Introduction

We assessed the radiosensitivity of lung metastases based on primary histology using a validated gene signature and model lung metastases for the genomically adjusted radiation dose (GARD).

Methods

Tissue samples were identified from our prospective observational protocol. The radiosensitivity index (RSI) 10 gene assay was run on samples and calculated alongside GARD using the previously published algorithms. A cohort of 105 patients with 137 lung metastases treated with SBRT at our institution was used for clinical correlation.

Results

A total of 138 unique metastatic lung lesions were identified for inclusion from our institution’s tissue biorepository. There were significant differences in the RSI of lung metastases based on histology. In order of decreasing radioresistance, the median RSIs were endometrial adenocarcinoma (0.49), soft tissue sarcoma (0.47), melanoma (0.44), rectal adenocarcinoma (0.43), renal cell carcinoma (0.33), head and neck squamous cell cancer (0.33), colon adenocarcinoma (0.32), and breast adenocarcinoma (0.29), p=0.002. We modeled GARD for these samples and identified the BED necessary to optimize local control. The 12 and 24 month Kaplan-Meier rates of local control for radioresistant vs radiosensitive histologies from our clinical correlation cohort following lung SBRT were 92%/87% and 100%, respectively (p=0.02).

Conclusions

In this analysis, we note significant differences in radiosensitivity based on primary histology of lung metastases and model the BED necessary to optimize local control. This study suggests primary histology may be an additional factor to consider in lung SBRT dose selection and dose personalization may be feasible.

中文翻译：

---

通过基因组学调整的辐射剂量通过主要组织学对肺转移瘤的放射敏感性及其对立体定向放射治疗的意义

介绍

我们使用经过验证的基因签名，根据主要组织学评估了肺转移的放射敏感性，并通过基因组调整的放射剂量（GARD）对肺转移进行了模型化。

方法

从我们的前瞻性观察方案中识别出组织样本。对样品进行放射敏感性指数（RSI）10基因测定，并使用先前发布的算法与GARD一起计算。在我院采用队列研究的105例患者进行了137例肺转移，用于临床相关性。

结果

从我们机构的组织生物库中总共鉴定出138个独特的转移性肺部病变。根据组织学，肺转移的RSI有显着差异。为了降低放射抵抗力，中位RSI为子宫内膜腺癌（0.49），软组织肉瘤（0.47），黑素瘤（0.44），直肠腺癌（0.43），肾细胞癌（0.33），头颈鳞状细胞癌（0.33）。 ，结肠腺癌（0.32）和乳腺腺癌（0.29），p = 0.002。我们为这些样品建模了GARD，并确定了优化局部控制所必需的BED。在我们的临床相关队列中，肺SBRT后的12个月和24个月Kaplan-Meier局部控制的放射抗性对比放射敏感性组织学检出率分别为92％/ 87％和100％（p = 0.02）。

结论

在此分析中，我们注意到基于肺转移的主要组织学，放射敏感性存在显着差异，并建立了优化局部控制所必需的BED模型。这项研究表明，原发性组织学可能是在肺SBRT剂量选择中要考虑的另一个因素，并且剂量个性化可能是可行的。