Efficacy and Safety of Postoperative Concurrent Chemoradiotherapy for Extrahepatic Cholangiocarcinoma and Gallbladder Carcinoma: A Multicenter Prospective Phase II Study

Efficacy and Safety of Postoperative Concurrent Chemoradiotherapy for Extrahepatic Cholangiocarcinoma and Gallbladder Carcinoma: A Multicenter Prospective Phase II Study

This is a multicenter, open-label, single-arm, prospective Phase II clinical trial. The study enrolls patients with extrahepatic cholangiocarcinoma or gallbladder carcinoma who have undergone curative resection and harbor high-risk recurrence factors, including: 1) narrow resection margin (including R1 resection); 2) positive circumferential resection margin; 3) T stage ≥ T3-4; 4）positive regional lymph nodes. All patients will receive postoperative concurrent chemoradiotherapy (CCRT) with intensity-modulated radiotherapy (IMRT) or volumetric modulated arc therapy (VMAT). The high-risk volumes of the primary tumor bed and metastatic lymph node beds will be irradiated to 48-60 Gy in 20-25 fractions. Retroperitoneal and intra-abdominal lymph nodes will receive 50-57.5 Gy in 20-25 fractions, and lymphatic drainage regions will be treated to 40-45 Gy in 20-25 fractions. During radiotherapy, concurrent oral capecitabine will be administered at a dose of 1,600 mg/m² on Days 1-14, every 21 days for 2 cycles. Following the completion of radiotherapy, maintenance oral capecitabine will be continued at 2,000 mg/m² on Days 1-14, every 21 days for 6 cycles. For patients intolerant to capecitabine, S-1 will be substituted: concurrent S-1 40-50 mg twice daily on Days 1-28, every 42 days for 1 cycle, followed by maintenance S-1 40-60 mg twice daily on Days 1-28, every 42 days for 3 cycles.

The primary study endpoint is the 2-year recurrence-free survival (RFS) rate. Secondary study endpoints include the 2-year overall survival (OS) rate, locoregional control rate, and incidence of grade ≥3 adverse events.

A total of 92 patients are planned for enrollment in this trial.

Inclusion Criteria:

• Aged 18-80 years

• Underwent curative resection for newly diagnosed disease, with postoperative pathology confirming extrahepatic cholangiocarcinoma or gallbladder adenocarcinoma

• Postoperative pathology with ≥1 high-risk factor for recurrence

  1. Narrow resection margin (<1 cm), including R1 resection
  2. Positive circumferential resection margin
  3. T stage ≥ T3-4
  4. Positive regional lymph nodes

• Postoperative liver function: Child-Pugh grade A5-B7

• No recurrence or metastasis before postoperative radiotherapy

• ECOG performance status 0-2

• Expected survival >3 months

• Routine blood tests: Neutrophils ≥1.0×10⁹/L, hemoglobin ≥80 g/L, platelets ≥100×10⁹/L

• Liver function: Total bilirubin <1.5×upper limit of normal (ULN), plus one of the following:

  1. ALT and AST ≤2.5×ULN
  2. ALT ≤1.5×ULN and AST ≤6×ULN (excluding AST elevation due to myocardial infarction)

• Renal function: Creatinine and blood urea nitrogen ≤2.5×ULN

• Voluntary participation and signed informed consent

Exclusion Criteria:

• History of other malignant tumors (except papillary thyroid carcinoma, basal cell carcinoma of the skin, and cervical carcinoma in situ)
• Severe comorbidities (e.g., myocardial infarction, arrhythmia, psychiatric disorders)
• Prior abdominal radiotherapy
• Post-organ transplantation
• Symptomatic moderate-severe ascites within 4 months postoperatively
• ≥4 months since surgery