Questions: 1. Does accelerated radiotherapy improve loco-regional control or survival as compared with conventionally fractionated radiotherapy in patients with newly diagnosed, locally advanced (stage III-IV) squamous cell carcinoma of the head and neck who are deemed suitable for radiotherapy with curative intent? 2. What is the toxicity associated with accelerated fractionation? 3. Can these novel regimens enhance the therapeutic ratio (benefits to toxicity)? Perspective: Evidence was selected and reviewed by two members of the Head and Neck Cancer Disease Site Group (DSG) of the Cancer Care Ontario Practice Guidelines Initiative and by methodologists. This guideline has been reviewed and approved by the DSG, which comprises medical and radiation oncologists, surgeons, and one community representative. A draft version of the guideline was circulated to 112 clinicians for input, using a 21-item feedback questionnaire. The return rate was 47%, and 37% of the practitioners completed the entire questionnaire. Of the respondents, 79% agreed that the document should be approved as a practice guideline, and 95% agreed that they would use it in their clinical practice. Methodology: Relevant evidence was identified by a systematic search of the MEDLINE (1966-2000) and CANCERLIT (1983-2000) databases, the Cochrane Library (Issue 3, 2000), and conference proceedings. Evidence review was limited to randomised trials and meta-analyses of randomised trials that compared accelerated radiotherapy with conventional radiotherapy in patients with locally advanced (stage III-IV) squamous cell carcinoma of the head and neck. Overall survival and locoregional control were the primary outcomes of interest. Results: Search results. Eleven randomised trials (12 comparisons) of accelerated radiotherapy versus conventional radiotherapy met the inclusion criteria. Five of these trials were published only in abstract form. Benefits. Six randomised trials (two of eight trials of rapid acceleration, and four of four trials of modest acceleration) demonstrated a significant increase in locoregional control in favour of accelerated radiotherapy. One trial of modest acceleration demonstrated a significant increase in overall survival. Pooling of data was attempted, but the analysis was limited by incomplete information in recently published abstracts. Harms. A clinically significant but manageable increase in acute toxicity has been reported for all of the accelerated regimens. The late toxicity produced by rapid acceleration has proven unacceptable. Data on the late toxicity of modestly accelerated regimens is incomplete.