Part 1 book “Manual of clinical oncology” has contents: Biology of cancer and implications for clinical oncology, nuclear medicine, radiation oncology, systemic therapy agents, cancer immunotherapy, cancer survivorship, lung cancer, gastrointestinal tract cancers, breast cancer, gynecologic cancers,… and other contents.
Manual of Clinical Oncology Manual of Clinical Oncology 8TH E D I T I O N Editors Bartosz Chmielowski, MD, PhD Associate Clinical Professor Jonsson Comprehensive Cancer Center Division of Hematology and Oncology University of California, Los Angeles Los Angeles, California Mary Territo, MD Emeritus Professor of Medicine Division of Hematology and Oncology David Geffen School of Medicine University of California, Los Angeles Los Angeles, California Executive Editor: Rebecca Gaertner Acquisitions Editor: Ryan Shaw Editorial Coordinator: Emily Buccieri and Emilie Moyer Marketing Manager: Rachel Mante Leung Senior Production Project Manager: Alicia Jackson Design Coordinator: Terry Mallon Manufacturing Coordinator: Beth Welsh Prepress Vendor: SPi Global 8th edition Copyright © 2017 Wolters Kluwer Previous Editions Copyright © 2009, 2004, and 2000 by Lippincott Williams & Wilkins, a Wolters Kluwer business; Copyright © 1995, 1988, and 1983 by Little, Brown & Company 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) Printed in China Library of Congress Cataloging-in-Publication Data Names: Chmielowski, Bartosz, editor | Territo, Mary C., editor Title: Manual of clinical oncology / editors, Bartosz Chmielowski, Mary Territo Other titles: Manual of clinical oncology (Casciato) Description: Eighth edition | Philadelphia : Wolters Kluwer, [2017] | Includes bibliographical references and index Identifiers: LCCN 2016044205 | ISBN 9781496349576 Subjects: | MESH: Neoplasms—diagnosis | Neoplasms—therapy | Medical Oncology—methods | Handbooks Classification: LCC RC262.5 | NLM QZ 39 | DDC 616.99/4—dc23 LC record available at https://lccn.loc.gov/2016044205 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 Contributors Russell K Brynes, MD Professor of Clinical Pathology Chief, Hematopathology Service Department of Pathology Keck School of Medicine University of Southern California Los Angeles, California Pranatharthi H Chandrasekar, MD, FACP, FIDSA Professor, Internal Medicine and Infectious Diseases Chief, Division of Infectious Diseases Wayne State University Chief, Infectious Diseases Karmanos Cancer Institute Detroit, Michigan Howard A Chansky, MD Professor and Chair Department of Orthopaedics and Sports Medicine University of Washington School of Medicine Seattle, Washington Bartosz Chmielowski, MD, PhD Associate Clinical Professor Jonsson Comprehensive Cancer Center Division of Hematology and Oncology University of California, Los Angeles Los Angeles, California Darin J Davidson, MD, MHSc, FRCSC Assistant Professor Musculoskeletal Oncology Service Program Director, Musculoskeletal Oncology Fellowship Department of Orthopaedics and Sports Medicine University of Washington School of Medicine Seattle, Washington Lisa M DeAngelis, MD Professor of Neurology Weill Cornell Medical College Chair, Department of Neurology Memorial Sloan Kettering Cancer Center New York, New York Chaitanya R Divgi, MD Professor of Radiology Executive Vice-Chair, Research Chief of Nuclear Medicine and Molecular Imaging Department of Radiology Columbia University New York, New York Alexandra Drakaki, MD, PhD Assistant Professor of Medicine and Urology Director—Genitourinary Medical Oncology Program Division of Hematology and Oncology Institute of Urologic Oncology University of California, Los Angeles Los Angeles, California Martin J Edelman, MD, FACP Professor of Medicine Head, Section of Solid Tumor Oncology Associate Director, Division of Hematology and Oncology University of Maryland Greenebaum Cancer Center University of Maryland School of Medicine Baltimore, Maryland Lawrence H Einhorn, MD Distinguished Professor of Medicine Department of Medicine—Hematology/Oncology Indiana University Indianapolis, Indiana Herbert Eradat, MD, MS Assistant Clinical Professor of Medicine UCLA Lymphoma Program Division of Hematology and Oncology David Geffen School of Medicine at UCLA Los Angeles, California Robert A Figlin, MD, FACP Steven Spielberg Family Chair in Hematology Oncology Professor of Medicine and Biomedical Sciences Director, Division of Hematology and Oncology Deputy Director Samuel Oschin Comprehensive Cancer Institute Cedars-Sinai Medical Center Los Angeles, California Charles A Forscher, MD Medical Director, Sarcoma Program Samuel Oschin Cancer Center Cedars-Sinai Medical Center Assistant Clinical Professor David Geffen School of Medicine at UCLA Los Angeles, California David R Gandara, MD Professor of Medicine Director, Thoracic Oncology Program Senior Advisor to the Director UC Davis Comprehensive Cancer Center Sacramento, California Patricia A Ganz, MD Distinguished Professor Health Policy and Management and Medicine UCLA Fielding School of Public Health David Geffen School of Medicine at UCLA Director, Cancer Prevention and Control Research Jonsson Comprehensive Cancer Center Los Angeles, California Axel Grothey, MD Professor of Oncology Department of Oncology Mayo Clinic College of Medicine Rochester, Minnesota Shireen N Heidari, MD Fellow in Palliative Medicine UCLA Department of Medicine, Palliative Care Service Los Angeles, California Siwen Hu-Lieskovan, MD, PhD Assistant Clinical Professor Division of Hematology and Oncology Department of Medicine David Geffen School of Medicine at UCLA Los Angeles, California Carole G H Hurvitz, MD Emeritus Director Pediatric Hematology Oncology Cedars Sinai Medical Center Samuel Oschin Comprehensive Cancer Institute 10 Figure 16-1 Papillary thyroid cancer initial management flow sheet IV PHEOCHROMOCYTOMA A Epidemiology and etiology PCCs are rare tumors; they belong to the APUD system and produce symptoms by elaborating catecholamines Extra-adrenal PCCs are called paragangliomas Certain hereditary syndromes are associated with an increased risk for PCC or paraganglioma Dominantly inherited MEN2 (see Section I.C) Dominantly transmitted PCC Neurofibromatosis type (von Recklinghausen disease) von Hippel-Lindau disease Familial paraganglioma syndromes due to mutations in succinic dehydrogenase subunits B and D As many as one-third of patients with an apparently sporadic PCC may, in fact, harbor a germ-line mutation in one of these genes Screening for these mutations should be considered in all patients, and certainly performed in patients with bilateral, extra-adrenal, or malignant PCCs, patients with a family history of one of the syndromes, patients diagnosed with a PCC before the age of 20 years, or patients with other phenotypic features of one of the hereditary syndromes B Pathology and natural history PCC originates in the adrenal medulla (90% of patients) or in the paraganglia of the sympathetic nervous system Bilateral PCC frequently occurs in inherited syndromes and in 10% of noninherited cases Metastases to bone, liver, and lung occur in 10% of cases of PCC, and about 20% of paragangliomas, despite a histologically benign appearance Metastases frequently have an indolent growth pattern but are lethal because they often produce cardiovascular complications Metastases are often detected at the time of diagnosis of the primary tumor but can appear up to 20 years later Hyperglycemia is common in patients with PCC Patients also have an increased incidence of gallstones C Diagnosis Symptoms and signs 626 a Symptoms The most common symptoms of PCC are episodes of various combinations of the following: headache, sweating, tachycardia, palpitations, pallor, nausea, and feeling of impending death Episodes may be triggered by exercise, emotional upset, alcohol ingestion, physical examination in the area of the tumor, or micturition Vague complaints of anxiety, tremulousness, fever, dyspnea, or angina are often mistaken for psychosomatic illness or thyrotoxicosis b Hypertension is present in 90% of patients The hypertension is fixed (66% of patients) or paroxysmal (33%) Orthostatic hypotension occurs in 70% of patients c Catecholamine cardiomyopathy Patients may have cardiovascular collapse after a vague history of arrhythmias and anxiety d Patients with small tumors, such as might be found when screening patients with a family history of a hereditary PCC syndrome or when evaluating patients with incidentally discovered adrenal masses, are often asymptomatic; the lack of symptoms does not exclude PCC Selection of patients for study All patients with an incidentally discovered adrenal mass should be screened for PCC The presence of PCC should be sought in patients with hypertension and any of the following: a Age < 45 years b A family history of a hereditary PCC syndrome c Episodic attacks typical of the syndrome d Young patients without hypertension but with documented atrial arrhythmia, evidence of an unexplained hypermetabolic state, or cardiomyopathy should be screened for PCC and thyrotoxicosis Chemical tests a Catecholamine metabolites Measurement of plasma free metanephrines appears to be the most sensitive technique (98%) to detect PCC Ideally, the sample should be drawn following an overnight fast and after the patient has been at rest, preferably supine, for 15 to 30 minutes There is a 5% false-positive rate using this assay Twenty-four–hour urine collections for measurement of fractionated metanephrines are nearly as sensitive and specific as plasma free metanephrines Plasma catecholamine 627 assays are also available but require meticulous technique in sample collection and handling and are susceptible to elevation from minimal stimulation Elevated levels of catecholamines or their metabolites suggest the presence of PCC and mandate further studies (1) Misleading elevations in catecholamine metabolites Many drugs affect either the metabolism or assay of catecholamines In particular, phenothiazines, tricyclic antidepressants, drugs that are catecholamines (e.g., isoproterenol) or catecholamine releasers (e.g., ephedrine, amphetamines, methylxanthines), methyldopa, labetalol, phenoxybenzamine, acetaminophen, buspirone, monoamine oxidase inhibitors, sulfasalazine, and cocaine can falsely elevate both serum and urine catecholamines and their metabolites If possible, these medications should be discontinued for up to weeks before sampling Additionally, physiologic stress from extreme illness and/or hospitalization raises catecholamines and should be taken into consideration when ordering and interpreting results collected from hospitalized patients (2) Misleading low metanephrine values may result from incomplete urine collections or from the use of αmethylparatyrosine, clonidine, reserpine, or guanethidine Radiographic techniques are used for localization of tumor in patients once clear biochemical evidence of PCC is established a CT is preferred to MRI as the initial imaging modality Chest, abdomen, and pelvis should be evaluated b MRI is useful in patients with metastatic disease, particularly in the evaluation of head and neck paragangliomas c Isotope scanning with 123I-metaiodobenzylguanidine may be useful in demonstrating PCC, especially in extra-adrenal sites Octreotide scanning appears to be less sensitive Positron emission tomography scanning utilizing FDG or 18F-fluoroDOPA has been reported to be particularly useful in cases of malignant PCC D Management Pharmacologic control of PCC is essential before invasive diagnostic tests or surgery is done a Phenoxybenzamine, given in initial doses of 10 to 20 mg PO 628 twice daily, is a pure α-adrenergic blocker that controls both episodic and fixed hypertension; doses are increased until blood pressure and episodes are well controlled Other α-adrenergic blockers may also be used (e.g., doxazosin in doses up to 20 mg/d) b Propranolol, 10 to 40 mg PO given four times daily, is a βadrenergic blocker that is useful for treating sweating, hypermetabolism, and arrhythmias Propranolol should be used only after adequate α-adrenergic blockade is established to avoid worsening of hypertension c Labetalol, a combined α- and β-adrenergic blocker, can also be used in doses of 200 to 600 mg given twice daily d α-Methylparatyrosine (metyrosine) blocks catecholamine synthesis in doses of to g/d PO and may be added on to αblockade High cost and side effects of severe fatigue and extrapyramidal symptoms make this drug a less favorable option, but it can be used in high-risk patients e Calcium channel blockers such as amlodipine (10 to 20 mg/d), nifedipine (30 to 90 mg/d), and verapamil (180 to 540 mg/d) may also be used Surgery a Before surgery Long-acting α- and β-adrenergic blockers should be given for to 14 days preoperatively and continued throughout surgery Close attention should be paid to maintaining fluid and electrolyte balance Preoperative volume expansion with highsodium diet and fluid intake is recommended to prevent postoperative hypotension b During surgery The perioperative mortality rate due to catecholamine excess is up to 3% Hypertensive episodes, which may occur while the tumor is being manipulated, are managed with nitroprusside infusion, rapid intravenous boluses of phentolamine, and nicardipine infusion Hypotensive episodes, which occur after the tumor’s blood supply has been isolated, should be treated with intravenous fluids c After surgery Hypertension may develop as a result of fluid overload during surgery and is treated with intravenous furosemide and fluid restriction until the blood pressure is controlled Rebound hypoglycemia following removal of 629 catecholamine excess is common, and plasma glucose levels should be monitored closely in the postoperative period, with dextrose infusion as needed Monitoring for and treatment of adrenal insufficiency are indicated All patients should have plasma free metanephrines or 24-hour urine metanephrines measured to weeks after surgery Plasma or urine metanephrines should be repeated at yearly follow-up examinations indefinitely in all patients Metastatic disease a RT is useful for palliating locally symptomatic metastases b The usefulness of chemotherapy for unresectable disease is not established, although the combination of cyclophosphamide, vincristine, and dacarbazine produces objective responses in many patients Symptoms of catecholamine excess are managed pharmacologically (see Section IV.D.1) c Some patients may respond to therapeutic doses of 131Imetaiodobenzylguanidine V ADRENAL CORTICAL CARCINOMA A Epidemiology Adrenal cancer is rare, with an incidence of 0.5 to 2.0 cases per million per year It causes 0.2% of cancer deaths The average age at diagnosis is 40 years, but the tumor occurs at all ages About 60% of the patients are women Adrenal cortical cancer may occur as a component of Li-Fraumeni syndrome, MEN1, Gardner syndrome, Lynch syndrome, and Beckwith-Wiedemann syndrome B Pathology and natural history Adrenal cancers are highly aggressive; they frequently metastasize to lungs, liver, and other organs and are large and bulky at the time of diagnosis About two-thirds of these tumors produce functional corticosteroids, including cortisol, aldosterone, androgens, and estrogens C Diagnosis Symptoms and signs a Hormonally inactive tumors are discovered due to symptoms of abdominal mass effect in 30% of patients and as incidental tumors in 15% to 20% of patients with adrenal cancer b Hormonally active tumors present with the following: (1) Rapid virilization (hirsutism, clitoromegaly, oligomenorrhea, 630 or amenorrhea) in women (2) Gynecomastia in men (3) Precocious puberty (4) Cushing syndrome with hypertension and glucose intolerance Adrenal function tests Patients with the above clinical symptoms, and/or a suspicious adrenal mass, should have basal serum cortisol, ACTH, dehydroepiandrosterone sulfate (DHEAS), 17hydroxyprogesterone, androstenedione, testosterone, and estradiol measured In addition, evaluation for excess cortisol production should be performed with the dexamethasone suppression test and the 24-hour urine collection for free cortisol a Dexamethasone suppression test Following the administration of mg of dexamethasone at 11:00 p.m., serum cortisol is measured before 9:00 a.m the next morning; serum cortisol is usually suppressed to 10 to 13 Hounsfield units, and demonstrate 20 pmol/L) and C-peptide (>0.6 ng/mL) in the presence of hypoglycemia (glucose < 55 mg/dL) usually is diagnostic of insulinoma or sulfonylurea ingestion If symptoms of hypoglycemia develop at any time, blood glucose, insulin, and C-peptide levels should be measured; if the glucose concentration is 6 years), especially involving perioral and perigenital regions, also the fingers, legs, and feet) They may have mild hyperglycemia, normocytic anemia, and elevated fasting blood glucagon levels, usually in the 500 to 1,000 pg/mL range (normal is 3 cm, and occur in the distal pancreas About half have metastasized at the time of discovery Diagnosis a Symptoms include high-volume watery diarrhea, muscle weakness due to hypokalemia, flushing, psychosis, and hypotension b Laboratory studies (1) Serum chemistry studies may show hypokalemia, hypochlorhydria, hyperglycemia and hypercalcemia (2) Low stool osmotic gap (