Department of Orthopaedics, Duke University, Durham, North Carolina, USA.
Department of Pathology, Duke University, Durham, North Carolina, USA.
Cancer Med. 2022 Jan;11(1):194-206. doi: 10.1002/cam4.4428. Epub 2021 Nov 27.
Current standard of care for most intermediate and high-grade soft-tissue sarcomas (STS) includes limb-preserving surgical resection with either neoadjuvant radiation therapy (NRT) or adjuvant radiation therapy. To date, there have been a few studies that attempt to correlate histopathologic response to NRT with oncologic outcomes in patients with STS.
Using our institutional database, we identified 58 patients who received NRT followed by surgical resection for primary intermediate or high-grade STS and 34 patients who received surgical resection without NRT but did receive adjuvant radiation therapy or did not receive any radiation therapy. We analyzed four histologic parameters of response to therapy: residual viable tumor, fibrosis/hyalinization, necrosis, and infarction (each ratiometrically determined). Data were stratified into two binary groups. Unadjusted, 5- and 10-year overall survival, and relapsed-free survival (RFS) were calculated using the Kaplan-Meier method.
Analysis of pathologic characteristics showed that patients treated with NRT demonstrate significantly higher tumor infarction, higher tumor fibrosis/hyalinization, and a lower percent viable tumor compared with patients not treated with NRT (p < 0.0001). Based on Kaplan-Meier curve analysis and multivariate cox proportional hazard model for OS and RFS, patients treated with NRT and showing >12.5% tumor fibrosis/hyalinization have significantly higher overall survival and recurrence-free survival at 5 and 10 years.
We have identified three histopathologic characteristics-fibrosis, hyalinization, and infarction-that may serve as predictive biomarkers of response to NRT for STS patients. Future prospective studies will be needed to confirm this association.
目前,大多数中高级软组织肉瘤(STS)的标准治疗方法包括保肢手术切除,联合新辅助放疗(NRT)或辅助放疗。迄今为止,已有少数研究试图将 NRT 的组织病理学反应与 STS 患者的肿瘤学结果相关联。
我们使用机构数据库,确定了 58 名接受 NRT 后行手术切除的原发性中高级 STS 患者,以及 34 名未接受 NRT 但接受辅助放疗或未接受任何放疗的患者。我们分析了治疗反应的四个组织病理学参数:残留存活肿瘤、纤维化/玻璃样变性、坏死和梗死(每个参数均通过比率确定)。数据分为两组。使用 Kaplan-Meier 方法计算未调整的 5 年和 10 年总生存率和无复发生存率(RFS)。
病理特征分析表明,与未接受 NRT 的患者相比,接受 NRT 的患者肿瘤梗死程度更高,肿瘤纤维化/玻璃样变性程度更高,存活肿瘤百分比更低(p<0.0001)。基于 Kaplan-Meier 曲线分析和 OS 和 RFS 的多变量 Cox 比例风险模型,接受 NRT 且肿瘤纤维化/玻璃样变性程度>12.5%的患者,5 年和 10 年的总生存率和无复发生存率显著更高。
我们已经确定了三种组织病理学特征——纤维化、玻璃样变性和梗死,它们可能成为 STS 患者对 NRT 反应的预测生物标志物。未来需要前瞻性研究来证实这种关联。