Background Patients with radioactive iodine (131I, RAI)-refractory locally advanced or metastatic differentiated thyroid cancer (DTC) have a poor prognosis due to the lack of effective treatment options. Methods This multicentre, randomized (1:1), double-blind, placebo-controlled, phase 3 study (DECISION; NCT00984282) investigated sorafenib (400 mg orally twice-daily) in patients with RAI-refractory locally advanced or metastatic DTC progressing within the past 14 months. The primary endpoint was progression-free survival (PFS) by central independent review. Patients receiving placebo could crossover to open-label sorafenib upon progression. Archival tumour tissue was examined for BRAF and RAS mutations. Serum thyroglobulin was measured at baseline and each visit. Findings A total of 417 patients were randomized to sorafenib (n=207) or placebo (n=210). Sorafenib treatment significantly improved PFS compared with placebo (hazard ratio, 0·59; 95% confidence interval, 0·45–0·76; P<0·0001; median 10·8 vs. 5·8 months, respectively). PFS improvement was seen in all pre-specified clinical and genetic biomarker subgroups irrespective of mutation status. There was no statistically significant difference in overall survival (hazard ratio, 0·80; 95% confidence interval, 0·54–1·19; P=0·14); median overall survival had not been reached and 150 (71%) patients receiving placebo crossed over to sorafenib upon progression. Response rates (all partial responses) were 12·2% (24/196; sorafenib) and 0·5% (1/201; placebo; p<0·0001). Median thyroglobulin levels increased in the placebo group, and decreased, then paralleled treatment responses in the sorafenib group. Most adverse events were grade 1 or 2. The most common treatment-emergent adverse events in the sorafenib arm were hand–foot skin reaction (76·3%), diarrhoea (68·6%), alopecia (67·1%), and rash/desquamation (50·2%). Interpretation Sorafenib significantly improved PFS compared with placebo in patients with progressive RAI-refractory DTC. Adverse events were consistent with the known sorafenib safety profile. These results suggest that sorafenib represents a new treatment option for patients with progressive RAI-refractory DTC.

SummaryBackgroundXerostomia is the most common late side-effect of radiotherapy to the head and neck. Compared with conventional radiotherapy, intensity-modulated radiotherapy (IMRT) can reduce irradiation of the parotid glands. We assessed the hypothesis that parotid-sparing IMRT reduces the incidence of severe xerostomia.MethodsWe undertook a randomised controlled trial between Jan 21, 2003, and Dec 7, 2007, that compared conventional radiotherapy (control) with parotid-sparing IMRT. We randomly assigned patients with histologically confirmed pharyngeal squamous-cell carcinoma (T1–4, N0–3, M0) at six UK radiotherapy centres between the two radiotherapy techniques (1:1 ratio). A dose of 60 or 65 Gy was prescribed in 30 daily fractions given Monday to Friday. Treatment was not masked. Randomisation was by computer-generated permuted blocks and was stratified by centre and tumour site. Our primary endpoint was the proportion of patients with grade 2 or worse xerostomia at 12 months, as assessed by the Late Effects of Normal Tissue (LENT SOMA) scale. Analyses were done on an intention-to-treat basis, with all patients who had assessments included. Long-term follow-up of patients is ongoing. This study is registered with the International Standard Randomised Controlled Trial register, number ISRCTN48243537.Findings47 patients were assigned to each treatment arm. Median follow-up was 44·0 months (IQR 30·0–59·7). Six patients from each group died before 12 months and seven patients from the conventional radiotherapy and two from the IMRT group were not assessed at 12 months. At 12 months xerostomia side-effects were reported in 73 of 82 alive patients; grade 2 or worse xerostomia at 12 months was significantly lower in the IMRT group than in the conventional radiotherapy group (25 [74%; 95% CI 56–87] of 34 patients given conventional radiotherapy vs 15 [38%; 23–55] of 39 given IMRT, p=0·0027). The only recorded acute adverse event of grade 2 or worse that differed significantly between the treatment groups was fatigue, which was more prevalent in the IMRT group (18 [41%; 99% CI 23–61] of 44 patients given conventional radiotherapy vs 35 [74%; 55–89] of 47 given IMRT, p=0·0015). At 24 months, grade 2 or worse xerostomia was significantly less common with IMRT than with conventional radiotherapy (20 [83%; 95% CI 63–95] of 24 patients given conventional radiotherapy vs nine [29%; 14–48] of 31 given IMRT; p<0·0001). At 12 and 24 months, significant benefits were seen in recovery of saliva secretion with IMRT compared with conventional radiotherapy, as were clinically significant improvements in dry-mouth-specific and global quality of life scores. At 24 months, no significant differences were seen between randomised groups in non-xerostomia late toxicities, locoregional control, or overall survival.InterpretationSparing the parotid glands with IMRT significantly reduces the incidence of xerostomia and leads to recovery of saliva secretion and improvements in associated quality of life, and thus strongly supports a role fo...

Low-dose radioiodine plus thyrotropin alfa was as effective as high-dose radioiodine, with a lower rate of adverse events. (Funded by Cancer Research UK; ClinicalTrials.gov number, NCT00415233.).

Purpose: To conduct a phase I clinical trial with a second-generation oncolytic herpes simplex virus (HSV) expressing granulocyte macrophage colony-stimulating factor (Onco VEX GM-CSF