Hypofractionated proton and carbon ion beam radiotherapy for sacrococcygeal chordoma (ISAC): An open label, randomized, stratified, phase II trial.

INTRODUCTION: Sacrococcygeal chordomas have high recurrence rates and are challenging to treat. METHODS: In this phase II prospective, randomized, stratified trial, the safety and feasibility of hypofractionated ion radiation therapy were investigated. The primary focus was monitored through the incidence of Grade 3-5 NCI-CTC-AE toxicity. Secondary endpoints included local progression-free (LPFS) and overall survival (OS). RESULTS: The study enrolled 82 patients with primary (87 %) and recurrent (13 %) inoperable or incompletely resected sacral chordomas from January 2013 to July 2022, divided equally into proton therapy (Arm A) and carbon ion beam therapy (Arm B) groups, each receiving a total dose of 64 Gy (RBE) in 16 fractions, 5-6 fractions per week. Overall 74 % of patients received no previous surgery and 66 % of tumors were confirmed by a brachyury staining. The mean and median Gross Tumor Volume at the time of treatment (GTV) was 407 ml and 185 ml, respectively. The median follow-up of the surviving patients was 44.7 months, and the 2-year and 4-year OS rates were 96 % and 81 %, respectively. Factors such as smaller GTV and younger age trended towards better OS. The LPFS after 2-year and 4-year was 84 % and 70 %, respectively. Male gender emerged as a significant predictor of LPFS. There was no significant difference between the treatment groups. We observed five grade 4 wound healing disorders (6 %). CONCLUSION: The initial response rates were promising; however local control was not sustained. More comparative research on fractionation schemes is essential to refine treatment approaches for inoperable sacral chordoma.

Longitudinal Evaluation of Biomechanical Indices in Fellow Eyes of Patients With Keratoconus Classified as Having Very Asymmetric Ectasia With Normal Topography.

PURPOSE: To evaluate the biomechanical longitudinal variability and progression of tomographically normal fellow eyes of patients with keratoconus. METHODS: Of 513 patients with keratoconus, 30 patients with tomographically normal fellow eyes were included in this study. Tomographic and biomechanical parameters of the Pentacam and Corvis ST (Oculus Optikgeräte GmbH) were analyzed in multiple follow-up examinations, including the ABCD grading, Belin/Ambrósio Enhanced Ectasia total deviation index (BAD-D), Corvis Biomechanical Index (CBI), Corvis Biomechanical Factor (CBiF), and Tomographic and Biomechanical Index (TBI). A mixed regression model was applied. The results were compared to a healthy control group (n = 17) and a keratoconus group (n = 20). RESULTS: Within a maximum observation period of 3.3 years, no fellow eye (0%) showed a progression to tomographically evident keratoconus. No significant change in tomographic or biomechanical parameters was detected over the study period. The indices BAD-D, CBI, CbiF, and TBI exhibited a certain variability over time, whereas the tomographic ABC parameters and maximum keratometry barely changed. This was also shown in the control group and for all parameters in the keratoconus group, except the TBI. CONCLUSIONS: During the observation period none of the normal fellow eyes progressed to tomographically detectable keratoconus. However, biomechanical parameters CBI, CbiF, and TBI showed pathological values in 43.3% of eyes and certain variability. Subsequent studies with a longer observation period are warranted to confirm the biomechanical trends seen in this study and to rate the ability of single measurements to diagnose early keratoconus. [J Refract Surg. 2024;40(1):e48-e56.].

Refractive outcomes after DMEK: meta-analysis.

In this meta-analysis and systematic literature review of refractive outcomes after Descemet membrane endothelial keratoplasty (DMEK), the extent of the refractive shift and an overview of reasons for refractive shift after DMEK are provided. The PubMed library was screened for articles containing the terms "Descemet membrane endothelial keratoplasty," "DMEK," "Descemet membrane endothelial keratoplasty combined with cataract surgery," "triple-DMEK" combined with "refractive outcomes," "refractive shift," and "hyperopic shift." The refractive outcomes after DMEK were analyzed and compared using a fixed and random effects model. The overall mean change of the spherical equivalent outcome when compared with the preoperative value in cases of DMEK or when compared with the preoperative target refraction in cases of DMEK combined with cataract surgery was +0.43 diopters (D) (95% CI, 0.31-0.55). When DMEK is combined with cataract surgery, a target refraction of -0.5 D is recommended to achieve emmetropia. Changes in the posterior corneal curvature are identified as the main cause of the refractive hyperopic shift.

Magnetic resonance guided adaptive stereotactic body radiotherapy for lung tumors in ultracentral location: the MAGELLAN trial (ARO 2021-3).

BACKGROUND: Stereotactic Body Radiotherapy (SBRT) is a standard treatment for inoperable primary and secondary lung tumors. In case of ultracentral tumor location, defined as tumor contact with vulnerable mediastinal structures such as the proximal bronchial tree (PBT) or esophagus, SBRT is associated with an increased risk for severe complications. Magnetic resonance (MR)-guided SBRT can mitigate this risk based on gated dose delivery and daily plan adaptation. The MAGELLAN trial aims to find the maximum tolerated dose (MTD) of MR-guided SBRT of ultracentral lung tumors (ULT). PATIENTS AND METHODS: MAGELLAN is a prospective phase I dose escalation trial. A maximum of 38 patients with primary and secondary ULT with a tumor size ≤ 5 cm will be enrolled. Ultracentral location is defined as an overlap of the planning target volume (PTV) with the PBT or esophagus. Patients are treated at a 0.35 Tesla MR-linac (MRIdian® Linac, ViewRay Inc. ) employing a gating strategy and daily plan adaptation. Dose escalation starts at 10 × 5.5 Gy (biologically effective dose BED3/10: 155.83 Gy/85.25 Gy), may proceed up to 10 × 6.5 Gy (BED3/10: 205.83 Gy/107.25 Gy) and is guided by a customized time-to-event continual reassessment method (TITE CRM) with backup element, which alternately assigns patients to dose escalation and backup cohorts. DISCUSSION: The results of the MAGELLAN trial will guide further research and clinical implementation of MR-guided SBRT as ablative treatment of ULT. Moreover, the combination of MR-guided radiotherapy with TITE-CRM including a backup element may serve as blueprint for future radiation dose escalation studies in critical locations. TRIAL REGISTRATION: Registered at ClinicalTrials.gov: NCT04925583 on 14th June 2021.

Development and Verification of an Adjustment Factor for Determining the Axial Length Using Optical Biometry in Silicone Oil-Filled Eyes.

The aim of this prospective clinical study was to establish and verify an adaptation for axial length (AL) measurement in silicone oil (SO)-filled pseudophakic eyes with a Scheimpflug and partial coherence interferometry (PCI)-based biometer. The AL was measured with a Pentacam AXL (OCULUS Optikgeräte GmbH, Wetzler, Germany) and IOLMaster 700 (Carl Zeiss Meditec, Jena, Germany). The coefficients of variation (CoV) and the mean systematic difference (95% confidence interval (CI)) between the devices were calculated. After implementing a setting for measuring AL in tamponaded eyes with a Pentacam based on data of 29 eyes, another 12 eyes were examined for verification. The mean AL obtained with the Pentacam was 25.53 ± 1.94 mm (range: 21.70 to 30.76 mm), and with IOLMaster, 24.73 ± 1.97 mm (ranged 20.84 to 29.92 mm), resulting in a mean offset of 0.80 ± 0.08 mm (95% CI: 0.77, 0.83 mm), p < 0.001. The AL values of both devices showed a strong linear correlation (r = 0.999). Verification data confirmed good agreement, with a statistically and clinically non-significant mean difference of 0.02 ± 0.04 (95% CI: -0.01, 0.05) mm, p = 0.134. We implemented a specific adaptation for obtaining reliable AL values in SO-filled eyes with the Pentacam AXL.

Construction of a biomechanical head and neck motion model as a guide to evaluation of deformable image registration.

The use of deformable image registration methods in the context of adaptive radiotherapy leads to uncertainties in the simulation of the administered dose distributions during the treatment course. Evaluation of these methods is a prerequisite to decide if a plan adaptation will improve the individual treatment. Current approaches using manual references limit the validity of evaluation, especially for low-contrast regions. In particular, for the head and neck region, the highly flexible anatomy and low soft tissue contrast in control images pose a challenge to image registration and its evaluation. Biomechanical models promise to overcome this issue by providing anthropomorphic motion modelling of the patient. We introduce a novel biomechanical motion model for the generation and sampling of different postures of the head and neck anatomy. Motion propagation behaviour of the individual bones is defined by an underlying kinematic model. This model interconnects the bones by joints and thus is capable of providing a wide range of motion. Triggered by the motion of the individual bones, soft tissue deformation is described by an extended heterogeneous tissue model based on the chainmail approach. This extension, for the first time, allows the propagation of decaying rotations within soft tissue without the necessity for explicit tissue segmentation. Overall motion simulation and sampling of deformed CT scans including a basic noise model is achieved within 30 s. The proposed biomechanical motion model for the head and neck site generates displacement vector fields on a voxel basis, approximating arbitrary anthropomorphic postures of the patient. It was developed with the intention of providing input data for the evaluation of deformable image registration.