Radiotherapy and Smell Function in Head and Neck Cancer: A Nonrandomized Clinical Trial

A substantial proportion of patients with head and neck cancer (HNC) experience smell dysfunction during or after radiotherapy (RT). However, prospectively collected data for smell dysfunction have been limited, especially in the era of intensity-modulated RT (IMRT).

To evaluate the association of RT with olfactory function in patients with HNC receiving IMRT, including changes in olfactory function over time.

This nonrandomized clinical trial enrolled patients with histologically confirmed HNC between January 1, 2021, and December 1, 2023, who underwent curative treatment with IMRT at Chang Gung Memorial Hospital in Taiwan. Participants scheduled for RT underwent olfactory function assessment using the Taiwan Smell Identification Test at multiple time points, including before RT; at the end of RT; and at 1, 3, 6, and 12 months after treatment. Nasal endoscopy was used to rule out confounding nasal conditions.

Intensity-modulated RT with and without concurrent chemotherapy.

The association between Taiwan Smell Identification Test scores and olfactory region radiation dose was analyzed using linear regression, and an estimative model was developed to calculate a threshold dose.

A total of 63 patients (median [range] age, 55 [32-75] years; 52 male [82.5%]) with normal olfactory function before RT were included. The most common primary cancer site was the oral cavity and oropharynx (37 participants [58.7%]), followed by the nasopharynx (16 participants [25.4%]). A moderate positive correlation was observed between radiation dose and olfactory dysfunction. Receiver operating characteristic analysis identified 22 Gy as a potential inflection point for estimating olfactory impairment. By multivariable analysis, a mean radiation dose to the olfactory region exceeding 22 Gy was the only independent risk factor for olfactory dysfunction (odds ratio, 20.65; 95% CI, 2.60-164.35). Some patients treated with high-dose radiation experienced persistent olfactory dysfunction of up to 1 year.

This study found a dose-dependent association between RT and olfactory dysfunction in patients with HNC, identifying 22 Gy as an important inflection point. To minimize the risk of long-term olfactory impairment, optimizing RT planning by carefully adjusting radiation dose and target area may be beneficial.

ISRCTN14947812.