Ultrasensitive detection and tracking of circulating tumor DNA to predict relapse and survival in patients with locally advanced cervical cancer: phase III CALLA trial analyses.

In the global randomized CALLA trial (NCT03830866), the addition of durvalumab during and after CRT did not significantly improve progression-free survival(PFS) in a biomarker-unselected intent-to-treat population.

在名为CALLA的全球随机试验（NCT03830866）中，CRT期间及之后添加durvalumab并未显著改善未选择生物标志物的意向治疗人群的无进展生存（PFS）。

We analyzed the association of ultrasensitive circulating tumor DNA (ctDNA) and circulating human papillomavirus (cHPV) DNA detection with relapse and survival in the largest dataset in LACC to date.

我们分析了超敏循环肿瘤DNA（ctDNA）和循环人乳头瘤病毒（cHPV）DNA检测与复发和生存之间的关联，这是迄今为止在局部晚期宫颈癌（LACC）中最大的数据集。

patients_and_methods

In CALLA, adult women with stage IB2-IIB node-positive or IIIA-IVA any node-status LACC were randomized 1 : 1 to receive durvalumab + CRT or CRT alone.

在CALLA研究中，将IB2-IIB期伴有淋巴结转移或IIIA-IVA期任何淋巴结状态的成年女性局部晚期宫颈癌患者随机分为1:1，接受durvalumab联合放化疗（CRT）或仅接受放化疗。

The NeXT Personal® (Personalis) ultrasensitive tumor-informed assay with up to 1800 patient-specific variants was used for ctDNA and cHPV DNA analysis at baseline, cycle 3 day 1 (C3D1, post-CRT), and C6D1 (3 months post-CRT).

使用了NeXT Personal® (Personalis) 超敏肿瘤特异性检测，最多可检测1800种患者特异性变异，用于基线、第3周期第1天（C3D1，放疗后）和C6D1（放疗后3个月）的循环肿瘤DNA（ctDNA）和循环高危型人乳头瘤病毒DNA（cHPV DNA）分析。

Correlations were analyzed between ctDNA/cHPV DNA detection and outcomes [PFS, overall survival(OS)].

分析了循环肿瘤DNA（ctDNA）/循环高危型人乳头瘤病毒DNA（cHPV DNA）检测与临床结果（无进展生存期（PFS）、总生存（OS））之间的相关性。

Results

ctDNA was detected in 98.9% (183/185) of baseline samples, with no difference between treatment arms.

在基线样本中，ctDNA的检出率为98.9%（183/185），治疗组之间无差异。

Detection levels of ctDNA were predictive of disease progression and survival at baseline: hazard ratios (95% confidence intervals) comparing PFS and OS, respectively, in the ctDNA less than median versus ctDNA greater than median subgroups were 0.61 (0.28-1.35) and 0.55 (0.23-1.35) with durvalumab + CRT, and 0.49 (0.26-0.95) and 0.65 (0.33-1.28) with CRT.

基线时，ctDNA的检测水平预示着疾病的进展和生存期：在ctDNA低于中位数与ctDNA高于中位数的亚组中，分别比较无进展生存期（PFS）和总生存（OS），使用durvalumab + CRT的亚组的风险比（95%置信区间）为0.61（0.28-1.35）和0.55（0.23-1.35），而仅使用CRT的亚组为0.49（0.26-0.95）和0.65（0.33-1.28）。

Post-treatment trends were similar and independent of stage or lymph node status. ctDNA detection at C3D1 occurred a median of 164 days (95% confidence interval85-250) days before clinical progression.

治疗后的趋势相似，且与分期或淋巴结状态无关。在C3D1检测到ctDNA的中位时间为临床进展前164天（95%置信区间85-250天）。

Baseline cHPV DNA levels were similar but were only predictive following treatment.

基线cHPV DNA水平相似，但仅在治疗后具有预测性。

Conclusions

This study demonstrates the potential utility of ultrasensitive detection of ctDNA as a predictive and prognostic marker of disease progression and OS in LACC independent of disease stage.

本研究展示了超灵敏检测循环肿瘤DNA（ctDNA）作为预测和预后标志物的潜力，用于评估局部晚期宫颈癌（LACC）的疾病进展和总生存（OS），且这一作用与疾病阶段无关。