Honoré N, van Marcke C, Galot R, Helaers R, Ambroise J, van Maanen A, Mendola A, Dahou H, Marbaix E, Van Eeckhout P, Longton E, Magremanne M, Schmitz S, Limaye N, Machiels J-P
Pôle oncologie, Institut de Recherche Clinique et Expérimentale, Université catholique de Louvain (UCLouvain), Brussels, Belgium; Department of Medical Oncology, Institut Roi Albert II, Cliniques universitaires Saint-Luc, Brussels, Belgium.
Human Molecular Genetics, de Duve Institute, Université catholique de Louvain (UCLouvain), Brussels, Belgium.
Ann Oncol. 2023 Dec;34(12):1175-1186. doi: 10.1016/j.annonc.2023.09.3102. Epub 2023 Oct 23.
Forty to fifty percent of patients with locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) relapse despite multimodal treatment. Circulating tumor DNA (ctDNA) has the potential to detect minimal residual disease (MRD) after curative-intent therapy and to identify earlier which patients will progress. We developed a tumor-agnostic plasma ctDNA assay to detect MRD in unselected LA SCCHN with the aim of predicting progression-free survival (PFS) and overall survival without the need for tumor sequencing.
A 26-gene next-generation sequencing panel was constructed that included the most frequently mutated genes in SCCHN and two HPV-16 genes. MRD was assessed in each patient through an in-house informatic workflow informed by somatic mutations identified in the corresponding pre-treatment plasma sample. The presence of MRD was defined as the detection of ctDNA in one plasma sample collected within 1-12 weeks of the end of curative treatment. The primary endpoint was the PFS rate at 2 years. At least 32 patients were planned for inclusion with the hypothesis that PFS at 2 years was >80% in MRD-negative patients and <30% in MRD-positive patients (α = 0.05, β = 0.9).
We sequenced DNA from 116 plasma samples derived from 53 LA SCCHN patients who underwent curative-intent treatment. ctDNA was detected in 41/53 (77%) patients in the pre-treatment samples. Out of these 41 patients, 17 (41%) were MRD positive after treatment. The 2-year PFS rate was 23.53% (9.9% to 55.4%) and 86.6% (73.4% to 100%) in MRD-positive and MRD-negative patients, respectively (P < 0.05). Median survival was 28.37 months (14.30 months-not estimable) for MRD-positive patients and was not reached for the MRD-negative cohort (P = 0.011).
Our ctDNA assay detects MRD in LA SCCHN and predicts disease progression and survival without the need for tumor sequencing, making this approach easily applicable in daily practice.
尽管接受了多模式治疗，但40%至50%的局部晚期头颈部鳞状细胞癌（LA SCCHN）患者仍会复发。循环肿瘤DNA（ctDNA）有潜力在根治性治疗后检测微小残留病（MRD），并更早地识别哪些患者会进展。我们开发了一种不依赖肿瘤类型的血浆ctDNA检测方法，以检测未经选择的LA SCCHN患者中的MRD，目的是预测无进展生存期（PFS）和总生存期，而无需进行肿瘤测序。
构建了一个包含26个基因的下一代测序面板，其中包括SCCHN中最常发生突变的基因和两个HPV - 16基因。通过内部信息分析流程，根据相应治疗前血浆样本中鉴定出的体细胞突变，对每位患者的MRD进行评估。MRD的存在定义为在根治性治疗结束后1至12周内采集的一份血浆样本中检测到ctDNA。主要终点是2年时的PFS率。计划至少纳入32例患者，假设MRD阴性患者2年时的PFS>80%，MRD阳性患者<30%（α = 0.05，β = 0.9）。
我们对53例接受根治性治疗的LA SCCHN患者的116份血浆样本进行了DNA测序。在治疗前样本中，41/53（77%）的患者检测到ctDNA。在这41例患者中，17例（41%）治疗后MRD呈阳性。MRD阳性和MRD阴性患者的2年PFS率分别为23.53%（9.9%至55.4%）和86.6%（73.4%至100%）（P < 0.05）。MRD阳性患者的中位生存期为28.37个月（14.30个月 - 不可估计），MRD阴性队列未达到中位生存期（P = 0.011）。
我们的ctDNA检测方法可检测LA SCCHN患者中的MRD，并预测疾病进展和生存期，无需进行肿瘤测序，使该方法易于在日常实践中应用。
