Effectiveness Without Efficacy: Cautionary Tale from a Landmark Breast Cancer Randomized Controlled Trial.
Effectiveness Without Efficacy: Cautionary Tale from a Landmark Breast Cancer Randomized Controlled Trial.
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DOI：
10.7150/jca.79797
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发表时间：
2023
影响因子：
3.9
通讯作者：
Bedrosian I
中科院分区：
文献类型：
--
作者：
Shen Y;Ning J;Lin HY;Shaitelman SF;Kuerer HM;Bedrosian I
背景：“旧的”随机对照试验确立了保乳治疗(BCT)和全乳房切除术(TM)治疗早期乳腺癌的等效性，而最近的文献报道BCT可提高存活率。为了协调这一点，我们进行了模拟研究，并重新分析了B-06试验数据。方法：用BCT和TM估计总生存率(OS)、乳腺癌特异性死亡(BCSD)和其他死因特异性死亡(OCSD)的累积发病函数的分布。计算两组受试者的限制性平均生存时间(RMST)差和危险比。给定估计的分布，我们模拟每个手臂的特定原因死亡时间，通过模拟未接受放射治疗的患者的BCT-ARM OCSD时间，评估在不同样本量、随访时间和修改的设置下测试OS、BCSD和OCSD治疗差异的能力。结果：经200个月随访，RMST测量的平均BCT-over-TM增量OS组为3.7个月，BCSD组为4.5个月。将试验规模增加到每臂5,000个，使用RMST和BCSD检测操作系统优势的可能性分别为79.2%和92.4%。144个月后，BCT组的OCSD与TM相比有不成比例的增加，尤其是在治疗后200个月。当使用未接受放射治疗的患者模拟BCT的OCSD时间时，估计OS增益增加到4.4个月，功率增加到92.2%。结论：BCT组晚期过多的其他原因死亡，可能是由于辐射，以及样本量的限制，限制了报告BCT优越性的能力。考虑到B-06试验时代提供的辐射，BCT和TM在很大程度上保持相同。
Background: “Old” randomized controlled trials established breast conserving therapy (BCT) and total mastectomy (TM) equivalence for treating early breast cancer, whereas recent literature report improved survival with BCT. To reconcile this, we performed a simulation study and re-analyzed B-06 trial data. Methods: We estimated the distributions for overall survival (OS), cumulative incidence functions for breast-cancer-specific death (BCSD) and other causes-specific death (OCSD) by BCT and TM. The restricted mean survival time (RMST) difference and hazard ratio between the two arms were estimated. Given the estimated distributions, we simulated cause-specific death times from each arm, evaluating the power to test treatment difference in OS, BCSD, and OCSD with different sample sizes, follow-up times, and a modified setting by simulating BCT-arm OCSD times from the distribution of patients not receiving radiation. Results: With 200 months follow-up, the average BCT-over-TM gain measured by RMST was 3.7 months for OS and 4.5 months for BCSD. Increasing the trial size to 5,000 per arm, there is a 79.2% chance to detect the OS benefit with RMST and 92.4% for BCSD. A nonproportional increase of OCSD in BCT compared to TM was observed after 144 months, and particularly after 200 months post treatments. When OCSD times of BCT were simulated using patients not receiving radiation, the estimated OS gain increased to 4.4 months, and the power increased to 92.2%. Conclusions: The late excess other-cause-death, likely due to radiation, in the BCT arm and sample size constraints limited the power to report BCT superiority. Given radiation delivered in the era of B-06 trial, BCT and TM remain largely equivalent.
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影响因子：
158.5
作者：
Darby, Sarah C.;Ewertz, Marianne;Hall, Per
通讯作者：
Hall, Per
影响因子：
6.2
作者：
Hwang, E. Shelley;Lichtensztajn, Daphne Y.;Gomez, Scarlett Lin;Fowble, Barbara;Clarke, Christina A.
通讯作者：
Clarke, Christina A.
影响因子：
10.3
作者：
van Dongen, JA;Voogd, AC;Bartelink, H
通讯作者：
Bartelink, H
影响因子：
2
作者：
Beyersmann, Jan;Latouche, Aurelien;Schumacher, Martin
通讯作者：
Schumacher, Martin
影响因子：
13.8
作者：
Ito C;Hashimoto A;Uemura K;Oba K
通讯作者：
Oba K