NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®)
`
`Gastric Cancer
`
`Version 3.2016
`
`NCCN.org
`
`Continue
`
`Version 3.2016, 08/03/16 © National Comprehensive Cancer Network, Inc. 2016, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®..
`
`Ex. 1045-0001
`
`

`
`Printed by M Ratain on 11/6/2016 3:05:03 PM. For personal use only. Not approved for distribution. Copyright © 2016 National Comprehensive Cancer Network, Inc., All Rights Reserved.
`
`NCCN Guidelines Version 3.2016 Panel Members
`Gastric Cancer
`
`NCCN Guidelines Index
`Gastric Cancer Table of Contents
`Discussion
`
`*Jaffer A. Ajani, MD/Chair † ¤
`The University of Texas
`MD Anderson Cancer Center
`
`*
`
`Thomas A. D’Amico, MD/Vice Chair ¶
`Duke Cancer Institute
`
`Khaldoun Almhanna, MD, MPH †
`Moffitt Cancer Center
`
`David J. Bentrem, MD, MS ¶
`Robert H. Lurie Comprehensive
`Cancer Center of Northwestern
`University
`
`Joseph Chao, MD †
`City of Hope Comprehensive
`Cancer Center
`
`Prajnan Das, MD, MS, MPH §
`The University of Texas
`MD Anderson Cancer Center
`
`Crystal S. Denlinger, MD †
`Fox Chase Cancer Center
`
`Michael Gibson, MD, PhD † ‡ Þ
`Case Comprehensive Cancer
`Center/University Hospitals
`Seidman Cancer Center and
`Cleveland Clinic Taussig
`Cancer Institute
`
`Robert E. Glasgow, MD ¶
`Huntsman Cancer Institute
`at the University of Utah
`
`James A. Hayman, MD, MBA §
`University of Michigan
`Comprehensive Cancer Center
`
`Steven Hochwald, MD ¶
`Roswell Park Cancer Institute
`
`Wayne L. Hofstetter, MD ¶
`The University of Texas
`MD Anderson Cancer Center
`
`Lawrence R. Kleinberg, MD §
`The Sidney Kimmel
`Comprehensive Cancer
`Center at Johns Hopkins
`
`W. Michael Korn, MD ¤ †
`UCSF Helen Diller Family
`Comprehensive Cancer Center
`
`Stephen Leong, MD †
`University of Colorado
`Cancer Center
`
`Catherine Linn, MD Þ
`Vanderbilt-Ingram Cancer Center
`
`A. Craig Lockhart, MD, MHS †
`Siteman Cancer Center
`at Barnes-Jewish Hospital
`and Washington University
`School of Medicine
`
`*
`
`David H. Ilson, MD, PhD † Þ
`Memorial Sloan Kettering
`Cancer Center
`
`Quan P. Ly, MD ¶
`Fred & Pamela Buffett
`Cancer Center
`
`Kyle A. Perry, MD ¶
`The Ohio State University
`Comprehensive Cancer Center -
`James Cancer Hospital and
`Solove Research Institute
`
`George A. Poultsides, MD, MS ¶
`Stanford Cancer Institute
`
`Walter J. Scott, MD ¶
`Fox Chase Cancer Center
`
`Vivian E. Strong, MD ¶
`Memorial Sloan Kettering Cancer Center
`
`Mary Kay Washington, MD, PhD ≠
`Vanderbilt-Ingram Cancer Center
`
`Benny Weksler, MD, MBA ¶
`The University of Tennessee
`Health Science Center
`
`Christopher G. Willett, MD §
`Duke Cancer Institute
`
`Cameron D. Wright, MD ¶
`Massachusetts General Hospital
`Cancer Center
`
`Debra Zelman, JD ¥
`Debbie’s Dream Foundation:
`Curing Stomach Cancer
`
`Paul Fanta, MD ‡
`UC San Diego Moores Cancer Center
`
`Dawn Jaroszewski, MD ¶
`Mayo Clinic Cancer Center
`
`Farhood Farjah, MD ¶
`Fred Hutchinson Cancer Research
`Center/Seattle Cancer Care Alliance
`
`Kimberly L. Johung, MD, PhD §
`Yale Cancer Center/
`Smilow Cancer Hospital
`
`Charles S. Fuchs, MD, MPH †
`Dana-Farber/Brigham and Women’s
`Cancer Center
`
`Rajesh N. Keswani, MD ¤ Þ
`Robert H. Lurie Comprehensive
`Cancer Center of Northwestern
`University
`
`Mary F. Mulcahy, MD ‡ †
`Robert H. Lurie Comprehensive
`Cancer Center of Northwestern
`University
`
`Mark B. Orringer, MD ¶
`University of Michigan
`Comprehensive Cancer Center
`
`Hans Gerdes, MD ¤ Þ
`Memorial Sloan Kettering
`Cancer Center
`NCCN
`Nicole McMillian, MS
`NCCN Guidelines Panel Disclosures
`Hema Sundar, PhD
`Version 3.2016, 08/03/16 © National Comprehensive Cancer Network, Inc. 2016, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®..
`
`Continue
`
`† Medical oncology
`¤ Gastroenterology
`¶ Surgery/Surgical oncology
`Þ Internal medicine
`
`§ Radiotherapy/Radiation oncology
`‡ Hematology/Hematology oncology
`≠ Pathology
`¥ Patient advocate
`*Writing committee member
`
`Ex. 1045-0002
`
`

`
`Printed by M Ratain on 11/6/2016 3:05:03 PM. For personal use only. Not approved for distribution. Copyright © 2016 National Comprehensive Cancer Network, Inc., All Rights Reserved.
`
`NCCN Guidelines Version 3.2016 Sub-Committees
`Gastric Cancer
`
`NCCN Guidelines Index
`Gastric Cancer Table of Contents
`Discussion
`
`Principles of Systemic Therapy
`Mary F. Mulcahy, MD ‡ †/Lead
`Robert H. Lurie Comprehensive Cancer
`Center of Northwestern University
`
`Jaffer A. Ajani, MD † ¤
`The University of Texas
`MD Anderson Cancer Center
`
`Khaldoun Almhanna, MD, MPH †
`Moffitt Cancer Center
`
`Crystal S. Denlinger, MD †
`Fox Chase Cancer Center
`
`David H. Ilson, MD, PhD † Þ
`Memorial Sloan Kettering Cancer Center
`
`A. Craig Lockhart, MD, MHS †
`Siteman Cancer Center at Barnes-
`Jewish Hospital and Washington
`University School of Medicine
`
`Stephen Leong, MD †
`University of Colorado
`Cancer Center
`
`Principles of Endoscopic Staging and Therapy
`Hans Gerdes, MD ¤ Þ/Lead
`Memorial Sloan Kettering Cancer Center
`
`Rajesh N. Keswani, MD ¤ Þ
`Robert H. Lurie Comprehensive Cancer
`Center of Northwestern University
`
`Principles of Pathologic Review and HER2-neu Testing
`Mary Kay Washington, MD, PhD ≠
`Vanderbilt-Ingram Cancer Center
`
`NCCN Guidelines Panel Disclosures
`Version 3.2016, 08/03/16 © National Comprehensive Cancer Network, Inc. 2016, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®..
`
`Principles of Palliative/Best Supportive Care
`Rajesh N. Keswani, MD ¤ Þ/Lead
`Robert H. Lurie Comprehensive Cancer
`Center of Northwestern University
`
`Hans Gerdes, MD ¤ Þ
`Memorial Sloan Kettering Cancer Center
`
`Mary F. Mulcahy, MD ‡
`Robert H. Lurie Comprehensive
`Cancer Center of Northwestern University
`
`Principles of Genetic Risk Assessment
`Mary Kay Washington, MD, PhD ≠/Co-Lead
`Vanderbilt-Ingram Cancer Center
`
`Crystal S. Denlinger, MD †
`Fox Chase Cancer Center
`
`David H. Ilson, MD, PhD † Þ
`Memorial Sloan Kettering Cancer Center
`
`Mark B. Orringer, MD ¶
`University of Michigan
`Comprehensive Cancer Center
`
`Vivian E. Strong, MD ¶
`Memorial Sloan Kettering Cancer Center
`
`Continue
`
`Principles of Surgery
`Vivian E. Strong, MD ¶/Lead
`Memorial Sloan Kettering Cancer Center
`
`David J. Bentrem, MD, MS ¶
`Robert H. Lurie Comprehensive Cancer
`Center of Northwestern University
`
`Robert E. Glasgow, MD ¶
`Huntsman Cancer Institute
`at the University of Utah
`
`George A. Poultsides, MD, MS ¶
`Stanford Cancer Institute
`
`Principles of Radiation Therapy
`Lawrence R. Kleinberg, MD §/Lead
`The Sidney Kimmel Comprehensive
`Cancer Center at Johns Hopkins
`
`Prajnan Das, MD, MS, MPH §
`The University of Texas
`MD Anderson Cancer Center
`
`James A. Hayman, MD, MBA §
`University of Michigan
`Comprehensive Cancer Center
`
`Christopher Willett, MD §
`Duke Cancer Institute
`
`¤ Gastroenterology
`¶ Surgery/Surgical oncology
`Þ Internal medicine
`§ Radiotherapy/Radiation oncology
`‡ Hematology/Hematology oncology
`≠ Pathology
`
`Ex. 1045-0003
`
`

`
`Printed by M Ratain on 11/6/2016 3:05:03 PM. For personal use only. Not approved for distribution. Copyright © 2016 National Comprehensive Cancer Network, Inc., All Rights Reserved.
`
`NCCN Guidelines Version 3.2016 Table of Contents
`Gastric Cancer
`
`NCCN Guidelines Index
`Gastric Cancer Table of Contents
`Discussion
`
`NCCN Gastric Cancer Guidelines Panel Members
`NCCN Gastric Cancer Guidelines Sub-Committee Members
`Summary of the Guidelines Updates
`Workup and Additional Evaluation (GAST-1)
`Conclusions of Multidisciplinary Review (GAST-2)
`Surgical Outcomes for Patients Who Have Not Received Preoperative Therapy (GAST-3)
`Surgical Outcomes for Patients Who Have Received Preoperative Therapy (GAST-4)
`Post Treatment Assessment/Additional Management (GAST-5)
`Follow-up/Surveillance, Recurrence (GAST-6)
`Palliative Management (GAST-7)
`Principles of Endoscopic Staging and Therapy (GAST-A)
`Principles of Pathologic Review and HER2-neu Testing (GAST-B)
`Principles of Surgery (GAST-C)
`Principles of Genetic Risk Assessment for Gastric Cancer (GAST-D)
`Principles of Multidisciplinary Team Approach for Esophagogastric Cancers (GAST-E)
`Principles of Systemic Therapy (GAST-F)
`Principles of Radiation Therapy (GAST-G)
`Principles of Palliative Care/Best Supportive Care (GAST-H)
`Staging (ST-1)
`
`Clinical Trials: NCCN believes that
`the best management for any cancer
`patient is in a clinical trial.
`Participation in clinical trials is
`especially encouraged.
`To find clinical trials online at NCCN
`Member Institutions, click here:
`nccn.org/clinical_trials/physician.html.
`NCCN Categories of Evidence and
`Consensus: All recommendations
`are category 2A unless otherwise
`specified.
`See NCCN Categories of Evidence
`and Consensus.
`
`The NCCN Guidelines® are a statement of evidence and consensus of the authors regarding their views of currently accepted approaches to treatment.
`Any clinician seeking to apply or consult the NCCN Guidelines is expected to use independent medical judgment in the context of individual clinical
`circumstances to determine any patient’s care or treatment. The National Comprehensive Cancer Network® (NCCN®) makes no representations or
`warranties of any kind regarding their content, use or application and disclaims any responsibility for their application or use in any way. The NCCN
`Guidelines are copyrighted by National Comprehensive Cancer Network®. All rights reserved. The NCCN Guidelines and the illustrations herein may not
`be reproduced in any form without the express written permission of NCCN. ©2016.
`
`Version 3.2016, 08/03/16 © National Comprehensive Cancer Network, Inc. 2016, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®..
`
`Ex. 1045-0004
`
`

`
`Printed by M Ratain on 11/6/2016 3:05:03 PM. For personal use only. Not approved for distribution. Copyright © 2016 National Comprehensive Cancer Network, Inc., All Rights Reserved.
`
`NCCN Guidelines Index
`Gastric Cancer Table of Contents
`Discussion
`
`NCCN Guidelines Version 3.2016 Updates
`Gastric Cancer
`Updates in Version 3.2016 of the NCCN Guidelines for Gastric Cancer from Version 2.2016 include:
`• The Discussion text has been updated to reflect the changes in the algorithm. (MS-1)
`Updates in Version 2.2016 of the NCCN Guidelines for Gastric Cancer from Version 1.2016 include:
`GAST-6
`• Follow-up/Surveillance: Third bullet revised, "Radiologic imaging Chest/Abdominal CT with contrast or upper GI endoscopy, as clinically
`indicated."
`GAST-F--Principles of Systemic Therapy
`• Heading revised: “Systemic Therapy for Metastatic or Locally Advanced Cancer...” changed to “Systemic Therapy for Unresectable Locally
`Advanced, Recurrent or Metastatic Disease...”
`GAST-H--Principles of Palliative/Best Supportive Care
`• This section was extensively revised.
`Updates in Version 1.2016 of the NCCN Guidelines for Gastric Cancer from Version 3.2015 include:
`Global Changes
`• Notations for clinical (c), surgical (yp), and pathological (p) staging were added to the tumor classifcation as appropriate throughout the
`guidelines.
`GAST-1
`• Workup:
`Seventh bullet revised: "Endoscopic resection (ER) may contribute to accurate staging of early-stage cancers (T1a or T1b)."
`Twelfth bullet revised: "Smoking cessation advice, counseling, and pharmacotherapy as indicated."
`• Locoregional pathway: "Medically fit, unresectable" changed to "Surgically unresectable."
`• Additional Evaluation: Revised recommendation "Consider laparoscopy with cytology."
`• Footnote "f" revised: "Smoking cessation guidelines are available from the U.S. Public Health Service at: http://www.ahrq.gov/professionals/
`clinicians-providers/guidelines-recommendations/tobacco/clinicians/update/treating_tobacco_use08.pdf. See NCCN Guidelines for Smoking
`Cessation."
`• Footnote "i" revised: "Medically able to tolerate major abdominal surgery."
`• Footnote "j" revised: "Medically unfit patients Medically unable to tolerate major surgery or medically fit patients who decline surgery."
`• Footnote "k" revised: "Laparoscopy with cytology is performed to evaluate for peritoneal spread when considering chemoradiation or
`surgery. Laparoscopy with cytology is not indicated if a palliative resection is planned. Laparoscopy with cytology is indicated for clinical
`stage T1b or higher."
`
`GAST-2
`• Under the new column heading "Conclusions of Multidisciplinary Review" revised pathways, "Laparoscopic findings of Locoregional
`disease (cM0)" and "Laparoscopic findings of Metastatic disease (cM1)."
`• Primary treatment for cT2 or higher, Any N: Revised, "Preoperative Perioperative chemotherapy (category 1)."
`
`GAST-3
`• Postoperative management for R0 resection; pT2, N0: "Chemotherapy for patients who have undergone primary D2 lymph node dissection"
`UPDATES
`removed as an option.
`1 OF 2
`Version 3.2016, 08/03/16 © National Comprehensive Cancer Network, Inc. 2016, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®..
`
`Continued
`
`Ex. 1045-0005
`
`

`
`Printed by M Ratain on 11/6/2016 3:05:03 PM. For personal use only. Not approved for distribution. Copyright © 2016 National Comprehensive Cancer Network, Inc., All Rights Reserved.
`
`NCCN Guidelines Version 3.2016 Updates
`Gastric Cancer
`
`NCCN Guidelines Index
`Gastric Cancer Table of Contents
`Discussion
`
`GAST-4
`• After R0 resection, tumor classification revised: "T2, N0" changed
`to "Node negative (yp Any T, N0)" and "T3, T4, Any N or Any T, N+"
`changed to "Node positive (yp Any T, N+)."
`
`GAST-5
`• First column revised: "Medically fit, Unresectable disease or Non-
`surgical..."
`
`GAST-6
`Follow-up/Surveillance: Third bullet revised, "Radiologic imaging or
`upper GI endoscopy, as clinically indicated."
`
`GAST-A (2 of 4) Principles of Endoscopy Staging and Therapy
`• The following terms were revised: "T-stage category" and
`"M-stage category."
`
`GAST-C (1 of 2) Principles of Surgery
`• Section heading revised: "N Staging Category Determination."
`Second bullet revised: "If laparoscopy with cytology is
`performed as a separate procedure, peritoneal washings should
`be performed as well."
`• The term "jejunostomy tube" changed to "feeding tube"
`
`GAST-F: Principles of Systemic Therapy
`1 of 11
`• Third bullet revised: "For metastatic adenocarcinoma trastuzumab
`can be added to chemotherapy if tumor overexpresses HER2-neu.
`Trastuzumab should be added to chemotherapy for HER2-neu
`overexpressing metastatic adenocarcinoma."
`• Footnote references were updated.
`2 of 11
`• Preoperative Chemoradiation: "Irinotecan and cisplatin
`(category 2B)" removed as an option.
`• Perioperative Chemotherapy:
`ECF (epirubicin, cisplatin, and fluorouracil) changed from
`category 1 to category 2B.
`ECF modifications changed from category 2A to category 2B for
`all modifications.
`Version 3.2016, 08/03/16 © National Comprehensive Cancer Network, Inc. 2016, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®..
`
`GAST-F: Principles of Systemic Therapy (continued)
`3 of 11 Systemic Therapy for Metastatic or Locally Advanced
`Cancer (where local therapy is not indicated)
`• First-Line Therapy; Preferred Regimens
`"DCF (docetaxel, cisplatin, and fluorouracil) (category 1)"
`removed as an option.
`The following regimens were removed from the list of "Preferred
`Regimens" and added to the list of "Other Regimens"
` ◊ DCF modifications
` ◊ ECF (epirubicin, cisplatin, and fluorouracil) (category 1)
` ◊ ECF modifications (category 1)
`• First-Line Therapy; Other Regimens
`"Docetaxel and irinotecan" removed as an option.
`• The "Alternative Regimens for Consideration" section was
`removed along with the following systemic therapy options:
`Mitomycin and irinotecan
`Mitomycin and fluorouracil
`4 of 11 Principles of Systemic Therapy—Regimens and Dosing
`Schedules
`• The Regimen and dosing schedules pages were updated to reflect
`the changes on GAST- 2 of 11 and GAST-F 3 of 11.
`10 of 11
`• The reference pages were updated to reflect the changes in the
`algorithm.
`
`GAST-G 3 of 4 Principles of Radiation
`• Supportive Care: The following bullet was removed: "Vitamin B12,
`iron, and calcium level should be closely monitored, especially
`for patients receiving postoperative treatment. Monthly B12 shots
`may be needed because of loss of intrinsic factor. Iron absorption
`is reduced without gastric acid. Oral supplementation, given with
`acid such as orange juice, can often maintain adequate levels.
`Calcium supplementation should also be encouraged."
`
`UPDATES
`2 OF 2
`
`Ex. 1045-0006
`
`

`
`Printed by M Ratain on 11/6/2016 3:05:03 PM. For personal use only. Not approved for distribution. Copyright © 2016 National Comprehensive Cancer Network, Inc., All Rights Reserved.
`
`WORKUP
`• H&P
`• Upper GI endoscopy and biopsya
`• Chest/abdomen/pelvic CT with oral
`and IV contrast
`• PET-CT evaluation if no evidence of M1
`diseaseb and if clinically indicated
`• CBC and comprehensive chemistry
`profile
`• Endoscopic ultrasound (EUS) if no
`evidence of M1 disease (preferred)
`• Endoscopic resection (ER) may
`contribute to accurate staging of early-
`stage cancers (T1a or T1b)c
`• Biopsy of metastatic disease as
`clinically indicated
`• HER2-neu testing if metastatic
`adenocarcinoma is documented/
`suspectedd
`• Assess Siewert categorye
`• Nutritional assessment and counseling
`• Smoking cessation advice, counseling,
`and pharmacotherapy as indicatedf
`• Screen for family historyg
`
`CLINICAL
`STAGEh
`
`cTis
`or
`cT1a
`
`Locoregional
`(cM0)
`
`Stage IV
`(cM1)
`
`NCCN Guidelines Index
`Gastric Cancer Table of Contents
`Discussion
`
`ADDITIONAL
`EVALUATION
`
`Medically fiti
`
`Non-surgical candidatej
`
`Medically fit,e,i
`potentially
`resectable
`
`Surgicallye,i
`unresectable
`
`Non-surgical
`candidatej
`
`Multidisciplinary
`review preferredl
`
`See GAST-2
`
`Consider
`laparoscopy
`with
`cytologyk
`(category 2B)
`
`Palliative
`Management
`(see GAST-7)
`
`aSee Principles of Endoscopic Staging and Therapy (GAST-A).
`bMay not be appropriate for T1.
`cEMR may also be therapeutic for early-stage disease/lesions.
`dSee Principles of Pathologic Review and HER2-neu Testing (GAST-B).
`eSee Principles of Surgery (GAST-C).
`fSee NCCN Guidelines for Smoking Cessation.
`gSee Principles of Genetic Risk Assessment for Gastric Cancer (GAST-D). Also see NCCN
`Guidelines for Colorectal Cancer Screening and NCCN Guidelines for Genetic/Familial
`High-Risk Assessment: Breast and Ovarian.
`
`hSee Staging (ST-1) for tumor classification.
`iMedically able to tolerate major surgery.
`jMedically unable to tolerate major surgery or medically fit patients who
`decline surgery.
`kLaparoscopy with cytology is performed to evaluate for peritoneal spread
`when considering chemoradiation or surgery. Laparoscopy with cytology is
`not indicated if a palliative resection is planned. Laparoscopy with cytology
`is indicated for clinical stage T1b or higher.
`lSee Principles of Multidisciplinary Team Approach (GAST-E).
`
`GAST-1
`
`NCCN Guidelines Version 3.2016
`Gastric Cancer
`
`Note: All recommendations are category 2A unless otherwise indicated.
`Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged.
`
`Version 3.2016, 08/03/16 © National Comprehensive Cancer Network, Inc. 2016, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.
`
`Ex. 1045-0007
`
`

`
`Printed by M Ratain on 11/6/2016 3:05:03 PM. For personal use only. Not approved for distribution. Copyright © 2016 National Comprehensive Cancer Network, Inc., All Rights Reserved.
`
`CONCLUSIONS OF MULTIDISCIPLINARY
`REVIEW
`
`cTis or cT1a
`
`Non-surgical
`candidatej
`Medically fit e,i
`
`Medically fit,e,i
`potentially
`resectable
`
`cT1b
`
`cT2 or higher,
`Any N
`
`FINAL STAGEh
`
`PRIMARY TREATMENT
`
`NCCN Guidelines Index
`Gastric Cancer Table of Contents
`Discussion
`
`ERa
`ERa
`or
`Surgerye,i
`Surgeryd,e,m
`Surgeryd,e,m
`or
`Perioperative chemotherapyn
`(category 1)
`or
`Preoperative chemoradiationn,o
`(category 2B)
`
`Endoscopic
`surveillancea
`
`Surgical Outcomes
`for Patients Who
`Have Not Received
`Preoperative Therapy
`(see GAST-3)
`
`Surgical Outcomes
`for Patients Who Have
`Received Preoperative
`Therapy (see GAST-4)
`
`Surgeryd,e,m
`
`Locoregional
`disease (cM0)
`
`Surgically,e
`unresectable
`
`Concurrent fluoropyrimidine- or taxane-based
`chemoradiationn,o (category 1)
`or
`Chemotherapyn
`
`Non-surgical candidatej
`
`Metastatic disease (cM1)
`aSee Principles of Endoscopic Staging and Therapy (GAST-A).
`dSee Principles of Pathologic Review and HER2-neu Testing (GAST-B).
`eSee Principles of Surgery (GAST-C).
`hSee Staging (ST-1) for tumor classification.
`iMedically able to tolerate major surgery.
`
`Concurrent fluoropyrimidine- or taxane-based
`chemoradiationn,o (category 1) (Definitive)
`or
`Palliative Management (see GAST-7)
`Palliative Management (see GAST-7)
`jMedically unable to tolerate major surgery or medically fit patients who decline surgery.
`mSurgery as primary therapy is appropriate for ≥T1b cancer or actively bleeding cancer,
`or when postoperative therapy is preferred.
`nSee Principles of Systemic Therapy (GAST-F).
`oSee Principles of Radiation Therapy (GAST-G).
`
`Post-Treatment
`Assessment/
`Additional
`Management
`(see GAST-5)
`Post-Treatment
`Assessment/
`Additional
`Management
`(see GAST-5)
`
`GAST-2
`
`NCCN Guidelines Version 3.2016
`Gastric Cancer
`
`Note: All recommendations are category 2A unless otherwise indicated.
`Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged.
`
`Version 3.2016, 08/03/16 © National Comprehensive Cancer Network, Inc. 2016, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.
`
`Ex. 1045-0008
`
`

`
`Printed by M Ratain on 11/6/2016 3:05:03 PM. For personal use only. Not approved for distribution. Copyright © 2016 National Comprehensive Cancer Network, Inc., All Rights Reserved.
`
`NCCN Guidelines Index
`Gastric Cancer Table of Contents
`Discussion
`
`SURGICAL OUTCOMES/CLINICAL
`PATHOLOGIC FINDINGS
`(Patients Have Not Received
`Preoperative Chemotherapy or
`Chemoradiation)
`
`TUMOR
`CLASSIFICATIONh
`pTis or
`pT1, N0
`
`R0 resectionp
`
`pT2, N0
`
`pT3, pT4, Any N
`or Any pT, N+
`
`R1 resectionp
`
`R2 resectionp
`
`pM1
`
`POSTOPERATIVE MANAGEMENT
`
`Surveillance
`Surveillance
`or
`Fluoropyrimidine (fluorouracil or capecitabine)n,q
`then fluoropyrimidine-based chemoradiation,n,o
`then fluoropyrimidine (fluorouracil or capecitabine)n,q for
`selected patientsr
`
`Fluoropyrimidine (fluorouracil or capecitabine)n,q
`then fluoropyrimidine-based chemoradiation,n,o
`then fluoropyrimidine (fluorouracil or capecitabine)n,q
`(category 1)
`or
`Chemotherapy for patients who have undergone primary D2
`lymph node dissectione,n
`Chemoradiationn,o (fluoropyrimidine-based)
`Chemoradiationn,o (fluoropyrimidine-based)
`or
`Palliative Management (see GAST-7), as clinically indicated
`
`Follow-up
`(see GAST-6)
`
`Palliative
`Management
`(see GAST-7)
`
`eSee Principles of Surgery (GAST-C).
`hSee Staging (ST-1) for tumor classification.
`nSee Principles of Systemic Therapy (GAST-F).
`oSee Principles of Radiation Therapy (GAST-G).
`pR0 = No cancer at resection margins, R1 = Microscopic residual cancer, R2 = Macroscopic residual cancer or M1.
`qSmalley SR, Benedetti JK, Haller DG, et al. Updated analysis of SWOG-directed intergroup study 0116: a phase III trial of adjuvant radiochemotherapy versus
`observation after curative gastric cancer resection. J Clin Oncol 2012;30:2327-2333. See Principles of Systemic Therapy (GAST-F).
`rHigh-risk features include poorly differentiated or higher grade cancer, lymphovascular invasion, neural invasion, or <50 years of age or patients who did not undergo
`D2 lymph node dissection.
`
`GAST-3
`
`NCCN Guidelines Version 3.2016
`Gastric Cancer
`
`Note: All recommendations are category 2A unless otherwise indicated.
`Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged.
`
`Version 3.2016, 08/03/16 © National Comprehensive Cancer Network, Inc. 2016, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.
`
`Ex. 1045-0009
`
`

`
`Printed by M Ratain on 11/6/2016 3:05:03 PM. For personal use only. Not approved for distribution. Copyright © 2016 National Comprehensive Cancer Network, Inc., All Rights Reserved.
`
`NCCN Guidelines Index
`Gastric Cancer Table of Contents
`Discussion
`
`SURGICAL OUTCOMES/CLINICAL
`PATHOLOGIC FINDINGS
`(Patients Have Received
`Preoperative Chemotherapy or
`Chemoradiation)
`
`R0 resectionp
`
`R1 resectionp
`
`R2 resectionp
`
`ypM1
`
`TUMOR
`CLASSIFICATIONh
`
`POSTOPERATIVE MANAGEMENT
`
`Node negative
`(yp Any T, N0)
`
`Surveillance
`or
`Chemotherapy,n
`if received preoperatively (category 1)
`
`Node positive
`(yp Any T, N+)
`
`Chemotherapy,n
`if received preoperatively (category 1)
`
`Chemoradiationn,o (fluoropyrimidine-based),
`only if not received preoperatively
`
`Chemoradiationn,o (fluoropyrimidine-based)
`only if not received preoperatively
`or
`Palliative Management (see GAST-7), as clinically indicated
`
`hSee Staging (ST-1) for tumor classification.
`nSee Principles of Systemic Therapy (GAST-F).
`oSee Principles of Radiation Therapy (GAST-G).
`pR0 = No cancer at resection margins, R1 = Microscopic residual cancer, R2 = Macroscopic residual cancer or M1.
`
`Follow-up
`(see GAST-6)
`
`Palliative
`Management
`(see GAST-7)
`
`GAST-4
`
`NCCN Guidelines Version 3.2016
`Gastric Cancer
`
`Note: All recommendations are category 2A unless otherwise indicated.
`Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged.
`
`Version 3.2016, 08/03/16 © National Comprehensive Cancer Network, Inc. 2016, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.
`
`Ex. 1045-0010
`
`

`
`Printed by M Ratain on 11/6/2016 3:05:03 PM. For personal use only. Not approved for distribution. Copyright © 2016 National Comprehensive Cancer Network, Inc., All Rights Reserved.
`
`POST-TREATMENT
`ASSESSMENT
`
`OUTCOME
`
`NCCN Guidelines Index
`Gastric Cancer Table of Contents
`Discussion
`
`ADDITIONAL
`MANAGEMENT
`
`Unresectable disease or
`Non-surgical candidatej
`following primary
`treatment
`
`Restaging:
`• Chest/abdomen/pelvic CT
`with oral and IV contrast
`• CBC and comprehensive chemistry
`profile
`• PET/CT scan as clinically indicated
`
`Resectable and medically operable
`
`Unresectable
`or
`Medically inoperable
`and/or
`Metastatic disease
`
`Surgery
`(preferred),d,e
`if appropriate
`or
`Follow-up
`(see GAST-6)
`
`Palliative
`Management
`(see GAST-7)
`
`dSee Principles of Pathologic Review and HER2-neu Testing (GAST-B).
`eSee Principles of Surgery (GAST-C).
`jMedically unable to tolerate major surgery or medically fit patients who decline surgery.
`
`GAST-5
`
`NCCN Guidelines Version 3.2016
`Gastric Cancer
`
`Note: All recommendations are category 2A unless otherwise indicated.
`Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged.
`
`Version 3.2016, 08/03/16 © National Comprehensive Cancer Network, Inc. 2016, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.
`
`Ex. 1045-0011
`
`

`
`Printed by M Ratain on 11/6/2016 3:05:03 PM. For personal use only. Not approved for distribution. Copyright © 2016 National Comprehensive Cancer Network, Inc., All Rights Reserved.
`
`NCCN Guidelines Index
`Gastric Cancer Table of Contents
`Discussion
`
`FOLLOW-UP/SURVEILLANCE
`
`RECURRENCE
`
`Consider surgeryd,e
`or
`Palliative Management
`(GAST-7)
`
`Locoregional
`recurrences
`
`Resectable and
`medically operable
`
`Unresectable
`or medically
`inoperable
`
`See Palliative Management
`(GAST-7)
`
`Metastatic
`disease
`
`See Palliative Management
`(GAST-7)
`
`• H&P
`every 3–6 mo for 1–2 y,
`every 6–12 mo for 3–5 y,
`then annually
`• CBC and chemistry
`profile as indicated
`• Chest/Abdominal CT
`with contrast or upper
`GI endoscopy, as
`clinically indicated
`• Monitor for nutritional
`deficiency (eg, B12
`and iron) in surgically
`resected patients and
`treat as indicated
`
`dSee Principles of Pathologic Review and HER2-neu Testing (GAST-B).
`eSee Principles of Surgery (GAST-C).
`sReview if surgery is appropriate for patients with isolated local recurrences. Surgery should be considered as an option for locoregional recurrence in medically fit
`patients.
`
`GAST-6
`
`NCCN Guidelines Version 3.2016
`Gastric Cancer
`
`Note: All recommendations are category 2A unless otherwise indicated.
`Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged.
`
`Version 3.2016, 08/03/16 © National Comprehensive Cancer Network, Inc. 2016, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.
`
`Ex. 1045-0012
`
`

`
`Printed by M Ratain on 11/6/2016 3:05:03 PM. For personal use only. Not approved for distribution. Copyright © 2016 National Comprehensive Cancer Network, Inc., All Rights Reserved.
`
`NCCN Guidelines Index
`Gastric Cancer Table of Contents
`Discussion
`
`PERFORMANCE STATUS
`
`PALLIATIVE
`MANAGEMENT
`
`Karnofsky performance score ≥60%
`or
`ECOG performance score ≤2
`
`Systemic therapyn
`or
`Clinical trial
`or
`Palliative/Best supportive caret
`
`Karnofsky performance score <60%
`or
`ECOG performance score ≥3
`
`Palliative/Best supportive caret
`
`Unresectable locally
`advanced, Locally
`recurrent or metastatic
`disease
`
`nSee Principles of Systemic Therapy (GAST-F).
`tSee Principles of Palliative Care/Best Supportive Care (GAST-H).
`
`GAST-7
`
`NCCN Guidelines Version 3.2016
`Gastric Cancer
`
`Note: All recommendations are category 2A unless otherwise indicated.
`Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged.
`
`Version 3.2016, 08/03/16 © National Comprehensive Cancer Network, Inc. 2016, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.
`
`Ex. 1045-0013
`
`

`
`Printed by M Ratain on 11/6/2016 3:05:03 PM. For personal use only. Not approved for distribution. Copyright © 2016 National Comprehensive Cancer Network, Inc., All Rights Reserved.
`
`NCCN Guidelines Index
`Gastric Cancer Table of Contents
`Discussion
`
`PRINCIPLES OF ENDOSCOPIC STAGING AND THERAPY
`Endoscopy has become an important tool in the diagnosis, staging, treatment, and palliation of patients with gastric cancer. Although some
`endoscopy procedures can be performed without anesthesia, most are performed with conscious sedation administered by the endoscopist
`or assisting nurse or deeper anesthesia (monitored anesthesia care) provided by the endoscopist and nurse, a nurse anesthetist, or an
`anesthesiologist. Some patients who are at risk for aspiration during endoscopy may require general anesthesia.
`
`DIAGNOSIS
`• Diagnostic and surveillance endoscopies are performed with the goal of determining the presence and location of neoplastic disease and
`to biopsy any suspicious lesion. Thus, an adequate endoscopic exam addresses both of these components. The location of the tumor in
`the stomach (cardia, fundus, body, antrum, and pylorus) and relative to the esophagogastric junction (EGJ) for proximal tumors should be
`carefully recorded to assist with treatment planning and follow-up examinations.
`• Multiple (6–8) biopsies using standard size endoscopy forceps should be performed to provide adequate sized material for histologic
`interpretation, especially in the setting of an ulcerated lesion.1,2 Larger forceps may improve the yield.
`• Endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) can be performed in the evaluation of small lesions.
`EMR or ESD of focal nodules ≤2 cm can be safely performed to provide a larger specimen that can be better assessed by the pathologist,
`providing greater information on degree of differentiation, the presence of lymphovascular invasion (LVI), and the depth of infiltration,
`thereby providing accurate T-staging.3 Such excisional biopsies have the potential of being therapeutic.4
`• Cytologic brushings or washing