Department of Pathology; Department of Neurology, Division of Neuro-Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
Neuro Oncol. 2017 Nov 29;19(12):1640-1650. doi: 10.1093/neuonc/nox120.
Due to the decreasing prevalence of IDH1 mutations in older patients, the 2016 World Health Organization (WHO) classification of brain tumors proposed not to perform sequencing for isocitrate dehydrogenase (IDH) in glioblastoma patients ≥55 years old. We present a cost-effectiveness analysis to estimate the financial impact of these guidelines.
From 2010 to 2015 we performed 1023 IDH tests in gliomas, amounting to ~$1.09 million in direct laboratory test costs. Samples were tested using R132H-specific immunohistochemistry, DNA sequencing validated for detection of noncanonical IDH1/2 mutations, or both methods.
In cases tested by DNA sequencing, the fraction of non-R132H mutations was 5.4%, which included only 2 high-grade gliomas in patients ≥55 years (0.9%). When remodeling the optimal age cutoff in our patient population using 5-year age-binning, we found a 10-times higher pretest probability for the presence of a noncanonical IDH1 mutation in the setting of a negative IDH1-R132H immunohistochemistry result in patients <55 years. Applying the independently confirmed age cutoff of 55 years to glioblastoma patients (64%) would result in $403200 saved (43%). By not performing sequencing in patients ≥55 years, the turn-around time to final integrated neuropathological diagnosis is reduced by 53%, allowing these patients to gain earlier benefits from personalized genomic medicine.
The negligible prevalence of noncanonical IDH mutations in glioblastoma patients ≥55 years argues against universal IDH sequencing in this population. We predict that adoption of this age-based sequencing cutoff recommendation from the 2016 WHO guidelines will result in significant cost and time savings throughout the global health care system.
由于 IDH1 突变在老年患者中的患病率下降,2016 年世界卫生组织(WHO)脑肿瘤分类建议,对于年龄≥55 岁的胶质母细胞瘤患者,不进行异柠檬酸脱氢酶(IDH)测序。我们提出一项成本效益分析,以评估这些指南的经济影响。
2010 年至 2015 年,我们对 1023 例胶质瘤进行了 IDH 检测,直接实验室检测费用约为 109 万美元。使用 R132H 特异性免疫组织化学、针对非典型 IDH1/2 突变检测的 DNA 测序,或两种方法进行了检测。
在通过 DNA 测序检测的病例中,非 R132H 突变的比例为 5.4%,其中仅在≥55 岁的患者中发现了 2 例高级别胶质瘤(0.9%)。当使用 5 年年龄分组对我们的患者人群中的最佳年龄截止值进行重塑时,我们发现,在 IDH1-R132H 免疫组织化学结果为阴性的情况下,年龄<55 岁的患者中存在非典型 IDH1 突变的先验概率高 10 倍。将 55 岁的年龄截止值应用于胶质母细胞瘤患者(64%),将节省 403200 美元(43%)。对于≥55 岁的患者,不进行测序,可将最终综合神经病理学诊断的周转时间缩短 53%,使这些患者更早地受益于个性化基因组医学。
年龄≥55 岁的胶质母细胞瘤患者中非典型 IDH 突变的发生率极低,因此不建议对该人群进行普遍的 IDH 测序。我们预测,全球医疗保健系统将采用 2016 年 WHO 指南中的基于年龄的测序截止值建议,从而节省大量成本和时间。