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Pancreatic Neoplasms: HELP
Articles by Steven J. Cohen
Based on 21 articles published since 2010
(Why 21 articles?)
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Between 2010 and 2020, Steve J. Cohen wrote the following 21 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 / Anonymous5390728. ·UCSF Helen Diller Family Comprehensive Cancer Center. ·J Natl Compr Canc Netw · Pubmed #22679115.

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

2 Guideline Pancreatic adenocarcinoma. 2010

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

ABSTRACT: -- No abstract --

3 Review Personalized medicine in sporadic pancreatic cancer without homologous recombination-deficiency: are we any closer? 2016

Vijayvergia, Namrata / Cohen, Steven J. ·Department of Hematology and Oncology, Fox Chase Cancer Center, Philadelphia, PA 19111, USA. ·J Gastrointest Oncol · Pubmed #27747087.

ABSTRACT: Pancreatic adenocarcinoma is the fourth leading cause of cancer related death in the United States. Most patients are diagnosed at a late stage and despite recent advances in chemotherapeutic approaches, outcomes are poor. With the introduction of combination chemotherapy, novel biomarkers are clearly needed to identify subsets of patients likely to benefit from these therapies. Advances in our understanding of the molecular drivers of pancreatic cancer offer the hope of personalized therapy that may benefit our patients. In this review, we summarize the current knowledge about the biology of pancreatic cancer and its implication for treatment. We discuss recent advances in targeted therapies and the role of potential biomarkers in predicting response to established therapies. We also review novel therapeutic approaches that may be able to fulfill the promise of personalized therapy for pancreatic cancer.

4 Review Emerging therapies for advanced gastroenteropancreatic neuroendocrine tumors. 2011

Gupta, Sameer / Engstrom, Paul F / Cohen, Steven J. ·Fox Chase Cancer Center, Philadelphia, PA 19111, USA. ·Clin Colorectal Cancer · Pubmed #21813338.

ABSTRACT: Neuroendocrine tumors comprise a heterogeneous group of neoplasms derived from peptide- and amine-producing cells of the neuroendocrine system. Gastroenteropancreatic NET are differentiated into tumors and carcinomas based on their malignant potential and subdivided into those arising from the pancreas (islet cell tumors or pancreatic NET) and the more classical gut "carcinoids". Moderate to well differentiated NET have historically been considered rare tumors but recent epidemiological statistics suggest that their frequency has increased substantially over the past three decades. While the incidence of NET is increasing, data from both the US and UK demonstrate no improvement in outcomes over a similar time period. Due to the generally indolent biology of NET, most patients present with advanced disease before symptoms become apparent. In patients with localized NET, the 5-year survival rates after resection range from 60 to 90%, while regional lymph node involvement decreases the 5-year survival rates after surgery to 50-75%. Patients with distant metastases have a 5 year survival rate of approximately 25-40%. Conventional cytotoxic chemotherapy is of unclear benefit in patients with these generally slow growing tumors. Multiple agents have been tested in Phase 2 and Phase 3 trials. In general, the lack of major objective responses with significant toxicities has limited routine use of traditional chemotherapy agents and has emphasized the need to develop new agents in these diseases. This review will focus on emerging molecularly-targeted treatments with an emphasis on their underlying biologic and preclinical rationale.

5 Clinical Trial A Phase 2 Randomized, Double-Blind, Multicenter Trial of Imexon Plus Gemcitabine Versus Gemcitabine Plus Placebo in Patients With Metastatic Chemotherapy-naïve Pancreatic Adenocarcinoma. 2018

Cohen, Steven J / Zalupski, Mark M / Conkling, Paul / Nugent, Francis / Ma, Wen Wee / Modiano, Manuel / Pascual, Rolan / Lee, Fa Chyi / Wong, Lucas / Hersh, Evan. ·Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA. · Department of Internal Medicine, University of Michigan, Ann Arbor, MI. · US Oncology (Virginia Oncology Associates), Norfolk, VA. · Lahey Clinic, Burlington, MA. · Roswell Park Cancer Institute, Buffalo, NY. · Arizona Clinical Research Center. · Northern Indiana Cancer Research Consortium, South Bend, IN. · University of New Mexico, Albuquerque, NM. · Scott and White Hospital and Clinics, Temple, TX. · Amplimed Corporation, Tuscon, AZ. ·Am J Clin Oncol · Pubmed #26709865.

ABSTRACT: BACKGROUND: Imexon is a cyanoaziridine-derived iminopyrrolidone which has synergistic cytotoxicity with gemcitabine. A phase 1 study of the combination demonstrated good tolerance with encouraging clinical activity and thus we conducted this randomized phase II study. MATERIALS AND METHODS: Patients with measurable, metastatic, treatment-naive pancreatic adenocarcinoma were randomized 1:1 to receive gemcitabine at 1000 mg/m days 1, 8, and 15 with either imexon, 875 mg/m or placebo days 1, 8, and 15 every 28 days. The primary endpoint was overall survival. Secondary endpoints included progression-free survival and response rate. RESULTS: A total of 142 patients were randomized, 72 to the imexon containing arm and 70 to the placebo arm. Patients in the imexon arm received an average of 3.6 cycles (range, 1 to 23) compared with 4.4 (range, 1 to 21) in the placebo arm. There was no increased rate of ≥grade 3 toxicity in the imexon arm. Seven patients had objective responses in the imexon arm (13.7%), whereas 9 did in the placebo arm (17%). In the imexon arm, 23 patients had ≥50% reduction in CA 19-9 from baseline (33%), whereas 22 did in the placebo arm (31.4%). The median progression-free survival was 2.8 months in the imexon arm (95% confidence interval [CI], 2.0-4.1 m) and 3.8 months in the placebo arm (95% CI, 2.2-4.7 m), P=0.504. The median overall survival time in the imexon arm was 5.2 months (95% CI, 4.2-6.7 m) as compared with 6.8 m (95% CI, 4.9-8.5 m) in the placebo arm, P=0.6822. CONCLUSIONS: The combination of imexon and gemcitabine does not result in improved outcome as initial therapy of metastatic pancreatic adenocarcinoma.

6 Clinical Trial A phase 1b study of erlotinib in combination with gemcitabine and nab-paclitaxel in patients with previously untreated advanced pancreatic cancer: an Academic Oncology GI Cancer Consortium study. 2016

Cohen, Steven J / O'Neil, Bert H / Berlin, Jordan / Ames, Patricia / McKinley, Marti / Horan, Julie / Catalano, Patricia M / Davies, Angela / Weekes, Colin D / Leichman, Lawrence. ·Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA, 19111-2497, USA. steven.cohen@fccc.edu. · Indiana University Simon Cancer Center, Indianapolis, IN, USA. · Vanderbilt-Ingram Cancer Center, Nashville, TN, USA. · Abrazo Community Health Network, Phoenix, AZ, USA. · Aptium Oncology, Criterium, Inc., Los Angeles, CA, USA. · Novella Clinical, Boulder, CO, USA. · Champions Oncology, Hackensack, NJ, USA. · University of Colorado School of Medicine, Aurora, CO, USA. · New York University, New York, NY, USA. ·Cancer Chemother Pharmacol · Pubmed #26886016.

ABSTRACT: PURPOSE: Addition of either nab-paclitaxel or erlotinib to gemcitabine to treat advanced pancreatic cancer has demonstrated overall survival benefit. This study was conducted to evaluate the tolerability and safety of combining all three drugs and assess preliminary evidence of efficacy. METHODS: In this open-label, phase 1b study, patients with previously untreated, advanced pancreatic cancer were treated in 28-day cycles with intravenous gemcitabine/nab-paclitaxel on days 1, 8, and 15, and once daily oral erlotinib. A standard "3 + 3" design was used. Dose level 1 (DL1) for gemcitabine (mg/m(2))/nab-paclitaxel (mg/m(2))/erlotinib (mg) was 1000/125/100, respectively, with de-escalation to DL-1 (1000/100/100), DL-2b (1000/75/100), and DL-3 (1000/75/75). The maximum tolerated dose (MTD) was defined by occurrence of dose-limiting toxicity (DLT) in ≤1 of six patients within the first cycle. Efficacy was assessed with CT scans performed at two-cycle intervals. RESULTS: Nineteen patients were enrolled. DLTs occurred in two patients at DL1, three patients at DL-1, two patients at DL-2b, and one patient at DL-3. The MTD for the combination of gemcitabine/nab-paclitaxel/erlotinib was DL-3 (1000/75/75). In analyses of efficacy among 14 evaluable patients, partial responses were observed in four of six patients at DL1, one of two patients at DL-2b, and two of six patients at DL-3. CONCLUSION: The addition of erlotinib to gemcitabine and nab-paclitaxel is not tolerable at standard single-agent dosing of all drugs. However, significant clinical activity was noted, even at DL-3. Further study of the combination will need to incorporate reduced dosing.

7 Clinical Trial (90)Y-clivatuzumab tetraxetan with or without low-dose gemcitabine: A phase Ib study in patients with metastatic pancreatic cancer after two or more prior therapies. 2015

Picozzi, Vincent J / Ramanathan, Ramesh K / Lowery, Maeve A / Ocean, Allyson J / Mitchel, Edith P / O'Neil, Bert H / Guarino, Michael J / Conkling, Paul R / Cohen, Steven J / Bahary, Nathan / Frank, Richard C / Dragovich, Tomislav / Bridges, Benjamin B / Braiteh, Fadi S / Starodub, Alexander N / Lee, Fa-Chyi / Gribbin, Thomas E / Richards, Donald A / Lee, Marie / Korn, Ronald L / Pandit-Taskar, Neeta / Goldsmith, Stanley J / Intenzo, Charles M / Sheikh, Arif / Manzone, Timothy C / Horne, Heather / Sharkey, Robert M / Wegener, William A / O'Reilly, Eileen M / Goldenberg, David M / Von Hoff, Daniel D. ·Virginia Mason Medical Center, Seattle, WA, United States. · Virginia G. Piper Cancer Center at Scottsdale Healthcare/TGen, Scottsdale, AZ, United States. · Memorial Sloan-Kettering Cancer Center, New York, NY, United States. · Weill Cornell Medical College, New York, NY, United States. · Kimmel Cancer Center of Thomas Jefferson University, Philadelphia, PA, United States. · UNC Lineberger Comprehensive Cancer Center, Chapel Hill, NC, United States. · Helen F. Graham Cancer Center at Christiana Care Health System, Newark, DE, United States. · US Oncology Phase II Group, Virginia Oncology Associates, Norfolk, VA, United States. · Fox Chase Cancer Center, Philadelphia, PA, United States. · University of Pittsburgh Medical Center, Pittsburgh, PA, United States. · Whittingham Cancer Center at Norwalk Hospital, Norwalk, CT, United States. · Banner MD Anderson Cancer Center, Gilbert, AZ, United States. · St Luke's Mountain States Tumor Institute, Meridian, ID, United States. · Comprehensive Cancer Centers of Nevada, Las Vegas, NV, United States. · Indiana University Health Center for Cancer Care, Goshen, IN, United States. · University of New Mexico Health Science Center, Albuquerque, NM, United States. · Lacks Cancer Center, Saint Mary's Health Care, Grand Rapids, MI, United States. · Tyler Cancer Center, US Oncology Research, Tyler, TX, United States. · Immunomedics, Inc., Morris Plains, NJ, United States. · Immunomedics, Inc., Morris Plains, NJ, United States; Center for Molecular Medicine and Immunology/Garden State Cancer Center, Morris Plains, NJ, United States. Electronic address: dmg.gscancer@att.net. ·Eur J Cancer · Pubmed #26187510.

ABSTRACT: BACKGROUND: For patients with metastatic pancreatic adenocarcinoma, there are no approved or established treatments beyond the 2nd line. A Phase Ib study of fractionated radioimmunotherapy was undertaken in this setting, administering (90)Y-clivatuzumab tetraxetan (yttrium-90-radiolabelled humanised antibody targeting pancreatic adenocarcinoma mucin) with or without low radiosensitising doses of gemcitabine. METHODS: Fifty-eight patients with three (2-7) median prior treatments were treated on Arm A (N=29, (90)Y-clivatuzumab tetraxetan, weekly 6.5 mCi/m(2)doses×3, plus gemcitabine, weekly 200 mg/m(2) doses×4 starting 1 week earlier) or Arm B (N=29, (90)Y-clivatuzumab tetraxetan alone, weekly 6.5 mCi/m(2)doses×3), repeating cycles after 4-week delays. Safety was the primary endpoint; efficacy was also evaluated. RESULTS: Cytopaenias (predominantly transient thrombocytopenia) were the only significant toxicities. Fifty-three patients (27 Arm A, 26 Arm B, 91% overall) completed ⩾1 full treatment cycles, with 23 (12 Arm A, 11 Arm B; 40%) receiving multiple cycles, including seven (6 Arm A, 1 Arm B; 12%) given 3-9 cycles. Two patients in Arm A had partial responses by RECIST criteria. Kaplan-Meier overall survival (OS) appeared improved in Arm A versus B (hazard ratio [HR] 0.55, 95% CI: 0.29-0.86; P=0.017, log-rank) and the median OS for Arm A versus Arm B increased to 7.9 versus 3.4 months with multiple cycles (HR 0.32, P=0.004), including three patients in Arm A surviving >1 year. CONCLUSIONS: Clinical studies of (90)Y-clivatuzumab tetraxetan combined with low-dose gemcitabine appear feasible in metastatic pancreatic cancer patients beyond 2nd line and a Phase III trial of this combination is now underway in this setting.

8 Clinical Trial Multi-institutional phase I study of low-dose ultra-fractionated radiotherapy as a chemosensitizer for gemcitabine and erlotinib in patients with locally advanced or limited metastatic pancreatic cancer. 2014

Konski, Andre / Meyer, Joshua E / Joiner, Michael / Hall, Michael J / Philip, Philip / Shields, Anthony / McSpadden, Erin / Choi, Minsig / Adaire, Beth / Duncan, Gail / Meropol, Neal J / Cescon, Terrence P / Cohen, Steven J. ·Department of Radiation Oncology, Wayne State University, Barbara Ann Karmanos Cancer Center, Detroit, USA. Electronic address: andre.konski@uphs.upenn.edu. · Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, USA. · Department of Radiation Oncology, Wayne State University, Barbara Ann Karmanos Cancer Center, Detroit, USA. · Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, USA. · Department of Oncology, Wayne State University, Barbara Ann Karmanos Cancer Center, Detroit, USA. · Clinical Trials Office, Fox Chase Cancer Center, Philadelphia, USA. · University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, USA. · Reading Hospital and Medical Center, Reading, USA. ·Radiother Oncol · Pubmed #25441058.

ABSTRACT: PURPOSE: Gemcitabine (G) has been shown to sensitize pancreatic cancer to radiotherapy but requires lower doses of G and thus delays aggressive systemic treatment, potentially leading to distant failure. We initiated a phase I trial combining ultra-fractionated low-dose radiotherapy with full dose G and erlotinib in the treatment of patients with advanced pancreatic cancer. METHODS: Patients with locally advanced or metastatic pancreatic cancer confined to the abdomen and an ECOG performance status (PS) of 0-1 who had received 0-1 prior regimens (without G or E) and no prior radiotherapy were eligible. Patients were treated in 21 day cycles with G IV days 1 & 8, E once PO QD, and twice daily RT fractions separated by at least 4h on days 1, 2, 8, and 9. Whole abdominal RT fields were used. Primary endpoint was to define dose limiting toxicity (DLT) and the maximum tolerated dose (MTD). RESULTS: 27 patients (median age 64 years and 15 male) were enrolled between 11/24/08 and 4/12/12. 1 patient withdrew consent prior to receiving any protocol therapy. 17 patients had a PS of 1. The majority of patients were stage IV. One DLT was noted out of 7 patients at dose level (DL) 1. Subsequently no DLTs were noted in 3 patients each enrolled at DL2-4 or 11 patients in the expansion cohort. The majority of grade 3 toxicities were hematologic with 1 grade 5 bowel perforation in dose level 1 in cycle 4. Best response in 24 evaluable patients: PR (8), stable (15), PD 1. Median survival for the entire group was 9.1 months. CONCLUSION: This phase I study combining low-dose ultra-fractionated RT as a sensitizer to full dose G plus E was well tolerated with encouraging efficacy. This represents a novel strategy worthy of further investigation in advanced pancreatic cancer patients.

9 Clinical Trial Treatment of advanced pancreatic carcinoma with 90Y-Clivatuzumab Tetraxetan: a phase I single-dose escalation trial. 2011

Gulec, Seza A / Cohen, Steven J / Pennington, Kenneth L / Zuckier, Lionel S / Hauke, Ralph J / Horne, Heather / Wegener, William A / Teoh, Nick / Gold, David V / Sharkey, Robert M / Goldenberg, David M. ·Goshen Center for Cancer Care, Goshen, Indiana, USA. ·Clin Cancer Res · Pubmed #21527562.

ABSTRACT: PURPOSE: Humanized antibody hPAM4 specifically binds a mucin glycoprotein expressed in pancreatic adenocarcinomas. This phase I study evaluated a single dose of (90)Y-clivatuzumab tetraxetan ((90)Y-labeled hPAM4) in patients with advanced pancreatic cancer. EXPERIMENTAL DESIGN: Twenty-one patients (4 stage III; 17 stage IV) received (111)In-hPAM4 for imaging and serum sampling before (90)Y-hPAM4. Study procedures evaluated adverse events, safety laboratories, computed tomography (CT) scans, biomarkers, pharmacokinetics, radiation dosimetry, and immunogenicity (HAHA). RESULTS: (111)In-hPAM4 showed normal biodistribution with radiation dose estimates to red marrow and solid organs acceptable for radioimmunotherapy and with tumor targeting in 12 patients. One patient withdrew before (90)Y-hPAM4; otherwise, 20 patients received (90)Y doses of 15 (n = 7), 20 (n = 9), and 25 mCi/m(2) (n = 4). Treatment was well tolerated; the only significant drug-related toxicities were (NCI CTC v.3) grade 3 to 4 neutropenia and thrombocytopenia increasing with (90)Y dose. There were no bleeding events or serious infections, and most cytopenias recovered to grade 1 within 12 weeks. Three patients at 25 mCi/m(2) encountered dose-limiting toxicity with grade 4 cytopenias more than 7 days, establishing 20 mCi/m(2) as the maximal tolerated (90)Y dose. Two patients developed HAHA of uncertain clinical significance. Most patients progressed rapidly and with CA19-9 levels increasing within 1 month of therapy, but 7 remained progression-free by CT for 1.5 to 5.6 months, including 3 achieving transient partial responses (32%-52% tumor diameter shrinkage). CONCLUSION: (90)Y-Clivatuzumab tetraxetan was well tolerated with manageable hematologic toxicity at the maximal tolerated (90)Y dose, and is a potential new therapeutic for advanced pancreatic cancer.

10 Clinical Trial Phase II and coagulation cascade biomarker study of bevacizumab with or without docetaxel in patients with previously treated metastatic pancreatic adenocarcinoma. 2011

Astsaturov, Igor A / Meropol, Neal J / Alpaugh, R Katherine / Burtness, Barbara A / Cheng, Jonathan D / McLaughlin, Sue / Rogatko, André / Xu, Zhiheng / Watson, James C / Weiner, Louis M / Cohen, Steven J. ·Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA 19111–2497, USA. ·Am J Clin Oncol · Pubmed #20458210.

ABSTRACT: PURPOSE: Treatment options are limited for advanced pancreatic cancer progressive after gemcitabine therapy. The vascular endothelial growth factor pathway is biologically important in pancreatic cancer, and docetaxel has modest antitumor activity. We evaluated the role of the anti-vascular endothelial growth factor antibody bevacizumab as second-line treatment for patients with metastatic pancreatic cancer. DESIGN: Patients with metastatic adenocarcinoma of the pancreas who had progressive disease on a gemcitabine-containing regimen were randomized to receive bevacizumab alone or bevacizumab in combination with docetaxel. RESULTS: Thirty-two patients were enrolled; 16 to bevacizumab alone (Arm A) and 16 to bevacizumab plus docetaxel (Arm B). Toxicities were greater in Arm B with the most common grade 3/4 nonhematologic toxicities including fatigue, diarrhea, dehydration, and anorexia. No confirmed objective responses were observed. At 4 months, 2 of the 16 patients in Arm A and 3 of the 16 patients in Arm B were free from progression. The study was stopped according to the early stopping rule for futility. Median progression-free survival and overall survival were 43 days and 165 days in Arm A and 48 days and 125 days in Arm B. Elevated d-dimer levels and thrombin-antithrombin complexes were associated with decreased survival and increased toxicity. CONCLUSION: Bevacizumab with or without docetaxel does not have antitumor activity in gemcitabine-refractory metastatic pancreatic cancer. Baseline and on-treatment d-dimer and thrombin-antithrombin complex levels are associated with increased toxicity and decreased survival.

11 Article Predictors of Hematologic Toxicity and Chemotherapy Dose Intensity in Patients Undergoing Chemoradiation for Pancreatic Cancer. 2018

Shaikh, Talha / Wang, Lora S / Egleston, Brian / Burki, Meher / Hoffman, John P / Cohen, Steven J / Meyer, Joshua E. ·Departments of Radiation Oncology. · Biostatistics. · Medical Oncology. · Surgical Oncology, Fox Chase Cancer Center, Philadelphia, PA. ·Am J Clin Oncol · Pubmed #26325492.

ABSTRACT: OBJECTIVES: Intensity-modulated radiation therapy (IMRT) has been shown to decrease abdominal toxicity in patients undergoing chemoradiation (CRT) for pancreatic cancer. We evaluated whether IMRT impacts the rates of hematologic toxicity and chemotherapy dose intensity in patients undergoing CRT. METHODS: We retrospectively reviewed patients with borderline resectable or locally advanced pancreatic cancer undergoing CRT between 2006 and 2012. Exclusion criteria included receipt of non-gemcitabine therapy, chemotherapy before CRT, or abnormal baseline hematologic indices. Endpoints included total gemcitabine dose received, dose intensity, unplanned dose reductions, and hematologic toxicity (WBC, ANC, platelet, and hemoglobin). Patient/treatment factors were evaluated for their relationship to the above endpoints during CRT and within the first 3 months post-CRT. Statistical analysis was performed using the Fisher exact test and regression models. Because of the multiple comparisons in the presented analysis, a false discovery rate adjustment was performed at the 5% false discovery rate level. RESULTS: Eighty-five patients met the inclusion criteria. Fifty-eight (68.2%) patients received treatment with IMRT, and 27 (31.8%) patients were treated with 3D-conformal radiation. During CRT, there was no relationship between radiation technique and gemcitabine dose received, dose intensity, or hematologic grade 3+ toxicity. Post-CRT, there was no relationship between radiation technique and total gemcitabine dose received, dose intensity, or dose reduction. Patients receiving IMRT were more likely to have ANC grade 3+ toxicity (P=0.007) post-CRT, although this was no longer statistically significant after correction. There were no other relationships between treatment technique and hematologic toxicity. CONCLUSIONS: IMRT technique may be associated with higher hematologic toxicity in patients undergoing CRT for pancreatic cancer. Given the expanding use of CRT, additional study is needed to identify the impact of IMRT on myelosuppression in these patients.

12 Article Dosimetric predictors of hematologic toxicity in patients undergoing concurrent gemcitabine-based chemoradiation for localized pancreatic cancer. 2016

Shaikh, Talha / Wang, Lora S / Egleston, Brian / Burki, Meher / Hoffman, John P / Cohen, Steven J / Meyer, Joshua E. ·Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania. · Department of Biostatistics, Fox Chase Cancer Center, Philadelphia, Pennsylvania. · Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania. · Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania. · Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania. Electronic address: Joshua.Meyer@fccc.edu. ·Pract Radiat Oncol · Pubmed #27032572.

ABSTRACT: PURPOSE: This study was undertaken to identify parameters associated with hematologic toxicity or chemotherapy dose modification in patients undergoing concurrent chemoradiation (CRT) with gemcitabine for localized pancreatic cancer. METHODS AND MATERIALS: We reviewed patients with localized pancreatic cancer undergoing CRT between 2006 and 2012. Exclusion criteria included receipt of nongemcitabine therapy, chemotherapy before CRT, or abnormal baseline hematologic indices. The T11-L3 vertebrae were contoured as bone marrow region at risk. Linear and logistic regression models were used to test associations between dosimetric parameters and gemcitabine dose modification or hematologic toxicity during or within 3 months following CRT. Receiver operator curves were generated to identify threshold doses for hematologic toxicity. RESULTS: Forty-nine patients were included. During CRT, the maximum thoracolumbar dose was associated with grade 2+ neutropenia during CRT (P = .017) and the volume receiving 5 Gy (V5) was associated with grade 2+ leukopenia (P = .041). Post-CRT, thoracolumbar mean dose (P = .015), V5 (P = .01), and V10 (P = .012) were associated with increased grade 2+ neutropenia. On multivariable analysis, the thoracolumbar maximum dose (P = .045) and V5 (P = .045) were associated with grade 2+ neutropenia and grade 2+ leukopenia during CRT, respectively. Post-CRT, the mean dose (P = .046), V5 (P = .019), and V10 (P = .037) were associated with increased grade 2+ neutropenia. A maximum dose of 48.02 Gy and V5 of 57.6% were identified as predictors of toxicity during CRT. A V5 of 56.6%, V10 of 47.05%, and mean dose of 11.67 Gy were identified as predictors of post-CRT hematologic toxicity. Post-CRT, there was a trend toward increased dose modifications with increased V5 (P = .065). CONCLUSIONS: In our dataset, the thoracolumbar mean dose, maximum dose, V5, and V10 correlated with hematologic toxicity during CRT and post-CRT in patients with localized pancreatic cancer. Because of the high rates of distant failure and importance of systemic therapy in these patients, this may be an important consideration during treatment planning.

13 Article Prognostic Significance of MUC-1 in Circulating Tumor Cells in Patients With Metastatic Pancreatic Adenocarcinoma. 2016

Dotan, Efrat / Alpaugh, R Katherine / Ruth, Karen / Negin, Benjamin P / Denlinger, Crystal S / Hall, Michael J / Astsaturov, Igor / McAleer, Cecilia / Fittipaldi, Patricia / Thrash-Bingham, Catherine / Meropol, Neal J / Cohen, Steven J. ·From the *Department of Medical Oncology, †Protocol Support Laboratory, and ‡Biostatistics Facility, Fox Chase Cancer Center, Philadelphia, PA; §South Jersey Regional Hospital, Vineland, NJ; ∥Clinical Trials Office, Fox Chase Cancer Center, Philadelphia, PA; and ¶Division of Hematology and Oncology, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH. ·Pancreas · Pubmed #26967453.

ABSTRACT: OBJECTIVES: Development of targeted therapies for pancreatic cancer could be enhanced by a reliable method for noninvasive tumor cell assessment. In this pilot study, we isolated and phenotypically characterized circulating tumor cells (CTCs) from patients with metastatic pancreatic cancer and explored their relationship to clinical outcome. METHODS: Peripheral blood from 50 patients was collected at treatment initiation and first disease evaluation for CTC enumeration and phenotyping by CellSearch® system. Expression of human mucin 1 (MUC-1) was performed. RESULTS: Forty-eight and 37 patients had evaluable samples at baseline and first disease evaluation, respectively. The cohort was 62% male, with a median age of 63 years. At least 1 CTC per 7.5 mL was detected in 23 patients (48%) pretreatment and 11 patients (30%) at first disease evaluation. No difference was seen in overall survival between patients with 1 or more CTCs versus no CTC at baseline (P = 0.14). Patients with MUC-1 expressing CTC (n = 10) had shorter median overall survival compared with those with MUC-1 negative CTC (n = 13; 2.7 vs 9.6 m; P = 0.044). CONCLUSIONS: Circulating tumor cell enumeration and phenotypic characterization from metastatic pancreatic cancer patients are feasible. No correlation was found between CTC isolation and survival. However, the presence of MUC-1 expressing CTC demonstrated a trend toward inferior survival.

14 Article Patterns of care and outcomes of older versus younger patients with metastatic pancreatic cancer: A Fox Chase Cancer Center experience. 2015

Vijayvergia, Namrata / Dotan, Efrat / Devarajan, Karthik / Hatahet, Kamel / Rahman, Farah / Ricco, Julianna / Lewis, Bianca / Gupta, Sameer / Cohen, Steven J. ·Deparment of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA. Electronic address: namrata.vijayvergia@fccc.edu. · Deparment of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA. · Department of Biostatistics and Bioinformatics, Fox Chase Cancer Center, Philadelphia, PA, USA. · Department of General Internal Medicine, Temple University Hospital, Philadelphia, PA, USA. · Bryn Mawr Medical Associates, Bryn Mawr, PA, USA. ·J Geriatr Oncol · Pubmed #26296909.

ABSTRACT: BACKGROUND: Older patients with metastatic pancreatic cancer (mPC) are poorly represented in clinical trials. We compared patterns of care and outcomes of patients with mPC < and >65 yrs (Group 1 and Group 2, respectively) treated at Fox Chase Cancer Center (FCCC) to identify predictors of survival and better understand the treatment approaches. METHODS: Charts of 579 patients with mPC treated at FCCC from 2000 to 2010 were reviewed. Group 1 and Group 2 were compared with respect to baseline, treatment characteristics, and overall survival (OS) after diagnosis of metastatic disease. RESULTS: 299 patients in Group 1 (median age 57) and 280 patients in Group 2 (median age 73) were evaluated. Patients in Group 2 were less likely to receive any chemotherapy for mPC compared to Group 1 (65% vs 75%, p=0.001) and if treated were less likely to receive more than one agent (37% vs 53%, p<0.001). Survival was comparable between the two groups (p=0.16) and Charlson Co-morbidity Index did not emerge as a prognostic factor. Longer OS was associated with higher number of agents used in both groups (p<0.001). Liver metastases conferred worse survival (p=0.02) while lung metastases conferred better survival in both groups (p=0.002). CONCLUSIONS: Older mPC patients are less likely to receive chemotherapy and receive fewer agents yet have similar OS compared to younger patients. OS improves with increasing number of agents, supporting the use of combination chemotherapy in healthy older patients. Our findings encourage enrollment of older patients with mPC with good performance status onto clinical trials with stratification by site of metastases.

15 Article Dose escalation with a vessel boost in pancreatic adenocarcinoma treated with neoadjuvant chemoradiation. 2015

Wang, Lora S / Shaikh, Talha / Handorf, Elizabeth A / Hoffman, John P / Cohen, Steven J / Meyer, Joshua E. ·Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania. · Department of Biostatistics, Fox Chase Cancer Center, Philadelphia, Pennsylvania. · Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania. · Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania. · Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania. Electronic address: joshua.meyer@fccc.edu. ·Pract Radiat Oncol · Pubmed #26077273.

ABSTRACT: PURPOSE: Patients with pancreatic adenocarcinoma (PAC) are often treated with neoadjuvant chemoradiation (NACRT) in hopes of downstaging their disease for potential surgical resection. We hypothesized that increasing the radiation dose to the area of the tumor abutting the vessel(s) of concern would increase the rate of surgical resection in patients with borderline resectable PAC (BRPAC) and locally advanced PAC (LAPAC) treated with NACRT. METHODS AND MATERIALS: We retrospectively reviewed consecutive cases of BRPAC and LAPAC treated with NACRT from January 2006 to December 2013, with or without a vessel boost (VB), at a single institution. The primary endpoints were rate of R0/R1 potentially curative surgical resection and acute toxicity. Univariate analysis with the Fisher exact test was performed to evaluate the effect of each variable. Multiple logistic regression was used to adjust for the following covariates: year of diagnosis, age, sex, carbohydrate antigen 19-9 (CA19-9) level at diagnosis, and BRPAC or LAPAC. RESULTS: Of the 104 patients identified, 22% (n = 23) received a VB (median, 54 Gy; range, 54-64 Gy), and 78% (n = 81) received no boost (median, 50.4 Gy; range, 48.6-52.2 Gy). More patients in the VB group were treated from 2010 to 2013 (P < .001) and with intensity modulated radiation therapy (P = .002). Other baseline characteristics were balanced. After adjustment for covariates, there was a statistical trend toward increased surgical resection in patients who received a VB (odds ratio [OR], 2.77; 95% confidence interval [CI], 0.89-8.57; P = .077). Age (≥70 years; OR, 0.42; 95% CI, 0.16-1.05; P = .064) and LAPAC (OR, 0.32; 95% CI, 0.09-1.09; P = .068) also trended toward significance. CA19-9 ≥47.9 U/mL (OR, 0.24; 95% CI, 0.08-0.71; P = .010) was significant on multivariate analysis. There was no significant difference in acute or late toxicity between groups. CONCLUSIONS: In our retrospective series, dose escalation was associated with an improved surgical resection rate in BRPAC and LAPAC patients treated with NACRT, although this improvement was not statistically significant.

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

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

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

17 Article Neoadjuvant chemoradiation and duration of chemotherapy before surgical resection for pancreatic cancer: does time interval between radiotherapy and surgery matter? 2014

Chen, Kathryn T / Devarajan, Karthik / Milestone, Barton N / Cooper, Harry S / Denlinger, Crystal / Cohen, Steven J / Meyer, Joshua E / Hoffman, John P. ·Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA, kathryn.chen@gmail.com. ·Ann Surg Oncol · Pubmed #24276638.

ABSTRACT: BACKGROUND: Neoadjuvant chemoradiation and chemotherapy provided for borderline or locally advanced, potentially resectable pancreatic adenocarcinoma improves resectability rates. Response to therapy is also an important prognostic factor. There are no data in the literature regarding optimal time interval or duration of chemotherapy after chemoradiation before surgery, and pathologic response rates. Using our database, we evaluated these relationships and the effect on overall and progression-free survival. METHODS: We retrospectively analyzed the records of 83 patients who underwent neoadjuvant chemoradiation for locally advanced, potentially resectable, and borderline resectable pancreatic cancers before definitive resection. We divided patients into three groups according to time interval between completion of chemoradiation and resection: group A (0-10 weeks), group B (11-20 weeks), and group C (>20 weeks). After chemoradiation, patients underwent ongoing chemotherapy before resection. Pathologic response was defined as major (>95% fibrosis), partial (50-94% fibrosis), or minor (<50% fibrosis). RESULTS: There were 56 patients in group A, 17 patients in group B, and 10 patients in group C. Patients in groups B and C were significantly more likely to experience a major response than group A (p < 0.013). Patients in group C had significantly increased median progression-free and overall survival (p < 0.05). Multivariable classification and regression tree analysis demonstrated pathologic response to be the only significant factor in overall survival. CONCLUSIONS: Patients who underwent a prolonged time interval after neoadjuvant chemoradiation with ongoing chemotherapy were more likely to have an improved pathologic response at time of surgical resection, which was associated with improved median overall survival.

18 Article Impact of preoperative therapy on patterns of recurrence in pancreatic cancer. 2014

Papavasiliou, Pavlos / Hoffman, John P / Cohen, Steven J / Meyer, Joshua E / Watson, James C / Chun, Yun Shin. ·Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA. ·HPB (Oxford) · Pubmed #23458131.

ABSTRACT: BACKGROUND: A theoretical advantage of preoperative therapy in pancreatic adenocarcinoma is that it facilitates the early treatment of micrometastases and reduces postoperative systemic recurrence. METHODS: Medical records of 309 consecutive patients undergoing resection of adenocarcinoma in the head of the pancreas were reviewed. Survival was calculated using the Kaplan-Meier method. Associations between preoperative therapy and patterns of recurrence were determined using chi-squared analysis. RESULTS: Preoperative therapy was administered to 108 patients and upfront surgery was performed in 201 patients. Preoperative therapy was associated with a significantly longer median disease-free survival of 14 months compared with 12 months in patients submitted to upfront surgery (P = 0.035). The rate of local disease as a component of first site of recurrence was significantly lower with preoperative therapy (11.3%) than with upfront surgery (22.9%) (P = 0.016). Preoperative therapy was associated with a lower rate of hepatic metastasis (21.7%) than upfront surgery (34.3%) (P = 0.026). Preoperative therapy did not affect rates of peritoneal or pulmonary metastasis. CONCLUSIONS: Preoperative therapy for pancreatic cancer was associated with longer disease-free survival and lower rates of local and hepatic recurrences. These data support the use of preoperative therapy to reduce systemic and local failures after resection.

19 Article Locally advanced pancreatic cancer. 2012

Auriemma, William S / Berger, Adam C / Bar-Ad, Voichita / Boland, Patrick M / Cohen, Steve J / Roche-Lima, Caio Max S / Morris, Gloria J. ·Colorectal Cancer Specialists of NE PA, Scranton, PA, USA. ·Semin Oncol · Pubmed #22846869.

ABSTRACT: -- No abstract --

20 Article Significance of pathologic response to preoperative therapy in pancreatic cancer. 2011

Chun, Yun Shin / Cooper, Harry S / Cohen, Steven J / Konski, Andre / Burtness, Barbara / Denlinger, Crystal S / Astsaturov, Igor / Hall, Michael J / Hoffman, John P. ·Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA. yunshin.chun@fccc.edu ·Ann Surg Oncol · Pubmed #21947697.

ABSTRACT: BACKGROUND: Pathologic response to preoperative therapy is increasingly recognized as an important prognostic factor in solid tumors. The impact of pathologic response on survival in pancreatic adenocarcinoma is not well established. METHODS: Data on 135 consecutive patients treated with chemoradiation followed by pancreatectomy for adenocarcinoma of the pancreatic head and/or body between July 1987 and May 2009 were reviewed. Histopathologic examination was performed in 107 patients to determine pathologic response, defined as minor (<50% fibrosis relative to residual neoplastic cells), partial (50-94% fibrosis), or major (95-100% fibrosis). RESULTS: Minor, partial, and major pathologic response rates were 17% (n = 18), 64% (n = 68), and 19% (n = 21), including a 7% (n = 8) complete pathologic response rate. Pathologic response correlated with R0 resection (P = 0.019), negative lymph nodes (P = 0.006), and smaller tumor size (P = 0.001). Median survival rates by pathologic response were as follows: 17 months [95% confidence interval (CI), 0-36 months] for minor response, 20 months (95% CI, 17-23 months) for partial response, and 66 months (95% CI, 8-124 months) for major response (minor versus partial response, P = not significant; partial versus major response, P < 0.001). On multivariate analysis, major pathologic response was the only factor significantly associated with improved survival (P = 0.025; hazard ratio, 2.26). CONCLUSIONS: Major pathologic response to preoperative therapy occurs in a minority of patients with pancreatic adenocarcinoma and is independently associated with prolonged survival.

21 Article Defining venous involvement in borderline resectable pancreatic cancer. 2010

Chun, Yun Shin / Milestone, Barton N / Watson, James C / Cohen, Steven J / Burtness, Barbara / Engstrom, Paul F / Haluszka, Oleh / Tokar, Jeffrey L / Hall, Michael J / Denlinger, Crystal S / Astsaturov, Igor / Hoffman, John P. ·Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA. yunshin.chun@fccc.edu ·Ann Surg Oncol · Pubmed #20725860.

ABSTRACT: BACKGROUND: Pancreatic adenocarcinoma impinging the portal and/or superior mesenteric vein (PV-SMV) is classified as borderline resectable, and preoperative chemoradiation is recommended to increase the margin-negative resection rate. There is no consensus about what degree of venous impingement constitutes borderline resectability. METHODS: All patients undergoing potentially curative pancreatectomy for pancreatic adenocarcinoma were reviewed. Venous involvement was classified by preoperative computed tomography according to Ishikawa types: (I) normal, (II) smooth shift without narrowing, (III) unilateral narrowing, (IV) bilateral narrowing, (V) bilateral narrowing with collateral veins. RESULTS: From 1990-2009, 109 patients underwent resection of pancreatic adenocarcinoma involving the PV-SMV. Seventy-four patients received preoperative chemoradiation, whereas 35 did not. Patients who received preoperative therapy had a significantly longer median overall survival rate of 23 months compared with 15 months for patients without preoperative therapy (P = 0.001). Preoperative chemoradiation was associated with higher R0 resection rate and negative lymph nodes (both P < 0.0001) but did not affect the need for vein resection. When stratified by Ishikawa types, preoperative therapy was associated with improved overall survival among patients with types II and III but not types IV and V. Similarly, the correlation between preoperative therapy and R0 resection rate was observed only among patients with Ishikawa types II and III. CONCLUSIONS: Preoperative therapy for borderline resectable pancreatic adenocarcinoma is associated with higher margin-negative resection and survival rates in patients with Ishikawa type II and III tumors, defined as a smooth shift or unilateral narrowing of the PV-SMV. Patients with bilateral venous narrowing were less likely to benefit from preoperative treatment.