Programme in Gastrointestinal Cancer

The Programme in Gastrointestinal (GI) Cancer is part of the School of Cancer and Pharmaceutical Sciences at King's College London (KCL). It includes research into many diseases of the gastrointestinal tract, although most research is directed towards cancer, oesophago-gastric cancer in particular, and associated conditions. Cancer of the oesophagus or stomach is characterised by a poor overall prognosis. The main curative treatment is demanding, and includes extensive surgery. A high proportion of these patients present with advanced disease that precludes curative treatment, but with improvements in diagnostics, staging and management, the 5-year survival following surgery now reaches 50% in specialist centres.

The Upper Gastrointestinal Department at Guy’s & St Thomas’ Foundation Trust (GSTT) is one of the highest volume centres in Europe for the management of oesophageal and gastric cancer. Recent advances in oncology (peri-operative chemotherapy), surgery (centralisation, enhanced recovery, minimally-invasive surgery) and multi-disciplinary working (anaesthetics, gastroenterology, radiology, dietetics, physiotherapy, specialist nursing) have improved patient outcomes. The Programme in GI Cancer spans a broad field of interests and strongly promotes collaborative working, within KCL, nationally and internationally.

Members

Francesca Ciccarelli

Professor of Cancer Genomics

Vicky Goh

Chair of Clinical Cancer Imaging

Jesper Lagergren

Professor of Upper Gastrointestinal Cancer and Honorary Consultant Surgeon

Debashis Sarker

Senior Lecturer and Consultant in Medical Oncology

Manil Subesinghe

Clinical Lecturer in PET imaging

Mieke Van Hemelrijck

Professor in Cancer Epidemiology

Claire Wells

Professor in Cancer Cell Biology

Clinical upper gastro-intestinal cancer research

With large and comprehensive databases of oesophago-gastric cancer surgery, we have a longstanding reputation for high-quality clinical research in this area. Major contributions to several large international data collaborations are testaments to this. The group regularly presents work at national and international conferences and regularly publishes in high impact factor journals. With collaborations in KCL, within the UK and internationally, the scope of clinical research is wide. We recruit research students at a range of levels. Current studies: PRE-EMPT (prospective trial examining pre-habilitation prior to upper GI surgery), response assessment in oesophageal cancer, esophageal cancer complications group, oesophago-gastric anastomosis audit.

Early detection of oesophago-gastric cancer

GSTT/KCL has a high-volume centre for patients with Barrett’s oesophagus, providing endoscopic eradication therapy of dysplasia (radio-frequency ablation) and early cancer (endoscopic mucosal resection or submucosal dissection). We have a track record of research in this field with a view to improving the detection and management of early cancer and risk stratifying patients with pre-malignant conditions. Current studies: A comparison of endoscopic mucosal resection with oesophagectomy for early oesophageal cancer, staging of early oesophageal cancer, SPIT study (in collaboration with University College London), breath test study (in collaboration with Imperial College London).

Translational upper gastro-intestinal research

We collect clinical data and specimens (blood, tissue) and collaborate with several basic scientists within KCL and outside. We are one of the largest contributors to Oesophageal Cancer Clinical and Molecular Stratification (OCCAMS), a national oesophago-gastric cancer study, and have contributed to International Cancer Genome Consortium (ICGC). Current studies: Sub-studies based on OCCAMS data (MIMOSA – assessing the role of magnetic resonance imaging in oesophageal cancer, tumour morphology, lymph node regression), PAK proteins in oesophageal cancer, vaccine development in oesophago-gastric cancers.

Living with and beyond cancer

For many years the pioneering cancer “survivorship” clinic (Nurse specialist and Dietitian led with Surgical / Gastroenterology input) at GSTT has improved the follow-up of patients undergoing major oesophago-gastric surgery. We have a focus on nutrition, anaemia and symptom management in the lead up to and following surgery. A major aim is to improve the overall health-related quality of life of this patient group throughout the care pathway and beyond. Current studies: Symptom management after major upper gastrointestinal cancer surgery (RESTORE - national collaboration to define and standardise the symptoms and conditions that commonly occur after oesophago-gastrectomy).

Benign upper gastro-intestinal research

With one of the largest oesophageal laboratories in the UK and a large database of patients investigated for benign conditions of the upper gastrointestinal tract, this group aims to improve the outcomes of patients with conditions associated with upper gastrointestinal cancer, i.e. gastro-oesophageal reflux disease, achalasia (and other motility disorders) and gallstones. Current studies: POEM versus balloon dilatation for achalasia (European RCT), Sunflower (UK RCT examining MRCP prior to laparoscopic cholecystectomy), inlet patch HALO RFA vs sham (National RCT).

Pancreatic cancer research

We have active research on pancreatic cancer within the programme. It includes exploring implications for molecular targeting, both within tumour cells and associated cells in the tumour microenvironment and investigating the relation between PDAC cells and immune cells. In parallel we are working with other researchers to find novel ways to deliver therapeutics, explore how ultrasound technology could be utilised and test novel pathways. Collaborative work has yielded a repository of PDAC organoids. There is also on-going work to explore the feasibility of immune therapies in the PDAC setting including CAR T-cell treatment.

10 selected publications:

Holmberg D, Santoni G, von Euler-Chelpin MC, Färkkilä M, Kauppila JH, Maret-Ouda J, Ness-Jensen E, Lagergren J. Incidence and Mortality in Upper Gastrointestinal Cancer After Negative Endoscopy for Gastroesophageal Reflux Disease. Gastroenterology 2022;162:431-8.

Moore J, Kumar S, Santaolalla A, Patel P, Kapiris M, Van Hemelrijk M, Maisey N, Hill M, Lagergren J, Gossage JA, Kelly M, Baker CR, Allum WH, Cunningham D, Davies AR. Effect of peri-operative chemotherapy regimen on survival in the treatment of locally advanced oesophago-gastric adenocarcinoma - a comparison of the FLOT and 'MAGIC' regimens. Eur J Cancer 2022;163:180-8.

Moore JL, Davies AR, Santaolalla A, Van Hemelrijck M, Maisey N, Lagergren J, Gossage JA, Kelly M, Baker CR; Guy’s and St. Thomas’ Esophago-gastric Research Group. Clinical relevance of the tumor location-modified Laurén classification system for gastric cancer in a Western population. Ann Surg Oncol 2022 2022 Jan 18. doi: 10.1245/s10434-021-11252-y.

Zylstra J, Whyte GP, Beckmann K, Santaolalla A, Pate J, Gervais-Andre L, Tham G, Green M, Baker C, Kelly M, Waters J, Maisey N, Lagergren J , Goh V, Gossage J, Browning M, Davies AR. Exercise prehabilitation during neo-adjuvant chemotherapy may enhance tumour regression in oesophageal cancer. Br J Sports Med 2022 doi: 10.1136/bjsports-2021-104243.

Rusu RI, Fox MR, Tucker E, Zeki S, Dunn JM, Jafari J, Warburton F, Wong T. Validation of the Lyon classification for GORD diagnosis: acid exposure time assessed by prolonged wireless pH monitoring in healthy controls and patients with erosive oesophagitis. Gut 2021;70:2230-7.

Maret-Ouda J, Markar SR, Lagergren J. Gastroesophageal reflux disease: A review. JAMA 2020;324:2536-47.

Aboul-Enein MS, Knight W, Wulaningsih W, Foley DM, Dellaportas JD, Zylstra J, Baker CR, Kelly M, Smyth E, Lagergren J, Maisey N, Allum WH, Gossage JA, Cunningham D, Davies AR. The role of surgery after prolonged primary chemotherapy for advanced oesophageal adenocarcinoma. J Surg Oncol 2021;124:1296-1305.

Bott RK, Beckmann K, Zylstra J, Wilkinson MJ, X Knight WRC, Baker CR, Kelly M, Maisey N, Waters J, Van Hemelrijck M, Smyth EC, Allum WH, Cunningham D, Lagergren J, Gossage JA, Davies AR. Adjuvant therapy following oesophagectomy for adenocarcinoma in patients with a positive resection margin. Br J Surg 2020;107:1801–10.

Smyth EC, Nyamundanda G, Cunningham D, Fontana E, Ragulan C, Tan IB, Lin SJ, Wotherspoon A, Nankivell M, Fassan M, Lampis A, Hahne JC, Davies AR, Lagergren J, Gossage JA, Maisey N, Green M, Zylstra JL, Allum WH, Langley RE, Tan P, Valeri N, Sadanandam A. A seven-Gene Signature assay improves prognostic risk stratification of perioperative chemotherapy treated gastroesophageal cancer patients from the MAGIC trial. Ann Oncol 2018;29:2356-62.

Lagergren J, Smyth E, Cunningham D, Lagergren P. Oesophageal cancer: Seminar. Lancet 2017;390:2383-96.

Representation in the Nobel Assembly that awards the Nobel Prize in Physiology or Medicine (Jesper Lagergren since 2017).
United European Gastroenterology Research Prize in 2017 of 100,000 € (Jesper Lagergren).
Cancer Research United Kingdom (CRUK) grant (Jesper Lagergren).

Exercise prehabilitation during neo-adjuvant chemotherapy may enhance tumour regression in oesophageal cancer – results from a prospective non-randomised trial

The study, showing evidence of enhanced chemotherapy response in patients undergoing exercise prehabilitation, was selected for a BMJ press release to coincide with World Cancer day and received coverage in the national press. This prestigious achievement highlights the considerable current interest in the role of exercise in cancer treatment.

Patient perspectives on key symptoms and preferences for follow-up after upper gastro-intestinal cancer surgery

The largest patient survey in oesophageal cancer focusing on symptom management during follow-up after treatment. This was performed in collaboration with the Oesophageal Patients Association and is currently in press. It forms the initial patient-facing aspect of the RESTORE study.

Upper GI Cancer Educational half-day

We arrange an annual Upper GI Cancer Educational half-day at the Houses of Parliament, where we and external guests present recent updates regarding the treatment and management of patients with cancer of the oesophagus or stomach.

Co-ordinator