Department of Medicine, Division of Digestive and Liver Diseases, New York Presbyterian Columbia University Medical Center, New York, New York.
Department of Medicine, Division of General Medicine, New York Presbyterian Columbia University Medical Center, New York, New York.
Clin Gastroenterol Hepatol. 2020 Apr;18(4):822-829.e4. doi: 10.1016/j.cgh.2019.06.009. Epub 2019 Jun 18.
BACKGROUND & AIMS: Carriers of pathogenic variants in CDH1 have a high risk of hereditary diffuse gastric cancer (HDGC). Guidelines recommend prophylactic total gastrectomy (PTG) at age 20-30 years, although there is controversy over the optimal age. We developed a simulation model to analyze the effects of PTG at different ages on quality-adjusted life-years (QALYs), cancer mortality, and life expectancy.
We used a Markov model of HDGC progression associated with pathogenic variants in CDH1 to simulate outcomes of hypothetical cohorts with different ages at time of PTG (ages 20-79 years). Model inputs including health state transition probabilities, mortality and complication rates, quality of life utility values, and endoscopic surveillance sensitivity were derived from publications. The primary outcome, used to determine the optimal strategy, was age at which PTG yielded the highest QALYs. Secondary outcomes were cancer mortality and unadjusted life-years.
Our model found that for men, the optimal age for PTG is 39 years, resulting in 32.01 incremental QALYs, 58.81 life-years (biologic age, 72.81 years), and lifetime cancer mortality of 8.5%. Incorporating endoscopic surveillance prior to PTG decreased cancer mortality to 6.7%, but had lower QALYs (31.59). PTG at age 30 reduced cancer mortality to 3.2%, with 31.45 incremental QALYs. For women, the optimal age for PTG was calculated to be 30 years, with 33.09 incremental QALYs, 66.17 life-years (biologic age, 80.17 years), and lifetime cancer mortality of 1.6%. Addition of endoscopic surveillance did not decrease the risk of HDGC mortality in women.
Using a Markov model of HDGC progression associated with pathogenic variants in CDH1 to simulate outcomes, we found the optimal ages for PTG to be 39 years for men and 30 years for women, when QALYs are the primary endpoint. These ages for PTG are older than those of current recommendations.
携带 CDH1 致病性变异的患者具有发生遗传性弥漫性胃癌（HDGC）的高风险。指南建议在 20-30 岁时进行预防性全胃切除术（PTG），尽管在最佳年龄方面存在争议。我们开发了一个模拟模型，以分析不同年龄进行 PTG 对质量调整生命年（QALYs）、癌症死亡率和预期寿命的影响。
我们使用与 CDH1 致病性变异相关的 HDGC 进展的马尔可夫模型来模拟不同 PTG 年龄（20-79 岁）的假设队列的结果。模型输入包括健康状态转移概率、死亡率和并发症发生率、生活质量效用值以及内镜监测敏感性，均来自出版物。主要结局是用于确定最佳策略的 PTG 年龄，即产生最高 QALYs 的年龄。次要结局是癌症死亡率和未经调整的寿命年。
我们的模型发现，对于男性，PTG 的最佳年龄是 39 岁，可获得 32.01 个增量 QALYs、58.81 个寿命年（生物学年龄为 72.81 岁）和终生癌症死亡率为 8.5%。在 PTG 之前进行内镜监测可将癌症死亡率降低至 6.7%，但 QALYs 较低（31.59）。30 岁时进行 PTG 可将癌症死亡率降低至 3.2%，可获得 31.45 个增量 QALYs。对于女性，PTG 的最佳年龄计算为 30 岁，可获得 33.09 个增量 QALYs、66.17 个寿命年（生物学年龄为 80.17 岁）和终生癌症死亡率为 1.6%。女性中，内镜监测并不能降低 HDGC 死亡率的风险。
使用与 CDH1 致病性变异相关的 HDGC 进展的马尔可夫模型来模拟结果，我们发现，当 QALYs 是主要终点时，男性的最佳 PTG 年龄为 39 岁，女性为 30 岁。这些 PTG 年龄比目前的建议年龄更大。
