结肠癌寡转移疾病的临床和遗传驱动因素
Clinical and genetic drivers of oligo-metastatic disease in colon cancer.
作者信息
Ottaiano Alessandro, Santorsola Mariachiara, Sirica Roberto, Mauro Annabella Di, Di Carlo Antonella, Ianniello Monica, Sabbatino Francesco, Castiello Rosa, Peschio Francesca Del, Cascella Marco, Perri Francesco, Capuozzo Maurizio, Martucci Nicola, Mercadante Edoardo, Borzillo Valentina, Di Franco Rossella, Izzo Francesco, Granata Vincenza, Picone Carmine, Petrillo Antonella, Berretta Massimiliano, Stilo Salvatore, Tarotto Luca, Carratù Anna Chiara, Ferrara Gerardo, Tathode Madhura, Cossu Alessia Maria, Bocchetti Marco, Caraglia Michele, Nasti Guglielmo, Savarese Giovanni
机构信息
SSD-Innovative Therapies for Abdominal Metastases, IRCCS "G. Pascale", Istituto Nazionale Tumori di Napoli, Via M. Semmola, Naples 80131, Italy.
SSD-Innovative Therapies for Abdominal Metastases, IRCCS "G. Pascale", Istituto Nazionale Tumori di Napoli, Via M. Semmola, Naples 80131, Italy.
出版信息
Neoplasia. 2025 Feb;60:101111. doi: 10.1016/j.neo.2024.101111. Epub 2024 Dec 21.
BACKGROUND
Oligo-metastatic disease (OMD) in colon cancer patients exhibits distinct clinical behavior compared to poly-metastatic disease (PMD), with a more responsive and indolent course. This study aims to identify clinical and biological factors uniquely associated with oligo-metastatic behavior.
METHODS
Metastatic colon cancer patients from an academic center underwent genetic characterization. OMD was defined as ≤3 lesions per organ, each with a total diameter <70 mm and none exceeding 25 mm. Tumor DNA sequencing by NGS utilized the TruSight Oncology 500 kit. Overall survival (OS) was determined from metastasis diagnosis until death using Kaplan-Meier analysis. Multivariate Cox regression examined prognostic links between clinicopathological and genetic factors. Associations with metastatic patterns were evaluated using Chi-square.
RESULTS
The analysis involved 104 patients (44 with OMD, 60 with PMD). OMD was more prevalent in males (P = 0.0299) and with single organ involvement (P = 0.0226). Multivariate analysis adjusted for age (>70 vs. <70 years), gender (male vs. female), tumor side (right vs. left), metastatic involvement (more than one site vs. one site), response to first-line therapy (disease control vs. no disease control), and RAS/BRAF variants (wild-type vs. mutated) identified OMD vs. PMD as the strongest independent predictor of survival (HR: 0.14; 95 % CI: 0.06-0.33; P<0.0001). OMD patients exhibited distinct molecular characteristics, including lower frequencies of BRAF p.V600E (P=0.0315) and KRAS mutations (P=0.0456), as well as a higher frequency of high tumor mutational burden (P=0.0127). Additionally, by integrating data from public datasets and our case study, we hypothesize that some gene alterations (i.e.: BRAF, SMAD4, RAF1, and mTOR) may prevent OMD occurrence.
CONCLUSION
OMD, characterized by male predominance, single-site involvement, and distinct molecular features in colon cancer, suggests the need for tailored management strategies.
背景
与多转移疾病（PMD）相比，结肠癌患者的寡转移疾病（OMD）表现出独特的临床行为，病程更具反应性且进展缓慢。本研究旨在确定与寡转移行为独特相关的临床和生物学因素。
方法
来自一个学术中心的转移性结肠癌患者接受了基因特征分析。OMD定义为每个器官≤3个病灶，每个病灶总直径<70mm，且无超过25mm的病灶。通过二代测序（NGS）进行肿瘤DNA测序，使用TruSight Oncology 500试剂盒。总生存期（OS）从转移诊断至死亡，采用Kaplan-Meier分析确定。多变量Cox回归分析临床病理和基因因素之间的预后联系。使用卡方检验评估与转移模式的相关性。
结果
分析涉及104例患者（44例OMD，60例PMD）。OMD在男性中更常见（P = 0.0299），且多为单器官受累（P = 0.0226）。在对年龄（>70岁与<70岁）、性别（男性与女性）、肿瘤部位（右侧与左侧）、转移受累情况（多个部位与一个部位）、一线治疗反应（疾病控制与无疾病控制）以及RAS/BRAF变异（野生型与突变型）进行多变量分析后，发现OMD与PMD是生存的最强独立预测因素（HR：0.14；95%CI：0.06 - 0.33；P<0.0001）。OMD患者表现出独特的分子特征，包括BRAF p.V600E突变频率较低（P = 0.0315）和KRAS突变频率较低（P = 0.0456），以及高肿瘤突变负荷频率较高（P = 0.0127）。此外，通过整合公共数据集和我们的病例研究数据，我们假设某些基因改变（即：BRAF、SMAD4、RAF1和mTOR）可能会阻止OMD的发生。
结论
OMD在结肠癌中以男性为主、单部位受累且具有独特分子特征为特点，这表明需要制定针对性的管理策略。
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