Critical Issues in Head and Neck Oncology Key Concepts from the Seventh THNO Meeting Jan B. Vermorken Volker Budach C. René Leemans Jean-Pascal Machiels Piero Nicolai Brian O’Sullivan Editors 123 Critical Issues in Head and Neck Oncology Jan B. Vermorken • Volker Budach C. René Leemans • Jean-Pascal Machiels Piero Nicolai • Brian O’Sullivan Editors Critical Issues in Head and Neck Oncology Key Concepts from the Seventh THNO Meeting Editors Jan B. Vermorken Volker Budach Department of Medical Oncology Departments for Radiation Oncology and Antwerp University Hospital, Edegem Radiotherapy Belgium and Faculty of Medicine and Charite University Medicine Berlin Health Sciences, University of Antwerp Berlin Antwerp Germany Belgium Jean-Pascal Machiels C. René Leemans Oncology Department of Otolaryngology – Head and Cliniques Universitaires Saint-Luc Neck Surgery Woluwe-Saint-Lambert Amsterdam University Medical Centers Belgium Vrije Universiteit Amsterdam Brian O’Sullivan The Netherlands Department of Radiation Oncology The Princess Margaret Cancer Centre Piero Nicolai University of Toronto Section of Otorhinolaryngology – Head and Toronto Neck Surgery, Department of Neurosciences ON University of Padua Canada Padua Italy This book is an Open Acesss Publication ISBN 978-3-030-63233-5 ISBN 978-3-030-63234-2 (eBook) https://doi.org/10.1007/978-3-030-63234-2 © The Editor(s) (if applicable) and The Author(s) 2021 Open Access This book is licensed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license and indicate if changes were made. The images or other third party material in this book are included in the book's Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the book's Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specifc statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. The publisher, the authors and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, expressed or implied, with respect to the material contained herein or for any errors or omissions that may have been made. The publisher remains neutral with regard to jurisdictional claims in published maps and institutional affliations. This Springer imprint is published by the registered company Springer Nature Switzerland AG The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland Preface The seventh Trends in Head and Neck Oncology (THNO-7) took place in the Crowne Plaza City Center in Athens, Greece, November 7–9, 2019, and was orga- nized by the same coordinating team as the ffth and the sixth version with support from Pharma and practical logistical support from Congress Care. The conference was endorsed by the European Head and Neck Society (EHNS) and the European Organization for Research and Treatment of Cancer (EORTC). As on previous occasions, the setup was educational, with a multidisciplinary focus. Case presenta- tions, organized by our colleagues in Athens (Dr. Amanda Psyrri and Dr. Athanassios Argiris) and some members of the coordinating team, induced a lively interaction between faculty and audience and underlined the importance of individualized patient care. Thanks to the dedication of all the faculty members this book will be available soon after the actual meeting, guaranteeing the most up-to-date informa- tion in this rapidly evolving feld. We are most grateful to all the faculty members for their efforts in realizing this important goal. Edegem, Belgium Jan B. Vermorken Berlin, Germany Volker Budach Amsterdam, The Netherlands C. René Leemans Louvain-la-Neuve, Belgium Jean-Pascal Machiels Padua, Italy Piero Nicolai Toronto, Canada Brian O’Sullivan v Contents Part I Biomarkers in Head and Neck Squamous Cell Cancer (HNSCC) 1 Promising Biomarkers for Early Diagnosis and Prognosis Prediction �������������������������������������������������������������������������������� 3 Philip Sloan and Max Robinson 2 Biomarkers for Hypoxia, HPVness, and Proliferation from Imaging Perspective . 13 Sebastian Sanduleanu, Simon Keek, Lars Hoezen, and Philippe Lambin 3 Mechanisms of Cetuximab Resistance and How to Overcome It ���������������������������������������������������������������������������������������������� 21 Ines De Pauw, Carolien Boeckx, and An Wouters 4 The Role of Liquid Biopsies for Monitoring Disease Evolution ���������� 53 Ingeborg Tinhofer 5 NK Cells in Immunotherapy: How Important Are They? . 65 Denaro Nerina and Marco Carlo Merlano 6 Biomarkers for Immune Modulatory Treatment in Head and Neck Squamous Cell Carcinoma (HNSCC) . 83 Danny Rischin Part II Primary Disease 7 Novel Approaches in Surgical Management: How to Assess Surgical Margins �������������������������������������������������������������������������� 95 Marco Ferrari, Nausica Montalto, and Piero Nicolai vii viii Contents 8 The Surgical Approach to Elderly Patients with HNSCC �������������������� 111 Andreas Dietz 9 Contemporary Opportunities in Nonsurgical Management of Locoregionally Advanced Head and Neck Squamous Cell Carcinoma . 119 Shao Hui Huang, Avinash Pilar, Jishi Li, Zhiyuan Xu, and Brian O’Sullivan 10 High-Dose Three-Weekly or Low-Dose Weekly Cisplatin during Radiation, What to Prefer? . 139 Petr Szturz and Jan B. Vermorken 11 Where and when to Use Induction Chemotherapy in Head and Neck Squamous Cell Cancer . 155 Jan B. Vermorken 12 Prognostic Role of p16/HPV in Non- oropharyngeal Head and Neck Squamous Cell Cancer (HNSCC) �������������������������������� 181 Stavros Gkolfnopoulos, Panagiota Economopoulou, and Amanda Psyrri 13 Is there a Role for Neoadjuvant Targeted Therapy and Immunotherapy? �������������������������������������������������������������������������������������� 193 Simon Beyaert and Jean-Pascal Machiels 14 Is there a Role for Adjuvant Targeted and Immunotherapies in Patients with Locoregionally-Advanced Head and Neck Cancer? �������������������������������������������������������������������������� 205 Kevin J. Harrington 15 Optimal Supportive Measures during Primary Treatment . 221 Paolo Bossi and Luigi Lorini Part III Recurrent and/or Metastatic Disease 16 Salvage Surgery in Head and Neck Cancer . 233 Stijn van Weert, Sat Parmar, and C. René Leemans 17 Re-Irradiation for Local Relapses or Second Primaries: When and how? ���������������������������������������������������������������������������������������������������������� 247 Volker Budach and Alexander Thieme 18 New and Promising Targeted Therapies in First and Second-Line Settings �������������������������������������������������������������������������������� 277 Dylan F. Roden, Jennifer M. Johnson, Petr Szturz, Paolo Bossi, and Athanassios Argiris Contents ix 19 Update of Immune Therapies in Recurrent/Metastatic Head and Neck Cancer ���������������������������������������������������������������������������� 297 Danny Rischin Part IV Rare Head and Neck Cancers 20 Patients with Rare Head Neck Cancers: Do They Need a Different Approach? �������������������������������������������������������������������� 309 Carla M. L. van Herpen Part V Nasopharynx Cancer 21 Epidemiological Aspects in Nasopharyngeal Cancer. 319 Gemma Gatta 22 New Developments in the Management of Nasopharyngeal Carcinoma . 327 Xiaoshuang Niu and Yungan Tao 23 New Drugs for Recurrent or Metastatic Nasopharyngeal Cancer �������������������������������������������������������������������������� 337 Olubukola Ayodele and Lillian L. Siu Part VI Keynote Lecture 24 Innovation and Advances in Precision Medicine in Head and Neck Cancer ���������������������������������������������������������������������������� 355 Geoffrey Alan Watson, Kirsty Taylor, and Lillian L. Siu Part I Biomarkers in Head and Neck Squamous Cell Cancer (HNSCC) Chapter 1 Promising Biomarkers for Early Diagnosis and Prognosis Prediction Philip Sloan and Max Robinson Introduction There have been several recent reviews of biomarkers in relation to head and neck cancer [1–4] and although many markers show a degree of utility, none have so far translated into routine practice, apart from p16 testing for oro-pharyngeal squamous cell carcinoma [5] and PDL-1 prior to the administration of nivolumab or pembro- lizumab in recurrent/metastatic squamous cell carcinoma [6]. Modern cellular pathology laboratories do routinely use a wide range of diagnostic biomarkers for immunohistochemical and molecular testing of biopsy material, however. Quality assurance is important, both for the laboratory processes and the interpretative diag- nostic skills of the pathologist when using biomarkers [7]. For many types of can- cer, accredited testing is routinely performed to guide therapy, but in head and neck cancer, such testing is only slowly fnding applications. To achieve accreditation for such companion