Hypofractionated Radiotherapy Combined With Immunochemotherapy for Conversion Treatment of Gastroesophageal Junction Adenocarcinoma

Korábbi kezelés

• History of or concurrent other malignancies within the past 5 years, excluding cured basal cell carcinoma, squamous cell carcinoma of the skin, or carcinoma in situ of the cervix.
• Known allergy to any component of the investigational drugs, history of severe hypersensitivity, or any contraindication to study drugs.
• Clinically significant upper gastrointestinal bleeding within 30 days prior to enrollment or randomization.
• Active autoimmune or inflammatory diseases requiring immunosuppressive therapy within 2 years prior to treatment, including but not limited to:
  • Inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis, diverticulitis),
  • Systemic lupus erythematosus,
  • Sarcoidosis,
  • Tuberculosis,
  • Wegener's granulomatosis,
  • Myasthenia gravis,
  • Graves' disease,
  • Rheumatoid arthritis,
  • Hypophysitis,
  • Uveitis,
  • Glomerulonephritis,
  • Nephrotic syndrome,
  • Fanconi syndrome, or renal tubular acidosis. Exceptions: type 1 diabetes, hypothyroidism controlled by hormone replacement, and non-systemically treated dermatologic conditions (e.g., vitiligo, psoriasis, alopecia).
• Use of systemic corticosteroids or immunosuppressants within 2 weeks prior to study treatment.
  • Inhaled or topical corticosteroids and adrenal replacement doses (equivalent to ≤10 mg/day prednisone) are permitted.
  • Short-term (<7 days) corticosteroids are allowed for non-autoimmune conditions or prophylaxis (e.g., contrast allergy).
• Major surgery (e.g., craniotomy, thoracotomy, or laparotomy) within 4 weeks prior to the first dose, or planned major surgery during the study period.
• Gastrointestinal perforation and/or fistula within 6 months prior to enrollment; history of arterial/venous thrombotic events such as stroke (excluding clinically stable infarction per investigator), deep vein thrombosis, or pulmonary embolism.
• Participation in another interventional clinical trial within 30 days prior to first dose or planning to do so during the current study.

Más betegség

• Participants who meet any of the following conditions will be excluded:
• Evidence of peritoneal or multi-organ metastatic disease, as confirmed by chest and abdominal CT, bone scan, or MRI (in cases with suspected osseous lesions).
• History of congenital pulmonary fibrosis, drug-induced pneumonitis, active pulmonary tuberculosis, or CT-confirmed active pneumonia; interstitial lung disease requiring steroid treatment.
• History of immunodeficiency, HIV infection (positive HIV 1/2 antibodies), congenital or acquired immunodeficiency disorders, or history of organ transplantation.
• Active hepatitis B (HBsAg positive) or active hepatitis C infection. Patients with past or controlled HBV/HCV infection may be eligible.
• Severe gastrointestinal conditions that may impair oral medication absorption (e.g., dysphagia, chronic diarrhea, intestinal obstruction).
• History of substance abuse or uncontrolled psychiatric disorders.
• Any other condition deemed by the investigator to pose significant risk to patient safety or interfere with study conduct.

Laborértékek

• Uncontrolled or serious comorbidities, including:
  • Poorly controlled hypertension (SBP ≥150 mmHg or DBP ≥100 mmHg despite medication)
  • Myocardial infarction, ischemia (grade II or above), acute coronary syndrome within 6 months, arrhythmia (e.g., QTc ≥480 ms, atrial fibrillation), or uncontrolled angina
  • NYHA class III-IV heart failure, LVEF <50%, severe valvular disease, cardiomyopathy of any cause
  • History of stroke or transient ischemic attack within screening period
  • Active or uncontrolled infection
  • Severe liver disease (e.g., cirrhosis, decompensated liver disease, chronic active hepatitis) affecting tolerability to treatment
  • Poorly controlled diabetes (fasting glucose >10 mmol/L)
  • Proteinuria ≥++ on dipstick or >1.0 g/24 h on urine protein quantification
• Coagulation disorders (INR >1.5 or APTT >1.5 × ULN), bleeding tendency, or current use of thrombolytics or anticoagulants.
  • Known hereditary or acquired bleeding/thrombotic conditions (e.g., hemophilia, coagulopathy, thrombocytopenia, hypersplenism).
  • History of significant hemoptysis (≥2.5 mL/day) or massive bleeding within 2 months.
  • Gastrointestinal bleeding, bleeding gastric ulcer, positive fecal occult blood (++ or above), vasculitis, or active bleeding within 3 months.
  • Long-term use of warfarin/heparin or high-dose antiplatelet therapy (aspirin ≥300 mg/day or clopidogrel ≥75 mg/day).

Egyéb

• Diagnosed as mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H) by immunohistochemistry or gene testing.
• Unhealed wounds or fractures of clinical significance.
• Severe malnutrition.
• Pregnant or breastfeeding women, or subjects (male or female within one year of menopause) unwilling to use effective contraception.
• Unwilling or unable to comply with study procedures.

• Participants must meet all of the following criteria:
• Histologically and/or cytologically confirmed diagnosis of locally advanced gastroesophageal junction adenocarcinoma (GEJA), Siewert type I-III, with staging of cT3-4, any N, M0 or cT2 N+, M0, according to the AJCC 8th edition.
• Resectable locally advanced disease as determined by multidisciplinary team (MDT) assessment.
• Age ≥18 years, regardless of sex.
• ECOG performance status of 0 or 1.
• Estimated life expectancy of ≥3 months.
• No prior anti-tumor therapy.
• At least one measurable lesion per RECIST v1.1, defined as:
  • Lesion ≥1 cm in longest diameter on spiral CT, or
  • Lesion ≥2 cm in longest diameter on conventional CT or MRI.
  • Imaging must be performed within 28 days prior to enrollment.
• Adequate organ function within 14 days prior to treatment, as defined below (Note: No RBC or platelet transfusion or use of G-CSF within 14 days prior to hematology testing):
  • Hematologic:
  • Hemoglobin ≥9 g/dL (without transfusion)
  • ANC ≥1.5 × 10⁹/L
  • WBC ≥3.0 × 10⁹/L (without G-CSF)
  • Platelets ≥75 × 10⁹/L (without IL-11 or TPO)
  • Biochemical:
  • Total bilirubin ≤1.5 × ULN
  • AST and ALT ≤2.5 × ULN
  • Serum creatinine ≤1.5 × ULN or creatinine clearance ≥60 mL/min (Cockcroft-Gault formula)
  • Albumin ≥25 g/L (2.5 g/dL)
  • Coagulation (within 7 days prior to enrollment):
  • INR <1.5
  • APTT <1.5 × ULN
  • INR or PT ≤1.5 × ULN
• For patients with active hepatitis B or C:
  • Antiviral therapy must be initiated ≥14 days before enrollment
  • HBV DNA ≤500 IU/mL or ≤2500 copies/mL; HCV RNA undetectable
  • Must agree to continue antiviral therapy during the study
• Left ventricular ejection fraction (LVEF) ≥50% by echocardiography.
• Women of childbearing potential:
  • Negative serum or urine pregnancy test within 7 days prior to enrollment
  • Agree to use effective contraception during the study and for at least 3 months after the last dose
  • Must not breastfeed or donate/retrieve ova within 60 days after the last dose
  • Effective contraception must be continued for at least 6 months after last dose of chemotherapy
• Men must be surgically sterile or agree to use effective contraception during the study and for at least 3 months after the last dose.
• Voluntarily signed informed consent with good compliance and willingness to complete study procedures and follow-up.