Institute for Technology Assessment, Massachusetts General Hospital, Boston, USA; Gastroenterology Division, Massachusetts General Hospital, Boston, USA; Radiology Department, Massachusetts General Hospital, Boston, USA.
Institute for Technology Assessment, Massachusetts General Hospital, Boston, USA; Gastroenterology Division, Massachusetts General Hospital, Boston, USA.
EBioMedicine. 2015 Nov 4;2(12):1980-6. doi: 10.1016/j.ebiom.2015.11.005. eCollection 2015 Dec.
BRCA2 mutation carriers are at increased risk for multiple cancers including pancreatic adenocarcinoma (PAC). Our goal was to compare the effectiveness of different PAC screening strategies in BRCA2 mutation carriers, from the standpoint of life expectancy.
A previously published Markov model of PAC was updated and extended to incorporate key aspects of BRCA2 mutation carrier status, including competing risks of breast- and ovarian-cancer specific mortality. BRCA2 mutation carriers were modeled and analyzed as the primary cohort for the analysis. Additional higher risk BRCA2 cohorts that were stratified according to the number of first-degree relatives (FDRs) with PAC were also analyzed. For each cohort, one-time screening and annual screening were evaluated, with screening starting at age 50 in both strategies. The primary outcome was net gain in life expectancy (LE) compared to no screening. Sensitivity analysis was performed on key model parameters, including surgical mortality and MRI test performance.
One-time screening at age 50 resulted in a LE gain of 3.9 days for the primary BRCA2 cohort, and a gain of 5.8 days for those with BRCA2 and one FDR. Annual screening resulted in LE loss of 12.9 days for the primary cohort and 1.3 days for BRCA2 carriers with 1 FDR, but resulted in 20.6 days gained for carriers with 2 FDRs and 260 days gained for those with 3 FDRs. For patients with ≥ 3 FDRs, annual screening starting at an earlier age (i.e. 35-40) was optimal.
Among BRCA2 mutation carriers, aggressive screening regimens may be ineffective unless additional indicators of elevated risk (e.g., 2 or more FDRs) are present. More clinical studies are needed to confirm these findings.
American Cancer Society - New England Division - Ellison Foundation Research Scholar Grant (RSG-15-129-01-CPHPS).
BRCA2 基因突变携带者患多种癌症（包括胰腺腺癌）的风险增加。我们的目标是从预期寿命的角度比较 BRCA2 基因突变携带者不同胰腺腺癌筛查策略的有效性。
对以前发表的胰腺腺癌 Markov 模型进行了更新和扩展，纳入了 BRCA2 基因突变携带者状态的关键方面，包括乳腺癌和卵巢癌特异性死亡率的竞争风险。将 BRCA2 基因突变携带者建模并作为分析的主要队列进行分析。还根据一级亲属（FDR）患胰腺腺癌的人数对 BRCA2 高风险队列进行了分层分析。对于每个队列，评估了一次性筛查和年度筛查，两种策略均从 50 岁开始筛查。主要结局是与不筛查相比，预期寿命（LE）的净收益。对关键模型参数（包括手术死亡率和 MRI 测试性能）进行了敏感性分析。
50 岁时进行一次性筛查，主要 BRCA2 队列的 LE 增加了 3.9 天，BRCA2 基因突变携带者且有一个 FDR 的 LE 增加了 5.8 天。年度筛查导致主要队列的 LE 减少了 12.9 天，BRCA2 基因突变携带者且有一个 FDR 的 LE 减少了 1.3 天，但对于有 2 个 FDR 的携带者，LE 增加了 20.6 天，对于有 3 个 FDR 的携带者，LE 增加了 260 天。对于 FDR≥3 的患者，从 35-40 岁开始进行年度筛查是最佳选择。
在 BRCA2 基因突变携带者中，除非存在其他风险升高的指标（例如，2 个或更多 FDR），否则积极的筛查方案可能无效。需要更多的临床研究来证实这些发现。
美国癌症协会-新英格兰分部-埃里森基金会研究学者资助（RSG-15-129-01-CPHPS）。
