Showing papers by "Koichi Hirata published in 2019"

Randomized phase II trial of survivin 2B peptide vaccination for patients with HLA‐A24‐positive pancreatic adenocarcinoma

Abstract: The prognosis of advanced pancreatic adenocarcinoma is still extremely poor. This study sought to determine the efficacy of, and immunological response to, peptide vaccination therapy in patients with this disease. In this multicenter randomized phase II study, patients with advanced pancreatic adenocarcinoma after gemcitabine and/or tegafur/gimeracil/oteracil were randomly assigned to 3 groups that each received a 2-step treatment course. In Step 1, the groups received treatments of: (i) survivin 2B peptide (SVN-2B) plus interferon-β (IFNβ); (ii) SVN-2B only; or (iii) placebo until the patients show progression. In Step 2, all patients who consented to participate received 4 treatments with SVN-2B plus IFNβ. The primary endpoint was progression-free survival (PFS) after initiation of Step 1 treatment. Secondary endpoints included immunological effects assessed by analysis of PBMCs after Step 1. Eighty-three patients were randomly assigned to receive SVN-2B plus IFNβ (n = 30), SVN-2B (n = 34), or placebo (n = 19). No significant improvement in PFS was observed. Survivin 2B-specific CTLs were found to be increased in the SVN-2B plus IFNβ group by tetramer assay. Among patients who participated in Step 2, those who had received SVN-2B plus IFNβ in Step 1 showed better overall survival compared with those who had received placebo in Step 1. Patients vaccinated with SVN-2B plus IFNβ did not have improved PFS, but showed significant immunological reaction after vaccination. Subgroup analysis suggested that a longer SVN-2B plus IFNβ vaccination protocol might confer survival benefit. (Clinical trial registration number: UMIN 000012146).

Immunohistological Analysis of Pancreatic Carcinoma After Vaccination With Survivin 2B Peptide: Analysis of an Autopsy Series

Abstract: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of cancer by providing new options in addition to existing therapies. However, peptide vaccination therapies still represent an attractive approach, because of the antigen specificity. We identified survivin 2B peptide (SVN-2B), a 9-mer antigenic peptide encoded by survivin, and an SVN-2B peptide vaccine-based phase II randomized clinical trial targeting unresectable and refractory pancreatic carcinoma was undertaken. The SVN-2B peptide vaccine did not have any statistically significant clinical benefits in that study. Therefore, we undertook an autopsy study to analyze the immune status of the pancreatic cancer lesions at the histological level. Autopsies were carried out in 13 patients who had died of pancreatic cancer, including 7 who had received SVN-2B peptide vaccination and 6 who had not, as negative controls. The expression of immune-related molecules was analyzed by immunohistochemical staining. Cytotoxic T lymphocytes were analyzed by tetramer staining and enzyme-linked immunospot assay. Histological analysis revealed dense infiltration of CD8+ T cells in some lesions in patients who had received the SVN-2B peptide vaccine. A high rate of programmed cell death ligand 1 expression in cancer cells was observed in these cases, indicating that CTLs were induced by SVN-2B peptide vaccination and had infiltrated the lesions. The lack of a significant antitumor effect was most likely attributable to the expression of immune checkpoint molecules. These findings suggest that the combination of a tumor-specific peptide vaccine and an ICI might be a promising approach to the treatment of pancreatic carcinoma in the future.

Study Protocol of the Japan NEN Registry: A Multicenter, Prospective Registry of Patients with Pancreatic, Gastrointestinal, Pulmonary, Bronchial, and Thymic Neuroendocrine Neoplasm

Abstract: Introduction: Both the diagnosis and the treatment of patients with neuroendocrine neoplasm (NEN) have recently improved globally. Since little data has been presented on the current situation of NEN treatment in Japan, Japan Neuroendocrine Tumor Society (JNETS) established the Japan NEN Registry study and constructed a registry of Japanese NEN patients with a primary site of the pancreas gastrointestinal tract, lungs, bronchi, and thymus in order to clarify the current status of NEN treatment in Japan. Methods and analysis: The Japan NEN Registry study is a large, multi-institutional prospective cohort study designed by JNETS to clarify actual clinical practice and corresponding outcomes for patients with pathologically diagnosed NENs. At enrollment, demographic characteristics, baseline values and survival event information are reported in an electronic case report form via website. The primary endpoint is overall survival time starting from the date of diagnosis, while the secondary endpoint is progression-free survival starting from the first date of each treatment. Ethics and dissemination: This study is being conducted in accordance with the Declaration of Helsinki and Ethical Guidelines for Clinical Research. The protocol of this cohort study was created in December 2014 and approved by the ethics review committee of Kyoto University Hospital (version 1.0 approval no. E2383, dated Jan 5, 2015). It was subsequently revised to collect treatment information and follow-up clinical outcomes in December 2018, and the ethics review committee of Kyoto University Hospital approved the protocol (Approval No. R1857-1, date April 19, 2019), and the individual institutional review boards of all participating facilities approved this study (TRIAL REGISTRATION: UMIN-CTR: UMIN000016380). The results of this study will be submitted to peer-reviewed international papers. Trial registration: UMIN-CTR: UMIN000016380 Strengths and limitations of this study: • This registration is proposed to provide real-time information on the status of NEN patients in Japan which has not been elucidated so far. • We intend to prospectively collect information on treatments for these patients with corresponding outcomes. • This study allows quantitative, descriptive, and comparative analyses, which will evaluate associations among risk factors, treatment, and outcomes for NEN in Japan.

Current status of projects for developing cancer-related clinical practice guidelines in Japan and recommendations for the future

Abstract: The current status and adoption of cancer-related clinical practice guidelines in Japan has not been elucidated yet. The purpose of this study was to propose roles and suggestions to develop future cancer-related clinical guidelines. A questionnaire consisting of four domains with a total of 17 questions was developed. We distributed the questionnaire to 28 specific academic organizations in Japan which have developed any cancer-related clinical practice guidelines and which were funded by the Ministry of Health, Labor, and Welfare. Most organizations have investigated nationwide dissemination and adoption of clinical practice guidelines. The rate of adoption in clinical practice was estimated at approximately ≥ 70%. However, organizations with smaller budgets reported surveying approximately 60% of the time, whereas the ones with larger budgets reported approximately 100% success in surveying about their guidelines. The presidents of the organizations agreed that a new organization operated directly by the national government was necessary. In Japan, to develop cancer-related clinical practice guidelines, a study of clinical validation is necessary. Sufficient funds must be available to support the project to maintain and revise the guidelines. Furthermore, legal and ethical issues should be solved before establishing any registry system.

Current status of site-specific cancer registry system for the clinical researches: aiming for future contribution by the assessment of present medical care

Abstract: The current status of site-specific cancer registry has not been elucidated, but sufficient system is found in some societies. The purpose of this study was to clear the present condition of site-specific cancer registries in Japan and to suggest for the improvement. The questionnaire was conducted by the study group of the Ministry of Health, Labor, and Welfare. It consisted of 38 questions, conflicts of interest, clinical research method, informed consent and funding for registry. We distributed this questionnaire to 28 academic societies, which had published the clinical practice guideline(s) assessed under Medical Information Network Distribution Service (MINDS). The concept of the importance in assessment for medical quality by the data of the site-specific cancer registry was in good consensus. But the number of the society with the mature registry was limited. The whole-year registry with the scientific researches in the National Clinical Database (NCD) and in the Translational Research Informatics Center (TRI) might seem to be in success, because assured enhancement may be estimated. Now, academic societies have the structural factors, i.e., the financial limitation in the registry maintenance and the data analysis, and in the difficulty of employment of the researchers with skill and talent. To manage the site-specific cancer registry effectively, the scientific registry system will be essentially important. Each academic society had much experienced highly qualified clinical researches in past. Accordingly, the scientific suggestion and co-operation should be of great importance for the improvement.