Minimal Residual Disease Enhances Prognostic Stratification beyond Pathologic Response in Resectable Non-Small Cell Lung Cancer.

Although pathologic complete response (pCR) correlates with excellent survival outcomes, some patients without pCR still exhibit long-term survival. In this study, we evaluate the added value of minimal residual disease (MRD).

尽管病理完全缓解（pCR）与极佳的生存结果相关，但一些没有pCR的患者仍然表现出长期生存。在这项研究中，我们评估了微小残留病（MRD）的附加价值。

experimental_design

MRD was assessed in 60 patients from the NADIM II trial (NCT03838159) using the Guardant Reveal assay.

在NADIM II试验（NCT03838159）中，使用Guardant Reveal检测法评估了60名患者的微小残留病灶（MRD）。

In NADIM II, patients with NSCLC without EGFR or ALK alterations were randomly assigned to receive neoadjuvant nivolumab plus chemotherapy (experimental arm) or chemotherapy alone, followed by surgery.

在NADIM II试验中，未发现EGFR或ALK突变的非小细胞肺癌（NSCLC）患者被随机分配接受新辅助纳武利尤单抗加化疗（实验组）或仅接受化疗，随后进行手术。

Patients in the experimental arm with R0 resection received adjuvant nivolumab.

实验组中接受R0切除术的患者接受了辅助性纳武单抗治疗。

Results

The MRD detection rate was 9.6%.

微小残留病灶(MRD)的检测率为9.6%。

MRD after surgery or during adjuvant treatment was associated with inferior event-free survival (EFS) and overall survival[OS; hazard ratio(HR): 10.2; 95% confidence interval(CI), 3.7-28.3 and HR: 10.0; 95% CI, 2.0-49.9, respectively].

手术后或辅助治疗期间的微小残留病灶（MRD）与较差的无事件生存（EFS）和总生存（OS）相关（危险比[HR]：10.2；95%置信区间[CI]，3.7-28.3和HR：10.0；95% CI，2.0-49.9，分别）。

All patients with MRD-negative plasma samples in at least two time points were alive [HR: not estimable (NE), P < 0.001], with only one relapse (HR: 41.6; 95% CI, 5.0-348.8), corresponding to a patient relapsing with a single brain metastasis.

所有至少两个时间点MRD阴性的血浆样本患者均存活（HR：无法估计[NE]，P < 0.001），仅有一例复发（HR：41.6；95% CI，5.0-348.8），对应于仅有一个脑转移的患者复发。

MRD enhanced the prognostic value of pCR for both EFS (P < 0.001) and OS (P = 0.015).

微小残留病(MRD)增强了病理完全缓解(pCR)对无进展生存期(EFS) (P < 0.001)和总生存(OS) (P = 0.015)的预后价值。

Among non-pCR patients, MRD remained a significant prognostic marker (HR: 6.2; 95% CI, 2.2-17.1 and HR: 6.5; 95% CI, 1.3-32.5, for EFS and OS respectively).

在非pCR患者中，微小残留病(MRD)仍然是一个显著的预后标志物（无进展生存期(EFS)的HR: 6.2; 95% 置信区间, 2.2-17.1和总生存(OS)的HR: 6.5; 95% 置信区间, 1.3-32.5）。

All non-pCR patients with MRD-negative results in at least two time points were alive (HR: NE, P = 0.025), with one relapse (HR: 19.9; 95% CI, 2.4-165.6), corresponding to the aforementioned case.

所有非pCR患者在至少两个时间点的MRD阴性结果均为存活（HR: 未确定, P = 0.025），其中一例复发（HR: 19.9; 95% 置信区间, 2.4-165.6），对应前述病例。

Conclusions

MRD may refine prognostic evaluation beyond pCR in resectable NSCLC undergoing perioperative chemoimmunotherapy.

MRD可能在可切除NSCLC患者接受围手术期化疗免疫治疗后，对pCR之外的预后评估进行细化。