Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea.
Department of Rehabilitation Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
Ann Surg. 2021 Jul 1;274(1):170-178. doi: 10.1097/SLA.0000000000003491.
The aim of this study was to identify the comprehensive risk factors for lymphedema, thereby enabling a more informed multidisciplinary treatment decision-making.
Lymphedema is a serious long-term complication in breast cancer patients post-surgery; however, the influence of multimodal therapy on its occurrence remains unclear.
We retrospectively collected treatment-related data from 5549 breast cancer patients who underwent surgery between 2007 and 2015 at our institution. Individual radiotherapy plans were reviewed for regional nodal irradiation (RNI) field design and fractionation type. We identified lymphedema risk factors and used them to construct nomograms to predict individual risk of lymphedema. Nomograms were validated internally using 100 bootstrap samples and externally using 2 separate datasets of 1877 Asian and 191 Western patients.
Six hundred thirty-nine patients developed lymphedema during a median follow-up of 60 months. The 3-year lymphedema incidence was 10.5%; this rate increased with larger irradiation volumes (no RNI vs RNI excluding axilla I-II vs RNI including axilla I-II: 5.7% vs 16.8% vs 24.1%) and when using conventional fractionation instead of hypofractionation (13.5% vs 6.8%). On multivariate analysis, higher body mass index, larger number of dissected nodes, taxane-based regimen, total mastectomy, larger irradiation field, and conventional fractionation were strongly associated with lymphedema (all P < 0.001). Nomograms constructed based on these variables showed good calibration and discrimination internally (concordance index: 0.774) and externally (0.832 for Asian and 0.820 for Western patients).
Trimodality breast cancer treatment factors interact to promote lymphedema. Lymphedema risk can be decreased by deintensifying node dissection, chemotherapy regimen, and field and dose of radiotherapy. Deescalation strategies on a multidisciplinary basis might minimize lymphedema risk.
本研究旨在确定淋巴水肿的综合风险因素，从而为更具针对性的多学科治疗决策提供依据。
淋巴水肿是乳腺癌患者术后的一种严重且长期的并发症；然而，多模态治疗对其发生的影响尚不清楚。
我们回顾性地收集了 2007 年至 2015 年期间在我院接受手术治疗的 5549 例乳腺癌患者的治疗相关数据。对局部淋巴结照射（RNI）野设计和分割类型的个体化放疗计划进行了审查。我们确定了淋巴水肿的风险因素，并使用这些因素构建了预测个体淋巴水肿风险的列线图。通过 100 次自举样本对列线图进行内部验证，并使用另外 2 组分别来自亚洲的 1877 例患者和西方的 191 例患者的数据进行外部验证。
5549 例患者中有 639 例在中位随访 60 个月时发生淋巴水肿。3 年淋巴水肿发生率为 10.5%；该发生率随照射体积的增大而增加（无 RNI 与 RNI 不包括腋窝 I-II 区与 RNI 包括腋窝 I-II 区：5.7%、16.8%和 24.1%），且常规分割而非超分割时发生率也更高（13.5%比 6.8%）。多变量分析显示，较高的体重指数、更多的淋巴结清扫数目、紫杉烷类药物为基础的治疗方案、全乳切除术、更大的照射野和常规分割与淋巴水肿密切相关（均 P < 0.001）。基于这些变量构建的列线图在内部（一致性指数：0.774）和外部（亚洲患者为 0.832，西方患者为 0.820）均具有良好的校准度和区分度。
三模态乳腺癌治疗因素相互作用促进淋巴水肿的发生。通过减少淋巴结清扫、化疗方案、放疗野和剂量，可以降低淋巴水肿的风险。基于多学科的降阶策略可能会最小化淋巴水肿的风险。
