Parotid Gland Stem Cell Sparing Radiation Therapy for Patients With Head and Neck Cancer: A Double-Blind Randomized Controlled Trial

Roel J.H.M Steenbakkers,Maria I Van Rijn–Dekker,Monique A Stokman,Roel G.J Kierkels,Arjen Van Der Schaaf,Johanna G.M Van Den Hoek,Hendrik P Bijl,Maria C.A Kramer,Robert P Coppes,Johannes A Langendijk,Peter Van Luijk

doi:10.1016/j.ijrobp.2021.09.023

Roel J.H.M Steenbakkers, Maria I Van Rijn–Dekker + Show 9 more

Open Access

https://doi.org/10.1016/j.ijrobp.2021.09.023

Copy DOI

Abstract

Radiation therapy for head and neck cancer frequently leads to salivary gland damage and subsequent xerostomia. The radiation response of the parotid glands of rats, mice, and patients critically depends on dose to parotid gland stem cells, mainly located in the gland's main ducts (stem cell rich [SCR] region). Therefore, this double-blind randomized controlled trial aimed to test the hypothesis that parotid gland stem cell sparing radiation therapy preserves parotid gland function better than currently used whole parotid gland sparing radiation therapy. Patients with head and neck cancer (n=102) treated with definitive radiation therapy were randomized between standard parotid-sparing and stem cell sparing (SCS) techniques. The primary endpoint was >75% reduction in parotid gland saliva production compared with pretreatment production (FLOW12M). Secondary endpoints were several aspects of xerostomia 12 months after treatment. Fifty-four patients were assigned to the standard arm and 48 to the SCS arm. Only dose to the SCR regions (contralateral 16 and 11 Gy [P=.004] and ipsilateral 26 and 16 Gy [P=.001] in the standard and SCS arm, respectively) and pretreatment patient-rated daytime xerostomia (35% and 13% [P=.01] in the standard and SCS arm, respectively) differed significantly between the arms. In the SCS arm, 1 patient (2.8%) experienced FLOW12M compared with 2 (4.9%) in the standard arm (P=1.00). However, a trend toward better relative parotid gland salivary function in favor of SCS radiation therapy was shown. Moreover, multivariable analysis showed that mean contralateral SCR region dose was the strongest dosimetric predictor for moderate-to-severe patient-rated daytime xerostomia and grade ≥2 physician-rated xerostomia, the latter including reported alteration in diet. No significantly better parotid function was observed in SCS radiation therapy. However, additional multivariable analysis showed that dose to the SCR region was more predictive of the development of parotid gland function-related xerostomia endpoints than dose to the entire parotid gland.

Highlights

70% of all patients treated for head and neck cancer (HNC) receive radiation therapy
After exclusion of 143 patients, mostly due to insufficient pretreatment parotid gland salivary flow production, 106 patients were randomized between the 2 study arms (Fig. E2)
Twelve months after radiation therapy, 6 patients had died and another 3 patients were lost to follow-up because of disease progression in the standard radiation therapy (ST-RT) arm

Summary

Introduction

70% of all patients treated for head and neck cancer (HNC) receive radiation therapy. When administering radiation to cancerous tissue, adjacent normal tissues are inevitably coirradiated. Exposure of the salivary glands to radiation frequently results in loss of gland function (hyposalivation) within the first weeks of radiation therapy.[1] Hyposalivation can cause xerostomia and other side effects, such as alterations in speech and taste and difficulties with mastication and deglutition.[2] Xerostomia is the most frequently reported side effect after HNC radiation therapy and has a major effect on quality of life of these patients.[2,3]

Objectives

Methods

Results

Discussion

Conclusion