Session Item

Post radiation mucosal ulcers (PRMU) can have a huge negative impact on quality of life in patients with oropharyngeal squamous cell carcinoma (OPSCC). However, information on risk factors, and in particular on the impact of hypofractionation, is scarce. Therefore, the goal of this study was to determine the pattern of late PRMU development and to identify risk factors after hypofractionated and conventional radiotherapy for OPSCC.

We performed a retrospective cohort study in 332 consecutive OPSCC patients with cT1-T4N0-N3M0 disease. Patients were included who survived at least one year after treatment with curative intent between January 2009 and June 2016. Patients were treated using: 1) conventional IMRT (70 Gy in 2 Gy fractions), or 2) IMRT  (46 Gy in 2 Gy fractions) followed by a hypofractionated stereotactic body radiotherapy (SBRT) boost (16.5 Gy in 5.5 Gy fractions). Grade ≥ 2 PRMU (i.e. symptomatic PRMU according to CTCAE v5.0) was scored in case one or more ulcers were observed > 3 months after the last RT fraction. Two types of PRMU were distinguished: late PRMU arising several months after RT and PRMU directly evolving from malignant tissue without the evidence of remaining tumor tissue. Patient and treatment related risk factors were analyzed with uni- and multivariable regression analysis. In a subgroup of 25 patients imaging at time of PRMU was available. The PRMU in these patients were delineated on the original planning CT scan and location with respect to isodose lines was determined.

A total of 64 patients developed PRMU grade ≥ 2, with a two year cumulative incidence of 19%. For conventional fractionation, all PRMU occurred within 9 months (N=18). For the hypofractionation boost group (N = 46), 31 PRMU developed within 9 months, and an additional 15 PRMU developed after 9 to 22 months post-RT (see figure). All PRMU were successfully managed (50% with HBOT), with none developing into grade 3 PRMU. 34% of PRMU persisted after more than 6 months. The cumulative incidence of PRMU after the hypofractionation boost was significantly higher compared to conventional fractionation (26% vs 12% at two yrs; p = 0.003). In the hypofractionation boost group, tonsil subsite (SHR = 2.70; p = 0.003), female (SHR = 2.07; p = 0.016), and acute tube feeding (SHR = 3.10; p < 0.001) were associated with increased PRMU risk in multivariable regression. In the conventional fractionation group, no statistically significant risk factors were identified. 17% of PRMU (N = 11) developed directly after tumor regression and the remaining 83% were late PRMU (see table). All 25 delineated PRMU were situated within the 95% isodose lines.

The increased risk of PRMU should be considered when introducing hypofractionation in radiotherapy of oropharyngeal cancer. In this group, requiring a feeding tube (surrogate for severe acute mucositis) and being female was associated with increased risk.