Image1_Quantified CIN Score From Cell-free DNA as a Novel Noninvasive Predictor of Survival in Patients With Spinal Metastasis.JPEG (355.47 kB)

Image1_Quantified CIN Score From Cell-free DNA as a Novel Noninvasive Predictor of Survival in Patients With Spinal Metastasis.JPEG

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posted on 2021-12-09, 05:05 authored by Su Chen, Minglei Yang, Nanzhe Zhong, Dong Yu, Jiao Jian, Dongjie Jiang, Yasong Xiao, Wei Wei, Tianzhen Wang, Yan Lou, Zhenhua Zhou, Wei Xu, Wan Wan, Zhipeng Wu, Haifeng Wei, Tielong Liu, Jian Zhao, Xinghai Yang, Jianru Xiao

Purpose: Most currently available scores for survival prediction of patients with bone metastasis lack accuracy. In this study, we present a novel quantified CIN (Chromosome Instability) score modeled from cfDNA copy number variation (CNV) for survival prediction.

Experimental Design: Plasma samples collected from 67 patients with bone metastases from 11 different cancer types between November 2015 and May 2016 were sent through low-coverage whole genome sequencing followed by CIN computation to make a correlation analysis between the CIN score and survival prognosis. The results were validated in an independent cohort of 213 patients.

Results: During the median follow-up period of 598 (95% CI 364–832) days until December 25, 2018, 124 (44.3%) of the total 280 patients died. Analysis of the discovery dataset showed that CIN score = 12 was the optimal CIN cutoff. Validation dataset showed that CIN was elevated (score ≥12) in 87 (40.8%) patients, including 5 (5.75%) with head and neck cancer, 11 (12.6%) with liver and gallbladder cancer, 11 (12.6%) with cancer from unidentified sites, 21 (24.1%) with lung cancer, 7 (8.05%) with breast cancer, 4 (4.60%) with thyroid cancer, 6 (6.90%) with colorectal cancer, 4 (4.60%) with kidney cancer, 2 (2.30%) with prostate cancer, and 16 (18.4%) with other types of cancer. Further analysis showed that patients with elevated CIN were associated with worse survival (p < 0.001). For patients with low Tokuhashi score (≤8) who had predictive survival of less than 6 months, the CIN score was able to distinguish patients with a median overall survival (OS) of 443 days (95% CI 301–585) from those with a median OS of 258 days (95% CI 184–332).

Conclusion: CNV examination in bone metastatic cancer from cfDNA is superior to the traditional predictive model in that it provides a noninvasive and objective method of monitoring the survival of patients with spine metastasis.