Surgically defined locally advanced pancreatic cancer (LAPC) is considered unresectable, but there is no evidence of distant metastasis. Therefore, chemotherapy is used as a first-line therapy for systemic control and local therapies, such as radiation therapy, are considered as the next step. Because local tumor control is important, a combination of chemotherapy and radiation therapy is the current standard of care for patients with LAPC. Chemoradiotherapy for local progression can improve pancreatic pain, obstructive symptoms, and quality of life in many patients. However, conventional chemoradiotherapy usually takes 6–7 weeks to complete and involves a risk of acute and late toxicity; therefore, topical treatments with greater efficacy and shorter treatment periods should be developed 2,4,10.
Requirements for highly reproducible treatment setting
1) Position of PTV and OAR: Loi et al. reported that anatomical interfraction variations lead to increases in the OAR dose during SBRT for the routine imaging of pancreatic cancer using integrated CT/CyberKnife and may allow the implementation of strategies to reduce the risk of OAR over-radiation during pancreatic SBRT 5.
2) Respiratory motion control: Campbell et al. compared two competing exercise management methods: abdominal compression (AC) and the respiratory gating of pancreatic SBRT. The reduction owing to compression was significant in the anterior–posterior/up–down direction, but the decrease owing to gating was significant in all directions. Respiratory gating also showed better coverage in scenarios with reduced margins. Respiratory gating is the most effective strategy for reducing pancreatic SBRT movement and may allow the administration of increased doses of radiation through reduced target margins 11.
3) Combined use of images (magnetic resonance imaging [MRI]): Tyagi et al. reported that AC is a viable option for treating patients with LAPC with ablative doses on MRI-guided radiation therapy systems. However, intrafraction motion management is critical and can result in gastrointestinal OARs moving into high dose PTV areas 12.
4) Manipulating the shape of organs (the stomach): As a characteristic of the stomach, the size and morphology of the stomach can vary based on drinking water. In addition, by keeping the amount of water consumed constant in the stomach, the positional relationships of the abdominal organs with each other can be made similar each time. The morphology of the stomach in particular changes depending on the amount of gas and water in the stomach, even during irradiation 13–15.
In our simulation study, we found a positive correlation between the stomach size and dose to the OARs (stomach and pancreas). As the dose to the intestinal tract leads not only to ulcer formation but also to severe intestinal perforation, it is necessary to reduce D 0.1 cc to the maximum possible extent 16.
Therefore, we propose the following methods:
1) Maintain the morphology at the time of cone beam computed tomography (CBCT) and at the time of irradiation of the stomach with butylscopolamine 13;
2) Perform irradiation in the morning on an empty stomach 13;
3) Identify the positional relationship of the stomach with other organs by placing a gold marker in the pancreas 6;
4) Correctly identify the position of the gastrointestinal organs using magnetic resonance (MR)-Linac 17.
In this study, a simulation was performed using a patient with normal weight. People with obesity have high amounts of visceral fat; hence, the stomach and pancreas may be separated. There is a need to examine whether the gastric pretreatment administered to patients with obesity is necessary. It is also necessary to consider the case of a thin person. If of the amount visceral fat is large, it may be possible to separate the OAR from the target organ, and the reduction of weight before irradiation may theoretically be possible. However, it may be unrealistic owing to the progression of cancer.
Nevertheless, we did not find an effect of irradiation on OARs other than the stomach and pancreas in this study. Considering this, the aforementioned noninvasive pretreatment may be beneficial.
The number of indications for SBRT is expected to increase in the future. Establishing a method to protect OARs by using a minimum prescribed dose is necessary 7. There are techniques for artificially moving the position of OARs (sometimes PTV) to exclude the heart from the irradiation field; for example, respiratory synchronization in breast conserving therapy of left breast cancer is performed to reduce the radiation dose to the heart. In addition, techniques for three-dimensional alignment on the body surface have been used 18. MR-Linac has made it possible to understand information regarding the surface and the deeper parts of the body; however, there is a lack of such devices in the market. Therefore, it may be useful to assess whether the organ position can be controlled by pretreatment.
Limitations to this study
This was a simulation study in which highly accurate methods were combined. We previously reported that butylscopolamine could be used on an empty stomach for hemostatic irradiation for gastric cancer and that the shape of the stomach would be similar on CBCT. We formulated a similar hypothesis for pancreatic cancer; however, pancreatic cancer tends to metastasize and may not be similar to gastric cancer. In this regard, it is necessary to investigate the correlation between gastric volume and dose to the stomach in patients with pancreatic cancer 8.