Clinical studies of ion beam therapy have been performed at the Lawrence Berkeley Laboratory (LBL), National Institute of Radiological Sciences (NIRS), Gesellschaft für Schwerionenforschung (GSI), ...and Deutsches Krebsforschungszentrum (DKFZ), in addition to the development of equipment, biophysical models, and treatment planning systems. Although cancers, including brain tumors and pancreatic cancer, have been treated with the Bevalac’s neon-ion beam at the LBL (where the first clinical research was conducted), insufficient results were obtained owing to the limited availability of neon-ion beams and immaturity of related technologies. However, the 184-Inch Cyclotron’s helium-ion beam yielded promising results for chordomas and chondrosarcomas at the base of the skull. Using carbon-ion beams, NIRS has conducted clinical trials for the treatment of common cancers for which radiotherapy is indicated. Because better results than X-ray therapy results have been obtained for lung, liver, pancreas, and prostate cancers, as well as pelvic recurrences of rectal cancer, the Japanese government recently approved the use of public medical insurance for carbon-ion radiotherapy, except for lung cancer. GSI obtained better results than LBL for bone and soft tissue tumors, owing to dose enhancement enabled by scanning irradiation. In addition, DKFZ compared treatment results of proton and carbon-ion radiotherapy for these tumors. This article summarizes a series of articles (Parts 1–3) and describes future issues of immune ion beam therapy and linear energy transfer optimization.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Radiation therapy for cancer using the Bragg peak of an ion beam has been making steady progress after being proposed by Robert Wilson in 1946. At the end of 2020, 12 dedicated treatment devices ...existed in operation worldwide, and approximately 40,000 patients have been treated with ion beams (mostly carbon ions). To date, ion beam therapy is superior to other treatments for rare cancers in the head and neck as well as bone and soft tissues; however, most recently, evidence submitted in Japan for the 2022 revision of public health insurance shows that ion beam therapy outperforms photon therapy for intractable common cancers such as pancreatic cancer and liver cancer. This may greatly expand its indications. Lawrence Berkeley Laboratory in the United States started research of ion beam therapy, National Institute of Radiological Sciences in Japan built the first dedicated device Heavy Ion Accelerator in Chiba and started systematic clinical research, and GSI in Germany developed the scanning irradiation method and rotating gantry for the first time. This paper presents the history and future challenges of ion beam therapy in three fields: accelerator and beam delivery system, physical/biological model and treatment planning system, and clinical research. This study is divided into three parts describing the achievements and roles of the three laboratories. In Part 1, accelerator and beam delivery system are described.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
When an ion beam penetrates deeply into the body, its kinetic energy decreases, and its biological effect increases due to the change of the beam quality. To give a uniform biological effect to the ...target, it is necessary to reduce the absorbed dose with the depth. A bio-physical model estimating the relationship between ion beam quality and biological effect is necessary to determine the relative biological effectiveness (RBE) of the ion beam that changes with depth. For this reason, Lawrence Berkeley Laboratory, National Institute of Radiological Sciences (NIRS) and GSI have each developed their own model at the starting of the ion beam therapy. Also, NIRS developed a new model at the starting of the scanning irradiation. Although the Local Effect Model (LEM) at the GSI and the modified Microdosimetric Kinetic Model (MKM) at the NIRS, the both are currently used, can similarly predict radiation quality-induced changes in surviving fraction of cultured cell, the clinical RBE-weighted doses for the same absorbed dose are different. This is because the LEM uses X-rays as a reference for clinical RBE, whereas the modified MKM uses carbon ion beam as a reference and multiplies it by a clinical factor of 2.41. Therefore, both are converted through the absorbed dose. In PART 2, I will describe the development of such a bio-physical model, as well as the birth and evolution of a treatment planning system and image guided radiotherapy.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
4.
History of medical physics Endo, Masahiro
Radiological physics and technology,
12/2021, Volume:
14, Issue:
4
Journal Article
Peer reviewed
Medical physics began with the development of safe handling of radium, such as protecting medical personnel from radiation when radium radiation is used to treat cancer. By the end of World War II, ...the field of medical physics had expanded to the development of safe and reliable treatments for cancer with radiation and quantification of radiation dose, which is called dosimetry that is required to evaluate the therapeutic effect. The rapid development of nuclear technology during World War II made it possible to use large amounts of radioisotopes (RI) produced in nuclear reactors, and the medical use of RI gave birth to clinical nuclear medicine. Since knowledge and skills in radiation measurement and RI handling were required for the development and clinical use of its equipment, nuclear medicine physics was added to medical physics after the war. The invention of computed tomography (CT) in 1972 had a great impact on clinical medicine, while the development of magnetic resonance imaging (MRI) began around that time. As a result, the development of CT and MRI, as well as the study of their image characteristics, which had not necessarily been regarded as the field of medical physics before, was added to that field as radiation diagnostic physics. This review outlines the history of developments in medical physics, and touches on the first medical physicists in Europe and the United States. It also briefly explains the beginning of medical physics and the world-class medical physics achievements in Japan.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
A simple, reasonably accurate method was proposed for fatigue limit prediction in ductile cast irons (DCIs) containing small defects, employing an easy‐to‐use prediction equation. A technique was ...also presented for the estimation of the statistical effects of complex structural discontinuities, as characterized by graphite and casting defects. The validity of these approaches was confirmed by the experimental results obtained via rotating‐bending fatigue tests on six DCIs, with varying distributions of graphite nodule size and different matrix structures.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
T2-FLAIR mismatch sign is known as a highly specific imaging marker of IDH-mutant astrocytomas. This study was intended to clarify what the T2-FLAIR mismatch sign represents by pathological analysis ...of lower-grade gliomas rediagnosed in accordance with the WHO 2016 classification. We retrospectively analyzed the records of 64 patients diagnosed with WHO grade II and III diffuse gliomas between June 2009 and November 2018. T2-FLAIR mismatch sign was found in 10 (45%) out of 22 patients with IDH-mutant astrocytoma, 1 (5%) out of 20 with oligodendroglioma, and 1 (5%) out of 22 with IDH-wild-type astrocytoma. T2-FLAIR mismatch sign as a marker of IDH-mutant astrocytomas showed positive predictive value of 83%. Among 22 patients with IDH-mutant astrocytomas, microcystic change was found in eight, of which seven showed T2-FLAIR mismatch sign. Microcystic change was significantly associated with T2-FLAIR mismatch sign (P < 0.01). From multi-sampling in a patient, abundant microcysts were observed upon HE staining of specimens from the T2-FLAIR mismatched region, while microcysts were hardly observed from the T2-FLAIR matched one. All three protoplasmic astrocytomas among our IDH-mutant astrocytomas presented T2-FLAIR mismatch sign. In conclusion, T2-FLAIR mismatch sign may reflect microcyst formation in IDH-mutant astrocytomas and be common in IDH-mutant protoplasmic astrocytoma.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
•The interferential effect of graphite on fatigue limit of ductile cast iron is negligibly small.•A method to predict the lower bound fatigue limit is presented.•Effects of microstructural ...inhomogeneities and multiaxial loading condition are considered.•The method is convenient for practical engineers since no fatigue test is necessary.•Fatigue tests are performed for cast irons with ferritic, pearlitic and bulls-eye microstructures.
The fatigue strength of ductile cast iron is influenced by microstructural inhomogeneities (i.e., graphite, casting defects and matrix structures composed of different phases). In particular, the presence of small casting defects such as micro-shrinkage cavity can frequently cause not only significant deterioration but also large scatter in fatigue strength. Therefore, the laboratory fatigue tests with a limited number of small-sized specimens could result in a non-conservative estimation. For such a material, the prediction for the lower bound of the scatter in fatigue strength is essential from a practical perspective. In this study, a novel method is presented to predict the lower bound based upon the information of microstructural inhomogeneities and loading conditions. This method offers such an advantage that the lower bound can be reasonably predicted without conducting time-consuming fatigue tests. The predictive capability of the method was verified by comparing to the experimental results obtained in rotating-bending, torsion and combined tension–torsion fatigue tests of ductile cast irons with ferritic, pearlitic and bulls-eye structures.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The efficacy of gefitinib for patients with non‐adenocarcinoma non‐small‐cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations is unclear, because only a small ...percentage of patients enrolled in the clinical trials to evaluate the efficacy of gefitinib for tumors harboring EGFR mutation were non‐adenocarcinoma NSCLC. A pooled analysis was conducted to clarify the efficacy of gefitinib for non‐adenocarcinoma NSCLC patients harboring EGFR mutations. A systematic search of the PUBMED databases was conducted to identify all clinical reports that contained advanced non‐adenocarcinoma NSCLC patients harboring EGFR mutations and treated with gefitinib. The selected patients were advanced non‐adenocarcinoma NSCLC patients harboring EGFR mutations who were treated with gefitinib and described in reports containing the data of the histology, status of EGFR mutations and response to gefitinib. This study selected 33 patients from 15 reports. Twenty‐seven and three of the 33 patients were squamous cell carcinoma and adenosquamous cell carcinoma, respectively. One patient each had large‐cell carcinoma, pleomorphic carcinoma and spindle cell carcinoma. Twenty‐one patients (64%) had sensitive EGFR mutations. The response rate (RR), disease control rate (DCR) and median progression‐free survival (mPFS) was 27%, 67–70% and 3.0 months, respectively. These factors were statistically significantly inferior in the non‐adenocarcinoma NSCLC patients harboring EGFR mutations to adenocarcinoma patients harboring EGFR mutations selected from the same published reports (RR: 27%vs 66%, P = 0.000028; DCR: 67–70%vs 92–93%, P = 0.000014; mPFS: 3.0 vs 9.4 months, P = 0.0001, respectively). Gefitinib is less effective in non‐adenocarcinoma NSCLC harboring EGFR mutations than adenocarcinoma harboring EGFR mutations. (Cancer Sci 2011; 102: 1032–1037)
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
•The influence of artificial defects on the fatigue limit is investigated.•The fatigue limit can be estimated using the √area parameter model.•For defects larger than √area=80μm, the fatigue limit is ...determined by ΔKth,lc.•The stress ratio dependency is determined.•Drilled holes with diameters >50μm cannot be compared with corrosion pits.
Fatigue tests were performed on 17-4PH stainless steel specimens containing small artificial defects, with area ranging from 30 to 900μm at stress ratios, R, of −1, 0.05 and 0.4. An investigation was thus conducted to examine the influence of various types of small artificial defects on fatigue strength, including circumferential notches, corrosion pits, drilled holes and pre-cracked holes. The fatigue limit was determined by the threshold condition for the propagation of a crack emanating from the defects. The threshold stress intensity factor range, ΔKth, exhibited a defect size dependency for area≤80µm , and it became a constant value for area>80µm independent of R. Based on the area parameter model and a material constant of ΔKth for long cracks, the fatigue limit could be predicted as a function of R, with the exception of drilled holes with relatively large diameters of 100 and 300μm, for which the fatigue limit was determined by the critical condition for crack initiation. When artificial defects were absent or non-detrimental, intrinsic defects, such as non-metallic inclusions, were found to control the fatigue strength and, in addition, were responsible for the scatter in the fatigue limit. The proposed method enables the quantitative evaluation of the lower bound of the scatter as a function of the number of test specimens, or the overall control volume of fatigue-loaded components.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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