Table 1 Inclusion and exclusion criteria for the SCOPE1 trial

1. Histologically confirmed carcinoma of the oesophagus (adenocarcinoma or squamous cell or undifferentiated carcinoma) or Siewert Type 1 tumour of the gastro-oesophageal junction (GOJ) or Siewert Type 2 with no more than 2 cm mucosal extension into the stomach.

2. Age 18 or over

3. Have been selected to receive potentially curative definitive CRT by a specialist Upper GI MDT including a designated Upper GI surgeon.

4. Not suitable for surgery either for medical reasons or through patient choice.

5. Tumours staged with both endoscopic ultrasound (EUS) and spiral CT scan to be T1-4, N0-1 confirming localised, non-metastatic disease (both within 7 weeks prior to randomisation, but the most recent within 4 weeks). An attempted but failed or contra-indicated EUS is acceptable. Tumours should be staged according to the 6th edition of the American Joint Committee on Cancer's (AJCC) Cancer Staging Manual

6. Total disease length (primary and lymph nodes) less than or equal to 10 cm defined by EUS or CT if EUS attempted but failed or contra-indicated.

7. WHO Performance status 0-1

8. Adequate cardiovascular function for safe delivery of CRT in the opinion of the principal investigator

9. Adequate respiratory function for safe delivery of CRT in the opinion of the Principal Investigator

10. Adequate bone marrow and hepatic function (within 1 week prior to randomisation):

• Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L

• White blood cell count ≥ 3 × 10⁹/L

• Platelets ≥ 100 × 10⁹/L

• Haemoglobin (Hb) ≥ 10 g/dL (patients' Hb should be corrected to > 10 g/dl before treatment)

• Adequate liver function (within 1 week prior to randomisation)

• Serum bilirubin ≤ 1.5× ULN

• ALT/AST ≤ 2.5× ULN

• ALP ≤ 3× ULN

11. Adequate renal function (within 1 week prior to randomisation): Glomerular filtration rate (GFR) assessed by EDTA clearance to be > 40 mL/min (or estimated by Cockcroft-Gault formula to be > 60 mL/min)

12. Patients who are fit to receive all protocol treatment.

13. Patients who are able and willing to administer capecitabine.

14. Patients who are of child bearing age are willing to use contraception.

15. Patients who have completed baseline quality of life questionnaires

16. Patients who have provided written informed consent prior to randomisation

Exclusion Criteria

If any of the following criteria apply, patients cannot be included in the trial:

1. Patients who have had previous treatment for invasive oesophageal carcinoma or gastro-oesophageal junction carcinoma (not including PDT or laser therapy for high grade dysplasia/carcinoma in-situ).

2. Patients with metastatic disease i.e. M1a or M1b according to UICC TNM version 6.

3. Patients with any previous treatment for malignancy which will compromise ability to deliver definitive mediastinal CRT or may compromise survival (does not include patients with squamous cell carcinoma).

4. Patients who have had a previous malignancy during the previous 5 years

5. Patients with significant (> 2 cm) extension of tumour into the stomach

6. Patients with unstable angina or uncontrolled hypertension or cardiac failure or other clinically significant cardiac disease

7. Patients who have had major surgery or major trauma in the 4 weeks prior to randomisation.

8. Patients who have been treated with a monoclonal antibody in the 4 weeks prior to randomisation.

9. Patients who have been treated with radiotherapy in the 3 months prior to randomisation

10. Patients who need continued treatment with a contraindicated concomitant medication or therapy

11. Patients with known dihydropyrimidine dehydrogenase (DPD) deficiency

12. Patients with hearing impairment or sensory-motor neuropathy of WHO grade > 2

13. Women who are pregnant