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Hepatobiliary (HPB) Oncology and Neuroendocrine Tumour Service
1
Hepatobiliary (HPB)
Oncology & Neuroendocrine
Tumour Service
Hepatobiliary (HPB) Oncology and Neuroendocrine Tumour Service
2
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.
Hepatobiliary (HPB) Oncology and Neuroendocrine Tumour Service
3
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)
Hepatobiliary (HPB) Oncology and Neuroendocrine Tumour Service
4
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
Hepatobiliary (HPB) Oncology and Neuroendocrine Tumour Service
5
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
Hepatobiliary (HPB) Oncology and Neuroendocrine Tumour Service
6
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.
Hepatobiliary (HPB) Oncology and Neuroendocrine Tumour Service
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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.
Hepatobiliary (HPB) Oncology and Neuroendocrine Tumour Service
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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.
Hepatobiliary (HPB) Oncology and Neuroendocrine Tumour Service
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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.
Hepatobiliary (HPB) Oncology and Neuroendocrine Tumour Service
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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”
Hepatobiliary (HPB) Oncology and Neuroendocrine Tumour Service
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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”
Hepatobiliary (HPB) Oncology and Neuroendocrine Tumour Service
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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)
Hepatobiliary (HPB) Oncology and Neuroendocrine Tumour Service
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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.
Hepatobiliary (HPB) Oncology and Neuroendocrine Tumour Service
14
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