Skladowski 2006.

Methods	Location of trial: Poland. Number of centres: 1. Funding: Polish Scientific Research Committee (grant #4PO5 B15208). Trial ID: not stated.
Participants	Inclusion criteria: histologically proven squamous cell carcinoma with primary tumour in oropharynx, hypopharynx oral cavity or supraglottic larynx, T2‐4, N0‐1, aged ≤ 70 years, WHO performance status ≤ 2 and no other neoplastic disorders. Exclusion criteria: weight loss more than 10% in past 3 months, radiologically confirmed infiltration of mandible or thyroid cartridge or refusal. Recruitment period: December 1993 to June 1996. OC: 22/100 (22%). OP: 28/100 (28%). OC+OP: 50/100 (50%). Number randomised: 100. Number analysed: 100.
Interventions	Accelerated radiotherapy versus conventional radiotherapy Accelerated (n = 51): 2 Gy per fraction, 7 daily fractions per week to total of 66 Gy ± 2 Gy for T2, & 70 Gy ± 2 Gy for T3‐4 with overall treatment time of 33‐36 days. Large fields covering the whole clinical target volume were used Monday to Friday and at weekends a smaller field, limited to primary tumour and involved nodes only, was irradiated. Patients were hospitalised for the duration of the treatment. Conventional (n = 49): 2 Gy per day, 5 times per week, to a total of 66 Gy ± 2 Gy for T2 and 70 Gy ± 2 Gy for T3‐4 with overall treatment time of 47‐50 days. Small fields were used as a shrinking fields technique during last week of treatment. From 1995 the fraction size was changed from 2 Gy to 1.8 Gy in both arms "due to the high rate of mucosal necrosis."
Outcomes	Primary: local tumour control. Secondary: overall survival, morbidity free survival, disease free survival, acute and late toxicity. Duration of follow‐up: median follow‐up 96 months (59‐123 months).
Notes	Sample size calculation: to detect an expected increase in local tumour control in the CAIR arm of 24% it was estimated that about 200 patients were required with α = 0.05 and 1‐β = 0.90 (2‐sided test). Investigators planned an interim analysis and possible change to protocol, to detect unacceptable treatment toxicity, or unexpectedly high benefit. HR data taken from graphs (no numbers at risk).
Risk of bias
Bias	Authors' judgement	Support for judgement
Adequate sequence generation?	Low risk	"Simple randomisation stratified by site of primary tumour, TNM Stage with 1:1 arm allocation, was made at Bureau of Trials at the Instiute using random numbers."
Allocation concealment?	Low risk	Sealed envelope method used.
Blinding ‐ Outcome Assessors	High risk	Not mentioned.
Incomplete outcome data addressed?	Low risk	No drop outs post‐randomisation. 2 in accelerated group and 1 in conventional group did not complete treatment.
Free of selective reporting?	Low risk	Important outcomes of response, survival and toxicity reported.
Free of other bias?	Unclear risk	Fraction size reduced in both groups from 2 Gy to 1.8 Gy in 1995 in response to planned interim analysis. Accelerated group were hospitalised throughout treatment and received a higher rate of systemic corticosteroids and/or antibiotics for severe mucositis ‐ 90% compared to 48% in control group.