Pick Topic
Review Topic
List Experts
Examine Expert
Save Expert
  Site Guide ··   
Pancreatic Neoplasms: HELP
Articles by Ross Allen Abrams
Based on 26 articles published since 2010
(Why 26 articles?)
||||

Between 2010 and 2020, R. Abrams wrote the following 26 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Guideline Radiotherapy technical considerations in the management of locally advanced pancreatic cancer: American-French consensus recommendations. 2012

Huguet, Florence / Goodman, Karyn A / Azria, David / Racadot, Severine / Abrams, Ross A. ·Department of Radiation Oncology, Tenon Hospital, APHP, University Paris VI, Paris, France. florence.huguet@tnn.aphp.fr ·Int J Radiat Oncol Biol Phys · Pubmed #22768988.

ABSTRACT: Pancreatic carcinoma is a leading cause of cancer-related mortality. Approximately 30% of pancreatic cancer patients present with locally advanced, unresectable nonmetastatic disease. For these patients, two therapeutic options exist: systemic chemotherapy or chemoradiotherapy. Within this context, the optimal technique for pancreatic irradiation is not clearly defined. A search to identify relevant studies was undertaken using the Medline database. All Phase III randomized trials evaluating the modalities of radiotherapy in locally advanced pancreatic cancer were included, as were some noncontrolled Phase II and retrospective studies. An expert panel convened with members of the Radiation Therapy Oncology Group and GERCOR cooperative groups to review identified studies and prepare the guidelines. Each member of the working group independently evaluated five endpoints: total dose, target volume definition, radiotherapy planning technique, dose constraints to organs at risk, and quality assurance. Based on this analysis of the literature, we recommend either three-dimensional conformal radiation therapy or intensity-modulated radiation therapy to a total dose of 50 to 54 Gy at 1.8 to 2 Gy per fraction. We propose gross tumor volume identification to be followed by an expansion of 1.5 to 2 cm anteriorly, posteriorly, and laterally, and 2 to 3 cm craniocaudally to generate the planning target volume. The craniocaudal margins can be reduced with the use of respiratory gating. Organs at risk are liver, kidneys, spinal cord, stomach, and small bowel. Stereotactic body radiation therapy should not be used for pancreatic cancer outside of clinical trials. Radiotherapy quality assurance is mandatory in clinical trials. These consensus recommendations are proposed for use in the development of future trials testing new chemotherapy combinations with radiotherapy. Not all of these recommendations will be appropriate for trials testing radiotherapy dose or dose intensity concepts.

2 Guideline Radiation Therapy Oncology Group consensus panel guidelines for the delineation of the clinical target volume in the postoperative treatment of pancreatic head cancer. 2012

Goodman, Karyn A / Regine, William F / Dawson, Laura A / Ben-Josef, Edgar / Haustermans, Karin / Bosch, Walter R / Turian, Julius / Abrams, Ross A. ·Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA. goodmank@mskcc.org ·Int J Radiat Oncol Biol Phys · Pubmed #22483737.

ABSTRACT: PURPOSE: To develop contouring guidelines to be used in the Radiation Therapy Oncology Group protocol 0848, a Phase III randomized trial evaluating the benefit of adjuvant chemoradiation in patients with resected head of pancreas cancer. METHODS AND MATERIALS: A consensus committee of six radiation oncologists with expertise in gastrointestinal radiotherapy developed stepwise contouring guidelines and an atlas for the delineation of the clinical target volume (CTV) in the postoperative treatment of pancreas cancer, based on identifiable regions of interest and margin expansions. Areas at risk for subclinical disease to be included in the CTV were defined, including nodal regions, anastomoses, and the preoperative primary tumor location. Regions of interest that could be reproducibly contoured on postoperative imaging after a pancreaticoduodenectomy were identified. Standardized expansion margins to encompass areas at risk were developed after multiple iterations to determine the optimal margin expansions. RESULTS: New contouring recommendations based on CT anatomy were established. Written guidelines for the delineation of the postoperative CTV and normal tissues, as well as a Web-based atlas, were developed. CONCLUSIONS: The postoperative abdomen has been a difficult area for effective radiotherapy. These new guidelines will help physicians create fields that better encompass areas at risk and minimize dose to normal tissues.

3 Review ACR Appropriateness Criteria® Resectable Pancreatic Cancer. 2017

Jones, William E / Suh, W Waren / Abdel-Wahab, May / Abrams, Ross A / Azad, Nilofer / Das, Prajnan / Dragovic, Jadranka / Goodman, Karyn A / Jabbour, Salma K / Konski, Andre A / Koong, Albert C / Kumar, Rachit / Lee, Percy / Pawlik, Timothy M / Small, William / Herman, Joseph M / Anonymous4490897. ·*University of Texas Health Science Center at San Antonio, San Antonio ¶University of Texas MD Anderson Cancer Center, Houston, TX †Cancer Center of Santa Barbara, Santa Barbara §§Stanford Cancer Institute, Stanford ¶¶University of California Los Angeles, Los Angeles, CA ‡Cleveland Clinic, Cleveland, OH ***Stritch School of Medicine Loyola University Chicago, Maywood §Rush University Medical Center, Chicago, IL ∥Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, American Society of Clinical Oncology †††Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University ##Johns Hopkins University, Baltimore, MD, American College of Surgeons #Henry Ford Hospital, Detroit, MI **University of Colorado School of Medicine Anschutz Medical Campus, Aurora, CO ††Rutgers Cancer Institute of New Jersey, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ ‡‡University of Pennsylvania, The Chester County Hospital, West Chester, PA ∥∥Banner MD Anderson Cancer Center, Gilbert, AZ. ·Am J Clin Oncol · Pubmed #28230650.

ABSTRACT: Management of resectable pancreatic adenocarcinoma continues to present a challenge due to a paucity of high-quality randomized studies. Administration of adjuvant chemotherapy is widely accepted due to the high risk of systemic spread associated with pancreatic adenocarcinoma, but the role of radiation therapy is less clear. This paper reviews literature associated with resectable pancreatic cancer to include prognostic factors to aid in the selection of patients appropriate for adjuvant therapies. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

4 Review ACR Appropriateness Criteria® Borderline and Unresectable Pancreas Cancer. 2016

Anonymous19880874 / Small, William / Hayes, John P / Suh, W Warren / Abdel-Wahab, May / Abrams, Ross A / Azad, Nilofer / Das, Prajnan / Dragovic, Jadranka / Goodman, Karyn A / Jabbour, Salma K / Jones, William E / Konski, Andre A / Koong, Albert C / Kumar, Rachit / Lee, Percy / Pawlik, Timothy M / Herman, Joseph M. · ·Oncology (Williston Park) · Pubmed #27422109.

ABSTRACT: The American College of Radiology Appropriateness Criteria® are evidence-based guidelines for specific clinical conditions that are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. The panel reviewed the pertinent literature and voted on five variants to establish appropriate recommended treatment of borderline and unresectable pancreatic cancer. The guidelines reviewed the use of radiation, chemotherapy, and surgery. Radiation technique, dose, and targets were evaluated, as was the recommended chemotherapy, administered either alone or concurrently with radiation. This report will aid clinicians in determining guidelines for the optimal treatment of borderline and unresectable pancreatic cancer.

5 Review Role of chemoradiotherapy in the adjuvant and neoadjuvant settings for resectable pancreatic cancer. 2014

Sen, N / Falk, S / Abrams, R A. ·Department of Radiation Oncology, Rush University Medical Center, Chicago, USA. Electronic address: Neilayan_Sen@rush.edu. · Department of Oncology, Bristol Haematology and Oncology Centre, Bristol, UK. · Department of Radiation Oncology, Rush University Medical Center, Chicago, USA. ·Clin Oncol (R Coll Radiol) · Pubmed #25024090.

ABSTRACT: Pancreatic cancer is the 10th most commonly diagnosed malignancy in the USA and the fourth most common cause of cancer-related death. Worldwide, the mortality incidence ratio approaches 98%. Although only 15-20% of patients present with resectable disease, there is international consensus that complete surgical resection (R0, i.e. grossly and microscopically negative margins) is a vital part of any curative treatment paradigm. Despite advances in surgical technique, peri-operative care, chemotherapy and radiation delivery techniques over the past two decades, 5 year overall survival rates for resected pancreatic cancer with modern therapies remain around 20-25%. There is level I evidence for adjuvant chemotherapy in fully resected pancreatic cancer, but randomised trials examining the role of adjuvant chemoradiotherapy to date do not provide clear support for radiation therapy in this setting. In addition, efforts to increase the proportion of long-term survivors have recently centred on increasing the resectability of locoregional disease by incorporating neoadjuvant treatment before definitive surgery. Post-hoc analysis of randomised data as well as retrospective reviews have shown that there are several independent prognostic factors that may have considerable impact on survival outcomes, complicating interpretation and comparison of historical data. There is considerable interest in adjuvant and neoadjuvant therapy, but there is significant controversy as to whether radiation is of value, especially in the adjuvant context. Herein, we explore the sources of those controversies.

6 Review Supportive care considerations during concurrent chemoradiotherapy for pancreatic adenocarcinoma: lessons learned from clinical experience. 2013

Wang-Gillam, Andrea / Abrams, Ross A / Posner, Mitchell C / Pisters, Peter W T / Picozzi, Vincent J. ·*Division of Hematology-Oncology, Siteman Cancer Center, Washington University in St. Louis School of Medicine, St. Louis, MO †Department of Radiation Oncology, Rush University Medical Center ‡Department of Surgery, University of Chicago Medical Center, Chicago, IL §Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX ∥Cancer and Digestive Diseases Institutes, Virginia Mason Medical Center, Seattle, WA. ·Am J Clin Oncol · Pubmed #22237148.

ABSTRACT: Concurrent chemotherapy and radiotherapy (chemoradiotherapy) for the management of pancreatic adenocarcinoma in either adjuvant or locally regional advanced settings produces predictable acute toxicities that are proportional in severity to the intensity and type of systemic therapy and to the parameters of radiotherapy. In addition, relevant to the adjuvant setting, surgery for pancreatic cancer often produces physiologic alterations that may impact a patient's ability to tolerate chemoradiotherapy. Failures to anticipate, monitor, and proactively manage the effects of surgery and toxicities of chemoradiotherapy can result in the need for unplanned treatment interruptions and/or inability to complete all planned therapy. In this review, complications of pancreatic cancer itself and of pancreatic resection as well as toxicities of chemoradiotherapy are delineated, and approaches to their management before, during, and after chemoradiotherapy are presented. Planning for the treatment of side effects before the anticancer therapy begins facilitates therapy administration and improves patient tolerance.

7 Review Evolving concepts regarding the use of radiotherapy in the adjuvant management of periampullary pancreatic adenocarcinoma. 2012

Abrams, Ross Allen. ·Department of Radiation Oncology, Rush University Medical Center, Chicago, IL 60612-3833, USA. Ross_A_Abrams@rush.edu ·Cancer J · Pubmed #23187851.

ABSTRACT: Presently, many oncologists feel that radiotherapy should not be part of curative intent, adjuvant management for pancreatic adenocarcinoma ("pancreatic cancer"). Historically, among oncologists who provided adjuvant therapy in this context, radiotherapy was included. This review examines the historical development of this controversy as well as (a) the history and principles of systemic and regional adjuvant therapy, (b) relevant nonsurgical studies using combined radiotherapy and chemotherapy for curative intent management of locally unresectable pancreatic cancer, (c) relevant results from surgical adjuvant studies using combined radiotherapy and chemotherapy for curative intent management of resected pancreatic cancer, and (d) results from phase III cooperative group studies of the adjuvant management of pancreatic cancer. Whether we conclude that adjuvant management should be used in a given clinical context depends on the disease and stage-specific results with surgery alone, risk of local and/or systemic failure, efficacy of chemotherapy and radiotherapy for addressing subclinical disease in this context, and the quality of data and studies available for making these assessments. In some settings where locoregional and systemic failure are codominant, both radiotherapy and chemotherapy are required for optimal results. For the adjuvant management of pancreatic cancer, many relevant studies with chemoradiotherapy have had serious limitations because they were nonrandomized, otherwise flawed in design and/or execution, inadequately stratified for currently known prognostic factors, or did not adequately consider radiotherapy technical details and quality assurance. As demonstrated in a secondary analysis of Radiation Therapy Oncology Group trial 9704, these factors are sufficiently powerful, when inadequately recognized and considered, to have obscured the potential therapeutic benefit of radiotherapy. Progress in pancreatic cancer has been hard to achieve. There are many indications that radiotherapy should be of benefit in the curative intent management of pancreatic cancer and we can ill afford to dismiss its use inappropriately. Therefore, well-designed, scientifically based, and appropriately executed phase III cooperative group studies aimed at providing improved clinical outcomes and addressing radiotherapy questions are both appropriate and necessary. Radiation Therapy Oncology Group trial 0848, currently accruing and ongoing, has been designed to clarify the role of radiotherapy in the adjuvant management of pancreatic cancer.

8 Review Radiotherapy in the adjuvant management of pancreatic adenocarcinoma: is it helpful? 2012

Abrams, Ross A. ·Department of Radiation Oncology, Rush University Medical Center, Atrium Bldg, Ground Floor, 500 S. Paulina, Chicago, IL 60612, USA. ross_a_abrams@rush.edu ·Expert Rev Gastroenterol Hepatol · Pubmed #22375521.

ABSTRACT: Curative-intent management for pancreatic adenocarcinoma requires gross total resection. Only 15-20% of patients are eligible for resection and of these only approximately 20% are long-term survivors. Adjuvant and neoadjuvant approaches have been, and are being, sought to improve upon surgical results. Radiotherapy has a role in the adjuvant management of many gastrointestinal malignancies and historically has also had a role in the adjuvant management of pancreatic adenocarcinoma. However, the role of radiotherapy in the management of pancreatic adenocarcinoma has been called into question. This review examines this controversy and the underlying issues and considers current efforts towards resolving them, as well as some likely future developments.

9 Clinical Trial Long-term results and recurrence patterns from SCALOP: a phase II randomised trial of gemcitabine- or capecitabine-based chemoradiation for locally advanced pancreatic cancer. 2017

Hurt, C N / Falk, S / Crosby, T / McDonald, A / Ray, R / Joseph, G / Staffurth, J / Abrams, R A / Griffiths, G / Maughan, T / Mukherjee, S. ·Centre for Trials Research, Cardiff University, 6th Floor, Neuadd Meirionnydd, Heath Park, Cardiff CF14 4YS, UK. · Bristol Haematology and Oncology Centre, Bristol BS2 8ED, UK. · Velindre Cancer Centre, Velindre Hospital, Velindre Road, Cardiff CF14 2TL, UK. · Beatson West of Scotland Cancer Centre, 1053 Great Western Road, Glasgow G12 0YN, UK. · Department of Radiation Oncology, Rush University Medical Center, 500 S. Paulina, 013 Atrium Building, Chicago, IL 60612, USA. · Southampton Clinical Trials Unit, University of Southampton, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK. · CRUK MRC Oxford Institute for Radiation Oncology Gray Laboratories, Oxford University, Oxford OX3 7DQ, UK. ·Br J Cancer · Pubmed #28376080.

ABSTRACT: BACKGROUND: SCALOP, a randomised, phase II trial, tested the activity and safety of gemcitabine (GEM)-based and capecitabine (CAP)-based chemoradiation (CRT) for locally advanced pancreatic cancer (LAPC). Here we present the long-term outcomes. METHODS: Eligibility: histologically proven LAPC ⩽7 cm. Following 12 weeks of induction GEMCAP chemotherapy (three cycles: GEM 1000 mg m RESULTS: One-hundred fourteen patients (28 UK centres) were registered between 24 December 2009 and 25 October 2011, and 74 were randomised (CAP-RT=36; GEM-RT=38). At the time of this analysis, 105 of the 114 patients had died and the surviving 9 patients had been followed up for a median of 10.9 months (IQR: 2.9-18.7). Updated median OS was 17.6 months (95% CI: 14.6-22.7) in the CAP-CRT arm and 14.6 months (95% CI: 11.1-16.0) in the GEM-CRT arm (intention-to-treat adjusted hazard ratio (HR): 0.68 (95% CI: 0.38-1.21, P=0.185)); median progression-free survival (PFS) was 12.0 months (95% CI: 10.0-15.2) in the CAP-CRT arm and 10.4 months (95% CI: 8.8-12.7) in the GEM-CRT arm (intention-to-treat adjusted HR: 0.60 (95% CI: 0.32-1.14, P=0.120)). In baseline multivariable model, age ⩾65 years, better performance status, CA19.9<613 IU l CONCLUSIONS: CAP-CRT remains the superior regimen. SCALOP showed that patients with CA19.9 <46 IU ml

10 Clinical Trial Comparison of investigator-delineated gross tumour volumes and quality assurance in pancreatic cancer: Analysis of the on-trial cases for the SCALOP trial. 2016

Fokas, Emmanouil / Spezi, Emiliano / Patel, Neel / Hurt, Chris / Nixon, Lisette / Chu, Kwun-Ye / Staffurth, John / Abrams, Ross / Mukherjee, Somnath. ·Department of Oncology, CRUK/MRC Institute for Radiation Oncology, University of Oxford, UK. · School of Engineering, Cardiff University, UK. · Oxford University Hospital NHS Foundation Trust, UK. · Wales Cancer Trials Unit, Centre for Trials Research, Cardiff University, UK. · Department of Oncology, CRUK/MRC Institute for Radiation Oncology, University of Oxford, UK; Oxford University Hospital NHS Foundation Trust, UK. · Institute of Cancer and Genetics, Cardiff University, UK; Cardiff NCRI RTTQA Centre, Velindre NHS Trust, UK. · Department of Radiation Oncology, Rush University Medical Center, Chicago, USA. · Department of Oncology, CRUK/MRC Institute for Radiation Oncology, University of Oxford, UK; Oxford University Hospital NHS Foundation Trust, UK. Electronic address: somnath.mukherjee@oncology.ox.ac.uk. ·Radiother Oncol · Pubmed #27497804.

ABSTRACT: BACKGROUND AND PURPOSE: We performed a retrospective central review of tumour outlines in patients undergoing radiotherapy in the SCALOP trial. MATERIALS AND METHODS: The planning CT scans were reviewed retrospectively by a central review team, and the accuracy of investigators' GTV (iGTV) and PTV (iPTV) was compared to the trials team-defined gold standard (gsGTV and gsPTV) using the Jaccard Conformity Index (JCI) and Geographical Miss Index (GMI). The prognostic value of JCI and GMI was also assessed. The RT plans were also reviewed against protocol-defined constraints. RESULTS: 60 patients with diagnostic-quality planning scans were included. The median whole volume JCI for GTV was 0.64 (IQR: 0.43-0.82), and the median GMI was 0.11 (IQR: 0.05-0.22). For PTVs, the median JCI and GMI were 0.80 (IQR: 0.71-0.88) and 0.04 (IQR: 0.02-0.12) respectively. Tumour was completely missed in 1 patient, and⩾50% of the tumour was missed in 3. Patients with JCI for GTV⩾0.7 had 7.12 (95% CIs: 1.83-27.67, p=0.005) higher odds of progressing by 9months in multivariate analysis. Major deviations in RT planning were noted in 4.5% of cases. CONCLUSIONS: Radiotherapy workshops and real-time central review of contours are required in RT trials of pancreatic cancer.

11 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.

12 Clinical Trial Health-Related Quality of Life in SCALOP, a Randomized Phase 2 Trial Comparing Chemoradiation Therapy Regimens in Locally Advanced Pancreatic Cancer. 2015

Hurt, Christopher N / Mukherjee, Somnath / Bridgewater, John / Falk, Stephen / Crosby, Tom / McDonald, Alec / Joseph, George / Staffurth, John / Abrams, Ross A / Blazeby, Jane M / Bridges, Sarah / Dutton, Peter / Griffiths, Gareth / Maughan, Tim / Johnson, Colin. ·Wales Cancer Trials Unit, College of Biomedical and Life Sciences, Cardiff University, Cardiff, Wales, United Kingdom. Electronic address: hurtcn@cardiff.ac.uk. · Cancer Research UK/MRC Oxford Institute for Radiation Oncology, Oxford University, NIHR Biomedical Research, Oxford, United Kingdom. · UCL Cancer Institute, London, United Kingdom. · Bristol Haematology and Oncology Centre, Bristol, United Kingdom. · Velindre Cancer Centre, Velindre Hospital, Cardiff, Wales, United Kingdom. · Beatson West of Scotland Cancer Centre, Glasgow, Scotland, United Kingdom. · Institute of Cancer and Genetics, Cardiff University, Cardiff, Wales, United Kingdom. · Department of Radiation Oncology, Rush University Medical Center, Chicago, Illinois. · Division of Surgery, Head and Neck, University Hospitals Bristol National Health Service Foundation Trust, Bristol and School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom. · Wales Cancer Trials Unit, College of Biomedical and Life Sciences, Cardiff University, Cardiff, Wales, United Kingdom. · Centre for Statistics in Medicine, University of Oxford, Oxford, United Kingdom. · Southampton Clinical Trials Unit, Faculty of Medicine, Southampton University, Southampton General Hospital, Southampton, United Kingdom. · University Surgical Unit, Faculty of Medicine, University Hospital Southampton, Southampton, United Kingdom. ·Int J Radiat Oncol Biol Phys · Pubmed #26530749.

ABSTRACT: PURPOSE: Chemoradiation therapy (CRT) for patients with locally advanced pancreatic cancer (LAPC) provides survival benefits but may result in considerable toxicity. Health-related quality of life (HRQL) measurements during CRT have not been widely reported. This paper reports HRQL data from the Selective Chemoradiation in Advanced Localised Pancreatic Cancer (SCALOP) trial, including validation of the QLQ-PAN26 tool in CRT. METHODS AND MATERIALS: Patients with locally advanced, inoperable, nonmetastatic carcinoma of the pancreas were eligible. Following 12 weeks of induction gemcitabine plus capecitabine (GEMCAP) chemotherapy, patients with stable and responding disease were randomized to a further cycle of GEMCAP followed by capecitabine- or gemcitabine-based CRT. HRQL was assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and the EORTC Pancreatic Cancer module (PAN26). RESULTS: A total of 114 patients from 28 UK centers were registered and 74 patients randomized. There was improvement in the majority of HRQL scales during induction chemotherapy. Patients with significant deterioration in fatigue, appetite loss, and gastrointestinal symptoms during CRT recovered within 3 weeks following CRT. Differences in changes in HRQL scores between trial arms rarely reached statistical significance; however, where they did, they favored capecitabine therapy. PAN26 scales had good internal consistency and were able to distinguish between subgroups of patients experiencing toxicity. CONCLUSIONS: Although there is deterioration in HRQL following CRT, this resolves within 3 weeks. HRQL data support the use of capecitabine- over gemcitabine-based chemoradiation. The QLQ-PAN26 is a reliable and valid tool for use in patients receiving CRT.

13 Clinical Trial Comparison of investigator-delineated gross tumor volumes and quality assurance in pancreatic cancer: Analysis of the pretrial benchmark case for the SCALOP trial. 2015

Fokas, Emmanouil / Clifford, Charlotte / Spezi, Emiliano / Joseph, George / Branagan, Jennifer / Hurt, Chris / Nixon, Lisette / Abrams, Ross / Staffurth, John / Mukherjee, Somnath. ·Radiotherapy Physics Department, University Hospitals Birmingham NHS Foundation Trust, UK. Electronic address: emmanouil.fokas@oncology.ox.ac.uk. · Department of Oncology, University of Oxford, UK. · Department of Medical Physics, Velindre Hospital, Cardiff, UK. · Velindre Cancer Centre, Velindre Hospital, Cardiff, UK. · Oncology Department, Northampton General Hospital, UK. · Wales Cancer Trials Unit, Cardiff University, UK. · Department of Radiation Oncology, Rush University Medical Center, Chicago, USA. · Institute of Cancer and Genetics, Cardiff University, UK; Cardiff NCRI RTTQA Centre, Velindre NHS Trust, UK. · Radiotherapy Physics Department, University Hospitals Birmingham NHS Foundation Trust, UK. ·Radiother Oncol · Pubmed #26328939.

ABSTRACT: BACKGROUND AND PURPOSE: To evaluate the variation in investigator-delineated volumes and assess plans from the radiotherapy trial quality assurance (RTTQA) program of SCALOP, a phase II trial in locally advanced pancreatic cancer. MATERIALS AND METHODS: Participating investigators (n=25) outlined a pre-trial benchmark case as per RT protocol, and the accuracy of investigators' GTV (iGTV) and PTV (iPTV) was evaluated, against the trials team-defined gold standard GTV (gsGTV) and PTV (gsPTV), using both qualitative and geometric analyses. The median Jaccard Conformity Index (JCI) and Geographical Miss Index (GMI) were calculated. Participating RT centers also submitted a radiotherapy plan for this benchmark case, which was centrally reviewed against protocol-defined constraints. RESULTS: Twenty-five investigator-defined contours were evaluated. The median JCI and GMI of iGTVs were 0.57 (IQR: 0.51-0.65) and 0.26 (IQR: 0.15-0.40). For iPTVs, these were 0.75 (IQR: 0.71-0.79) and 0.14 (IQR: 0.11-0.22) respectively. Qualitative analysis showed largest variation at the tumor edges and failure to recognize a peri-pancreatic lymph node. There were no major protocol deviations in RT planning, but three minor PTV coverage deviations were identified. . CONCLUSIONS: SCALOP demonstrated considerable variation in iGTV delineation. RTTQA workshops and real-time central review of delineations are needed in future trials.

14 Clinical Trial Gemcitabine-based or capecitabine-based chemoradiotherapy for locally advanced pancreatic cancer (SCALOP): a multicentre, randomised, phase 2 trial. 2013

Mukherjee, Somnath / Hurt, Christopher N / Bridgewater, John / Falk, Stephen / Cummins, Sebastian / Wasan, Harpreet / Crosby, Tom / Jephcott, Catherine / Roy, Rajarshi / Radhakrishna, Ganesh / McDonald, Alec / Ray, Ruby / Joseph, George / Staffurth, John / Abrams, Ross A / Griffiths, Gareth / Maughan, Tim. ·Gray Institute for Radiation Oncology and Biology, University of Oxford, NIHR Oxford Biomedical Research Centre, Oxford, UK. somnath.mukherjee@oncology.ox.ac.uk ·Lancet Oncol · Pubmed #23474363.

ABSTRACT: BACKGROUND: In the UK, chemotherapy is the standard treatment for inoperable, locally advanced, non-metastatic pancreatic cancer. Chemoradiotherapy is also an acceptable treatment option, for which gemcitabine, fluorouracil, or capecitabine can be used as concurrent chemotherapy agents. We aimed to assess the activity, safety, and feasibility of both gemcitabine-based and capecitabine-based chemoradiotherapy after induction chemotherapy for patients with locally advanced pancreatic cancer. METHODS: In this open-label, randomised, two-arm, phase 2 trial, patients aged 18 years or older with histologically proven, locally advanced pancreatic cancer (with a tumour diameter of 7 cm or less) were recruited from 28 UK centres between Dec 24, 2009 and Oct 25, 2011. After 12 weeks of induction gemcitabine and capecitabine chemotherapy (three cycles of gemcitabine [1000 mg/m(2) on days 1, 8, 15 of a 28-day cycle] and capecitabine [830 mg/m(2) twice daily on days 1-21 of a 28-day cycle]), patients with stable or responding disease, tumour diameter of 6 cm or less, and WHO performance status 0-1 were randomly assigned to receive a further cycle of gemcitabine and capecitabine chemotherapy followed by either gemcitabine (300 mg/m(2) once per week) or capecitabine (830 mg/m(2) twice daily, Monday to Friday only), both in combination with radiation (50·4 Gy in 28 fractions). Randomisation (1:1) was done via a central computerised system and used stratified minimisation. The primary endpoint was 9-month progression-free survival, analysed by intention to treat including only those patients with valid CT assessments. This trial is registered with ISRCTN, number 96169987. FINDINGS: 114 patients were registered and 74 were randomly allocated (38 to the gemcitabine group and 36 to the capecitabine group). After 9 months, 22 of 35 assessable patients (62·9%, 80% CI 50·6-73·9) in the capecitabine group and 18 of 35 assessable patients (51·4%, 39·4-63·4) in the gemcitabine group had not progressed. Median overall survival was 15·2 months (95% CI 13·9-19·2) in the capecitabine group and 13·4 months (95% CI 11·0-15·7) in the gemcitabine group (adjusted hazard ratio [HR] 0·39, 95% CI 0·18-0·81; p=0·012). 12-month overall survival was 79·2% (95% CI 61·1-89·5) in the capecitabine group and 64·2 (95% CI 46·4-77·5) in the gemcitabine group. Median progression-free survival was 12·0 months (95% CI 10·2-14·6) in the capecitabine group and 10·4 months (95% CI 8·9-12·5) in the gemcitabine group (adjusted HR 0·60, 95% CI 0·32-1·12; p=0·11). Eight patients in the capecitabine group had an objective response at 26 weeks, as did seven in the gemcitabine group. More patients in the gemcitabine group than in the capecitabine group had grade 3-4 haematological toxic effects (seven [18%] vs none, p=0·008) and non-haematological toxic effects (ten [26%] vs four [12%], p=0·12) during chemoradiation treatment; the most frequent events were leucopenia, neutropenia, and fatigue. Two patients in the capecitabine group progressed during the fourth cycle of induction chemotherapy. Of the 34 patients in the capecitabine group who received chemoradiotherapy, 25 (74%) received the full protocol dose of radiotherapy, compared with 26 (68%) of 38 patients in the gemcitabine group. Quality-of-life scores were not significantly different between the treatment groups. INTERPRETATION: Our results suggest that a capecitabine-based regimen might be preferable to a gemcitabine-based regimen in the context of consolidation chemoradiotherapy after a course of induction chemotherapy for locally advanced pancreatic cancer. However, these findings should be interpreted with caution because the difference in the primary endpoint was non-significant and the number of patients in the trial was small. FUNDING: Cancer Research UK.

15 Clinical Trial Prognostic significance of carbohydrate antigen 19-9 in unresectable locally advanced pancreatic cancer treated with dose-escalated intensity modulated radiation therapy and concurrent full-dose gemcitabine: analysis of a prospective phase 1/2 dose escalation study. 2013

Vainshtein, Jeffrey M / Schipper, Matthew / Zalupski, Mark M / Lawrence, Theodore S / Abrams, Ross / Francis, Isaac R / Khan, Gazala / Leslie, William / Ben-Josef, Edgar. ·Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan, USA. jvainsh@med.umich.edu ·Int J Radiat Oncol Biol Phys · Pubmed #23265573.

ABSTRACT: PURPOSE: Although established in the postresection setting, the prognostic value of carbohydrate antigen 19-9 (CA19-9) in unresectable locally advanced pancreatic cancer (LAPC) is less clear. We examined the prognostic utility of CA19-9 in patients with unresectable LAPC treated on a prospective trial of intensity modulated radiation therapy (IMRT) dose escalation with concurrent gemcitabine. METHODS AND MATERIALS: Forty-six patients with unresectable LAPC were treated at the University of Michigan on a phase 1/2 trial of IMRT dose escalation with concurrent gemcitabine. CA19-9 was obtained at baseline and during routine follow-up. Cox models were used to assess the effect of baseline factors on freedom from local progression (FFLP), distant progression (FFDP), progression-free survival (PFS), and overall survival (OS). Stepwise forward regression was used to build multivariate predictive models for each endpoint. RESULTS: Thirty-eight patients were eligible for the present analysis. On univariate analysis, baseline CA19-9 and age predicted OS, CA19-9 at baseline and 3 months predicted PFS, gross tumor volume (GTV) and black race predicted FFLP, and CA19-9 at 3 months predicted FFDP. On stepwise multivariate regression modeling, baseline CA19-9, age, and female sex predicted OS; baseline CA19-9 and female sex predicted both PFS and FFDP; and GTV predicted FFLP. Patients with baseline CA19-9 ≤ 90 U/mL had improved OS (median 23.0 vs 11.1 months, HR 2.88, P<.01) and PFS (14.4 vs 7.0 months, HR 3.61, P=.001). CA19-9 progression over 90 U/mL was prognostic for both OS (HR 3.65, P=.001) and PFS (HR 3.04, P=.001), and it was a stronger predictor of death than either local progression (HR 1.46, P=.42) or distant progression (HR 3.31, P=.004). CONCLUSIONS: In patients with unresectable LAPC undergoing definitive chemoradiation therapy, baseline CA19-9 was independently prognostic even after established prognostic factors were controlled for, whereas CA19-9 progression strongly predicted disease progression and death. Future trials should stratify by baseline CA19-9 and incorporate CA19-9 progression as a criterion for progressive disease.

16 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).

17 Clinical Trial A phase I/II trial of intensity modulated radiation (IMRT) dose escalation with concurrent fixed-dose rate gemcitabine (FDR-G) in patients with unresectable pancreatic cancer. 2012

Ben-Josef, Edgar / Schipper, Mathew / Francis, Isaac R / Hadley, Scott / Ten-Haken, Randall / Lawrence, Theodore / Normolle, Daniel / Simeone, Diane M / Sonnenday, Christopher / Abrams, Ross / Leslie, William / Khan, Gazala / Zalupski, Mark M. ·Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan, USA. edgar.ben-josef@uphs.upenn.edu ·Int J Radiat Oncol Biol Phys · Pubmed #22543215.

ABSTRACT: PURPOSE: Local failure in unresectable pancreatic cancer may contribute to death. We hypothesized that intensification of local therapy would improve local control and survival. The objectives were to determine the maximum tolerated radiation dose delivered by intensity modulated radiation with fixed-dose rate gemcitabine (FDR-G), freedom from local progression (FFLP), and overall survival (OS). METHODS AND MATERIALS: Eligibility included pathologic confirmation of adenocarcinoma, radiographically unresectable, performance status of 0-2, absolute neutrophil count of ≥ 1,500/mm(3), platelets ≥ 100,000/mm(3), creatinine <2 mg/dL, bilirubin <3 mg/dL, and alanine aminotransferase/aspartate aminotransferase ≤ 2.5 × upper limit of normal. FDR-G (1000 mg/m(2)/100 min intravenously) was given on days -22 and -15, 1, 8, 22, and 29. Intensity modulated radiation started on day 1. Dose levels were escalated from 50-60 Gy in 25 fractions. Dose-limiting toxicity was defined as gastrointestinal toxicity grade (G) ≥ 3, neutropenic fever, or deterioration in performance status to ≥ 3 between day 1 and 126. Dose level was assigned using TITE-CRM (Time-to-Event Continual Reassessment Method) with the target dose-limiting toxicity (DLT) rate set to 0.25. RESULTS: Fifty patients were accrued. DLTs were observed in 11 patients: G3/4 anorexia, nausea, vomiting, and/or dehydration (7); duodenal bleed (3); duodenal perforation (1). The recommended dose is 55 Gy, producing a probability of DLT of 0.24. The 2-year FFLP is 59% (95% confidence interval [CI]: 32-79). Median and 2-year overall survival are 14.8 months (95% CI: 12.6-22.2) and 30% (95% CI 17-45). Twelve patients underwent resection (10 R0, 2 R1) and survived a median of 32 months. CONCLUSIONS: High-dose radiation therapy with concurrent FDR-G can be delivered safely. The encouraging efficacy data suggest that outcome may be improved in unresectable patients through intensification of local therapy.

18 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.

19 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.

20 Clinical Trial A lethally irradiated allogeneic granulocyte-macrophage colony stimulating factor-secreting tumor vaccine for pancreatic adenocarcinoma. A Phase II trial of safety, efficacy, and immune activation. 2011

Lutz, Eric / Yeo, Charles J / Lillemoe, Keith D / Biedrzycki, Barbara / Kobrin, Barry / Herman, Joseph / Sugar, Elizabeth / Piantadosi, Steven / Cameron, John L / Solt, Sara / Onners, Beth / Tartakovsky, Irena / Choi, Miri / Sharma, Rajni / Illei, Peter B / Hruban, Ralph H / Abrams, Ross A / Le, Dung / Jaffee, Elizabeth / Laheru, Dan. ·Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA. ·Ann Surg · Pubmed #21217520.

ABSTRACT: PURPOSE: Surgical resection provides the only possibility of cure for pancreas cancer. A standard adjuvant approach has not been established. We tested the safety and efficacy of a granulocyte-macrophage colony-stimulating factor (GM-CSF)-based immunotherapy administered in patients with resected pancreatic adenocarcinoma. PATIENTS AND METHODS: A single institution phase II study of 60 patients with resected pancreatic adenocarcinoma was performed. Each immunotherapy treatment consisted of a total of 5 × 108 GM-CSF-secreting cells distributed equally among 3 lymph node regions. The first immunotherapy treatment was administered 8 to 10 weeks after surgical resection. Subsequently, patients received 5-FU based chemoradiation. Patients who remained disease-free after completion of chemoradiotherapy received treatments 2 to 4, each 1 month apart. A fifth and final booster was administered 6 months after the fourth immunotherapy. The primary endpoint was disease free survival and secondary endpoints were overall survival and toxicity, and the induction of mesothelin specific T cell responses. RESULTS: The median disease-free survival is 17.3 months (95% CI, 14.6-22.8) with median survival of 24.8 months (95% CI, 21.2-31.6). The administration of immunotherapy was well tolerated. In addition, the post-immunotherapy induction of mesothelin-specific CD8+ T cells in HLA-A1+ and HLA-A2+patients correlates with disease-free survival. CONCLUSIONS: An immunotherapy approach integrated with chemoradiation is safe and demonstrates an overall survival that compares favorably with published data for resected pancreas cancer. These data suggest additional boost immunotherapies given at regular intervals beyond 1 year postsurgery should be tested in future studies, and provide the rationale for conducting a multicenter phase II study.

21 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.

22 Clinical Trial Multicenter phase II trial of adjuvant therapy for resected pancreatic cancer using cisplatin, 5-fluorouracil, and interferon-alfa-2b-based chemoradiation: ACOSOG Trial Z05031. 2011

Picozzi, V J / Abrams, R A / Decker, P A / Traverso, W / O'Reilly, E M / Greeno, E / Martin, R C / Wilfong, L S / Rothenberg, M L / Posner, M C / Pisters, P W T / Anonymous451075. ·Department of Medical Oncology, Virginia Mason Medical Center, Seattle, WA 98111, USA. hemvjp@vmmc.org ·Ann Oncol · Pubmed #20670978.

ABSTRACT: BACKGROUND: The American College of Surgeons Oncology Group sought to confirm the efficacy of a novel interferon-based chemoradiation regimen in a multicenter phase II trial. PATIENTS AND METHODS: Patients with resected (R0/R1) adenocarcinoma of the pancreatic head were treated with adjuvant interferon-alfa-2b (3 million units s.c. on days 1, 3, and 5 of each week for 5.5 weeks), cisplatin (30 mg/m(2) i.v. weekly for 6 weeks), and continuous infusion 5-fluorouracil (5-FU; 175 mg·m(2)/day for 38 days) concurrently with external-beam radiation (50.4 Gy). Chemoradiation was followed by two 6-week courses of continuous infusion 5-FU (200 mg·m(2)/day). The primary study end point was 18-month overall survival from protocol enrollment (OS18); an OS18 ≥65% was considered a positive study outcome. RESULTS: Eighty-nine patients were enrolled. Eighty-four patients were assessable for toxicity. The all-cause grade ≥3 toxicity rate was 95% (80 patients) during therapy. No long-term toxicity or toxicity-related deaths were noted. At 36-month median follow-up, the OS18 was 69% [95% confidence interval (CI) 60% to 80%]; the median disease-free survival and overall survival were 14.1 months (95% CI 11.0-20.1 months) and 25.4 months (95% CI 23.4-34.1 months), respectively. CONCLUSIONS: Notwithstanding promising multi-institutional efficacy results, further development of this regimen will require additional modifications to mitigate toxic effects.

23 Article Marital Status and Overall Survival in Patients with Resectable Pancreatic Cancer: Results of an Ancillary Analysis of NRG Oncology/RTOG 9704. 2020

Reyngold, Marsha / Winter, Kathryn A / Regine, William F / Abrams, Ross A / Safran, Howard / Hoffman, John P / Mowat, Rex B / Hayes, John P / Kessel, Ivan L / DiPetrillo, Thomas / Narayan, Samir / Chen, Yuhchyau / Ben-Josef, Edgar / Delouya, Guila / Suh, John H / Meyer, Joshua / Haddock, Michael G / Feldman, Marvin / Gaur, Rakesh / Yost, Kathleen / Peterson, Richard A / Sherr, David L / Moughan, Jennifer / Crane, Christopher H. ·Memorial Sloan Kettering Cancer Center, New York, New York, USA. · NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvania, USA. · University of Maryland Marlene and Stewart Greenebaum Cancer Center, Baltimore, Maryland, USA. · Rush University Medical Center, Chicago, Illinois, USA. · Rhode Island Hospital, Providence, Rhode Island, USA. · Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA. · Toledo Community Hospital Oncology Program, Community Clinical Oncology Program, Toledo, Ohio, USA. · Northwestern Memorial Hospital, Chicago, Illinois, USA. · University of Texas Medical Branch, Galveston, Texas, USA. · Lifespan Cancer Institute, Providence, Rhode Island, USA. · Michigan Cancer Research Consortium, Grand Rapid, Michigan, USA. · University of Rochester, Rochester, New York, USA. · University of Pennsylvania Medical Center, Philadelphia, Pennsylvania, USA. · Centre Hospitalier de l'Université de Montréal, Montreal, Quebec, Canada. · Cleveland Clinic Foundation, Cleveland, Ohio, USA. · Mayo Clinic, Rochester, New York, USA. · Sinai Hospital of Baltimore, Baltimore, Maryland, USA. · Kansas City Community Clinical Oncology Program, Prairie Village, Kansas, USA. · Grand Rapids Community Clinical Oncology Program, Grand Rapids, Michigan, USA. · St. Francis Regional Medical Center, Shakopee, Minnesota, USA. · The Brooklyn Hospital Center, New York, New York, USA. ·Oncologist · Pubmed #32162826.

ABSTRACT: BACKGROUND: Several registry-based analyses suggested a survival advantage for married versus single patients with pancreatic cancer. The mechanisms underlying the association of marital status and survival are likely multiple and complex and, therefore, may be obscured in analyses generated from large population-based databases. The goal of this research was to characterize this potential association of marital status with outcomes in patients with resected pancreatic cancer who underwent combined modality adjuvant therapy on a prospective clinical trial. MATERIALS AND METHODS: This is an ancillary analysis of 367 patients with known marital status treated on NRG Oncology/RTOG 97-04. Survival analysis was performed using the Kaplan-Meier method and compared using the log-rank test. Multivariate analysis was performed using the Cox proportional hazards regression model. RESULTS: Of 367 patients, 271 (74%) were married or partnered and 96 (26%) were single. Married or partnered patients were more likely to be male. There was no association between marital status and overall survival (OS) or disease-free survival (DFS) on univariate (hazard ratio [HR], 1.09 and 1.01, respectively) or multivariate analyses (HR, 1.05 and 0.98, respectively). Married or partnered male patients did not have improved survival compared with female or single patients. CONCLUSION: Ancillary analysis of data from NRG Oncology/RTOG 97-04 demonstrated no association between marital and/or partner status and OS or DFS in patients with resected pancreatic cancer who received adjuvant postoperative chemotherapy followed by concurrent external beam radiation therapy and chemotherapy. Clinical trial identification number. NCT00003216. IMPLICATIONS FOR PRACTICE: Several population-based studies have shown an epidemiological link between marital status and survival in patients with pancreatic cancer. A better understanding of this association could offer an opportunity to improve outcomes through psychosocial interventions designed to mitigate the negative effects of not being married. Based on the results of this analysis, patients who have undergone a resection and are receiving adjuvant therapy on a clinical trial are unlikely to benefit from such interventions. Further efforts to study the association between marital status and survival should be focused on less selected subgroups of patients with pancreatic cancer.

24 Article Glycogen Synthase Kinase 3 Beta Predicts Survival in Resected Adenocarcinoma of the Pancreas. 2015

Ben-Josef, Edgar / George, Asha / Regine, William F / Abrams, Ross / Morgan, Meredith / Thomas, Dafydd / Schaefer, Paul L / DiPetrillo, Thomas A / Fromm, Mitchel / Small, William / Narayan, Samir / Winter, Kathryn / Griffith, Kent A / Guha, Chandan / Williams, Terence M. ·University of Pennsylvania, Philadelphia, Pennsylvania. edgar.ben-josef@uphs.upenn.edu. · Radiation Therapy Oncology Group-Statistical Center, Philadelphia, Pennsylvania. · University of Maryland Medical Systems, Baltimore, Maryland. · Rush University Medical Center, Chicago, Illinois. · University of Michigan Medical School, Ann Arbor, Michigan. · Toledo Community Hospital Oncology Program CCOP, Toledo, Ohio. · Providence, Rhode Island. · Akron General Medical Center, Akron, Ohio. · Northwestern Memorial Hospital, Chicago, Illinois. · Michigan Cancer Research Consortium CCOP, Ann Arbor, Michigan. · Montefiore Medical Center, Moses Campus, Bronx, New York. · Ohio State University Medical Center, Columbus, Ohio. ·Clin Cancer Res · Pubmed #26240274.

ABSTRACT: PURPOSE: GSK3β is a protein kinase that can suppress a number of key oncoproteins. We have previously shown in preclinical models of pancreatic ductal adenocarcinoma (PDAC) that inhibition of GSK3β causes stabilization and nuclear translocation of β-catenin, poor differentiation, proliferation, and resistance to radiation. The objective of this study was to determine its utility as a biomarker of clinical outcomes. EXPERIMENTAL DESIGN: Automated Quantitative Immunofluorescence Analysis (AQUA) of GSK3β was performed on a tissue microarray with samples from 163 patients treated on RTOG 9704. On the basis of findings in an exploratory cohort, GSK3β was analyzed as a categorical variable using its upper quartile (>Q3) as a cut point. Overall survival (OS) and disease-free survival (DFS) were estimated with the Kaplan-Meier method, and GSK3β groupings were compared using the log-rank test. Univariable and multivariable Cox proportional hazards models were used to determine associations between GSK3β and OS/DFS. RESULTS: The 3-year OS rates for GSK3β≤Q3 versus GSK3β >Q3 were 16% (95% confidence intervals; CI, 10%-23%) and 30% (95% CI, 17%-44%), respectively, P = 0.0082. The 3-year DFS rates were 9% (95% CI, 5%-15%) and 20% (95% CI, 9%-33%) respectively, P value = 0.0081. On multivariable analysis, GSK3β was a significant predictor of OS. Patients with GSK3β >Q3 had a 46% reduced risk of dying of pancreatic cancer (HR, 0.54; 95% CI, 0.31-0.96, P value = 0.034). The HR for DFS was 0.65 (95% CI, 0.39-1.07; P value = 0.092). CONCLUSIONS: GSK3β expression is a strong prognosticator in PDAC, independent of other known factors such as tumor (T) stage, nodal status, surgical margins and CA19-9. Clin Cancer Res; 21(24); 5612-8. ©2015 AACR.

25 Article Standardization of surgical and pathologic variables is needed in multicenter trials of adjuvant therapy for pancreatic cancer: results from the ACOSOG Z5031 trial. 2011

Katz, Matthew H G / Merchant, Nipun B / Brower, Steven / Branda, Megan / Posner, Mitchell C / William Traverso, L / Abrams, Ross A / Picozzi, Vincent J / Pisters, Peter W T / Anonymous7990671. ·Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. mhgkatz@mdanderson.org ·Ann Surg Oncol · Pubmed #20811779.

ABSTRACT: BACKGROUND: Standardization of surgical and pathologic techniques is crucial to the interpretation of studies evaluating adjuvant therapies for pancreatic cancer (PC). METHODS: To assess the degree to which treatment administered prior to enrollment of patients in trials of adjuvant therapy is quality controlled, the operative and pathology reports of patients in American College of Surgeons Oncology Group (ACOSOG) Z5031-a national trial of chemoradiation following pancreaticoduodenectomy (PD)-were rigorously evaluated. We analyzed variables with the potential to influence staging or outcome. RESULTS: 80 patients reported to have undergone R0 (75%) or R1 (25%) pylorus-preserving (38%) or standard (62%) PD were evaluated. A search for metastases was documented in 96% of cases. The proximity of the tumor to the superior mesenteric vein was reported in 69%; vein resection was required in 9% and lateral venorrhaphy in 14%. The method of dissection along the superior mesenteric artery (SMA) was described in 68%, being ultrasonic dissection (17%), stapler (24%), and clamp and cut (59%). SMA skeletonization was described in 25%, and absence of disease following resection was documented in 24%. The surgeon reported marking the critical SMA margin in 25%; inking was documented in 65% of cases and evaluation of the SMA margin was reported in 47%. A range of 1-49 lymph nodes was evaluated. Only 34% of pathology reports met College of American Pathologists criteria. CONCLUSIONS: Trials of adjuvant therapy following PD suffer from a lack of standardization and quality control prior to patient enrollment. These data suggest areas for improvement in the design of multidisciplinary treatment protocols.

Next