Chemotherapy in Mesothelioma Project. ChiMP. Mick Peake, Jill Lemon, Liz Darlison, Jeremy Steele, Richard Stephens, Paul Taylor, Sally Moore

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1 Chemotherapy in Mesothelioma Project ChiMP Mick Peake, Jill Lemon, Liz Darlison, Jeremy Steele, Richard Stephens, Paul Taylor, Sally Moore March 2011 Page 1 of 33

2 Table of contents 1. Introduction 4 Background 4 The Chemotherapy in Mesothelioma Project (ChiMP) 4 2. Methods 5 3. Recruitment 6 4. Patient characteristics 7 5. The number of patients given chemotherapy Reported toxicities Conclusions References Acknowledgements Appendix 1; National Steering Committee Appendix 2; Data set Appendix 3; Participating networks Appendix 4; Patients recruited by network 33 Page 2 of 33

3 Table of figures and tables Figure 1; Patient disposition 6 Figure 2; Patients recruited by network 6 Figure 3; Sex of patients 7 Figure 4; Age distribution 7 Figure 5; Disease laterality/site 8 Figure 6; Performance Status at entry 8 Figure 7; Cell Type 9 Figure 8; Number of patients receiving chemotherapy by network 11 Figure 9; Chemotherapy regimen 13 Figure 10; Treatment regimens by age 13 Figure 11; Treatment by performance status 14 Figure 12; Chemotherapy by age in patients with PS of 0 or 1 14 Figure 13; Chemotherapy by cell type 15 Figure 14; Number of cycles for first line chemotherapy 16 Figure 15; First line response by regimen 17 Figure 16; Reasons for stopping first-line treatment 18 Figure 17; Reasons for no immediate treatment 18 Table 1; Patients receiving chemotherapy by network 12 Table 2; Reported toxicities 19 Table 3; Pre and post treatment symptoms 20 Page 3 of 33

4 1. Introduction Background At the time the ChiMP project was started, the UK incidence of mesothelioma had been increasing rapidly since the late 1960s when national data on Mesothelioma first began to be collected 1. Also at the time we conceived the project, well over 2000 people a year were diagnosed with mesothelioma in the UK 2 and numbers were predicted to increase to a peak of around deaths per year occurring between the years Most patients diagnosed with mesothelioma die within eighteen months 4 with the range in median survival being 4-18 months, depending on the population studied. This dismal prognosis is, in many cases, accompanied by a variety of distressing physical symptoms, particularly chest pain, breathlessness and severe fatigue. To compound the misfortune of mesothelioma patients, unlike many other tumour sites, clinicians lack the benefit of mandated national guidelines. This contributes to a variation in management that is based on the experience and opinion of individual doctors. Additionally, mesothelioma is a relatively uncommon tumour with wide regional variation in incidence which means that some clinicians see very small numbers of new cases each year. On November 1st, 2004 Lilly UK announced that Alimta (Pemetrexed) would soon be available for the treatment of patients diagnosed with mesothelioma, it being the first licensed chemotherapy treatment for malignant pleural mesothelioma, in combination with Cisplatin. A standard treatment for those considered suitable looked imminent although approval for use within the NHS was necessary via the National Institute of Clinical Excellence (NICE). The appraisal process took over three years to complete and eventually in January 2008 NICE granted approval. It became apparent, through the lengthy approval process, that whilst individual clinicians could discuss the mesothelioma chemotherapy practice in their own geographical area, there was little or no understanding of the collective practice across England and there appeared to be a variation in what was being offered; this lack of understanding led Mesothelioma UK to secure funding to develop a time limited national chemotherapy audit project. The Chemotherapy in Mesothelioma Project (ChiMP) ChiMP was a one year national audit project, launched on 1st February 2008, with the aim of clarifying what, where and how much chemotherapy treatment was being prescribed to mesothelioma patients in England. Once completed, it was hoped that the audit would help the funders of health care assess the likely cost impact of chemotherapy treatment in Mesothelioma, by providing evidence of: the characteristics of the patient group being treated; their fitness for treatment; the levels of toxicity they experience. Additionally, it should demonstrate where such patients are being treated and give an insight into the frequency of suitable patients not being treated and perhaps some insight into why this occurs. Page 4 of 33

5 2. Methods This project comprised a time-limited national audit of the use of chemotherapy in mesothelioma. The recruitment period was 1 st February 2008 to 31 st January Firstly, a National Steering Committee (Appendix 1) was established to oversee the development and analysis of the project. A data set was agreed. A project data manager was appointed. In order to maximise participation, a user-friendly data collection form (Appendix 2) was designed and access to ChiMP for participants was arranged via the project data manager or the Mesothelioma UK website. Additionally, a ChiMP information leaflet was designed and created. Since this was entirely an audit of current clinical practice with no use of identifiable patient data, it was agreed that ethical committee approval would not be required. All lung multidisciplinary teams (MDTs), oncology centres and Lung Cancer Nurse Specialists in the UK Cancer Networks were contacted and invited to participate. (Please note: There have been area changes within the Cancer Networks since this data was collected). The project was then introduced to the British Thoracic Oncology Group (BTOG) in January 2008 and enrolment began. A quarterly Newsletter was circulated. Audit collation support (including site visits) was offered. Data collection was anonymised. We asked teams to register all sequential patients referred from a lung MDT to an oncologist for a consideration of chemotherapy. There were no limitations on age or performance status (PS). Patients with incomplete data have not been included in the main analyses, with the exception of those where only details on disease site or laterality were missing. Page 5 of 33

Figure 1; Patient disposition This document reports on the 681 patients with complete data from 31 regional health networks (Figure 2).

6 3. Recruitment Eighty-six sites from 35 networks (Appendix 3) registered for the audit. Of these, 31 networks recruited 736 patients (Figure 1). Figure 1; Patient disposition This document reports on the 681 patients with complete data from 31 regional health networks (Figure 2). Figure 2; Patients recruited by network A further 55 patients did not have complete data and results have not been presented in this report. Of these 55 patients, no data were submitted for 30 patients; 25 patients were excluded due to incomplete data. Page 6 of 33

4. Patient characteristics Patient characteristics were typical of patients presenting with mesothelioma. The majority (83%) of patients were male (Figure 3).

7 4. Patient characteristics Patient characteristics were typical of patients presenting with mesothelioma. The majority (83%) of patients were male (Figure 3). Just over half (56%) the patients were aged between 61 and 75 (Figure 4).Just over half (56%) the patients presented with right sided pleural disease (Figure 4). Almost half the patients (45%) were PS 1 at entry (Figure 5). Cell type is shown in Figure 7; the majority (57%) of tumours were epithelioid. Figure 3; Sex of patients Figure 4; Age distribution Page 7 of 33

8 Figure 5; Disease laterality/site Figure 6; Performance Status at entry Page 8 of 33

9 Figure 7; Cell Type Page 9 of 33

10 5. The number of patients given chemotherapy Of the 681 patients with complete data, 364 (53%) were given chemotherapy. Of the 55 patients without complete data, whose results were therefore excluded from the analyses, 18 (33%) received chemotherapy, 6 (11%) received no chemotherapy, and for 31 patients no data were recorded. The number of patients given chemotherapy by network is shown in Figure 8 and Table 1. Network numbers and abbreviations are given in Appendix 2. Page 10 of 33

11 Figure 8; Number of patients receiving chemotherapy by network Page 11 of 33

12 Table 1; Patients receiving chemotherapy by network Network Code Network Patients With Data N Patients receiving Chemotherapy n (%) 35 G Midlands 4 4 (100) 25 SW London (97) 11 Pan B ham (95) 24 SE London (94) 30 Th Valley (89) 12 A W Mid 8 7 (88) 2 Grt Man + Cheshire (81) SWW Wales SW (74) 29 3 Counties 13 9 (69) 21 West London 3 2 (67) SCH Sc Highlands 6 4 (67) 23 NE London (61) 14 Derby/Burton (58) 8 N Trent (54) 32 S/WS/Hants (50) SCG ScGrampion 2 1 (50) 34 Kent/Medway (48) 15 Leics/N hants (47) 1 Lancs/STH Cumbria (46) 26 Devon/SW 16 7 (44) 36 N England 20 8 (40) 27 Dorset (39) SEW Wales SE 11 4 (36) 6 Yorks (33) 22 N London 3 1 (33) 31 CS Coast (29) 37 Anglia (26) 3 Mside + Cheshire 24 0 (0) 13 Mid Trent 1 0 (0) 38 S Essex 1 0 (0) Page 12 of 33

13 There was a large regional variation in the percentage of patients given chemotherapy, with a range of zero to 100% among the networks. Excluding those who recruited less than 10 patients, the highest chemotherapy rates were in South West London, Pan- Birmingham, and South East London, all of which treated more than 90% of registered patients. The lowest rates were in Merseyside and Cheshire, Central South Coast and Anglia, all of which treated less than a third of registered patients (none in Merseyside and Cheshire). Of those 364 patients with data who received chemotherapy, the majority (60%) were given a combination of Pemetrexed and Cisplatin; 28% were treated with Pemetrexed and Carboplatin and 2% with Pemetrexed alone. A further 9% received other chemotherapy (Figure 9). Figure 9; Chemotherapy regimen Figure 10; Treatment regimens by age As one would expect, a higher percentage of patients in the younger age groups received chemotherapy (Figure 10). Chemotherapy was given to 83% of patients aged less than 50 years of age, 25% of patients aged and to 14% of patients aged 81 years or more. The specific regimens chosen were similar for each age group except for the use of Carboplatin which was more often used in older patients. Page 13 of 33

Figure 11; Treatment by performance status Figure 12; Chemotherapy by age in patients with PS of 0 or 1 Patients with better PS were given chemotherapy more frequently than patients with poorer PS

14 Figure 11; Treatment by performance status Figure 12; Chemotherapy by age in patients with PS of 0 or 1 Patients with better PS were given chemotherapy more frequently than patients with poorer PS (Figure 11) with all but 3 patients treated having a PS of 0-2, and the very large majority (92%) being PS 0 or 1. The range of regimens chosen was similar for each PS group. Chemotherapy by age in patients with PS of 0 or 1 is shown in Figure 12. Page 14 of 33

15 The specific chemotherapy regimen chosen was also similar for each cell type (Figure 13), proportions of patients receiving Pemetrexed/Cisplatin or Pemetrexed/Carboplatin not being dependent on tumour cell type. Figure 13; Chemotherapy by cell type Of the 364 patients with complete data who received treatment, 326 received first line treatment. The number of cycles given in this first line treatment is shown in Figure 14. Six cycles were given to just under 30% of patients receiving either Pemetrexed/Cisplatin or Pemetrexed/Carboplatin. Page 15 of 33

16 Figure 14; Number of cycles for first line chemotherapy PEM: Pemetrexed; CISP: Cisplatin; CARB Carboplatin; GEM Gemcitabine; IPM: Irinotecan, Mitomycin and Cisplatin; MVP: Mitomycin C, Vinblastine and Cisplatin. Page 16 of 33

17 Response to first line therapy is shown in Figure 15. Five (2%) patients showed a complete response to Pemetrexed/Cisplatin. Partial responses were seen in 28% of patients treated with Pemetrexed/Cisplatin, 21% of patients treated with Pemetrexed/Carboplatin and 31% of patients treated with other regimens. Reasons for stopping first-line treatment are shown in Figure 16. Just under half the patients given Pemetrexed/Cisplatin or Pemetrexed/Carboplatin stopped treatment having completed their planned course. The percentage of patients stopping due to toxicity was greatest in patients treated with chemotherapy classed as other. Figure 15; First line response by regimen Page 17 of 33

Figure 16; Reasons for stopping first-line treatment The most common reason for giving no immediate treatment (44%) was that the patient was judged

18 Figure 16; Reasons for stopping first-line treatment The most common reason for giving no immediate treatment (44%) was that the patient was judged not fit to receive it (Figure 17). Just over one quarter of the patients declined treatment. Figure 17; Reasons for no immediate treatment Page 18 of 33

19 6. Reported toxicities Nine regional networks (network Numbers: 1, 6, 8, 25, 26, 27, 29, 32, SWW) reported post-treatment toxicities. These nine networks treated 158 patients and post-treatment toxicities reported on these patients are shown in Table 2. Table 2; Reported toxicities Toxicities Pem/Cis Pem/Carb Vinorelbine Other Neutropenia Anaemia Vomiting Nausea Constipation Neuropathy (bortezimib) Renal Respondents were asked to record the occurrence of pain, cough, dyspnoea, sweating, fatigue and anorexia both pre- and post-treatment. Results are shown in Table 3. Page 19 of 33

20 Table 3; Pre and post treatment symptoms Pain Pre-treatment grade Cough n No change Worsened Improved Unknown N/A N/A 0 0 Pre-treatment grade Dyspnoea n No change Worsened Improved Unknown N/A Pre-treatment grade Sweating n No change Worsened Improved Unknown N/A Pre-treatment grade Fatigue n No change Worsened Improved Unknown N/A Pre-treatment grade Anorexia n No change Worsened Improved Unknown N/A N/A 2 Pre-treatment n No change Worsened Improved Unknown grade N/A Page 20 of 33

21 7. Conclusions As far as we are aware, this is the largest survey of chemotherapy usage in mesothelioma in routine clinical practice. The characteristics of the study population were typical of patients presenting with mesothelioma. The majority (83%) of patients were male; just over half (56%) the patients were aged between 61 and 75;.just over half (56%) the patients presented with right sided pleural disease. Almost half the patients (45%) were PS 1 at entry; the majority (57%) of tumours were epithelioid. It has to be remembered that these patients had been selected by the Multi-Disciplinary Teams as fit enough for at least consideration of active treatment by an oncologist. Regarding fitness for treatment, 493 (72%) were PS 0 or 1. Surprisingly, 170 (34%) of these PS0-1 patients received no treatment after having seen the oncologist. Of those patients treated, the majority (60%) received Pemetrexed/Cisplatin and a significant minority (28%) received Pemetrexed/Carboplatin. Reported toxicities were very low. It is likely that this was due to significant underreporting. Occurrence rates for some symptoms were specifically sought: pain, cough, dyspnoea, sweating, fatigue and anorexia. No statistical analysis has been performed on these data. However, it is clear that symptom improvement was achieved for many patients. Page 21 of 33

22 8. References 1. McElvenny DM, Darnton AJ, Price MJ, Hodgson JT (2005), Mesothelioma mortality in Great Britain from 1968 to Occup Med (Lond) Mar;55(2): Cancer Research UK 2005 Website 3. Peto J, Hodgson J, McElvenny D Darnton A and Price M. (2005), The expected burden of mesothelioma mortality in Great retain from 2002 to British Journal of Cancer (2005) 92, Clayson H (2003), Suffering in mesothelioma: concepts and contexts. European Journal of Palliative Care 2003 ;11:5, pg PD Taylor, R Goldstein, H Anderson, C Berrisford, D Smith, P Taylor, B Townley, N Thatcher (2007), Pemetrexed based chemotherapy for malignant mesothelioma; a retrospective analysis of 100 consecutively treated patient. BTOG 2007 Poster Presentation. 9. Acknowledgements The authors would like to thank the Cancer Centres and their representatives who participated and members of the Mesothelioma Nurse Action Team for supporting this project. Mesothelioma UK also acknowledges and thanks Eli Lilly and Company Limited for providing an unrestricted educational grant in June 2007 to allow Mesothelioma UK to develop and conduct this project. Page 22 of 33

23 10. Appendix 1; National Steering Committee Dr Michael D Peake (Chair) Consultant and Senior Lecturer in Respiratory Medicine Clinical Lead, National Cancer Intelligence Network National Clinical Lead, NHS Cancer Improvement The University Hospitals of Leicester NHS Trust, Leicester Liz Darlison Macmillan Consultant Nurse, Mesothelioma UK, The University Hospitals of Leicester NHS Trust, Leicester Sally Moore Cancer Nurse Specialist, Guys & St Thomas's, London Dr Jeremy Steele MD MRCP Consultant in Medical Oncology at St Bartholomew s Hospital, the Royal London Hospital and the London Chest Hospital, London Richard J Stephens Senior Research Scientist, Cancer Division, Medical Research Council, London Dr Paul Taylor Consultant Medical Oncologist at Wythenshaw Hospital, Manchester Jill Lemon ChiMP Project Manager, Mesothelioma UK, The University Hospitals of Leicester NHS Trust, Leicester Page 23 of 33

24 11. Appendix 2; Data set Page 24 of 33

25 Page 25 of 33

26 Page 26 of 33

27 12. Appendix 3; Participating networks Registration Number for hospital site No1 Hospital Name Leicester Royal Infirmary Network Number Network Number and name 15 Leicester/Northants/Kettering (Leics/N hants) No2 Derby Royal Infirmary 14 Derby/Burton (East Midlands Zone) No3 Queens Hospital Burton 14 Derby/Burton ( East Midlands Zone) No4 Clatterbridge Hospital Wirrell 3 3 Merseyside/Cheshire (Mers/Ch) No5 Northampton General Hospital 15 Leicester/Northants/Kettering (Leics/N hants) No6 Kettering General Hospital 15 Leicester/Northants/Kettering (Leics/N hants) No7 Guy s and St Thomas s 24 South East London (SE London) Hospital London No8 Torbay Hospital South Devon 26 Peninsula No9A Dorset Cancer Centre 27 Dorset Poole 9B Dorset County Hospital 27 Dorset 9C- Was registered to No 67 No10 No11 Royal Bournemouth Hospital Kingsmill Hospital Nottingham Sherwood Forest NHS Trust Queen Alexandra Hospital Portsmouth 27 Dorset 13 Mid Trent 31 Central South Coast (CS Coast) No12 Castle Hill Hospital Hull 7 Humber & Yorkshire Coast No 13 No14 No15 Medway Maritime Hospital St Mary s Hospital London Luton & Dunstable McMillan Centre 34 Kent & Medway (Kent/Medway) 21 West London 21 West London Page 27 of 33

28 Registration Number for hospital site No16 No17 No18 No19 No20 No21 No22 No23 No24 No25 Hospital Name East Surrey Hospital (Affiliated to St Lukes Cancer Centre for treatment) Russells Hall Hospital Dudley West/Mid Walsgrave Hospital Coventry Royal Berkshire Hospital Reading Selly Oak Hospital Birmingham Weston General Hospital Somerset Papworth Hospital Cambridge Salisbury District Hospital Wiltshire St Peters Hospital Guildford Surrey St Luke s Cancer Centre Royal Surrey Network Number Network Number and name 32 Surrey, West Sussex & Hampshire (S/WS/Hants) 11 Pan Birmingham (Pan B ham) 12 Arden (A W Mid) 30 Thames Valley 11 Pan Birmingham (Pan B ham) 27 Dorset 37 Anglia 31 Central South Coast (CS Coast) 32 Surrey, West Sussex & Hampshire (S/WS/Hants) 32 Surrey, West Sussex & Hampshire (S/WS/Hants) No26 No27 No28 No29 No30 Frimley Park Hospital Camberley Surrey (Affiliated to St Lukes& Royal Surrey) Llandough Hospital Cardiff Royal Marsden Hospital Surrey Royal Marsden Fultham Road North Devon District Hospital St Richards Hospital Chichester 32 Surrey, West Sussex & Hampshire (S/WS/Hants) CVW Cardiff & Vale NHS Trust Wales 25 South West London (SW London) 26 Peninsula 32 Surrey, West Sussex & Hampshire (S/WS/Hants) No31 No32 No33 Twinned with Newcross Hospital 50 Radcliffe Hospital Oxford Lung Ca MDT (Churchill) Princess Royal Hospital Haywards Heath Sussex. Staffordshire General Hospital (Dr Brammer serves Newcross) 30 Thames Valley (Th Valley) 33 Sussex 35 Greater Midlands (G Midlands) Page 28 of 33

29 Registration Number for hospital site Hospital Name Network Number Network Number and name No34A Christie Hospital 2 Greater Manchester & Cheshire (G Man/Cheshire) No34B Wythenshaw Hospital 2 Greater Manchester & Cheshire (G Man/Cheshire) No34C Leighton Hospital 2 Greater Manchester & Cheshire (G Man/Cheshire) No35 No36 Twinned with 78 Northern General Sheffield No37 No38 North Hampshire Hospital Basingstoke Western Park Hospital Sheffield South end Hospital London South Mead Hospital North Bristol 32 Surrey, West Sussex & Hampshire (S/WS/Hants) 8 North Trent (N Trent) 38 South Essex (S Essex) 28 Avon & Somerset & Wiltshire (Av/Som/Wilts) No39 No40 No41 No42 No43 Royal Sussex County Hospital Royal Free Hospital Hampstead Royal Hampshire County Hospital Southampton General Hospital Aintree Chest Centre Liverpool (Treated at Clatterbridge) No44 Somerset Cancer Centre Musgrove Park Hospital No45 Walsgrave Hospital - The Arden cancer Centre Coventry (patients registered to No 18) No46 No47 No48 No49 James Paget Hospital Norfolk/Suffolk Peterborough District Hospital Harrogate District Hospital Yorkshire Good Hope Hospital Birmingham 33 Sussex 22 North London (N London) 32 Surrey, West Sussex & Hampshire (S/WS/Hants) 31 Central South Coast (CS Coast) 3 Merseyside & Cheshire (Mers/Ch) 27 Dorset 12 Arden (A W Mid) 16 Norfolk & Waveney 37 West Anglia 6 Yorkshire (Yorks) 11 Pan Birmingham (Pan B ham) Page 29 of 33

30 Registration Number for hospital site No50 Twinned with 33 Staffordshire General No51 Hospital Name New Cross Hospital Wolverhampton (Staffordshire) Newcastle upon Tyne Hospitals (Royal Victoria, The Freeman Hospital, Newcastle General) Network Number Network Number and name 35 Greater Midlands (G Midlands) 36 North of England No52 York Hospital 6 Yorkshire (Yorks) No53 No54 No55 No56 CNS No57 No58 Mount Vernon Cancer Centre (Watford General Hospital) Huddersfield Royal Infirmary Oncology Dept Furness General Hospital Morecombe Bay East Kent Hospitals Trust William Harvey Hospital, Willesborough Bronglais General Hospital Aberystwyth Pendle Community Hospital Lancashire East Lancashire Hospital Trust 20 Mount Vernon West Herts Trust 6 Yorkshire (Yorks) 1 Lancashire & Cumbria 34 Kent & Medway (Kent/Medway) SWW South West Wales 1 Lancashire & Cumbria (Lancs/Cumbria) No59 Royal Gwent Hospital SEW Gwent Health Care Wales No60 GlanCwyd North Wales CDW Conwy & Denbighshire Wales Cancer Treatment Centre Bodewyddan Denbighshire No61 Aberdeen Royal Infirmary SCG Scotland Grampian No62 No63 Alaw Oncology Unit, Ysbyty, Bwynedd University Hospital of North Durham NWW Bangor Wales 36 North of England Page 30 of 33

31 Registration Number for hospital site Hospital Name Network Number No64 Basildon Hospital 19 South Essex Network Number and name No65 No66 No67 9C Twinned with No 9 Dorset Ca Centre Nevill Hall Abergavenney SEW Gwent Health Care Wales Wales Singleton Hospital Swansea SWW South West Wales South Wales (To include Morriston Hospital and Neath and Port Talbot) Royal Bournemouth Hospital 27 Dorset No68 Bradford Royal Infirmary 6 Yorkshire (Yorks) No69 No70 No71 No72 St Barts and The London Hospital University Hospitals Nottingham (City/Queens) The Churchill Hospital Oxford Ninewells Hospital Stefani Unit Dundee 23 North East London (NE London) 13 Mid Trent 30 Thames Valley (Th Valley) SCT Scotland Tayside (Tayside) No73 The Lancaster Royal Infirmary and West Moreland Hospital Kendall 1 Lancashire & Cumbria (Lancs/S Cumbria) No74 Sunderland Royal Hospital 36 North of England (N England) No75 Darrent Valley Hospital Kent 34 Kent & Medway (Kent/Medway) No76 No77 Clayton Hospital Northgate Wakefield Raigmore Hospital Inverness Scotland 6 Yorkshire (Yorks) SCH Scotland Highlands (Sc Highlands) No78 Twinned with No 36 Western Park Hospital Sheffield Northern General Hospital Sheffield 8 North Trent (N Trent) Page 31 of 33

32 Registration Number for hospital site No 79 Hospital Name Lancashire Trust Preston Hospital and Chorley Hospital Network Number Network Number and name 1 Lancashire & Cumbria (Lancs/S Cumbria) No 80 Hereford Hospital 29 3 Counties No 81 No 82 No 83 No 84 No 85. No 86 Kent & Canterbury Hospital Canterbury QEQM(Queen Elizabeth Queen Mother) Margate Kent North Middlesex University Hospital Oncology Day Unit West Wales General Hospital Carmarthen West Wales St James Hospital Oncology Unit Bexley Wing. Airedale Hospital Keighley WestYorkshire 34 Kent & Medway (Kent/Medway) 34 Kent & Medway (Kent/Medway) 22 North London (N London) WW 6 Yorkshire (Yorks) 6 Yorkshire (Yorks) Page 32 of 33

33 12. Appendix 4; Patients recruited by network Page 33 of 33

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