Session Item

In 2018, we started to treat oropharyngeal cancer (OPC) patients with intensity modulated proton therapy (IMPT). Some of these patients developed radiation ulcers in the high dose area raising questions regarding RBE effects. Therefore, the main aim was to evaluate if IMPT increased the risk of radiation ulcers compared to modern photon techniques (IMRT and VMAT) and to identify risk factors for radiation ulcers.

This was a retrospective analysis of prospectively collected data. 

Patients had to meet the following eligibility criteria: histologically proven OPC; treated with definitive radiotherapy (RT) either or not combined with concurrent chemotherapy or cetuximab; curative intent; use of IMRT or VMAT (photons) or IMPT to a total dose of 70 Gy or 70 GY_RBE (constant RBE 1.1), respectively and included in our prospective data registration program.

For the selection of OPC patients for IMPT, the model-based approach was used.

The primary endpoint was the cumulative incidence of radiation ulcers grade³1 at 1 year after start of RT (ULCER_1-year). Univariate and multivariable analyses were performed using the Cox proportional hazard model. 

From 2007 to 2020, 498 patients met the eligibility criteria. Before Jan 2018, 371 OPC patients were treated with photons. From Jan 2018 to Dec 2020, 81 patients were treated with IMPT and 46 patients with photons.

In univariate analysis, ULCER_1-year was 10.5% after photons and 10.8% after IMPT (p=0.478). Most ulcers 47 (87%) were scored as grade 1 (no complaints) or grade 2 (conservative treatment), while 7 patients (13%) progressed into grade³3 (requiring surgery, life-threatening or death). Median time to first occurrence was similar between both groups: 5.0 months (IQR: 3.6 to 7.2) after photons and 5.8 months (IQR: 4.4-10.1) after IMPT. No difference was noted regarding recovery which was 4.1 months (IQR: 2.5-6.9) and 4.6 months (IQR: 2.4-7.8) after photons and IMPT, respectively.

Multivariable analysis identified 4 risk factors, including T-stage, ulcerative/exophytic growth pattern, smoking during treatment and ACE-27 comorbidity score (Table 1). When IMPT was forced into this multivariable model, IMPT was again not associated with an increased risk of the cumulative risk of radiation ulcer (P=0.546).

Based on the multivariable analysis, 3 risk groups were defined (Table 1), which was a strong predictor for the risk of ULCER_1-year (Figure 1)

This is the first population-based prospective cohort study investigating ULCER_1-year  among OPC patients treated with curative intent. IMPT is not associated with an increased risk of radiation ulcers compared to photons. The most important risk factors for ULCER_1-year are: T3-T4; ulcerative/exophytic growth pattern, smoking during RT and co-morbidity.  Although often considered dose limiting, most ulcers recover with conservative treatment measures.