Pick Topic
Review Topic
List Experts
Examine Expert
Save Expert
  Site Guide ··   
Pancreatic Neoplasms: HELP
Articles by Edgar Ben-Josef
Based on 24 articles published since 2008
||||

Between 2008 and 2019, Edgar Ben-Josef wrote the following 24 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 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 / Anonymous1061005. ·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.

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 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 / Anonymous3820673. · ·J Natl Compr Canc Netw · Pubmed #20876541.

ABSTRACT: -- No abstract --

4 Review Neoadjuvant therapy of pancreatic cancer: the emerging paradigm? 2012

Lim, Kian-Huat / Chung, Eugene / Khan, Adeel / Cao, Dengfeng / Linehan, David / Ben-Josef, Edgar / Wang-Gillam, Andrea. ·Medical Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. ·Oncologist · Pubmed #22250057.

ABSTRACT: Pancreatic cancer remains one of the deadliest cancers due to difficulty in early diagnosis and its high resistance to chemotherapy and radiation. It is now clear that even patients with potentially resectable disease require multimodality treatment including chemotherapy and/or radiation to improve resectability and reduce recurrence. Tremendous efforts are currently being invested in refining preoperative staging to identify optimal surgical candidates, and also in developing various neoadjuvant or adjuvant regimens to improve surgical outcome. Although at present no studies have been done to directly compare the benefit of neoadjuvant versus adjuvant approaches, accumulating evidence suggests that the neoadjuvant approach is probably beneficial for a subset of the patient population, particularly those with borderline resectable disease in which complete surgical resection is almost certainly unachievable. In this article, we review the literature and rationales of neoadjuvant chemotherapy and chemoradiation, as well as their potential limitations and caveats. We also review the pathological findings following neoadjuvant therapies, and potential surgical complications that may be associated with neoadjuvant therapies.

5 Review Chemoradiotherapy for unresectable pancreatic cancer. 2008

Ben-Josef, Edgar / Lawrence, Theodore S. ·Department of Radiation Oncology, University of Michigan Medical Center, UH-B2C490 1500 East Medical Center Drive, Ann Arbor, MI, 48109-0010, USA. edgarb@med.umich.edu ·Int J Clin Oncol · Pubmed #18463955.

ABSTRACT: Treatment options for unresectable pancreatic cancer, including concurrent chemoradiotherapy, chemotherapy alone, and chemotherapy followed by chemoradiotherapy, are largely ineffective and result in a median survival of approximately 10-12 months. Although quality data on the benefit of radiotherapy in unresectable pancreatic cancer are lacking, it seems unlikely that the low-efficacy chemotherapy used for pancreatic cancer would control gross disease. Current regimens deliver low, ineffective doses of radiation and are associated with high rates of local failure. New technological advances, such as intensity-modulated radiotherapy, now allow the safe delivery of high-dose, highly conformal radiotherapy concurrently with full systemic doses of chemotherapy. We review new knowledge related to pattern of failure, target definition, and target motion and discuss the implications of these data on modern radiotherapy treatment planning and delivery. While it is clear that breakthroughs in treatment would come mostly from advances in systemic therapy, the evidence suggests that radiotherapy should not fall out of use, but rather be intensified.

6 Clinical Trial A phase I dose escalation trial of nab-paclitaxel and fixed dose radiation in patients with unresectable or borderline resectable pancreatic cancer. 2018

Shabason, Jacob E / Chen, Jerry / Apisarnthanarax, Smith / Damjanov, Nevena / Giantonio, Bruce / Loaiza-Bonilla, Arturo / O'Dwyer, Peter J / O'Hara, Mark / Reiss, Kim A / Teitelbaum, Ursina / Wissel, Paul / Drebin, Jeffrey A / Vollmer, Charles / Kochman, Michael / Mick, Rosemarie / Vergara, Norge / Jhala, Nirag / Doucette, Abigail / Lukens, John N / Plastaras, John P / Metz, James M / Ben-Josef, Edgar. ·Department of Radiation Oncology, Perelman School of Medicine at the University of Pennsylvania, PCAM-2 West, 3400 Civic Center Blvd., Philadelphia, PA, 19104, USA. jacob.shabason@uphs.upenn.edu. · Department of Radiation Oncology, Perelman School of Medicine at the University of Pennsylvania, PCAM-2 West, 3400 Civic Center Blvd., Philadelphia, PA, 19104, USA. · Department of Radiation Oncology, University of Washington School of Medicine, Seattle, WA, USA. · Division of Hematology/Oncology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. · Department of Surgery, Memorial Sloane Kettering Cancer Center, New York, NY, USA. · Department of Surgery, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. · Gastroenterology Division, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. · Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. · Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. · Department of Pathology and Laboratory Medicine, Temple University Hospital, Philadelphia, PA, USA. ·Cancer Chemother Pharmacol · Pubmed #29362902.

ABSTRACT: PURPOSE: Patients with locally advanced pancreatic cancer typically have poor outcomes, with a median survival of approximately 16 months. Novel methods to improve outcomes are needed. Nab-paclitaxel (Abraxane) has shown efficacy in pancreatic cancer and is FDA-approved for metastatic disease in combination with gemcitabine. Nab-paclitaxel is also a promising radiosensitizer based on laboratory studies, but it has never been clinically tested with definitive radiotherapy for locally advanced pancreatic carcinoma. METHODS: We performed a phase 1 study using a 3 + 3 dose escalation strategy to determine the safety and tolerability of dose-escalated nab-paclitaxel with fractionated radiotherapy for patients with unresectable or borderline resectable pancreatic cancer. Following induction chemotherapy with two cycles of nab-paclitaxel and gemcitabine, patients were treated with weekly nab-paclitaxel and daily radiotherapy to a dose of 52.5 Gy in 25 fractions. Final dose-limiting toxicity (DLT) determination was performed at day 65 after the start of radiotherapy. RESULTS: Nine patients received nab-paclitaxel at a dose level of either 100 mg/m CONCLUSIONS: The combination of fractionated radiation and weekly full dose nab-paclitaxel was safe and well-tolerated.

7 Clinical Trial Quality of life in a prospective, multicenter phase 2 trial of neoadjuvant full-dose gemcitabine, oxaliplatin, and radiation in patients with resectable or borderline resectable pancreatic adenocarcinoma. 2014

Serrano, Pablo E / Herman, Joseph M / Griffith, Kent A / Zalupski, Mark M / Kim, Edward J / Bekaii-Saab, Tanios S / Ben-Josef, Edgar / Dawson, Laura A / Ringash, Jolie / Wei, Alice C. ·Department of Surgery, University Health Network, University of Toronto, Toronto, ON, Canada. · Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland. · Center for Cancer Biostatistics, Biostatistics Unit, University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan. · Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan; University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan. · Division of Medical Oncology, Department of Internal Medicine, The Ohio State University Medical Center, Columbus, Ohio. · Princess Margaret Cancer Center, University Health Network, Toronto, ON, Canada. · Princess Margaret Cancer Center, University Health Network, Toronto, ON, Canada; Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada. · Department of Surgery, University Health Network, University of Toronto, Toronto, ON, Canada; Princess Margaret Cancer Center, University Health Network, Toronto, ON, Canada; Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada. Electronic address: alice.wei@uhn.ca. ·Int J Radiat Oncol Biol Phys · Pubmed #25104069.

ABSTRACT: PURPOSE: To determine the health-related quality of life (QOL) during and after neoadjuvant chemoradiation therapy and surgery for patients with pancreatic adenocarcinoma. METHODS AND MATERIALS: Participants of a prospective, phase 2 multi-institutional trial treated with neoadjuvant chemoradiation followed by surgery completed QOL questionnaires (European Organization for Research and Treatment in Cancer Quality of Life Questionnaire version 3.0 [EORTC-QLQ C30], EORTC-Pancreatic Cancer module [EORTC-PAN 26], and Functional Assessment of Cancer Therapy Hepatobiliary and Pancreatic subscale [FACT-Hep]) at baseline, after 2 cycles of neoadjuvant therapy, after surgery, at 6 months from initiation of therapy, and at 6-month intervals for 2 years. Mean scores were compared with baseline. A change >10% was considered a minimal clinically important difference. RESULTS: Of 71 participants in the trial, 55 were eligible for QOL analysis. Compliance ranged from 32% to 74%. The EORTC-QLQ C30 global QOL did not significantly decline after neoadjuvant therapy, whereas the Functional Assessment of Cancer Therapy global health measure showed a statistically, but not clinically significant decline (-8, P=.02). This was in parallel with deterioration in physical functioning (-14.1, P=.001), increase in diarrhea (+16.7, P=.044), and an improvement in pancreatic pain (-13, P=.01) as per EORTC-PAN 26. Because of poor patient compliance in the nonsurgical group, long-term analysis was performed only from surgically resected participants (n=36). Among those, global QOL returned to baseline levels after 6 months, remaining near baseline through the 24-month visit. CONCLUSIONS: The study regimen consisting of 2 cycles of neoadjuvant therapy was completed without a clinically significant QOL deterioration. A transient increase in gastrointestinal symptoms and a decrease in physical functioning were seen after neoadjuvant chemoradiation. In those patients who underwent surgical resection, most domains returned back to baseline levels by 6 months.

8 Clinical Trial A multi-institutional phase 2 study of neoadjuvant gemcitabine and oxaliplatin with radiation therapy in patients with pancreatic cancer. 2013

Kim, Edward J / Ben-Josef, Edgar / Herman, Joseph M / Bekaii-Saab, Tanios / Dawson, Laura A / Griffith, Kent A / Francis, Isaac R / Greenson, Joel K / Simeone, Diane M / Lawrence, Theodore S / Laheru, Daniel / Wolfgang, Christopher L / Williams, Terence / Bloomston, Mark / Moore, Malcolm J / Wei, Alice / Zalupski, Mark M. ·Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA. ·Cancer · Pubmed #23720019.

ABSTRACT: BACKGROUND: The purpose of this study was to evaluate preoperative treatment with full-dose gemcitabine, oxaliplatin, and radiation therapy (RT) in patients with localized pancreatic cancer. METHODS: Eligibility included confirmation of adenocarcinoma, resectable or borderline resectable disease, a performance status ≤2, and adequate organ function. Treatment consisted of two 28-day cycles of gemcitabine (1 g/m(2) over 30 minutes on days 1, 8, and 15) and oxaliplatin (85 mg/m(2) on days 1 and 15) with RT during cycle 1 (30 Gray [Gy] in 2-Gy fractions). Patients were evaluated for surgery after cycle 2. Patients who underwent resection received 2 cycles of adjuvant chemotherapy. RESULTS: Sixty-eight evaluable patients received treatment at 4 centers. By central radiology review, 23 patients had resectable disease, 39 patients had borderline resectable disease, and 6 patients had unresectable disease. Sixty-six patients (97%) completed cycle 1 with RT, and 61 patients (90%) completed cycle 2. Grade ≥3 adverse events during preoperative therapy included neutropenia (32%), thrombocytopenia (25%), and biliary obstruction/cholangitis (14%). Forty-three patients underwent resection (63%), and complete (R0) resection was achieved in 36 of those 43 patients (84%). The median overall survival was 18.2 months (95% confidence interval, 13-26.9 months) for all patients, 27.1 months (95% confidence interval, 21.2-47.1 months) for those who underwent resection, and 10.9 months (95% confidence interval, 6.1-12.6 months) for those who did not undergo resection. A decrease in CA 19-9 level after neoadjuvant therapy was associated with R0 resection (P = .02), which resulted in a median survival of 34.6 months (95% confidence interval, 20.3-47.1 months). Fourteen patients (21%) are alive and disease free at a median follow-up of 31.4 months (range, 24-47.6 months). CONCLUSIONS: Preoperative therapy with full-dose gemcitabine, oxaliplatin, and RT was feasible and resulted in a high percentage of R0 resections. The current results are particularly encouraging, because the majority of patients had borderline resectable disease.

9 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.

10 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.

11 Clinical Trial Radiation therapy with full-dose gemcitabine and oxaliplatin for unresectable pancreatic cancer. 2012

Hunter, Klaudia U / Feng, Felix Y / Griffith, Kent A / Francis, Isaac R / Lawrence, Theodore S / Desai, Sameer / Murphy, James D / Zalupski, Mark M / Ben-Josef, Edgar. ·Department of Radiation Oncology, University of Michigan, Ann Arbor, MI 48109-0010, USA. ·Int J Radiat Oncol Biol Phys · Pubmed #22208966.

ABSTRACT: PURPOSE: We completed a Phase I trial of gemcitabine and oxaliplatin with concurrent radiotherapy in patients with previously untreated pancreatic cancer. The results of a subset of patients with unresectable disease who went on to receive planned additional therapy are reported here. METHODS AND MATERIALS: All patients received two 28-day cycles of gemcitabine (1,000 mg/m(2) on Days 1, 8, and 15) and oxaliplatin (40-85 mg/m(2) on Days 1 and 15, per a dose-escalation schema). Radiation therapy was delivered concurrently with Cycle 1 (27 Gy in 1.8-Gy fractions). At 9 weeks, patients were reassessed for resectability. Those deemed to have unresectable disease were offered a second round of treatment consisting of 2 cycles of gemcitabine and oxaliplatin and 27 Gy of radiation therapy (total, 54 Gy). Radiation was delivered to the gross tumor volume plus 1 cm by use of a three-dimensional conformal technique. We used the Common Terminology Criteria for Adverse Events to assess acute toxicity. Late toxicity was scored per the Radiation Therapy Oncology Group scale. Computed tomography scans were reviewed to determine pattern of failure, local response, and disease progression. Kaplan-Meier methodology and Cox regression models were used to evaluate survival and freedom from failure. RESULTS: Thirty-two patients from the Phase I dose-escalation study had unresectable disease, three of whom had low-volume metastatic disease. Of this group, 16 patients went on to receive additional therapy to complete a total of 4 cycles of chemotherapy and 54 Gy of concurrent radiation. For this subset, 38% had at least a partial tumor response at a median of 3.2 months. Median survival was 11.8 months (range, 4.4-26.3 months). The 1-year freedom from local progression rate was 93.8% (95% confidence interval, 63.2-99.1). CONCLUSIONS: Radiation therapy to 54 Gy with concurrent full-dose gemcitabine and oxaliplatin is well tolerated and results in favorable rates of local tumor response and 1-year freedom from local progression.

12 Clinical Conference Pancreatic gross tumor volume contouring on computed tomography (CT) compared with magnetic resonance imaging (MRI): Results of an international contouring conference. 2018

Hall, William A / Heerkens, Hanne D / Paulson, Eric S / Meijer, Gert J / Kotte, Alexis N / Knechtges, Paul / Parikh, Parag J / Bassetti, Michael F / Lee, Percy / Aitken, Katharine L / Palta, Manisha / Myrehaug, Sten / Koay, Eugene J / Portelance, Lorraine / Ben-Josef, Edgar / Erickson, Beth A. ·Department of Radiation Oncology, Medical College of Wisconsin and Clement J. Zablocki VA Medical Center, Milwaukee, Wisconsin. Electronic address: whall@mcw.edu. · UMC Utrecht, Department of Radiation Oncology, Utrecht, the Netherlands. · Department of Radiation Oncology, Medical College of Wisconsin and Clement J. Zablocki VA Medical Center, Milwaukee, Wisconsin. · Department of Radiology, Medical College of Wisconsin, Milwaukee, Wisconsin. · Department of Radiation Oncology, Washington University, St. Louis, Missouri. · Department of Radiation Oncology, University of Wisconsin Madison, Madison, Wisconsin. · Department of Radiation Oncology, University of California Los Angeles, Los Angeles, California. · Department of Radiation Oncology, Royal Marsden, London, England. · Department of Radiation Oncology, Duke University, Durham, North Carolina. · Department of Radiation Oncology, Sunnybrook Hospital, Toronto, Canada. · Department of Radiation Oncology, MD Anderson Cancer Center, Houston, Texas. · Department of Radiation Oncology, University of Miami, Miami, Florida. · Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania. ·Pract Radiat Oncol · Pubmed #29426692.

ABSTRACT: PURPOSE: Accurate identification of the gross tumor volume (GTV) in pancreatic adenocarcinoma is challenging. We sought to understand differences in GTV delineation using pancreatic computed tomography (CT) compared with magnetic resonance imaging (MRI). METHODS AND MATERIALS: Twelve attending radiation oncologists were convened for an international contouring symposium. All participants had a clinical and research interest in pancreatic adenocarcinoma. CT and MRI scans from 3 pancreatic cases were used for contouring. CT and MRI GTVs were analyzed and compared. Interobserver variability was compared using Dice's similarity coefficient (DSC), Hausdorff distances, and Jaccard indices. Mann-Whitney tests were used to check for significant differences. Consensus contours on CT and MRI scans and constructed count maps were used to visualize the agreement. Agreement regarding the optimal method to determine GTV definition using MRI was reached. RESULTS: Six contour sets (3 from CT and 3 from MRI) were obtained and compared for each observer, totaling 72 contour sets. The mean volume of contours on CT was significantly larger at 57.48 mL compared with a mean of 45.76 mL on MRI, P = .011. The standard deviation obtained from the CT contours was significantly larger than the standard deviation from the MRI contours (P = .027). The mean DSC was 0.73 for the CT and 0.72 for the MRI (P = .889). The conformity index measurement was similar for CT and MRI (P = .58). Count maps were created to highlight differences in the contours from CT and MRI. CONCLUSIONS: Using MRI as a primary image set to define a pancreatic adenocarcinoma GTV resulted in smaller contours compared with CT. No differences in DSC or the conformity index were seen between MRI and CT. A stepwise method is recommended as an approach to contour a pancreatic GTV using MRI.

13 Article Prognostic Value of c-MET Expression in Patients With Pancreatic Cancer Receiving Adjuvant and Neoadjuvant Chemoradiation Therapy. 2018

Cuneo, Kyle C / Morgan, Meredith A / Griffith, Kent A / Hawkins, Peter G / Greenson, Joel K / Ben-Josef, Edgar / Lawrence, Theodore S / Zalupski, Mark M. ·Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan. Electronic address: kcuneo@umich.edu. · Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan. · Department of Biostatistics, University of Michigan, Ann Arbor, Michigan. · Department of Pathology, University of Michigan, Ann Arbor, Michigan. · Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania. · Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan. ·Int J Radiat Oncol Biol Phys · Pubmed #29229329.

ABSTRACT: PURPOSE: To determine the prognostic significance of c-MET expression and develop a predictor of distant failure in patients with resectable pancreatic cancer treated with chemoradiation. METHODS AND MATERIALS: We used a tissue microarray to study protein expression by immunohistochemistry in 102 patients treated surgically for pancreatic cancer. Two cores per patient were blindly scored from 0 (no staining) to 3 (strong staining) by a single pathologist. The Kaplan-Meier method was used to determine time to local and distant failure, overall survival, and progression-free survival. P values were calculated with the log-rank test. RESULTS: High tumor expression of c-MET was associated with a shorter time to distant failure in patients receiving neoadjuvant (n=23) or neoadjuvant therapy (n=73) (median 8.9 months vs 22.0 months, P=.0010). We then examined the ability of incorporating 2 known biomarkers, thymidylate synthase and DPC4 (SMAD4), with c-MET to risk-stratify patients. This multi-protein predictor divided our cohort into groups of similar numbers and was predictive of distant failure (median 13.4 months vs 24.2 months, P=.0094) but not of local control. CONCLUSION: c-MET is potentially predictive of distant failure. Using c-MET, DPC4, and thymidylate synthase, we developed a multi-protein predictor that could be used to risk-stratify patients and guide decisions regarding the sequencing of locoregional and systemic therapies in pancreatic cancer.

14 Article Tumor-Derived CCL2 Mediates Resistance to Radiotherapy in Pancreatic Ductal Adenocarcinoma. 2017

Kalbasi, Anusha / Komar, Chad / Tooker, Graham M / Liu, Mingen / Lee, Jae W / Gladney, Whitney L / Ben-Josef, Edgar / Beatty, Gregory L. ·Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania. · Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. · Division of Hematology-Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. · Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania. gregory.beatty@uphs.upenn.edu. ·Clin Cancer Res · Pubmed #27354473.

ABSTRACT: PURPOSE: Local tumor growth is a major cause of morbidity and mortality in nearly 30% of patients with pancreatic ductal adenocarcinoma (PDAC). Radiotherapy is commonly used for local disease control in PDAC, but its efficacy is limited. We studied the impact of selectively intervening on radiotherapy-induced inflammation as an approach to overcome resistance to radiotherapy in PDAC. EXPERIMENTAL DESIGN: PDAC cell lines derived from primary pancreatic tumors arising spontaneously in Kras RESULTS: Ablative radiotherapy alone had minimal impact on PDAC growth but led to a significant increase in CCL2 production by tumor cells and recruitment of Ly6C CONCLUSIONS: PDAC responds to radiotherapy by producing CCL2, which recruits Ly6C

15 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.

16 Article Caveolin-1 is Associated with Tumor Progression and Confers a Multi-Modality Resistance Phenotype in Pancreatic Cancer. 2015

Chatterjee, Moumita / Ben-Josef, Edgar / Thomas, Dafydd G / Morgan, Meredith A / Zalupski, Mark M / Khan, Gazala / Andrew Robinson, Charles / Griffith, Kent A / Chen, Ching-Shih / Ludwig, Thomas / Bekaii-Saab, Tanios / Chakravarti, Arnab / Williams, Terence M. ·The Ohio State University Medical Center, Arthur G. James Comprehensive Cancer Center and Richard J. Solove Research Institute, Columbus, OH 43210. · Hospital of the University of Pennsylvania, Philadelphia, PA, 19104. · University of Michigan Medical Center, Ann Arbor, MI, 48109. · Henry Ford Hospital System, West Bloomfield, MI, 48322. ·Sci Rep · Pubmed #26065715.

ABSTRACT: Caveolin-1 (Cav-1) is a 21 kDa protein enriched in caveolae, and has been implicated in oncogenic cell transformation, tumorigenesis, and metastasis. We explored roles for Cav-1 in pancreatic cancer (PC) prognostication, tumor progression, resistance to therapy, and whether targeted downregulation could lead to therapeutic sensitization. Cav-1 expression was assessed in cell lines, mouse models, and patient samples, and knocked down in order to compare changes in proliferation, invasion, migration, response to chemotherapy and radiation, and tumor growth. We found Cav-1 is overexpressed in human PC cell lines, mouse models, and human pancreatic tumors, and is associated with worse tumor grade and clinical outcomes. In PC cell lines, disruption/depletion of caveolae/Cav-1 reduces proliferation, colony formation, and invasion. Radiation and chemotherapy up-regulate Cav-1 expression, while Cav-1 depletion induces both chemosensitization and radiosensitization through altered apoptotic and DNA repair signaling. In vivo, Cav-1 depletion significantly attenuates tumor initiation and growth. Finally, Cav-1 depletion leads to altered JAK/STAT, JNK, and Src signaling in PC cells. Together, higher Cav-1 expression is correlated with worse outcomes, is essential for tumor growth and invasion (both in vitro and in vivo), is responsible for promoting resistance to therapies, and may serve as a prognostic/predictive biomarker and target in PC.

17 Article DEPTOR has growth suppression activity against pancreatic cancer cells. 2014

Li, Hua / Sun, Grace Y / Zhao, Yongchao / Thomas, Dafydd / Greenson, Joel K / Zalupski, Mark M / Ben-Josef, Edgar / Sun, Yi. ·Division of Radiation and Cancer Biology, Department of Radiation Oncology, University of Michigan, Ann Arbor, MI 48109, USA. · Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA. · Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA. · Division of Radiation and Cancer Biology, Department of Radiation Oncology, University of Michigan, Ann Arbor, MI 48109, USA. Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, Zhejiang, P.R. China. ·Oncotarget · Pubmed #25544749.

ABSTRACT: DEPTOR was reported as a naturally occurring inhibitor of mTORC1 and mTORC2. The role of DEPTOR in the growth and survival of pancreatic cancer cells has not previously been determined. Here we report that while DEPTOR shows a cytoplasmic expression in both normal pancreatic acinar and islet cells in a patchy manner, its expression is reduced in PanIN1 and PanIN2 and completely lost in 100 out of 101 pancreatic ductal adenocarcinoma (PDAC) tissues. Ectopic DEPTOR expression in two pancreatic cancer cell lines, Panc-1 and Miapaca-2, caused a significant 1) suppression of anchorage-dependent growth in monolayer culture, particularly under conditions with growth factor deprivation; 2) decreased clonogenic survival, and 3) suppressed anchorage-independent growth in soft agar. These effects are attributable to moderate induction of apoptosis and growth arrest at the S and G2/M phases, in a cell line dependent manner. Furthermore, ectopic DEPTOR expression moderately inhibited mTORC1 activity, as demonstrated by reduced phosphorylation of S6K, S6, and 4E-BP1. Taken together, these data suggest that DEPTOR has a tumor suppressive activity against pancreatic cancer cells, and its loss of expression may contribute to pancreatic tumorigenesis.

18 Article A dosimetric comparison of proton and photon therapy in unresectable cancers of the head of pancreas. 2014

Thompson, Reid F / Mayekar, Sonal U / Zhai, Huifang / Both, Stefan / Apisarnthanarax, Smith / Metz, James M / Plastaras, John P / Ben-Josef, Edgar. ·University of Pennsylvania, Philadelphia, Pennsylvania 19104. · Thomas Jefferson University, Philadelphia, Pennsylvania 19107. · University of Washington, Seattle, Washington 98109. ·Med Phys · Pubmed #25086521.

ABSTRACT: PURPOSE: Uncontrolled local growth is the cause of death in ∼ 30% of patients with unresectable pancreatic cancers. The addition of standard-dose radiotherapy to gemcitabine has been shown to confer a modest survival benefit in this population. Radiation dose escalation with three-dimensional planning is not feasible, but high-dose intensity-modulated radiation therapy (IMRT) has been shown to improve local control. Still, dose-escalation remains limited by gastrointestinal toxicity. In this study, the authors investigate the potential use of double scattering (DS) and pencil beam scanning (PBS) proton therapy in limiting dose to critical organs at risk. METHODS: The authors compared DS, PBS, and IMRT plans in 13 patients with unresectable cancer of the pancreatic head, paying particular attention to duodenum, small intestine, stomach, liver, kidney, and cord constraints in addition to target volume coverage. All plans were calculated to 5500 cGy in 25 fractions with equivalent constraints and normalized to prescription dose. All statistics were by two-tailed paired t-test. RESULTS: Both DS and PBS decreased stomach, duodenum, and small bowel dose in low-dose regions compared to IMRT (p < 0.01). However, protons yielded increased doses in the mid to high dose regions (e.g., 23.6-53.8 and 34.9-52.4 Gy for duodenum using DS and PBS, respectively; p < 0.05). Protons also increased generalized equivalent uniform dose to duodenum and stomach, however these differences were small (<5% and 10%, respectively; p < 0.01). Doses to other organs-at-risk were within institutional constraints and placed no obvious limitations on treatment planning. CONCLUSIONS: Proton therapy does not appear to reduce OAR volumes receiving high dose. Protons are able to reduce the treated volume receiving low-intermediate doses, however the clinical significance of this remains to be determined in future investigations.

19 Article Screening for depression, sleep-related disturbances, and anxiety in patients with adenocarcinoma of the pancreas: a preliminary study. 2012

Boyd, Andrew D / Brown, Doris / Henrickson, Chris / Hampton, Janet / Zhu, Bin / Almani, Farideh / Ben-Josef, Edgar / Zalupski, Mark / Simeone, Diane M / Taylor, Jeremy M G / Armitage, Roseanne / Riba, Michelle. ·Department of Biomedical and Health Information Sciences, University of Illinois at Chicago, 1919 W Taylor Street MC 530, Chicago, IL 60612, USA. boyda@uic.edu ·ScientificWorldJournal · Pubmed #22666142.

ABSTRACT: PURPOSE: Screening for depression, sleep-related disturbances, and anxiety in patients with diagnosed adenocarcinoma of the pancreas. MATERIALS AND METHODS: Patients were evaluated at initial consultation and subsequent visits at the multidisciplinary pancreatic cancer clinic at our University Cancer Center. Cross-sectional and longitudinal psychosocial distress was assessed utilizing Personal Health Questionnaire 9 (PHQ9) to screen for depression and monitor symptoms, the Penn State Worry Questionnaire (PSWQ) for generalized anxiety, and the University of Michigan Sleep Questionnaire to monitor sleep symptoms. RESULTS: Twenty-two patients diagnosed with pancreatic cancer participated during the 6-month pilot study with longitudinal followup for thirteen patients. In this study, mild-to-moderate depressive symptoms, anxiety, and potential sleep problems were common. The main finding of the study was 23% of the patients who were part of this pilot project screened positive for moderately severe major depressive symptoms, likely anxiety disorder or a potential sleep disorder during the study. One patient screened positive for moderately severe depressive symptoms in longitudinal followup. CONCLUSIONS: Depression, anxiety, and sleep problems are evident in patients with pancreatic cancer. Prospective, longitudinal studies, with larger groups of patients, are needed to determine if these comorbid symptoms impact outcome and clinical course.

20 Article GSK3beta and beta-catenin modulate radiation cytotoxicity in pancreatic cancer. 2010

Watson, Richard L / Spalding, Aaron C / Zielske, Steven P / Morgan, Meredith / Kim, Alex C / Bommer, Guido T / Eldar-Finkelman, Hagit / Giordano, Thomas / Fearon, Eric R / Hammer, Gary D / Lawrence, Theodore S / Ben-Josef, Edgar. ·Department of Radiation Oncology, University of Michigan Medical School, Ann Arbor, MI, USA. ·Neoplasia · Pubmed #20454507.

ABSTRACT: BACKGROUND: Knowledge of factors and mechanisms contributing to the inherent radioresistance of pancreatic cancer may improve cancer treatment. Irradiation inhibits glycogen synthase kinase 3beta (GSK3beta) by phosphorylation at serine 9. In turn, release of cytosolic membrane beta-catenin with subsequent nuclear translocation promotes survival. Both GSK3beta and beta-catenin have been implicated in cancer cell proliferation and resistance to death. METHODS: We investigated pancreatic cancer cell survival after radiation in vitro and in vivo, with a particular focus on the role of the function of the GSK3beta/beta-catenin axis. RESULTS: Lithium chloride, RNAi-medicated silencing of GSK3beta, or the expression of a kinase dead mutant GSK3beta resulted in radioresistance of Panc1 and BxPC3 pancreatic cancer cells. Conversely, ectopic expression of a constitutively active form of GSK3beta resulted in radiosensitization of Panc1 cells. GSK3beta silencing increased radiation-induced beta-catenin target gene expression as measured by studies of AXIN2 and LEF1 transcript levels. Western blot analysis of total and phosphorylated levels of GSK3beta and beta-catenin showed that GSK3beta inhibition resulted in stabilization of beta-catenin. Xenografts of both BxPC3 and Panc1 with targeted silencing of GSK3beta exhibited radioresistance in vivo. Silencing of beta-catenin resulted in radiosensitization, whereas a nondegradable beta-catenin construct induced radioresistance. CONCLUSIONS: These data support the hypothesis that GSK3beta modulates the cellular response to radiation in a beta-catenin-dependent mechanism. Further understanding of this pathway may enhance the development of clinical trials combining drugs inhibiting beta-catenin activation with radiation and chemotherapy in locally advanced pancreatic cancer.

21 Article Gemcitabine-based combination chemotherapy followed by radiation with capecitabine as adjuvant therapy for resected pancreas cancer. 2009

Desai, Sameer / Ben-Josef, Edgar / Griffith, Kent A / Simeone, Diane / Greenson, Joel K / Francis, Isaac R / Hampton, Janet / Colletti, Lisa / Chang, Alfred E / Lawrence, Theodore S / Zalupski, Mark M. ·Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109-0934, USA. ·Int J Radiat Oncol Biol Phys · Pubmed #19409732.

ABSTRACT: PURPOSE: To report outcomes for patients with resected pancreas cancer treated with an adjuvant regimen consisting of gemcitabine-based combination chemotherapy followed by capecitabine and radiation. PATIENTS AND METHODS: We performed a retrospective review of a series of patients treated at a single institution with a common postoperative adjuvant program. Between January 2002 and August 2006, 43 resected pancreas cancer patients were offered treatment consisting of 4, 21-day cycles of gemcitabine 1 g/m(2) intravenously over 30 min on Days 1 and 8, with either cisplatin 35 mg/m(2) intravenously on Days 1 and 8 or capecitabine 1500 mg/m(2) orally in divided doses on Days 1-14. After completion of combination chemotherapy, patients received a course of radiotherapy (54 Gy) with concurrent capecitabine (1330 mg/m(2) orally in divided doses) day 1 to treatment completion. RESULTS: Forty-one patients were treated. Median progression-free survival for the entire group was 21.7 months (95% confidence interval 13.9-34.5 months), and median overall survival was 45.9 months. In multivariate analysis a postoperative CA 19-9 level of >or=180 U/mL predicted relapse and death. Toxicity was mild, with only two hospitalizations during adjuvant therapy. CONCLUSIONS: A postoperative adjuvant program using combination chemotherapy with gemcitabine and either cisplatin or capecitabine followed by radiotherapy with capecitabine is tolerable and efficacious and should be considered for Phase III testing in this group of patients.

22 Article Characterization of pancreatic tumor motion using cine MRI: surrogates for tumor position should be used with caution. 2009

Feng, Mary / Balter, James M / Normolle, Daniel / Adusumilli, Saroja / Cao, Yue / Chenevert, Thomas L / Ben-Josef, Edgar. ·Department of Radiation Oncology, University of Michigan, USA. ibrahim.diallo@igr.fr ·Int J Radiat Oncol Biol Phys · Pubmed #19395190.

ABSTRACT: PURPOSE: Our current understanding of intrafraction pancreatic tumor motion due to respiration is limited. In this study, we characterized pancreatic tumor motion and evaluated the application of several radiotherapy motion management strategies. METHODS AND MATERIALS: Seventeen patients with unresectable pancreatic cancer were enrolled in a prospective internal review board-approved study and imaged during shallow free-breathing using cine MRI on a 3T scanner. Tumor borders were agreed on by a radiation oncologist and an abdominal MRI radiologist. Tumor motion and correlation with the potential surrogates of the diaphragm and abdominal wall were assessed. These data were also used to evaluate planning target volume margin construction, respiratory gating, and four-dimensional treatment planning for pancreatic tumors. RESULTS: Tumor borders moved much more than expected. To provide 99% geometric coverage, margins of 20 mm inferiorly, 10 mm anteriorly, 7 mm superiorly, and 4 mm posteriorly are required. Tumor position correlated poorly with diaphragm and abdominal wall position, with patient-level Pearson correlation coefficients of -0.18-0.43. Sensitivity and specificity of gating with these surrogates was also poor, at 53%-68%, with overall error of 35%-38%, suggesting that the tumor may be underdosed and normal tissues overdosed. CONCLUSIONS: Motion of pancreatic tumor borders is highly variable between patients and larger than expected. There is substantial deformation with breathing, and tumor border position does not correlate well with abdominal wall or diaphragmatic position. Current motion management strategies may not account fully for tumor motion and should be used with caution.

23 Article Radiotherapy for pancreatic neuroendocrine tumors. 2009

Contessa, Joseph N / Griffith, Kent A / Wolff, Elizabeth / Ensminger, William / Zalupski, Mark / Lawrence, Theodore S / Ben-Josef, Edgar. ·Department of Radiation Oncology, University of Michigan, Ann Arbor, MI 48109, USA. ·Int J Radiat Oncol Biol Phys · Pubmed #19327905.

ABSTRACT: PURPOSE: Pancreatic neuroendocrine tumors (PNTs) are rare malignant neoplasms considered to be resistant to radiotherapy (RT), although data on efficacy are scarce. We reviewed our institutional experience to further delineate the role of RT for patients with PNTs. METHODS AND MATERIALS: Between 1986 and 2006, 36 patients with PNTs were treated with RT to 49 sites. Of these 36 patients, 23 had radiographic follow-up data, which were used to determine the tumor response rate and freedom from local progression. Long-term toxicity was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events. RESULTS: The overall response rate to RT was 39% (13% complete response, 26% partial response, 56% stable disease, and 4% progressive disease). A significant difference in the freedom from local progression between the groups receiving either greater than or less than the median 2 Gy/fraction biologically equivalent dose of 49.6 Gy was found, with all radiographic progression occurring in patients who had received RT is an effective modality for achieving local control in patients with PNTs. RT produces high rates of symptomatic palliation and freedom from local progression. Prospective trials of radiotherapy for PNTs are warranted.

24 Minor Radiotherapy improves survival in unresectable pancreatic cancer: small trial but big (and credible) results. 2012

Ben-Josef, Edgar / Taylor, Jeremy M G / Lawrence, Theodore S. · ·J Clin Oncol · Pubmed #22412130.

ABSTRACT: -- No abstract --