Agrawal Sushma, Kapoor Vishwas, Rahul Rahul, Singh Ashish, Mishra Prabhakar, Saxena Rajan
Departments of Radiotherapy, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India.
Departments of Biostatistics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India.
Int J Radiat Oncol Biol Phys. 2025 May 1;122(1):10-18. doi: 10.1016/j.ijrobp.2024.11.099. Epub 2024 Dec 14.
Chemotherapy (CT) is the standard of care for patients presenting with unresectable advanced gallbladder carcinoma (GBC) but their prognosis remains poor. The value of consolidation CT and radiation therapy (RT) after initial CT is uncertain. We, therefore, conducted a single-center open-label randomized trial evaluating consolidation CTRT versus observation after 4 cycles of CT in patients whose disease did not progress during CT (partial responders/stable disease).
Responders to 4 cycles of CT were randomized (1:1) to CTRT versus observation (n = 135). CTRT was delivered using 3-dimensional-conformal RT (Field in the field when required) along with concurrent capecitabine. The dose of RT was 45 Gy in 25 fractions to GBC and lymphatics followed by a boost of 9 Gy in 5 fractions to the GBC. The primary endpoint was overall survival (OS) which was calculated from the date of randomization.
A total of 67 patients were randomized to observation and 68 to CTRT. Consolidation CTRT led to an improvement in median OS from 4 to 10 months (hazard ratio, 0.43; 95% CI, 0.32-0.62; P < .001). The actual median OS from accrual was 7 months (95% CI, 6.114-7.88 months) versus 13 months (95% CI, 11.13 -14.84 months). Adverse events (grade 3 or higher) because of CTRT were nausea (3%), anemia (9%), gastrointestinal bleeding (5.8%), and hepatotoxicity (13%). Functional Assessment of Cancer Therapy-General score and the Functional Assessment of Cancer Therapy-Hepatobiliary score did not deteriorate because of CTRT compared with observation (P values, .053 and .097).
To our knowledge, this is the first-ever randomized study in a low-middle-income country setting to demonstrate that consolidation CTRT significantly prolonged OS without deterioration in quality of life and should be the alternative standard of care in advanced unresectable GBC.
化疗（CT）是不可切除的晚期胆囊癌（GBC）患者的标准治疗方法，但其预后仍然较差。初始CT后巩固性CT和放射治疗（RT）的价值尚不确定。因此，我们开展了一项单中心开放标签随机试验，评估在CT期间疾病未进展的患者（部分缓解者/疾病稳定者）接受4个周期CT后巩固性CTRT与观察等待的疗效。
对4个周期CT有反应的患者按1:1随机分为CTRT组和观察等待组（n = 135）。CTRT采用三维适形放疗（必要时采用野中野技术）并联合卡培他滨。放疗剂量为GBC和淋巴管接受45 Gy，分25次给予，随后GBC再接受9 Gy，分5次给予推量照射。主要终点为总生存期（OS），从随机分组日期开始计算。
共有67例患者随机分配至观察等待组，68例患者随机分配至CTRT组。巩固性CTRT使中位OS从4个月提高到10个月（风险比，0.43；95% CI，0.32 - 0.62；P <.001）。从入组开始计算的实际中位OS为7个月（95% CI, 6.114 - 7.88个月），而CTRT组为13个月（95% CI, 11.13 - 14.84个月）。CTRT导致的不良事件（3级或更高）包括恶心（3%）、贫血（9%）、胃肠道出血（5.8%）和肝毒性（13%）。与观察等待组相比，CTRT并未导致癌症治疗通用功能评估评分和癌症治疗肝胆功能评估评分恶化（P值分别为0.053和0.097）。
据我们所知，这是在低收入和中等收入国家环境中进行的第一项随机研究，证明巩固性CTRT显著延长了OS，且生活质量没有恶化，应成为晚期不可切除GBC的替代标准治疗方法。
