Protocol variations and their influence on the final outcome: critical review of the split-course base of tongue study of the RTOG

Abstract

A critical review of the protocol variations in an RTOG prospective randomized multi-institutional clinical trial has been conducted. The objective of the review was to identify variables that might have affected the results of the study. Compliance with general guidelines and specific technical treatment parameters of the Split-Course Radiation Therapy Protocol for Carcinoma of the Base of the Tongue (RTOG #71-02) was analyzed. A +/- 5% variation of the time-dose-fractionation factors, using the NSD and TDF formulae and their respective protocol ratios (ratio between actual case NSD and TDF level and what the protocol recommended), has been defined as fully acceptable. Seventy-two percent of the 141 study cases were within this category. Minor variation has been defined as one resulting in a +/- 6% to +/- 15% deviation from the study values (15.3% of cases). Major and unacceptable variation was a deviation of +/- 16% or more from the research plan (12.7% of cases). After identifying the different variations and correlating them with the clinical results, we conclude that these deviations did not affect the final results to a significant or identifiable degree.