We examined the efficacy and toxicity of proton beam therapy (PBT) for treating advanced cholangiocarcinoma.

The uptake of boron into tumor cells is a key factor in the biological effects of boron neutron capture therapy (BNCT). The uptake of boron agents is suppressed in hypoxic conditions, but the mechanism of hypoxia-induced modulation of suppression of boron uptake is not clear. Therefore, we evaluated whether hypoxia-inducible factor 1α (HIF-1α) contributes to attenuation of the antitumor effects of BNCT in hypoxic tumor cells. We also tested whether YC-1, a HIF-1α-targeting inhibitor, has therapeutic potential with BNCT. To elucidate the mechanism of attenuation of the effects of BNCT caused by hypoxia, deferoxamine (DFO) was used in experiments. Cells were incubated in normal oxygen, hypoxic conditions (1% O2) or 5 μM DFO for 24 h. Then, cells were treated with 10B-boronophenylalanine (BPA) for 2 h and boron accumulation in cells was evaluated. To clarify the relationship between HIF-1α and L-type amino acid transporter 1 (LAT1), gene expression was evaluated by a using HIF-1α gene knockdown technique. Finally, to improve attenuation of the effects of BNCT in hypoxic cells, BNCT was combined with YC-1. Boron uptake was continuously suppressed up to 2 h after administration of BPA by 5 μM DFO treatment. In cells treated with 5 μM DFO, LAT1 expression was restored in HIF-1α-knocked down samples in all cell lines, revealing that HIF-1α suppresses LAT1 expression in hypoxic cells. From the results of the surviving fraction after BNCT combined with YC-1, treatment with YC-1 sensitized the antitumor effects of BNCT in cells cultured in hypoxia.

Adenoid cystic carcinoma (ACC) is a very rare epithelial tumor of the salivary glands. Surgical resection is considered to be a standard therapy. However, the optimal treatment strategy for managing advanced cases has not yet been established. This study evaluated the efficacy and toxicity of proton beam therapy (PBT) combined with selective intra-arterial infusion chemotherapy (IAIC) using weekly cisplatin for locally advanced ACC of the base of the tongue. Between March 2009 and February 2018, 15 patients were treated. The median follow-up duration was 56 (range: 15–116) months. The 5-year local control and overall survival rates were 89% and 76%, respectively. With regard to late toxicities, grade 2 osteoradionecrosis was found in one patient and grade 5 pharyngeal necrosis was observed in one patient. Considering most cases were significantly advanced and inoperable, this therapy was effective in controlling the primary tumor, preserving function and maintaining the quality of life. Although improvements are needed to reduce adverse events, PBT in combination with IAIC can be a treatment option for locally advanced ACC of the base of the tongue.

Purpose: To investigate the dosimetric impact of changes in the large bowel content during proton therapy (PT) with simultaneous integrated boost (SIB) for locally advanced pancreatic cancer (LAPC).Materials and methods: Fifteen patients with LAPC were included in this study. The SIB method was performed using five fields according to our standard protocol. A total dose of 67.5 Gy(relative biological effectiveness [RBE]) was prescribed in 25 fractions using the SIB method. A dose of 45 Gy(RBE) was prescribed for the entire planning target volume (PTV) by using four main fields. The remaining 22.5 Gy(RBE) was prescribed to the PTV excluding for the gastrointestinal tract using one subfield. Five simulated doses were obtained by the forward dose calculations with the Hounsfield units (HU) override to the large bowel to 50, 0, −100, −500, and −1000, respectively. The dose‐volume indices in each plan were compared using the 50 HU plan as a reference.Results: At D₉₈ of the clinical target volume (CTV) and spinal cord‐D_2cc, when the density of the large bowel was close to that of gas, there were significant differences compared to the reference plan (p < 0.05). By contrast, no significant difference was observed in stomach‐D_2cc duodenum‐D_2cc, small bowel‐D_2cc, kidneys‐V₁₈, and liver‐D_mean under any of the conditions. There were no cases in which the dose constraint of organs at risk, specified by our institution, was exceeded.Conclusion: Density change in the large bowel was revealed to significantly affect the doses of the CTV and spinal cord during PT with SIB for LAPC. For beam arrangement, it is important to select a gantry angle that prevents the large bowel from passing as much as possible. If this is unavoidable, it is important to carefully observe the gas image on the beam path during daily image guidance and to provide adaptive re‐planning as needed.