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The American Cancer Society’s Oncology in Practice Clinical Management The American Cancer Society is a global grassroots force of nearly million volunteers dedicated to ­saving lives, celebrating lives, and leading the fight for a world without ­cancer From breakthrough ­research, to free lodging near treatment, a live helpline, free rides to treatment, and convening powerful ­activists to create awareness and impact, the Society is the only organization attacking cancer from every angle For more information go to www.cancer.org The American Cancer Society’s Oncology in Practice Clinical Management Edited by The American Cancer Society Atlanta, Georgia, USA  This edition first published 2018 © 2018 The American Cancer Society All rights reserved No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, except as permitted by law Advice on how to obtain permission to reuse material from this title is available at http://www.wiley.com/go/permissions The right of The American Cancer Society to be identified as the authors of the editorial material in this work has been asserted in accordance with law Registered Office(s) John Wiley & Sons, Inc., 111 River Street, Hoboken, NJ 07030, USA John Wiley & Sons Ltd, The Atrium, Southern Gate, Chichester, West Sussex, PO19 8SQ, UK Editorial Office 9600 Garsington Road, Oxford, OX4 2DQ, UK For details of our global editorial offices, customer services, and more information about Wiley products visit us at www.wiley.com Wiley also publishes its books in a variety of electronic formats and by print‐on‐demand Some content that appears in standard print versions of this book may not be available in other formats Limit of Liability/Disclaimer of Warranty The contents of this work are intended to further general scientific research, understanding, and discussion only and are not intended and should not be relied upon as recommending or promoting scientific method, diagnosis, or treatment by physicians for any particular patient In view of ongoing research, equipment modifications, changes in governmental regulations, and the constant flow of information relating to the use of medicines, equipment, and devices, the reader is urged to review and evaluate the information provided in the package insert or instructions for each medicine, equipment, or device for, among other things, any changes in the instructions or indication of usage and for added warnings and precautions While the publisher and authors have used their best efforts in preparing this work, they make no representations or warranties with respect to the accuracy or completeness of the contents of this work and specifically disclaim all warranties, including without limitation any implied warranties of merchantability or fitness for a particular purpose No warranty may be created or extended by sales representatives, written sales materials or promotional statements for this work The fact that an organization, website, or product is referred to in this work as a citation and/or potential source of further information does not mean that the publisher and authors endorse the information or services the organization, website, or product may provide or recommendations it may make This work is sold with the understanding that the publisher is not engaged in rendering professional services The advice and strategies contained herein may not be suitable for your situation You should consult with a specialist where appropriate Further, readers should be aware that websites listed in this work may have changed or disappeared between when this work was written and when it is read Neither the publisher nor authors shall be liable for any loss of profit or any other commercial damages, including but not limited to special, incidental, consequential, or other damages Library of Congress Cataloging‐in‐Publication Data Names: American Cancer Society, editor Title: The American Cancer Society’s Oncology in Practice : clinical management / edited by American Cancer Society Other titles: American Cancer Society textbook of clinical oncology (2018) | Textbook of clinical oncology Description: Hoboken, NJ : Wiley, 2018 | Includes bibliographical references and index | Identifiers: LCCN 2017027177 (print) | LCCN 2017028088 (ebook) | ISBN 9781118592076 (pdf ) | ISBN 9781118591963 (epub) |   ISBN 9781118517642 (cloth) Subjects: | MESH: Neoplasms Classification: LCC RC263 (ebook) | LCC RC263 (print) | NLM QZ 200 | DDC 616.99/4–dc23 LC record available at https://lccn.loc.gov/2017027177 Cover design by Wiley Cover image: © Tendo/Shutterstock Set in 9.5/11.5 pt Warnock by SPi Global, Pondicherry, India 10 9 8 7 6 5 4 3 2 1 v Contents Editorial Board and Reviewers  ix List of Contributors  x Introduction  xviii Section | Thoracic Cancers 1   Lung Cancer  Suresh S Ramalingam and Fadlo R Khuri   Other Thoracic Malignancies  22 Brandon H Tieu, Mehee Choi, Kyle Robinson, and Charles R Thomas, Jr Section | Digestive System Cancers 33   Esophageal Cancer  35 Ravi Shridhar, Khaldoun Almhanna, Sarah E Hoffe, Matthew Biagioli, Domenico Coppola, and Kenneth L. Meredith   Gastric Adenocarcinoma  54 Roger H Kim, Quyen D Chu, and Benjamin D Li   Small Bowel Cancer (Excluding Gastrointestinal Stromal Tumors and Carcinoid)  69 Alireza Hamidian Jahromi, Roger H Kim, Quyen D Chu, and Benjamin D Li   Adenocarcinoma of the Pancreas  82 Quyen D Chu, Erkut Borazanci, Roger H Kim, and Guillermo Sangster   Liver Cancers  100 Celina Ang, Sonia Reichert, and Randall F Holcombe   Biliary Tract Cancers/Cholangiocarcinomas  117 Celina Ang, Sonia Reichert, and Randall F Holcombe   Colon and Rectal Cancer  124 Lauren Kosinski, Ben George, Kiran K Turaga, Candice A Johnstone, and Mohammad Mahmoud 10 Anal Cancer  149 Cathy Eng, Ravi Shridhar, Emily Chan, Nataly Silva, Liana Tsikitis, Susan Hedlund, Michael D Chuong, and Charles R Thomas, Jr 11 Gastrointestinal Stromal Tumors  163 Rian M Hasson Charles, Stanley W Ashley, and Chandrajit P Raut vi Contents Section | Head and Neck 175 12 Oral Cavity and Oropharyngeal Cancer  177 Avinash V Mantravadi and Michael G Moore 13 Salivary Gland Cancer  192 Daniel Brickman and Neil D Gross 14 Larynx Cancer  201 Emma B Holliday, Blaine D Smith, Neil D Gross, Clifton D Fuller, and David I Rosenthal 15 Nasal and Paranasal Sinus Cancer  211 Emma B Holliday, Michael E Kupferman, Clifton D Fuller, and Ehab Hanna 16 Nasopharyngeal Cancer  218 Jamie M Pawlowski, Emma B Holliday, and Clifton D Fuller Section | Urinary System 225 17 Renal Cell Carcinoma  227 Jonathan Mathias and Brian Rini 18 Bladder Cancer and Other Urothelial Sites  237 Michael C Risk, Ayman Soubra, and Badrinath R Konety Section | Female Reproductive Cancer 251 19 Ovarian, Fallopian Tube, and Primary Peritoneal Cancer  253 Michael L Pearl, Erin E Stevens, and Joyce Varughese 20 Uterine Corpus Cancer  268 Mario Javier Pineda and John R Lurain 21 Cervical Cancer  288 Merieme Klobocista, Mark H Einstein, and Carolyn D Runowicz 22 Vaginal Cancer  304 Christina Gauthreaux, Anna Kuan‐Celarier, and Carolyn D Runowicz 23 Vulvar Cancer  310 Carolyn D Runowicz 24 Gestational Trophoblastic Disease  318 Alok Pant and John R Lurain Section | Male Reproductive Cancers 329 25 Testicular Cancer  331 Costantine Albany, Nasser Hanna, and Lawrence H Einhorn 26 Prostate Cancer  344 Bobby C Liaw and William K Oh 27 Penile Cancer  363 David Bowes and Juanita Crook Contents Section | Breast Cancer 375 28 Breast Cancer, Including Brief Discussion of Male Breast Cancer  377 Elisavet Paplomata and Ruth O’Regan Section | Hematologic Cancers 397 29 Myeloid Malignancies  399 Joshua F Zeidner, Darshan Roy, Alexander Perl, and Ivana Gojo 30 Lymphoid Leukemias in Adults  422 Nilanjan Ghosh, Jocelyn L Wozney, and Michael R Grunwald 31 Hodgkin Lymphoma in Adults  434 Satish Shanbhag and Richard Ambinder 32 Non‐Hodgkin Lymphoma in Adults  444 Loretta J Nastoupil, Jean L Koff, Leon Bernal‐Mizrachi, and Christopher R Flowers 33 Multiple Myeloma  463 Giada Bianchi and Kenneth C Anderson Section | Skin Cancer 485 34 Melanoma 487 Justin M Ko, Alan C Geller, and Susan M Swetter  35 Non‐Melanoma Skin Cancers  502 H William Higgins, II and Martin A Weinstock Section 10 | Endocrine Cancers 519 36 Thyroid Cancer  521 Maria E Cabanillas, Steven P Weitzman, Ramona Dadu, Ted Gansler, and Mark Zafereo 37 Adrenal Cortical Carcinoma and Pheochromocytoma  532 Robert Dreicer, Moshe C Ornstein, Kriti Mittal, Jordan Reynolds, Joseph Klink, Christopher Przybycin, and Jorge A Garcia 38 Pituitary Tumors  542 Adriana G Ioachimescu and Nelson M Oyesiku 39 Gastroenteropancreatic Neuroendocrine Tumors  552 Jonathan Strosberg Section 11 | Cancer of the Nervous System and Eye 571 40 Central Nervous System and Peripheral Nerves  573 D Ryan Ormond, Alexandros Bouras, Michael Moore, Matthew Gary, Paula Province Warren, Roshan Prabhu, Kathleen M Egan, Srikant Rangaraju, Christina Appin, Constantinos Hadjipanayis, Burt Nabors, Alfredo Voloschin, and Jeffrey J Olson 41 Malignant Tumors of the Eye  608 Devron H Char and Tia B Cole vii viii Contents Section 12 | Bone and Soft Tissue Tumors 617 42 Sarcomas of Bone in Adults  619 Mrinal Gounder, Yoshiya Yamada, and Nicola Fabbri 43 Sarcoma of Soft Tissue  631 Mrinal Gounder, Vinod Ravi, Yoshiya Yamada, Richard Carvajal, and Aimee Crago Section 13 | Cancer of Unknown Primary, Paraneoplastic Syndromes, and Peritoneal Carcinomatosis 645 44 Cancer of Unknown Primary Site  647 John D Hainsworth and F Anthony Greco 45 Paraneoplastic Syndromes  661 Lorraine C Pelosof and David E Gerber 46 Peritoneal Surface Malignancies  675 Kiran K Turaga Section 14 | Pediatric and Adolescent Oncology 683 47 Pediatric Cancers  685 Stephanie B Dixon, Lisa M Force, Pratiti Bandopadhayay, Peter Manley, Carlos Rodriguez‐Galindo, Lewis B. Silverman, and Karen J Marcus Index  729 742 Index k K‐RAS mutations lung cancer  pancreatic cancer  83 Kaposi sarcoma (KS)  514–515 conjunctival 609 keratoacanthoma (KAC)  508–509 clinical features  509, 509 diagnosis 509 incidence 508 pathology 509 risk factors  508 subtypes 509 treatment 509 ketoconazole, Cushing disease  549 KIT mutations acute myeloid leukemia  404 gastrointestinal stromal tumors  163–165, 170, 639 melanoma 489 testicular cancer  331 Klatskin tumors  117 Klinefelter syndrome  331 l Lambert–Eaton myasthenic syndrome (LEMS) 664, 665, 668 lanreotide, neuroendocrine tumors 559–560 antiproliferative effect  560 combined therapy  560–561 laparoscopic treatment adrenal cancer  536 colon cancer  130 endometrial carcinoma  275–276 gastric cancer  60 gastrointestinal stromal tumors  168 see also diagnostic laparoscopy laparoscopic‐assisted digital gastrectomy (LADG) 60 lapatinib, breast cancer  387, 390–391 large cell carcinoma, lung  laryngectomy 203–207 larynx cancer  201–208, 203 diagnosis 202 follow‐up 207–208 incidence 201 metastatic disease  202 mortality 201 pathology 202 prevention 201–202 risk factors  201 staging 202, 204–205 survivorship 207–208 treatment 202–207 advanced cancer  206–207 early stage glottic cancer  203–205 early stage subglottic cancer  206 early stage supraglottic cancer  206 laser surgery eye malignancies  612 larynx cancer  206 oropharyngeal cancer  188 vulvar intraepithelial neoplasia  313 leiomyosarcoma  280, 281–282, 638–639 see also soft tissue sarcoma lenalidomide mantle cell lymphoma  454 multiple myeloma  470, 473, 474–475 maintenance therapy  476 myelodysplastic syndromes  402 lentigo maligna melanoma  489, 490, 491, 491 lenvatinib, thyroid cancer  528, 529 leptomeningeal disease (LMD)  597–598 clinical features  597 diagnosis 598, 598 treatment 598 letrozole, breast cancer  387–388, 389 leukemia see acute myeloid leukemia (AML); chronic myeloid leukemia (CML); lymphoid leukemias leukocytoclastic vasculitis  667, 669 leukoplakia 180 levonorgestrel intrauterine device, endometrial hyperplasia management 269 Leydig cell tumors (LCTs) ovarian 264 testicular 334 lichen planus  180 limbic encephalitis (LE)  665 lipiodol, hepatocellular carcinoma  107 liposarcoma  631, 639 subtypes 632 see also soft tissue sarcoma lips 178 see also oral cavity/oropharyngeal cancer liver cancer see hepatocellular carcinoma (HCC); intrahepatic bile duct cancer liver metastases  138 chemotherapy 139 metastasectomy 139–140 liver transplantation cholangiocarcinoma 119 hepatocellular carcinoma  106 Milan criteria  106 metastatic neuroendocrine tumors 563 Li–Fraumeni syndrome  578, 632, 712, 714 lobectomy lung cancer  10 thyroid cancer  524 lumbar puncture, pediatric ALL  686 lung cancer  3–17 adenocarcinoma  4, diagnosis 5–6 elderly patients  15–16 follow‐up 17 incidence 3 metastases 6 radiation therapy  11 mortality 3 nonsmall cell (NSCLC)  4, 11–16 palliative therapy  11, 16–17 paraneoplastic syndromes  pathology 4–5 molecular 5, risk factors  3–4 screening 6 small cell (SCLC)  4–5, 16–17 squamous cell carcinoma  4, staging 6, 7–8 lymph node map 9 survivorship 17 treatment 8 maintenance therapy  12–13, 14 radiation therapy  10–11 salvage therapy  13, 13, 17 surgery  9–10, 17 systemic therapy  11–17, 11 targeted therapy  13–16, 14 lymph nodes gastric 58, 59, 59 lung cancer staging  management see specific types of cancer neck 205 see also sentinel lymph node biopsy lymphadenectomy bladder cancer  243 cervical cancer  293, 295, 297 colorectal cancer  129–130 gastric cancer  58–60, 60 gastrointestinal stromal tumors  168 Index Merkel cell carcinoma  512 pancreatic cancer  90 penile cancer  365–366, 370 renal cell carcinoma  230 testicular cancer  336, 338 thyroid cancer  527 urothelial carcinoma  245 vaginal cancer  307–308 vulvar cancer  315 see also neck dissection lymphedema, chronic, soft tissue sarcoma association  631–632 lymphoblastic lymphoma  694 lymphoid leukemias  422–429 acute lymphoblastic (ALL)  422–424 see also specific types lymphoma Burkitt  78, 442, 454 colorectal 124 diffuse large B‐cell (DLBCL)  78, 454–456 allogeneic stem cell transplantation 456 epidemiology 454–455 first‐line treatment  455 pathophysiology 455 second‐line therapy  455–456 intraocular 614, 614 mantle cell (MCL)  453–454 marginal zone (MZL)  452–453 gastric 452–453 nodal 453 nongastric 453 splenic 453 peripheral T‐cell (PTCL)  456 salivary gland  195 small bowel  69–70 pathology 71 staging 75, 76 treatment 78 small lymphocytic (SLL)  452 see also follicular lymphoma; Hodgkin lymphoma; non‐Hodgkin lymphoma (NHL); primary CNS lymphoma (PCNSL) Lynch syndrome  71, 125, 245 diagnostic criteria  125 endometrial carcinoma association 269–270 m magnetic resonance imaging (MRI) adrenal cancer  535 anal cancer  150 astrocytoma 579–580 functional imaging  581, 581 bladder cancer  239–240 bone sarcomas  620 breast cancer  379, 381 cholangiocarcinoma 118 gastrointestinal stromal tumors  164, 165 glioma 713 hepatocellular carcinoma  102 lung cancer  nasopharyngeal cancer  219 neuroendocrine tumors  557 oral cavity/oropharyngeal cancers  182, 182 pancreatic cancer  85 penile cancer  365 renal cell carcinoma  228 salivary gland cancer  195 sinonasal cancer  212, 212 small bowel cancer  73 soft tissue sarcoma  633 spinal tumors  591 magnetic resonance spectroscopy (MRS), astrocytoma  580–581 male breast cancer  391 malignant bowel obstruction  679 malignant peripheral nerve sheath tumor (MPNST)  587–588 malignant peritoneal mesothelioma 675 malignant pleural mesothelioma (MPM) 25–28 diagnosis 26 follow‐up 28 incidence 25 pathology 25–26 risk factors  25 staging 26, 27 treatment 26–28 chemotherapy 28 radiation therapy  26–28 surgery 26 malnutrition, colorectal cancer  142 mammalian target of rapamycin (mTOR) inhibitors hepatocellular carcinoma  110 mantle cell lymphoma  454 neuroendocrine tumors  561 renal cell carcinoma  231–232 MammaPrint® prognostic score  384 mammography 379 mandibular invasion  186 mantle cell lymphoma (MCL)  453–454 allogeneic stem cell transplantation 454 first‐line treatment  453–454 relapsed disease  454 MAP kinase pathway, hepatocellular carcinoma 110 marginal zone lymphoma (MZL)  452–453 gastric 452–453 nodal 453 nongastric 453 Masaoka‐Koga staging, thymic malignancies 23, 23 mastectomy 384–385 prophylactic 378 mastocytosis 413 maxillofacial prosthodontics  187 MC1R variants, melanoma association 488 medulloblastoma  574, 586–587, 714–716 classification 714–715 diagnosis 715 etiology and risk factors  714 follow‐up and late effects  716 incidence 714 presentation 715 staging 715, 715 treatment 715–716 megestrol acetate, endometrial hyperplasia 269 MEK inhibitor therapy, melanoma  497 melanoma 487–498 choroidal  611, 612 conjunctival 609 diagnosis 492, 492 follow‐up 497–498 incidence 487 iris 613, 613 mortality 487 pathology 489–491 histopathology 491 signaling pathways  489 subtypes 489–490, 490, 490, 491 prognostic factors  487–488 clinical factors  488 melanoma subtype  488 tumor thickness  487 risk factors  487, 488–489 staging 492–493 survivorship 498 treatment 493–497 adjuvant systemic therapy 494–495 743 744 Index melanoma (cont’d ) advanced disease  495–497, 495 chemotherapy  495, 496 immunomodulatory drugs  496 immunotherapy 494–495, 496–497 metastatic disease  494 surgery 493–494 uveal 611–612, 612, 613 vaccines 495 vaginal 306, 306 vulvar 312 treatment 315 melphalan, multiple myeloma  474, 475 meningioma  574, 589 Simpson grading scale  592, 592 spinal 592 Merkel cell carcinoma (MCC) 509–513 clinical features  510 diagnosis 510 incidence 509–510 metastatic disease  510 mortality 510 pathology 510 recurrence 512–513 risk factors  510 staging 510, 511–512 treatment 510–513 mesothelioma see malignant peritoneal mesothelioma; malignant pleural mesothelioma (MPM) metastases bone 11 brain  11, 594–596 clinical features  594–595 diagnosis 595 prophylactic cranial irradiation  17 treatment 595–596, 596 choroidal 613–614 liver 138, 140 chemotherapy 139 metastasectomy 139–140 peritoneal 675–677 pulmonary 140 salivary gland  195 spinal 593–594 clinical findings  593 diagnosis 593–594 treatment 594 metastasizing mixed tumors  194 metastatic disease adrenal cancer  536 anal cancer  150, 154–157 inguinal lymph node management 154 breast cancer  389–391, 652–653 HER2‐negative 391 HER2‐positive 390–391 HR‐positive 389–390 cervical cancer  290, 293, 295, 297 cholangiocarcinoma 120 colorectal cancer  137–138 liver metastases  138, 139–140, 140 palliative and end‐of‐life care  142 treatment planning  139–140, 140 endometrial cancer  273–274, 278–279 patterns of metastatic dissemination 276 gastrointestinal stromal tumors  164, 170–171 gestational trophoblastic disease  322 intracranial 594–596 larynx cancer  202 lung cancer  radiation therapy  11 melanoma 494 Merkel cell carcinoma  510 nasopharyngeal cancer  221 neuroblastoma 698–699 neuroendocrine tumors  553, 555, 563 oral cavity/oropharyngeal cancer 179 osteosarcoma 696 pancreatic cancer  92–94 penile cancer  370–371 prostate cancer  352–358 renal cell carcinoma  230 retinoblastoma 711 sinonasal cancer  211–212 soft tissue sarcoma  634, 638–639 testicular cancer  332, 336–338 thyroid cancer  528, 529 vulvar cancer  312 methotrexate acute lymphoblastic leukemia  423 breast cancer  385 gestational trophoblastic disease  322–324 intraocular lymphoma  614 osteosarcoma 626 primary CNS lymphoma  597 microcystins 101 microRNAs adrenal cancer  533 non‐Hodgkin lymphoma  447 microsatellite instability, colorectal cancer 126 microwave ablation, hepatocellular carcinoma 107 midostaurin, acute myeloid leukemia 407 Milan criteria for liver transplantation 106 minimal residual disease (MRD) testing, pediatric ALL  686 minimally invasive adenocarcinoma (MIA) 4 mitomycin C (MMC) anal cancer  150–153 bladder cancer  241 eye malignancies  608 mitotane adrenal cancer  536–537 Cushing disease  549 mitoxantrone, prostate cancer  353, 354, 355 Model for End State Liver Disease (MELD) score  106 Mohs micrographic surgery melanoma 493 penile cancer  367 skin cancer (non‐melanoma)  504, 508, 509, 510, 513 molar pregnancy see hydatidiform mole monoclonal antibodies, multiple myeloma  473, 474 monoclonal B‐cell lymphocytosis (MBL) 425 monoclonal gammopathy of undetermined significance (MGUS)  463–464, 467 mucinous tumors appendiceal 676 endometrial carcinoma  270–271 ovarian 255–256, 257 mucoepidermoid carcinoma (MEC) 193 mucosal melanoma (MM)  212 mucosal‐associated lymphoid tissue (MALT)  78, 452–453 multidetector computed tomography (MDCT) hepatocellular carcinoma  102 pancreatic cancer  84–85, 84 multiple endocrine neoplasia (MEN)  522, 528, 555–556 adrenal adenoma and  543 multiple myeloma (MM)  463–478 diagnosis  464, 466, 467–469, 468 Index genetics 465, 465 histopathology 464–465 incidence 463 mortality 463 pathogenesis 463–464, 472 presentation 465–467, 466 prevention 463 risk factors  463 staging 469, 469 survivorship 477–478 treatment 469–478, 471 allogeneic stem cell transplantation 476 ancillary therapy  477 autologous stem cell transplantation 475–476 histone deacetylase inhibitors  473, 474 immunomodulatory drugs  472, 473 maintenance therapy  476 monoclonal antibodies  473, 474 non‐transplant candidates 474–475 proteasome inhibitors  470–474, 473 recurrent disease  476–477 transplant candidates  475–476 MUTYH‐associated polyposis  70 myasthenia gravis (MG)  22, 665, 668 Myc mutations, non‐Hodgkin lymphoma  447, 454 MYCN amplification medulloblastoma 715 neuroblastoma  699, 700 myelodysplastic syndromes (MDS)  399, 400–403 classification 400–401, 401, 405 etiology 400 genetics 400 incidence 400 pathogenesis 400 pediatric 689 presentation 400 risk stratification/prognosis  401, 402 therapy 401–403 allogeneic stem cell transplantation 403 combination chemotherapy  403 hypomethylating agents  402–403 immunosuppression 402 supportive care  401–402 myelofibrosis 415 primary (PMF)  412, 413 therapy 415 myeloid malignancies  399–415 myeloproliferative neoplasms (MPN)  399, 410–413 classification 413 epidemiology 412–413 genetics 413 pathogenesis 413 presentation 412–413 therapy 414–415, 414 see also chronic myeloid leukemia (CML) myoepithelial carcinoma  194 n N‐acetyltransferase (NAT2) 237 nasal cavity cancer see sinonasal cancer nasopharyngeal cancer (NPC) 218–221 diagnosis 219 follow‐up 221 incidence 218 metastatic disease  221 mortality 218 pathology 218 prevention 218 risk factors  218 staging 219–220, 219 treatment 220–221 NCCN staging, pancreatic cancer  86, 87 necitumumab, lung cancer  14–15 neck dissection larynx cancer  207 oral cavity/oropharyngeal cancer  186–188 salivary gland cancer  198 sinonasal cancer  214 thyroid cancer  528 necrolytic migratory erythema (NME) 555 nelarabine, acute lymphoblastic leukemia 424 Nelson syndrome  549 neorectum construction  132, 135 nephrectomy 229–230 partial 229 nephroblastoma see Wilm’s tumor (WT) nephroureterectomy 245 neuroblastoma 698–701 diagnosis 699 follow‐up and late effects  701 incidence 698 presentation 698–699 staging 699–700, 700 treatment 700–701 neuroendocrine cancer of unknown primary site  648, 651, 655 neuroendocrine tumors (NETs), gastroenteropancreatic 124, 552–564 biology 555–556 classification 552–553 clinical features  553–555 appendiceal tumors  554 colorectal tumors  554 gastroduodenal tumors  553–554 midgut tumors  553 nonfunctioning pancreatic NETs 555 pancreatic tumors  554–555 diagnosis 556–558 imaging 557–558 immunohistochemical markers 556 serum and urine markers  556–557 genetic syndromes  555–556 incidence 555 metastatic disease  553, 555, 563 prognosis 564 staging 553 treatment 558–563 localized tumors  558–559 systemic therapy  559–563 targeted therapies  562–563 neurofibroma 587 spinal 593 neurofibromatosis (NF) type and 2  578, 587 soft tissue sarcoma association  632, 712 nevoid basal cell carcinoma syndrome 502 NF‐κB activation, non‐Hodgkin lymphoma 447 nilotinib, chronic myeloid leukemia  411, 412 nivolumab adrenal cancer  538 hepatocellular carcinoma  110 Hodgkin lymphoma  439 lung cancer  13, 13, 15 melanoma 496–497 renal cell carcinoma  231 745 746 Index nodal marginal zone lymphoma 453–454 nodular melanoma  489, 490, 490 non‐Hodgkin lymphoma (NHL)  70, 444–456 allogeneic stem cell transplantation 452–456 B‐cell  445–447, 449–456 cells of origin  447, 448 classification 444–445, 445, 692, 693 diagnosis  448–449, 693 epigenetic changes  446–447 follow‐up 456 genetics 446–447 affected signaling pathways  447 incidence  444, 692 management by subtype  449–456 follicular lymphoma (FL)  449–452 mantle cell lymphoma  453–454 marginal zone lymphomas  452–453 pediatric 692–695 treatment 694 prognostic indices  450 staging 694, 694 survivorship 456 T‐cell  447–448, 456 cells of origin  448 see also primary CNS lymphoma (PCNSL) non‐melanoma skin cancers atypical fibroxanthoma (AFX) 513–514 basal cell carcinoma (BCC)  502–505 clinical features  504–505, 504 diagnosis 504 incidence 502 pathology 504 risk factors  502–503 treatment 504–505 dermatofibrosarcoma protuberans (DFSP) 513 Kaposi sarcoma (KS)  514–515 keratoacanthoma (KAC)  508–509, 509 melanoma see melanoma Merkel cell carcinoma (MCC) 509–513 squamous cell carcinoma (SSC) 505–508 clinical features  505–506, 505 diagnosis 506 incidence 505 pathology 508 risk factors  505 staging 506–508, 506–507 treatment 508 nonalcoholic fatty liver disease (NAFLD) 100 nongastric marginal zone lymphoma 453 nonsmall cell lung cancer (NSCLC) 4 chemotherapy 12–16 early stage disease  16 locally advanced disease  16 maintenance therapy  12–13 salvage therapy  13, 17 elderly patients  16 radiation therapy  10–11 surgical treatment  9–10, 17 see also lung cancer nonsteroidal anti‐inflammatory drugs (NSAIDs), Barret esophagus prevention 41 nuclear and cytoplasmic neuronal antigens (NCNA)  664 nucleophosmin‐1 (NPM1) mutations, acute myeloid leukemia  404 o obesity breast cancer association  377–378 ovarian cancer association  254 renal cell carcinoma association  227 obinituzumab chronic lymphocytic leukemia  427 follicular lymphoma  452 occupational exposure bladder cancer association  237 lung cancer association  multiple myeloma association  463 salivary gland cancer association  192 sinonasal cancer association  211 soft tissue sarcoma association  631 OctreoScan® 557–558 octreotide, neuroendocrine tumors  559–560 antiproliferative effect  560 combined therapy  560–561 radiolabelled octreotide  562–563 ofatumumab, chronic lymphocytic leukemia 427 Okuda staging system, hepatocellular carcinoma 104 olaparib, ovarian cancer  262 oligodendroglioma  575, 584 omacetaxine, chronic myeloid leukemia 412 omeprazole 41 oncocytoma 228 Oncotype DX® assay  384 ophthalmic tumors see eye malignancies opsoclonus/myoclonus syndrome  699 oral cavity/oropharyngeal cancer  177–189 anatomy 178–179 lymphatic drainage  179, 180 oral cavity  178, 179 oropharynx 178–179, 180 biopsy 182 etiology 177–178 evaluation 181–182 imaging 182, 182 physical examination  181–182, 181 follow‐up 189 incidence 177 metastatic disease  179 mortality 177 pathogenesis 180–181 pathology 180 presentation 181 prevention 178 risk factors  177 staging 182–185, 183–186 survivorship 189 treatment 185–189 chemotherapy 189 radiation therapy  188–189 surgery 186–188, 187, 188 see also salivary gland cancer oral contraception, gestational trophoblastic disease  322 oral prosthodontics  187 orbital tumors  609–610 therapy 611 orchiectomy  332–336, 338 organ transplantation melanoma association  488 non‐melanoma skin cancer association  502, 505 ornithine decarboxylase (ODC)  543 oropharyngeal cancer see oral cavity/ oropharyngeal cancer orthotopic liver transplantation (OLT) cholangiocarcinoma 119 hepatocellular carcinoma  106 osimertinib, lung cancer  14 osteosarcoma  619, 620 diagnosis 696 Index etiology and risk factors  695 follow‐up and late effects  696–697 incidence 695 metastatic disease  696 pathology 695 pediatric 695–697 presentation 695–696 therapy  626–627, 696 see also bone sarcoma OVA‐1 blood test  254 ovarian cancer  253–260 imaging 255 incidence 253 mortality 253 palliative care  262 pathology 255–256 simultaneous endometrial and ovarian tumors  271 peritoneal metastases  677 post‐treatment surveillance  260–261, 260 presentation 254–255 recurrence 261–262, 261 risk factors  253–254 age 253 genetic factors  254 HRT 254 obesity 254 reproductive factors  253–254 screening 254 staging 255, 256 stromal tumors  254 treatment 256–260 chemotherapy 259–260, 261–262, 261 cytoreductive surgery  258–259, 260 maintenance therapy  260 neoadjuvant therapy  259–260 surgery 256–259 targeted therapies  260 ovarian germ cell tumors (OGCTs)  254, 262–264 classification  258, 262 late effects  263–264 pathology 262 persistence, progression or recurrence 263 presentation 262 recurrence 263 surveillance 263 treatment 262–263 chemotherapy 263–264 surgery 262–263 ovarian suppression, breast cancer  390 ovarian tumor classification  257–258 overlap MDS/MPN neoplasms  399, 413–414 oxaliplatin cervical cancer  295 colorectal cancer  137, 138 germ cell tumors  339–340 pancreatic cancer  94 p paclitaxel breast cancer  385, 386–387 cervical cancer  295 endometrial carcinoma  278, 280 lung cancer  12, 16 nab‐paclitaxel 12 metastatic anal cancer  157 ovarian cancer  259 maintenance therapy  260 penile cancer  370–371 testicular cancer  338, 339–340 Paget disease, extramammary  313 pain management lung cancer  11 pancreatic cancer  94 palbociclib, breast cancer  389, 390 palliative therapy cholangiocarcinoma  119, 120 colorectal cancer  142 gastric cancer  63 leptomeningeal disease  598 lung cancer  11, 16–17 ovarian cancer  262 pancreatic cancer  94–95 penile cancer  370–371 prostate cancer  357–358 renal cell carcinoma  232 small bowel cancer  78 pamidronate breast cancer metastases  391 multiple myeloma bone disease  477 pancreastatin 557 pancreatic adenocarcinoma  82–95 biology 83 clinical presentation  83–84 familial form  82–83 imaging 84–86, 84, 85 incidence 82 mortality 82 palliative care  94–95 risk factors  82–83 staging 86, 86, 87 surgical treatment  84 treatment 86–94 adjuvant therapy  87–89, 88 borderline resectable cancer  89–90, 90 localized and resectable cancer 87–89, 88 locally advanced cancer (LAPC) 91–92, 93, 94 metastatic disease  92–94 neoadjuvant therapy  89–92, 89 pancreatic enzyme replacement  95 pancreatic intraepithelial neoplasm (PanIN) 83 pancreatic neuroendocrine tumors  554–555 treatment 558 pancreaticoduodenectomy 91, 91, 92, 119 pancreaticojejunostomy 91 pancreatitis, hereditary  82 panitumumab, cholangiocarcinoma 120 panobinostat, multiple myeloma  473, 474 Pap smear test  289, 290 papillary urothelial neoplasm of low malignant potential (PUNLMP)  238, 242 paraganglioma 587 spinal 593 paranasal sinus cancer see sinonasal cancer paraneoplastic cerebellar degeneration (PCD)  665 paraneoplastic pemphigus (PNP)  667 paraneoplastic syndromes  661 constitutional 661 dermatologic and rheumatologic  667–668, 668 endocrine 662–664, 663 hematologic 668–669, 670 neurologic 664–668, 665–666 Paris staging system, gastrointestinal lymphoma 75, 76 Parkinson disease, melanoma association 488 parotid glands  195 see also salivary gland cancer parotidectomy 197–198 pazopanib gastrointestinal stromal tumors  170 ovarian cancer  260 renal cell carcinoma  231 soft tissue sarcoma  639 747 748 Index PC leukemia  467 pediatric cancers  685–716 acute lymphoblastic leukemia (ALL)  685–688 classification 686 CNS‐directed treatment  688 diagnosis 686 etiology and risk factors  685–686 follow‐up and late effects  688 incidence 685 prognostic factors  686–687 risk‐stratified therapy  687 treatment phases  687–688 acute myeloid leukemia (AML)  688–691 classification 690, 690 diagnosis 690 etiology and risk factors  689 follow‐up and late effects  691 incidence 689 presentation 689 treatment 690–691 Ewing sarcoma  697–698 classification 697 diagnosis 697–698 etiology and risk factors  697 follow‐up and late effects  698 incidence 697 presentation 697 treatment 698 germ cell tumors  706–708 diagnosis 707 etiology and risk factors  706 follow‐up and late effects  708 incidence 706 pathology 706 presentation 707 treatment 707–708 glioma 712–714 classification 712–713 diagnosis 713 etiology 712 follow‐up and late effects  714 incidence 712 presentation 713 treatment 713–714 Hodgkin lymphoma  691–692 classification 691 etiology and risk factors  691 follow‐up and late effects  692 incidence 691 presentation 691 treatment 691–692 medulloblastoma 714–716 classification 714–715 diagnosis 715 etiology and risk factors  714 follow‐up and late effects  716 incidence 714 presentation 715 staging 715, 715 treatment 715–716 neuroblastoma 698–701 diagnosis 699 follow‐up and late effects  701 incidence 698 presentation 698–699 staging 699–700, 700 treatment 700–701 non‐Hodgkin lymphoma  692–695 anaplastic large cell lymphoma  694–695 Burkitt lymphoma  693, 694 classification 692, 693 diffuse large B‐cell lymphoma  694 etiology and risk factors  692 follow‐up and late effects  695 incidence 692 lymphoblastic lymphoma  694 presentation and diagnosis  693 staging 693–694, 694 treatment 694–695 osteosarcoma 695–697 diagnosis 696 etiology and risk factors  695 follow‐up and late effects 696–697 incidence 695 pathology 695 presentation 695–696 treatment 696 retinoblastoma 708–712 etiology and risk factors  708–709 follow‐up and late effects 711–712 incidence 708 pathology 709 presentation and diagnosis  709 staging 709, 710 treatment 709–711 rhabdomyosarcoma 704–706 diagnosis 704–705 follow‐up and late effects  706 incidence 704 pathology 704 staging 705, 705, 706 treatment 706–707 Wilm’s tumor  701–704 associated syndromes  701–702, 702 classification 702 etiology and risk factors  701–702 follow‐up and late effects 703–704 incidence 701 presentation and diagnosis 702–703 staging 703, 703 treatment 703 pegvisomant, acromegaly  548 pembrolizumab cholangiocarcinoma 120 lung cancer  13, 13, 15 melanoma 496 pemetrexed lung cancer  12–13 maintenance therapy  12–13 salvage therapy  13 mesothelioma 28 see also chemotherapy penile cancer  363–371 diagnosis 364–365 etiology 363–364 follow‐up 371 histopathology 364 incidence 363 molecular pathology  364 mortality 363 prevention 364 quality of life impact  371 recurrence 371 staging 365–366, 365–366 treatment 366–371 early nonsuperficial lesions  366, 367–370 metastatic disease  370–371 palliative therapy  370–371 radiotherapy 367–370 superficial lesions  366–367 surgery 367 pentostatin, hairy cell leukemia  429 peptide receptor radiotherapy (PRRT), neuroendocrine tumors 562–563 percutaneous ethanol ablation, hepatocellular carcinoma  107 peretinoin, hepatocellular carcinoma 107 perihilar tumors  117 perineural tumor invasion  588 peripheral nerve tumors  587–588 Index peripheral T‐cell lymphoma (PTCL) 456 peritoneal cancer index (PCI)  676, 677, 679 peritoneal malignancies  675–679 diagnosis 677–678 malignant bowel obstruction  679 primary 675 carcinomatosis  653, 675 malignant mesothelioma  675 sarcomatosis 675 secondary 675–677 colorectal carcinomas  676 epithelial appendiceal neoplasms (EAN) 676 gastric cancer  676–677 ovarian cancer  677 treatment 678–679, 678 pertuzumab, breast cancer  390 petrosphenoidal syndrome of Jacod 219 Peutz‐Jegher’s syndrome  71 pharyngeal cancer see nasopharyngeal cancer (NPC); oral cavity/ oropharyngeal cancer pheochromoctyoma 532–538 diagnosis 534–535 imaging 535 immunohistochemistry 533 pathology 533 risk factors  532 staging 535 treatment 536–538 chemotherapy 537 surgery 536 targeted therapy  538 Philadelphia (Ph) chromosome  410, 423, 687 phimosis 363 phlebotomy, polycythemia vera  414 photocoagulation, retinoblastoma 709–710 photodynamic therapy (PDT), cholangiocarcinoma 119 pilocytic astrocytoma  584, 592, 712 pineal region tumors  586 pioglitazone exposure, bladder cancer association 238 pituitary apoplexy  544 pituitary gland  544 pituitary tumors  542–549 adenomas  542, 543 atypical 544 familial 543 carcinomas 542 classification  543 diagnosis 544–545 acromegaly 544–545 Cushing disease  545 nonfunctioning adenomas (NFPA) 544 prolactinomas 544 rare functioning tumors  545 incidence 542 incidentaloma 544 metastases 542 mortality 542 pathogenesis 543 pathology 543–544 risk factors  543 treatment 546–549 aggressive adenomas  549 radiation therapy  546–549 surgery 545–546, 547 placental site trophoblastic tumor (PSTT) 319, 320 treatment 325 see also gestational trophoblastic disease (GTD) plasma cells, multiple myeloma 463–464 plasma cell dyscrasia  468 plasmacytoma 467 platelet‐derived growth factor receptor (PDGFR) mutations CNS tumors  579 gastrointestinal stromal tumors  163–164, 165, 639 pleomorphic xanthoastrocytoma  584 pleural effusions lung cancer  mesothelioma 26 pneumonectomy 10 pneumonitis, radiation‐related  11 POEMS syndrome  469 polycythemia vera (PV)  412 therapy 414 polymorphous adenocarcinoma  193 polymyalgia rheumatica (PMR)  668 polyps cervical  290 gastrointestinal 125 pomalidomide, multiple myeloma  470, 473 ponatinib acute lymphoblastic leukemia  424 chronic myeloid leukemia  412 portal vein embolization  119 portal vein resection  90 positron emission tomography (PET) adrenal cancer  535 anal cancer  150 astrocytoma 580 bladder cancer  240 bone sarcomas  620 breast cancer  381 cancer of unknown primary site  650, 651 cervical cancer  293 esophageal cancer  36, 43, 45 gastric cancer  57 gastrointestinal stromal tumors  164 Hodgkin lymphoma  436, 437, 691 lung cancer  6, 10 melanoma follow‐up  497–498 metastatic skin cancer (non‐melanoma) 510 multiple myeloma  465 nasopharyngeal cancer  219 neuroendocrine tumors  558 oral cavity/oropharyngeal cancers 182 pancreatic cancer  85, 85 peritoneal malignancies  677 small bowel cancer  73–74, 74 soft tissue sarcoma  633 testicular cancer  332 Predictor Analysis of Microarray (PAM) 50 384 pregnancy, cervical cancer  295–296 primary acquired melanosis (PAM) 609 primary CNS lymphoma (PCNSL)  596–597 diagnosis 597, 597 presentation 597 treatment 597 primary cutaneous neuroendocrine carcinoma see Merkel cell carcinoma (MCC) primary myelofibrosis (PMF)  412, 413 therapy 415 primary peritoneal cancer  253–264 presentation 254–255 staging 255, 256 treatment 256 chemotherapy 259 primitive neuroectodermal tumors (PNETs)  586, 640 proctectomy 130–131, 134 postproctectomy syndrome 142–143 749 750 Index progesterone receptor expression, breast cancer  379–380, 384 progestin therapy endometrial carcinoma  279 recurrent disease  279 endometrial hyperplasia  269 prolactinoma 542 diagnosis 544 treatment 546 prolymphocytic leukemia (PLL) 428–429 prophylactic cranial irradiation (PCI) 17 prostate cancer  344–358 diagnosis 346–347 incidence 344, 345 metastatic disease  352–358 chemohormonal therapy  352–353 metastatic disease prostate cancer bone‐directed therapy  357–358 chemotherapy 353–354, 355 immunotherapy 356–357, 357 radionuclide therapy  357, 357 secondary hormonal therapy 354–356 molecular markers  345 mortality 344 recurrence 351 risk factors  344–346 risk stratification  349 screening 346, 346 staging 347–348, 348 prognostic stage groups  349 subtypes 347, 347 treatment 348–358 active surveillance  348–349 androgen deprivation therapy (ADT)  349, 350–351, 352 radiation therapy  349–350 radical prostatectomy  349–351 salvage therapy  351–352 prostate‐specific antigen (PSA)  344, 346, 348, 351 cancer of unknown primary site  649, 653 prostatectomy 349–351 prostatic urothelial carcinoma 245–246 proteasome inhibitors, multiple myeloma 470–474, 473 pseudomyxoma peritonei  256 pulmonary metastases  140 pure red cell aplasia (PRCA)  669, 670 pylorus‐sparing Whipple procedure  91, 92 q 5q‐syndrome 400 quizartinib, acute myeloid leukemia 407 r radiation exposure see ionizing radiation exposure radiation therapy acromegaly 548 anal cancer  150–153, 157–158 inguinal lymph node management 154 intensity‐modulated therapy (IMRT) 154, 155, 156 techniques 157–158 treatment breaks  158 astrocytoma 581–582 bone sarcoma  624–626 pediatric patients  696 radiotherapy as cause  619 brain metastases  11, 595, 596 prophylactic cranial irradiation  17 breast cancer  385 cervical cancer  296 cholangiocarcinoma 120 CNS tumors  577 colorectal cancer  132–134, 135 external beam RT  133 particle RT  134 diffuse large B‐cell lymphoma  455 endometrial carcinoma  276 postoperative 276–277 recurrent disease  279–280 esophageal cancer  43 Ewing sarcoma  698 eye malignancies  609, 612, 614 follicular lymphoma  451, 452 glioblastoma 582, 583 gliomas 713–714 hepatocellular carcinoma  108 Hodgkin lymphoma  436, 437–438 long‐term complications  440–441 pediatric patients  692 larynx cancer  203–207, 207, 208 lung cancer  10–11 palliative 11 SCLC 17 marginal zone lymphomas  453 medulloblastoma 715 mesothelioma 26–28 nasopharyngeal cancer  220 oral cavity/oropharyngeal cancer  188–189 pancreatic cancer  87–89 penile cancer  367–370, 369 pituitary tumors  546–549 prostate cancer  349–350 renal cell carcinoma  232 retinoblastoma  710, 711 rhabdomyosarcoma 706 salivary gland cancer  197 selective internal radiotherapy (SIRT) 563 seminoma 334–336 sinonasal cancer  213, 214–215, 215 skin cancer (non‐melanoma)  508, 512, 513 soft tissue sarcoma  636 spinal metastases  594 thymic malignancies  24, 25 thyroid cancer  529 vaginal cancer  307–308 vulvar cancer  315 Wilm’s tumor  703, 704 see also brachytherapy; chemoradiotherapy radiation‐associated sarcomagenesis (RAS) 631 radioactive iodine ablation (RAI), thyroid cancer  527–528 radiofrequency ablation cholangiocarcinoma 119 hepatocellular carcinoma  107 liver metastases  138 renal cell carcinoma  229 radiologic studies, small bowel cancer 71 radionuclide therapy neuroendocrine tumors  562–563 prostate cancer  357, 357 radiosurgery see stereotactic radiosurgery (SRS) radium‐223 therapy, prostate cancer 357 radon exposure, lung cancer association 4 raloxifene, breast cancer risk reduction 378–379 ramucirumab esophageal cancer  49 gastric cancer  63 hepatocellular carcinoma  110 lung cancer  14 Index ranitidine 41 RECIST (Response Evaluation Criteria in Solid Tumors) guidelines  110 rectal cancer follow‐up and surveillance  141 radiation therapy  132–134, 135 external beam RT  133 particle RT  134 recurrence 141 squamous cell carcinoma  124 staging 129, 130 surgical treatment  130–132, 132, 133, 134 neorectum construction  132, 135 quality grading  132 see also colorectal cancer (CRC) rectal carcinoid tumors  554 red meat consumption  70 Reed–Sternberg cells  434, 691 regorafenib, gastrointestinal stromal tumors  170, 639 regorafenib, hepatocellular carcinoma 109 renal cell carcinoma  227–233 follow‐up 232–233 imaging 228, 229 incidence 227 inherited forms  228 metastatic disease  230 molecular pathology  228 mortality 227 palliative therapy  232 presentation 228 recurrence 230 risk factors  227–228 staging 228–229, 230 survivorship 233 treatment 229–232 immunotherapy 231 large tumors  229–230 localized disease  229 systemic therapy  230–231 targeted therapy  230, 231–232, 232, 233 renal cysts  228 RET mutations, thyroid cancer  522 retinoblastoma 708–712 etiology and risk factors  708–709 follow‐up and late effects  711–712 incidence 708 osteosarcoma association  695 pathology 709 presentation and diagnosis  709 staging 709, 710 treatment 709–711 bilateral retinoblastoma  710–711 chemotherapy  710, 711 CNS disease  711 extraocular retinoblastoma  711 focal therapies  709–710 metastatic retinoblastoma  711 radiotherapy 710 surgery 709 unilateral retinoblastoma  710 retromolar trigone  178, 180 see also oral cavity/oropharyngeal cancer retroparotid syndrome of Villaret  219 retroperitoneal lymph node dissection (RPLND)  336, 338 rhabdomyosarcoma  631, 640, 704–706 diagnosis 704–705 follow‐up and late effects  706 incidence 704 pathology 704 staging 705, 705, 706 subtypes 704 treatment 705–706 see also soft tissue sarcoma ribociclib 389 Richter transformation  428 ricolinostat, multiple myeloma  476 rituximab chronic lymphocytic leukemia  427 diffuse large B‐cell lymphoma  455 follicular lymphoma  451–452 maintenance therapy  452 hairy cell leukemia  429 Hodgkin lymphoma  440 intraocular lymphoma  614 mantle cell lymphoma  453–454 marginal zone lymphomas  453 robotic surgery colorectal cancer  130, 132 endometrial carcinoma  276 esophagectomy 42–43 oropharyngeal cancer  188 Rombo syndrome  503 Roux‐en‐Y reconstruction  57–58, 58 ruxolitinib, polycythemia vera  415 s sacral nerve stimulation  143, 159 salivary duct carcinoma  194 salivary gland cancer  192–198, 193 diagnosis 195–197 biopsy 197 examination 195 imaging 195–197 follow‐up 198 incidence 192 mortality 192 pathology 192–195 acinic cell carcinoma  193 adenocarcinoma 194–195 adenoid cystic carcinoma  193 basal cell adenocarcinoma  194 carcinoma ex pleomorphic adenoma 194 epithelial–myoepithelial carcinoma 194 lymphoma 195 metastasizing mixed tumors  194 mucoepidermoid carcinoma  193 myoepithelial carcinoma  194 polymorphous adenocarcinoma 193 salivary duct carcinoma  194 small cell carcinoma  194 squamous cell carcinoma  194 prognosis 198 risk factors  192 staging  196, 197 survivorship 198 treatment 197–198 sarcoma Kaposi (KS)  514–515 conjunctival 609 small cell  640 uterine 280–282 vaginal 305–306, 306 see also bone sarcoma; Ewing sarcoma; soft tissue sarcoma sarcoma botyroides  305, 306 sarcomatoid carcinoma, bladder  239 satraplatin, prostate cancer  354, 355 schwannoma 587 spinal 591–592, 591 screening actionable molecular alterations  656 anal cancer  149 breast cancer  379 cervical cancer  289 cholangiocarcinoma 118 colorectal cancer  126 endometrial carcinoma  269 esophageal cancer  41 hepatocellular carcinoma  101–102, 102 lung cancer  ovarian cancer  254 prostate cancer  346, 346 small bowel cancer  71 751 752 Index seizures, brain tumor patients  577 selective estrogen receptor modulators (SERMs) 378 selective internal radiotherapy (SIRT) 563 seminoma 332–333 presentation 334 surveillance 334 treatment 334–336 sentinel lymph node biopsy melanoma 493–494 penile cancer  366 sinonasal cancer  214 skin cancer (non‐melanoma)  507, 508, 510 vulvar cancer  313 serotonin secretion, neuroendocrine tumors 553 diagnostic assays  556–557 serous tumors endometrial 271 ovarian 255, 257 salivary gland  192–193 Sertoli–Leydig cell tumors ovarian 264 testicular 334 sex cord–stromal tumors (SCSTs) ovarian 254, 258, 264 chemotherapy 264 presentation 264 surgery 264 testicular  333, 334 treatment 340 sexual dysfunction anal cancer survivors  158–159 colorectal cancer survivors  143 penile cancer survivors  371 Siewert classification, gastroesophageal junction cancers  36 Simpson–Golabi–Behmel syndrome  702 sinonasal cancer  211–215 diagnosis 212, 212 follow‐up 215 incidence 211 metastatic disease  211–212 mortality 211 pathology 211–212 risk factors  211 staging 212–213, 213 survivorship 215 treatment 213–215 neck management  214 primary tumor surgery  213–214, 214 radiation therapy  214–215, 215 systemic therapy  215 sipuleucel‐T, prostate cancer  356–357, 357 skin cancers see melanoma; non‐ melanoma skin cancers small bowel cancer  69–78 diagnosis 71 CT 71–74, 72, 73 endoscopy 74–75 enteroclysis 72–73 MRI 73 PET‐CT 73–74, 74 radiologic assessment  71 follow‐up 78 incidence 69 mortality 69 pathology 71 risk factors  69–71 inherited conditions  70–71 lifestyle factors  69–70 underlying conditions  70 screening 71 staging 75, 75, 76 survivorship 78 treatment 75–78 chemoradiation 76–78, 77 chemotherapy  76, 78 palliative therapy  78 surgery 76 small cell carcinoma bladder 247 cervical 290 salivary gland  194 small cell lung cancer (SCLC)  4–5 chemotherapy 16–17 radiation therapy  17 recurrence 16 see also lung cancer small cell sarcoma  640 small lymphocytic lymphoma (SLL) 452 small renal masses (SRMs) see renal cell carcinoma smoking bladder cancer association  237, 238 gastric cancer association  54 larynx cancer association  201 liver cancer association  101 lung cancer association  3, 17 cessation importance  17 oral cavity/oropharyngeal cancer association 177 pancreatic cancer association  82 penile cancer association  364 renal cell carcinoma association  227 small bowel cancer association  69 smooth muscle tumors of uncertain malignant potential (STUMP) 281 soft tissue sarcoma  631–640 diagnosis 632–633 etiology 631–632 genetic syndromes  632 incidence 631 metastatic disease  634, 638–639 mortality 631 natural history  632 pathology 633–634 presentation 632 recurrence  635, 638 staging 634, 634 treatment 634–638 chemotherapy 636–638, 636, 637 radiotherapy 636 surgery 634–635 solitary plasmacytoma  467 somatostatin analog (SSA) therapy, neuroendocrine tumors  559–560 antiproliferative effect  560 combined therapy  560–561 radiolabeled SSAs  562–563 somatostatin‐receptor scintigraphy  557–558 sonidegib, skin cancer  504 sorafenib 109 acute myeloid leukemia  407 hepatocellular carcinoma  107, 108–109 combination therapy  109 response evaluation  110 renal cell carcnoma  231 thyroid cancer  528 speech therapy  187 spinal cord compression  11, 574, 591, 593 spinal tumors  590–593 diagnosis 591 differential diagnosis  590 metastases 593–594 clinical findings  593 diagnosis 593–594 treatment 594 presentation 590–591 treatment 591 see also central nervous system (CNS) tumors; specific tumors splenectomy, myelofibrosis  415 splenic marginal zone lymphoma  453 Index squamous cell carcinoma (SCC) anal 150 bladder 246–247 cancer of unknown primary site  648, 650–651, 654–655 cervical 290 conjunctival 608 endometrial 271 esophageal 35–36 staging 36, 37–40 gastrointestinal 124 larynx 202, 203, 207, 207, 208 lung 4 molecular pathology  oral cavity/oropharyngeal  177, 180, 182 penile 364, 366 salivary gland  194 sinonasal  211, 215 skin 505–508, 505 vaginal 305 vulvar  310, 311–312 stem cell transplantation see allogeneic stem cell transplantation (SCT); autologous stem cell transplantation (SCT) stereotactic body radiation therapy (SBRT), lung cancer  10–11 stereotactic needle biopsy, astrocytoma 580 stereotactic radiosurgery (SRS) brain metastases  11, 595–596 Cushing disease  548–549 pituitary tumors  546 Stewart–Treves syndrome  631–632 stomach cancer see gastric adenocarcinoma streptozocin adrenal cancer  537 neuroendocrine tumors  562 stromal tumors, endometrial  281 see also gastrointestinal stromal tumors (GISTs); sex cord– stromal tumors (SCSTs) subacute sensory neuropathy  666 subependymal giant cell astrocytoma  584, 712 sublingual glands  195 see also salivary gland cancer submandibular glands  195 see also salivary gland cancer subungual melanoma  491 sunitinib adrenal cancer  538 gastrointestinal stromal tumors  170, 639 hepatocellular carcinoma  110 neuroendocrine tumors  561 pheochromocytoma 538 renal cell carcinoma  231 thymic carcinoma  24 sunlamp use, melanoma association 488–489 superficial spreading melanoma  489, 490, 490, 491 survivorship, lung cancer  17 swallowing 178–179 therapy 187 see also dysphagia Sweet syndrome  668, 668, 669 synaptophysin 556 syndrome of inappropriate antidiuretic hormone (SIADH)  662, 663 syrinx 592 t T‐cell development  447–448 talimogene laherparepvec (T‐vec), melanoma 497 tamoxifen, breast cancer  387 metastatic disease  390 risk reduction  378–379 tanning bed use, melanoma association 488–489 temozolomide CNS tumors  577 astrocytoma  582, 583 glioblastoma 582 glioma 714 neuroendocrine tumors  462 pituitary adenoma  549 temsirolimus adrenal cancer  538 renal cell carcinoma  232 teratoma  262, 333, 334, 338 pediatric 707 testicular cancer  331–340 diagnosis 332 etiology 331–332 single nucleotide polymorphisms  331–332, 332 incidence 331 metastatic disease  336–338 metastatic patterns  332 prognostic system  337 mortality 331 pathology 332–333 presentation 333–334 recurrent disease  338–340, 338, 339 prognostic factors  339, 339 staging  333 treatment 334–340, 335 advanced disease  336–338 nonseminomatous germ cell tumors 336 postchemotherapy surgery  338 salvage therapy  338–340, 338 seminoma 334–336 testicular dysgenesis  331 thalidomide, multiple myeloma  470, 473, 475 maintenance therapy  476 thoracentesis 26 three‐dimensional conformal radiation therapy (3DCRT), esophageal cancer 47–49 thrombocytosis, paraneoplastic  669, 670 thrombophilia 668 thymectomy 24 thymic carcinoma  22–28 diagnosis 22–23 follow‐up 25 mortality 22 pathology 22 staging 23, 23 subtypes 22 treatment 24 chemotherapy 24 radiation therapy  24, 25 surgery 24 thymoma 22–28 diagnosis 22–23 follow‐up 25 incidence 22 mortality 22 pathology 22 recurrence 25 staging 23, 23 subtypes 22 treatment 24 chemotherapy 24 radiation therapy  24 surgery 24 thyroid cancer  521–529 classification 521–522 diagnosis 523–524, 524 fine needle aspiration  523–525 follow‐up  528, 529 incidence 521 molecular pathology  524 mortality 521 753 754 Index thyroid cancer (cont’d ) presentation 523 risk factors  522–523 demographic factors  522 heritable conditions  522 iodine deficiency  523 ionizing radiation  522–523 staging 524, 525–527 survivorship  528, 529 treatment 524–529 anaplastic thyroid cancer  529 differentiated thyroid cancer 524–528 medullary thyroid cancer 528–529 metastatic disease  528, 529 radioactive iodine ablation 527–528 refractory disease  528 surgery  524–527, 528 TSH suppression  528 thyroid stimulating hormone (TSH) suppression 528 TSHomas 545 thyroid transcription factor (TTF‐1) 4 tivantinib, hepatocellular carcinoma 109 TNM staging adrenal cancer  535 anal cancer  150, 151 bladder cancer  239–240, 240 bone sarcoma  621, 623 breast cancer  381–384, 382–383 cervical cancer  290, 291 colorectal cancer  127–128, 127–128 fallopian tube cancer  255, 256 gastric cancer  56–57, 56 gastrointestinal stromal tumors  165 hepatocellular carcinoma  104, 104 larynx cancer  202, 204–205 lung cancer  6, 7–8 mesothelioma 26, 27 nasopharyngeal cancer  219–220, 219 neuroendocrine tumors  553 oral cavity/oropharyngeal cancers 182–185, 183–185 ovarian cancer  256 pancreatic cancer  86, 86 penile cancer  365–366 pheochromocytoma 535 primary peritoneal cancer  255, 256 prostate cancer  347, 348 renal cell carcinoma  228–229, 230 salivary gland cancer  196, 197 sinonasal cancer  212–213, 213 skin cancer (non‐melanoma)  506–507, 511–512 small bowel cancer  75 soft tissue sarcoma  634, 634 testicular cancer  333 thymic malignancies  23 thyroid cancer  524, 525–527 vaginal cancer  307 vulvar cancer  312, 313 tobacco smoking see smoking tongue 178, 180 surgical treatment  186, 187 see also oral cavity/oropharyngeal cancer tonsillectomy 651 topotecan cervical cancer  295 lung cancer  17 toremifene, breast cancer  390 total mesorectal excision  130, 132 quality grading  132, 132 total parenteral nutrition (TPN), colorectal cancer patients  142 TP53 mutations breast cancer  380–381, 384 CNS tumors  579 ovarian cancer  255 skin cancer  504 vulvar cancer  312 trabectedin, soft tissue sarcoma  638–639 tracheostomy 205 trametinib lung cancer  15 melanoma 497 trans‐arterial chemoembolization  119–120 see also embolic therapies transarterial chemoembolization (TACE) hepatocellular carcinoma  107–108 drug‐eluting bead TACE  108 liver metastases  563 transarterial radioembolization (TARE), hepatocellular carcinoma  108 transient myeloproliferative disorder (TMD) 689 transpupillary thermotherapy, retinoblastoma 710 transurethral resection of bladder tumor (TURBT)  239, 241, 242, 244 transvaginal ultrasound (TVUS) endometrial carcinoma  270 ovarian cancer  254 trastuzumab breast cancer  386, 388 metastatic disease  390 trastuzamab‐DM1 391 esophageal cancer  49 gastric cancer  63 trauma, soft tissue sarcoma association 632 TSHoma 545 tuberous sclerosis  556, 578, 584, 712 tubular carcinoma, breast  379 tumor lysis syndrome  423, 424, 427, 428 tumor markers see biomarkers; specific markers Turcot syndrome  578, 712, 714 tyrosine kinase inhibitor (TKI) therapy acute lymphoblastic leukemia  423–424 acute myeloid leukemia  407 adrenal cancer  538 chronic lymphocytic leukemia  427 chronic myeloid leukemia  411, 412 response monitoring  411 gastrointestinal stromal tumors  166, 170 hepatocellular carcinoma  109 lung cancer  5, 14 neuroendocrine tumors  561 renal cell carcinoma  231 thyroid cancer  528 u ulcerative colitis  125 ultrasound breast cancer  379 endometrial carcinoma  270 gestational trophoblastic disease  321 ovarian cancer  255 testicular cancer  332 see also endoscopic ultrasound (EUS) ultraviolet radiation (UVR) eye malignancy association  608 melanoma association  487, 488 indoor tanning  488–489 non‐melanoma skin cancer association  502, 505 upper urinary tract urothelial carcinoma (UUT‐UCC) 245 urachal adenocarcinoma  246 staging  246 Index ureterectomy 245 urinary bladder cancer see bladder cancer urinary cytology  241 urothelial cell carcinoma (UCC) bladder 237 pathology 238–239 see also bladder cancer prostatic 245–246 upper urinary tract  245 uterine corpus cancer  268 see also endometrial carcinoma uterine sarcoma  280–282 classification 280 uveal melanoma  611–612, 612, 613 v vaccines human papillomavirus  149, 178, 289 melanoma 495 vaginal cancer  304–308 etiology 304 follow‐up 308 incidence 304 mortality 304 pathology 305–306, 306 adenocarcinoma 305 melanoma 306, 306 sarcoma 305–306, 306 squamous cell carcinoma  305 presentation 304–305 prevention 304 routes of spread  306–307, 306 staging 307, 307 treatment 307–308 treatment‐related complications  308 vaginal intraepithelial neoplasia (VAIN)  304–305, 305 diagnosis 305 pathology 305 treatment 307 vandetanib, thyroid cancer  528, 529 vascular endothelial growth factor (VEGF) inhibitors cholangiocarcinoma 120 lung cancer  13–14 renal cell carcinoma  231 vasoactive intestinal peptide (VIP)  555 VIPoma 555 vemurafenib hairy cell leukemia  429 melanoma 497 venetoclax chronic lymphocytic leukemia  427 multiple myeloma  477 venous thromboembolism (VTE)  661 verrucous carcinoma larynx 202 vaginal 305 vulvar  311, 312 vestibular schwannoma (VS)  587 vinblastine, testicular cancer  336–337 vincristine adrenal cancer  537 gestational trophoblastic disease  324 vinflunine, bladder cancer  244 VIPoma 555 vismodegib, skin cancer  504 vitamin C, gastric cancer relationship 54 VLX1570, multiple myeloma  477 vocal cord cancer  202, 203 see also larynx cancer von Hippel–Lindau syndrome (VHL)  228, 556 von Recklinghausen’s neurofibromatosis (NF1) 164 vulvar cancer  310–316 etiology 310, 311 follow‐up 315–316 incidence 310 metastatic disease  312 mortality 310 pathology 311–313 Bartholin gland cancer  312–313 basal cell carcinoma  313 extramammary Paget disease  313 melanoma 312 squamous cell carcinoma  311–312 verrucous carcinoma  312 presentation 311, 311 prevention 310 recurrence 315–316 staging  312, 313 survivorship 316 treatment 314–315 chemotherapy 315 melanoma 315 radiation therapy  315 surgery 314–315, 314 survival rates  315 vulvar intraepithelial neoplasia (VIN)  310, 311 pathology 311 treatment 313 vulvectomy 314, 314 w WAGR syndrome  702 Whipple procedure  91, 91, 119 pylorus‐sparing 91, 92 Whipple triad  554 Wilm’s tumor (WT)  701–704 classification 702 etiology and risk factors  701–702 associated syndromes  701–702, 702 follow‐up and late effects  703–704 incidence 701 presentation and diagnosis  702–703 staging 703, 703 treatment 703 wireless capsule endoscopy  74–75 y 90 Y‐ibritumomab tiuxetan, follicular lymphoma 452 yolk sac tumor (YST)  333 presentation 334 z zoledronic acid breast cancer  388, 391 multiple myeloma bone disease  477 prostate cancer  353, 357–358 renal cell carcinoma  232 Zollinger–Ellison syndrome  555 755 WILEY END USER LICENSE AGREEMENT Go to www.wiley.com/go/eula to access Wiley’s ebook EULA ... annually, lung cancer is the most common cancer in China in both men and women Based on the increasing incidence of cigarette smoking in the developing world, it is estimated that most lung cancers... for developing lung cancer Though the prevalence of cigarette smoking is declining in the US, it is increasing at an alarming rate in developing and third world countries Consequently, the number... in patients with lung cancer The 7th Edition of the American Joint Committee on Cancer (AJCC) and the Union for International Cancer Control (UICC) system introduced in 2010 is in use until the

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