Clinical characteristics between synchronous and metachronous colorectal liver metastases
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ABSTRACT:
DISEASE(S): Colorectal Cancer
PROVIDER: 2682914 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
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Project description:Purpose:To investigate differences in clinical characteristics and mutational patterns between synchronous and metachronous colorectal liver metastases (CLMs). Patients and methods:From June 2008 to December 2014, patients with RAS wild-type CLMs treated at Zhongshan Hospital, Fudan University were included. DNA extracted from formalin-fixed paraffin-embedded tissue of primary tumors was sequenced with next-generation sequencing for single-nucleotide polymorphism of 96 genes according to custom panel. Mutations were compared between synchronous and metachronous liver metastases and correlated with clinical characteristics. Results:A total of 161 patients were included: 93 patients with synchronous CLM and 68 patients with metachronous CLM. Patients with metachronous CLM were obviously elder. For pathology of primary tumors, synchronous CLMs were larger in size, poorly differentiated, and more frequently local advanced and lymph node positive. For evaluation of liver metastases, synchronous CLM had more and larger metastatic lesions. The median number of mutations in synchronous CLMs was significantly higher than in metachronous group (22 vs. 18, p<0.001). EGFR rs2227983 is the most prevalent mutation in both groups and only a part of prevalent mutations is shared in both groups. Prevalent mutations were correlated with many clinical characteristics. EGFR rs2227983, RBMXL3 rs12399211, and PTCH1 rs357564 were prognostic for latency of metachronous CLM. Conclusion:Clinically, synchronous CLMs, compared with metachronous CLMs, were younger and showed heavier tumor burden for both primaries and liver metastases. Genetically, we identified different mutational patterns between synchronous and metachronous CLMs and several correlations between mutations and clinical characteristics. Further researches were needed to confirm these potential key mutations of CLMs.
| S-EPMC6118248 | biostudies-literature
Project description:BackgroundMetastases are the leading cause of mortality in cancer patients. Linear and parallel are the two prominent models of metastatic progression. Metastases can be detected synchronously along with the primary tumor or metachronously, following treatment of localized disease. The aim of the study was to determine whether synchronous metastases (SM) and metachronous metastases (MM) differ only in lead-time or stem from different biological processes.Materials and methodsWe retrospectively studied the chest CTs of 791 patients inflicted by eleven malignancy types that were treated in our institution in the years 2010-2020. Patient's population included 396 with SM and 395 with MM. The diameter of 15,427 lung metastases was measured. Clonal origin was deduced from the linear/parallel ratio (LPR)-a computerized analysis of metastases diameters. LPR of 1 suggests pure linear dissemination and - 1 pure parallel.ResultsPatients with MM were significantly older (average of 62.9 vs 60.7 years, p = 0.02), and higher percentage of them were males (58.7% vs 51.1%, p = 0.03). Median overall survival of patients with MM and SM was remarkably similar (23 months and 26 months respectively, p = 0.774) when calculated from the time of metastases diagnosis. Parallel dissemination (LPR ≤ 0) was found in 35.4% of patients with MM compared to only 19.8% of the patients with SM (p < 0.00001).ConclusionPatients with SM and MM differ in demography and in clonal origin. Different therapeutic approaches may be considered in these two conditions.
| S-EPMC10465669 | biostudies-literature
Project description:BackgroundControversy exists on emergency setting as a risk factor for peritoneal metastases (PM) in colon cancer patients. Data in patients with obstruction are scarce. The aim of this study was to determine the incidence of synchronous and metachronous PM, risk factors for the development of metachronous PM, and prognostic implications within a large nationwide cohort of left-sided obstructive colon cancer (LSOCC).MethodsPatients with LSOCC treated between 2009 and 2016 were selected from the Dutch ColoRectal Audit. Additional treatment and long-term outcome data were retrospectively collected from original patient files in 75 hospitals in 2017.ResultsIn total, 3038 patients with confirmed obstruction and without perforation were included. Synchronous PM (at diagnosis or < 30 days postoperatively) were diagnosed in 148/2976 evaluable patients (5.0%), and 3-year cumulative metachronous PM rate was 9.9%. Multivariable Cox regression analyses revealed pT4 stage (HR 1.782, 95% CI 1.191-2.668) and pN2 stage (HR 2.101, 95% CI 1.208-3.653) of the primary tumor to be independent risk factors for the development of metachronous PM. Median overall survival in patients with or without synchronous PM was 20 and 63 months (p < 0.001) and 3-year overall survival of patients that did or did not develop metachronous PM was 48.1% and 77.0%, respectively (p < 0.001).ConclusionThis population based study revealed a 5.0% incidence of synchronous peritoneal metastases in patients who underwent resection of left-sided obstructive colon cancer. The subsequent 3-year cumulative metachronous PM rate was 9.9%, with advanced tumor and nodal stage as independent risk factors for the development of PM.
| S-EPMC7334250 | biostudies-literature
Project description:BackgroundWe aimed to evaluate the clinical significance of microvessel density (MVD), lymphatic vessel density (LVD), and cancer-associated fibroblasts (CAFs) in relation to tumor location in advanced colorectal cancer (CRC).MethodsUsing immunohistochemistry, we examined 181 advanced CRC patients for CD31 and D2-40 to measure MVD and LVD, respectively, α-smooth muscle actin (SMA) and desmin to identify CAFs, and PTEN to examine genetic changes of CAFs. To evaluate the regional heterogeneity of these properties, we examined tissue from four sites (the center and periphery of the primary cancer, a distant metastasis, and a lymph node metastasis) in each patient.ResultsMVD, LVD, and CAFs showed significant heterogeneity with respect to the tumor location. LVD was the greatest in the center of the primary cancers and the amount of CAFs was the lowest in distant metastases. In distant metastases, those from the lung had higher LVD and MVD, but fewer CAFs than those from the liver, peritoneum, or ovary. Patients with low MVD and LVD in the center of the primary cancer had worse outcomes and patients with few CAFs in distant metastases and in the primary tumor had a lower survival rate. PTEN expression in CAFs in distant metastases was lost in 11 of 181 CRC patients (6.1%), which was associated with a worse prognosis.ConclusionsThe microenvironment, including cancer-associated microvasculature and fibroblasts, is heterogeneous with respect to the tumor location in CRC patients. Therefore, heterogeneity of microenvironments should be taken into account when managing CRC patients.
| S-EPMC3958375 | biostudies-literature
Project description:Patients with advanced colorectal cancer (CRC) with distant metastases have a poor prognosis. We evaluated the clinicopathological relevance of GRP94 expression in these cases. The immunohistochemical expression of GRP94 was studied in 189 CRC patients with synchronous (SM; n = 123) and metachronous metastases (MM; n = 66), using tissue microarray; the association between GRP94 expression, outcome, and tumor-infiltrating lymphocytes (TILs) was also evaluated. GRP94 was expressed in 64.6% (122/189) patients with CRC; GRP94 positivity was found in 67.5% and 59.1% patients with SM and MM, respectively. In the SM group, high GRP94 expression was more common in patients with a higher density of CD4+ TILs (p = 0.002), unlike in the MM group. Survival analysis showed that patients with GRP94 positivity had significantly favorable survival (p = 0.030); after multivariate analysis, GRP94 only served as an independent prognostic factor (p = 0.034; hazard ratio, 0.581; 95% confidence interval, 0.351-0.961) in the SM group. GRP94 expression was detected in 49.4% of metastatic sites and showed significant heterogeneity between primary and metastatic lesions (p = 0.012). GRP94 is widely expressed in CRC with distant metastases; its expression was associated with favorable prognosis in the SM group, unlike in the MM group.
| S-EPMC8267630 | biostudies-literature
Project description:BackgroundColorectal cancer is a highly prevalent and deadly. The most common metastatic site is the liver. We performed a whole exome sequencing analysis of a series of metachronous colorectal cancer liver metastases (mCLM) and matched non-malignant liver tissues to investigate the genomic profile of mCLM and explore associations with the patients' prognosis and therapeutic modalities.MethodsDNA samples from mCLM and non-malignant liver tissue pairs (n = 41) were sequenced using whole exome target enrichment and their germline and somatic genetic variability, copy number variations, and mutational signatures were assessed for associations with relapse-free (RFS) and overall survival (OS).ResultsOur genetic analysis could stratify all patients into existing targeted therapeutic regimens. The most commonly mutated genes in mCLM were TP53, APC, and KRAS together with PIK3CA and several passenger genes like ABCA13, FAT4, PCLO, and UNC80. Patients with somatic alterations in genes from homologous recombination repair, Notch, and Hedgehog pathways had significantly prolonged RFS, while those with altered MYC pathway genes had poor RFS. Additionally, alterations in the JAK-STAT pathway were prognostic of longer OS. Patients bearing somatic variants in VIPR2 had significantly shorter OS and those with alterations in MUC16 prolonged OS. Carriage of the KRAS-12D variant was associated with shortened survival in our and external datasets. On the other hand, tumor mutation burden, mismatch repair deficiency, microsatellite instability, mutational signatures, or copy number variation in mCLM had no prognostic value.ConclusionsThe results encourage further molecular profiling for personalized treatment of colorectal cancer liver metastases discerning metachronous from synchronous scenarios.
| S-EPMC10676609 | biostudies-literature
Project description:BackgroundThis study aimed to compare treatment strategies and survival of patients with synchronous colorectal peritoneal metastases (CPM) and patients with metachronous CPM in a nationwide cohort.MethodsAll patients from the Netherlands Cancer Registry with synchronous or metachronous CPM whose primary colorectal cancer (CRC) was diagnosed between 1 January and 30 June 2015 were included in the study. Treatments were categorized as (A) cytoreductive surgery and hyperthermic intraperitoneal chemotherapy [CRS-HIPEC]; (B) palliative treatment; or (C) best supportive care. Overall survival (OS) for all the patients and disease-free survival (DFS) for those who underwent CRS-HIPEC were compared between the two groups.ResultsOf 7233 patients, 743 had a diagnosis of CPM, including 409 patients with synchronous CPM and 334 patients with metachronous CPM. The median OS was 8.1 months for the patients with synchronous CPM versus 12 months for the patients with metachronous CPM (p = 0.003). After multivariable correction, OS no longer differed between the patients with synchronous CPM and those with metachronous CPM (HR 1.03 [0.83-1.27]). The patients with metachronous CPM more often underwent CRS-HIPEC than the patients with synchronous CPM (16 % vs 8 %; p = 0.001). The two groups did not differ statistically in terms of DFS and OS (median DFS, 21.5 vs 14.1 months, respectively; p = 0.094; median OS, 37.8 vs. 35.8 months, respectively; p = 0.553).ConclusionThis population-based study showed that survival for the patients with synchronous CPM and patients with metachronous CPM did not significantly differ. This suggests that a similar prognosis may be expected for patients selected for treatment regardless of the onset of CPM.
| S-EPMC8591028 | biostudies-literature
Project description:BackgroundTo develop a radiomics model based on pretreatment whole-liver portal venous phase (PVP) contrast-enhanced CT (CE-CT) images for predicting metachronous liver metastases (MLM) within 24 months after rectal cancer (RC) surgery.MethodsThis study retrospectively analyzed 112 RC patients without preoperative liver metastases who underwent rectal surgery between January 2015 and December 2017 at our institution. Volume of interest (VOI) segmentation of the whole-liver was performed on the PVP CE-CT images. All 1316 radiomics features were extracted automatically. The maximum-relevance and minimum-redundancy and least absolute shrinkage and selection operator methods were used for features selection and radiomics signature constructing. Three models based on radiomics features (radiomics model), clinical features (clinical model), and radiomics combined with clinical features (combined model) were built by multivariable logistic regression analysis. Receiver operating characteristic (ROC) curves were used to assess the diagnostic performance of models, and calibration curve and the decision curve analysis were performed to evaluate the clinical application value.ResultsIn total, 52 patients in the MLM group and 60 patients in the non-MLM group were enrolled in this study. The radscore was built using 16 selected features and the corresponding coefficients. Both the radiomics model and the combined model showed higher diagnostic performance than clinical model (AUCs of training set: radiomics model 0.84 (95% CI, 0.76-0.93), clinical model 0.65 (95% CI, 0.55-0.75), combined model 0.85 (95% CI, 0.77-0.94); AUCs of validation set: radiomics model 0.84 (95% CI, 0.70-0.98), clinical model 0.58 (95% CI, 0.40-0.76), combined model 0.85 (95% CI, 0.71-0.99)). The calibration curves showed great consistency between the predicted value and actual event probability. The DCA showed that both the radiomics and combined models could add a net benefit on a large scale.ConclusionsThe radiomics model based on preoperative whole-liver PVP CE-CT could predict MLM within 24 months after RC surgery. Clinical features could not significantly improve the prediction efficiency of the radiomics model.
| S-EPMC9465956 | biostudies-literature
Project description:BackgroundLiver metastases from cancer of unknown primary (CUPL) constitute a rare disease, particularly among individuals younger than 50 years old. This paper aims to investigate the clinical characteristics of patients with CUPL and analyze prognostic differences across distinct age groups.MethodsData pertaining to patients with CUPL were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching (PSM) was employed to adjust for clinical variables. Cox regression analysis identified risk factors influencing overall survival (OS), while competing-risk analyses were conducted to determine prognostic factors for cancer-specific survival (CSS). Survival differences were compared using the Kaplan-Meier method and cumulative incidence function (CIF).ResultsThe study encompassed 4,691 patients, with 319 (6.8%) in the age <50 years group and 4,372 (93.2%) in the age ≥50 years group. Individuals with unexplained liver metastases exhibited a 1-year OS rate of 14.7% and a 1-year CSS rate of 23%. Following matching, age, histology, brain metastases, and chemotherapy were identified as independent prognostic factors affecting OS. Additionally, race, grade, histology, brain metastases, and chemotherapy were recognized as independent prognostic factors influencing CSS. Notably, the age <50 years group demonstrated superior OS and CSS compared to the age ≥50 years group before and after PSM. Among patients undergoing chemotherapy, the age <50 years group exhibited enhanced OS and CSS compared to their age ≥50 years counterparts. Furthermore, in individuals subjected to radiotherapy, the age <50 years group demonstrated superior OS, although no significant difference in CSS was observed.ConclusionsThe survival prognosis of patients with CUPL was found to be poor. However, both OS and CSS were more favorable in the age <50 years group compared to the age ≥50 years group. Additionally, radiotherapy and chemotherapy were associated with an OS benefit for patients in the age <50 years group.
| S-EPMC11319942 | biostudies-literature
Project description:Despite distant metastases being the critical factor affecting patients' survival, they remain poorly understood. Our study thus aimed to molecularly characterize colorectal cancer liver metastases (CRCLMs) and explore whether molecular profiles differ between Synchronous (SmCRC) and Metachronous (MmCRC) colorectal cancer. This characterization was performed by whole exome sequencing, whole transcriptome, whole methylome, and miRNAome. The most frequent somatic mutations were in APC, SYNE1, TP53, and TTN genes. Among the differently methylated and expressed genes were those involved in cell adhesion, extracellular matrix organization and degradation, neuroactive ligand-receptor interaction. The top up-regulated microRNAs were hsa-miR-135b-3p and -5p, and the hsa-miR-200-family while the hsa-miR-548-family belonged to the top down-regulated. MmCRC patients evinced higher tumor mutational burden, a wider median of duplications and deletions, and a heterogeneous mutational signature than SmCRC. Regarding chronicity, a significant down-regulation of SMOC2 and PPP1R9A genes in SmCRC compared to MmCRC was observed. Two miRNAs were deregulated between SmCRC and MmCRC, hsa-miR-625-3p and has-miR-1269-3p. The combined data identified the IPO5 gene. Regardless of miRNA expression levels, the combined analysis resulted in 107 deregulated genes related to relaxin, estrogen, PI3K-Akt, WNT signaling pathways, and intracellular second messenger signaling. The intersection between our and validation sets confirmed the validity of our results. We have identified genes and pathways that may be considered as actionable targets in CRCLMs. Our data also provide a valuable resource for understanding molecular distinctions between SmCRC and MmCRC. They have the potential to enhance the diagnosis, prognostication, and management of CRCLMs by a molecularly targeted approach.
| S-EPMC10172672 | biostudies-literature