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There are several reports of hepatic resection for postoperative hepatic metastatic recurrence of esophageal cancer. However, it is unclear whether surgery is the best local treatment for liver metastases. Thus, this study aimed to retrospectively analyze proton beam therapy (PBT) for postoperative liver metastatic recurrence of esophageal cancer without extrahepatic lesions and examine outcomes and adverse events. This single-center historical cohort study selected patients who underwent PBT at our proton therapy center between 2012 and 2018. The patients were selected based on the following criteria: primary esophagus carcinoma was resection and metachronous liver oligometastasis recurrence without extrahepatic tumors and no more than three liver metastases. This study included seven males with a median age of 66 (range, 58–78) years, and 15 lesions were included in the study. The median tumor size was 22.6 (7–55.3) mm. The most frequent dose was 72.6 Gy relative biological effect (RBE)/22 fractions (fr) for four lesions and 64 Gy (RBE)/8 fr for four lesions. The median survival time was 35.5 (13.2–119.4) months. The 1-, 2- and 3-year overall survival (OS) rates were 100%, 57.1% and 42.9%, respectively. The median progression-free survival (PFS) time was 8.7 (1.2–44.1) months. The 1-, 2- and 3-year PFS rates were 28.6%. The 1-, 2- and 3-year local control (LC) rates were 100%. No grade ≥4 radiation-induced adverse events (AEs) were observed. We conclude that PBT can be considered an alternative to hepatic resection for recurrent liver metastases postoperative esophageal cancer.

The purpose of this study was to outline the course and profile of adverse events specific to boron neutron capture therapy (BNCT) for head and neck cancer. This was a sub-analysis of the phase II JHN002 trial. Patients received 400 mg/kg borofalan(10B), followed by neutron irradiation. The course of adverse events after BNCT was documented in the JHN002 Look Up study. Patients were grouped into face/front (FF), face/lateral (FL) and neck (N) beam groups according to the point of skin incidence of the epithermal neutron beam axis, and the profile of adverse events dependent on beam incidence position was examined. The courses of adverse events in eight recurrent squamous cell carcinoma (R-SCC) and 13 recurrent or locally advanced non-SCC cases were analyzed. Median interval to complete recovery was 23 days (interquartile range (IQR), 14–48 days) for oral mucositis, 40 days (IQR, 24–56 days) for dermatitis, 58 days (IQR, 53–80 days) for dysgeusia and 156 days (IQR, 82–163 days) for alopecia. In the FF beam group, parotitis (P = 0.007) was less frequent, while oral mucositis (P = 0.032), fatigue (P = 0.002), conjunctivitis (P = 0.001), epistaxis (P = 0.001) and abdominal discomfort (P = 0.029) tended to be more frequent than in the FL and N beam groups. Courses and irradiation site-specific profiles of adverse events in BNCT for head and neck cancer were identified. This profile may be useful for considering interventions to prevent exacerbation of treatment-related adverse events on BNCT.

Background and purpose Boron neutron capture therapy (BNCT) can be performed without reactors due to development of cyclotron-based epithermal neutron source (C-BENS), which is optimized for treatment for deeper-seated tumors. The purpose of this study was to evaluate efficacy and safety of cyclotron-based BNCT with borofalan (10B) for recurrent or locally advanced head and neck cancer. Materials and methods In this open-label, phase II JHN002 trial of BNCT using C-BENS with borofalan (10B), patients with recurrent squamous cell carcinoma (R-SCC) or with recurrent/locally advanced non-squamous cell carcinoma (R/LA-nSCC) of the head and neck were intravenously administered 400 mg/kg borofalan (10B), followed by neutron irradiation. The tumor dose was determined passively as the mucosal maximum dose of 12 Gy-Eq. The primary endpoint was the objective response rate (ORR). Post-trial observational JHN002 Look Up study was planned for evaluating locoregional progression-free survival (LRPFS). Results Eight R-SCC and 13 R/LA-nSCC patients were enrolled. All R-SCC patients had prior radiotherapy with a median dose of 65.5 Gy (range, 59.4–76.0 Gy). The ORR for all patients was 71%, and complete response/partial response were 50%/25% in R-SCC and 8%/62% in R/LA-nSCC. The 2-year overall survival for R-SCC and R/LA-nSCC were 58% and 100%, respectively. The median LRPFS was 11.5 months for R-SCC. Frequently observed adverse events included alopecia (95%), hyperamylasemia (86%), and nausea (81%). Conclusion These data suggest that BNCT using C-BENS with borofalan (10B) is a promising treatment option for patients with R-SCC or R/LA-nSCC of the head and neck.

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.

There are no existing reports on proton beam therapy (PBT) for local control (LC) of liver metastasis of colorectal cancer (LMCRC). We calculated the LC rate of PBT for LMCRC and explored the influence of each factor on the LC rate.Cases in which PBT was performed at our center between 2009 and 2018 were retrospectively selected from the database. Patients with LMCRC without extrahepatic lesions and no more than three liver metastases were included. Effectiveness was assessed based on LC, overall survival (OS), and progression-free survival (PFS) rates. Adverse events (AEs) are described. Factors that may be related to LC were also investigated.This study included 23 men and 18 women, with a median age of 66 (range 24-87) years. A total of 63 lesions were included in the study. The most frequent dose was 72.6 Gy (relative biological effectiveness)/22 fractions. The median follow-up period was 27.6 months. The 3‑year LC, OS, and PFS rates were 54.9%, 61.6%, and 16.7%, respectively. Our multivariate analysis identified the distance between the tumor and the gastrointestinal (GI) tract as a factor associated with LC (P = 0.02). No grade ≥ 3 AEs were observed. None of the patients experienced liver failure during the acute or late phase.Care must be taken with tumors that have reduced planning target volume coverage owing to organs at risk restrictions, especially in tumors near the GI tract.

Boron neutron capture therapy (BNCT) can be performed without reactors due to development of cyclotron-based epithermal neutron source (C-BENS), which is optimized for treatment for deeper-seated tumors. The purpose of this study was to evaluate efficacy and safety of cyclotron-based BNCT with borofalan (In this open-label, phase II JHN002 trial of BNCT using C-BENS with borofalan (Eight R-SCC and 13 R/LA-nSCC patients were enrolled. All R-SCC patients had prior radiotherapy with a median dose of 65.5 Gy (range, 59.4-76.0 Gy). The ORR for all patients was 71%, and complete response/partial response were 50%/25% in R-SCC and 8%/62% in R/LA-nSCC. The 2-year overall survival for R-SCC and R/LA-nSCC were 58% and 100%, respectively. The median LRPFS was 11.5 months for R-SCC. Frequently observed adverse events included alopecia (95%), hyperamylasemia (86%), and nausea (81%).These data suggest that BNCT using C-BENS with borofalan (

ObjectiveThe purpose of this cross-sectional study was to evaluate the efficacy and safety of proton beam therapy for liver metastatic recurrence in gastric cancer patients.MethodsConsecutive patients who underwent proton beam therapy from 2010 to 2015 were isolated from our institutional database. Patients with extrahepatic metastatic lesions were excluded. Seven patients were enrolled. The median diameter of target lesions was 31 mm (13–68 mm). The most frequent dosage was 72.6 Gy equivalent in 22 fractions. The effectiveness was assessed based on the local control, overall survival and progression-free survival rates. The local control, overall survival and progression-free survival rates were calculated using the Kaplan–Meier method. Adverse events were described according to the patients’ medical records.ResultsThe median follow-up period was 41.7 months (20.7–66.3 months). The 3-year local control, overall survival and progression-free survival rates were 85.7, 68.6 and 43%, respectively. All patients completed proton beam therapy without interruption. No grade ≥3 adverse events were observed.ConclusionsProton beam therapy might be a treatment option for patients with liver metastasis of gastric cancer.

Background The purpose of the present study was to evaluate retrospectively the efficacy and safety of proton beam therapy for elderly patients (≥80 years of age) with non-small cell lung cancer. Methods Patients diagnosed with T1–4 N0 M0 non-small cell lung cancer and treated with proton beam therapy between January 2009 and 2015 were recruited from our database retrospectively. Toxicity was evaluated using The Common Terminology Criteria for Adverse Events version 4.0. Results Thirty-five patients, including 25 (71%) with clinically inoperable lung cancer, were administered proton beam therapy. The median age was 82 years (range: 80–87 years), and the median follow-up time was 34 months (range: 10–72 months). The median dose of proton beam therapy was 80.0 Gy relative biological effectiveness (RBE) (range: 60.0–80.0 Gy [RBE]), and all patients completed the treatments. All patients were followed for at least 23 months or until their death. The 3-year overall survival rate was 67.2% (90.0% in patients with operable lung cancer, and 58.2% in those with inoperable lung cancer). The 3-year local control rate was 86.5%. Two patients presented with grade 2 pneumonitis. The occurrence rate of grade 2 pneumonitis was significantly correlated with a high lung V20 (p = 0.030), and a high mean lung dose (p = 0.030), and a low ratio of lung volume spared from 0.05 Gy (RBE) dose (total lung volume minus lung volume irradiated at least 0.05 Gy [RBE]) (p = 0.030). However, there were no cases of grade 3 or higher radiation pneumonitis. Conclusions This study suggests that the proton beam therapy was feasible for elderly patients with non-small cell lung cancer and can be considered as one of the treatment choices for elderly patients with lung cancer.

Purpose This study was conducted to evaluate the safety and efficacy of proton beam therapy for large hepatocellular carcinoma (HCC). Methods Twenty-four patients with a HCC larger than 5.0 cm were treated with proton beam therapy at our institution between 2008 and 2015. Results The clinical stage was I in 2 patients, II in 9 patients and IIIB in 13 patients. Ten of the 24 patients were not surgical candidates because of advanced HCC or old age. Median tumor size was 90 mm (range, 50-180 mm). Median total dose delivered was 72.6 Gray-equivalents (GyE) in 22 fractions (range, 60.8-85.8 GyE). Median follow-up period was 17.5 months (range, 3-70 months). Local control rate at 2 years was 87.0%. The 2-year overall survival rate was 52.4%. The predominant tumor progression pattern was new hepatic tumor development outside the irradiated field. No acute or late treatment-related toxicity of Grade 3 or higher other than dermatitis was observed. Conclusions These results demonstrate that proton beam therapy offers an effective and safe method for treating patients with large HCC. Proton beam therapy represents a promising modality for treatment of large-volume HCC.

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.

In Japan, biomedical researches are regulated by several statutes and several administrative guidelines. As to the regulation of embryo research, the Act on Regulation of Human Cloning Techniques regulates researches on cloned human embryos and certain embryos with both human and animal genetic elements. There are also several guidelines regulating specific area of research such as genome analysis, gene therapy clinical research, ES-cell research, and so on. However, there was no statute or guideline that regulates genomic improvement of embryos or germ-line cells in general. So, active discussions on the regulation of genome editing occurred in 2016, and temporarily the Expert Panel on Bioethics (EPB) and its subpart (“Task Force”) decided a policy to allow only one type of research using embryos genetically modified by genome-editing technology. The discussion on regulation system has been so confused, and that is probably a reflection of the cultural background of Japanese politics and the law.

The aim of this study was to evaluate the efficacy and safety of proton beam therapy for patients with locally recurrent parotid cancer. Between 2009 and 2012, ten patients with locally recurrent parotid gland cancer were treated with proton beam therapy (70.2 Gy equivalents in 32 fractions) with or without intra-arterial infusion chemotherapy of cisplatin (50 mg/body/week, for a total of 5–8 weeks). The median follow-up was 24 months (range 10–49 months). The 1-year overall survival and local control rates were 80 %, and the 3-year overall survival and local control rates were 60 %. None of the patients experienced grade 3–5 toxicities in the treatment or the follow-up periods. These findings suggest that proton beam therapy could be applied effectively and safely for patients with locally recurrent parotid gland cancer.

Aim The purpose of this study was to clarify the efficacy and toxicities of re-irradiation using proton beam therapy combined with weekly intra-arterial chemotherapy for recurrent oral cancer. Methods Between October 2009 and July 2014, 34 patients who had recurrent oral cancer were treated by proton beam therapy combined with intra-arterial infusion chemotherapy at the Southern Tohoku Proton Therapy Center, Japan. Results For all patients, the median follow-up was 25 months (range, 3–77 months). After treatment, 22 patients (65%) achieved a complete response, and 12 patients (35%) achieved a partial response at the primary tumor site. One-year and 2-year overall survival (OS) rates were 62% and 42%, respectively. One-year and 2-year LC rates were 77% and 60%, respectively. No treatment-related deaths were observed during the treatment and follow-up periods. Conclusion Re-irradiation using proton beam therapy combined with weekly intra-arterial chemotherapy improved OS and local control rates compared with other treatment modalities and could become a new treatment modality for patients with recurrent oral cancer.

Background The purpose of this study was to evaluate the efficacy and toxicities of proton beam therapy combined with intra-arterial infusion chemotherapy via superficial temporal and occipital arteries for recurrent oral cavity squamous cell carcinoma (SCC). Methods Between October 2009 and June 2013, 46 patients with recurrent oral cavity SCC were treated by proton beam therapy combined with intra-arterial infusion chemotherapy of cisplatin (CDDP) and docetaxel. Treatment consisted of proton beam therapy (28.6–74.8 GyE in 13–34 fractions) and intra-arterial infusion chemotherapy (CDDP, 30–50 mg/body/week; docetaxel, 5–25 mg/body/week). Results One-year and 2-year overall survival (OS) rates were 65% and 46%, respectively. One-year and 2-year local control rates were 81% and 70%, respectively. Conclusion These findings suggest that proton beam therapy combined with intra-arterial infusion chemotherapy could be applied effectively and safely for patients with recurrent oral cavity SCC. © 2016 Wiley Periodicals, Inc. Head Neck, 2016

The effect of proton beam therapy (PBT) on various cancers is controversial. We aimed to evaluate the efficacy and safety of PBT with alternating chemoradiotherapy (ACRT) for patients with stage I–III esophageal cancer. Two cycles of systemic chemotherapy with a continuous infusion of 5‐fluorouracil (5‐FU) on days 1–5 and a 5h infusion of nedaplatin (NDP) on day 6 were accompanied by thoracic irradiation using X‐ray therapy and PBT. During the first half of the treatment, X‐rays were delivered to the prophylactic area. During the second half of the treatment, proton beams were used to irradiate the involved field. To reduce the dose of cardiac irradiation, proton beams were delivered with posterior and posterior oblique angles. Between January 2009 and December 2012, 47 patients were enrolled in this study. The median follow‐up duration was 29 months for all patients and 40 months for survivors. The 3 year overall survival rate, progression‐free survival rate, and local control rate were 59.2%, 56.3%, and 69.8%, respectively. With respect to grade 3–4 late toxicities, there were no pleural or pericardial effusions, but two patients (4.3%) had esophageal stenosis, one patient (2.1%) had fistula, and two patients (4.3%) developed radiation pneumonitis. PBT with ACRT might have the potential to reduce the risk of cardiac damage and might become one of the primary methods of esophageal cancer treatment.

This study aimed to evaluate the therapeutic effect and toxicity of proton beam therapy in combination with intra-arterial infusion chemotherapy in patients with squamous cell carcinoma of the maxillary gingiva. Between December 2010 and March 2016, 30 patients with T4 squamous cell carcinoma of the maxillary gingiva were treated with radiotherapy and retrograde intra-arterial infusion chemotherapy using cisplatin (20&ndash, 40 mg/m2, 4&ndash, 6 times). Radiotherapy was basically administered using boost proton beam therapy for primary tumor and neck lymph node tumors, following 36&ndash, 40 Gy photon radiation therapy delivered to the prophylactic area, to a total dose of 70.4&ndash, 74.8 Gy. The median follow-up was 33 months. The 3-year local control and overall survival rates were 69% and 59%, respectively. Major grade 3 or higher acute toxicities included mucositis, neutropenia, and dermatitis in 12 (40%), 5 (17%), and 3 (10%) patients, respectively. No grade 3 or higher late toxicities were observed. These results suggested that proton beam therapy in combination with intra-arterial infusion chemotherapy was not inferior to other treatment protocols and should be considered as a safe and effective option in patients with T4 squamous cell carcinoma of the maxillary gingiva.

Proton beam therapy (PBT), compared with conventional radiotherapy, can deliver high-dose radiation to a tumor, while minimizing doses delivered to surrounding normal tissues. The better dose distribution of PBT may contribute to the improvement in local control rate and reduction in late adverse events. We evaluated therapeutic results and toxicities of PBT combined with selective intra-arterial infusion chemotherapy (PBT-IACT) in patients with stage III–IVB squamous cell carcinoma of the tongue. After 2 systemic chemotherapy courses and whole-neck irradiation (36 Gy in 20 fractions), we administered concurrent chemoradiotherapy comprising PBT for the primary tumor [28.6–33 Gy(RBE) in 13–15 fractions] and for the metastatic neck lymph node [33–39.6 Gy(RBE) in 15–18 fractions] with weekly retrograde intra-arterial chemotherapy by continuous infusion of cisplatin with sodium thiosulfate. Between February 2009 and September 2012, 33 patients were enrolled. The median follow-up duration was 43 months. The 3-year overall survival, progression-free survival, local control rate, and regional control rate for the neck were 87.0, 74.1, 86.6, and 83.9 %, respectively. Major acute toxicities >grade 3 included mucositis in 26 cases (79 %), neutropenia in 17 cases (51 %), and dermatitis in 11 cases (33 %). Late grade 2 osteoradionecrosis was observed in 1 case (3 %). PBT-IACT for stage III–IVB tongue cancer has an acceptable toxicity profile and showed good treatment results. This protocol should be considered as a treatment option for locally advanced tongue cancer.

Background. Evidence has suggested that radiation therapy with a lower dose per fraction may be a reasonable option for the treatment of centrally located non-small cell lung cancer (NSCLC). The aim of this study was to evaluate the safety and efficacy of two proton beam therapy (PBT) protocols for stage I NSCLC and to determine prognostic factors.Material and methods. This study included patients clinically diagnosed with stage I NSCLC. Based on the location of the tumor, one of the two PBT protocols was administered. Patients with peripherally located tumors were given 66 Gy relative biological dose effectiveness (RBE) over 10 fractions (Protocol A) while patients with centrally located tumors were given 80 Gy (RBE) over 25 fractions (Protocol B).Results. Between January 2009 and May 2012, 56 eligible patients were enrolled (protocol A: 32 patients; protocol B: 24 patients). The three-year overall survival (OS), progression-free survival (PFS), and local control (LC) rates were 81.3% [95% confidence interval (CI) 75.9–86.7%], 73.4% (95% CI 67.2–79.6%), and 96.0% (95% CI 93.2–98.8%), respectively. There were no significant differences in outcomes between the two protocols. Late grade 2 and 3 pulmonary toxicities were observed in nine patients (13.4%) and one patient (1.5%), respectively; no grade 4 or 5 toxicities were observed. Sex, age, performance status, T-stage, operability, and tumor pathology were not associated with OS and PFS. Only maximum standardized uptake value (SUVmax; < 5 vs. ≥ 5) was identified as a significant prognostic factor for OS and PFS.Conclusion. Both high-dose PBT protocols achieved high LC rates with tolerable toxicities in stage I NSCLC patients, and SUVmax was a significant prognostic factor.

Polymorphous low-grade adenocarcinoma is a rare malignant tumor that mainly occurs in salivary glands, particularly in the hard palate. To date, surgery has been the most commonly used treatment method with the aim of achieving negative margins of resection. Here, we report a case of a 51-year-old woman who presented with a painless growing mass in her oral cavity with Rouviere’s lymph node metastasis. Laboratory data showed severe anemia because of bleeding from the tumor. We inserted two catheters into the bilateral external carotid arteries via the superficial temporal arteries, and began continuous intra-arterial infusion with cisplatin and a cisplatin-neutralizing agent. The bleeding stopped after the first infusion, and we continued with weekly arterial cisplatin infusion and proton beam therapy (70.4 GyE in 32 fractions). A decrease in tumor volume has been maintained for 2 years, with no evidence of new metastasis.

Background We planned a phase I study of weekly arterial infusion of docetaxel and cisplatin via a superficial temporal artery for recurrent head and neck cancer to determine the optimal dose. Methods The dose of cisplatin was fixed and the dose of docetaxel was escalated from 8 mg/m2, with an increase of 2 mg/m2 per step, to identify the maximum tolerated dose (MTD). In total, 4 courses of weekly chemotherapy were administered. Results Twelve patients were recruited to this trial. The MTD of docetaxel was 14 mg/m2. At this dose level, dose-limiting toxicity was observed in 2 of 3 patients. One patient experienced grade 3 leukopenia, while the other experienced grade 3 leukopenia. Myelosuppression was the dose-limiting toxicity for this regimen. Conclusion The recommended dose for weekly arterial infusion of docetaxel was identified as 12 mg/m2 combined with weekly cisplatin at 40 mg/m2, with 4 courses of each. © 2011 Wiley Periodicals, Inc. Head Neck, 2011

To determine whether anticancer drugs delivered via arterial infusion can permeate entire tumors using a new MRI flow check method. We infused 20 ml of contrast medium (2 ml of Gd-GDPA plus 18 ml of normal saline) over a period of 10 min using a continuous injection pump, then immediately performed MRI using a 1.5 T unit. Images were obtained in 5-mm-thick continuous sections in two or three planes (axial, coronal, and sagittal) depending on the extent of the tumor, and enhanced fast gradient echo 3 D (EFGRE3D) images with a special inversion at lipids were photographed using a neurovascular array coil. The new MRI flow check method delineated an area of tongue cancer perfused with drugs more accurately than conventional methods.The MRI flow check method provides accurate information about areas of arterial infusion.

Purpose This study designed photon and proton treatment plans for patients treated with hypofractionated proton radiotherapy (PT) at the Southern Tohoku Proton Therapy Center (STPTC). We then calculated dosimetric parameters and compared results with simulated treatment plans for stereotactic body radiotherapy (SBRT), using dose--volume histograms to clearly explain differences in dose distributions between PT and SBRT. Methods and Materials Twenty-one patients with stage I non-small-cell lung cancer (stage IA, n = 15 patients; stage IB, n = 6 patients) were studied. All tumors were located in the peripheral lung, and total dose was 66 Gray equivalents (GyE) (6.6 GyE/fraction). For treatment planning, beam incidence for proton beam technique was restricted to two to three directions for PT, and seven or eight noncoplanar beams were manually selected for SBRT to achieve optimal planning target volume (PTV) coverage and minimal dose to organs at risk. Results Regarding lung tissues, mean dose, V5, V10, V13, V15, and V20 values were 4.6 Gy, 13.2%, 11.4%, 10.6%, 10.1%, and 9.1%, respectively, for PT, whereas those values were 7.8 Gy, 32.0%, 21.8%, 17.4%, 15.3%, and 11.4%, respectively, for SBRT with a prescribed dose of 66 Gy. Pearson product moment correlation coefficients between PTV and dose--volume parameters of V5, V10, V15, and V20 were 0.45, 0.52, 0.58, and 0.63, respectively, for PT, compared to 0.52, 0.45, 0.71, and 0.74, respectively, for SBRT. Conclusions Correlations between dose--volume parameters of the lung and PTV were observed and may indicate that PT is more advantageous than SBRT when treating a tumor with a relatively large PTV or several tumors.

2009年2月～2010年1月までの間に超選択的動注化学療法と陽子線治療の併用療法を施行した進行舌癌13例を対象とした。年齢の中央値は63歳，男女比は男／女＝9/4，病理はすべて扁平上皮癌，病期はIII／IVA＝2/11，頸部リンパ節はN0/N1/N2b/N2c＝3/3/3/4であり，手術の場合，舌の全摘・亜全摘となる症例のみとした。治療の一次効果は13例中12例をcomplete response （CR），1例をpartial response（PR）と判定した。経過観察中にPRの1症例を加えた計4例に局所再発を認め，頸部リンパ節再発を計2例認めた。経過観察期間の中央値は12ヵ月と短いが，13例中8例は無病生存中であり，舌の局所制御率は69.2%（9/13）頸部リンパ節に関しては80.0%（8/10）であった。遠隔転移は1例もみられていない。再発症例の検討から，動注環流域確認の重要性が再確認された。経過観察期間は短いが，従来の放射線治療で問題とされてきた下顎骨・歯牙への晩期障害は認められておらず，晩期障害の軽減に有効である可能性が示唆された。また，通常の放射線治療では制御困難である頸部リンパ節の制御率向上の可能性が示唆された。

The purpose of this study was to evaluate the efficacy and toxicities of proton beam therapy combined with intra-arterial infusion chemotherapy via superficial temporal and occipital arteries for recurrent oral cavity squamous cell carcinoma (SCC).Between October 2009 and June 2013, 46 patients with recurrent oral cavity SCC were treated by proton beam therapy combined with intra-arterial infusion chemotherapy of cisplatin (CDDP) and docetaxel. Treatment consisted of proton beam therapy (28.6-74.8 GyE in 13-34 fractions) and intra-arterial infusion chemotherapy (CDDP, 30-50 mg/body/week; docetaxel, 5-25 mg/body/week).One-year and 2-year overall survival (OS) rates were 65% and 46%, respectively. One-year and 2-year local control rates were 81% and 70%, respectively.These findings suggest that proton beam therapy combined with intra-arterial infusion chemotherapy could be applied effectively and safely for patients with recurrent oral cavity SCC. © 2016 Wiley Periodicals, Inc. Head Neck 38:1145-1151, 2016.

OBJECTIVE This study aimed to evaluate the efficacy and toxicity of proton beam therapy combined with cisplatin intra-arterial infusion via a superficial temporal artery as treatment for maxillary sinus carcinoma. METHODS Twenty-six patients with confirmed maxillary sinus carcinoma were enrolled in this study from May 2009 to April 2011. Patients underwent proton beam therapy and intra-arterial infusion chemotherapy with cisplatin. RESULTS The median total dose was 70.4 GyE per 32 fractions, and the median dose of cisplatin was 300 mg/body for six cycles of intra-arterial infusion. The 3-year overall survival rate was 58% for all patients (n = 26), 58% for patients with stage T4 disease (n = 12), 57% for patients with

The single nucleotide polymorphism (SNP) rs13438494 in intron 24 of PCLO was significantly associated with bipolar disorder in a meta-analysis of genome-wide association studies. In this study, we performed functional minigene analysis and bioinformatics prediction of splicing regulatory sequences to characterize the deep intronic SNP rs13438494. We constructed minigenes with A and C alleles containing exon 24, intron 24, and exon 25 of PCLO to assess the genetic effect of rs13438494 on splicing. We found that the C allele of rs13438494 reduces the splicing efficiency of the PCLO minigene. In addition, prediction analysis of enhancer/silencer motifs using the Human Splice Finder web tool indicated that rs13438494 induces the abrogation or creation of such binding sites. Our results indicate that rs13438494 alters splicing efficiency by creating or disrupting a splicing motif, which functions by binding of splicing regulatory proteins, and may ultimately result in bipolar disorder in affected people.

Background We examined the efficacy and toxicity of proton beam therapy (PBT) for treating advanced cholangiocarcinoma. Methods The clinical data and outcomes of 28 cholangiocarcinoma patients treated with PBT between January 2009 and August 2011 were retrospectively examined. The Kaplan–Meier method was used to estimate overall survival (OS), progression-free survival (PFS), and local control (LC) rates, and the log-rank test to analyze the effects of different clinical and treatment variables on survival. Acute and late toxicities were assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Results The median age of the 17 male and 11 female patients was 71 years (range, 41 to 84 years; intrahepatic/peripheral cholangiocarcinoma, n = 6; hilar cholangiocarcinoma/Klatskin tumor, n = 6; distal extrahepatic cholangiocarcinoma, n = 3; gallbladder cancer, n = 3; local or lymph node recurrence, n = 10; size, 20–175 mm; median 52 mm). The median radiation dose was 68.2 Gy (relative biological effectiveness [RBE]) (range, 50.6 to 80 Gy (RBE)), with delivery of fractions of 2.0 to 3.2 Gy (RBE) daily. The median follow-up duration was 12 months (range, 3 to 29 months). Fifteen patients underwent chemotherapy and 8 patients, palliative biliary stent placement prior to PBT. OS, PFS, and LC rates at 1 year were 49.0%, 29.5%, and 67.7%, respectively. LC was achieved in 6 patients, and was better in patients administered a biologically equivalent dose of 10 (BED10) > 70 Gy compared to those administered 70 Gy. Gastrointestinal toxicities, especially those of the duodenum, are dose-limiting toxicities associated with PBT, and early metastatic progression remains a treatment obstacle.

An academic legal colloquium was held under the title ?Globalization and Law?in Tokyo in September/October 2005. The present volume is published in German and Japanese and is a starting-point for academics in both countries.