Pick Topic
Review Topic
List Experts
Examine Expert
Save Expert
  Site Guide ··   
Pancreatic Neoplasms: HELP
Articles by Alan B. Benson
Based on 24 articles published since 2010
(Why 24 articles?)

Between 2010 and 2020, A. Benson wrote the following 24 articles about Pancreatic Neoplasms.
+ Citations + Abstracts
1 Guideline Pancreatic Adenocarcinoma, Version 2.2017, NCCN Clinical Practice Guidelines in Oncology. 2017

Tempero, Margaret A / Malafa, Mokenge P / Al-Hawary, Mahmoud / Asbun, Horacio / Bain, Andrew / Behrman, Stephen W / Benson, Al B / Binder, Ellen / Cardin, Dana B / Cha, Charles / Chiorean, E Gabriela / Chung, Vincent / Czito, Brian / Dillhoff, Mary / Dotan, Efrat / Ferrone, Cristina R / Hardacre, Jeffrey / Hawkins, William G / Herman, Joseph / Ko, Andrew H / Komanduri, Srinadh / Koong, Albert / LoConte, Noelle / Lowy, Andrew M / Moravek, Cassadie / Nakakura, Eric K / O'Reilly, Eileen M / Obando, Jorge / Reddy, Sushanth / Scaife, Courtney / Thayer, Sarah / Weekes, Colin D / Wolff, Robert A / Wolpin, Brian M / Burns, Jennifer / Darlow, Susan. · ·J Natl Compr Canc Netw · Pubmed #28784865.

ABSTRACT: Ductal adenocarcinoma and its variants account for most pancreatic malignancies. High-quality multiphase imaging can help to preoperatively distinguish between patients eligible for resection with curative intent and those with unresectable disease. Systemic therapy is used in the neoadjuvant or adjuvant pancreatic cancer setting, as well as in the management of locally advanced unresectable and metastatic disease. Clinical trials are critical for making progress in treatment of pancreatic cancer. The NCCN Guidelines for Pancreatic Adenocarcinoma focus on diagnosis and treatment with systemic therapy, radiation therapy, and surgical resection.

2 Guideline Appropriateness of systemic treatments in unresectable metastatic well-differentiated pancreatic neuroendocrine tumors. 2015

Strosberg, Jonathan R / Fisher, George A / Benson, Al B / Anthony, Lowell B / Arslan, Bulent / Gibbs, John F / Greeno, Edward / Iyer, Renuka V / Kim, Michelle K / Maples, William J / Philip, Philip A / Wolin, Edward M / Cherepanov, Dasha / Broder, Michael S. ·Jonathan R Strosberg, Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, United States. ·World J Gastroenterol · Pubmed #25741154.

ABSTRACT: AIM: To evaluate systemic treatment choices in unresectable metastatic well-differentiated pancreatic neuroendocrine tumors (PNETs) and provide consensus treatment recommendations. METHODS: Systemic treatment options for pancreatic neuroendocrine tumors have expanded in recent years to include somatostatin analogs, angiogenesis inhibitors, inhibitors of mammalian target of rapamycin and cytotoxic agents. At this time, there is little data to guide treatment selection and sequence. We therefore assembled a panel of expert physicians to evaluate systemic treatment choices and provide consensus treatment recommendations. Treatment appropriateness ratings were collected using the RAND/UCLA modified Delphi process. After studying the literature, a multidisciplinary panel of 10 physicians assessed the appropriateness of various medical treatment scenarios on a 1-9 scale. Ratings were done both before and after an extended discussion of the evidence. Quantitative measurements of agreement were made and consensus statements developed from the second round ratings. RESULTS: Specialties represented were medical and surgical oncology, interventional radiology, and gastroenterology. Panelists had practiced for a mean of 15.5 years (range: 6-33). Among 202 rated scenarios, disagreement decreased from 13.2% (26 scenarios) before the face-to-face discussion of evidence to 1% (2) after. In the final ratings, 46.5% (94 scenarios) were rated inappropriate, 21.8% (44) were uncertain, and 30.7% (62) were appropriate. Consensus statements from the scenarios included: (1) it is appropriate to use somatostatin analogs as first line therapy in patients with hormonally functional tumors and may be appropriate in patients who are asymptomatic; (2) it is appropriate to use everolimus, sunitinib, or cytotoxic chemotherapy therapy as first line therapy in patients with symptomatic or progressive tumors; and (3) beyond first line, these same agents can be used. In patients with uncontrolled secretory symptoms, octreotide LAR doses can be titrated up to 60 mg every 4 wk or up to 40 mg every 3 or 4 wk. CONCLUSION: Using the Delphi process allowed physician experts to systematically obtain a consensus on the appropriateness of a variety of medical therapies in patients with PNETs.

3 Guideline Pancreatic Adenocarcinoma, version 2.2012: featured updates to the NCCN Guidelines. 2012

Tempero, Margaret A / Arnoletti, J Pablo / Behrman, Stephen W / Ben-Josef, Edgar / Benson, Al B / Casper, Ephraim S / Cohen, Steven J / Czito, Brian / Ellenhorn, Joshua D I / Hawkins, William G / Herman, Joseph / Hoffman, John P / Ko, Andrew / Komanduri, Srinadh / Koong, Albert / Ma, Wen Wee / Malafa, Mokenge P / Merchant, Nipun B / Mulvihill, Sean J / Muscarella, Peter / Nakakura, Eric K / Obando, Jorge / Pitman, Martha B / Sasson, Aaron R / Tally, Anitra / Thayer, Sarah P / Whiting, Samuel / Wolff, Robert A / Wolpin, Brian M / Freedman-Cass, Deborah A / Shead, Dorothy A / Anonymous5390728. ·UCSF Helen Diller Family Comprehensive Cancer Center. ·J Natl Compr Canc Netw · Pubmed #22679115.

ABSTRACT: The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Pancreatic Adenocarcinoma discuss the workup and management of tumors of the exocrine pancreas. These NCCN Guidelines Insights provide a summary and explanation of major changes to the 2012 NCCN Guidelines for Pancreatic Adenocarcinoma. The panel made 3 significant updates to the guidelines: 1) more detail was added regarding multiphase CT techniques for diagnosis and staging of pancreatic cancer, and pancreas protocol MRI was added as an emerging alternative to CT; 2) the use of a fluoropyrimidine plus oxaliplatin (e.g., 5-FU/leucovorin/oxaliplatin or capecitabine/oxaliplatin) was added as an acceptable chemotherapy combination for patients with advanced or metastatic disease and good performance status as a category 2B recommendation; and 3) the panel developed new recommendations concerning surgical technique and pathologic analysis and reporting.

4 Guideline Pancreatic adenocarcinoma. 2010

Tempero, Margaret A / Arnoletti, J Pablo / Behrman, Stephen / Ben-Josef, Edgar / Benson, Al B / Berlin, Jordan D / Cameron, John L / Casper, Ephraim S / Cohen, Steven J / Duff, Michelle / Ellenhorn, Joshua D I / Hawkins, William G / Hoffman, John P / Kuvshinoff, Boris W / Malafa, Mokenge P / Muscarella, Peter / Nakakura, Eric K / Sasson, Aaron R / Thayer, Sarah P / Tyler, Douglas S / Warren, Robert S / Whiting, Samuel / Willett, Christopher / Wolff, Robert A / Anonymous3900673. · ·J Natl Compr Canc Netw · Pubmed #20876541.

ABSTRACT: -- No abstract --

5 Review Therapy of locally advanced pancreatic adenocarcinoma: unresectable and borderline patients. 2011

Kircher, Sheetal M / Krantz, Seth B / Nimeiri, Halla S / Mulcahy, Mary F / Munshi, Hidayatullah G / Benson, Al B. ·Division of Hematology/Oncology, Northwestern University, Chicago, IL 60611, USA. ·Expert Rev Anticancer Ther · Pubmed #21999129.

ABSTRACT: Systemic chemotherapy for advanced pancreatic cancer is commonly used in practice; however, the optimal strategy for both neoadjuvant and adjuvant therapy in this disease remains controversial. A particular challenge remains in patients who are considered to be locally advanced and either unresectable or borderline resectable. Offering optimal neoadjuvant therapy to this group of patients may give them the opportunity to have a curative surgical approach. This article will discuss the potential role of neoadjuvant therapy in borderline, potentially resectable pancreatic cancer. It will also discuss areas of interest in potential targets as the biology of pancreatic adenocarcinoma is further explored.

6 Review The effects of bevacizumab on postoperative complications in patients undergoing colorectal and pancreatic cancer resection. 2010

Cheon, E C / Small, W / Strouch, M J / Krantz, S B / Rademaker, A / Mulcahy, M F / Benson, A B / Bentrem, D J / Talamonti, M S. ·Department of Surgery, Mount Sinai Hospital, University of Illinois at Chicago, Chicago, Illinois, USA. ·J Surg Oncol · Pubmed #20812264.

ABSTRACT: Bevacizumab (Avastin™; rhuMab VEGF), a monoclonal antibody targeting vascular endothelial growth factor (VEGF), has seen increased use in the perioperative treatment of colorectal and pancreatic cancer. Little is known, however, regarding its impact on surgical outcomes in patients undergoing resection. The objective of this review was to examine if the addition of bevacizumab to existing neoadjuvant regimens increases morbidity after cancer resection.

7 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.

8 Clinical Trial A Phase II Randomized, Double-Blind, Placebo-Controlled Study of Simtuzumab or Placebo in Combination with Gemcitabine for the First-Line Treatment of Pancreatic Adenocarcinoma. 2017

Benson, Al B / Wainberg, Zev A / Hecht, J Randolph / Vyushkov, Dmitry / Dong, Hua / Bendell, Johanna / Kudrik, Fred. ·Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois, USA a-benson@northwestern.edu. · David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California, USA. · Budgetary Healthcare Institution of Omsk Region, Clinical Oncologic Dispensary, Omsk, Russia. · Gilead Sciences, Inc., Foster City, California, USA. · Sarah Cannon Research Institute, Nashville, Tennessee, USA. · South Carolina Oncology Associates, Columbia, South Carolina, USA. ·Oncologist · Pubmed #28246206.

ABSTRACT: LESSONS LEARNED: The safety profile in the gemcitabine/simtuzumab group was similar to that in the gemcitabine/placebo group.The addition of simtuzumab to gemcitabine does not improve clinical outcomes in patients with metastatic pancreatic adenocarcinoma ABSTRACT: Background.The humanized IgG4 monoclonal antibody simtuzumab inhibits the extracellular matrix-remodeling enzyme lysyl oxidase-like 2 maintaining pathological stroma in tumors. METHODS: Adult patients with metastatic pancreatic adenocarcinoma (mPaCa) were randomly assigned to receive intravenous gemcitabine, 1,000 mg/m RESULTS: Of 240 patients, 80 were randomly assigned to gemcitabine/simtuzumab 700 mg, 79 to gemcitabine/simtuzumab 200 mg, and 81 to gemcitabine/placebo. After a median follow-up of 3.0, 1.9, and 3.4 months for gemcitabine/simtuzumab 700 mg, gemcitabine/simtuzumab 200 mg, and gemcitabine/placebo, respectively, the median PFS was 3.7 months (adjusted hazard ratio [HR], 95% confidence interval [CI], CONCLUSION: The addition of simtuzumab to gemcitabine did not improve clinical outcomes in patients with mPaCa.

9 Clinical Trial Randomized Phase II Trial of Irinotecan/Docetaxel or Irinotecan/Docetaxel Plus Cetuximab for Metastatic Pancreatic Cancer: An Eastern Cooperative Oncology Group Study. 2016

Burtness, Barbara / Powell, Mark / Catalano, Paul / Berlin, Jordan / Liles, Darla K / Chapman, Andrew E / Mitchell, Edith / Benson, Al B. ·*Department of Medical Oncology, Fox Chase Cancer Center ∥Department of Internal Medicine, Thomas Jefferson University School of Medicine, Philadelphia, PA †Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA ‡Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, TN §East Carolina University School of Medicine, Greenville, NC ¶Lurie Cancer Center, Northwestern University, Chicago, IL. ·Am J Clin Oncol · Pubmed #24685886.

ABSTRACT: OBJECTIVES: The primary objective was to determine the response rate in patients with metastatic pancreatic cancer treated in first line with irinotecan/docetaxel combination (Arm A) or with irinotecan/docetaxel/cetuximab combination (Arm B). Secondary endpoints were progression-free survival (PFS), overall survival (OS), toxicity, and the rate of thromboembolic events with prophylactic enoxaparin sodium. PATIENTS AND METHODS: Patients were eligible who had measurable, metastatic adenocarcinoma of the pancreas, and normal bilirubin. All patients received anticoagulation. Docetaxel (35 mg/m) and irinotecan (50 mg/m) were administered once a week for 4 weeks followed by 2 weeks rest (Arm A) alone or with the addition of cetuximab (Arm B). The primary endpoint was response rate. RESULTS: A total of 87 eligible patients were enrolled and treated. Grade 3/4 toxicity was observed in 74% of patients in Arm A and 76% in Arm B. The principal grade 3/4 toxicity was diarrhea. Response rates were 4.5% in Arm A and 7% in Arm B. Median PFS and OS were 3.9 and 6.5 months in Arm A and 4.5 and 5.4 months in Arm B. CONCLUSIONS: Docetaxel/irinotecan combination is associated with considerable toxicity. Objective responses were infrequent and addition of cetuximab in an unselected population was not beneficial, but PFS and OS were comparable with those achieved with other regimens. Docetaxel/irinotecan therapy is active in metastatic pancreatic cancer.

10 Clinical Trial Five year results of US intergroup/RTOG 9704 with postoperative CA 19-9 ≤90 U/mL and comparison to the CONKO-001 trial. 2012

Berger, Adam C / Winter, Kathryn / Hoffman, John P / Regine, William F / Abrams, Ross A / Safran, Howard / Freedman, Gary M / Benson, Alan B / Macdonald, John / Willett, Christopher G. ·Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA. adam.berger@jefferson.edu ·Int J Radiat Oncol Biol Phys · Pubmed #22682806.

ABSTRACT: PURPOSE: Radiation Therapy Oncology Group (RTOG) trial 9704 was the largest randomized trial to use adjuvant chemoradiation therapy for patients with pancreatic cancer. This report analyzes 5-year survival by serum level of tumor marker CA 19-9 of ≤90 vs >90 U/mL and compares results to the those of the CONKO-001 trial. METHODS AND MATERIALS: CA 19-9 expression was analyzed as a dichotomized variable (≤90 vs >90 U/mL). Cox proportional hazard models were used to identify the impact of the CA 19-9 value on overall survival (OS). Actuarial estimates of OS were calculated using the Kaplan-Meier method. RESULTS: Both univariate (hazard ratio [HR] = 3.2; 95% confidence interval [CI], 2.3-4.3, P<.0001) and multivariate (HR = 3.1; 95% CI, 2.2-4.2, P<.0001) analyses demonstrated a statistically significant decrease in OS for CA 19-9 serum level of ≥90 U/mL. For patients in the gemcitabine (Gem) treatment arm with CA 19-9 <90 U/mL, median survival was 21 months. For patients with CA 19-9 ≥90 U/mL, this number dropped to 10 months. In patients with pancreatic head tumors in the Gem treatment arm with RT quality assurance per protocol and CA 19-9 of <90 U/mL, median survival and 5-year rate were 24 months and 34%. In comparison, the median survival and 5-year OS rate for patients in the Gem arm of the CONKO trial were 22 months and 21%. CONCLUSIONS: This analysis demonstrates that patients with postresection CA 19-9 values ≥90 U/mL had a significantly worse survival. Patients with pancreatic head tumors treated with Gem with CA 19-9 serum level of <90 U/mL and per protocol RT had favorable survival compared to that seen in the CONKO trial. CA 19-9 is a stratification factor for the current RTOG adjuvant pancreas trial (0848).

11 Clinical Trial Failure to adhere to protocol specified radiation therapy guidelines was associated with decreased survival in RTOG 9704--a phase III trial of adjuvant chemotherapy and chemoradiotherapy for patients with resected adenocarcinoma of the pancreas. 2012

Abrams, Ross A / Winter, Kathryn A / Regine, William F / Safran, Howard / Hoffman, John P / Lustig, Robert / Konski, Andre A / Benson, Al B / Macdonald, John S / Rich, Tyvin A / Willett, Christopher G. ·Department of Radiation Oncology, Rush University Medical Center, Chicago, IL 60612, USA. ·Int J Radiat Oncol Biol Phys · Pubmed #21277694.

ABSTRACT: PURPOSE: In Radiation Therapy Oncology Group 9704, as previously published, patients with resected pancreatic adenocarcinoma received continuous infusion 5-FU and concurrent radiotherapy (5FU-RT). 5FU-RT treatment was preceded and followed by randomly assigned chemotherapy, either 5-FU or gemcitabine. This analysis explored whether failure to adhere to specified RT guidelines influenced survival and/or toxicity. METHODS AND MATERIALS: RT requirements were protocol specified. Adherence was scored as per protocol (PP) or less than per protocol (This is the first Phase III, multicenter, adjuvant protocol for pancreatic adenocarcinoma to evaluate the impact of adherence to specified RT protocol guidelines on protocol outcomes. Failure to adhere to specified RT guidelines was associated with reduced survival and, for patients receiving gemcitabine, trend toward increased nonhematologic toxicity.

12 Clinical Trial Fluorouracil-based chemoradiation with either gemcitabine or fluorouracil chemotherapy after resection of pancreatic adenocarcinoma: 5-year analysis of the U.S. Intergroup/RTOG 9704 phase III trial. 2011

Regine, William F / Winter, Kathryn A / Abrams, Ross / Safran, Howard / Hoffman, John P / Konski, Andre / Benson, Al B / Macdonald, John S / Rich, Tyvin A / Willett, Christopher G. ·Department of Radiation Oncology, University of Maryland, Baltimore, MD, USA, wregine@umm.edu ·Ann Surg Oncol · Pubmed #21499862.

ABSTRACT: BACKGROUND: The impact of the addition of gemcitabine to 5-fluorouracil (5-FU) chemoradiation (CRT) on 5-year overall survival (OS) in resected pancreatic adenocarcinoma are presented with updated results of a phase III trial. METHODS: After resection of pancreatic adenocarcinoma, patients were randomized to pre- and post-CRT 5-FU versus pre- and post-CRT gemcitabine. 5-FU was provided continuously at 250 mg/m(2)/day, and gemcitabine was provided at 1000 mg/m(2) weekly. Both were provided over 3 weeks before and 12 weeks after CRT. CRT was provided at 50.4 Gy with continuously provided 5-FU. The primary end point was survival for all patients and for patients with tumor of the pancreatic head. RESULTS: Four hundred fifty-one patients were eligible. Univariate analysis showed no difference in OS. Pancreatic head tumor patients (n = 388) had a median survival and 5-year OS of 20.5 months and 22% with gemcitabine versus 17.1 months and 18% with 5-FU. On multivariate analysis, patients on the gemcitabine arm with pancreatic head tumors experienced a trend toward improved OS (P = 0.08). First site of relapse local recurrence in 28% of patients versus distant relapse in 73%. CONCLUSIONS: The sequencing of 5-FU CRT with gemcitabine as done in this trial is not associated with a statistically significant improvement in OS. Despite local recurrence being approximately half of that reported in previous adjuvant trials, distant disease relapse still occurs in ≥ 70% of patients. These findings serve as the basis for the recently activated EORTC/U.S. Intergroup RTOG 0848 phase III adjuvant trial evaluating the impact of CRT after completion of a full course of gemcitabine.

13 Clinical Trial The influence of total nodes examined, number of positive nodes, and lymph node ratio on survival after surgical resection and adjuvant chemoradiation for pancreatic cancer: a secondary analysis of RTOG 9704. 2011

Showalter, Timothy N / Winter, Kathryn A / Berger, Adam C / Regine, William F / Abrams, Ross A / Safran, Howard / Hoffman, John P / Benson, Al B / MacDonald, John S / Willett, Christopher G. ·Department of Radiation Oncology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA. ·Int J Radiat Oncol Biol Phys · Pubmed #20934270.

ABSTRACT: PURPOSE: Lymph node status is an important predictor of survival in pancreatic cancer. We performed a secondary analysis of Radiation Therapy Oncology Group (RTOG) 9704, an adjuvant chemotherapy and chemoradiation trial, to determine the influence of lymph node factors--number of positive nodes (NPN), total nodes examined (TNE), and lymph node ratio (LNR ratio of NPN to TNE)--on OS and disease-free survival (DFS). PATIENT AND METHODS: Eligible patients from RTOG 9704 form the basis of this secondary analysis of lymph node parameters. Actuarial estimates for OS and DFS were calculated using Kaplan-Meier methods. Cox proportional hazards models were performed to evaluate associations of NPN, TNE, and LNR with OS and DFS. Multivariate Cox proportional hazards models were also performed. RESULTS: There were 538 patients enrolled in the RTOG 9704 trial. Of these, 445 patients were eligible with lymph nodes removed. Overall median NPN was 1 (min-max, 0-18). Increased NPN was associated with worse OS (HR=1.06, p=0.001) and DFS (HR=1.05, p=0.01). In multivariate analyses, both NPN and TNE were associated with OS and DFS. TNE>12, and >15 were associated with increased OS for all patients, but not for node-negative patients (n=142). Increased LNR was associated with worse OS (HR=1.01, p<0.0001) and DFS (HR=1.006, p=0.002). CONCLUSION: In patients who undergo surgical resection followed by adjuvant chemoradiation, TNE, NPN, and LNR are associated with OS and DFS. This secondary analysis of a prospective, cooperative group trial supports the influence of these lymph node parameters on outcomes after surgery and adjuvant therapy using contemporary techniques.

14 Clinical Trial Phase II trial of full-dose gemcitabine and bevacizumab in combination with attenuated three-dimensional conformal radiotherapy in patients with localized pancreatic cancer. 2011

Small, William / Mulcahy, Mary F / Rademaker, Alfred / Bentrem, David J / Benson, Al B / Weitner, Bing Bing / Talamonti, Mark S. ·Department of Radiation Oncology, Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois 60611, USA. wsmall@nmff.org ·Int J Radiat Oncol Biol Phys · Pubmed #20598452.

ABSTRACT: PURPOSE: To evaluate response rate, survival, and toxicity in patients with nonmetastatic pancreatic cancer treated with gemcitabine, bevacizumab, and radiotherapy. METHODS AND MATERIALS: Patients received three cycles of therapy over 10 weeks. In total, treatment consisted of intravenous (IV) gemcitabine, 1,000 mg/m(2), every 1 to 2 weeks (7 doses), IV bevacizumab, 10 mg/kg every 2 weeks (5 doses), and 36 Gy of radiotherapy (2.4-Gy fractions during cycle two). Response was assessed by cross-sectional imaging and carbohydrate antigen 19-9 (CA 19-9) levels. Patients with resectable tumors underwent surgery 6 to 8 weeks after the last dose of bevacizumab. Maintenance gemcitabine and bevacizumab doses were delivered to patients who had unresected tumors and no progression. RESULTS: Twenty-eight of the 32 enrolled patients completed all three cycles. The median follow-up was 11.07 months. Most grade 3 or 4 toxicities occurred in the initial treatment phase; the most frequent toxicities were leukopenia (21%), neutropenia (17%), and nausea (17%). At week 10, 1 patient (4%) had a complete response, 2 patients (7%) had partial responses, 21 patients (75%) had stable disease, and 4 patients (14%) had progressive disease. The median pretreatment and posttreatment CA 19-9 levels (25 patients) were 184.3 and 57.9 U/ml, respectively (p = 0.0006). One of 10 patients proceeding to surgery experienced a major complication. Two of 6 patients undergoing resection had complete pathologic responses. The median progression-free and overall survival durations were 9.9 months and 11.8 months, respectively. CONCLUSIONS: The combination of full-dose gemcitabine, bevacizumab, and radiotherapy was active and was not associated with a high rate of major surgical complications.

15 Clinical Trial Randomized phase II study of gemcitabine plus radiotherapy versus gemcitabine, 5-fluorouracil, and cisplatin followed by radiotherapy and 5-fluorouracil for patients with locally advanced, potentially resectable pancreatic adenocarcinoma. 2010

Landry, Jerome / Catalano, Paul J / Staley, Charles / Harris, Wayne / Hoffman, John / Talamonti, Mark / Xu, Natalie / Cooper, Harry / Benson, Al B. ·Department of Radiation Oncology, Emory University School of Medicine, Atlanta, Georgia 30322, USA. jerome@radonc.emory.org ·J Surg Oncol · Pubmed #20461765.

ABSTRACT: PURPOSE: A randomized phase II trial (E1200) was designed to assess toxicities and surgical resection rates in two neoadjuvant gemcitabine-based chemoradiation regimens in patients with borderline resectable pancreatic cancer. The trial was terminated early due to poor accrual. PATIENTS AND METHODS: Patients with borderline resectable adenocarcinomas of the pancreas were enrolled. Arm A patients (n = 10) received gemcitabine 500 mg/m(2) IV weekly for 6 weeks, with radiation to 50.4 Gy followed by surgical resection. Arm B patients (n = 11) received preoperative gemcitabine 175 mg/m(2) on days 1, 5, 29, and 33, cisplatin 20 mg/m(2) on days 1-5 and 29-32, 5-FU 600 mg/m(2) on days 1-5 and 29-32, followed by radiation with continuous infusion 5-FU 225 mg/m(2) for 6 weeks. All patients received adjuvant gemcitabine 1,000 mg/m(2) weekly x 3 for five cycles. RESULTS: Three patients in arm A, and two patients in arm B were resected. Hematologic toxicity was comparable between the two arms except more patients in arm B developed grade 3 or 4 thrombocytopenia than those in arm A. Arm B had fewer grade 1-2 GI toxicities although more patients (45%) experienced grade 3-4 GI toxicity. CONCLUSIONS: This phase II trial showed that both regimens were tolerable, and resectability and survival were comparable to previous studies.

16 Article Ipilimumab and Gemcitabine for Advanced Pancreatic Cancer: A Phase Ib Study. 2020

Kamath, Suneel D / Kalyan, Aparna / Kircher, Sheetal / Nimeiri, Halla / Fought, Angela J / Benson, Al / Mulcahy, Mary. ·Division of Hematology and Oncology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA. · Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, Illinois, USA. · Developmental Therapeutics Program, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA. · Division of Biostatistics, Department of Preventative Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA. ·Oncologist · Pubmed #31740568.

ABSTRACT: BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) remains resistant to chemotherapy and immunotherapy individually because of its desmoplastic stroma and immunosuppressive tumor microenvironment. Synergizing cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) immune checkpoint blockade with chemotherapy could overcome these barriers. Here we present results of a phase Ib trial combining ipilimumab and gemcitabine in advanced PDAC. MATERIALS AND METHODS: This was a single-institution study with a 3 + 3 dose-escalation design. The primary objective was to determine the maximum tolerated dose (MTD). Secondary objectives included determining the toxicity profile, objective response rate (ORR), median progression-free survival (PFS), and overall survival (OS). RESULTS: Twenty-one patients were enrolled, 13 during dose escalation and 8 at the MTD. The median age was 66 years, 62% were female, 95% had stage IV disease, and 67% had received at least one prior line of therapy. The primary objective to establish the MTD was achieved at doses of ipilimumab 3 mg/kg and gemcitabine 1,000 mg/m CONCLUSION: Gemcitabine and ipilimumab is a safe and tolerable regimen for PDAC with a similar response rate to gemcitabine alone. As in other immunotherapy trials, responses were relatively durable in this study. IMPLICATIONS FOR PRACTICE: Gemcitabine and ipilimumab is a safe and feasible regimen for treating advanced pancreatic cancer. Although one patient in this study had a relatively durable response of nearly 20 months, adding ipilimumab to gemcitabine does not appear to be more effective than gemcitabine alone in advanced pancreatic cancer.

17 Article Precision Medicine and Pancreatic Cancer: A Gemcitabine Pathway Approach. 2016

Farrell, James J / Moughan, Jennifer / Wong, Jonathan L / Regine, William F / Schaefer, Paul / Benson, Al B / Macdonald, John S / Liu, Xiyong / Yen, Yun / Lai, Raymond / Zheng, Zhong / Bepler, Gerold / Guha, Chandan / Elsaleh, Hany. ·From the *Yale Center for Pancreatic Disease, Yale School of Medicine, New Haven, CT; †Statistics and Data Management Center, NRG Oncology, Philadelphia, PA; ‡Department of Medicine, John A Burns School of Medicine, University of Hawaii, Honolulu, HI; §Department of Radiation Oncology, University of Maryland, Baltimore, MD; ∥Oncology Program, Toledo Clinic, Toledo, OH; ¶Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL; #Saint Vincent Comprehensive Cancer Center, New York; and **The Oncology Consortia of Criterium Inc, Saratoga Springs, NY; ††California Cancer Institute, Temple City, CA; ‡‡Graduate Institute of Medical Sciences, College of Medicine, and §§Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan; ∥∥Department of Pathology, Cross Cancer Center, University of Alberta, Edmonton, Alberta, Canada; ¶¶Department of Pathology, H. Lee Moffitt Cancer Center, Tampa, FL; ##Karmanos Cancer Institute; and ***Department of Oncology and Cancer Biology Graduate Program, Wayne State University, Detroit, MI; †††Department of Radiation Oncology, Montifiore Medical Center, Bronx, NY; and ‡‡‡Department of Radiation Oncology, The Canberra Hospital, Australian National University, Canberra, Australia. ·Pancreas · Pubmed #27748721.

ABSTRACT: OBJECTIVES: There is a need for validated predictive markers of gemcitabine response to guide precision medicine treatment in pancreatic cancer. We previously validated human equilibrative nucleoside transporter 1 as a predictive marker of gemcitabine treatment response using Radiation Therapy Oncology Group 9704. Controversy exists about the predictive value of gemcitabine metabolism pathway biomarkers: deoxycytidine kinase (DCK), ribonucleotide reductase 1 (RRM1), RRM2, and p53R2. METHODS: Radiation Therapy Oncology Group 9704 prospectively randomized 538 patients after pancreatic resection to receive either 5-fluorouracil or gemcitabine. Tumor DCK, RRM1, RRM2, and p53R protein expressions were analyzed using a tissue microarray and immunohistochemistry and correlated with treatment outcome (overall survival and disease-free survival) by unconditional logistic regression analysis. RESULTS: There were 229 patients eligible for analysis from both the 5-fluorouracil and gemcitabine arms. Only RRM2 protein expression, and not DCK, RRM1, or p53R2 protein expression, was associated with survival in the gemcitabine treatment arm. CONCLUSIONS: Despite limited data from other nonrandomized treatment data, our data do not support the predictive value of DCK, RRM1, or p53R2. Efforts should focus on human equilibrative nucleoside transporter 1 and possibly RRM2 as valid predictive markers of the treatment response of gemcitabine in pancreatic cancer.

18 Article Is There Efficacy Beyond Cytotoxic Chemotherapy for Pancreatic Cancer? 2016

Kalyan, Aparna / Benson, Al B. ·Northwestern University, Chicago, IL aparna.kalyan@northwestern.edu. · Northwestern University, Chicago, IL. ·J Oncol Pract · Pubmed #27621333.

ABSTRACT: -- No abstract --

19 Article Locally Advanced, Unresectable Pancreatic Cancer: American Society of Clinical Oncology Clinical Practice Guideline. 2016

Balaban, Edward P / Mangu, Pamela B / Khorana, Alok A / Shah, Manish A / Mukherjee, Somnath / Crane, Christopher H / Javle, Milind M / Eads, Jennifer R / Allen, Peter / Ko, Andrew H / Engebretson, Anitra / Herman, Joseph M / Strickler, John H / Benson, Al B / Urba, Susan / Yee, Nelson S. ·Edward P. Balaban, Cancer Care Partnership, State College · Edward P. Balaban and Nelson S. Yee, Penn State Hershey Cancer Institute, Hershey, PA · Pamela B. Mangu, American Society of Clinical Oncology, Alexandria, VA · Alok A. Khorana, Cleveland Clinic · Jennifer R. Eads, University Hospitals Seidman Cancer Center, Case Western Reserve University, Cleveland, OH · Manish A. Shah, The Weill Cornell Medical Center · Peter Allen, Memorial Sloan Kettering Cancer Center, New York, NY · Somnath Mukherjee, University of Oxford, Oxford, United Kingdom · Christopher H. Crane and Milind M. Javle, The University of Texas MD Anderson Cancer Center, Houston, TX · Andrew H. Ko, University of California San Francisco Comprehensive Cancer Center, San Francisco, CA · Anitra Engebretson, Patient Representative, Portland, OR · Joseph M. Herman, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD · John H. Strickler, Duke University Medical Center, Durham, NC · Al B. Benson III, Lurie Comprehensive Cancer Center of Northwestern, Chicago, IL · and Susan Urba, University of Michigan Cancer Center, Ann Arbor, MI. ·J Clin Oncol · Pubmed #27247216.

ABSTRACT: PURPOSE: To provide evidence-based recommendations to oncologists and others for treatment of patients with locally advanced, unresectable pancreatic cancer. METHODS: American Society of Clinical Oncology convened an Expert Panel of medical oncology, radiation oncology, surgical oncology, gastroenterology, palliative care, and advocacy experts and conducted a systematic review of the literature from January 2002 to June 2015. Outcomes included overall survival, disease-free survival, progression-free survival, and adverse events. RESULTS: Twenty-six randomized controlled trials met the systematic review criteria. RECOMMENDATIONS: A multiphase computed tomography scan of the chest, abdomen, and pelvis should be performed. Baseline performance status and comorbidity profile should be evaluated. The goals of care, patient preferences, psychological status, support systems, and symptoms should guide decisions for treatments. A palliative care referral should occur at first visit. Initial systemic chemotherapy (6 months) with a combination regimen is recommended for most patients (for some patients radiation therapy may be offered up front) with Eastern Cooperative Oncology Group performance status 0 or 1 and a favorable comorbidity profile. There is no clear evidence to support one regimen over another. The gemcitabine-based combinations and treatments recommended in the metastatic setting (eg, fluorouracil, leucovorin, irinotecan, and oxaliplatin and gemcitabine plus nanoparticle albumin-bound paclitaxel) have not been evaluated in randomized controlled trials involving locally advanced, unresectable pancreatic cancer. If there is local disease progression after induction chemotherapy, without metastasis, then radiation therapy or stereotactic body radiotherapy may be offered also with an Eastern Cooperative Oncology Group performance status ≤ 2 and an adequate comorbidity profile. If there is stable disease after 6 months of induction chemotherapy but unacceptable toxicities, radiation therapy may be offered as an alternative. Patients with disease progression should be offered treatment per the ASCO Metastatic Pancreatic Cancer Treatment Guideline. Follow-up visits every 3 to 4 months are recommended. Additional information is available at www.asco.org/guidelines/LAPC and www.asco.org/guidelines/MetPC and www.asco.org/guidelineswiki.

20 Article Quantitative Sensory Testing at Baseline and During Cycle 1 Oxaliplatin Infusion Detects Subclinical Peripheral Neuropathy and Predicts Clinically Overt Chronic Neuropathy in Gastrointestinal Malignancies. 2016

Reddy, Sangeetha M / Vergo, Maxwell T / Paice, Judith A / Kwon, Nancy / Helenowski, Irene B / Benson, Al B / Mulcahy, Mary F / Nimeiri, Halla S / Harden, Robert N. ·Division of Hematology/Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX. Electronic address: smreddy1@mdanderson.org. · Geisel School of Medicine, Section of Palliative Medicine, Dartmouth Hitchcock Medical Center, Lebanon, NH. · Division of Hematology/Oncology, Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL. · Department of Biobehavioral Sciences, Columbia University, New York, NY. · Department of Preventive Medicine, Northwestern University, Chicago, IL. · Center for Pain Studies, Rehabilitation Institute of Chicago and Department of Physical Medicine and Rehabilitation, Northwestern University Feinberg School of Medicine, Chicago, IL. ·Clin Colorectal Cancer · Pubmed #26337211.

ABSTRACT: PURPOSE: Oxaliplatin neurotoxicity has a spectrum of manifestations from an often reversible acute neurotoxicity to a more irreversible "stocking and glove" chronic neuropathy that is associated with high morbidity. Quantitative sensory testing (QST) is a noninvasive psychometric testing method that can potentially be used in the clinic setting to measure subclinical neurologic changes early on to identify patients that will experience chronic oxaliplatin-induced peripheral neuropathy at 1 year. PATIENTS AND METHODS: Thirty patients with gastrointestinal malignancies who were receiving oxaliplatin were recruited. QST and patient-reported outcomes were assessed at baseline; during infusion cycles 1, 2, 4, and 6; and at 1 year. National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.0, chronic neuropathy scores were assessed at the 1-year time point. The variables at each time point were evaluated for prediction of 1-year chronic neuropathy scores. RESULTS: We found that patients with preexisting subclinical neuropathy were more likely to experience grades 2 and 3 chronic neuropathy than were those who did not have this condition (heat detection threshold, Spearman correlation coefficient (rs) = 0.39; P = .037; pellet retrieval time, rs = 0.47; P = .024). Patients in whom thermal and cutaneous sensory deficits developed with cycle 1 infusion were also more likely to experience grades 2 and 3 neuropathy at 1 year (cold detection threshold, rs = 0.50; P = .007; heat detection threshold, rs = 0.39; P = .042; cutaneous detection threshold, rs = 0.42; P = .043). CONCLUSION: QST provides a noninvasive, commercially available, and feasible clinical test to select patients, even before oxaliplatin treatment, who are likely to experience moderate to severe chronic peripheral neuropathy.

21 Article Pancreatic adenocarcinoma, version 2.2014: featured updates to the NCCN guidelines. 2014

Tempero, Margaret A / Malafa, Mokenge P / Behrman, Stephen W / Benson, Al B / Casper, Ephraim S / Chiorean, E Gabriela / Chung, Vincent / Cohen, Steven J / Czito, Brian / Engebretson, Anitra / Feng, Mary / Hawkins, William G / Herman, Joseph / Hoffman, John P / Ko, Andrew / Komanduri, Srinadh / Koong, Albert / Lowy, Andrew M / Ma, Wen Wee / Merchant, Nipun B / Mulvihill, Sean J / Muscarella, Peter / Nakakura, Eric K / Obando, Jorge / Pitman, Martha B / Reddy, Sushanth / Sasson, Aaron R / Thayer, Sarah P / Weekes, Colin D / Wolff, Robert A / Wolpin, Brian M / Burns, Jennifer L / Freedman-Cass, Deborah A. ·From UCSF Helen Diller Family Comprehensive Cancer Center; Moffitt Cancer Center; St. Jude Children's Research Hospital/The University of Tennessee Health Science Center; Robert H. Lurie Comprehensive Cancer Center of Northwestern University; Memorial Sloan Kettering Cancer Center; Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance; City of Hope Comprehensive Cancer Center; Fox Chase Cancer Center; Duke Cancer Institute; Pancreatic Cancer Action Network (PanCAN); University of Michigan Comprehensive Cancer Center; Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins; Stanford Cancer Institute; UC San Diego Moores Cancer Center; Roswell Park Cancer Institute; Vanderbilt-Ingram Cancer Center; Huntsman Cancer Institute at the University of Utah; The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute; Massachusetts General Hospital Cancer Center; University of Alabama at Birmingham Comprehensive Cancer Center; Fred & Pamela Buffett Cancer Center at The Nebraska Medical Center; University of Colorado Cancer Center; The University of Texas MD Anderson Cancer Center; Dana-Farber/Brigham and Women's Cancer Center; and National Comprehensive Cancer Network. ·J Natl Compr Canc Netw · Pubmed #25099441.

ABSTRACT: The NCCN Guidelines for Pancreatic Adenocarcinoma discuss the diagnosis and management of adenocarcinomas of the exocrine pancreas and are intended to assist with clinical decision-making. These NCCN Guidelines Insights summarize major discussion points from the 2014 NCCN Pancreatic Adenocarcinoma Panel meeting. The panel discussion focused mainly on the management of borderline resectable and locally advanced disease. In particular, the panel discussed the definition of borderline resectable disease, role of neoadjuvant therapy in borderline disease, role of chemoradiation in locally advanced disease, and potential role of newer, more active chemotherapy regimens in both settings.

22 Article Development and validation of a symptom index for advanced hepatobiliary and pancreatic cancers: the National Comprehensive Cancer Network Functional Assessment of Cancer Therapy (NCCN-FACT) Hepatobiliary-Pancreatic Symptom Index (NFHSI). 2012

Butt, Zeeshan / Parikh, Neehar D / Beaumont, Jennifer L / Rosenbloom, Sarah K / Syrjala, Karen L / Abernethy, Amy P / Benson, Al B / Cella, David. ·Department of Medical Social Sciences, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA. z-butt@northwestern.edu ·Cancer · Pubmed #22605658.

ABSTRACT: BACKGROUND: The 45-item Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep) questionnaire assesses health-related quality of life in patients with liver, bile duct, and pancreatic cancers. Although the FACT-Hep was initially derived from patient input, this study's researchers sought to verify adequate coverage of items by soliciting open-ended input from patients with advanced disease. METHODS: As part of a larger study in collaboration with the National Comprehensive Cancer Network (NCCN), 50 people (60% male, 80% caucasian, average age 60.4 years) with stage 3 or 4 hepatobiliary or pancreatic cancer were recruited. Participants generated and ranked up to 10 important symptoms and concerns that physicians should monitor when assessing the value of chemotherapy. Patients were also able to provide open-ended, qualitative information that was evaluated systematically. Ten expert physicians also provided input on priority symptoms. RESULTS: The resulting 18-item NCCN-FACT Hepatobiliary-Pancreatic Symptom Index (NFHSI-18) demonstrated high internal consistency (α = .89) and moderate to strong correlations with measures of physical well-being (ρ = .76), emotional well-being (ρ = 0.52), and functional well-being (ρ = 0.57). Scores on the NFHSI-18 were also highly correlated with the original hepatobiliary scale of the FACT-Hep (ρ = .82; all P < .001). Compared with patients with better performance status, patients with poor performance status had worse NFHSI-18 symptom scores, F(3,47) = 9.74; P = .0003. CONCLUSIONS: The NFHSI-18 assesses symptoms of importance to patients with hepatobiliary and pancreatic cancers and demonstrates promising measurement properties. The scale is a good candidate for brief symptom assessment in clinical trials.

23 Article Gemcitabine alone versus gemcitabine plus radiotherapy in patients with locally advanced pancreatic cancer: an Eastern Cooperative Oncology Group trial. 2011

Loehrer, Patrick J / Feng, Yang / Cardenes, Higinia / Wagner, Lynne / Brell, Joanna M / Cella, David / Flynn, Patrick / Ramanathan, Ramesh K / Crane, Christopher H / Alberts, Steven R / Benson, Al B. ·Indiana University Melvin and Bren Simon Cancer Center, 980 West Walnut St, Suite C528, Indianapolis, IN 46202, USA. ploehrer@iupui.edu ·J Clin Oncol · Pubmed #21969502.

ABSTRACT: PURPOSE: The purpose of this trial was to evaluate the role of radiation therapy with concurrent gemcitabine (GEM) compared with GEM alone in patients with localized unresectable pancreatic cancer. PATIENTS AND METHODS: Patients with localized unresectable adenocarcinoma of the pancreas were randomly assigned to receive GEM alone (at 1,000 mg/m(2)/wk for weeks 1 to 6, followed by 1 week rest, then for 3 of 4 weeks) or GEM (600 mg/m(2)/wk for weeks 1 to 5, then 4 weeks later 1,000 mg/m(2) for 3 of 4 weeks) plus radiotherapy (starting on day 1, 1.8 Gy/Fx for total of 50.4 Gy). Measurement of quality of life using the Functional Assessment of Cancer Therapy-Hepatobiliary questionnaire was also performed. RESULTS: Of 74 patients entered on trial and randomly assigned to receive GEM alone (arm A; n = 37) or GEM plus radiation (arm B; n = 34), patients in arm B had greater incidence of grades 4 and 5 toxicities (41% v 9%), but grades 3 and 4 toxicities combined were similar (77% in A v 79% in B). No statistical differences were seen in quality of life measurements at 6, 15 to 16, and 36 weeks. The primary end point was survival, which was 9.2 months (95% CI, 7.9 to 11.4 months) and 11.1 months (95% CI, 7.6 to 15.5 months) for arms A and B, respectively (one-sided P = .017 by stratified log-rank test). CONCLUSION: This trial demonstrates improved overall survival with the addition of radiation therapy to GEM in patients with localized unresectable pancreatic cancer, with acceptable toxicity.

24 Minor Chemotherapy: Gemcitabine remains the standard of care for pancreatic cancer. 2010

Berlin, Jordan / Benson, Al B. · ·Nat Rev Clin Oncol · Pubmed #20190797.

ABSTRACT: -- No abstract --