Background: Cladribine is a synthetic deoxyadenosine analogue in development as an oral multiple sclerosis (MS) therapy. Objective: To report in detail the safety findings from the 96-week, phase III, double-blind CLARITY study, which evaluated treatment with cladribine tablets in relapsing-remitting MS. Methods: A total of 1,326 patients were randomized 1 : 1 : 1 to two short-course regimens of cladribine tablets (3.5 or 5.25 mg/kg cumulative dose over 96 weeks) or placebo. Safety assessments included monitoring for adverse events (AEs), routine physical and neurologic examinations and frequent laboratory parameter assessments. Results: Of the randomized patients, 88.6% completed treatment with cladribine tablets versus 86.3% with placebo. Lymphopenia was the most commonly reported AE in patients treated with cladribine tablets and was anticipated based on the mechanism of action. The incidence of infections was 48.3% with cladribine tablets and 42.5% with placebo, with 99.1% and 99.0% rated mild-to-moderate by investigators. Herpes zoster infections developed in 20 (2.3%) cladribinetreated patients; all cases were dermatomal. There were no herpes zoster infections in the placebo group. Nine (1.0%) patients experienced events related to uterine leiomyomas in the cladribine tablets groups versus one (0.2%) with placebo. Three isolated cases of malignancy were reported in cladribine-treated patients during the study; a fourth was reported during post-study surveillance. A pre-malignant cervical carcinoma in situ was also reported. The incidence of malignancies during the study did not exceed the expected rate in a population standardized for country, gender and age. Conclusion: The safety and tolerability profile observed in the CLARITY study together with the reported efficacy support the potential for cladribine tablets as an MS therapy.
T he high dose of radiation delivered via stereotactic radiosurgery (SRS) requires accurate and reproducible immobilization of the head. 7 Accuracy within a range of 1-2 mm is essential to limit irradiation of surrounding anatomical structures. A rigid stereotactic head frame has traditionally been used for fixation in Gamma Knife (GK) radiosurgery. 20 Frame-based fixation allows for precise delivery of a single high-dose fraction of radiation treatment. Motion error associated with frame-based fixation is estimated to be ≤ 1-1.5 mm. 12 New SRS strategies for the treatment of large intracranial lesions have trended toward the use of multifractionation stereotactic radiotherapy (SRT) treatments. But head frame placement is invasive, involving 4-point fixation us-ABBREVIATIONS CBCT = cone-beam computed tomography; GK = Gamma Knife; IR = infrared; LINAC = linear accelerator; SRS = stereotactic radiosurgery; SRT = stereotactic radiotherapy. OBJECTIVE The Leksell Gamma Knife Icon (GK Icon) radiosurgery system can utilize cone-beam computed tomography (CBCT) to evaluate motion error. This study compares the accuracy of frame-based and frameless mask-based fixation using the Icon system. METHODS A retrospective cohort study was conducted to evaluate patients who had undergone radiosurgery with the GK Icon system between June and December 2017. Patients were immobilized in either a stereotactic head frame or a noninvasive thermoplastic mask with stereotactic infrared (IR) camera monitoring. Setup error was defined as displacement of the skull in the stereotactic space upon setup as noted on pretreatment CBCT compared to its position in the stereotactic space defined by planning MRI for frame patients and defined as skull displacement on planning CBCT compared to its position on pretreatment CBCT for mask patients. For frame patients, the intrafractionation motion was measured by comparing pretreatment and posttreatment CBCT. For mask patients, the intrafractionation motion was evaluated by comparing pretreatment CBCT and additional CBCT obtained during the treatment. The translational and rotational errors were recorded. RESULTS Data were collected from 77 patients undergoing SRS with the GK Icon. Sixty-four patients underwent frame fixation, with pre-and posttreatment CBCT studies obtained. Thirteen patients were treated using mask fixation to deliver a total of 33 treatment fractions. Mean setup and intrafraction translational and rotation errors were small for both fixation systems, within 1 mm and 1° in all axes. Yet mask fixation demonstrated significantly larger intrafraction errors than frame fixation. Also, there was greater variability in both setup and intrafraction errors for mask fixation than for frame fixation in all translational and rotational directions. Whether the GK treatment was for metastasis or nonmetastasis did not influence motion uncertainties between the two fixation types. Additionally, monitoring IR-based intrafraction motion for mask fixation-i.e., the number of treatment stoppages due to re...
Pelvic radiation is a commonly utilized treatment for malignancy of the genitourinary and lower gastrointestinal tract. Radiation proctitis and the resultant clinical picture varies from asymptomatic to potentially life threatening. Similarly, treatment options also vary greatly, from medical therapy to surgical intervention. Commonly utilized medical therapy includes sucralfate enemas, antibiotics, 5-aminosalicylic acid derivatives, probiotics, antioxidants, short-chain fatty acids, formalin instillation and fractionated hyperbaric oxygen. More invasive treatments include endoscopic-based, focally ablative interventions such as dilation, heater and bipolar cautery, neodymium/yttrium aluminum garnet argon laser, radiofrequency ablation or argon plasma coagulation. Despite its relatively common frequency, there is a dearth of existing literature reporting head-to-head comparisons of the various treatment options via a randomized controlled approach. The purpose of our review was to present the reader a consolidation of the existing evidence-based literature with the goal of highlighting the comparative effectiveness and risks of the various treatment approaches. Finally, we outline a pragmatic approach to the treatment of radiation proctitis. In light of the lack of randomized data, our goal is to pursue as least invasive an approach as possible, with escalation of care tailored to the severity of the patient's symptoms. For those cases that are clinically asymptomatic or only mildly symptomatic, observation or medical management can be considered. Once a patient fails such management or symptoms become more severe, invasive procedures such as endoscopically based focal ablation or surgical intervention can be considered. Although not all recommendations are supported by level I evidence, reported case series and single-institutional studies in the literature suggest that successful treatment with cessation of symptoms can be obtained in the majority of cases.
OBJECTIVEThe authors sought to compare the dosimetric quality of hypofractionated stereotactic radiosurgery in treating sizeable brain tumors across the following treatment platforms: GammaKnife (GK) Icon, CyberKnife (CK) G4, volumetric modulated arc therapy (VMAT) on the Varian TrueBeam STx, double scattering proton therapy (DSPT) on the Mevion S250, and intensity modulated proton therapy (IMPT) on the Varian ProBeam.METHODSIn this retrospective study, stereotactic radiotherapy treatment plans were generated for 10 patients with sizeable brain tumors (> 3 cm in longest diameter) who had been treated with VMAT. Six treatment plans, 20–30 Gy in 5 fractions, were generated for each patient using the same constraints for each of the following radiosurgical methods: 1) GK, 2) CK, 3) coplanar arc VMAT (VMAT-C), 4) noncoplanar arc VMAT (VMAT-NC), 5) DSPT, and 6) IMPT. The coverage; conformity index; gradient index (GI); homogeneity index; mean and maximum point dose of organs at risk; total dose volume (V) in Gy to the normal brain for 2 Gy (V2), 5 Gy (V5), and 12 Gy (V12); and integral dose were compared across all platforms.RESULTSAmong the 6 techniques, GK consistently produced a sharper dose falloff despite a greater central target dose. GK gave the lowest GI, with a mean of 2.7 ± 0.1, followed by CK (2.9 ± 0.1), VMAT-NC (3.1 ± 0.3), and VMAT-C (3.5 ± 0.3). The highest mean GIs for the proton beam treatments were 3.8 ± 0.4 for DSPT and 3.9 ± 0.4 for IMPT. The GK consistently targeted the lowest normal brain volume, delivering 5 to 12 Gy when treating relatively smaller- to intermediate-sized lesions (less than 15–20 cm3). Yet, the differences across the 6 modalities relative to GK decreased with the increase of target volume. In particular, the proton treatments delivered the lowest V5 to the normal brain when the target size was over 15–20 cm3 and also produced the lowest integral dose to the normal brain regardless of the target size.CONCLUSIONSThis study provides an insightful understanding of dosimetric quality from both photon and proton treatment across the most advanced stereotactic radiotherapy platforms.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.