Purpose: Vertebral compression fracture (VCF) is increasingly recognized as an adverse event after spine stereotactic body radiotherapy (SBRT). We report a multi-institutional study aimed at clarifying the risk and predictive factors associated with VCF. Patients and Methods: A total of 252 patients with 410 spinal segments treated with SBRT were included. The primary outcome was the development of VCF (a new VCF or progression of a baseline VCF). In addition to various patient-, treatment-, and tumor-specific factors, the Spinal Instability Neoplastic Scoring (SINS) system was applied to determine predictive value. Results: The median follow-up was 11.5 months (range, 0.03 to 113 months). The median and mean overall survival rates were 16 and 26 months, respectively. We observed 57 fractures (57 of 410, 14%), with 47% (27 of 57) new fractures and 53% (30 of 57) fracture progression. The median time to VCF was 2.46 months (range, 0.03 to 43.01 months), and 65% occurred within the first 4 months. The 1- and 2-year cumulative incidences of fracture were 12.35% and 13.49%, respectively. Multivariable analysis identified dose per fraction (greatest risk for ≥ 24 Gy v 20 to 23 Gy v ≤ 19 Gy), in addition to three of the six original SINS criteria: baseline VCF, lytic tumor, and spinal deformity, as significant predictors of VCF. Conclusion: Caution must be observed when treating with ≥ 20 Gy/fraction, in particular, for patients with lytic tumor, spinal misalignment, and a baseline VCF. Frequent short-term follow-up is required, as nearly two thirds of all VCF occurred within the first 4 months. We also conclude that SINS may have utility in predicting patients at high risk of SBRT-induced VCF.

Despite the completion of numerous phase II studies, a standard of care treatment has yet to be defined for metastatic uveal melanoma (mUM). To determine benchmarks of progression free survival (PFS) and overall survival (OS), we carried out a meta-analysis using individual patient level trial data. Individual patient variables and survival outcomes were requested from 29 trials published from 2000 to 2016. Univariable and multivariable analysis were carried out for prognostic factors. The variability between trial arms and between therapeutic agents on PFS and OS was investigated. OS data were available for 912 patients. The median PFS was 3.3 months (95% CI 2.9-3.6) and 6-month PFS rate was 27% (95% CI 24-30). Univariable analysis showed male sex, elevated (i.e. > versus ≤ upper limit of normal) lactate dehydrogenase (LDH), elevated alkaline phosphatase (ALP) and diameter of the largest liver metastasis (≥3 cm versus <3 cm) to be substantially associated with shorter PFS. Multivariable analysis showed male sex, elevated LDH and elevated ALP were substantially associated with shorter PFS. The most substantial factors associated with 6-month PFS rate, on both univariable and multivariable analysis were elevated LDH and ALP. The median OS was 10.2 months (95% CI 9.5-11.0) and 1 year OS was 43% (95% CI 40-47). The most substantial prognostic factors for shorter OS by univariable and multivariable analysis were elevated LDH and elevated ALP. Patients treated with liver directed treatments had statistically significant longer PFS and OS. Benchmarks of 6-month PFS and 1-year OS rates were determined accounting for prognostic factors. These may be used to facilitate future trial design and stratification in mUM.

It is unknown what proportion of long-term lung function decline in cystic fibrosis (CF) is explained by pulmonary exacerbations. The aim of this study was to determine how exacerbations requiring hospitalisation contribute to the course of CF lung disease.This was a retrospective cohort study. The primary outcome was the rate of decline of forced expiratory volume in 1 s (FEV₁) % predicted.Out of 851 subjects, 415 (48.8%) subjects had ≥1 exacerbation. After adjustment for confounders, the annual rate of FEV₁decline in those without an exacerbation was 1.2% per yr (95% CI 1.0–1.5), compared with 2.5% per yr (95% CI 2.1–2.8) in those with an exacerbation. The proportion of overall FEV₁decline associated with ≥1 exacerbation was 52% (95% CI 35.0–68.9). For a given number of exacerbations, the annual rate of FEV₁decline was greatest in subjects with ≤6 months between exacerbations.Half of FEV₁decline seen in CF patients was associated with pulmonary exacerbations. Time between exacerbations, specifically ≤6 months between exacerbations, plays an important contribution to overall lung function decline. These findings support using time to next exacerbation as a clinical end-point for CF trials.

Our previous systematic review of geriatric assessment (GA) in oncology included a literature search up to November 2010. However, the quickly evolving field warranted an update. Aims of this review: (i) provide an overview of all GA instruments developed and/or in use in the oncology setting; (ii) evaluate effectiveness of GA in predicting/modifying outcomes (e.g. treatment decision impact, treatment toxicity, mortality, use of care). Systematic review of literature published between November 2010 and 10 August 2012. English, Dutch, French and German-language articles reporting cross-sectional or longitudinal, intervention or observational studies of GA instruments were included. Data sources: MEDLINE, EMBASE, PsycINFO, CINAHL and Cochrane Library. Two researchers independently reviewed abstracts, abstracted data and assessed the quality using standardized forms. A meta-analysis method of combining proportions was used for the outcome impact of GA on treatment modification with studies included in this update combined with those included in our previous systematic review on the use of GA. Thirty-five manuscripts reporting 34 studies were identified. Quality of most studies was moderate to good. Eighteen studies were prospective, 11 cross-sectional and 5 retrospective. Three studies examined treatment decision-making impact and found decisions changed for fewer than half of assessed patients (weighted percent modification is 23.2% with 95% confidence interval (20.3% to 26.1%). Seven studies reported conflicting findings regarding predictive ability of GA for treatment toxicity/complications. Eleven studies examined GA predictions of mortality, and reported that instrumental activities of daily living, poor performance status and more numerous GA deficits were associated with increased mortality risk. Other outcomes could not be meta-analyzed. Consistent with our previous review, several domains of GA are associated with adverse outcomes. However, further research examining effectiveness of GA on treatment decisions and oncologic outcomes is needed.

Spine stereotactic body radiotherapy (SBRT) is increasingly being applied to the postoperative spine metastases patient. Our aim was to identify clinical and dosimetric predictors of local control (LC) and survival. Eighty patients treated between October 2008 and February 2012 with postoperative SBRT were identified from our prospective database and retrospectively reviewed. The median follow-up was 8.3 months. Thirty-five patients (44%) were treated with 18–26 Gy in 1 or 2 fractions, and 45 patients (56%) with 18–40 Gy in 3–5 fractions. Twenty-one local failures (26%) were observed, and the 1-year LC and overall survival (OS) rates were 84% and 64%, respectively. The most common site of failure was within the epidural space (15/21, 71%). Multivariate proportional hazards analysis identified systemic therapy post-SBRT as the only significant predictor of OS (P = .02) and treatment with 18–26 Gy/1 or 2 fractions (P = .02) and a postoperative epidural disease grade of 0 or 1 (0, no epidural disease; 1, epidural disease that compresses dura only, P = .003) as significant predictors of LC. Subset analysis for only those patients (n = 48/80) with high-grade preoperative epidural disease (cord deformed) indicated significantly greater LC rates when surgically downgraded to 0/1 vs 2 (P = .0009). Postoperative SBRT with high total doses ranging from 18 to 26 Gy delivered in 1–2 fractions predicted superior LC, as did postoperative epidural grade.