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Problem Solving in Acute Oncology Second Edition
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Problem Solving in Acute Oncology Second Edition
Edited by Alison Young, MBChB, MD, FRCP Consultant in Medical Oncology, Leeds Cancer Centre, St James’s University Hospital, Leeds Teaching Hospitals NHS Trust, Leeds
Ruth E. Board, BSc, MBChB, PhD, FRCP Consultant in Medical Oncology, Rosemere Cancer Centre, Royal Preston Hospital, Lancashire Teaching Hospitals NHS Foundation Trust, Preston
Pauline Leonard, MBBS (Hons), MD, FRCP Consultant in Medical Oncology, Whittington Health NHS Trust, London
Tim Cooksley, MBChB (Hons), FRCPE Consultant in Acute Medicine, Manchester University NHS Foundation Trust, Manchester; The Christie NHS Foundation Trust, Manchester
Andrew Stewart, BA, MBChB, MD, FRCPE, FRCPath Consultant in Haematology, Bristol Haematology and Oncology Centre, University Hospitals Bristol NHS Foundation Trust, Bristol; Weston General Hospital, Weston Area Health NHS Trust, Weston-super-Mare
Caroline Michie, MBChB, MRCP (UK), FRCPE Consultant in Medical Oncology, Edinburgh Cancer Centre, Western General Hospital, NHS Lothian, Edinburgh; Honorary Clinical Senior Lecturer, University of Edinburgh, Edinburgh
Published in association with the Association of Cancer Physicians EBN HEALTH OXFORD, UK
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Second edition published 2020 First edition published 2014
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ISBN 13 978 0 99559 543 9
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Contents
Contributors viii Preface xiv Acknowledgements xv Abbreviations xvii
SECTION ONE Perspectives 01 Acute Oncology Services: Past, Present and Future, Ruth E. Board 1 02 Nursing Developments in Acute Oncology, Jo Wilkinson, 7 Christine Rhall 03 Carcinoma of Unknown Primary, Pauline Leonard, Christine Rhall 11 04 The Oncology Patient in the Acute Medical Unit, Will Marshall, 18 Tim Cooksley 05 Which Cancer Patients Should Be Admitted to Critical Care? 22 Phil Haji-Michael 06 Acute Oncology Services in the Devolved Nations, Rosie Roberts, 28 Cathy Hutchison, Moyra Mills 07 Cancer Emergencies in the Community, Sinead Clarke, 31 Joanne Stonehouse, Joanne Wilkinson, Susan Jones
SECTION TWO Case Studies Complications of Systemic Therapy 01 Febrile Neutropenia, Rohan Shotton, Amy Ford 37 02 Tumour Lysis Syndrome, Christopher Parrish, Gordon Cook 47 03 Antiangiogenic Therapy, Louise McKee, Gordon Urquhart 52 04 Cardiac Toxicity, Pankaj Punia, Chris Plummer 59 05 Liver Problems, Gemma Dart, Dan Swinson, Rebecca Jones 64 06 Acute Kidney Injury, Lucy Wyld, Christy Ralph, Andrew Lewington 72 07 Anticancer Treatment and the Kidney, Lucy Wyld, Christy Ralph, 78 Andrew Lewington 08 Metabolic Complications, Mahabuba Hossain, Carmel Pezaro, 84 Jennifer Walsh, Emma Rathbone, Janet Brown 09 Diabetes, Jenny Seligmann, Dan Swinson, Stephen Gilbey 89
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vi Contents
10 Cutaneous Manifestations of Systemic Cancer Therapy, 96 Mehran Afshar, Laura Camburn 11 Acute Diarrhoea and Mucositis, Jordan Appleyard, Daniel Lee, 101 D. Alan Anthoney 12 Peripheral Neurotoxicity, Greg Heath, Susan Short, Helen Ford 108 13 Central Neurotoxicity, Greg Heath, Susan Short, Helen Ford 113 14 Chemotherapy-Induced Lung Toxicity, Lisa Owen, 117 Satiavani Ramasamy, Dan Stark, Martyn Kennedy 15 Metastatic Melanoma with Rash and Diarrhoea after Treatment 123 with Immune Checkpoint Inhibitors, Nadina Tinsley, Ruth E. Board 16 Side Effects of Complex Treatment of Metastatic Lung Cancer with 128 Chemotherapy and an Immune Checkpoint Inhibitor, Ajay Sudan, Alastair Greystoke 17 Rare Immune-Related Adverse Events Associated with Immune 133 Checkpoint Inhibitors, Anna Claire Olsson-Brown 18 Complications of CAR T Cell Therapy, Adam Bond, Rachel Protheroe 141
Complications of Radiotherapy 19 Radiation Pneumonitis, Saif Yousif, P. Hadjiyiannakis 148 20 Radiation-Induced Head and Neck Mucositis, Arafat Mirza 153 21 Management of Radiotherapy-Related Acute Skin Reactions, 160 Deborah Williamson, Rachel Rigby 22 Toxicity Related to Pelvic Radiotherapy, Rohan Iype, Alison Birtle 169 23 CNS Toxicity of Radiotherapy, Simon Gray, Chin Chin Lim, 172 Catherine Mitchell
Complications of Cancer 24 Metastatic Spinal Cord Compression, Richard Heywood, 177 Vinton Cheng, Naveen Vasudev 25 Superior Vena Cava Obstruction, Rachel Bird, Jane Hook 183 26 Brain Metastases, Allison Hall, Pooja Jain, Andrew Brodbelt 187 27 Paraneoplastic Syndromes, Greg Heath, Susan Short, Helen Ford 194 28 Venous Thromboembolism, Nick Wreglesworth, Anna Mullard, 199 Helen Innes 29 Malignant Renal Obstruction, Andrew Viggars, Sunjay Jain, 205 Naveen Vasudev
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Contents vii
30 Management of Malignant Ascites, Benjamin Pickwell-Smith, 211 Alison Young 31 New Pleural Effusion,Keith Howell, Pooja Jain 217 32 Metabolic Complications of Malignancy: Hypercalcaemia, 225 Eliyaz Ahmed, Richard Griffiths, Sid McNulty 33 Metabolic Complications of Malignancy: Hyponatraemia, 229 Richard Griffiths, Sid McNulty 34 Bowel Obstruction, Gemma Dart, Alison Young 233 35 Malignant Pericardial Effusion,Madhuchanda Chatterjee, 239 Judith Carser, Nick Palmer, Chris Campbell, Simon Williams 36 Hyperviscosity Syndrome, Hyperleucocytosis and Leucostasis, 245 Nikesh Chavda, Andrew Stewart
Acute Palliative Care and Pain Control 37 Metastatic Small Cell Lung Cancer and Chest Wall Pain, 250 Tammy Oxley, Karen Neoh, Michael Bennett 38 Neuropathic Cancer Pain, Adam Hurlow, Michael Bennett 255
Index 260
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Contributors
Dr Mehran Afshar, Consultant in Medical Oncology, St George’s University Hospitals NHS Foundation Trust, London Dr Eliyaz Ahmed, Specialist Registrar in Clinical Oncology, Clatterbridge Cancer Centre NHS Foundation Trust, Wirral Dr D. Alan Anthoney, Consultant in Medical Oncology, Leeds Cancer Centre, St James’s University Hospital, Leeds Teaching Hospitals NHS Trust, Leeds Mr Jordan Appleyard, Medical Student, Barts and The London School of Medicine and Dentistry, Queen Mary University of London; Leeds Cancer Centre, St James’s University Hospital, Leeds Teaching Hospitals NHS Trust, Leeds Professor Michael Bennett, St Gemma’s Professor of Palliative Medicine, University of Leeds, Leeds Dr Rachel Bird, Staff Grade in Oncology, Leeds Cancer Centre, St James’s University Hospital, Leeds Teaching Hospitals NHS Trust, Leeds Dr Alison Birtle, Consultant in Clinical Oncology, Rosemere Cancer Centre, Royal Preston Hospital, Lancashire Teaching Hospitals NHS Foundation Trust, Preston; Honorary Senior Lecturer, University of Manchester, Manchester Dr Ruth E. Board, Consultant in Medical Oncology, Rosemere Cancer Centre, Royal Preston Hospital, Lancashire Teaching Hospitals NHS Foundation Trust, Preston Dr Adam Bond, Registrar in Haematology, Bristol Haematology and Oncology Centre, University Hospitals Bristol NHS Foundation Trust, Bristol Mr Andrew Brodbelt, Consultant in Neurosurgery, The Walton Centre NHS Foundation Trust, Liverpool; Honorary Clinical Senior Lecturer, University of Liverpool, Liverpool Professor Janet Brown, Honorary Consultant in Medical Oncology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield; Professor of Translational Medical Oncology, University of Sheffield, Sheffield Dr Laura Camburn, Specialist Registrar in Medical Oncology, St George’s University Hospitals NHS Foundation Trust, London Dr Chris Campbell, Foundation Year 2 Doctor, The Christie NHS Foundation Trust, Manchester Dr Judith Carser, Consultant in Medical Oncology, Clatterbridge Cancer Centre NHS Foundation Trust, Wirral Dr Madhuchanda Chatterjee, Specialist Registrar in Clinical Oncology, Clatterbridge Cancer Centre NHS Foundation Trust, Wirral
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Contributors ix
Dr Nikesh Chavda, Lymphoma Clinical Fellow, Bristol Haematology and Oncology Centre, University Hospitals Bristol NHS Foundation Trust, Bristol Dr Vinton Cheng, Specialty Registrar in Medical Oncology, Leeds Cancer Centre, St James’s University Hospital, Leeds Teaching Hospitals NHS Trust, Leeds Dr Sinead Clarke, GP Adviser, Treatment and Recovery, Macmillan Cancer Support, London Professor Gordon Cook, Professor of Haematology and Myeloma Studies, Leeds Cancer Centre, Leeds Teaching Hospitals NHS Trust, Leeds Dr Tim Cooksley, Consultant in Acute Medicine, Manchester University NHS Foundation Trust, Manchester; The Christie NHS Foundation Trust, Manchester Dr Gemma Dart, Registrar in Medical Oncology, Leeds Cancer Centre, St James’s University Hospital, Leeds Teaching Hospitals NHS Trust, Leeds Dr Amy Ford, Consultant in Medical Oncology, Royal Lancaster Infirmary, University Hospitals of Morecambe Bay NHS Foundation Trust, Lancaster Dr Helen Ford, Consultant in Neurology, Leeds Centre for Neurosciences, Leeds Teaching Hospitals NHS Trust, Leeds Dr Stephen Gilbey, Consultant in Endocrinology, Leeds Teaching Hospitals NHS Trust, Leeds Dr Simon Gray, Academic Foundation Doctor, Rosemere Cancer Centre, Royal Preston Hospital, Lancashire Teaching Hospitals NHS Foundation Trust, Preston Dr Alastair Greystoke, Senior Lecturer and Honorary Consultant in Medical Oncology, Northern Centre for Cancer Care, Freeman Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne Dr Richard Griffiths, Consultant in Medical Oncology, Clatterbridge Cancer Centre NHS Foundation Trust, Wirral Dr P. Hadjiyiannakis, Consultant in Clinical Oncology, Lancashire Teaching Hospitals NHS Foundation Trust, Preston Dr Phil Haji-Michael, Consultant in Anaesthesia and Critical Care, The Christie NHS Foundation Trust, Manchester Dr Allison Hall, Consultant in Clinical Oncology, Clatterbridge Cancer Centre NHS Foundation Trust, Wirral Dr Greg Heath, Consultant in Medical Ophthalmology, York Teaching Hospitals NHS Foundation Trust, York Dr Richard Heywood, Core Medical Trainee, Leeds Cancer Centre, St James’s University Hospital, Leeds Teaching Hospitals NHS Trust, Leeds Dr Jane Hook, Consultant in Medical Oncology, Leeds Cancer Centre, St James’s University Hospital, Leeds Teaching Hospitals NHS Trust, Leeds Dr Mahabuba Hossain, Researcher in Clinical Oncology, Barisal Biotechnology UK Ltd, Bangladesh
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x Contributors
Dr Keith Howell, Staff Grade in Oncology, Leeds Cancer Centre, St James’s University Hospital, Leeds Teaching Hospitals NHS Trust, Leeds Dr Adam Hurlow, Consultant in Palliative Medicine, Leeds Teaching Hospitals NHS Trust, Leeds Dr Cathy Hutchison, Cancer Consultant Nurse, Beatson West of Scotland Cancer Centre, NHS Greater Glasgow and Clyde, Glasgow Dr Helen Innes, Consultant in Medical Oncology, Clatterbridge Cancer Centre NHS Foundation Trust, Wirral Dr Rohan Iype, Registrar in Clinical Oncology, Rosemere Cancer Centre, Royal Preston Hospital, Lancashire Teaching Hospitals NHS Foundation Trust, Preston Dr Pooja Jain, Consultant in Clinical Oncology, Leeds Cancer Centre, St James’s University Hospital, Leeds Teaching Hospitals NHS Trust, Leeds Mr Sunjay Jain, Consultant in Urology, St James’s University Hospital, Leeds Teaching Hospitals NHS Trust, Leeds Dr Rebecca Jones, Consultant Hepatologist, Liver Unit, St James’s University Hospital, Leeds Teaching Hospitals NHS Trust, Leeds Ms Susan Jones, Macmillan Cancer Support Acute Oncology Clinical Nurse Specialist, Mid Cheshire Hospitals NHS Foundation Trust Dr Martyn Kennedy, Consultant in Respiratory Medicine, Leeds Centre for Respiratory Medicine, St James’s University Hospital, Leeds Teaching Hospitals NHS Trust, Leeds Dr Daniel Lee, Consultant in Medical Oncology, Leeds Cancer Centre, St James’s University Hospital, Leeds Teaching Hospitals NHS Trust, Leeds Dr Pauline Leonard, Consultant in Medical Oncology, Whittington Health NHS Trust, London Dr Andrew Lewington, Consultant in Renal Medicine and Honorary Clinical Associate Professor, St James’s University Hospital, Leeds Teaching Hospitals NHS Trust, Leeds Dr Chin Chin Lim, Consultant in Clinical Oncology, Lancashire Teaching Hospitals NHS Foundation Trust, Preston Louise McKee, Specialist Pharmacist in Oncology, Aberdeen Royal Infirmary, NHS Grampian, Aberdeen Dr Sid McNulty, Consultant in Diabetes and Endocrinology, St Helens and Knowsley Teaching Hospitals NHS Trust, St Helens Dr Will Marshall, Clinical Fellow, Manchester University NHS Foundation Trust, Manchester Dr Caroline Michie, Consultant in Medical Oncology, Edinburgh Cancer Centre, Western General Hospital, NHS Lothian, Edinburgh; Honorary Clinical Senior Lecturer, University of Edinburgh, Edinburgh Dr Moyra Mills, Macmillan Cancer Support Improvement Manager, Northern Health and Social Care Trust, Northern Ireland
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Contributors xi
Dr Arafat Mirza, Consultant in Clinical Oncology, Lancashire Teaching Hospitals NHS Foundation Trust, Preston Dr Catherine Mitchell, Consultant in Clinical Oncology, Rosemere Cancer Centre, Royal Preston Hospital, Lancashire Teaching Hospitals NHS Foundation Trust, Preston Dr Anna Mullard, Consultant in Medical Oncology, Betsi-Cadwaladr University Health Board, Bangor Dr Karen Neoh, Locum Consultant in Palliative Medicine, St Gemma’s Hospice, Leeds Dr Anna Claire Olsson-Brown, Fellow in Clinical Research, University of Liverpool, Liverpool; Registrar in Medical Oncology, Clatterbridge Cancer Centre NHS Foundation Trust, Wirral Dr Lisa Owen, Consultant in Clinical Oncology, Leeds Cancer Centre, St James’s University Hospital, Leeds Teaching Hospitals NHS Trust, Leeds Dr Tammy Oxley, Specialist Registrar in Palliative Medicine, St Gemma’s Hospice, Leeds Dr Nick Palmer, Consultant in Cardiology, Liverpool Heart and Chest Hospital, NHS Foundation Trust, Liverpool Dr Christopher Parrish, Consultant in Haematology, St James’s Institute of Oncology, Leeds Cancer Centre, St James’s University Hospital, Leeds Teaching Hospitals NHS Trust, Leeds Dr Carmel Pezaro, Locum Consultant in Oncology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield; Yorkshire Cancer Research Senior Research Fellow, University of Sheffield, Sheffield Dr Benjamin Pickwell-Smith, Registrar in Medical Oncology, Leeds Cancer Centre, St James’s University Hospital, Leeds Teaching Hospitals NHS Trust, Leeds Dr Chris Plummer, Consultant in Cardiology, Freeman Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne Dr Rachel Protheroe, Consultant in Haematology, Bristol Haematology and Oncology Centre, University Hospitals Bristol NHS Foundation Trust, Bristol Dr Pankaj Punia, Consultant in Medical Oncology, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham Dr Christy Ralph, Consultant in Medical Oncology, Leeds Cancer Centre, St James’s University Hospital, Leeds Teaching Hospitals NHS Trust, Leeds Dr Satiavani Ramasamy, Consultant in Clinical Oncology, Leeds Cancer Centre, St James’s University Hospital, Leeds Teaching Hospitals NHS Trust, Leeds Dr Emma Rathbone, Consultant in Medical Oncology, Calderdale and Huddersfield NHS Foundation Trust, Huddersfield Ms Christine Rhall, Macmillan Acute Oncology Lead Nurse, St Helens and Knowsley Teaching Hospitals NHS Trust, Merseyside Ms Rachel Rigby, Advanced Clinical Practitioner, Rosemere Cancer Centre, Royal Preston Hospital, Lancashire Teaching Hospitals NHS Foundation Trust, Preston
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xii Contributors
Ms Rosie Roberts, Chemotherapy Specialist Nurse and Acute Oncology Project Manager, Velindre Cancer Centre, Velindre University NHS Trust, Cardiff Dr Jenny Seligmann, Clinical Lecturer in Medical Oncology, Leeds Cancer Centre, St James’s University Hospital, Leeds Teaching Hospitals NHS Trust, Leeds Professor Susan Short, Consultant in Clinical Oncology, St James’s University Hospital, Leeds Teaching Hospitals NHS Trust, Leeds; Professor of Clinical Oncology and Neuro-Oncology, University of Leeds, Leeds Dr Rohan Shotton, Specialty Registrar in Medical Oncology, The Christie NHS Foundation Trust, Manchester Dr Dan Stark, Consultant in Medical Oncology, Leeds Cancer Centre, St James’s University Hospital, Leeds Teaching Hospitals NHS Trust, Leeds Dr Andrew Stewart, Consultant in Haematology, Bristol Haematology and Oncology Centre, University Hospitals Bristol NHS Foundation Trust, Bristol; Weston General Hospital, Weston Area Health NHS Trust, Weston-super-Mare Ms Joanne Stonehouse, Macmillan Cancer Support Project Manager, South Western Ambulance Service NHS Foundation Trust, Exeter Dr Ajay Sudan, Registrar in Medical Oncology, Northern Centre for Cancer Care, Freeman Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne Dr Dan Swinson, Consultant in Medical Oncology, Leeds Cancer Centre, St James’s University Hospital, Leeds Teaching Hospitals NHS Trust, Leeds Dr Nadina Tinsley, Specialist Registrar in Medical Oncology, The Christie NHS Foundation Trust, Manchester Dr Gordon Urquhart, Consultant in Medical Oncology, Aberdeen Royal Infirmary, NHS Grampian, Aberdeen Dr Naveen Vasudev, Consultant in Medical Oncology, Leeds Cancer Centre, St James’s University Hospital, Leeds Teaching Hospitals NHS Trust, Leeds Dr Andrew Viggars, Specialty Registrar in Clinical Oncology, Leeds Cancer Centre, St James’s University Hospital, Leeds Teaching Hospitals NHS Trust, Leeds Dr Jennifer Walsh, Senior Clinical Lecturer, Academic Unit of Bone Metabolism, University of Sheffield, Sheffield Ms Jo Wilkinson, Lead Acute Oncology/Chemotherapy Nurse, Lancashire Teaching Hospitals NHS Foundation Trust, Preston Dr Simon Williams, Consultant in Cardiology, The Christie NHS Foundation Trust, Manchester; Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester Dr Deborah Williamson, Consultant in Clinical Oncology, Rosemere Cancer Centre, Royal Preston Hospital, Lancashire Teaching Hospitals NHS Foundation Trust, Preston Dr Nick Wreglesworth, Specialist Registrar in Medical Oncology, North Wales Cancer Treatment Centre, Glan Clwyd Hospital, Rhyl
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Contributors xiii
Dr Lucy Wyld, Specialist Registrar in Palliative Medicine, St James’s University Hospital, Leeds Teaching Hospitals NHS Trust, Leeds Dr Alison Young, Consultant in Medical Oncology, Leeds Cancer Centre, St James’s University Hospital, Leeds Teaching Hospitals NHS Trust, Leeds Dr Saif Yousif, Consultant in Clinical Oncology, Rosemere Cancer Centre, Royal Preston Hospital, Lancashire Teaching Hospitals NHS Foundation Trust, Preston
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xiv Preface Preface
The development and delivery of acute oncology services, both nationally and internationally, have undoubtedly improved the care of cancer patients, the management of acute complications of cancer and its treatment, and our approaches to diagnosing patients who present with cancer and no obvious primary site. The development of acute oncology services has addressed the needs of patients who present acutely to the healthcare system with findings that suggest the possibility of a malignancy, by ensuring they get access to early specialist oncology input. This reducesdelays in diagnosis and in the inappropriate investigation of patients too unwell to be considered for systemic anticancer treatment, and facilitates the timely start of treatment. The development of acute oncology services has also ensured that patients who develop acute complications of their cancer or their treatment are seen, evaluated and managed promptly by clinicians with the right skills and facilities, and are provided with a supportive and holistic acute cancer care service throughout their journey. Key appointments in acute oncology, many at consultant and nurse practitioner level, have been made across the NHS and there is continued growth and expansion.
There remains a need to ensure that practitioners are kept fully informed and up-to-date about the appropriate clinical care to be provided in the setting of acute oncology. It is also important to continue a dialogue on the best way to deliver acute oncology services in a hard-pressed healthcare service. Since the first edition of Problem Solving in Acute Oncology was published in 2014, there has been continued development and expansion of services across the UK. The importance of the involvement of primary care in delivering acute oncology nationally has been increasingly recognized, leading to the development of ever stronger links between the two. Closer working with acute medicine physicians has also improved the care of acute oncology patients; work is ongoing to encourage closer collaboration between acute oncology services and clinical haematology.
The establishment of a biannual national acute oncology conference has provided a valuable opportunity for the multidisciplinary members of acute oncology teams nationally to share best practice and innovation. This updated text is particularly helpful and timely. It will again serve as a valuable resource for those who continue to develop excellent acute oncology services, as well as provide a source of training and an update for clinicians working in this challenging clinical area. The Association of Cancer Physicians is to be congratulated for bringing about this valuable additional resource, which is the seventh book in the Problem Solving series. We may look forward to further contributions in the future.
Alison Young, Ruth E. Board, Pauline Leonard, Tim Cooksley, Andrew Stewart and Caroline Michie, Editors
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Acknowledgements xv Acknowledgements
Editors The editors and authors are grateful to all the patients who have inspired them to prepare this book and work together to improve patient care. The editors, authors and publisher are most grateful to the Executive Committee of the Association of Cancer Physicians for their support and advice during development of the book. We are grateful to Duncan Enright and Beverley Martin at EBN Health for their expert work, support, goodwill and interest in our purpose in preparing the book, and Nicole Goldman, who coordinated and oversaw the book’s preparation and organization. Dr Young would like to acknowledge the support of the University of Leeds and Leeds Teaching Hospitals NHS Trust. Dr Board would like to acknowledge the support of the Univer- sity of Manchester and Lancashire Teaching Hospitals NHS Foundation Trust. Dr Michie would like to acknowledge the support of NHS Lothian and the Chief Scientist Office, NHS Research Scotland. Dr Leonard would like to acknowledge the support of the Whittington Health NHS Trust. Dr Cooksley would like to acknowledge the support of Manchester University NHS Foun- dation Trust and The Christie NHS Foundation Trust. Dr Stewart would like to acknowledge the support of University Hospitals Bristol NHS Foundation Trust and of former colleagues at the University Hospitals of North Midlands NHS Trust. Alison Young, Ruth E. Board, Pauline Leonard, Tim Cooksley, Andrew Stewart and Caroline Michie Association of Cancer Physicians The Problem Solving series of cancer-related books is developed and prepared by the Association of Cancer Physicians, often in partnership with one or more other specialist medical organiza- tions. As the representative body for medical oncologists in the UK, the Association of Cancer Physicians has a broad set of aims, including education for its own members and for non-members, including interested clinicians, healthcare professionals and the public. The Problem Solving series is a planned sequence of publications that derive from a programme of annual scientific work- shops initiated in 2014 with ‘Problem Solving in Acute Oncology’ followed by ‘Problem Solving in Older Cancer Patients’, ‘Problem Solving Through Precision Oncology’, ‘Problem Solving in Patient-Centred and Integrated Cancer Care’, ‘Problem Solving in Immunotherapy’ and, most recently, ‘Problem Solving in Acute Oncology, 2nd edition’. The publications involve considerable work from members and other contributors; this work is done without remuneration, as an educational service. The books have been well received and we are delighted with their standard. Problem Solving in Older Cancer Patients, Problem Solving Through Precision Oncology and Problem Solving in Patient-Centred and Integrated Cancer
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xvi Acknowledgements
Care were awarded the BMA prize for best oncology book of the year in 2016, 2017 and 2018, respectively. The Association of Cancer Physicians wishes to thank all the contributors to this and previous publications and those yet to come. David Cunningham, Chairman, Association of Cancer Physicians Peter Selby, President, Association of Cancer Physicians
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Abbreviations
ACE Accelerate, Coordinate, Evaluate G6PDD Glucose-6-phosphate ACTH Adrenocorticotropic hormone dehydrogenase deficiency AKI Acute kidney injury GCSF Granulocyte colony-stimulating ALK Anaplastic lymphoma kinase factor ALP Alkaline phosphatase GFR Glomerular filtration rate ALT Alanine aminotransferase GIST Gastrointestinal stromal tumour AMU Acute medical unit GLP-1 Glucagon-like peptide 1 AOHC Acute oncology ‘hot clinic’ HBcAb Hepatitis B core antibody ASTCT American Society for HBeAg Hepatitis B virus e antigen Transplantation and Cellular HBsAg Hepatitis B virus surface antigen Therapy HBV Hepatitis B virus ATP Adenosine triphosphate HER2 Human epidermal growth factor BRAF Serine/threonine-protein kinase receptor 2 B-Raf HFS Hand–foot syndrome BSA Body surface area HLH Haemophagocytic CAR Chimeric antigen receptor lymphohistiocytosis CAT Cancer-associated thrombosis HVS Hyperviscosity syndrome CK Cytokeratin ICANS Immune effector cell-associated CKD Chronic kidney disease neurotoxicity syndrome COPD Chronic obstructive pulmonary ICE Immune effector cell-associated disease encephalopathy CRC Colorectal cancer ICPI Immune checkpoint inhibitor CRMP5 Collapsing response mediator IgA Immunoglobulin A protein 5 IGF-1 Insulin-like growth factor 1 CRP C-reactive protein IgG Immunoglobulin G CRS Cytokine release syndrome IgM Immunoglobulin M CSF Cerebrospinal fluid IL-6 Interleukin-6 CTCAE Common Terminology Criteria for irAE Immune-related adverse event Adverse Events IVAC Ifosfamide, etoposide, cytarabine CTLA-4 Cytotoxic T lymphocyte-associated LDH Lactate dehydrogenase protein 4 LH Luteinizing hormone CUP Carcinoma of unknown primary LMWH Low-molecular-weight heparin DOAC Direct oral anticoagulant LVEF Left ventricular ejection fraction DPD Dihydropyrimidine dehydrogenase MAS Macrophage activation syndrome EGFR Epidermal growth factor receptor MASCC Multinational Association for eGFR Estimated glomerular filtration Supportive Care in Cancer rate MDC Multidisciplinary diagnostic centre ER Oestrogen receptor MDT Multidisciplinary team FSH Follicle-stimulating hormone MPE Malignant pericardial effusion 5-FU Fluorouracil MRC Medical Research Council
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xviii Abbreviations
MSCC Metastatic spinal cord compression RTOG Radiation Therapy Oncology Group MUO Malignancy of unknown origin SACT Systemic anticancer therapy NEWS2 Revised National Early Warning SCLC Small cell lung cancer Score SGLT2 Sodium–glucose co-transporter 2 PCN Percutaneous nephrostomy SIAD Syndrome of inappropriate PD-1 Programmed cell death protein 1 antidiuresis PDGF Platelet-derived growth factor SRS Stereotactic radiosurgery PD-L1 Programmed death-ligand 1 SVCO Superior vena cava obstruction PFT Pulmonary function test TKI Tyrosine kinase inhibitor PR Progesterone receptor TLS Tumour lysis syndrome PRES Posterior reversible TPE Therapeutic plasma exchange encephalopathy syndrome TSH Thyroid-stimulating hormone PSA Prostate-specific antigen TTF Thyroid transcription factor PTHrP Parathyroid hormone-related protein UGI Upper gastrointestinal RANK Receptor activator of nuclear factor UKONS UK Oncology Nursing Society kappa-B VEGF Vascular endothelial growth factor RANKL Receptor activator of nuclear factor VEGFR Vascular endothelial growth factor kappa-B ligand receptor R-CODOX-M Cyclophosphamide, vincristine, VTE Venous thromboembolism doxorubicin, methotrexate, WBC White blood cell count cytarabine, rituximab WBRT Whole brain radiotherapy RILI Radiation-induced lung injury WTE Working time equivalent RPA Recursive partitioning analysis
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This book is dedicated to Dr Ernie Marshall, Consultant Medical Oncologist, and Philippa Jones, Oncology Nurse Specialist, for their work in developing acute oncology services in the UK.
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Section One 01 PERSPECTIVE 01 Acute Oncology Services: Past, Present and Future
Ruth E. Board
Development of acute oncology services The National Chemotherapy Advisory Group was established to advise the National Cancer Director and the Department of Health on the development and delivery of high-quality chemo- therapy services. In 2009 it published a report recommending the development of acute oncology services to address the concerns raised in the 2008 National Confidential Enquiry into Patient Outcome and Death.1,2 The enquiry had raised concerns in a number of areas about the care of cancer patients. Specifically, in regard to deaths within 30 days of receiving systemic antican- cer therapy (SACT), the enquiry reported that in only 35% of patients who died within 30 days of receiving SACT was their care judged to be good. There was room for improvement in the care provided to 49% of patients, and in 8% of cases the care provided was less than satisfactory. Alarmingly, in 27% (115/429) of cases, the enquiry found that SACT had caused or hastened death. Furthermore, it highlighted the fact that many patients received SACT in specialist cancer centres but ultimately were admitted with complications of cancer treatment to their local hospital. It was found that 42% of all unwell cancer patients were admitted under general medicine rather than to a specialist oncology ward, yet 43% had grade 3 or 4 SACT-related toxicity on admission; 15% of patients were not admitted to the centre where their SACT had been administered. The subsequent 2009 National Chemotherapy Advisory Group report gave a number of recom- mendations to improve patient care and safety and described the need for acute oncology services: ‘Acute oncology encompasses both the management of patients who develop severe complica- tions following chemotherapy or as a consequence of their previously diagnosed cancer, as well as the management of patients who present as emergencies with previously undiagnosed cancer. Acute oncology therefore necessarily involves clinicians working in emergency departments and in acute medicine, as well as in oncology and related disciplines.’2 The recommendations included the principles that all hospitals with emergency departments should establish an acute oncology service, the service should develop local policies and procedures for the treatment of cancer pa- tients, there should be appropriate training for clinical staff in the identification and management of acute oncology presentations and there should be access to urgent specialist oncological advice on the care of cancer patients admitted as an emergency. New national peer review measures reflected the National Chemotherapy Advisory Group recommendations and focused on the timely review of patients admitted as an emergency to hos- pital by a member of the acute oncology team and oncology consultant, the 1 h door-to-needle time for the treatment of neutropenic sepsis, timely investigation and management of metastatic spinal cord compression (MSCC), and development and training in acute oncology emergencies, at that time totalling 22 defined emergencies ranging from hypercalcaemia to pleural effusion and chemotherapy-related diarrhoea.3 These priorities, with specific targets to aim for and monitor, were reinforced by a 2008 NICE guideline on MSCC4 and a 2012 NICE guideline on prevention and management of neutropenic sepsis.5
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Problem Solving in Acute Oncology 2 Perspectives
However, the initial awareness and importance of acute oncology services was fragmented throughout the UK. Published evidence of the benefit of the services was sparse and there were differences around the country in both enthusiasm and financial support for them. The 2012/13 national acute oncology service peer review of the 183 services showed a median of only 50% compliance with nationally agreed measures, with some trusts achieving <20% of the required peer review indicators.6 Nevertheless, audits of newly developed services across the country dem- onstrated reduced length of stay and potential bed savings. A 6 month pilot study evaluating a new acute oncology service at a single hospital in a small patient cohort reported a significant reduction in length of hospital stay and time to investigations,7 and a larger cancer network- based study (Merseyside and Cheshire) reported a reduced length of stay of 3.1 days per inpatient episode in a population of over 3000 patients reviewed at multiple acute hospital trusts, equating to a potential saving of £2 million.8 One important aspect of acute oncology was the recognition that not only did known cancer patients require increased support by specialists but also there was an unmet need for patients admitted to hospitals with an emergency presentation of a new cancer. The audit of admissions to Merseyside and Cheshire demonstrated that 51% of acute oncology admissions were due to complications of cancer, 30% were considered complications of treatment and 19% were new diagnoses of malignancy. A subgroup of the new diagnoses was recognized to be patients with malignancy of unknown origin (MUO) or carcinoma of unknown primary (CUP), comprising a group lacking coordinated care, investigation and management. The NICE guideline on CUP9 expected that many consultant oncologists who developed a specialist interest in CUP would also be involved in organizing and delivering aspects of the acute oncology service for newly present- ing patients with previously undiagnosed cancer, and indeed many acute oncology service teams embraced this new aspect of acute oncology.
Current status of acute oncology services Acute oncology services in the UK have evolved into differing models depending on local resources and service design. The early proposed requirement for consultant oncology leadership and early face-to-face patient review in every hospital has posed logistical and financial prob- lems compounded by the limited number of available trained oncologists. Many acute oncology services are predominantly nurse led, with variable input from consultant oncologists. While different models have developed across hospitals, in particular with differences between stand alone cancer centres and traditional district general hospitals, the principles of providing acute oncology remain urgent triage and review of oncology inpatients, defined protocols and path- ways for treatment, early specialist review and the availability of 24 h advice from an oncology consultant. Acute oncology services are now embedded in most hospital trusts in England and develop- ment is gathering pace in the devolved nations as the importance and benefit of these services become clear. The nursing workforce has expanded to deliver acute oncology services, and the UK Oncology Nursing Society has been instrumental in defining national protocols for acuteoncology. Its triage tool is used widely across the country to give healthcare professionals a common language when defining toxicity and to determine the need for assessment of acute oncology presentations. Its management guidance was updated in 2018 to include novel immunotherapy toxicity;10 and the society’s acute oncology subgroup has recently developed competencies which they hope will provide a universal standard for acute oncology requirements.
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Chapter 01: Acute Oncology Services: Past, Present and Future 3
Recent unpublished data from the Association of Cancer Physicians and the Royal College of Radiologists from a survey of medical and clinical oncologists revealed that, of the 700 respond- ents (trainees and consultants) from across the UK, approximately half had a formal timetabled acute oncology session in their job plan, with two-thirds of the total providing some level of acute oncology support during the week. However, challenges treating an increasing number of patients requiring SACT and radiotherapy can make it difficult for consultant oncologists to find suffi cient time to deliver an acute oncology service directly, and expansion of the workforce and use of other allied health professionals are critical to achieving full national coverage of a dedicated acute oncology service. Alongside nurses, other professionals such as specialist or consultant radiographers may support the acute oncology service particularly where palliative radiotherapy for symptom control or advice on toxicities for radiotherapy are required. Specialist radiographers, nurses and physiotherapists have also been integral to the development of MSCC services, which are vital to ensuring multidisciplinary discussions and decision making for this group of patients. In 2017, clinical advice to cancer alliances for the commissioning of acute oncology services reflected the changing face of acute oncology.11 The key priorities were: (1) to establish a robust and fully functional acute oncology service in every hospital, with an emergency department and/ or specialist oncology beds; and (2) to align the acute oncology service with the urgent care strat- egy. Recognizing the huge increase in total emergency presentations and admissions over recent years, the new guidance focuses less on inpatient care and more on unplanned emergency care and admission avoidance. It outlines 7 days’ working for acute oncology teams, key performance indicators and key responsibilities for commissioners and primary and secondary healthcare pro- viders. Traditional acute oncology services remain central, with timely inpatient reviews, develop- ment and implementation of pathways, protocols and staff training to improve safety and quality of emergency care, and adherence to NICE guidance for neutropenic sepsis, MSCC and MUO/ CUP. Also included is the expansion of acute oncology services to deliver services to promote admission avoidance and reduce emergency admissions, with 24 h helplines and the development of rapid access clinics and ambulatory care. In response to the changing needs of patients and the healthcare service, and reflecting the 2017 clinical advice to cancer alliances, acute oncology provision has shifted over recent years, recognizing that early specialist review can not only facilitate early intervention and discharge for inpatients but can also help prevent admissions and treat patients in the community providing there is good acute oncology support. The development of specific ambulatory care units for acute oncology, or ‘hot clinics’, working together with dedicated SACT helplines can ensure that admis- sion to hospital is only for those requiring inpatient stay. One area of interest is early discharge for low-risk patients with neutropenic sepsis. Scoring systems, such as the Multinational Association for Supportive Care in Cancer score and Clinical Index of Stable Febrile Neutropenia, have been developed and validated to identify low-risk patients. When managed by an experienced acute oncology team, patients determined to be low risk may be discharged home with oral antibiotics and appropriate follow-up, thus avoiding hospital admission.12 CUP and MUO multidisciplinary teams have their own specific national quality standards and in many cases are embedded within existing acute oncology services. Early involvement of the service in patients with confirmed malignancy can facilitate investigations and treatment, and, importantly, facilitate discussions with patients too unwell for active treatment about the appro- priateness of invasive tests. Some acute oncology teams have been involved in the Accelerate, Coordinate, Evaluate programme,13 a joint initiative between NHS England, Cancer Research UK, Macmillan Cancer Support and the Department of Health’s policy research units. The second
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Problem Solving in Acute Oncology 4 Perspectives
wave of the programme focuses on the potential for multidisciplinary diagnostic centre-based pathways to support earlier and faster detection of cancers among patients with non-specific symptoms, often referred to as ‘vague symptoms’, who do not meet current thresholds for urgent referral. This is a new area for oncology where traditionally the diagnosis of cancer has already been determined, placing the acute oncology team within the diagnostic arena.
Changing face of acute oncology In the UK, cancer incidence rates have increased by 13% since the early 1990s, with 359,960 cases reported in 2015.14 Cancer was the cause of death in over 1 in 4 deaths in the UK in 2016.15 It is estimated that the incidence of cancer will continue to rise over the next 20 years and, together with a rise in the population, a continued rise in the ageing population and increasing demands on emergency medicine, acute oncology services will need to adapt and grow to meet this rising need. The recent announcement by the Joint Royal Colleges of Physicians’ Training Board, in response to the shape of training review, allocates medical oncology as a type 2 specialty without dual training in acute medicine, recognizing the need for dedicated time to train fully in oncol- ogy but also the need for acute oncology to support the acute medical take directly. Expansion of acute oncology teams and services is essential in supporting colleagues in both acute and emer- gency medicine. Data collection to illustrate the benefits of acute oncology teams is critical to informing com- missioners of the need to support such services. Early descriptive audits of setting up an acute oncology service in hospitals with no prior service have clearly demonstrated the importance of these services, with documented reduction in length of stay and bed savings.7,8 Nationally collated data on key performance indicators of acute oncology services will be collected in the Cancer Outcomes and Services Dataset, facilitating regional comparisons. What is more difficult to capture in numerical or binary charts is the effect on patient experience, safety and enhanced communication between departments that an acute oncology service can bring. One challenge acute oncology teams face in the future is how best to articulate and demonstrate these qualita- tive benefits. The use of technology to collate data and inform decisions is another exciting area of develop- ment in acute oncology. Patient-reported outcome measures and self-reporting of toxicities by patients can aid early intervention and management of toxicities. A number of these are in devel- opment and, importantly, some are being evaluated in the context of clinical trials to demonstrate how they could be used to guide treatment and toxicity management. Data on web-based reporting systems demonstrate that clinician-led interventions in response to patient reports of worsening symptoms can improve rates of survival, and this is a promising area of outpatient management.16 Technology can not only aid data collection and outcome monitoring; the development of acute oncology education apps and online resources could help acute oncology services to reach a wider number of healthcare professionals who may encounter cancer patients. Acute oncology teams have already been required to develop in response to the evolving face of SACT and other cancer treatments. The explosion of checkpoint immunotherapies into cancer treatment has led to new protocols and algorithms, with large numbers of training courses and conferences to educate physicians and nurses about these new agents. In the future, acute oncol- ogy teams will need to be alert to new treatments and therapies to ensure patients admitted are looked after by teams with sufficient breadth of knowledge and training. In the near future, the introduction of cellular chimeric antigen receptor T cell therapies is one such example.
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Chapter 01: Acute Oncology Services: Past, Present and Future 5
There is a real need to develop evidence-based practice in acute oncology. The development of a national group to drive acute oncology research is essential, with optimal treatment for immuno therapy toxicities and treatment of MUO patients high on the agenda. The expansion of acute oncology into the community and primary care will be another important development. Keeping patients well and out of hospital remains a primary aim, and education and involvement of primary care, community services and paramedics will help guide treatment and the need for hospital admission, particularly when care is palliative and the focus is on symptom control. There remains much work to do in collaborating with the wider hospital healthcare team (emergency medicine, ambulatory care and specialists, in particular those in haematology and palliative care), where there is a distinct crossover and sharing of patients. Despite a back- ground of increasing patient numbers and a stretched NHS workforce, acute oncology teams are rising to the challenge to ensure that cancer patients continue to receive effective, safe and high-quality care.
References 1 Mort D, Lansdown M, Smith N, et al. (2008). For better, for worse? A review of the care of patients who died within 30 days of receiving systemic anti-cancer therapy. A report by the National Confidential Enquiry into Patient Outcome and Death (2008). Available from: www.ncepod.org.uk/2008report3/Downloads/SACT_summary.pdf (accessed 9 April 2019). 2 National Chemotherapy Advisory Group (2009). Chemotherapy services in England: ensuring quality and safety. Available from: https://webarchive.nationalarchives.gov. uk/20130104232541/http://www.dh.gov.uk/prod_consum_dh/groups/dh_digitalassets/ documents/digitalasset/dh_104501.pdf (accessed 8 April 2019). 3 National Cancer Peer Review–National Cancer Action Team (2011). Manual for cancer services. Acute oncology – including metatastic [sic] spinal cord compression measures. Available from: https://assets.publishing.service.gov.uk/government/uploads/system/ uploads/attachment_data/file/216121/dh_125889.pdf (accessed 25 May 2019). 4 National Institute for Health and Care Excellence (2008). Metastatic spinal cord compression in adults: risk assessment, diagnosis and management. Clinical guideline CG75. Available from: www.nice.org.uk/guidance/CG75 (accessed 8 April 2019). 5 National Institute for Health and Care Excellence (2012). Neutropenic sepsis: prevention and management in people with cancer. Clinical guideline CG151. Available from: www.nice.org. uk/guidance/cg151 (accessed 8 April 2019). 6 National Cancer Peer Review Programme. Acute oncology cancer services report 2012/13. London: NHS England. 7 King J, Ingham-Clark C, Parker C, et al. Towards saving a million bed days: reducing length of stay through an acute oncology model of care for inpatients diagnosed as having cancer. BMJ Qual Saf 2011; 20: 718–24. 8 Neville-Webbe HL, Carser JE, Wong H, et al. The impact of a new acute oncology service in acute hospitals: experience from the Clatterbridge Cancer Centre and Merseyside and Cheshire Cancer Network. Clin Med (Lond) 2013; 13: 565–9. 9 National Institute for Health and Care Excellence (2010). Metastatic malignant disease of unknown primary origin in adults: diagnosis and management. Clinical guideline CG104. Available from: www.nice.org.uk/guidance/cg104 (accessed 8 April 2019).
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10 UK Oncology Nursing Society (2018). Acute oncology initial management guidelines. Available from: www.ukons.org/site/assets/files/1134/acute_oncology_initial_management_ guidelines.pdf (accessed 25 May 2019). 11 NHSE Chemotherapy Clinical Reference Group (2017). Clinical advice to cancer alliances on commissioning of acute oncology services, including metastatic spinal cord compression. Available from: www.cmcanceralliance.nhs.uk/application/files/5315/4279/3425/Clinical_ Advice_for_the_Provision_of_Acute_Oncology_Services_Oct_2017.pdf (accessed 8 April 2019). 12 Cooksley T, Campbell G, Al-Sayed T, et al. A novel approach to improving ambulatory outpatient management of low risk febrile neutropenia: an enhanced supportive care clinic. Support Care Cancer 2018; 26: 2937–40. 13 Cancer Research UK. Accelerate, Coordinate, Evaluate (ACE) programme. Available from: www.cancerresearchuk.org/health-professional/diagnosis/accelerate-coordinate-evaluate- ace-programme (accessed 9 April 2019). 14 Cancer Research UK (2018). Cancer in the UK 2018. Available from: https://www. cancerresearchuk.org/sites/default/files/state_of_the_nation_apr_2018_v2_0.pdf (accessed 25 June 2019) 15 Cancer Research UK. Cancer statistics for the UK. Available from: www.cancerresearchuk. org/health-professional/cancer-statistics-for-the-uk (accessed 8 April 2019). 16 Basch EM, Deal AM, Dueck AC, et al. Overall survival results of a trial assessing patient- reported outcomes for symptom monitoring during routine cancer treatment. JAMA 2017; 318: 197–8.
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