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Becky Krumm and production of the 19th edition of the Medical Senior Managing Editor Knowledge Self-Assessment Program" (MKSAP* 19) made by the following people: Jackie Twomey Associate Managing Editor Graphic Design: Barry Moshinski (Director, Graphic Services), Mike Ripca (Technical Administrator, Graphic Julia Nawrocki Services), Raymond DeJohn (Designer, Graphic Services) Digital Content Associate/Editor Production/Systems: Dan Hoffmann (Director, Linnea Donnarumma Information Technology), Scott Hurd (Manager, Content Senior Medical Editor Systems), Neil Kohl (Senior Architect), and Chris Amanda Cowley Patterson (Senior Architect). Medical Editor MKSAP 19 Digital: Under the leadership of Steven Spadt Sandy Crump (Senior Vice President, Technology), the development Medical Editor of the digital version of MKSAP 19 was implemented by ACP’s Digital Products and Services Department, directed Georgette Forgione and led by Brian Sweigard (Director, Digital Products Medical Editor and Services). Other members of the team included Dan Beth Goldner Barron (Senior Web Application Developer/Architect), Medical Editor Callie Cramer (Data Visualization/Web Developer), Chris Forrest (Senior Web Application Developer), Kathleen Suzanne Meyers Hoover (Senior Web Developer), Kara Regis (Manager, Medical Editor User Interface Design and Development), Brad Lord Elise Paxson (Senior Web Application Developer/Architect), and John Medical Editor McKnight (Senior Web Developer).

Becky Krumm and production of the 19th edition of the Medical Senior Managing Editor Knowledge Self-Assessment Program" (MKSAP* 19) made by the following people: Jackie Twomey Associate Managing Editor Graphic Design: Barry Moshinski (Director, Graphic Services), Mike Ripca (Technical Administrator, Graphic Julia Nawrocki Services), Raymond DeJohn (Designer, Graphic Services) Digital Content Associate/Editor Production/Systems: Dan Hoffmann (Director, Linnea Donnarumma Information Technology), Scott Hurd (Manager, Content Senior Medical Editor Systems), Neil Kohl (Senior Architect), and Chris Amanda Cowley Patterson (Senior Architect). Medical Editor MKSAP 19 Digital: Under the leadership of Steven Spadt Sandy Crump (Senior Vice President, Technology), the development Medical Editor of the digital version of MKSAP 19 was implemented by ACP’s Digital Products and Services Department, directed Georgette Forgione and led by Brian Sweigard (Director, Digital Products Medical Editor and Services). Other members of the team included Dan Beth Goldner Barron (Senior Web Application Developer/Architect), Medical Editor Callie Cramer (Data Visualization/Web Developer), Chris Forrest (Senior Web Application Developer), Kathleen Suzanne Meyers Hoover (Senior Web Developer), Kara Regis (Manager, Medical Editor User Interface Design and Development), Brad Lord Elise Paxson (Senior Web Application Developer/Architect), and John Medical Editor McKnight (Senior Web Developer). Chuck Graver The College also wishes to acknowledge that many other Finance and Operations Administrator persons, too numerous to mention, have contributed to the production of this program. Without their dedicated Kimberly Kerns efforts, this program would not have been possible. Administrative Coordinator

Chuck Graver The College also wishes to acknowledge that many other Finance and Operations Administrator persons, too numerous to mention, have contributed to the production of this program. Without their dedicated Kimberly Kerns efforts, this program would not have been possible. Administrative Coordinator Disclosures of relationships with any entity producing, MKSAP Resource Page marketing, reselling, or distributing health care goods or services consumed by, or used on, patients. Individuals not The MKSAP Resource Page (www.acponline.org/mksap19- listed below have nothing to disclose. resources) provides access to MKSAP 19 online answer sheets for transcribing answers from the print edition; access to Caroline Block, MD, Section Editor MKSAP 19 Digital; Board Basics"; information on Continuing Research/Grants Medical Education (CME), Maintenance of Certification (MOC), Bayer, Pfizer, Bristol Myers Squibb, Genzyme, Millennium, and international Continuing Professional Development Odonate Therapeutics, Inc. (CPD) and MOC; errata; and other new information. Davoren Chick, MD, FACP Other (Owner) International MOC/CPD Coding 101, LLC Information and instructions on submission of interna- Tabassum Salam, MD, MBA, FACP tional MOC/CPD is available by accessing the CME/MOC/ Consultantship CPD tab on the left navigation menu of MKSAP 19 Digital. Johnson and Johnson

Disclosures of relationships with any entity producing, MKSAP Resource Page marketing, reselling, or distributing health care goods or services consumed by, or used on, patients. Individuals not The MKSAP Resource Page (www.acponline.org/mksap19- listed below have nothing to disclose. resources) provides access to MKSAP 19 online answer sheets for transcribing answers from the print edition; access to Caroline Block, MD, Section Editor MKSAP 19 Digital; Board Basics"; information on Continuing Research/Grants Medical Education (CME), Maintenance of Certification (MOC), Bayer, Pfizer, Bristol Myers Squibb, Genzyme, Millennium, and international Continuing Professional Development Odonate Therapeutics, Inc. (CPD) and MOC; errata; and other new information. Davoren Chick, MD, FACP Other (Owner) International MOC/CPD Coding 101, LLC Information and instructions on submission of interna- Tabassum Salam, MD, MBA, FACP tional MOC/CPD is available by accessing the CME/MOC/ Consultantship CPD tab on the left navigation menu of MKSAP 19 Digital. Johnson and Johnson Leonard B. Saltz, MD Continuing Medical Education Research/Grants The American College of Physicians is accredited by the Taiho Pharmaceuticals Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for Acknowledgments physicians.

Leonard B. Saltz, MD Continuing Medical Education Research/Grants The American College of Physicians is accredited by the Taiho Pharmaceuticals Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for Acknowledgments physicians. The American College of Physicians (ACP) gratefully The American College of Physicians designates this endur- acknowledges the special contributions to the development ing material, MKSAP 19, for a maximum of 300 AMA PRA

Category 1 CreditsTM. Physicians should claim only the the MKSAP 19 Resource Page, may be used to transcribe credit commensurate with the extent of their participa- answers onto the online answer sheets. Users may tion in the activity. then submit their answers to qualify for CME credits or MOC points (see below for information on Opting in for Up to 18 AMA PRA Category 1 CreditsTM are available from MOC). Users who prefer to record their answers on a August 31, 2021, to August 31, 2024, for the MKSAP 19 paper answer sheet should save their answer sheet for Oncology section. future use. Users who study with MKSAP 19 print can also submit their answers directly within MKSAP 19 Digital by accessing the self-assessment questions dash- Learning Objectives board and selecting the preferred subspecialty section The learning objectives of MKSAP 19 are to: to begin answering questions.

Category 1 CreditsTM. Physicians should claim only the the MKSAP 19 Resource Page, may be used to transcribe credit commensurate with the extent of their participa- answers onto the online answer sheets. Users may tion in the activity. then submit their answers to qualify for CME credits or MOC points (see below for information on Opting in for Up to 18 AMA PRA Category 1 CreditsTM are available from MOC). Users who prefer to record their answers on a August 31, 2021, to August 31, 2024, for the MKSAP 19 paper answer sheet should save their answer sheet for Oncology section. future use. Users who study with MKSAP 19 print can also submit their answers directly within MKSAP 19 Digital by accessing the self-assessment questions dash- Learning Objectives board and selecting the preferred subspecialty section The learning objectives of MKSAP 19 are to: to begin answering questions. e Close gaps between actual care in your practice and 2. Users of MKSAP 19 Digital can enter their answers within preferred standards of care, based on best evidence the digital program by accessing the self-assessment e Diagnose disease states that are less common and some- questions dashboard and selecting the preferred subspe- times overlooked or confusing cialty section to begin answering questions and clicking e Improve clinical management decisions that affect the Submit CME button once they qualify for CME and patient safety and quality of care are ready to submit. Learners should keep in mind their e Determine when to refer patients for care by medical yearly CME and MOC deadlines when determining the subspecialists, surgeons, and other members of the health appropriate time to submit. care team

e Close gaps between actual care in your practice and 2. Users of MKSAP 19 Digital can enter their answers within preferred standards of care, based on best evidence the digital program by accessing the self-assessment e Diagnose disease states that are less common and some- questions dashboard and selecting the preferred subspe- times overlooked or confusing cialty section to begin answering questions and clicking e Improve clinical management decisions that affect the Submit CME button once they qualify for CME and patient safety and quality of care are ready to submit. Learners should keep in mind their e Determine when to refer patients for care by medical yearly CME and MOC deadlines when determining the subspecialists, surgeons, and other members of the health appropriate time to submit. care team e Pass the ABIM Certification Examination Learners’ CME/MOC submission progress will be shown on e Pass the ABIM Maintenance of Certification Examination the MKSAP 19 Digital CME/MOC/CPD page.

e Close gaps between actual care in your practice and 2. Users of MKSAP 19 Digital can enter their answers within preferred standards of care, based on best evidence the digital program by accessing the self-assessment e Diagnose disease states that are less common and some- questions dashboard and selecting the preferred subspe- times overlooked or confusing cialty section to begin answering questions and clicking e Improve clinical management decisions that affect the Submit CME button once they qualify for CME and patient safety and quality of care are ready to submit. Learners should keep in mind their e Determine when to refer patients for care by medical yearly CME and MOC deadlines when determining the subspecialists, surgeons, and other members of the health appropriate time to submit. care team e Pass the ABIM Certification Examination Learners’ CME/MOC submission progress will be shown on e Pass the ABIM Maintenance of Certification Examination the MKSAP 19 Digital CME/MOC/CPD page. Opting in for MOC Target Audience MKSAP 19 users can opt in for simultaneous submission of e General internal medicine specialists, including primary CME and MOC points as they answer self-assessment ques- care physicians and hospitalists tions. To opt in, users will be required to complete a form e Internal medicine subspecialists who desire to remain up requesting their name, date of birth, and ABIM number. to date in internal medicine The MOC Opt-in Form will be presented during a user’s e Residents preparing for the ABIM Internal Medicine first CME submission and needs to be completed only once. Certification Examination e Physicians engaged in the ABIM Maintenance of Certification Longitudinal Assessment Option, pre- ABIM Maintenance of Certification paring for the ABIM Internal Medicine Maintenance of Successful completion of the CME activity, which includes Certification Examination, or engaged with the ABIM participation in the evaluation component, enables Focused Practice in Hospital Medicine program the participant to earn up to 300 medical knowledge MOC points in the ABIM’s MOC program. It is the CME activity provider’s responsibility to submit participant Earn CME Credits or MOC Points Online completion information to ACCME for the purpose of To earn CME credits or to apply for MOC points, MKSAP granting MOC credit. users need to answer at least one of two questions correctly (earning a score of at least 50%) and click the Submit CME button. Each single MKSAP 19 self-assessment question Disclosure Policy qualifies for one quarter of a CME credit hour or ABIM It is the policy of the American College of Physicians (ACP) MOC point. to ensure balance, independence, objectivity, and scientific rigor in all of its educational activities. To this end, and con- MKSAP 19 Subscribers can enter their self-assessment sistent with the policies of the ACP and the Accreditation question answers and submit for CME/MOC in two Council for Continuing Medical Education (ACCME), con- ways: tributors to all ACP continuing medical education activities 1. Users of MKSAP 19 Complete who prefer to use their are required to disclose all relevant financial relationships print books and a paper answer sheet to study and record with any entity producing, marketing, re-selling, or dis- their answers can use the printed answer sheet at the tributing health care goods or services consumed by, or back of this book to record their answers. The corre- used on, patients. Contributors are required to use generic sponding online answer sheets, which are available on names in the discussion of therapeutic options and are

required to identify any unapproved, off-label, or investiga- High Value Care Key Points tive use of commercial products or devices. Where a trade Key Points in the text that relate to High Value Care concepts name is used, all available trade names for the same product (that is, concepts that discuss balancing clinical benefit with type are also included. If trade-name products manufac- costs and harms) are designated by the HVC icon [HVC]. tured by companies with whom contributors have rela- tionships are discussed, contributors are asked to provide evidence-based citations in support of the discussion. The Educational Disclaimer information is reviewed by the committee responsible for The editors and publisher of MKSAP 19 recognize that the producing this content. If necessary, adjustments to topics development of new material offers many opportunities or contributors’ roles in content development are made to for error. Despite our best efforts, some errors may persist balance the discussion. Further, all readers of this content in print. Drug dosage schedules are, we believe, accurate are asked to evaluate it for evidence of commercial bias and and in accordance with current standards. Readers are send any relevant comments to mksap_editors@acponline. advised, however, to ensure that the recommended dos- org so that future decisions about content and contributors ages in MKSAP 19 concur with the information provided can be made in light of this information. in the product information material. This is especially important in cases of new, infrequently used, or highly toxic drugs. Application of the information in MKSAP 19 Resolution of Conflicts remains the professional responsibility of the practitioner. To resolve all conflicts of interest and influences of vested The primary purpose of MKSAP 19 is educational. interests, ACP’s content planners used best evidence and Information presented, as well as publications, technol- updated clinical care guidelines in developing content, ogies, products, and/or services discussed, is intended to when such evidence and guidelines were available. All inform subscribers about the knowledge, techniques, and content underwent review by external peer reviewers not experiences of the contributors. A diversity of professional on the committee to ensure that the material was balanced and unbiased. Contributors’ disclosure information can be opinion exists, and the views of the contributors are their

required to identify any unapproved, off-label, or investiga- High Value Care Key Points tive use of commercial products or devices. Where a trade Key Points in the text that relate to High Value Care concepts name is used, all available trade names for the same product (that is, concepts that discuss balancing clinical benefit with type are also included. If trade-name products manufac- costs and harms) are designated by the HVC icon [HVC]. tured by companies with whom contributors have rela- tionships are discussed, contributors are asked to provide evidence-based citations in support of the discussion. The Educational Disclaimer information is reviewed by the committee responsible for The editors and publisher of MKSAP 19 recognize that the producing this content. If necessary, adjustments to topics development of new material offers many opportunities or contributors’ roles in content development are made to for error. Despite our best efforts, some errors may persist balance the discussion. Further, all readers of this content in print. Drug dosage schedules are, we believe, accurate are asked to evaluate it for evidence of commercial bias and and in accordance with current standards. Readers are send any relevant comments to mksap_editors@acponline. advised, however, to ensure that the recommended dos- org so that future decisions about content and contributors ages in MKSAP 19 concur with the information provided can be made in light of this information. in the product information material. This is especially important in cases of new, infrequently used, or highly toxic drugs. Application of the information in MKSAP 19 Resolution of Conflicts remains the professional responsibility of the practitioner. To resolve all conflicts of interest and influences of vested The primary purpose of MKSAP 19 is educational. interests, ACP’s content planners used best evidence and Information presented, as well as publications, technol- updated clinical care guidelines in developing content, ogies, products, and/or services discussed, is intended to when such evidence and guidelines were available. All inform subscribers about the knowledge, techniques, and content underwent review by external peer reviewers not experiences of the contributors. A diversity of professional on the committee to ensure that the material was balanced and unbiased. Contributors’ disclosure information can be opinion exists, and the views of the contributors are their found with the list of contributors’ names and those of ACP own and not those of the ACP. Inclusion of any material in the program does not constitute endorsement or rec- principal staff listed in the beginning of this book. ommendation by the ACP. The ACP does not warrant the safety, reliability, accuracy, completeness, or usefulness Language Reflecting Diversity, Equity, of and disclaims any and all liability for damages and and Inclusion Within MKSAP 19 claims that may result from the use of information, publi-

found with the list of contributors’ names and those of ACP own and not those of the ACP. Inclusion of any material in the program does not constitute endorsement or rec- principal staff listed in the beginning of this book. ommendation by the ACP. The ACP does not warrant the safety, reliability, accuracy, completeness, or usefulness Language Reflecting Diversity, Equity, of and disclaims any and all liability for damages and and Inclusion Within MKSAP 19 claims that may result from the use of information, publi- MKSAP 19’s Editors and contributors commit to using cations, technologies, products, and/or services discussed language and images that support ACP’s commitment to in this program.

found with the list of contributors’ names and those of ACP own and not those of the ACP. Inclusion of any material in the program does not constitute endorsement or rec- principal staff listed in the beginning of this book. ommendation by the ACP. The ACP does not warrant the safety, reliability, accuracy, completeness, or usefulness Language Reflecting Diversity, Equity, of and disclaims any and all liability for damages and and Inclusion Within MKSAP 19 claims that may result from the use of information, publi- MKSAP 19’s Editors and contributors commit to using cations, technologies, products, and/or services discussed language and images that support ACP’s commitment to in this program. being an anti-racist organization that supports diversity, equity, and inclusion throughout health care and health Publisher's Information education. ACP also continues to ensure diversity among Copyright © 2021 American College of Physicians. All MKSAP’s physician-contributors. When appropriate, the rights reserved. MKSAP Editors will also rely on MKSAP 19 Digital’s expanded use of multimedia enhancements, including video and audio, This publication is protected by copyright. No part of to explore and more fully explain issues surrounding the this publication may be reproduced, stored in a retrieval presentation of MKSAP 19 clinical content as it relates to race system, or transmitted in any form or by any means, elec- and ethnicity. MKSAP 19 users are encouraged to contact tronic or mechanical, including photocopy, without the the Editors at mksap_editors@acponline.org to help us express consent of the ACP. MKSAP 19 is for individual identify opportunities for improvement in this area. use only. Only one account per subscription will be per- mitted for the purpose of earning CME credits and MOC points and for other authorized uses of MKSAP 19. Hospital-Based Medicine For the convenience of subscribers who provide care in hospital settings, comprehensive hospital-focused content Disclaimer Regarding Direct Purchases aligned with the ABIM Focused Practice in Hospital from Online Retailers Medicine blueprint is integrated throughout the syllabus, CME and/or MOC for MKSAP 19 is available only to custom- and self-assessment questions that are specific to the hospi- ers who purchase the program directly from ACP. ACP will tal setting are specially designated with the blue hospitalist not set up MKSAP CME/MOC accounts for purchasers of icon (€)). MKSAP sold by unauthorized sellers (e.g., Amazon, eBay),

being an anti-racist organization that supports diversity, equity, and inclusion throughout health care and health Publisher's Information education. ACP also continues to ensure diversity among Copyright © 2021 American College of Physicians. All MKSAP’s physician-contributors. When appropriate, the rights reserved. MKSAP Editors will also rely on MKSAP 19 Digital’s expanded use of multimedia enhancements, including video and audio, This publication is protected by copyright. No part of to explore and more fully explain issues surrounding the this publication may be reproduced, stored in a retrieval presentation of MKSAP 19 clinical content as it relates to race system, or transmitted in any form or by any means, elec- and ethnicity. MKSAP 19 users are encouraged to contact tronic or mechanical, including photocopy, without the the Editors at mksap_editors@acponline.org to help us express consent of the ACP. MKSAP 19 is for individual identify opportunities for improvement in this area. use only. Only one account per subscription will be per- mitted for the purpose of earning CME credits and MOC points and for other authorized uses of MKSAP 19. Hospital-Based Medicine For the convenience of subscribers who provide care in hospital settings, comprehensive hospital-focused content Disclaimer Regarding Direct Purchases aligned with the ABIM Focused Practice in Hospital from Online Retailers Medicine blueprint is integrated throughout the syllabus, CME and/or MOC for MKSAP 19 is available only to custom- and self-assessment questions that are specific to the hospi- ers who purchase the program directly from ACP. ACP will tal setting are specially designated with the blue hospitalist not set up MKSAP CME/MOC accounts for purchasers of icon (€)). MKSAP sold by unauthorized sellers (e.g., Amazon, eBay), vi

with whom ACP has no relationship. We do not honor third Independence Mall West, Philadelphia, PA 19106-1572, or party sales. CME credits and MOC points cannot be awarded email your request to mksap_editors@acponline.org. to those purchasers who have purchased the program from MKSAP 19 ISBN: 978-1-938245-75-6 non-authorized sellers. Oncology ISBN: 978-1-938245-79-4 Printed in the United States of America. Unauthorized Use of This Book Is Against the Law For order information in the U.S. or Canada call 800-ACP- 1915. All other countries call 215-351-2600 (Monday to Unauthorized reproduction of this publication is unlaw- Friday, 9 aM - 5 pM ET). Fax inquiries to 215-351-2799 or ful. ACP prohibits reproduction of this publication or any email to custserv@acponline.org. of its parts in any form either for individual use or for distribution. ACP will consider granting an individual permission to Errata and Revisions reproduce only limited portions of this publication for his Errata and Revisions for MKSAP 19 will be available or her own exclusive use. Send requests in writing to MKSAP* through MKSAP 19 Digital at mksap19.acponline.org as Permissions, American College of Physicians, 190 N. new information becomes known to the editors. vii