Liver Metastasis Group Research Articles

CT feature of irregular extensive ulceration as a predictor of liver metastasis in gastric gastrointestinal stromal tumours.

This study aimed to investigate whether the computed tomography (CT) finding of irregular extensive ulceration (IEU) can serve as a predictor of liver metastasis (LIM) in patients with gastric gastrointestinal stromal tumours (GISTs). This study retrospectively collected clinical and imaging data from 286 patients diagnosed with low-, intermediate-, or high-risk gastric GISTs, or primary lesions with LIM from three medical institutions. The patients were categorised into non-LIM and LIM groups according to whether they had synchronous or metachronous LIM. Multivariate logistic regression analyses were performed to identify significant predictors of LIM. Additionally, receiver operating characteristic (ROC) curve, subgroup, and pathologic-radiologic correlation analyses were conducted. A total of 124 patients were ultimately enroled. There were significant differences in sex, site, growth pattern, size, shape, ulceration and Ki-67 expression between LIM and non-LIM groups. ROC curve analysis demonstrated that IEU had the highest area under the curve for predicting LIM (AUC = 0.842; 95% CI: 0.760-0.924; p < 0.001). Multivariate analysis indicated that IEU was the most significant independent predictor of high LIM risk (OR = 88.62; 95% CI: 2.80-2803.54; p = 0.011). Subgroup analysis showed that IEU was more frequently associated with male sex, age ≤ 55 years, proximal sites, irregular shapes, mixed growth patterns, and a high Ki-67 expression. The CT feature of IEU serves as an independent predictor of LIM in gastric GISTs and is strongly associated with high Ki-67 expression. Question Accurate assessment of LIM risk in patients with gastric GISTs is crucial, yet current non-invasive predictors remain inadequate. Findings IEU on CT is an independent predictor of LIM, with high diagnostic accuracy and a significant association with elevated Ki-67 expression. Clinical relevance IEU on CT scans enables non-invasive risk stratification for LIM in gastric GISTs. Our study refined the assessment of ulceration types, highlighting significant heterogeneity, which may guide personalised treatment strategies.

Single-Cell RNA Sequencing Revealing that MMP12+ Macrophages are Associated with Cancer Liver Metastasis.

We aimed to explore the MMP12+ macrophages function in liver metastasis of Colorectal cancer [CRC]. CRC has a high incidence, and a great many patients develop liver metastases. Some studies have found that macrophages may participate in the liver metastasis of CRC. This study aimed to determine the factors and major signaling pathways of MMP12+ macrophages affecting liver metastasis of CRC. The single-cell RNA sequencing [scRNA-seq] data of CRC and bulk transcriptome data were downloaded. After filtering scRNA-seq data, dimensionality reduction and clustering were performed to identify different cell subgroups. The FindAll- Markers function was used to calculate the differentially expressed genes in each cell subgroup, and the genes in the promising set were uploaded to the DAVID database to analyze the biological processes to which these genes were enriched. Differentially expressed genes among macrophage subgroups were selected by the AverageExpression function. Then, the CIBERSORT algorithm was used to compute the proportion of each macrophage subgroup in each bulk tissue and determine the most significant macrophage subgroup. The dynamic changes of gene expression in macrophage subgroup were computed by Pseudotime. Finally, CellChat was applied to investigate the effect of the macrophage subgroup on epithelial cells and the ligand-receptor effect of B cells and T cells. Clustering scRNA-seq data showed a larger proportion of macrophages in liver metastases. The proportion of MMP12+ macrophage subtypes increased gradually among normal, tumor, and liver metastasis groups, and MMP12+ macrophages were associated with angiogenesis, cell migration, and inhibited T cell proliferation. The Pseudotime showed higher expression levels of genes related to angiogenesis and enhanced TGF-β signaling pathway and the negative regulation of T cell proliferation with the occurrence of liver metastasis in MMP12+ macrophages. MMP12+ macrophages can promote the proliferation of epithelial cells and inhibit the activation of T cells and B cells. MMP12+ macrophages promoted liver metastasis of CRC by influencing angiogenesis, TGF-β signaling pathway expression, and regulation of T cells and B cells.

The combined detection of carcinoembryonic antigen, carcinogenic antigen 125, and carcinogenic antigen 19-9 in colorectal cancer patients.

Hepatic metastases are common and difficult to treat after colorectal cancer (CRC) surgery. The predictive value of carcinoembryonic antigen (CEA), cancer antigen (CA) 125 and CA19-9 combined tests for liver metastasis is unclear. To evaluate predictive value of combined tests for CEA, CA125, and CA19-9 levels in patients with liver metastases of CRC. The retrospective study included patients with CRC alone (50 cases) and patients with CRC combined with liver metastases (50 cases) who were hospitalized between January 2021 and January 2023. Serum CEA, CA125 and CA19-9 levels were compared between the two groups, and binary logistic regression was used to analyze the predictive value of the combination of these tumor markers in liver metastasis. In addition, we performed receiver operating characteristic (ROC) curve analysis to assess its diagnostic accuracy. The results showed that the serum CEA, CA125 and CA19-9 levels in the CRC with liver metastasis group were significantly higher than those in the CRC alone group. Specifically, the average serum CEA level in the CRC with liver metastasis group was 162.03 ± 810.01 ng/mL, while that in the CRC alone group was 5.71 ± 9.76 ng/mL; the average serum CA125 levels were 43.47 ± 83.52 U/mL respectively. and 13.5 ± 19.68 U/mL; the average serum CA19-9 levels were 184.46 ± 473.13 U/mL and 26.55 ± 43.96 U/mL respectively. In addition, binary logistic regression analysis showed that CA125 was significant in predicting CRC liver metastasis (P < 0.05). ROC curve analysis results showed that the areas under the ROC curves of CEA, CA125 and CA19-9 were 0.607, 0.692 and 0.586. These results suggest that combined detection of these tumor markers may help early detection and intervention of CRC liver metastasis, thereby improving patient prognosis.

Prediction and analysis of albumin-bilirubin score combined with liver function index and carcinoembryonic antigen on liver metastasis of colorectal cancer.

Colorectal cancer (CRC) is a common malignant tumor, and liver metastasis is one of the main recurrence and metastasis modes that seriously affect patients' survival rate and quality of life. Indicators such as albumin bilirubin (ALBI) score, liver function index, and carcinoembryonic antigen (CEA) have shown some potential in the prediction of liver metastasis but have not been fully explored. To evaluate its predictive value for liver metastasis of CRC by conducting the combined analysis of ALBI, liver function index, and CEA, and to provide a more accurate liver metastasis risk assessment tool for clinical treatment guidance. This study retrospectively analyzed the clinical data of patients with CRC who received surgical treatment in our hospital from January 2018 to July 2023 and were followed up for 24 months. According to the follow-up results, the enrolled patients were divided into a liver metastasis group and a nonliver metastasis group and randomly divided into a modeling group and a verification group at a ratio of 2:1. The risk factors for liver metastasis in patients with CRC were analyzed, a prediction model was constructed by least absolute shrinkage and selection operator (LASSO) logistic regression, internal validation was performed by the bootstrap method, the reliability of the prediction model was evaluated by subject-work characteristic curves, calibration curves, and clinical decision curves, and a column graph was drawn to show the prediction results. Of 130 patients were enrolled in the modeling group and 65 patients were enrolled in the verification group out of the 195 patients with CRC who fulfilled the inclusion and exclusion criteria. Through LASSO regression variable screening and logistic regression analysis. The ALBI score, alanine aminotransferase (ALT), and CEA were found to be independent predictors of liver metastases in CRC patients [odds ratio (OR) = 8.062, 95% confidence interval (CI): 2.545-25.540], (OR = 1.037, 95%CI: 1.004-1.071) and (OR = 1.025, 95%CI: 1.008-1.043). The area under the receiver operating characteristic curve (AUC) for the combined prediction of CRLM in the modeling group was 0.921, with a sensitivity of 78.0% and a specificity of 95.0%. The H-index was 0.921, and the H-L fit curve had χ2 = 0.851, a P value of 0.654, and a slope of the calibration curve approaching 1. This indicates that the model is extremely accurate, and the clinical decision curve demonstrates that it can be applied effectively in the real world. We conducted internal verification of one thousand resamplings of the modeling group data using the bootstrap method. The AUC was 0.913, while the accuracy was 0.869 and the kappa consistency was 0.709. The combination prediction of liver metastasis in patients with CRC in the verification group had an AUC of 0.918, sensitivity of 85.0%, specificity of 95.6%, C-index of 0.918, and an H-L fitting curve with χ 2 = 0.586, P = 0.746. The ALBI score, ALT level, and CEA level have a certain value in predicting liver metastasis in patients with CRC. These three criteria exhibit a high level of efficacy in forecasting liver metastases in patients diagnosed with CRC. The risk prediction model developed in this work shows great potential for practical application.

Prognostic value of a nomogram model for postoperative liver metastasis of colon cancer.

Colon cancer is one of the most common malignant tumors of the digestive system. Liver metastasis after colon cancer surgery is the primary cause of death in patients with colon cancer. To construct a novel nomogram model including various factors to predict liver metastasis after colon cancer surgery. We retrospectively analyzed 242 patients with colon cancer who were admitted and underwent radical resection for colon cancer in Zhejiang Provincial People's Hospital from December 2019 to December 2022. Patients were divided into liver metastasis and non-liver metastasis groups. Sex, age, and other general and clinicopathological data (preoperative blood routine and biochemical test indexes) were compared. The risk factors for liver metastasis were analyzed using single-factor and multifactorial logistic regression. A predictive model was then constructed and evaluated for efficacy. Systemic inflammatory index (SII), C-reactive protein/albumin ratio (CAR), red blood cell distribution width (RDW), alanine aminotransferase, preoperative carcinoembryonic antigen level, and lymphatic metastasis were different between groups (P < 0.05). SII, CAR, and RDW were risk factors for liver metastasis after colon cancer surgery (P < 0.05). The area under the curve was 0.93 for the column-line diagram prediction model constructed based on these risk factors to distinguish whether liver metastasis occurred postoperatively. The actual curve of the column-line diagram predicting the risk of postoperative liver metastasis was close to the ideal curve, with good agreement. The prediction model curves in the decision curve analysis showed higher net benefits for a larger threshold range than those in extreme cases, indicating that the model is safer. Liver metastases after colorectal cancer surgery could be well predicted by a nomogram based on the SII, CAR, and RDW.

Fusobacteria alterations are associated with colorectal cancer liver metastasis and a poor prognosis.

Liver metastasis is a major cause of mortality in patients with advanced stages of colorectal cancer (CRC). The gut microbiota has been demonstrated to influence the progression of liver diseases, potentially providing novel perspectives for diagnosis, treatment and research. However, the gut microbial characteristics in CRC with liver metastasis (LM) and with no liver metastasis (NLM) have not yet been fully established. In the present study, high-throughput 16S RNA sequencing technology was employed, in order to examine the gut microbial richness and composition in patients with CRC with LM or NLM. A discovery cohort (cohort 2; LM=18; NLM=36) and a validation cohort (cohort 3; LM=13; NLM=41) were established using fresh feces. In addition, primary carcinoma tissue samples were also analyzed (LM=8 and NLM=10) as a supplementary discovery cohort (cohort 1). The findings of the present study indicated that the intestinal microbiota richness and diversity were increased in the LM group as compared to the NLM group. A significant difference was observed in species composition between the LM and NLM group. In the two discovery cohorts with two different samples, the dominant phyla were consistent, but varied at lower taxonomic levels. Phylum Fusobacteria presented consistent and significant enrichment in LM group in both discovery cohorts. Furthermore, with the application of a random forest model and receiver operator characteristic curve analysis, Fusobacteria was identified as a potential biomarker for LM. Moreover, Fusobacteria was also a poor prognosis factor for survival. Importantly, the findings were reconfirmed in the validation cohort. On the whole, the findings of the present study demonstrated that CRC with LM and NLM exhibit distinct gut microbiota characteristics. Fusobacteria detection thus has potential for use in predicting LM and a poor prognosis of patients with CRC.

Abstract 5528: Adaptive immune cells in colorectal cancer between normal mucosa, primary tumor and liver metastasis

Abstract Introduction: We aimed to assess the role of local adaptive immunity in the metastatic process by comparing densities of adaptive immune cells between normal colorectal mucosa (NM), primary colorectal cancer (pCRC) and liver metastases (LM) in patients with synchronous and metachronous disease. Patients and Methods: We enrolled patients, who underwent resection of pCRC and LM in Pilsen University Hospital between 1999 and 2022. 56 patients presented with LM (stage IV, synchronous) and 43 patients (stage II/III) developed LM later (metachronous). After immunohistochemical staining and whole slide scanning densities of CD3+ and CD8+ T cells and CD20+ B cells were quantified in NM, pCRC and LM using QuPath software. In pCRC and LM cell densities were measured in tumor center (TC), inner margin (IM), outer margin (OM) and peritumor (PT) region. IM and OM were defined as 500 µm on each side of the invasive tumor border. Results: For all examined cells in both groups we found smaller densities in TC of pCRC and LM compared to NM (Table). In pCRC of synchronous group compared to LM densities of all cells were smaller in IM and OM and densities of CD3+ and CD8+ cells were smaller in PT region. In pCRC of metachronous group compared to LM densities of all cells were greater in TC, densities of CD3+ were smaller in OM and PT region, whereas densities of CD20+ cells were smaller only in OM. Compared to metachronous group patients with synchronous metastases had smaller densities of CD3+ T cells in IM and CD8+ T cells in TC and IM of pCRC. Conclusion: Development of pCRC is accompanied by decreased densities of T and B cells in TC compared to NM, which further decrease in metachronous LM. Lower densities of T and B cells in IM and OM and T cells in PT region of pCRC compared to LM is a hallmark of synchronous group. TC of pCRC harbors larger numbers of T and B cells compared to LM in metachronous group. Low numbers of CD3+ and CD8+ T cells in IM and CD8+ T cells in TC of primary CRC may contribute to development of synchronous metastases. Densities of CD3+, CD8+ and CD20+ cells per mm2 of the tissue (median) Patients witn liver metastases Synchronous Metachronous NM pCRC LM NM pCRC LM CD3 NM 1014 1042 CD3 TC 313p&amp;lt;0.05 to NM 249p&amp;lt;0.05 to NM 338p&amp;lt;0.05 to NM 199p&amp;lt;0.05 to NM and pCRC CD3 IM 252 431p&amp;lt;0.05 to pCRC 393p&amp;lt;0.05 to pCRC in synchronous group 483 CD3 OM 521 1437p&amp;lt;0.05 to pCRC 649 1953p&amp;lt;0.05 to pCRC CD3 PT 479 873p&amp;lt;0.05 to pCRC 447 987p&amp;lt;0.05 to pCRC CD8 NM 319 390 CD8 TC 58p&amp;lt;0.05 to NM 52p&amp;lt;0.05 to NM 102p&amp;lt;0.05 to NM and to pCRC in synchronous group 52p&amp;lt;0.05 to NM and pCRC CD8 IM 65 96p&amp;lt;0.05 to pCRC 102p&amp;lt;0.05 to pCRC in synchronous group 120 CD8 OM 206 559p&amp;lt;0.05 to pCRC 310 363 CD8 PT 177 369p&amp;lt;0.05 to pCRC 218 291 CD20 NM 331 215 CD20 TC 32p&amp;lt;0.05 to NM 11p&amp;lt;0.05 to NM 27p&amp;lt;0.05 to NM 12p&amp;lt;0.05 to NM and pCRC CD20 IM 20 39p&amp;lt;0.05 to pCRC 20 33 CD20 OM 137 327p&amp;lt;0.05 to pCRC 134 303p&amp;lt;0.05 to pCRC CD20 PT 153 224 196 213 Citation Format: Andriy Trailin, Wenjing Ye, Esraa Ali, Sergii Pavlov, Lenka Cervenkova, Filip Ambrozkiewicz, Ondrej Vycital, Ondrej Daum, Vaclav Liska, Kari Hemminki. Adaptive immune cells in colorectal cancer between normal mucosa, primary tumor and liver metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5528.

Abstract 2961: Investigating the role of aging and treatment-induced senescence in the metastatic liver cancer tumor microenvironment

Abstract Liver senescence, marked by the progressive decline in hepatic cell function and regenerative capacity, plays a vital role in the context of aging, chronic liver diseases, and cancer progression, particularly when influenced by anti-cancer therapies. This study is designed to extensively characterize liver senescence under two specific conditions: replicative aging and therapy-induced changes. We examined liver samples from 20 individuals, covering a wide age range (young, &amp;lt;40 years; old, &amp;gt;60 years), and 16 cases of colorectal cancer (CRC) liver metastasis (ages 37-66). Our integrative approach melds single-nucleus RNA-sequencing (snRNA-seq) and ATAC-sequencing (snATAC-seq) to investigate the transcriptomic and epigenetic landscapes across a spectrum of liver cell types, including hepatocytes, cholangiocytes, stellate cells, liver sinusoidal endothelial cells, and diverse immune cells. Key findings include an upregulation of senescence markers such as CDKN1A, CDKN2A, and HMGB1, particularly in specific hepatocytes from older individuals and various cell types in the CRC liver metastasis group. Furthermore, we noted a distinctive senescence-associated secretory phenotype (SASP) across multiple immune cell types in our treated CRC liver metastasis group and upregulation of treatment-induced senescence gene signatures, such as SenCan. Moreover, hepatic stellate cells from older subjects exhibited augmented senescence-related gene signatures (SenSig) and transcription factors (SenMayo), with myofibroblast-like and FAP+ stellate cells showing a marked senescence phenotype, evidenced by elevated SASP molecule expression (CCL2, SERPINE1, GLB1, IGFBP7, IGFBP3).Incorporating advanced high-resolution imaging techniques, our study delves into the detailed morphological characteristics and spatial distribution of senescence markers within the liver in the setting of replicative aging and treatment-induced senescence. This study sheds light on the heterogeneity and intricacies of senescence-associated gene expression within liver cell populations. By combining comprehensive multiomic data with advanced high-resolution spatial profiling, we aim to decipher unique senescence phenotypes in the context of both replicative and treatment-induced senescence. Our work highlights the significance of cellular senescence in liver pathologies and cancer progression, suggesting new directions for therapeutic interventions that target these complex dynamics. Citation Format: Kelsey Gallant, Alla Karpova, Xiang Li, Michael Iglesia, Andrew Houston, Daniel Rapp, Chien-Wei Peng, Clara Liu, John Herdon, Feng Chen, Ryan Fields, Li Ding. Investigating the role of aging and treatment-induced senescence in the metastatic liver cancer tumor microenvironment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2961.

Non-neoplastic Liver Lesions after Biliary Stenting: Gadoxetic Acid-enhanced MRI Findings and Clinical association.

Non-neoplastic liver lesions show low signal intensity in the hepatobiliary phase (HBP) of gadoxetic acid-enhanced magnetic resonance imaging (EOB-MRI) after biliary stenting and require differentiation from liver metastases. The study aimed to evaluate the imaging findings and clinical association of non-neoplastic liver lesions showing hypointensity in the HBP of EOB-MRI after biliary stenting, and assess their differentiation from liver metastases. This study included 30 patients who underwent EOB-MRI after biliary stenting for pancreaticobiliary malignancies. Among these, 7 patients had pathologically diagnosed non-neoplastic liver lesions, which appeared hypointense in the HBP, and were categorized into the non-neoplastic group. The remaining 23 patients without non-neoplastic liver lesions were included in the control group. Additionally, 29 patients with liver metastasis were included in the liver metastasis group. Clinical associations and imaging features were compared between the groups. A history of cholangitis and two or more biliary interventional procedures were significantly more frequently observed in the non-neoplastic group (p=0.002 and p=0.01, respectively) than in the control groups. Regarding the imaging findings, the liver-to-lesion signal intensity ratio in the HBP in the liver metastasis group was significantly higher than that in the non-neoplastic group (2.13 vs. 1.53, p=0.002). Additionally, liver metastases were visualized significantly more clearly on diffusion-weighted images (p=0.033) and HBP images (p<0.001) in comparison to non-neoplastic lesions. Non-neoplastic liver lesions due to biliary inflammation may be observed in the HBP of EOB-MRI in patients after biliary stenting. These lesions may be associated with a history of cholangitis and repeated biliary intervention procedure, and need to be differentiated from liver metastases.

Survival Benefit of Primary Tumor Resection Combined With Chemotherapy in Patients With Unresectable Colorectal Mucinous Adenocarcinoma With Liver Metastasis.

To evaluate the survival benefit of combining primary tumor resection (PTR) and chemotherapy in patients with unresectable colorectal mucinous adenocarcinoma with liver metastasis (UCR-MAC-LM). We obtained data from the surveillance, epidemiology, and end results database for patients with UCR-MAC-LM from 2010 to 2017. Clinicopathological characteristics were analyzed using the χ2 test. Propensity score matching was performed to balance baseline characteristics. Kaplan-Meier analysis and log-rank tests were used to estimate and compare survival outcomes. Univariate and multivariate Cox regression analyses were conducted to identify the prognostic factors. A total of 10,178 patients with unresectable colorectal adenocarcinoma with liver metastasis were included, of whom 6.01% (n=612) had UCR-MAC-LM. The UCR-MAC-LM group had a higher proportion of female patients, a greater number of elderly patients, an increased incidence of right colon localization, larger tumor size, and higher T and N staging than the unresectable colorectal non-mucinous adenocarcinoma with liver metastasis group (P<0.05). Multivariate analysis identified several independent prognostic factors (P<0.05). Patients with unresectable colorectal adenocarcinoma with liver metastasis who underwent PTR+C had superior survival rates compared with those who received PTR/C alone or no treatment (cancer-specific survival, P<0.05; overall survival, P<0.05). Subgroup analysis revealed that 17 of 22 groups of patients with UCR-MAC-LM who received PTR+C had significantly prolonged long-term survival compared with those who received PTR/C alone. This surveillance, epidemiology, and end results-based study indicates that PTR+C may offer a survival advantage for a specific subgroup of patients with UCR-MAC-LM compared with PTR/C alone. Nonetheless, additional clinical trials are necessary to validate these findings.

Efficacy and safety of EGFR-TKIs in combination with angiogenesis inhibitors as first-line therapy for advanced EGFR-mutant non-small-cell lung cancer: a systematic review and meta-analysis

BackgroundFor patients with advanced non-small-cell lung cancer (NSCLC) with EGFR mutations, the suggested course of action is epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs). Even with a high disease control rate, a majority of patients develop acquired EGFR-TKIs resistance and eventually advance. To increase the benefits of treatment, clinical trials are increasingly exploring the value of EGFR-TKIs combined with angiogenesis inhibitors as a first-line treatment in advanced NSCLC carrying EGFR mutations.MethodUsing PubMed, EMBASE and Cochrane Library, to locate published full-text articles in print or online, a thorough literature search was done from the database's inception to February 2021. Additionally, oral presentation RCTs from ESMO and ASCO were obtained. We sifted out RCTs that used EGFR-TKIs along with angiogenesis inhibitors as first-line therapy for advanced EGFR-mutant NSCLC. ORR, AEs, OS, and PFS were the endpoints. Review Manager version 5.4.1 was used for data analysis.ResultsOne thousand eight hundred twenty-one patients were involved in 9 RCTs. According to the results, combining EGFR-TKIs with angiogenesis inhibitors therapy prolonged PFS of advanced EGFR-mutation NSCLC patients on the whole [HR:0.65 (95%CI: 0.59~0.73, P<0.00001)]. No significant statistical difference was identified between the combination group and single drug group in OS(P=0.20) and ORR (P=0.11). There are more adverse effects when EGFR-TKIs are used in combination with angiogenesis inhibitors than when used alone.ConclusionThe combination of EGFR-TKIs and angiogenesis inhibitors prolonged PFS in patients with EGFR-mutant advanced NSCLC, but the OS and ORR benefit was not significant, and the risk of adverse events was higher, more pronounced with hypertension and proteinuria; PFS in subgroups suggested that the combination was associated with better PFS in the smoking, liver metastasis, and no brain metastasis groups, and the included studies suggested that the smoking group , liver metastasis group, and brain metastasis group may have a potential OS benefit.

Gut Streptococcus is a microbial marker for the occurrence and liver metastasis of pancreatic cancer.

Gut microbiome plays an indispensable role in the occurrence and progression in various diseases. The incidence of pancreatic cancer (PC) and liver metastasis (PCLM) are high, most of them are found in advanced stage. Therefore, it is particularly necessary to search for predictive biomarkers, which are helpful for early detection and treatment, and thus improve the survival rate and quality of life of PC patients. We retrospectively analyzed 44 pancreatic cancer patients (P group, n = 44) and 50 healthy people (N group, n = 50) from March 21, 2021 and August 2, 2022. Among all PC patients, we divided them into liver metastasis group (LM group, n = 27) and non-liver metastasis group (non-LM group, n = 17). DNA was extracted and 16S ribosomal RNA (16S rRNA) gene sequencing was performed. SPSS was used for statistical analyses and all bioinformatics analyses were based on QIIME2, p < 0.05 were considered statistically significant. The microbial richness and diversity of group P and LM were higher than that of group N and non-LM. LEfSe analysis found that Streptococcus was a significantly different microorganism, which was further identified by random forest (RF) model, and its ability to predict PC and PCLM was verified by ROC curve. We demonstrated significant differences in intestinal microbiome composition between PC patients and healthy people, and found that Streptococcus is a potential biomarker for early prediction of PC and PCLM, which is critical for early diagnosis of diseases.

Effects of stereotactic body radiotherapy for clinical outcomes of patients with liver metastasis and hepatocellular carcinoma: A retrospective study.

This retrospective clinical study described the treatment efficacy and safety of stereotactic body radiotherapy (SBRT) for patients of hepatocellular carcinoma (HCC) and liver metastasis tumors. The therapeutic effect and prognosis of patients with liver cancer treated with stereotactic body radiation therapy (SBRT) at the Fudan University Shanghai Cancer Center (Shanghai, China) between July 2011 and December 2020 were retrospectively analyzed. Overall survival (OS), local control (LC) rates and progression-free survival (PFS) were evaluated using Kaplan-Meier analysis and the log-rank test. Local progression was defined as tumor growth after SBRT on dynamic computed tomography follow-up. Treatment-related toxicities were assessed according to the Common Terminology Criteria for Adverse Events version 4. A total of 36 patients with liver cancer were enrolled in the present study. The prescribed dosages (14 Gy in 3 fractions or 16 Gy in 3 fractions) were applied for SBRT treatments. The median follow-up time was 21.4 months. The median OS time was 20.4 [95% confidence interval (CI): 6.6-34.2] months, and the 2-year OS rates for the total population, HCC group and liver metastasis group were 47.5, 73.3 and 34.2%, respectively. The median PFS time was 17.3 (95% CI: 11.8-22.8) months and the 2-year PFS rates for the total population, HCC group and liver metastasis group were 36.3, 44.0 and 31.4%, respectively. The 2-year LC rates for the total population, HCC group and liver metastasis group were 83.4, 85.7 and 81.6%, respectively. The most common grade IV toxicity for the HCC group was liver function impairment (15.4%), followed by thrombocytopenia (7.7%). There were no grade III/IV radiation pneumonia or digestive discomfort. The present study aimed to explore a safe, effective and non-invasive treatment method for liver tumors. At the same time, the innovation of the present study is to find a safe and effective prescription dose of SBRT in the absence of consensus on guidelines.

Metastasis pattern and prognosis in children with neuroblastoma

BackgroundWe aimed to investigate the different metastases and prognoses of neuroblastoma (NB) and determine the risk factors of metastasis.MethodData of 1224 patients with NB were obtained from the Surveillance, Epidemiology and End Results database (2010–2018). Pearson’s chi-square test, Kaplan–Meier analysis, multivariable logistic regression and Cox regression analysis were used to determine the factors associated with prognosis.ResultsThe overall incidence of NB was an age-adjusted rate of 8.2 patients per 1,000,000 children. In total, 1224 patients were included in our study, with 599 patients (48.9%) exhibiting distant metastases. Compared to patients with non-metastatic NB, a greater proportion of patients with metastatic NB were under 1 year, male, had an adrenal primary site, unilateral tumour, a tumour size > 10 cm, neuroblastoma-not otherwise specified (NB-NOS), second malignant neoplasms and were more likely to choose radiotherapy and chemotherapy. Multivariate Cox regression showed that metastasis was an independent risk factor for overall survival (OS) and cancer-specific survival (CSS). The survival rate of non-metastatic patients with NB was better than those with metastasis (OS: hazard ratio (HR): 0.248, P < 0.001; CSS: HR: 0.267, P < 0.001). The bone and liver were the two most common isolated metastatic sites in NB. However, no statistical difference was observed in OS and CSS between the only bone metastasis group, only liver metastasis group and bone metastasis combined with liver metastasis group (all P > 0.05). Additionally, age at diagnosis > 1 year (odds ratio (OR): 3.295, P < 0 .001), grades III–IV (OR: 26.228, P < 0 .001) and 5–10 cm tumours (OR: 1.781, P < 0 .001) increased the risk of bone metastasis of NB. Moreover, no surgical treatment (OR: 2.441, P < 0 .001) increased the risk of liver metastasis of NB.ConclusionMetastatic NB has unique clinicopathological features, with the bone and liver as the most common single metastatic sites of NB. Therefore, more aggressive treatment is recommended for high-risk children with NB displaying distant metastases.

Pretreatment levels of serum alkaline phosphatase are associated with the prognosis of patients with non‑small cell lung cancer receiving immune checkpoint inhibitors.

Immune checkpoint inhibitors (ICIs) have been an encouraging treatment method in non-small cell lung cancer (NSCLC). However, bone and liver metastases are considered to restrain immunotherapy efficacy. Since serum alkaline phosphatase (ALP) is associated with bone and liver metastases, it was investigated whether serum ALP could be a novel biomarker to predict the efficacy of ICIs treatment. In the present study, 143 patients with NSCLC receiving ICIs treatment were retrospectively analyzed. The objective response rate (ORR) was compared between the ALP high and low groups, bone metastasis and non-bone metastasis groups, and liver metastasis or non-liver metastasis groups. The associations between clinical characteristics, including ALP level, bone or liver metastasis and median progression-free survival (mPFS) time were analyzed by univariate and multivariate Cox regression analysis. It was found that bone metastasis was associated with a lower ORR (24 vs. 43%; P<0.05) and shorter mPFS (10.2 vs. 17.3 months; P=0.010) in patients with NSCLC receiving ICIs. Liver metastasis was associated with lower ORR (22 vs. 38%; P<0.05), but not with mPFS (P=0.119). The ALP level was higher in patients with bone or liver metastasis than in those without (119.6 or 103.6 vs. 83.3 U/l, respectively; P<0.05). Higher ALP levels were also associated with bone or liver metastasis, lower ORR (20 vs. 39%; P<0.05) and shorter mPFS (8.5 vs. 15.4 months; P=0.009). Cox regression analysis demonstrated that ALP was an independent prognostic indicator of mPFS (hazard ratio, 1.856; 95% confidence interval, 1.030-3.343; P=0.040). In conclusion, pretreatment levels of serum ALP might be a predictive indicator of clinical outcome in patients with NSCLC after ICIs treatment.

Abstract P5-02-39: Efficacy of fulvestrant-based therapies in treating HR-positive, HER2-negative breast cancer with liver metastasis

Abstract Background: Hormone receptor-positive (HR+) metastatic breast cancer (MBC) contributes to nearly 70% of breast cancer-related deaths. The liver is the third most common site for metastasis in breast cancer, and liver involvement has been found to have a poor prognosis. One contributing factor is resistance to hormonal treatments. Furthermore, estrogen receptor alpha gene (ESR1) activating mutations, which are enriched in metastatic tumors of the viscera such as the liver, have been linked specifically to resistance against hormone-blocking therapies. We seek to characterize the efficacy of specific treatment modalities, including hormone therapy, immunomodulators, radiotherapy, chemotherapy, and the role of ESR1 mutations in poor treatment response of MBC with liver metastasis. Methods: We conducted a retrospective matched cohort study of 3388 adults with HR+/HER2- MBC with liver and non-liver involvement, who were treated at MD Anderson Cancer Center from 1997-2021. Patients with liver and non-liver metastasis were matched by age at breast cancer diagnosis, race, BMI, and stage. All patients underwent fulvestrant monotherapy or fulvestrant-based combination therapy with CDK4/6 inhibitors, mTOR kinase inhibitors (everolimus), or PI3K inhibitors (alpelisib). We compared the overall and metastatic survival of patients with liver vs. non-liver metastasis on different treatment regimens. We also evaluated the impact of chemotherapy administered for metastasis. Results: Patients with liver metastasis experienced shorter overall and metastatic survival across all treatment regimens (HR, 1.44; 95% CI 1.34-1.57; P&amp;lt;.001). The addition of targeted therapies to fulvestrant offered a survival benefit over fulvestrant alone in patients with non-liver metastasis. However, this benefit did not extend to the liver metastasis group. Independent of chemotherapy, liver metastasis was found to be a negative prognostic factor. Patients with first metastasis to the liver did not significantly differ in survival when compared to those who developed liver metastasis at a later stage. ESR1 mutations were identified in only a minority of the cohort (4%), but a higher prevalence of liver metastasis was found in patients with ESR1 mutations (49%) vs. the wild type group (45%). Independent of ESR1 status, patients with liver metastasis were found to have worse survival. Conclusion: We found liver metastasis to be a negative prognostic factor in patients with MBC independent of ESR1 status. While novel fulvestrant-based combination therapies have been promising for MBC, similar survival benefits are not seen in those with liver metastasis. Liver metastasis proves to be aggressive and difficult to treat, and current therapies are insufficient. Citation Format: Christine Chien, Zeynep Madak-Erdogan, Mahima Goel, Suma Gangidi, Debu Tripathy, Akshara Singareeka Raghavendra. Efficacy of fulvestrant-based therapies in treating HR-positive, HER2-negative breast cancer with liver metastasis [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-02-39.

Treatment outcome after sequential chemotherapy with cisplatin-etoposide, amrubicin and nogitecan in patients with treatment-related pure small-cell neuroendocrine prostate cancer.

This study retrospectively reviewed the clinical characteristics and treatment outcomes of patients with histologically diagnosed treatment-related pure small-cell neuroendocrine prostate cancer. We retrospectively evaluated data for 13 patients with treatment-related neuroendocrine prostate cancer who were diagnosed between May 2015 and February 2022. Standardized systemic therapies of etoposide plus cisplatin (or carboplatin), amrubicin and nogitecan were selected as sequential treatments. Cancer-specific survival and progression-free survival were evaluated as the primary endpoint. The Cox proportional hazards model was used to evaluate the relationships between treatment regimens, clinical variables, cancer-specific survival and progression-free survival. The median cancer-specific survival after diagnosis for all patients was 22.4months (range 1.3-33.4months). The median progression-free survival was 9.3months after first-line etoposide plus cisplatin (or carboplatin) treatment (n=13); 4.2months after second-line amrubicin treatment (n=4); and>15months after third-line nogitecan treatment (n=2). The median progression-free survival after first-line chemotherapy of the liver metastasis (-) group was 10.2months, and that of the (+) group was 5.3months (P=0.015, hazard ratio=11.6, 95% confidence interval=1.01-133.7). No clinicopathological parameters were identified as significant independent predictors of cancer-specific survival in univariate analysis. Sequential chemotherapy with etoposide plus cisplatin (or carboplatin), amrubicin and nogitecan may be helpful for patients with treatment-related pure small-cell neuroendocrine prostate cancer. Early biopsy of metastases and initiation of effective therapy is essential for patients with progressive castration-resistant prostate cancer and low prostate-specific antigen.

Evaluation of the safety and efficacy of ultrasound-guided percutaneous radiofrequency ablation for hepatocellular carcinoma and liver metastases adjacent to the gallbladder

Objective To evaluate the safety and efficacy of ultrasound-guided percutaneous radiofrequency ablation (RFA) in patients with hepatocellular carcinoma (HCC) and liver metastases adjacent to the gallbladder (GB). Materials and methods A total of 113 patients with 118 liver lesions (63 HCC lesions and 55 liver metastases) adjacent to the gallbladder underwent RFA between March 2011 and June 2019. Gallbladder-related complications and technique effectiveness rates were evaluated based on the classification of liver tumors and the distance between the lesion and the gallbladder. Results Gallbladder-related complications were observed in 13 patients. Among the patients with HCC, there was no significant difference between the ≤0.5 cm and >0.5 cm groups (p = .282). However, among the patients with liver metastases, the incidence of gallbladder-related complications in the ≤0.5 cm group was significantly higher than that in the >0.5 cm group (p = .025). The overall incidence of complications was significantly higher in the ≤0.5 cm group than in the >0.5 cm group (p = .020). Among the patients with lesions ≤3 cm, the technical effectiveness rate in the HCC group was significantly higher than in the liver metastasis group (p = .036). Conclusion RFA is a safe and effective treatment option for liver tumors adjacent to the gallbladder. Patients with lesions ≤0.5 cm from the gallbladder had higher gallbladder-related complications, especially patients with liver metastases. Among patients with lesions ≤3 cm, RFA showed greater technical effectiveness for treating HCC than for treating liver metastases.

Extracranial metastasis sites correlate to the incidence risk of brain metastasis in stage IV non-small cell lung cancer: a population-based study.

The aim of this study was to analyse the correlation of extracranial metastasis sites (ECMs) to the incidence risk of brain metastasis (BMs) in stage IV non-small cell lung cancer (NSCLC). 18349 newly diagnosed patients were retrospectively analysed, and 4919 pairs of cases were matched by propensity score matching in a 1:1 ratio. Alternative factors were analysed by multivariable logistic regression analysis. And the interaction analysis and subgroup analysis were carried out. The incidences of Brain, Lung, Liver, Bone, Multiple and Other metastasis were 26.9%, 20.2%, 4.6%, 19.9%, 16.9% and 38.3%, respectively. Results suggested that Age, Race, Histological type, Grade, T stage, N stage and Organ metastasis site were risk factors (p < 0.05). The interaction analysis suggested interaction effects between the Primary site, T stage, N stage and Organ metastasis site. The subgroup analysis showed that the Organ metastasis site and the risk of BMs were statistically significant except that the Overlapping subgroup (p = 0.267) of the Primary site. And the incidence risk of BMs in Lung metastasis, Liver metastasis and Bone metastasis groups was lower than that in other metastasis group (OR 1, p < 0.05). There was no significant difference between the Multiple metastasis group and the other metastasis group (OR 1.091, p = 0.169). Advanced age, non-Asian/Pacific Islander, non-squamous cell carcinoma, poorly differentiated grade, and higher T/N stage were risk factors for increased BMs in stage IV NSCLC, and the ECMs were associated with the risk of BMs.

Immunotherapy and tumor mutational burden in cancer patients with liver metastases: A meta and real word cohort analysis.

The predictive effects of liver metastases for immune-checkpoint inhibitors (ICIs) and the relationship between tumor mutational burden (TMB) and liver metastases (LM) remain unclear. A systematic review and meta-analysis were conducted to explore the heterogeneity of ICIs efficacy between patients with or without LM. A pan-cancer cohort of 1,661 patients who received ICIs was downloaded and analyzed to assess the association between TMB and LM. Of 21053 studies identified in our search, eight single-arm studies and 24 randomized controlled trials were included. Overall, 17957 patients with advanced or metastatic cancers (4805 patients (26.8%) with LM and 13151 patients (73.2%) without LM) were enrolled. The pooled objective response rate (ORR) was 8.5% (95% CI 4%-13%) in the LM group versus 21% (95% CI 16%-21%) in the non-LM group. The pooled hazard ratio (HR) for death was 0.85 (95% CI 0.80-0.90) in the LM group treated with ICIs compared with the standard of care. In patients without LM who were treated with ICIs, the pooled HR for death was 0.78 (95% CI 0.73-0.82) compared with the standard of care. The difference in efficacy between patients with or without LM treated with ICIs was significant (p=0.04). Pan-cancer analysis revealed that the TMB-high rate was 10.8% in liver metastatic lesions versus 21.4% in other metastatic lesions (p=0.004). In addition, TMB was also significantly associated with OS as a binary cutoff (p=0.05) and was an independent prognostic variable (HR=0.98, P=0.047) as a continuous variable in patients with LM. In patients with LM, the efficacy of immunotherapy was attenuated, but TMB-high could predict better survival outcomes.