Pick Topic
Review Topic
List Experts
Examine Expert
Save Expert
  Site Guide ··   
Pancreatic Neoplasms: HELP
Articles by Albert C. Koong
Based on 48 articles published since 2008
||||

Between 2008 and 2019, Albert Koong wrote the following 48 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Guideline Pancreatic Adenocarcinoma, Version 2.2017, NCCN Clinical Practice Guidelines in Oncology. 2017

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

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

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

Tempero, Margaret A / Arnoletti, J Pablo / Behrman, Stephen W / Ben-Josef, Edgar / Benson, Al B / Casper, Ephraim S / Cohen, Steven J / Czito, Brian / Ellenhorn, Joshua D I / Hawkins, William G / Herman, Joseph / Hoffman, John P / Ko, Andrew / Komanduri, Srinadh / Koong, Albert / Ma, Wen Wee / Malafa, Mokenge P / Merchant, Nipun B / Mulvihill, Sean J / Muscarella, Peter / Nakakura, Eric K / Obando, Jorge / Pitman, Martha B / Sasson, Aaron R / Tally, Anitra / Thayer, Sarah P / Whiting, Samuel / Wolff, Robert A / Wolpin, Brian M / Freedman-Cass, Deborah A / Shead, Dorothy A / Anonymous1061005. ·UCSF Helen Diller Family Comprehensive Cancer Center. ·J Natl Compr Canc Netw · Pubmed #22679115.

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

3 Review Management of Borderline Resectable Pancreatic Cancer. 2018

Toesca, Diego A S / Koong, Amanda J / Poultsides, George A / Visser, Brendan C / Haraldsdottir, Sigurdis / Koong, Albert C / Chang, Daniel T. ·Department of Radiation Oncology, Stanford Cancer Institute, Stanford, California. · Department of Surgery, Stanford Cancer Institute, Stanford, California. · Department of Medical Oncology, Stanford Cancer Institute, Stanford, California. · Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. · Department of Radiation Oncology, Stanford Cancer Institute, Stanford, California. Electronic address: dtchang@stanford.edu. ·Int J Radiat Oncol Biol Phys · Pubmed #29722658.

ABSTRACT: With the rapid development of imaging modalities and surgical techniques, the clinical entity representing tumors that are intermediate between resectable and unresectable pancreatic adenocarcinoma has been identified has been termed "borderline resectable" (BR). These tumors are generally amenable for resection but portend an increased risk for positive margins after surgery and commonly necessitate vascular resection and reconstruction. Although there is a lack of consensus regarding the appropriate definition of what constitutes a BR pancreatic tumor, it has been demonstrated that this intermediate category carries a particular prognosis that is in between resectable and unresectable disease. In order to downstage the tumor and increase the probability of clear surgical margins, neoadjuvant therapy is being increasingly utilized and studied. There is a lack of high-level evidence to establish the optimal treatment regimen for BR tumors. When resection with negative margins is achieved after neoadjuvant therapy, the prognosis for BR tumors approaches and even exceeds that for resectable disease. This review presents the current definitions, different treatment approaches, and the clinical outcomes of BR pancreatic cancer.

4 Review ACR Appropriateness Criteria® Resectable Pancreatic Cancer. 2017

Jones, William E / Suh, W Waren / Abdel-Wahab, May / Abrams, Ross A / Azad, Nilofer / Das, Prajnan / Dragovic, Jadranka / Goodman, Karyn A / Jabbour, Salma K / Konski, Andre A / Koong, Albert C / Kumar, Rachit / Lee, Percy / Pawlik, Timothy M / Small, William / Herman, Joseph M / Anonymous5660897. ·*University of Texas Health Science Center at San Antonio, San Antonio ¶University of Texas MD Anderson Cancer Center, Houston, TX †Cancer Center of Santa Barbara, Santa Barbara §§Stanford Cancer Institute, Stanford ¶¶University of California Los Angeles, Los Angeles, CA ‡Cleveland Clinic, Cleveland, OH ***Stritch School of Medicine Loyola University Chicago, Maywood §Rush University Medical Center, Chicago, IL ∥Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, American Society of Clinical Oncology †††Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University ##Johns Hopkins University, Baltimore, MD, American College of Surgeons #Henry Ford Hospital, Detroit, MI **University of Colorado School of Medicine Anschutz Medical Campus, Aurora, CO ††Rutgers Cancer Institute of New Jersey, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ ‡‡University of Pennsylvania, The Chester County Hospital, West Chester, PA ∥∥Banner MD Anderson Cancer Center, Gilbert, AZ. ·Am J Clin Oncol · Pubmed #28230650.

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

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

Anonymous970875 / Small, William / Hayes, John P / Suh, W Warren / Abdel-Wahab, May / Abrams, Ross A / Azad, Nilofer / Das, Prajnan / Dragovic, Jadranka / Goodman, Karyn A / Jabbour, Salma K / Jones, William E / Konski, Andre A / Koong, Albert C / Kumar, Rachit / Lee, Percy / Pawlik, Timothy M / Herman, Joseph M. · ·Oncology (Williston Park) · Pubmed #27422109.

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

6 Review Treatment Approaches to Locally Advanced Pancreatic Adenocarcinoma. 2015

Pollom, Erqi L / Koong, Albert C / Ko, Andrew H. ·Department of Radiation Oncology, Stanford Cancer Center, Stanford University, 875 Blake Wilbur Drive, MC5847, Stanford, CA 94305-5847, USA. · Division of Hematology/Oncology, University of California San Francisco, 1600 Divisadero Street, 4th Floor, Box 1705, San Francisco, CA 94115, USA. Electronic address: andrewko@medicine.ucsf.edu. ·Hematol Oncol Clin North Am · Pubmed #26226908.

ABSTRACT: This article focuses on the management of locally advanced pancreatic cancer, which should be treated as a distinct entity separate from metastatic disease and borderline resectable disease. Although the role, timing, and sequencing of radiation relative to systemic therapy in this disease are controversial, an emerging treatment paradigm involves induction chemotherapy, followed by consolidative chemoradiation in patients who do not progress. In addition, new chemotherapy regimens as well as novel radiosensitizers have shown promise and need to be tested further in the locally advanced setting. Advances in radiotherapy have enabled stereotactic body radiotherapy and should continue to be prospectively evaluated.

7 Review Stereotactic body radiation therapy in pancreatic cancer: the new frontier. 2014

Moningi, Shalini / Marciscano, Ariel E / Rosati, Lauren M / Ng, Sook Kien / Teboh Forbang, Roland / Jackson, Juan / Chang, Daniel T / Koong, Albert C / Herman, Joseph M. ·Department of Radiation Oncology and Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, 401 N. Broadway, Weinberg Suite 1440, Baltimore, MD 21231, USA. ·Expert Rev Anticancer Ther · Pubmed #25183386.

ABSTRACT: Pancreatic cancer (PCA) remains a disease with a poor prognosis. The majority of PCA patients are unable to undergo surgical resection, which is the only potentially curative option at this time. A combination of chemotherapy and chemoradiation (CRT) are standard options for patients with locally advanced, unresectable disease, however, local control and patient outcomes remains poor. Stereotactic body radiation therapy (SBRT) is an emerging treatment option for PCA. SBRT delivers potentially ablative doses to the pancreatic tumor plus a small margin over a short period of time. Early studies with single-fraction SBRT demonstrated excellent tumor control with high rates of toxicity. The implementation of SBRT (3-5 doses) has demonstrated promising outcomes with favorable tumor control and toxicity rates. Herein we discuss the evolving role of SBRT in PCA treatment.

8 Review Stereotactic body radiotherapy in the treatment of pancreatic cancer. 2014

Trakul, Nicholas / Koong, Albert C / Chang, Daniel T. ·Department of Radiation Oncology, Keck School of Medicine of University of Southern California, Los Angeles, CA. · Department of Radiation Oncology, Stanford University School of Medicine and Cancer Center, Stanford, CA. · Department of Radiation Oncology, Stanford University School of Medicine and Cancer Center, Stanford, CA. Electronic address: dtchang@stanford.edu. ·Semin Radiat Oncol · Pubmed #24635871.

ABSTRACT: Most patients diagnosed with pancreatic cancer are unable to have a curative surgical resection. Chemoradiation is a standard of care treatment for patients with locally advanced unresectable disease, but local failure rates are high with conventionally fractionated radiotherapy. However, stereotactic body radiotherapy (SBRT) or stereotactic ablative radiotherapy offers an alternative type of radiation therapy, which allows for the delivery of high-dose, conformal radiation. The high doses and shorter overall treatment time with SBRT may provide advantages in local control, disease outcomes, quality of life, and cost-effectiveness, and further investigation is currently underway. Here, we review the technology behind SBRT for pancreatic malignancy and its future direction in the overall management of pancreatic cancer.

9 Review Modern radiation therapy techniques for pancreatic cancer. 2012

Trakul, Nicholas / Koong, Albert C / Maxim, Peter G / Chang, Daniel T. ·Department of Radiation Oncology, Stanford University School of Medicine and Cancer Center, Stanford, CA 94305, USA. dtchang@stanford.edu ·Gastroenterol Clin North Am · Pubmed #22341260.

ABSTRACT: Radiation therapy is a rapidly evolving field, and recent technical advances have spurred an increasing number of new treatments as well as marked improvements in previously existing treatments. Despite a growing body of published evidence demonstrating that radiotherapy for the treatment of pancreatic cancer is improving in efficacy and safety, the ultimate effect on patient outcomes remains to be seen. It is an unfortunate fact that the majority of pancreatic cancer patients will ultimately have metastases and succumb to distant disease. Thus, improvements in local tumor control engendered by these recent advances will have little impact on overall survival without the coincident development of better systemic treatment regimens.

10 Review Stereotactic body radiation therapy for gastrointestinal malignancies. 2011

Minn, A Yuriko / Koong, Albert C / Chang, Daniel T. ·Department of Radiation Oncology, Stanford University Medical Center, Stanford, Calif., USA. ·Front Radiat Ther Oncol · Pubmed #21625166.

ABSTRACT: Stereotactic body radiotherapy (SBRT) is an emerging treatment for pancreas cancer and liver tumors. Early data suggest excellent control rates for locally advanced pancreas cancer. However, due to the close proximity of the duodenum and stomach, steps to effectively minimize toxicities must be taken through image guidance of treatments. SBRT for liver tumors has also shown high rates of local control with low risks for hepatic toxicity. Careful selection of cases for SBRT is essential to achieve disease control and to minimize toxicity for patients. In treatment, attention must be paid to minimizing exposure of nearby normal tissues, including ribs, skin and bowel as well as the functioning organs surrounding the tumors. There is no accepted standard for the SBRT dose/fractionation schedule for these cases and the optimal strategy will likely depend on the size, number and location of lesions for each patient. However, the published data seem to suggest an overall dose-response effect. To realize the clinical potential of SBRT for these tumors, investigations are needed to determine optimum fractionation schedules and to integrate its use with systemic chemotherapy programs.

11 Clinical Trial Patient-reported outcomes of a multicenter phase 2 study investigating gemcitabine and stereotactic body radiation therapy in locally advanced pancreatic cancer. 2016

Rao, Avani D / Sugar, Elizabeth A / Chang, Daniel T / Goodman, Karyn A / Hacker-Prietz, Amy / Rosati, Lauren M / Columbo, Laurie / O'Reilly, Eileen / Fisher, George A / Zheng, Lei / Pai, Jonathan S / Griffith, Mary E / Laheru, Daniel A / Iacobuzio-Donahue, Christine A / Wolfgang, Christopher L / Koong, Albert / Herman, Joseph M. ·Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland. · Department of Biostatistics and Epidemiology, Johns Hopkins University School of Medicine, Baltimore, Maryland. · Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California. · Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York. · Department of Medical Oncology, Memorial Sloan Kettering Cancer Center, New York, New York. · Department of Medical Oncology, Stanford University School of Medicine, Stanford, California. · Department of Medical Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland. · University of California at San Francisco School of Medicine, San Francisco, California. · Department of Surgical Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland. · Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland. Electronic address: joe@jhmi.edu. ·Pract Radiat Oncol · Pubmed #27552809.

ABSTRACT: PURPOSE: We previously reported clinical outcomes and physician-reported toxicity of gemcitabine and hypofractionated stereotactic body radiation therapy (SBRT) in locally advanced pancreatic cancer (LAPC). Here we prospectively investigate the impact of gemcitabine and SBRT on patient-reported quality of life (QoL). METHODS AND MATERIALS: Forty-nine LAPC patients received 33 Gy SBRT (6.6 Gy daily fractions) upfront or after ≤3 doses of gemcitabine (1000 mg/m RESULTS: Forty-three (88%) patients completed pre-SBRT questionnaires. Of these, 88% and 51% completed questionnaires at 1FUP and 2FUP, respectively. There was no change in global QoL from pre-SBRT to 1FUP (P = .17) or 2FUP (P > .99). Statistical and clinical improvements in pancreatic pain (P = .001) and body image (P = .007) were observed from pre-SBRT to 1FUP. Patients with 1FUP and 2FUP questionnaires reported statistically and clinically improved body image (P = .016) by 4 months. Although pancreatic pain initially demonstrated statistical and clinical improvement (P = .020), scores returned to enrollment levels by 2FUP (P = .486). A statistical and clinical decline in role functioning (P = .002) was observed in patients at 2FUP. CONCLUSIONS: Global QoL scores are not reduced with gemcitabine and SBRT. In this exploratory analysis, patients experience clinically relevant short-term improvements in pancreatic cancer-specific symptoms. Previously demonstrated acceptable clinical outcomes combined with these favorable QoL data indicate that SBRT can be easily integrated with other systemic therapies and may be a potential standard of care option in patients with LAPC.

12 Clinical Trial A Novel Biomarker Panel Examining Response to Gemcitabine with or without Erlotinib for Pancreatic Cancer Therapy in NCIC Clinical Trials Group PA.3. 2016

Shultz, David B / Pai, Jonathan / Chiu, Wayland / Ng, Kendall / Hellendag, Madeline G / Heestand, Gregory / Chang, Daniel T / Tu, Dongsheng / Moore, Malcolm J / Parulekar, Wendy R / Koong, Albert C. ·Princess Margaret Cancer Centre, Toronto, Ontario, Canada. · School of Medicine, University of California San Francisco, San Francisco, United States of America. · Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA, United States of America. · Kaiser Permanente Medical Center, San Francisco, United States of America. · Moores Cancer Center, University of California San Diego, La Jolla, CA, United States of America. · NCIC Clinical Trials Group, Queen's University, Kingston, Canada. · British Columbia Cancer Agency, Vancouver, British Columbia, CA, United States of America. ·PLoS One · Pubmed #26808546.

ABSTRACT: PURPOSE: NCIC Clinical Trials Group PA.3 was a randomized control trial that demonstrated improved overall survival (OS) in patients receiving erlotinib in addition to gemcitabine for locally advanced or metastatic pancreatic cancer. Prior to therapy, patients had plasma samples drawn for future study. We sought to identify biomarkers within these samples. EXPERIMENTAL DESIGN: Using the proximity ligation assay (PLA), a probe panel was built from commercially available antibodies for 35 key proteins selected from a global genetic analysis of pancreatic cancers, and used to quantify protein levels in 20 uL of patient plasma. To determine if any of these proteins levels independently associated with OS, univariate and mulitbaraible Cox models were used. In addition, we examined the associations between biomarker expression and disease stage at diagnosis using Fisher's exact test. The correlation between Erlotinib sensitivity and each biomarkers was assessed using a test of interaction between treatment and biomarker. RESULTS AND CONCLUSION: Of the 569 eligible patients, 480 had samples available for study. Samples were randomly allocated into training (251) and validation sets (229). Among all patients, elevated levels of interleukin-8 (IL-8), carcinoembryonic antigen (CEA), hypoxia-inducible factor 1-alpha (HIF-1 alpha), and interleukin-6 were independently associated with lower OS, while IL-8, CEA, platelet-derived growth factor receptor alpha and mucin-1 were associated with metastatic disease. Patients with elevated levels of receptor tyrosine-protein kinase erbB-2 (HER2) expression had improved OS when treated with erlotinib compared to placebo. In conclusion, PLA is a powerful tool for identifying biomarkers from archived, small volume serum samples. These data may be useful to stratify patient outcomes regardless of therapeutic intervention. TRIAL REGISTRATION: ClinicalTrials.gov NCT00040183.

13 Clinical Trial Phase 2 multi-institutional trial evaluating gemcitabine and stereotactic body radiotherapy for patients with locally advanced unresectable pancreatic adenocarcinoma. 2015

Herman, Joseph M / Chang, Daniel T / Goodman, Karyn A / Dholakia, Avani S / Raman, Siva P / Hacker-Prietz, Amy / Iacobuzio-Donahue, Christine A / Griffith, Mary E / Pawlik, Timothy M / Pai, Jonathan S / O'Reilly, Eileen / Fisher, George A / Wild, Aaron T / Rosati, Lauren M / Zheng, Lei / Wolfgang, Christopher L / Laheru, Daniel A / Columbo, Laurie A / Sugar, Elizabeth A / Koong, Albert C. ·Department of Radiation Oncology & Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland. ·Cancer · Pubmed #25538019.

ABSTRACT: BACKGROUND: This phase 2 multi-institutional study was designed to determine whether gemcitabine (GEM) with fractionated stereotactic body radiotherapy (SBRT) results in acceptable late grade 2 to 4 gastrointestinal toxicity when compared with a prior trial of GEM with single-fraction SBRT in patients with locally advanced pancreatic cancer (LAPC). METHODS: A total of 49 patients with LAPC received up to 3 doses of GEM (1000 mg/m(2)) followed by a 1-week break and SBRT (33.0 gray [Gy] in 5 fractions). After SBRT, patients continued to receive GEM until disease progression or toxicity. Toxicity was assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events [version 4.0] and the Radiation Therapy Oncology Group radiation morbidity scoring criteria. Patients completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30) and pancreatic cancer-specific QLQ-PAN26 module before SBRT and at 4 weeks and 4 months after SBRT. RESULTS: The median follow-up was 13.9 months (range, 3.9-45.2 months). The median age of the patients was 67 years and 84% had tumors of the pancreatic head. Rates of acute and late (primary endpoint) grade ≥ 2 gastritis, fistula, enteritis, or ulcer toxicities were 2% and 11%, respectively. QLQ-C30 global quality of life scores remained stable from baseline to after SBRT (67 at baseline, median change of 0 at both follow-ups; P>.05 for both). Patients reported a significant improvement in pancreatic pain (P = .001) 4 weeks after SBRT on the QLQ-PAN26 questionnaire. The median plasma carbohydrate antigen 19-9 (CA 19-9) level was reduced after SBRT (median time after SBRT, 4.2 weeks; 220 U/mL vs 62 U/mL [P<.001]). The median overall survival was 13.9 months (95% confidence interval, 10.2 months-16.7 months). Freedom from local disease progression at 1 year was 78%. Four patients (8%) underwent margin-negative and lymph node-negative surgical resections. CONCLUSIONS: Fractionated SBRT with GEM results in minimal acute and late gastrointestinal toxicity. Future studies should incorporate SBRT with more aggressive multiagent chemotherapy.

14 Clinical Trial Baseline metabolic tumor volume and total lesion glycolysis are associated with survival outcomes in patients with locally advanced pancreatic cancer receiving stereotactic body radiation therapy. 2014

Dholakia, Avani S / Chaudhry, Muhammad / Leal, Jeffrey P / Chang, Daniel T / Raman, Siva P / Hacker-Prietz, Amy / Su, Zheng / Pai, Jonathan / Oteiza, Katharine E / Griffith, Mary E / Wahl, Richard L / Tryggestad, Erik / Pawlik, Timothy / Laheru, Daniel A / Wolfgang, Christopher L / Koong, Albert C / Herman, Joseph M. ·Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland. · Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, Maryland. · Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California. · Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland. · Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland. · Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland. Electronic address: jherma15@jhmi.edu. ·Int J Radiat Oncol Biol Phys · Pubmed #24751410.

ABSTRACT: PURPOSE: Although previous studies have demonstrated the prognostic value of positron emission tomography (PET) parameters in other malignancies, the role of PET in pancreatic cancer has yet to be well established. We analyzed the prognostic utility of PET for patients with locally advanced pancreatic cancer (LAPC) undergoing fractionated stereotactic body radiation therapy (SBRT). MATERIALS AND METHODS: Thirty-two patients with LAPC in a prospective clinical trial received up to 3 doses of gemcitabine, followed by 33 Gy in 5 fractions of 6.6 Gy, using SBRT. All patients received a baseline PET scan prior to SBRT (pre-SBRT PET). Metabolic tumor volume (MTV), total lesion glycolysis (TLG), and maximum and peak standardized uptake values (SUVmax and SUVpeak) on pre-SBRT PET scans were calculated using custom-designed software. Disease was measured at a threshold based on the liver SUV, using the equation Livermean + [2 × Liversd]. Median values of PET parameters were used as cutoffs when assessing their prognostic potential through Cox regression analyses. RESULTS: Of the 32 patients, the majority were male (n=19, 59%), 65 years or older (n=21, 66%), and had tumors located in the pancreatic head (n=27, 84%). Twenty-seven patients (84%) received induction gemcitabine prior to SBRT. Median overall survival for the entire cohort was 18.8 months (95% confidence interval [CI], 15.7-22.0). An MTV of 26.8 cm(3) or greater (hazard ratio [HR] 4.46, 95% CI 1.64-5.88, P<.003) and TLG of 70.9 or greater (HR 3.08, 95% CI 1.18-8.02, P<.021) on pre-SBRT PET scan were associated with inferior overall survival on univariate analysis. Both pre-SBRT MTV (HR 5.13, 95% CI 1.19-22.21, P=.029) and TLG (HR 3.34, 95% CI 1.07-10.48, P=.038) remained independently associated with overall survival in separate multivariate analyses. CONCLUSIONS: Pre-SBRT MTV and TLG are potential predictive factors for overall survival in patients with LAPC and may assist in tailoring therapy.

15 Clinical Trial Single-fraction stereotactic body radiation therapy and sequential gemcitabine for the treatment of locally advanced pancreatic cancer. 2011

Schellenberg, Devin / Kim, Jeff / Christman-Skieller, Claudia / Chun, Carlene L / Columbo, Laurie Ann / Ford, James M / Fisher, George A / Kunz, Pamela L / Van Dam, Jacques / Quon, Andrew / Desser, Terry S / Norton, Jeffrey / Hsu, Annie / Maxim, Peter G / Xing, Lei / Goodman, Karyn A / Chang, Daniel T / Koong, Albert C. ·Department of Radiation Oncology, BC Cancer Agency, Surrey, British Columbia, Canada. ·Int J Radiat Oncol Biol Phys · Pubmed #21549517.

ABSTRACT: PURPOSE: This Phase II trial evaluated the toxicity, local control, and overall survival in patients treated with sequential gemcitabine and linear accelerator-based single-fraction stereotactic body radiotherapy (SBRT). METHODS AND MATERIALS: Twenty patients with locally advanced, nonmetastatic pancreatic adenocarcinoma were enrolled on this prospective single-institution, institutional review board-approved study. Gemcitabine was administered on Days 1, 8, and 15, and SBRT on Day 29. Gemcitabine was restarted on Day 43 and continued for 3-5 cycles. SBRT of 25 Gy in a single fraction was delivered to the internal target volume with a 2- 3-mm margin using a nine-field intensity-modulated radiotherapy technique. Respiratory gating was used to account for breathing motion. Follow-up evaluations occurred at 4-6 weeks, 10-12 weeks, and every 3 months after SBRT. RESULTS: All patients completed SBRT and a median of five cycles of chemotherapy. Follow-up for the 2 remaining alive patients was 25.1 and 36.4 months. No acute Grade 3 or greater nonhematologic toxicity was observed. Late Grade 3 or greater toxicities occurred in 1 patient (5%) and consisted of a duodenal perforation (G4). Three patients (15%) developed ulcers (G2) that were medically managed. Overall, median survival was 11.8 months, with 1-year survival of 50% and 2-year survival of 20%. Using serial computed tomography, the freedom from local progression was 94% at 1 year. CONCLUSION: Linear accelerator-delivered SBRT with sequential gemcitabine resulted in excellent local control of locally advanced pancreatic cancer. Future studies will address strategies for reducing long-term duodenal toxicity associated with SBRT.

16 Clinical Trial Gemcitabine chemotherapy and single-fraction stereotactic body radiotherapy for locally advanced pancreatic cancer. 2008

Schellenberg, Devin / Goodman, Karyn A / Lee, Florence / Chang, Stephanie / Kuo, Timothy / Ford, James M / Fisher, George A / Quon, Andrew / Desser, Terry S / Norton, Jeffrey / Greco, Ralph / Yang, George P / Koong, Albert C. ·Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA, USA. ·Int J Radiat Oncol Biol Phys · Pubmed #18395362.

ABSTRACT: PURPOSE: Fractionated radiotherapy and chemotherapy for locally advanced pancreatic cancer achieves only modest local control. This prospective trial evaluated the efficacy of a single fraction of 25 Gy stereotactic body radiotherapy (SBRT) delivered between Cycle 1 and 2 of gemcitabine chemotherapy. METHODS AND MATERIALS: A total of 16 patients with locally advanced, nonmetastatic, pancreatic adenocarcinoma received gemcitabine with SBRT delivered 2 weeks after completion of the first cycle. Gemcitabine was resumed 2 weeks after SBRT and was continued until progression or dose-limiting toxicity. The gross tumor volume, with a 2-3-mm margin, was treated in a single 25-Gy fraction by Cyberknife. Patients were evaluated at 4-6 weeks, 10-12 weeks, and every 3 months after SBRT. RESULTS: All 16 patients completed SBRT. A median of four cycles (range one to nine) of chemotherapy was delivered. Three patients (19%) developed local disease progression at 14, 16, and 21 months after SBRT. The median survival was 11.4 months, with 50% of patients alive at 1 year. Patients with normal carbohydrate antigen (CA)19-9 levels either at diagnosis or after Cyberknife SBRT had longer survival (p <0.01). Acute gastrointestinal toxicity was mild, with 2 cases of Grade 2 (13%) and 1 of Grade 3 (6%) toxicity. Late gastrointestinal toxicity was more common, with five ulcers (Grade 2), one duodenal stenosis (Grade 3), and one duodenal perforation (Grade 4). A trend toward increased duodenal volumes radiated was observed in those experiencing late effects (p = 0.13). CONCLUSION: SBRT with gemcitabine resulted in comparable survival to conventional chemoradiotherapy and good local control. However, the rate of duodenal ulcer development was significant.

17 Article Germline cancer susceptibility gene variants, somatic second hits, and survival outcomes in patients with resected pancreatic cancer. 2019

Yurgelun, Matthew B / Chittenden, Anu B / Morales-Oyarvide, Vicente / Rubinson, Douglas A / Dunne, Richard F / Kozak, Margaret M / Qian, Zhi Rong / Welch, Marisa W / Brais, Lauren K / Da Silva, Annacarolina / Bui, Justin L / Yuan, Chen / Li, Tingting / Li, Wanwan / Masuda, Atsuhiro / Gu, Mancang / Bullock, Andrea J / Chang, Daniel T / Clancy, Thomas E / Linehan, David C / Findeis-Hosey, Jennifer J / Doyle, Leona A / Thorner, Aaron R / Ducar, Matthew D / Wollison, Bruce M / Khalaf, Natalia / Perez, Kimberly / Syngal, Sapna / Aguirre, Andrew J / Hahn, William C / Meyerson, Matthew L / Fuchs, Charles S / Ogino, Shuji / Hornick, Jason L / Hezel, Aram F / Koong, Albert C / Nowak, Jonathan A / Wolpin, Brian M. ·Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA. matthew_yurgelun@dfci.harvard.edu. · Department of Medicine, Brigham & Women's Hospital, Boston, MA, USA. matthew_yurgelun@dfci.harvard.edu. · Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA. · Department of Medicine, Brigham & Women's Hospital, Boston, MA, USA. · Department of Medicine, Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY, USA. · Department of Radiation Oncology, Stanford Cancer Institute, Stanford, CA, USA. · Department of Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA, USA. · Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA. · Department of Medicine, Division of Hematology/Oncology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA. · Department of Surgery, Brigham & Women's Hospital and Harvard Medical School, Boston, MA, USA. · Department of Surgery, University of Rochester Medical Center, Rochester, NY, USA. · Department of Pathology, University of Rochester Medical Center, Rochester, NY, USA. · Department of Pathology, Brigham & Women's Hospital and Harvard Medical School, Boston, MA, USA. · Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, Boston, MA, USA. · Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, USA. · Yale Cancer Center, Yale School of Medicine, New Haven, CT, USA. · Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. ·Genet Med · Pubmed #29961768.

ABSTRACT: PURPOSE: Germline variants in double-strand DNA damage repair (dsDDR) genes (e.g., BRCA1/2) predispose to pancreatic adenocarcinoma (PDAC) and may predict sensitivity to platinum-based chemotherapy and poly(ADP) ribose polymerase (PARP) inhibitors. We sought to determine the prevalence and significance of germline cancer susceptibility gene variants in PDAC with paired somatic and survival analyses. METHODS: Using a customized next-generation sequencing panel, germline/somatic DNA was analyzed from 289 patients with resected PDAC ascertained without preselection for high-risk features (e.g., young age, personal/family history). All identified variants were assessed for pathogenicity. Outcomes were analyzed using multivariable-adjusted Cox proportional hazards regression. RESULTS: We found that 28/289 (9.7%; 95% confidence interval [CI] 6.5-13.7%) patients carried pathogenic/likely pathogenic germline variants, including 21 (7.3%) dsDDR gene variants (3 BRCA1, 4 BRCA2, 14 other dsDDR genes [ATM, BRIP1, CHEK2, NBN, PALB2, RAD50, RAD51C]), 3 Lynch syndrome, and 4 other genes (APC p.I1307K, CDKN2A, TP53). Somatic sequencing and immunohistochemistry identified second hits in the tumor in 12/27 (44.4%) patients with germline variants (1 failed sequencing). Compared with noncarriers, patients with germline dsDDR gene variants had superior overall survival (hazard ratio [HR] 0.54; 95% CI 0.30-0.99; P = 0.05). CONCLUSION: Nearly 10% of PDAC patients harbor germline variants, although the majority lack somatic second hits, the therapeutic significance of which warrants further study.

18 Article Hyperfractionated abdominal reirradiation for gastrointestinal malignancies. 2018

Hunt, Andrew / Das, Prajnan / Minsky, Bruce D / Koay, Eugene J / Krishnan, Sunil / Herman, Joseph M / Taniguchi, Cullen / Koong, Albert / Smith, Grace L / Holliday, Emma B. ·University of Texas Health San Antonio Long School of Medicine, San Antonio, TX, USA. · The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd Unit 97, Houston, TX, 77030, USA. · The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd Unit 97, Houston, TX, 77030, USA. ebholliday@mdanderson.org. ·Radiat Oncol · Pubmed #30086784.

ABSTRACT: BACKGROUND: We sought to determine the role of abdominal reirradiation for patients presenting with recurrent or new primary gastrointestinal (GI) malignancies. At our institution, we have established a hyperfractionated, accelerated reirradiation regimen consisting of 39 Gray (Gy) in 26 twice-daily fractions. Although this regimen is used frequently in the pelvis, we sought to determine its toxicity and efficacy for abdominal tumors. METHODS: Twenty-four patients who received abdominal reirradiation with a hyperfractionated, accelerated approach from 2000 to 2017 were identified. Overall survival (OS) and local progression-free survival (LPFS) were calculated using the Kaplan-Meier method. Several patient, tumor and treatment characteristics were evaluated on univariate analyses for association with OS and LPFS using a Cox proportional hazards model. RESULTS: Of the twenty-four patients identified, the majority (n = 11, 46%) had pancreatic adenocarcinoma as their primary disease but also included upper GI adenocarcinoma (n = 4), colon adenocarcinoma (n = 3), hepatobiliary cancers (n = 4) and other malignancies (n = 2). The majority of patients received 45-50.4Gy in 1.8Gy fractions as their initial abdominal radiation course. The median reirradiation dose was 39Gy in 26 twice-daily fractions with a minimum six hour interval. The median [interquartile range (IQR)] interval between the courses of radiotherapy was 28 [18.6-38.9] months. Only palliative reirradiation intent was associated with decreased OS. While colon adenocarcinoma primary was significantly associated with increased LPFS, the sample size was small (n = 3). The 1-yr rate of LPFS was 38%. The median [IQR] duration of freedom from local progression was 8 [3.8-19.2] months. The 1-year OS was 50% and the median (IQR) OS was 14 [6.3-19.6] months. Thirteen patients (54%) had acute side effects with one patient experiencing G3 nausea and one experiencing a G4 bleed; the remaining patients experienced G1-G2 symptoms. CONCLUSION: Hyperfractionated, accelerated reirradiation to the abdomen was relatively well-tolerated but provided limited local control to recurrent or second primary abdominal malignancies. Reirradiation could play a role in treating these patients with palliative or curative intent, but alternative strategies for delivering increased biologically effective dose should be further explored.

19 Article Altered exocrine function can drive adipose wasting in early pancreatic cancer. 2018

Danai, Laura V / Babic, Ana / Rosenthal, Michael H / Dennstedt, Emily A / Muir, Alexander / Lien, Evan C / Mayers, Jared R / Tai, Karen / Lau, Allison N / Jones-Sali, Paul / Prado, Carla M / Petersen, Gloria M / Takahashi, Naoki / Sugimoto, Motokazu / Yeh, Jen Jen / Lopez, Nicole / Bardeesy, Nabeel / Fernandez-Del Castillo, Carlos / Liss, Andrew S / Koong, Albert C / Bui, Justin / Yuan, Chen / Welch, Marisa W / Brais, Lauren K / Kulke, Matthew H / Dennis, Courtney / Clish, Clary B / Wolpin, Brian M / Vander Heiden, Matthew G. ·Koch Institute for Integrative Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA. · Dana-Farber Cancer Institute, Boston, MA, USA. · Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada. · Mayo Clinic, Rochester, MN, USA. · Department of Surgery, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. · University of California San Diego School of Medicine, La Jolla, CA, USA. · Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA. · MD Anderson, Department of Radiation Oncology, Houston, TX, USA. · Stanford Cancer Institute, Stanford, CA, USA. · David Geffen School of Medicine at University of California, Los Angeles, CA, USA. · Section of Hematology/Oncology, Boston University and Boston Medical Center, Boston, MA, USA. · Broad Institute of MIT and Harvard University, Cambridge, MA, USA. · Dana-Farber Cancer Institute, Boston, MA, USA. bwolpin@partners.org. · Koch Institute for Integrative Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA. mvh@mit.edu. · Dana-Farber Cancer Institute, Boston, MA, USA. mvh@mit.edu. · Broad Institute of MIT and Harvard University, Cambridge, MA, USA. mvh@mit.edu. ·Nature · Pubmed #29925948.

ABSTRACT: Malignancy is accompanied by changes in the metabolism of both cells and the organism

20 Article Multiplex Proximity Ligation Assay to Identify Potential Prognostic Biomarkers for Improved Survival in Locally Advanced Pancreatic Cancer Patients Treated With Stereotactic Body Radiation Therapy. 2018

Rao, Avani D / Liu, Yufei / von Eyben, Rie / Hsu, Charles C / Hu, Chen / Rosati, Lauren M / Parekh, Arti / Ng, Kendall / Hacker-Prietz, Amy / Zheng, Lei / Pawlik, Timothy M / Laheru, Daniel A / Jaffee, Elizabeth M / Weiss, Matthew J / Le, Dung T / Hruban, Ralph H / De Jesus-Acosta, Ana / Wolfgang, Christopher L / Narang, Amol K / Chang, Daniel T / Koong, Albert C / Herman, Joseph M. ·Department of Radiation Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland. Electronic address: avani.rao@jhmi.edu. · Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California. · Department of Radiation Oncology, University of Arizona Cancer Center, Tucson, Arizona. · Department of Radiation Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland. · Division of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland. · Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland. · Department of Radiation Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland; Division of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland. · Department of Radiation Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland. · Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland. ·Int J Radiat Oncol Biol Phys · Pubmed #29157747.

ABSTRACT: PURPOSE: To explore seromarker levels for associations with outcomes in locally advanced pancreatic cancer (LAPC) patients who received chemotherapy and stereotactic body radiation therapy (SBRT). METHODS AND MATERIALS: Serum from LAPC patients in 2 prospective trials of hypofractionated SBRT (5-6.6 Gy × 5) was collected before SBRT. Proximity ligation assay quantified the expression levels of 36 pancreatic cancer-specific candidate seromarkers: Axl, BMP2, CA 125, CA 19-9, CEA, CXCL-1/6/9/10, EGFR, Gas6, Her2, IGF-2, IGFBP-2/3/7, IL-6/6Ra/7/8/12, mesothelin, MMP-1/2/3/7, osteopontin, PDGFRa, PDK1, PF4, RegIV, SPARC, TGF-β, VEGF-A/D, and YKL40. Seromarker values were log transformed owing to log-normal distribution of the values, and Cox regression analysis was performed to assess for any association with overall survival. The Benjamini-Hochberg method was used to control for a false discovery rate (FDR) of only 10%. RESULTS: Sixty-four patients with LAPC were included. No clinical factors (including surgical resection, receipt of pre-SBRT chemotherapy, receipt of post-SBRT chemotherapy, performance status, and age) or potential biomarkers in the panel were associated with improved survival in this cohort after application of the FDR correction. Potential prognostic factors for improved survival for future investigation included surgical resection (P=.007, adjusted P=.153) and the serum expression of IL-8 (P=.006, adjusted P=.153), CA 19-9 (P=.031, adjusted P=.377), and MMP-1 (P=.036, adjusted P=.377). CONCLUSIONS: These data explore the expression of a panel of proteins in pre-SBRT serum of LAPC patients in the context of a conservative FDR correction. None of the clinical factors or expression levels of the serum proteins were found to be associated with survival; however, IL-8, CA 19-9, and MMP-1 were highlighted as possible candidates warranting inclusion in future seromarker studies in the ongoing efforts to identify tools for risk stratification and treatment allocation in LAPC.

21 Article Albumin and Neutrophil-Lymphocyte Ratio (NLR) Predict Survival in Patients With Pancreatic Adenocarcinoma Treated With SBRT. 2018

Alagappan, Muthuraman / Pollom, Erqi L / von Eyben, Rie / Kozak, Margaret M / Aggarwal, Sonya / Poultsides, George A / Koong, Albert C / Chang, Daniel T. ·Department of Radiation Oncology, Stanford University Medical Center, Stanford Cancer Institute. · Department of Surgery, Stanford University, Stanford, CA. ·Am J Clin Oncol · Pubmed #26757436.

ABSTRACT: PURPOSE: To determine if pretreatment nutritional status and inflammatory markers correlate with survival in patients with locally advanced pancreatic adenocarcinoma treated with stereotactic body radiotherapy (SBRT). MATERIALS AND METHODS: We retrospectively reviewed 208 patients with newly diagnosed, locally advanced pancreatic adenocarcinoma treated with SBRT at our institution from 2002 to 2014. Laboratory values were collected before SBRT, including hemoglobin, platelets, albumin, red blood cell, white blood cell, neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio, and tumor markers CA 19-9 and CEA. Patients were followed every 3 months with computed tomography (CT) and/or positron emission tomography-CT imaging to monitor for local recurrence and overall survival (OS). RESULTS: Median follow-up after SBRT was 7.5 months (interquartile range, 4.6 to 12.0 mo) for all patients. Median OS for patients with NLR>5 compared with NLR≤5 was 6.9 and 8.5 months, respectively (P=0.0057). On univariate analysis, receipt of chemotherapy (P=0.05, hazard ratio [HR]=0.69), increased albumin (P=0.002, HR=0.64), increased red blood cell (P=0.05, HR=0.75), increased lymphocyte count (P=0.002, HR=0.66), decreased CEA (P=0.01, HR=0.96), and NLR≤5 (P=0.01, HR=0.65) correlated with improved OS. On multivariate analysis, higher albumin (P=0.03, HR=0.70), receipt of chemotherapy (P=0.007, HR=0.56), and NLR≤5 (P=0.02, HR=0.66) correlated with better survival. CONCLUSIONS: Preradiotherapy low albumin levels and NLR>5 correlate with decreased survival in patients with locally advanced pancreatic adenocarcinoma treated with SBRT, indicating the prognostic value of systemic inflammatory markers (such as NLR) and a role of nutritional supplementation to improve outcomes in these patients. Further investigation is warranted.

22 Article A p53 Super-tumor Suppressor Reveals a Tumor Suppressive p53-Ptpn14-Yap Axis in Pancreatic Cancer. 2017

Mello, Stephano S / Valente, Liz J / Raj, Nitin / Seoane, Jose A / Flowers, Brittany M / McClendon, Jacob / Bieging-Rolett, Kathryn T / Lee, Jonghyeob / Ivanochko, Danton / Kozak, Margaret M / Chang, Daniel T / Longacre, Teri A / Koong, Albert C / Arrowsmith, Cheryl H / Kim, Seung K / Vogel, Hannes / Wood, Laura D / Hruban, Ralph H / Curtis, Christina / Attardi, Laura D. ·Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA 94305, USA. · Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305, USA. · Department of Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305, USA. · Princess Margaret Cancer Centre, Structural Genomics Consortium and Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada. · Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA 94305, USA; Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305, USA. · Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA. · Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305, USA. · Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. · Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA. · Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA 94305, USA; Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: attardi@stanford.edu. ·Cancer Cell · Pubmed #29017057.

ABSTRACT: The p53 transcription factor is a critical barrier to pancreatic cancer progression. To unravel mechanisms of p53-mediated tumor suppression, which have remained elusive, we analyzed pancreatic cancer development in mice expressing p53 transcriptional activation domain (TAD) mutants. Surprisingly, the p53

23 Article Lymph node metastases in resected pancreatic ductal adenocarcinoma: predictors of disease recurrence and survival. 2017

Morales-Oyarvide, Vicente / Rubinson, Douglas A / Dunne, Richard F / Kozak, Margaret M / Bui, Justin L / Yuan, Chen / Qian, Zhi Rong / Babic, Ana / Da Silva, Annacarolina / Nowak, Jonathan A / Khalaf, Natalia / Brais, Lauren K / Welch, Marisa W / Zellers, Caitlin L / Ng, Kimmie / Chang, Daniel T / Miksad, Rebecca A / Bullock, Andrea J / Tseng, Jennifer F / Swanson, Richard S / Clancy, Thomas E / Linehan, David C / Findeis-Hosey, Jennifer J / Doyle, Leona A / Hornick, Jason L / Ogino, Shuji / Fuchs, Charles S / Hezel, Aram F / Koong, Albert C / Wolpin, Brian M. ·Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, 450 Brookline Avenue, Boston, MA 02215, USA. · Department of Medicine, Division of Hematology and Oncology, Wilmot Cancer Institute, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA. · Department of Radiation Oncology, Stanford Cancer Institute, 269 Campus Drive West, Stanford, CA 94305-5152, USA. · Department of Epidemiology, Harvard TH Chan School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA. · Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA. · Division of Gastroenterology, Hepatology, and Endoscopy, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA. · Department of Hematology and Oncology, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA. · Department of Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA. · Department of Surgery, Brigham and Women's Hospital and Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA. · Department of Surgery, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA. · Department of Pathology, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA. · Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, 1840 Old Spanish Trail, Houston, TX 77054, USA. ·Br J Cancer · Pubmed #28982112.

ABSTRACT: BACKGROUND: Few studies have simultaneously assessed the prognostic value of the multiple classification systems for lymph node (LN) metastases in resected pancreatic ductal adenocarcinoma (PDAC). METHODS: In 600 patients with resected PDAC, we examined the association of LN parameters (AJCC 7th and 8th editions, LN ratio (LNR), and log odds of metastatic LN (LODDS)) with pattern of recurrence and patient survival using logistic regression and Cox proportional hazards regression, respectively. Regression models adjusted for age, sex, margin status, tumour grade, and perioperative therapy. RESULTS: Lymph node metastases classified by AJCC 7th and 8th editions, LNR, and LODDS were associated with worse disease free-survival (DFS) and overall survival (OS) (all P CONCLUSIONS: American Joint Committee on Cancer 8th edition LN classification is an effective and practical tool to predict outcomes in patients with resected PDAC. However, the prognostic value of LN metastases is attenuated in patients with positive resection margins and distal pancreatectomies.

24 Article BLIMP1 Induces Transient Metastatic Heterogeneity in Pancreatic Cancer. 2017

Chiou, Shin-Heng / Risca, Viviana I / Wang, Gordon X / Yang, Dian / Grüner, Barbara M / Kathiria, Arwa S / Ma, Rosanna K / Vaka, Dedeepya / Chu, Pauline / Kozak, Margaret / Castellini, Laura / Graves, Edward E / Kim, Grace E / Mourrain, Philippe / Koong, Albert C / Giaccia, Amato J / Winslow, Monte M. ·Department of Genetics, Stanford University School of Medicine, Stanford, California. · Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California. · Cancer Biology Program, Stanford University School of Medicine, Stanford, California. · Department of Pathology, Stanford University School of Medicine, Stanford, California. · Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California. · Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California. · Department of Pathology, University of California, San Francisco, San Francisco, California. · Department of Genetics, Stanford University School of Medicine, Stanford, California. mwinslow@stanford.edu. ·Cancer Discov · Pubmed #28790031.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is one of the most metastatic and deadly cancers. Despite the clinical significance of metastatic spread, our understanding of molecular mechanisms that drive PDAC metastatic ability remains limited. By generating a genetically engineered mouse model of human PDAC, we uncover a transient subpopulation of cancer cells with exceptionally high metastatic ability. Global gene expression profiling and functional analyses uncovered the transcription factor BLIMP1 as a driver of PDAC metastasis. The highly metastatic PDAC subpopulation is enriched for hypoxia-induced genes, and hypoxia-mediated induction of BLIMP1 contributes to the regulation of a subset of hypoxia-associated gene expression programs. These findings support a model in which upregulation of BLIMP1 links microenvironmental cues to a metastatic stem cell character.

25 Article Assessing local progression after stereotactic body radiation therapy for unresectable pancreatic adenocarcinoma: CT versus PET. 2017

Toesca, Diego A S / Pollom, Erqi L / Poullos, Peter D / Flynt, Lesley / Cui, Yi / Quon, Andrew / von Eyben, Rie / Koong, Albert C / Chang, Daniel T. ·Radiation Oncology Department, Stanford University School of Medicine, Stanford, California. · Radiology Department, Stanford University School of Medicine, Stanford, California. · Nuclear Medicine Department, Stanford University School of Medicine, Stanford, California. · Radiation Oncology Department, Stanford University School of Medicine, Stanford, California. Electronic address: dtchang@stanford.edu. ·Pract Radiat Oncol · Pubmed #28274396.

ABSTRACT: PURPOSE: Evaluation of local tumor progression (LP) has typically been defined by contrast-enhanced computed tomography (CT) imaging after stereotactic body radiation therapy (SBRT) for locally advanced pancreatic cancer (PDAC). The purpose of this study is to determine the benefit of adding 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging to CT for LP assessment of PDAC after SBRT. METHODS AND MATERIALS: We retrospectively reviewed pretreatment, follow-up images, and outcomes of all patients treated with definitive SBRT for unresectable PDAC between December 2002 and December 2015 at our institution. For each patient, we independently analyzed LP both by CT and by FDG-PET criteria, using the Response Evaluation Criteria In Solid Tumors version 1.1 and the FDG-PET Response Evaluation Criteria In Solid Tumors version 1.0, respectively. RESULTS: Among 206 patients treated with definitive SBRT for unresectable PDAC, we identified 30 with LP on follow-up. Four did not undergo follow-up FDG-PET. Median time to LP after SBRT was 7.5 months (range, 2-25 months). Of the 26 patients with LP who had follow-up FDG-PET, 21 were diagnosed by FDG-PET (80.7%), 14 by CT (53.8%), and 9 by both FDG-PET and CT (34.6%). Use of CT alone revealed only 53.8% of cases of LP detected when FDG-PET and CT were combined. The cumulative incidence of LP, based on competing risk of death, at 1 and 2 years after SBRT was 9.6% and 16.7% by CT and 11% and 29.1% by FDG-PET, respectively. CONCLUSION: FDG-PET increases the chance of detecting LP of unresectable PDAC after SBRT and can have an important impact on reported outcomes. We recommend obtaining FDG-PET to assess treatment response when evaluating efficacy of SBRT and taking its use into account when comparing clinical data.

Next