BMC Cancer 2009, 9:372 http://www.biomedcentral.com/1471-2407/9/372 version 3.0). Volume changes were measured on gadolin- ium-enhanced T1 weighted MPR images, using the Splicer software v 2.6 (Surgical Planning Laboratory, Brigham and Women's Hospital, Boston, MA [21]). Statistical analysis Results were expressed as means ± standard deviations (SDs) for quantitative variables, while frequencies and proportions (%) were used for categorical variables. The non-parametric correlation coefficient of Spearman was calculated for measuring the association between two quantitative variables. Survival curves were determined by the Kaplan-Meier method and compared by the log-rank test. Calculations were always carried out on the maxi- mum number of data available. Missing data were not replaced. Results were considered to be significant at the 5% critical level (p < 0.05). Data analysis was carried out using SAS (version 9.1 for Windows) and S-PLUS (version 6.2) statistical packages by AA and SV (Department of Medical Statistics, University of Liège, Belgium). Immunochemistry and MGMT promoter analysis Histology of the tumor samples obtained at the time of initial surgery was reviewed in all patients by an experi- enced neuropathologist (MD). NF-kappaB p65 staining of patient 6's tumor was performed using a monoclonal anti- body to p65 (Santa Cruz Biotechnology) and as described previously [2]. MGMT promoter analysis was performed by Oncomethylome Sciences (Liege, Belgium), as described previously [22]. Results Patient demographics The relevant demographic and clinical characteristics of the patients included in the study are listed in [see addi- tional file 2: Table S2A]. At the time of interim analysis, performed as scheduled, nine males and one female patient, aged 32-62 yr (median: 53.5) had been enrolled in and completed the study between May, 2005 and Janu- ary, 2007. All patients had undergone surgery, standard radiation therapy (54-60 Gy) and a course of chemother- apy with alkylating agents prior to their inclusion in the present study. Nine patients were thus on temozolomide chemotherapy prior to their inclusion in the study. One patient was on a BCNU regimen. All patients had been off these cytotoxic medications for at least 4 weeks prior to the initiation of their Sulfasalazine treatment, and none had manifested severe side effects. Patient #4 and 6 had however experienced mild headaches and nausea while on temozolomide, and patient #7 had presented tran- siently decreased white cell counts on this regimen. All patients were free of those symptoms at the time of inclu- sion in ISRCTN45828668. Eight patients had a diagnosis of recurrent glioblastoma multiforme and two suffered progressive anaplastic astro- cytomas. MGMT promoter methylation analysis, assessed in all tumors at the time of initial resection, provided une- quivocal results in 8 patients, and demonstrated a pro- moter methylation in only one tumor (patient # 3). KPS scores at the time of inclusion ranged from 40 to 70, with a median of 50. The initial tumor volume was on average 67.7 ± 31.9 ml (range: 30.8 - 134 ml). Primary objective #1: treatment-associated toxicity Adverse events that occurred over the duration of the study are reported in tables S2B [see additional file 2: Table S2B] and S3 [see additional file 3], together with the initial KPS of the patients and daily dose of Sulfasalazine intake. All patients experienced adverse events (AEs) of grade 1 to 3 (CTCAE V 3.0), with an average of 7.2 ± 2.6 (range 4 - 11, median 7.5). Four (40%) patients devel- oped a grade 4 toxicity, two of whom subsequently devel- oped grade 5 (i.e., lethal) SAEs. The number of adverse events of grade 1 to 3 and the occurrence of adverse events of grade 4 were not related to the dose of sulfasalazine (p = 0.44 and p = 0.17 respectively). Both patients encoun- tering grade 5 adverse events were in the 1.5 g/day dose (p = 0.094). Of the grade 1-3 AEs, 5 patients developed significant T2 MRI changes, believed to result from an increased peritu- moral oedema and accompanied by increased cephalalgia (Figure 1). Proteinuria was encountered in 6 patients dur- ing sulfasalazine treatment. Bone marrow toxicity was finally encountered in 4 patients (neutropenia in 2, lym- SFuiglfuasrleaz1ine-associated peritumor oedema Sulfaslazine-associated peritumor oedema. T2 MRI scans obtained at inclusion, prior to Sulfasalazine treatment in patient #4, and 8 days after the initiation of sulfaslaazine treatment (6 g/day). The images demonstrate an increased peritumoral oedema and the developing midline shift. This patient alo developed severe headaches and withdrew from the study. Page 3 of 8 (page number not for citation purposes)