Discovery of 5-phenyl-3-ureidothiophene-2-carboxamides as protective agents for ALS patient iPSC-derived motor neurons.

We discovered novel neuroprotective compounds by phenotypic screening using SOD1-mutant amyotrophic lateral sclerosis (ALS) patient induced pluripotent stem cell (iPSC)-derived motor neurons. Mechanistic analysis showed that the protective effect of initial hit compound 1 was likely due to the inhibition of MAP4Ks, including MAP4K4, a member of the MAP4K kinase family. Structural transformation led to compound 15f, which showed improved MAP4K4 inhibitory activity and superior neuroprotective effects compared to 1 in motor neurons.

Safety and Efficacy of Single-Fraction Carbon-Ion Radiotherapy for Early-Stage Lung Cancer with Interstitial Pneumonia.

Patients with lung cancer complicated by interstitial pneumonia (IP) often lose treatment options early owing to acute exacerbation of IP concerns. Carbon-ion radiotherapy (CIRT) can provide superior tumor control and low toxicity at high dose concentrations. We conducted a retrospective analysis of the efficacy and tolerability of a single-fraction CIRT using 50 Gy for IP-complicated lung cancer.

Outcomes of carbon ion radiotherapy compared with segmentectomy for ground glass opacity-dominant early-stage lung cancer.

Purpose: This study aimed to compare the outcomes of patients with ground-grass opacity (GGO)-dominant non-small cell lung cancer (NSCLC) who were treated with carbon ion radiotherapy (CIRT) versus segmentectomy.

Methods: A retrospective review of medical records was conducted. The study included 123 cases of clinical stage 0/IA peripheral NSCLC treated with single-fraction CIRT from 2003 to 2012, 14 of which were determined to be GGO-dominant and were assigned to CIRT group.

Comparative Analysis of Photon Stereotactic Radiotherapy and Carbon-Ion Radiotherapy for Elderly Patients with Stage I Non-Small-Cell Lung Cancer: A Multicenter Retrospective Study.

The emergence of an aging society and technological advances have made radiotherapy, especially stereotactic body radiotherapy (SBRT), a common alternative to surgery for elderly patients with early stage non-small-cell lung cancer (NSCLC). Carbon-ion radiotherapy (CIRT) is also an attractive treatment option with potentially lower toxicity for elderly patients with comorbidities. We compared the clinical outcomes of the two modalities using Japanese multicenter data.

Comprehensive analysis of Japanese nationwide cohort data of particle beam therapy for pulmonary, liver and lymph node oligometastases: particle beam therapy versus high-precision X-ray radiotherapy.

Japanese national oncological experts convened to evaluate the efficacy and safety of particle beam therapy (PT) for pulmonary, liver and lymph node oligometastases (P-OM, L-OM and LN-OM, respectively) and to conduct a statistically comparative analysis of the local control (LC) rate and overall survival (OS) rate of PT versus those of X-ray stereotactic body radiotherapy (X-SBRT) and X-ray intensity-modulated radiotherapy (X-IMRT). They conducted [1] an analysis of the efficacy and safety of metastasis-directed therapy with PT for P-OM, L-OM and LN-OM using a Japanese nationwide multi-institutional cohort study data set; [2] a systematic review of X-ray high-precision radiotherapy (i.e.

The Risk Factors for Radiation Pneumonitis After Single-Fraction Carbon-Ion Radiotherapy for Lung Cancer or Metastasis.

There are no studies on the risk factors of radiation pneumonitis (RP) after carbon-ion radiotherapy at a dose of 50 Gy (relative biological effectiveness (RBE)) in a single fraction. The objective of this study was to identify factors associated with RP after radiotherapy, including dose-volume parameters. Ninety-eight patients without a history of thoracic radiotherapy who underwent treatment for solitary lung tumors between July 2013 and April 2016 were retrospectively analyzed.

Long-term clinical outcomes after 12-fractionated carbon-ion radiotherapy for localized prostate cancer.

There are no clinical reports of long-term follow-up after carbon-ion radiotherapy (CIRT) using a dose of 51.6 Gy (relative biological effectiveness [RBE]) in 12 fractions for localized prostate cancer, or of a comparison of clinical outcomes between passive and scanning beam irradiation. A total of 256 patients with localized prostate cancer who received CIRT at a dose of 51.

Differentiation between non-small cell lung cancer and radiation pneumonitis after carbon-ion radiotherapy by F-FDG PET/CT texture analysis.

The differentiation of non-small cell lung cancer (NSCLC) and radiation pneumonitis (RP) is critically essential for selecting optimal clinical therapeutic strategies to manage post carbon-ion radiotherapy (CIRT) in patients with NSCLC. The aim of this study was to assess the ability of F-FDG PET/CT metabolic parameters and its textural image features to differentiate NSCLC from RP after CIRT to develop a differential diagnosis of malignancy and benign lesion. We retrospectively analyzed F-FDG PET/CT image data from 32 patients with histopathologically proven NSCLC who were scheduled to undergo CIRT and 31 patients diagnosed with RP after CIRT.

Carbon-ion Radiotherapy for Colorectal Cancer.

Heavy-ion radiotherapy (RT) is a kind of particle RT, and carbon-ion beam constitutes the primary delivery method of heavy-ion RT. Unlike the conventional photon modalities, particle RT, in particular carbon-ion radiotherapy (CIRT), offers unique physical and biological advantages. Particle therapy allows for substantial dose delivery to tumors with minimal surrounding tissue damage.

Carbon-ion radiotherapy for octogenarians with locally advanced non-small-cell lung cancer.

Purpose: The clinical significance of carbon-ion radiotherapy (CIRT) for octogenarians with locally advanced non-small-cell lung cancer (LA-NSCLC) remains unclear. We aimed to evaluate the clinical outcomes of CIRT alone for octogenarians with LA-NSCLC.

Materials And Methods: We evaluated 32 patients who underwent CIRT alone between 1997 and 2015.

Long Term Results of Single-Fraction Carbon-Ion Radiotherapy for Non-small Cell Lung Cancer.

Background: The purpose of the present study was to evaluate the efficacy and safety of single-fraction carbon-ion radiotherapy (CIRT) in patients with non-small cell lung cancer.

Methods: Patients with histologically confirmed non-small cell lung cancer, stage T1-2N0M0, and treated with single-fraction CIRT (50Gy (relative biological effectiveness)) between June 2011 and April 2016 were identified in our database and retrospectively analyzed. Toxicity was evaluated using the Common Terminology Criteria for Adverse Events version 4.

Safety and Efficacy of Carbon-ion Radiotherapy Alone for Stage III Non-small Cell Lung Cancer.

Background/aim: We evaluated the efficacy and safety of carbon-ion radiotherapy (CIRT) alone for Stage III non-small-cell lung cancer (NSCLC).

Patients And Methods: Data of 65 patients (median age=73 years) with Stage III NSCLC who underwent CIRT alone in the QST Hospital, Chiba, Japan, between 1997 and 2015 were retrospectively analysed. The median dose was 72.

First prospective feasibility study of carbon-ion radiotherapy using compact superconducting rotating gantry.

Objective: We had developed compact rotating gantry for carbon ion using superconducting magnets in 2015 which became clinically operational in 2017. The objective of this study was to assess the clinical feasibility and safety of using compact rotating gantry with three-dimensional active scanning in delivery of carbon-ion radiotherapy (C-ion RT) for relatively stationary tumours.

Methods: A prospective feasibility study was conducted with 10 patients who had been treated with C-ion RT using compact rotating gantry between April 2017 and April 2018 at Hospital of the National Institute of Radiological Sciences (NIRS) for head and neck and prostate cancers.

Carbon-ion radiotherapy for lymph node oligo-recurrence: a multi-institutional study by the Japan Carbon-Ion Radiation Oncology Study Group (J-CROS).

Background: The efficacy of carbon-ion radiotherapy (C-ion RT) for lymph node (LN) oligo-recurrence has only been evaluated in limited single-center studies. We aimed to investigate the benefit of C-ion RT for LN oligo-recurrence in a large multi-center study.

Methods: Patients who received C-ion RT between December 1996 and December 2015 at 4 participating facilities and who met the following eligibility criteria were included: (i) histological or clinical diagnosis of LN recurrence; (ii) controlled primary lesion; (iii) no recurrence other than LN; (iv) LN recurrence involved in a single lymphatic site; and (v) age ≥ 20 years.

Clinical outcomes of carbon-ion radiotherapy for locally advanced non-small-cell lung cancer.

The efficacy and safety of carbon-ion radiotherapy (CIRT) for locally advanced non-small-cell lung cancer (LA-NSCLC) remain unclear. We reported the clinical outcomes of CIRT for LA-NSCLC. Data for 141 eligible patients who received CIRT between 1995 and 2015 were retrospectively analyzed.

Scanned carbon-ion beam therapy throughput over the first 7 years at National Institute of Radiological Sciences.

Introduction: In the 7 years since our facility opened, we have treated >2000 patients with pencil-beam scanned carbon-ion beam therapy.

Methods: To summarize treatment workflow, we evaluated the following five metrics: i) total number of treated patients; ii) treatment planning time, not including contouring procedure; iii) quality assurance (QA) time (daily and patient-specific); iv) treatment room occupancy time, including patient setup, preparation time, and beam irradiation time; and v) daily treatment hours. These were derived from the oncology information system and patient handling system log files.

Tumor Control Probability Analysis for Single-Fraction Carbon-Ion Radiation Therapy of Early-Stage Non-small Cell Lung Cancer.

Purpose: To investigate the suitability of the linear-quadratic (LQ) and universal survival curve (USC) models in describing the 3-year tumor control probability data of patients with stage I non-small cell lung cancer treated with carbon-ion radiation therapy. Carbon-ion radiation therapy was given at a total dose of 59.4 to 95.

Effects of carbon ion beam alone or in combination with cisplatin on malignant mesothelioma cells .

Malignant mesothelioma (MM) is extremely aggressive and a typical refractory cancer. In this study we investigated how effective on killing MM cells by carbon ion beam alone or in combination with cisplatin (CDDP) . Carbon ion beam (at the center of SOBP with 50 keV/µm of average LET) dose-independently suppressed MM cells MESO-1 and H226 cell viability and in combination with CDDP (25 μM) significantly enhanced its action.

Feasibility of carbon-ion radiotherapy for re-irradiation of locoregionally recurrent, metastatic, or secondary lung tumors.

Intrathoracic recurrence after carbon-ion radiotherapy for primary or metastatic lung tumors remains a major cause of cancer-related deaths. However, treatment options are limited. Herein, we report on the toxicity and efficacy of re-irradiation with carbon-ion radiotherapy for locoregionally recurrent, metastatic, or secondary lung tumors.

Carbon-ion radiotherapy for patients with advanced stage non-small-cell lung cancer at multicenters.

Carbon-ion radiation therapy (CIRT) for advanced non-small-cell lung cancer (NSCLC) has not been well studied to date. This paper aimed to analyze a retrospective multicenter survey for detecting problems with the use of CIRT for Stage II and III NSCLC (7th UICC TNM Staging System). Inclusion was restricted to patients with Stage II and III NSCLC who received CIRT from November 2003 to December 2014.

Carbon-ion radiotherapy for non-small cell lung cancer with interstitial lung disease: a retrospective analysis.

Background: Lung cancer is frequently complicated by interstitial lung disease (ILD). Treatment protocols for lung cancer patients with ILD have not been established; surgery, chemotherapy, and radiotherapy can all cause acute exacerbation of ILD. This study evaluated the toxicity and efficacy of carbon ion radiotherapy (CIRT) in patients with non-small cell lung cancer (NSCLC) and ILD.

Carbon-ion re-irradiation for recurrences after initial treatment of stage I non-small cell lung cancer with carbon-ion radiotherapy.

Purpose: To investigate carbon-ion radiotherapy (CIRT) for in-field recurrence of stage I non-small cell lung cancer (NSCLC) initially treated with CIRT.

Materials And Methods: From January 2007 to March 2014, patients initially treated for stage I NSCLC with CIRT and relapsed in-field were candidates. Overall survival (OS) rate, local control (LC) rate, progressive free survival (PFS) rate, dose to the lungs and skin, and adverse effects were analyzed.

Prognostic analysis of radiation pneumonitis: carbon-ion radiotherapy in patients with locally advanced lung cancer.

Background: Carbon-ion radiotherapy (CIRT) is a promising treatment for locally advanced non-small-cell lung cancer, especially for patients with inoperable lung cancer. Although the incidence of CIRT-induced radiation pneumonitis (RP) ≥ grade 2 ranges from 2.5 to 9.

Gating window dependency on scanned carbon-ion beam dose distribution and imaging dose for thoracoabdominal treatment.

Objective: To explore the trade-off between dose assessment and imaging dose in respiratory gating with radiographic fluoroscopic imaging, we evaluated the relationship between dose assessment and fluoroscopic imaging dose in various gating windows, retrospectively.

Methods: Four-dimensional (4D) CT images acquired for 10 patients with lung and liver tumours were used for 4D treatment planning for scanned carbon ion beam. Imaging dose from two oblique directions was calculated by the number of images multiplied by the air kerma per image.