Standard whole prostate gland radiotherapy with and without lesion boost in prostate cancer: Toxicity in the FLAME randomized controlled trial.

PURPOSE: To compare toxicity rates in patients with localized prostate cancer treated with standard fractionated external beam radiotherapy (EBRT) with or without an additional integrated boost to the macroscopically visible tumour. MATERIAL AND METHODS: FLAME is a phase 3 multicentre RCT (NCT01168479) of patients with pathologically confirmed localized intermediate or high-risk prostate cancer. The standard treatment arm (n = 287) received a dose to the entire prostate of 77 Gy in 35 fractions. The dose-escalated treatment arm (n = 284) received 77 Gy in 35 fractions to the entire prostate, with an integrated boost up to 95 Gy to the multi-parametric MRI-defined (macroscopic) tumour within the prostate. Treatment related toxicity was measured using the CTCAE version 3.0. Grade 2 or worse GU or GI events up to two years were compared between groups by presenting proportions and by Generalized Estimating Equations (GEE) analyses for repeated measures. RESULTS: Ninety percent of the 571 men randomly assigned between September 2009 and January 2015 had high-risk disease (Ash 2000), of whom nearly 66% were prescribed hormonal therapy up to three years. Median follow-up was 55 months at the time of this analysis. Toxicity prevalence rates for both GI and GU increased until the end of treatment and regressed thereafter, with no obvious differences across treatment groups. Late cumulative GI toxicity rates were 11.1% and 10.2% for the standard and dose-escalated group, respectively. These rates were 22.6% and 27.1% for GU toxicity. GEE analyses showed that both GU toxicity and GI toxicity (≥grade 2) up to two years after treatment were similar between arms (OR 1.02 95%CI 0.78-1.33p = 0.81 and (OR 1.19 95%CI 0.82-1.73p = 0.38), respectively. CONCLUSIONS: In intermediate- and high-risk prostate cancer patients, focal dose escalation integrated with standard EBRT did not result in an increase in GU and GI toxicity when compared to the standard treatment up to two years after treatment. This suggests that the described focal dose escalation technique is safe and feasible.

Limited evidence for effects of intranasal corticosteroids on symptom relief for recurrent acute rhinosinusitis.

OBJECTIVE: To systematically review the evidence base on the effectiveness of intranasal corticosteroids in adult patients with recurrent acute rhinosinusitis. Data Sources Pubmed, EMBASE, and the Cochrane Library. REVIEW METHODS: A comprehensive search was performed up to March 20, 2013. Two reviewers independently screened publications on title and abstract. Design of selected studies was assessed on directness of evidence and risk of bias. For included studies, risk differences with 95% confidence intervals were extracted or recalculated. RESULTS: Of 1850 unique records, 3 trials were included. Risk of bias was high and directness of evidence was low for 2 trials, the third trial had low risk of bias with moderate directness of evidence. They found a statistical significant difference for the median number of days to clinical success (defined as patients' report of symptoms to be cured or much improved) favoring intranasal corticosteroids (6 days) over placebo (9 days), while the difference in proportion of patients reporting clinical success after 21 days of treatment was 20% favoring intranasal corticosteroids over placebo. CONCLUSION AND RECOMMENDATION: The evidence for the benefit of intranasal corticosteroids on symptom relief in adult patients with recurrent acute rhinosinusitis is rather limited (ie, 3 trials are available; the best evidence is derived from 1 low risk of bias trial providing moderate directness of evidence that intranasal corticosteroids may speed up relief of symptoms in patients with recurrent acute rhinosinusitis). A large methodologically rigorous randomized trial in antibiotic-naïve patients is needed to provide a more definite recommendation.