Stem cell sparing radiotherapy for head and neck cancer patients: a double-blind randomized controlled trial

BACKGROUND Radiotherapy for head and neck cancer (HNC) frequently leads to salivary gland damage and xerostomia. Previously it was demonstrated in rats, mice and patients that the radiation response of parotid glands critically depends on dose to its stem cells, mainly located in the main salivary gland ducts. Therefore, reducing dose to these High Stem Cell Density (HSCD) regions may prevent xerostomia. METHODS To test this hypothesis, 102 HNC patients treated with definitive radiotherapy with or without systemic treatment, were included in a double-blind randomized, controlled trial (RCT) (ClinicalTrials.gov number NCT01955239). Patients were randomized between standard parotid sparing and novel stem cell sparing (SCS) techniques. Primary and secondary endpoints were reduction of saliva production <25% from baseline (FLOW12M) and patient-rated daytime xerostomia (XER12M) twelve months after treatment. RESULTS Fifty-four patients were assigned to the standard arm and 48 to the SCS arm. Only mean dose to the HSCD regions differed significantly between the arms (contralateral 16 and 11 Gy (p = 0.004) and ipsilateral 26 and 16 Gy (p = 0.001), standard and SCS arm respectively). One FLOW12M occurred in the SCS arm, compared with three in the standard arm (p = 0.72). Relative parotid gland salivary function was consistently better in the SCS arm, albeit not reaching statistical significance. Prevalence of XER12M did not differ significantly (42% and 37% (p = 0.86), respectively). Nonetheless, multivariable analysis showed mean dose to the contralateral HSCD region was the most important dosimetric predictor for XER12M. CONCLUSIONS In this double-blind RCT, a trend of better parotid function was shown for patients treated with SCS radiotherapy. No significant reduction of XER12M was present. However, the contralateral HSCD region dose was the strongest dosimetric predictor, suggesting dose to the HSCD region is more important for development of xerostomia than dose to the entire parotid gland.