寡转移定向立体定向体部放疗（SBRT）后长期生存的临床和分子标志物。

Clinical and molecular markers of long-term survival after oligometastasis-directed stereotactic body radiotherapy (SBRT).

作者信息

Wong Anthony C, Watson Sydeaka P, Pitroda Sean P, Son Christina H, Das Lauren C, Stack Melinda E, Uppal Abhineet, Oshima Go, Khodarev Nikolai N, Salama Joseph K, Weichselbaum Ralph R, Chmura Steven J

机构信息

Department of Radiation and Cellular Oncology, the University of Chicago, Chicago, Illinois.

Department of Public Health Sciences, the University of Chicago, Chicago, Illinois.

出版信息

Cancer. 2016 Jul 15;122(14):2242-50. doi: 10.1002/cncr.30058. Epub 2016 May 20.

DOI:10.1002/cncr.30058

PMID:27206146

Abstract

BACKGROUND

The selection of patients for oligometastasis-directed ablative therapy remains a challenge. The authors report on clinical and molecular predictors of survival from a stereotactic body radiotherapy (SBRT) dose-escalation trial for oligometastases.

METHODS

Patients who had from 1 to 5 metastases, a life expectancy of >3 months, and a Karnofsky performance status of >60 received escalating SBRT doses to all known cancer sites. Time to progression, progression-free survival, and overall survival (OS) were calculated at the completion of SBRT, and clinical predictors of OS were modeled. Primary tumor microRNA expression was analyzed to identify molecular predictors of OS.

RESULTS

Sixty-one evaluable patients were enrolled from 2004 to 2009. The median follow-up was 2.3 years for all patients (range, 0.2-9.3 years) and 6.8 years for survivors (range, 2.0-9.3 years). The median, 2-year, and 5-year estimated OS were 2.4 years, 57%, and 32%, respectively. The rate of progression after SBRT was associated with an increased risk of death (hazard ratio [HR], 1.44; 95% confidence interval [CI], 1.24-1.82). The time from initial cancer diagnosis to metastasis (HR, 0.98; 95% CI, 0.98-0.99), the time from metastasis to SBRT (HR, 0.98; 95% CI, 0.98-0.99), and breast cancer histology (HR, 0.12; 95% CI, 0.07-0.37) were significant predictors of OS. In an exploratory analysis, a candidate classifier using expression levels of 3 microRNAs (miR-23b, miR-449a, and miR-449b) predicted survival among 17 patients who had primary tumor microRNA expression data available.

CONCLUSIONS

A subset of oligometastatic patients achieves long-term survival after metastasis-directed SBRT. Clinical features and primary tumor microRNA expression profiling, if validated in an independent dataset, may help select oligometastatic patients most likely to benefit from metastasis-directed therapy. Cancer 2016;122:2242-50. © 2016 American Cancer Society.

摘要

背景

选择适合寡转移定向消融治疗的患者仍然是一项挑战。作者报告了一项针对寡转移的立体定向体部放射治疗（SBRT）剂量递增试验的生存临床和分子预测因素。

方法

有1至5个转移灶、预期寿命>3个月且卡氏功能状态>60的患者接受递增的SBRT剂量照射所有已知癌症部位。在SBRT完成时计算进展时间、无进展生存期和总生存期（OS），并对OS的临床预测因素进行建模。分析原发性肿瘤微小RNA表达以确定OS的分子预测因素。

结果

2004年至2009年共纳入61例可评估患者。所有患者的中位随访时间为2.3年（范围0.2 - 9.3年），幸存者的中位随访时间为6.8年（范围2.0 - 9.3年）。中位、2年和5年估计OS分别为2.4年、57%和32%。SBRT后的进展率与死亡风险增加相关（风险比[HR]，1.44；95%置信区间[CI]，1.24 - 1.82）。从最初癌症诊断到转移的时间（HR，0.98；95% CI，0.98 - 0.99）、从转移到SBRT的时间（HR，0.98；95% CI，0.98 - 0.99）以及乳腺癌组织学类型（HR，0.12；95% CI，0.07 - 0.37）是OS的显著预测因素。在一项探索性分析中，使用3种微小RNA（miR - 23b、miR - 449a和miR - 449b）表达水平的候选分类器预测了17例有原发性肿瘤微小RNA表达数据患者的生存情况。