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Pancreatic Neoplasms: HELP
Articles by Peter J. Allen
Based on 116 articles published since 2010
(Why 116 articles?)
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Between 2010 and 2020, P. J. Allen wrote the following 116 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4 · 5
1 Guideline ACR Appropriateness Criteria 2017

Anonymous6400925 / Qayyum, Aliya / Tamm, Eric P / Kamel, Ihab R / Allen, Peter J / Arif-Tiwari, Hina / Chernyak, Victoria / Gonda, Tamas A / Grajo, Joseph R / Hindman, Nicole M / Horowitz, Jeanne M / Kaur, Harmeet / McNamara, Michelle M / Noto, Richard B / Srivastava, Pavan K / Lalani, Tasneem. ·Principal Author, University of Texas MD Anderson Cancer Center, Houston, Texas. Electronic address: aqayyum@mdanderson.org. · Research Author, University of Texas MD Anderson Cancer Center, Houston, Texas. · Panel Chair, Johns Hopkins University School of Medicine, Baltimore, Maryland. · Memorial Sloan Kettering Cancer Center, New York, New York; American College of Surgeons. · University of Arizona, Banner University Medical Center, Tucson, Arizona. · Montefiore Medical Center, Bronx, New York. · Columbia University, New York, New York; American Gastroenterological Association. · University of Florida College of Medicine, Gainesville, Florida. · New York University Medical Center, New York, New York. · Northwestern University, Chicago, Illinois. · University of Texas MD Anderson Cancer Center, Houston, Texas. · University of Alabama Medical Center, Birmingham, Alabama. · The Warren Alpert School of Medicine at Brown University, Providence, Rhode Island. · University of Illinois College of Medicine, Chicago, Illinois; American College of Physicians. · Specialty Chair, University of Washington, Seattle, Washington. ·J Am Coll Radiol · Pubmed #29101993.

ABSTRACT: Pancreatic adenocarcinoma is associated with poor overall prognosis. Complete surgical resection is the only possible option for cure. As such, increasingly complex surgical techniques including sophisticated vascular reconstruction are being used. Continued advances in surgical techniques, in conjunction with use of combination systemic therapies, and radiation therapy have been suggested to improve outcomes. A key aspect to surgical success is reporting of pivotal findings beyond absence of distant metastases, such as tumor size, location, and degree of tumor involvement of specific vessels associated with potential perineural tumor spread. Multiphase contrast-enhanced multidetector CT and MRI are the imaging modalities of choice for pretreatment staging and presurgical determination of resectability. Imaging modalities such as endoscopic ultrasound and fluorine-18-2-fluoro-2-deoxy-D-glucose imaging with PET/CT are indicated for specific scenarios such as biopsy guidance and confirmation of distant metastases, respectively. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

2 Guideline Pathologic Evaluation and Reporting of Intraductal Papillary Mucinous Neoplasms of the Pancreas and Other Tumoral Intraepithelial Neoplasms of Pancreatobiliary Tract: Recommendations of Verona Consensus Meeting. 2016

Adsay, Volkan / Mino-Kenudson, Mari / Furukawa, Toru / Basturk, Olca / Zamboni, Giuseppe / Marchegiani, Giovanni / Bassi, Claudio / Salvia, Roberto / Malleo, Giuseppe / Paiella, Salvatore / Wolfgang, Christopher L / Matthaei, Hanno / Offerhaus, G Johan / Adham, Mustapha / Bruno, Marco J / Reid, Michelle D / Krasinskas, Alyssa / Klöppel, Günter / Ohike, Nobuyuki / Tajiri, Takuma / Jang, Kee-Taek / Roa, Juan Carlos / Allen, Peter / Fernández-del Castillo, Carlos / Jang, Jin-Young / Klimstra, David S / Hruban, Ralph H / Anonymous6190823. ·*Department of Pathology, Emory University School of Medicine and Winship Cancer Institute, Atlanta, GA †Department of Pathology, Massachusetts General Hospital, Boston, MA ‡Department of Pathology, Tokyo Women's Medical University, Tokyo, Japan §Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY ¶Department of Pathology, University of Verona, Verona, Italy ||Department of Surgery, Massachusetts General Hospital, Boston, MA **Department of Surgery, University of Verona, Verona, Italy ††Department of Surgery, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD ‡‡Departments of Surgery, University of Bonn, Bonn, Germany §§Departments of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands ¶¶Department of Surgery, Edouard Herriot Hospital, HCL, Lyon, France ||||Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands ***Departments of Pathology, Technical University, Munich, Germany †††Department of Pathology, Showa University Fujigaoka Hospital, Yokohama, Japan ‡‡‡Department of Pathology, Tokai University Hachioji Hospital, Tokyo, Japan §§§Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea ¶¶¶Department of Pathology, Pontificia Universidad Católica de Chile, Santiago, Chile ||||||Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY ****Department of Surgery, Massachusetts General Hospital, Boston, MA ††††Department of Surgery, Seoul National University Hospital, Seoul, Korea ‡‡‡‡Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD. ·Ann Surg · Pubmed #25775066.

ABSTRACT: BACKGROUND: There are no established guidelines for pathologic diagnosis/reporting of intraductal papillary mucinous neoplasms (IPMNs). DESIGN: An international multidisciplinary group, brought together by the Verona Pancreas Group in Italy-2013, was tasked to devise recommendations. RESULTS: (1) Crucial to rule out invasive carcinoma with extensive (if not complete) sampling. (2) Invasive component is to be documented in a full synoptic report including its size, type, grade, and stage. (3) The term "minimally invasive" should be avoided; instead, invasion size with stage and substaging of T1 (1a, b, c; ≤ 0.5, > 0.5-≤ 1, > 1 cm) is to be documented. (4) Largest diameter of the invasion, not the distance from the nearest duct, is to be used. (5) A category of "indeterminate/(suspicious) for invasion" is acceptable for rare cases. (6) The term "malignant" IPMN should be avoided. (7) The highest grade of dysplasia in the non-invasive component is to be documented separately. (8) Lesion size is to be correlated with imaging findings in cysts with rupture. (9) The main duct diameter and, if possible, its involvement are to be documented; however, it is not required to provide main versus branch duct classification in the resected tumor. (10) Subtyping as gastric/intestinal/pancreatobiliary/oncocytic/mixed is of value. (11) Frozen section is to be performed highly selectively, with appreciation of its shortcomings. (12) These principles also apply to other similar tumoral intraepithelial neoplasms (mucinous cystic neoplasms, intra-ampullary, and intra-biliary/cholecystic). CONCLUSIONS: These recommendations will ensure proper communication of salient tumor characteristics to the management teams, accurate comparison of data between analyses, and development of more effective management algorithms.

3 Editorial Significance of pathologic response to preoperative therapy in pancreatic cancer: the future ain't what it used to be. 2011

Allen, Peter J. · ·Ann Surg Oncol · Pubmed #21947699.

ABSTRACT: -- No abstract --

4 Review How Long Should Patients with Cystic Lesions of the Pancreas Be Followed? 2018

McIntyre, Caitlin A / Allen, Peter J. ·Department of Surgery, Hepatopancreatobiliary Service, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA. · Department of Surgery, Hepatopancreatobiliary Service, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA. Electronic address: allenp@mskcc.org. ·Adv Surg · Pubmed #30098614.

ABSTRACT: -- No abstract --

5 Review FOLFIRINOX for locally advanced pancreatic cancer: a systematic review and patient-level meta-analysis. 2016

Suker, Mustafa / Beumer, Berend R / Sadot, Eran / Marthey, Lysiane / Faris, Jason E / Mellon, Eric A / El-Rayes, Bassel F / Wang-Gillam, Andrea / Lacy, Jill / Hosein, Peter J / Moorcraft, Sing Yu / Conroy, Thierry / Hohla, Florian / Allen, Peter / Taieb, Julien / Hong, Theodore S / Shridhar, Ravi / Chau, Ian / van Eijck, Casper H / Koerkamp, Bas Groot. ·Department of Surgery, Erasmus University Medical Centre, Rotterdam, Netherlands. · Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA. · Department of Hepatogastroenterology, Antoine Beclère Hospital, Assistance publique-Hôpitaux de Paris, Paris Sud University, Clamart, France. · Department of Hematology-Oncology, Massachusetts General Hospital, Boston, MA, USA. · Department of Radiation Oncology, H Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA. · Department of Hematology and Medical Oncology, Emory University, Atlanta, GA, USA. · Department of Medicine, Washington University School of Medicine, Saint Louis, MO, USA. · Department of Medicine, Yale Cancer Center, Yale School of Medicine, New Haven, CT, USA. · Department of Medicine, Division of Medical Oncology, University of Kentucky-Markey Cancer Center, Lexington, KY, USA. · Department of Medicine, The Royal Marsden National Health Service Foundation Trust, London and Surrey, UK. · Department of Medical Oncology, Institut de Cancérologie de Lorraine and Lorraine University, Vandoeuvre-lès-Nancy, France. · Department of Hematology, Medical Oncology, Hemostasis, Rheumatology and Infectious Diseases, Paracelsus Medical University of Salzburg, Salzburg, Austria. · Department of Gastroenterology and Digestive Oncology, Georges Pompidou European Hospital, Assistance publique-Hôpitaux de Paris, Sorbonne Paris Cité, Paris Descartes University, Cancer Research Personalized Medicine (CARPEM), Paris, France. · Department of Radiation Oncology, Florida Hospital Cancer Institute, Orlando, FL, USA. · Department of Surgery, Erasmus University Medical Centre, Rotterdam, Netherlands. Electronic address: b.grootkoerkamp@erasmusmc.nl. ·Lancet Oncol · Pubmed #27160474.

ABSTRACT: BACKGROUND: 35% of patients with pancreatic cancer have unresectable locally advanced disease at diagnosis. Several studies have examined systemic chemotherapy with FOLFIRINOX (leucovorin and fluorouracil plus irinotecan and oxaliplatin) in patients with locally advanced pancreatic cancer. We aimed to assess the effectiveness of FOLFIRINOX as first-line treatment in this patient population. METHODS: We systematically searched Embase, MEDLINE (OvidSP), Web of Science, Scopus, PubMed Publisher, Cochrane, and Google Scholar from July 1, 1994, to July 2, 2015, for studies of treatment-naive patients of any age who received FOLFIRINOX as first-line treatment of locally advanced pancreatic cancer. Our primary outcome was overall survival. Secondary outcomes were progression-free survival; rates of grade 3 or 4 adverse events; and the proportion of patients who underwent radiotherapy or chemoradiotherapy, surgical resection after FOLFIRINOX, and R0 resection. We evaluated survival outcomes with the Kaplan-Meier method with patient-level data. Grade 3 or 4 adverse events, and the proportion of patients who underwent subsequent radiotherapy or chemoradiotherapy or resection, were pooled in a random-effects model. FINDINGS: We included 13 studies comprising 689 patients, of whom 355 (52%) patients had locally advanced pancreatic cancer. 11 studies, comprising 315 patients with locally advanced disease, reported survival outcomes and were eligible for patient-level meta-analysis. Median overall survival from the start of FOLFIRINOX ranged from 10·0 months (95% CI 4·0-16·0) to 32·7 months (23·1-42·3) across studies with a pooled patient-level median overall survival of 24·2 months (95% CI 21·7-26·8). Median progression-free survival ranged from 3·0 months (95% CI not calculable) to 20·4 months (6·5-34·3) across studies with a patient-level median progression-free survival of 15·0 months (95% 13·8-16·2). In ten studies comprising 490 patients, 296 grade 3 or 4 adverse events were reported (60·4 events per 100 patients). No deaths were attributed to FOLFIRINOX toxicity. The proportion of patients who underwent radiotherapy or chemoradiotherapy ranged from 31% to 100% across studies. In eight studies, 154 (57%) of 271 patients received radiotherapy or chemoradiotherapy after FOLFIRINOX. The pooled proportion of patients who received any radiotherapy treatment was 63·5% (95% CI 43·3-81·6, I(2) 90%). The proportion of patients who underwent surgical resection for locally advanced pancreatic cancer ranged from 0% to 43%. The proportion of patients who had R0 resection of those who underwent resection ranged from 50% to 100% across studies. In 12 studies, 91 (28%) of 325 patients underwent resection after FOLFIRINOX. The pooled proportion of patients who had resection was 25·9% (95% CI 20·2-31·9, I(2) 24%). R0 resection was reported in 60 (74%) of 81 patients. The pooled proportion of patients who had R0 resection was 78·4% (95% CI 60·2-92·2, I(2) 64%). INTERPRETATION: Patients with locally advanced pancreatic cancer treated with FOLFIRINOX had a median overall survival of 24·2 months-longer than that reported with gemcitabine (6-13 months). Future research should assess these promising results in a randomised controlled trial, and should establish which patients might benefit from radiotherapy or chemoradiotherapy or resection after FOLFIRINOX. FUNDING: None.

6 Review Therapeutic Approach to Cystic Neoplasms of the Pancreas. 2016

Al Efishat, Mohammad / Allen, Peter J. ·Department of Surgery, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA; Department of Surgery, Johns Hopkins Hospital, 600 N Wolfe Street, Baltimore, MD 21287, USA. · Department of Surgery, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA. Electronic address: allenp@mskcc.org. ·Surg Oncol Clin N Am · Pubmed #27013369.

ABSTRACT: Management of cystic neoplasms of the pancreas is challenging as it relies on radiologic and cyst fluid markers to discriminate between benign and pre-cancerous lesions, however their ability to predict malignancy is limited. While asymptomatic serous cystadenomas can be managed conservatively, mucinous cystic neoplasms and intraductal papillary mucinous neoplasms are more difficult to manage. A selective approach, based on the preoperative likelihood of high-grade dysplasia or invasive disease, is the standard of care. Research is focusing on the development of pre-operative markers for identifying high risk lesions, which will spare patients with low-risk or benign lesions the risks of pancreatectomy.

7 Review Cystic Neoplasms of the Pancreas. 2016

Chandwani, Rohit / Allen, Peter J. ·Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065; email: chandwar@mskcc.org , allenp@mskcc.org. ·Annu Rev Med · Pubmed #26565675.

ABSTRACT: Cystic neoplasms of the pancreas are being identified at an increasing frequency largely due to the increased use of abdominal cross-sectional imaging. These neoplasms represent a heterogeneous group of tumors with various genetic alterations, molecular features, and risks of malignancy. Despite the use of high-resolution radiographic studies, endoscopic evaluation, cyst fluid analysis, and novel molecular diagnostics, many of these lesions remain difficult to classify without operative resection. These diagnostic challenges are coupled with an improving but limited understanding of the natural history of these neoplasms. Treatment of pancreatic cystic neoplasms therefore remains controversial but consists largely of a selective tumor-specific approach to surgical resection. Future research remains necessary to better discriminate the biological behavior of these tumors in order to more appropriately select patients for operative intervention.

8 Review Premalignant cystic neoplasms of the pancreas. 2015

Dudeja, Vikas / Allen, Peter J. ·Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY. · Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY. Electronic address: allenp@mskcc.org. ·Semin Oncol · Pubmed #25726053.

ABSTRACT: Due to increasing utilization of cross-sectional imaging, asymptomatic pancreatic cysts are frequently being diagnosed. Many of these cysts have premalignant potential and offer a unique opportunity for cancer prevention. Mucinous cystic neoplasm and intraductal papillary mucinous neoplasm are the major premalignant cystic neoplasms of pancreas. The prediction of the risk of malignancy (incidental and future risk of malignant transformation) and balancing the risks of watchful waiting with that of operative management with associated mortality and morbidity is the key to the management of these lesions. We review the literature that has contributed to the development of our approach to the management of these cystic neoplasms. We provide an overview of the key features used in diagnosis and in predicting malignancy. Particular attention is given to the natural history and management decision making.

9 Review Minimally-invasive vs open pancreaticoduodenectomy: systematic review and meta-analysis. 2014

Correa-Gallego, Camilo / Dinkelspiel, Helen E / Sulimanoff, Isabel / Fisher, Sarah / Viñuela, Eduardo F / Kingham, T Peter / Fong, Yuman / DeMatteo, Ronald P / D'Angelica, Michael I / Jarnagin, William R / Allen, Peter J. ·Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY. · Division of Gynecologic Oncology, New York Presbyterian Hospital, Weill Cornell Medical Center, New York, NY. · Medical Library, Memorial Sloan-Kettering Cancer Center, New York, NY. · Department of Surgery, Emory University Hospital, Atlanta, GA. · Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY. Electronic address: allenp@mskcc.org. ·J Am Coll Surg · Pubmed #24275074.

ABSTRACT: -- No abstract --

10 Review Pancreatic metastasectomy: the Memorial Sloan-Kettering experience and a review of the literature. 2014

Untch, Brian R / Allen, Peter J. ·Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York. ·J Surg Oncol · Pubmed #24122337.

ABSTRACT: Isolated pancreatic metastases may occur in patients with many types of cancer. Several retrospective case series have been published demonstrating the feasibility of resection in selected patients. Here we report our experience with pancreatic metastasectomy in 70 patients and review the published literature. Our findings suggest that long-term survival is associated with resection in selected patients but these outcomes must be weighed against the significant morbidity that is associated with pancreatic resection.

11 Clinical Trial Percutaneous Peritoneal Lavage for the Rapid Staging of Gastric and Pancreatic Cancer. 2017

Pak, Linda M / Coit, Daniel G / Eaton, Anne A / Allen, Peter J / D'Angelica, Michael I / DeMatteo, Ronald P / Jarnagin, William R / Strong, Vivian E / Kingham, T Peter. ·Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA. · Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA. · Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA. kinghamt@mskcc.org. ·Ann Surg Oncol · Pubmed #28058561.

ABSTRACT: BACKGROUND: Positive peritoneal cytology is classified as M1 disease in gastric and pancreatic cancer. While peritoneal cytology is typically obtained by laparoscopic peritoneal lavage, this study sought to examine the feasibility and safety of performing this percutaneously, with monitored anesthesia care and in combination with other diagnostic procedures to condense and expedite the staging process. METHODS: Patients with gastric or pancreatic cancer scheduled for laparoscopy with peritoneal lavage were prospectively enrolled to undergo intraoperative percutaneous peritoneal lavage prior to laparoscopic peritoneal lavage. Saline was infused through a percutaneously-inserted catheter and fluid was collected for peritoneal cytology. Three-quadrant washings collected during laparoscopy were also sent for peritoneal cytology. The primary outcome was to evaluate the sensitivity and specificity of percutaneous peritoneal lavage for detecting positive peritoneal cytology compared with the gold standard of laparoscopic peritoneal lavage, while the secondary outcome was to determine safety. RESULTS: Percutaneous peritoneal lavage was successfully performed in 70 of 76 patients (92%). Ten of 48 gastric cancer patients (21%) and three of 22 pancreatic cancer patients (14%) had positive percutaneous and laparoscopic peritoneal cytology. Two additional gastric cancer patients had positive laparoscopic peritoneal cytology only. Sensitivity and specificity of percutaneous peritoneal lavage compared with laparoscopic peritoneal lavage were 87% and 100%, respectively. No complications occurred with percutaneous peritoneal lavage. CONCLUSIONS: Percutaneous peritoneal lavage is a safe and effective minimally invasive alternative to laparoscopic peritoneal lavage for the diagnosis of metastatic gastric and pancreatic cancer. It is possible this can be utilized in an outpatient setting, such as during endoscopy, to allow for earlier diagnosis of M1 disease and decreased time to appropriate treatment.

12 Clinical Trial Human Trial of a Genetically Modified Herpes Simplex Virus for Rapid Detection of Positive Peritoneal Cytology in the Staging of Pancreatic Cancer. 2016

Kelly, Kaitlyn J / Wong, Joyce / Gönen, Mithat / Allen, Peter / Brennan, Murray / Coit, Daniel / Fong, Yuman. ·Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, United States. · Department of Epidemiology and Statistics, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, United States. · Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, United States. Electronic address: yfong@coh.org. ·EBioMedicine · Pubmed #27322463.

ABSTRACT: INTRODUCTION: Patients with peritoneal dissemination of pancreatic adenocarcinoma do not benefit from surgical resection, but radiologic and cytologic detection of peritoneal cancer lack sensitivity. This trial sought to determine if an oncolytic virus may be used as a diagnostic agent to detect peritoneal cancer. METHODS: Peritoneal washings from patients with pancreatic adenocarcinoma were incubated with the enhanced green fluorescent protein (eGFP)-expressing oncolytic herpes simplex virus (HSV) NV1066. eGFP-positive or negative status was recorded for each specimen and compared to results obtained by conventional cytologic evaluation. These results were correlated with recurrence and survival for patients who underwent R0 resection. RESULTS: Of 82 patients entered in this trial, 12 (15%) had positive cytology and 50 (61%) had virally-mediated eGFP positive cells in peritoneal washings. All cytology-positive patients were also eGFP positive. HSV-mediated fluorescence detection had sensitivities of 94% and 100% for detection of any and peritoneal metastatic disease; respectively. Median recurrence free and disease specific survival were 6.5 and 18.3months for eGFP positive patients, versus 12.2 and 36.2months for eGFP negative patients (P=0.01 and 0.19); respectively. CONCLUSIONS: A genetically modified HSV can be used as a highly sensitive diagnostic agent for detection of micro-metastatic disease in patients with pancreatic adenocarcinoma and may improve patient selection for surgery.

13 Clinical Trial Health-Related Quality of Life After Pancreatectomy: Results From a Randomized Controlled Trial. 2016

Eaton, Anne A / Gonen, Mithat / Karanicolas, Paul / Jarnagin, William R / D'Angelica, Michael I / DeMatteo, Ronald / Kingham, T Peter / Allen, Peter J. ·Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA. eatona@mskcc.org. · Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA. · Odette Cancer Research Program, Sunnybrook Health Sciences Center, Toronto, ON, Canada. · Hepatopancreatobiliary Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA. ·Ann Surg Oncol · Pubmed #26786091.

ABSTRACT: BACKGROUND: A recent prospective randomized trial demonstrated that prophylactic pasireotide reduces the incidence of pancreatic complications (PC) after resection. This secondary analysis aimed to describe quality of life (QoL) before and after resection, to characterize the impact of PC on QoL, and to assess whether pasireotide improves QoL. METHODS: A randomized, double-blind, placebo-controlled trial of preoperative pasireotide in patients undergoing pancreatectomy was conducted. Participants completed the European Organization for Research and Treatment of Cancer (EORTC) C30 and PAN26 modules preoperatively and on postoperative days 14 and 60. Scores were compared using t tests. The percentage of patients with clinically important worsening (a decline ≥0.5 times the baseline standard deviation) was reported. RESULTS: All questionnaires were completed by 87 % (260/300) of the patients. No major differences were observed between the pasireotide and placebo groups. Therefore, the data were pooled for further analyses. A significant worsening of function at 14 days was detected on all the PAN26 and C30 function scales except hepatic and emotional functioning (EF), and on all the C30 symptom scales. More than 75 % of the patients experienced clinically important worsening of fatigue, pain, and role functioning. Most effects persisted at 60 days, with the 60-day EF significantly better than at baseline (p = 0.03). PC were associated with worse outcomes on most function scales. CONCLUSIONS: During the 14 days after resection, patients can be expected to have a significant decline in QoL. Many symptoms abate by 60 days, and EF improves. PC were associated with impaired QoL in several domains. Although pasireotide effectively reduced PC, its effect did not appear to translate to improved QoL in this sample of 300 patients.

14 Clinical Trial A single-arm, nonrandomized phase II trial of neoadjuvant gemcitabine and oxaliplatin in patients with resectable pancreas adenocarcinoma. 2014

OʼReilly, Eileen M / Perelshteyn, Anna / Jarnagin, William R / Schattner, Mark / Gerdes, Hans / Capanu, Marinela / Tang, Laura H / LaValle, Joseph / Winston, Corinne / DeMatteo, Ronald P / DʼAngelica, Michael / Kurtz, Robert C / Abou-Alfa, Ghassan K / Klimstra, David S / Lowery, Maeve A / Brennan, Murray F / Coit, Daniel G / Reidy, Diane L / Kingham, T Peter / Allen, Peter J. ·*Gastrointestinal Oncology Service †Department of Medicine ‡Hepatopancreaticobiliary Surgery Service §Gastroenterology and Nutrition Service Departments of ¶Epidemiology and Biostatistics ‖Pathology **Radiology ††Surgery; and ‡‡Gastric and Mixed Tumor Service, Memorial Sloan-Kettering Cancer Center, New York, NY. ·Ann Surg · Pubmed #24901360.

ABSTRACT: BACKGROUND: The role for neoadjuvant systemic therapy in resectable pancreas adenocarcinoma remains undefined. OBJECTIVE: We evaluated the efficacy of gemcitabine and oxaliplatin administered as preoperative therapy in patients with resectable pancreas adenocarcinoma. METHODS: Eligible patients were screened using computed tomography-pancreas angiography, laparoscopy, endoscopic ultrasonography, and fine-needle aspiration cytology to identify 38 patients who received 4 cycles of neoadjuvant gemcitabine 1000 mg/m intravenously over 100 minutes and oxaliplatin 80 mg/m intravenously over 2 hours, every 2 weeks. Patients whose tumors remained resectable at restaging proceeded to operation and subsequently received 5 cycles of adjuvant gemcitabine (1000 mg/m intravenously over 30 minutes days 1, 8, and 15 every 4 weeks). The primary endpoint was 18-month overall survival and secondary endpoints included radiological, tumor marker and pathological response to neoadjuvant therapy, time to recurrence, patterns of failure, and feasibility of obtaining preoperative core biopsies. RESULTS: Thirty-five of 38 patients (92%) completed neoadjuvant therapy. Twenty-seven patients underwent tumor resection (resectability rate 71%), of which 26 initiated adjuvant therapy for a total of 23 patients (60.5%) who completed all planned therapy. The 18-month survival was 63% (24 patients alive). The median overall survival for all 38 patients was 27.2 months (95% confidence interval: 17-NA) and the median disease-specific survival was 30.6 months (95% confidence interval: 19-NA). CONCLUSIONS: This study met its endpoint and provided a signal suggesting that exploration of neoadjuvant systemic therapy is worthy of further investigation in resectable pancreas adenocarcinoma. Improved patient selection and more active systemic regimens are key. Clinical trials identification: NCT00536874.

15 Clinical Trial Survival after resection of pancreatic adenocarcinoma: results from a single institution over three decades. 2012

Winter, Jordan M / Brennan, Murray F / Tang, Laura H / D'Angelica, Michael I / Dematteo, Ronald P / Fong, Yuman / Klimstra, David S / Jarnagin, William R / Allen, Peter J. ·Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. winterj@mskcc.org ·Ann Surg Oncol · Pubmed #21761104.

ABSTRACT: BACKGROUND: Randomized trials have demonstrated a benefit associated with adjuvant therapy for pancreatic cancer, and retrospective studies have demonstrated improvements in postoperative mortality. The purpose of this study was to evaluate whether these improvements could be identified in a cohort of patients who underwent resection for pancreatic cancer at a single institution over three decades. METHODS: Short- (30 days), intermediate- (1 year), and long-term survival were compared between decades. Long-term survival focused on patients who survived at least 1 year to minimize the effects of perioperative mortality and patient selection. RESULTS: Between 1983 and 2009, 1147 pancreatic resections were performed for ductal adenocarcinoma, including 123 resections in the 1980s, 399 in the 1990s, and 625 in the 2000s. The 30-day mortality rates were 4.9%, 1.5% (P = 0.03 vs. 1980s), and 1.3% (P = 0.007 vs. 1980s). The 1-year mortality rates were 42%, 31% (P < 0.001 vs. 1980s), and 24% (P < 0.001 vs. 1980s and 1990s). In the group of patients who survived 1 year, the overall survivals were 23.2 months, 25.6 months (P = 0.6 vs. 1980s), and 24.5 months (P = 0.2 vs. 1980s). In a multivariate analysis adjusted for pathologic features, the decade of resection was not a significant predictor of long-term survival (hazard ratio = 1.1, P = 0.3). CONCLUSIONS: Patients who underwent resection for pancreatic cancer between 2000 and 2009 experienced improved operative mortality and 1-year survival compared to those who underwent resection in the 1980s, while the long-term survival was similar over all three decades. These results underscore the need for early detection strategies and more effective adjuvant therapies for patients with pancreatic cancer.

16 Article CT radiomics associations with genotype and stromal content in pancreatic ductal adenocarcinoma. 2019

Attiyeh, Marc A / Chakraborty, Jayasree / McIntyre, Caitlin A / Kappagantula, Rajya / Chou, Yuting / Askan, Gokce / Seier, Kenneth / Gonen, Mithat / Basturk, Olca / Balachandran, Vinod P / Kingham, T Peter / D'Angelica, Michael I / Drebin, Jeffrey A / Jarnagin, William R / Allen, Peter J / Iacobuzio-Donahue, Christine A / Simpson, Amber L / Do, Richard K. ·Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA. · Department of Pathology, Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA. · Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA. · Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, C-276F, New York, NY, 10065, USA. dok@mskcc.org. ·Abdom Radiol (NY) · Pubmed #31243486.

ABSTRACT: 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). Radiomic features of the tumor were extracted from the preoperative CT scan and used to predict genotype and stromal content. RESULTS: The cohort for analysis consisted of 35 patients. Genomic and IHC analysis revealed alterations in KRAS in 34 (97%) patients, and changes in expression of CDKN2A in 29 (83%), SMAD4 in 16 (46%), and in TP53 in 29 (83%) patients. Models created from radiomic features demonstrated associations with SMAD4 status and the number of genes altered. The number of genes altered was the only significant predictor of overall survival (p = 0.016). By linear regression analysis, a prediction model for stromal content achieved an R CONCLUSIONS: In this study, we demonstrate that in PDAC SMAD4 status and tumor stromal content can be predicted using radiomic analysis of preoperative CT imaging. These data show an association between resectable PDAC imaging features and underlying tumor biology and their potential for future precision medicine.

17 Article Cross Validation of the Monoclonal Antibody Das-1 in Identification of High-Risk Mucinous Pancreatic Cystic Lesions. 2019

Das, Koushik K / Geng, Xin / Brown, Jeffrey W / Morales-Oyarvide, Vicente / Huynh, Tiffany / Pergolini, Ilaria / Pitman, Martha B / Ferrone, Cristina / Al Efishat, Mohammad / Haviland, Dana / Thompson, Elizabeth / Wolfgang, Christopher / Lennon, Anne Marie / Allen, Peter / Lillemoe, Keith D / Fields, Ryan C / Hawkins, William G / Liu, Jingxia / Castillo, Carlos Fernandez-Del / Das, Kiron M / Mino-Kenudson, Mari. ·Division of Gastroenterology, Washington University, St Louis, Missouri. Electronic address: k.das@wustl.edu. · Division of Gastroenterology, Rutgers-Robert Wood Johnson Medical School, New Brunswick, New Jersey. · Division of Gastroenterology, Washington University, St Louis, Missouri. · Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts. · Deparment of Pathology, Massachusetts General Hospital, Boston, Massachusetts. · Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York. · Department of Pathology, Johns Hopkins School of Medicine, Baltimore, Maryland. · Department of Surgery Johns Hopkins School of Medicine, Baltimore, Maryland. · Division of Gastroenterology, Johns Hopkins School of Medicine, Baltimore, Maryland. · Department of Surgery, Washington University, St Louis, Missouri. · Deparment of Pathology, Massachusetts General Hospital, Boston, Massachusetts. Electronic address: mminokenudson@partners.org. ·Gastroenterology · Pubmed #31175863.

ABSTRACT: BACKGROUND & AIMS: Although pancreatic cystic lesions (PCLs) are frequently and incidentally detected, it is a challenge to determine their risk of malignancy. In immunohistochemical and enzyme-linked immunosorbent assay (ELISA) analyses of tissue and cyst fluid from pancreatic intraductal papillary mucinous neoplasms, the monoclonal antibody Das-1 identifies those at risk for malignancy with high levels of specificity and sensitivity. We aimed to validate the ability of Das-1 to identify high-risk PCLs in comparison to clinical guidelines and clinical features, using samples from a multicenter cohort. METHODS: We obtained cyst fluid samples of 169 PCLs (90 intraductal papillary mucinous neoplasms, 43 mucinous cystic neoplasms, and 36 non-mucinous cysts) from patients undergoing surgery at 4 tertiary referral centers (January 2010 through June 2017). Histology findings from surgical samples, analyzed independently and centrally re-reviewed in a blinded manner, were used as the reference standard. High-risk PCLs were those with invasive carcinomas, high-grade dysplasia, or intestinal-type intraductal papillary mucinous neoplasms with intermediate-grade dysplasia. An ELISA with Das-1 was performed in parallel using banked cyst fluid samples. We evaluated the biomarker's performance, generated area under the curve values, and conducted multivariate logistic regression using clinical and pathology features. RESULTS: The ELISA for Das-1 identified high-risk PCLs with 88% sensitivity, 99% specificity, and 95% accuracy, at a cutoff optical density value of 0.104. In 10-fold cross-validation analysis with 100 replications, Das-1 identified high-risk PCLs with 88% sensitivity and 98% specificity. The Sendai, Fukuoka, and American Gastroenterological Association guideline criteria identified high-risk PCLs with 46%, 52%, and 74% accuracy (P for comparison to Das-1 ELISA <.001). When we controlled for Das-1 in multivariate regression, main pancreatic duct dilation >5 mm (odds ratio, 14.98; 95% confidence interval, 2.63-108; P < .0012), main pancreatic duct dilation ≥1 cm (odds ratio, 47.9; 95% confidence interval, 6.39-490; P < .0001), and jaundice (odds ratio, 6.16; 95% confidence interval, 1.08-36.7; P = .0397) were significantly associated with high-risk PCLs. CONCLUSIONS: We validated the ability of an ELISA with the monoclonal antibody Das-1 to detect PCLs at risk for malignancy with high levels of sensitivity and specificity. This biomarker might be used in conjunction with clinical guidelines to identify patients at risk for malignancy.

18 Article Pilot study of rapid MR pancreas screening for patients with BRCA mutation. 2019

Corrias, Giuseppe / Raeside, Mitchell C / Agostini, Andrea / Huicochea-Castellanos, Sandra / Aramburu-Nunez, David / Paudyal, Ramesh / Shukla-Dave, Amita / Smelianskaia, Olga / Capanu, Marinela / Zheng, Junting / Fung, Maggie / Kelsen, David P / Mangino, Debra A / Robson, Mark E / Goldfrank, Deborah J / Carter, Jean / Allen, Peter J / Conti, Bettina / Monti, Serena / Do, Richard K G / Mannelli, Lorenzo. ·Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA. · Department of Radiology, University of Cagliari, Cagliari, Italy. · Department of Radiology, Università Politecnica delle Marche, Ancona, Italy. · Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, NY, USA. · Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA. · GE Healthcare, Global MR Applications and Workflow, New York, NY, USA. · Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA. · Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA. · Policlinico Umberto I, Department of Radiology, Sapienza University of Rome, Rome, Italy. · IRCCS SDN, Naples, Italy. · Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA. mannellilorenzo@yahoo.it. ·Eur Radiol · Pubmed #30689033.

ABSTRACT: PURPOSE: To develop and optimize a rapid magnetic resonance imaging (MRI) screening protocol for pancreatic cancer to be performed in conjunction with breast MRI screening in breast cancer susceptibility gene (BRCA)-positive individuals. METHODS: An IRB-approved prospective study was conducted. The rapid screening pancreatic MR protocol was designed to be less than 10 min to be performed after a standard breast MRI protocol. Protocol consisted of coronal NT T2 SSFSE, axial NT T2 SSFSE and axial NT rFOV FOCUS DWI, and axial T1. Images were acquired with the patient in the same prone position of breast MRI using the built-in body coil. Image quality was qualitatively assessed by two radiologists with 12 and 13 years of MRI experience, respectively. The imaging protocol was modified until an endpoint of five consecutive patients with high-quality diagnostic images were achieved. Signal-to-noise ratio and contrast-to-noise ratio were assessed. RESULTS: The rapid pancreas MR protocol was successfully completed in all patients. Diagnostic image quality was achieved for all patients. Excellent image quality was achieved for low b values; however, image quality at higher b values was more variable. In one patient, a pancreatic neuroendocrine tumor was found and the patient was treated surgically. In four patients, small pancreatic cystic lesions were detected. In one subject, a hepatic mass was identified and confirmed as adenoma by liver MRI. CONCLUSION: Rapid MR protocol for pancreatic cancer screening is feasible and has the potential to play a role in screening BRCA patients undergoing breast MRI. KEY POINT: • Develop and optimize a rapid magnetic resonance imaging (MRI) screening protocol for pancreatic cancer to be performed in conjunction with breast MRI screening in BRCA mutation positive individuals.

19 Article ASO Author Reflections: Progression after Resection of Noninvasive or Microinvasive Intraductal Papillary Mucinous Neoplasms. 2018

Al Efishat, Mohammad / Allen, Peter J. ·Department of Surgery, Hepatopancreatobiliary Service, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. · Department of Surgery, Hepatopancreatobiliary Service, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. allenp@mskcc.org. ·Ann Surg Oncol · Pubmed #30324467.

ABSTRACT:

20 Article CT radiomics to predict high-risk intraductal papillary mucinous neoplasms of the pancreas. 2018

Chakraborty, Jayasree / Midya, Abhishek / Gazit, Lior / Attiyeh, Marc / Langdon-Embry, Liana / Allen, Peter J / Do, Richard K G / Simpson, Amber L. ·Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA. · Department of Strategy and Innovation, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA. · Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA. · Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA. ·Med Phys · Pubmed #30176047.

ABSTRACT: PURPOSE: Intraductal papillary mucinous neoplasms (IPMNs) are radiographically visible precursor lesions of pancreatic cancer. Despite standard criteria for assessing risk, only 18% of cysts are malignant at resection. Thus, a large number of patients undergo unnecessary invasive surgery for benign disease. The ability to identify IPMNs with low or high risk of transforming into invasive cancer would optimize patient selection and improve surgical decision-making. The purpose of this study was to investigate quantitative CT imaging features as markers for objective assessment of IPMN risk. METHODS: This retrospective study analyzed pancreatic cyst and parenchyma regions extracted from CT scans in 103 patients to predict IPMN risk. Patients who underwent resection between 2005 and 2015 with pathologically proven branch duct (BD)-IPMN and a preoperative CT scan were included in the study. Expert pathologists categorized IPMNs as low or high risk following resection as part of routine clinical care. We extracted new radiographically inspired features as well as standard texture features and designed prediction models for the categorization of high- and low-risk IPMNs. Five clinical variables were also combined with imaging features to design prediction models. RESULTS: Using images from 103 patients and tenfold cross-validation technique, the novel radiographically inspired imaging features achieved an area under the receiver operating characteristic curve (AUC) of 0.77, demonstrating their predictive power. The combination of these features with clinical variables obtained the best performance (AUC = 0.81). CONCLUSION: The present study demonstrates that features extracted from pretreatment CT images can predict the risk of IPMN. Development of a preoperative model to discriminate between low-risk and high-risk IPMN will improve surgical decision-making.

21 Article Organoid Profiling Identifies Common Responders to Chemotherapy in Pancreatic Cancer. 2018

Tiriac, Hervé / Belleau, Pascal / Engle, Dannielle D / Plenker, Dennis / Deschênes, Astrid / Somerville, Tim D D / Froeling, Fieke E M / Burkhart, Richard A / Denroche, Robert E / Jang, Gun-Ho / Miyabayashi, Koji / Young, C Megan / Patel, Hardik / Ma, Michelle / LaComb, Joseph F / Palmaira, Randze Lerie D / Javed, Ammar A / Huynh, Jasmine C / Johnson, Molly / Arora, Kanika / Robine, Nicolas / Shah, Minita / Sanghvi, Rashesh / Goetz, Austin B / Lowder, Cinthya Y / Martello, Laura / Driehuis, Else / LeComte, Nicolas / Askan, Gokce / Iacobuzio-Donahue, Christine A / Clevers, Hans / Wood, Laura D / Hruban, Ralph H / Thompson, Elizabeth / Aguirre, Andrew J / Wolpin, Brian M / Sasson, Aaron / Kim, Joseph / Wu, Maoxin / Bucobo, Juan Carlos / Allen, Peter / Sejpal, Divyesh V / Nealon, William / Sullivan, James D / Winter, Jordan M / Gimotty, Phyllis A / Grem, Jean L / DiMaio, Dominick J / Buscaglia, Jonathan M / Grandgenett, Paul M / Brody, Jonathan R / Hollingsworth, Michael A / O'Kane, Grainne M / Notta, Faiyaz / Kim, Edward / Crawford, James M / Devoe, Craig / Ocean, Allyson / Wolfgang, Christopher L / Yu, Kenneth H / Li, Ellen / Vakoc, Christopher R / Hubert, Benjamin / Fischer, Sandra E / Wilson, Julie M / Moffitt, Richard / Knox, Jennifer / Krasnitz, Alexander / Gallinger, Steven / Tuveson, David A. ·Cold Spring Harbor Laboratory, Cold Spring Harbor, New York. · Johns Hopkins University, Division of Hepatobiliary and Pancreatic Surgery, Baltimore, Maryland. · PanCuRx Translational Research Initiative, Ontario Institute for Cancer Research, Toronto, Ontario, Canada. · Swiss Federal Institute of Technology Lausanne (EPFL), School of Life Sciences, Swiss Institute for Experimental Cancer Research (ISREC), Laboratory of Tumor Heterogeneity and Stemness in Cancer, Lausanne, Switzerland. · Department of Medicine, Stony Brook University, Stony Brook, New York. · Memorial Sloan Kettering Cancer Center, New York, New York. · University of California, Davis, Comprehensive Cancer Center, Division of Hematology and Oncology, Sacramento, California. · New York Genome Center, New York, New York. · Department of Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania. · SUNY Downstate Medical Center, Department of Medicine, New York, New York. · Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW), Utrecht, the Netherlands. · University Medical Center (UMC), Utrecht, the Netherlands. · Princess Maxime Center (PMC), Utrecht, the Netherlands. · Department of Pathology, Johns Hopkins University, Baltimore, Maryland. · Dana-Farber Cancer Institute, Broad Institute, Boston, Massachusetts. · Department of Surgery, Stony Brook University, Stony Brook, New York. · Department of Pathology, Stony Brook University, Stony Brook, New York. · Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Division of Gastroenterology, Hempstead, New York. · Department of Surgery, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York. · Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania, Philadelphia, Pennsylvania. · Department of Medicine, University of Nebraska Medical Center, Omaha, Nebraska. · Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska. · University of Nebraska Medical Center, Eppley Institute for Research in Cancer and Allied Diseases, Fred & Pamela Buffet Cancer Center, Omaha, Nebraska. · Wallace McCain Centre for Pancreatic Cancer, Department of Medical Oncology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada. · Department of Pathology and Laboratory Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York. · Division of Medical Oncology, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York. · Weill Cornell Medical College, New York, New York. · Department of Pathology, University Health Network, University of Toronto, Toronto, Ontario, Canada. · Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada. · Department of Biomedical Informatics, Stony Brook University, Stony Brook, New York. · PanCuRx Translational Research Initiative, Ontario Institute for Cancer Research, Toronto, Ontario, Canada. dtuveson@cshl.edu steven.gallinger@uhn.ca. · Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada. · Hepatobiliary/Pancreatic Surgical Oncology Program, University Health Network, Toronto, Ontario, Canada. · Cold Spring Harbor Laboratory, Cold Spring Harbor, New York. dtuveson@cshl.edu steven.gallinger@uhn.ca. ·Cancer Discov · Pubmed #29853643.

ABSTRACT: Pancreatic cancer is the most lethal common solid malignancy. Systemic therapies are often ineffective, and predictive biomarkers to guide treatment are urgently needed. We generated a pancreatic cancer patient-derived organoid (PDO) library that recapitulates the mutational spectrum and transcriptional subtypes of primary pancreatic cancer. New driver oncogenes were nominated and transcriptomic analyses revealed unique clusters. PDOs exhibited heterogeneous responses to standard-of-care chemotherapeutics and investigational agents. In a case study manner, we found that PDO therapeutic profiles paralleled patient outcomes and that PDOs enabled longitudinal assessment of chemosensitivity and evaluation of synchronous metastases. We derived organoid-based gene expression signatures of chemosensitivity that predicted improved responses for many patients to chemotherapy in both the adjuvant and advanced disease settings. Finally, we nominated alternative treatment strategies for chemorefractory PDOs using targeted agent therapeutic profiling. We propose that combined molecular and therapeutic profiling of PDOs may predict clinical response and enable prospective therapeutic selection.

22 Article Progression Patterns in the Remnant Pancreas after Resection of Non-Invasive or Micro-Invasive Intraductal Papillary Mucinous Neoplasms (IPMN). 2018

Al Efishat, Mohammad / Attiyeh, Marc A / Eaton, Anne A / Gönen, Mithat / Basturk, Olca / Klimstra, David / D'Angelica, Michael I / DeMatteo, Ronald P / Kingham, T Peter / Balachandran, Vinod / Jarnagin, William R / Allen, Peter J. ·Department of Surgery, Hepatopancreatobiliary Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA. · Department of Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA. · Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA. · Department of Surgery, Hepatopancreatobiliary Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA. allenp@mskcc.org. ·Ann Surg Oncol · Pubmed #29589164.

ABSTRACT: BACKGROUND: Although IPMN are thought to represent a whole-gland disease, segmental resection remains the most frequently performed treatment. We sought to determine the rates, patterns, and predictors of IPMN progression in the pancreatic remnant following segmental resection of noninvasive or microinvasive IPMN. METHODS: A prospectively maintained database was queried to identify all patients who underwent resection of noninvasive or microinvasive IPMN (≤ 10 mm of invasive component) between 1989 and 2015. Progression (recurrence) was defined as either the development of cancer, a new IPMN cystic lesion > 1 cm or ≥ 50% increase in the diameter of residual IPMN lesions in the remnant. Univariate and multivariate cox regression models were created to determine predictors of progression. RESULTS: A total of 319 patients underwent resection for noninvasive and microinvasive IPMN. The median age was 68, 53% had branch-duct (BD) IPMN, and 6% had microinvasive disease. After a median follow-up of 42 months, 71 patients (22%) experienced IPMN progression. Within this group of 71 patients, 11 (16% of recurrence) developed invasive cancer in the pancreatic remnant after a median of 28 months. Twelve patients (17%) experienced progression > 5 years following initial resection. On multivariate analysis, a distal location of the initial lesion was associated with an increased risk of progression (multivariate hazards ratio = 2.43, confidence interval 1.47-4.0, p < 0.001). CONCLUSIONS: In this study, 22% of patients had disease progression following resection of noninvasive or microinvasive IPMN; 16% of these progressions represented invasive disease. These patients represent a high-risk group and should undergo long-term radiographic surveillance.

23 Article Prospective Evaluation of Germline Alterations in Patients With Exocrine Pancreatic Neoplasms. 2018

Lowery, Maeve A / Wong, Winston / Jordan, Emmet J / Lee, Jonathan W / Kemel, Yelena / Vijai, Joseph / Mandelker, Diana / Zehir, Ahmet / Capanu, Marinela / Salo-Mullen, Erin / Arnold, Angela G / Yu, Kenneth H / Varghese, Anna M / Kelsen, David P / Brenner, Robin / Kaufmann, Erica / Ravichandran, Vignesh / Mukherjee, Semanti / Berger, Michael F / Hyman, David M / Klimstra, David S / Abou-Alfa, Ghassan K / Tjan, Catherine / Covington, Christina / Maynard, Hannah / Allen, Peter J / Askan, Gokce / Leach, Steven D / Iacobuzio-Donahue, Christine A / Robson, Mark E / Offit, Kenneth / Stadler, Zsofia K / O'Reilly, Eileen M. ·Department of Medicine. · David M. Rubenstein Center for Pancreatic Cancer Research. · Department of Medicine, Weill Cornell. · Robert and Kate Niehaus Center for Inherited Genomics. · Center for Molecular Oncology. · Department of Pathology. · Department of Epidemiology and Biostatistics. · Department of Surgery. ·J Natl Cancer Inst · Pubmed #29506128.

ABSTRACT: Background: Identification of pathogenic germline alterations (PGAs) has important clinical and therapeutic implications in pancreas cancer. We performed comprehensive germline testing (GT) in an unselected prospective cohort of patients with exocrine pancreatic neoplasms with genotype and phenotype association to facilitate identification of prognostic and/or predictive biomarkers and examine potential therapeutic implications. Methods: Six hundred fifteen unselected patients with exocrine pancreatic neoplasms were prospectively consented for somatic tumor and matched sample profiling for 410-468 genes. GT for PGAs in 76 genes associated with cancer susceptibility was performed in an "identified" manner in 356 (57.9%) patients and in an "anonymized" manner in 259 (42.1%) patients, using an institutional review board-approved protocol. Detailed clinical and pathological features, response to platinum, and overall survival (OS) were collected for the identified cohort. OS was analyzed with Kaplan-Meier curves. Results: PGAs were present in 122 (19.8%) of 615 patients involving 24 different genes, including BRCA1/2, ATM, PALB2, and multiple additional genes associated with the DNA damage response pathway. Of 122 patients with germline alterations, 41.8% did not meet current guidelines for GT. The difference in median OS was not statistically significant between patients with and without PGA (50.8 months, 95% confidence interval = 34.5 to not reached, two-sided P = .94). Loss of heterozygosity was found in 60.0% of BRCA1/2. Conclusions: PGAs frequently occur in pancreas exocrine neoplasms and involve multiple genes beyond those previously associated with hereditary pancreatic cancer. These PGAs are therapeutically actionable in about 5% to 10% of patients. These data support routinely offering GT in all pancreatic ductal adenocarcimona patients with a broad panel of known hereditary cancer predisposition genes.

24 Article Brain Metastases in Pancreatic Ductal Adenocarcinoma: Assessment of Molecular Genotype-Phenotype Features-An Entity With an Increasing Incidence? 2018

Jordan, Emmet J / Lowery, Maeve A / Basturk, Olca / Allen, Peter J / Yu, Kenneth H / Tabar, Viviane / Beal, Kathryn / Reidy, Diane L / Yamada, Yoshiya / Janjigian, Yelena / Abou-Alfa, Ghassan K / O'Reilly, Eileen M. ·Gastrointestinal Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY. · Gastrointestinal Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY; David M. Rubenstein Center for Pancreatic Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY; Weill Cornell Medical College, New York, NY. · Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY. · Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY. · Gastrointestinal Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY; Weill Cornell Medical College, New York, NY. · Department of Neurosurgery, Memorial Sloan Kettering Cancer Center, New York, NY. · Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY. · Gastrointestinal Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY; David M. Rubenstein Center for Pancreatic Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY; Weill Cornell Medical College, New York, NY. Electronic address: oreillye@mskcc.org. ·Clin Colorectal Cancer · Pubmed #29496399.

ABSTRACT: PURPOSE: To assess clinical characteristics of patients with metastatic pancreas ductal adenocarcinoma (PDAC) and brain metastases (BM), and to assess somatic and germ-line molecular profiles where performed. PATIENTS AND METHODS: Patients with PDAC and BM between January 1990 and January 2016 were identified. Molecular characteristics of somatic and germ-line testing where performed in the subset of patients who had provided informed consent. Somatic alterations were assessed by either MSK-IMPACT testing (>340 key cancer genes) or Sequenom testing (8-gene panel). Overall survival was calculated from date of diagnosis to either date of last follow-up or death. Survival after BM was calculated from date of diagnosis of BM by radiology or pathology to either date of last follow-up or death. RESULTS: From a total of 5824 patients with PDAC identified from January 2000 to January 2016, twenty-five patients (0.4%) had BM. Median age at PDAC diagnosis was 58 years. Median time to the development of BM from initial PDAC diagnosis was 17 months (range, 0-79 months). Median overall survival after BM diagnosis was 1.5 months (range, 1-31 months). Overall survival for patients who had craniotomy (n = 4) was 11 months (range, 1-31 months), with 2 long-term survivors at 21 and 31 months, respectively. Four patients had leptomeningeal disease. Six of 25 patients had germ-line testing, and 3 had BRCA mutations (2 BRCA1 and 1 BRCA2). Somatic profiling identified KRAS mutations in 100% (4 G12D, 2 G12V, and 1 Q61K). CONCLUSION: BM from PDAC is a rare event. We identified a speculative association of germ-line BRCA1/2 alterations with BM in PDAC, which requires corroboration. Survival after BM development is poor; prolonged survival occurred in selected patients via a multidisciplinary approach.

25 Article Survival Prediction in Pancreatic Ductal Adenocarcinoma by Quantitative Computed Tomography Image Analysis. 2018

Attiyeh, Marc A / Chakraborty, Jayasree / Doussot, Alexandre / Langdon-Embry, Liana / Mainarich, Shiana / Gönen, Mithat / Balachandran, Vinod P / D'Angelica, Michael I / DeMatteo, Ronald P / Jarnagin, William R / Kingham, T Peter / Allen, Peter J / Simpson, Amber L / Do, Richard K. ·Department of Surgery - Hepatopancreatobiliary Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA. · Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA. · Department of Surgery - Hepatopancreatobiliary Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA. simpsonl@mskcc.org. · Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA. ·Ann Surg Oncol · Pubmed #29380093.

ABSTRACT: BACKGROUND: Pancreatic cancer is a highly lethal cancer with no established a priori markers of survival. Existing nomograms rely mainly on post-resection data and are of limited utility in directing surgical management. This study investigated the use of quantitative computed tomography (CT) features to preoperatively assess survival for pancreatic ductal adenocarcinoma (PDAC) patients. METHODS: A prospectively maintained database identified consecutive chemotherapy-naive patients with CT angiography and resected PDAC between 2009 and 2012. Variation in CT enhancement patterns was extracted from the tumor region using texture analysis, a quantitative image analysis tool previously described in the literature. Two continuous survival models were constructed, with 70% of the data (training set) using Cox regression, first based only on preoperative serum cancer antigen (CA) 19-9 levels and image features (model A), and then on CA19-9, image features, and the Brennan score (composite pathology score; model B). The remaining 30% of the data (test set) were reserved for independent validation. RESULTS: A total of 161 patients were included in the analysis. Training and test sets contained 113 and 48 patients, respectively. Quantitative image features combined with CA19-9 achieved a c-index of 0.69 [integrated Brier score (IBS) 0.224] on the test data, while combining CA19-9, imaging, and the Brennan score achieved a c-index of 0.74 (IBS 0.200) on the test data. CONCLUSION: We present two continuous survival prediction models for resected PDAC patients. Quantitative analysis of CT texture features is associated with overall survival. Further work includes applying the model to an external dataset to increase the sample size for training and to determine its applicability.

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