Impact of 2-staged stereotactic radiosurgery for treatment of brain metastases ≥ 2 cm.

OBJECTIVE Stereotactic radiosurgery (SRS) is the primary modality for treating brain metastases. However, effective radiosurgical control of brain metastases ≥ 2 cm in maximum diameter remains challenging and is associated with suboptimal local control (LC) rates of 37%-62% and an increased risk of treatment-related toxicity. To enhance LC while limiting adverse effects (AEs) of radiation in these patients, a dose-dense treatment regimen using 2-staged SRS (2-SSRS) was used. The objective of this study was to evaluate the efficacy and toxicity of this treatment strategy. METHODS Fifty-four patients (with 63 brain metastases ≥ 2 cm) treated with 2-SSRS were evaluated as part of an institutional review board-approved retrospective review. Volumetric measurements at first-stage stereotactic radiosurgery (first SSRS) and second-stage SRS (second SSRS) treatments and on follow-up imaging studies were determined. In addition to patient demographic data and tumor characteristics, the study evaluated 3 primary outcomes: 1) response at first follow-up MRI, 2) time to local progression (TTP), and 3) overall survival (OS) with 2-SSRS. Response was analyzed using methods for binary data, TTP was analyzed using competing-risks methods to account for patients who died without disease progression, and OS was analyzed using conventional time-to-event methods. When needed, analyses accounted for multiple lesions in the same patient. RESULTS Among 54 patients, 46 (85%) had 1 brain metastasis treated with 2-SSRS, 7 patients (13%) had 2 brain metastases concurrently treated with 2-SSRS, and 1 patient underwent 2-SSRS for 3 concurrent brain metastases ≥ 2 cm. The median age was 63 years (range 23-83 years), 23 patients (43%) had non-small cell lung cancer, and 14 patients (26%) had radioresistant tumors (renal or melanoma). The median doses at first and second SSRS were 15 Gy (range 12-18 Gy) and 15 Gy (range 12-15 Gy), respectively. The median duration between stages was 34 days, and median tumor volumes at the first and second SSRS were 10.5 cm3 (range 2.4-31.3 cm3) and 7.0 cm3 (range 1.0-29.7 cm3). Three-month follow-up imaging results were available for 43 lesions; the median volume was 4.0 cm3 (range 0.1-23.1 cm3). The median change in volume compared with baseline was a decrease of 54.9% (range -98.2% to 66.1%; p < 0.001). Overall, 9 lesions (14.3%) demonstrated local progression, with a median of 5.2 months (range 1.3-7.4 months), and 7 (11.1%) demonstrated AEs (6.4% Grade 1 and 2 toxicity; 4.8% Grade 3). The estimated cumulative incidence of local progression at 6 months was 12% ± 4%, corresponding to an LC rate of 88%. Shorter TTP was associated with greater tumor volume at baseline (p = 0.01) and smaller absolute (p = 0.006) and relative (p = 0.05) decreases in tumor volume from baseline to second SSRS. Estimated OS rates at 6 and 12 months were 65% ± 7% and 49% ± 8%, respectively. CONCLUSIONS 2-SSRS is an effective treatment modality that resulted in significant reduction of brain metastases ≥ 2 cm, with excellent 3-month (95%) and 6-month (88%) LC rates and an overall AE rate of 11%. Prospective studies with larger cohorts and longer follow-up are necessary to assess the durability and toxicities of 2-SSRS.

Impact of cervicothoracic region stereotactic spine radiosurgery on adjacent organs at risk.

OBJECTIVE Stereotactic radiosurgery (SRS) of the spine is a conformal method of delivering a high radiation dose to a target in a single or few (usually ≤ 5) fractions with a sharp fall-off outside the target volume. Although efforts have been focused on evaluating spinal cord tolerance when treating spinal column metastases, no study has formally evaluated toxicity to the surrounding organs at risk (OAR), such as the brachial plexus or the oropharynx, when performing SRS in the cervicothoracic region. The aim of this study was to evaluate the radiation dosimetry and the acute and delayed toxicities of SRS on OAR in such patients. METHODS Fifty-six consecutive patients (60 procedures) with a cervicothoracic spine tumor involving segments within C5-T1 who were treated using single-fraction SRS between February 2006 and July 2014 were included in the study. Each patient underwent CT simulation and high-definition MRI before treatment. The clinical target volume and OAR were contoured on BrainScan and iPlan software after image fusion. Radiation toxicity was evaluated using the common toxicity criteria for adverse events and correlated to the radiation doses delivered to these regions. The incidence of vertebral body compression fracture (VCF) before and after SRS was evaluated also. RESULTS Metastatic lesions constituted the majority (n = 52 [93%]) of tumors treated with SRS. Each patient was treated with a median single prescription dose of 16 Gy to the target. The median percentage of tumor covered by SRS was 93% (maximum target dose 18.21 Gy). The brachial plexus received the highest mean maximum dose of 17 Gy, followed by the esophagus (13.8 Gy) and spinal cord (13 Gy). A total of 14 toxicities were encountered in 56 patients (25%) during the study period. Overall, 14% (n = 8) of the patients had Grade 1 toxicity, 9% (n = 5) had Grade 2 toxicity, 2% (n = 1) had Grade 3 toxicity, and none of the patients had Grade 4 or 5 toxicity. The most common (12%) toxicity was dysphagia/odynophagia, followed by axial spine pain flare or painful radiculopathy (9%). The maximum radiation dose to the brachial plexus showed a trend toward significance (p = 0.066) in patients with worsening post-SRS pain. De novo and progressive VCFs after SRS were noted in 3% (3 of 98) and 4% (4 of 98) of vertebral segments, respectively. CONCLUSIONS From the analysis, the current SRS doses used at the Cleveland Clinic seem safe and well tolerated at the cervicothoracic junction. These preliminary data provide tolerance benchmarks for OAR in this region. Because the effect of dose-escalation SRS strategies aimed at improving local tumor control needs to be balanced carefully with associated treatment-related toxicity on adjacent OAR, larger prospective studies using such approaches are needed.

Association Between Radiation Necrosis and Tumor Biology After Stereotactic Radiosurgery for Brain Metastasis.

BACKGROUND: The primary dose-limiting toxicity of stereotactic radiosurgery (SRS) is radiation necrosis (RN), which occurs after approximately 5% to 10% of treatments. This adverse event may worsen neurologic deficits, increase the frequency and cost of imaging, and necessitate prolonged treatment with steroids or antiangiogenic agents. Previous investigations have primarily identified lesion size and dosimetric constraints as risk factors for RN in small populations. We hypothesized that disease histology, receptor status, and mutational status are associated with RN. METHODS AND MATERIALS: All patients presenting with brain metastasis between 1997 and 2015 who underwent SRS and subsequent radiographic follow-up at a single tertiary-care institution were eligible for inclusion. The primary outcome was the cumulative incidence of radiographic RN. Multivariate competing risks regression was used to identify biological risk factors for RN. RESULTS: 1939 patients (5747 lesions) were eligible for inclusion; 285 patients (15%) experienced radiographic RN after the treatment of 427 (7%) lesions. After SRS, the median time to RN was 7.6 months. After multivariate analysis, graded prognostic assessment, renal pathology, lesion diameter, and the heterogeneity index remained independently predictive of RN in the pooled cohort. In subset analyses of individual pathologies, HER2-amplified status (hazard ratio [HR] 2.05, P=.02), BRAF V600+ mutational status (HR 0.33, P=.04), lung adenocarcinoma histology (HR 1.89, P=.04), and ALK rearrangement (HR 6.36, P<.01) were also associated with RN. CONCLUSIONS: In the present investigation constituting the largest series of RN, several novel risk factors were identified, including renal histology, lung adenocarcinoma histology, HER2 amplification, and ALK/BRAF mutational status. These risk factors may be used to guide clinical trial design incorporating biological risk stratification or dose escalation. Future studies determining the optimal timing of targeted therapies are warranted to further define the risk of RN.

Barriers to life jacket use among adult recreational boaters.

OBJECTIVE: To identify barriers to life jacket use. DESIGN: Cross-sectional survey. SETTING: Nine public boat ramps in western Washington State, USA, August-November, 2008. PARTICIPANTS: 675 adult boaters (>18 years) on motor boats <26 feet long. MAIN OUTCOME: Low or no life jacket use (0-50% of time) versus high life jacket use (51-100% of time). RESULTS: Low/no life jacket use (0-50% of time) was associated with longer boat length (per foot, risk ratio [RR] 1.03, 95% CI 1.02 to 1.05), alcohol use (RR 1.11, 95% CI 1.01 to 1.20), perception of life jackets as 'uncomfortable' (RR 1.29, 95% CI 1.09 to 1.52), perceived greater level of swimming ability (RR 1.25, 95% CI 1.03 to 1.53 for 'expert swimmer') and possibly with lack of confidence that a life jacket may save one from drowning (RR 1.13, 95% CI 0.96 to 1.32). Low life jacket use was less likely when an inflatable life jacket was the primary life jacket used by a subject (RR 0.77, 95% CI 0.63 to 0.94), a child was onboard (RR 0.88, 95% CI 0.79 to 0.99) or if the respondent had taken a boating safety class (RR 0.94, 95% CI 0.87 to 1.01). CONCLUSIONS: Life jacket use may increase with more comfortable devices, such as inflatable life jackets, and with increased awareness of their efficacy in preventing drowning. Boater education classes may be associated with increased life jacket use among adults.

Too small for a seatbelt: predictors of booster seat use by child passengers.

OBJECTIVES: Motor vehicle injury is the leading cause of injury death for children 4 to 8 years of age. Although booster seat use in this age group substantially reduces the risk of injury, most children are currently restrained by seatbelts designed for adults. The objective of this study was to measure booster seat use directly, determine factors predictive of proper child restraint, and assess parental reasons for booster use and nonuse. METHODS: We conducted a cross-sectional, observational study in Seattle, Washington, Spokane, Washington, and Portland, Oregon, from February to April 2000. Drivers were surveyed in their vehicles after picking up children from schools and child care centers. Trained observers recorded child age, weight, and height and directly observed restraint use. Observed restraint use was compared with the recommended restraint method based on the child's weight and age. Data were analyzed using multivariate logistic regression, adjusted for clustering by car and site. RESULTS: We observed 2880 children traveling in cars, 1539 of whom were eligible for booster seat use. Eighty-eight percent of drivers agreed to respond to our survey. Only 16.5% of children for whom a booster seat was recommended were properly restrained, compared with 80% of younger children for whom a child safety seat was recommended and 55% of children for whom an adult seatbelt was recommended. Relative to a 4-year-old booster-eligible child, a 6-year-old was only half as likely to use a booster seat (odds ratio [OR]: 0.47; 95% confidence interval [CI]: 0.31-0.71) and an 8-year-old almost never used a booster seat (OR: 0.04; 95% CI: 0.01-0.19). Booster use was more common when the driver wore a seatbelt (OR: 3.1; 95% CI: 1.8-5.4). Parents whose children were using booster seat cited "safety" (61%) and "child comfort and visibility" (12%) as their primary concerns. When a child was not using a booster seat, parents most often believed that their child was "too big for a car seat" (56%), reported that the seat was in another vehicle (9%), or stated that they "had not heard" of booster seats (8%). CONCLUSIONS: Many parents still incorrectly believe that children are safe in a seatbelt and have outgrown the need for a car seat. These results demonstrate the need for public education campaigns to educate parents about booster seat use.

Use of child booster seats in motor vehicles following a community campaign: a controlled trial.

CONTEXT: Once children have outgrown car seats, booster seats protect from injury better than lap and shoulder belts alone. However, the majority of children aged 4 to 8 years use only an adult seat belt. OBJECTIVE: To evaluate the effectiveness of a multifaceted community booster seat campaign in increasing observed booster seat use among child passengers in motor vehicles. DESIGN: Prospective, nonrandomized, controlled community intervention trial. SETTING AND PARTICIPANTS: The campaign was initiated in 4 communities in the greater Seattle, Wash, area between January 2000 and March 2001. Eight communities in Portland, Ore, and Spokane, Wash, served as control sites. We observed 3609 booster-eligible children (those aged 4-8 years and weighing 18-36 kg [40-80 lb]). MAIN OUTCOME MEASURE: Observed booster seat use 15 months after the start of the campaign. RESULTS: Before the campaign began, 13.3% of eligible children in the intervention communities and 17.3% in the control communities were using booster seats, adjusting for child age, driver seat belt use, and sex of driver. Fifteen months after the start of the campaign, adjusted booster seat use had increased to 26.1% in the intervention communities and 20.2% in the control communities (P =.008 for the difference in time trends between intervention and control communities). CONCLUSION: These data suggest that a multifaceted community education campaign can significantly increase the use of child booster seats.