Roesel Raffaello, Epistolio Samantha, Molinari Francesca, Saletti Piercarlo, De Dosso Sara, Valli Mariacarla, Franzetti-Pellanda Alessandra, Deantonio Letizia, Biggiogero Maira, Spina Paolo, Popeskou Sotirios Georgios, Cristaudi Alessandra, Mongelli Francesco, Mazzucchelli Luca, Stefanini Federico Mattia, Frattini Milo, Christoforidis Dimitri
Department of Visceral Surgery, Regional Hospital of Lugano, Ente Ospedaliero Cantonale, Lugano, Switzerland.
Istituto Cantonale di Patologia, Ente Ospedaliero Cantonale, Locarno, Switzerland.
Front Oncol. 2022 Jun 28;12:900945. doi: 10.3389/fonc.2022.900945. eCollection 2022.
Circulating tumor DNA (ctDNA) correlates with the response to therapy in different types of cancer. However, in patients with locally advanced rectal cancer (LARC), little is known about how ctDNA levels change with neoadjuvant chemoradiation (Na-ChRT) and how they correlate with treatment response. This work aimed to explore the value of serial liquid biopsies in monitoring response after Na-ChRT with the hypothesis that this could become a reliable biomarker to identify patients with a complete response, candidates for non-operative management.
Twenty-five consecutive LARC patients undergoing long-term Na-ChRT therapy were included. Applying next-generation sequencing (NGS), we characterized DNA extracted from formalin-fixed paraffin embedded diagnostic biopsy and resection tissue and plasma ctDNA collected at the following time points: the first and last days of radiotherapy (T, T), at 4 (T), 7 (T) weeks after radiotherapy, on the day of surgery (T), and 3-7 days after surgery (T). On the day of surgery, a mesenteric vein sample was also collected (T). The relationship between the ctDNA at those time-points and the tumor regression grade (TRG) of the surgical specimen was statistically explored.
We found no association between the disappearance of ctDNA mutations in plasma samples and pathological complete response (TRG1) as ctDNA was undetectable in the majority of patients from Tend on. However, we observed that the poor (TRG 4) response to Na-ChRT was significantly associated with a positive liquid biopsy at the T.
ctDNA evaluation by NGS technology may identify LARC patients with poor response to Na-ChRT. In contrast, this technique does not seem useful for identifying patients prone to developing a complete response.
循环肿瘤DNA（ctDNA）与不同类型癌症的治疗反应相关。然而，对于局部晚期直肠癌（LARC）患者，关于ctDNA水平如何随新辅助放化疗（Na-ChRT）变化以及它们与治疗反应如何相关，我们知之甚少。这项研究旨在探讨连续液体活检在监测Na-ChRT后反应中的价值，假设这可以成为识别完全缓解患者（非手术治疗候选者）的可靠生物标志物。
纳入25例接受长期Na-ChRT治疗的连续LARC患者。应用下一代测序（NGS）技术，我们对从福尔马林固定石蜡包埋的诊断活检组织、切除组织以及在以下时间点采集的血浆ctDNA中提取的DNA进行了特征分析：放疗的第一天和最后一天（T₁、T₂）、放疗后4周（T₃）、7周（T₄）、手术当天（T₅）以及手术后3 - 7天（T₆）。手术当天还采集了肠系膜静脉样本（T₇）。对这些时间点的ctDNA与手术标本的肿瘤退缩分级（TRG）之间的关系进行了统计学探索。
我们发现血浆样本中ctDNA突变的消失与病理完全缓解（TRG1）之间没有关联，因为从T₄开始大多数患者的ctDNA无法检测到。然而，我们观察到对Na-ChRT反应较差（TRG 4）与T₃时液体活检呈阳性显著相关。
通过NGS技术评估ctDNA可能识别出对Na-ChRT反应较差的LARC患者。相比之下，这项技术似乎对识别易于出现完全缓解的患者没有用处。
