Proton Beam Radiotherapy versus Intensity-Modulated Radiotherapy in Olfactory Neuroblastoma: A Multi-institutional Propensity-Matched Study

Introduction: Olfactory neuroblastoma (ONB) is a rare sinonasal malignancy that can present with locally advanced disease. Previous studies have demonstrated that post-resection radiotherapy can provide a survival and recurrence advantage in patients with ONB, particularly in the setting of higher stage and histologic grade. Two of the main methods of radiotherapy delivery include proton beam radiotherapy (PBRT) and intensity-modulated radiotherapy (IMRT). The differences in the effectiveness of these two methods have been studied in other fields including head and neck cancer; however, no studies comparing the two methods have been studied for patients with ONB. Therefore, the purpose of this study is to compare the differences in survival and recurrence for ONB patients being treated with PBRT and IMRT using propensity-matched cohorts from a multi-institutional database.

Methods: This modern-era multicenter data originated from the retrospective review of electronic health records (EHRs) of all patients who presented with ONB between 2005 and 2021 at nine academic, tertiary care centers within North America. Only patients treated with either IMRT or PBRT were included in the study. Clinicopathologic features including treatment modalities, pathologic and MRI imaging status, modified Kadish staging systems, Hyams grading, margin status, and follow-up time. Outcomes collected for analysis included local recurrence-free survival (Local-RFS), regional recurrence-free survival (Regional-RFS), total recurrence-free survival (RFS), and overall surval (OS). Propensity matching of age, gender, Hyams grade, modified Kadish staging, resection margin status, and chemotherapy use (Table 1) between treatment modalities was confirmed with chi-square and Fisher’s exact tests. Statistical analysis was done using Kaplan–Meier curves and log-rank tests.

Results: Of the 205 ONB patients treated with surgical resection and adjuvant radiation therapy for curative intent, 18 patients were identified to receive PBRT. This cohort was then matched to the current standard of IMRT at a 1:1 ratio for a total of 36 patients in this multi-institutional study. The average follow-up time for IMRT was 71.7 (SD, 52.9) months and for PBRT was 53.2 (SD, 39.5) months (p = 0.24). For IMRT, the 5-year local-RFS, Regional-RFS, RFS and 5-year OS were 69.2, 92.9, 64.8, and 80.8%, respectively. For PBRT, the 5-year local-RFS, Regional-RFS, RFS and 5-year OS were 90.9, 79.7, 56.7, and 85.7%, respectively. Similarly, there were no differences in local RFS (p = 0.34, [Fig. 1]), regional RFS (p = 0.29, [Fig. 2]), total recurrence-free survival (p = 0.4, [Fig. 3]), and overall survival (p = 0.52, [Fig. 4]) between patients treated with PBRT and IMRT.

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Conclusion: This study is the first to compare the effectiveness of IMRT and PBRT in patients with advanced olfactory neuroblastoma. These findings support that IMRT and PBRT are comparable in overall survival and recurrence-free survival as treatment methods for advanced stage/grade olfactory neuroblastoma. Future investigations comparing quality-of-life outcomes between these radiotherapy modalities are needed to better delineate patient-centered treatments for ONB.