Abstract：
OBJECTIVE: Current radiotherapy guidelines rely heavily on imaging-based monitoring. Liquid biopsy monitoring promises to complement imaging by providing frequent systemic information about the tumor. In particular, cell-free DNA (cfDNA) sequencing offers a tumor-agnostic approach, which lends itself to monitoring heterogeneous cohorts of cancer patients.
METHODS: We collected plasma cfDNA from oligometastatic patients (OMD) and head-and-neck cancer patients (SCCHN) at six time points before, during, and after radiotherapy, and compared them to the plasma samples of healthy and polymetastatic volunteers. We performed low-pass (on average 7x) whole-genome sequencing on 93 plasma cfDNA samples and correlated copy number alterations and fragment length distributions to clinical and imaging findings.
RESULTS: We observed copy number alterations in 4/7 polymetastatic cancer patients, 1/7 OMD and 1/7 SCCHN patients, these patients\' imaging showed progression following radiotherapy. Using unsupervised learning, we identified cancer-specific fragment length features that showed a strong correlation with copy number-based tumor fraction estimates. In 4/4 HPV-positive SCCHN patient samples, we detected viral DNA that enabled the monitoring of very low tumor fraction samples.
CONCLUSIONS: Our results indicate that an elevated tumor fraction is associated with tumor aggressiveness and systemic tumor spread. This information may be used to adapt treatment strategies. Further, we show that by detecting specific sequences such as viral DNA, the sensitivity of detecting cancer from cell-free DNA sequencing data can be greatly increased.
METHODS: We collected plasma cfDNA from oligometastatic patients (OMD) and head-and-neck cancer patients (SCCHN) at six time points before, during, and after radiotherapy, and compared them to the plasma samples of healthy and polymetastatic volunteers. We performed low-pass (on average 7x) whole-genome sequencing on 93 plasma cfDNA samples and correlated copy number alterations and fragment length distributions to clinical and imaging findings.
RESULTS: We observed copy number alterations in 4/7 polymetastatic cancer patients, 1/7 OMD and 1/7 SCCHN patients, these patients\' imaging showed progression following radiotherapy. Using unsupervised learning, we identified cancer-specific fragment length features that showed a strong correlation with copy number-based tumor fraction estimates. In 4/4 HPV-positive SCCHN patient samples, we detected viral DNA that enabled the monitoring of very low tumor fraction samples.
CONCLUSIONS: Our results indicate that an elevated tumor fraction is associated with tumor aggressiveness and systemic tumor spread. This information may be used to adapt treatment strategies. Further, we show that by detecting specific sequences such as viral DNA, the sensitivity of detecting cancer from cell-free DNA sequencing data can be greatly increased.
摘要：
目的：目前的放射治疗指南严重依赖影像监测。液体活检监测有望通过提供有关肿瘤的频繁全身信息来补充成像。特别是,无细胞DNA（cfDNA）测序提供了一种与肿瘤无关的方法，这有助于监测癌症患者的异质队列。
方法：我们在之前的六个时间点收集了寡转移患者（OMD）和头颈部癌症患者（SCCHN）的血浆cfDNA，during,放疗后，并将它们与健康和多转移志愿者的血浆样本进行比较。我们对93个血浆cfDNA样品进行了低通（平均7倍）全基因组测序，并将拷贝数改变和片段长度分布与临床和影像学发现相关联。
结果：我们观察到4/7多转移癌患者的拷贝数改变，1/7OMD和1/7SCCHN患者，这些患者的影像学表现为放疗后进展。使用无监督学习，我们确定了与基于拷贝数的肿瘤分数估计值具有强相关性的癌症特异性片段长度特征.在4/4HPV阳性SCCHN患者样本中，我们检测到病毒DNA,这使得能够监测非常低的肿瘤分数样本.
结论：我们的结果表明，肿瘤分数升高与肿瘤侵袭性和全身肿瘤扩散有关。该信息可用于调整治疗策略。Further,我们发现通过检测病毒DNA等特定序列,从无细胞DNA测序数据中检测癌症的灵敏度可以大大提高。
方法：我们在之前的六个时间点收集了寡转移患者（OMD）和头颈部癌症患者（SCCHN）的血浆cfDNA，during,放疗后，并将它们与健康和多转移志愿者的血浆样本进行比较。我们对93个血浆cfDNA样品进行了低通（平均7倍）全基因组测序，并将拷贝数改变和片段长度分布与临床和影像学发现相关联。
结果：我们观察到4/7多转移癌患者的拷贝数改变，1/7OMD和1/7SCCHN患者，这些患者的影像学表现为放疗后进展。使用无监督学习，我们确定了与基于拷贝数的肿瘤分数估计值具有强相关性的癌症特异性片段长度特征.在4/4HPV阳性SCCHN患者样本中，我们检测到病毒DNA,这使得能够监测非常低的肿瘤分数样本.
结论：我们的结果表明，肿瘤分数升高与肿瘤侵袭性和全身肿瘤扩散有关。该信息可用于调整治疗策略。Further,我们发现通过检测病毒DNA等特定序列,从无细胞DNA测序数据中检测癌症的灵敏度可以大大提高。
