Publications by authors named "Caitlin A Mcintyre"
Despite many decades of research, pancreatic ductal adenocarcinoma (PDAC) remains one of the most difficult cancers to diagnose and treat effectively. Although there have been improvements in the 5-year overall survival rate, it is still very low at 12.5%.
View Article and Find Full Text PDFArticle Synopsis
- Scientists studied 91 cases of pancreatic cancer to understand how the DNA changes in these cancers and what that means for patients.
- They found that having a lot of mutations in the cancer's early development was linked to shorter survival times.
- Different types of tumors showed varying patterns in how they spread and changed, which means pancreatic cancer can act in more than one way in patients.
KRAS mutations in pancreatic ductal adenocarcinoma (PDAC) are suggested to vary in oncogenicity but the implications for human patients have not been explored in depth. We examined 1,360 consecutive PDAC patients undergoing surgical resection and find that KRAS mutations are enriched in early-stage (stage I) disease, owing not to smaller tumor size but increased node-negativity. KRAS tumors are associated with decreased distant recurrence and improved survival as compared to KRAS.
View Article and Find Full Text PDFObjective: We sought to comprehensively profile tissue and cyst fluid in patients with benign, precancerous, and cancerous conditions of the pancreas to characterize the intrinsic pancreatic microbiome.
Summary Background Data: Small studies in pancreatic ductal adenocarcinoma (PDAC) and intraductal papillary mucinous neoplasm (IPMN) have suggested that intra-pancreatic microbial dysbiosis may drive malignant transformation.
Methods: Pancreatic samples were collected at the time of resection from 109 patients.
Article Synopsis
- - The study aimed to analyze the recurrence patterns and treatment outcomes for patients with pancreatic neuroendocrine tumors (PanNETs) after curative surgery, noting that recurrence occurs in 10% to 15% of cases.
- - Out of 1402 patients analyzed over an average of 4.8 years, the five-year recurrence rates were 13% for distant recurrence, almost 1.4% for locoregional, and 0.8% for abdominal nodal recurrence, with subsequent recurrences increasing mortality risk significantly.
- - Patients receiving treatment after recurrence predominantly utilized somatostatin analogs and targeted therapies, and while five-year overall survival after the first recurrence was 74.6%, there
Background: Early-Onset (EO) pancreatic neuroendocrine tumor (PanNET) is a rare disease, but whether it is clinically different from late-onset (LO) PanNET is unknown. Our study aimed to evaluate clinical differences and disease outcomes between EO-PanNET and LO-PanNET and to compare sporadic EO-PanNET with those with a hereditary syndrome.
Methods: Patients with localized PanNET who underwent pancreatectomy at Memorial Sloan Kettering between 2000 and 2017 were identified.
Despite insights gained by bulk DNA sequencing of cancer it remains challenging to resolve the admixture of normal and tumor cells, and/or of distinct tumor subclones; high-throughput single-cell DNA sequencing circumvents these and brings cancer genomic studies to higher resolution. However, its application has been limited to liquid tumors or a small batch of solid tumors, mainly because of the lack of a scalable workflow to process solid tumor samples. Here we optimize a highly automated nuclei extraction workflow that achieves fast and reliable targeted single-nucleus DNA library preparation of 38 samples from 16 pancreatic ductal adenocarcinoma patients, with an average library yield per sample of 2867 single nuclei.
View Article and Find Full Text PDFBackground: Nonfunctional pancreatic neuroendocrine tumors display a wide range of biological behavior, and nodal disease is associated with metastatic disease and poorer survival. The aim of this study was to develop a tool to predict nodal disease in patients with small (≤2 cm) nonfunctional pancreatic neuroendocrine tumors.
Methods: A multicenter retrospective study was performed on patients undergoing resection for small nonfunctional pancreatic neuroendocrine tumors.
Background: Liver metastasis (LM) after pancreatic ductal adenocarcinoma (PDAC) resection is common but difficult to predict and has grave prognosis. We combined preoperative clinicopathological variables and quantitative analysis of computed tomography (CT) imaging to predict early LM.
Methods: We retrospectively evaluated patients with PDAC submitted to resection between 2005 and 2014 and identified clinicopathological variables associated with early LM.
Purpose: Preoperative radiographic differentiation of mucinous cystic neoplasms (MCN) and simple cysts (SLC) of the liver is challenging. Previous data have demonstrated that the finding of septations arising from the cyst wall without indentation on cross-sectional imaging is associated with MCN. We aim to assess whether this radiographic feature is diagnostic of MCN.
View Article and Find Full Text PDFObjective: Prospective evaluation of 2 clinical-molecular models in patients with unknown pathology who underwent endoscopic ultrasound with fine-needle aspiration (EUS-FNA) for a cystic lesion of the pancreas.
Summary Of Background Data: Preoperative prediction of histologic subtype (mucinous vs nonmucinous) and grade of dysplasia in patients with pancreatic cystic neoplasms is challenging. Our group has previously published 2 clinical-molecular nomograms for intraductal papillary mucinous neoplasms (IPMN) that incorporated both clinical/radiographic features and cyst fluid protein markers (sFASL, CA72-4, MMP9, IL-4).
Article Synopsis
- The study focused on patients with locally advanced pancreatic adenocarcinoma (PDAC) who were treated with induction FOLFIRINOX to improve surgical outcomes and survival rates.
- It reviewed the cases of 200 patients, where 70% received radiation therapy and about 18% were able to undergo surgery after treatment.
- Findings showed that resected patients had a median overall survival of 36 months, while patients who remained unresectable but stable had a median survival of about 24 months, highlighting the potential for further treatment optimization in unresectable cases.
Purpose: The therapeutic management of pancreatic neuroendocrine tumors (PanNETs) is based on pathological tumor grade assessment. A noninvasive imaging method to grade tumors would facilitate treatment selection. This study evaluated the ability of quantitative image analysis derived from computed tomography (CT) images to predict PanNET grade.
View Article and Find Full Text PDFBackground: Neutrophil-to-lymphocyte ratio (NLR) has been reported as prognostic in pancreatic ductal adenocarcinoma (PDAC). Data about NLR changes during neoadjuvant therapy (NAT) and its relationship with pathological tumor response and survival are lacking.
Methods: Pancreatic ductal adenocarcinoma patients with NAT followed by resection between 2009 and 2015 were identified from a prospective database.
Purpose: To evaluate the associations between computed tomography (CT) imaging features extracted from the structured American Pancreatic Association (APA)/Society of Abdominal Radiology (SAR) template and overall survival in patients with resected pancreatic ductal adenocarcinoma (PDAC).
Methods: This retrospective analysis included consecutive patients with PDAC who consented to genomic tumor testing and underwent preoperative imaging and curative intent surgical resection from December 2006 to July 2017. Two radiologists assessed preoperative CT imaging using the APA/SAR PDAC-reporting template.
Our paper contributes to the burgeoning field of surgical data science. Specifically, multimodal integration of relevant patient data is used to determine who should undergo a complex pancreatic resection. Intraductal papillary mucinous neoplasms (IPMNs) represent cystic precursor lesions of pancreatic cancer with varying risk for malignancy.
View Article and Find Full Text PDFBackground: A subset of patients have no risk factors for the development of hepatocellular carcinoma (HCC). We evaluated differences in clinical variables between patients with and without risk factors who underwent surgical resection.
Methods: A prospectively maintained database was queried for patients who underwent R0/R1 resection of HCC between 1992 and 2016.
Background: KRAS, TP53, CDKN2A, and SMAD4 are established driver genes in pancreatic ductal adenocarcinoma (PDAC). This study was aimed at determining whether the mutational status of driver genes and those involved in DNA repair pathways are associated with clinical outcomes for individuals who undergo resection.
Methods: Eligible individuals were those who underwent resection of PDAC and consented to targeted sequencing of their primary tumor via Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT).
Background: The association between a positive surgical margin and local recurrence after resection of pancreatic adenocarcinoma (PDAC) has been reported. Assessment of the location of the a positive margin and the specific site of local recurrence has not been well described.
Methods: A prospectively maintained database was queried for patients who underwent R0/R1 pancreaticoduodenectomy for PDAC between 2000 and 2015.
Purpose: Genomic methods can identify homologous recombination deficiency (HRD). Rigorous evaluation of their outcome association to DNA damage response-targeted therapies like platinum in pancreatic ductal adenocarcinoma (PDAC) is essential in maximizing therapeutic outcome.
Experimental Design: We evaluated progression-free survival (PFS) and overall survival (OS) of patients with advanced-stage PDAC, who had both germline- and somatic-targeted gene sequencing.
Entosis is a type of regulated cell death that promotes cancer cell competition. Though several studies have revealed the molecular mechanisms that govern entosis, the clinical and genetic correlates of entosis in human tumors is less well understood. Here we reviewed entotic cell-in-cell (CIC) patterns in a large single institution sequencing cohort (MSK IMPACT clinical sequencing cohort) of more than 1600 human pancreatic ductal adenocarcinoma (PDAC) samples to identify the genetic and clinical correlates of this cellular feature.
View Article and Find Full Text PDFObjective: To evaluate the influence of consensus guidelines on the management of intraductal papillary mucinous neoplasms (IPMN) and the subsequent changes in pathologic outcomes.
Background: Over time, multiple guidelines have been developed to identify high-risk IPMN. We hypothesized that the development and implementation of guidelines should have increased the percentage of resected IPMN with high-risk disease.
Purpose: The aim of this study was to investigate the relationship between CT imaging phenotypes and genetic and biological characteristics in pancreatic ductal adenocarcinoma (PDAC).
Methods: In this retrospective study, consecutive patients between April 2015 and June 2016 who underwent PDAC resection were included if previously consented to a targeted sequencing protocol. Mutation status of known PDAC driver genes (KRAS, TP53, CDKN2A, and SMAD4) in the primary tumor was determined by targeted DNA sequencing and results were validated by immunohistochemistry (IHC).
Objectives: Preoperative determination of the grade of dysplasia in intraductal papillary mucinous neoplasms (IPMNs) is necessary for optimal management. Previous data have suggested that serum neutrophil-to-lymphocyte ratio (NLR) can predict invasive disease in patients with IPMN.
Methods: A prospectively maintained database was queried for consecutive patients who underwent resection of IPMN.