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We explain the rationale for metabolically adaptive radiation dose escalation in stage III non–small-cell lung cancer and describe the design of a Canadian phase II randomized trial investigating this approach. In the trial, patients are randomized to either conventional chemoradiation treatment (60 Gy in 30 fractions) or metabolically adaptive chemoradiation, where fluorodeoxyglucose-avid tumor sub-volumes receive an integrated boost dose to a maximum of 85 Gy in 30 fractions. The trial sample size is 78 patients, and the target population is patients with newly diagnosed, inoperable stage III non–small-cell lung cancer treated with radical intent chemoradiation. The primary objective of the trial is to determine if dose escalation to metabolically active sub-volumes will reduce 2-year local-regional failure rate from 42.3% to 22.3%, when compared with standard treatment. The secondary objectives are to determine the effect of dose escalation on overall survival, progression-free survival, quality of life, and rate of grade 3 to 5 toxicities.