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Lipids interfere with absorbance measurements conducted using colorimetric methods. To monitor lipemia, some systems measure absorbance using an analyzer. This report describes a novel case of interference with the lipemia index without lipemia. A 64-year-old woman with giant basal cell carcinoma underwent resection and sentinel lymph node biopsy. The patient had been subcutaneously injected with patent blue during sentinel lymph node resection. After surgery, her serum and urine were yellow-green, and the lipemia index, calculated by measuring absorbance at 658 nm (main wavelength) and 694 nm (secondary wavelength) using a JCA-BM8040 chemistry analyzer, was high. The absorbance spectrum of the patient's serum and patent blue solution were compared to determine the cause of the high lipemia index. The patient's serum and the patent blue solution showed absorption at wavelengths between 540 and 698 nm. Moreover, the absorbance was concentration-dependent for patent blue. These results thus indicated that the patient's serum contained patent blue. Here, we report a case wherein patent blue affected the lipemia index. Thus, it must be noted that patent blue injection may yield inaccurate results when evaluating lipemia index., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Integrase strand transfer inhibitors (INSTIs) are recommended as first-line ART for people living with HIV (PLWH) in most guidelines. The INSTI-resistance-associated mutation E157Q, a highly prevalent (2%-5%) polymorphism of the HIV-1 (human immunodeficiency virus type 1) integrase gene, has limited data on optimal first-line ART regimens. We assessed the virological outcomes of various first-line ART regimens in PLWH with E157Q in real-world settings., Methods: A multicentre retrospective observational study was conducted on PLWH who underwent integrase genotypic drug-resistance testing before ART initiation between 2008 and 2019 and were found to have E157Q. Viral suppression (<50 copies/mL) rate at 24 and 48 weeks, time to viral suppression and time to viral rebound (≥100 copies/mL) were compared among the first-line ART regimens., Results: E157Q was detected in 167 (4.1%) of 4043 ART-naïve PLWH. Among them, 144 had available clinical data after ART initiation with a median follow-up of 1888 days. Forty-five started protease inhibitors + 2 NRTIs (PI group), 33 started first-generation INSTI (raltegravir or elvitegravir/cobicistat) + 2 NRTIs (INSTI-1 group), 58 started once-daily second-generation INSTI (dolutegravir or bictegravir) + 2 NRTIs (INSTI-2 group) and eight started other regimens. In the multivariate analysis, the INSTI-2 group showed similar or favourable outcomes compared with the PI group for viral suppression rates, time to viral suppression and time to viral rebound. Two cases in the INSTI-1 group experienced virological failure., Conclusions: The general guideline recommendation of second-generation INSTI-based first-line ART for most PLWH is also applicable to PLWH harbouring E157Q., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The purpose of this survey was to examine the status of radiotherapy in Japan based on the cases registered in the Japanese Radiation Oncology Database (JROD), from 2015 to 2021, and to provide basic data to help improve the usefulness of the JROD in the future. The study population consisted of patients who underwent radiotherapy between 2014 and 2020 and did not opt out of the study. The survey item data analyzed in this study were entered into the database at each radiotherapy institution by referring to medical records from the preceding year. Our results show that the number of registered radiotherapy institutions and cases increased by ~50% in 2019 compared to those in 2015 (to 113 institutions and 60 575 cases, respectively). Among the survey item categories, the registration rate was lowest for prognostic information (13.9% on average over the 7-year period). In terms of the Japanese Society for Radiation Oncology disease site, the breast; lung, trachea and mediastinum and urogenital sites accounted for >50% of the total cases. The average survival and mortality rates over the 7-year study period were 67.4 and 17.4%, respectively. The X-ray radiotherapy completion rate exceeded 90% for all years and across all disease categories. 192Ir-based brachytherapy and 223Ra-based radionuclide therapy accounted for an average of 61.9 and 44.6%, respectively, of all corresponding cases over the 7-year period. In conclusion, this survey enables us to infer the actual status of radiotherapy in Japan based on the analysis of relevant nationwide data., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

Objective: Presence of autoantibodies against troponin I (cTnI) or T (cTnT) has been reported to interfere with troponin assays. However, the extent of the interference with the measurement has not been explored sufficiently. The aims of this study were to examine the frequencies of autoantibodies against troponin I and troponin T and how much these antibodies would affect the measurement., Methods: The study comprised 52 subjects who visited Hokkaido University Hospital with suspected ischemic heart diseases. To evaluate the presence of autoantibodies, we calculated the recoveries of cTnI or cTnT after immunoglobulin G depletion, and the distributions of peaks reactive with cTnI or cTnT by high-performance liquid chromatography were examined., Results: Autoantibodies against cTnI and cTnT were identified in 8 subjects (15.4%) and 1 subject (1.9%), respectively. Although the greatest difference between cTnI and cTnT was 32-fold, the distributions of cTnI-to-cTnT ratios in groups with and without anti-cTnI were not statistically different., Conclusion: Autoantibodies against cTnI were more frequent by several fold than those against cTnT. Their presence did not significantly expand the discrepancy between cTnI and cTnT assays., (© The Author(s) 2022. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

This article describes the ongoing structure of radiation oncology in Japan in terms of equipment, personnel, patient load and geographic distribution to identify and overcome any existing limitations. From May 2016 to August 2018, the Japanese Society for Radiation Oncology conducted a questionnaire based on the Japanese national structure survey of radiation oncology in 2015. Data were analyzed based on the institutional stratification by the annual number of new patients treated with radiotherapy per institution. The estimated annual numbers of new and total (new plus repeat) patients treated with radiation were 225 000 and 271 000, respectively. Additionally, the estimated cancer incidence was 891 445 cases with approximately 25.2% of all newly diagnosed patients being treated with radiation. The types and numbers of treatment devices actually used included linear accelerator (linac; n = 936), Gamma Knife (n = 43), 60Co remote afterloading system (RALS; n = 21), and 192Ir RALS (n = 129). The linac system used dual-energy functions in 754 units, 3D conformal radiotherapy functions in 867, and intensity-modulated radiotherapy (IMRT) functions in 628. There were 899 Japan Radiological Society/Japanese Society for Radiation Oncology-certified radiation oncologists (RO), 1213.9 full-time equivalent (FTE) ROs, 2394.2 FTE radiotherapy technologists (RTT), 295.7 FTE medical physicists, 210.2 FTE radiotherapy quality managers, and 906.1 FTE nurses. The frequency of IMRT use significantly increased during this time. In conclusion, the Japanese structure of radiation oncology has clearly improved in terms of equipment and utility although there was a shortage of personnel in 2015., (© The Author(s) 2022. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Coronavirus disease 2019 (COVID-19) has rapidly evolved to become a global pandemic, largely owing to the transmission of its causative virus through asymptomatic carriers. Detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in asymptomatic people is an urgent priority for the prevention and containment of disease outbreaks in communities. However, few data are available in asymptomatic persons regarding the accuracy of polymerase chain reaction testing. In addition, although self-collected saliva samples have significant logistical advantages in mass screening, their utility as an alternative specimen in asymptomatic persons is yet to be determined., Methods: We conducted a mass screening study to compare the utility of nucleic acid amplification, such as reverse-transcription polymerase chain reaction testing, using nasopharyngeal swab (NPS) and saliva samples from each individual in 2 cohorts of asymptomatic persons: the contact-tracing cohort and the airport quarantine cohort., Results: In this mass screening study including 1924 individuals, the sensitivities of nucleic acid amplification testing with NPS and saliva specimens were 86% (90% credible interval, 77%-93%) and 92% (83%-97%), respectively, with specificities >99.9%. The true concordance probability between the NPS and saliva tests was estimated at 0.998 (90% credible interval, .996-.999) given the recent airport prevalence of 0.3%. In individuals testing positive, viral load was highly correlated between NPS and saliva specimens., Conclusion: Both NPS and saliva specimens had high sensitivity and specificity. Self-collected saliva specimens are valuable for detecting SARS-CoV-2 in mass screening of asymptomatic persons., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

We aimed to evaluate the impact of rotational setup errors on the doses received during postoperative volumetric-modulated arc therapy (VMAT) for cervical cancer. Overall, 121 cone-beam computed tomography (CBCT) sets from 20 patients were rigidly registered to reference computed tomography (CT) sets based on bony landmarks. The rotational setup errors (pitch, yaw and roll) were calculated. Then, 121 CT sets involving rotational setup errors were created, and the dose distribution in these CT sets were recalculated. The recalculated dosimetric parameters for the clinical target volume (CTV) and organs at risk (OAR) were compared to the reference values, and the correlation coefficients between the dosimetric parameter differences and rotational setup errors were calculated. Only the pitch setup error was moderately correlated with CTV coverage (r ≥ 0.40) and strongly correlated with V45 for the bladder (r ≥ 0.91) and V40 for the rectum, small bowel and bone marrow (r ≥ 0.91). The maximum dosimetric difference in a single fraction and overall fractions was -1.59% and -0.69% in D98 for the CTV, 11.72% and 5.17% in V45 for the bladder and -8.03% and -4.68% in V40 for the rectum, respectively. In conclusion, rotational setup errors only slightly impact dose coverage during postoperative cervical cancer VMAT. However, the pitch setup error occasionally affected the doses received by the bladder or the rectum in the overall fraction when the error was systematic. Thus, rotational setup errors should be corrected by adjusting six-degree-of-freedom (DOF) couches to reduce dosimetric differences in the OARs., (© The Author(s) 2021. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

Objective: To evaluate the safety and efficacy of hypofractionated whole breast irradiation for Asian women after breast-conserving surgery. This is an updated report with 5-year follow-up., Methods and Materials: Asian women who had invasive breast cancer with clinical tumor size ≤3 cm, pN0-1c and negative inked margins were enrolled. Hypofractionated whole breast irradiation of 42.56 Gy/16 fractions was delivered, and boost irradiation of 10.64 Gy/4 fractions was added when the surgical margin was ≤5 mm. The primary endpoint was the proportion of grade ≥ 2 late adverse reactions within 3 years. Secondary endpoints included early adverse events, overall survival, disease-free survival, ipsilateral breast relapse-free survival, late adverse reactions and cosmetic outcome. Toxicities were evaluated using CTCAE ver3.0. Cosmetic outcomes were assessed using a 4-point scale and CTCAE ver3.0 for hyper/hypopigmentation, breast nipple/areolar deformity and breast volume/deformity., Results: Between February 2010 and August 2012, 312 patients were enrolled, and 306 received hypofractionated whole breast irradiation. Median follow-up was 70.5 (range 7.6-88.9) months. The proportion of grade ≥ 2 late adverse reactions within 3 years was 4.3% (90% confidence interval 2.5-6.7%). Grade 2 early adverse events occurred in 38 (12.4%); none had grade 3/4. Five-year overall survival, disease-free survival and ipsilateral breast relapse-free survival were 98.7, 95.4 and 98.0%, respectively. Of the 304 evaluable patients, 29 (9.5%; 95% confidence interval 6.5-13.4%) had grade 2/3 late adverse reactions; none had grade 4/5. At 5 years, 70/289 (24.2%) showed any worsening of breast cosmetic changes., Conclusions: Hypofractionated whole breast irradiation is considered a standard treatment for Asian women with margin-negative invasive breast cancer after breast-conserving surgery., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

The immobilization of patients with a bite block (BB) carries the risk of interpersonal infection, particularly in the context of pandemics such as COVID-19. Here, we compared the intra-fractional patient setup error (intra-SE) with and without a BB during fractionated intracranial stereotactic irradiation (STI). Fifteen patients with brain metastases were immobilized using a BB without a medical mask, while 15 patients were immobilized without using a BB and with a medical mask. The intra-SEs in six directions (anterior-posterior (AP), superior-inferior (SI), left-right (LR), pitch, roll, and yaw) were calculated by using cone-beam computed tomography images acquired before and after the treatments. We analyzed a total of 53 and 67 treatment sessions for the with- and without-BB groups, respectively. A comparable absolute mean translational and rotational intra-SE was observed (P > 0.05) in the AP (0.19 vs 0.23 mm with- and without-BB, respectively), SI (0.30 vs 0.29 mm), LR (0.20 vs 0.29 mm), pitch (0.18 vs 0.27°), roll (0.23 vs 0.23°) and yaw (0.27 vs 22°) directions. The resultant planning target volume (PTV) margin to compensate for intra-SE was <1 mm. No statistically significant correlation was observed between the intra-SE and treatment times. A PTV margin of <1 mm was achieved even when patients were immobilized without a BB during STI dose delivery., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

This paper describes the ongoing structure of radiation oncology in Japan in terms of equipment, personnel, patient load and geographic distribution to identify and overcome any existing limitations. From December 2014 to July 2017, the Japanese Society for Radiation Oncology conducted a questionnaire based on the Japanese national structure survey of radiation oncology in 2013. Data were analyzed based on institutional stratification by the annual number of new patients treated with radiotherapy per institution. The estimated annual numbers of new and total (new plus repeat) patients treated with radiation were 216 000 and 257 000, respectively. Additionally, the estimated cancer incidence was 862 452 cases with ~25.0% of all newly diagnosed patients being treated with radiation. The types and numbers of treatment devices actually used included linear accelerator (LINAC; n = 880), Gamma Knife (n = 45), 60Co remote afterloading system (RALS; n = 23) and 192Ir RALS (n = 128). The LINAC system used dual-energy functions in 675 units, 3D conformal radiotherapy functions in 785 and intensity-modulated radiotherapy (IMRT) functions in 494. There were 831 Japan Radiological Society/Japanese Society for Radiation Oncology-certified radiation oncologists, 1130.6 full-time equivalent (FTE) radiation oncologists, 2214.6 FTE radiotherapy technologists, 196.6 FTE medical physicists, 183.8 FTE radiotherapy quality managers and 856.7 FTE nurses. The frequency of IMRT use significantly increased during this time. In conclusion, the Japanese structure of radiation oncology has clearly improved in terms of equipment and utility although there was a shortage of personnel in 2013., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

We evaluated the evolving structure of radiation oncology in Japan in terms of equipment, personnel, patient load and geographic distribution to identify and overcome any existing limitations. From March 2012 to August 2015, the Japanese Society for Radiation Oncology conducted a questionnaire based on the Japanese national structure survey of radiation oncology in 2011. Data were analyzed based on the institutional stratification by the annual number of new patients treated with radiotherapy per institution. The estimated annual numbers of new and total (new plus repeat) patients treated with radiation were 211 000 and 250 000, respectively. Additionally, the estimated cancer incidence was 851 537 cases with approximately 24.8% of all newly diagnosed patients being treated with radiation. The types and numbers of treatment devices actually used included linear accelerator (LINAC; n = 836), telecobalt (n = 3), Gamma Knife (n = 46), 60Co remote afterloading system (RALS; n = 24), and 192Ir RALS (n = 125). The LINAC system used dual-energy functions in 619 units, 3D conformal radiotherapy functions in 719 and intensity-modulated radiotherapy (IMRT) functions in 412. There were 756 JRS or JASTRO-certified radiation oncologists, 1018.5 full-time equivalent (FTE) radiation oncologists, 2026.7 FTE radiotherapy technologists, 149.1 FTE medical physicists, 141.5 FTE radiotherapy quality managers and 716.3 FTE nurses. The frequency of IMRT use significantly increased during this time. To conclude, although there was a shortage of personnel in 2011, the Japanese structure of radiation oncology has clearly improved in terms of equipment and utility., (© The Author(s) 2019. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.)

Objectives: The objective of this study is to elucidate the efficacy and safety of autologous haematopoietic stem cell transplantation (HSCT) for Japanese patients with systemic sclerosis (SSc)., Methods: A phase II clinical trial included SSc patients diagnosed within the last three years having at least one of the following clinical features: diffuse skin sclerosis with modified Rodman total thickness skin score (mRSS) ≥ 15, refractory digital ulcer or interstitial lung disease (ILD). HSCT were performed after conditioning using cyclophosphamide., Results: Fourteen patients were enrolled and underwent HSCT. Median follow-up period was 137 months. Overall survival or event-free survival rate was 93% or 40% at 10 years, respectively. Eight patients (57%) achieved more than a 50% decrease in mRSS from baseline within six months after HSCT. Six patients (43%) required additional immunosuppressive treatments due to progression of diffuse skin sclerosis and/or ILD during follow-up period. Adverse events related to HSCT occurred in six patients (43%). Severe cardiomyopathy occurred in two patients, and one of them had a fatal course., Conclusion: HSCT is a feasible treatment bringing favourable results to more than half of our patients with SSc. Careful selection of the patients is essential for whom benefited from HSCT, considering the risk-benefit balance of the treatment.

Background: Shorter duration of infusion of monoclonal antibody treatments may reduce treatment burden and improve healthcare resource utilization., Methods: This phase II study recruited Japanese patients with previously untreated CD20+ B-cell non-Hodgkin lymphoma. Patients received intravenous obinutuzumab 1000 mg by regular infusion on Days 1, 8 and 15 of Cycle 1, followed by 90-min shorter duration of infusion in up to seven subsequent cycles, provided they received ≥3 regular infusions without any grade ≥3 infusion-related reactions and had a lymphocyte count <5.0 × 109 cells/l. Standard cyclophosphamide, doxorubicin, vincristine and prednisolone chemotherapy was given in Cycles 1-6. The primary endpoints were as follows: incidence of grade ≥3 infusion-related reactions in Cycle 2 in patients who started shorter duration of infusion in Cycle 2, serum obinutuzumab concentrations and pharmacokinetic parameters and the time course of cytokine release. Adverse events and serious adverse events were monitored., Results: Of 35 patients treated, 28 completed eight cycles; 31 started shorter duration of infusion in Cycle 2 and two patients in subsequent cycles. Two patients discontinued before starting shorter duration of infusion. No grade ≥3 infusion-related reactions occurred in Cycle 2. Twenty-one infusion-related reactions (all grades 1-2) were reported in 17/35 (49%) patients overall, mostly in Cycle 1 (18/21 infusion-related reactions [86%]). Grade ≥3 AEs occurring in ≥10% of patients included neutropenia/neutrophil count decreased (66%) and leukopenia/white blood cell count decreased (23%). Steady-state pharmacokinetics of obinutuzumab were attained in Cycle 2 and were not affected by shorter duration of infusion. No relevant cytokine elevations were reported with shorter duration of infusion., Conclusions: Regular infusion and shorter duration of infusion of obinutuzumab have comparable tolerability and pharmacokinetics in Japanese patients.

With the advancement of chemotherapy, a laryngeal preservation (LP) strategy was explored with the aim of improving maintenance of quality of life. Induction chemotherapy (ICT) following radiotherapy (RT) was considered a viable option because of its high initial response rate without hampering of overall survival (OS). Subsequently, concurrent chemoradiotherapy (CCRT) using CDDP became the standard of care for LP, showing the best LP ratio. For enhancing treatment intensity, ICT with taxan + CDDP + 5-FU (TPF-ICT) followed by RT showed superiority over ICT with CDDP + 5-FU (PF-ICT) followed by RT. Given that almost all randomized controlled trials investigating ICT include not only operable (endpoint, LP) but also inoperable (endpoint, OS) cases, physicians are faced with a dilemma regarding application in daily practice. In addition, increased treatment intensity causes augmentation of adverse events, which might reduce compliance. Thereafter, cetuximab, an effective drug with fewer adverse effects [bioradiotherapy (BRT)], emerged as another option. However, little evidence has confirmed its superiority over RT (or CCRT) in laryngeal cancer subpopulations. In spite of these developments, the OS of patients with laryngeal cancer has not improved for several decades. In fact, several studies indicated a decrease in OS during the 1990s, probably due to overuse of CCRT. Fortunately, the latter was not the case in most institutions. Currently, no other treatment has better OS than surgery. The eligibility criteria for LP and/or surgery largely depend upon the available expertise and experience, which differ from one institution to another. Therefore, a multidisciplinary team is required for the treatment of LP., (© The Author 2017. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.)

We investigated whether methods conventionally used to evaluate patient-specific QA in volumetric-modulated arc therapy (VMAT) for intracranial tumors detect clinically relevant dosimetric errors. VMAT plans with coplanar arcs were designed for 37 intracranial tumors. Dosimetric accuracy was validated by using a 3D array detector. Dose deviations between the measured and planned doses were evaluated by gamma analysis. In addition, modulation complexity score for VMAT (MCSv) for each plan was calculated. Three-dimensional dose distributions in patient anatomy were reconstructed using 3DVH software, and clinical deviations in dosimetric parameters between the 3DVH doses and planned doses were calculated. The gamma passing rate (GPR)/MCSv and the clinical dose deviation were evaluated using Pearson's correlation coefficient. Significant correlation (P < 0.05) between the clinical dose deviation and GPR was observed with both the 3%/3 mm and 2%/2 mm criteria in clinical target volume (D99), brain (D2), brainstem (D2) and chiasm (D2), albeit that the correlations were not 'strong' (0.38 < |r| < 0.54). The maximum dose deviations of brainstem were up to 4.9 Gy and 2.9 Gy for Dmax and D%, respectively in the case of high GPR (98.2% with 3%/3 mm criteria). Regarding MCSv, none of the evaluated organs showed a significant correlation with clinical dose deviation, and correlations were 'weak' or absent (0.01 < |r| < 0.21). The use of high GPR and MCSv values does not always detect dosimetric errors in a patient. Therefore, in-depth analysis with the DVH for patient-specific QA is considered to be preferable for guaranteeing safe dose delivery., (© The Author 2017. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.)

Early laryngeal, especially glottic, cancer is a good candidate for radiotherapy because obvious early symptoms (e.g. hoarseness) make earlier treatment possible and with highly successful localized control. This type of cancer is also a good model for exploring the basic principles of radiation oncology and several key findings (e.g. dose, fractionation, field size, patient fixation, and overall treatment time) have been noted. For example, unintended poor outcomes have been reported during transition from 60Cobalt to linear accelerator installation in the 1960s, with usage of higher energy photons causing poor dose distribution. In addition, shell fixation made precise dose delivery possible, but simultaneously elevated toxicity if a larger treatment field was necessary. Of particular interest to the radiation therapy community was altered fractionation gain as a way to improve local tumor control and survival rate. Unfortunately, this interest ceased with advancements in chemotherapeutic agents because alternate fractionation could not improve outcomes in chemoradiotherapy settings. At present, no form of acceleration can potentially compensate fully for the lack of concurrent chemotherapy. In addition, the substantial workload associated with this technique made it difficult to add extra fractionation routinely in busy clinical hospitals. Hypofractionation, on the other hand, uses a larger single fractionation dose (2-3 Gy), making it a reasonable and attractive option for T1-T2 early glottic cancer because it can improve local control without the additional workload. Recently, Japan Clinical Oncology Group study 0701 reprised its role in early T1-T2 glottic cancer research, demonstrating that this strategy could be an optional standard therapy. Herein, we review radiotherapy history from 60Cobalt to modern linear accelerator, with special focus on the role of alternate fractionation., (© The Author 2017. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.)

The aim of this study was to compare three strategies for intensity-modulated radiotherapy (IMRT) for 20 head-and-neck cancer patients. For simultaneous integrated boost (SIB), doses were 66 and 54 Gy in 30 fractions for PTVboost and PTVelective, respectively. Two-phase IMRT delivered 50 Gy in 25 fractions to PTVelective in the First Plan, and 20 Gy in 10 fractions to PTVboost in the Second Plan. Sequential SIB (SEQ-SIB) delivered 55 Gy and 50 Gy in 25 fractions, respectively, to PTVboost and PTVelective using SIB in the First Plan and 11 Gy in 5 fractions to PTVboost in the Second Plan. Conformity indexes (CIs) (mean ± SD) for PTVboost and PTVelective were 1.09 ± 0.05 and 1.34 ± 0.12 for SIB, 1.39 ± 0.14 and 1.80 ± 0.28 for two-phase IMRT, and 1.14 ± 0.07 and 1.60 ± 0.18 for SEQ-SIB, respectively. CI was significantly highest for two-phase IMRT. Maximum doses (Dmax) to the spinal cord were 42.1 ± 1.5 Gy for SIB, 43.9 ± 1.0 Gy for two-phase IMRT and 40.3 ± 1.8 Gy for SEQ-SIB. Brainstem Dmax were 50.1 ± 2.2 Gy for SIB, 50.5 ± 4.6 Gy for two-phase IMRT and 47.4 ± 3.6 Gy for SEQ-SIB. Spinal cord Dmax for the three techniques was significantly different, and brainstem Dmax was significantly lower for SEQ-SIB. The compromised conformity of two-phase IMRT can result in higher doses to organs at risk (OARs). Lower OAR doses in SEQ-SIB made SEQ-SIB an alternative to SIB, which applies unconventional doses per fraction., (© The Author 2016. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.)

Objective: To estimate selective neck irradiation omitting surgical Sublevel IIb., Methods: Bilateral necks of 47 patients (94 necks) were subjected to definitive radiotherapy for supraglottic cancer. Sixty-nine and 25 necks were clinically node negative (cN-) and clinically node positive (cN+), respectively. We subdivided Sublevel IIb by the international consensus guideline for radiotherapy into Sublevel IIb/a, directly posterior to the internal jugular vein, and Sublevel IIb/b, which was behind Sublevel IIb/a and coincided with surgical Sublevel IIb. Bilateral (Sub)levels IIa, III, IV and IIb/a were routinely irradiated, whereas Sublevel IIb/b was omitted from the elective clinical target volume in 73/94 treated necks (78%)., Results: Two patients presented with ipsilateral Sublevel IIb/a metastases. No Sublevel IIb/b metastasis was observed. Five patients experienced cervical lymph node recurrence; Sublevel IIb/a recurrence developed in two patients, whereas no Sublevel IIb/b recurrence occurred even in the cN- necks of cN+ patients or cN0 patients. The 5-year regional control rates were 91.5% for Sublevel IIb/b-omitted patients and 77.8% for Sublevel IIb/b treated patients., Conclusions: Selective neck irradiation omitting Sublevel IIb/b did not compromise regional control and could be indicated for cN- neck of supraglottic cancer., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

The aim of the this study was to validate the use of an average intensity projection (AIP) for volumetric-modulated arc therapy for stereotactic body radiation therapy (VMAT-SBRT) planning for a moving lung tumor located near the diaphragm. VMAT-SBRT plans were created using AIPs reconstructed from 10 phases of 4DCT images that were acquired with a target phantom moving with amplitudes of 5, 10, 20 and 30 mm. To generate a 4D dose distribution, the static dose for each phase was recalculated and the doses were accumulated by using the phantom position known for each phase. For 10 patients with lung tumors, a deformable registration was used to generate 4D dose distributions. Doses to the target volume obtained from the AIP plan and the 4D plan were compared, as were the doses obtained from each plan to the organs at risk (OARs). In both phantom and clinical study, dose discrepancies for all parameters of the dose volume (D(min), D(99), D(max), D(1) and D(mean)) to the target were <3%. The discrepancies of D(max) for spinal cord, esophagus and heart were <1 Gy, and the discrepancy of V20 for lung tissue was <1%. However, for OARs with large respiratory motion, the discrepancy of the D(max) was as much as 9.6 Gy for liver and 5.7 Gy for stomach. Thus, AIP is clinically acceptable as a planning CT image for predicting 4D dose, but doses to the OARs with large respiratory motion were underestimated with the AIP approach., (© The Author 2015. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.)

Objective: A second lung cancer is occasionally observed in patients who underwent surgical resection of the index lung cancer. The purpose of this study is to evaluate stereotactic body radiation therapy for second lung cancer., Methods: Fifty-one medically inoperable patients who underwent stereotactic body radiation therapy for second lung cancer were the subjects: 31 cases of multiple primary lung cancer and 20 of pulmonary metastasis from the index cancer. Clinical stage was T1a in 27 patients, T1b in 13 patients and T2a in 11 patients, and 70% of subjects had impaired respiratory function. Histology of second lung cancer was adenocarcinoma in 16 patients, squamous cell carcinoma in 9 patients and not assessed in 25 patients. The interval between index cancer operation and stereotactic body radiation therapy was 31 months (range: 4-171). The total stereotactic body radiation therapy doses were 48 Gy in 4 fractions or 60 Gy in 10 fractions., Results: With the median follow-up of 36 months, 3-year overall survival rates were 62% with the median survival time of 46 months. Cause-specific survival was 73% at 3 years. Overall survival for multiple primary lung cancer and pulmonary metastasis was quite similar: 62 and 61% at 3 years, respectively. Three-year overall survival was 77% for T1a and 43% for T1b or T2a. Grade 2 pulmonary toxicities occurred in five patients and one patient died of Grade 5 pneumonitis., Conclusions: Even though the subjects were medically inoperable, the survival outcomes of stereotactic body radiation therapy were favorable. Furthermore, having acceptable toxicity, stereotactic body radiation therapy is feasible and could be an option for multiple primary lung cancer and pulmonary metastasis after surgical resection for the index cancer., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

The purpose of this study was to analyze the patterns of care and outcomes of patients with FIGO Stage I/II cervical cancer who underwent definitive radiotherapy (RT) at multiple Japanese institutions. The Japanese Radiation Oncology Study Group (JROSG) performed a questionnaire-based survey of their cervical cancer patients who were treated with definitive RT between January 2000 and December 2005. A total of 667 patients were entered in this study. Although half of the patients were considered suitable for definitive RT based on the clinical features of the tumor, about one-third of the patients were prescribed RT instead of surgery because of poor medical status. The RT schedule most frequently utilized was whole-pelvic field irradiation (WP) of 30 Gy/15 fractions followed by WP with midline block of 20 Gy/10 fractions, and high-dose-rate intracavitary brachytherapy (HDR-ICBT) of 24 Gy/4 fractions prescribed at point A. Chemotherapy was administered to 306 patients (46%). The most frequent regimen contained cisplatin (CDDP). The median follow-up time for all patients was 65 months (range, 2-135 months). The 5-year overall survival (OS), pelvic control (PC) and disease-free survival (DFS) rates for all patients were 78%, 90% and 69%, respectively. Tumor diameter and nodal status were significant prognostic indicators for OS, PC and DFS. Chemotherapy has potential for improving the OS and DFS of patients with bulky tumors, but not for non-bulky tumors. This study found that definitive RT for patients with Stage I/II cervical cancer achieved good survival outcomes., (© The Author 2015. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.)

While it has been expected that X-ray laser will be widely applied to biomedical studies, this has not been achieved to date and its biological effects such as DNA damage have not been evaluated. As a first step for its biological application, we developed a culture cell irradiation system, particularly designed for a plasma-driven soft X-ray laser pulse, to investigate whether the soft X-ray laser is able to induce DNA double strand breaks (DSBs) in living cells or not. The human adenocarcimona cell line A549 was irradiated with the soft X-ray laser at a photon energy of 89 eV and the repair focus formation of the DSBs was assessed by immunofluorescence staining with antiphosphorylated DNA-PKcs (p-DNA-PKcs), ATM (p-ATM) and γ-H2AX antibody. The p-DNA-PKcs, ATM, and γ-H2AX foci were clearly identified after soft X-ray laser irradiation. Furthermore, the increase in the X-ray laser shot number, even from a single shot, results in the increase in p-DNA-PKcs foci. These results are the first evidence that the 89 eV soft X-ray laser is able to induce DSB in living cells. Our study demonstrated that this irradiation system is a useful tool for investigating the radiobiological effect of soft X-ray laser., (© The Author 2015. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.)

The purpose of this study was to determine the outcomes and optimal practice patterns of definitive radiotherapy for primary vaginal cancer. Between 1993 and 2012, 49 patients were treated with definitive radiotherapy for primary vaginal cancer in three hospitals. Of these, 15 patients (31%) had clinically positive regional lymph node metastasis. A total of 34 patients (70%) received external beam radiotherapy with high-dose-rate brachytherapy (interstitial or intracavitary), and 8 (16%) (with small superficial Stage I tumors) were treated with local radiotherapy. The median follow-up was 33 months (range: 1-169 months). The 3-year overall survival (OS), disease-free survival (DFS), and loco-regional control (LRC) rates were 83%, 59% and 71%, respectively. In multivariate analysis, the histological type (P = 0.044) was significant risk factors for LRC. In Federation of Gynecology and Obstetrics (FIGO) Stage I cases, 3 of 8 patients (38%) who did not undergo prophylactic lymph node irradiation had lymph node recurrence, compared with 2 of 12 patients (17%) who underwent prophylactic pelvic irradiation. For Stage III-IV tumors, the local recurrence rate was 50% and the lymph node recurrence rate was 40%. Patients with FIGO Stage I/II or clinical Stage N1 had a higher recurrence rate with treatment using a single modality compared with the recurrence rate using combined modalities. In conclusion, our treatment outcomes for vaginal cancer were acceptable, but external beam radiotherapy with brachytherapy (interstitial or intracavitary) was needed regardless of FIGO stage. Improvement of treatment outcomes in cases of FIGO Stage III or IV remains a significant challenge., (© The Author 2015. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.)

Technical developments in radiotherapy (RT) have created a need for systematic quality assurance (QA) to ensure that clinical institutions deliver prescribed radiation doses consistent with the requirements of clinical protocols. For QA, an ideal dose verification system should be independent of the treatment-planning system (TPS). This paper describes the development and reproducibility evaluation of a Monte Carlo (MC)-based standard LINAC model as a preliminary requirement for independent verification of dose distributions. The BEAMnrc MC code is used for characterization of the 6-, 10- and 15-MV photon beams for a wide range of field sizes. The modeling of the LINAC head components is based on the specifications provided by the manufacturer. MC dose distributions are tuned to match Varian Golden Beam Data (GBD). For reproducibility evaluation, calculated beam data is compared with beam data measured at individual institutions. For all energies and field sizes, the MC and GBD agreed to within 1.0% for percentage depth doses (PDDs), 1.5% for beam profiles and 1.2% for total scatter factors (Scps.). Reproducibility evaluation showed that the maximum average local differences were 1.3% and 2.5% for PDDs and beam profiles, respectively. MC and institutions' mean Scps agreed to within 2.0%. An MC-based standard LINAC model developed to independently verify dose distributions for QA of multi-institutional clinical trials and routine clinical practice has proven to be highly accurate and reproducible and can thus help ensure that prescribed doses delivered are consistent with the requirements of clinical protocols., (© The Author 2014. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.)

Objective: The purpose of this study was to clarify operational situations, treatment planning and processes, quality assurance and quality control with relevance to stereotactic radiotherapy, intensity-modulated radiotherapy and image-guided radiotherapy in Japan., Methods: We adopted 109 items as the quality indicators of high-precision radiotherapy to prepare a questionnaire. In April 2012, we started to publicly open the questionnaire on the website, requesting every institution with radiotherapy machines for response. The response ratio was 62.1% (490 out of 789 institutions responded)., Results: Two or more radiotherapy technologists per linear accelerator managed linear accelerator operation in ∼90% of the responded institutions while medical physicists/radiotherapy quality managers were engaged in the operation in only 64.9% of the institutions. Radiotherapy certified nurses also worked in only 18.4% of the institutions. The ratios of the institutions equipped for stereotactic radiotherapy of lung tumor, intensity-modulated radiotherapy and image-guided radiotherapy were 43.3, 32.6 and 46.8%, respectively. In intensity-modulated radiotherapy planning, radiation oncologists were usually responsible for delineation while medical physicists/radiotherapy quality managers or radiotherapy technologists set up beam in 33.3% of the institutions. The median time required for quality assurance of intensity-modulated radiotherapy at any site of brain, head and neck and prostate was 4 h. Intensity-modulated radiotherapy quality assurance activity had to be started after clinical hours in >60% of the institutions., Conclusions: This study clarified one major issue in the current high-precision radiotherapy in Japan. A manpower shortage should be corrected for high-precision radiotherapy, especially in the area relevant to quality assurance/quality control., (© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Purpose: Antiemetic effectiveness and safety of aprepitant in patients with hematologic malignancy receiving multiday chemotherapy were evaluated., Methods: All data were retrospectively collected from the Kyushu University Hospital's electronic medical record system. Patients age 20 years or older with hematologic malignancies who received multiday chemotherapy were included in the study. All patients received 3 mg of granisetron i.v. 30 minutes before chemotherapy administration. Patients in the aprepitant group received 125 mg of aprepitant orally 60-90 minutes before administration of the first moderately to highly emetogenic chemotherapy (day 1). On day 2 or thereafter, an 80-mg oral dose of aprepitant was administered in the morning for up to five days. The primary endpoint was the percentage of patients who achieved complete response (CR)., Results: A total of 42 patients were treated with aprepitant and granisetron as antiemetic prophylaxis between April and December 2010 (aprepitant group), and 40 patients were treated with only granisetron between March 1, 2009, and March 31, 2010, before the introduction of aprepitant. The percentage of patients who achieved CR in the aprepitant group was significantly higher than that in the control group (p = 0.01). Factors that were significantly associated with non-CR included the prophylactic use of aprepitant and chemotherapies containing ≥4 g/m(2)/day of cytarabine. The rates of adverse drug events (ADEs) did not significantly differ between groups., Conclusion: The addition of aprepitant to granisetron increased the antiemetic effect without influencing ADEs in patients treated with moderately to highly emetogenic multiday chemotherapy for hematologic malignancies.

The ongoing structure of radiation oncology in Japan in terms of equipment, personnel, patient load and geographic distribution was evaluated in order to radiation identify and improve any deficiencies. A questionnaire-based national structure survey was conducted from March 2010 to January 2011 by the Japanese Society for Therapeutic Radiology and Oncology (JASTRO). These data were analyzed in terms of the institutional stratification of the Patterns of Care Study (PCS). The total numbers of new cancer patients and total of cancer patients (new and repeat) treated with radiation in 2009 were estimated at 201,000 and 240,000, respectively. The type and numbers of systems in actual use consisted of Linac (816), telecobalt (9), Gamma Knife (46), (60)Co remote afterloading system (RALS) (29) and (192)Ir RALS systems (130). The Linac systems used dual energy function for 586 (71.8%), 3DCRT for 663 (81.3%) and IMRT for 337 units (41.3%). There were 529 JASTRO-certified radiation oncologists (ROs), 939.4 full-time equivalent (FTE) ROs, 113.1 FTE medical physicists and 1836 FTE radiation therapists. The frequency of interstitial radiation therapy use for prostate and of intensity-modulated radiotherapy increased significantly. PCS stratification can clearly identify the maturity of structures based on their academic nature and caseload. Geographically, the more JASTRO-certified physicians there were in a given area, the more radiation therapy tended to be used for cancer patients. In conclusion, the Japanese structure has clearly improved during the past 19 years in terms of equipment and its use, although a shortage of manpower and variations in maturity disclosed by PCS stratification remained problematic in 2009.

Objective: The aim of this study is to evaluate the mechanism of long-term effect of autologous haematopoietic stem cell transplantation (ASCT) in treatment of SSc., Methods: Eleven patients (three males and eight females) with SSc were enrolled. Blood mononuclear cells were harvested after mobilization treatment with CYC and G-CSF. CD34+ haematopoietic stem/progenitor cell fractions were purified and cryopreserved. Patients were transplanted with > 2 × 10(6)/kg autologous CD34+ cells after high-dose CYC (50 mg/kg for 4 days) conditioning. Immune reconstitution was evaluated serially by analysing lymphocyte subpopulations for 36 months., Results: Progressive improvement of skin sclerosis has been observed for 3 years in most of the patients. The serum level of anti-Scl-70, an auto-antibody specific to SSc, was progressively decreased after ASCT. Improvement of skin sclerosis was significantly associated with the change in the serum anti-Scl-70 level after ASCT at 36 months. Serum levels of KL-6 and surfactant protein D, indicators for interstitial pneumonia activity, were also significantly decreased. The number of CD8+ T cells immediately recovered within a month after ASCT, while the number of CD4+ T cells remained low for >36 months post-transplant. The majority of CD4+ cells were memory but not naïve T cells, and regulatory CD4+ T cells were not recovered. Th1/Th2 ratio was significantly increased after ASCT., Conclusions: ASCT with purified CD34+ cells was effective in controlling the disease activity of SSc. Th1/Th2 ratio was significantly increased for at least 3 years after ASCT.

We previously showed that carbon ion irradiation can inhibit the expression of the anillin (ANLN) gene, which is regulated by the activation of the phosphatidylinositol-3-kinase (PI3K)/Akt signaling pathway associated with metastasis. The purpose of this study is to compare the effects of carbon ion irradiation on the PI3K/Akt signaling pathway to those of photon irradiation. Our study showed that carbon ion irradiation of human lung adenocarcinoma cells A549 decreased their invasion more effectively than photon irradiation did. We found that carbon ion irradiation reduced the nuclear localization of ANLN at lower dose, but did not affect its expression. Low-dose carbon ion irradiation also reduced the level of phosphorylated Akt compared to untreated controls, whereas photon irradiation did not. These results suggest that carbon ion irradiation effectively suppresses the metastatic potential of A549 cells by suppressing the PI3K/Akt signaling pathway.

Superb biological effectiveness and dose conformity represent a rationale for heavy-ion therapy, which has thus far achieved good cancer controllability while sparing critical normal organs. Immediately after irradiation, heavy ions produce dense ionization along their trajectories, cause irreparable clustered DNA damage, and alter cellular ultrastructure. These ions, as a consequence, inactivate cells more effectively with less cell-cycle and oxygen dependence than conventional photons. The modes of heavy ion-induced cell death/inactivation include apoptosis, necrosis, autophagy, premature senescence, accelerated differentiation, delayed reproductive death of progeny cells, and bystander cell death. This paper briefly reviews the current knowledge of the biological aspects of heavy-ion therapy, with emphasis on the authors' recent findings. The topics include (i) repair mechanisms of heavy ion-induced DNA damage, (ii) superior effects of heavy ions on radioresistant tumor cells (intratumor quiescent cell population, TP53-mutated and BCL2-overexpressing tumors), (iii) novel capacity of heavy ions in suppressing cancer metastasis and neoangiogenesis, and (iv) potential of heavy ions to induce secondary (especially breast) cancer.

Objective: To assess compliance with the radiotherapy protocol of a multi-institutional prospective study (JAROG0401/JROSG04-2), which investigated the efficacy and toxicity of definitive radiotherapy using high-dose-rate intracavitary brachytherapy (HDR-ICBT) for early-stage uterine cervical cancer patients., Methods: Individual case reviews (ICRs) were performed on all 60 study participants. Radiotherapy data were submitted to the quality assurance (QA) committee, which performed ICRs on 16 QA items according to previously selected criteria. The items focused on quality of external beam radiotherapy (EBRT), HDR-ICBT and both. Each item was determined to be either acceptable or a deviation. The QA committee performed ICR three times as planned, two during the patient accrual and the final one just after the final patient accrued. The QA results of the first and second reviews were reported back to the investigators after each ICR., Results: In 40 cases (67%), all 16 QA items were classified as acceptable. One deviation was found in 16 cases, two deviations were identified in 3 cases and three deviations were noted in 1 case. The most frequently observed deviation was missing the rules for determining point A (10 cases). The items described by quantitative values, such as prescribed doses, certain time intervals and overall treatment time, were well followed. The proportion of deviations gradually decreased during the ICR process., Conclusions: The present ICR demonstrated the favorable radiotherapy compliance with the JAROG0401/JROSG04-2 protocol. The QA process using ICRs can potentially be used to improve the quality of radiotherapy, including HDR-ICBT in the multi-institutional prospective studies for cervical cancer.

Objective: The purpose of this study is to identify the treatment planning process for Japanese patients with localized prostate cancer., Methods: The Patterns of Care Study conducted a random survey of 61 institutions nationwide. Detailed information was collected on prostate cancer patients without distant metastases who were irradiated during the periods 2003-05. Radiation treatment planning and delivery were evaluated in 397 patients who were treated radically with external photon beam radiotherapy., Results: Computed tomography data were used for planning in approximately 90% of the patients. Contrast was rarely used for treatment planning. Simulations and treatments were performed in the supine position in almost all patients. Immobilization devices were used in only 15% of the patients. Verification of the treatment fields using portal films or electric portal imaging devices was performed in most of the patients. However, regular or multiple verifications in addition to initial treatment and/or portal volume changes were performed in only 30% of the patients. Typical beam arrangements for treatment of the prostate consisted of a four-field box. Three-dimensional conformal techniques were applied less frequently in non-academic hospitals than in academic ones. Modernized multileaf collimators with leaf widths < or =10 mm were used in about two-thirds of the patients. Although the total doses given to the prostate were affected by the leaf widths, there were no significant differences between leaf widths of 5 and 10 mm., Conclusions: The results of the survey identified certain patterns in the current treatment planning and delivery processes for localized prostate cancer in Japan.

Objective: To evaluate the patterns of pretreatment diagnostic assessment in uterine cervical cancer patients treated with definitive radiotherapy in Japan., Methods: The Japanese Patterns of Care Study working group conducted a second extramural audit survey of 68 institutions and collected specific information on 631 patients with cervical cancer. All patients were treated with radiotherapy in 1999-2001. Of these, 324 patients treated without surgery were the subjects of this study., Results: International Federation of Gynecology and Obstetrics-prescribed diagnostic procedures were performed at moderate rates in our study cohort. The performance rates of chest X-ray, intravenous urography, cystoscopy, and proctoscopy were 74, 54, 53, and 33%, respectively. Cross sectional imaging studies were frequently performed. Pelvic CT, abdominal CT, and pelvic MRI were performed in 88, 80, and 76%, respectively. Lymphangiography (1%) and surgical evaluation (1%) were rarely done. Only one patient underwent PET scans in this survey period., Conclusions: This study demonstrated the patterns of pretreatment diagnostic assessment in cervical cancer patients treated with definitive radiotherapy in Japan.

Primary plasma cell leukaemia (PCL) is a rare, aggressive neoplasm of plasma cell dyscrasia. Conventional chemotherapy is usually ineffective, with an overall survival of only 8 months. Here, we describe a 42-year-old man with primary PCL, who was successfully treated with haploidentical (2-HLA loci mismatched) haematopoietic stem-cell transplantation (HSCT). To overcome the human leukocyte antigen (HLA) disparity, in vivo T-cell purging by the pre-transplant administration of antithymocyte globulin followed by a conventional prophylactic treatment against graft-versus-host disease (GVHD) resulted in an avoidance of severe GVHD as well as infectious complications. The patient has maintained complete remission for 13 months after haploidentical HSCT, indicating that a graft-versus-PCL effect might be preserved. Haploidentical HSCT can be a potentially curative treatment for patients with primary PCL who do not have an HLA-identical donor.

Background: The Japan Patterns of Care Study (JPCS) conducted two national surveys to identify changes associated with the treatment process of care for patients undergoing breast-conserving therapy (BCT). Between the two national surveys, the Japanese Breast Cancer Society published its treatment guideline for BCT., Method: The first survey collected data on 865 patients treated between 1995 and 1997 (JPCS-1), and the second on 746 patients treated between1999 and 2001 (JPCS-2) by extramural audits., Results: There was a shift to an older age distribution in JPCS-2 compared with JPCS-1. In JPCS-2, the average patient age was 53.9 compared with 51.5 in JPCS-1 (P < 0.001). There was a reduction in the extent of breast surgery and the proportion of the patients who received quadrantectomy was 57.0% in JPCS-1 and 30.3% in JPCS-2 (P < 0.001). In JPCS-2, a cast or shell for immobilization was used at a significantly higher rate of 52.9% compared with 32.6% for JPCS-1 (P < 0.001). The rate of boost irradiation was increased in JPCS-2, especially for patients with a positive surgical margin; it was significantly increased to 83.5% in JPCS-2 compared with 53.9% in JPCS-1 (P < 0.001)., Conclusions: The second survey revealed a rapid change in the trend of the treatment of BCT in Japan and represented high compliance of the treatment guideline for BCT published by the Japanese Breast Cancer Society (JBCS) in 1999.

Background: The third Japanese Patterns of Care Study (JPCS) was conducted for esophageal cancer patients receiving radiotherapy (RT). The aim of this study is to analyse the data of the non-surgery group., Methods: Of the 621 patients receiving RT from 1999 to 2001, 385 non-surgical patients were analysed., Results: Median age was 71 years and 85% were male. Karnofsky performance status (KPS) was > or =80 in 71% and better in T1 cases than in T2-4 cases. Ninety-nine per cent had squamous cell carcinoma and 56% had the main lesion in the middle thoracic esophagus. Twenty-one per cent had T1 disease, 12% T2, 38% T3 and 29% T4. Endoscopic ultrasound was used in 29% and mainly in T1 cases. Endoscopic mucosal resection was performed in 40% of mucosal cancer. Utilization of chemotherapy had remarkably increased compared with the 1995-1997 JPCS (61% versus 35%), however was significantly less in T1 cases than in T2-4 cases. The most frequently used agents for concurrent use were 5-fluorouracil and cisplatin. The median total dose of external beam RT (ERT) was 60 Gy and did not differ between T1 and T2-4 cases and also in comparison with the 1995-1997 JPCS. Brachytherapy was used in 10% and mainly in T1 cases., Conclusions: Utilization of chemotherapy had remarkably increased. However the common treatment for T1 cases was RT alone. The standard dose of ERT was 60 Gy in spite of the increase in chemotherapy administration. Moreover, this survey showed significant differences in many parameters of treatment process between T1 and T2-4 cases.

Background: We evaluated the efficacy of our quality assurance (QA) program of radiation therapy (RT) in a prospective phase II study. This is the first description of the experience of the Japan Radiation Oncology Group (JAROG) with this program., Methods: Clinical records, all diagnostic radiological films or color photos that depicted the extent of disease of 37 patients with stage IEA extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) were collected for review. Radiation therapy charts, simulation films or digitally reconstructed radiographs, portal films and isodose distributions at the central axis plan were also reviewed. All documents were digitally processed, mounted on Microsoft PowerPoint, and for security returned from researchers by mail in CD-ROM format. The QA committee members reviewed all documents centrally, utilizing the slide show functionality., Results: All patients were prescribed their specified dose to the dose specification point in accordance with the protocol. Three patients were regarded as deviations, because of a smaller margin than that specified in the protocol (n = 2) or a prolonged overall treatment time (n = 1). No violations were observed in this study., Conclusions: This is the first report with regard to the QA program in MALT lymphoma. We demonstrated that our QA program was simple and inexpensive. We also confirmed that the radiation oncologists in Japan adhered closely to the protocol guidelines.

Objective: To evaluate the changing trends of standards and practices for postoperative radiotherapy (RT) for patients with prostate cancer in Japan., Methods: The Japanese Patterns of Care Study (PCS) conducted a national survey in 84 institutions from 1996 to 1998 (PCS96-98) and 76 institutions from 1999 to 2001 (PCS99-01). Detailed information relevant to RT was collected on a total of 169 patients (64 from 1996 to 1998 and 105 from 1999 to 2001) with prostate cancer who had undergone radical prostatectomy., Results: The fraction of clinical T3-4 tumours before prostatectomy decreased from 63% in the period 1996-98 to 26% in the period 1999-2001 (P = 0.0004). The pre-RT prostate-specific antigen level was significantly lower in 1999-2001 than in 1996-98 (P = 0.0002). We did not find a significant difference in the percentage of patients who received pelvic irradiation in the time periods between PCS96-98 and PCS99-01 (P = 0.18). Although the median radiation doses of 60 Gy were not changed between the surveys, various doses (from 20 to 74.6 Gy) were delivered to the prostatic bed. In the 1999-2001 survey, 73 of 105 patients received a median dose of 56 Gy in an adjuvant setting, while the other 32 received a median dose of 60 Gy in a salvage setting (P = 0.0015)., Conclusion: These data suggest that consensus has not been reached on the practice and management of postoperative RT for patients with prostate cancer in Japan.

Background: Three prospective randomized clinical trials (RCT) in the 1990s demonstrated the survival benefit of postmastectomy radiotherapy (PMRT) for patients with locally advanced breast cancer. The present study was performed to evaluate whether the Patterns of Care Study (PCS) fulfills a role in monitoring the patterns of changes in clinical practices in Japan., Methods: The first survey (JPCS-1) involved 79 Japanese facilities by two-stage cluster sampling of facilities and patients, and was carried out during 1998-2000. JPCS-1 included 1124 patients with breast cancer who were treated between 1995 and 1997. The second survey (JPCS-2) was carried out during 2001-2003, involving 827 patients who were treated between 1999 and 2001 in 76 facilities., Results: Patients with adverse risk factors, including pathologically axillary positive nodes (> or =4) and/or advanced primary disease (pT3-4) accounted for 57% of the patients who received PMRT in JPCS-1 and 72% of those in JPCS-2 (P = 0.039). The multiple radiotherapy target volume including the chest wall and regional lymph nodes was applied in 18% of the patients in JPCS-1 and 44% of those in JPCS-2 (P < 0.001). However, the dose distribution was calculated in only 42% of the patients in both surveys (P = 0.467)., Conclusions: The eligibility and the target volume for PMRT were influenced by the outcome of RCT, but the quality of radiotherapy did not improve sufficiently. The PCS survey is useful to monitor the changes in patterns of clinical practice and can clarify some problems with radiotherapy techniques.

3-Deoxyglucosone (3-DG), a dicarbonyl compound produced by glycation, plays a role in the modification and cross-linking of long-lived proteins. We synthesized [3H]3-DG from [3H]glucose and developed an internalization assay system using HPLC to examine its cellular metabolism. When smooth muscle cells or human umbilical vein endothelial cells were incubated with [3H]3-DG, it was found that [3H]3-DG was internalized by cells in a time dependent manner. The rate of internalization was reduced when the cells were incubated at 4 degrees C or treated with phenylarsine oxide (PAO). By monitoring [3H]3-DG taken up by cells, it was confirmed that 3-DG is reduced to 3-deoxyfructose (3-DF) and that this reaction was inhibited by an aldo-keto reductase inhibitor (ARI). The presence of 3-DG led to an increase in reactive oxygen species levels in the cells and subsequent apoptosis, and the effect was enhanced by pretreatment with ARI. These results suggest that 3-DG is internalized by cells and reduced to 3-DF by aldo-keto reductases, and that the internalized 3-DG is responsible for the production of intracellular oxidative stress.

Background: The Patterns of Care Study evaluated standards of practice for patients with clinically localized prostate cancer treated with radiotherapy in Japan. This study examined the influence of institutional stratification on care for patients receiving radical external beam radiotherapy., Methods: A national survey of 66 institutions was conducted using two-stage cluster sampling, and detailed information was accumulated on 283 patients who received radiotherapy between 1999 and 2001., Results: In A (academic) and B (non-academic) institutions, more than 80% of patients had intermediate or unfavorable risk disease. Although there were no significant differences in disease characteristics between A and B institutions, institutional stratification significantly affected radiotherapy practice patterns, such as the use of a CT-based treatment planning (A1: 91.5%, B: 77.1%; P = 0.0007) and the use of conformal therapy (A: 56.4%, B: 24.1%; P < 0.0001). CT-based treatment planning and conformal therapy significantly influenced total radiation dose (P < 0.0001 for each). Hormonal therapy was commonly used in both A and B institutions (A: 89.0%, B: 90.7%). Many patients with a favorable prognosis (A: 62.5%, B: 91.7%) received hormonal therapy, and most patients with unfavorable risk disease (A: 93.6%, B: 91.6%) also received hormonal therapy., Conclusion: During the period 1999-2001, the majority of prostate cancer patients treated in Japan with radical external beam radiotherapy had advanced diseases. Institutional stratification significantly affected radiotherapy practice patterns, with the notable exception that radiotherapy was commonly combined with hormonal therapy regardless of the institutional stratification and individual risk.

Background: The Patterns of Care Study (PCS), started in the 1970's, is a well-known study used for clinical quality assurance (QA) in radiation oncology in the United States. PCS has been introduced in Japan since 1996., Methods: Three national PCS surveys have been performed by means of external audit to evaluate patterns of care for the patients with carcinoma of any of esophagus and cervix treated with radiation between 1992 and 1994, for those with carcinoma of any of esophagus, cervix, breast, lung and prostate between 1995 and 1997, and for those with any of the five disease sites between 1999 and 2001. In the first PCS, feasibility of the study was confirmed. In the second PCS, two-stage cluster sampling of institutions and patients was performed and national averages for the survey items were calculated as QA measures. In the third PCS, additional imaging data were collected. The Japan/USA PCS workshops were held at San Francisco in 2001 and at Tokyo in 2003., Results: Significant variations in process and structure were observed according to institutional stratification. In academic institutions, external beam energy > or =6 MV for deep-seated tumors of esophagus, lung, prostate and cervix, and brachytherapy for those of cervix and esophagus were used more frequently. There was an average of less than one full-time equivalent radiation oncologist in most non-academic institutions. These variations influenced the outcomes. There were also significant differences between USA and Japan in various aspects, e.g. a difference in radiation dose of 20% for uterine cervix cancer patients. It is higher in the USA. The number of new cancer patients requiring radiation is increasing steeply (120,000 in 2000 and 170,000 in 2005). Based on PCS data, structural guidelines were published and distributed throughout Japan., Conclusion: PCS is useful for establishing the clinical QA for radiation oncology as well as other specialties through detailed monitoring and evaluation of their structures, processes and outcomes.

Objective: The aim of this study is to establish Japanese national practice patterns for uterine cervical cancer patients who received radiotherapy without surgery., Methods: The Japanese Patterns of Care Study (JPCS) conducted a national survey of 73 institutions using two-stage cluster sampling, and collected specific information on 591 patients with uterine cervical cancer treated by radiotherapy without planned surgery between 1995 and 1997., Results: The median age of the patients was 70 years. Karnofsky performance status (KPS) was >/=90 for 37%. Most patients (95%) had histology of squamous cell carcinoma. Ten percent were stage I, 29% stage II, 48% stage III and 13% stage IVA. Photon beams of 10-14 MV were the most used for external beam radiotherapy (EBRT). The beam energy utilized varied significantly by institution strata. Midline block was used in approximately 70% of institutions. Intracavitary brachytherapy (ICBT) was performed in 77%. Institution strata correlated significantly with the ICBT application. The majority of patients (89%) were treated with high-dose-rate (HDR) ICBT. The median single point A dose of HDR-ICBT was 600 cGy. The median summated point A dose from EBRT and HDR-ICBT was 5800 cGy (range: 1196-8600). The median overall treatment time including ICBT was 49 days. Twenty-four percent of the patients received chemotherapy. Concurrent chemoradiation was performed in 5%., Conclusions: The JPCS established the Japanese national practice patterns of care for uterine cervical cancer patients treated with radiotherapy without planned surgery between 1995 and 1997. This survey demonstrated that the institutional strata significantly affected several practice patterns.

Objective: To report the preliminary results of a study to delineate the changing trends in radical external beam radiotherapy usage for prostate cancer between the 1996-1998 and 1999-2001 survey periods in Japan., Methods: The 1996-1998 Patterns of Care Study (PCS) and the 1999-2001 PCS in Japan reviewed the detailed information on 694 patients with prostate cancer treated with radiotherapy. Of them, 298 patients with clinically localized prostate cancer treated with radical external beam radiotherapy in A1 and B1 institutions were selected for analysis (1996-1998 PCS, 117 patients; 1999-2001 PCS, 181 patients)., Results: High-risk prostate cancer (defined as T3-T4 tumors, a pretreatment prostate-specific antigen level >20 ng/ml, and/or poorly differentiated adenocarcinoma) was diagnosed in 82.1% of the patients in the 1996-1998 PCS and in significantly less (70.2%) of those in the 1999-2001 PCS (P = 0.021). Moreover, significantly earlier T stages (T1-T2: 49.7%) and more well-differentiated tumors (24.7%) were found between 1999 and 2001 than between 1996 and 1998 (T1-T2: 31.9%, well-differentiated tumors: 13.9%). Although only 6.1% of patients were treated with radiotherapy by patient's choice in 1996-1998, a larger proportion (32.2%) chose this treatment in 1999-2001. The median radiation dose was 65.0 Gy (range, 24-74 Gy) in 1996-1998 and increased to 69 Gy (range, 14-80 Gy) in 1999-2001. The percentage of radiation doses <60 Gy was 20.5% in 1996-1998 but only 2.2% in 1999-2001. Moreover, the incidence of treatment with total doses of > or =70 Gy was higher in 1999-2001 (43.9%) than in 1996-1998 (19.7%). These increased radiation doses were predominantly observed in B1 institutions. Although the usage of > or =10 MV was significantly increased in 1999-2001 (82.0%) compared with that in 1996-1998 (65.8%), conformal therapy administered to 52.1% of patients in 1996-1998 was almost the same (55.8%) in 1999-2001. The median number of full-time equivalent (FTE) radiation oncologists (2.4 in A1 institutions and only 0.6 in B1 institutions) in 1996-1998 increased slightly in 1999-2001 (2.7 in A1 institutions, 0.7 in B1 institutions), but remained low in B1 institutions., Conclusions: In Japan, there is a trend to fewer high-risk prostate cancer patients being treated with radical external beam radiotherapy. An increasing percentage of patients chose radiotherapy and also increased radiation doses, which might reflect the growing acceptance of radical external beam radiotherapy as a treatment of choice for prostate cancer in Japan. Therefore, to optimize delivery of radiotherapy, more advanced equipment and more FTE radiation oncologists are warranted.

Objective: To determine the average national practice of postoperative radiotherapy for uterine cervical cancer in Japan., Methods: The Japanese Patterns of Care Study (PCS) reviewed the process of care employed for 455 uterine cervical cancer patients who were treated with surgery followed by postoperative radiotherapy (RT) during 1995-1997. Cases with missing data were excluded from calculations of percentage and significance for each of the surveyed items., Results: According to FIGO stages, 198 patients (45%) were in stage I, 52 patients (12%) were in stage IIA, 146 patients (33%) were in stage IIB and 46 patients (10%) were in stage III/IVA. The most common surgical procedure among the patients was radical hysterectomy (73%). Three hundred and seventy patients (82%) were treated with external beam RT (ERT) alone, and 74 patients (17%) were treated with a combination of ERT and intracavitary RT (ICRT). A midline block was used for the pelvic field in 63 patients (14%). Only seven patients (2%) were treated with extended field ERT. Pelvic ERT was most often performed using AP-PA opposed fields for 431 patients (97%). A majority of the patients (312 patients, 70%) were treated with a total dose of 45.0-50.4 Gy for ERT. Chemotherapy (CT) was administered to 178 patients (40%), neoadjuvant preoperative CT was administered to 80 patients (22%) and concurrent CT with postoperative RT was administered to 29 patients (8%)., Conclusion: This PCS established the national practice average of postoperative RT for uterine cervical cancer. Follow-up studies need to be conducted to determine whether the observed differences in treatment processes affect outcomes.

Background: A Patterns of Care Study (PCS) has been conducted to evaluate the standards of practice for prostate cancer patients treated with radiotherapy in Japan. This study examines the influence of institutional stratification on the process of care for patients receiving radical external beam radiotherapy for prostate cancer in the 1999-2001 PCS in Japan. These PCS results were compared with those of the 1999 PCS in the USA., Methods: A national survey of 36 institutions was conducted using two-stage cluster sampling and detailed information was accumulated on 305 clinically localized prostate cancer patients who received radiotherapy between 1999 and 2001. Of these, 181 patients treated with radical external beam radiotherapy were selected and the preliminary results were analyzed. Institutions were classified as A1 (academic institutions treating >or=430 patients a year) or B1 (non-academic institutions treating >or=130 patients a year)., Results: In both A1 and B1 institutions, more than 80% of the patients had intermediate or unfavorable risk diseases. There were no significant differences in the patients' disease characteristics between A1 and B1 institutions, while the institutional stratification significantly affected the patterns of radiotherapy; such as the beam energy (>or=10 MV, A1 89.9%, B1 72.2%; P = 0.0022), the use of a CT simulator (A1 91.0%, B1 80.0%; P = 0.0340) and the administration of conformal therapy (A1 85.0%, B1 20.5%; P < 0.0001). The median number of full-time equivalent (FTE) radiation oncologists was 2.7 in A1 institutions and only 0.7 in B1 institutions. Median radiation doses of 66.00 Gy (A1 institutions) and 69.00 Gy (B1 institutions) were delivered and hormonal therapy was commonly used before, during and after radiotherapy, with a mean duration of 1.3 years (88.0% in A1 institutions; 90.0% in B1 institutions). In comparing the results of PCS in Japan (1999-2001) with those in the USA (1999), patients in Japan were found to have more advanced primary diseases with higher PSA levels than those in the USA. The median prescribed dose to the primary tumor was not significantly different between the two countries (69.00 Gy in Japan and 70.45 Gy in the USA). Conversely, almost half of the patients in the USA were treated with higher prescription dose levels (>or=72 Gy), whereas only 9.4% of the Japanese patients received these dose levels. Hormonal therapy was used more frequently in Japan (88.1% of the patients) than in the USA (50% of the patients). Most of the Japanese patients with a favorable prognosis (72.0%) were treated with hormonal therapy, compared with 30% in the USA. On the other hand, most of the patients in the unfavorable risk group were treated with radiotherapy in conjunction with hormonal therapy both in Japan (91.1%) and the USA (81%)., Conclusions: During the period 1999-2001, the majority of the prostate cancer patients treated in Japan with radical external beam radiotherapy had advanced diseases and institutional stratification significantly affected the patterns of radiotherapy. In both academic and non-academic institutions, radiotherapy in conjunction with long-term hormonal therapy was commonly used. In comparison with the 1999 PCS in the USA, Japanese patients had more advanced diseases, but the higher prescribed doses (>or=72 Gy) were less common in Japan. Administration rates of hormonal therapy for favorable risk patients were different between Japan and the USA. On the other hand, for unfavorable risk patients, radiotherapy in conjunction with hormonal therapy appeared to be an accepted approach both in Japan and in the USA.

Background: This is the first study to examine the characteristics and changes of the patterns of radiotherapy for prostate cancer in Japan., Methods: The Japanese Patterns of Care Study (PCS) conducted a random survey of 84 institutions nationwide. Detailed information was collected on prostate cancer patients without distant metastases, who received radiotherapy during 1996-1998 and 1999-2001., Results: The patients were divided into three groups: The Fresh Group (n = 338) was treated with radical radiotherapy with photon beams; the Surgery Group (n = 115) was treated after prostatectomy; and the Hormone-Refractory Group (n = 117) was treated after progression from hormonal therapy. In the Fresh Group, there was a decline in the fraction of patients with T3-4 tumors, from 65.2% in 1996-1998 to 43.9% in 1999-2001. In 1999-2001, a higher median dose of 69 Gy was irradiated as compared to 65 Gy in 1996-1998. In particular, the fraction of the patients treated with doses >or=70 Gy increased from 16.4% to 46.3%. In the Surgery Group, the percentage of clinical T3-4 tumors before prostatectomy decreased from 71.4% in 1996-1998 to 16.2% in 1999-2001. The median radiation dose of 60 Gy did not change, but the 1999-2001 results showed a decrease in the use of doses <60 Gy. In the Hormone-Refractory Group, the median dose increased from 60 Gy in 1996-1998 to 67 Gy in 1999-2001., Conclusion: These data suggest that radiation doses for prostate cancer in Japan have increased dramatically within a short period of time.

Background: The Patterns of Care Study (USPCS) by the American College of Radiology (ACR) has made significant contributions to improvements in the procedures of care for patients with breast cancer in the USA. The purpose of this study was to identify problems associated with the process of care for patients undergoing post-mastectomy radiotherapy (PMRT) in Japan compared with those in the USA., Methods: The Japanese Patterns of Care Study Subgroup (JPCS) conducted a national survey in 1998-2000, involving 79 institutions and using two-stage cluster sampling of institutions and patients, which showed that between 1995 and 1997 PMRT was performed on 258 patients. The survey of the USPCS, involving 55 institutions, found that 407 patients received PMRT between 1998 and 1999., Results: More than three axillary positive nodes were detected in 54% of the patients covered by the JPCS and in 46% of those covered by the USPCS. The clinical set-up of radiation treatment was planned without the aid of computed tomography or X-ray simulation for 25% of the JPCS patients and for 6% of the USPCS patients. The chest wall of 31% of the JPCS patients and of 98% of the USPCS patients was irradiated. The JPCS showed that inappropriate radiation techniques such as parallel opposed fields for chest wall irradiation were used for 3% of the patients in academic facilities, but for 25% of those in non-academic facilities (P = 0.0002)., Conclusion: There is ample room for improvement in radiation treatment planning and chest wall irradiation techniques in Japan.