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Hepatobiliary (HPB) Oncology and Neuroendocrine Tumour Service

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Hepatobiliary (HPB)

Oncology & Neuroendocrine

Tumour Service


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Operational Structure

Hepatobiliary (HPB) Oncology

All new HPB patients (including cancers of the

pancreas, liver [hepatocellular carcinoma], bile

ducts [cholangio-carcinoma], gallbladder, and

ampulla) are discussed and assessed through

one of two specialist HPB MDTs (at

Manchester Royal infirmary and North

Manchester General Hospital) serving the

Greater Manchester population of 3.2 million.

Patients undergoing surgery do so at one of

these surgical sites.

Where systemic anticancer therapy (SACT) is

indicated, patients are referred to the HPB

Oncology team for assessment and treatment.

New patients are seen either at North

Manchester General Hospital or the Christie.

There is a core clinical team that deals with

HPB Oncology.

Personnel

Consultants

(Medical

Oncology)

Prof Juan Valle

Dr Richard Hubner

Dr Was Mansoor

Consultants

(Clinical

Oncology)

Dr Lubna Bhatt

Clinical Nurse

Specialist

Lynne McCallum

Nurse Clinician Christina Rigby

Research Nurses Delyth McEntee

Eileen Jones

Claire Taylor

Helen Staiger

Clinical / Research

Fellows

Dr Angela Lamarca

Clinical Trial Co-

ordinators

Aleem Iqbal

Monika Burek

Neuroendocrine Tumour (NET) Service

The Christie has been a designated Centre of

Excellence for the management of patients

with NETs since 2011 (by the European

Neuroendocrine Tumour Society, ENETS). All

new NET patients are discussed/assessed

through the specialist NET MDT (at The

Christie) serving the Greater Manchester

population of 3.2 million.


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Patients undergoing surgery do so at sites

depending on specialist expertise (e.g. HPB

surgical centres for pancreatic tumours; The

Christie for intestinal tumours; cardiothoracic

centre at University Hospital of South

Manchester for cardiac valve replacement,

etc.).

Where SACT is indicated, all new patients are

seen through a specialist NET Clinic, an

Endocrinology Clinic or Dr Mansoor’s Upper GI

clinic.

For patients with an inheritable predisposition,

a referral is made to the Clinical Genetics

teams at either Central Manchester

Foundation Trust or Salford Hospitals NHS

Trust.

The Christie is the centre for delivery of SACT

for HPB and NET patients.

The Christie is the centre for delivery of

radiotherapy (including external beam

radiotherapy or liver radio-embolisation for

HPB patients; and additionally radionuclide

therapy for NET patients).

All patients are considered for available clinical

trials (detailed below).

All patients are invited to participate in the

Manchester Cancer Research Centre (MCRC)

Biobank (from Feb 2013).

The HPB/NET service provides second

opinions at the request of patients, GPs or

secondary/tertiary care.

In addition, due to the complex nature of

neuroendocrine tumours and the peer review

requirements (by ENETS) there is a

comprehensive NET team reflecting the multi-

disciplinarity of the assessment and treatment

strategy of these patients as detailed in the

table :

Personnel – additional to those already

listed under HPB oncology

Consultants

(Endocrinology)

Prof Peter Trainer

Dr Claire Higham

Consultants

(Oncology)

Dr Was Mansoor

Consultants

(Gastroenterology)

Dr Mark Kelly

Consultants

(Surgery)

Mr Derek O’Reilly

(HPB)

Mr Paul Fulford (GI)


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Consultants

(Radiology)

DPrakash Manoharan

(also Nuclear

Medicine)

Dr Bent Taylor

Dr Damian Mullan

Dr Jeremy Lawrance

Consultants

(Pathology)

Dr Bipasha

Chakrabarty

Dr Daisuke Nonaka

Consultants

(Nuclear Medicine)

Dr Amarjot Chander

Dr Thomas

Westwood

Nursing Margaret Roberts

Activity

Primary Tumour Site N

Pancreas 181

Cholangio-carcinoma 83

Hepatocellular Carcinoma 59

Gallbladder Cancer 25

Ampulla 17

Others 12

Neuroendocrine 122

Total 499

Treatment Intent HPB NET

Adjuvant 46 13

Cannot be determined 11 12

Curative 17 36

Neoadjuvant 10 0

Palliative 293 61

Total 377 122

Service Development 2013/14

The Christie was designated as a Centre of

Excellence for the treatment of patients with

NETs in 2011 (one of 11 such centres across

Europe); this was renewed following a planned

3-year audit in March 2014.

There is a merger implementation plan

underway to merge the two HPB surgical

centres (Manchester Royal Infirmary and North

Manchester General Hospital) to a single

surgical centre at Central Manchester

Foundation Trust; expected merger date Oct

2014. While this will consolidate the surgical


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expertise, little impact is anticipated with

respect to patients referred to HPB oncology

who will continue to have access to treatment

and clinical trials.

The first meeting of the HPB Pathway Board

(Chaired by Mr Derek O’Reilly) is scheduled

for Monday 14th April 2014; Prof Valle has

been appointed to the Board (as the Research

Lead).

Following investment by the University of

Manchester, there will be two new posts

appointed to the team; a Clinical Senior

Lecturer / Honorary Consultant in Medical

Oncology (interview date 01/04/2014) and a

project manager. These appointments will

enable the HPB/NET team to consolidate,

sustain and develop further clinical research

activities.

During 2013-2014 the HPB team has

undertaken a “Joint-working” project with the

Palliative Care team (under a QUIPP initiative)

aimed at streamlining the process of patient

referral to end-of-life care (including

improvement of documentation of end-of-life

discussions, communication with GPs

regarding Gold Standards Framework register

and liaison with community palliative care

teams). This successful initiative is included in

the audit programme.

Outcomes – Click Here

http://www.christie.nhs.uk/our-standards/clinical-outcomes/the-christie-outcomes.aspx


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Peer Reviewed Publications 2013/14

Summary statement: the team have published 18 peer-reviewed papers during 2013-14. In addition,

the cisplatin/gemcitabine combination in advanced biliary tract cancer (Valle NEJM 2010) has been

adopted into the following guidelines over 2013-14: British Society of Gastroenterology (BSG),

European Association for the Study of the Liver (EASL), International Liver Cancer Association (ILCA)

and National Comprehensive Cancer Network (NCCN, USA).

1. Phase II Trial of Cetuximab and Conformal Radiotherapy Only in Locally Advanced

Pancreatic Cancer with Concurrent Tissue Sampling Feasibility Study.

Rembielak AI, Jain P, Jackson AS, Green MM, Santorelli GR, Whitfield GA, Crellin A, Garcia-

Alonso A, Radhakrishna G, Cullen J, Taylor MB, Swindell R, West CM, Valle J, Saleem A, Price

PM.

Transl Oncol. 2014 Feb 1;7(1):55-64. eCollection 2014 Feb.

2. Determination of the optimal echocardiographic scoring system to quantify carcinoid heart

disease.

Dobson R, Cuthbertson DJ, Jones J, Valle JW, Keevil B, Chadwick C, Poston GP, Burgess MI.

Neuroendocrinology. 2014;99(2):85-93. doi: 10.1159/000360767. Epub 2014 Feb 28.

3. A comparison of diagnostic imaging modalities for colorectal liver metastases.

Bonanni L, De'liguori Carino N, Deshpande R, Ammori BJ, Sherlock DJ, Valle JW, Tam E,

O'Reilly DA.

Eur J Surg Oncol. 2014 May;40(5):545-50. doi: 10.1016/j.ejso.2013.12.023. Epub 2014 Jan 15.


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4. Capecitabine and streptozocin ± cisplatin in advanced gastroenteropancreatic

neuroendocrine tumours.

Meyer T, Qian W, Caplin ME, Armstrong G, Lao-Sirieix SH, Hardy R, Valle JW, Talbot DC,

Cunningham D, Reed N, Shaw A, Navalkissoor S, Luong TV, Corrie PG.

Eur J Cancer. 2014 Mar;50(5):902-11. doi: 10.1016/j.ejca.2013.12.011. Epub 2014 Jan 17.

5. Optimal duration and timing of adjuvant chemotherapy after definitive surgery for ductal

adenocarcinoma of the pancreas: ongoing lessons from the ESPAC-3 study.

Valle JW, Palmer D, Jackson R, Cox T, Neoptolemos JP, Ghaneh P, Rawcliffe CL, Bassi C,

Stocken DD, Cunningham D, O'Reilly D, Goldstein D, Robinson BA, Karapetis C, Scarfe A,

Lacaine F, Sand J, Izbicki JR, Mayerle J, Dervenis C, Oláh A, Butturini G, Lind PA, Middleton MR,

Anthoney A, Sumpter K, Carter R, Büchler MW.

J Clin Oncol. 2014 Feb 20;32(6):504-12. doi: 10.1200/JCO.2013.50.7657. Epub 2014 Jan 13.

6. Cisplatin and gemcitabine for advanced biliary tract cancer: a meta-analysis of two

randomised trials.

Valle JW, Furuse J, Jitlal M, Beare S, Mizuno N, Wasan H, Bridgewater J, Okusaka T.

Ann Oncol. 2014 Feb;25(2):391-8. doi: 10.1093/annonc/mdt540. Epub 2013 Dec 18.

7. Pancreatic cancer hENT1 expression and survival from gemcitabine in patients from the

ESPAC-3 trial.

Greenhalf W, Ghaneh P, Neoptolemos JP, Palmer DH, Cox TF, Lamb RF, Garner E, Campbell F,

Mackey JR, Costello E, Moore MJ, Valle JW, McDonald AC, Carter R, Tebbutt NC, Goldstein D,

Shannon J, Dervenis C, Glimelius B, Deakin M, Charnley RM, Lacaine F, Scarfe AG, Middleton

MR, Anthoney A, Halloran CM, Mayerle J, Oláh A, Jackson R, Rawcliffe CL, Scarpa A, Bassi C,

Büchler MW; European Study Group for Pancreatic Cancer.

J Natl Cancer Inst. 2014 Jan;106(1):djt347. doi: 10.1093/jnci/djt347. Epub 2013 Dec 3.


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8. A systematic review of non-surgical treatments for pancreatic neuroendocrine tumours.

Valle JW, Eatock M, Clueit B, Gabriel Z, Ferdinand R, Mitchell S.

Cancer Treat Rev. 2014 Apr;40(3):376-89. doi: 10.1016/j.ctrv.2013.08.007. Epub 2013 Sep 8.

Review. Erratum in: Cancer Treat Rev. 2014 Sep;40(8):1037.

9. The effects of gemcitabine and capecitabine combination chemotherapy and of low-dose

adjuvant GM-CSF on the levels of myeloid-derived suppressor cells in patients with

advanced pancreatic cancer.

Annels NE, Shaw VE, Gabitass RF, Billingham L, Corrie P, Eatock M, Valle J, Smith D, Wadsley

J, Cunningham D, Pandha H, Neoptolemos JP, Middleton G.

Cancer Immunol Immunother. 2014 Feb;63(2):175-83. doi: 10.1007/s00262-013-1502-y. Epub

2013 Nov 29.

10. The association of a panel of biomarkers with the presence and severity of carcinoid heart

disease: a cross-sectional study.

Dobson R, Burgess MI, Banks M, Pritchard DM, Vora J, Valle JW, Wong C, Chadwick C, George

K, Keevil B, Adaway J, Ardill JE, Anthoney A, Hofmann U, Poston GJ, Cuthbertson DJ.

PLoS One. 2013 Sep 12;8(9):e73679. doi: 10.1371/journal.pone.0073679. eCollection 2013.

11. Outcome of second-line chemotherapy for biliary tract cancer.

Bridgewater J, Palmer D, Cunningham D, Iveson T, Gillmore R, Waters J, Harrison M, Wasan H,

Corrie P, Valle J.

Eur J Cancer. 2013 Apr;49(6):1511. doi: 10.1016/j.ejca.2012.11.024. Epub 2012 Dec 20.


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12. Gemcitabine plus capecitabine in unselected patients with advanced pancreatic cancer.

Hubner RA, Worsnop F, Cunningham D, Chau I.

Pancreas. 2013 Apr;42(3):511-5. doi: 10.1097/MPA.0b013e31826c6aee.

13. Evaluation of pituitary function.

Cheer K, Trainer PJ.

Handb Clin Neurol. 2014;124:141-9. doi: 10.1016/B978-0-444-59602-4.00010-1.

14. The harmonisation of growth hormone measurements: taking the next steps.

Wieringa GE, Sturgeon CM, Trainer PJ.

Clin Chim Acta. 2014 May 15;432:68-71. doi: 10.1016/j.cca.2014.01.014. Epub 2014 Feb 6.

Review.

15. Control of growth hormone and IGF1 in patients with acromegaly in the UK: responses to

medical treatment with somatostatin analogues and dopamine agonists.

Howlett TA, Willis D, Walker G, Wass JA, Trainer PJ; UK Acromegaly Register Study Group

(UKAR-3).

Clin Endocrinol (Oxf). 2013 Nov;79(5):689-99. doi: 10.1111/cen.12207. Epub 2013 Apr 24.

16. The use of mass spectrometry to improve the diagnosis and the management of the HPA

axis.

Monaghan PJ, Keevil BG, Trainer PJ.

Rev Endocr Metab Disord. 2013 Jun;14(2):143-57. doi: 10.1007/s11154-013-9240-1. Review.


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17. Thymoma and thymic carcinoma in the target therapies era.

Lamarca A, Moreno V, Feliu J.

Cancer Treat Rev. 2013 Aug;39(5):413-20. doi: 10.1016/j.ctrv.2012.11.005. Epub 2012 Dec 20.

Review.

18. Phaeochromocytoma and Acromegaly: a unifying diagnosis.

Mumby C, Davis JR, Trouillas J, Higham CE.

Endocrinol Diabetes Metab Case Rep. 2014;2014:140036. doi: 10.1530/EDM-14-0036. Epub

2014 May 1.

Presentations (in reverse date order):

31.03.2014 Pancreatic Cancer Study Day; Manchester

“The Future for Pancreatic Cancer”

25.03.2014 Regional Pancreatic Cancer meeting; Manchester

“Updates from ASCO-GI 2014” and Chair / Facilitator

12.03.2014 GBI-HPBA (GB/Ireland HPB Association) Annual Meeting; Leamington Spa

“Down-staging chemotherapy for Hepatobiliary Malignancies”

14.02.2014 Beaujon Conference - Paris, France

“Pancreatic Cancer – the state of play in 2014”


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07.02.2014 5th European Symposium on Liver Directed Cancer Therapy; Rome, Italy

“Using 90Y-Microspheres - Multidisciplinary Discussion”

29.11.2013 Pancreatic Society of Great Britain and Ireland; Liverpool

“Novel agents for pancreatic neuroendocrine tumours”

25.11.2013 UKI NETS National Conference; London

“Chemotherapy is first-line treatment for pancreatic metastatic NETs”

25.11.2013 UKI NETS National Conference; London, 25 Nov 2013

“The past year in NETs: 2013”

07.09.2013 Indo-UK Oncology Summit, Chennai, India

“Establishing a coordinated research programme: lessons from biliary tract cancer”

30.08.2013 1st Manchester International Medical Student Cancer Conference; Manchester, UK:

Speaker at opening plenary session

“The Archaeology of Cancer”

04.07.2013 World Congress in GI Cancer; Barcelona, Spain

Meet the Expert Concurrent Session: “Cholangiocarcinoma and gallbladder cancer”


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03.07.2013 World Congress in GI Cancer; Barcelona, Spain

“Should patients with resected bile duct cancer receive and adjuvant treatment?”

10.05.2013 Friday Oncology Seminar Series; Manchester

“Same Drugs – Different Diseases”

15.04.2013 NIHR Clinical Research Facility Showcase Event; Manchester

“Translating Research into Clinical Practice…the Next Steps”

13.04.2013 Rad Society / 51 Club Meeting; Manchester

“From small acorns….” [Advanced Biliary Tract Cancer]

Grants awarded:

PanORAMA: Pancreatic Cancer Predisposition, Obesity-Related Deposition Assessment using

MR ImAging (Pancreatic Cancer-UK)

SIEGE: scheduling nab-paclitaxel with gemcitabine, randomised phase II 1st-line pancreas

(Celgene)

Development of blood-borne biomarkers for improving treatment selection for pancreatic cancer

patients (Pancreatic Cancer UK)

ABC-06: phase III, of active symptom control (ASC) alone vs. ASC with oxaliplatin/5-FU chemo

(2nd-line) (Cancer Research-UK)

Somatostatin receptors and Ki-67 in HCCs (Novartis)

European Society of Medical Oncology Translational Fellowship (ESMO)


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Clinical Audit

The HPB/NET team have an active audit programme; the following are registered audits (registration

number) in 2013-14:

Outcome of pathology review and discrepancies in reporting of gastrointestinal endocrine tumours

(11/768)

Hepatobiliary Cancer Nurse Specialist at the Christie – Your Views (12/937)

End of Life Care Ongoing Audit - Upper GI (Qtr1 2013)

UKINETS National Audit of the Use of Sunitinib and Everolimus for Patients with Pancreatic

Neuroendocrine Tumours (pNETs) (12/949)

Audit of decision making, documentation and communication following discussion at the

neuroendocrine multidisciplinary meeting (CA12/921)

Surgical follow up for patients with neuroendocrine tumours - is there scope for a nurse led

service? (PE13/1141)

Advanced Hepatobiliary and Neuroendocrine Cancers in the Greater Manchester and Cheshire

Cancer Network: Equity of Access and Trends 2002-2012

The Neuroendocrine (NET) service - your views (13/1147)

End of Life Care Ongoing Audit – HPB (April - Sept 2013)

In addition:

30-day mortality audit: the team meet on a monthly basis (first Monday of the month) to discuss

30-day mortality cases.


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Educational Activity

Medical students are attached to the HPB/NET team for clinical experience; in addition medical

student project options were supervised.

Specialty Registrars (SpRs) on the Medical Oncology rotation are attached to the HPB/NET team for

3-months. Educational opportunities include participation in the HPB and NET specialist MDTs, out-

patient clinics (including research clinics), journal club, research meetings, and opportunities for

involvement in audits, presentations and publications. Prof Valle is a member of the Medical Oncology

SpR Specialist Training subcommittee.

A Translational Fellow (Dr Lamarca) was appointed following award of the Fellowship by ESMO. A

number of projects are underway which will lead to peer-reviewed presentations and publications. It is

anticipated that this will be the first of a number of such appointments over the next few years.

A major focus is on post-graduate education (see list of presentations, above) which include

presentations at international meetings. During 2013-14 this has included:

- World Congress GI Cancer (Barcelona)

- Indo-UK Oncology Summit

- European Symposium on Liver Directed Cancer Therapy

- Beaujon Conference