Geltzeiler, Mathew

ABSTRACT Background Olfactory neuroblastoma (ONB) exhibits variable recurrence patterns, with significant late recurrences occurring years after treatment. We investigated cutoff periods to define late recurrence and identified predictors that distinguish patients at risk of late recurrence from those considered cured. Methods From a multi‐institutional cohort of 219 ONB patients treated at nine centers, we analyzed 77 patients with documented recurrence. Using a 48‐month cutoff to define early (< 48 months) versus late (≥ 48 months) recurrence, we evaluated 35 clinical, anatomic, and treatment variables using Firth penalized logistic regression across three comparisons: (1) late versus early recurrence timing, (2) late recurrence versus no recurrence, and (3) early recurrence versus no recurrence. Results Thirty‐four of the 77 (44.2%) recurrences were classified as late. Among the 77 patients who recurred, smaller tumor volume (OR 0.243, p = 0.035) and lower novel Dulguerov staging (OR 0.802, p = 0.038) were associated with late, rather than early recurrence. When patients with late recurrence were compared to those who remained disease‐free, radiographic skull base bone involvement was the strongest independent predictor (OR 2.90, 95% CI 1.14–8.64, p = 0.025), and this effect strengthened after adjusting for tumor volume (OR 3.80, p = 0.029). Pathologic dural invasion (OR 3.29, p = 0.013), Kadish stage (OR 2.02, p = 0.026), and T‐stage (OR 1.32, p = 0.040) were also significant. Conclusions A 48‐month cutoff effectively stratifies ONB recurrence risk. Skull base bone involvement independently predicts recurrence when compared to nonrecurrent cases and uniquely persists as a risk factor for late recurrence. These findings establish skull base bone involvement as a novel biomarker for risk‐stratified surveillance protocols.

Background: Sinonasal malignancies (SNM) are rare cancers associated with poor prognosis and impaired quality of life (QOL). The 22-question Sino-Nasal Outcome Test (SNOT-22) has been used to assess QOL in patients with SNM. Objective: To determine the minimal clinically important difference (MCID) for the SNOT-22 in patients with SNM. Methods: About 264 patients with SNM were drawn from a prospective, longitudinal, multi-institutional study. SNOT-22 scores were collected at pre-treatment baseline and follow-up through 5 years post-treatment. Cronbach’s alpha was used to assess the internal consistency of the SNOT-22. Distribution-based approaches were used to estimate the MCID. Multivariable regression identified factors associated with SNOT-22 improvement exceeding the determined MCID. Results: Cronbach’s alpha was >.85. The estimated MCIDs were: 1.44 (Cohen’s effect size), 1.32 (standard error of the mean), 10.45 (1/2 of baseline standard deviation), and 3.67 (minimum detectable change). The mean MCID across methods was 4.22. Multivariable regression demonstrated higher odds of clinically meaningful improvement from baseline in patients with early-stage disease (odds ratio (OR) 3.510, P = .035), no neck irradiation (OR 11.050, P = .014), and neoadjuvant therapy (OR 16.667, P = .047). Conclusions: The SNOT-22 MCID was estimated as 4.22 in a large multi-center cohort of patients with SNM, suggesting that relatively small QOL changes are clinically relevant. When applying the MCID to the current cohort, advanced stage, treatment of neck disease, and not requiring neoadjuvant therapy were predictive of worse QOL.

Abstract This review aims to update recent advancements in the management and treatment of olfactory neuroblastoma (ONB) based on discussions and topics highlighted during the 2024 North American Skull Base Society session “Literature Review: What's New in Olfactory Neuroblastoma?” A systematic review was conducted using PubMed/MEDLINE, focusing on relevant studies published between January 2022 and June 2024. Data were organized into themes: prognostication and staging, surgical concepts, biomarkers/genomics, imaging, syndrome of inappropriate antidiuretic hormone release and hyponatremia, chemotherapy, and radiotherapy. Out of 289 initial records, 46 studies met eligibility criteria. Key findings include the proposed integration of Hyams grading and dural infiltration with traditional staging for better prognostic accuracy, a shift toward less invasive surgical techniques while maintaining clear resection margins, and the identification of biomarkers for improved diagnosis and targeted therapy. Advanced imaging modalities like DOTA-peptide tomography (positron emission tomography–computed tomography/magnetic resonance imaging) were highlighted for their diagnostic value. Variability in induction chemotherapy outcomes underscores the need for personalized treatment plans, and new radiotherapy techniques offer promising results with improving morbidity. Recent advancements in ONB management have enhanced prognostic accuracy, molecular diagnostics, imaging techniques, and treatment outcomes. Continuous research is necessary to optimize these strategies and further improve patient survival and quality of life.

Importance Adjuvant radiotherapy can improve locoregional control and survival in patients with olfactory neuroblastoma (ONB), particularly with advanced-stage and histologic-grade disease. Standard radiotherapy treatment is with intensity-modulated radiotherapy (IMRT). Proton beam radiotherapy (PBRT) provides theoretical advantages in greater sparing of dose to uninvolved organs at risk. Objective To investigate if there are differences in the effectiveness and radiation treatment–related adverse events (RTAEs) between adjuvant IMRT and PBRT for patients with ONB. Design, Setting, and Participants This propensity score–matched cohort study included patients with ONB treated between February 2005 and April 2021 with either IMRT or PBRT at 9 academic tertiary care centers in North America. Patients were matched 1:2 based on age, modified Kadish stage, and Hyams grade. Data were analyzed from July 2024 to January 2025. Exposure Adjuvant IMRT or adjuvant PBRT. Main Outcomes and Measures Local recurrence-free survival (RFS), any RFS, and overall survival (OS). RTAEs, ie, grade 2 events or higher based on Common Terminology Criteria for Adverse Events, were recorded for both modalities. Results Of 54 included patients, 27 (50%) were female, and the mean (SD) age was 46.2 (15.4) years. A total of 18 were treated with PBRT and 36 were treated with IMRT. Most patients had modified Kadish stage C disease (33 of 54 [61%]), and 24 patients (44%) had Hyams grade III or IV disease. The RTAE rate was 20% (8 of 40); IMRT had a rate of 21% (6 of 29), and PBRT had a rate of 18% (2 of 11). The difference in the point estimates for 10-year RFS showed a potential clinical benefit favoring IMRT, although the wide confidence interval indicates uncertainty (10-year RFS: IMRT, 63.3%; 95% CI, 44.6-89.8; PBRT, 37.8%; 95% CI, 14.2-100; difference, 25.5 percentage points; 95% CI, −17.6 to 68.6). There were no clinically meaningful differences in 10-year local RFS (IMRT, 75.6%; 95% CI, 59.8-95.4; PBRT, 72.7%; 95% CI, 45.2-100; difference, 2.9 percentage points; 95% CI, −35.9 to 41.7) or 10-year OS (IMRT, 61.8%; 95% CI, 42.8-89.1; PBRT, 57.1%; 95% CI, 24.3-100; difference, 4.7 percentage points; 95% CI, −49.2 to 58.6), although wide confidence intervals indicate considerable uncertainty. Conclusions and Relevance Due to the imprecision of estimates, no definitive conclusions can be made regarding the comparative effectiveness of IMRT vs PBRT for patients with ONB. These preliminary data may inform the design of appropriately powered prospective studies evaluating the efficacy of PBRT vs IMRT in this population.