Proton beam therapy for intrahepatic cholangiocarcinoma: A multicenter prospective registry study in Japan

Introduction: Intrahepatic cholangiocarcinoma (ICC) can be treated with chemotherapy in unresectable cases, but outcomes are poor. Proton beam therapy (PBT) may provide an alternative treatment and has good dose concentration that may improve local control. Methods: Fifty-nine patients who received initial PBT for ICC from May 2016 to June 2018 at nine centers were included in the study. The treatment protocol was based on the policy of the Japanese Society for Radiation Oncology. Forty patients received 72.6-76 Gy (RBE) in 20-22 fr, 13 received 74.0-76.0 Gy (RBE) in 37-38 fr, and 6 received 60-70.2 Gy (RBE) in 20-30 fr. Overall survival (OS) and progression-free survival (PFS) were estimated by Kaplan-Meier analysis. Results: The 59 patients (35 men, 24 women; median age 71 years; range 41-91 years) had PS of 0 (n=47), 1 (n=10) and 2 (n=2). Nine patients had hepatitis and all 59 cases were considered inoperable. The Child-Pugh class was A (n=46), B (n=7), and unknown (n=6); the median maximum tumor diameter was 5.0 cm (range 2.0-15.2 cm); and the clinical stage was I (n=12), II (n=19), III (n=10), and IV (n=18). At the last follow-up, 17 patients were alive (median follow-up 36.7 months; range 24.1-49.9 months) and 42 had died. The median OS was 21.7 months (95% CI 14.8-34.4 months). At the last follow-up, 37 cases had recurrence, including 10 with local recurrence. The median PFS was 7.5 months (95% CI 6.1-11.3 months). In multivariable analyses, Child-Pugh class was significantly associated with OS and PFS, and Child-Pugh class and hepatitis were significantly associated with local recurrence. Four patients (6.8%) had late adverse events of Grade 3 or higher. Discussion/Conclusion. PBT gives favorable treatment outcomes for unresectable ICC without distant metastasis and may be particularly effective in cases with large tumors

Existence of a Neuropathic Pain Component in Patients with Osteoarthritis of the Knee

∙ The authors have no financial conflicts of interest. © Copyright: Yonsei University College of Medicine 2012 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial Licens

Hydrophobic Amino Acid Tryptophan Shows Promise as a Potential Absorption Enhancer for Oral Delivery of Biopharmaceuticals

Cell-penetrating peptides (CPPs) have great potential to efficiently deliver drug cargos across cell membranes without cytotoxicity. Cationic arginine and hydrophobic tryptophan have been reported to be key component amino acids for cellular internalization of CPPs. We recently found that l-arginine could increase the oral delivery of insulin in its single amino acid form. Therefore, in the present study, we evaluated the ability of another key amino acid, tryptophan, to enhance the intestinal absorption of biopharmaceuticals. We demonstrated that co-administration with l-tryptophan significantly facilitated the oral and intestinal absorption of the peptide drug insulin administered to rats. Furthermore, l-tryptophan exhibited the ability to greatly enhance the intestinal absorption of other peptide drugs such as glucagon-like peptide-1 (GLP-1), its analog Exendin-4 and macromolecular hydrophilic dextrans with molecular weights ranging from 4000 to 70,000 g/mol. However, no intermolecular interaction between insulin and l-tryptophan was observed and no toxic alterations to epithelial cellular integrity—such as changes to cell membranes, cell viability, or paracellular tight junctions—were found. This suggests that yet to be discovered inherent biological mechanisms are involved in the stimulation of insulin absorption by co-administration with l-tryptophan. These results are the first to demonstrate the significant potential of using the single amino acid l-tryptophan as an effective and versatile bioavailability enhancer for the oral delivery of biopharmaceuticals

How did the particle therapy grow in the Japanese radiation therapy

Purpose/Objective(s):In Japan, we have experienced the particle therapy for more than tenyears. The Japan Clinical Study Group of Particle Therapy (JCPT) studiedthe achievements of the Japanese particle therapy from 2002 to 2009. Ourstudy group covered the all Japanese particle therapy institutions. Theaim of the paper is to disclose the status of the Japanese particletherapy and to analyze the change of the number of the therapy.\nMaterials/Methods:The JCPT member consisted of the eight particle therapy institutions.Each hospital was (1) Southern Tohoku Proton Therapy Center, (2) ProtonMedical Research Center, University of Tsukuba, (3) Division ofRadiation Oncology, National Cancer Center, (4) Research Center forCharged Particle Therapy, National Institute of Radiological Sciences,(5) Proton Therapy Division, Shizuoka Cancer Center Hospital, (6) TheWakasa Wan Energy Research Center, (7) Hyogo Ion Beam Medical center and(8) Gunma University. The JCPT office gathered each institution\u27s annualreport and analyzed the number of treatments. Particle therapy wasdivided into a proton therapy and a carbon ion therapy. We analyzed thedisease, gender and age distributions.\nResults:The number of particle therapy treatment from 2002 to 2009 reached10,782. Each annual number of particle therapy was 520 (244 proton:p,276 carbon:c) in 2002, 794 (474 p, 320 c) in 2003, 1082 (699 p, 383 c)in 2004, 1276 (803 p, 473 c) in 2005, 1453 (827 p, 626 c) in 2006, 1712(923 p, 789 c) in 2007, 1712 (781 p, 931 c) in 2008, 2233 (1278 p, 955c) in 2009. The number of patients according to the primary lesionranged 198 (164 p, 34 c) for CNS tumors, 1448 (815 p, 633 c) for Headand Neck tumors, 1241 (742 p, 499 c) for lung tumors, 112 (77 p, 35 c)for upper digestive organ tumors, 1257 (947 p, 310 c) for liver tumors,151 (42 p, 109 c) for pancreas tumors, 73 (8 p, 65 c) for gynecologicaltumors, 2509 (1770 p, 739 c) for prostate tumors, 659 (118 p, 541 c) forbone and soft tissue tumors, 246 (44 p, 202 c) for recurrent rectaltumors and 1275 (438 p, 837 c) for other or unclassified tumors. Thetreatment for prostate cancer was a major target. The genderdistribution of the patients treated by the particle therapy was 7933for male and 2849 for female. The male patients were almost three timesas many as the female patients.\nConclusions:This paper reports the activity of Japanese particle therapy for 8years. We think that the analysis of the particle therapy is veryimportant for the radiation oncology. We will be able to realize thedesirable co-operation between the JCPT hospitals and establish theJapanese database concerned with the proton and carbon ion therapy.This study was supported by Grants-in-Aid for Scientific Research(2009-Gan Ippan-008) from the Ministry of Health, Labor and Welfare ofJapan

Correlations of post-implant regional dosimetric parameters at 24 hours and one month, with clinical results of low-dose-rate brachytherapy for localized prostate cancer

Purpose : To evaluate the correlations of post-implant regional dosimetrics at 24 hours (24 h) and 1 month after implant procedures, with clinical outcomes of low-dose-rate (LDR) brachytherapy for localized prostate cancer. Material and methods : Between January 2008 and December 2014, 130 consecutive patients treated for localized prostate cancer, receiving definitive iodine-125 ( 125 I) brachytherapy treatment were retrospectively analyzed. All patients underwent post-implant CT imaging for dosimetric analysis at 24 h and 1 month after implantation procedure. Prostate contours were divided into quadrants: anterior-superior (ASQ), posterior-superior (PSQ), anterior-inferior (AIQ), and posterior-inferior (PIQ). Predictive factors and cut-off values of biochemical failure-free survival (BFFS) and toxicities of LDR brachytherapy were analyzed. Results : The median follow-up time was 69.5 months. Seven patients (5.4%) had biochemical failure. The 3-year and 5-year BFFS rates were 96.7% and 93.1%, respectively. On multivariate analysis, prostate-specific antigen and Gleason score were significant prognostic factors for biochemical failure. D 90 (the minimal dose received by 90% of the volume) of PSQ and PIQ at 24 h, and D 90 of PSQ at 1 month were also significant factors. The cut-off values of PSQ D 90 were 145 Gy at 24 h and 160 Gy at 1 month. D 90 of the whole prostate was not significant at 24 h and at 1 month. D 90 of PSQ at 1 month was a significant factor for rectal hemorrhage. Conclusions : Post-implant D 90 of PSQ is significantly associated with BFFS for localized prostate cancer not only at 1 month, but also at 24 hours. D 90 of PSQ at 1 month is also a significant factor for rectal hemorrhage

How did the particle therapy grow in the Japanese radiation therapy

Purpose/Objective(s): In Japan, we have experienced the particle therapy for more than tenyears. The Japan Clinical Study Group of Particle Therapy (JCPT) studiedthe achievements of the Japanese particle therapy from 2002 to 2009. Ourstudy group covered the all Japanese particle therapy institutions. Theaim of the paper is to disclose the status of the Japanese particletherapy and to analyze the change of the number of the therapy.\nMaterials/Methods:The JCPT member consisted of the eight particle therapy institutions.Each hospital was (1) Southern Tohoku Proton Therapy Center, (2) ProtonMedical Research Center, University of Tsukuba, (3) Division ofRadiation Oncology, National Cancer Center, (4) Research Center forCharged Particle Therapy, National Institute of Radiological Sciences,(5) Proton Therapy Division, Shizuoka Cancer Center Hospital, (6) TheWakasa Wan Energy Research Center, (7) Hyogo Ion Beam Medical center and(8) Gunma University. The JCPT office gathered each institution\u27s annualreport and analyzed the number of treatments. Particle therapy wasdivided into a proton therapy and a carbon ion therapy. We analyzed thedisease, gender and age distributions.\nResults:The number of particle therapy treatment from 2002 to 2009 reached10,782. Each annual number of particle therapy was 520 (244 proton:p,276 carbon:c) in 2002, 794 (474 p, 320 c) in 2003, 1082 (699 p, 383 c)in 2004, 1276 (803 p, 473 c) in 2005, 1453 (827 p, 626 c) in 2006, 1712(923 p, 789 c) in 2007, 1712 (781 p, 931 c) in 2008, 2233 (1278 p, 955c) in 2009. The number of patients according to the primary lesionranged 198 (164 p, 34 c) for CNS tumors, 1448 (815 p, 633 c) for Headand Neck tumors, 1241 (742 p, 499 c) for lung tumors, 112 (77 p, 35 c)for upper digestive organ tumors, 1257 (947 p, 310 c) for liver tumors,151 (42 p, 109 c) for pancreas tumors, 73 (8 p, 65 c) for gynecologicaltumors, 2509 (1770 p, 739 c) for prostate tumors, 659 (118 p, 541 c) forbone and soft tissue tumors, 246 (44 p, 202 c) for recurrent rectaltumors and 1275 (438 p, 837 c) for other or unclassified tumors. Thetreatment for prostate cancer was a major target. The genderdistribution of the patients treated by the particle therapy was 7933for male and 2849 for female. The male patients were almost three timesas many as the female patients.\nConclusions:This paper reports the activity of Japanese particle therapy for 8years. We think that the analysis of the particle therapy is veryimportant for the radiation oncology. We will be able to realize thedesirable co-operation between the JCPT hospitals and establish theJapanese database concerned with the proton and carbon ion therapy.This study was supported by Grants-in-Aid for Scientific Research(2009-Gan Ippan-008) from the Ministry of Health, Labor and Welfare ofJapan.ASTRO　５２nd Annual Meetin