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We developed a Fe:ZnSe chirped pulse amplifier with a KTA-based optical parametric amplifier, achieving 0.6 mJ pulses at 4-micron wavelength. It should be inherently carrier envelope phase stable and applicable to strong field science.

In the treatment of non-small cell lung cancers, there is an increasing demand for less invasive stereotactic body radiotherapy (SBRT) compared to surgery. Local recurrence (LR) significantly impacts prognosis, and factors such as histological type and tumor size have been considered as LR risks. In this study, we retrospectively examined LR risks from the perspective of dose coverage to the target. Patients with clinical stage IA1-IIA squamous cell carcinoma (SCC) or adenocarcinoma (ADC), who were treated with SBRT, were included in the analysis. Doses of 44–52 Gy were prescribed to the isocenter of planning target volume (PTV) according to the respective tumor diameters. The primary endpoint was LR. Age, sex, performance status, smoking, forced expiratory volume 1L, tumor diameter, biologically effective doses (BED) in α/β = 10 were evaluated for the clinical factors. As for dose parameters, mean, minimum, and maximum doses, D99, D98, D95, D90, D80, D50, and homogeneity index (HI) of the gross tumor volume (GTV), internal target volume (ITV), and PTV were evaluated. To evaluate the relationship between risk factors and LR, the univariate analyses were performed with the Gray test for clinical factors and with the Fine-Gray model for dose parameters. The multivariate analysis was conducted using the Fine-Gray model. Among the 198 patients analyzed, median age was 77 years. Of these, 63 and 135 patients were in the SCC and ADC groups, respectively. Mean, minimum, and maximum doses, D99, D98, D95, D90, D80, D50, and HI were 99.8, 95.4, 102.6, 96.5, 96.9 97.4, 98.1, 98.7, 99.9, and 1.1 in GTV, 99.5, 92.6, 102.9, 95.0, 95.6, 96.3, 97.1, 98.1, 99.6, and 1.1 in ITV, and 98.5, 83.5, 102.9, 89.6, 90.9, 93.0, 94.8, 96.4, 98.9, and 1.2 in PTV, respectively. The median follow-up period was 48.5 months. The 3-year LR rates of all patients, SCC and ADC groups were 13.4%, 23.0%, and 9.3%, respectively. In the univariate analysis of clinical factors, tumor diameter, BED, histological type were associated with LR in all patients (p = 0.023, 0.025, and 0.013, respectively). No factor was associated with LR in the ADC group, while BED was associated with LR in the SCC group (p = 0.034). In the univariate analysis of dose parameters, no factor was associated with LR in all patients and the SCC group, while only HI of GTV was associated with LR in the ADC group (p = 0.027). In the multivariate analysis, no factor was associated with LR in all patients. ITV mean, ITV D90, ITV D80, ITV D50, and PTV D50 were associated with LR in the SCC group (p = 0.011, 0.044, 0.031, 0.013, and 0.037, respectively), while GTV minimum and GTV HI were associated with LR in the ADC group (p = 0.029 and 0.015, respectively). In the SCC group, the coverage of PTV D50 and several parameters of ITV showed a significant correlation with LR after SBRT. The coverage of ITV is considered particularly crucial in SBRT for SCC tumors. [ABSTRACT FROM AUTHOR]

To identify risk factors and bronchial dose constraints for radiation pneumonitis (RP) after stereotactic body radiotherapy (SBRT) in patients with central early-stage non-small cell lung cancer (NSCLC). We reviewed 245 patients with early-stage NSCLC treated with SBRT, and 79 patients with a tumor within 3 cm of the main or lobar bronchus were included in this study. The median prescribed dose and fraction were 50 Gy and 4 fractions, respectively. The primary endpoint was grade ≥ 2 RP. Gray's test was performed to examine the relationship between clinical risk factors and grade ≥2 RP, and the Fine-Gray model was used for a multivariate analysis. The effects of each dose parameter on grade ≥2 RP were evaluated with the Fine-Gray model and optimal thresholds were tested using receiver operating characteristic (ROC) curves. Among a total of 79 patients analyzed. The median age of patients was 77 years. The median follow-up period was 43 months. The 4-year cumulative incidence of grade ≥2 RP was 22.5% (G2, 11 patients; G3, 6 patients; ≥G4, none). The multivariate analysis of clinical factors identified age, the location of the lobes, and the solid component diameter as significant factors for grade ≥2 RP (p = 0.018, 0.005, and 0.002, respectively). Regarding bronchial parameters, V10-V40Gy and D0.1-D5cc correlated with the development of RP. Among all parameters of the bronchus and lung, only bronchial parameters exceeded AUC of 0.72 for grade ≥2 RP. Parameters with AUC exceeding 0.72 were bronchus V20Gy (AUC, 0.728), V15Gy (AUC, 0.736), and V10Gy (AUC, 0.723), with respective thresholds of 0.41, 1.2, and 1.8 cc. Bronchus V15Gy ≤1.2 cc serves as the best indicator for the prevention of grade ≥2 RP. In SBRT for central early-stage NSCLC, bronchus V15Gy ≤1.2 cc is the definitive indicator for preventing grade ≥2 RP. [ABSTRACT FROM AUTHOR]

A hydrogel spacer injection between the prostate and rectum is reported to reduce the risk of rectal toxicity in radiotherapy for prostate cancer. We present a case of an ectopic injection of hydrogel spacer. The patient was a 77-year-old male with intermediate-risk prostate cancer. It was planned that he would receive intensity modulated radiation therapy(IMRT), and a hydrogel spacer was inserted. Three days after insertion, the patient had a fever of 38.6℃ and presented frequent urination and perineal pain. Swelling and heat sensation were observed in the perineum. CRP was 12.00 mg/dL and the white blood cell count was as high as 9,300/μL. T2-weighted images showed a 5.3×1.9 cm high-intensity area around the lower urethra. Ectopic injection of hydrogel spacer and concomitant infection were diagnosed. Upon administering antibiotic treatment, his symptoms and inflammation improved immediately. Four months after hydrogel spacer insertion, T2-weighted images showed a high-intensity area in the lower urethra and around the ischial bone, which was attributed to the remaining hydrogel spacer. The hydrogel spacer and his symptoms completely disappeared at 9 months after hydrogel spacer insertion.

Objective: To evaluate the impact of daily fraction doses on late genitourinary (GU) toxicity after salvage radiotherapy (SRT) for prostate cancer., Methods: This multi-institutional retrospective study included 212 patients who underwent SRT between 2008 and 2018. All patients received image-guided intensity-modulated SRT at a median dose of 67.2 Gy in 1.8-2.3 Gy/fraction. The cumulative rates of late grade ≥2 GU and gastrointestinal (GI) toxicities were compared using Gray test, stratified by the ≤2.0 Gy/fraction (n = 137) and ≥2.1 Gy/fraction groups (n = 75), followed by multivariate analyses. The total dose was represented as an equivalent dose in 2-Gy fractions (EQD2) with α/β = 3 Gy., Results: After a median follow-up of 63 months, the cumulative rates of 5-year late grade ≥2 GU and GI toxicities were 14% and 2.5%, respectively. The cumulative rates of 5-year late grade ≥2 GU toxicity in the ≥2.1 Gy/fraction and ≤2.0 Gy/fraction groups were 22% and 10%, respectively (P = .020). In the multivariate analysis, ≥2.1 Gy/fraction was still associated with an increased risk of late grade ≥2 GU toxicity (hazard ratio, 2.37; 95% confidence interval, 1.12-4.99; P = .023), while the total dose was not significant., Conclusion: The present results showed that ≥2.1 Gy/fraction resulted in a higher incidence of late grade ≥2 GU toxicity in SRT., Advances in Knowledge: The impact of fraction doses on late GU toxicity after SRT remains unknown. The results suggest that higher fraction doses may increase the risk of late GU toxicity in SRT., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Institute of Radiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background and Purpose: Interfractional geometrical and anatomical variations impact the accuracy of proton therapy for pancreatic cancer. This study investigated field-in-field (FIF) and simultaneous integrated boost (SIB) concepts for scanned proton therapy treatment with different beam configurations., Materials and Methods: Robustly optimized treatment plans for fifteen patients were generated using FIF and SIB techniques with two, three, and four beams. The prescribed dose in 20 fractions was 60 Gy(RBE) for the internal gross tumor volume (IGTV) and 46 Gy(RBE) for the internal clinical target volume. Verification computed tomography (vCT) scans was performed on treatment days 1, 7, and 16. Initial treatment plans were recalculated on the rigidly registered vCTs. V 100% and D 95% for targets and D 2cm 3 for the stomach and duodenum were evaluated. Robustness evaluations (range uncertainty of 3.5 %) were performed to evaluate the stomach and duodenum dose-volume parameters., Results: For all techniques, IGTV V 100% and D 95% decreased significantly when recalculating the dose on vCTs (p < 0.001). The median IGTV V 100% and D 95% over all vCTs ranged from 74.2 % to 90.2 % and 58.8 Gy(RBE) to 59.4 Gy(RBE), respectively. The FIF with two and three beams, and SIB with two beams maintained the highest IGTV V 100% and D 95% . In robustness evaluations, the ΔD 2cm 3 of stomach was highest in two beams plans, while the ΔD 2cm 3 of duodenum was highest in four beams plans, for both concepts., Conclusion: Target coverage decreased when recalculating on CTs at different time for both concepts. The FIF with three beams maintained the highest IGTV coverage while sparing normal organs the most., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

We compared survival outcomes of high-dose concomitant boost radiotherapy (HDCBRT) and conventional dose radiotherapy (CRT) for newly diagnosed glioblastoma (GB). Patients treated with intensity-modulated radiation therapy for newly diagnosed GB were included. In HDCBRT, specific targets received 69, 60, and 51 Gy in 30 fractions, while 60 Gy in 30 fractions was administered with a standard radiotherapy method in CRT. Overall survival (OS) and progression-free survival (PFS) were compared using the Log-rank test, followed by multivariate Cox analysis. The inverse probability of treatment weighting (IPTW) method was also applied to each analysis. Among 102 eligible patients, 45 received HDCBRT and 57 received CRT. With a median follow-up of 16 months, the median survival times of OS and PFS were 21 and 9 months, respectively. No significant differences were observed in OS or PFS in the Kaplan-Meier analyses. In the multivariate analysis, HDCBRT correlated with improved OS (hazard ratio, 0.49; 95% confidence interval, 0.27-0.90; P = 0.021), and this result remained consistent after IPTW adjustments (P = 0.028). Conversely, dose suppression due to the proximity of normal tissues and IMRT field correlated with worse OS and PFS (P = 0.008 and 0.049, respectively). A prospective study with a stricter protocol is warranted to validate the efficacy of HDCBRT for GB., (© 2024. The Author(s).)

Physical exercise interventions to prevent falls for older adults at risk of falling are widespread in many countries; however, there is insufficient knowledge of the impact of long-term exercise on the fall discriminating ability of existing fall-prediction indicators. This study measured physical and cognitive indicators of the fall risk, including the timed up and go (TUG), walking speed (WS), and plantar tactile threshold (PTT), in 124 community-dwelling older adults with care needs who were continuing an exercise program. Logistic regression analyses were used to determine factors associated with falls in the 87 participants who could adhere to the exercise continuously for 12 months. The PTT was significantly higher in fallers, while the TUG and WS did not differ significantly between fallers and non-fallers. The only index significantly associated with falls was the PTT ( OR  = 1.20). The fall identification ability was better for PTT (AUC = 0.63), whereas TUG (AUC = 0.57) and WS (AUC = 0.52) were lower than previously reported scores. In conclusion, long-term exercise was found to improve scores on the fallprediction indicators by physical performance, but to decrease their ability to identify future falls. PTT may complement the ability to identify falls in such elderly populations., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Intramedullary spinal cord metastasis(ISCM)often causes spinal cord neuropathy and should be treated as an oncologic emergency. However, it recurs in most cases after treatment, ISCM is a disease with a very unfavorable prognosis. Herein, we report a successfully treated case of ISCM with emergent and high-dose radiotherapy. A 53-year-old woman had difficulty walking without assistance 2 years after surgery for ovarian cancer. She received emergent radiotherapy at a total dose of 50 Gy in 25 fractions. Her neurological symptoms dramatically improved over 3 weeks after radiotherapy. ISCM has been controlled using the imaging tests at 5 years after radiotherapy. We believe that both emergent and high-dose radiotherapy were effective for ISCM.

Introduction: In this simulation study, we examined the effects of a de-escalation strategy with a reduced dose to subclinical nodal regions in patients with human papillomavirus (HPV)-associated oropharyngeal carcinoma (OPC)., Methods: We created two patterns of intensity-modulated radiotherapy for 16 patients with HPV-associated OPC. In the standard and de-escalation plans, the initial field including elective nodal regions received 46 and 30 Gy, followed by 20 and 36 Gy to the cutdown field, respectively. Comparison metrics were set for each organ at risk (OAR). We compared these metric values and the probability of adverse effects based on the normal tissue complication probability (NTCP) model between the two plans., Results: Both plans generally met the dose constraints for the targets and all OAR. Among the comparison metrics, the mean doses to the brain, pharyngeal constrictor muscle, thyroid, and skin and the dose to a 1 % volume of the skin were higher in the standard plan than in the de-escalation plan ( P  = 0.031, 0.007, < 0.001, < 0.001, and 0.006, respectively). NTCP analyses revealed that the probability of adverse effects in the ipsilateral parotid gland and thyroid was higher in the standard plan than in the de-escalation plan (standard vs. de-escalation plans: ipsilateral parotid gland, 6.4 % vs. 5.0 %, P  = 0.016; thyroid, 3.3 % vs. 0.5 %, P  < 0.001)., Conclusions: A de-escalation strategy with elective nodal regions is a promising treatment to prevent a decline in the quality of life in patients with HPV-associated OPC, particularly xerostomia, dysphagia, and hypothyroidism., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Background and Purpose: The present study investigated the relationships between the risk of radiation-induced rib fractures (RIRF) and clinical and dosimetric factors in stereotactic body radiotherapy (SBRT) for early-stage non-small cell lung cancer (NSCLC). We also examined dosimetric parameters associated with symptomatic or asymptomatic RIRF and the dosimetric threshold for symptomatic RIRF., Materials and Methods: We reviewed 244 cases of early-stage NSCLC treated with SBRT. Gray's test and the Fine-Gray model were performed to examine the relationships between clinical and dosimetric factors and grade ≥ 2 (i.e., symptomatic) RIRF. The effects of each dose parameter on grade ≥ 1 and ≥ 2 RIRF were assessed with the Fine-Gray model. The t -test was used to compare each dose parameter between the grade 1 and grade ≥ 2 groups. Optimal thresholds were tested using receiver operating characteristic (ROC) curves., Results: With a median follow-up period of 48 months, the 4-year cumulative incidence of grade ≥ 1 and grade ≥ 2 RIRF were 26.4 % and 8.0 %, respectively. Regarding clinical factors, only age was associated with the development of grade ≥ 2 RIRF (p = 0.024). Among dosimetric parameters, only V40Gy significantly differed between the grade 1 and grade ≥ 2 groups (p = 0.015). The ROC curve analysis of grade ≥ 2 RIRF showed that the optimal diagnostic thresholds for D3cc, D4cc, D5cc, and V40Gy were 45.86 Gy (area under the curve [AUC], 0.706), 39.02 Gy (AUC, 0.705), 41.62 Gy (AUC, 0.702), and 3.83 cc (AUC, 0.730), respectively. These results showed that V40Gy ≤ 3.83 cc was the best indicator of grade ≥ 2 RIRF. The 4-year incidence of grade ≥ 2 RIRF in the V40Gy ≤ 3.83 cc vs. > 3.83 cc groups was 1.8 % vs. 14.2 % (p = 0.001)., Conclusion: The present results recommend V40Gy ≤ 3.83 cc as the threshold for grade ≥ 2 RIRF in SBRT., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

Background/aim: The 8 th edition of the American Joint Committee on Cancer staging system classifies oropharyngeal cancer (OPC) by the expression of p16. The discrepancy observed in this system between pathological and clinical N-stages in p16-positive OPC has provoked controversy. Therefore, this study investigated prognostic factors not included in the new staging system for p16-positive OPC patients., Patients and Methods: Patients with non-metastatic OPC receiving radiotherapy were reviewed. Clinical lymph node statuses were reassessed based on contrast-enhanced computed tomography and fluorodeoxyglucose positron emission tomography. Overall survival (OS) and cause-specific survival (CSS) were analyzed using multivariate analyses to adjust baseline imbalances., Results: In total, 166 OPC patients were reviewed. Among them, 81 patients with p16-positive were analyzed. Three or more lymph node metastases (LNM) were observed in 21 p16-positive OPCs. Retropharyngeal lymph node metastasis (Rp) was found in 12. Three-year OS, CSS, and progression-free survival rates in p16-positive patients were 76, 88, and 81%, respectively. In multivariate analyses of p16-positive OPC, LNM ≥3 was a prognostic factor of OS (hazard ratio=9.30, p<0.001) and CSS (hazard ratio=17.80, p=0.005). Rp was associated with poor CSS (hazard ratio=8.73, p=0.03). In N0-1 p16-positive patients, LNM ≥3 trended to be associated with poor OS (hazard ratio=3.93, p=0.06). CSS in patients with Rp was unfavorable (hazard ratio=70.16, p=0.05)., Conclusion: LNM ≥3 and Rp may be predictive of OS and CCS in p16-positive OPC. These are also possibly used to subcategorize p16-positive cN0-1 OPC. Further validation of lymph node staging is needed to refine the clinical staging system., (Copyright © 2023, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Competing Interests: None disclosed.

Angiosarcoma of the scalp and face (ASF) is a rare, aggressive tumor often treated with multimodal therapy, including radiation therapy (RT). This study assessed RT outcomes for ASF and identified prognostic factors. Data from 68 non-metastatic ASF patients undergoing RT with or without other therapies were analyzed. Median radiation dose was 66 Gy in 33 fractions (interquartile range (IQR) 60-70 Gy in 28-35 fractions). Local control (LC), progression-free survival (PFS), and overall survival (OS) rates were calculated using Kaplan-Meier analysis. Multivariate analyses and adverse event evaluation were conducted. Median patient age was 75 years (IQR 71-80 years), with a median follow-up of 17 months (IQR 11-42 months). One-/three-year LC rates were 57/37%, PFS rates were 44/22%, and OS rates were 81/44%. Multivariate analyses showed that an equivalent dose in a 2 Gy fraction (EQD 2 ) >66 Gy correlated with improved LC (HR 2.35, 95% CI 1.03-5.32, p = 0.041). Combining chemotherapy (HR 2.43, 95% CI 1.08-5.46, p = 0.032) or surgery (HR 2.41, 95% CI 1.03-5.59, p = 0.041) improved PFS. No factors influenced OS. Late grade 3+ toxicities occurred in 1%, with one patient developing a grade 4 skin ulcer. These findings suggest that EQD 2 > 66 Gy and combining chemotherapy or surgery can enhance LC or PFS in ASF. Further prospective studies are needed to determine the optimal treatment strategy for this rare malignancy, particularly in elderly patients.

We aimed to examine outcomes and toxicities of intensity-modulated radiation therapy (IMRT) with the central shielding (CS) technique for patients with uterine cervical cancer. This retrospective study included 54 patients with International Federation of Gynecology and Obstetrics IB-IVA cancer. Whole pelvic radiotherapy or extended-field radiotherapy were performed at the dose of 50.4 Gy in 28 fractions with helical tomotherapy (HT). Six patients had para-aortic lymph node metastases. The CS technique with HT was utilized after a total dose of 28.8-41.4 Gy to reduce doses to the rectum and bladder. The prescribed dose of intracavitary brachytherapy was mainly 18-24 Gy in three or four fractions at point A. Concurrent chemotherapy was used for 47 patients (87%). Median follow-up time was 56 months. Seventeen patients (31%) developed recurrence. The recurrence of the cervix was observed in two patients (4%). The 5-year rates of the locoregional control, progression-free survival (PFS) and overall survival were 79, 66 and 82%, respectively. Among several factors evaluated, histological type of adenocarcinoma was only a significantly worse prognostic factor for PFS by multivariate analysis (hazard ratio, 4.9 [95% confidence interval, 1.3-18], P = 0.018). Grade 2 or higher late toxicities were observed in nine patients (17%). Two patients (4%) each had grade 3 proctitis and grade 3 ileus, respectively. No grade 4 toxicity or treatment-related death was observed. The results suggest that IMRT with the CS technique allows a high local control without increasing the risk of complications for cervical cancer patients., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

Background and Purpose: The present study attempted to identify risk factors for symptomatic radiation pneumonitis (RP) after stereotactic body radiotherapy (SBRT) in patients with early-stage non-small cell lung cancer (NSCLC)., Materials and Methods: We reviewed 244 patients with early-stage NSCLC treated with SBRT. The primary endpoint was the incidence of grade ≥2 RP. Gray's test was performed to examine the relationship between clinical risk factors and grade ≥2 RP, and the Fine-Gray model was used for a multivariate analysis. The effects of each dose parameter on grade ≥2 RP were evaluated with the Fine-Gray model and optimal thresholds were tested using receiver operating characteristic (ROC) curves., Results: With a median follow-up period of 48 months, the 4-year cumulative incidence of grade ≥2 RP was 15.3%. Gray's test revealed that tumor size, a central tumor, interstitial pneumonia, and the biologically effective dose correlated with RP. In the multivariate analysis, a central tumor and interstitial pneumonia remained significant factors (p < 0.001, p = 0.002). Among dose parameters, the total lung volume (%) receiving at least 8 Gy (V8), V10, V20, and the mean lung dose correlated with RP (p = 0.012, 0.011, 0.022, and 0.014, respectively). The results of the Fine-Gray model and ROC curve analyses showed that V10 >16.7% was the best indicator of symptomatic RP among dose parameters., Conclusion: The present results suggest that a central tumor and interstitial pneumonia are independent risk factors for symptomatic RP and lung V10 ≤16.7% is recommended as the threshold in SBRT., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

We compared recurrence patterns between adenocarcinoma (ADC) and squamous cell carcinoma (SCC) after stereotactic body radiotherapy (SBRT) for early-stage lung cancer. Patients with ADC and SCC histology, who were treated with SBRT for clinical stage IA1-IIA lung cancer at our institution, were included in the analysis. The rates of disease-free survival (DFS), overall survival (OS), local recurrence (LR), lymph node metastasis (LNM), and distant metastasis (DM) were calculated using the Kaplan-Meier method or the cumulative incidence function. Among the 204 patients analyzed, 138 and 66 were in the ADC and SCC groups, respectively. The median follow-up period was 60 months. The five-year DFS and OS rates were 57% vs. 41% and 69% vs. 48% in the ADC and SCC groups, respectively ( p = 0.015 and 0.019, respectively). In the multivariate analysis, the histological type was not associated with DFS or OS. Five-year LR, LNM, and DM rates were 10% vs. 24%, 12% vs. 20%, and 25% vs. 27% in the ADC and SCC groups, respectively ( p = 0.0067, 0.074, and 0.67, respectively). The multivariate analysis identified the histological type of SCC as an independent factor for LR (hazard ratio, 2.41; 95% confidence interval, 1.21-4.77; p = 0.012). The present results suggest that the risk of LR after SBRT is higher for SCC than for ADC.

Background: Radiobiological daily changes within tumors are considered to be quite different between stereotactic radiotherapy (SRT) (e.g., 50 Gy in 4 fractions) and conventional radiotherapy (e.g., 60 Gy in 30 fractions). We aim to assess the optimal interval of irradiation in SRT and compare outcomes of daily irradiation with irradiation at two- to three-day intervals in SRT for patients with one to five brain metastases (BM)., Methods: This study is conducted as a multicenter open-label randomized phase II trial. Patients aged 20 or older with one to five BM, less than 3.0 cm diameter, and Karnofsky Performance Status ≥70 are eligible. A total of 70 eligible patients will be enrolled. After stratifying by the number of BMs (1, 2 vs. 3-5) and diameter of the largest tumor (< 2 cm vs. ≥ 2 cm), we randomly assigned patients (1:1) to receive daily irradiation (Arm 1), or irradiation at two- to three-day intervals (Arm 2). Both arms are performed with total dose of 27-30 Gy in 3 fractions. The primary endpoint is an intracranial local control rate, defined as intracranial local control at initially treated sites. We use a randomized phase II screening design with a two-sided α of 0∙20. The phase II trial is positive with p < 0.20. All analyses are intention to treat. This study is registered with the UMIN-clinical trials registry, number UMIN000048728., Discussion: This study will provide an assessment of the impact of SRT interval on local control, survival, and toxicity for patients with 1-5 BM. The trial is ongoing and is recruiting now., Trial Registration: UMIN000048728. Date of registration: August 23, 2022. https://center6.umin.ac.jp/cgi-bin/ctr/ctr&#95;view&#95;reg.cgi?recptno=R000055515 ., (© 2022. The Author(s).)

We demonstrate spectral peak formation in a mode-locked solid-state laser that contains a gas cell inside the cavity. Symmetric spectral peaks appear in the course of sequential spectral shaping through resonant interaction with molecular rovibrational transitions and nonlinear phase modulation in the gain medium. The spectral peak formation is explained as that narrowband molecular emissions triggered by an impulsive rovibrational excitation are superposed on the broadband spectrum of the soliton pulse by constructive interference. The demonstrated laser, which exhibits comb-like spectral peaks at molecular resonances, potentially provides novel tools for ultrasensitive molecular detection, vibration-mediated chemical reaction control, and infrared frequency standards.

Reports of zoonotic infections caused by the filarial nematode Onchocerca japonica have recently increased in Japan. A 69-year-old woman living in Sosa City, Chiba Prefecture, Kanto Region, Honshu, developed a painful nodule at the metacarpophalangeal joint of the index finger of her right hand. The causative agent was identified as a female O. japonica based on the histopathological characteristics (i.e., cuticle with transverse triangular ridges but without inner striae) of the biopsy specimens of the nodule. The species identification was corroborated by cox1 gene sequencing of the worm tissues isolated from paraffin-embedded sections of the specimens. Subsequent to the excision of the nodule, followed by anthelmintic treatment, the patient remained asymptomatic. Human infection with O. japonica has not previously been reported in Kanto Region, Eastern Honshu. The present case is likely linked to the recent expansion of the geographic range of the Japanese wild boar into this area., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

We demonstrate high-sensitivity vibrational absorption spectroscopy in the 2-micron wavelength range by using a mode-locked Cr:ZnS laser. Interferometric subtraction and multichannel detection across the broad laser spectrum realize simultaneous background-free detection of multiple vibrational modes over a spectral span of >380 cm -1 . Importantly, we achieve detection of small absorbance on the order of 10 -4 , which is well below the detection limit of conventional absorption spectroscopy set by the detector dynamic range. The results indicate the promising potential of the background-free method for ultrasensitive and rapid detection of trace gases and chemicals.

We developed a diode-pumped, mode-locked polycrystalline Cr:ZnS oscillator using single-walled carbon nanotubes as a saturable absorber. The oscillator exhibits self-start mode-locking operation, generating sub-100 fs pulses with an average power of 300 mW. We found a unique feature in which the intensity noise originating from relaxation oscillation is suppressed by inherent second harmonic generation in polycrystalline Cr:ZnS. The observed noise suppression is reproduced by a theoretical model that includes an instantaneous nonlinear loss.

Amid the increasing potential of ultrafast mid-infrared (mid-IR) laser sources based on transition metal doped chalcogenides such as Cr:ZnS, Cr:ZnSe, and Fe:ZnSe lasers, there is a need for direct and sensitive characterization of mid-IR mode-locked laser pulses that work in the nanojoule energy range. We developed a two-dimensional spectral shearing interferometry (2DSI) setup to successfully demonstrate the direct electric-field reconstruction of Cr:ZnS mode-locked laser pulses with a central wavelength of 2.3 µm, temporal duration of 30.3 fs, and energies of 3 nJ. The reconstructed electric field is in reasonable agreement with an independently measured intensity autocorrelation trace, and the quantitative reliability of the 2DSI measurement is verified from a material dispersion evaluation. The presented implementation of 2DSI, including a choice of nonlinear crystal as well as the use of high-throughput dispersive elements and a high signal-to-noise ratio near-IR spectrometer, would benefit future development of ultrafast mid-IR lasers and their applications.

Background: Standard treatments for small cell carcinoma of the cervix (SCCC) have not been established. In this study, we aimed to estimate the optimal treatment strategy for SCCC., Methods: This was a multicenter retrospective study. Medical records of patients with pathologically proven SCCC treated between 2003 and 2016 were retrospectively analyzed. Overall survival (OS) was plotted using the Kaplan-Meier method. Log-rank tests and Cox regression analysis were used to assess the differences in survival according to stage, treatment strategy, and chemotherapy regimen., Results: Data of 78 patients were collected, and after excluding patients without immunohistopathological staining, 65 patients were evaluated. The median age of the included patients was 47 (range: 24-83) years. The numbers of patients with International Federation of Gynecology and Obstetrics (FIGO) 2018 stages I-IIA, IIB-IVA, IVB were 23 (35%), 34 (52%), and 8 (12%), respectively. Of 53 patients who had undergone chemotherapy, 35 and 18 received SCCC and non-SCCC regimens as their first-line chemotherapy regimen, respectively. The 5-year OS for all patients was 49%, while for patients with FIGO stages I-IIA, IIB-IVA, IVB, it was 60, 50, and 0%, respectively. The 5-year OS rates for patients who underwent treatment with SCCC versus non-SCCC regimens were 59 and 13% (p < 0.01), respectively. This trend was pronounced in locally advanced stages. Multivariate analysis showed that FIGO IVB at initial diagnosis was a significant prognostic factor in all patients. Among the 53 patients who received chemotherapy, the SCCC regimen was associated with significantly better 5-year OS in both the uni- and multivariate analyses., Conclusion: Our results suggest that the application of an SCCC regimen such as EP or IP as first-line chemotherapy for patients with locally advanced SCCC may play a key role in OS. These findings need to be validated in future nationwide, prospective clinical studies., (© 2021. The Author(s).)

Aims: We explored the use of pulverized medication as a new method to prevent intentional drug overdose., Methods: This case study presents data obtained from the medical records of two female patients, aged 19 and 27 years, who presented with schizophrenia and neurodevelopmental disorder, respectively. Both patients provided written informed consent. Medication was administered to the two patients in powdered form, as opposed to in tablet form, in an attempt to prevent intentional drug overdose., Results: This administration method successfully prevented intentional drug overdose for 3 and 5 years in each case, respectively. However, case-control or prospective cohort studies are needed to rule out biases, including cognitive bias., Conclusion: Pulverizing medication is a simple and effective means of preventing intentional drug overdose by restricting access to the means of suicide, regardless of the type of mental disorder., (© 2021 The Authors. Neuropsychopharmacology Reports published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of Neuropsychopharmacology.)

Pleural dissemination is a common pattern of failure after initial treatment of thymoma and thymic carcinoma, but there is no standardized treatment. As these tumors are relatively radiosensitive, we investigated the effectiveness of radiotherapy. Twenty patients underwent 33 series of local radiotherapy for 96 pleural dissemination lesions after initial treatment. Conventional radiotherapy (CRT), tomotherapy, and combination of the two were employed in 19, 13, and 1 series, respectively. The median follow-up period after the first irradiation for pleural dissemination was 46 months (range, 14-161). For all 20 patients, overall survival (OS) rates from initial radiotherapy for pleural dissemination were 100% at three years and 86% at five years. Progression-free survival (PFS) rates after 33 series of radiotherapy were 30% at three years and 16% at five years. Local control (LC) rates for 96 lesions were 98% at three years and 96% at five years. In-field recurrence was observed in only two among the 96 lesions. One patient (5%) developed grade 3 radiation pneumonitis and another (5%) developed grade 3 pericardial effusion. No other serious adverse events were observed. When disseminated nodules can be covered within localized fields, local radiotherapy may be a treatment option. Using tomotherapy, multiple lesions can be treated safely., (© The Author(s) 2021. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

Background: In neurosurgery, it is important to use local hemostatic agents. We have explored a more powerful method of hemostasis by the combination of commercially available hemostatic agents with fibrin glue in the hopes of synergistic effects., Method: A bleeding model was constructed by puncturing the rabbit posterior vena cava with a needle. After applying the sample to the bleeding point, compression was performed for 10 s. If temporary hemostasis was achieved after pressure release, a 30 s wash was performed to confirm that ultimate hemostasis was achieved. Up to three hemostasis attempts were performed on the same bleeding point until hemostasis was achieved, and the number of attempts required for hemostasis was counted. If hemostasis was not achieved after three attempts, it was counted as four times. Four groups were evaluated: (1) gelatin sponge alone, (2) gelatin sponge + fibrin glue, (3) oxidized cellulose alone, and (4) oxidized cellulose + fibrin glue; each group was tested 16 times., Results: The median value (range minimum value-maximum value) of the number of hemostatic attempts in Group 1 to Group 4 was 3 (1-4), 1 (1-1), 4 (4-4), and 4 (2-4). In Group 2, there were two test exclusions owing to deviations of the test procedure., Conclusions: The compatibility of gelatin sponge and fibrin glue was very good, with a very strong and rapid hemostatic effect compared to other methods, showed its usefulness. This combination method may be effective for a variety of venous hemorrhages in neurosurgery.

We study the saturable absorption properties of single-walled carbon nanotubes (SWCNTs) with a large diameter of 2.2 nm and the corresponding exciton resonance at a wavelength of 2.4 µm. At resonant excitation, a large modulation depth of approximately 30 % and a small saturation fluence of a few tens of µJ/cm 2 are evaluated. The temporal response is characterized by an instantaneous rise and a subpicosecond recovery. We also utilize the SWCNTs to realize sub-50 fs, self-start mode locking in a Cr:ZnS laser, revealing that the film thickness is an important parameter that affects the possible pulse energy and duration. The results prove that semiconductor SWCNTs with tailored diameters exceeding 2 nm are useful for passive mode locking in the mid-infrared range.

Background: To treat multiple targets separated in the craniocaudal direction within a short time, we invented a new technique using multiple static-port tomotherapy with the dynamic-jaw mode and named it the pseudo-DJDC (pDJDC) technique. We compared the pDJDC plans and helical tomotherapy plans using the dynamic-jaw mode (HDJ) for multiple targets. In the pDJDC plans, we used a beam set with 2-7 ports to the targets at the same level in the craniocaudal direction, and employed another beam set for other targets using different port angles (9-12 angles in total)., Methods: In seven patients, two plans using the pDJDC and HDJ techniques were compared. For multiple targets (n = 2-6), 20-60 Gy in 2- to 7.5-Gy fractions were prescribed for the planning target volumes at D50%. The conformity index, uniformity index (D5%/D95%), dose distribution in the lung, and treatment time were evaluated., Results: The median conformity index of all seven patients was 3.0 for the pDJDC plans and 2.4 for the HDJ plans (P = 0.031). The median uniformity indices of the planning target volume (n = 25) for the two plans were 1.048 and 1.057, respectively (P = 0.10). For five patients with thoracic targets, the median mean lung doses were 2.6 Gy and 2.4 Gy, respectively (P = 0.63). The median V5Gy and V20Gy of the lungs in the five patients were 11.8% and 8.5% (P = 0.63), and 1.6% and 2.1% (P = 0.31), respectively. The pDJDC plans reduced the treatment time by 48% compared to the HDJ plans (median: 462 and 884 sec, respectively, P = 0.031)., Conclusion: The pDJDC technique allows treatment of multiple targets in almost half the time of the HDJ technique. The pDJDC plans were comparable to the HDJ plans in dose distribution, although the conformity index deteriorated., (© 2020 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.)

Background: Despite advances in chemotherapy, curing multiple liver metastases is quite rare. Even when response is obtained, regrowth of the tumors is almost inevitable. We aimed to evaluate the efficacy and adverse events of helical tomotherapy for chemo-refractory multiple liver metastases., Methods: Forty-five patients with chemo-refractory multiple (3-10) liver metastases after standard systemic chemotherapy entered the single-institutional prospective study. Liver metastases were the major disease; however, 31 also had uncontrolled primary lesions and/or other metastases. The prescribed dose was 55 Gy in 25 fractions. The median planning target volume (PTV) and normal liver volume (NLV) of first treatment were 128 cm 3 and 1175 cm 3 , respectively. The median of V 15Gy , V 30Gy , and mean dose to NLV were 45%, 23%, and 19.4 Gy, respectively., Results: Forty-two patients (93%) completed the planned treatment. Median survival time (MST) for all patients was 8 months, and the 1-year survival rate was 29%. The median local control (LC) period was 5 months and the 6-month control rate of irradiated tumors was 33%. A ≥30% decrease in tumor markers was observed in 31%. The most common grade 3 toxicity was lymphocytopenia (40%), followed by fatigue (6%). Radiation-induced liver disease (RILD) was not observed. Pancreatic cancer as the primary tumor, distant metastases outside the liver, low pretreatment neutrophil-to-lymphocyte ratio (NLR), and low pretreatment monocyte-to-lymphocyte ratio (MLR) were associated with poorer prognoses., Conclusions: Helical tomotherapy for chemo-refractory multiple liver metastases is a feasible and potentially effective treatment. Incorporating tomotherapy into the first-line treatment in combination with systemic chemotherapy should be considered., Trial Registration Number: CROG 12005., (© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

We develop a mode-locked Cr:ZnS polycrystalline laser using single-walled carbon nanotubes (SWCNTs) that have resonant absorption at the wavelength of 2.4 μm. The laser generates ultrashort pulses of 49 fs duration, a 2.4 μm center wavelength, and a 9.2 THz (176 nm) spectral span at a repetition rate of 76 MHz. We also confirm self-starting of the mode-locked operation. SWCNTs, if appropriately controlled in terms of their diameters, prove to be useful as ultrafast saturable absorbers in the mid-infrared region.

Despite insufficient laboratory data, radiotherapy after intratumoral injection of hydrogen peroxide (H 2 O 2 ) is increasingly being used clinically for radioresistant tumors. Especially, this treatment might become an alternative definitive treatment for early and advanced breast cancer in patients who refuse any type of surgery. The purpose of this study was to investigate the biological effects and appropriate combination methods of irradiation and H 2 O 2 in vivo. SCCVII tumor cells transplanted into the legs of C3H/HeN mice were used. Chronological changes of intratumoral distribution of oxygen bubbles after injection of H 2 O 2 were investigated using computed tomography. The effects of H 2 O 2 alone and in combination with single or five-fraction irradiation were investigated using a growth delay assay. The optimal timing of H 2 O 2 injection was investigated. Immunostaining of tumors was performed using the hypoxia marker pimonidazole. Oxygen bubbles decreased gradually and almost disappeared after 24 h. Administration of H 2 O 2 produced 2-3 days' tumor growth delay. Tumor regrowth was slowed further when H 2 O 2 was injected before irradiation. The group irradiated immediately after H 2 O 2 injection showed the longest tumor growth delay. Dose-modifying factors were 1.7-2.0 when combined with single irradiation and 1.3-1.5 with fractionated irradiation. Pimonidazole staining was weaker in tumors injected with H 2 O 2 . H 2 O 2 injection alone had modest antitumor effects. Greater tumor growth delays were demonstrated by combining irradiation and H 2 O 2 injection. The results of the present study could serve as a basis for evaluating results of various clinical studies on this treatment., (© 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Neuroleptic malignant syndrome (NMS) is often considered to be a precipitating factor for diabetic coma, such as a hyperosmolar hyperglycemic state (HHS). The combination of NMS and a systemic illness such as HHS can be difficult to diagnose because NMS may mask the coexisting condition. Although this coexistence is rare, it may be fatal if not detected early. We report a case of HHS in a 47-year-old male patient that developed after the distinguishing features of NMS had subsided. After the diagnosis of HHS, his recovery was a result of intravenous administration of soluble human insulin and fluid supplementation. Physicians caring for patients with diabetes who are also treated with neuroleptic agents should be aware that NMS may precipitate the development of secondary hyperglycemia despite a history of well-controlled blood glucose levels.

mRNA from single cells was quantified using real-time RT-PCR after recording the address and reporter protein activity with chemiluminescence, fluorescence, and electrochemical techniques, using luciferase, green fluorescent protein, and secreted alkaline phosphatase. mRNA copy number ranging from below 10(3) to 10(7) in single cells showed a lognormal distribution for both externally introduced reporter genes and internally expressed genes. The fluctuation in the gene expression decreased with the increase of the number of cells picked but did not decrease with the increase of mRNA copy number per cell. We found that the correlation coefficients for mRNA and protein expression in logarithmic plot at single-cell level were much lower than 1.00., (Copyright © 2010 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.)

Ethylnitrosourea-induced central and peripheral nerve tumors in Sprague-Dawley rats were tested for GFAP (Glial Fibrillary Acidic Protein), S-100 protein, NSE (Neuron Specific Enolase) and Anti-Leu 7 (HNK-1) immunoreactivity utilizing the ABC method (avidin-biotin-complex) for GFAP, S-100 protein and NSE, and the PAP method (peroxidase-antiperoxidase) for Anti-Leu 7. Peripheral nerve neurinomas were consistently positive for S-100 protein and consistently negative for GFAP and Anti-Leu 7. Neurinomas would occasionally exhibit positive staining for NSE (2 of 55 tumors). The staining intensity for S-100 protein varied from strongly positive in differentiated neurinomas to weakly positive in anaplastic tumors. Neoplastic and reactive astrocytes exhibited positive staining for both S-100 protein and GFAP. Variation in the GFAP staining intensity of glial tumors correlated with the degree of differentiation as anaplastic tumors did not stain with the same intensity as their more differentiated counterparts. Oligodendrogliomas exhibited occasional immunoreactivity to S-100 protein (3 of 36 tumors). NSE reactivity in oligodendrogliomas was rarely observed (1 tumor in 36) and immunoreactivity against GFAP or Anti-Leu 7 was consistently absent. Anti-Leu 7 and NSE proved to be of little value in the classification of ENU-induced neural tumors.

Changes in cytoskeletal organization in T9 anaplastic glioma cells have been examined during morphological changes induced by nerve growth factor (NGF) and by glia maturation factor (GMF). Indirect immunofluorescent labeling of cytoskeletal proteins has revealed that while neither GMF nor NGF induces expression of glial fibrillary acidic protein in this cell line, changes in cytoskeletal organization induced by these factors show some features similar to those observable during maturation of normal glial cells. Changing cell shapes induced by these factors are clearly outlined by the prominent distribution of microfilaments along cellular margins. Microtubules and intermediate filaments gradually extend during morphological changes and fill the characteristic cytoplasmic processes induced by NGF and GMF.

Administration of nerve growth factor (NGF) to the offspring of Sprague-Dawley rats transplacentally exposed to 50 mg/kg ethylnitrosourea on the 20th day of gestation resulted in a significant reduction of trigeminal and peripheral nerve neurinomas. Forty, 60, and 80 micrograms of NGF was administered in five s.c. doses, one dose on each of days 12-16, 90-94, and 210-214 postnatally. Of the 34 rats in the NGF-treated group, 11 animals were affected with trigeminal nerve neurinomas as compared to 18/34 in the NGF-untreated group (P less than 0.05). In the peripheral nerves (spinal cord nerve roots) there were five and 11 neurinomas, respectively, in each group of 34 rats. When the total numbers of neurinomas (trigeminal and peripheral nerves) between these groups were compared (16/34 versus 29/34), the significance of neurinoma reduction was P less than 0.01. Five trigeminal and two peripheral neurinomas in the NGF-untreated group were shown by immunohistochemical staining to contain nerve growth factor receptor protein, whereas none of the neurinomas in the NGF-treated group were positive for the receptor protein. The results obtained from this experiment lend support to the hypothesis that NGF has the capability to reduce the oncogenic consequences of ethylnitrosourea exposure perhaps by the process of maturation and/or differentiation of the transformed cells, and that this effect may depend upon the presence of receptor binding sites.