It is not known how surgery on patients with advanced gastric cancer contributes to survival. In recent years, evidence for the effectiveness of hemostatic RT for gastric cancer has gradually increased, and it has become necessary to assess the therapeutic effect after irradiation 1, 2, 18. In this study, we observed that changes in ADC and CEA are correlated. Additionally, ADC may indicate a biological change earlier than CEA, and the ratios of ADC and CEA may be important factors predicting the therapeutic effects of treatment.
By improving the diagnostic accuracy of MRI for stage T and N gastric cancer, the findings are similar to those of endoscopic ultrasound and CT 8–15. The usefulness of MRI for determining the effects of chemotherapy is also increasing. However, the methodology of hemostatic RT has not been well-established in pretreatment settings using butylscopolamine and CT/MRI including DW-MRI, and it is important to establish a noninvasive method for determining the effect of hemostatic RT.
DW-MRI (as measured by the ADC values) is useful for evaluating gastric cancer 7–9, 19. A weak correlation was found between an increase in the ratio of the ADC value and a decrease in the ratio of the CEA values (measured before and 1 or 3 months after RT). If the outlier in the top-left part of the plot in Figure 4a is excluded, the ratio of ADC (before RT/1 month after RT) and the ratio of CEA (before RT/1 month after RT) showed an inverse correlation (r = −0.154). Similarly, if the outlier in Figure 4b is excluded, the ratio of ADC (before RT/3 months after RT) and the ratio of CEA (before RT/3 months after RT) showed a strong inverse correlation (r = −0.736). As our study only included eight cases, increasing the number of cases may clarify the roles of the ratios of ADC and CEA.
Recently, preoperative tumor, node, and metastases (TNM) stage diagnosis has been established using DW-MRI 10, 14, 15. Additionally, DW-MRI is increasingly used to estimate the therapeutic effect of treatment, especially in chemotherapy.
For RT, the stomach shape must remain the same before, during, and after treatment, so RT was administered on an empty stomach. In addition to DW images, we also assessed T1-weighted, T2-weigted, and fat saturation T2-weighted images. These are useful for observing the size of the gastric tumor (thickness of the stomach wall) and are required for qualitative measurement. DW-MRI is considered to be better for functional (biological) evaluation.
Previously, pretreatment stage diagnosis and the response to chemotherapy and RT had been measured by dilating the gastric content as much as possible with water to help locate the tumor by extending the stomach wall 14, 15. Stomach distension is certainly useful for determining tumor size, but when it comes to RT, it is necessary to reduce the size of the stomach. If this is not done, it would be difficult to irradiate in the same manner because of a large difference between the pretreatment diagnosis (on a stomach full of water) and treatment plan CT/MRI images (on an empty stomach). Therefore, pretreatment diagnosis and RT planning must be done using the same settings.
Due to the small number of cases in this study, no statistically significant relationship was found with survival time. In a previous study, hemostatic RT for gastric cancer was successful in 25 of 31 cases, but the median survival time was 91 (range, 46–299) days, and there were many cases of recurrence after 3 months 1.
Considering that the ADC value decreased earlier than the CEA value raises the possibility that the ADC value may detect changes in the tumor earlier than the CEA value (Figure 3). An inverse correlation in the ratios of ADC and CEA was observed in the subanalysis, which was strong if the outlier in the subanalysis was excluded. Nevertheless, future studies investigating the relationship between the ADC and CEA values on a larger sample population are warranted.
As this study only included eight cases that survived up to 3 months after treatment, the hemostatic effect naturally appeared after 1 month (hemoglobin and CEA values in the blood test), and all patients showed a partial response. Endoscopic findings showed that hemostasis was nearly achieved, with some tumors being scarred and some being ulcerated.
There is an inverse correlation between the ADC value and T and N staging 11–15, which may be useful in predicting the response to neoadjuvant therapy. These values may potentially also serve as prognostic factors in assessing gastric cancer aggression.
When using ADC values in clinical practice, there is a lack of consensus on how to calculate and interpret them. They are calculated based on the region of interest, which can be drawn manually and be based on T2W or DW-MRI images with different b values (800–1200). Some authors suggest using the maximum ADC value, whereas others consider the average ADC value. This undermines the direct comparison of ADC value results between studies and emphasizes the need for careful protocol standardization, image analysis, and measurement reproducibility between centers before implementation.
Three of the six men and both women in this study were able to receive chemotherapy. The fact that chemotherapy can be performed means that there is a hemostatic effect, and the general condition has improved, and it is considered a treatment bias when chemotherapy can be performed. Our results suggest that the presence of chemotherapy may contribute to survival. Two of the five patients were treated with nivolumab, and both survived for >1 year. The relationship between RT and immunotherapy has been reported by Herrera et al. 20. Additionally, RT and immunotherapy are involved in hemostatic RT for gastric cancer, and hence, further investigation is needed.
In conclusion, the usefulness of DW-MRI has been reported mainly for solid tumors. Herein, we evaluated the usefulness of DW-MRI for gastric cancer using a tumor marker in RT settings. We showed that changes in the ADC values and changes in the CEA values are correlated using ratios (before/1 or 3 months after RT). Additionally, 3 months after treatment, a decrease in ADC appeared earlier than a decrease in CEA. Our findings suggest that ADC may represent biological changes earlier than CEA.