The use of personalized biomarkers and liquid biopsies to monitor treatment response and disease recurrence in locally advanced rectal cancer after neoadjuvant chemoradiation
The use of personalized biomarkers and liquid biopsies to monitor treatment response and disease recurrence in locally advanced rectal cancer after neoadjuvant chemoradiation
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DOI：
10.18632/oncotarget.5256
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发表时间：
2015-11-10
期刊：
影响因子：
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通讯作者：
Camargo, Anamaria A.
中科院分区：
文献类型：
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作者：
Carpinetti, Paola;Donnard, Elisa;Camargo, Anamaria A.
新辅助放化疗 (nCRT) 加手术是局部晚期直肠癌的主要治疗方法。 nCRT 后观察到不同程度的肿瘤消退，并研究了替代治疗策略，包括密切监测而不立即手术，以避免肿瘤完全消退的患者免受根治性手术的潜在不良后果的影响。然而，反应的临床和放射学评估并不能准确识别具有完全反应的患者。此外，监测复发对于这些患者同样重要，因为早期发现复发可以进行挽救性切除和辅助干预。我们报告了使用液体活检和个性化生物标志物来监测直肠癌患者对 nCRT 的治疗反应并检测残留疾病和复发。我们对四种直肠肿瘤的全基因组进行了测序，以确定患者特异性的染色体重排，这些重排用于监测诊断时以及 nCRT 和随访期间收集的液体活检中的循环肿瘤 DNA (ctDNA)。我们将 ctDNA 水平与 nCRT 的临床、放射学和病理学反应进行了比较。我们的结果表明，个性化生物标志物和液体活检可能对微小残留疾病的检测不敏感。然而，它可以有效地用于监测 nCRT 的治疗反应，并在 CEA 水平升高和放射学诊断之前检测疾病复发。在评估肿瘤对全身治疗和疾病进展的反应时，也观察到了类似的良好结果。我们的研究支持使用个性化生物标志物和液体活检来定制直肠癌患者的管理，但是，需要在更大的队列中进行复制才能将该策略引入临床实践。
Neoadjuvant chemoradiotherapy (nCRT) followed by surgery is the mainstay treatment for locally advanced rectal cancer. Variable degrees of tumor regression are observed after nCRT and alternative treatment strategies, including close surveillance without immediate surgery, have been investigated to spare patients with complete tumor regression from potentially adverse outcomes of radical surgery. However, clinical and radiological assessment of response does not allow accurate identification of patients with complete response. In addition, surveillance for recurrence is similarly important for these patients, as early detection of recurrence allows salvage resections and adjuvant interventions. We report the use of liquid biopsies and personalized biomarkers for monitoring treatment response to nCRT and detecting residual disease and recurrence in patients with rectal cancer. We sequenced the whole-genome of four rectal tumors to identify patient-specific chromosomal rearrangements that were used to monitor circulating tumor DNA (ctDNA) in liquid biopsies collected at diagnosis and during nCRT and follow-up. We compared ctDNA levels to clinical, radiological and pathological response to nCRT. Our results indicate that personalized biomarkers and liquid biopsies may not be sensitive for the detection of microscopic residual disease. However, it can be efficiently used to monitor treatment response to nCRT and detect disease recurrence, preceding increases in CEA levels and radiological diagnosis. Similar good results were observed when assessing tumor response to systemic therapy and disease progression. Our study supports the use of personalized biomarkers and liquid biopsies to tailor the management of rectal cancer patients, however, replication in a larger cohort is necessary to introduce this strategy into clinical practice.