Table 1 Inclusion and exclusion criteria for the NEOSCOPE trial

Patients meeting any of the following criteria may be included in the trial:

1.

Histologically confirmed operable oesophageal cancer [adenocarcinoma]

2.

T3/T4 with any N stage OR N1 with any T stage (TNM6). This will be equivalent to T3/T4a with any N stage OR N1-3 with any T stage (TNM7). T4a tumours should;

   a. involve only the diaphragm or crura, or

   b. invade only the mediastinal pleura, or

   c. breach the gastric serosa (TNM 7).

Tumours with nodal disease (N1-3) affecting the origin of the left gastric and splenic artery with the coeliac axis (formerly staged as M1a in TNM 6) can be included.

3.

Maximum disease (T + N) length 8 cm staged with EUS and CT/PET with maximum extent of primary disease below the gastro-oesophageal junction being 3 cm.

4.

WHO performance status 0–1 and patient fit to be treated with combined modality therapy (chemotherapy and radiotherapy prior to surgery).

5.

Adequate respiratory and cardiac function: FEV1 > 1.5 litres and cardiac ejection fraction ≥50% on echocardiography or MUGA. These assessments should normally be performed within 4 weeks prior to randomisation. CPEX testing is allowable but must not replace the above investigations. Patients who have had their assessments done over 4 weeks prior to randomisation or have had borderline results may still be eligible provided that they have approval from the CI through the NeoSCOPE trial team.

6.

Adequate haematological, renal, and hepatic function:

  a. Liver function tests ≤1.5 × ULN

  b. White blood cell count ≥ 3 × 10⁹/l; platelets ≥ 100 × 10⁹/l.

  c. Glomerular filtration rate (GFR) >50 ml/minute calculated or measured.

The above assessments should normally be performed within 1 week prior to randomisation. Patients who have had their assessments done over 1 week prior to randomisation or have had borderline results may still be eligible provided that they have approval from the CI through the trial team.

7.

The patient has provided written informed consent.

8.

The patient is at least 18 years old.

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

1.

Oesophageal cancer with histology other than adenocarcinoma

2.

Uncontrolled angina pectoris, myocardial infarction within 6 months, heart failure, clinically significant uncontrolled cardiac arrhythmias, or any patient with a clinically significant abnormal ECG.

3.

Patients with any previous treatment for oesophageal carcinoma.

4.

Siewert type 3 oesophago-gastric tumours.

5.

Lower limit of the endoscopically visible primary tumour should not involve stomach for more than 3 cm distal to the gastro-oesophageal junction.

6.

T4 tumours invading contiguous structures other than diaphragm, crura or mediastinal pleura.

7.

Patients with disease in any of the following areas on the CT scan, EUS or other staging investigation:

  a. Evidence of metastases in liver, lung, bone or other distant metastases.

  b. Abdominal para aortic lymphadenopathy >1 cm diameter on CT or >6 mm diameter on EUS.

  c. Invasion of tracheo-bronchial tree, aorta, pericardium or lung.

8.

Lymphadenopathy encasing the coeliac axis (as described above, patients with single nodes lying anterior to the origin of the splenic artery and anterior to the origin of the coeliac axis are not excluded).

9.

Any patient with a single significant medical condition which is thought likely to compromise his or her ability to tolerate any of the above therapies.

10.

Specific contra-indications to surgery, chemotherapeutic agents (including known allergies to chemotherapy) or radiotherapy.

11.

Patients with another previous or current malignant disease which in the judgement of the treating investigator is likely to interfere with treatment or the assessment of response.

12.

Pregnant or lactating women and fertile women who will not be using contraception during the trial.