dCRT vs. Surgery in Resectable ESCC Patients Achieving cCR/PR After Induction Chemoimmunotherapy

Prior treatment

• Prior surgery for esophageal cancer;
• Poor nutritional status, weight loss of ≥10% in the previous 2 months, with no significant improvement after nutritional intervention;
• Major surgery or severe trauma within 4 weeks before formal enrollment;
• Received or receiving any of the following treatments in the past:
  • Radiotherapy or targeted therapy;
  • Participation in a study of an investigational agent or device within 4 weeks before the first dose of study treatment;
  • Use of systemic corticosteroids at a dose \>10 mg/day prednisone equivalent or other systemic immunosuppressive therapy within 2 weeks before formal enrollment, except for inhaled or topical corticosteroids, physiologic hormone-replacement therapy, and short-term corticosteroids used for prophylaxis or treatment of allergic reactions, nausea, or vomiting;
  • Receipt of a live vaccine or antitumor vaccine within 4 weeks before formal enrollment;
• Any active autoimmune disease or history of autoimmune disease (e.g., interstitial pneumonitis, uveitis, enteritis, hepatitis, pituitary gland inflammation, vasculitis, myocarditis, nephritis, hyperthyroidism, hypothyroidism); Except for patients with vitiligo or those who had asthma or allergies in childhood but did not need any intervention as adults; patients with autoimmune-mediated hypothyroidism treated with stable doses of thyroid replacement hormone and type I diabetes mellitus treated with stable doses of insulin may be included;
• Severe infections (CTCAE \> grade 2), such as severe pneumonia requiring hospitalisation, bacteraemia, infectious co-morbidities, etc., within 4 weeks before formal enrollment; Baseline chest imaging suggestive of active lung inflammation, signs and symptoms of infection requiring oral or intravenous antibiotic treatment within 2 weeks before the first use of study treatment, except for prophylactic antibiotic use;
• Active tuberculosis infection detected by history or CT examination, or history of active tuberculosis infection within 1 year before enrollment or more than 1 year previously without regular treatment;
• Previously diagnosed with any other malignancy within 5 years before the first use of the investigational drug, except for malignancies with low risk of metastasis and death (5-year survival rate\>90%), such as adequately treated basal cell or squamous cell skin cancer or cervical carcinoma in situ.

Other illness

• Risk of gastrointestinal bleeding, esophageal fistula or esophageal perforation;
• Diagnosis of immunodeficiency, including positive HIV test, other acquired/congenital immunodeficiency diseases, organ transplantation and allogeneic bone marrow transplantation;
• Diagnosis of uncontrolled cardiac clinical symptoms or disease such as: a. NYHA II or above heart failure; b. unstable angina; c. myocardial infarction within 1 year; d. clinically significant supraventricular or ventricular arrhythmias requiring clinical intervention;
• History of interstitial lung disease or non-infectious pneumonia, or pulmonary insufficiency ≥ grade 3 as confirmed by pulmonary function tests;
• Active hepatitis B infection (HBV DNA \>2000 IU/mL) or active hepatitis C infection with detectable HCV RNA;
• Known hypersensitivity or contraindication to camrelizumab, nab-paclitaxel, carboplatin, or any component of the protocol-defined study treatments;

Lab values

• Presence of abnormal sodium, potassium, and calcium laboratory test values greater than grade 1 within 2 weeks prior to enrollment that do not improve with treatment;

Other

• Esophageal fistulae due to infiltration of the primary tumor；
• Uncontrollable pleural effusion, pericardial effusion, or ascites that requires repeated drainage;
• As judged by the investigator, the subject has other factors that may lead to forced termination of the study midway.

• Volunteered to participate, cooperated with follow-up visits.
• Aged 18 - 75 years (inclusive), male or female.
• Histologically confirmed, resectable locally advanced ESCC, defined as cT1N1-3M0 or cT2-4aN0-3M0 according to the AJCC 8th edition, with cCR or PR achieved after 2-3 cycles of induction chemoimmunotherapy consisting of a permitted PD-1 inhibitor combined with a taxane and a platinum agent.
• Presence of measurable and/or non-measurable lesions as defined by Japanese Classification of Esophageal Cancer (12th Edition);
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1.
• Life expectancy ≥ 3 months.
• The function of major organs meets the following requirements:
  • Absolute neutrophil count (ANC) ≥ 1.5×10\^9/L;
  • Platelets ≥ 80×10\^9/L;
  • Hemoglobin ≥ 9 g/dL;
  • Serum albumin ≥ 2.8 g/dL;
  • Total bilirubin ≤ 1.5 × ULN, ALT, AST and/or ALP ≤ 2.5 × ULN;
  • Serum creatinine ≤ 1.5 × ULN or creatinine clearance ≥ 60 mL/min;
  • International normalized ratio (INR) and activated partial thromboplastin time (APTT) ≤ 1.5× ULN (subjects on stable doses of anticoagulation therapy, such as low molecular weight heparin or warfarin, and with INR within the expected therapeutic range of the anticoagulant can be screened);
• Comprehensive baseline staging evaluation prior to induction chemoimmunotherapy, including esophagogastroduodenoscopy with biopsy and/or EUS, contrast-enhanced CT of the neck, chest, and upper abdomen, MRI in patients without contraindications, and an upper gastrointestinal contrast study. PET/CT may be performed when clinically indicated and feasible.
• Patients of childbearing potential must use a medically approved contraceptive method (such as intrauterine device, contraceptive pills, or condoms) during the study treatment period and within 6 months after the end of the study treatment; serum Human Chorionic Gonadotropin (HCG) or urine HCG test must be negative within 72 hours before study enrollment; and must not be breastfeeding.