The "ultimate" hypofractionated RT regimen of 60 Gy given in 3 fractions of 20 Gy each has been demonstrated to be feasible and highly effective in patients with medically inoperable Stage I NSCLC tumors measuring up to 7 cm and located outside the central airways (Timmerman et al, 2006). However, the same regimen was associated with a high incidence of severe toxicity if applied to central airway. Since most tumors in patients with Stage III and IV NSCLC are located centrally, a novel hypofractionated regimen needs to be developed specifically for them.