The goal of this clinical trial is to learn if hypofractionation of definitive chemoradiotherapy can treat patients with locally advanced esophageal cancer. The main question it aims to answer is if this treatment is feasible and safe. We also want to investigate the toxicity, in particular the radiation-induced lymphopenia.

Normally, definitive chemoradiotherapy for patients with locally advanced esophageal cancer consist of 28 fractions of 1.8 Gy with concurrent 6 cycles of carboplatin and paclitaxel in 5.5 weeks. In this study, participants will receive 20 fractions of 2.4 Gy with concurrent 6 cycles of carboplatin and paclitaxel in 4 weeks. The follow-up will be conform standard-of-care.

Inclusion Criteria:

• Age ≥18 years.

• Histologically confirmed oesophageal or GOJ carcinoma (adenocarcinoma, squamous cell carcinoma, adenosquamous carcinoma, large cell carcinoma or undifferentiated carcinoma).

• An oesophageal tumour location can involve the proximal, middle and/or distal third of the oesophagus.

• If the tumour extends below the GOJ into the cardia, the bulk of the tumour must involve the oesophagus or GOJ (i.e. Siewert type I or II). The tumour should not extend more than 5 cm into the stomach.

• Clinical stage cT1N1-3M0 or cT2-4aN0-3M0, using the Tumour-Node-Metastasis classification system (TNM, 8th edition), deemed suitable for definitive CRT with curative intent.

• No evidence of distant metastases (M0), as confirmed by standard staging procedures including Fluorine-18 Fluorodeoxyglucose (18F-FDG) PET/CT.

• World Health Organization (WHO) performance status 0-2.

• Adequate hematologic, renal, and hepatic function:

  • Platelet count ≥100 × 10⁹/L
  • Absolute neutrophil count ≥1.5 × 10⁹/L
  • Glomerular filtration rate ≥50 mL/min
  • Total bilirubin ≤1.5 × upper normal limit

• Written informed consent obtained before any study-specific procedures.

• Able to comply with study procedures and scheduled follow-up.

Exclusion Criteria:

• High grade dysplasia without histological evidence of invasive carcinoma.
• Presence of distant metastases (M1).
• Patients with pathological lymph nodes at both supraclavicular and celiac trunk level.
• Prior thoracic or upper abdominal radiotherapy that would preclude safe delivery of the planned radiotherapy dose.
• Prior chemotherapy for oesophageal or gastric cancer.
• Presence of an oesophageal stent.
• Active uncontrolled infection.
• Clinically significant comorbidities that would preclude safe administration of CRT (e.g. severe pulmonary, cardiac, or hepatic impairment).
• Pregnancy or breastfeeding.
• Known hypersensitivity to paclitaxel, carboplatin, or any of their excipients.
• History of malignancies, with the exception of basal cell carcinoma of the skin, ductal carcinoma in situ of breast, cervical intraepithelial neoplasia of uterine cervix, or other malignancies that do not interfere with the prognosis of oesophageal cancer.

Due to the sensitivity of the collected data, the data itself cannot be published or shared without restrictions. We will consult the Data Protection Officer and Research Data Management regarding potential for sharing the data, and Legal Research Support regarding setting up conditions for reuse.