UNASSIGNED: Magnetic resonance-guided radiation therapy (MRgRT) utilization is rapidly expanding worldwide, driven by advanced capabilities including continuous intrafraction visualization, automatic triggered beam delivery, and on-table adaptive replanning (oART). Our objective was to describe patterns of 0.35Tesla(T)-MRgRT (MRIdian) utilization in the United States (US) among early adopters of this novel technology.
UNASSIGNED: Anonymized administrative data from all US MRIdian treatment systems were extracted for patients completing treatment from 2014 to 2020. Detailed treatment information was available for all MRIdian linear accelerator (linac) systems and some cobalt systems.
UNASSIGNED: Seventeen systems at 16 centers delivered 5736 courses and 36,389 fractions (fraction details unavailable for 1223 cobalt courses), of which 21.1% were adapted. Ultra-hypofractionation (UHfx) (1-5 fractions) was used in 70.3% of all courses. At least one adaptive fraction was used for 38.5% of courses (average 1.7 adapted fractions/course), with higher oART use in UHfx dose schedules (47.7% of courses, average 1.9 adapted fractions per course). The most commonly treated organ sites were pancreas (20.7%), liver (16.5%), prostate (12.5%), breast (11.5%), and lung (9.4%). Temporal trends show a compounded annual growth rate (CAGR) of 59.6% in treatment courses delivered, with a dramatic increase in use of UHfx to 84.9% of courses in 2020 and similar increase in use of oART to 51.0% of courses.
UNASSIGNED: This is the first comprehensive study reporting patterns of utilization among early adopters of MRIdian in the US. Intrafraction MR image-guidance, advanced motion management, and increasing adoption of adaptive radiation therapy has led to a substantial transition to ultra-hypofractionated regimens. 0.35 T-MRgRT has been predominantly used to treat abdominal and pelvic tumors with increasing use of on-table adaptive replanning, which represents a paradigm shift in radiation therapy.

The disability, mortality and costs due to ionizing radiation (IR)-induced osteoporotic bone fractures are substantial and no effective therapy exists. Ionizing radiation increases cellular oxidative damage, causing an imbalance in bone turnover that is primarily driven via heightened activity of the bone-resorbing osteoclast. We demonstrate that rats exposed to sublethal levels of IR develop fragile, osteoporotic bone. At reactive surface sites, cerium ions have the ability to easily undergo redox cycling: drastically adjusting their electronic configurations and versatile catalytic activities. These properties make cerium oxide nanomaterials fascinating. We show that an engineered artificial nanozyme composed of cerium oxide, and designed to possess a higher fraction of trivalent (Ce3+) surface sites, mitigates the IR-induced loss in bone area, bone architecture, and strength. These investigations also demonstrate that our nanozyme furnishes several mechanistic avenues of protection and selectively targets highly damaging reactive oxygen species, protecting the rats against IR-induced DNA damage, cellular senescence, and elevated osteoclastic activity in vitro and in vivo. Further, we reveal that our nanozyme is a previously unreported key regulator of osteoclast formation derived from macrophages while also directly targeting bone progenitor cells, favoring new bone formation despite its exposure to harmful levels of IR in vitro. These findings open a new approach for the specific prevention of IR-induced bone loss using synthesis-mediated designer multifunctional nanomaterials.

UNASSIGNED: There is no curative treatment option for patients with unresectable intrahepatic, cholangiocarcinoma (IHC). The aim of this study was to evaluate the efficacy of; radiation segmentectomy/lobectomy using Y90-labeled glass microspheres in patients with; unresectable IHC.
UNASSIGNED: This IRB-approved, single-center study included, 16 patients (age: 67 ± 7.7 years) with IHC who received radiation segmentectomy or lobectomy, treatment using Y90-labeled glass microspheres between May 2009 and October 2019. Radiation, segmentectomy/lobectomy was defined as at least 190 Gy dose delivered into treated liver; volume.
UNASSIGNED: The median OS from IHC diagnosis was 22.7 months (95% CI: 13.9-66.1) and from, radioembolization it was 7 months (95% CI: 4.33-54.17). Patients who did not receive, chemotherapy before the radioembolization had significantly longer median OS (26.8 vs. 5.9, months, P = 0.03). Four patients had >20 months survival after radioembolization, including 2, patients with survival of 42 and 54 months. There was no 30-day mortality and no severe, complications.
UNASSIGNED: Radiation segmentectomy/lobectomy is safe with minimal side effects. The median, OS of the study group is modest; however, 4 patients (25%) showed excellent survival. These results suggest a need for a larger study to define the IHC patient group who could, most benefit from this procedure.

UNASSIGNED: Spinal metastasis is the most common metastatic skeletal disease in cancer patients. Metastatic epidural spinal cord compression (MESCC), which occurs in 5-14% of cancer patients, is an oncological emergency because it may cause a permanent neurological deficit. Separation surgery followed by stereotactic ablative radiotherapy (SABR), so-called \"hybrid therapy,\" has shown effectiveness in local control of spinal metastasis and has become an integral treatment option for patients with MESCC. Therefore, we performed a meta-analysis and meta-regression analysis to clarify the local progression rate of hybrid therapy and the risk factors for local progression.
UNASSIGNED: We searched PubMed, EMBASE, Scopus, Cochrane Library, and Web of Science databases from inception to December 2021. Meta-analyses of proportions were used to analyze the data using a random-effects model to calculate the pooled 1-year local progression rate and confidence interval. Subgroup analyses were performed using meta-analyses of odds ratio (OR) for comparisons between groups. We also conducted a meta-regression analysis to identify the factors that caused heterogeneity.
UNASSIGNED: A total of 661 patients from 13 studies (10 retrospective and 3 prospective) were included in the final meta-analysis. The quality of the included studies assessed using the Newcastle - Ottawa scale ranged from poor to fair (range, 4-6). The pooled local progression rate was 10.2 % (95 % confidence interval [CI], 7.8-12.8 %; I2 = 30 %) and 13.7 % (95 % CI, 9.3-18.8 %; I2 = 55 %) at postoperative 1 and 2 years, respectively. The subgroup analysis indicated that patients with a history of prior radiotherapy (OR, 5.14; 95 % CI, 1.71-15.51) and lower radiation dose per fraction (OR, 4.57; 95 % CI, 1.88-11.13) showed significantly higher pooled 1-year local progression rates. In the moderator analysis, the 1-year local progression rate was significantly associated with the proportion of patients with a history of prior radiotherapy (p = 0.036) and those with colorectal cancer as primary origin (p < 0.001).
UNASSIGNED: The pooled 1-year local progression rate of hybrid therapy for MESCC was 10.2%. In subgroup and moderator analyses, a lower radiation dose per fraction, history of prior radiotherapy, and colorectal cancer showed a significant association with the 1-year local progression rate.

UNASSIGNED: Radiation has been used in the treatment of retinoblastoma. Herein, we present the novel use of palladium-103 plaque brachytherapy as primary treatment.
UNASSIGNED: An 8-year-old asymptomatic girl presented was found to have a solitary peripheral retinoblastoma in her right eye. She was treated with primary palladium-103 plaque brachytherapy (47.4 Gray over 5 consecutive days). A secondary, vitreous hemorrhage noted 46 months after irradiation was successfully controlled by laser tumor-demarcation. With 19-years follow up, there has been no clinical scleropathy, or local tumor recurrence. The eye yields 20/20 vision and there has been no systemic metastasis.
UNASSIGNED: Palladium-103 plaque brachytherapy successfully controlled retinoblastoma, while preserving the globe, vision, and life.

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UNASSIGNED: Recent advances in the treatment algorithm of locally advanced rectal cancer (LARC) have significantly improved complete response (CR) rates and disease-free survival (DFS), but therapy resistance, with its substantial impact on outcomes and survival, remains a major challenge. Our group has recently unraveled a critical role of interleukin-1α (IL-1α) signaling in activating inflammatory cancer-associated fibroblasts (iCAFs) and mediating radiation-induced senescence, extracellular matrix (ECM) accumulation, and ultimately therapy resistance. We here summarize the recently initiated ACO/ARO/AIO-21 phase I trial, testing the IL-1 receptor antagonist (IL-1 RA) anakinra in combination with fluoropyrimidine-based chemoradiotherapy (CRT) for advanced rectal cancer.
UNASSIGNED: The ACO/ARO/AIO-21 is an investigator-driven, prospective, open-labeled phase I drug-repurposing trial assessing the maximum tolerated dose (MTD) of capecitabine administered concurrently to standard preoperative radiotherapy (45 Gy in 25 fractions followed by 9 Gy boost in 5 fractions) in combination with fixed doses of the IL1-RA anakinra (100 mg, days -10 to 30). Capecitabine will be administered using a 3 + 3 dose-escalation design (500 mg/m2 bid; 650 mg/m2 bid; 825 mg/m2 bid, respectively) from day 1 to day 30. Response assessment including digital rectal examination (DRE), endoscopy and pelvic magnetic resonance imaging (MRI) is scheduled 10 weeks after completion of CRT. For patients achieving clinical complete response (cCR), primary non-operative management is provided. In case of non-cCR immediate total mesorectal excision (TME) will be performed. Primary endpoint of this phase I trial is the MTD of capecitabine.
UNASSIGNED: Based on extensive preclinical research, the ACO/ARO/AIO-21 phase I trial will assess whether the IL-1RA anakinra can be safely combined with fluoropyrimidine-based CRT in rectal cancer. It will further explore the potential of IL-1 inhibition to overcome therapy resistance and improve response rates. A comprehensive translational research program will expand our understanding from a clinical perspective and may help translate the results into a randomized phase II trial.

BACKGROUND: Micro-computed tomography (μCT) is a valuable imaging modality for longitudinal quantification of bone volumes to identify disease or treatment effects for a broad range of conditions that affect bone health. Complex structures, such as the hindpaw with up to 31 distinct bones in mice, have considerable analytic potential, but quantification is often limited to a single bone volume metric due to the intensive effort of manual segmentation. Herein, we introduce a high-throughput, user-friendly, and semi-automated method for segmentation of murine hindpaw μCT datasets.
METHODS: In vivo μCT was performed on male (n = 4; 2-8-months) and female (n = 4; 2-5-months) C57BL/6 mice longitudinally each month. Additional 9.5-month-old male C57BL/6 hindpaws (n = 6 hindpaws) were imaged by ex vivo μCT to investigate the effects of resolution and integration time on analysis outcomes. The DICOMs were exported to Amira software for the watershed-based segmentation, and watershed markers were generated automatically at approximately 80% accuracy before user correction. The semi-automated segmentation method utilizes the original data, binary mask, and bone-specific markers that expand to the full volume of the bone using watershed algorithms.
RESULTS: Compared to the conventional manual segmentation using Scanco software, the semi-automated approach produced similar raw bone volumes. The semi-automated segmentation also demonstrated a significant reduction in segmentation time for both experienced and novice users compared to standard manual segmentation. ICCs between experienced and novice users were >0.9 (excellent reliability) for all but 4 bones.
CONCLUSIONS: The described semi-automated segmentation approach provides remarkable reliability and throughput advantages. Adoption of the semi-automated segmentation approach will provide standardization and reliability of bone volume measures across experienced and novice users and between institutions. The application of this model provides a considerable strategic advantage to accelerate various research opportunities in pre-clinical bone and joint analysis towards clinical translation.

BACKGROUND: The potential of patient symptoms being monitored longitudinally in radiotherapy (RT) is still unexploited. When novel technologies like online adaptive MR-guided radiotherapy (MRgRT) are evaluated, weekly electronic patient-reported outcomes (ePROs) may add knowledge about the symptom trajectory. This study aimed at evaluating feasibility, usability and acceptance of weekly ePRO among patients receiving pelvic radiotherapy.
METHODS: In a mixed-methods convergent design, a prospective pilot study enrolled patients referred to pelvic radiotherapy with curative intent. Patients used their own device at home to self-report PRO weekly during and four weeks following radiotherapy and week 8, 12, and 24 (paper-questionnaire as an alternative). Feasibility was extracted from the ePRO software. The Patient Feedback Form and patient interviews were used to explore usability and patient acceptance. Patients were informed that clinicians had no access to PRO responses.
RESULTS: In total, 40 patients were included; 32 patients with prostate cancer and 8 with cervical cancer (consent rate 87%), median age 68 (36-76). The majority did digital reporting (93%). 85% of patients responded to ≥80% of the weekly questionnaires with 91% average adherence to weekly completion (60% for follow-up), although lower for patients ≥age 70. Time spent on ePRO (97%) and frequency of reporting (92%) was considered appropriate. Interviews (n = 14) revealed the application was usable and the patients requested real-time feedback from the clinicians.
CONCLUSIONS: Recruitment for ePRO during radiotherapy was feasible and adherence to weekly self-reporting high. The digital application was usable and weekly frequency and time spent acceptable. Real-time feedback from the clinicians is requested by the patients.