Risk of Acute and Late Xerostomia in Pediatric Head and Neck Cancer Patients Treated with Radiotherapy: Initial Results from the Pediatric Normal Tissue Effects in the Clinic (PENTEC) Initiative

Abstract

Radiation-induced xerostomia is a relatively common complication of definitive radiotherapy (RT) of the head and neck in the pediatric cancer population. The PENTEC head and neck (HN) task force aims to quantify radiation dose effects and the impact of critical risk factors. Through a systematic review of available literature, we analyzed the relationship between RT dose and this toxicity. A PubMed search of peer-reviewed literature was performed for articles published between January 1964 and June 2017, that evaluated xerostomia and dental effects among pediatric cancer patients who received radiotherapy. Of 2201 abstracts identified, only four reports had quantitative dosimetric and xerostomia data that could be used for mathematical modeling. The incidence of toxicity was modeled employing a normal tissue complication probability (NTCP) model using a two-parameter logistic fit. Three papers with 75 children treated for nasopharyngeal cancer reported dosimetric parameters and development of grade ≥ 2 xerostomia. Acute and late grade ≥ 2 xerostomia incidence along with dosimetric data (median dose, D50% and D80% to parotid glands) from 36 patients treated with RT (Laskar 2008) were used to determine the model parameters. About half of the patients were treated with 3-D conformal RT (mean parotid dose 57 Gy) and the rest with IMRT (mean parotid dose 38.3 Gy) with an incidence of acute grade ≥ 2 xerostomia of 88.2% and 31.6% and late grade ≥ 2 xerostomia of 64.7% and 15.8% respectively. The two other reports validate these results. In a paper with 34 patients whose right and left parotid glands received a mean dose of 35.8 and 35.3 Gy, the acute and late grade ≥ 2 xerostomia rates were 32.4% and 8.8% (Tao 2013). In another paper of 5 patients whose mean parotid doses were ≤ 26 Gy, 1 developed a late grade 2 xerostomia (Louis 2007). Another paper with 133 patients that received RT to the salivary glands for mostly Hodgkin lymphoma and rhabdomyosarcoma reported acute and late ≥ grade 1 xerostomia and median maximal doses consistent with the logistic model parameterized using Laskar data (Bolling 2015). In the same paper, children who received concurrent chemotherapy had more acute (p = 0.005) and late xerostomia (p = 0.026) compared to those not receiving concurrent chemotherapy. In this report we were able to build a logistic model based on quantitative dose and toxicity data from the current literature, and it demonstrates a dose response for acute and late xerostomia in pediatric patients treated with RT. Due to the variability and scarcity of data, it was not possible to establish other risk factors such as age and sex. PENTEC acknowledges logistical support from American Association of Physicists in Medicine