Multicenter Survival Analysis and Application of an Olfactory Neuroblastoma Staging Modification Incorporating Hyams Grade

Abstract

ImportanceCurrent olfactory neuroblastoma (ONB) staging systems inadequately delineate locally advanced tumors, do not incorporate tumor grade, and poorly estimate survival and recurrence.ObjectiveThe primary aims of this study were to (1) examine the clinical covariates associated with survival and recurrence of ONB in a modern-era multicenter cohort and (2) incorporate Hyams tumor grade into existing staging systems to assess its ability to estimate survival and recurrence.Design, Setting, and ParticipantsThis retrospective, multicenter, case-control study included patients with ONB who underwent treatment between January 1, 2005, and December 31, 2021, at 9 North American academic medical centers.InterventionStandard-of-care ONB treatment.Main Outcome and MeasuresThe main outcomes were overall survival (OS), disease-free survival (DFS), and disease-specific survival (DSS) as C statistics for model prediction.ResultsA total of 256 patients with ONB (mean [SD] age, 52.0 [15.6] years; 115 female [44.9%]; 141 male [55.1%]) were included. The 5-year rate for OS was 83.5% (95% CI, 78.3%-89.1%); for DFS, 70.8% (95% CI, 64.3%-78.0%); and for DSS, 94.1% (95% CI, 90.5%-97.8%). On multivariable analysis, age, American Joint Committee on Cancer (AJCC) stage, involvement of bilateral maxillary sinuses, and positive margins were associated with OS. Only AJCC stage was associated with DFS. Only N stage was associated with DSS. When assessing the ability of staging systems to estimate OS, the best-performing model was the novel modification of the Dulguerov system (C statistic, 0.66; 95% CI, 0.59-0.76), and the Kadish system performed most poorly (C statistic, 0.57; 95% CI, 0.50-0.63). Regarding estimation of DFS, the modified Kadish system performed most poorly (C statistic, 0.55; 95% CI, 0.51-0.66), while the novel modification of the AJCC system performed the best (C statistic, 0.70; 95% CI, 0.66-0.80). Regarding estimation of DSS, the modified Kadish system was the best-performing model (C statistic, 0.79; 95% CI, 0.70-0.94), and the unmodified Kadish performed the worst (C statistic, 0.56; 95% CI, 0.51-0.68). The ability for novel ONB staging systems to estimate disease progression across stages was also assessed. In the novel Kadish staging system, patients with stage VI disease were approximately 7 times as likely to experience disease progression as patients with stage I disease (hazard ratio [HR], 6.84; 95% CI, 1.60-29.20). Results were similar for the novel modified Kadish system (HR, 8.99; 95% CI, 1.62-49.85) and the novel Dulguerov system (HR, 6.86; 95% CI, 2.74-17.18).Conclusions and RelevanceThe study findings indicate that 5-year OS for ONB is favorable and that incorporation of Hyams grade into traditional ONB staging systems is associated with improved estimation of disease progression.

Treatment of unilateral olfactory neuroblastoma: Appropriate extent of surgical resection and potential for olfactory preservation

“…A randomized controlled trial with unilateral and bilateral ONB resection groups would offer the best perspective on outcome differences, but equipoise may be lacking among surgeons. Given the propensity for delayed recurrence and metastases, future studies must incorporate long‐term follow‐up data for unilateral resection patients 17 …”

Predictability of Olfactory Neuroblastoma Staging Systems—Reply

“…In Reply We appreciate the interest in our article, “Multicenter Survival Analysis and Application of an Olfactory Neuroblastoma Staging Modification Incorporating Hyams Grade,” shown by Sun et al in their Letter to the Editor. Their letter is a critique of the use of the Harrell C statistic, a statistical metric selected to discriminate the ability of novel olfactory neuroblastoma (ONB) staging systems to predict clinical outcomes.…”

Predictability of Olfactory Neuroblastoma Staging Systems

“…To the Editor Choby and colleagues conducted an extensive study to investigate if incorporation of Hyams grade into olfactory neuroblastoma staging systems would provide better prediction of clinical outcomes: overall survival (OS), disease-free survival (DFS), and disease-specific survival. They used C statistics as a metric to evaluate each working Cox model’s predictability.…”

“…First, the authors used the Harrell C statistic as the metric, which is known to be problematic. This C statistic estimates a population quantity that involves the censoring distribution of the study patients.…”

“…Finally, the study used a single data set with a modest sample size to build various working models and then assessed their relative merits. To avoid overfitting or being overly optimistic, it is customary to use 2 independent data sets, one set for training to derive candidate models and the other set for estimating the predictability of each model for model selection.…”