Dartmouth Cancer Center, Dartmouth-Hitchcock Medical Center/Geisel School of Medicine, Lebanon, NH; The Dartmouth Institute for Health Policy and Clinical Practice, Geisel School of Medicine, Lebanon, NH.
The Dartmouth Institute for Health Policy and Clinical Practice, Geisel School of Medicine, Lebanon, NH.
Clin Colorectal Cancer. 2022 Sep;21(3):e189-e195. doi: 10.1016/j.clcc.2022.05.001. Epub 2022 May 11.
Adjuvant fluoropyrimidine-based chemotherapy substantially reduces recurrence and mortality after resection of stage 3 colon cancer. While standard doses of 5-fluorouracil and capecitabine are safe for most patients, the risk of severe toxicity is increased for the approximately 6% of patients with dihydropyimidine dehydrogenase (DPD) deficiency caused by pathogenic DPYD gene variants. Pre-treatment screening for pathogenic DPYD gene variants reduces severe toxicity but has not been widely adopted in the United States.
We conducted a cost-effectiveness analysis of DPYD genotyping prior to fluoropyrimidine-based adjuvant chemotherapy for stage 3 colon cancer, covering the c.1129-5923C>G (HapB3), c.1679T>G (*13), c.1905+1G>A (*2A), and c.2846A>T gene variants. We used a Markov model with a 5-year horizon, taking a United States healthcare perspective. Simulated patients with pathogenic DPYD gene variants received reduced-dose fluoropyrimidine chemotherapy. The primary outcome was the incremental cost-effectiveness ratio (ICER) for DPYD genotyping.
Compared with no screening for DPD deficiency, DPYD genotyping increased per-patient costs by $78 and improved survival by 0.0038 quality-adjusted life years (QALYs), leading to an ICER of $20,506/QALY. In 1-way sensitivity analyses, The ICER exceeded $50,000 per QALY when the cost of the DPYD genotyping assay was greater than $286. In probabilistic sensitivity analysis using a willingness-to-pay threshold of $50,000/QALY DPYD genotyping was preferred to no screening in 96.2% of iterations.
Among patients receiving adjuvant chemotherapy for stage 3 colon cancer, screening for DPD deficiency with DPYD genotyping is a cost-effective strategy for preventing infrequent but severe and sometimes fatal toxicities of fluoropyrimidine chemotherapy.
辅助氟嘧啶类化疗显著降低了 3 期结肠癌切除术后的复发和死亡率。虽然大多数患者使用标准剂量的 5-氟尿嘧啶和卡培他滨是安全的，但由于致病性 DPYD 基因突变导致大约 6%的患者存在二氢嘧啶脱氢酶（DPD）缺乏，其发生严重毒性的风险增加。在氟嘧啶类辅助化疗前进行 DPYD 基因变异的筛查可降低严重毒性，但尚未在美国广泛采用。
我们进行了一项针对 3 期结肠癌氟嘧啶类辅助化疗前进行 DPYD 基因分型的成本效益分析，涵盖 c.1129-5923C>G（HapB3）、c.1679T>G（*13）、c.1905+1G>A（*2A）和 c.2846A>T 基因突变。我们使用了一个具有 5 年时间范围的 Markov 模型，从美国医疗保健的角度出发。模拟携带致病性 DPYD 基因突变的患者接受了低剂量氟嘧啶化疗。主要结果是 DPYD 基因分型的增量成本效益比（ICER）。
与不进行 DPD 缺乏筛查相比，DPYD 基因分型使每位患者的成本增加了 78 美元，并使生存质量提高了 0.0038 个质量调整生命年（QALY），导致 ICER 为 20506 美元/QALY。在单向敏感性分析中，当 DPYD 基因分型检测的成本大于 286 美元时，ICER 超过了 50000 美元/QALY。在使用 50000 美元/QALY 的意愿支付阈值进行的概率敏感性分析中，DPYD 基因分型在 96.2%的迭代中优于不进行筛查。
在接受 3 期结肠癌辅助化疗的患者中，使用 DPYD 基因分型筛查 DPD 缺乏症是预防氟嘧啶化疗罕见但严重且有时致命毒性的一种具有成本效益的策略。
