Yongye Chen1, Enlong Zhang 2, Qizheng Wang 1, Huishu Yuan1, Huishu Yuan1, Hongqing Zhuang1, and Ning Lang1
1Peking University Third Hospital, Beijing, China, 2Peking University International Hospital, Beijing, China
Synopsis
The imaging
methods used to evaluate the efficacy of radiosurgery in spinal metastases have
certain limitations. DCE-MRI can help determine the vascularity and
hemodynamics of tumors in vivo, and can be used to evaluate local tumor
response. Twenty-seven patients with 39 lesions were included. Post-treatment Kep,
ΔKtrans and ΔKep in the non-progressive disease group
were significantly lower than the corresponding values in progressive disease
group. Post-treatment Ve and ΔVe in the non-progressive
disease group were significantly higher than that of the progressive disease
group. ΔKtrans had the highest diagnostic efficiency, with an AUC of
0.821.
Introduction
Spinal metastases can cause
vertebral compression fractures, compress nerve roots and the spinal cord,
cause severe pain and neurological complications, and have a tremendous impact
on patients' quality of life. Unlike traditional palliative radiotherapy, CyberKnife
radiosurgery can deliver large doses of precise irradiation to spinal
metastases while minimizing dose to the surrounding sensitive tissues such as
the spinal cord, allowing local control of the lesion and improving the
stability of the spine [1].
At present, the evaluation of imaging efficacy mainly depends on the
morphological changes of the tumor before and after treatment, and conventional
MRI is the most commonly used imaging evaluation method. The increase in lesion
volume is usually defined as progression. However, the size of spinal tumors is
not easy to measure, and some tumors do not change significantly when assessed
using traditional imaging methods. Hwang et al. [2] showed that 49.4% of
spinal metastases remained unchanged in tumor volume after stereotactic
radiosurgery when imaged with conventional MRI. DCE-MRI can help determine the
vascularity and hemodynamics of tumors in vivo in a non-invasive manner [3],
and can be used to explore the survival status of spinal metastatic tumor cells
after treatment to evaluate local tumor response.Methods
We enrolled patients with spinal
metastases who were treated with CyberKnife radiosurgery. The first follow-up
was performed at 3 months after CyberKnife radiosurgery. The first follow-up
included conventional MRI and DCE-MRI scans, followed by a 3-month cycle of
follow-up examinations; MRI or CT examinations were performed according to
clinical needs. The imaging efficacy evaluation was based on the RECIST version
1.1 [4], and the lesions were
divided into progressive disease (PD) group and non-PD group according to the
evaluation results. The hemodynamic parameters (volume transfer constant [Ktrans],
rate constant [Kep], and extravascular space [Ve]) before
and after treatment between the groups were analyzed. Area under the curve
(AUC) values were calculated. Results
A total of
27 patients with 39 independent spinal lesions were included. Eighteen patients
had a single lesion each, while nine patients had multiple lesions. The median
follow-up time was 18.6 months (6.2-36.4), with a mean of 18.5 months. There
were 27 lesions in the non-PD group and 12 lesions in the PD group.
Post-treatment Kep, ΔKtrans and ΔKep in the
non-PD group (0.959 min-1, -32.6% and -41.1%, respectively) were significantly
lower than the corresponding values in PD group (1.429 min-1, 20.4% and -6.0%;
p < 0.05). Post-treatment Ve and ΔVe (0.223 and 27.8%,
respectively) in the non-PD group were significantly higher than that of the PD
group (1.429 min-1, 0.165 and -13.5%, p < 0.05). The representative lesions
in the non-PD group and the PD group are shown in Figure 1 and Figure
2. Among all parameters, ΔKtrans showed the highest diagnostic
efficiency, with an AUC of 0.821.Discussion
Early
predicting and assessing local tumor response are very important for the
treatment of patients. A robust radiation dose treatment regime to recurrent
tumor is essential for successful salvage, because recurrent tumor is likely to
cause acquired radiation resistance as tumors develop an adaptive response and
epigenetic changes [1]. Stereotactic
radiosurgery can destroy tumor blood vessels and inhibit neovascularization,
which leads to the destruction of the tumor internal microenvironment [5]. DCE-MRI
parameters can sensitively detect changes in the blood flow state of the lesion
tissue before and after treatment, and reflect the curative effect on the basis
of the magnitude of the parameter changes before and after treatment.
In our
study, Ktrans, Kep and Ve were found to be of
great value in evaluating the efficacy of CyberKnife radiosurgery in spinal
metastases. Ktrans and Kep
values are closely related to the state of tumor microcirculation and
angiogenesis. In comparison with normal blood vessels, tumor blood vessels have
higher permeability and perfusion, which means that tumor tissues have higher Ktrans
and Kep values [6].
Post-treatment Kep, ΔKtrans, and ΔKep in the
non-PD group were significantly lower than those in the PD group. This might be
due to the damage to the vascular structure of tumor tissues by radiation
therapy, which inhibited the regeneration of tumor blood vessels, leading to reductions
in post-treatment Ktrans, post-treatment Kep, ΔKtrans,
ΔKep. In contrast, tumors in the PD group were resistant to
radiotherapy, resulting in less damage to the structure and function of tumor
vascular tissues and more active tumor vascular regeneration, which ensured a
less obvious parameter decline, even increase. Post-treatment Ve and
ΔVe in the non-PD group were significantly higher than the PD group.
Ve represented the volume of extravascular extracellular space (EES)
per unit volume of tissue. Tumor tissue blood vessels were destroyed after
radiotherapy, and the intravascular space volume would decrease, so the EES
volume and its proportion would increase, resulting in an increase in Ve
[7]. Conclusion:
DCE-MRI, as
the best non-invasive examination method for reflecting tissue hemodynamic
information, has high accuracy in determining the early efficacy of CyberKnife radiosurgery.
It can compensate for the limitations of conventional MRI in the evaluation of
therapeutic efficacy, especially when the change in tumor morphology is not
obvious after treatment. This provides valuable information for future clinical
practice and guides doctors in planning treatment options.Acknowledgements
This study was supported in part by
the National Natural Science Foundation of China (81971578, 81701648), and the
Key Clinical Projects of the Peking University Third Hospital (BYSY2018007).References
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