Department of Radiation Oncology, Yonsei University College of Medicine, Seoul, Republic of Korea.
College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Int J Radiat Oncol Biol Phys. 2023 Aug 1;116(5):1218-1225. doi: 10.1016/j.ijrobp.2023.01.056. Epub 2023 Feb 4.
To develop and test a multivariable normal tissue complication probability (NTCP) model predicting lymphedema in patients with breast cancer receiving radiation therapy.
We retrospectively reviewed 1345 patients with breast cancer who received radiation therapy from 2 independent institutions. The patients were divided into a training cohort (institution A, n = 368, all treated with 3-dimensional conformal external beam radiation therapy [RT] with 2 Gy/fraction) and an external validation cohort (institution B, n = 977, treated either with 3-dimensional conformal external beam RT or with volumetric modulated RT and either with 1.8-2.0 Gy/fraction or with 2.67 Gy/fraction). Axillary-lateral thoracic vessel juncture (ALTJ) was delineated. The multivariable model was generated using dosimetric and clinical parameters. The performance of the model was comprehensively validated internally and externally.
During a median follow-up of 78.7 months for the entire cohort, 97 patients (7.2%) developed lymphedema. The multivariable model that took into account the number of lymph nodes dissected, as well as the volume of the ALTJ receiving a dose ≥35 Gy equivalent doses in 2-Gy fractions (ALTJ V35), showed good agreement between predicted and observed results for both internal and external validation (Hosmer-Lemeshow P value > .05). The area under the receiver operating characteristic curve (AUC) and negative log-likelihood values for the multivariable NTCP model were 0.89 and 0.19 in internal validation and 0.83 and 0.19 in external validation. In addition, the multivariable model performance was acceptable for hypofractionated regimens (AUC 0.70) and volumetric modulated arc therapy (AUC 0.69). The number of lymph nodes dissected and ALTJ V35 were found to be the most important factors influencing lymphedema after radiation therapy.
We first developed and validated the multivariable NTCP model for the lymphedema incidence in patients with breast cancer after radiation therapy. The multivariable NTCP model showed excellent performance and robustness in predicting lymphedema in both internal and completely independent external validations. The multivariable model for lymphedema prediction was robust and reliable for different treatment modalities and fractionation regimens.
开发并验证一个多变量正常组织并发症概率（NTCP）模型，用于预测接受放疗的乳腺癌患者的淋巴水肿。
我们回顾性分析了来自 2 家独立机构的 1345 例乳腺癌患者的资料。患者被分为训练队列（机构 A，n=368，均接受三维适形外照射放疗，分割剂量 2 Gy/次）和外部验证队列（机构 B，n=977，接受三维适形外照射放疗或容积调强放疗，分割剂量 1.8-2.0 Gy/次或 2.67 Gy/次）。勾画腋侧-胸外侧血管结合部（ALTJ）。采用剂量学和临床参数建立多变量模型。该模型在内部和外部进行了全面验证。
全队列中位随访 78.7 个月，97 例（7.2%）患者发生淋巴水肿。纳入淋巴结清扫数量和接受≥35 Gy 等效剂量 2 Gy 分割剂量的 ALTJ 体积（ALTJ V35）的多变量模型，内部和外部验证均显示出较好的预测效果与实际结果的一致性（Hosmer-Lemeshow P 值>.05）。多变量 NTCP 模型的受试者工作特征曲线下面积（AUC）和负对数似然值在内部验证中分别为 0.89 和 0.19，在外部验证中分别为 0.83 和 0.19。此外，对于分割剂量方案（AUC 0.70）和容积调强弧形治疗（AUC 0.69），多变量模型性能可接受。多变量分析显示，淋巴结清扫数量和 ALTJ V35 是放疗后淋巴水肿的最重要影响因素。
我们首次开发并验证了用于预测乳腺癌患者放疗后淋巴水肿发生率的多变量 NTCP 模型。该多变量 NTCP 模型在内部和完全独立的外部验证中均表现出优异的性能和稳健性。多变量淋巴水肿预测模型对于不同的治疗方式和分割方案具有稳健和可靠的预测能力。
