Rouzier Roman, Pusztai Lajos, Delaloge Suzette, Gonzalez-Angulo Ana M, Andre Fabrice, Hess Kenneth R, Buzdar Aman U, Garbay Jean-Remi, Spielmann Marc, Mathieu Marie-Christine, Symmans W Fraser, Wagner Peter, Atallah David, Valero Vicente, Berry Donald A, Hortobagyi Gabriel N
Department of Breast Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77230-1439, USA.
J Clin Oncol. 2005 Nov 20;23(33):8331-9. doi: 10.1200/JCO.2005.01.2898.
To combine clinical variables associated with pathologic complete response (pCR) and distant metastasis-free survival (DMFS) after preoperative chemotherapy (PC) into a prediction nomogram.
Data from 496 patients treated with anthracycline PC at the Institut Gustave Roussy were used to develop and calibrate a nomogram for pCR based on multivariate logistic regression. This nomogram was tested on two independent cohorts of patients treated at the M.D. Anderson Cancer Center. The first cohort (n = 337) received anthracycline; the second cohort (n = 237) received a combination of paclitaxel and anthracycline PC. A separate nomogram to predict DMFS was developed using Cox proportional hazards regression model.
The pCR nomogram based on clinical stage, estrogen receptor status, histologic grade, and number of preoperative chemotherapy cycles had good discrimination and calibration in the training and the anthracycline-treated validation sets (concordance indices, 0.77, 0.79). In the paclitaxel plus anthracycline group, when the predicted pCR rate was less than 14%, the observed rate was 7.5%; for a predicted rate of > or = 38%, the actual rate was 85%. For a predicted rate between 14% to 38%, the observed rates were 50% with weekly and 27% with 3-weekly paclitaxel. This indicates that patients with intermediate chemotherapy sensitivity benefit the most from the optimized schedule of paclitaxel. Patients unlikely to achieve pCR to anthracylines remain at low probability for pCR, even after inclusion of paclitaxel. The nomogram for DMFS had a concordance index of 0.72 in the validation set and outperformed other prediction tools (P = .02).
Our nomograms predict pCR accurately and can serve as a basis to integrate future molecular markers into a clinical prediction model.
将与术前化疗(PC)后病理完全缓解(pCR)及无远处转移生存期(DMFS)相关的临床变量整合到一个预测列线图中。
来自古斯塔夫·鲁西研究所接受蒽环类药物PC治疗的496例患者的数据,用于基于多因素逻辑回归开发和校准pCR列线图。该列线图在MD安德森癌症中心治疗的两个独立患者队列中进行了测试。第一个队列(n = 337)接受蒽环类药物治疗;第二个队列(n = 237)接受紫杉醇与蒽环类药物联合PC治疗。使用Cox比例风险回归模型开发了一个单独的预测DMFS的列线图。
基于临床分期、雌激素受体状态、组织学分级和术前化疗周期数的pCR列线图在训练集和蒽环类药物治疗的验证集中具有良好的区分度和校准度(一致性指数分别为0.77、0.79)。在紫杉醇加蒽环类药物组中,当预测的pCR率小于14%时,观察到的率为7.5%;对于预测率≥38%时,实际率为85%。对于预测率在14%至38%之间,每周使用紫杉醇时观察到的率为50%,每3周使用紫杉醇时为27%。这表明化疗敏感性中等的患者从优化的紫杉醇给药方案中获益最大。即使加入紫杉醇后,不太可能对蒽环类药物达到pCR的患者达到pCR的概率仍然很低。DMFS列线图在验证集中的一致性指数为0.72,优于其他预测工具(P = 0.02)。
我们的列线图能准确预测pCR,并可作为将未来分子标志物整合到临床预测模型中的基础。