Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Centre for Lymphoid Cancer, BC Cancer Agency, Vancouver, BC, Canada.
Blood. 2017 Jul 20;130(3):258-266. doi: 10.1182/blood-2017-03-691345. Epub 2017 Apr 13.
Transformation to aggressive lymphoma is a critical event in the clinical course of follicular lymphoma (FL) patients. Yet, it is a challenge to reliably predict transformation at the time of diagnosis. Understanding the risk of transformation would be useful for guiding and monitoring patients, as well as for evaluating novel treatment strategies that could potentially prevent transformation. Herein, we review the contribution of clinical, pathological, and genetic risk factors to transformation. Patients with multiple clinical high-risk factors are at elevated risk of transformation but we are currently lacking a prognostic index that would specifically address transformation rather than disease progression or overall survival. From the biological standpoint, multiple studies have correlated individual biomarkers with transformation. However, accurate prediction of this event is currently hampered by our limited knowledge of the evolutionary pathways leading to transformation, as well as the scarcity of comprehensive, large-scale studies that assess both the genomic landscape of alterations within tumor cells and the composition of the microenvironment. Liquid biopsies hold great promise for achieving precision medicine. Indeed, mutations detected within circulating tumor DNA may be a better reflection of the inherent intratumoral heterogeneity than the biopsy of a single site. Last, we will assess whether evidence exists in the literature that transformation might be prevented altogether, based on the choice of therapy for FL.
向侵袭性淋巴瘤的转化是滤泡性淋巴瘤（FL）患者临床病程中的一个关键事件。然而，在诊断时可靠地预测转化是一个挑战。了解转化的风险对于指导和监测患者，以及评估可能预防转化的新治疗策略是有用的。在此，我们回顾了临床、病理和遗传危险因素对转化的贡献。具有多个临床高危因素的患者转化风险增加，但我们目前缺乏专门针对转化而不是疾病进展或总生存的预后指标。从生物学角度来看，多项研究已经将单个生物标志物与转化相关联。然而，由于我们对导致转化的进化途径的了解有限，以及缺乏全面、大规模的研究来评估肿瘤细胞内改变的基因组景观和微环境的组成，因此目前仍难以准确预测这一事件。液体活检在实现精准医学方面具有巨大的潜力。事实上，在循环肿瘤 DNA 中检测到的突变可能比单个部位的活检更能反映肿瘤内固有的异质性。最后，我们将根据 FL 的治疗选择评估是否有文献证据表明可以完全预防转化。
