Predicting dose response to prostate cancer radiotherapy: validation of a radiation signature in the randomized phase III NRG/RTOG 0126 and SAKK 09/10 trials.

We investigated a previously developed Post-Operative Radiation Therapy Outcomes Score (PORTOS) to identify preferential benefit from radiation dose escalation (DE).

我们研究了先前开发的术后放疗结果评分（PORTOS），以确定从放射剂量递增（DE）中获得的优先益处。

materials_and_methods

PORTOS was evaluated in patients enrolled in SAKK 09/10 and NRG/RTOG 0126 with available tissue that passed quality control (n = 226, 215).

PORTOS 在 SAKK 09/10 和 NRG/RTOG 0126 研究中入组的患者中进行了评估，这些患者有可用的组织样本并通过了质量控制（n = 226, 215）。

PORTOS was evaluated in the published post-operative groups in SAKK 09/10 and in tertiles in NRG/RTOG 0126 as cut-offs had not been established for biopsy samples and definitive radiation patients.

在 SAKK 09/10 发表的术后组和 NRG/RTOG 0126 中的三分位数中评估了 PORTOS，因为对于活检样本和确定性放疗患者尚未建立截断值。

Clinical and molecular correlates in a real-world dataset of 42 407 prostatectomy and 31 107 biopsy samples were also analyzed.

在42,407份前列腺切除术样本和31,107份活检样本的真实世界数据集中，也分析了临床和分子相关性。

Results

In SAKK 09/10, the biomarker-treatment interaction was statistically significant between PORTOS (lower versus higher) and treatment arm for clinical progression-free survival. Only patients in the higher PORTOS group benefited from DE.

在SAKK 09/10研究中，PORTOS（较低与较高）与治疗组之间的生物标志物-治疗相互作用对于临床无进展生存期具有统计学显著性。只有在较高PORTOS组的患者从DE治疗中获益。

In NRG/RTOG 0126, in patients with a lower tertile PORTOS, there was no difference in Phoenix biochemical failure (BF).

在NRG/RTOG 0126研究中，对于PORTOS评分处于较低三分位数的患者，Phoenix生化失败（BF）没有差异。

However, for patients in the average and higher tertile PORTOS range, there was a significant benefit for DE for Phoenix BF.

然而，对于PORTOS评分处于平均和较高三分位数范围的患者，对于Phoenix生化失败（BF），去势治疗（DE）有显著的益处。

An interaction test indicated a significant difference in benefit for DE between higher and lower PORTOS groups.

交互作用测试显示，高PORTOS组与低PORTOS组在DE的获益上存在显著差异。

PORTOS was not strongly associated with clinicopathological variables in either trial or the large real-world dataset.

在任何试验或大型真实世界数据集中，PORTOS与临床病理变量之间没有强烈的关联。

In the latter, PORTOS was modestly associated with hypoxia signatures and strongly associated with immune signatures and subtypes.

在后者中，PORTOS 与缺氧特征呈适度相关，与免疫特征和亚型呈强相关。

Conclusions

In the SAKK 09/10 and RTOG 0126 randomized controlled trials, we demonstrated that PORTOS can potentially identify a subset of patients who benefit from DE, a subgroup that cannot be identified using clinicopathological or prognostic variables.

在SAKK 09/10和RTOG 0126的随机对照试验中，我们证明了PORTOS可以潜在地识别出从DE中受益的患者亚群，这是一个无法仅通过临床病理或预后变量识别的亚群。

These results suggest that PORTOS could be used clinically as a predictor of radiation response.

这些结果表明，PORTOS 可以作为临床中放射治疗反应的预测指标。