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Part 1 book “Pocket oncology” has contents: General oncology, radiation oncology, cancer biology, molecular diagnostics, molecular diagnostics, cancer genetics, cancer immunology, cancer pharmacology, cancer complications, pain and palliative care, cancer survivorship,… and other contents.
POCKET • NOTEBOOK Pocket ONCOLOGY Editors: NEIL VASAN, MD, PhD Chief Medical Oncology Fellow Department of Medicine Memorial Sloan Kettering Cancer Center New York, New York MARIA I CARLO, MD Assistant Attending Physician Genitourinary Oncology Service Department of Medicine Memorial Sloan Kettering Cancer Center New York, New York Advisors: ALEXANDER E DRILON, MD Clinical Director, Early Drug Development Service Assistant Attending, Thoracic Oncology Service Department of Medicine Memorial Sloan Kettering Cancer Center New York, New York MICHAEL A POSTOW, MD Assistant Attending Physician Melanoma and Immunotherapeutics Service Department of Medicine Memorial Sloan Kettering Cancer Center New York, New York Acquisitions Editor: Ryan Shaw Editorial Coordinator: Kayla Smull Editorial Assistant: Amy Masgay Marketing Manager: Rachel Mante Leung Production Project Manager: Marian Bellus Design Coordinator: Steve Druding Manufacturing Coordinator: Beth Welsh Prepress Vendor: Aptara, Inc Copyright © 2019 Wolters Kluwer All rights reserved This book is protected by copyright No part of this book may be reproduced or transmitted in any form or by any means, including as photocopies or scanned-in or other electronic copies, or utilized by any information storage and retrieval system without written permission from the copyright owner, except for brief quotations embodied in critical articles and reviews Materials appearing in this book prepared by individuals as part of their official duties as U.S government employees are not covered by the above-mentioned copyright To request permission, please contact Wolters Kluwer at Two Commerce Square, 2001 Market Street, Philadelphia, PA 19103, via email at permissions@lww.com, or via our website at lww.com (products and services) 10 9 8 7 6 5 4 3 2 1 Printed in China Library of Congress Cataloging-in-Publication Data Names: Vasan, Neil, editor | Carlo, Maria I., editor Title: Pocket oncology / editors, Neil Vasan, Maria I Carlo ; advisors, Alexander E Drilon, Michael A Postow Other titles: Pocket notebook Description: 2 | Philadelphia : Wolters Kluwer, [2018] | Series: Pocket notebook | Includes index Identifiers: LCCN 2017055849 | ISBN 9781496391063 Subjects: | MESH: Neoplasms | Handbooks Classification: LCC RC263 | NLM QZ 39 | DDC 616.99/4–dc23 LC record available at https://lccn.loc.gov/2017055849 This work is provided “as is,” and the publisher disclaims any and all warranties, express or implied, including any warranties as to accuracy, comprehensiveness, or currency of the content of this work This work is no substitute for individual patient assessment based upon healthcare professionals’ examination of each patient and consideration of, among other things, age, weight, gender, current or prior medical conditions, medication history, laboratory data and other factors unique to the patient The publisher does not provide medical advice or guidance and this work is merely a reference tool Healthcare professionals, and not the publisher, are solely responsible for the use of this work including all medical judgments and for any resulting diagnosis and treatments Given continuous, rapid advances in medical science and health information, independent professional verification of medical diagnoses, indications, appropriate pharmaceutical selections and dosages, and treatment options should be made and healthcare professionals should consult a variety of sources When prescribing medication, healthcare professionals are advised to consult the product information sheet (the manufacturer’s package insert) accompanying each drug to verify, among other things, conditions of use, warnings and side effects and identify any changes in dosage schedule or contraindications, particularly if the medication to be administered is new, infrequently used or has a narrow therapeutic range To the maximum extent permitted under applicable law, no responsibility is assumed by the publisher for any injury and/or damage to persons or property, as a matter of products liability, negligence law or otherwise, or from any reference to or use by any person of this work LWW.com We dedicate this handbook to our patients, whose unwavering courage in the face of adversity inspires us to be better physicians and human beings CONTRIBUTING AUTHORS Omar Abdel-Wahab, MD Assistant Member Human Oncology and Pathogenesis Program and Leukemia Service Department of Medicine Memorial Sloan Kettering Cancer Center New York, New York Ghassan Abou-Alfa, MD, MBA Associate Attending Physician Department of Medicine Memorial Sloan Kettering Cancer Center Associate Professor Department of Medicine Weill Cornell Medical College New York, New York Rajiv Agarwal, MD Medical Oncology Fellow Department of Medicine Memorial Sloan Kettering Cancer Center New York, New York Caroline Andrew, MD Chief Resident Department of Medicine Memorial Sloan Kettering Cancer Center New York, New York Kathryn C Arbour, MD Medical Oncology Fellow Department of Medicine Memorial Sloan Kettering Cancer Center New York, New York Scott T Avecilla, MD, PhD Medical and Scientific Director, Cell Therapy Laboratory Services Director, Donor Room and Apheresis Services Department of Laboratory Services Memorial Sloan Kettering Cancer Center New York, New York Shirin Bajaj, MD PGY-2 Resident Department of Dermatology New York University New York, New York Dean Bajorin, MD, FACP Attending Physician Genitourinary Oncology Service Department of Medicine Memorial Sloan Kettering Cancer Center Professor of Medicine Weill Cornell Medical College Caroline C Barbosa, MD Neuro-Oncology Fellow Department of Neurology Memorial Sloan Kettering Cancer Center New York, New York David A Barron, MD, PhD Radiation Oncology Resident Department of Radiation Oncology Memorial Sloan Kettering Cancer Center New York, New York Ellin Berman, MD Professor Leukemia Service Department of Medicine Memorial Sloan Kettering Cancer Center New York, New York Kristen K Beyer, PharmD, BCOP Chief Medical Officer Healthy Business Group Sag Harbor, New York Ankush Bhatia, MD Neuro-Oncology Fellow Department of Neurology Memorial Sloan Kettering Cancer Center New York, New York Agata A Bielska, MD, PhD Medical Oncology Fellow Department of Medicine Memorial Sloan Kettering Cancer Center New York, New York Mark H Bilsky, MD William E Snee Chair Attending Department of Neurosurgery Memorial Sloan Kettering Cancer Center Professor Department of Neurosurgery Weill Medical College of Cornell University New York, New York Victoria Blinder, MD, MSc Assistant Attending Immigrant Health and Cancer Disparities Service Department of Psychiatry and Behavioral Sciences Breast Medicine Service Department of Medicine Memorial Sloan Kettering Cancer Center New York, New York Kelly Bolton, MD Medical Oncology Fellow Department of Medicine Memorial Sloan Kettering Cancer Center New York, New York George J Bosl, MD The Patrick M Byrne Chair in Clinical Oncology Department of Medicine Memorial Sloan Kettering Cancer Center New York, New York Timothy Bowler, MD Medical Oncology Fellow Department of Medicine Memorial Sloan Kettering Cancer Center New York, New York Sheng F Cai, MD, PhD Assistant Attending Physician Leukemia Service Department of Medicine Memorial Sloan Kettering Cancer Center New York, New York Brian Campbell-Jimenez, MD Hospice and Palliative Medicine Fellow Department of Medicine Memorial Sloan Kettering Cancer Center New York, New York Maria I Carlo, MD Assistant Attending Physician Genitourinary Oncology Service Department of Medicine Memorial Sloan Kettering Cancer Center New York, New York Andrea Cercek, MD usually found in SCC but can be in mixed histology ROS 1 Rearrangements: 1–2% of ADCL, younger women, never smokers Usually negative for EGFR, KRAS, & ALK rearrangements (JCO 2012;30:863) Other actionable aberrations: BRAF 2%, RET Fusions 1%, HER2 Amp/Mt 3%, PIK3CA 50% (RR~45%) (NEJM 2016;375:1823) If PD-La 10/10 hpf), frequent necrosis Etiology and Clinical Manifestations Nearly exclusively seen in smokers, related to both smoking duration & intensity Most common presentation is large hilar mass w/ bulky mediastinal LAD Sx: Fatigue, cough, dyspnea, wt loss, debility, hemoptysis Paraneoplastic Syndromes Neurologic Lambert–Eaton (Affects 3% of SCLC pts) p/w symmetrical proximal muscle weakness, also w/ autonomic dysfxn (dry mouth, impotence), dx made clinically, confirmed by EMG & presence of Ab to voltagegated calcium channel, tx is to treat underlying malignancy Other Cerebellar degeneration, opsoclonus myoclonus, encephalitis, neuropathy Endocrine Ectopic ACTH secretion Cushing syndrome, causing muscle weakness, HTN, hirsutism, hypoglycemia, osteoporosis Ectopic ADH secretion SIADH, causing hyponatremia, seen in ~10% of pts w/ SCLC, causing cerebral edema, confusion, irritability, seizures Ectopic PTHrP secretion Tumor secretion of PTHrP, causing anorexia, vomiting, constipation, lethargy Molecular Biology Universal inactivation of TP53 & RB1 Mts: p53 (75–90%) (Oncogene 1991;6:1775), SOX2 Mts/amp (Nat Genet 2012;44:1111), FGFR1 amp (Nat Genet 2012;44:1104), inactivation of NOTCH (25%) (Nature 2015;524:47) Cytogenetics: Loss of heterozygosity (LOH) at 9p, 10q (PTEN) (Cancer Res 1997;57:400), deletion 3p (Cell 1996;85:17), loss of Rb gene function (13q14) (PNAS 1997;94:6933) Expression: DLL3 (Sci Transl Med 2015;7:302), Activation of telomerase, upregulation of c-kit (Clin Canc Res 2004;10:8214), c-myc (Oncogene 2006;25:130), bcl-2 Workup, Staging, Prognosis After tissue dx w/u includes imaging of chest, liver/adrenals, & CNS Staging Median OS 1-y Survival 5-y Survival Limited Dz Confined to ipsilateral hemithorax & w/in a single radiotherapy port 20 mos 60% 20% Extensive Dz Met dz outside the ipsilateral hemithorax 10 mos 30% 1% Poor prognostic factors include poor PS, wt loss, continued smoking, male sex, presence of paraneoplastic syndrome, elevated LDH Management—Limited Stage In rare cases, surgical resection may be curative for clinical stage 1 dz (5-y survival 40–50% for path stage 1–2 dz) (J Thorac Oncol 2009;4:1049), nodes need to be confirmed negative prior to resection, pts require (neo)adjuvant chemoRT Concurrent chemoRT w/ an OS benefit (NEJM 1992;327:1618), ORR of 80– 90%, 50–60% w/ CR Dose: 45 Gy twice daily better than ~45 Gy daily (NEJM 1999;340:265), survival benefit for adding RT w/ cycle 1 or 2 (JCO 1993;11:336) Platinum/etoposide is chemotherapy of choice, platinum/etoposide = platinum/irinotecan, although irinotecan seldom used in US, as ↑ tox (JCO 2009;27:2530), CIS = carboplatin (JCO 2012;30:1692) Management—Extensive Stage Highly responsive to chemotherapy/RT, but relapse common, ORR 60– 80%, CR in 15–20% Survival benefit to combination chemo, plat-based regimen typically used (↑ RR & improved survival), CIS/etoposide used 1st line based on efficacy & tox, ↑ RR but no difference in survival w/ CIS vs carboplatin Recommend 4–6 cycles of induction chemo, followed by observation Thoracic RT in pts w/ residual dz after systemic therapy, OS 13% vs 3% at 2 y (Lancet 2015; 385:36) No benefit to maintenance, ≥3 drug combos, alternating/sequential regimens Elderly pts: If PS adequate, proceed w/ standard plat doublet chemo Prophylactic Cranial Irradiation (PCI) Significant rate (17–38%) of CNS “failure” despite systemic response, CNS failure rate ~80% over 2 y PCI w/ in 4–8 wks after completion of chemo, MRI brain before proceeding LS-SCLC: After CR or significant regression to chemo ↓ brain mets, ↑ OS w/ PCI (NEJM 1999;34:476) ES-SCLC: If tumor response to chemo, ↓ brain mets, ↑ OS w/ PCI (NEJM 2007;357:664) Total dose of 25–30 Gy, can abbreviate if not PR or in ES-SCLC Toxicities: Fatigue, alopecia, neurocognitive impairment Management—Relapsed Disease Median survival after relapse 2–6 mos Prognostic factors: PS, tumor extent, time to relapse Sensitive dz: Initial PR/CR to Rx, progression ≥3 mos after last day of initial tx, high likelihood of response to additional Rx Refractory dz: Progression after ≤3 mos or lack of response during initial Rx, chance of response to additional Rx