Novel imaging biomarkers predict outcomes in stage III unresectable non-small cell lung cancer treated with chemoradiation and durvalumab.
Novel imaging biomarkers predict outcomes in stage III unresectable non-small cell lung cancer treated with chemoradiation and durvalumab.
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DOI：
10.1136/jitc-2021-003778
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发表时间：
2022-03
影响因子：
10.9
通讯作者：
Madabhushi A
中科院分区：
文献类型：
--
作者：
Jazieh K;Khorrami M;Saad A;Gad M;Gupta A;Patil P;Viswanathan VS;Rajiah P;Nock CJ;Gilkey M;Fu P;Pennell NA;Madabhushi A
具有里程碑意义的 durvalumab 作为 NSCLC 患者巩固治疗的研究（PACIFIC 试验）表明，局部晚期、不可切除的非小细胞肺癌 (NSCLC) 患者在放化疗 (CRT) 后接受 durvalumab（免疫疗法，IO）治疗后，无进展生存期 (PFS) 显着延长。在美国的临床实践中，durvalumab 继续用于各种程序性细胞死亡配体 1 (PD-L1) 表达水平的患者。虽然免疫疗法在多种癌症中显示出希望，但一些患者要么对治疗没有反应，要么在初次反应后出现癌症复发。到目前为止，尚不清楚谁将从这种疗法中受益，也不清楚治疗失败背后的机制是什么。总共纳入了 133 名不可切除的 III 期 NSCLC 患者，他们在 CRT 或单独 CRT 后接受了 durvalumab。 CRT 后接受 durvalumab IO 治疗的患者被随机分为训练组 (D1=59) 和测试组 (D2=59)，其余 15 名仅接受 CRT 治疗的患者被分组在 D3 中。提取目标结节内部和周围的放射组学纹理模式。建立放射组学风险评分 (RRS) 并用于预测 PFS 和总生存期 (OS)。根据中位 RRS 将患者分为高风险组和低风险组。发现 RRS 与 D1（HR=2.67，95%CI 1.85 至 4.13，p<0.05，C 指数=0.78）和 D2（HR=2.56，95%CI 1.63 至 4，p<0.05，C 指数=0.73）中的 PFS 显着相关。类似地，RRS分别与D1（HR=1.89，95%CI 1.3至2.75，p<0.05，C指数=0.67）和D2（HR=2.14，95%CI 1.28至3.6，p<0.05，C指数=0.69）中的OS相关。研究发现，在高 PD-L1（HR=3.01，95%CI 1.41 至 6.45，p=0.0044）和低 PD-L1（HR=2.74，95%CI 1.8 至 4.14，p=1.77e-06）组中，RRS 与 PFS 显着相关。此外，RRS 与高 PD-L1 组的 OS 不显着相关（HR=2.08，95%CI 0.98 至 4.4，p=0.054），但与低 PD-L1 组的 OS 显着相关（HR=1.61，95%CI 1.14 至 2.28，p=0.0062）。此外，RRS 分别与 D3 中的 PFS（HR=2.77，95%CI 1.17 至 6.52，p=0.019，C-index=0.77）和 OS（HR=2.62，95%CI 1.25 至 5.51，p=0.01，C-index=0.77）显着相关。 III 期不可切除 NSCLC 患者治疗前 CT 图像的肿瘤放射组学可预测 CRT 以及单独使用 durvalumab IO 和 CRT 的 PFS 和 OS。
The landmark study of durvalumab as consolidation therapy in NSCLC patients (PACIFIC trial) demonstrated significantly longer progression-free survival (PFS) in patients with locally advanced, unresectable non-small cell lung cancer (NSCLC) treated with durvalumab (immunotherapy, IO) therapy after chemoradiotherapy (CRT). In clinical practice in the USA, durvalumab continues to be used in patients across all levels of programmed cell death ligand-1 (PD-L1) expression. While immune therapies have shown promise in several cancers, some patients either do not respond to the therapy or have cancer recurrence after an initial response. It is not clear so far who will benefit of this therapy or what the mechanisms behind treatment failure are. A total of 133 patients with unresectable stage III NSCLC who underwent durvalumab after CRT or CRT alone were included. Patients treated with durvalumab IO after CRT were randomly split into training (D1=59) and test (D2=59) sets and the remaining 15 patients treated with CRT alone were grouped in D3. Radiomic textural patterns from within and around the target nodules were extracted. A radiomic risk score (RRS) was built and was used to predict PFS and overall survival (OS). Patients were divided into high-risk and low-risk groups based on median RRS. RRS was found to be significantly associated with PFS in D1 (HR=2.67, 95% CI 1.85 to 4.13, p<0.05, C-index=0.78) and D2 (HR=2.56, 95% CI 1.63 to 4, p<0.05, C-index=0.73). Similarly, RRS was associated with OS in D1 (HR=1.89, 95% CI 1.3 to 2.75, p<0.05, C-index=0.67) and D2 (HR=2.14, 95% CI 1.28 to 3.6, p<0.05, C-index=0.69), respectively. RRS was found to be significantly associated with PFS in high PD-L1 (HR=3.01, 95% CI 1.41 to 6.45, p=0.0044) and low PD-L1 (HR=2.74, 95% CI 1.8 to 4.14, p=1.77e-06) groups. Moreover, RRS was not significantly associated with OS in the high PD-L1 group (HR=2.08, 95% CI 0.98 to 4.4, p=0.054) but was significantly associated with OS in the low PD-L1 group (HR=1.61, 95% CI 1.14 to 2.28, p=0.0062). In addition, RRS was significantly associated with PFS (HR=2.77, 95% CI 1.17 to 6.52, p=0.019, C-index=0.77) and OS (HR=2.62, 95% CI 1.25 to 5.51, p=0.01, C-index=0.77) in D3, respectively. Tumor radiomics of pretreatment CT images from patients with stage III unresectable NSCLC were prognostic of PFS and OS to CRT followed by durvalumab IO and CRT alone.
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影响因子：
5.3
作者：
Khorrami, Mohammadhadi;Jain, Prantesh;Madabhushi, Anant
通讯作者：
Madabhushi, Anant
DOI：
10.6004/jnccn.2013.0084
发表时间：
2013-06-01
影响因子：
13.4
作者：
Ettinger, David S.;Akerley, Wallace;Hughes, Miranda
通讯作者：
Hughes, Miranda
影响因子：
7
作者：
Lanitis E;Irving M;Coukos G
通讯作者：
Coukos G
影响因子：
8
作者：
Graham K;Unger E
通讯作者：
Unger E
影响因子：
8
作者：
JAIN, AK;FARROKHNIA, F
通讯作者：
FARROKHNIA, F