Clinical implementation and initial experience with a 1.5 Tesla MR-linac for MR-guided radiotherapy for gynecologic cancer: An R-IDEAL stage 1/2a first in humans/feasibility study of new technology implementation

Purpose: Magnetic resonance imaging-guided linear accelerator systems (MR-linacs) can facilitate the daily adaptation of radiotherapy plans. Here, we report our early clinical experience using an MR-linac for adaptive radiotherapy of gynecologic malignancies. Methods and Materials: Treatments were planned with an Elekta Monaco v5.4.01 and delivered by a 1.5 Tesla Elekta Unity MR-linac. The system offers a choice of daily adaptation based on either position (ATP) or shape (ATS) of the tumor and surrounding normal structures. The ATS approach has the option of manually editing the contours of tumors and surrounding normal structures before the plan is adapted. Here we documented the duration of each treatment fraction; set-up variability (assessed by isocenter shifts in each plan) between fractions; and, for quality assurance, calculated the percentage of plans meeting the ;γ-criterion of 3%/3-mm distance to agreement. Deformable accumulated dose calculations were used to compare ATP plans with reference dose plans. Results: Of the 10 patients treated with 90 fractions on the MR-linac, most received boost doses to recurrence in nodes or isolated tumors. Each treatment fraction lasted a median 32 minutes; fractions were shorter with ATP than with ATS (30 min vs 42 min, P<0.0001). The γ-criterion for all fraction plans exceeded >90% (median 99.9%, range 92.4%-100%), i.e., all plans passed quality assurance testing. The average extent of isocenter shift was <0.5 cm in each axis. The accumulated dose to the gross tumor volume was within 10% of the reference plan for all ATP cases. Accumulated doses for lesions in the pelvic periphery were within 1% of the reference plan as opposed to -5.8% to -9.6% for central tumors. Conclusions: The MR-linac is a reliable and clinically feasible tool for treating patients with gynecologic cancer.

Irradiation-Induced Nasopharyngeal Necrosis in Newly Diagnosed Nasopharyngeal Carcinoma Treated by Intensity-Modulated Radiation Therapy: Clinical Characteristics and the Influence of Treatment Strategies

Purpose: To define the clinical characteristics of irradiation-induced nasopharyngeal necrosis (INN) after intensity-modulated radiotherapy (IMRT) and identify the influence of treatment strategies on INN in primary nasopharyngeal carcinoma (NPC) patients.Patients and methods: From 2008 to 2019, NPC patients pathologically diagnosed with INN after primary IMRT were reviewed. Those patients were matched with propensity scores for patients without INN in our center. The impact of treatment strategies on INN occurrence was assessed using univariate and multivariate logistic regression analysis. Results: The incidence rate of INN was 1.9% among the primary NPC population, and 53 patients with INN were enrolled. Headache and foul odor were the main symptoms, and 71.7% of cases had pseudomembrane during or at the end of radiotherapy. All patients were in early or middle stage INN, and no one presented with skull-based osteoradionecrosis. Then 212 non-INN patients were included based on propensity scores match. Overall survival (p=0.248) and progression-free survival (p=0.266) curves were similar between the INN and non-INN groups. Treatment strategies including combining chemotherapy or molecular targeted therapy with radiotherapy were not associated with INN occurrence, while boost dose (OR 7.360; 95% CI 2.301-23.547; P = 0.001) was a predictor factor for it. However, the optimal threshold for an accumulated dose to predict INN's occurrence was failed to determine.Conclusion: In the IMRT era, the severity of INN in primary NPC patients is lessened. This study showed that treatment strategies contributed little to develop INN, while the accumulated dose of radiation may relate to its occurrence.

Vergleich der biologischen Strahlenwirkung des β--Emitters 186Re mit 662 keV Photonenstrahlung auf die humane B-Zelllinie BV-173

Aim Aim of the study was to determine the effects of the β--emitter 186Re and 662 keV photon radiation in order to compare the biological effects of low dose rate (186Re) to high dose rate irradiation. Methods Prae-B-lymphocytes were exposed to 662 keV photon radiation or incubated with a liquid solution of 186Re. Cell count and viability were compared over the observation period of seven days, survival curves constructed and analysed at time of lowest cell-viability. Results Biphasic cell survival curves resulted for both radiation types. Survival curves were obtained at 24 h for photon radiation and 72 h for 186Re. The biphasic survival curve after photon radiation exposure can be explained by radiation hypersensitivity at doses below 1 Gy resulting in a D0 of 3.3 Gy. Doses exceeding 1.0 Gy showed a D0 of 10 Gy. The biphasic survival curve in case of 186Re incubation represents repair of sub lethal damage in the first section of the curve (D0 11.1 Gy) – in this case, biological effects of the β--emitter are attenuated by repair. Beyond an accumulated dose of 1.6 Gy, 186Re showed a steeper slope with a D0 of 4 Gy, corresponding to 2.5 times higher biological effects compared to acute photon irradiation (10 Gy). Conclusion Low dose rate radiation resulted in low biological effects at low doses. There is a threshold of accumulated dose above which biological effects of 186Re-incubation exceed those of photon irradiation.

Effect of Mechanical Activation and Gamma-Irradiation on Structural-Phase State of Ti-Al-C Powder Reagents

The influence of mechanical activation and gamma-irradiation on the structural-phase state of Ti-Al-C powder reagents was studied. The following compositions were used for research: 1) 78% Ti + 14% Al + 8% C; 2) 80% Ti + 12% Al + 8% C; 3) 81% Ti + 10% Al + 9% C. Mechanical activation of these compositions leads to an increase in the diffuse background, a decrease in the intensity of diffraction reflections of mixture components and a broadening of peaks, as well as micro-deformations. Depending on the ratio of components, the structural parameters can either increase in comparison with the initial ones, or decrease. The effect of gamma radiation with a dose rate of 1 Gy/s and accumulated dose of 3·104 Gy on the mechanocomposites of the Ti-Al-C system causes unsystematic change in crystal lattices of elements, which can be explained by radiation-stimulated diffusion. Gamma-irradiation also reduces micro-deformations that occur after mechanical activation, while crystallites of the components remain nanoscale.

Evaluating the risk of QTc prolongation associated with hydroxychloroquine use with antidepressants in lupus patients with fibromyalgia

Objective Hydroxychloroquine (HCQ) is widely used in patients with systemic lupus erythematosus (SLE) due to its immunomodulatory properties. Antidepressants are commonly used in patients with fibromyalgia syndrome (FMS). Both HCQ and antidepressants are reported to cause QTc prolongation, which potentially increases the risk for a lethal ventricular arrhythmia that can result in sudden death. The objective of the study is to investigate the risk of QTc prolongation associated with HCQ use concomitantly with antidepressants in lupus patients with FMS. Methods Outpatient 12-lead electrocardiograms (ECGs) were extracted from an electronic medical record and QTc intervals were calculated using the Bazett’s formula. QTc intervals in 135 lupus patients treated with HCQ with or without antidepressants were analyzed. Results We found taking HCQ was associated with mild QTc prolongation, and the prolongation was not affected by the length of time of HCQ use or the accumulated dose of HCQ. Concurrent use of HCQ and antidepressants had not further increased QTc intervals in this cohort. However, four patients on HCQ alone and three patients on HCQ and antidepressants were found QTc interval more than 500 milliseconds and most of these patients had underlying cardiological conditions. Conclusions It is important to evaluate lupus patient with ECG before and after starting HCQ, though our study suggests that while HCQ use did prolong the QTc in some, but the overall prolongation was subclinical, with or without antidepressants. ECG monitoring therefore is essential to identify new changes potentially related to drug use.