DCE-MRI is a widely used imaging method reflecting vascular perfusion and endothelial permeability of tumor microcirculation, which are regarded as the most important factors in assessment of chemotherapy response. The DCE-MRI parameters has not been a consensus regarding adequate semi quantitative and quantitative parameters representing treatment response. Until now, several researches have supported the effectiveness of DCE-MRI become an accepted non-invasive in assessing tumor necrosis and biomarker for the response of treatment in osteosarcoma [1].
In this study, the role of semi-quantitative and quantitative parameters derived from DCE-MRI data for prediction of treatment response to chemotherapy in patients osteosarcoma was investigated. Our semi-quantitative and quantitative parameters showed that there was significant difference in chemotherapy response between the good response and poor response groups after chemotherapy. These result consistent with previous study that semi-quantitative and quantitative parameters values of DCE-MRI are correlated each other [4].
The results from quantitative analysis of DCE-MRI in response assessment of chemothreapy in osteosarcoma were consistent with those of several previous studies [28–36]. The pre-chemotherapy Ktrans and Kep values did not differ significantly between good and poor responders. Our finding is in agreement with studies on Zhang et al study in 19 patients of osteosarcoma that has reported that Ktrans and Kep pre chemotherapy showed no significant differences between the good respond groups and poor respond groups [28]. The Ktrans and Kep values are closely associated with the degree of tumor microcirculation and angiogenesis. Tumor neovascularization leads to increased permeability and perfusion, which means higher Ktrans and Kep values compared with normal blood vessels [29]. Several studies found that there was significant relationship between tumors with high Ktrans values pre chemotherapy have better treatment response compared with those with low Ktrans values, because the chemotherapeutic drugs are delivered more effectively, and the radiosensitivity is higher [30–33]. However, the other study found contrary in Ktrans pre-chemotherapy values and therapy response in squamous cell carcinoma of head and neck, oral cancer and rectal cancer [32, 36, 38].
We also found that the Ktrans value in the good respond group showed a significant decrease after chemotherapy, a finding that corresponded well with those of previous studies, Guo et al. showed that there was a significantly difference between responders and non-responders in Ktrans and Kep at week 9 in osteosarcoma [1]. Other studies, Zhang et al. reported in comparison to the non-responder group, the Ktrans and Kep values in the responder group significantly lower after chemotherapy [28]. Kim et al. attributed the contrasting changes and ratios of Ktrans after chemotheraphy to a larger fibrotic area in good responders, but a substantial, residual, viable tumor area in poor responders [36]. Other study explained the decrease of Ktrans value by lower microvessel density after chemotherapy [37].
The findings of the study showed that Ktrans and Kep after chemotherapy were correlated significantly with histologic response. Good treatment responders had lower Ktrans and Kep values post chemotherapy compared with poor responders. Most research supported the associations of DCE-MRI parameters for the predictive potential of chemotherapy treatment response. Zhang et al. elucidate a similar relationship that following the end of treatment, responders had significantly lower Ktrans and Kep values than non-responders [28]. In a research by Giesel et al. non-responders showed an increase in Kep values throughout chemotherapy while responders showed a drop in Kep values [38]. This outcomes might be attributed to a reduction in microvascular density and permeability brought on by cytostatic and anti-angiogenic vascular disrupting effect.
The change in the Ve value is clinically important for determining how well a tumor responds to treatment [34]. However, Zhang et al. revealed no significant change Ve after complete of chemotherapy [28]. These results are consistent with the findings of our study. The Ve value represents the extracellular space which mean the motion space of water molecules, and is affected by blood flow. Increased blood flow can increase the contrast agent getting into the extracelullar space, so Ve cannot be used alone to evaluate the blood perfusion and extracelullar space. which the microvasculature structure of the tumor could alter following chemotherapy. However, there was no significant change in extracellular space. This may be caused by increased necrosis of tumor cells during chemotherapy, which results in an increase in extracellular space.
Semi quantitative DCE-MRI parameters that consist of the change in slope value and AUC in the good respond group showed a significant decrease after complete chemotherapy and TTP showed a significant increase in good response group after complete chemotherapy. Our results correspond to previous studies [2] that significantly longer TTP in good responders compared to poor-responders after NAC. It means decreased blood perfusion leads to slower in-flow of contrast in the tumor after NAC.
The result Max slope compared to the poor responders following the end of NAC, good responders showed a considerably greater slope (67% reduction) than poor responders (7% reduction). Others study revelead that predict good histologic response with reduction in slope > 60% reduction whereas < 60% was predictive of poor response [23, 29, 41].
The results of this study are the same as previous research that in the good respond group showed a significant decrease AUC after complete chemotherapy compared with poor respond grup [41–43]. Early response to chemotherapy causes the neoangiogenic arteries' vascular permeability to diminish, which lowers the pace of enhancement. Before and after the first treatment cycle, DCE-MRI parameters was examined by Johansen et al. in patients (n = 24) scheduled for NAC. AUC decreased in patients who had a clinical therapeutic response after just one cycle of NAC [41]. Sharma et al. study showed that IAUC was an important indicator of chemotherapeutic response following two cycles of NACT and IAUC showed an early change in responding patients [42]. DCE characteristics were assessed one week following induction chemotherapy by Powel et al. They evaluated the changes of Ktrans and IAUC60 between non-responders and responders in their cohort. Ktrans and IAUC significantly decreased in the responders group after therapy compared to before, falling by around 50% [43].
Our investigation was limited by the fact that all DCE-MRI characteristics for each patient were collected from a single, two dimensional slice across the tumor. Even if the positioning of the slices was carefully chosen based on earlier tests, variations in slice orientation and position could lead to greater variety in the outcomes of subsequent tests. Second, the relatively small sample size may limit the capacity to identify significant differences. Third, measurement inaccuracy may result from the delineation of the interest region being impacted by the radiologist's subjective assessment.
In summary, DCE-MRI can distinguish between patients who respond and those who do not during the NAC course of osteosarcoma using semi-quantitative and quantitative measures. To prevent ineffective NAC in poor responders, the DCE0MRI may be promising noninvasive prognostic markers for osteosarcoma. Therefore, additional research with a bigger sample size is necessary to confirm the utility of DCE-MRI in evaluating the effectiveness of chemotherapy in osteosarcoma.