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Purpose We performed a planning study to compare the dose distribution of the line scanning (LS) method with that of passive scattering (PS) method and volumetric modulated arc therapy (VMAT) for patients with localized prostate cancer. Methods Thirty patients treated in 2017–2019 were randomly selected. The dose constraints were the clinical target volume (CTV) D98 ≥ 73.0 Gy (RBE), rectal wall V65

To assess the safety and efficacy of proton beam therapy (PBT) for muscle-invasive bladder cancer (MIBC), we examined the outcomes of 36 patients with MIBC (cT2-4aN0M0) who were enrolled in the Proton-Net prospective registry study and received PBT with concurrent chemotherapy from May 2016 to June 2018. PBT was also compared with X-ray chemoradiotherapy in a systematic review (X-ray (photon) radiotherapy). The radiotherapy consisted of 40–41.4 Gy (relative biological effectiveness (RBE) delivered in 20–23 fractions to the pelvic cavity or the entire bladder using X-rays or proton beams, followed by a boost of 19.8–36.3 Gy (RBE) delivered in 10–14 fractions to all tumor sites in the bladder. Concurrently, radiotherapy was given with intra-arterial or systemic chemotherapy of cisplatin alone or in combination with methotrexate or gemcitabine. Overall survival (OS), progression-free survival (PFS) and local control (LC) rates were 90.8, 71.4 and 84.6%, respectively, after 3 years. Only one case (2.8%) experienced a treatment-related late adverse event of Grade 3 urinary tract obstruction, and no severe gastrointestinal adverse events occurred. According to the findings of the systematic review, the 3-year outcomes of XRT were 57–84.8% in OS, 39–78% in PFS and 51–68% in LC. The weighted mean frequency of adverse events of Grade 3 or higher in the gastrointestinal and genitourinary systems was 6.2 and 2.2%, respectively. More data from long-term follow-up will provide us with the appropriate use of PBT and validate its efficacy for MIBC.

We reviewed the outcomes of glioma patients enrolled in a prospective observational registry study of proton beam therapy (PBT) in Japan. The inclusion criteria were glioma patients registered in the Electronic Data Capture system, the Proton-net, between May 2016 and July 2019. Data on patient characteristics, treatments, late adverse events, survival status, recurrence and secondary tumors were extracted and statistically analyzed. The primary endpoint was the overall survival (OS) rate, and the secondary endpoints were the progression-free survival (PFS) rate and cumulative local recurrence rate (cLRR). Of the 65 primary brain tumor patients registered, 29 glioma patients from eight of 19 PBT facilities met the inclusion criteria. There were 19 glioblastoma patients, eight of other malignant gliomas, and two of low-grade gliomas. For glioblastomas, with a median follow-up period of 16 months, the median survival time was 21.2 months and the OS at 1, 2, 3 and 4 years were 77.4%, 44.9%, 23.9% and 23.9%, respectively. The median PFS period was 10.1 months, the 1, 2, 3 and 4-year PFS were 32.4%, 19.4%, 9.7% and 9.7%, respectively. The 1, 2, 3 and 4-year cLRR were 56.1%, 68.8%, 78.4 and 78.4%, respectively. Grade 3 brain necrosis was observed in two patients. No secondary tumor was observed. This is the first report on the current status of PBT for gliomas in Japan. For glioblastomas, the outcomes of PBT are estimated to be equivalent to historical data of photon therapy. The results of a prospective comparative evaluation of PBT and photon therapy are awaited.

To examine the efficacy and toxicity of particle beam therapy (PT) for biliary duct carcinoma (BDC) and compare the outcomes between extrahepatic BDC (eBDC) and intrahepatic BDC (iBDC). We analyzed multi-institutional data from May 2009 to December 2019. The primary endpoint was overall survival (OS), and the secondary endpoints were local control (LC), progression-free survival (PFS) and toxicity. We included 150 patients with unresectable BDC treated with PT using a median prescribed dose of 70.2 GyRBE (range, 44–77 GyRBE) in 25 fractions (range, 10–38 fractions). With a median follow-up of 13.0 months, median survival time (MST) was 21 months, and 2-year OS was 44.8%. For eBDC and iBDC, the MSTs were 20 and 23 months, respectively. Two-year PFS and LC rates were 20.6% and 66.5%, respectively. Vascular invasion, prescribed dose and serum tumor marker level (carcinoembryonic antigen: CEA) were identified as poor prognostic factors for OS. A higher radiation dose EQD2 ≥ 67 Gy showed superior OS, with a hazard ratio of 0.341. The radiation dose of PT is an important predisposing factor for overall survival. The MST for patients with eBDC given a higher radiation dose was 25 months, compared to 15 months for those given the lower dose and 23 months for patients with iBDC (all iBDC given higher doses). iBDC and eBDC duct carcinomas showed equivalent outcomes with PT, especially when treated with a high radiation dose. In detailed analysis, baseline CEA level in iBDC, and radiation dose and GTV in eBDC were statistically significant predicators for OS. Acute and late toxicity grade ≥3 occurred in 2.2% and 2.7% of patients, respectively, including two late grade-5 toxicities. In conclusion, PT showed good efficacy for BDC, both eBDC and iBDC, with a low incidence of severe toxicity.

Purpose To assess the correlation between postimplant dosimetric quantifiers and the genitourinary (GU) toxicity of low-dose rate brachytherapy for prostate cancer. Methods and Materials The minimum urethral dose (UD10, 30, and 90) and the percent volume of the urethra receiving the prescription dose (V100, V150) were calculated from the postimplant dose-volume histograms of 182 patients. We then calculated various urethral biologically equivalent doses (uBEDs) using different values of the α/β ratio and tissue repair half-time (t1/2) and examined the correlations with GU toxicity. Results Common dosimetric quantifiers, such as UD90 (brachytherapy) + UD50 (external beam radiotherapy), showed no correlation with Grade ≥ 2 GU toxicity. There was a significant correlation between Grade ≥2 GU toxicity and uBED when the α/β value was 0.5 or 1 Gy and t1/2 was 0.5–2.5 h. An uBED (α/β = 1.0, t1/2 = 0.5) had the largest hazard ratio for GU toxicity, and it was also significantly correlated with Grade ≥ 2 GU toxicity according to multivariate analysis. Conclusions We observed a significant correlation of uBED with GU toxicity when α/β was 0.5 or 1.0 Gy and t1/2 was 0.5–2.5 h. As the simple formula we used has not been verified in basic experiments, more data are needed to validate our results.

An 18-year-old man presented with sudden vision loss in his left eye. Magnetic resonance imaging revealed a tumor that had invaded the left optic nerve, originating from the left posterior ethmoid sinus. Immunohistochemical analyses identified positive staining for NUT protein in the nuclei of tumor cells. We diagnosed locally advanced NUT carcinoma (NC) and initiated concurrent chemoradiotherapy (CCRT), consisting of chemotherapy with vincristine, doxorubicin, and cyclophosphamide, alternating with ifosphamide and etoposide, plus radiation therapy. The patient achieved a complete response. CCRT can be a useful treatment option for adolescent and young-adult patients with locally advanced unresectable NC.

Purpose Although proton therapy is controversial, it has been used to treat localized prostate cancer over the past 2 decades. The purpose of this study is to examine the long-term efficacy and toxicity of proton therapy for localized prostate cancer. Methods and Materials This was a retrospective observational study of 2021 patients from 2003 to 2014 at a single institution. Patients were classified using the risk groups defined by the National Comprehensive Cancer Network guidelines, version 4.2019. Ninety-eight percent of the patients received 74 Gy (relative biological effectiveness) in 37 fractions. Fifty-one and 6% of the patients received neoadjuvant and adjuvant androgen deprivation therapy, respectively. The outcomes were the time of freedom from biochemical relapse and the time to late toxicity by the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0. The outcomes were estimated using the Kaplan-Meier method and were analyzed using multivariable Cox proportional hazards models. Results The median follow-up period was 84 months (interquartile range, 60-110). The 5- and 10-year freedom from biochemical relapse rates were 100% and 100%, 99% and 88%, 93% and 86%, 90% and 79%, 88% and 68%, and 76% and 63% for the very low, low, favorable intermediate, unfavorable intermediate, high, and very high-risk groups, respectively. Patients with higher risk experienced biochemical relapse after shorter periods. The 5-year rates of grade 2 or higher late genitourinary and gastrointestinal toxicity were 2.2% and 4.0%, respectively. The results of multivariable analyses indicate that younger patients more often experienced biochemical relapse. Conclusions This study demonstrates the favorable biochemical controls of proton therapy even in advanced localized prostate cancer patients with a low incidence of late toxicities, supporting the feasibility of conducting prospective clinical trials. The risk groups defined by the National Comprehensive Cancer Network guidelines, version 4.2019, are useful to classify patients with localized prostate cancer. Our findings might suggest the necessity to develop a treatment strategy that accounts for the patient’s age.

The aim of this retrospective study was to report long‐term clinical outcomes in patients treated with proton therapy (PT) for localized prostate cancer. Between 2001 and 2014, 1375 consecutive patients were treated with PT. Patients were classified into prognostic risk groups based on the National Comprehensive Cancer Network criteria. Freedom from biochemical relapse (FFBR), cancer‐specific survival (CSS) and incidence of late gastrointestinal (GI)/genitourinary (GU) toxicities were calculated. Multivariate analysis was performed to identify clinical prognostic factors for FFBR and late toxicities. The median follow‐up period was 70 months (range, 4–145 months). In total, 99% of patients received 74 Gy (relative biologic effectiveness [RBE]); 56% of patients received neoadjuvant androgen deprivation therapy. For the low‐, intermediate‐, high‐, and very high‐risk groups, 5‐year FFBR was 99% (95% confidence intervals [CI], 96–100%), 91% (95% CI, 88–93%), 86% (95% CI, 82–89%), and 66% (95% CI, 53–76%), respectively, and 5‐year CSS was 100% (95% CI, 100–100%), 100% (95% CI, 100–100%) , 99% (95% CI, 97–100%), and 95% (95% CI, 94–98%), respectively. Patient age, T classification, Gleason score, prostate‐specific antigen, and percentage of positive cores were significant prognostic factors for FFBR. Grade 2 or higher GI and GU toxicities were 3.9% and 2.0%. Patient age was a prognostic factor for both late GI and GU toxicities. This study represents the largest cohort of patients treated with PT for localized prostate cancer, with the longest follow‐up to date. Our results demonstrate that the biochemical control of PT is favorable particularly for high‐ and very high‐risk patients with lower late genitourinary toxicity and indicates the necessity of considering patient age in the treatment protocols.

We investigate the tritium-doping enhancement of polystyrene by ultraviolet (UV) laser and hydrogen plasma irradiation. Tritium-doped polystyrene films are fabricated by the Wilzbach method with UV laser and hydrogen plasma. The 266-nm laser-irradiated, 355-nm laser-irradiated, and hydrogen plasma-irradiated polystyrene films exhibit higher PSL intensities and specific radioactivities than the non-irradiated sample. Tritium doping by UV laser irradiation can be largely affected by the laser wavelength because of polystyrene’s absorption. In addition, UV laser irradiation is more localized and concentrated at the spot of laser irradiation, while hydrogen plasma irradiation results to a more uniform doping concentration even at low partial pressure and short irradiation time. Both UV laser and plasma irradiations can nevertheless be utilized to fabricate tritium-doped polystyrene targets for future laser fusion experiments. With a high doping rate and efficiency, a 1% tritium-doped polystyrene shell target having 7.6 × 10 11 Bq g −1 specific radioactivity can be obtained at a short period of time thereby decreasing tritium consumption and safety management costs.

Background: Androgen deprivation therapy (ADT) combined with radiation therapy benefits intermediate- and high-risk prostate cancer (PC) patients. The optimal ADT duration in combination with high-dose proton beam therapy (PBT) remains unknown. Methods: Intermediate- and high-risk PC patients treated with PBT combined with ADT for various durations were analyzed retrospectively. To assess the relationship between ADT and biochemical relapse-free (bRF) rate, Cox proportional hazards models including T stage, prostate specific antigen (PSA) level, Gleason score (GS), and total radiation dose were used. Results: In the intermediate-risk PC patients (n = 520), ADT use improved bRF (HR 0.49, 95% CI 0.26&ndash, 0.93, p = 0.029), especially in those with multiple intermediate-risk factors (T2b&ndash, 2c, PSA 10&ndash, 20 ng/mL, and GS 7). In the high-risk PC patients (n = 555), a longer ADT duration (&gt, 6 months) conferred a benefit for bRF (HR 0.54, 95% CI 0.32&ndash, 0.90, p = 0.018), which was most apparent in patients with multiple high-risk factors (T3a&ndash, 4, PSA &gt, 20 ng/mL, and GS &ge, 8) treated with ADT for &ge, 21 months. Conclusions: Short-term (&le, 6 months) ADT is beneficial for intermediate-risk PC patients, but likely unnecessary for those with a single risk factor, whereas ADT for &gt, 6 months is necessary for high-risk PC patients and ADT for &ge, 21 months might be optimal for those with multiple risk factors in combination of high-dose PBT.

Background and purpose Late rectal bleeding is one of the severe adverse events after radiotherapy for prostate cancer. New biomarkers are needed to allow a personalized treatment. Materials and methods Four patients each with grade 0–1 or grade 2–3 rectal bleeding were randomly selected for miRNA array to examine miRNA expression in peripheral blood lymphocytes (PBLs). Based on results of miRNA array, 1 of 348 miRNAs was selected for microRNA assays. Then, expression of DNA-dependent protein kinase mRNA and miR-99a was analyzed in the PBLs of 97 patients. PBLs were exposed to 4Gy of X-ray ex-vivo. Results In the discovery cohort, grade 2–3 rectal bleeding was significantly higher in the Ku80 P =0.011). In radiation-induced expression of miR-99a, grade 2–3 rectal bleeding was significantly higher in the miR-99a IR(+)/IR(−) >0.93 group compared with ⩽0.93 group ( P =0.013). Most patients with grade 2–3 rectal bleeding were in the group with low Ku80 and high miR-99a expression. In the validation cohort, similar results were obtained. Conclusion A combination of low Ku80 expression and highly-induced miR-99a expression could be a promising marker for predicting rectal bleeding after radiotherapy.

Background and purpose The aim of this study was to retrospectively analyse the outcomes of cases of adenoid cystic carcinomas (ACCs) of the head and neck that were treated at a single institution with particle therapy consisting of either protons or carbon ions. Methods and materials Between February 2002 and March 2012, 80 patients were treated with proton therapy (PT) or carbon ion therapy (CIT) alone. PT and CIT were employed in 40 (50%) patients each, and more than half of the patients received 65.0 GyE in 26 fractions ( n =47, 59%). Results The median duration of follow-up was 38months (range, 6–115months). For all patients, the 5-year for overall survival (OS) rate, progression-free survival (PFS) rate, and local control (LC) rate were 63%, 39%, and 75%, respectively. No significant differences between PT and CIT were observed. The 5-year LC rates for T4 and inoperable cases were 66% and 68%, respectively. Twenty-one patients (26%) experienced grade 3 or greater late toxicities, including three patients who developed grade 5 bleeding from nasopharyngeal ulcers. Conclusions Particle radiotherapy for ACC achieves favourable LC, and its efficacy in inoperable or T4 cases is promising. There were no significant differences between PT and CIT in terms of OS, PFS and LC.

In patients undergoing radiotherapy for localized prostate cancer, dose–volume histograms and clinical variables were examined to search for correlations between radiation treatment planning parameters and late rectal bleeding. We analyzed 129 patients with localized prostate cancer who were managed from 2002 to 2010 at our institution. They were treated with 3D conformal radiation therapy (3D-CRT, 70 Gy/35 fractions, 55 patients) or intensity-modulated radiation therapy (IMRT, 76 Gy/38 fractions, 74 patients). All radiation treatment plans were retrospectively reconstructed, dose–volume histograms of the rectum were generated, and the doses delivered to the rectum were calculated. Time to rectal bleeding ranged from 9–53 months, with a median of 18.7 months. Of the 129 patients, 33 patients had Grade 1 bleeding and were treated with steroid suppositories, while 25 patients with Grade 2 bleeding received argon plasma laser coagulation therapy (APC). Three patients with Grade 3 bleeding required both APC and blood transfusion. The 5-year incidence rate of Grade 2 or 3 rectal bleeding was 21.8% for the 3D-CRT group and 21.6% for the IMRT group. Univariate analysis showed significant differences in the average values from V65 to V10 between Grades 0–1 and Grades 2–3. Multivariate analysis demonstrated that patients with V65 ≥ 17% had a significantly increased risk (P = 0.032) of Grade 2 or 3 rectal bleeding. Of the 28 patients of Grade 2 or 3 rectal bleeding, 17 patients (60.7%) were cured by a single session of APC, while the other 11 patients required two sessions. Thus, none of the patients had any further rectal bleeding after the second APC session.

This study sought to demonstrate the feasibility of estimating the source strength during implantation in brachytherapy. The requirement for measuring the strengths of the linked sources was investigated. The utilized sources were (125)I with air kerma strengths of 8.38-8.63 U (μGy m(2) h(-1)). Measurements were performed with a plastic scintillator (80 mm × 50 mm × 20 mm in thickness). For a source-to-source distance of 10.5 mm and at source speeds of up to 200 mm s(-1), a counting time of 10 ms and a detector-to-needle distance of 5 mm were found to be the appropriate measurement conditions. The combined standard uncertainty (CSU) with the coverage factor of 1 (k = 1) was ∼15% when using a grid to decrease the interference by the neighboring sources. Without the grid, the CSU (k = 1) was ∼5%, and an 8% overestimation due to the neighboring sources was found to potentially cause additional uncertainty. In order to improve the accuracy in estimating source strength, it is recommended that the measurment conditions should be optimized by considering the tradeoff between the overestimation due to the neighboring sources and the intensity of the measured value, which influences the random error.

The post-implantation dosimetry for brachytherapy using Monte Carlo calculation by EGS5 code combined with the source strength regression was investigated with respect to its validity. In this method, the source strength for the EGS5 calculation was adjusted with the regression, so that the calculation would reproduce the dose monitored with the glass rod dosimeters (GRDs) on a water phantom. The experiments were performed, simulating the case where one of two (125)I sources of Oncoseed 6711 was lacking strength by 4-48%. As a result, the calculation without regression was in agreement with the GRD measurement within 26-62%. In this case, the shortage in strength of a source was neglected. By the regression, in order to reflect the strength shortage, the agreement was improved up to 17-24%. This agreement was also comparable with accuracy of the dose calculation for single source geometry reported previously. These results suggest the validity of the dosimetry method proposed in this study.

The aim of this study is to demonstrate the feasibility of estimating the strength of the moving radiation source during patient implantation. The requirement for the counting time was investigated by comparing the results of the measurements for the static source with those for the source moving at 2, 5, 10 and 20 cm s(-1). The utilized source was (125)I with an air-kerma strength of 0.432 U (μGym(2)h(-1)). The detector utilized was a plastic scintillation detector (8 cm × 5 cm × 2 cm in thickness) set at 8 cm away from the needle to guide the source. Experiments were conducted in order to determine the most desirable counting time. Analysis using the maximum of the measured values while the source passed through the needle indicated that the results for the moving source increased more than those for the static source as the counting time decreased. The combined standard uncertainty, with the coverage factor of 1, was within 4% at the counting time of 100 ms. This investigation supported the feasibility of the method proposed for estimating the source strength during the implantation procedure, regardless of the source speed. The method proposed is a potential option for reducing the risk of accidental replacements of sources with those of incorrect strengths.

This study investigated the maximum tolerated dose (MTD) of S-1 with concurrent radiotherapy in patients with head and neck cancer, based on the frequency of dose-limiting toxicities (DLT). S-1 was administered orally at escalating doses from 40 mg/m(2) b.i.d. on the days of delivering radiotherapy, which was given at a total dose of 64-70 Gy in 32-35 fractions over 6-7 weeks. A total of 12 patients (3 patients at 40 mg/m(2), 6 patients at 60 mg/m(2), and 3 patients at 80 mg/m(2)) were enrolled in this trial. At the dose of 80 mg/m(2), two of the three patients developed DLT (Grade 3 anorexia and rhabdomyolysis) due to S-1, so the MTD was determined to be 80 mg/m(2). Among the 12 enrolled patients, 9 (75%) showed a complete response and 3 (25%) showed a partial response. The overall response rate was 100%. The recommended dose of S-1 with concurrent radiotherapy is 60 mg/m(2).

Direct-drive implosion experiments on the GEKKO XII laser (9 kJ, 0.5 μm, 2 ns) with deuterium and tritium (DT) exchanged plastic hollow shell targets demonstrated fuel areal densities (ρR) of ˜0.1 g/cm2 and fuel densities of ˜600 times liquid density at fuel temperatures of ˜0.3 keV. (The density and ρR values refer only to DT and do not include carbons in the plastic targets.) These values are to be compared with thermonuclear ignition conditions, i.e., fuel densities of 500–1000 times liquid density, fuel areal densities greater than 0.3 g/cm2, and fuel temperatures greater than 5 keV. The irradiation nonuniformity in these experiments was significantly reduced to a level of ρR was directly measured with the neutron activation of Si, which was originally compounded in the plastic targets. The fuel densities were estimated from the ρR values using the mass conservation relation, where the ablated mass was separately measured using the time-dependent X-ray emission from multilayer targets. Although the observed densities were in agreement with one-dimensional calculation results with convergence ratios of 25–30, the observed neutron yields were significantly lower than those of the calculations. This suggests the implosion uniformity is not sufficient to create a hot spark in which most neutrons should be generated.

PURPOSE The aim of this study was to develop a dose calculation method which is applicable to the interseed attenuation and the geometry lacking the equilibrium radiation scatter conditions in brachytherapy. METHODS The dose obtained from measurement with a radiophotoluminescent glass rod dosimeter (GRD) was compared to the dose calculated with the Monte Carlo (MC) code "EGS5," using the 125I source structure detailed in by Kennedy et al. The GRDs were irradiated with 125I Oncoseed 6711 in a human head phantom. The phantom was a cylinder made of 2 mm thick PMMA with a diameter of 18 cm and length of 16 cm. Some of the GRD positions were so close to the phantom surface that the backscatter margin was less than 5 cm, insufficient for photons. RESULTS The EGS5 simulations were found to reproduce the relative dose distributions as measured with the GRDs to within 25% uncertainty in the geometry lacking the equilibrium radiation scatter conditions. The absolute value of the GRD measurement agreed with the American Association of Physicist in Medicine Task Group No 43 Updated Protocol (AAPM-TG43U1) formalism to within 3% of the reference point (r = 1 cm, theta = 90 degrees), where the TG43U1 is especially reliable because of the abundant data accumulation in composing the formalism. The factor to normalize the measured or calculated dose to the TG43U1 estimate at the reference point was evaluated to be 0.97 for the GRD measurement and 1.8 for the MC calculation, which uses the integration of the apparent activity with the time as the amount of disintegration during the irradiation. Also, F(r,theta) and g(r) estimated by this calculation method were consistent with those proposed in the TG43U1. CONCLUSIONS The results of this investigation support the validity of both the MC calculation method and GRD measurement in this study as well as the TG-43U1 formalism. Also, this calculation is applicable to interseed attenuation and the geometry lacking the equilibrium radiation scatter.

Background and purpose 5-Chloro-2,4-dihydroxypyridine (Gimeracil) is a component of an oral fluoropyrimidine derivative S-1. Gimeracil is originally added to S-1 to yield prolonged 5-FU concentrations in tumor tissues by inhibiting dihydropyrimidine dehydrogenase, which degrades 5-FU. We found that Gimeracil by itself had the radiosensitizing effect. Methods and materials We used various cell lines deficient in non-homologous end-joining (NHEJ) or homologous recombination (HR) as well as DLD-1 and HeLa in clonogenic assay. γ-H2AX focus formation and SCneo assay was performed to examine the effects of Gimeracil on DNA double strand break (DSB) repair mechanisms. Results Results of γ-H2AX focus assay indicated that Gimeracil inhibited DNA DSB repair. It did not sensitize cells deficient in HR but sensitized those deficient in NHEJ. In SCneo assay, Gimeracil reduced the frequency of neo-positive clones. Additionally, it sensitized the cells in S-phase more than in G0/G1. Conclusions Gimeracil inhibits HR. Because HR plays key roles in the repair of DSBH caused by radiotherapy, Gimeracil may enhance the efficacy of radiotherapy through the suppression of HR-mediated DNA repair pathways.

Hyperfractionated accelerated radiotherapy without a split (AF) has been performed to improve the local control probability of early glottic carcinomas since 1990 in the authors’ institution. Here, they report their experience treating early glottic cancer patients with AF in a single institution who have a long follow-up period. 131 T1 N0 M0 glottic cancers and 65 T2 N0 M0 glottic cancers were treated with conventional fractionation (CF) from 1984 to 1989 and with AF since 1990. CF consisted of five daily fractions of 2 Gy per week, to a total dose of 64 Gy. AF consisted of 1.72 Gy per fraction, two fractions per day, 5 days a week, to a total dose of 55 or 58.5 Gy. The 5-year local control probability for T1 tumors was 94% with 58.5 Gy and 87% with 55 Gy of AF, whereas it amounted to 80% with CF. For T2 tumors, it was 56% with 58.5 Gy and 68% with 55 Gy of AF, whereas it amounted to 64% with CF. The data of T2 should be evaluated with caution due to the small number of patients. Patients with AF had more severe mucosal reactions but no severe late reactions. AF significantly improved the local control rates for T1 glottic cancer.

Derivatives of 2,4-dioxo-5-benzylidene-3-thiazolidineacetamide were prepared and the fungicidal and the bactericidal activities of twenty-three related compounds were examined. In vitro tests at a concentration of 10 mg/l, some derivatives showed moderate or considerable inhibition against Pyricularia oryzae (P. oryzae), Rhizoctonia solani (R. solani), and Septoria tritici, but only modest activity against Botrytis cinerea and Burkhorderia gluma. The activity of a few compounds was enhanced by co-application of salicyl hydroxymate (SHAM), which is known to potentiate the fungicidal activity of strobilurins. In pot tests at a concentration of 500 mg/l, some compounds showed appreciable activity against rice blast, late blight on tomatoes, downy mildew on cucumbers, or leaf rust on wheat. Of these compounds N,N-dimethyl-2,4-dioxo-5-benzyl-3-thiazolidineacetamide completely removed the downy mildew. Most of them showed only modest activity against gray mold on cucumbers.

症例は18歳女性．生来健康だったが，ウコン，女性ホルモン剤を内服していたところ黄疸，肝障害を認めた．肝生検では形質細胞浸潤，ロゼット形成を伴う肝硬変像を呈し，実質には著明な出血壊死を認めた．腹部CTでは脾腫，胃腎シャントを認め，内視鏡では胃・食道静脈瘤を認めた．自己免疫性肝炎（AIH）の国際診断基準スコアは治療前で+15であり，背景肝としてAIHが考えられた．大循環シャントが形成されており，ある期間をかけてAIHから肝硬変に進展した後に急性肝障害が加わったと推測された．

長期にラミブジン (LAM) 投与がなされたB型慢性肝炎症例を対象として, LAM耐性株の出現に伴う肝炎再燃の予測および投与中止時期決定のため, B型肝炎ウイルス (HBV) DNAの推移を高感度定量法を用いて検討した. HBV DNA陽性のB型慢性活動性肝炎で, 24カ月以上LAM投与が継続された8症例 (35～59歳, 男性が7例, F3が4例, HBe抗原陽性が3例, ゲノタイプは全例C型, コアプロモーターは全例変異型) を対象とした. HBV DNA定量法としてTMA-HPA法, アンプリコアHBVモニター法に加え, 超高感度検出系のHBV RTD-PCR direct (DIRECT) 法を導入した. 検討の結果, 4例において長期経過後にDNA量の再上昇およびYMDD変異株の出現が認められたが, 4例ともLAM投与経過中にDNA量の軽度上昇がみられていた. 1例においては経過中のDNA量の上昇をDIRECT法においてのみ捉えられており, LAM投与症例においてHBV DNAの推移を観察していく上でDIRECT法の有用性が示唆された.

Background. The purpose of the present study was to present the treatment outcomes of particle therapy for indeterminate pulmonary nodules (IPNs) diagnosed as stage I non-small cell lung cancer, including a comparative analysis involving pathologically proven lung cancer (PPLC).Material and methods. A total of 54 patients (57 lesions) who underwent particle therapy for IPNs were enrolled in this study. Median patient age was 76 (range 52–87) years. T-classification was: T1a, 30; T1b, 16; and T2a, 11. Particle therapy using protons or carbon ions was delivered at total doses of 52.8–80 Gy equivalent in 4–26 fractions. The PPLC cohort included 111 patients.Results. The median follow-up time was 41 (range 7–90) months. For all IPN patients, the three-year overall survival, progression-free survival, local control and distant progression-free survival rates were 90%, 72%, 94% and 79%, respectively. Grade 2 toxicities were radiation pneumonitis (19%), dermatitis (9%), rib fracture (2%), chest wall pain (2%) and neuropathy (2%). No ≥ grade 3 toxicities were observed. In univariate analysis, the IPN group showed significantly better survival relative to the PPLC group. However, after adjustment for baseline imbalances between these two groups in multivariate analysis, pathological confirmation did not correlate with survival.Conclusions. Particle therapy for IPNs provided favorable outcomes with minimal toxicities, which may be comparable to those for PPLC patients. Further studies are needed to clarify the optimal management of IPN patients.

Background: Alcohol abuse can induce brain atrophy, but it only occurs in some alcoholics. Many inflammatory cytokines such as tumor necrosis factor (TNF) are produced rapidly in the brain by experimental or clinical injury. Method: To investigate whether genetic polymorphism of TNF was related to alcoholic brain atrophy, we determined restriction fragment-length polymorphisms of the TNF-β genes in 72 male alcoholics. Computed tomography was used to determine the severity of brain atrophy. Results: Digestion with NcoI and MspI after polymerase chain reaction amplification showed that the TNFB 1 allele frequency was significantly higher in patients with brain atrophy than in those without brain atrophy (X 2 = 10.20, p = 0.0034). A multivariate analysis that included age, total alcohol intake, ADH2 genotype, and TNF-β genotype showed that the ADH2 1 /2 1 genotype and TNFB 1 /B 1 genotype are independently associated with alcoholic brain atrophy. These findings suggest that the TNFB 1 allele may be associated with alcoholic brain atrophy.

This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The chairs were Victor R. Preedy and Junko Adachi. The presentations were (1) Alcoholic myopathy: Past, present and future, by Timothy J. Peters and Victor R. Preedy; (2) Protein adducts in the type I and II fiber-predominant muscles of the ethanol-fed rat, by Simon Worrall, Seppo Parkkila, and Onni Niemela; (3) Hydroperoxides and changes in alcoholic myopathy, by Junko Adachi, Migiwa Asamo, and Yasuhino Ueno; and (4) A close association between testicular atrophy, muscle atrophy, and the increase in protein catabolism after chronic ethanol administration, by Kunihiko Takeda, Masayoshi Yamauchi, Kazuhiko Sakamoto, Masaru Takagi, Hisato Nakajima, and Gotaro Toda.

At ILE, Osaka University, the development of large shells for a future laser fusion reactor and the improvement of the characterization technique for plastic shells used in current implosion experiments with the GEKKO XII laser system have been conducted. In the former, large polystyrene shells with 30–150-μm walls have been successfully fabricated using the conventional emulsion method. Our experimental results indicate that there is some centering force by which a non-uniform emulsion becomes uniform during the solidification process in the emulsion method. A model for this centering force is presented.

多分割照射法では，放射線生物学的には二つの異なった概念がその理論的根拠になっている。1つは低線量では細胞の回復能力が晩期組織反応の方が早期組織反応より大きいことで，過分割照射法はこのことに基づいている。もう1つは腫瘍幹細胞の増殖速度が治療期間中の後半に著しく加速されることで，これを克服するために加速分割照射法が提唱された。上記の二つの概念は独立した現象であり，線量分割法よっては，両方の線量分割法の要素が含まれる場合もあると考えられる。これらの照射法の臨床における効果は，ある程度は分割照射のL-Qモデルにより予測可能と考えられる。しかし，多分割照射と化学療法の同時併用するような場合は，単純化した放射線生物学モデルで予測する事は困難である。従って，その有効性の検証には，慎重に計画されたランダマイズ試験が必要である。

A metastable form of LiFeO 2 with α-NaFeO-type structure (layered LiFeO) was synthesized directly from α-FeOOH or FeCl 3 . 6H 2 O by hydrothermal reaction at 230°C using aqueous mixed-alkaline solutions such as LiOH HO-KOH or LiOH HO-NaOH. Highly crystallized samples could be obtained by a one-step process. The yield of the layered LiFeO strongly depends on the composition of the starting mixture. Preliminary tests on electrochemical lithium deintercalation/intercalation show poor performance between 4.5 and 1.5 V.

The irradiation uniformity of the GEKKO XII laser has been improved by implementing the state-of-the-art beam smoothing and laser control techniques in the system. Non-uniformity modes higher than 20 are improved to less than 1% RMS by introducing partially coherent light, while the lower modes are improved to 3 - 4% RMS. Implosion experiments were carried out with the new GEKKO XII: a fast-rise square pulse preceded by a pre-pulse was used to suppress the Rayleigh - Taylor instability at the acceptable expense of implosion efficiency. The experimental results are compared with a pusher-fuel mixing model combined with a one-dimensional hydrodynamic simulation. The degradation of experimentally obtained neutrons is mainly attributed to the lower-mode asymmetry. Recent results of planar target experiments on hydrodynamic instabilities are also presented. Particular emphasis is given to the noticeable reduction of fluid instability by the flushing of an external x-ray over the target surface prior to the main drive pulse, leading to suppression of the initial imprint amplitude by the pre-formed plasma