133 Proton therapy significantly reduces acute and late toxicity in nasopharyngeal cancer.

The aim of the study was to test the hypothesis that Intensity Modulated Proton Therapy (IMPT) reduces acute and late radiation toxicity in nasopharyngeal cancer (NPC) patients compared to photon-based radiation techniques including IMRT and VMAT. The study population of this prospective cohort study was composed of 131 NPC patients treated with curative radiotherapy (RT) or chemoradiotherapy. Between July 2007 and December 2017, all patients were treated with IMRT or VMAT. Since January 2018, 97 out of 99 patients (98%) qualified for IMPT according to model-based selection. All patients were included in a prospective data registration program in which acute and late toxicity was prospectively scored weekly during RT and at fixed time points after RT (6 weeks, 6, 12, 18 and 24 months). To determine the overall effect on acute and late toxicity, the Weighted Overall Toxicity Burden (WOTB) was calculated, defined as the sum of all toxicities weighted by toxicity grading. In addition, the WOTB Area Under the Curve (WOTB-AUC) was calculated representing the WOTB from the start of treatment until 24 months after completion of treatment. The two groups were well balanced regarding gender, age, race, T-stage, N-stage, AJCC-stage, and EBV-status. However, there was a significant difference regarding the chemotherapy regimens used between the two groups. In the photon cohort, 33% of patients were treated with conventional RT, 7% with concurrent chemoradiation, 2% with induction chemotherapy + concurrent chemoradiation and 57% with concurrent chemoradiation + adjuvant chemotherapy, while this was 25%, 37%, 36% and 2% in the proton cohort, respectively. The mean dose to all relevant organs at risk (i.e., oral cavity, pharyngeal constrictor muscles, parotid, and submandibular glands) were significantly lower with IMPT compared to photons. This was particularly true for the mean dose to the oral cavity which decreased from 27.2 Gy with IMRT/ VMAT to 10.7 Gy with IMPT (p<0.001). From January 2018, a plan comparison was made in all NPC patients referred for radiotherapy to our centre between IMPT and VMAT. In total, 97 out of 99 patients qualified for protons based on the estimated risk difference on dysphagia and xerostomia resulting from the dose reductions obtained with IMPT. IMPT resulted in significant reductions of various acute and late toxicities (Figure 1), including xerostomia, loss of taste, dysphagia, tube feeding dependence, sore mouth, and mucosal reactions. Only acute dermatitis was significantly worse at the end of IMPT, but completely recovered at 5 weeks after treatment in all patients. [Display omitted] The WOTB was significantly lower after IMPT (Figure 2) at all time points. In the IMPT group, the WOTB-AUC as measure for overall toxicity was 68% lower. The WOTB-AUC reduction was 60% in the acute phase (week 1 to 7), 69% in the recovery phase (from end of treatment to 6 months after RT) and 70% in the late phase (from 6 to 24 months after RT). In this prospective cohort study, patients treated with IMPT had statistically significant and clinically relevant reductions of various acute and late toxicities as compared to modern photon techniques like IMRT and VMAT as a historical control group. [ABSTRACT FROM AUTHOR]