Session Item

Radiotherapy of sinonasal carcinoma (SNC) carries a substantial risk of normal tissue exposure and late morbidity (fig.1).

Proton therapy may spare normal tissue and thus reduce late morbidity. To generate proper selection strategies for proton therapy, investigation of late toxicity is crucial. This study aimed to estimate incidence and severity of late morbidity after intensity modulated radiation therapy (IMRT) for SNC.

Patients from two Danish institutions who were alive and without recurrence after IMRT for SNC from 2008 through 2016 were eligible for the study (n=43). Late morbidity was evaluated with a battery of standardized neurocognitive tests, cerebral diffusion MRI, comprehensive objective ophthalmological examination, blood samples, and olfactory function testing. Patient reported outcome was collected using EORTC-QLQ-C30+BN20, SNOT-22 and HADS.

Twenty-seven of 43 eligible patients were enrolled; median age was 67 years (range 47-83). See table 1.

Cognitive function: Compared with normative data, patients scored lower on tests of processing speed, attention, working memory, memory and learning, and verbal fluency (p-values<0.05). Poorer working memory was statistically significant associated with higher mean doses to the right hippocampus, right frontal lobe, and both temporal lobes. Poorer performance on verbal fluency was statistically significant associated with higher mean doses to both frontal lobes. Ocular toxicity: Seven patients had radiation-induced ocular toxicity, one being enucleated due to toxicity. We found correlations between grade 2 and 3 radiation-induced visual acuity impairment (CTCAE 4.0) and maximum dose to the optic nerve (p=0.029 and 0.037) as well as constraint-violations to the optic nerve (p=0.002 and <0.001). Pituitary toxicity: Six patients (22%) had abnormal hormonal functioning in the gonadal-, and the thyroid axis, but no dose-response correlation was detected. One patient exhibited pan-hypopituitarism and substitutional therapy was initiated. Olfactory function: Sixteen patients (59%) had age-adjusted impaired olfactory function, which was worse in patients who underwent surgery compared with those treated with IMRT alone (p=0.01). Diffusion MRI: Voxel-by-voxel analyses on several functional diffusion parameters and analyses of atrophy and dose-distribution will be undertaken. Patient reported outcomes: In the global quality of life analysis, the most affected domains were social and emotional functions, while fatigue and insomnia were the most severely reported symptoms.

We found substantial long-term morbidity after radiation therapy for SNC across different organs at risk. Based on the current findings, a nationwide prospective registration of morbidity following treatment for SNC has been initiated by the Danish Head and Neck Cancer (DAHANCA) group, and a prospective trial of proton therapy for sinonasal cancer is currently being implemented (DAHANCA36b).