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Area of residual tumor (ART) can predict prognosis after post neoadjuvant therapy resection for pancreatic ductal adenocarcinoma.

ABSTRACT: An increasing number of patients with pancreatic ductal adenocarcinoma (PDAC) have undergone resection after neoadjuvant therapy (NAT). We have reported Area of Residual Tumor (ART) as a useful pathological assessment method to predict patient outcomes after post NAT resection in various cancer types. The aim of this study was to assess the prognostic performance of ART in PDAC resected after NAT. Sixty-three patients with PDAC after post NAT resection were analyzed. The viable residual tumor area was outlined and the measurement of ART was performed using morphometric software. The results were compared with those of the College of American Pathologist (CAP) regression grading. Of 63 cases, 39 (62%) patients received chemoradiation therapy and 24 (38%) received chemotherapy only. The median value of ART was 163 mm2. Large ART with 220 mm2 as the cut-off was significantly associated with lymphatic invasion, vascular invasion and perineural invasion, while CAP regression grading was not associated with any clinicopathological features. By multivariate analysis, large ART (?220 mm2) was an independent predictor of shorter relapse free survival. Together with our previous reports, an ART-based pathological assessment may become a useful method to predict patient outcomes after post NAT resection across various cancer types.

SUBMITTER: Okubo S

PROVIDER: S-EPMC6868132 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Area of residual tumor (ART) can predict prognosis after post neoadjuvant therapy resection for pancreatic ductal adenocarcinoma.

Okubo Satoshi S Kojima Motohiro M Matsuda Yoko Y Hioki Masayoshi M Shimizu Yasuhiro Y Toyama Hirochika H Morinaga Soichiro S Gotohda Naoto N Uesaka Katsuhiko K Ishii Genichiro G Mino-Kenudson Mari M Takahashi Shinichiro S

Scientific reports 20191120 1

An increasing number of patients with pancreatic ductal adenocarcinoma (PDAC) have undergone resection after neoadjuvant therapy (NAT). We have reported Area of Residual Tumor (ART) as a useful pathological assessment method to predict patient outcomes after post NAT resection in various cancer types. The aim of this study was to assess the prognostic performance of ART in PDAC resected after NAT. Sixty-three patients with PDAC after post NAT resection were analyzed. The viable residual tumor ar ...[more]

PMID: 31748528

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Project description:BACKGROUND:Neoadjuvant therapy (NAT) represents a paradigm shift in the management of patients with pancreatic ductal adenocarcinoma (PDAC) with perceived benefits including a higher R0 rate. However, it is unclear whether NAT affects the sites and patterns of recurrence after surgery. This review seeks to compare sites and patterns of recurrence after resection between patients undergoing upfront surgery (US) or after NAT. METHODS:The EMBASE, SCOPUS, PubMed, and Cochrane library databases were systematically searched to identify eligible studies that compare recurrence patterns between patients who had NAT (followed by resection) with those that had US. The primary outcome included site-specific recurrence. RESULTS:26 articles were identified including 4986 patients who underwent resection. Borderline resectable pancreatic cancer (BRPC, 47% 1074/2264) was the most common, followed by resectable pancreatic cancer (RPC 42%, 949/2264). The weighted overall recurrence rates were lower among the NAT group, 63.4% vs. 74% (US) (OR 0.67 (CI 0.52-0.87), p = 0.006). The overall weighted locoregional recurrence rate was lower amongst patients who received NAT when compared to US (12% vs 27% OR 0.39 (CI 0.22-0.70), p = 0.004). In BRPC, locoregional recurrence rates improved with NAT (NAT 25.8% US 37.7% OR 0.62 (CI 0.44-0.87), p = 0.007). NAT was associated with a lower weighted liver recurrence rate (NAT 19.4% US 30.1% OR 0.55 (CI 0.34-0.89), p = 0.023). Lung and peritoneal recurrence rates did not differ between NAT and US cohorts (p = 0.705 and p = 0.549 respectively). NAT was associated with a significantly longer weighted mean time to first recurrence 18.8 months compared to US (15.7 months) (OR 0.18 (CI 0.05-0.32), p = 0.015). CONCLUSION:NAT was associated with lower overall recurrence rate and improved locoregional disease control particularly for those with BRPC. Although the burden of liver metastases was less, there was no overall effect upon distant metastatic disease.

Project description:BackgroundPancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies and is not a clinically homogeneous disease, but subsets of patients with distinct prognosis and response to therapy can be identified by genome-wide analyses. Mutations in major PDAC driver genes were associated with poor survival. By bioinformatics analysis, we identified protocadherins among the most frequently mutated genes in PDAC suggesting an important role of these genes in the biology of this tumor. Promoter methylation of protocadherins has been suggested as a prognostic marker in different tumors, but in PDAC this epigenetic modification has not been extensively studied. Thus, we evaluated whether promoter methylation of three frequently mutated protocadherins, PCDHAC2, PCDHGC5 and PCDH10 could be used as survival predictors in PDAC patients.MethodsDNA extracted from 23 PDACs and adjacent non-neoplastic pancreatic tissues were bisulfite treated. Combined Bisulfite Restriction Analysis (COBRA) coupled to denaturing high-performance liquid chromatography (dHPLC) detection and bisulfite genomic sequencing (BGS) were used to determine the presence of methylated CpG dinucleotides in the promoter amplicons analyzed.ResultsIn an exploratory analysis, two protocadherins showed the same pattern of CpG methylation in PDAC and adjacent non-neoplastic pancreatic tissues: lack of methylation for PCDHAC2, complete methylation for PCDHGC5. Conversely, the third protocadherin analyzed, PCDH10, showed a variable degree of CpG methylation in PDAC and absence of methylation in adjacent non-neoplastic pancreatic tissues. At Kaplan-Meier analysis, high levels of PCDH10 methylation defined according to the receiver operating characteristic (ROC) curve analysis were significantly associated with worse progression-free survival (PFS) rates (P = 0.008), but not with overall survival (OS). High levels of PCDH10 methylation were a prognostic factor influencing PFS (HR = 4.0: 95% CI, 1.3-12.3; P = 0.016), but not the OS.ConclusionsIn this study, we show for the first time that the methylation status of PCDH10 can predict prognosis in PDAC patients with a significant impact on the outcome in terms of progression-free survival. High levels of PCDH10 promoter methylation could be useful to identify patients at high risk of disease progression, contributing to a more accurate stratification of PDAC patients for personalized clinical management.

Project description:ObjectivesThis study aimed to develop and externally validate a nomogram for predicting liver metastasis after radical resection in patients with pancreatic ductal adenocarcinoma (PDAC).MethodsA total of 247 PDAC patients who underwent radical resection were retrospectively reviewed from January 2015 to March 2022 at Ningbo Medical Centre Lihuili Hospital Eastern Section, and used as a training cohort to develop the nomogram. 83 PDAC patients from the Ningbo Medical Centre Lihuili Hospital Xingning Section were enrolled as the validation cohort. The postoperative liver metastasis was recorded during the follow-up, and the liver metastasis-free survival was defined as the time from operation to the date of liver metastasis diagnosis or death. The nomogram was established based on independent prognostic factors selected by LASSO and multivariate Cox regression model. The performance was assessed using the concordance index (C-index) and calibration curves. The receiver operating characteristic (ROC) curve and decision curve analysis (DCA) were used to determine the clinical utility of the nomogram model.ResultsFrom the training cohort of 247 patients, a total of 132 patients developed liver metastasis during the follow-up, the 1-, 2- and 3- year liver metastasis-free survival were 52.4%, 43.5% and 40% respectively. The LASSO and multivariate Cox regression analysis indicated that postoperative CA125 (hazard ratio [HR] = 1.007, p <0.001), tumor differentiation (HR = 1.640, p = 0.010), tumor size (HR = 1.520, p = 0.029), lymph node ratio (HR = 1.897, p = 0.002) and portal/superior mesenteric/splenic vein invasion degree (PV/SMV/SV) (HR = 2.829, p <0.001) were the independent factors of liver metastasis. A nomogram with independent factors was developed and the C-index was 0.760 (95% confidence interval [CI], 0.720-0.799) and 0.739 (95% CI, 0.669-0.810) in the training and validation cohorts, respectively. The areas under curve (AUC) of the nomogram at 1-, 2- and 3-year were 0.815, 0.803 and 0.773 in the training cohort, and 0.765, 0.879 and 0.908 in the validation cohort, respectively, higher than those in TNM stage. Decision curve analysis (DCA) analysis revealed that the nomogram model provided superior net benefit in clinical utility. Liver metastasis-free survival curves showed a significant discriminatory ability for liver metastasis risk based on the nomogram (p <0.001).ConclusionsThe nomogram showed high accuracy in predicting liver metastasis for PDAC after radical resection, and may serve as a clinical support tool to guide personalized and prescient intervention.

Project description:BackgroundThe immune response in the tumor microenvironment (TME) plays a crucial role in cancer progression and recurrence. We aimed to develop an immune-related gene (IRG) signature to improve prognostic predictive power and reveal the immune infiltration characteristics of pancreatic ductal adenocarcinoma (PDAC).MethodsThe Cancer Genome Atlas (TCGA) PDAC was used to construct a prognostic model as a training cohort. The International Cancer Genome Consortium (ICGC) and the Gene Expression Omnibus (GEO) databases were set as validation datasets. Prognostic genes were screened by using univariate Cox regression. Then, a novel optimal prognostic model was developed by using least absolute shrinkage and selection operator (LASSO) Cox regression. Cell type identification by estimating the relative subsets of RNA transcripts (CIBERSORT) and estimation of stromal and immune cells in malignant tumors using expression data (ESTIMATE) algorithms were used to characterize tumor immune infiltrating patterns. The tumor immune dysfunction and exclusion (TIDE) algorithm was used to predict immunotherapy responsiveness.ResultsA prognostic signature based on five IRGs (MET, ERAP2, IL20RB, EREG, and SHC2) was constructed in TCGA-PDAC and comprehensively validated in ICGC and GEO cohorts. Multivariate Cox regression analysis demonstrated that this signature had an independent prognostic value. The area under the curve (AUC) values of the receiver operating characteristic (ROC) curve at 1, 3, and 5 years of survival were 0.724, 0.702, and 0.776, respectively. We further demonstrated that our signature has better prognostic performance than recently published ones and is superior to traditional clinical factors such as grade and tumor node metastasis classification (TNM) stage in predicting survival. Moreover, we found higher abundance of CD8+ T cells and lower M2-like macrophages in the low-risk group of TCGA-PDAC, and predicted a higher proportion of immunotherapeutic responders in the low-risk group.ConclusionsWe constructed an optimal prognostic model which had independent prognostic value and was comprehensively validated in external PDAC databases. Additionally, this five-genes signature could predict immune infiltration characteristics. Moreover, the signature helped stratify PDAC patients who might be more responsive to immunotherapy.

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Area of residual tumor (ART) can predict prognosis after post neoadjuvant therapy resection for pancreatic ductal adenocarcinoma.

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Area of residual tumor (ART) can predict prognosis after post neoadjuvant therapy resection for pancreatic ductal adenocarcinoma.

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