Ronald Brand

Abstract Most patients treated for single or multiple brain metastases die from progression of extracranial tumor activity. This makes it uncertain whether the combination of neurosurgery and radiontherapy for treatment of single brain metastasis will lead to better results than less invasive treatment with radiotherapy alone. The effect of neurosurgical excision plus radiotherapy was compared with radiotherapy alone in a prospectively randomized trial with 63 evaluable patients with systemic cancer and a radiological diagnosis of single brain metastasis. Radiotherapy was given to the whole brain by a novel scheme of 2 faractions per day of each 2 Gy for a total of 40 Gy. Before randomization, patients were stratified by site (lung cancer vs nonlung cancer) and status of extracranial disease (progressive vs. stable). Survival as such and functionally independent survival (FIS; defined as world Health Organization performance status ≤ 1 and neurological funcition ≤ 1) were compared between both treatment arms. The combined treatment compared with radiotherapy alone led to a longer survival ( p =0.04) and a longer FIS ( p =0.06). This was most pronounced in patients with stable extracranial disease (median survival, 12vs 7 mo; median FIS 9 vs 4 Mo). Patients with progressive extracranial cancer had a median overall survival of 5 months and a FIS of 2.5 months irrespective of given treatment. Improvement in functional status occurred more rapidly and for longer periods of time after neurosurgial excision and radiotherapy than after radiotherpy alone. Patients older than 60 years had a hazard ratio of dying of 2.74( p =0.001) compared with younger patients, but in both age groups the combined treatment did better then radiotherapy alone. We coclude that patients with single brain metastasis and stable extracranial tumor activity should be treated with surgical excision and radiotherapy. For patients with progressive extracranial disease during the previous 3 months, radiotherapy alone appears to be sufficient. After treatment of single brain metastasis, parients remain functionally independent until a few months before death.

BACKGROUND: Lumbar-disk surgery often is performed in patients who have sciatica that does not resolve within 6 weeks, but the optimal timing of surgery is not known. METHODS: We randomly assigned 283 patients who had had severe sciatica for 6 to 12 weeks to early surgery or to prolonged conservative treatment with surgery if needed. The primary outcomes were the score on the Roland Disability Questionnaire, the score on the visual-analogue scale for leg pain, and the patient's report of perceived recovery during the first year after randomization. Repeated-measures analysis according to the intention-to-treat principle was used to estimate the outcome curves for both groups. RESULTS: Of 141 patients assigned to undergo early surgery, 125 (89%) underwent microdiskectomy after a mean of 2.2 weeks. Of 142 patients designated for conservative treatment, 55 (39%) were treated surgically after a mean of 18.7 weeks. There was no significant overall difference in disability scores during the first year (P=0.13). Relief of leg pain was faster for patients assigned to early surgery (P<0.001). Patients assigned to early surgery also reported a faster rate of perceived recovery (hazard ratio, 1.97; 95% confidence interval, 1.72 to 2.22; P<0.001). In both groups, however, the probability of perceived recovery after 1 year of follow-up was 95%. CONCLUSIONS: The 1-year outcomes were similar for patients assigned to early surgery and those assigned to conservative treatment with eventual surgery if needed, but the rates of pain relief and of perceived recovery were faster for those assigned to early surgery. (Current Controlled Trials number, ISRCTN26872154 [controlled-trials.com].).

OBJECTIVE: To define variations in the cellular infiltrate and in the expression of monokines in synovial tissue (ST) from rheumatoid arthritis (RA) patients with different durations of disease and different levels of disease activity. METHODS: The immunohistologic features of synovial biopsy specimens from 31 patients with early RA (< 1 year) and 35 patients with longstanding RA (> 5 years) were compared. The possible associations between these features and local disease activity, as measured by the score for pain in the biopsied knee joint were also evaluated. RESULTS: The immunohistologic features were not dependent on disease duration. We found a positive correlation between the scores for knee pain and the semiquantitative scores for the number of macrophages, as well as the expression of interleukin-6 and tumor necrosis factor alpha, whereas the correlation with the scores for CD4+ T cells was negative. Multivariate analysis showed that these correlations were highly statistically significant (P < 0.003). CONCLUSION: The results do not support the view that inflammatory mechanisms in the synovial tissues of RA patients differ between early and late stages of the disease. The findings presented here are consistent with the concept that early RA is the result of a synovitis process of longer duration and that macrophage-derived cytokines play an important role in maintaining the clinical signs of inflammation.

From 2002 to 2007, 103 patients with primary myelofibrosis or postessential thrombocythemia and polycythemia vera myelofibrosis and a median age of 55 years (range, 32-68 years) were included in a prospective multicenter phase 2 trial to determine efficacy of a busulfan (10 mg/kg)/fludarabine (180 mg/m(2))-based reduced-intensity conditioning regimen followed by allogeneic stem cell transplantation from related (n = 33) or unrelated donors (n = 70). All but 2 patients (2%) showed leukocyte and platelet engraftment after a median of 18 and 22 days, respectively. Acute graft-versus-host disease grade 2 to 4 occurred in 27% and chronic graft-versus-host disease in 43% of the patients. Cumulative incidence of nonrelapse mortality at 1 year was 16% (95% confidence interval, 9%-23%) and significantly lower for patients with a completely matched donor (12% vs 38%; P = .003). The cumulative incidence of relapse at 3 years was 22% (95% confidence interval, 13%-31%) and was influenced by Lille risk profile (low, 14%; intermediate, 22%; and high, 34%; P = .02). The estimated 5-year event-free and overall survival was 51% and 67%, respectively. In a multivariate analysis, age older than 55 years (hazard ratio = 2.70; P = .02) and human leukocyte antigen-mismatched donor (hazard ratio = 3.04; P = .006) remained significant factors for survival. The study was registered at www.clinicaltrials.gov as #NCT 00599547.