Phase I trial of myeloablative conditioning with 3-day total marrow and lymphoid irradiation for leukemia.

This prospective phase I trial aimed to determine the recommended dose of 3-day total marrow and lymphoid irradiation (TMLI) for a myeloablative conditioning regimen by increasing the dose per fraction. The primary end-point of this single-institution dose escalation study was the recommended TMLI dose based on the frequency of dose-limiting toxicity (DLT) ≤100 days posthematopoietic stem cell transplantation (HSCT); a 3 + 3 design was used to evaluate the safety of TMLI. Three dose levels of TMLI (14/16/18 Gy in six fractions over 3 days) were set. The treatment protocol began at 14 Gy. Dose-limiting toxicities were defined as grade 3 or 4 nonhematological toxicities. Nine patients, with a median age of 42 years (range, 35-48), eight with acute lymphoblastic leukemia and one with chronic myeloblastic leukemia, received TMLI followed by unrelated bone marrow transplant. The median follow-up period after HSCT was 575 days (range, 253-1037). Three patients were enrolled for each dose level. No patient showed DLT within 100 days of HSCT. The recommended dose of 3-day TMLI was 18 Gy in six fractions. All patients achieved neutrophil engraftment at a median of 19 days (range, 14-25). One-year overall and disease-free survival rates were 83.3% and 57.1%, respectively. Three patients experienced relapse, and no nonrelapse mortality was documented during the observation period. One patient died due to disease relapse 306 days post-HSCT. The recommended dose of 3-day TMLI was 18 Gy in six fractions. The efficacy evaluation of this regimen is currently being planned in a phase II study.

A virtual audit system for intensity-modulated radiation therapy credentialing in Japan Clinical Oncology Group clinical trials: A pilot study.

PURPOSE: The Medical Physics Working Group of the Radiation Therapy Study Group at the Japan Clinical Oncology Group is currently developing a virtual audit system for intensity-modulated radiation therapy dosimetry credentialing. The target dosimeters include films and array detectors, such as ArcCHECK (Sun Nuclear Corporation, Melbourne, Florida, USA) and Delta4 (ScandiDos, Uppsala, Sweden). This pilot study investigated the feasibility of our virtual audit system using previously acquired data. METHODS: We analyzed 46 films (32 and 14 in the axial and coronal planes, respectively) from 29 institutions. Global gamma analysis between measured and planned dose distributions used the following settings: 3%/3 mm criteria (the dose denominator was 2 Gy), 30% threshold dose, no scaling of the datasets, and 90% tolerance level. In addition, 21 datasets from nine institutions were obtained for array evaluation. Five institutions used ArcCHECK, while the others used Delta4. Global gamma analysis was performed with 3%/2 mm criteria (the dose denominator was the maximum calculated dose), 10% threshold dose, and 95% tolerance level. The film calibration and gamma analysis were conducted with in-house software developed using Python (version 3.9.2). RESULTS: The means ± standard deviations of the gamma passing rates were 99.4 ± 1.5% (range, 92.8%-100%) and 99.2 ± 1.0% (range, 97.0%-100%) in the film and array evaluations, respectively. CONCLUSION: This pilot study demonstrated the feasibility of virtual audits. The proposed virtual audit system will contribute to more efficient, cheaper, and more rapid trial credentialing than on-site and postal audits; however, the limitations should be considered when operating our virtual audit system.

Local control of stereotactic body radiotherapy with dynamic tumor tracking for lung tumors: a propensity score-matched analysis.

BACKGROUND: Dynamic tumor tracking (DTT) is a method of respiratory motion management in radiotherapy. It reduces the radiation field but risks delivering an insufficient radiation dose to the tumor. We investigated the local control of DTT-stereotactic body radiotherapy (SBRT) for lung tumors. METHODS: Patients treated with SBRT for early-stage, non-small-cell lung cancer and lung metastases (2013-18) were retrospectively reviewed. Patients with tumor motion >1 cm were treated with DTT-SBRT (DTT group); those with tumor motion ≤1 cm were treated with static-SBRT (static group). A static planning target volume for the static-SBRT plan was also created for patients in the DTT group, and planning target volume reduction relative to the planning target volume for the DTT-SBRT plan was assessed. Patients were matched in a 1:1 ratio using a propensity score predictive of the SBRT technique. RESULTS: Of the 245 lesions in 218 patients (median follow-up, 25.4 months), 69 were treated with DTT-SBRT and 176 with static-SBRT. The median planning target volume reduction in the DTT group was 30.3%. After propensity score matching, 124 lesions were included (62 per group). Two-year local control rates for the DTT and static groups were 94.2 and 95.9%, respectively, for all lesions (P = 0.19) and 96.3 and 94.5%, respectively, for matched lesions (P = 0.79). In univariate analysis, DTT-SBRT was not associated with local control for all lesions (hazard ratio, 2.06; P = 0.20) or matched lesions (hazard ratio, 1.22; P = 0.79). No grade 4/5 toxicities were observed. CONCLUSIONS: DTT-SBRT for lung tumors reduced the planning target volume, but not local control rates. DTT was useful for respiratory motion management.

Assessment of using a gamma index analysis for patient-specific quality assurance in Japan.

PURPOSE: The Task Group 218 (TG-218) report was published by the American Association of Physicists in Medicine in 2018, recommending the appropriate use of gamma index analysis for patient-specific quality assurance (PSQA). The paper demonstrates that PSQA for radiotherapy in Japan appropriately applies the gamma index analysis considering TG-218. MATERIALS/METHODS: This survey estimated the acceptance state of radiotherapeutic institutes or facilities in Japan for the guideline using a web-based questionnaire. To investigate an appropriate PSQA of the facility-specific conditions, we researched an optimal tolerance or action level for various clinical situations, including different treatment machines, clinical policies, measurement devices, staff or their skills, and patient conditions. The responded data were analyzed using principal component analysis (PCA) and multidimensional scaling (MDS). The PCA focused on factor loading values of the first contribution over 0.5, whereas the MDS focused on mapped distances among data. RESULTS: Responses were obtained from 148 facilities that use intensity-modulated radiation therapy (IMRT), which accounted for 42.8% of the probable IMRT use in Japan. This survey revealed the appropriate application of the following universal criteria for gamma index analysis from the guideline recommendation despite the facility-specific variations (treatment machines/the number of IMRT cases/facility attributes/responded [representative] expertise or staff): (a) 95% pass rate, (b) 3% dose difference and 2-mm distance-to-agreement, and (c) 10% threshold dose. Conditions (a)-(c) were the principal components of the data by the PCA method and were mapped in a similar distance range, which was easily clustered from other gamma index analytic factors by the MDS method. Conditions (a)-(c) were the universally essential factors for the PSQA in Japan. CONCLUSION: We found that the majority of facilities using IMRT in each region of Japan complied with the guideline and conducted PSQA with deliberation under the individual facility-specific conditions.

Determining the recommended dose of stereotactic body radiotherapy boost in patients with cervical cancer who are unsuitable for intracavitary brachytherapy: a phase I dose-escalation study.

OBJECTIVE: Some patients are ineligible for intracavitary brachytherapy (ICBT) for locally advanced cervical cancer. Stereotactic body radiotherapy (SBRT) could be a good treatment option for such patients. This phase I clinical trial aimed to determine the recommended SBRT boost dose for ICBT-ineligible cervical cancer patients. METHODS: Patients with untreated uterine cervical cancer (clinical stages IB1-IIIB) who were ineligible for ICBT were enrolled. Radiotherapy consisted of whole-pelvis radiotherapy (45 Gy in 25 fractions) followed by SBRT. Three dose levels of SBRT (19.5/21/22.5 Gy in three fractions) were set; the treatment protocol began at 21 Gy (level 2). The 'rolling-six' design study was used to establish the recommended dose of SBRT. Each dose level covered three or six patients. The primary endpoint included dose-limiting toxicity (DLT), defined as the occurrence of grade 3 (or worse) non-hematologic adverse effects within 6 months after SBRT. RESULTS: The median follow-up after registration was 17 (range, 8-32) months. Three patients were enrolled in study level 2 (SBRT of 21 Gy); none of the patients exhibited DLT within 6 months after treatment completion. In study level 3 (SBRT of 22.5 Gy), three patients did not exhibit DLT. Although all six patients achieved locoregional control during follow-up, one patient treated with level 2 SBRT experienced distant metastases 14 months after registration. CONCLUSIONS: The recommended dose of SBRT boost was 22.5 Gy in three fractions. We plan to conduct a phase II multi-center clinical trial using the methodology obtained from the current study.

Population-based asymmetric margins for moving targets in real-time tumor tracking.

BACKGROUND: Both geometric and dosimetric components are commonly considered when determining the margin for planning target volume (PTV). As dose distribution is shaped by controlling beam aperture in peripheral dose prescription and dose-escalated simultaneously integrated boost techniques, adjusting the margin by incorporating the variable dosimetric component into the PTV margin is inappropriate; therefore, geometric components should be accurately estimated for margin calculations. PURPOSE: We introduced an asymmetric margin-calculation theory using the guide to the expression of uncertainty in measurement (GUM) and intra-fractional motion. The margins in fiducial marker-based real-time tumor tracking (RTTT) for lung, liver, and pancreatic cancers were calculated and were then evaluated using Monte Carlo (MC) simulations. METHODS: A total of 74 705, 73 235, and 164 968 sets of intra- and inter-fractional positional data were analyzed for 48 lung, 48 liver, and 25 pancreatic cancer patients, respectively, in RTTT clinical trials. The 2.5th and 97.5th percentiles of the positional error were considered representative values of each fraction of the disease site. The population-based statistics of the probability distributions of these representative positional errors (PD-RPEs) were calculated in six directions. A margin covering 95% of the population was calculated using the proposed formula. The content rate in which the clinical target volume (CTV) was included in the PTV was calculated through MC simulations using the PD-RPEs. RESULTS: The margins required for RTTT were at most 6.2, 4.6, and 3.9 mm for lung, liver, and pancreatic cancer, respectively. MC simulations revealed that the median content rates using the proposed margins satisfied 95% for lung and liver cancers and 93% for pancreatic cancer, closer to the expected rates than the margins according to van Herk's formula. CONCLUSIONS: Our proposed formula based on the GUM and motion probability distributions (MPD) accurately calculated the practical margin size for fiducial marker-based RTTT. This was verified through MC simulations.

Phase I/II study of stereotactic body radiotherapy boost in patients with cervical cancer ineligible for intracavitary brachytherapy.

PURPOSE: Stereotactic body radiotherapy (SBRT) boost is a promising treatment for cervical cancer patients who are ineligible for intracavitary brachytherapy (ICBT). The aim of this multicenter, single-arm, phase I/II study was to prospectively evaluate the efficacy and toxicity of SBRT boost. MATERIALS AND METHODS: ICBT-ineligible patients with untreated cervical cancer were enrolled. Patients underwent whole-pelvic radiotherapy (45 Gy in 25 fractions) with SBRT boost to the primary lesion. In the phase I dose-escalation cohort (3 + 3 design), patients were treated with SBRT boost of 21 or 22.5 Gy in three fractions. Although dose-limiting toxicity was not confirmed, a dose of 21 Gy was selected for the phase II cohort because it was difficult to reproduce the pelvic organs position in two patients during the phase I trial. The primary endpoint was 2-year progression-free survival. RESULTS: Twenty-one patients (phase I, n = 3; phase II, n = 18) were enrolled between April 2016 and October 2020; 17 (81%) had clinical stage III-IV (with para-aortic lymph node metastases) disease. The median (range) follow-up was 40 (10-84) months. The initial response was complete response in 20 patients and partial response in one patient. The 2-year locoregional control, progression-free survival, and overall survival rates were 84%, 67%, and 81%, respectively. Grade ≥ 3 toxicity was confirmed in one patient each in the acute (diarrhea) and late (urinary tract obstruction) phases. CONCLUSION: These findings suggested that a SBRT boost is more effective than the conventional EBRT boost and can be an important treatment option for ICBT-ineligible patients with cervical cancer. STUDY REGISTRATION: This study was registered at the University Hospital Medical Information Network Clinical Trials Registry (UMIN000036845).

Technical note: A universal worksheet for failure mode and effects analysis-A project of the Japanese College of Medical Physics.

BACKGROUND: Failure mode and effects analysis (FMEA), which is an effective tool for error prevention, has garnered considerable attention in radiotherapy. FMEA can be performed individually, by a group or committee, and online. PURPOSE: To meet the needs of FMEA for various purposes and improve its accessibility, we developed a simple, self-contained, and versatile web-based FMEA risk analysis worksheet. METHODS: We developed an FMEA worksheet using Google products, such as Google Sheets, Google Forms, and Google Apps Script. The main sheet was created in Google Sheets and contained elements necessary for performing FMEA by a single person. Automated tasks were implemented using Apps Script to facilitate multiperson FMEA; these functions were built into buttons located on the main sheet. RESULTS: The usability of the FMEA worksheet was tested in several situations. The worksheet was feasible for individual, multiperson, seminar, meeting, and online purposes. Simultaneous online editing, automated survey form creation, automatic analysis, and the ability to respond to the form from multiple devices, including mobile phones, were particularly useful for online and multiperson FMEA. Automation enabled through Google Apps Script reduced the FMEA workload. CONCLUSIONS: The FMEA worksheet is versatile and has a seamless workflow that promotes collaborative work for safety.

Plan complexity metrics for head and neck VMAT competition plans.

Previous plan competitions have largely focused on dose metric assessments. However, whether the submitted plans were realistic and reasonable from a quality assurance (QA) perspective remains unclear. This study aimed to investigate the relationship between aperture-based plan complexity metrics (PCM) in volumetric modulated arc therapy (VMAT) competition plans and clinical treatment plans verified through patient-specific QA (PSQA). In addition, the association of PCMs with plan quality was examined. A head and neck (HN) plan competition was held for Japanese institutions from June 2019 to July 2019, in which 210 competition plans were submitted. Dose distribution quality was quantified based on dose-volume histogram (DVH) metrics by calculating the dose distribution plan score (DDPS). Differences in PCMs between the two VMAT treatment plan groups (HN plan competitions held in Japan and clinically accepted HN VMAT plans through PSQA) were investigated. The mean (± standard deviation) DDPS for the 98 HN competition plans was 158.5 ± 20.6 (maximum DDPS: 200). DDPS showed a weak correlation with PCMs with a maximum r of 0.45 for monitor unit (MU); its correlation with some PCMs was "very weak." Significant differences were found in some PCMs between plans with the highest 20% DDPSs and the remaining plans. The clinical VMAT and competition plans revealed similar distributions for some PCMs. Deviations in PCMs for the two groups were comparable, indicating considerable variability among planners regarding planning skills. The plan complexity for HN VMAT competition plans increased for high-quality plans, as shown by the dose distribution. Direct comparison of PCMs between competition plans and clinically accepted plans showed that the submitted HN VMAT competition plans were realistic and reasonable from the QA perspective. This evaluation may provide a set of criteria for evaluating plan quality in plan competitions.

Radiological imaging protection: a study on imaging dose used while planning computed tomography for external radiotherapy in Japan.

Previous studies have primarily focused on quality of imaging in radiotherapy planning computed tomography (RTCT), with few investigations on imaging doses. To our knowledge, this is the first study aimed to investigate the imaging dose in RTCT to determine baseline data for establishing national diagnostic reference levels (DRLs) in Japanese institutions. A survey questionnaire was sent to domestic RT institutions between 10 October and 16 December 2021. The questionnaire items were volume computed tomography dose index (CTDIvol), dose-length product (DLP), and acquisition parameters, including use of auto exposure image control (AEC) or image-improving reconstruction option (IIRO) for brain stereotactic irradiation (brain STI), head and neck (HN) intensity-modulated radiotherapy (IMRT), lung stereotactic body radiotherapy (lung SBRT), breast-conserving radiotherapy (breast RT), and prostate IMRT protocols. Details on the use of motion-management techniques for lung SBRT were collected. Consequently, we collected 328 responses. The 75th percentiles of CTDIvol were 92, 33, 86, 23, and 32 mGy and those of DLP were 2805, 1301, 2416, 930, and 1158 mGy·cm for brain STI, HN IMRT, lung SBRT, breast RT, and prostate IMRT, respectively. CTDIvol and DLP values in institutions that used AEC or IIRO were lower than those without use for almost all sites. The 75th percentiles of DLP in each treatment technique for lung SBRT were 2541, 2034, 2336, and 2730 mGy·cm for free breathing, breath holding, gating technique, and real-time tumor tracking technique, respectively. Our data will help in establishing DRLs for RTCT protocols, thus reducing imaging doses in Japan.

Identification of reproducible radiomic features from on-board volumetric images: A multi-institutional phantom study.

BACKGROUND: Radiomics analysis using on-board volumetric images has attracted research attention as a method for predicting prognosis during treatment; however, the lack of standardization is still one of the main concerns. PURPOSE: This study investigated the factors that influence the reproducibility of radiomic features extracted from on-board volumetric images using an anthropomorphic radiomics phantom. Furthermore, a phantom experiment was conducted with different treatment machines from multiple institutions as external validation to identify reproducible radiomic features. METHODS: The phantom was designed to be 35 × 20 × 20 cm with eight types of heterogeneous spheres (⌀ = 1, 2, and 3 cm). On-board volumetric images were acquired using 15 treatment machines from eight institutions. Of these, kilovoltage cone-beam computed tomography (kV-CBCT) image data acquired from four treatment machines at one institution were used as an internal evaluation dataset to explore the reproducibility of radiomic features. The remaining image data, including kV-CBCT, megavoltage-CBCT (MV-CBCT), and megavoltage computed tomography (MV-CT) provided by seven different institutions (11 treatment machines), were used as an external validation dataset. A total of 1,302 radiomic features, including 18 first-order, 75 texture, 465 (i.e., 93 × 5) Laplacian of Gaussian (LoG) filter-based, and 744 (i.e., 93 × 8) wavelet filter-based features, were extracted within the spheres. The intraclass correlation coefficient (ICC) was calculated to explore feature repeatability and reproducibility using an internal evaluation dataset. Subsequently, the coefficient of variation (COV) was calculated to validate the feature variability of external institutions. An absolute ICC exceeding 0.85 or COV under 5% was considered indicative of a highly reproducible feature. RESULTS: For internal evaluation, ICC analysis showed that the median percentage of radiomic features with high repeatability was 95.2%. The ICC analysis indicated that the median percentages of highly reproducible features for inter-tube current, reconstruction algorithm, and treatment machine were decreased by 20.8%, 29.2%, and 33.3%, respectively. For external validation, the COV analysis showed that the median percentage of reproducible features was 31.5%. A total of 16 features, including nine LoG filter-based and seven wavelet filter-based features, were indicated as highly reproducible features. The gray-level run-length matrix (GLRLM) was classified as containing the most frequent features (N = 8), followed by the gray-level dependence matrix (N = 7) and gray-level co-occurrence matrix (N = 1) features. CONCLUSIONS: We developed the standard phantom for radiomics analysis of kV-CBCT, MV-CBCT, and MV-CT images. With this phantom, we revealed that the differences in the treatment machine and image reconstruction algorithm reduce the reproducibility of radiomic features from on-board volumetric images. Specifically, the most reproducible features for external validation were LoG or wavelet filter-based GLRLM features. However, the acceptability of the identified features should be examined in advance at each institution before applying the findings to prognosis prediction.

[Questionnaire Survey of Japanese Medical Physicists on Working Conditions in 2020].

The questionnaire survey was conducted in 2020 to investigate the working conditions of qualified medical physicists in Japan. We developed a web-based system for administering the questionnaire and surveyed 1,228 qualified medical physicists. The number of received responses was 405. We summarized the results of the survey by job category. The obtained results showed that most of the people working as certified medical physicists met the following conditions: (1) position of healthcare occupation, (2) direct supervisor is a medical doctor or a medical physicist, (3) licensed or passed an examination for a Class I Radiation Protection Supervisor, (4) without the license of professional radiotherapy technologist, (5) master's or doctor's degree, (6) being assigned to the section that is different from the radiological technologist section. The average annual salary was approximately 600,000 yen higher for those employed as medical physicists than for those employed as radiotherapy technologists. The percentage of work performed by a certified medical physicist in radiation therapy greatly varies depending on whether the physicist is dedicated to treatment planning and equipment quality control. Alternatively, the proportion of the true duties of medical physicists in charge of radiation therapy, as considered by qualified medical physicists in radiation therapy, was the same regardless of whether they were working full-time or not. The results of this survey updated the working status of certified medical physicists in Japan. We will continue to conduct the survey periodically and update the information to contribute to the improvement of the working conditions of medical physicists and policy recommendations.

Outcomes of allogeneic haematopoietic stem cell transplantation with intensity-modulated total body irradiation by helical tomotherapy: a 2-year prospective follow-up study.

BACKGROUND AND OBJECTIVES: Intensity-modulated radiation therapy (IMRT) helps achieve good radiation dose conformity and precise dose evaluation. We conducted a single-centre prospective study to assess the safety and feasibility of total body irradiation with IMRT (IMRT-TBI) using helical tomotherapy in allogeneic haematopoietic stem cell transplantation (allo-HSCT). PATIENTS AND METHODS: Thirty-nine adult patients with haematological malignancy (acute lymphoblastic leukaemia [n = 21], chronic myeloid leukaemia [n = 6], mixed phenotype acute leukaemia [n = 5], acute myeloid leukaemia [n = 4], and malignant lymphoma [n = 3]) who received 12 Gy IMRT-TBI were enrolled with a median follow-up of 934.5 (range, 617-1254) d. At the time of transplantation, 33 patients (85%) achieved complete remission. The conditioning regimen used IMRT-TBI (12 Gy in 6 fractions twice daily, for 3 d) and cyclophosphamide (60 mg/kg/d, for 2 d), seven patients were combined with cytarabine, and five with etoposide. We set dose constraints for the lungs, kidneys and lens as the organs at risk. RESULTS: The mean doses for the lungs and kidneys were 7.50 and 9.11 Gy, respectively. The mean maximum dose for the lens (right/left) was 5.75/5.87 Gy. The 2-year overall survival (OS), disease-free survival (DFS), cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) were 69, 64, 18 and 18%, respectively. Thirty-six patients developed early adverse events (AEs) (including four patients with Grade 3/4 toxicities), most of which were reversible oral mucositis and may partially have been related to IMRT-TBI. However, the incidence of toxicity was comparable to conventional TBI-based conditioning transplantation. None of the patients developed primary graft failure, or Grade III-IV acute graft-versus-host disease (GVHD). In late complications, chronic kidney disease was observed in six patients, a lower incidence compared to conventional TBI-based conditioning transplantation. No radiation pneumonitis or cataracts were observed in any of the patients. CONCLUSIONS: IMRT-TBI is safe and feasible for haematological malignancies with acceptable clinical outcomes.KEY MESSAGESIMRT-TBI-helical tomotherapy aids in accurate dose calculation and conformity.It could be used without any considerable increase in the rate of TBI-related AEs.Allo-HSCT with IMRT-TBI may be an alternative to conventional TBI for clinical use.

Dose response of a radiophotoluminescent glass dosimeter for TomoTherapy, CyberKnife, and flattening-filter-free linear accelerator output measurements in dosimetry audit.

PURPOSE: We experimentally determined the radiophotoluminescent glass dosimeter (RPLD) dose responses for TomoTherapy, CyberKnife, and flattening-filter-free (FFF) linear accelerator (linac) outputs for dosimetry audits in Japan. METHODS: A custom-made solid phantom with a narrow central-axis spacing of three RPLD elements was used for output measurement to minimise the dose-gradient effect of the non-flattening filter beams. For RPLD dose estimation, we used the ISO 22127 formalism. Additional unit-specific correction factors were introduced and determined via the measured data. For TomoTherapy (7 units) and CyberKnife (4 units), the doses were measured under machine-specific reference fields. For FFF linac (5 units), in addition to the reference condition, we obtained the field-size effects for the range from 5×5 cm to 25×25 cm. RESULTS: The correction factors were estimated as 1.008 and 0.999 for TomoTherapy and CyberKnife, respectively. For FFF linac, they ranged from 1.011 to 0.988 for 6 MV and from 1.011 to 0.997 for 10 MV as a function of the side length of the square field from 5 to 25 cm. The estimated uncertainties of the absorbed dose to water measured by RPLD for the units were 1.32%, 1.35%, and 1.30% for TomoTherapy, CyberKnife, and FFF linac, respectively. A summary of the dosimetry audits of these treatment units using the obtained correction factors is also presented. The average percentage differences between the measured and hospital-stated doses were <1% under all conditions. CONCLUSION: RPLD can be successfully used as a dosimetry audit tool for modern treatment units.

The efficacy of memantine in the treatment of civilian posttraumatic stress disorder: an open-label trial.

Background: Currently, there is a paucity of pharmacological treatment options for posttraumatic stress disorder (PTSD), and the development of a novel pharmacotherapeutic approach has become a matter of great interest. Objective: We conducted a 12-week open-label clinical trial to examine the efficacy and safety of memantine, an N-methyl-D-aspartate receptor antagonist, in the treatment of civilian PTSD. Method: Thirteen adult patients with DSM-IV PTSD, all civilian women, were enrolled. They were monitored at an ambulatory care facility every week until 4 weeks and then every 4 weeks until 12 weeks. Memantine was added to each patient's current medication, with the initial dosage of 5 mg/day and then titrated. Concomitant medications were essentially kept unchanged during the trial. The primary outcome was PTSD diagnosis and severity assessed with the Posttraumatic Diagnostic Scale (PDS). Results: Of the 13 cases, one dropped out and two were discarded due to the protocol deviation, and the analysis was done for the remaining 10. Mean PDS total scores decreased from 32.3 ± 9.7 at baseline to 12.2 ± 7.9 at endpoint, which was statistically significant with a large effect (paired t-test: p = .002, d = 1.35); intrusion, avoidance, hyperarousal symptoms were all significantly improved from baseline to endpoint. Six patients no longer fulfilled the diagnostic criteria of PTSD at endpoint. Some adverse, but not serious, effects possibly related to memantine were observed, including sleep problems, sleepiness, sedation, weight change and hypotension. Conclusions: Memantine significantly reduced PTSD symptoms in civilian female PTSD patients and the drug was well tolerated. Future randomized controlled trials are necessary to verify the efficacy and safety of memantine in the treatment of PTSD.

Antecedentes: Actualmente, hay escasez de opciones de tratamiento farmacológico para el trastorno de estrés postraumático (TEPT), y el desarrollo de un enfoque farmacoterapéutico nuevo se ha transformado en materia de gran interés.Objetivo: Llevamos a cabo un ensayo clínico abierto de 12 semanas para examinar la eficacia y seguridad de memantina, un antagonista del receptor de N-metil-d-aspartato, en el tratamiento del TEPT en civiles.Método: Se inscribieron trece pacientes adultas con TEPT según DSM-IV, todas mujeres civiles. Fueron monitoreadas en un centro de atención ambulatoria semanalmente por 4 semanas, y luego cada 4 semanas hasta las 12 semanas. Se agregó memantina al tratamiento farmacológico actual de cada paciente, con dosis inicial de 5 mg/día y titulación posterior. Los fármacos concomitantes fueron mantenidos esencialmente sin cambios durante el estudio. El objetivo primario fue el diagnóstico de TEPT y su severidad, evaluada con la Escala de Diagóstico Postraumático (PDS, por su sigla en inglés).Resultados: De los 13 casos, uno abandonó y 2 fueron descartados debido a desvío del protocolo, y el análisis fue realizado con los 10 restantes. El puntaje total promedio de PDS disminuyó de 32.3 ± 9.7 en el basal a 12.2 ± 7.9 al término, lo que fue estadísticamente significativo con un tamaño de efecto grande (prueba t pareada: p=.002, d=1.35); los síntomas de intrusión, evitación e hiperactivación mejoraron todos en forma al término respecto a la basal. Seis pacientes dejaron de cumplir los criterios de TEPT al término. Se observaron algunos efectos adversos, pero no serios, posiblemente relacionados a memantina, que incluyeron problemas del sueño, somnolencia, sedación, cambios en el peso e hipotensión.Conclusiones: La memantina redujo significativamente los síntomas de TEPT en pacientes mujeres civiles con TEPT y el fármaco fue bien tolerado. Se requieren ensayos controlados aleatorizados en el futuro para verificar la eficacia y seguridad de la memantina en el tratamiento del TEPT.

Radiation protection in radiological imaging: a survey of imaging modalities used in Japanese institutions for verifying applicator placements in high-dose-rate brachytherapy.

Institutional imaging protocols for the verification of brachytherapy applicator placements were investigated in a survey study of domestic radiotherapy institutions. The survey form designed by a free on-line survey system was distributed via the mailing-list system of the Japanese Society for Radiation Oncology. Survey data of 75 institutions between August 2019 and October 2019 were collected. The imaging modalities used were dependent on resources available to the institutions. The displacement of a brachytherapy applicator results in significant dosimetric impact. It is essential to verify applicator placements using imaging modalities before treatment. Various imaging modalities used in institutions included a computed tomography (CT) scanner, an angiography X-ray system, a multi-purpose X-ray system and a radiotherapy simulator. The median total exposure time in overall treatment sessions was $\le$75 s for gynecological and prostate cancers. Some institutions used fluoroscopy to monitor the brachytherapy source movement. Institutional countermeasures for reducing unwanted imaging dose included minimizing the image area, changing the imaging orientation, reducing the imaging frequency and optimizing the imaging conditions. It is worth noting that half of the institutions did not confirm imaging dose regularly. This study reported on the usage of imaging modalities for brachytherapy in Japan. More caution should be applied with interstitial brachytherapy with many catheters that can lead to potentially substantial increments in imaging doses for monitoring the actual brachytherapy source using fluoroscopy. It is necessary to share imaging techniques, standardize imaging protocols and quality assurance/quality control among institutions, and imaging dose guidelines for optimization of imaging doses delivered in radiotherapy should be developed.

Report dose-to-medium in clinical trials where available; a consensus from the Global Harmonisation Group to maximize consistency.

PURPOSE: To promote consistency in clinical trials by recommending a uniform framework as it relates to radiation transport and dose calculation in water versus in medium. METHODS: The Global Quality Assurance of Radiation Therapy Clinical Trials Harmonisation Group (GHG; www.rtqaharmonization.org) compared the differences between dose to water in water (Dw,w), dose to water in medium (Dw,m), and dose to medium in medium (Dm,m). This was done based on a review of historical frameworks, existing literature and standards, clinical issues in the context of clinical trials, and the trajectory of radiation dose calculations. Based on these factors, recommendations were developed. RESULTS: No framework was found to be ideal or perfect given the history, complexity, and current status of radiation therapy. Nevertheless, based on the evidence available, the GHG established a recommendation preferring dose to medium in medium (Dm,m). CONCLUSIONS: Dose to medium in medium (Dm,m) is the preferred dose calculation and reporting framework. If an institution's planning system can only calculate dose to water in water (Dw,w), this is acceptable.

Evaluation of the effect of user-guided deformable image registration of thoracic images on registration accuracy among users.

User-guided deformable image registration (DIR) has allowed users to actively participate in the DIR process and is expected to improve DIR accuracy. The purpose of this study was to evaluate the time required for and effect of user-guided DIR on registration accuracy for thoracic images among users. In this study, 4-dimensional computed tomographic images of 10 thoracic cancer patients were used. The dataset for these patients was provided by DIR-Lab (www.dir-lab.com) and included a coordinate list of anatomical landmarks (300 bronchial bifurcations). Four medical physicists from different institutions performed DIR between peak-inhale and peak-exhale images with/without the user-guided DIR tool, Reg Refine, implemented in MIM Maestro (MIM software, Cleveland, OH). DIR accuracy was quantified by using target registration errors (TREs) for 300 anatomical landmarks in each patient. The average TREs with user-guided DIR in the 10 images by the 4 medical physicists were 1.48, 1.80, 3.46, and 3.55 mm, respectively, whereas the TREs without user-guided DIR were 3.28, 3.45, 3.56, and 3.28 mm, respectively. The average times taken by the 4 physicists to use the user-guided DIR were 10.0, 6.7, 7.1, and 8.0 min, respectively. This study demonstrated that user-guided DIR can improve DIR accuracy and requires only a moderate amount of time (<10 min). However, 2 of the 4 users did not show much improvement in DIR accuracy, which indicated the necessity of training prior to use of user-guided DIR.

Questionnaire survey on treatment planning techniques for lung stereotactic body radiotherapy in Japan.

This study aimed to obtain details regarding treatment planning techniques for lung stereotactic body radiation therapy (SBRT) employed at each institution in Japan by using a questionnaire survey. An Internet questionnaire survey on SBRT procedures performed in 2016 was conducted by the QA/QC committee of the Japan Society of Medical Physics from April to June 2017. The questionnaire assessed two aspects: the environment for SBRT at each institution and the treatment planning techniques with and without respiratory motion management techniques (RMMT). Of the 309 evaluated responses, 218 institutions had performed SBRT. A total of 186 institutions performed SBRT without RMMT and 139 institutions performed SBRT with RMMT. When respiratory motion was ≥10 mm, 69 institutions applied RMMT. The leading RMMT were breath holding (77 institutions), respiratory gating (49 institutions) and real-time tumor tracking (11 institutions). The most frequently used irradiation technique was 3D conformal radiotherapy, which was used in 145 institutions without RMMT and 119 institutions with RMMT. Computed tomography (CT) images acquired under free breathing were mostly used for dose calculation for patients treated without RMMT. The usage ratio of IMRT/VMAT to SBRT is low in Japan, compared to elsewhere in the world (<20% vs ≥70%). Among the available dose calculation algorithms, superposition convolution was the most frequently used regardless of RMMT; however, 2% of institutions have not yet made heterogeneity corrections. In the prescription setting, about half of the institutions applied point prescriptions. The survey results revealed the most frequently used conditions, which may facilitate standardization of treatment techniques in lung SBRT.

An overview of the medical-physics-related verification system for radiotherapy multicenter clinical trials by the Medical Physics Working Group in the Japan Clinical Oncology Group-Radiation Therapy Study Group.

The Japan Clinical Oncology Group-Radiation Therapy Study Group (JCOG-RTSG) has initiated several multicenter clinical trials for high-precision radiotherapy, which are presently ongoing. When conducting multi-center clinical trials, a large difference in physical quantities, such as the absolute doses to the target and the organ at risk, as well as the irradiation localization accuracy, affects the treatment outcome. Therefore, the differences in the various physical quantities used in different institutions must be within an acceptable range for conducting multicenter clinical trials, and this must be verified with medical physics consideration. In 2011, Japan's first Medical Physics Working Group (MPWG) in the JCOG-RTSG was established to perform this medical-physics-related verification for multicenter clinical trials. We have developed an auditing method to verify the accuracy of the absolute dose and the irradiation localization. Subsequently, we credentialed the participating institutions in the JCOG multicenter clinical trials that were using stereotactic body radiotherapy (SBRT) for lungs, intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) for several disease sites, and proton beam therapy (PT) for the liver. From the verification results, accuracies of the absolute dose and the irradiation localization among the participating institutions of the multicenter clinical trial were assured, and the JCOG clinical trials could be initiated.