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Pancreatic Neoplasms: HELP
Articles by Natalia Khalaf
Based on 8 articles published since 2010
(Why 8 articles?)
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Between 2010 and 2020, Natalia Khalaf wrote the following 8 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Editorial Metabolic Alterations as a Signpost to Early Pancreatic Cancer. 2019

Khalaf, Natalia / Wolpin, Brian M. ·Department of Medicine, Section of Gastroenterology and Hepatology, Baylor College of Medicine, Houston, Texas. Electronic address: Natalia.khalaf@bcm.edu. · Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts. Electronic address: bwolpin@partners.org. ·Gastroenterology · Pubmed #30926350.

ABSTRACT: -- No abstract --

2 Article Family history of cancer, Ashkenazi Jewish ancestry, and pancreatic cancer risk. 2019

Hamada, Tsuyoshi / Yuan, Chen / Yurgelun, Matthew B / Perez, Kimberly / Khalaf, Natalia / Morales-Oyarvide, Vicente / Babic, Ana / Nowak, Jonathan A / Rubinson, Douglas A / Giannakis, Marios / Ng, Kimmie / Kraft, Peter / Stampfer, Meir J / Giovannucci, Edward L / Fuchs, Charles S / Ogino, Shuji / Wolpin, Brian M. ·Department of Oncologic Pathology, Dana-Farber Cancer Institute and Harvard Medical School, 450 Brookline Avenue, Boston, MA, 02215, USA. · Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, 450 Brookline Avenue, Boston, MA, 02215, USA. · Department of Epidemiology, Harvard T.H. Chan School of Public Health, 677 Huntington Avenue, Boston, MA, 02115, USA. · Division of Gastroenterology, Hepatology, and Endoscopy, Brigham and Women's Hospital and Harvard Medical School, 75 Francis Street, Boston, MA, 02115, USA. · Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, 75 Francis Street, Boston, MA, 02115, USA. · Broad Institute of Massachusetts Institute of Technology and Harvard, 415 Main Street, Cambridge, MA, 02142, USA. · Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 75 Francis Street, Boston, MA, 02115, USA. · Department of Biostatistics, Harvard T.H. Chan School of Public Health, 677 Huntington Avenue, Boston, MA, 02115, USA. · Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 181 Longwood Avenue, Boston, MA, 02115, USA. · Department of Nutrition, Harvard T.H. Chan School of Public Health, 677 Huntington Avenue, Boston, MA, 02115, USA. · Yale Cancer Center, 333 Cedar Street, New Haven, CT, 06510, USA. · Department of Medicine, Yale School of Medicine, 333 Cedar Street, New Haven, CT, 06510, USA. · Smilow Cancer Hospital, 20 York Street, New Haven, CT, 06519, USA. · Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, 450 Brookline Avenue, Boston, MA, 02215, USA. bwolpin@partners.org. ·Br J Cancer · Pubmed #30867564.

ABSTRACT: BACKGROUND: Individuals with a family history of cancer may be at increased risk of pancreatic cancer. Ashkenazi Jewish (AJ) individuals carry increased risk for pancreatic cancer and other cancer types. METHODS: We examined the association between family history of cancer, AJ heritage, and incident pancreatic cancer in 49 410 male participants of the prospective Health Professionals Follow-up Study. Hazard ratios (HRs) were estimated using multivariable-adjusted Cox proportional hazards models. RESULTS: During 1.1 million person-years (1986-2016), 452 participants developed pancreatic cancer. Increased risk of pancreatic cancer was observed in individuals with a family history of pancreatic (HR, 2.79; 95% confidence interval [CI], 1.28-6.07) or breast cancer (HR, 1.40; 95% CI, 1.01-1.94). There was a trend towards higher risk of pancreatic cancer in relation to a family history of colorectal cancer (HR, 1.21; 95% CI, 0.95-1.55) or AJ heritage (HR, 1.29; 95% CI, 0.94-1.77). The risk was highly elevated among AJ men with a family history of breast or colorectal cancer (HR, 2.61 [95% CI, 1.41-4.82] and 1.92 [95% CI, 1.05-3.49], respectively). CONCLUSION: Family history of pancreatic cancer was associated with increased risk of this malignancy. Family history of breast or colorectal cancer was associated with the increased risk among AJ men.

3 Article Germline cancer susceptibility gene variants, somatic second hits, and survival outcomes in patients with resected pancreatic cancer. 2019

Yurgelun, Matthew B / Chittenden, Anu B / Morales-Oyarvide, Vicente / Rubinson, Douglas A / Dunne, Richard F / Kozak, Margaret M / Qian, Zhi Rong / Welch, Marisa W / Brais, Lauren K / Da Silva, Annacarolina / Bui, Justin L / Yuan, Chen / Li, Tingting / Li, Wanwan / Masuda, Atsuhiro / Gu, Mancang / Bullock, Andrea J / Chang, Daniel T / Clancy, Thomas E / Linehan, David C / Findeis-Hosey, Jennifer J / Doyle, Leona A / Thorner, Aaron R / Ducar, Matthew D / Wollison, Bruce M / Khalaf, Natalia / Perez, Kimberly / Syngal, Sapna / Aguirre, Andrew J / Hahn, William C / Meyerson, Matthew L / Fuchs, Charles S / Ogino, Shuji / Hornick, Jason L / Hezel, Aram F / Koong, Albert C / Nowak, Jonathan A / Wolpin, Brian M. ·Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA. matthew_yurgelun@dfci.harvard.edu. · Department of Medicine, Brigham & Women's Hospital, Boston, MA, USA. matthew_yurgelun@dfci.harvard.edu. · Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA. · Department of Medicine, Brigham & Women's Hospital, Boston, MA, USA. · Department of Medicine, Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY, USA. · Department of Radiation Oncology, Stanford Cancer Institute, Stanford, CA, USA. · Department of Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA, USA. · Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA. · Department of Medicine, Division of Hematology/Oncology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA. · Department of Surgery, Brigham & Women's Hospital and Harvard Medical School, Boston, MA, USA. · Department of Surgery, University of Rochester Medical Center, Rochester, NY, USA. · Department of Pathology, University of Rochester Medical Center, Rochester, NY, USA. · Department of Pathology, Brigham & Women's Hospital and Harvard Medical School, Boston, MA, USA. · Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, Boston, MA, USA. · Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, USA. · Yale Cancer Center, Yale School of Medicine, New Haven, CT, USA. · Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. ·Genet Med · Pubmed #29961768.

ABSTRACT: PURPOSE: Germline variants in double-strand DNA damage repair (dsDDR) genes (e.g., BRCA1/2) predispose to pancreatic adenocarcinoma (PDAC) and may predict sensitivity to platinum-based chemotherapy and poly(ADP) ribose polymerase (PARP) inhibitors. We sought to determine the prevalence and significance of germline cancer susceptibility gene variants in PDAC with paired somatic and survival analyses. METHODS: Using a customized next-generation sequencing panel, germline/somatic DNA was analyzed from 289 patients with resected PDAC ascertained without preselection for high-risk features (e.g., young age, personal/family history). All identified variants were assessed for pathogenicity. Outcomes were analyzed using multivariable-adjusted Cox proportional hazards regression. RESULTS: We found that 28/289 (9.7%; 95% confidence interval [CI] 6.5-13.7%) patients carried pathogenic/likely pathogenic germline variants, including 21 (7.3%) dsDDR gene variants (3 BRCA1, 4 BRCA2, 14 other dsDDR genes [ATM, BRIP1, CHEK2, NBN, PALB2, RAD50, RAD51C]), 3 Lynch syndrome, and 4 other genes (APC p.I1307K, CDKN2A, TP53). Somatic sequencing and immunohistochemistry identified second hits in the tumor in 12/27 (44.4%) patients with germline variants (1 failed sequencing). Compared with noncarriers, patients with germline dsDDR gene variants had superior overall survival (hazard ratio [HR] 0.54; 95% CI 0.30-0.99; P = 0.05). CONCLUSION: Nearly 10% of PDAC patients harbor germline variants, although the majority lack somatic second hits, the therapeutic significance of which warrants further study.

4 Article Prediagnosis Use of Statins Associates With Increased Survival Times of Patients With Pancreatic Cancer. 2018

Hamada, Tsuyoshi / Khalaf, Natalia / Yuan, Chen / Morales-Oyarvide, Vicente / Babic, Ana / Nowak, Jonathan A / Qian, Zhi Rong / Ng, Kimmie / Rubinson, Douglas A / Kraft, Peter / Giovannucci, Edward L / Stampfer, Meir J / Fuchs, Charles S / Ogino, Shuji / Wolpin, Brian M. ·Department of Oncologic Pathology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts. · Division of Gastroenterology, Hepatology, and Endoscopy, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. · Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts; Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts. · Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts. · Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. · Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts; Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, Massachusetts. · Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, Massachusetts. · Yale Cancer Center, New Haven, Connecticut; Department of Medicine, Yale School of Medicine, New Haven, Connecticut; Smilow Cancer Hospital, New Haven, Connecticut. · Department of Oncologic Pathology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts; Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts; Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. · Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts. Electronic address: bwolpin@partners.org. ·Clin Gastroenterol Hepatol · Pubmed #29474971.

ABSTRACT: BACKGROUND & AIMS: Statin medications, most commonly prescribed to reduce lipid levels and prevent cardiovascular disease, may be associated with longer survival times of patients with cancer. However, the association of statins with outcomes of patients with pancreatic adenocarcinoma is not clear. METHODS: We analyzed the association of statin use before a diagnosis of pancreatic cancer with survival times of 648 participants in the Nurses' Health Study and Health Professionals Follow-up Study who were diagnosed with pancreatic adenocarcinoma from 2000 through 2013. We estimated hazard ratios (HRs) for overall mortality using Cox proportional hazards models with adjustment for potential confounders. We assessed the temporal association between prediagnosis statin use and cancer survival by 2-year lag periods to account for a possible latency period between statin use and cancer survival. RESULTS: Regular statin use before diagnosis of pancreatic cancer was associated with modestly prolonged survival compared with nonregular use (adjusted HR, 0.82; 95% CI, 0.69-0.97; P = .02). A 1-month longer median survival was observed in regular statin users compared with nonregular users. Regular statin use within the 2 years prior to cancer diagnosis was most strongly associated with longer survival. We observed no statistically significant effect modification by smoking status, body mass index, diabetes, or cancer stage (all P CONCLUSIONS: Regular statin use before diagnosis of pancreatic cancer was associated with modest increases in survival times in 2 large prospective cohort studies.

5 Article Statin use and pancreatic cancer risk in two prospective cohort studies. 2018

Hamada, Tsuyoshi / Khalaf, Natalia / Yuan, Chen / Babic, Ana / Morales-Oyarvide, Vicente / Qian, Zhi Rong / Nowak, Jonathan Andrew / Ng, Kimmie / Kraft, Peter / Rubinson, Douglas Adam / Stampfer, Meir Jonathan / Giovannucci, Edward Luciano / Fuchs, Charles Stewart / Ogino, Shuji / Wolpin, Brian Matthew. ·Department of Oncologic Pathology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA. · Division of Gastroenterology, Hepatology, and Endoscopy, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. · Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, 450 Brookline Avenue, Boston, MA, 02215, USA. · Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA. · Program in MPE Molecular Pathological Epidemiology, Department of Patholog, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. · Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA. · Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. · Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA. · Yale Cancer Center, New Haven, CT, USA. · Department of Medicine, Yale School of Medicine, New Haven, CT, USA. · Smilow Cancer Hospital, New Haven, CT, USA. · Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, 450 Brookline Avenue, Boston, MA, 02215, USA. bwolpin@partners.org. ·J Gastroenterol · Pubmed #29362938.

ABSTRACT: BACKGROUND: Statins, 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, are common lipid-lowering agents and may reduce the risk of several cancer types including pancreatic cancer. However, the association between statin use and pancreatic cancer risk has not been fully evaluated in prospective studies. METHODS: We studied the association between statin use and incident pancreatic cancer in 113,059 participants from the prospective Nurses' Health Study and Health Professionals Follow-up Study. Statin use was self-reported via study questionnaires and updated biennially. Hazard ratios (HRs) and 95% confidence intervals (CIs) for incidence of pancreatic cancer were estimated using multivariable Cox proportional hazards models with adjustment for potential confounders. RESULTS: In total, 583 participants developed incident pancreatic cancer during 1.4 million person-years of follow-up. No difference was identified in pancreatic cancer risk for regular versus non-regular statin users (multivariable-adjusted HR 0.98; 95% CI 0.82-1.16). There was no significant heterogeneity in the association of statin use with pancreatic cancer risk between the cohorts. Similarly, longer duration of regular statin use was not associated with decreased risk of pancreatic cancer (P CONCLUSIONS: Regular statin use was not associated with pancreatic cancer risk in two large prospective cohort studies in the U.S.

6 Article Regular Use of Aspirin or Non-Aspirin Nonsteroidal Anti-Inflammatory Drugs Is Not Associated With Risk of Incident Pancreatic Cancer in Two Large Cohort Studies. 2018

Khalaf, Natalia / Yuan, Chen / Hamada, Tsuyoshi / Cao, Yin / Babic, Ana / Morales-Oyarvide, Vicente / Kraft, Peter / Ng, Kimmie / Giovannucci, Edward / Ogino, Shuji / Stampfer, Meir / Cochrane, Barbara B / Manson, JoAnn E / Clish, Clary B / Chan, Andrew T / Fuchs, Charles S / Wolpin, Brian M. ·Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women's Hospital, Boston, Massachusetts. · Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts. · Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts. · Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts. · Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Program of MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. · School of Nursing, University of Washington, Seattle, Washington. · Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Division of Preventive Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. · Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts. · Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts; Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. · Yale Cancer Center at Yale School of Medicine and Smilow Cancer Hospital, New Haven, Connecticut. · Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts. Electronic address: bwolpin@partners.org. ·Gastroenterology · Pubmed #29229401.

ABSTRACT: BACKGROUND & AIMS: Use of aspirin and/or non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) reduces the risk of several cancers, but it is not clear if use of these drugs is associated with risk of pancreatic cancer. METHODS: We evaluated aspirin and non-aspirin NSAID use and risk of pancreatic adenocarcinoma in 141,940 participants from the Health Professionals Follow-up Study and Nurses' Health Study using multivariable-adjusted Cox proportional hazards regression. We considered several exposure classifications to model differing lag times between NSAID exposure and cancer development. We also conducted a nested case-control study of participants from 3 prospective cohorts using conditional logistic regression to evaluate pre-diagnosis levels of plasma salicylurate, a major metabolite of aspirin, in 396 pancreatic cancer cases and 784 matched individuals without pancreatic cancer (controls). RESULTS: In the prospective cohort study, 1122 participants developed pancreatic adenocarcinoma over 4.2 million person-years. Use of aspirin or non-aspirin NSAIDs was not associated with pancreatic cancer risk, even after considering several latency exposure classifications. In a pre-planned subgroup analysis, regular aspirin use was associated with reduced pancreatic cancer risk among participants with diabetes (relative risk, 0.71; 95% CI, 0.54-0.94). In the nested case-control study, pre-diagnosis levels of salicylurate were not associated with pancreatic cancer risk (odds ratio, 1.08; 95% CI, 0.72-1.61; P CONCLUSIONS: Regular aspirin or non-aspirin NSAID use was not associated with future risk of pancreatic cancer in participants from several large prospective cohort studies. A possible reduction in risk for pancreatic cancer among people with diabetes who regularly use aspirin should be further examined in preclinical and human studies.

7 Article Association of Alterations in Main Driver Genes With Outcomes of Patients With Resected Pancreatic Ductal Adenocarcinoma. 2018

Qian, Zhi Rong / Rubinson, Douglas A / Nowak, Jonathan A / Morales-Oyarvide, Vicente / Dunne, Richard F / Kozak, Margaret M / Welch, Marisa W / Brais, Lauren K / Da Silva, Annacarolina / Li, Tingting / Li, Wanwan / Masuda, Atsuhiro / Yang, Juhong / Shi, Yan / Gu, Mancang / Masugi, Yohei / Bui, Justin / Zellers, Caitlin L / Yuan, Chen / Babic, Ana / Khalaf, Natalia / Aguirre, Andrew / Ng, Kimmie / Miksad, Rebecca A / Bullock, Andrea J / Chang, Daniel T / Tseng, Jennifer F / Clancy, Thomas E / Linehan, David C / Findeis-Hosey, Jennifer J / Doyle, Leona A / Thorner, Aaron R / Ducar, Matthew / Wollison, Bruce / Laing, Angelica / Hahn, William C / Meyerson, Matthew / Fuchs, Charles S / Ogino, Shuji / Hornick, Jason L / Hezel, Aram F / Koong, Albert C / Wolpin, Brian M. ·Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts. · Department of Oncologic Pathology, Dana-Farber Cancer Institute, Boston, Massachusetts. · Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. · Division of Hematology and Oncology, Department of Medicine, Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, New York. · Department of Radiation Oncology, Stanford Cancer Institute, Stanford, California. · Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts. · Division of Gastroenterology, Hepatology, and Endoscopy, Brigham and Women's Hospital, Boston, Massachusetts. · Department of Hematology and Oncology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts. · Department of Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts. · Department of Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. · Department of Surgery, University of Rochester Medical Center, Rochester, New York. · Department of Pathology, University of Rochester Medical Center, Rochester, New York. · Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, Boston, Massachusetts. · Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts. · Division of Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. · Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston. ·JAMA Oncol · Pubmed #29098284.

ABSTRACT: Importance: Although patients with resected pancreatic adenocarcinoma are at high risk for disease recurrence, few biomarkers are available to inform patient outcomes. Objective: To evaluate the alterations of the 4 main driver genes in pancreatic adenocarcinoma and patient outcomes after cancer resection. Design, Setting, and Participants: This study analyzed protein expression and DNA alterations for the KRAS, CDKN2A, SMAD4, and TP53 genes by immunohistochemistry and next-generation sequencing in formalin-fixed, paraffin-embedded tumors in 356 patients with resected pancreatic adenocarcinoma who were treated at the Dana-Farber/Brigham and Women's Cancer Center (October 26, 2002, to May 21, 2012), University of Rochester Medical Center (March 1, 2006, to November 1, 2013), or Stanford Cancer Institute (September 26, 1995, to May 22, 2013). Associations of driver gene alterations with disease-free survival (DFS) and overall survival (OS) were evaluated using Cox proportional hazards regression with estimation of hazard ratios (HRs) and 95% CIs and adjustment for age, sex, tumor characteristics, institution, and perioperative treatment. Data were collected September 9, 2012, to June 28, 2016, and analyzed December 17, 2016, to March 14, 2017. Main Outcomes and Measures: The DFS and OS among patients with resected pancreatic adenocarcinoma. Results: Of the 356 patients studied, 191 (53.7%) were men and 165 (46.3%) were women, with a median (interquartile range [IQR]) age of 67 (59.0-73.5) years. Patients with KRAS mutant tumors had worse DFS (median [IQR], 12.3 [6.7 -27.2] months) and OS (20.3 [11.3-38.3] months) compared with patients with KRAS wild-type tumors (DFS, 16.2 [8.9-30.5] months; OS, 38.6 [16.6-63.1] months) and had 5-year OS of 13.0% vs 30.2%. Particularly poor outcomes were identified in patients with KRAS G12D-mutant tumors, who had a median (IQR) OS of 15.3 (9.8-32.7) months. Patients whose tumors lacked CDKN2A expression had worse DFS (median, 11.5 [IQR, 6.2-24.5] months) and OS (19.7 [10.9-37.1] months) compared with patients who had intact CDKN2A (DFS, 14.8 [8.2-30.5] months; OS, 24.6 [14.1-44.6] months). The molecular status of SMAD4 was not associated with DFS or OS, whereas TP53 status was associated only with shorter DFS (HR, 1.33; 95% CI, 1.02-1.75; P = .04). Patients had worse DFS and OS if they had a greater number of altered driver genes. Compared with patients with 0 to 2 altered genes, those with 4 altered genes had worse DFS (HR, 1.79 [95% CI, 1.24-2.59; P = .002]) and OS (HR, 1.38 [95% CI, 0.98-1.94; P = .06]). Five-year OS was 18.4% for patients with 0 to 2 gene alterations, 14.1% for those with 3 alterations, and 8.2% for those with 4 alterations. Conclusions and Relevance: Patient outcomes are associated with alterations of the 4 main driver genes in resected pancreatic adenocarcinoma.

8 Article Lymph node metastases in resected pancreatic ductal adenocarcinoma: predictors of disease recurrence and survival. 2017

Morales-Oyarvide, Vicente / Rubinson, Douglas A / Dunne, Richard F / Kozak, Margaret M / Bui, Justin L / Yuan, Chen / Qian, Zhi Rong / Babic, Ana / Da Silva, Annacarolina / Nowak, Jonathan A / Khalaf, Natalia / Brais, Lauren K / Welch, Marisa W / Zellers, Caitlin L / Ng, Kimmie / Chang, Daniel T / Miksad, Rebecca A / Bullock, Andrea J / Tseng, Jennifer F / Swanson, Richard S / Clancy, Thomas E / Linehan, David C / Findeis-Hosey, Jennifer J / Doyle, Leona A / Hornick, Jason L / Ogino, Shuji / Fuchs, Charles S / Hezel, Aram F / Koong, Albert C / Wolpin, Brian M. ·Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, 450 Brookline Avenue, Boston, MA 02215, USA. · Department of Medicine, Division of Hematology and Oncology, Wilmot Cancer Institute, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA. · Department of Radiation Oncology, Stanford Cancer Institute, 269 Campus Drive West, Stanford, CA 94305-5152, USA. · Department of Epidemiology, Harvard TH Chan School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA. · Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA. · Division of Gastroenterology, Hepatology, and Endoscopy, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA. · Department of Hematology and Oncology, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA. · Department of Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA. · Department of Surgery, Brigham and Women's Hospital and Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA. · Department of Surgery, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA. · Department of Pathology, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA. · Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, 1840 Old Spanish Trail, Houston, TX 77054, USA. ·Br J Cancer · Pubmed #28982112.

ABSTRACT: BACKGROUND: Few studies have simultaneously assessed the prognostic value of the multiple classification systems for lymph node (LN) metastases in resected pancreatic ductal adenocarcinoma (PDAC). METHODS: In 600 patients with resected PDAC, we examined the association of LN parameters (AJCC 7th and 8th editions, LN ratio (LNR), and log odds of metastatic LN (LODDS)) with pattern of recurrence and patient survival using logistic regression and Cox proportional hazards regression, respectively. Regression models adjusted for age, sex, margin status, tumour grade, and perioperative therapy. RESULTS: Lymph node metastases classified by AJCC 7th and 8th editions, LNR, and LODDS were associated with worse disease free-survival (DFS) and overall survival (OS) (all P CONCLUSIONS: American Joint Committee on Cancer 8th edition LN classification is an effective and practical tool to predict outcomes in patients with resected PDAC. However, the prognostic value of LN metastases is attenuated in patients with positive resection margins and distal pancreatectomies.