Growth in eligibility criteria content and failure to accrue among National Cancer Institute (NCI)-affiliated clinical trials.

BACKGROUND: Cancer trial accrual is a national priority, yet up to 20% of trials fail to accrue. Trial eligibility criteria growth may be associated with accrual failure. We sought to quantify eligibility criteria growth within National Cancer Institute (NCI)-affiliated trials and determine impact on accrual. METHODS: Utilizing the Aggregated Analysis of ClinicalTrials.gov, we analyzed phase II/III interventional NCI-affiliated trials initiated between 2008 and 2018. Eligibility criteria growth was assessed via number of unique content words within combined inclusion and exclusion criteria. Association between unique word count and accrual failure was evaluated with multivariable logistic regression, adjusting for known predictors of failure. Medical terms associated with accrual failure were identified via natural language processing and categorized. RESULTS: Of 1197 trials, 231 (19.3%) failed due to low accrual. Accrual failure rate increased with eligibility criteria growth, from 11.8% in the lowest decile (12-112 words) to 29.4% in the highest decile (445-750 words). Median eligibility criteria increased over time, from 214 (IQR [23, 282]) unique content words in 2008 to 417 (IQR [289, 514]) in 2018 (r2  = 0.73, P < 0.001). Eligibility criteria growth was independently associated with accrual failure (OR: 1.09 per decile, 95% CI [1.03-1.15], p = 0.004). Eighteen exclusion criteria categories were significantly associated with accrual failure, including renal, pulmonary, and diabetic, among others (Bonferroni-corrected p < 0.001). CONCLUSIONS: Eligibility criteria content growth is increasing dramatically among NCI-affiliated trials and is strongly associated with accrual failure. These findings support national initiatives to simplify eligibility criteria and suggest that further efforts are warranted to improve cancer trial accrual.

Delineating the Subarachnoid Space in the Adult Lumbosacral Spine Using Computed Tomographic Myelography: An Aid for Clinical Target Volume Delineation in Craniospinal Irradiation.

Purpose: Our aim was to characterize the patterns of cerebrospinal fluid (CSF) extension in the lumbosacral spine using computed tomography (CT) myelograms to provide an evidence base for clinical target volume (CTV) definition in adults receiving craniospinal irradiation. Methods and Materials: This was a retrospective analysis of diagnostic CT lumbar myelograms performed in 30 patients between the ages of 22 and 50. Lateral extension of CSF beyond the thecal sac was measured along each lumbar and sacral nerve root to the nearest millimeter, as was the distance of inferior extension of CSF beyond the caudal end of the thecal sac. Each patient's lateral and inferior CSF extensions were mapped onto a standardized CT data set to create a model target volume in the lumbosacral spine that would contain the aggregate observed CSF distributions from the analyzed CT myelograms. The median extension distances, interquartile ranges, and 90th percentile for distance at each level were calculated. Results: The median lateral extension of CSF along nerve roots beyond the thecal sac-as measured perpendicular to the longitudinal axis-increased from 0 mm (interquartile range [IQR], 0-4 mm) at L1 to 8 mm (IQR, 6-12 mm) at S1 and 0 mm (IQR, 0-0 mm) at S4. The 90th percentile ranged from 5 to 14 mm laterally, with a pattern partially extending into the S1 and S2 sacral foramen. Median CSF extension inferior to the caudal sac was 5 mm (IQR, 2-8 mm), with 90% of patients within 12 mm. An atlas was generated to guide CTV delineation for highly conformal radiation techniques. Conclusion: These results provide information on patterns of CSF extension in the lumbosacral spine of adults and can serve as a model for CTV guidelines that balance comprehensive coverage of the CSF compartment while minimizing the dose to nontarget tissues.

Measurement of Phacoemulsification Vacuum Pressure in the Oertli CataRhex3.

Purpose: To determine the actual vacuum pressure generated by the Oertli CataRhex 3® (Oertli), using an external measuring system. Methods: The effective vacuum pressure created by the Oertli was measured with a pressure device that was continuous with the vacuum tubing system while closed to the external environment. Measurements were taken with the machine set to 300 and 500 mmHg at flow rates of 20, 35, and 50 mL/min and at bottle heights of 60, 80, and 100 cm. Pressures were recorded after the foot pedal was depressed to vacuum setting (second position), and the pressure was allowed to stabilize. Subsequently, it was compared to the pressure value displayed by the machine. Results: Externally measured vacuum pressure was on average 13.02% greater (39.05 mmHg) than displayed vacuum pressure at 300 mmHg (P < 0.005) and 8.60% greater (42.98 mmHg) than displayed vacuum at 500 mmHg (P < 0.005). The average difference between displayed and measured pressure increased with increasing bottle heights. Conclusion: On average, the vacuum pressure generated in the Oertli was found to be significantly higher than the machine's reading when the machine was set at 300 mmHg and 500 mmHg. Adjusting vacuum had variable effects on the measured versus displayed pressure readings.

Optimization of Phacoemulsification Tip Gauge on the Oertli CataRhex3 in an in vitro Setting.

Purpose: To evaluate the effect of each of the tip sizes available for the Oertli CataRhex3® phacoemulsification machine on efficiency. Methods: Porcine lenses were fixed in formalin for 2 hours, then cut into 3.0 mm cubes. We studied three Oertli tips, all of which had a 30-degree bevel: easyTip 2.2 mm (20G), easyTip 2.8 mm (19G), and CO-MICS (21G). For the 19G and 20G tips, vacuum was set at 600 mmHg, irrigation rate at 50 mL/min, continuous power 70%, and bottle height 85 cm. For the 21G tip, vacuum was set at 450 mmHg; irrigation and power settings were identical to those used for the easyTip tips. We measured time to removal and chatter events to determine efficiency. Results: Results from 20 trials for each tip showed that the larger the gauge size, the more quickly lens fragments were removed. Chatter events demonstrated an increasing trend with smaller tip gauge. The 19G tip used an average time to fragment removal of 2.8 seconds; the 20G, 3.2 seconds; and the 21G, 4.6 seconds. Increasing tip diameter from 21G to 20G decreased emulsification time by 33% (P = 0.02). Increasing the diameter from 21G to 19G further decreased time to emulsification by 42% (P = 0.003). The 21G tip had a mean 1.4 events/cube; 20G, 0.35 events; and 19G, 0.1 events. Differences in mean chatter events for each tip were each statistically significant. Conclusion: These data suggest that when evaluated by chatter events and emulsification time, the 2.8 mm (19G) easyTip proves to have greatest efficiency.

Effects on phacoemulsification efficiency and chatter at variable longitudinal ultrasound settings when combined with constant torsional energy.

PURPOSE: To evaluate longitudinal power settings for optimally efficient lens fragment removal, using the Centurion machine. SETTING: John A. Moran Eye Center, University of Utah, Salt Lake City, USA. DESIGN: Experimental study. METHODS: Porcine lens nuclei were cut into 2.0 mm cubes. Experiments were conducted at 100% torsional power; vacuum set at 500 mm Hg, aspiration 50 mL/min, and intraocular pressure 110 mm Hg. A 20-degree tip with a 30-degree bevel was used. Longitudinal power was tested between 20% and 100%. Efficiency (time for fragment removal) and chatter (the number of times the fragment bounced from the tip) were measured. RESULTS: A linear increase in efficiency was observed from 20% to 100% longitudinal power (R = 0.9281, slope = -0.0271). An efficiency slope change occurred at 60% power, with the largest incremental change in efficiency between 20% and 60% (R = 0.9756, slope = -0.0394) and a lesser change between 60% and 100% (R = 0.9827, slope = -0.0121). Chatter analysis showed minimal events at 20% to 60%, but a significant increase at >80% (P = .005). This increase appeared to be incremental (R = 0.8929). CONCLUSIONS: Increasing longitudinal power, with all other settings constant, increased efficiency. Greatest efficiency gains were observed between 20% and 60%. At 80% and 100%, chatter events increased significantly. With a goal of recommending optimally efficient settings while minimizing excess energy and chatter, adding 60% of longitudinal power to 100% torsional power was shown to be the best setting to increase efficiency and avoid repulsion in these vacuum and aspiration settings.