Genomic and Molecular Analyses Identify Molecular Subtypes of Pancreatic Cancer Recurrence (original) (raw)
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Academic Radiology, 2019
Materials and Methods: Ninety patients with recurrent pancreatic cancer were retrospectively included in the study. 74.4% had pancreatic head tumors (group 1) and 25.6% pancreatic body and/or tail tumor (group 2). The tumor localization, operative technique, TNM stage, the R-status, tumor grade, lymphovascular, and perineural invasion were recorded. Location of local tumor recurrence, lymph node recurrence, or organ metastases were analyzed on the basis of follow-up CT imaging. Results: Mean recurrence time was 17.4 § 13.2 months. The most common recurrence type was local recurrence (84.4%), followed by lymph node (15.5%), liver (14.4%), and lung metastasis (6.7%). The predominant site of local recurrence in pancreatic head tumors was close to superior mesenteric artery, common hepatic artery, and/or celiac artery (57.4%), followed by area defined by portal vein, inferior vena cava, CA or superior mesenteric artery (31.2%). Patients with pancreatic body and/or tail carcinoma had higher incidence (p = 0.003) of metastatic disease comparing to pancreatic head tumors, while resection margin was the most common type of local tumor recurrence, seen in 46.7% cases versus 8.2% of patients with pancreatic head tumors (p < 0.001). Conclusion: The most common recurrence type in patients with resected pancreatic carcinoma was local recurrence along cardinal arteries. The localization of primary tumor influences the type of tumor relapse and site of local recurrence.
Cancers
The genomic heterogeneity of pancreatic ductal adenocarcinoma (PDAC) is becoming increasingly appreciated. We aimed to evaluate the ability of a triple biomarker panel (S100A4, Ca-125, and mesothelin) to predict: (i) genetic PDAC subtypes; (ii) clinical phenotypes; and (iii) the optimal treatment strategy (neoadjuvant vs. surgery-first) in resectable and borderline resectable PDAC. Patients who underwent resection for resectable and borderline resectable PDAC were included from one single-institutional cohort and one multi-institutional cohort from the Australian Pancreatic Genome Initiative (APGI). Tumors were immunohistochemically evaluated for S100A4, Ca-125, and mesothelin, and a subset from the APGI cohort underwent RNA sequencing. This study included 252 and 226 patients from the single institution and the APGI cohorts, respectively. Triple-negative biomarker status correlated with non-squamous PDAC genotypes (p = 0.020), lower rates of distant recurrence (p = 0.002), and long...
Is Reporting of Recurrence Data Important in Pancreatic Cancer?
2004
Therapeutic approaches to patients with pancreatic cancer have undergone a paradigm shift in recent years. However, little is known about the outcome of patients with recurrent pancreatic cancer who undergo treatment. The purpose of this study was to identify patients with recurrent pancreatic cancer and to determine whether treatment after recurrence had any effect on outcome. A review of all patients undergoing surgical resection with curative intent revealed 70 patients with documented recurrence and complete medical records. Patients were grouped into three categories: group 1 included those who received treatment after recurrence (n = 45), group 2 included those who were not offered treatment (n = 9), and group 3 included those with poor performance status who received no treatment (n = 16). The median overall survival for the three groups was 26, 18, and 14.5 months for groups 1, 2, and 3, respectively (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;.00001). The median survival after recurrence was 10 months, 6 months, and 1 month, respectively, for the three groups (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;.0001). This is the first series we are aware of that compares the outcomes of patients who received treatment after recurrence of pancreatic cancer with the outcomes of those who received no treatment. In this series, it seems that patients who were well enough to tolerate additional therapy had a longer survival than those who received supportive care only. This may be important in the analysis of adjuvant therapy trials of pancreatic cancer with survival as an end point.
Impact of preoperative therapy on patterns of recurrence in pancreatic cancer
HPB, 2014
Background: A theoretical advantage of preoperative therapy in pancreatic adenocarcinoma is that it facilitates the early treatment of micrometastases and reduces postoperative systemic recurrence. Methods: Medical records of 309 consecutive patients undergoing resection of adenocarcinoma in the head of the pancreas were reviewed. Survival was calculated using the Kaplan-Meier method. Associations between preoperative therapy and patterns of recurrence were determined using chi-squared analysis. Results: Preoperative therapy was administered to 108 patients and upfront surgery was performed in 201 patients. Preoperative therapy was associated with a significantly longer median disease-free survival of 14 months compared with 12 months in patients submitted to upfront surgery (P = 0.035). The rate of local disease as a component of first site of recurrence was significantly lower with preoperative therapy (11.3%) than with upfront surgery (22.9%) (P = 0.016). Preoperative therapy was associated with a lower rate of hepatic metastasis (21.7%) than upfront surgery (34.3%) (P = 0.026). Preoperative therapy did not affect rates of peritoneal or pulmonary metastasis. Conclusions: Preoperative therapy for pancreatic cancer was associated with longer disease-free survival and lower rates of local and hepatic recurrences. These data support the use of preoperative therapy to reduce systemic and local failures after resection.
A prospective clinical and biological database for pancreatic adenocarcinoma: the BACAP cohort
BMC Cancer, 2018
Background: The prognosis for pancreatic cancer remains poor despite diagnostic advances and treatments with new chemotherapeutic regimens. The five year survival rate remains below 3%. Consequently, there is an urgent need for new treatments to significantly improve the prognosis. In addition, there is a big gap in terms of the screening, early diagnosis and prevention of pancreatic cancer the incidence of which is increasing dramatically. Methods: Design: the BACAP cohort is a prospective multicenter pancreatic cancer cohort (pancreatic ductal carcinoma) with clinical and multiple biological samples; Participating centers: 15 French academic and private hospitals; Study Population: any cytologically and/or histologically proven pancreatic carcinoma regardless of the stage (resectable, borderline, locally advanced or metastatic) or treatment (surgery, palliative chemotherapy, best supportive care). At least 1500 patients will be included. Clinical data collected include: disease presentation, epidemiological and social factors, baseline biology, radiology, endoscopic ultrasound, staging, pathology, treatments, follow-up (including biological and radiological), and survival. All these data are collected and stored through an e-observation system at a centralized data center. Biological samples and derived products (i.e. before any treatment): blood, saliva, endoscopic ultrasound-guided fine needle aspiration materials from the primary tumor, fine needle biopsy of metastases and surgically resected tissue. DNA and RNA are extracted from fine needle aspiration materials and are quantified and characterized for quality. Whole blood, plasma and serum are isolated from blood samples. Frozen tissues were specifically allocated to the cohort. All derived products and saliva are stored at − 80°C. Main end-points: i) to centralize clinical data together with multiple biological samples that are harmonized in terms of sampling, the post sampling process and storage; ii) to identify new molecular markers for the diagnosis, prognosis and possibly the predictive response to pancreatic cancer surgery and or chemotherapy. Discussion: The BACAP cohort is a unique prospective biological clinical database that provides the opportunity to identify correlations between the presence/expression of a broad panel of biomarkers (DNA, RNA, miRNA, proteins, etc.), epidemiological and social data, various clinical situations, various stages and the differentiation of the tumor, treatments and survival.
Validation and comparison of the molecular classifications of pancreatic carcinomas
Molecular cancer, 2017
Four molecular classifications of pancreatic ductal adenocarcinoma (PDAC), biologically and clinically relevant and based on gene expression profiles, were established in the recent years, including the Collisson's, Moffitt's ("tumor" and "stroma" classifications), and Bailey's classifications. The aim of this study was to validate the prognostic value of the Moffitt's classifications and to compare the Collisson's, Moffitt's, and Bailey's classifications in a large series of samples. We collected clinical and gene expression data of PDAC samples from 15 public data sets, resulting in a total of 846 primary cancer samples, including 601 with survival annotation. All samples were classified according to each of the four multigene classifiers. We confirmed the independent prognostic value of the Moffitt "tumor", Moffitt "stroma", and Bailey's classifications, but not that of the Collisson's classification. Des...