The incorporation of magnetic resonance (MR) imaging in radiotherapy (RT) workflows improves contouring precision, yet it introduces geometrical uncertainties when registered with computed tomography ...(CT) scans. Synthetic CT (sCT) images could minimize these uncertainties and streamline the RT workflow. This study aims to compare the contouring capabilities of sCT images with conventional CT-based/MR-assisted RT workflows, with an emphasis on managing artefacts caused by surgical fixation devices (SFDs).
The study comprised a commissioning cohort of 100 patients with cranial tumors treated using a conventional CT-based/MR-assisted RT workflow and a validation cohort of 30 patients with grade IV glioblastomas treated using an MR-only workflow. A CE-marked artificial-intelligence-based sCT product was utilized. The delineation accuracy comparison was performed using dice similarity coefficient (DSC) and average Hausdorff distance (AHD). Artefacts within the commissioning cohort were visually inspected, classified and an estimation of thickness was derived using Hausdorff distance (HD). For the validation cohort, boolean operators were used to extract artefact volumes adjacent to the target and contrasted to the planning treatment volume.
The combination of high DSC (0.94) and low AHD (0.04 mm) indicates equal target delineation capacity between sCT images and conventional CT scans. However, the results for organs at risk delineation were less consistent, likely because of voxel size differences between sCT images and CT scans and absence of standardized delineation routines. Artefacts observed in sCT images appeared as enhancements of cranial bone. When close to the target, they could affect its definition. Therefore, in the validation cohort the clinical target volume (CTV) was expanded towards the bone by 3.5 mm, as estimated by HD analysis. Subsequent analysis on cone-beam CT scans showed that the CTV adjustment was enough to provide acceptable target coverage.
The tested sCT product performed on par with conventional CT in terms of contouring capability. Additionally, this study provides both the first comprehensive classification of metal artefacts on a sCT product and a novel method to assess the clinical impact of artefacts caused by SFDs on target delineation. This methodology encourages similar analysis for other sCT products.
To evaluate interobserver variability in clinical target volume (CTV) delineation in gastric cancer performed with the help of a delineation guide.
Ten radiotherapy centers that participate in the ...CRITICS Phase III trial were provided with a delineation atlas, preoperative CT scans, a postoperative planning CT scan, and clinical information for a gastric cancer case and were asked to construct a CTV and create a dosimetric plan according to departmental policy.
The volumes of the CTVs and planning target volumes (PTVs) differed greatly, with a mean (SD) CTV volume of 392 (176) cm(3) (range, 240-821 cm(3)) and PTV volume of 915 (312) cm(3) (range, 634-1677 cm(3)). The overlapping volume was 376 cm(3) for the CTV and 890 cm(3) for the PTV. The greatest differences in the CTV were seen at the cranial and caudal parts. After planning, dose coverage of the overlapping PTV volume showed less variability than the CTV.
In this series of 10 plans, variability of the CTV in postoperative chemoradiotherapy for gastric cancer is large. Strict and clear delineation guidelines should be provided, especially in Phase III multicenter studies. Adaptations of these guidelines should be evaluated in clinical studies.
Radiotherapy of liver metastases is commonly being performed with photon-beam based stereotactic body radiation therapy (SBRT). The high risk for radiation-induced liver disease (RILD) is a limiting ...factor in these treatments. The use of proton-beam based SBRT could potentially improve the sparing of the healthy part of the liver. The aim of this study was to use estimations of normal tissue complication probability (NTCP) to identify liver-metastases patients that could benefit from being treated with intensity-modulated proton therapy (IMPT), based on the reduction of the risk for RILD.
Ten liver metastases patients, previously treated with photon-beam based SBRT, were retrospectively planned with IMPT. A CTV-based robust optimisation (accounting for setup and range uncertainties), combined with a PTV-based conventional optimisation, was performed. A robustness criterion was defined for the CTV (V
> 98% for at least 10 of the 12 simulated scenarios). The NTCP was estimated for different endpoints using the Lyman-Kutcher-Burman model. The ΔNTCP (NTCP
- NTCP
) for RILD was registered for each patient. The patients for which the NTCP (RILD) < 5% were also identified. A generic relative biological effectiveness of 1.1 was assumed for the proton beams.
For all patients, the objectives set for the PTV and the robustness criterion set for the CTV were fulfilled with the IMPT plans. An improved sparing of the healthy part of the liver, right kidney, lungs, spinal cord and the skin was achieved with the IMPT plans, compared to the SBRT plans. Mean liver doses larger than the threshold value of 32 Gy led to NTCP values for RILD exceeding 5% (7 patients with SBRT and 3 patients with the IMPT plans). ΔNTCP values (RILD) ranging between - 98% and - 17% (7 patients) and between 0 and 2% (3 patients), were calculated.
In this study, liver metastases patients that could benefit from being treated with IMPT, based on the NTCP reductions, were identified. The clinical implementation of such a model-based approach to select liver metastases patients to proton therapy needs to be made with caution while considering the uncertainties involved in the NTCP estimations.
IntroductionThe use of proton therapy increases globally despite a lack of randomised controlled trials demonstrating its efficacy and safety. Proton therapy enables sparing of non-neoplastic tissue ...from radiation. This is principally beneficial and holds promise of reduced long-term side effects. However, the sparing of seemingly non-cancerous tissue is not necessarily positive for isocitrate dehydrogenase (IDH)-mutated diffuse gliomas grade 2–3, which have a diffuse growth pattern. With their relatively good prognosis, yet incurable nature, therapy needs to be delicately balanced to achieve a maximal survival benefit combined with an optimised quality of life.Methods and analysisPRO-GLIO (PROton versus photon therapy in IDH-mutated diffuse grade 2 and 3 GLIOmas) is an open-label, multicentre, randomised phase III non-inferiority study. 224 patients aged 18–65 years with IDH-mutated diffuse gliomas grade 2–3 from Norway and Sweden will be randomised 1:1 to radiotherapy delivered with protons (experimental arm) or photons (standard arm). First intervention-free survival at 2 years is the primary endpoint. Key secondary endpoints are fatigue and cognitive impairment, both at 2 years. Additional secondary outcomes include several survival measures, health-related quality of life parameters and health economy endpoints.Ethics and disseminationTo implement proton therapy as part of standard of care for patients with IDH-mutated diffuse gliomas grade 2–3, it should be deemed safe. With its randomised controlled design testing proton versus photon therapy, PRO-GLIO will provide important information for this patient population concerning safety, cognition, fatigue and other quality of life parameters. As proton therapy is considerably more costly than its photon counterpart, cost-effectiveness will also be evaluated. PRO-GLIO is approved by ethical committees in Norway (Regional Committee for Medical & Health Research Ethics) and Sweden (The Swedish Ethical Review Authority) and patient inclusion has commenced. Trial results will be published in international peer-reviewed journals, relevant conferences, national and international meetings and expert forums.Trial registration numberClinicalTrials.gov Registry (NCT05190172).
Background The optimal chemotherapy in patients with advanced gastric carcinoma (GC) is yet to be determined. We compared sequential administration of docetaxel and irinotecan, both in combination ...with infused 5-fluorouracil/leucovorin (5-Fu/Lv), and randomly assigned patients to start with either of the two. Methods Patients with previously untreated locally advanced or metastatic GC and with measurable lesions (response evaluation criteria in solid tumors; RECIST) were randomly assigned to start with docetaxel 45 mg/m² (arm T) or irinotecan 180 mg/m² (arm C) with bolus/44-h infusion of 5-Fu/Lv (day 1 every 2 weeks). After four courses, there was a prescheduled crossover to the alternative regimen for four additional courses. Results Eighty-one patients were randomized and 78 started treatment. Complete and partial responses were seen in 31 (40%) patients after 8 weeks and in 32 (41%) after 16 weeks, with similar results in both study arms. The median overall survival (OS) was 11.5 and 10.6 months in arms T and C, respectively (P = 0.3). The two schedules were feasible and did not differ in the overall rate of severe adverse events (SAEs). Conclusion This is the first randomized comparison of two of the newer cytostatic drugs in GC therapy. No differences favoring either arm T or arm C were found with respect to response rate, OS, or toxicity. The median OS of 11 months indicates that sequential administration of the two combinations is effective and is similar to triple combinations. Thus, comparable efficacy to platinum combinations appears to be obtained with newer, less toxic regimens when given sequentially.
The LAP07 multicenter randomized study assessed whether chemoradiation therapy increases overall survival versus continuation chemotherapy in patients whose locally advanced pancreatic cancer was ...controlled after 4 months of induction chemotherapy. This analysis investigated whether failure to adhere to radiation therapy (RT) guidelines influenced survival and toxicity.
This is a planned analysis of secondary objectives in the framework of a randomized international phase 3 trial. The protocol included detailed written RT guidelines. All participating institutions undertook an initial benchmark case to check adherence to protocol guidelines. Centers with major deviation were not allowed to include patients until they achieved a significant improvement and rigorously followed the guidelines. On-trial RT quality assurance consisted of a central review of treatment plan with dose-volume histograms for each patient. Adherence to guidelines was graded as per protocol (PP), minor deviation (MiD), or major deviation (MaD).
Fifty-seven benchmark cases were evaluated, 26% were classified as PP, 60% were MiD, and 14% were MaD. Among the 442 included patients, 133 patients were randomized in the chemoradiation therapy arm, and 117 patients were assessable for RT quality analysis. RT quality was graded as PP in 38.5% of patients, MiD in 43.6% of patients, and MaD in 17.9% of patients. The most frequent protocol violations were dose distribution heterogeneities. Median overall survival was 17 months with PP and MiD versus 13.4 months with MaD (hazard ratio HR, 1.63; 95% confidence interval CI, 0.99-2.71; P = .055). There was no difference in terms of progression-free survival (HR, 1.09; 95% CI, 0.66-1.8; P = .72). Patients with MaD had more nausea than patients treated PP or with MiD (P = .0045).
MaD was associated with a trend for worst survival. There was no difference in terms of progression-free survival. Because of the low rate of major deviations, their effects on the LAP07 trial results may be negligeable.
Proton-beam therapy of large abdominal cancers has been questioned due to the large variations in tissue density in the abdomen. The aim of this study was to evaluate the importance of these ...variations for the dose distributions produced in adjuvant radiotherapy of gastric cancer (GC), implemented with photon-based volumetric modulated arc therapy (VMAT) or with proton-beam single-field uniform-dose (SFUD) method.
Eight GC patients were included in this study. For each patient, a VMAT- and an SFUD-plan were created. The prescription dose was 45 Gy (IsoE) given in 25 fractions. The plans were prepared on the original CT studies and the doses were thereafter recalculated on two modified CT studies (one with extra water filling and the other with expanded abdominal air-cavity volumes).
Compared to the original VMAT plans, the SFUD plans resulted in reduced median values for the V18 of the left kidney (26%), the liver mean dose (14.8 Gy (IsoE)) and the maximum dose given to the spinal cord (26.6 Gy (IsoE)). However, the PTV coverage decreased when the SFUD plans were recalculated on CT sets with extra air- (86%) and water-filling (87%). The added water filling only led to minor dosimetric changes for the OARs, but the extra air caused significant increases of the median values of V18 for the right and left kidneys (10% and 12%, respectively) and of V10 for the liver (12%). The density changes influenced the dose distributions in the VMAT plans to a minor extent.
SFUD was found to be superior to VMAT for the plans prepared on the original CT sets. However, SFUD was inferior to VMAT for the modified CT sets.
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