5.1.1. Dosing Strategies

Fractionated radiation is the primary method of radiotherapy for cancer patients, including for the treatment of HNC, but causes cell toxicity and other severe side effects. Fractionated radiation divides the total curative dose into a series of smaller doses, which allows the patient to better tolerate and maintain the treatment. Conventional fractionated radiotherapy for HNC patients is commonly prescribed as 2 Gy per day, five days per week, for multiple weeks, to a total dose of 70 Gy [18]. Multiple small radiation doses allow non-tumor cells to recover between IR exposures, while more severely damaging malignant cells due to their high proliferation rates. A meta-analysis, including 34 trials and 11,969 HNC patients (with primarily late-stage tumors of the oropharynx and larynx), comparing different subtypes of fractionated radiation found that hyper-fractionated radiation, where a patient receives the same total curative dose of radiation, but in two fractions per day (totaling 4 Gy/day), showed improved overall survival and progression-free survival when compared to conventional fractionation (2 Gy/day). However, these more intensive radiation schedules induced more severe side effects, including increased instances of mucositis, which caused RT patients to go on feeding tubes more frequently [176]. Overall, hyper-fractionated radiation was less feasible than conventional approaches due to the cost, scheduling difficulties and the increased severity of side effects. Other altered fractionation dosing schedules, including increasing the IR doses per day and shortening the total time to curative dose, were evaluated, but these treatments did not show improvement in disease outcomes

or sparing organs at risk compared to conventional fractionation [176]. While fractionated therapies are more efficacious as cancer treatments, there is currently no evidence that hyper-fractionated radiotherapy or other altered fractionated dosing schedules have any effect on decreasing the incidence of xerostomia [19,176].
