The Dosimetric Impact of Interfractional Organ-at-Risk Movement During Liver Stereotactic Body Radiation Therapy.

PURPOSE: Stereotactic body radiation therapy (SBRT) is an effective therapy for treating liver malignancies. However, little is known about interfractional dose variations to adjacent organs at risk (OARs). We examine the effects of interfractional organ movement and setup variation on dose delivered to OARs in patients receiving liver SBRT. METHODS AND MATERIALS: Thirty patients treated with liver SBRT were analyzed. Daily image guidance with diagnostic quality computed tomography-on-rails imaging was performed before each fraction. In phase 1, these daily images were used to delineate all OARs including the liver, heart, right kidney, esophagus, stomach, duodenum, and large bowel in 10 patients. In phase 2, only OARS in close proximity to the target were contoured in 20 additional patients. Dose distribution on each daily computed tomography was generated, and daily doses to each OAR were recorded and compared with clinical thresholds to determine whether a daily dose excess (DDE) occurred. RESULTS: In phase 1, significant interfractional dose differences between planned and delivered dose to OARs were observed, but differences were rarely clinically significant, with just 1 DDE. In phase 2, multiple DDEs were recorded for OARs close to the target, mainly involving the stomach, heart, and esophagus. Tumors in the hilum and liver segments I, IV, and VIII were the most common locations for DDEs. On root cause analysis, 3 etiologies of DDE emerged: craniocaudal shift (69.2%), anatomic changes (28.2%), and anteroposterior shifts (2.6%). CONCLUSIONS: OARs close to liver lesions may receive higher doses than expected during SBRT owing to interfractional variations in OARs relative to the target. These differences in planned versus expected dose can lead to toxicity. Efforts to better evaluate OARs with daily image guidance may help reduce risks. Application of adaptive replanning and improved and real-time image guidance could mitigate risks of toxicity, and further study into their applications is warranted.

Assessment of Consistency Between Peer-Reviewed Publications and Clinical Trial Registries.

Importance: Clinical trial registries are intended to increase clinical research transparency by nonselectively identifying and documenting clinical trial designs and outcomes. Inconsistencies in reported data undermine the utility of such registries and have previously been noted in general medical literature. Objective: To assess whether inconsistencies in reported data exist between ophthalmic literature and clinical trial registries. Design, Setting, and Participants: In this retrospective, cross-sectional study, interventional clinical trials published from January 1, 2014, to December 31, 2014, in the American Journal of Ophthalmology, JAMA Ophthalmology, and Ophthalmology were reviewed. Observational, retrospective, uncontrolled, and post hoc reports were excluded, yielding a sample size of 106 articles. Data collection was performed from January through September 2016. Data review and adjudication continued through January 2017. Main Outcomes and Measures: If possible, articles were matched to registry entries listed in the ClinicalTrials.gov database or in 1 of 16 international registries indexed by the World Health Organization International Clinical Trials Registry Platform version 3.2 search engine. Each article-registry pair was assessed for inconsistencies in design, results, and funding (each of which was further divided into subcategories) by 2 reviewers and adjudicated by a third. Results: Of 106 trials that met the study criteria, matching registry entries were found for 68 (64.2%), whereas no matching registry entries were found for 38 (35.8%). Inconsistencies were identified in study design, study results, and funding sources, including specific interventions in 8 (11.8%), primary outcome measure (POM) designs in 32 (47.1%), and POM results in 48 (70.6%). In addition, numerous data pieces were unreported, including analysis methods in 52 (76.5%) and POM results in 38 (55.9%). Conclusions and Relevance: Clinical trial registries were underused in this sample of ophthalmology clinical trials. For studies with registry data, inconsistency rates between published and registered data were similar to those previously reported for general medical literature. In most cases, inconsistencies involved missing data, but explicit discrepancies in methods and/or data were also found. Transparency and credibility of published trials may be improved by closer attention to their registration and reporting.