PDAC is the fourth leading cause of cancer-related deaths worldwide, and the incidence is still rising[ 15]. By 2030, the mortality rate of PDAC is estimated to reach second place among malignant tumors[ 16]. Although surgical resection provides a potential treatment for pancreatic adenocarcinoma, only 15% – 20% of patients are suitable for therapeutic pancreatectomy[ 17]. Additionally, about 50% of patients have tumor recurrence after radical surgery. This high recurrence rate is reportedly related to the minimal residual disease on the border of the unresected intact tissue[ 18, 19]. Fortunately, IORT may be used to eliminate residual tumor tissue by irradiating the tumor bed with high doses of radiation. Therefore, IORT is used in patients with LAPC, including resectable or marginal resectable cases[20, 21].
In the past, IORT was performed with an electronic energy source emitting 6–20 MeV high-power electron beams, but radiation-related severe complications can occur[9, 22]. The Mobetron system is the most extensively used device in IORT, and it also has a therapeutic impact on LAPC because of its high electron-beam energy and good radiotherapy effect for deep tumors (> 2 cm)[23]. However, it also brings various adverse reactions, such as gastrointestinal bleeding, bile-duct fibrosis, peripheral nerve reactions, and other pancreas-related complications[23]. It also exerts essential effects on the posterior organs and structures (such as the vertebral body and spinal cord), which is the main complication of IORT for PDAC. Therefore, patients who undergo IORT for pancreatic cancer through the traditional system must accept the risk of developing severe radiotherapy-associated toxicities.
In the present study, we used the INTRABEAM system for IORT and found that the INTRABEAM system was safe for patients with LAPC in IORT. Compared with the traditional system, the INTRABEAM system had advantages in of security. First, it can generate X-rays (30– 50 kV) that are softer, shallower, and have lower energy than the traditional system[24, 25]. Second, it provides low penetration and fast attenuation of radiation dose, an improvement from the development of minimally invasive surgery[26]. Additionally, given the low penetration, the clinical surface can receive relatively high radiation doses. However, no consensus exists regarding the radiation dose for the IORT of patients with LAPC when using the INTRABEAM system. In our study, we used a conservative radiation dose of 10– 15 Gy in the clinical setting. We achieved the effective irradiation intensity when the source applicator was < 5mm from the target tissue. Notably, our patients did not develop radiotherapy-related complications.
Moreover, the appropriate size of the source applicator can be selected according to the size of the tumor and tumor bed when using the INTRABEAM system, thereby facilitating the personalization of IORT. In this study, we set the diameters of the source applicator that could irradiate the entire tumor bed. We stayed far away from normal tissue as much as possible, which averaged 4.7 (3– 6) cm. Before performing the radiotherapy, we used a saline-soaked gauze covering the applicator surrounding to protect the bowel and ensure the localization of radiation to the tumor bed area. No gastrointestinal adverse reactions such as gastrointestinal bleeding, diarrhea, and abdominal pain occurred, suggesting that our bowel protection was successful.
In our study, the 1-year survival rate and median survival time of patients were 70% and 15 months, which were similar to a recent work[27]. Previous studies have reported that IORT could offer excellent local control and substantial pain relief for patients with LAPC, consistent with our results[22, 28, 29]. However, distant metastasis was the main reason for treatment failure, and only local treatment was inadequate for tumor control[30]. The significant benefits of additional chemotherapy for tumor control have also been reported[31, 32]. Therefore, we believe that using the INTRABEAM system, combining chemotherapy may achieve better tumor control and OS in patients with LAPC.
This work had some limitations. First, the study was retrospective and had a relatively small sample. Second, the data originated from a single center. Future studies should be large-scale randomized controlled trials from multiple centers to determine the optimal therapeutic approach.