Genomic-Adjusted Radiation Dose Model May Improve Patient Outcomes

作者：高级Medwirenews记者Lynda Williams撰写

medwireNews: A genomics-based approach to radiation treatment planning may improve patient outcomes by taking into account the clinical heterogeneity of radiation response found within tumour types, researchers suggest in柳叶刀肿瘤学。

The US team combined the radiosensitivity index – which uses gene expression data to classify tumours as radiosensitive or radioresistant – with information on physical radiation dose to create the genomic-adjusted radiation dose (GARD), a measure of the biological effect of a specific radiation dose in an individual patient.

To test the hypothesis that GARD could improve patient outcomes compared with standard radiotherapy dosing, Javier Torres-Roca, from Moffitt Cancer Center in Tampa, Florida, and co-workers pooled data from 11 studies including 1615 patients with cancers of the breast, head and neck, pancreas or endometrium, non-small-cell lung cancer, melanoma or glioma.

研究人员计算了75.4％的GARD，其中75.4％的患者接受了放射疗法和假标准治疗时间表的GARD。

“尽管这些现代人群中物理辐射剂量的范围仅限于在护理标准的值附近的值，并以标准分数尺寸交付，但GARD揭示了广泛的预测生物学效应，从而使人们能够以更高的分辨率了解结果”，但调查人员说。

在汇总分析中，GARD与第一次复发和总体生存的时间有显着相关性，在经过放射治疗的患者中，危险比分别为0.98和0.97，而假GARD和这些DID的患者中这些结果之间没有相关性。没有接受放射疗法。

There was a significant interaction between GARD and actual receipt of radiotherapy for the prediction of overall survival but not for time to first recurrence, the researchers say.

And further analysis indicated that GARD was a “significant linear variable” for both time to first recurrence and overall survival, with an increase in GARD units translating to a decrease in the GARD-specific relative hazard ratios for both endpoints, including in 3-year probability analyses.

By contrast, there was no significant association between the actual or sham physical dose of radiation received and time to first recurrence or overall survival, the researchers say.

Javier Torres-Roca and co-authors suggest that differences in the biological effect of radiation may explain why radiation dose escalation does not always translate to improved survival in clinical trials.

他们写道：“一种基于GARD的方法可以理解这种对剂量升级的不均匀反应：有些患者在接受不必要的额外剂量和相关的毒性时受益，而另一些患者则可能受到伤害。”患者将从剂量优化中受益最大，允许对个性化放疗剂量进行下一代试验。”

The researchers emphasize that they do not suggest “abandoning physical dose of radiation, but instead, like the CT scanner did for x-ray, we suggest enhancing dose with another dimension—genomic data—allowing us to see each individual patient’s potential for radiotherapy benefit at a higher resolution.”

The authors of a linked comment say there are important questions to be answered before GARD can be used to individualise radiotherapy in the clinic, such as the impact on GARD of systemic therapy and changes in the tumour microenvironment or the use of hypofractionated radiotherapy regimens.

然而，来自以色列拉马特·甘（Ramat Gan）的Sheba医学中心的Orit Kaidar-Person，并共同评估者同意：“应采用基于GARD的放射治疗框架作为试验设计的新范式，并建议开发和开发该测定法根据美国国家癌症研究所制定的一系列标准，纳入临床试验中。”

他们总结说：“通过支持此类项目，包括旨在识别与放射性毒性敏感性相关的遗传变异的项目，我们可以为患者采取更个性化的放射治疗方法。”

References

• Scott JG，Setor G，Ellsworth P，et al。Pan-cancer prediction of radiotherapy benefit using genomic-adjusted radiation dose (GARD): a cohort-based pooled analysis。Lancet Oncol; Advance online publication 4 August 2021.doi：10.1016/s1470-2045（21）00347-8
• Kaidar-Person O, Poortmans P, Salgado R.基因组调整辐射剂量以个性化放射疗法。Lancet Oncol; Advance online publication 4 August 2021.https://doi.org/10.1016/s1470-2045(21)00411-3