1059 - Proton Beam Therapy vs. IMRT for Nasopharyngeal Carcinoma: Differential Late Toxicity Profile at 5 Years
Presenter(s)
N. Taghizadeh Mortezaei1, I. C. Silva Lima1, E. A. Weyman2, S. I. Goldberg3, and A. W. Chan1,4; 1Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 2Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA, 3Massachusetts General Hospital, Boston, MA, 4MIT Sloan School of Management, Massachusetts Institute of Technology, Cambridge, MA
Purpose/Objective(s): Proton therapy offers a dosimetric advantage over intensity-modulated radiation therapy (IMRT) by significantly reducing low-to-moderate radiation doses to healthy tissues. Both modalities are standard for nasopharyngeal carcinoma (NPC), yet comparative data on long-term outcomes remain scarce. The purpose of this study was to directly compare the tumor control rates and late toxicity profiles at 5 years between proton therapy and IMRT in patients with NPC.
Materials/Methods: Between July 2003 and December 2024, 110 patients with newly diagnosed, non-metastatic nasopharyngeal carcinoma were treated with definitive IMRT (n = 47) or proton beam therapy (n = 63) +/- chemotherapy at our institution. 82.7 percent of patients were diagnosed at AJCC Stage III and IV. The median radiation dose for the gross target volume (GTV) was 70 Gy, while the clinical target volume (CTV) received a median dose of 60 Gy. The Kaplan-Meier product-limit method was used to estimate local control. Radiation-related treatment toxicity was graded per CTCAE v5.0. Grade =2 late toxicity, defined as 6 to 60 months post-radiation, was analyzed using cumulative incidence functions, with death and recurrence as competing risks. Multivariable Fine–Gray regression was used to estimate sub-distribution hazard ratios (sHR).
Results: Patients in the proton cohort had more advanced disease, with higher rates of AJCC stage IV (p=0.019) and T4 tumors (p=0.014). Proton therapy was more commonly delivered in the earlier treatment period (before 2014) compared with IMRT (<0.001). The mean oral cavity dose was significantly greater with IMRT (26.5 ± 6.6 Gy vs 16.4 ± 10.4 Gy, p < 0.001). The median follow-up was significantly longer in the proton group (94.68 months) compared with the IMRT group (59.64 months) (p = 0.009). The 5-year local control rate was 86.3% (95% CI, 74.5%–92.9%) for the proton group compared to 90.2% (95% CI: 75.8%–96.3%) for the IMRT group (p = 0.55). Rates of late grade =2 toxicity occurred in 78.3% of IMRT patients compared with 67.8% in proton patients (p = 0.332). Rates of Grade =3 toxicity was similar between the two groups (6.5% vs 6.8%, p = 1.00). There was a significantly higher incidence of grade =2 temporal lobe toxicity (TLE), defined by new temporal lobe enhancement on MRI with or without symptoms, in patients treated with proton therapy than those treated with IMRT (p = 0.008). The incidence of grade =2 dry mouth in patients treated with proton was lower when compared with patients treated with IMRT (p = 0.067). After adjusting for T stage and treatment period, proton therapy was associated with a lower cumulative incidence of Grade =2 late toxicity compared with IMRT (sHR 0.67, 95% CI 0.42–1.06), although this difference did not reach statistical significance (p = 0.086).
Conclusion: IMRT and proton have similar local control rates and grade =2 late toxicity. The late toxicity profiles differed, however, with proton patients experiencing lower rates of dry mouth and higher rates of temporal lobe enhancement.