The diverse array of dose-fractionation regimens in routine clinical usage can seem bewildering for any new clinician practicing radiotherapy. Understanding the clinical and laboratory rationale behind these schedules is an essential part of the training, allowing the personal practice to be grounded upon the many successes, and of course, setbacks of the last century.

Most tumors, such as head and neck squamous cell carcinoma (HNSCC), exhibit high α/β ratios, indicating a lower sensitivity to fraction size. Similarly, early (acute) normal tissue reactions. Some tumors now have strong evidence of a lower α/β ratio.  An alternative formulation is the equivalent dose in 2 Gy fractions, which allows the comparison of dose-fractionation regimens to familiar 2 Gy per fraction schedules. If the tumor α/β ratio exceeds late toxicity α/β ratios, then the therapeutic ratio may be widened by hyperfractionation. Six out of seven trials provided a pure investigation of the effect of acceleration in HNSCC, randomizing patients between the standard five fractions per week versus six fractions per week.

In essence, the total dose and fractionation remained unchanged; however, a statistically significant improvement in locoregional control (60% vs. 70%) was observed. The linear-quadratic model continues to find a direct clinical application. PACE  and FAST-FORWARD trials examined the role of profoundly hypofractionated accelerated radiotherapy for, respectively, localized prostate cancer and adjuvant breast treatment.