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Diagnostic pathways and treatment options in oesophago-gastric cancer 1.45pm – 2.30pm
Mr Sacheen Kumar
Consultant Upper GI Surgeon
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The Royal Marsden Diagnostic Pathways & Treatment Options in OG Cancer – 19th June 2019 2
National Oesophago-Gastric Cancer Audit 2018
Oesophago-Gastric Cancer
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Oesophageal and gastric cancer - aetiology
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Oesophageal
— Smoking — Alcohol — Reflux — Barrett’s — Obesity — Achalasia — Family History — Corrosives
Gastric — Smoking — Alcohol — Helicobacter Pylori — Family history — Previous stomach surgery — Pernicious anaemia
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Endoscopic Appearance of OG Cancer
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Urgent Cross-Sectional Imaging, contacting Cancer
Nurse Specialist and Referral to Upper GI
Multidisciplinary Meeting
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Staging for OG Cancer
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CT scan Chest/Abdomen/Pelvis
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18F-FDG PET scan
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Endoscopic Ultrasound (T1/T4 disease)
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Peri-operative Pathway
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• Neo-adjuvant
• 3/4 cycles
Pre-op
• Oesophagectomy
• Gastrectomy
Surgery Adjuvant
3/4 cycles
Post op
Long and intensive - over 6 months
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Staging laparoscopy and OGD
— Oesophago-gastric cancers require accurate staging prior to surgery
— Need to distinguish potentially curable from likely incurable disease
— 2019 EORTC Gastrointestinal Cancer Conference: Controversial issues in the multimodal primary treatment of gastric, junctional and oesophageal adenocarcinoma recommends staging laparoscopy to diagnose peritoneal involvement before starting neoadjuvant treatment in all gastric cancers and in oesophago-gastric junctional (OGJ) type II and III
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Use of staging CT and CT PET
— With traditional use of Computed Tomography (CT) imaging alone, staging laparoscopy has been shown to change management in up to 40% of cases
— The staging ability of CT and its sensitivity in detecting small volume metastases is continually improving
— This is further enhanced with use of Positron Emission Tomography (PET)-CT
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Advantages and limitations of CT PET
— FDG-PET has been shown to have a higher sensitivity for detection of metastatic disease compared to CT
— In oesophageal and OGJ FDG-PET led to upstaging 15% of patients from M0 to M1 disease and downstaging of 7% of the patients
— Overall sensitivity of FDG-PET/CT for detecting gastric cancer is lower than for most other malignancies
— Gastric cancer only PET avid in 65-80% (poor for diffuse type) and changes management in 5%.
— Limited efficacy for small lesions <5mm
— Potential for false-positive e.g., benign tumours, inflammatory processes
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Methods
— Over the last 3 years, between 2016 – 2019
— Data was analysed from prospectively maintained electronic patient records at a tertiary referral cancer centre
— All patients with gastric, OGJ or oesophageal cancer undergoing a staging laparoscopy were included
— All patients were imaged pre-operatively with a staging CT scan and a PET-CT.
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Accepted for presentation at ESSO Meeting 2019
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RMH Staging Laparoscopy Data
— 162 patients underwent staging laparoscopy (116 males, 72%)
— Median patient age was 65 (range 40-85) years
— Cancer types were 69 (42%) gastric and 93 (58%) oesophageal/OGJ; of these, 11 patients were classified as distal oesophageal, 24 were Siewert I, 32 were Siewert II and 26 were Siewert III
— Tumour types included adenocarcinoma in 161 patients, of those, 25 (15%) had signet ring morphology, and 1 Squamous Cell Carcinoma of the distal oesophagus
— Tumour stage was predominantly T3 (n=109, 67%) and T4 (n=32, 20%)
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Accepted for presentation at ESSO Meeting 2019
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Results
— Staging laparoscopy changed management in 31 (19%) patients (25% in gastric and 15% in oesophageal/OGJ cancer).
— Previously undetected metastatic disease was seen in 15 patients (9%), with peritoneal disease (n=14) and liver lesions (n=1) observed.
— 12 patients (7%) had locally advanced disease
— 4 (2%) patients were judged unfit for major surgery
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Accepted for presentation at ESSO Meeting 2019
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Study Conclusions
— Staging laparoscopy continues to be an important diagnostic modality in the treatment pathway of oesphago-gastric cancers
— It reduces the risk of surgery without benefit for the patient, especially in gastric and OGJ Type 2 & 3 cancers
— Despite recent advances in imaging techniques and expert interpretation, there are still limitations of radiology alone in assessing extent of disease and suitability for curative resection.
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Accepted for presentation at ESSO Meeting 2019
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Key Trials in Oesophago-Gastric Cancer
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Surgery for OG Cancer
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Aim of Resection
Complete resection of primary tumour (R0)
Clear margins
Lymphadenectomy (>15 nodes)
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• Neo-adjuvant
• 3/4 cycles
Pre-op
• Oesophagectomy
• Gastrectomy
Surgery Adjuvant
3/4 cycles
Post op
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SIEWERT AEG-Classification
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Siewert et al. Brit. J. Surg. 2003; 85: 11
Centre of tumour 2cm above or below
gastro-oesophageal junction
Defining the centre is NOT easy
• Endoscopy
• Imaging
Decisions based only on the centre ?Too
simplistic
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Mobilisation - blood supply of the stomach
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Lymph nodes draining the stomach
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Pattern of lymph node spread En bloc resection
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Leers et al. J Thor & Cardio 2009; 138: 594
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EORTC Consensus - St Gallen 2012
Type I – Oesophago-Gastrectomy
Type II – Oesophago-Gastrectomy or
Extended Total Gastrectomy
Type I & II – Mediastinal Lymphadenectomy
– 2 field
Type III - Extended Total Gastrectomy
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Lutz et al. Eur J Cancer 2012; 48: 2941-53
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Minimally Invasive Approach
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Oesophago-Gastric Junctional Adenocarcinoma
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Extent of resection
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Roux-en-Y gastrojejunostomy
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Roux-en-Y oesophagojejunostomy
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Survival
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One year age-standardised net survival for adults 2011-2015 by
Cancer Alliance and STP - Oesophageal Cancer
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Source:- Office of National Statistics sourced from National Cancer Registration Service https://www.ons.gov.uk/peoplepopulationandcommunity/healthandsocialcare/conditionsanddiseases/datasets/geographicpatternsofcancersurvivalinengland RAG rating (95% confidence interval) Green highlight -Rate is better than England overall rate Red highlight - Rate is worse than England overall rate
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One year age-standardised net survival for adults 2011-2015 by Cancer Alliance
and STP - Stomach Cancer
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Source:- Office of National Statistics sourced from National Cancer Registration Service https://www.ons.gov.uk/peoplepopulationandcommunity/healthandsocialcare/conditionsanddiseases/datasets/geographicpatternsofcancersurvivalinengland RAG rating (95% confidence interval) Green highlight -Rate is better than England overall rate Red highlight - Rate is worse than England overall rate
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Innovations in OG Cancer
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Improving Outcomes in OG cancer
— Incidence of OG Cancer – endoscopy-based screening programmes
— are not cost-effective
— Historically poor awareness of the disease
— Ongoing Studies – International UGI Surgery Collaboration
— The Future • Early detection of the disease • Personalised Medicine & new chemotherapeutic treatments • Novel Endoscopic, Interventional & Surgical Approaches • Optimal Staging techniques
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A trial looking at the Cytosponge test in GP surgeries for
people with heartburn symptoms (BEST3)
Early Diagnosis Technologies
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Colorectal cancer screening with odour material by canine scent detection Hideto Sonoda, Shunji Kohnoe, Tetsuro Yamazato, Yuji Satoh, Gouki Morizono, Kentaro Shikata, Makoto Morita, Akihiro Watanabe, Masaru Morita,Yoshihiro Kakeji, Fumio Inoue, Yoshihiko Maehara Gut 2011; 60: 814-819 — Volatile Organic Compounds (VOCs) routinely measured in:
• Assessment of environmental contamination • Flavour and fragrance industry • Counter-Terrorism
— Endogenous VOCs potentially hold the key to identification of biomarkers for
underlying disease processes
Early Diagnosis Technologies
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Early Diagnosis Technologies
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Endoscopy & AR
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Robotic Surgery
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Robotic Surgery
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Mass Spec Cancer Staging
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Multivariable analysis comparing lipidomic profiles (m/z 600-1000) of
esophageal adenocarcinoma (EA, red), Barrett’s dysplasia (BD, orange), Barrett’s
metaplasia (BM, blue), inflamed esophageal epithelium (IEE, light green) and
healthy esophageal epithelium (HEE, dark green). a) Principal component
analysis score plot. Each point is the average of multiple mass spectra
representative of that tissue type within a single sample from one patient. b)
representative mass spectra of tissue types and; c) Heat map of 86 samples; d)
Recursive Maximum Margin criterion (RMMC) supervised analysis score plot of
cohort 2; e) Leave one out cross-validated RMMC score plot as per confusion
matrix; f) Confusion matrix of leave one out internal cross validation with
Mahalanobis distance classifier.
Unpublished data
Mass Spec Cancer Staging
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The Microbiome
⬆ Reactive
aldehydes
Lipid peroxidatio
n
Schiff base
adduction
DNA mutation
Protein denaturation
Lipid carbonylation
Effect of pH
Decreased microbial diversity in oesophageal adenocarcinoma tissue compared
with tissue from healthy control patients
Cancer group Positive control Healthy group0
1
2
3
4
5
6
7
8
9
10
pH
No difference in proton pump inhibitor/H2-receptor
antagonist use amongst 3 groups
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Thank you
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