (post-CRS-HIPEC), aiming to retrospectively analyze outcomes. Results: Fifty-seven patients were included and classified as: pre-CRS-HIPEC (n = 11), sim-CRS-HIPEC (n = 29), and post-CRS-HIPEC (n = 17). Median Peritoneal Cancer Index (PCI) was 8; 13 patients had severe complications (Clavien-Dindo ≥ 3), and no 90-day mortality. Median OS was 48 months after CRS-HIPEC. PCI was a predictor of OS (hazard ratio: 1.11, P < 0.001). We observed no difference in short or long-term outcomes between intervention groups. Discussion: This study demonstrated that patients with CLM having CRS-HIPEC had comparable OS to reports on CRS-HIPEC only, likely explained by a low PCI. Simultaneous CLM resection did not increase the risk of severe complications. Conclusions: In this national cohort, CRS-HIPEC and CLM intervention offers long-term survival, suggesting that this treatment may be offered to selected patients with PM-CRC and CLM. [ABSTRACT FROM AUTHOR]

Background/Objectives: Neuroendocrine neoplasms (NEN) are heterogeneous entities. Despite considerable advancement in the field, almost 50% of patients have metastatic disease, when liver transplantation (LT) is one of the possible treatments offering a cure in well-selected patients. Methods: The present study aims to systematically review all the literature from 2000 onwards on using LT for patients with NEN-LM, with particular attention to the risk factors of death and recurrence. Results: LT offers 5-year OS ranging from 52 to 74% and 5-year TFS rates ranging from 39 to 62%, with even better results published from 2009 onwards. The main risk factors for patient deaths are related to unfavorable primary tumor pathology, higher liver involvement, and simultaneous LT and primary resection. Similarly, recurrence is higher related to poor tumor grade and differentiation, and in the case of an older recipient age. Conclusions: Applying uniform criteria and a more in-depth understanding of the relevant prognostic factors contribute to a better selection of candidates for curative LT due to NEN metastases. LT for unresectable or liver-restricted NENs has a relevant place in the treatment algorithm and has achieved excellent results in recent decades, but more international efforts are needed to further improve outcomes. [ABSTRACT FROM AUTHOR]

Objective: This retrospective cohort study aimed to explore the surgical outcomes and prognostic factors of resection of pulmonary metastases (PM) from colorectal cancer (CRC). Methods: Overall, 60 patients who underwent resection of PM from CRC between 2015 and 2021 at two institutions were reviewed. The primary outcome were overall survival (OS) and early recurrence after PM resection. The association between OS and right-sided colon cancer (RCC) was investigated. Early recurrence after PM resection was defined as recurrence within one year. Results: The 5-year OS after CRC resection was 83.8% (95% confidence interval [CI] 67.5–92.4) and after PM resection was 69.4% (95% CI 47.5–83.6). In total, 25 patients had recurrence after PM resection (16 within 1 year and 9 after 1 year). In multivariable analysis for OS, RCC (hazard ratio [HR] 4.370, 95% CI 1.020–18.73; p = 0.047) and early recurrence after resection of PM (HR 17.23, 95% CI 2.685–110.6; p = 0.003) were risk factors for poor OS. In multivariable analysis for early recurrence after PM resection, higher value of carcinoembryonic antigen (CEA) (> 5.0 mg/dL) before PM resection was a risk factor for early recurrence (HR 3.275, 95% CI 1.092–9.821; p = 0.034). Conclusion: The RCC and early recurrence after PM resection were poor prognosis factors of OS. Higher value of CEA before PM resection was an independent risk factor for early recurrence after resection of PM. Comparitive study between surgery and nonsurgery is necessary in patients with higher CEA values. [ABSTRACT FROM AUTHOR]

Opinion statement: Parenchymal liver metastases from ovarian cancer, occurring in 2–12.5% of cases, significantly worsen prognosis. While surgery and systemic treatments remain primary options, unresectable or chemotherapy-resistant multiple liver metastases pose a significant challenge. Recent advances in liver-directed therapies, including radiofrequency ablation, microwave ablation, cryoablation, transarterial chemoembolization (TACE), and radioembolization, offer potential treatment alternatives. However, the efficacy of these techniques is limited by factors such as tumor size, number, and location. The ideal candidate for tumor ablation is a patient with paucifocal disease, a single tumor up to 5 cm or up to 3 tumors smaller than 3 cm and tumors 1 cm away from major bile ducts and high-flow vessels. Transarterial chemoembolization could be performed in patients with less than 70% tumor load. Differently, radioembolization is available with less limitation on the sites or number of liver cancers. Radioembolization techniques are also able to downsize liver metastases. However, there are limited data regarding the outcomes of loco-regional therapy in patients with hepatic metastases from ovarian cancer. Advancing liver-directed therapies through interventional oncology, combined with robust data on the oncological efficacy of these local treatments, will validate their potential as effective locoregional therapies for liver metastases. This could offer a promising treatment option for patients with ovarian cancer and unresectable hepatic metastases. [ABSTRACT FROM AUTHOR]

Abstract Objective To explore the value of preoperative CT-based morphological heterogeneity (MH) for predicting local tumor disease-free survival (LTDFS) and progression-free survival (PFS) in patients with colorectal cancer liver metastases (CRLM). Methods The latest CT data of 102 CRLM patients were retrospectively analyzed. The morphological score of each liver metastasis was obtained, and the morphological heterogeneity difference (MHD) was calculated. The receiver operating characteristic (ROC) curve was drawn, and the cutoff value was found. The Kaplan-Meier method was used to draw survival curves of patients with or without MH. The Cox regression analysis was used to build the model with MH and clinical characteristics for predicting PFS. Results In 78 patients without MH, median PFS was 9.0 months (95% CI:6.5–11.5), while in 24 patients with MH, median PFS was 6.0 months (95% CI:4.0-8.1), indicating that MH significantly affected PFS (p = 0.001). MH affected PFS in both the chemotherapy group and the chemotherapy combined with targeted therapy group (p = 0.005, p = 0.043). MH, preoperative carcinoembryonic antigen (CEA) and chemotherapy after surgery were independent predictors for postoperative PFS in patients with CRLM. Conclusion Preoperative CT-based MH had good efficacy for predicting LTDFS and PFS of CRLM patients after surgical resection, regardless of preoperative treatment. MH is one of the independent predictors of PFS.

Lung cancer represents the most common cause of cancer-related death. Patients with non-small cell lung cancer (NSCLC) and liver metastases have worse prognosis, with an overall survival (OS) from three to six months. The majority of them have a poor response to chemotherapy, and the data are controversial regarding the response to immunotherapy. This could be because the liver is considered to be an immune-tolerant organ, which is characterized by T-cell anergy and immunosuppressive signals. This review evaluates current treatment options for patients with NSCLC and liver metastases. Combination therapies might be a better treatment option for this subgroup of patients. The addition of radiotherapy to immunotherapy could also be an option in selected patients. The resection of single liver metastasis should also be considered.

Lung cancer represents the most common cause of cancer related death. Patients with non-small cell lung cancer (NSCLC) and liver metastases (LM) have worse prognosis with an overall survival (OS) of three to six months. The aim of this study was to investigate long-term outcomes in patients with EGFR mutated (EGFRmut) lung adenocarcinoma as well as the presence of LM. (A total of 105 patients were included in the analysis). They were divided into two groups based on the presence of LM. OS was 13 months for the whole group and also 13 months for patients with and without LM. The 9-year survival rate for patients with and without LM was 12.5% and 3.4%, respectively. Further, the 9-year survival rate for the whole group of patients was 4.8%. There are few data about survival rates beyond 5 years for patients with locally advanced and metastatic EGFRmut NSCLC, mainly because patients with lung cancer rarely live for such a long time. Regarding patients with liver metastases, the results of our study showed similar outcomes compared to patients without LM. As these patients represent a significant number of patients, we need a wider range of therapeutic options. It might be that combination therapies represent a better therapeutic option.

The detection of liver metastases at an early stage is crucial to improve patients’ survival. Pancreatic neuroendocrine tumors (pNETs) and their metastases usually present as early and vividly enhancing tumors on contrast enhanced computed tomography (CECT). However, the use of contrast agents is a contraindication in patients with severely impaired kidney function. The incidence of chronic kidney disease (CKD) and malignancies increase with age, making both the treatment and imaging diagnostics a complicated process in an oncological setting among elderly patients. This case report presents the diagnostic path of an elderly patient with a long history of pNET, who developed severe CKD during treatment. The patient was diagnosed with metastatic liver disease in PET/CT and it was confirmed by an abbreviated magnetic resonance imaging (AMRI) protocol without contrast enhancement, while CECT did not show the presence of metastases. AMRI protocols without contrast enhancement can provide sufficient information about the presence of metastatic liver disease in oncological patients with comorbid CKD.

Laparoscopic ultrasound (LUS) combines both laparoscopy and ultrasound imaging of the peritoneum liver and retroperitoneum. LUS has not been described in treatments with pressurized intraperitoneal aerosol chemotherapy (PIPAC). We present our experience with LUS in patients undergoing PIPAC.

Background:The liver is the second most common organ involved by secondary neoplasms. Core needle biopsy of oncological patients requires an accurate histological diagnosis for the subsequent prescription of adequate management plans. Objectives:The aim of this study was to evaluate the diagnostic accuracy of core needle biopsy for suspected hepatic metastasis and to assess factors that influence the accuracy of the procedure. Materials and Methods:A cross-sectional study randomly enrolled 74 percutaneous ultrasound-guided core needle biopsies from patients with suspected hepatic neoplasm. A 16-gauge tru-cut biopsy needle was performed for all patients. Patient characteristics, procedure information, histopathology reports, and slides were collected from the Department of Histopathology at Al-Jamhorii Teaching Hospital, Mosul City, Iraq. All cases were analyzed using SPSS software, version 18.0. Results:Among 74 patients diagnosed with liver metastasis, the median age was 57 years (range 33–90 years) at the time of biopsy; of them, 61 patients (82.4%) reported a previous history of malignancy, P = 0.003. Histologically, metastatic adenocarcinoma was the most common neoplasm identified in 56 patients (75.7%), with the predominance of colorectal carcinoma. Forty-seven (63.5%) patients underwent two–five passes, which was statistically correlated with an increase in diagnostic accuracy (k = 0.21, 95% confidence interval [CI]= 0.038–1.189, P = 0.04). The overall sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of tru-cut biopsies were 100%, 97.1%, 95.7%, 100%, and 98.2%, respectively. Conclusions:The core needle biopsy is a reliable and valid diagnostic option for the histological assessment of suspected liver metastasis, particularly when supplemented by ancillary immunohistochemistry.

Abstract Background To retrospectively analyze the risk factors of liver metastases in patients with gastric cancer in a single center, and to establish a Nomogram prediction model to predict the occurrence of liver metastases. Methods A total of 96 patients with gastric cancer who were also diagnosed with liver metastasis (GCLM) and treated in our center from January 1, 2010 to December 31, 2020 were included. The clinical data of 1095 patients with gastric cancer who were diagnosed without liver metastases (GC) in our hospital from January 1, 2014 to December 31, 2017 were retrospectively compared by univariate and multivariate logistic regression. 309 patients diagnosed with gastric cancer in another medical center from January 1, 2014 to December 31, 2018 were introduced as external validation cohorts. Results Based on the training cohort, multivariate analysis revealed that tumor site (OR = 0.55, P = 0.046), N stage (OR = 4.95, P = 0.004), gender (OR = 0.04, P = 0.001), OPNI (OR = 0.95, P = 0.041), CEA (OR = 1.01, P = 0.018), CA724 (OR = 1.01, P = 0.006), CA242 (OR = 1.01, P = 0.006), WBC (OR = 1.13, P = 0.024), Hb (OR = 0.98, P

Abstract Immune checkpoint inhibitors (ICIs) have achieved remarkable success in clinical research and practice. Notably, liver metastasis is not sensitive to ICIs. Liver locoregional therapies can cause irreversible damage to tumor cells and release tumor antigens, thereby providing a rationale for immunotherapy treatments in liver metastasis. The combination therapy of ICIs with locoregional therapies is a promising option for patients with liver metastasis. Preclinical studies have demonstrated that combining ICIs with locoregional therapies produces a significantly synergistic anti-tumor effect. However, the current evidence for the efficacy of ICIs combined with locoregional therapies remains insufficient. Therefore, we review the literature on the mechanisms of locoregional therapies in treating liver metastasis and the clinical research progress of their combination with ICIs.

Background Pathological response of liver metastases (LM) from colorectal carcinoma (CRC) to neoadjuvant therapy is a known prognostic factor associated with recurrence and survival. The aim of this study was to compare the performance of two prognostic scores in patients who underwent surgery for colorectal cancer liver metastases (CRCLM), specifically in stage IV disease. Methods We conducted a study on patients with stage IV colorectal cancer who received preoperative chemotherapy (CT) followed by liver metastasis (LM) resection between 2015 and 2021. Among these patients, 57% had synchronous metastases (diagnosed at the same time as the primary tumor), while the remaining cases were metachronous (diagnosed after the primary tumor). Pathological response was evaluated using both the Rubbia-Brandt tumor regression grade (TRG) and the Blazer scoring system. We then assessed the performance of these two prognostic scores based on homogeneity (using the likelihood ratio, LR+), monotonicity, and discriminative ability (using the area under the receiver operating characteristic [ROC] curve, AUC). Results 70 cases were included in the study. Mean age was 56 years. The sex ratio (males/females) was 2.2. Forty patients were stage IV (57%) with synchronous all CRCLMs. The overall survival, all stages combined, was 85.5% at 12 months, 41.7% at 24 months and 19.3% at 36 months. The median survival was better in case of major response (TRG1/TRG2) evaluated at 40.1 and 41.1 months after diagnosis. In cases of partial response (TRG3), the median survival was 32.1 months. In cases with no response (TRG4/TRG5), survival was estimated at 29.9 and 18.5 months. The Rubbia-Brandt TRG had the highest LR+ (10.95). The LR+ of the Rubbia-Brandt score was greater than 10, so it was a test with very strong contribution. The LR+ of the Blazer score was between 5 and 10, it was a test with strong contribution. The Rubbia-Brandt TRG had the highest linearity value (10.73). With a higher AUC of the ROC curve (0.8), the Rubbia-Brandt TRG was better at predicting survival than the Blazer score. Conclusion Surgical resection is the gold standard for CRCLM, with improved prognosis from neoadjuvant chemotherapy. Pathological response to CT is a key prognostic factor, and the Rubbia Brandt TRG system enhances survival predictivity when combined with ypTN stage.

Background: The liver is a frequent location of metastatic disease in various malignant tumor entities. Computed tomography (CT) is the most frequently employed modality for initial diagnosis. However, liver metastases may only be delineated vaguely on CT. Calculating radiomics features in feature maps can unravel textures not visible to the human eye on a standard CT reconstruction (SCTR). This study aimed to investigate the comparative diagnostic accuracy of radiomics feature maps and SCTR for liver metastases. Materials and methods: Forty-seven patients with hepatic metastatic colorectal cancer were retrospectively enrolled. Whole-liver maps of original radiomics features were generated. A representative feature was selected for each feature class based on the visualization of example lesions from five patients. These maps and the conventional CT image data were viewed and evaluated by four readers in terms of liver parenchyma, number of lesions, visual contrast of lesions and diagnostic confidence. T-tests and chi²-tests were performed with a significance cut off of p<0.05 to compare the feature maps with SCRT, and the data were visualized as boxplots. Results: Regarding the number of lesions detected, SCTR showed superior performance compared to radiomics maps. However, the feature map for firstorder RootMeanSquared was ranked superior in terms of very high visual contrast in 57.4% of cases, compared to 41.0% in standard reconstructions (p < 0.001). All other radiomics maps ranked significantly lower in visual contrast when compared to SCTR. For diagnostic confidence, firstorder RootMeanSquared reached very high ratings in 47.9% of cases, compared to 62.8% for SCTR (p < 0.001). The conventional CT images showed superior results in all categories for the other features investigated. Conclusion: The application of firstorder RootMeanSquared feature maps may help visualize faintly demarcated liver lesions by increasing visual contrast. However, reading of SCTR remains necessary for diagnostic confidence. [ABSTRACT FROM AUTHOR]

To develop and validate a deep learning radiomics (DLR) model based on contrast-enhanced computed tomography (CT) to identify the primary source of liver metastases. In total, 657 liver metastatic lesions, including breast cancer (BC), lung cancer (LC), colorectal cancer (CRC), gastric cancer (GC), and pancreatic cancer (PC), from 428 patients were collected at three clinical centers from January 2018 to October 2023 series. The lesions were randomly assigned to the training and validation sets in a 7:3 ratio. An additional 112 lesions from 61 patients at another clinical center served as an external test set. A DLR model based on contrast-enhanced CT of the liver was developed to distinguish the five pathological types of liver metastases. Stepwise classification was performed to improve the classification efficiency of the model. Lesions were first classified as digestive tract cancer (DTC) and non-digestive tract cancer (non-DTC). DTCs were divided into CRC, GC, and PC and non-DTCs were divided into LC and BC. To verify the feasibility of the DLR model, we trained classical machine learning (ML) models as comparison models. Model performance was evaluated using accuracy (ACC) and area under the receiver operating characteristic curve (AUC). The classification model constructed by the DLR algorithm showed excellent performance in the classification task compared to ML models. Among the five categories task, highest ACC and average AUC were achieved at 0.563 and 0.796 in the validation set, respectively. In the DTC and non-DTC and the LC and BC classification tasks, AUC was achieved at 0.907 and 0.809 and ACC was achieved at 0.843 and 0.772, respectively. In the CRC, GC, and PC classification task, ACC and average AUC were the highest, at 0.714 and 0.811, respectively. The DLR model is an effective method for identifying the primary source of liver metastases. [ABSTRACT FROM AUTHOR]

A large pooled analysis of liver oligometastases, classified accordingly to the ESTRO/EORTC recommendations, treated by stereotactic radiotherapy (SBRT) and Radiosurgery (SRS) was carried out. The clinical and dosimetric data of patients who underwent SBRT/SRS for liver metastases were analysed in terms of efficacy and toxicity profile. In particular, the Local Control (LC), the Distant Metastases Free Survival (DMFS), the Disease-Free Survival (DFS), the Overall Survival (OS), and the Next Systemic Therapy Free Survival (NEST-FS) rates were analysed. 113 patients (M/F: 49/64), accounting for a total of 150 hepatic lesions (March 2006–February 2023) in two Italian radiotherapy Institutions were evaluated. Median age was 67 years old (36–92) and 48 (42.5%) patients had at least one comorbidity. The majority of the lesions were induced (30.7%) or repeated oligoprogressive (12.7%) metastases. 98 lesions were treated with more than one daily fraction (mainly 50 Gy in 5 fractions), while 52 were radiosurgery treatments (mainly 32 Gy). The treatment response at 3–4 months was evaluable in 147 lesions: complete response was 32.0%, partial response 17.0%, and stable disease 32.0%. Actuarial LC, DMFS, DFS, OS, and NEST-FS at 1 year were 75.8%, 37.7%, 34.9%, 78.7%, and 59.4% respectively; while actuarial LC, DMFS, DFS, OS, and NEST-FS at 2 years were 52.1%, 24.9%, 21.9%, 51.3%, and 36.8%, respectively. The achievement of complete response, synchronous oligometastases, and no treatment interruptions correlated with a more favorable outcomes. As per the toxicity profile, we registered only two acute and one late toxicity cases higher than grade 2. Stereotactic treatment for liver metastases seems to be a safe and promising option in terms of local control. The best results in term of outcomes have been obtained in patients with complete response, synchronous oligometastases, favorable histology, and no treatment interruptions. [ABSTRACT FROM AUTHOR]

Most patients with metastatic colorectal cancer (mCRC) have limited treatment options following standard-of-care therapy. VEGFR-tyrosine kinase inhibitors (TKIs) have demonstrated clinical activity in mCRC in combination with immune checkpoint inhibitors (ICIs), particularly in patients without liver metastases. The TKI zanzalintinib (XL092) targets VEGFR, MET and TAM kinases, proteins that are involved in tumor growth, angiogenesis, metastasis and immunosuppression. Zanzalintinib has immunomodulatory properties that may enhance response to ICIs. Presented is the design of STELLAR-303, a global, phase III, open-label, randomized study evaluating zanzalintinib plus atezolizumab versus regorafenib in patients with non-MSI-H mCRC who progressed during/after or are refractory/intolerant to standard-of-care therapy. The primary end point is overall survival in patients without liver metastases. Clinical Trial Registration:NCT05425940 (ClinicalTrials.gov) Plain Language Summary Metastatic colorectal cancer (mCRC) is cancer of the colon or rectum that has spread to other parts of the body, most often to the liver, lungs and abdomen. People with mCRC that has worsened after initial treatment have limited options. Zanzalintinib is a novel oral investigational drug that can slow or stop cancer growth. It works by blocking certain proteins that play important roles in the development, growth and spread of cancer. Zanzalintinib may also help improve the effectiveness of another class of cancer drugs called immune checkpoint inhibitors (ICIs), which work by activating the patient's immune system to fight cancer. Here, we describe the design of STELLAR-303, an ongoing study that is comparing the effects of combining zanzalintinib and an ICI drug called atezolizumab with an approved treatment for mCRC called regorafenib. About 900 participants with mCRC will be enrolled in the study worldwide. To be included in the study, participants must have mCRC that worsened after previous therapies and must not have a high level of microsatellite instability, which is a specific feature of some mCRCs. Participants will be randomly given one of the two treatments. The main goal of the study is to evaluate zanzalintinib plus atezolizumab compared with regorafenib by measuring the length of time participants are alive after starting treatment, specifically in patients with mCRC that has not spread to the liver. Additionally, the study will look at the side effects with each treatment. The study is currently seeking participants. Tweetable Abstract STELLAR-303 is a randomized phase III study evaluating the novel TKI zanzalintinib plus the ICI atezolizumab in patients with previously treated non-MSI-H metastatic colorectal cancer. Patient enrollment is ongoing globally. Article highlights Background & rationale Patients with metastatic colorectal cancer (mCRC) have a poor prognosis and limited treatment options following progression on standard of care therapies. Immune checkpoint inhibitors (ICIs) are approved in microsatellite instability-high (MSI-H) and mismatch repair-deficient mCRC. However, efficacy of these treatments is limited in non-MSI-H or proficient mismatch repair (pMMR) disease. Agents targeting the VEGF pathway in combination with ICIs have been evaluated in non-MSI-H mCRC and have demonstrated encouraging clinical activity. Studies have shown that mCRC patients without liver metastases may derive greater benefit from TKI-ICI combinations than those with liver metastases. Zanzalintinib (XL092) is a tyrosine kinase inhibitor that targets MET, VEGFR and the TAM kinases. Inhibition of these kinases may suppress tumor growth and proliferation and promote an immunopermissive tumor microenvironment, which may enhance response to ICIs such as atezolizumab. Zanzalintinib has shown anti-tumor activity alone and in combination with ICIs in the preclinical setting and has demonstrated immunomodulatory effects, increasing pro-inflammatory immune cells and decreasing immunosuppressive cells. STELLAR-303 study design STELLAR-303 (NCT05425940) is a global, open-label, randomized, phase III study. Approximately 874 patients with non-MSI-H mCRC (with and without liver metastases) who have progressed during/after or are intolerant to standard of care therapies will be randomized 1:1 to oral zanzalintinib plus intravenous atezolizumab or to oral regorafenib. Eligibility criteria Eligible patients are aged ≥18 years and have histologically/cytologically confirmed adenocarcinoma of the colon or rectum that is non-MSI-H and pMMR; MSI/MMR status will be documented and determined by tissue-based analysis. A prespecified number of patients with/without liver metastases will be enrolled. Patients must have received standard of care therapy for mCRC and radiographically progressed or be refractory or intolerant to these therapies; progression during treatment or within 4 months of the most recent therapy is required. Patients who received prior zanzalintinib, regorafenib, trifluridine-tipiracil, or PD-L1/PD-1 targeting ICIs are ineligible. End points The primary end point is overall survival (OS) in patients without liver metastases. Secondary end points are OS in all randomized patients (assessed with hierarchical testing); progression-free survival, objective response rate and duration of response per RECIST v1.1 by investigator in patients without liver metastases and in all randomized patients; and safety. Status The study is actively enrolling patients in the USA, Europe and Asia-Pacific regions. Conclusion STELLAR-303 will assess the efficacy and safety of zanzalintinib plus atezolizumab in patients with previously treated non-MSI-H mCRC, a population with unmet need. [ABSTRACT FROM AUTHOR]

Background Sigmoid colon cancer is a common type of colorectal cancer, frequently leading to liver metastasis. Predicting cause-specific survival and overall survival in patients with sigmoid colon cancer metastasis to liver is challenging because of the lack of suitable models. Methods Patients with sigmoid colon cancer metastasis to liver (2010-2017) in the Surveillance, Epidemiology, and End Results (SEER) Program were recruited. Patients were split into training and validation groups (7:3). Prognostic factors were identified using competing risk and Cox proportional hazards models, and nomograms for cause-specific survival and overall survival were developed. Model performance was evaluated with the concordance index and calibration curves, with a 2-sided P value less than  .05 considered statistically significant. Results A total of 4981 sigmoid colon cancer with liver metastasis patients were included, with a median follow-up of 20 months (interquartile range [IQR] = 9-33 months). During follow-up, 72.25% of patients died (68.44% from sigmoid colon cancer, 3.81% from other causes). Age, race, grade, T stage, N stage, surgery, chemotherapy, carcinoembryonic antigen, tumor deposits, lung metastasis, and tumor size were prognostic factors for cause-specific survival and overall survival. The models demonstrated good discrimination and calibration performance, with C index values of 0.79 (95% confidence interval [CI] = 0.78 to 0.80) for cause-specific survival and 0.74 (95% CI = 0.73 to 0.75) for overall survival. A web-based application for real-time cause-specific survival predictions was created, accessible at https://shuaishao.shinyapps.io/SCCLM/. Conclusion Prognostic factors for sigmoid colon cancer with liver metastasis patients were identified based on the SEER database, and nomograms for cause-specific survival and overall survival showed good performance. A web-based application was developed to predict sigmoid colon cancer with liver metastasis–specific survival, aiding in survival risk stratification. [ABSTRACT FROM AUTHOR]

Purpose: To compare the efficacy of first‐line regimens based on programmed cell death (or ligand) [PD‐(L)1] blockade in extensive‐stage small‐cell lung cancer (ES‐SCLC) patients with or without liver metastases (LM), and to identify optimal treatment strategies. Methods: Network meta‐analysis of randomized controlled trials (RCTs) comparing chemo‐immunotherapy (CIT) and chemotherapy (CT) in ES‐SCLC patients stratified by LM. Overall survival (OS) and progression‐free survival (PFS) were evaluated using hazard ratios (HRs) and 95% confidence intervals (CIs). Results: Seven RCTs involving 3658 ES‐SCLC patients (1243 with LM, 2415 without LM) were analyzed. For patients with LM, the combination therapies of anti‐PD‐1 + CT (HR, 0.67; 95% CI, 0.54%–0.82%; p < 0.001) and anti‐PD‐L1 + CT + anti‐angiogenesis (HR, 0.84; 95% CI, 0.71%–0.99%; p = 0.042) demonstrated superior efficacy in prolonging OS compared to CT alone. The anti‐PD‐1 + CT regimen had the highest cumulative probability of 91.6% for extending OS in patients with LM. For patients without LM, all CIT regimens resulted in improved OS compared to CT alone, with the regimen of anti‐angiogenesis + anti‐PD‐L1 + CT ranking first and having the highest cumulative probability of 95.5% for prolonging OS. Conclusions: CIT is effective for ES‐SCLC patients regardless of LM status. For patients with LM, PD‐1 blockade combined with CT is the best option. For patients without LM, the most beneficial regimen is the combination of anti‐angiogenesis, PD‐L1 blockade, and CT. [ABSTRACT FROM AUTHOR]

Background: Although survival outcomes for neuroendocrine liver metastases (NETLM) are improved with liver-direct therapies (LDT), including hepatic debulking and nonsurgical trans-arterial embolization, the benefit is less established in the setting of concurrent extrahepatic disease (EHD). We performed a population-based study to characterize the rates of LDT being performed for NETLM with EHD patients and whether LDT is associated with survival outcomes. Methods: Patients with NETLM and EHD were identified using the California Cancer Registry database merged with data from the California Office of Statewide Health Planning and Development between 2000 and 2012. Demographics, clinical characteristics, and survival outcomes were analyzed for these patients with and without LDT. Results: 327 NETLM patients with EHD were identified. EHD sites included lung, peritoneum, bone, and brain. A total of 71 (22%) of these patients underwent LDT. Compared to NETLM with EHD patients who did not undergo LDT, patients who received LDT had longer median overall survival (27 vs. 16 months, p = 0.006). Within the LDT group, 23 patients underwent liver resection. Liver resection was associated with longer median overall survival compared to nonsurgical LDT (138 vs. 13 months, p < 0.001). Conclusions: LDT candidacy should be determined for patients on a case-by-case basis, but the presence of EHD should not preclude LDT with appropriate patient selection. [ABSTRACT FROM AUTHOR]

Purpose of review: This article aims to illustrate the current state of investigations and management of liver metastases in patients with Neuroendocrine Neoplasms. Neuroendocrine tumours (NETs) are rising in incidence globally and have become the second most prevalent gastrointestinal malignancy in UK and USA. Frequently, patients have metastatic disease at time of presentation. The liver is the most common site of metastases for gastro-enteropancreatic NETs. Characterisation of liver metastases with imaging is important to ensure disease is not under-staged. Recent Findings: Magnetic resonance imaging and positron emission tomography are now becoming standard of care for imaging liver metastases. There is an increasing armamentarium of therapies available for management of NETs and loco-regional therapy for liver metastases. The data supporting surgical and loco-regional therapy is reviewed with focus on role of liver transplantation. Summary: It is important to use appropriate imaging and classification of NET liver metastases. It is key that decisions regarding approach to treatment is undertaken in a multidisciplinary team and that individualised approaches are considered for management of patients with metastatic NETs. [ABSTRACT FROM AUTHOR]

Objective: To determine the diagnostic accuracy of contrast-enhanced ultrasound (CEUS) compared with contrast-enhanced computed tomography (CECT), magnetic resonance imaging (MRI), and Fluorine-18-deoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) for diagnosing suspected liver metastases in patients with newly diagnosed colorectal cancer (CRC). Methods: The meta-analysis using the bivariate model included studies on patients with newly diagnosed CRC only and excluded patients with non-CRC liver metastases, known liver metastases, patients treated with chemotherapy and local treatments, e.g. hepatic resection or radiofrequency ablation. We used QUADAS-2 to assess the methodological quality of the studies. Results: We included 32 studies, 6 studies evaluated the accuracy of CEUS (n = 937 participants), 26 studies evaluated CECT (n = 2,582), 8 studies evaluated MRI (n = 564) and 6 studies evaluated FDG-PET/CT (n = 813). Sensitivity: FDG-PET/CT 94.4% [95% CI: 90.7–98.1%], MRI 92.9% [95% CI: 88.8–97.0%], CEUS 86.1% [95% CI: 78.0–94.3%] and CECT 84.6% [95% CI: 79.3–89.9%]. Specificity FDG-PET/CT 97.9% [95% CI: 95.9–99.9%], CEUS 96.1% [95% CI: 93.6–98.6%], MRI 94.4% [95% CI: 90.5–98.3%], and CECT 94.3% [95% CI: 91.8–96.8%]. Conclusion: FDG-PET/CT had significantly higher sensitivity and specificity than CECT, and significantly higher sensitivity than CEUS. MRI had a significantly higher sensitivity than CEUS, but a lower non-significant specificity. CECT had the lowest sensitivity and specificity. PROSPERO registration details: CRD42017055015 and CRD42017082996. [ABSTRACT FROM AUTHOR]

Simple Summary: Colorectal cancer (CRC) remains a leading cancer-related mortality cause. More than a third of CRC patients develop liver metastases during the course of the disease, contributing to poor prognosis. Thermal ablation techniques are currently recommended as a local curative option for selected small liver metastases. Thermal ablation (TA) includes a wide variety of different modalities, like radiofrequency ablation (RFA), microwave ablation (MWA) and cryoablation (CRA). This comprehensive review outlines the role of image-guided ablation in the treatment of colorectal liver metastatic (CLM) disease. Colorectal cancer is a major cause of cancer-related mortality, with liver metastases occurring in over a third of patients, and is correlated with poor prognosis. Despite surgical resection being the primary treatment option, only about 20% of patients qualify for surgery. Current guidelines recommend thermal ablation either alone or combined with surgery to treat limited hepatic metastases, provided that all visible disease can be effectively eradicated. Several ablation modalities, including radiofrequency ablation, microwave ablation, cryoablation, irreversible electroporation and histotripsy, are part of the percutaneous ablation armamentarium. Thermal ablation, including radiofrequency, microwave ablation and cryoablation, can offer local tumor control rates comparable to limited resection for selected tumors that can be ablated with margins. This review aims to encapsulate the current clinical evidence regarding the efficacy and oncologic outcomes after percutaneous ablation for the treatment of colorectal liver metastatic disease. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors (ICIs) have achieved remarkable success in clinical research and practice. Notably, liver metastasis is not sensitive to ICIs. Liver locoregional therapies can cause irreversible damage to tumor cells and release tumor antigens, thereby providing a rationale for immunotherapy treatments in liver metastasis. The combination therapy of ICIs with locoregional therapies is a promising option for patients with liver metastasis. Preclinical studies have demonstrated that combining ICIs with locoregional therapies produces a significantly synergistic anti-tumor effect. However, the current evidence for the efficacy of ICIs combined with locoregional therapies remains insufficient. Therefore, we review the literature on the mechanisms of locoregional therapies in treating liver metastasis and the clinical research progress of their combination with ICIs. [ABSTRACT FROM AUTHOR]