Peritoneal Tumour Service Patient Day Christie 21st September

Peritoneal Tumour Service Patient Day Christie 21st September 2016 Research Professor Andrew G Renehan PhD FRCS FRCS(GenSurg) Colorectal & Peritoneal Oncology Centre, The Christie NHS Foundation Trust; Division of Molecular & Clinical Cancer Sciences, School of Medical Sciences, University of Manchester; Manchester Academic Health Science Centre Research framework 1. Pseudomyxoma peritonei (PMP) Appendiceal tumours 2. Appendiceal cancers 3. Peritoneal metastases from colorectal cancer Complications & mortality: cyto +HIPEC for PMP

No. of pts Complications (%) Mortality (%) Washington 501 40 2 Amsterdam 103 54

3 Winston-Salem 110 38 - Regensburg 28 36 7 Milan 33

33 3 Lyon 27 44 0 Vancouver 11 56 18

Sydney 50 48 4 Manchester (2009) 118 9 0 Yan et al. Systematic review cyto + HIPEC .. PMP Ann Surg Oncol 2007 Manchester update analysis Jan 2013 to Jun 2015 Prospective; monitored 3 monthly

N: 1105 major complex/major/ intermediate Grant Punnett 304 major peritoneal operations Lee Malcomson Manchester results: complications Complication grade Grade 0 Totals (N: 304) 180 (59) Grade 1 24 (8)

Grade 2 63 (21) Grade 3 29 (9.5) Grade 4 6 (2) Grade 5 2 (0.7) 12.5% App Tumour (N:230)

PMCR (N:74) 140 40 19 5 47 16 20 (9) 9 (12) 3 (1)

3 (4) 1 (0.4) 1 (1) 10.4% 17.6% UK & Ire. Peritoneal Tumour Services Reference treatment centres (appendiceal & PMCR) Hampshire Hospitals NHS FT The Christie NHS FT Other treatment centres (PMCR only) Mater Misericordiae University Hospital, Dublin Ninewells Hospital and Medical School, Dundee

Good Hope Hospital, Birmingham 6 Study Aim To develop a robust and reproducible framework in which to undertake a phase III trial in patients with PMCR suitable for CRS with or without HIPEC IDEAL Framework As CRS with HIPEC is a complex multicomponent component intervention, we propose to address this agenda using the principles of the IDEAL framework Idea Development Exploration Assessment

Long-term Study PMP: laboratory research Andrew Renehan Darren Roberts Peter Stern PMP: laboratory research Bowel cancer >50% Tumour PMP < 5% Tumour PMP cells Mucin

Laser Capture Microscopy Normal Epithelium Diseased Epithelium PMP: lab findings (1) PMP: lab findings (2) HIPEC Oxaliplatin 100 Clinical dose range 50 0

0.14 0.22 0.37 0.61 1.0 Future studies 1. Cell line high-through drug screens in PMP 2. Determine key driver genes in PMP 3. Characterise colorectal peritoneal metastases cancer with

Summary 1. Prospective outcome analyses 2. Trials (multi-step process) 3. Laboratory research Acknowledgements The Christie Colorectal & Peritoneal Oncology team Halstead ODwyer Butler Wilson Brown Selvasekar Fulford Tyrell Aziz Secretaries Minicozzi MDT coordinators Deshpande Kochhar

Mullin Saunders Braun Mullamitha Anaesthetists Theatre staff Perfusionists CCU staff Ward staff Chakrabarty Bowel Disease Research Foundation Christie data team Morrison Punnett Crichton Fernandez de-Silva

University of Manchester Emsley (statistics & methodology) Science laboratory Stern Roberts Brognard The patients