Analysis of treatment process time for real-time-image gated-spot-scanning proton-beam therapy (RGPT) system.

We developed a synchrotron-based real-time-image gated-spot-scanning proton-beam therapy (RGPT) system and utilized it to clinically operate on moving tumors in the liver, pancreas, lung, and prostate. When the spot-scanning technique is linked to gating, the beam delivery time with gating can increase, compared to that without gating. We aim to clarify whether the total treatment process can be performed within approximately 30 min (the general time per session in several proton therapy facilities), even for gated-spot-scanning proton-beam delivery with implanted fiducial markers.

Bone Sarcomas and Desmoids.

Bone sarcomas are rare tumors arising in bone, representing only a small fraction of solid malignant tumors. Desmoids are benign, infiltrative soft tissue neoplasms. Because of their scarcity and a paucity of data, the management of these tumors can be challenging, especially for clinicians who infrequently encounter these tumors.

Malignant Soft-Tissue Sarcomas.

Soft-tissue sarcomas are cancerous growths of mesenchymal tissues, most commonly arising from fat, muscles, and other connective tissues. Sarcomas are rare, representing only a small fraction of solid malignant tumors. Because of their scarcity and a relative paucity of data, the management of sarcomas can be challenging, especially for those who infrequently encounter these tumors.

Percutaneous insertion of hepatic fiducial true-spherical markers for real-time adaptive radiotherapy.

This study evaluated the success rate and complications of percutaneous implantation of hepatic fiducial true-spherical gold markers for real-time adaptive radiotherapy (RAR), which constitutes real-time image-guided radiotherapy with gating. We retrospectively evaluated 100 patients who underwent 116 percutaneous intrahepatic implantations of 2-mm-diameter, spherical, gold fiducial markers before RAR from 1999 to 2016, with Seldinger's method. We defined technical success as marker placement at the intended liver parenchyma, without mispositioning, and clinical success as successful tracking of the gold marker and completion of planned RAR.

Quantitative evaluation of image recognition performance of fiducial markers in real-time tumor-tracking radiation therapy.

Purpose: To quantitatively evaluate and compare the image recognition performance of multiple fiducial markers available in real-time tumor-tracking radiation therapy (RTRT).

Methods: Clinically available markers including sphere shape, coil shape, cylinder shape, line shape, and ball shape (folded line shape) were evaluated in liver and lung models of RTRT. Maximum thickness of the polymethyl metacrylate (PMMA) phantom that could automatically recognize the marker was determined by template-pattern matching.

A case of Fontan-related hepatocellular carcinoma successfully treated with proton beam therapy.

A 27-year-old woman was admitted to our hospital due to a liver tumor. She had been born late at 41 weeks of gestation and had heterotaxy syndrome, polysplenia, and complete transposition of the great arteries. She underwent percutaneous balloon angioplasty at 5 years of age and the Fontan procedure at 6 years of age.

Physical and biological impacts of collimator-scattered protons in spot-scanning proton therapy.

To improve the penumbra of low-energy beams used in spot-scanning proton therapy, various collimation systems have been proposed and used in clinics. In this paper, focused on patient-specific brass collimators, the collimator-scattered protons' physical and biological effects were investigated. The Geant4 Monte Carlo code was used to model the collimators mounted on the scanning nozzle of the Hokkaido University Hospital.

Clinical experience of craniospinal intensity-modulated spot-scanning proton therapy using large fields for central nervous system medulloblastomas and germ cell tumors in children, adolescents, and young adults.

The outcomes of intensity-modulated proton craniospinal irradiation (ipCSI) are unclear. We evaluated the clinical benefit of our newly developed ipCSI system that incorporates two gantry-mounted orthogonal online X-ray imagers with a robotic six-degrees-of-freedom patient table. Nine patients (7-19 years old) were treated with ipCSI.

A novel range-verification method using ionoacoustic wave generated from spherical gold markers for particle-beam therapy: a simulation study.

This study proposes a novel alternative range-verification method for proton beam with acoustic waves generated from spherical metal markers. When proton beam is incident on metal markers, most of the resulting pressure waves are confined in the markers because of the large difference in acoustic impedance between the metal and tissue. However, acoustic waves with frequency equal to marker's resonant frequency escape this confinement; the marker briefly acts as an acoustic transmitter.

Improving dosimetric outcome for hippocampus and cochlea sparing whole brain radiotherapy using spot-scanning proton arc therapy.

This feasibility study shows that Spot-scanning Proton Arc therapy (SPArc) is able to significantly reduce the dose to the hippocampus and cochlea compared to both Volumetric Modulated Arc Photon Therapy (VMAT) and the robust optimized Intensity Modulated Proton Therapy (ro-IMPT) plans in whole brain radiotherapy. Furthermore, SPArc not only improves plan robustness but could potentially deliver a treatment as efficient as ro-IMPT when proton system's energy layer switch time is less than 1 s.

A Literature Review of Proton Beam Therapy for Prostate Cancer in Japan.

Patients of proton beam therapy (PBT) for prostate cancer had been continuously growing in number due to its promising characteristics of high dose distribution in the tumor target and a sharp distal fall-off. Considering the large number of proton beam facilities in Japan, the further increase of patients undergoing this treatment is due to the emendations by Japanese National Health Insurance (NHI) and the development of medical equipment and technology, it is necessary to know what kind of research and advancements has been done on proton therapy for prostate cancer in the country. For these reasons, this literature review was conducted.

An analytical dose-averaged LET calculation algorithm considering the off-axis LET enhancement by secondary protons for spot-scanning proton therapy.

Purpose: To evaluate the biological effects of proton beams as part of daily clinical routine, fast and accurate calculation of dose-averaged linear energy transfer (LET ) is required. In this study, we have developed the analytical LET calculation method based on the pencil-beam algorithm (PBA) considering the off-axis enhancement by secondary protons. This algorithm (PBA-dLET) was then validated using Monte Carlo simulation (MCS) results.

Validation of the physical and RBE-weighted dose estimator based on PHITS coupled with a microdosimetric kinetic model for proton therapy.

The microdosimetric kinetic model (MKM) is widely used for estimating relative biological effectiveness (RBE)-weighted doses for various radiotherapies because it can determine the surviving fraction of irradiated cells based on only the lineal energy distribution, and it is independent of the radiation type and ion species. However, the applicability of the method to proton therapy has not yet been investigated thoroughly. In this study, we validated the RBE-weighted dose calculated by the MKM in tandem with the Monte Carlo code PHITS for proton therapy by considering the complete simulation geometry of the clinical proton beam line.

Checkpoint kinase 2 is dispensable for regulation of the p53 response but is required for G/M arrest and cell survival in cells with p53 defects under heat stress.

Hyperthermia induced by heat stress (HS) is known to inhibit proliferation and induce cell death in cancer. We previously demonstrated that checkpoint kinase 1 (Chk1) contributes to G/M arrest and cell survival under HS; however, the role of Chk2, a functional analog of Chk1, in regulation of the cell cycle and cell death under HS is still unknown. Here, we addressed the role of Chk2 using Molt-4 cells with p53-targeted shRNA (Molt-4/shp53) and parental control cells (Molt-4/V).

A simulation study on the dosimetric benefit of real-time motion compensation in spot-scanning proton therapy for prostate.

For proton spot scanning, use of a real-time-image gating technique incorporating an implanted marker and dual fluoroscopy facilitates mitigation of the dose distribution deterioration caused by interplay effects. This study explored the advantages of using a real-time-image gating technique, with a focus on prostate cancer. Two patient-positioning methods using fiducial markers were compared: (i) patient positioning only before beam delivery, and (ii) patient positioning both before and during beam delivery using a real-time-gating technique.

Clinical results of proton beam therapy for hepatocellular carcinoma over 5 cm.

Aim: This study aimed 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.

Identifying relations between imaging phenotypes and molecular subtypes of breast cancer: Model discovery and external validation.

Purpose: To determine whether dynamic contrast enhancement magnetic resonance imaging (DCE-MRI) characteristics of the breast tumor and background parenchyma can distinguish molecular subtypes (ie, luminal A/B or basal) of breast cancer.

Materials And Methods: In all, 84 patients from one institution and 126 patients from The Cancer Genome Atlas (TCGA) were used for discovery and external validation, respectively. Thirty-five quantitative image features were extracted from DCE-MRI (1.

Unsupervised Clustering of Quantitative Image Phenotypes Reveals Breast Cancer Subtypes with Distinct Prognoses and Molecular Pathways.

To identify novel breast cancer subtypes by extracting quantitative imaging phenotypes of the tumor and surrounding parenchyma and to elucidate the underlying biologic underpinnings and evaluate the prognostic capacity for predicting recurrence-free survival (RFS). We retrospectively analyzed dynamic contrast-enhanced MRI data of patients from a single-center discovery cohort ( = 60) and an independent multicenter validation cohort ( = 96). Quantitative image features were extracted to characterize tumor morphology, intratumor heterogeneity of contrast agent wash-in/wash-out patterns, and tumor-surrounding parenchyma enhancement.

A Nucleoside Anticancer Drug, 1-(3-C-Ethynyl-β-D-Ribo-Pentofuranosyl)Cytosine, Induces Depth-Dependent Enhancement of Tumor Cell Death in Spread-Out Bragg Peak (SOBP) of Proton Beam.

The effect of 1-(3-C-ethynyl-β-D-ribo-pentofuranosyl)cytosine (ECyd) on proton-induced cell death was evaluated in human lung carcinoma cell line A549 and Chinese hamster fibroblast cell line V79 to enhance relative biological effectiveness (RBE) within the spread-out Bragg peak (SOBP) of proton beams. Treatment with ECyd significantly enhanced the proton-induced loss of clonogenicity and increased senescence at the center, but not at the distal edge of SOBP. The p53-binding protein 1 foci formation assay showed that ECyd decelerated the rate of DNA double-strand break (DSB) repair at the center, but not the distal region of SOBP, suggesting that the ECyd-induced enhancement of proton-induced cell death is partially associated with the inhibition of DSB repair.

Impact of Real-Time Image Gating on Spot Scanning Proton Therapy for Lung Tumors: A Simulation Study.

Purpose: To investigate the effectiveness of real-time-image gated proton beam therapy for lung tumors and to establish a suitable size for the gating window (GW).

Methods And Materials: A proton beam gated by a fiducial marker entering a preassigned GW (as monitored by 2 fluoroscopy units) was used with 7 lung cancer patients. Seven treatment plans were generated: real-time-image gated proton beam therapy with GW sizes of ±1, 2, 3, 4, 5, and 8 mm and free-breathing proton therapy.

Automatic Estimation of Volumetric Breast Density Using Artificial Neural Network-Based Calibration of Full-Field Digital Mammography: Feasibility on Japanese Women With and Without Breast Cancer.

Breast cancer is the most common invasive cancer among women and its incidence is increasing. Risk assessment is valuable and recent methods are incorporating novel biomarkers such as mammographic density. Artificial neural networks (ANN) are adaptive algorithms capable of performing pattern-to-pattern learning and are well suited for medical applications.

Optimization and evaluation of multiple gating beam delivery in a synchrotron-based proton beam scanning system using a real-time imaging technique.

Purpose: To find the optimum parameter of a new beam control function installed in a synchrotron-based proton therapy system.

Methods: A function enabling multiple gated irradiation in the flat top phase has been installed in a real-time-image gated proton beam therapy (RGPT) system. This function is realized by a waiting timer that monitors the elapsed time from the last gate-off signal in the flat top phase.

Evaluation of the relative biological effectiveness of spot-scanning proton irradiation in vitro.

Variations in relative biological effectiveness (RBE) from a fixed value of 1.1 are critical in proton beam therapy. To date, studies estimating RBE at multiple positions relative to the spread-out Bragg peak (SOBP) have been predominantly performed using passive scattering methods, and limited data are available for spot-scanning beams.