NEOadjuvant Trial in Adenocarcinoma of the oEsophagus and oesophagoGastric Junction International Study (Neo-AEGIS)

Inclusion Criteria:

1. Histologically verified adenocarcinoma of the oesophagus or oesophago-gastric junctionbased on endoscopy (OGD)
2. CT-18FDG-PET performed in all patients for disease staging.
3. EUS in all patients unless luminal obstruction precludes sensitivity of the test.
4. Staging laparoscopy performed at the investigator's discretion for locally advancedAEG II and AEG III tumours .
5. Pre-treatment stage cT2-3, N0-3, M0.
6. Maximum tumour length should be no more than 8cm (equal to 8 cm is acceptable)
7. Male/female patients aged ≥18 years
8. ECOG Performance Status 0, 1 or 2 (Appendix F).
9. ASA I-II (Appendix F).
10. Adequate cardiac function. For all patients, an ejection fraction of > 50% isrequired. If patients have a known cardiac history (e.g. known ischemic disease,cardiomyopathy) an ejection fraction > 50% and cardiac clearance by a consultantcardiologist for major surgery and cancer therapies is required.
11. Adequate respiratory function. Patients should have pulmonary function tests completedwith a minimum FEV1 ≥ 1.5L. CPEX acceptable
12. Adequate bone marrow function: absolute neutrophil count (ANC) >1.5x109/l; white bloodcell count >3x109/l; platelets >100x109/l; haemoglobin (Hb) >9g/dl (can bepost-transfusion).
13. Adequate renal function: glomerular filtration rate >60ml/minute calculated using theCockcroft-Gault Formula (Appendix O).
14. Adequate liver function: serum bilirubin <1.5x ULN; AST <2.5x ULN and ALP <3x ULN (ULNas per institutional standard).
15. Written informed consent must be obtained from the patient before any study-trialspecific procedures are performed.
16. Women of child-bearing potential and male subjects must agree to use an effectivebarrier method of contraception for up to 6 months following discontinuation oftherapy. Effective contraception is defined as any medically recommended (orcombination of methods) as per standard of care.
17. Women of childbearing potential must have pregnancy excluded by urine or serumbeta-HCG testing within 7 days prior to treatment.

Exclusion Criteria:

1. Tumours of squamous histology.
2. Patients with advanced inoperable or metastatic oesophageal, junctional or gastricadenocarcinoma.
3. Disease length (total length of tumour plus node) greater than 10cm (up to 10 cm willbe allowed) -as measured by any modality or, if appropriate, combination ofmodalities-, unless in the opinion of the investigator in discussion with national RTlead, it is felt that OAR constraints are likely to be achievable.
4. Any prior chemotherapy for gastrointestinal cancer.
5. Prior abdominal or thoracic, chest wall or breast radiotherapy.
6. Patients who are unfit for surgery or cancer treatments based on cardiac disease.
7. Patients with acute systemic infections.
8. Patients who are receiving treatment with sorivudine or its chemical relatedanalogues, such as brivudine which is contraindicated with capecitabine and 5-fluorouracil administration.
9. Clinical COPD with significant obstructive airways disease classified by FEV1 < 1.5 Lor PaO2 less than 9kPa on room air
10. Known peripheral neuropathy >Grade 1 (absence of deep tendon reflexes as the soleneurological abnormality does not render the patient ineligible).
11. Known positive tests for human immunodeficiency virus (HIV) infection, acute orchronic active hepatitis B infection.
12. Any other malignancies within the last 5 years (other than curatively treated basalcell carcinoma of the skin and/or in situ carcinoma of the cervix)
13. Participation in other clinical trials of investigational or marketed agents for thetreatment of oesophageal cancer or other diseases within 30 days from registration. UKsites please refer to Group Specific Appendix
14. Women who are pregnant or breastfeeding.
15. Psychiatric illness/social situations that would limit compliance with studyrequirements.