Sanguineti 2005.

Methods	Location of trial: Italy. Number of centres: 4. Funding: not stated. Trial ID: not stated.
Participants	Inclusion criteria: pathologically proven squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx or larynx, and major surgical resection of primary disease and clinically involved neck lymph nodes without macroscopic residual; ECOG performance status ≤ 2 before radiotherapy, no distant metastases. Exclusion criteria: patients with other concurrent or previous (within 5 years) cancers other than basal cell carcinoma of the skin and in situ squamous cell carcinoma of the cervix. Recruitment period: March 1994 to August 2000. OC: 44/226 (19%). OP: 40/226 (18%). OC+OP: 84/226 (37%) (see notes). Number randomised: 226. Number analysed: 226.
Interventions	Accelerated radiotherapy with boost versus conventional radiotherapy Accelerated/boost (n = 113 (46 OC/OP patients)): 2 Gy/fraction, 5 fractions a week for 5 weeks. A concomitant boost of 1.4 Gy/fraction during first week and 1.6 Gy/fraction during fifth week of radiotherapy was given (total dose 64 Gy). Conventional (n = 113 (38 OC/OP patients)): 2 Gy/fraction, 5 fractions a week for 5 weeks (total 50 Gy) to areas at low risk of macroscopic disease and 6 weeks (total 60 Gy) to areas at high risk. All radiotherapy had to commence within 8 weeks following surgery. Surgery consisted of major surgical resection of both primary disease and clinically involved neck lymph nodes without macroscopic residual.
Outcomes	Primary: locoregional control. Secondary: overall survival, toxicity. Duration of follow‐up: 10 years.
Notes	Sample size: estimated that 224 patients would provide power of 80% (with an α error of 5%, 2‐sided) to detect improvement of 81% in the probability of locoregional control at 2 years in the accelerated radiotherapy group compared with 70% in the conventional group. HR calculated for OC/OP patients only using data supplied by authors.
Risk of bias
Bias	Authors' judgement	Support for judgement
Adequate sequence generation?	Low risk	"Computer generated list and stratified according to center and balanced by variable blocks."
Allocation concealment?	Low risk	"A centralized telephone call procedure to the unit of clinical epidemiology and trials in Genoa."
Blinding ‐ Outcome Assessors	High risk	Not mentioned.
Incomplete outcome data addressed?	Low risk	All randomised participants included in analysis for locoregional control and overall survival. For acute toxicity 221/226 participants analysed and for late toxicity 214/226 participants analysed.
Free of selective reporting?	Low risk	Important outcomes of overall survival, locoregional control and toxicity were reported.
Free of other bias?	Unclear risk	Groups appear similar at baseline. No other apparent bias.