Extended outpatient rehabilitation: its influence on symptom frequency, fatigue, and functional status for persons with progressive multiple sclerosis. Accelerated versus conventional fractionated postoperative radiotherapy for advanced head and neck cancer: results of a multicenter Phase III study.
To determine the influence of an extended outpatient rehabilitation program on symptom frequency, fatigue, and functional status for persons with multiple sclerosis (MS).
                Nonequivalent pretest/posttest control-group design, with posttest 1 year after initial assessment. Multiple regression analysis and analysis of covariance were used to control for symptom severity at the initial assessment and comorbid factors including depression, cognitive function, and social interaction. Effect sizes (ES) provided a descriptive measure of the change in outcomes.
                Outpatient multidisciplinary rehabilitation clinic.
                Forty-six patients with definite chronic progressive MS; 20 received treatment and 26 were in a nontreatment comparison group ("waiting list").
                Rehabilitation services for 5 hours, 1 day per week, over 1 year.
                The MS-Related Symptom Checklist composite score, fatigue frequency, and selected items from the Rehabilitation Institute of Chicago Functional Assessment Scale.
                Receiving treatment was a significant predictor of reduced symptom frequency (partial r2 = .26) at the 1-year follow-up. The ES adjusted for baseline values indicated substantial reductions in symptom frequency for the treatment group (EStreatment = .27 vs ESwaitlist = -.32). Fatigue was significantly reduced at the time of follow-up for the treatment group compared with the waiting list group (EStreatment = .46 vs ESwaitlist = -.20). There were no statistically significant differences among groups regarding functional status, but there appeared to be less loss of functional status in the treatment group compared with the waiting list group (EStreatment = -.07 vs ESwaitlist = -.70).
                An extended outpatient rehabilitation program for persons with definite progressive MS appears to effectively reduce fatigue and the severity of other symptoms associated with MS. To determine whether, in the postoperative setting, accelerated fractionation (AF) radiotherapy (RT) yields a superior locoregional control rate compared with conventional fractionation (CF) RT in locally advanced squamous cell carcinomas of the oral cavity, oropharynx, larynx, or hypopharynx.
                Patients from four institutions with one or more high-risk features (pT4, positive resection margins, pN >1, perineural/lymphovascular invasion, extracapsular extension, subglottic extension) after surgery were randomly assigned to either RT with one daily session of 2 Gy up to 60 Gy in 6 weeks or AF. Accelerated fractionation consisted of a "biphasic concomitant boost" schedule, with the boost delivered during the first and last weeks of treatment, to deliver 64 Gy in 5 weeks. Informed consent was obtained. The primary endpoint of the study was locoregional control. Analysis was on an intention-to-treat basis.
                From March 1994 to August 2000, 226 patients were randomized. At a median follow-up of 30.6 months (range, 0-110 months), 2-year locoregional control estimates were 80% +/- 4% for CF and 78% +/- 5% for AF (p = 0.52), and 2-year overall survival estimates were 67% +/- 5% for CF and 64% +/- 5% for AF (p = 0.84). The lack of difference in outcome between the two treatment arms was confirmed by multivariate analysis. However, interaction analysis with median values as cut-offs showed a trend for improved locoregional control for those patients who had a delay in starting RT and who were treated with AF compared with those with a similar delay but who were treated with CF (hazard ratio = 0.5, 95% confidence interval 0.2-1.1). Fifty percent of patients treated with AF developed confluent mucositis, compared with only 27% of those treated with CF (p = 0.006). However, mucositis duration was not different between arms. Although preliminary, actuarial Grade 3+ late toxicity estimates at 2 years were 18% +/- 4% and 27% +/- 6% for CF and AF, respectively (p = 0.10).
                Accelerated fractionation does not seem to be worthwhile for squamous cell carcinoma of the head and neck after resection; however, AF might be an option for patients who delay starting RT.
We were unable to achieve all of the objectives specified for the review. This review shows that the overall effect of CFX (administered as intensive schedule) in the treatment of progressive MS does not support its use in clinical practice.