Neoadjuvant Pembrolizumab Plus Chemotherapy for Resectable Locally Advanced Esophageal Squamous Cell Carcinoma

Inclusion Criteria:

* Histologically proven squamous cell carcinoma of the esophagus.
* Surgical resectable (T3 or T4b, N0 or N+, M0), as determined by Endoscopic Ultra Sound (EUS),Positron Emission Tomography/Computed Tomography (PET/CT), Esophageal MRI and enhanced CT scan of neck, thorax and abdomen.
* Tumor length longitudinal ≤ 10 cm; if larger than 10 cm, inclusion should be discussed with the principal investigator.
* 18≤Age.
* Tumor does not involve gastro-esophageal junction.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
* Adequate hematological, renal and hepatic functions defined as:

neutrophiles ≥ 1.5 x 109/L platelets ≥ 100 x 109/L alanine transaminase≤2 x upper normal limit hemoglobin ≥ 5.6 mmol total bilirubin ≤ 1.5 x upper normal limit creatinine clearance (Cockcroft) ≥60 ml/min

* Written, voluntary informed consent

Exclusion Criteria:

* Past or current history of malignancy other than entry diagnosis interfering with prognosis of esophageal cancer.
* T1, T2 tumors or in situ carcinoma.
* metastatic oesophageal cancer.
* Pregnancy (positive serum pregnancy test), planning to become pregnant, and lactation.
* Previous chemotherapy, radiotherapy, and/or treatment with checkpoint inhibitors.
* Clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) precluding major surgery.
* Pulmonary fibrosis and/or severely impaired lung function precluding major surgery.
* Pre-existing motor or sensory neurotoxicity greater than World Health Organization (WHO) grade 1.
* Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs).
* Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (\>10 mg/day prednisone or equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
* Dementia or altered mental status that would prohibit the understanding and giving of informed consent
* Serious underlying medical condition which would impair the ability of the patient to receive the planned treatment, including prior allergic reactions to drugs containing Cremophor, such as teniposide or cyclosporine.
* Has an active infection requiring systemic therapy which has not resolved 3 days (simple infection such as cystitis) to 7 days (severe infection such as pyelonephritis) prior to the first dose of trial treatment.
* Has a diagnosis of acute or chronic hepatitis B, hepatitis C, known immunodeficiency or human immunodeficiency virus (HIV).
* Patients with prior allogeneic stem cell or solid organ transplantation.