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新辅助放化疗后发生病理性坏死与软组织肉瘤的不良预后相关。

Pathologic necrosis following neoadjuvant radiotherapy or chemoradiotherapy is prognostic of poor survival in soft tissue sarcoma.

机构信息

Department of Orthopaedic Surgery, Medical College of Wisconsin, Milwaukee, WI, 53226, USA.

CGH Medical Center, Sterling, IL, 61081, USA.

出版信息

J Cancer Res Clin Oncol. 2019 May;145(5):1321-1330. doi: 10.1007/s00432-019-02885-4. Epub 2019 Mar 7.

Abstract

PURPOSE

Neoadjuvant radiotherapy ± chemotherapy and wide local excision is an accepted management of localized soft tissue sarcomas (STS). Necrosis is prognostic for survival in osteosarcomas, but the significance for STS is undetermined. This study aimed to determine if percent true necrosis, opposed to a combination of necrosis and fibrosis, leads to improved survival in extremity and trunk STS.

METHODS

From 2000 to 2015, 162 patients with STS were treated with neoadjuvant therapy and resection. Patient and tumor variables were reviewed, and resected specimens underwent pathological assessment. Necrosis was ratiometrically determined. Overall (OS), distant metastasis-free (DMFS), and progression-free survival (PFS) were calculated using Kaplan-Meier estimator. Survival was determined using the Fisher's exact test for univariate analysis (UVA) and logistic regression for multivariate analysis (MVA).

RESULTS

Median follow-up was 4.5 years and median necrosis was 24.97%. Necrosis predicted worse OS, DMFS, and PFS on UVA, and DMFS and PFS on MVA. Necrosis was positively correlated with size and grade. To mitigate the role of size, a sub-analysis of ≥ 10 cm tumors was performed revealing necrosis predicted decreased DMFS and PFS on UVA and MVA. In high-grade tumors, necrosis correlated with decreased DMFS and PFS on UVA. Necrosis did not predict OS in ≥ 10 cm or high-grade tumors.

CONCLUSIONS

Our data suggests necrosis may be an additional independent, prognostic variable with increased necrosis predicting a worse prognosis. Necrosis may not be a measure of treatment response and instead suggests more aggressive tumor biology as high-grade, large STS were associated with increased necrosis.

摘要

目的

新辅助放疗±化疗和广泛局部切除术是局部软组织肉瘤(STS)的一种公认的治疗方法。在骨肉瘤中,坏死与生存率相关,但在 STS 中的意义尚不确定。本研究旨在确定是否真正的坏死百分比,而不是坏死和纤维化的组合,可提高四肢和躯干 STS 的生存率。

方法

2000 年至 2015 年,162 例 STS 患者接受新辅助治疗和切除术。回顾患者和肿瘤变量,并对切除标本进行病理评估。采用比率法确定坏死。采用 Kaplan-Meier 估计器计算总生存率(OS)、无远处转移生存率(DMFS)和无进展生存率(PFS)。使用 Fisher 确切检验进行单变量分析(UVA)和逻辑回归进行多变量分析(MVA)来确定生存情况。

结果

中位随访时间为 4.5 年,中位坏死率为 24.97%。坏死在 UVA 中预测 OS、DMFS 和 PFS 较差,在 MVA 中预测 DMFS 和 PFS 较差。坏死与肿瘤大小和分级呈正相关。为了减轻肿瘤大小的作用,对≥10cm 肿瘤进行了亚分析,结果显示坏死在 UVA 和 MVA 中预测 DMFS 和 PFS 降低。在高级别肿瘤中,坏死与 UVA 中 DMFS 和 PFS 降低相关。坏死在≥10cm 或高级别肿瘤中均不预测 OS。

结论

我们的数据表明,坏死可能是一个额外的独立预后因素,增加的坏死预示着更差的预后。坏死可能不是治疗反应的衡量标准,而是提示更具侵袭性的肿瘤生物学,因为高级别、大的 STS 与增加的坏死相关。

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