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Pancreatic Neoplasms: HELP
Articles by Dr. J Abbruzzese
Based on 103 articles published since 2008
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Between 2008 and 2019, J. Abbruzzese wrote the following 103 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4 · 5
1 Editorial Adjuvant therapy for surgically resected pancreatic adenocarcinoma. 2008

Abbruzzese, James L. · ·JAMA · Pubmed #18319419.

ABSTRACT: -- No abstract --

2 Review Clinical Insights Into the Biology and Treatment of Pancreatic Cancer. 2016

Mettu, Niharika B / Abbruzzese, James L. ·Duke University Medical Center, Durham, NC niharika.mettu@duke.edu. · Duke University Medical Center, Durham, NC. ·J Oncol Pract · Pubmed #26759461.

ABSTRACT: Pancreatic cancer is a devastating disease with a universally poor prognosis. In 2015, it is estimated that there will be 48,960 new cases of pancreatic cancer and that 40,560 people will die of the disease. The 5-year survival rate is 7.2% for all patients with pancreatic cancer; however, survival depends greatly on the stage at diagnosis. Unfortunately, 53% of patients already have metastatic disease at diagnosis, which corresponds to a 5-year survival rate of 2.4%. Even for the 9% of patients with localized disease confined to the pancreas, the 5-year survival is still modest at only 27.1%. These grim statistics highlight the need for ways to identify cohorts of individuals at highest risk, methods to screen those at highest risk to identify preinvasive pathologic precursors, and development of effective systemic therapies. Recent clinical and translational progress has emphasized the relationship with diabetes, the role of the stroma, and the interplay of each of these with inflammation in the pathobiology of pancreatic cancer. In this article, we will discuss these relationships and how they might translate into novel management strategies for the treatment of this disease.

3 Review Consensus report of the national cancer institute clinical trials planning meeting on pancreas cancer treatment. 2009

Philip, Philip A / Mooney, Margaret / Jaffe, Deborah / Eckhardt, Gail / Moore, Malcolm / Meropol, Neal / Emens, Leisha / O'Reilly, Eileen / Korc, Murray / Ellis, Lee / Benedetti, Jacqueline / Rothenberg, Mace / Willett, Christopher / Tempero, Margaret / Lowy, Andrew / Abbruzzese, James / Simeone, Diane / Hingorani, Sunil / Berlin, Jordan / Tepper, Joel. ·Karmanos Cancer Institute, Wayne State University, Detroit, MI 48201, USA. philipp@karmanos.org ·J Clin Oncol · Pubmed #19858397.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer mortality, despite significant improvements in diagnostic imaging and operative mortality rates. The 5-year survival rate remains less than 5% because of microscopic or gross metastatic disease at time of diagnosis. The Clinical Trials Planning Meeting in pancreatic cancer was convened by the National Cancer Institute's Gastrointestinal Cancer Steering Committee to discuss the integration of basic and clinical knowledge in the design of clinical trials in PDAC. Major emphasis was placed on the enhancement of research to identify and validate the relevant targets and molecular pathways in PDAC, cancer stem cells, and the microenvironment. Emphasis was also placed on developing rational combinations of targeted agents and the development of predictive biomarkers to assist selection of patient subsets. The development of preclinical tumor models that are better predictive of human PDAC must be supported with wider availability to the research community. Phase III clinical trials should be implemented only if there is a meaningful clinical signal of efficacy and safety in the phase II setting. The emphasis must therefore be on performing well-designed phase II studies with uniform sets of basic entry and evaluation criteria with survival as a primary endpoint. Patients with either metastatic or locally advanced PDAC must be studied separately.

4 Clinical Trial An Intergroup Randomized Phase II Study of Bevacizumab or Cetuximab in Combination with Gemcitabine and in Combination with Chemoradiation in Patients with Resected Pancreatic Carcinoma: A Trial of the ECOG-ACRIN Cancer Research Group (E2204). 2018

Berlin, Jordan D / Feng, Yang / Catalano, Paul / Abbruzzese, James L / Philip, Philip A / McWilliams, Robert R / Lowy, Andrew M / Benson, Al B / Blackstock, A William. ·Vanderbilt-Ingram Cancer Center, Nashville, TN, USA. ·Oncology · Pubmed #29040974.

ABSTRACT: OBJECTIVES: Evaluate toxicity of two treatment arms, A (cetuximab) and B (bevacizumab), when combined with gemcitabine, and chemoradiation in patients with completely resected pancreatic carcinoma. Secondary objectives included overall survival (OS) and disease-free survival (DFS). METHODS: Patients with R0/R1 resection were randomized 1:1 to cetuximab or bevacizumab administered in combination with gemcitabine for two treatment cycles. Next three cycles included concurrent cetuximab/bevacizumab plus chemoradiation, followed by one cycle of cetuximab/bevacizumab. Cycles 7-12 included cetuximab/bevacizumab with gemcitabine. Cycles were 2 weeks. Frequency of specific toxicities was summarized for each treatment arm at two times during the study, after chemotherapy but prior to chemoradiation and after all therapy. RESULTS: A total of 127 patients were randomized (A, n = 65; B, n = 62). Prior to chemoradiation, the overall rate for toxicities of interest was 10% for arm A and 2% for arm B. After all therapy, the overall rates for toxicities of interest were 30 and 25% for arms A and B, respectively. Overall median OS and DFS were 17 and 11 months, respectively, which is not a significant improvement over expected survival rates for historical controls. CONCLUSIONS: Both treatments were tolerable with manageable toxicities, and were safe enough for a phase III trial had this been indicated.

5 Clinical Trial RECQ1 A159C Polymorphism Is Associated With Overall Survival of Patients With Resected Pancreatic Cancer: A Replication Study in NRG Oncology Radiation Therapy Oncology Group 9704. 2016

Li, Donghui / Moughan, Jennifer / Crane, Christopher / Hoffman, John P / Regine, William F / Abrams, Ross A / Safran, Howard / Liu, Chang / Chang, Ping / Freedman, Gary M / Winter, Kathryn A / Guha, Chandan / Abbruzzese, James L. ·Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas. Electronic address: dli@mdanderson.org. · NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvania. · Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas. · Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania. · Department of Radiation Oncology, University of Maryland, Baltimore, Maryland. · Rush University Medical Center, Chicago, Illinois. · Brown University Oncology Group, Providence, Rhode Island. · Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania. · Department of Radiation Oncology, Montefiore Medical Center, Bronx, New York. · Duke University Medical Center, Durham, North Carolina. ·Int J Radiat Oncol Biol Phys · Pubmed #26725729.

ABSTRACT: PURPOSE: To confirm whether a previously observed association between RECQ1 A159C variant and clinical outcome of resectable pancreatic cancer patients treated with preoperative chemoradiation is reproducible in another patient population prospectively treated with postoperative chemoradiation. METHODS AND MATERIALS: Patients were selected, according to tissue availability, from eligible patients with resected pancreatic cancer who were enrolled on the NRG Oncology Radiation Therapy Oncology Group 9704 trial of 5-fluorouacil (5-FU)-based chemoradiation preceded and followed by 5-FU or gemcitabine. Deoxyribonucleic acid was extracted from paraffin-embedded tissue sections, and genotype was determined using the Taqman method. The correlation between genotype and overall survival was analyzed using a Kaplan-Meier plot, log-rank test, and multivariate Cox proportional hazards models. RESULTS: In the 154 of the study's 451 eligible patients with evaluable tissue, genotype distribution followed Hardy-Weinberg equilibrium (ie, 37% had genotype AA, 43% AC, and 20% CC). The RECQ1 variant AC/CC genotype carriers were associated with being node positive compared with the AA carrier (P=.03). The median survival times (95% confidence interval [CI]) for AA, AC, and CC carriers were 20.6 (16.3-26.1), 18.8 (14.2-21.6), and 14.2 (10.3-21.0) months, respectively. On multivariate analysis, patients with the AC/CC genotypes were associated with worse survival than patients with the AA genotype (hazard ratio [HR] 1.54, 95% CI 1.07-2.23, P=.022). This result seemed slightly stronger for patients on the 5-FU arm (n=82) (HR 1.64, 95% CI 0.99-2.70, P=.055) than for patients on the gemcitabine arm (n=72, HR 1.46, 95% CI 0.81-2.63, P=.21). CONCLUSIONS: Results of this study suggest that the RECQ1 A159C genotype may be a prognostic or predictive factor for resectable pancreatic cancer patients who are treated with adjuvant 5-FU before and after 5-FU-based chemoradiation. Further study is needed in patients treated with gemcitabine to determine whether an association exists.

6 Clinical Trial Transport properties of pancreatic cancer describe gemcitabine delivery and response. 2014

Koay, Eugene J / Truty, Mark J / Cristini, Vittorio / Thomas, Ryan M / Chen, Rong / Chatterjee, Deyali / Kang, Ya'an / Bhosale, Priya R / Tamm, Eric P / Crane, Christopher H / Javle, Milind / Katz, Matthew H / Gottumukkala, Vijaya N / Rozner, Marc A / Shen, Haifa / Lee, Jeffery E / Wang, Huamin / Chen, Yuling / Plunkett, William / Abbruzzese, James L / Wolff, Robert A / Varadhachary, Gauri R / Ferrari, Mauro / Fleming, Jason B. · ·J Clin Invest · Pubmed #24614108.

ABSTRACT: BACKGROUND: The therapeutic resistance of pancreatic ductal adenocarcinoma (PDAC) is partly ascribed to ineffective delivery of chemotherapy to cancer cells. We hypothesized that physical properties at vascular, extracellular, and cellular scales influence delivery of and response to gemcitabine-based therapy. METHODS: We developed a method to measure mass transport properties during routine contrast-enhanced CT scans of individual human PDAC tumors. Additionally, we evaluated gemcitabine infusion during PDAC resection in 12 patients, measuring gemcitabine incorporation into tumor DNA and correlating its uptake with human equilibrative nucleoside transporter (hENT1) levels, stromal reaction, and CT-derived mass transport properties. We also studied associations between CT-derived transport properties and clinical outcomes in patients who received preoperative gemcitabine-based chemoradiotherapy for resectable PDAC. RESULTS: Transport modeling of 176 CT scans illustrated striking differences in transport properties between normal pancreas and tumor, with a wide array of enhancement profiles. Reflecting the interpatient differences in contrast enhancement, resected tumors exhibited dramatic differences in gemcitabine DNA incorporation, despite similar intravascular pharmacokinetics. Gemcitabine incorporation into tumor DNA was inversely related to CT-derived transport parameters and PDAC stromal score, after accounting for hENT1 levels. Moreover, stromal score directly correlated with CT-derived parameters. Among 110 patients who received preoperative gemcitabine-based chemoradiotherapy, CT-derived parameters correlated with pathological response and survival. CONCLUSION: Gemcitabine incorporation into tumor DNA is highly variable and correlates with multiscale transport properties that can be derived from routine CT scans. Furthermore, pretherapy CT-derived properties correlate with clinically relevant endpoints. TRIAL REGISTRATION: Clinicaltrials.gov NCT01276613. FUNDING: Lustgarten Foundation (989161), Department of Defense (W81XWH-09-1-0212), NIH (U54CA151668, KCA088084).

7 Clinical Trial Phase II trial of cetuximab, gemcitabine, and oxaliplatin followed by chemoradiation with cetuximab for locally advanced (T4) pancreatic adenocarcinoma: correlation of Smad4(Dpc4) immunostaining with pattern of disease progression. 2011

Crane, Christopher H / Varadhachary, Gauri R / Yordy, John S / Staerkel, Gregg A / Javle, Milind M / Safran, Howard / Haque, Waqar / Hobbs, Bridgett D / Krishnan, Sunil / Fleming, Jason B / Das, Prajnan / Lee, Jeffrey E / Abbruzzese, James L / Wolff, Robert A. ·Dept of Radiation Oncology, Unit 97, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX. ccrane@mdanderson.org ·J Clin Oncol · Pubmed #21709185.

ABSTRACT: PURPOSE: This phase II trial was designed to assess the efficacy and safety of cetuximab, gemcitabine, and oxaliplatin followed by cetuximab, capecitabine, and radiation therapy in locally advanced pancreatic cancer (LAPC). PATIENTS AND METHODS: Treatment-naive eligible patients (n = 69) received intravenous gemcitabine (1,000 mg/m(2)) and oxaliplatin (100 mg/m(2)) every 2 weeks for four doses, followed by radiation (50.4 Gy to the gross tumor only) with concurrent capecitabine (825 mg/m(2) twice daily on radiation treatment days). Cetuximab (500 mg/m(2)) was started on day 1 of chemotherapy and was continued every 2 weeks during chemotherapy and chemoradiotherapy. Diagnostic cytology specimens were immunostained for Smad4(Dpc4) expression. RESULTS: Median overall survival time was 19.2 months (95% CI, 14.2 to 24.2 months), and 1-year, 2-year, and 4-year actuarial overall survival rates were 66.0%, 25.02%, and 11.3%, respectively. Acneiform rash correlated with improved survival (P = .001), but initial CA19-9, borderline resectable initial stage, and surgical resection (n = 7) did not. The 1-year and 2-year radiographic local progression rates were 22.8% and 61.0%, respectively. The worst acute toxic effects were GI toxicity (32% and 10% for grades 2 and 3, respectively); fatigue (26% and 6% for grades 2 and 3, respectively); sensory neuropathy (9% and 1% for grades 2 and 3, respectively); and acneiform rash (54% and 3% for grades 2 and 3, respectively). Smad4(Dpc4) expression correlated with a local rather than a distant dominant pattern of disease progression (P = .016). CONCLUSION: This regimen appears effective and has acceptable toxicity. The primary end point (1-year overall survival rate > 45%) was met, with encouraging survival duration. Smad4(Dpc4) immunostaining correlated with the pattern of disease progression. Prospective validation of Smad4(Dpc4) expression in cytology specimens as a predictive biomarker is warranted and may lead to personalized treatment strategies for patients with localized pancreatic cancer.

8 Clinical Trial Bevacizumab plus gemcitabine and oxaliplatin as first-line therapy for metastatic or locally advanced pancreatic cancer: a phase II trial. 2011

Fogelman, David / Jafari, Mehrdad / Varadhachary, Gauri R / Xiong, Henry / Bullock, Susie / Ozer, Harold / Lin, E / Morris, Jeffrey / Cunningham, Patti / Bennett, Bronwyn / Abbruzzese, James L / Wolff, Robert A. ·MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 426, Houston, TX 77030, USA. dfogelman@mdanderson.org ·Cancer Chemother Pharmacol · Pubmed #21479635.

ABSTRACT: PURPOSE: The gemcitabine and oxaliplatin (GEMOX) has yielded among the longest progression-free survival durations in patients with advanced pancreatic cancer (APC). We postulated that adding bevacizumab would increase the effectiveness of GEMOX. METHODS: Eligible patients had stage III or IV pancreatic cancer, ECOG PS 0-2, and no prior gemcitabine. Treatment included 1,000 mg/m(2) intravenous gemcitabine over 100 min on day 1, 10 mg/kg intravenous bevacizumab on day 1, and 100 mg/m(2) oxaliplatin given on day 2. Cycles were repeated every 2 weeks. CT imaging was performed every 6 weeks. RESULTS: Fifty patients were enrolled: 14 had stage III disease, the remainder stage IV. Median age was 59 years. Fourty-five patients were ECOG 0-1. The grade 3-4 toxicity rate was 94%; fatigue (47%) and nausea (40%) were frequent. One patient died after a bowel perforation; a second died of a CVA. The median PFS was 4.9 months; median survival was 11.9 months; 1 year survival was 42%. Locally advanced patients lived 12.8 months; metastatic patients lived 10.2 months. Patients developing grade 3 hypertension were more likely to have a radiologic response (P = .012); survival among the top and bottom quintiles of hypertension was 14.7 and 6.2 months, respectively. Survival correlated with baseline CA 19-9 (P = .004) and radiologic response. The overall response rate was 36%; 34% demonstrated stable disease. CONCLUSIONS: The GEMOX/bevacizumab regimen demonstrated an excellent median overall survival but did not meet our objective of a 14 month median survival. Toxicity was significant. We do not recommend further evaluation of this regimen.

9 Clinical Trial A randomized phase II study of PX-12, an inhibitor of thioredoxin in patients with advanced cancer of the pancreas following progression after a gemcitabine-containing combination. 2011

Ramanathan, Ramesh K / Abbruzzese, James / Dragovich, Tomislav / Kirkpatrick, Lynn / Guillen, Jose M / Baker, Amanda F / Pestano, Linda A / Green, Sylvan / Von Hoff, Daniel D. ·Virgina G Piper Cancer Center, TGen, Scottsdale, AZ, 85259, USA. rramanathan@tgen.org ·Cancer Chemother Pharmacol · Pubmed #20461382.

ABSTRACT: PURPOSE: This study evaluated PX-12, a novel small molecule inhibitor of the proto-oncogene (Trx-1), in patients with previously treated advanced pancreatic cancer (APC). METHODS: PX-12 (54 or 128 mg/m²) was administered by 3-hour IV infusion daily × 5 days every 21 days (n = 17). Patients were randomized to either 54 or 128 mg/m² and then stratified based on CA 19-9 level (≥ 1,000 vs. < 1,000 U/ml) and SUV values on PET scans (≥ 7.0 vs. <7.0). The primary endpoint was based on a progression-free survival (PFS) at 4 months in ≥ 40% of patients, and required 40 patients in each arm. An amendment required elevated Trx-1 levels (> 18 ng/ml) as an entry criteria after the first 17 patients were accrued. RESULTS: Plasma Trx-1 levels were elevated in 3/28 (11%) patients screened for study. The grade of the expired metabolite odor was higher in the 128 mg/m² arm. Therapy was well tolerated, and Grade ≥ 3 adverse events were uncommon. The best response was stable disease in 2 patients. There was no consistent decrease in SUV, Trx-1 levels or CA 19-9 levels with therapy. No patients had a PFS of >4 months. Median PFS and survival were 0.9 months (95% CI 0.5-1.2) and 3.2 months (95% CI 2.4-4.2), respectively. CONCLUSIONS: Due to the lack of significant antitumor activity and unexpectedly low baseline Trx-1 levels, the study was terminated early. PX-12 does not appear to be active in unselected patients with previously treated APC.

10 Clinical Trial A phase II study of isoflavones, erlotinib, and gemcitabine in advanced pancreatic cancer. 2011

El-Rayes, Bassel Fuad / Philip, Philip A / Sarkar, Fazlul H / Shields, Anthony F / Ferris, Ann Marie / Hess, Kenneth / Kaseb, Ahmad O / Javle, Milind M / Varadhachary, Gauri R / Wolff, Robert A / Abbruzzese, James L. ·Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA. belraye@emory.edu ·Invest New Drugs · Pubmed #20107864.

ABSTRACT: BACKGROUND: The EGFR/Akt/NF-κB signalling pathway is frequently deregulated in pancreatic cancer and contributes to cell growth, metastasis and chemoresistance. An isoflavone, genistein, inactivates Akt and NF-κB and enhances the anti-tumor activity of erlotinib and gemcitabine in experimental systems of pancreas cancer. This phase II study was undertaken to determine the effects of adding isoflavone to a regimen of gemcitabine and erlotinib on survival in patients with advanced pancreatic cancer. METHODS: Eligibility included previously untreated patients with advanced pancreatic adenocarcinoma. Patients received gemcitabine 1,000 mg/m² on days 1, 8, and 15, and erlotinib 150 mg once daily P.O. on day 1 to day 28. Soy isoflavones (Novasoy®) were administered at a dose of 531 mg twice daily P.O. starting day -7 until the end of study participation. RESULTS: Twenty patients with advanced pancreas cancer were enrolled (median age 57.9 years). Sixteen patients had stage IV disease. The median number of cycles was 2 per patient. The median survival time was 5.2 months (95% CI, 4.6-N/A months). The probability of survival at 6 months was 50% (95% CI, 32-78%). CONCLUSIONS: The addition of soy isoflavones to gemcitabine and erlotinib did not appear to increase the survival of patients with advanced pancreatic cancer.

11 Clinical Trial Inhibition of the mammalian target of rapamycin (mTOR) in advanced pancreatic cancer: results of two phase II studies. 2010

Javle, Milind M / Shroff, Rachna T / Xiong, Henry / Varadhachary, Gauri A / Fogelman, David / Reddy, Shrikanth A / Davis, Darren / Zhang, Yujian / Wolff, Robert A / Abbruzzese, James L. ·Department of Gastrointestinal Medical Oncology, UT-M D Anderson Cancer Center, Houston, TX, USA. mjavle@mdanderson.org ·BMC Cancer · Pubmed #20630061.

ABSTRACT: BACKGROUND: The phosphoinositide 3-kinase (PI3K)/Akt pathway is constitutively activated in pancreatic cancer and the mammalian target of rapamycin (mTOR) kinase is an important mediator for its signaling. Our recent in vitro studies suggest that prolonged exposure of pancreatic cancer cells to mTOR inhibitors can promote insulin receptor substrate-PI3K interactions and paradoxically increase Akt phosphorylation and cyclin D1 expression in pancreatic cancer cells (negative feedback loop). The addition of erlotinib to rapamycin can down-regulate rapamycin-stimulated Akt and results in synergistic antitumor activity with erlotinib in preclinical tumor models. METHODS: Two studies prospectively enrolled adult patients with advanced pancreatic cancer, Eastern Cooperative Oncology Group performance status 0-1, adequate hematologic, hepatic and renal parameters and measurable disease. In Study A, temsirolimus was administered intravenously at 25 mg weekly. In Study B, everolimus was administered orally at 30 mg weekly and erlotinib was administered at 150 mg daily. The primary endpoint in both studies was overall survival at 6 months. Secondary endpoints included time to progression, progression-free survival, overall survival, response rate, safety and toxicity. Pretreatment tumor biopsies were analyzed by immunofluorescence and laser scanning cytometry for the expression of pmTOR/mTOR, pAkt/Akt, pErk/Erk, pS6, p4EBP-1 and PTEN. RESULTS: Five patients enrolled in Study A; Two patients died within a month (rapid disease progression and hemorrhagic stroke, respectively). One patient developed dehydration and another developed asthenia. Sixteen patients enrolled in Study B.: 12 males, all ECOG PS = 1. Median cycles = 1 (range 1-2). Grade 4 toxicity: hyponatremia (n = 1), Grade 3: diarrhea (n = 1), cholangitis (n = 3), hyperglycemia (n = 1), fatigue (n = 1). Grade 2: pneumonia (n = 2), dehydration (n = 2), nausea (n = 2), neutropenia (n = 1), mucositis (n = 2) & rash (n = 2). Four patients were hospitalized. Progressive disease occurred in 15 and 1 was non-evaluable. Pretreatment biopsies revealed a higher pAkt/Akt ratio in tumor specimens that in nonmalignant pancreatic tissue. No such trends were noted for the other biomarkers. CONCLUSIONS: Neither study with mTOR inhibitors demonstrated objective responses or disease stability. The negative feedback loop resulting from mTOR inhibition may account for the disease progression and toxicity noted in these studies. Future strategies should aim for a broader targeting of the PI3K pathway in pancreatic cancer. STUDY A: NCT 0075647. STUDY B: NCT00640978.

12 Clinical Trial Phase III study comparing gemcitabine plus cetuximab versus gemcitabine in patients with advanced pancreatic adenocarcinoma: Southwest Oncology Group-directed intergroup trial S0205. 2010

Philip, Philip A / Benedetti, Jacqueline / Corless, Christopher L / Wong, Ralph / O'Reilly, Eileen M / Flynn, Patrick J / Rowland, Kendrith M / Atkins, James N / Mirtsching, Barry C / Rivkin, Saul E / Khorana, Alok A / Goldman, Bryan / Fenoglio-Preiser, Cecilia M / Abbruzzese, James L / Blanke, Charles D. ·Wayne State University, Karmanos Cancer Institute, GI Oncology, Detroit, MI 48201, USA. philipp@karmanos.org ·J Clin Oncol · Pubmed #20606093.

ABSTRACT: PURPOSE: Patients with advanced pancreas cancer present with disease that is poorly responsive to conventional therapies. Preclinical and early clinical evidence has supported targeting the epidermal growth factor receptor (EGFR) signaling pathway in patients with pancreas cancer. This trial was conducted to evaluate the contribution of an EGFR-targeted agent to standard gemcitabine therapy. Cetuximab is a monoclonal antibody against the ligand-binding domain of the receptor. PATIENTS AND METHODS: Patients with unresectable locally advanced or metastatic pancreatic adenocarcinoma were randomly assigned to receive gemcitabine alone or gemcitabine plus cetuximab. The primary end point was overall survival. Secondary end points included progression-free survival, time to treatment failure, objective response, and toxicity. RESULTS: A total of 745 eligible patients were accrued. No significant difference was seen between the two arms of the study with respect to the median survival time (6.3 months for the gemcitabine plus cetuximab arm v 5.9 months for the gemcitabine alone arm; hazard ratio = 1.06; 95% CI, 0.91 to 1.23; P = .23, one-sided). Objective responses and progression-free survival were similar in both arms of the study. Although time to treatment failure was longer in patients on gemcitabine plus cetuximab (P = .006), the difference in length of treatment was only 2 weeks longer in the combination arm. Among patients who were studied for tumoral EGFR expression, 90% were positive, with no treatment benefit detected in this patient subset. CONCLUSION: In patients with advanced pancreas cancer, the anti-EGFR monoclonal antibody cetuximab did not improve the outcome compared with patients treated with gemcitabine alone. Alternate targets other than EGFR should be evaluated for new drug development.

13 Clinical Trial Polymorphisms of p16, p27, p73, and MDM2 modulate response and survival of pancreatic cancer patients treated with preoperative chemoradiation. 2009

Chen, Jinyun / Li, Donghui / Killary, Ann M / Sen, Subrata / Amos, Christopher I / Evans, Douglas B / Abbruzzese, James L / Frazier, Marsha L. ·Department of Epidemiology, University of Texas M. D. Anderson Cancer Center, Houston, 77030, USA. ·Ann Surg Oncol · Pubmed #19020940.

ABSTRACT: Genetic polymorphisms play an important role in clinical response to cytotoxic therapies. We hypothesized that polymorphisms in cell cycle genes may modulate response to preoperative chemoradiation and survival of pancreatic cancer patients. We evaluated 12 single-nucleotide polymorphisms (SNPs) of ten cell cycle genes in 88 patients with resectable adenocarcinoma of the pancreatic head who were treated with neoadjuvant concurrent gemcitabine and radiotherapy. Response was assessed by computerized tomography obtained before and 4-6 weeks after preoperative treatment. Time to tumor progression and survival after treatment were measured. Patients underwent pancreaticoduodenectomy (PD) if no disease progression was found at restaging after preoperative therapy. MDM2 T309G and p16 C580T genotype distributions were significantly different in the patients who underwent PD and those who did not (P = 0.025 for MDM2; P = 0.016 for p16). The MDM2 and p27 genotypes had a significant effect on survival times after treatment (log-rank test, P = 0.010 and P = 0.050, respectively). A strong joint effect of these two genes was observed (log-rank test, P = 0.010). The p73 and p16 polymorphic genotypes were significantly associated with shorter time to tumor progression (log-rank test, P = 0.021 and P = 0.039, respectively). A gene-dosage effect on time to tumor progression was observed for polymorphisms in the p73, p16, and MDM2 genes. The hazard ratios for patients with one, two, or three adverse genotypes were 2.13 (1.04-4.36), 3.18 (1.37-7.39), and 10.09 (3.17-32.05), respectively. These findings suggest these polymorphisms in the cell cycle genes are promising prognostic markers for patients with pancreatic cancer.

14 Clinical Trial Phase 2 trial of oxaliplatin plus capecitabine (XELOX) as second-line therapy for patients with advanced pancreatic cancer. 2008

Xiong, Henry Q / Varadhachary, Gauri R / Blais, Joan C / Hess, Kenneth R / Abbruzzese, James L / Wolff, Robert A. ·Center for Cancer and Blood Disorders, Fort Worth, Texas, USA. ·Cancer · Pubmed #18756532.

ABSTRACT: BACKGROUND: To the authors' knowledge, there is no established second-line chemotherapy for patients with pancreatic cancer who have received gemcitabine-based therapy. A phase 2 trial was conducted to explore the efficacy of capecitabine and oxaliplatin (XELOX) in patients with advanced pancreatic cancer previously who were treated with gemcitabine. METHODS: Patients aged < or = 65 years who had an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 1 received oxaliplatin at a dose of 130 mg/m(2) given on Day 1 and capecitabine at a dose of 1000 mg/m(2) twice daily for 14 days. For patients aged >65 years or with an ECOG PS of 2, the oxaliplatin dose was 110 mg/m(2) on Day 1 and the capecitabine dose was 750 mg/m(2) twice daily for 14 days. The treatment was repeated every 3 weeks. Tumor measurements were performed every 9 weeks and the primary study objective was 6-month overall survival. RESULTS: The study enrolled 41 patients. Of the 39 evaluable patients, 1 patient had a partial response and 10 patients demonstrated stable disease. The Kaplan-Meier estimate of the overall median survival was 23 weeks (95% confidence interval [95% CI], 17.0-31.0 weeks). Progression-free survival was 9.9 weeks (95% CI, 9.6-14.5 weeks). The 6-month and 1-year survival rates were 44% (95% CI, 31%-62%) and 21% (95% CI, 11%-38%), respectively. The most common grade 3-4 nonhematologic toxicity was fatigue (toxicity was graded using the National Cancer Institute Common Toxicity Criteria [version 2.0]). CONCLUSIONS: The combination of capecitabine and oxaliplatin is active in gemcitabine-pretreated patients with advanced pancreatic cancer, especially in patients with a good PS and those who have responded to first-line chemotherapy.

15 Clinical Trial Preoperative gemcitabine-based chemoradiation for patients with resectable adenocarcinoma of the pancreatic head. 2008

Evans, Douglas B / Varadhachary, Gauri R / Crane, Christopher H / Sun, Charlotte C / Lee, Jeffrey E / Pisters, Peter W T / Vauthey, Jean-Nicolas / Wang, Huamin / Cleary, Karen R / Staerkel, Gregg A / Charnsangavej, Chusilp / Lano, Elizabeth A / Ho, Linus / Lenzi, Renato / Abbruzzese, James L / Wolff, Robert A. ·Department of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA. devans@mdanderson.org ·J Clin Oncol · Pubmed #18640930.

ABSTRACT: PURPOSE: We conducted a phase II trial to assess the outcomes of patients who received preoperative gemcitabine-based chemoradiation and pancreaticoduodenectomy (PD) for stage I/II pancreatic adenocarcinoma. PATIENTS AND METHODS: Eligible patients with pancreatic head/uncinate process adenocarcinoma and radiographically defined potentially resectable disease received chemoradiation with 7 weekly intravenous (IV) infusions of gemcitabine (400 mg/m(2) IV over 30 minutes) plus radiation therapy (30 Gy in 10 fractions over 2 weeks). Patients underwent restaging 4 to 6 weeks after completion of chemoradiation and, in the absence of disease progression, were taken to surgery. RESULTS: The study enrolled 86 patients. At the time of restaging, disease progression or a decline in performance status precluded 13 patients from surgery. Seventy-three (85%) of 86 patients were taken to surgery, extrapancreatic disease was found in nine, and 64 (74%) of 86 underwent a successful PD. Median overall survival (86 patients) was 22.7 months with a 27% 5-year survival. Median survival was 34 months for the 64 patients who underwent PD and 7 months for the 22 unresected patients (P < .001). The 5-year survival for those who did and did not undergo PD was 36% and 0%, respectively. CONCLUSION: Preoperative gemcitabine-based chemoradiation followed by restaging and evaluation for surgery separated the study population into two different subsets: patients likely to benefit from PD (n = 64) and those in whom surgery would be unlikely to provide clinical benefit (n = 22). Furthermore, the encouraging overall survival observed in this large trial supports the continued investigation of gemcitabine-based preoperative therapy in resectable pancreatic cancer.

16 Clinical Trial Preoperative gemcitabine and cisplatin followed by gemcitabine-based chemoradiation for resectable adenocarcinoma of the pancreatic head. 2008

Varadhachary, Gauri R / Wolff, Robert A / Crane, Christopher H / Sun, Charlotte C / Lee, Jeffrey E / Pisters, Peter W T / Vauthey, Jean-Nicolas / Abdalla, Eddie / Wang, Huamin / Staerkel, Gregg A / Lee, Jeffrey H / Ross, William A / Tamm, Eric P / Bhosale, Priya R / Krishnan, Sunil / Das, Prajnan / Ho, Linus / Xiong, Henry / Abbruzzese, James L / Evans, Douglas B. ·Department of Gastrointestinal Medical Oncology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Box 426, Houston, TX 77030, USA. gvaradha@mdanderson.org ·J Clin Oncol · Pubmed #18640929.

ABSTRACT: PURPOSE: We conducted a phase II trial of preoperative gemcitabine and cisplatin chemotherapy in addition to chemoradiation (Gem-Cis-XRT) and pancreaticoduodenectomy (PD) for patients with stage I/II pancreatic adenocarcinoma. PATIENTS AND METHODS: Chemotherapy consisted of gemcitabine (750 mg/m(2)) and cisplatin (30 mg/m(2)) given every 2 weeks for four doses. Chemoradiation consisted of four weekly infusions of gemcitabine (400 mg/m(2)) combined with radiation therapy (30 Gy in 10 fractions administered over 2 weeks) delivered 5 days per week. Patients underwent restaging 4 to 6 weeks after completion of chemoradiation and, in the absence of disease progression, were taken to surgery. RESULTS: The study enrolled 90 patients; 79 patients (88%) completed chemo-chemoradiation. Sixty-two (78%) of 79 patients were taken to surgery and 52 (66%) of 79 underwent PD. The median overall survival of all 90 patients was 17.4 months. Median survival for the 79 patients who completed chemo-chemoradiation was 18.7 months, with a median survival of 31 months for the 52 patients who underwent PD and 10.5 months for the 27 patients who did not undergo surgical resection of their primary tumor (P < .001). CONCLUSION: Preoperative Gem-Cis-XRT did not improve survival beyond that achieved with preoperative gemcitabine-based chemoradiation (Gem-XRT) alone. The longer preoperative interval required more durable biliary decompression (metal stents) but was not associated with local tumor progression. The gemcitabine-based chemoradiation platform is a reasonable foundation on which to build future phase II multimodality trials for stage I/II pancreatic cancer incorporating emerging systemic therapies.

17 Clinical Trial Phase II trial of curcumin in patients with advanced pancreatic cancer. 2008

Dhillon, Navneet / Aggarwal, Bharat B / Newman, Robert A / Wolff, Robert A / Kunnumakkara, Ajaikumar B / Abbruzzese, James L / Ng, Chaan S / Badmaev, Vladimir / Kurzrock, Razelle. ·Department of Investigational Cancer Therapeutics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA. ·Clin Cancer Res · Pubmed #18628464.

ABSTRACT: PURPOSE: Pancreatic cancer is almost always lethal, and the only U.S. Food and Drug Administration-approved therapies for it, gemcitabine and erlotinib, produce objective responses in <10% of patients. We evaluated the clinical biological effects of curcumin (diferuloylmethane), a plant-derived dietary ingredient with potent nuclear factor-kappaB (NF-kappaB) and tumor inhibitory properties, against advanced pancreatic cancer. EXPERIMENTAL DESIGN: Patients received 8 g curcumin by mouth daily until disease progression, with restaging every 2 months. Serum cytokine levels for interleukin (IL)-6, IL-8, IL-10, and IL-1 receptor antagonists and peripheral blood mononuclear cell expression of NF-kappaB and cyclooxygenase-2 were monitored. RESULTS: Twenty-five patients were enrolled, with 21 evaluable for response. Circulating curcumin was detectable as drug in glucuronide and sulfate conjugate forms, albeit at low steady-state levels, suggesting poor oral bioavailability. Two patients showed clinical biological activity. One had ongoing stable disease for >18 months; interestingly, one additional patient had a brief, but marked, tumor regression (73%) accompanied by significant increases (4- to 35-fold) in serum cytokine levels (IL-6, IL-8, IL-10, and IL-1 receptor antagonists). No toxicities were observed. Curcumin down-regulated expression of NF-kappaB, cyclooxygenase-2, and phosphorylated signal transducer and activator of transcription 3 in peripheral blood mononuclear cells from patients (most of whom had baseline levels considerably higher than those found in healthy volunteers). Whereas there was considerable interpatient variation in plasma curcumin levels, drug levels peaked at 22 to 41 ng/mL and remained relatively constant over the first 4 weeks. CONCLUSIONS: Oral curcumin is well tolerated and, despite its limited absorption, has biological activity in some patients with pancreatic cancer.

18 Clinical Trial Single-nucleotide polymorphisms of DNA damage response genes are associated with overall survival in patients with pancreatic cancer. 2008

Okazaki, Taro / Jiao, Li / Chang, Ping / Evans, Douglas B / Abbruzzese, James L / Li, Donghui. ·Department of Gastrointestinal Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA. ·Clin Cancer Res · Pubmed #18381943.

ABSTRACT: PURPOSE: The goals of this study were to determine if single-nucleotide polymorphisms in DNA damage repair genes and cell cycle regulating genes affect clinical response to combined gemcitabine radiation therapy and the overall survival (OS) of patients with pancreatic cancer. EXPERIMENTAL DESIGN: We evaluated six single-nucleotide polymorphisms of the ATM, ATM and Rad3-related (ATR), CHEK1, and CHEK2 genes in 119 patients with potentially resectable pancreatic cancer who were enrolled in clinical trials at The University of Texas M. D. Anderson Cancer Center from February 1999 to January 2006, with follow-up until February 2007. Patients received neoadjuvant concurrent gemcitabine and radiation therapy with or without gemcitabine-cisplatin induction therapy. Genotypes were determined and tested for associations with OS by Kaplan-Meier estimation, the log-rank test, and Cox regression analysis. P values of These observations suggest that polymorphic variations of DNA damage response genes affect clinical response to gemcitabine radiation therapy and OS of patients with resectable pancreatic cancer.

19 Article Genetic variants in the platelet-derived growth factor subunit B gene associated with pancreatic cancer risk. 2018

Duan, Bensong / Hu, Jiangfeng / Liu, Hongliang / Wang, Yanru / Li, Hongyu / Liu, Shun / Xie, Jichun / Owzar, Kouros / Abbruzzese, James / Hurwitz, Herbert / Gao, Hengjun / Wei, Qingyi. ·Department of Gastroenterology, Institute of Digestive Diseases, Tongji Hospital, Tongji University School of Medicine, Shanghai, China. · Duke Cancer Institute, Duke University Medical Center, Durham, NC. · Department of Medicine, Duke University School of Medicine, Durham, NC. · Department of Gastroenterology, Shenyang Northern Hospital, Shenyang, Liaoning, China. · Department of Epidemiology, School of Public Health, Guangxi Medical University, Nanning, Guangxi, China. · Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, NC. · National Engineering Center for Biochip at Shanghai, Shanghai, China. · Department of Population Health Sciences, Duke University School of Medicine, Durham, NC. ·Int J Cancer · Pubmed #29168174.

ABSTRACT: The platelet-derived growth factor (PDGF) signaling pathway plays important roles in development and progression of human cancers. In our study, we aimed to identify genetic variants of the PDGF pathway genes associated with pancreatic cancer (PC) risk in European populations using three published genome-wide association study datasets, which consisted of 9,381 cases and 7,719 controls. The expression quantitative trait loci (eQTL) analysis was also performed using data from the 1000 Genomes, TCGA and GTEx projects. As a result, we identified two potential susceptibility loci (rs5757573 and rs6001516) of PDGFB associated with PC risk [odds ratio (OR) = 1.10, 95% confidence interval (CI) = 1.05-1.16, and p = 4.70 × 10

20 Article Diabetes, Pancreatogenic Diabetes, and Pancreatic Cancer. 2017

Andersen, Dana K / Korc, Murray / Petersen, Gloria M / Eibl, Guido / Li, Donghui / Rickels, Michael R / Chari, Suresh T / Abbruzzese, James L. ·Division of Digestive Diseases and Nutrition, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD. · Division of Endocrinology, Department of Medicine, and Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, and Indiana University Melvin and Bren Simon Cancer Center and Pancreatic Cancer Signature Center, Indianapolis, IN. · Department of Health Sciences Research, Mayo Clinic, Rochester, MN. · Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA. · Department of Gastrointestinal Medical Oncology, MD Anderson Cancer Center, Houston, TX. · Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA. · Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, MN. · Division of Medical Oncology, Department of Medicine, Duke University School of Medicine, Durham, NC james.abbruzzese@duke.edu. ·Diabetes · Pubmed #28507210.

ABSTRACT: The relationships between diabetes and pancreatic ductal adenocarcinoma (PDAC) are complex. Longstanding type 2 diabetes (T2DM) is a risk factor for pancreatic cancer, but increasing epidemiological data point to PDAC as also a cause of diabetes due to unknown mechanisms. New-onset diabetes is of particular interest to the oncology community as the differentiation of new-onset diabetes caused by PDAC as distinct from T2DM may allow for earlier diagnosis of PDAC. To address these relationships and raise awareness of the relationships between PDAC and diabetes, a symposium entitled Diabetes, Pancreatogenic Diabetes, and Pancreatic Cancer was held at the American Diabetes Association's 76th Scientific Sessions in June 2016. This article summarizes the data presented at that symposium, describing the current understanding of the interrelationships between diabetes, diabetes management, and pancreatic cancer, and identifies areas where additional research is needed.

21 Article Sequential Validation of Blood-Based Protein Biomarker Candidates for Early-Stage Pancreatic Cancer. 2017

Capello, Michela / Bantis, Leonidas E / Scelo, Ghislaine / Zhao, Yang / Li, Peng / Dhillon, Dilsher S / Patel, Nikul J / Kundnani, Deepali L / Wang, Hong / Abbruzzese, James L / Maitra, Anirban / Tempero, Margaret A / Brand, Randall / Firpo, Matthew A / Mulvihill, Sean J / Katz, Matthew H / Brennan, Paul / Feng, Ziding / Taguchi, Ayumu / Hanash, Samir M. ·Departments of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. · International Agency for Research on Cancer (IARC) Lyon, France. · Division of Medical Oncology, Duke University, Durham, NC, USA. · Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Pancreas Center, University of California San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA · Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh, Pittsburgh, PA, USA. · Department of Surgery, University of Utah School of Medicine, Salt Lake City, UT, USA. · Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. ·J Natl Cancer Inst · Pubmed #28376157.

ABSTRACT: Background: CA19-9, which is currently in clinical use as a pancreatic ductal adenocarcinoma (PDAC) biomarker, has limited performance in detecting early-stage disease. We and others have identified protein biomarker candidates that have the potential to complement CA19-9. We have carried out sequential validations starting with 17 protein biomarker candidates to determine which markers and marker combination would improve detection of early-stage disease compared with CA19-9 alone. Methods: Candidate biomarkers were subjected to enzyme-linked immunosorbent assay based sequential validation using independent multiple sample cohorts consisting of PDAC cases (n = 187), benign pancreatic disease (n = 93), and healthy controls (n = 169). A biomarker panel for early-stage PDAC was developed based on a logistic regression model. All statistical tests for the results presented below were one-sided. Results: Six out of the 17 biomarker candidates and CA19-9 were validated in a sample set consisting of 75 PDAC patients, 27 healthy subjects, and 19 chronic pancreatitis patients. A second independent set of 73 early-stage PDAC patients, 60 healthy subjects, and 74 benign pancreatic disease patients (combined validation set) yielded a model that consisted of TIMP1, LRG1, and CA19-9. Additional blinded testing of the model was done using an independent set of plasma samples from 39 resectable PDAC patients and 82 matched healthy subjects (test set). The model yielded areas under the curve (AUCs) of 0.949 (95% confidence interval [CI] = 0.917 to 0.981) and 0.887 (95% CI = 0.817 to 0.957) with sensitivities of 0.849 and 0.667 at 95% specificity in discriminating early-stage PDAC vs healthy subjects in the combined validation and test sets, respectively. The performance of the biomarker panel was statistically significantly improved compared with CA19-9 alone (P < .001, combined validation set; P = .008, test set). Conclusion: The addition of TIMP1 and LRG1 immunoassays to CA19-9 statistically significantly improves the detection of early-stage PDAC.

22 Article Preoperative Therapy and Pancreatoduodenectomy for Pancreatic Ductal Adenocarcinoma: a 25-Year Single-Institution Experience. 2017

Cloyd, Jordan M / Katz, Matthew H G / Prakash, Laura / Varadhachary, Gauri R / Wolff, Robert A / Shroff, Rachna T / Javle, Milind / Fogelman, David / Overman, Michael / Crane, Christopher H / Koay, Eugene J / Das, Prajnan / Krishnan, Sunil / Minsky, Bruce D / Lee, Jeffrey H / Bhutani, Manoop S / Weston, Brian / Ross, William / Bhosale, Priya / Tamm, Eric P / Wang, Huamin / Maitra, Anirban / Kim, Michael P / Aloia, Thomas A / Vauthey, Jean-Nicholas / Fleming, Jason B / Abbruzzese, James L / Pisters, Peter W T / Evans, Douglas B / Lee, Jeffrey E. ·Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, 1400 Pressler St, Unit 1484, Houston, TX, 77030, USA. · Department of Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Department of Gasteroenterology, University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Department of Diagnostic Imaging, University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Division of Medical Oncology, Department of Medicine, Duke University, Durham, NC, USA. · University Health Network, Toronto, ON, Canada. · Division of Surgical Oncology, Department of Surgery, The Medical College of Wisconsin, Milwaukee, WI, USA. · Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, 1400 Pressler St, Unit 1484, Houston, TX, 77030, USA. jelee@mdanderson.org. ·J Gastrointest Surg · Pubmed #27778257.

ABSTRACT: BACKGROUND: The purpose of this study was to evaluate a single-institution experience with delivery of preoperative therapy to patients with pancreatic ductal adenocarcinoma (PDAC) prior to pancreatoduodenectomy (PD). METHODS: Consecutive patients (622) with PDAC who underwent PD following chemotherapy and/or chemoradiation between 1990 and 2014 were retrospectively reviewed. Preoperative treatment regimens, clinicopathologic characteristics, operative details, and long-term outcomes in four successive time periods (1990-1999, 2000-2004, 2005-2009, 2010-2014) were evaluated and compared. RESULTS: The average number of patients per year who underwent PD following preoperative therapy as well as the proportion of operations performed for borderline resectable and locally advanced (BR/LA) tumors increased over time. The use of induction systemic chemotherapy, as well as postoperative adjuvant chemotherapy, also increased over time. Throughout the study period, the mean EBL decreased while R0 margin rates and vascular resection rates increased overall. Despite the increase in BR/LA resections, locoregional recurrence (LR) rates remained similar over time, and overall survival (OS) improved significantly (median 24.1, 28.1, 37.3, 43.4 months, respectively, p < 0.0001). CONCLUSIONS: Despite increases in case complexity, relatively low rates of LR have been maintained while significant improvements in OS have been observed. Further improvements in patient outcomes will likely require disruptive advances in systemic therapy.

23 Article The effects of curcumin (diferuloylmethane) on body composition of patients with advanced pancreatic cancer. 2016

Parsons, Henrique A / Baracos, Vickie E / Hong, David S / Abbruzzese, James / Bruera, Eduardo / Kurzrock, Razelle. ·Department of Medicine/Division of Palliative Care, University of Ottawa, Ontario, Canada. · Department of Oncology/Division of Palliative Care Medicine, University of Alberta, Edmonton, Alberta, Canada. · Department of Investigational Cancer Therapeutics (A Phase I Clinical Trials Program), The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. · Department of Medicine/Division of Oncology Duke University School of Medicine, Durham, North Carolina, USA. · Department of Palliative Care and Rehabilitation Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. · Division of Hematology & Oncology and Center for Personalized Cancer Therapy, Moores Cancer Center, University of California San Diego, San Diego, California, USA. ·Oncotarget · Pubmed #26934122.

ABSTRACT: BACKGROUND: Curcumin is a natural product that is often explored by patients with cancer. Weight loss due to fat and muscle depletion is a hallmark of pancreatic cancer and is associated with worse outcomes. Studies of curcumin's effects on muscularity show conflicting results in animal models. METHODS AND RESULTS: Retrospective matched 1:2 case-control study to evaluate the effects of curcumin on body composition (determined by computerized tomography) of 66 patients with advanced pancreatic cancer (22 treated,44 controls). Average age (SEM) was 63(1.8) years, 30/66(45%) women, median number of prior therapies was 2, median (IQR) time from advanced pancreatic cancer diagnosis to baseline image was 7(2-13.5) months (p>0.2, all variables). All patients lost weight (3.3% and 1.3%, treated vs. control, p=0.13). Treated patients lost more muscle (median [IQR] percent change -4.8[-9.1,-0.1] vs. -0.05%[-4.2, 2.6] in controls,p<0.001) and fat (median [IQR] percent change -6.8%[-15,-0.6] vs. -4.0%[-7.6, 1.3] in controls,p=0.04). Subcutaneous fat was more affected in the treated patients. Sarcopenic patients treated with curcumin(n=15) had survival of 169(115-223) days vs. 299(229-369) sarcopenic controls(p=0.024). No survival difference was found amongst non-sarcopenic patients. CONCLUSIONS: Patients with advanced pancreatic cancer treated with curcumin showed significantly greater loss of subcutaneous fat and muscle than matched untreated controls.

24 Article ABO non-O type as a risk factor for thrombosis in patients with pancreatic cancer. 2015

Li, Donghui / Pise, Mayurika N / Overman, Michael J / Liu, Chang / Tang, Hongwei / Vadhan-Raj, Saroj / Abbruzzese, James L. ·Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. · Department of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. ·Cancer Med · Pubmed #26275671.

ABSTRACT: ABO blood type has previously been identified as a risk factor for thrombosis and pancreatic cancer (PC). The aim of the study is to demonstrate the associations between ABO blood type and other clinical factors with the risk of thromboembolism (TE) in patients with PC. We conducted a retrospective study in 670 patients with pathologically confirmed pancreatic adenocarcinoma at the University of Texas MD Anderson Cancer Center. Clinical information was retrieved from medical records. ABO blood type was determined serologically and/or genetically. Logistic regression models, Kaplan-Meier plot, log-rank test, and Cox proportional hazard regression models were employed in data analysis. The incidence of TE was 35.2% in 670 patients who did not have TE prior to cancer diagnosis. Pulmonary embolism (PE) and deep vein thrombosis (DVT) consisted 44.1% of the TE events. Non-O blood type, pancreatic body/tail tumors, previous use of antithrombotic medication, and obesity (body mass index >30 kg/m(2) ) were significant predictors for TE in general. Blood type A and AB, low hemoglobin level (≤ 10 g/dL), obesity, metastatic tumor, and pancreatic body/tail tumors were significant predictors for PE and DVT. Patients with metastatic tumor or pancreatic body/tail tumors had a much higher frequency of early TE events (≤ 3 months after cancer diagnosis); and early TE occurrence was a significant independent predictor for increased risk of death. These observations suggest that ABO non-O blood type is an independent predictor for TE in PC. A better understanding of the risk factors for TE in PC may help to identify patients who are most likely to benefit from prophylactic anticoagulation therapy.

25 Article Family history as a marker of platinum sensitivity in pancreatic adenocarcinoma. 2015

Fogelman, David / Sugar, Elizabeth A / Oliver, George / Shah, Neeraj / Klein, Alison / Alewine, Christine / Wang, Huamin / Javle, Milind / Shroff, Rachna / Wolff, Robert A / Abbruzzese, James L / Laheru, Daniel / Diaz, Luis A. ·Department of G.I. Medical Oncology, M.D. Anderson Cancer Center, 1515 Holcombe Blvd., Unit 426, Houston, TX 77030, USA. · University of Texas/M.D. Anderson Cancer Center, 1515 Holcombe Blvd., Unit 426, Houston, TX 77096, USA. · Sidney Kimmel Cancer Center, The Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA. · Departments of Biostatistics and Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA. · Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe Street, Room E3537, Baltimore, MD 21205, USA. · 6300 Harry Hines Blvd. Ste 265, Dallas, TX 75235, USA. · Staten Island University Hospital, 475 Seaview Avenue, Staten Island, NY 10305, USA. · Departments of Pathology and Medicine, Johns Hopkins Medical Institutions, Baltimore, MD 21205, USA. · Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, 1650 Orleans St., Rm G89, Baltimore, MD 21231-1000, USA. · Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins School of Medicine, Baltimore, MD, USA. · Johns Hopkins Bloomberg School of Public Health, 1650 Orleans Street, CRB I Room 590, Baltimore, MD 21231, USA. · Department of Medical Oncology, NCI-National Cancer Institute, 10 Center Dr, Bldg 10/12N226, Bethesda, MD 20892, USA. · 1515 Holcombe Blvd., Unit 0085, Houston, TX 77030, USA. · Division of Medical Oncology, Duke University, 10 Searle Drive, 445 Seeley G Mudd Building, Durham, NC 27710, USA. · Swim Across America Laboratory, Ludwig Center for Cancer Genetics and Therapeutics at Johns Hopkins, 1650 Orleans Street, CRB I Room 590, Baltimore, MD 21231, USA. ·Cancer Chemother Pharmacol · Pubmed #26126726.

ABSTRACT: PURPOSE: Metastatic pancreatic adenocarcinoma is considered a uniformly fatal disease with a median survival of 1 year with modern chemotherapy. While a subset of patients achieve prolonged survival, few of the factors that define this group of patients are known. METHODS: For the determination of overall survival (OS), 549 patients with histologically confirmed metastatic pancreatic adenocarcinoma were evaluated. Emphasis was placed on treatment history and family history of breast, ovarian, and pancreatic cancers. To ensure a uniform metastatic population, patients treated with prior locoregional therapies (i.e., surgery or radiotherapy) were excluded as were patients with a prior history of stage I-III disease. RESULTS: Patients with family history or pedigree history of cancer had superior OS. This was especially true in patients with three or more relatives with either breast, ovarian, or pancreatic cancers [hazard ratio (HR) 0.49, 95 % confidence interval (CI) 0.30-0.80, p = 0.003]. First-line platinum chemotherapy was associated with a poor survival (hazard ratio for death 1.74, 95% CI 1.12-2.71, p = 0.01) for patients without a family history of these cancers but not for those without such a history (p = 0.31). In fact, as the number of relatives with these cancers increased, the OS survival improved for individuals receiving first-line platinum therapy (HR 0.76, 95 % CI 0.65-0.89, p = 0.0004), which was not the case for those receiving other therapies (p = 0.98). CONCLUSIONS: Treatment with platinum chemotherapy in patients with a family history of breast, ovarian, or pancreatic cancers was associated with a longer survival, whereas platinum use in patients without such a family history of cancer was associated with poor survival. These findings suggest that family history may serve as a predictive marker for platinum use in patients with metastatic pancreatic adenocarcinoma.

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