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Pancreatic Neoplasms: HELP
Articles by Michael J. Overman
Based on 17 articles published since 2010
(Why 17 articles?)
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Between 2010 and 2020, M. Overman wrote the following 17 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Clinical Trial Randomized, phase I/II study of gemcitabine plus IGF-1R antagonist (MK-0646) versus gemcitabine plus erlotinib with and without MK-0646 for advanced pancreatic adenocarcinoma. 2018

Abdel-Wahab, Reham / Varadhachary, Gauri R / Bhosale, Priya R / Wang, Xuemei / Fogelman, David R / Shroff, Rachna T / Overman, Michael J / Wolff, Robert A / Javle, Milind. ·Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 426, Houston, TX, 77030, USA. · Clinical Oncology Department, Assiut University Hospitals, Assiut, Egypt. · Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 426, Houston, TX, 77030, USA. mjavle@mdanderson.org. ·J Hematol Oncol · Pubmed #29843755.

ABSTRACT: BACKGROUND: Binding of insulin-like growth factor-I (IGF-1) to its receptor (IGF-1R) initiates downstream signals that activate PI3K/Akt/mTOR and MEK/Erk pathways, which stimulate cancer cell proliferation and induce drug resistance. Cross talk between IGF-1R and epidermal growth factor receptor (EGFR) mediates resistance to anti-EGFR agents. We studied safety, tolerability, and outcomes of MK-0646, IGF-1 monoclonal antibody, in combination with gemcitabine (G) ± erlotinib (E) in metastatic pancreatic cancer. METHODS: Our study included a phase I dose escalation and phase II randomization and expansion cohorts. A 3 + 3 dose escalation protocol was used to determine MK-0646 maximum tolerable dose (MTD) in combination with G ± E standard doses. For phase II, patients were randomized to arm A (G + MK), arm B (G + MK + E), or arm C (G + E). Primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS), disease control rate, toxicity, and correlation between OS and IGF-1 in patients treated with MK-0646. RESULTS: MK-0646 MTD was 10 mg/kg in combination with G and 5 mg/kg in combination with G + E. In randomization cohort, 15 patients were treated in each arm. Disease control rates were 50, 60, and 40% respectively. PFS was not different between the three arms. OS was significantly different between arm A (10.4 months) and C (5.7 months) (P = 0.02). However, addition of erlotinib in arm B yielded no OS benefit compared to arm A (P = 0.6). Plasma and tissue IGF-1 levels did not correlate with OS (P = 0.64, 0.87). Grade 3-4 toxicity during phase II cohorts were neutropenia (10/arm A, 14/arm B, 5/arm C), leukopenia (5/A, 5/B, 7/C), thrombocytopenia (8/A, 9/B, 2/C), hyponatremia (1/A, 3/B), and hyperglycemia (8/A, 1/B). CONCLUSIONS: MK-0646 was tolerable in combination with G and associated with improvement in OS but not PFS as compared with G + E. Tissue and serum IGF-1 did not correlate with clinical outcome. TRIAL REGISTRATION: This trial is registered in ClinicalTrial.gov under the Identifier NCT00769483 and registration date was October 9, 2008.

2 Article Comparison of immune infiltrates in melanoma and pancreatic cancer highlights VISTA as a potential target in pancreatic cancer. 2019

Blando, Jorge / Sharma, Anu / Higa, Maria Gisela / Zhao, Hao / Vence, Luis / Yadav, Shalini S / Kim, Jiseong / Sepulveda, Alejandro M / Sharp, Michael / Maitra, Anirban / Wargo, Jennifer / Tetzlaff, Michael / Broaddus, Russell / Katz, Matthew H G / Varadhachary, Gauri R / Overman, Michael / Wang, Huamin / Yee, Cassian / Bernatchez, Chantale / Iacobuzio-Donahue, Christine / Basu, Sreyashi / Allison, James P / Sharma, Padmanee. ·The Immunotherapy Platform, The University of Texas MD Anderson Cancer Center, Houston, TX 77054. · Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030. · Janssen Oncology Therapeutic Area, Janssen Research and Development, LLC, Pharmaceutical Companies of Johnson & Johnson, Spring House, PA 19477. · Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030. · Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030. · Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030. · Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030. · Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030. · David Rubenstein Pancreatic Cancer Research Center, Memorial Sloan Kettering Cancer Center, New York, NY 10065. · The Immunotherapy Platform, The University of Texas MD Anderson Cancer Center, Houston, TX 77054; jallison@mdanderson.org padsharma@mdanderson.org. · Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030. ·Proc Natl Acad Sci U S A · Pubmed #30635425.

ABSTRACT: Immune checkpoint therapy (ICT) has transformed cancer treatment in recent years; however, treatment response is not uniform across tumor types. The tumor immune microenvironment plays a critical role in determining response to ICT; therefore, understanding the differential immune infiltration between ICT-sensitive and ICT-resistant tumor types will help to develop effective treatment strategies. We performed a comprehensive analysis of the immune tumor microenvironment of an ICT-sensitive tumor (melanoma,

3 Article Evaluating for Pseudoprogression in Colorectal and Pancreatic Tumors Treated With Immunotherapy. 2018

Parseghian, Christine M / Patnana, Madhavi / Bhosale, Priya / Hess, Kenneth R / Shih, Ya-Chen Tina / Kim, Bumyang / Kopetz, Scott / Overman, Michael J / Varadhachary, Gauri R / Javle, Milind / Naing, Aung / Piha-Paul, Sarina / Hong, David / Le, Hung / Subbiah, Vivek / Pant, Shubham. ·Departments of Cancer Medicine. · Radiology. · Biostatistics, The University of Texas M.D. Anderson Cancer Center, Houston, TX. · Health Services Research, Section of Cancer Economics and Policy. · Gastrointestinal Medical Oncology, Division of Cancer Medicine. · Investigational Cancer Therapeutics. ·J Immunother · Pubmed #29668571.

ABSTRACT: Pseudoprogression has been observed in patients with various tumor types treated with immunotherapy. However, the frequency of pseudoprogression is unknown in gastrointestinal malignancies. Metastatic colorectal cancer (mCRC) and advanced pancreatic ductal adenocarcinoma (PDAC) patients who progressed on treatment with immunotherapy beyond RECIST version 1.1 criteria were analyzed. Degree of progression, tumor markers, time to progression, overall survival, Eastern Cooperative Oncology Group Performance Status (ECOG PS), and costs were analyzed for patients treated beyond progression (TBP) and not treated beyond progression. Fifty-nine of 159 (37%) patients with mCRC or PDAC were TBP (31 mCRC, 28 PDAC). Fifty-four of 59 (92%) patients were microsatellite stable. Zero of these 59 patients with initial treatment beyond progression demonstrated subsequent radiographic tumor shrinkage at a median 42 days from first scan documenting progression. A pseudoprogression rate of >6% could be excluded with 95% confidence. Compared with baseline, median growth on the first and second scan that showed progression was 29.8% and 43%, respectively. In those not treated beyond progression, median growth at first restaging was 31.2%. The trend in change in tumor size positively correlated with the trend in tumor markers in all patients TBP. Fifteen patients (25%) experienced grade 3/4 adverse events by continuing treatment beyond progression, whereas 19 (32%) experienced deterioration in ECOG PS. Pseudoprogression was not seen in microsatellite stable patients with mCRC or PDAC treated with immunotherapy. Changes in tumor markers correlated with changes in tumor volume. This data may help inform future treatment decisions and/or trial design in patients with mCRC or advanced PDAC treated with immunotherapy.

4 Article Imaging-based biomarkers: Changes in the tumor interface of pancreatic ductal adenocarcinoma on computed tomography scans indicate response to cytotoxic therapy. 2018

Amer, Ahmed M / Zaid, Mohamed / Chaudhury, Baishali / Elganainy, Dalia / Lee, Yeonju / Wilke, Christopher T / Cloyd, Jordan / Wang, Huamin / Maitra, Anirban / Wolff, Robert A / Varadhachary, Gauri / Overman, Michael J / Lee, Jeffery E / Fleming, Jason B / Tzeng, Ching Wei / Katz, Matthew H / Holliday, Emma B / Krishnan, Sunil / Minsky, Bruce D / Herman, Joseph M / Taniguchi, Cullen M / Das, Prajnan / Crane, Christopher H / Le, Ott / Bhosale, Priya / Tamm, Eric P / Koay, Eugene J. ·Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. · Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas. · Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. · Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. · Department of Gastrointestinal Oncology, Moffitt Cancer Center, Tampa Bay, Florida. · Department of Radiation Oncology, Memorial Sloan Cancer Center, New York, New York. · Department of Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston, Texas. ·Cancer · Pubmed #29370450.

ABSTRACT: BACKGROUND: The assessment of pancreatic ductal adenocarcinoma (PDAC) response to therapy remains challenging. The objective of this study was to investigate whether changes in the tumor/parenchyma interface are associated with response. METHODS: Computed tomography (CT) scans before and after therapy were reviewed in 4 cohorts: cohort 1 (99 patients with stage I/II PDAC who received neoadjuvant chemoradiation and surgery); cohort 2 (86 patients with stage IV PDAC who received chemotherapy), cohort 3 (94 patients with stage I/II PDAC who received protocol-based neoadjuvant gemcitabine chemoradiation), and cohort 4 (47 patients with stage I/II PDAC who received neoadjuvant chemoradiation and were prospectively followed in a registry). The tumor/parenchyma interface was visually classified as either a type I response (the interface remained or became well defined) or a type II response (the interface became poorly defined) after therapy. Consensus (cohorts 1-3) and individual (cohort 4) visual scoring was performed. Changes in enhancement at the interface were quantified using a proprietary platform. RESULTS: In cohort 1, type I responders had a greater probability of achieving a complete or near-complete pathologic response (21% vs 0%; P = .01). For cohorts 1, 2, and 3, type I responders had significantly longer disease-free and overall survival, independent of traditional covariates of outcomes and of baseline and normalized cancer antigen 19-9 levels. In cohort 4, 2 senior radiologists achieved a κ value of 0.8, and the interface score was associated with overall survival. The quantitative method revealed high specificity and sensitivity in classifying patients as type I or type II responders (with an area under the receiver operating curve of 0.92 in cohort 1, 0.96 in cohort 2, and 0.89 in cohort 3). CONCLUSIONS: Changes at the PDAC/parenchyma interface may serve as an early predictor of response to therapy. Cancer 2018;124:1701-9. © 2018 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

5 Article 4-1BB Agonist Focuses CD8 2017

Sakellariou-Thompson, Donastas / Forget, Marie-Andrée / Creasy, Caitlin / Bernard, Vincent / Zhao, Li / Kim, Young Uk / Hurd, Mark W / Uraoka, Naohiro / Parra, Edwin Roger / Kang, Ya'an / Bristow, Christopher A / Rodriguez-Canales, Jaime / Fleming, Jason B / Varadhachary, Gauri / Javle, Milind / Overman, Michael J / Alvarez, Hector A / Heffernan, Timothy P / Zhang, Jianhua / Hwu, Patrick / Maitra, Anirban / Haymaker, Cara / Bernatchez, Chantale. ·Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. · Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas. · Sheikh Ahmed Center for Pancreatic Cancer Research, The University of Texas MD Anderson Cancer Center, Houston, Texas. · Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas. · Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas. · Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. · Institute for Applied Cancer Science, The University of Texas MD Anderson Cancer Center, Houston, Texas. · Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. · Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. cbernatchez@mdanderson.org chaymaker@mdanderson.org. ·Clin Cancer Res · Pubmed #28947567.

ABSTRACT:

6 Article Association of Clinical Factors With a Major Pathologic Response Following Preoperative Therapy for Pancreatic Ductal Adenocarcinoma. 2017

Cloyd, Jordan M / Wang, Huamin / Egger, Michael E / Tzeng, Ching-Wei D / Prakash, Laura R / Maitra, Anirban / Varadhachary, Gauri R / Shroff, Rachna / Javle, Milind / Fogelman, David / Wolff, Robert A / Overman, Michael J / Koay, Eugene J / Das, Prajnan / Herman, Joseph M / Kim, Michael P / Vauthey, Jean-Nicolas / Aloia, Thomas A / Fleming, Jason B / Lee, Jeffrey E / Katz, Matthew H G. ·Department of Surgical Oncology; University of Texas MD Anderson Cancer Center, Houston. · Department of Pathology; University of Texas MD Anderson Cancer Center, Houston. · Department of Gastrointestinal Medical Oncology; University of Texas MD Anderson Cancer Center, Houston. · Department of Radiation Oncology; University of Texas MD Anderson Cancer Center, Houston. ·JAMA Surg · Pubmed #28700784.

ABSTRACT: Importance: We previously demonstrated that a major pathologic response to preoperative therapy, defined histopathologically by the presence of less than 5% viable cancer cells in the surgical specimen, is an important prognostic factor for patients with pancreatic ductal adenocarcinoma. However, to our knowledge, the patients most likely to experience a significant response to therapy are undefined. Objective: To identify clinical factors associated with major pathologic response in a large cohort of patients who underwent preoperative therapy and pancreatectomy for pancreatic ductal adenocarcinoma. Design, Setting, and Participants: Retrospective review of a prospectively maintained database at University of Texas MD Anderson Cancer Center. The study included 583 patients with histopathologically confirmed pancreatic ductal adenocarcinoma who received preoperative therapy prior to pancreatectomy between 1990 and 2015. Exposures: Preoperative therapy consisted of systemic chemotherapy alone (n = 38; 6.5%), chemoradiation alone (n = 261; 44.8%), or both (n = 284; 48.7%) prior to pancreatoduodenectomy (n = 514; 88.2%), distal pancreatectomy (n = 62; 10.6%), or total pancreatectomy (n = 7; 1.2%). Main Outcomes and Measures: Clinical variables associated with a major pathologic response (pathologic complete response or <5% residual cancer cells) were evaluated using logistic regression. Results: Among all patients, the mean (SD) age was 63.7 (9.2) years, and 53.0% were men. A major pathologic response was seen in 77 patients (13.2%) including 23 (3.9%) who had a complete pathologic response. The median overall survival duration was significantly longer for patients who had a major response than for those who did not (73.4 months vs 32.2 months, P < .001). On multivariate logistic regression, only age younger than 50 years, baseline serum cancer antigen 19-9 level less than 200 U/mL, and gemcitabine as a radiosensitizer were associated with a major response. The number of these positive factors was associated with the likelihood of a major response in a stepwise fashion (0, 7.5%; 1, 12.7%; 2, 16.9%; 3, 35.7%; P = .009). Conclusions and Relevance: Although a major pathologic response occurs infrequently following preoperative therapy for pancreatic ductal adenocarcinoma, it is associated with a significantly improved prognosis. Of the patient- and treatment-related factors we analyzed, only young age, low baseline cancer antigen 19-9, and gemcitabine as a radiosensitizer were associated with a major pathologic response. Given its association with long-term survival, better predictors of response and more effective preoperative regimens should be aggressively sought.

7 Article A predictive model of inflammatory markers and patient-reported symptoms for cachexia in newly diagnosed pancreatic cancer patients. 2017

Fogelman, David R / Morris, J / Xiao, L / Hassan, M / Vadhan, S / Overman, M / Javle, S / Shroff, R / Varadhachary, G / Wolff, R / Vence, L / Maitra, A / Cleeland, C / Wang, X S. ·Department of Gastrointestinal Medical Oncology, M.D. Anderson Cancer Center, 1515 Holcombe Blvd Unit 426, Houston, TX, 77030, USA. dfogelman@mdanderson.org. · Department of Biostatistics, M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA. · Department of Gastrointestinal Medical Oncology, M.D. Anderson Cancer Center, 1515 Holcombe Blvd Unit 426, Houston, TX, 77030, USA. · Department of Sarcoma Research, M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA. · Department of Immunology, M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA. · Department of Pathology, M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA. · Department of Symptom Research, M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA. ·Support Care Cancer · Pubmed #28111717.

ABSTRACT: BACKGROUND: Cachexia is a frequent manifestation of pancreatic cancer, can limit a patient's ability to take chemotherapy, and is associated with shortened survival. We developed a model to predict the early onset of cachexia in advanced pancreatic cancer patients. METHODS: Patients with newly diagnosed, untreated metastatic or locally advanced pancreatic cancer were included. Serum cytokines were drawn prior to therapy. Patient symptoms were recorded using the M.D. Anderson Symptom Inventory (MDASI). Our primary endpoint was either 10% weight loss or death within 60 days of the start of therapy. RESULTS: Twenty-seven of 89 patients met the primary endpoint (either having lost 10% of body weight or having died within 60 days of the start of treatment). In a univariate analysis, smoking, history symptoms of pain and difficulty swallowing, high levels of MK, CXCL-16, IL-6, TNF-a, and low IL-1b all correlated with this endpoint. We used recursive partition to fit a regression tree model, selecting four of 26 variables (CXCL-16, IL-1b, pain, swallowing difficulty) as important in predicting cachexia. From these, a model of two cytokines (CXCL-16 > 5.135 ng/ml and IL-1b < 0.08 ng/ml) demonstrated a better sensitivity and specificity for this outcome (0.70 and 0.86, respectively) than any individual cytokine or tumor marker. CONCLUSIONS: Cachexia is frequent in pancreatic cancer; one in three patients met our endpoint of 10% weight loss or death within 60 days. Inflammatory cytokines are better than conventional tumor markers at predicting this outcome. Recursive partitioning analysis suggests that a model of CXCL-16 and IL-1B may offer a better ability than individual cytokines to predict this outcome.

8 Article High prevalence of mutant KRAS in circulating exosome-derived DNA from early-stage pancreatic cancer patients. 2017

Allenson, K / Castillo, J / San Lucas, F A / Scelo, G / Kim, D U / Bernard, V / Davis, G / Kumar, T / Katz, M / Overman, M J / Foretova, L / Fabianova, E / Holcatova, I / Janout, V / Meric-Bernstam, F / Gascoyne, P / Wistuba, I / Varadhachary, G / Brennan, P / Hanash, S / Li, D / Maitra, A / Alvarez, H. ·Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA. · Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, USA. · Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, USA. · Sheikh Ahmed Pancreatic Cancer Research Center, The University of Texas MD Anderson Cancer Center, Houston, USA. · Genetic Epidemiology Group International Agency for Research on Cancer, Lyon, France. · Department of GI Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA. · Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Brno, Czech Republic. · Regional Authority of Public Health in Banska Bystrica, Banska Bystrica, Slovakia. · Institute of Public Health and Preventive Medicine, 2nd Faculty of Medicine, Charles University, Prague, Czech Republic. · Department of Preventive Medicine, Palacky University of Medicine, Olomouc, Czech Republic. · Department of Epidemiology and Public Health, Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic. · Department of Investigational Cancer Therapeutics and the Institute for Personalized Cancer Therapy, Houston, USA. · Section of Experimental Pathology, University of Texas M.D. Anderson Cancer Center, Houston, USA · Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, USA. ·Ann Oncol · Pubmed #28104621.

ABSTRACT: Background: Exosomes arise from viable cancer cells and may reflect a different biology than circulating cell-free DNA (cfDNA) shed from dying tissues. We compare exosome-derived DNA (exoDNA) to cfDNA in liquid biopsies of patients with pancreatic ductal adenocarcinoma (PDAC). Patients and methods: Patient samples were obtained between 2003 and 2010, with clinically annotated follow up to 2015. Droplet digital PCR was performed on exoDNA and cfDNA for sensitive detection of KRAS mutants at codons 12/13. A cumulative series of 263 individuals were studied, including a discovery cohort of 142 individuals: 68 PDAC patients of all stages; 20 PDAC patients initially staged with localized disease, with blood drawn after resection for curative intent; and 54 age-matched healthy controls. A validation cohort of 121 individuals (39 cancer patients and 82 healthy controls) was studied to validate KRAS detection rates in early-stage PDAC patients. Primary outcome was circulating KRAS status as detected by droplet digital PCR. Secondary outcomes were disease-free and overall survival. Results: KRAS mutations in exoDNA, were identified in 7.4%, 66.7%, 80%, and 85% of age-matched controls, localized, locally advanced, and metastatic PDAC patients, respectively. Comparatively, mutant KRAS cfDNA was detected in 14.8%, 45.5%, 30.8%, and 57.9% of these individuals. Higher exoKRAS MAFs were associated with decreased disease-free survival in patients with localized disease. In the validation cohort, mutant KRAS exoDNA was detected in 43.6% of early-stage PDAC patients and 20% of healthy controls. Conclusions: Exosomes are a distinct source of tumor DNA that may be complementary to other liquid biopsy DNA sources. A higher percentage of patients with localized PDAC exhibited detectable KRAS mutations in exoDNA than previously reported for cfDNA. A substantial minority of healthy samples demonstrated mutant KRAS in circulation, dictating careful consideration and application of liquid biopsy findings, which may limit its utility as a broad cancer-screening method.

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

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

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

10 Article Preoperative Chemoradiation for Pancreatic Adenocarcinoma Does Not Increase 90-Day Postoperative Morbidity or Mortality. 2016

Denbo, Jason W / Bruno, Morgan L / Cloyd, Jordan M / Prakash, Laura / Lee, Jeffrey E / Kim, Michael / Crane, Christopher H / Koay, Eugene J / Krishnan, Sunil / Das, Prajnan / Minsky, Bruce D / Varadhachary, Gauri / Shroff, Rachna / Wolff, Robert / Javle, Milind / Overman, Michael J / Fogelman, David / Aloia, Thomas A / Vauthey, Jean-Nicolas / Fleming, Jason B / Katz, Matthew H G. ·Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1484, Houston, TX, 77030, USA. · Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1484, Houston, TX, 77030, USA. mhgkatz@mdanderson.org. ·J Gastrointest Surg · Pubmed #27730398.

ABSTRACT: BACKGROUND: The impact of preoperative chemoradiation on postoperative morbidity and mortality of patients with pancreatic adenocarcinoma remains controversial. METHODS: Consecutive pancreatectomies for adenocarcinoma performed between 2011 and 2015 were prospectively monitored for 90 days by using a previously reported surveillance system to determine the association between preoperative chemoradiation and adverse events, pancreatic fistulae, readmissions, and mortality. RESULTS: Among 209 consecutive patients who underwent pancreatectomy, 159 (76 %) experienced at least one adverse event within 90 postoperative days. Patients who received preoperative chemoradiation (n = 137, 66 %) were more likely to have borderline resectable/locally advanced tumors, to have received induction chemotherapy, and to require vascular resection at pancreatectomy than those who did not receive chemoradiation (all P < 0.05). Nonetheless, there were no significant differences in the rates of severe complications, readmission, or mortality between these groups (all P > 0.05). Among patients who underwent pancreatoduodenectomy, the rate of pancreatic fistula was similar between those who received chemoradiation and those who did not (P = 0.96). In contrast, those who received chemoradiation prior to distal pancreatectomy had a lower rate of pancreatic fistula (P < 0.01). CONCLUSION: Preoperative chemoradiation is not associated with an increase in 90-day morbidity or mortality, and it may reduce the rate of pancreatic fistula following distal pancreatectomy.

11 Article Impact of hypofractionated and standard fractionated chemoradiation before pancreatoduodenectomy for pancreatic ductal adenocarcinoma. 2016

Cloyd, Jordan M / Crane, Christopher H / Koay, Eugene J / Das, Prajnan / Krishnan, Sunil / Prakash, Laura / Snyder, Rebecca A / Varadhachary, Gauri R / Wolff, Robert A / Javle, Milind / Shroff, Rachna T / Fogelman, David / Overman, Michael / Wang, Huamin / Maitra, Anirban / Lee, Jeffrey E / Fleming, Jason B / Katz, Matthew H G. ·Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. · Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. · Department of Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. · Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas. ·Cancer · Pubmed #27243381.

ABSTRACT: BACKGROUND: Previous studies have suggested that preoperative chemoradiation (CRT) is associated with an improved margin-negative resection rate among patients who undergo pancreatoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC). However, the optimal preoperative regimen has not been established. METHODS: All patients with PDAC who received chemotherapy and/or CRT followed by PD between 1999 and 2014 were retrospectively reviewed. The effects of 2 external-beam radiation regimens-a standard course of 50.4 Gy in 28 fractions and a hypofractionated course of 30 Gy in 10 fractions-were compared. Differences in clinicopathologic characteristics, locoregional recurrence (LR), and overall survival (OS) were assessed. RESULTS: Among 472 patients who received preoperative therapy, 224 (47.5%) received 30 Gy, 221 (46.8%) received 50.4 Gy, and 27 (5.7%) received chemotherapy alone. Patients who received 50.4 Gy were more likely to have advanced-stage disease and to have received induction and postoperative chemotherapy, but there was no difference in the R1 margin status, treatment effect, LR, or OS between the 2 radiation groups (all P values > .05). Patients who received preoperative CRT had a lower rate of LR than patients who received preoperative chemotherapy alone (P < .01). In a multivariate Cox proportional hazards analysis, 50.4 Gy was associated with OS and LR similar to those associated with 30 Gy, whereas the absence of preoperative radiation was associated with a higher rate of LR (odds ratio, 2.21; 95% confidence interval, 1.04-4.70) and similar OS. CONCLUSIONS: Preoperative hypofractionated CRT was associated with similar local control and OS in comparison with standard CRT in patients undergoing PD for PDAC. The use of chemotherapy alone without CRT was associated with poorer local control but similar survival. Cancer 2016. © 2016 American Cancer Society. Cancer 2016;122:2671-2679. © 2016 American Cancer Society.

12 Article Ampullary Cancers Harbor ELF3 Tumor Suppressor Gene Mutations and Exhibit Frequent WNT Dysregulation. 2016

Gingras, Marie-Claude / Covington, Kyle R / Chang, David K / Donehower, Lawrence A / Gill, Anthony J / Ittmann, Michael M / Creighton, Chad J / Johns, Amber L / Shinbrot, Eve / Dewal, Ninad / Fisher, William E / Anonymous400856 / Pilarsky, Christian / Grützmann, Robert / Overman, Michael J / Jamieson, Nigel B / Van Buren, George / Drummond, Jennifer / Walker, Kimberly / Hampton, Oliver A / Xi, Liu / Muzny, Donna M / Doddapaneni, Harsha / Lee, Sandra L / Bellair, Michelle / Hu, Jianhong / Han, Yi / Dinh, Huyen H / Dahdouli, Mike / Samra, Jaswinder S / Bailey, Peter / Waddell, Nicola / Pearson, John V / Harliwong, Ivon / Wang, Huamin / Aust, Daniela / Oien, Karin A / Hruban, Ralph H / Hodges, Sally E / McElhany, Amy / Saengboonmee, Charupong / Duthie, Fraser R / Grimmond, Sean M / Biankin, Andrew V / Wheeler, David A / Gibbs, Richard A. ·Department of Molecular and Human Genetics, Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA; Michael DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address: mgingras@bcm.edu. · Department of Molecular and Human Genetics, Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA. · Wolfson Wohl Cancer Research Centre, Institute for Cancer Sciences, University of Glasgow, Garscube Estate, Bearsden, Glasgow G61 1BD, UK; West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow G31 2ER, UK; The Kinghorn Cancer Centre and the Cancer Research Program Garvan Institute of Medical Research, Darlinghurst, Sydney, NSW 2010, Australia; South Western Sydney Clinical School, Faculty of Medicine, University of New South Wales, Liverpool, NSW 2170, Australia. · Department of Molecular and Human Genetics, Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA. · The Kinghorn Cancer Centre and the Cancer Research Program Garvan Institute of Medical Research, Darlinghurst, Sydney, NSW 2010, Australia; Department of Anatomical Pathology, Royal North Shore Hospital, St Leonards, Sydney, NSW 2065, Australia; Sydney Medical School, University of Sydney, Sydney, NSW 2006, Australia. · Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030, USA; Michael E. DeBakey Department of Veterans Affairs Medical Center, Houston, TX 77030, USA. · Department of Molecular and Human Genetics, Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA. · The Kinghorn Cancer Centre and the Cancer Research Program Garvan Institute of Medical Research, Darlinghurst, Sydney, NSW 2010, Australia. · Michael DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA; The Elkins Pancreas Center at Baylor College of Medicine, Houston, TX 77030, USA. · Department of Surgery, TU Dresden, 01307 Dresden, Germany. · Department of Surgery, Universitätsklinikum Erlangen, 91054 Erlangen, Germany. · Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. · Wolfson Wohl Cancer Research Centre, Institute for Cancer Sciences, University of Glasgow, Garscube Estate, Bearsden, Glasgow G61 1BD, UK; West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow G31 2ER, UK; Academic Unit of Surgery, Institute of Cancer Sciences, Glasgow Royal Infirmary, Level 2, New Lister Building, University of Glasgow, Glasgow G31 2ER, UK. · Sydney Medical School, University of Sydney, Sydney, NSW 2006, Australia; Department of Surgery, Royal North Shore Hospital, St Leonards, Sydney, NSW 2065, Australia. · Wolfson Wohl Cancer Research Centre, Institute for Cancer Sciences, University of Glasgow, Garscube Estate, Bearsden, Glasgow G61 1BD, UK. · Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, QLD 4072, Australia; QIMR Berghofer Medical Research Institute, Herston, Brisbane, QLD 4006, Australia. · Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, QLD 4072, Australia. · Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. · Department of Pathology, TU Dresden, 01307 Dresden, Germany. · Wolfson Wohl Cancer Research Centre, Institute for Cancer Sciences, University of Glasgow, Garscube Estate, Bearsden, Glasgow G61 1BD, UK; Department of Pathology, Southern General Hospital, Greater Glasgow and Clyde NHS, Glasgow G51 4TF, UK. · Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, the Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA. · Michael DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA; The Elkins Pancreas Center at Baylor College of Medicine, Houston, TX 77030, USA. · Department of Molecular and Human Genetics, Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Biochemistry and Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand. · Wolfson Wohl Cancer Research Centre, Institute for Cancer Sciences, University of Glasgow, Garscube Estate, Bearsden, Glasgow G61 1BD, UK; Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, QLD 4072, Australia. · Department of Molecular and Human Genetics, Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address: wheeler@bcm.edu. ·Cell Rep · Pubmed #26804919.

ABSTRACT: The ampulla of Vater is a complex cellular environment from which adenocarcinomas arise to form a group of histopathologically heterogenous tumors. To evaluate the molecular features of these tumors, 98 ampullary adenocarcinomas were evaluated and compared to 44 distal bile duct and 18 duodenal adenocarcinomas. Genomic analyses revealed mutations in the WNT signaling pathway among half of the patients and in all three adenocarcinomas irrespective of their origin and histological morphology. These tumors were characterized by a high frequency of inactivating mutations of ELF3, a high rate of microsatellite instability, and common focal deletions and amplifications, suggesting common attributes in the molecular pathogenesis are at play in these tumors. The high frequency of WNT pathway activating mutation, coupled with small-molecule inhibitors of β-catenin in clinical trials, suggests future treatment decisions for these patients may be guided by genomic analysis.

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

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

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

14 Article Clinicopathologic features and prognosis of duodenal adenocarcinoma and comparison with ampullary and pancreatic ductal adenocarcinoma. 2013

Zenali, Maryam / Overman, Michael J / Rashid, Asif / Broaddus, Russell B / Wang, Hua / Katz, Matthew H / Fleming, Jason B / Abbruzzese, James L / Wang, Huamin. ·Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030. ·Hum Pathol · Pubmed #24139211.

ABSTRACT: Because of the rarity of duodenal adenocarcinoma (DAC), the clinicopathologic features and prognostication data for DAC are limited. There are no published studies directly comparing the prognosis of DAC to that of ampullary adenocarcinoma (AA) and of pancreatic ductal adenocarcinoma (PDA) after resection. In this study, we examined the clinicopathologic features of 68 patients with DAC, 92 patients with AA, and 126 patients with PDA who underwent resection. Patient clinicopathologic and survival information were extracted from medical records. Statistical analysis was performed using Statistical Package for the Social Sciences with 2-sided significance level of .05. Patients with DAC had higher American Joint Committee on Cancer (AJCC) stage than AA patients (P = .001). Lymph node metastasis (P = .013) and AJCC stage (P = .02) correlated with overall survival in DAC patients. Patients with DAC or AA had lower frequencies of lymph node metastasis and positive margin and better survival than those with PDA (P < .05). However, no differences in nodal metastasis, margin status, or survival were observed between DAC patients and those with AA. Our study showed that lymph node metastasis and AJCC stage are important prognostic factors for overall survival in DAC patients. Patients with DAC had less frequent nodal metastasis and better prognosis than those with PDA. There was no significant difference in prognosis between DAC and AA.

15 Article Gene expression profiling of ampullary carcinomas classifies ampullary carcinomas into biliary-like and intestinal-like subtypes that are prognostic of outcome. 2013

Overman, Michael J / Zhang, Jiexin / Kopetz, Scott / Davies, Michael / Jiang, Zhi-Qin / Stemke-Hale, Katherine / Rümmele, Petra / Pilarsky, Christian / Grützmann, Robert / Hamilton, Stanley / Hwang, Rosa / Abbruzzese, James L / Varadhachary, Gauri / Broom, Bradley / Wang, Huamin. ·Department of Gastrointestinal Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, United States of America. moverman@mdanderson.org ·PLoS One · Pubmed #23776447.

ABSTRACT: BACKGROUND: Adenocarcinomas of the ampulla of Vater are classified as biliary cancers, though the exact epithelium of origin for these cancers is not known. We sought to molecularly classify ampullary adenocarcinomas in comparison to known adenocarcinomas of the pancreas, bile duct, and duodenum by gene expression analysis. METHODS: We analyzed 32 fresh-frozen resected, untreated periampullary adenocarcinomas (8 pancreatic, 2 extrahepatic biliary, 8 duodenal, and 14 ampullary) using the Affymetrix U133 Plus 2.0 genome array. Unsupervised and supervised hierarchical clustering identified two subtypes of ampullary carcinomas that were molecularly and histologically characterized. RESULTS: Hierarchical clustering of periampullary carcinomas segregated ampullary carcinomas into two subgroups, which were distinctly different from pancreatic carcinomas. Non-pancreatic periampullary adenocarcinomas were segregated into two subgroups with differing prognoses: 5 year RFS (77% vs. 0%, p = 0.007) and 5 year OS (100% vs. 35%, p = 0.005). Unsupervised clustering analysis of the 14 ampullary samples also identified two subgroups: a good prognosis intestinal-like subgroup and a poor prognosis biliary-like subgroup with 5 year OS of 70% vs. 28%, P = 0.09. Expression of CK7+/CK20- but not CDX-2 correlated with these two subgroups. Activation of the AKT and MAPK pathways were both increased in the poor prognostic biliary-like subgroup. In an independent 80 patient ampullary validation dataset only histological subtype (intestinal vs. pancreaticobiliary) was significantly associated with OS in both univariate (p = 0.006) and multivariate analysis (P = 0.04). CONCLUSIONS: Gene expression analysis discriminated pancreatic adenocarcinomas from other periampullary carcinomas and identified two prognostically relevant subgroups of ampullary adenocarcinomas. Histological subtype was an independent prognostic factor in ampullary adenocarcinomas.

16 Article A retrospective study of ampullary adenocarcinomas: overall survival and responsiveness to fluoropyrimidine-based chemotherapy. 2013

Jiang, Z-Q / Varadhachary, G / Wang, X / Kopetz, S / Lee, J E / Wang, H / Shroff, R / Katz, M / Wolff, R A / Fleming, J / Overman, M J. ·Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515Holcombe Blvd. Houston, TX 77030, USA. ·Ann Oncol · Pubmed #23704197.

ABSTRACT: BACKGROUND: Whether carcinomas of the ampulla of Vater should be classified with biliary tract tumors and treated in a similar manner remains unknown. We sought to compare the outcomes of similarly staged periampullary adenocarcinomas (AAs) and analyze the chemotherapy responsiveness of AAs. PATIENTS AND METHODS: A total of 905 patients with resected periampullary adenocarcinomas were identified from a prospective surgical registry from 1988 to 2010. A second cohort of 64 metastatic AA patients from 1992 to 2009 who received either front-line fluoropyrimidine-based or gemcitabine-based chemotherapy was also identified. RESULTS: Overall survival (OS) for AAs was similar to survival with duodenal adenocarcinomas, but was significantly different from both extrahepatic biliary and pancreatic adenocarcinomas (P < 0.001 for each comparison). In multivariate analysis, AAs had a significantly improved OS in comparison with extrahepatic biliary adenocarcinomas (HR = 1.97, P = 0.006). Fluoropyrimidine-based as opposed to gemcitabine-based chemotherapy for metastatic AAs resulted in a significant improvement in time to progression (P = 0.001) but only a trend toward benefit for OS (P = 0.07) in multivariate analysis. CONCLUSIONS: Differences in the natural history of ampullary and extrahepatic biliary adenocarcinomas exist. Analyses of metastatic ampullary adenocarcinomas suggest that fluoropyrimidine-based chemotherapy may represent a more appropriate front-line chemotherapy approach.

17 Article The addition of erlotinib to gemcitabine and cisplatin does not appear to improve median survival in metastatic pancreatic cancer. 2013

Khalil, Mohamed A / Qiao, Wei / Carlson, Peter / George, Binsah / Javle, Milind / Overman, Michael / Varadhachary, Gauri / Wolff, Robert A / Abbruzzese, James L / Fogelman, David R. ·M.D. Anderson Cancer Center, 1515 Holcombe Blvd Unit 426, Houston, TX, 77030, USA, MAKhalil1@mdanderson.org. ·Invest New Drugs · Pubmed #23645398.

ABSTRACT: Metastatic pancreatic cancer carries a poor prognosis, with median survival on the order of several months. There is evidence that combining gemcitabine with either erlotinib or cisplatin may be superior to single agent gemcitabine in patients with good performance (PS 0-1). We retrospectively compared outcomes of patients treated with either the three drug regimen of gemcitabine, cisplatin, and erlotinib (GCE) or the doublet of gemcitabine and cisplatin (GC) in order to assess the potential benefit of erlotinib. We also evaluated the role of erlotinib among smokers and non-smokers. We retrospectively analyzed 145 patients who presented between 2006 and 2009 with previously untreated metastatic pancreatic cancer initially treated at the M.D. Anderson cancer center with either GC or GCE. Information on tumor characteristics and overall survival time (OS) was collected by medical record review. Kaplan-Meier curves were used to estimate OS. Log rank tests were used to compare OS between groups. The Cox proportional hazards regression model was used to evaluate the ability of patient prognostic variables or treatment group to predict OS. A total of 71 patients were treated with GC, while 74 were treated with GCE. Cox analyses found no significant difference in overall survival (median 5.5 vs. 8.0 months, respectively, p-value=0.1). Small sampling numbers may have contributed to this result. One year survival was 23 % in the GCE group and 13 % in the GC group. Patients with poor performance status (PS=2-3) had worse survival as compared to patients with better performance status (PS=0-1, p=0.001). As in earlier studies, patients treated with more lines of therapy tended to have better survival (p <0.0001), and CA19-9 was found to be a significant predictor for OS (p=0.001). No statistical evidence of a survival difference was found between smokers and non-smokers in both treatment groups (p=0.72). In conclusion, though there was a trend towards improved survival with the addition of erlotinib to gemcitabine and cisplatin, this does not reach statistical significance.