Peter Allen

Positions:

Professor of Surgery

Surgical Oncology
School of Medicine

Chief, Division of Surgical Oncology

Surgical Oncology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

B.A. 1989

Harvard University

M.D. 1993

Dartmouth Medical School

Surgical Intern, Surgery

Walter Reed Army Medical Center

Surgical Resident, Surgery

Walter Reed Army Medical Center

Research Fellow

Memorial Sloan Kettering Cancer Center

Surgical Oncology Fellow, Surgery

Memorial Sloan Kettering Cancer Center

Grants:

Biomarker validation for intraductal papillary mucinous neoplasms of the pancreas

Administered By
Surgical Oncology
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Publications:

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

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 R2 value of 0.731 with a root mean square error of 19.5. 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.
Authors
Attiyeh, MA; Chakraborty, J; McIntyre, CA; Kappagantula, R; Chou, Y; Askan, G; Seier, K; Gonen, M; Basturk, O; Balachandran, VP; Kingham, TP; D'Angelica, MI; Drebin, JA; Jarnagin, WR; Allen, PJ; Iacobuzio-Donahue, CA; Simpson, AL; Do, RK
MLA Citation
Attiyeh, Marc A., et al. “CT radiomics associations with genotype and stromal content in pancreatic ductal adenocarcinoma..” Abdom Radiol (Ny), vol. 44, no. 9, Sept. 2019, pp. 3148–57. Pubmed, doi:10.1007/s00261-019-02112-1.
URI
https://scholars.duke.edu/individual/pub1396792
PMID
31243486
Source
pubmed
Published In
Abdom Radiol (Ny)
Volume
44
Published Date
Start Page
3148
End Page
3157
DOI
10.1007/s00261-019-02112-1

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

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.
Authors
Das, KK; Geng, X; Brown, JW; Morales-Oyarvide, V; Huynh, T; Pergolini, I; Pitman, MB; Ferrone, C; Al Efishat, M; Haviland, D; Thompson, E; Wolfgang, C; Lennon, AM; Allen, P; Lillemoe, KD; Fields, RC; Hawkins, WG; Liu, J; Castillo, CF-D; Das, KM; Mino-Kenudson, M
MLA Citation
Das, Koushik K., et al. “Cross Validation of the Monoclonal Antibody Das-1 in Identification of High-Risk Mucinous Pancreatic Cystic Lesions..” Gastroenterology, vol. 157, no. 3, Sept. 2019, pp. 720-730.e2. Pubmed, doi:10.1053/j.gastro.2019.05.014.
URI
https://scholars.duke.edu/individual/pub1405355
PMID
31175863
Source
pubmed
Published In
Gastroenterology
Volume
157
Published Date
Start Page
720
End Page
730.e2
DOI
10.1053/j.gastro.2019.05.014

Outcome of Pancreatic Cancer Surveillance Among High-Risk Individuals Tested for Germline Mutations in BRCA1 and BRCA2.

Germline mutations in BRCA1/2 are risk factors for pancreatic ductal adenocarcinoma (PDAC). The aim of this study was to evaluate whether results of surveillance for PDAC in high risk individuals (HRI) differ between those with and without a pathogenic BRCA1/2 mutation. This prospective study was conducted within the Pancreatic Tumor Registry at a major cancer center. There were 83 HRIs with ≥1 first-degree relative with PDAC who underwent surveillance and testing for pathogenic germline mutations in BRCA1/2 A secondary analysis includes 18 HRIs with known mutations in BRCA1/2 but with weaker family history. HRIs were evaluated over time using magnetic resonance cholangiopancreatography (MRCP) and endoscopic ultrasound when indicated by MRCP findings. We reviewed imaging results, blinded to mutation status. Demographic information was obtained from interviewer-administered questionnaires. The outcome was the proportion with any pancreatic abnormality identified at initial or follow-up surveillance. Among the 83 HRIs in the main analysis, 48 had a mutation in BRCA1/2 and 35 did not. Overall, 16 of 48 (33%) BRCA1/2-positive and 13 of 35 (37%) BRCA1/2-negative participants had pancreatic abnormalities on imaging; in each group, all but one finding was an intraductal papillary mucinous neoplasm. Among those with pathogenic mutations but weaker family history, results were similar: 7 of 18 (39%) with pancreatic abnormalities. Results of surveillance for pancreatic abnormalities on imaging are similar regardless of BRCA1/2 mutation status. While the results from this small study need confirmation in other studies, at present there does not appear to be increased yield from targeting individuals with BRCA1/2 mutations for surveillance.
Authors
Saldia, A; Olson, SH; Nunes, P; Liang, X; Samson, ML; Salo-Mullen, E; Marcell, V; Stadler, ZK; Allen, PJ; Offit, K; Kurtz, RC
MLA Citation
Saldia, Amethyst, et al. “Outcome of Pancreatic Cancer Surveillance Among High-Risk Individuals Tested for Germline Mutations in BRCA1 and BRCA2..” Cancer Prev Res (Phila), vol. 12, no. 9, Sept. 2019, pp. 599–608. Pubmed, doi:10.1158/1940-6207.CAPR-18-0272.
URI
https://scholars.duke.edu/individual/pub1410284
PMID
31337648
Source
pubmed
Published In
Cancer Prev Res (Phila)
Volume
12
Published Date
Start Page
599
End Page
608
DOI
10.1158/1940-6207.CAPR-18-0272

Benchmarks in Pancreatic Surgery: A Novel Tool for Unbiased Outcome Comparisons.

OBJECTIVE: To use the concept of benchmarking to establish robust and standardized outcome references after pancreatico-duodenectomy (PD). BACKGROUND: Best achievable results after PD are unknown. Consequently, outcome comparisons among different cohorts, centers or with novel surgical techniques remain speculative. METHODS: This multicenter study analyzes consecutive patients (2012-2015) undergoing PD in 23 international expert centers in pancreas surgery. Outcomes in patients without significant comorbidities and major vascular resection (benchmark cases) were analyzed to establish 20 outcome benchmarks for PD. These benchmarks were tested in a cohort with a poorer preoperative physical status (ASA class ≥3) and a cohort treated by minimally invasive approaches. RESULTS: Two thousand three hundred seventy-five (38%) low-risk cases out of a total of 6186 PDs were analyzed, disclosing low in-hospital mortality (≤1.6%) but high morbidity, with a 73% benchmark morbidity rate cumulated within 6 months following surgery. Benchmark cutoffs for pancreatic fistulas (B-C), severe complications (≥ grade 3), and failure-to-rescue rate were 19%, 30%, and 9%, respectively. The ASA ≥3 cohort showed comparable morbidity but a higher in hospital-mortality (3% vs 1.6%) and failure-to-rescue rate (16% vs 9%) than the benchmarks. The proportion of benchmark cases performed varied greatly across centers and continents for both open (9%-93%) and minimally invasive (11%-62%) PD. Centers operating mostly on complex PD cases disclosed better results than those with a majority of low-risk cases. CONCLUSION: The proposed outcome benchmarks for PD, established in a large-scale international patient cohort and tested in 2 different cohorts, may allow for meaningful comparisons between different patient cohorts, centers, countries, and surgical techniques.
Authors
Sánchez-Velázquez, P; Muller, X; Malleo, G; Park, J-S; Hwang, H-K; Napoli, N; Javed, AA; Inoue, Y; Beghdadi, N; Kalisvaart, M; Vigia, E; Walsh, CD; Lovasik, B; Busquets, J; Scandavini, C; Robin, F; Yoshitomi, H; Mackay, TM; Busch, OR; Hartog, H; Heinrich, S; Gleisner, A; Perinel, J; Passeri, M; Lluis, N; Raptis, DA; Tschuor, C; Oberkofler, CE; DeOliveira, ML; Petrowsky, H; Martinie, J; Asbun, H; Adham, M; Schulick, R; Lang, H; Koerkamp, BG; Besselink, MG; Han, H-S; Miyazaki, M; Ferrone, CR; Fernández-Del Castillo, C; Lillemoe, KD; Sulpice, L; Boudjema, K; Del Chiaro, M; Fabregat, J; Kooby, DA; Allen, P; Lavu, H; Yeo, CJ; Barroso, E; Roberts, K; Muiesan, P; Sauvanet, A; Saiura, A; Wolfgang, CL; Cameron, JL; Boggi, U; Yoon, D-S; Bassi, C; Puhan, MA; Clavien, P-A
MLA Citation
Sánchez-Velázquez, Patricia, et al. “Benchmarks in Pancreatic Surgery: A Novel Tool for Unbiased Outcome Comparisons..” Ann Surg, vol. 270, no. 2, Aug. 2019, pp. 211–18. Pubmed, doi:10.1097/SLA.0000000000003223.
URI
https://scholars.duke.edu/individual/pub1403257
PMID
30829701
Source
pubmed
Published In
Ann Surg
Volume
270
Published Date
Start Page
211
End Page
218
DOI
10.1097/SLA.0000000000003223

A multimodality test to guide the management of patients with a pancreatic cyst

Copyright © 2019 The Authors, some rights reserved. Pancreatic cysts are common and often pose a management dilemma, because some cysts are precancerous, whereas others have little risk of developing into invasive cancers. We used supervised machine learning techniques to develop a comprehensive test, CompCyst, to guide the management of patients with pancreatic cysts. The test is based on selected clinical features, imaging characteristics, and cyst fluid genetic and biochemical markers. Using data from 436 patients with pancreatic cysts, we trained CompCyst to classify patients as those who required surgery, those who should be routinely monitored, and those who did not require further surveillance. We then tested CompCyst in an independent cohort of 426 patients, with histopathology used as the gold standard. We found that clinical management informed by the CompCyst test was more accurate than the management dictated by conventional clinical and imaging criteria alone. Application of the CompCyst test would have spared surgery in more than half of the patients who underwent unnecessary resection of their cysts. CompCyst therefore has the potential to reduce the patient morbidity and economic costs associated with current standard-of-care pancreatic cyst management practices.
Authors
Springer, S; Masica, DL; Molin, MD; Douville, C; Thoburn, CJ; Afsari, B; Li, L; Cohen, JD; Thompson, E; Allen, PJ; Klimstra, DS; Schattner, MA; Max Schmidt, C; Yip-Schneider, M; Simpson, RE; Castillo, CFD; Mino-Kenudson, M; Brugge, W; Brand, RE; Singhi, AD; Scarpa, A; Lawlor, R; Salvia, R; Zamboni, G; Hong, SM; Hwang, DW; Jang, JY; Kwon, W; Swan, N; Geoghegan, J; Falconi, M; Crippa, S; Doglioni, C; Paulino, J; Schulick, RD; Edil, BH; Park, W; Yachida, S; Hijioka, S; Van Hooft, J; He, J; Weiss, MJ; Burkhart, R; Makary, M; Canto, MI; Goggins, MG; Ptak, J; Dobbyn, L; Schaefer, J; Sillman, N; Popoli, M; Klein, AP; Tomasetti, C; Karchin, R; Papadopoulos, N; Kinzler, KW; Vogelstein, B; Wolfgang, CL; Hruban, RH; Lennon, AM
MLA Citation
Springer, S., et al. “A multimodality test to guide the management of patients with a pancreatic cyst.” Science Translational Medicine, vol. 11, no. 501, July 2019. Scopus, doi:10.1126/scitranslmed.aav4772.
URI
https://scholars.duke.edu/individual/pub1403256
Source
scopus
Published In
Science Translational Medicine
Volume
11
Published Date
DOI
10.1126/scitranslmed.aav4772