Altered fractionation schemes in radiotherapy.

Hyperfractionation and hypofractionation combined with acceleration have been investigated in stage I-III NSCLC patients. In stage I tumors, hypofractionated radiation schedules given with highly conformal stereotactic body radiotherapy (SBRT) techniques have been proven safe and effective with local control rates > 85% and meanwhile have been accepted as the standard treatment in stage I patients who are medically unfit for surgery or who refuse resection. When comparing the dose-effect relationship derived from local control data of various clinical studies using conventional fractionation (CF) with that obtained from SBRT trials using doses per fraction from 7.5 to 30 Gy based on the linear quadratic model without parameters considering repopulation or hypoxia, the alpha/beta ratio for biological equivalent doses with the different fractionation schedules was found to be 8.2 (7.0-9.4) Gy for stage I NSCLC. From this, it can be concluded that using an alpha/beta value of 10 Gy for tumors is conservative, underestimating the BED of SBRT schedules relative to CF schedules with regard to tumor control. If repopulation is the dominant resistance-promoting factor for CF schedules and hypoxia for hypofractionated SBRT schedules, and the true alpha/beta value of tumors is assumed to be 10 Gy, then the observed alpha/beta value of 8.2 Gy can imply that the effect of repopulation during CF is higher than the effect of hypoxia during SBRT. Patients with locally advanced NSCLC in whom contraindications preclude the use of concurrent chemotherapy with CF radiotherapy may be treated outside clinical trials with CHART. Combinations of hyperfractionated-accelerated RT schedules with concurrent platinum-based chemotherapy have been proven safe and effective in stage III NSCLC patients.