Olfactory Neuroblastoma Patients Research Articles

Treatment Outcomes of Olfactory Neuroblastoma: A Multicenter Study by the Korean Sinonasal Tumor and Skull Base Surgery Study Group.

Due to the rarity of olfactory neuroblastoma (ONB), there is ongoing debate about optimal treatment strategies, especially for early-stage or locally advanced cases. Therefore, our study aimed to explore experiences from multiple centers to identify factors that influence the oncological outcomes of ONB. We retrospectively analyzed 195 ONB patients treated at nine tertiary hospitals in South Korea between December 1992 and December 2019. Kaplan-Meier survival analysis was used to evaluate oncological outcomes, and a Cox proportional hazards regression model was employed to analyze prognostic factors for survival outcomes. Furthermore, we conducted 1:1 nearest-neighbor matching to investigate differences in clinical outcomes according to the use of neoadjuvant chemotherapy. In our cohort, the 5-year overall survival (OS) rate was 78.6%, and the 5-year disease-free survival (DFS) rate was 62.4%. The Cox proportional hazards model revealed that the modified Kadish (mKadish) stage and Dulguerov T status were significantly associated with DFS, while the mKadish stage and Hyams grade were identified as prognostic factors for OS. The subgroup analyses indicated a trend toward improved 5-year DFS with dural resection in mKadish A and B cases, even though the result was statistically insignificant. Induction chemotherapy did not provide a survival benefit in this study after matching for the mKadish stage and nodal status. Clinical staging and pathologic grading are important prognostic factors in ONB. Dural resection in mKadish A and B did not show a significant survival benefit. Similarly, induction chemotherapy also did not show a survival benefit, even after stage matching.

The role of insulinoma-associated protein 1 in predicting the progression and prognosis of human olfactory neuroblastoma in China

ObjectiveRecent studies have suggested that insulinoma-associated protein 1 (INSM1) is a useful marker for pathological diagnosis of neuroendocrine tumors. In the present study, we investigated the association between INSM1 expression and prognosis in patients with olfactory neuroblastoma (ONB) and assessed the usefulness of INSM1 as a prognostic biomarker in these patients. MethodImmunohistochemistry was performed on 109 ONB patients who underwent endoscopic surgery at Beijing Tong Ren Hospital (Beijing, China) between June 2006 and November 2021 Patient age at the time of surgery ranged from 10 months to 72 years (mean age, 43.55 ± 13.47 years). In total, 63 (57.8%) and 46 (42.2%) tumors occurred in male and female patients, respectively. The percentages of grade I–IV cases were 13.8% (15/109), 36.7% (40/109), 29.4% (32/109) and 20.2% (22/109), respectively. ResultsThe expression rate (moderately/strongly positive) of INSM1 was significantly higher in high-grade (Ⅲ/Ⅳ; 83%; 45/54) than low-grade (Ⅰ/Ⅱ; 27%; 15/55) ONB cases. High expression levels of INSM1 were significantly positively associated with high pathological stage (p < 0.001), local recurrence, and death. Kaplan‑Meier analysis revealed that patients with high INSM1 expression had significantly shorter disease‑free survival (DFS) and mean survival (75.01 ± 10.71 vs. 158.56 ± 10.32) times, and shorter overall survival (OS). Multivariate Cox regression analysis revealed that INSM1 was an independent prognostic factor for DFS (HR: 4.963, 95%CI [2.11–10.84] p < 0.001) and OS (HR: 4.791, 95%CI [2.117–10.485], p < 0.001) after adjusting for sex, age, and tumor grade. In addition, INSM1 was an independent prognostic factor for DFS in patients treated with surgery (HR: 3.714, 95%CI [1.267–10.889], p = 0.017) and chemotherapy (HR: 5.574, 95%CI [1.584–19.612], p = 0.007). ConclusionINSM1 expression had a positive association with the prognosis of patients with ONB and could serve as a prognostic biomarker in these patients.

Genomic profiling and immune landscape of olfactory neuroblastoma in China.

Olfactory neuroblastoma (ONB) is a rare malignant neoplasm of the olfactory mucosa. The paucity of genomic data has prevented the development of individualized ONB treatments. Here, we investigated the genomic and immune landscape of ONB in Chinese patients. Whole exome sequencing (WES) and multiplex immunofluorescence (MIF) analysis were performed on tissue samples from 19 Chinese ONB patients. Patients were divided into low- and high-grade groups. Overall, 929 nonsynonymous alterations were identified in 18 (94.74%) ONB cases. The most prevalent altered cancer-related genes were CTNNB1 (16%) and ZNRF3 (16%). The most mutated oncogenic pathways were the WNT and RAS pathways. The median tumor mutation burden (TMB) was 0.45, ranging from 0 to 3.25. Only one case expressed PD-L1 (> 1%) in the tumor region. The percentage of CD8+ tumor-infiltrating lymphocytes (TILs) in the tumor region ranged from 0.03% to 84.9%, with a median of 1.08%. No significant differences were observed between the low- and high-grade groups for clinicopathological features, mutant genes, mutant pathways, TMB, tumor neoantigen burden (TNB), mutant-allele tumor heterogeneity (MATH), PD-L1 expression levels, or CD8+ TIL percentage. However, the low-grade group showed significantly more CD68+ macrophages in both the tumor and total region than the high-grade group. Notably, CD68+CD163- macrophages accounted for an average of 80.5% of CD68+ macrophages. This study presents data on the genomic and immune landscape of ONB cases in China. CTNNB1 and ZNRF3 were the most prevalent altered cancer-related genes. The results of TMB, PD-L1, and CD8+ Tils suggest that ONB may be insensitive to immunotherapy. M1 macrophages may be positively associated with the prognosis of ONB. In this study, the most prevalent altered cancer-related genes were CTNNB1 (16%) and ZNRF3 (16%). The most mutated oncogenic pathways were the WNT and RAS pathways. The median tumor mutation burden (TMB) was 0.45, ranging from 0 to 3.25. Only one (1/15) case expressed PD-L1 (> 1%) in the tumor region. However, the low-grade group showed significantly more CD68+ macrophages in both the tumor and total region than the high-grade group. The higher level of CD68-related macrophages indicates that M1 macrophages potentially play an important role in ONB development that is possibly associated with prognosis.

Fractionated Stereotactic Radiotherapy in the Management of Dural Recurrence of Olfactory Neuroblastoma

Treatment protocols for dural recurrence among esthesioneuroblastoma patients have not been standardized. We assess the outcomes of fractionated stereotactic radiotherapy (FSR) for patients with olfactory neuroblastoma (ONB) dura-based recurrences. We identified ONB patients with dura-based recurrences treated with FSR after prior radiotherapy who were enrolled between 2013 and 2022 in our prospective head and neck reirradiation and skull base registries. In-field tumor control (within 2 cm of prescribed radiotherapy volume) and out-of-field tumor control (non-contiguous or contralateral dura, nodal, or distant metastases) were analyzed. Thirteen patients with 28 dural lesions were included in this analysis. All patients were initially treated with surgery to their primary paranasal sinus disease; 69% with a craniofacial approach followed by adjuvant radiotherapy to a median dose of 63 Gy (range 60-72.4 Gy) prescribed to the resected tumor bed. Patients re-presented with dural recurrence at median 58.3 months (range 35.0 - 163.0 months) from completion of their initial treatment. Two patients underwent dural resections. On presentation of recurrence, 4 patients had 1 lesion treated, with a median of 2 lesions treated (range 1-4 lesions). All dural based tumors were treated with FSR to a median dose of 27 Gy in 3 fractions delivered QOD. 68Ga-DOTATATE PET/CT was utilized for FSR treatment planning in 31% of cases. The median follow up from FSR was 23.3 months (range: 13.1 - 51.6 months). The 1-year overall survival and progression free survival was 75% and 38%, respectively. The 1- and 2-year in-field control rate was 85% and 75%, respectively. Among treated lesions, 25 of 28 (89%) responded or remained stable following FSR. Two patients (3 lesions) had evidence of in-field radiographic progression at 17 and 9 months, respectively. Five patients (38%) experienced progression in the contralateral or non-contiguous dura, and 5 patients (38%) developed distant metastases. The overall out-of-field progression rate was 58% at 1 year. There was no grade 3 or higher toxicity observed. Three patients (23%) developed asymptomatic changes on MRI consistent with brain necrosis, all of which occurred in a previously irradiated region. In the largest single institution study of FSR reirradiation for ONB dural recurrence to date, high local control rates with minimal toxicity are attainable. However, subsequent out-of-field dural recurrences and/or distant metastases remain problematic.

Radiographic predictors of occult intracranial involvement in olfactory neuroblastoma patients.

Traditional management of olfactory neuroblastoma (ONB) includes margin-negative resection with removal of cribriform plate, dura, and olfactory bulb, regardless of intracranial disease. This approach may be overtreating certain patients. Our investigation examines risk factors associated with occult intracranial disease to optimize therapeutic outcomes. This retrospective, multi-institutional cohort study examined clinical covariates associated with occult intracranial involvement. Patient demographics, staging, Hyam's grade, and pathologic involvement of dura, olfactory bulb/tract, and brain were collected. Diagnostic imaging was reviewed. Positive and negative predictive value (NPV) were estimated along with effect size estimates. Cox hazard regression examined associations with overall survival (OS) and disease-free survival (DFS). A total of 224 subjects with new diagnoses of ONB (2005-2021) were identified. Skull base bone involvement on computed tomography (CT) had the highest NPV for pathologic dura (88.0%), olfactory bulb (88%), and brain involvement (97.3%). Hyam's grade category was significantly associated with dural involvement (φC =0.26; 95% confidence interval [CI]: 0.16, 0.42). Subjects without radiologic skull base involvement (n=66) had pathologic positivity of 12.1%. Within this subgroup, Hyam's grade was clinically significant for dural positivity (φ=0.34; 95% CI: -0.12, 0.71) with 28.6% involvement in high grade tumors. Neither clinical nor pathologic positivity of intracranial structures were associated with significantly different OS or DFS. Both CT and magnetic resonance imaging (MRI) had reasonably good NPV for involvement of dura and olfactory bulb. Higher Hyam's grade was associated with dural involvement. Patients with low-grade tumors not involving the skull base may be suitable for avoiding skull base resection; however, further investigation is warranted.

The role of ADC value and Ki-67 index in predicting the response to neoadjuvant chemotherapy in advanced stages of olfactory neuroblastoma.

To investigate the efficacy of pretreatment ADC and Ki-67 index in the prediction of the response to neoadjuvant chemotherapy (NACT) in advanced olfactory neuroblastoma (ONB) patients. A total of 21 advanced ONB patients (mean 43.48 years ± 14.26; range 25-69 years; 13 men and 8 women) with diffusion-weighted imaging (DWI) before NACT between June 2015 and October 2021 were retrospectively analyzed. Patients were categorized into responders and non-responders according to RECIST 1.1 after two cycles of NACT. The clinical data, ADCmean value, and Ki-67 index were analyzed. Kadish stage, ADCmean value, and Ki-67 index showed statistical significance between responders and non-responders. Patients with Kadish C stage were more likely to respond to platinum-based NACT (p = 0.035). Patients with the lower ADCmean value showed response to NACT (p = 0.002) and the cutoff point was 1.04 × 10-3 mm2/s. Patients with the higher Ki-67 index showed response to NACT (p = 0.003) and the cutoff point was 17.5%. Predictive performance of Ki-67 index and ADCmean value showed no significance between responders and non-responders (p = 0.865). A significant negative correlation was found between ADCmean value and Ki-67 index (r = -0.539, p = 0.038). The pretreatment ADCmean value, Ki-67 index and Kadish stage have the potential to predict the response to NACT in advanced ONB patients. This is the first study that investigated the feasibility of DWI in predicting the response to NACT in ONB patients and showed that Kadish stage, pretreatment ADCmean and Ki-67 index may play an important role in the prediction.

Survival impact of postoperative radiotherapy in patients with olfactory neuroblastoma: 513 cases from the SEER database

PuposeTo evaluate the impact of postoperative radiotherapy (PORT) on survival in olfactory neuroblastoma (ONB) patients with different tumor staging. Material and methodsPatients with ONB were selected in the Surveillance, Epidemiology and End Results (SEER) database from 2004–2016. Survival analyses were performed using Kaplan–Meier (K-M) method, Cox regression analysis, and competing risk model. ResultsA total of 513 patients were included in the study. Univariate and multivariate analysis results demonstrated that PORT was not an independent prognostic factor for overall survival (OS) of modified Kadish stage A and B patients (P=0.699 and P=0.248, respectively). Kadish stage C and D patients who underwent PORT had significantly better OS than those who did not undergo PORT (P=0.03 and P<0.0001). K-M curves revealed that the 5- and 10-year OS rates of patients who underwent PORT vs. non-PORT were 85.3% vs. 70.4% and 68.2% vs. 56.8% in stage C patients, respectively. For stage D patients, the 5-year OS rates were 70.7% and 42.6%, and 10-year OS rates were 53.4% and 29.5% in the PORT and non-PORT groups, respectively. The competitive risk model revealed that the 5-year cancer-specific cumulative mortality incidence decreased by 26.6% while the 10-year mortality incidence decreased by 41.4% in Kadish stage C patients who were treated using PORT; meanwhile, for Kadish stage D patients who were treated with PORT, the 5- and 10-year mortality incidences were reduced by 35.3% and 42.6%, respectively. Furthermore, we found that chemotherapy was not related to the prognosis of ONB patients (all P>0.05). ConclusionOur results indicate that PORT improved survival outcomes of modified Kadish stage C and D ONB patients. However, PORT may not affect survival for modified Kadish stage A and B individuals. Chemotherapy was not recommended for ONB; therefore, further studies are warranted to determine its therapeutic significance.

The Treatment Outcomes of Olfactory Neuroblastoma Patients With Frontal Lobe Invasion.

BackgroundTo investigate whether frontal lobe invasion (FLI) was an unfavorable prognostic factor in patients with olfactory neuroblastoma (ONB), and to explore the optimal treatment strategy for ONB patients with FLI.MethodsSome 37 patients with FLI were retrospectively studied, and 74 well-matched patients without FLI were enrolled as the control group. The long-term survivals were compared between the two groups.ResultsNo significant differences were found between the two groups in overall survival (OS), progression-free survival (PFS), locoregional failure-free survival (LRFS), and distant metastasis-free survival (DMFS) (all p >0.05). Multivariate analyses showed that FLI wasn’t an independent predictor for OS (HR = 1.100, 95% CI = 0.437–2.772, p = 0.840). Among the 37 patients with FLI, patients who received surgery combined with chemo-/radiotherapy showed better OS (89.4% vs. 53.6%, p = 0.001) and PFS (87.8% vs. 53.6%, p = 0.001) compared with those who didn’t undergo surgery.ConclusionsFLI wasn’t a poor prognostic factor for ONB patients. Endoscopic resection combined with radiotherapy was an effective therapeutic method for ONB patients with FLI.

Survival Associations between Patient Age and Treatment Modality in Olfactory Neuroblastoma: A Retrospective Population-Based Study.

Olfactory neuroblastoma (ONB) is a rare neuroepithelial-derived malignancy that usually presents in the nasal cavity. The rarity of ONB has led to conflicting reports regarding associations of patient age and ONB survival and outcome. Moreover, long-term outcomes of chemotherapy and other treatment modalities are speculated. Here, we aimed to compare survival outcomes across age groups through time and determine associations between treatment modality and survival. In this retrospective population-based study, we analyzed the SEER 2000–2016 Database for patients with ONB tumors. Using Kaplan–Meier survival analysis, a significant effect of age and cancer-specific survival (CSS) was observed; geriatric ONB patients had the lowest CSS overall. Generalized linear models and survival analyses demonstrated that CSS of the pediatric patient population was similar to the geriatric group through 100 months but plateaued thereafter and was the highest of all age groups. Radiation and surgery were associated with increased CSS, while chemotherapy was associated with decreased CSS. GLM results showed that tumor grade, stage and lymph node involvement had no CSS associations with age or treatment modality. Our results provide insight for future investigations of long-term outcomes associated with ONB patient age and treatment modality, and we conclude that survival statistics of ONB patients should be analyzed in terms of trends through time rather than fixed in time.

Gene Expression Profiling of Olfactory Neuroblastoma Helps Identify Prognostic Pathways and Define Potentially Therapeutic Targets.

Simple SummaryThe gene expression profile of ONB defines a group of patients with a dismal prognosis and identifies potentially targetable pathways. Better prognostic stratification may offer new tailored approaches for the treatment and follow-up of ONB. The integration of new therapeutic agents with standard surgical and RT strategies may improve the outcomes in cases with worse prognoses. Furthermore, the ontogenesis of ONB in basal and neural subtypes is mirrored by different transcriptional pathways, paving the way towards different therapeutic approaches. Olfactory neuroblastoma (ONB) is a rare sinonasal neoplasm with a peculiar behavior, for which limited prognostic factors are available. Herein, we investigate the transcriptional pathways altered in ONB and correlate them with pathological features and clinical outcomes. We analyze 32 ONB patients treated with curative intent at two independent institutions from 2001 to 2019 for whom there is available pathologic and clinical data. We perform gene expression profiling on primary ONB samples and carry out functional enrichment analysis to investigate the key pathways associated with disease-free survival (DFS). The median age is 53.5 years; all patients undergo surgery and a pure endoscopic approach is adopted in the majority of cases (81.2%). Most patients have advanced disease (stages III–IV, 81.2%) and 84.4% undergo adjuvant (chemo)radiotherapy. The median follow-up is 35 months; 11 (26.8%) patients relapse. Clinical characteristics (gender, stage and Hyams’ grade) are not associated with the outcomes. In contrast, TGF-beta binding, EMT, IFN-alpha response, angiogenesis, IL2-STAT5 and IL6-JAK-STAT3 signaling pathways are enriched in patients experiencing recurrence, and significantly associated with shorter DFS. Clustering of transcriptional profiles according to pathological features indicates two distinct molecular groups, defined by either cytokeratin-positive or -negative immunostaining. Definition of the characterizing ONB transcriptomic pathways may pave the way towards tailored treatment approaches.

Surgery as Single-Modality Treatment for Early-Stage Olfactory Neuroblastoma: An Institutional Experience, Systematic Review and Meta-analysis.

For olfactory neuroblastoma (ONB), the combination of surgical tumor resection and radiation therapy (RT) has been considered the "gold standard" in treatment protocols intended to cure. To summarize evidence on the treatment of ONB using surgery alone. A retrospective institutional case series, a systematic review of the literature, and an individual patient data (IPD) meta-analysis on only surgically treated ONB patients. At our institution, a total of 10 patients were treated through surgery alone and remained alive and free of disease at last follow-up. The IPD meta-analysis on 128 patients revealed a disease-free survival (DFS) and overall survival (OS) of 67.7% and 75.4% at 5 years and 57.1% and 71.9% at 10 years, respectively. Univariate analysis showed that Kadish stage C/D and Hyams grading III//IV significantly affected OS (P = 0.000 and P = 0.000) and DFS (P = 0.000 and P = 0.002). For low-risk patients, the DFS was 80.6% at 5 years and 67.8% at 10 years, respectively. Surgery alone is an equivalent alternative to combined treatment in carefully selected low-risk ONB patients with better outcome measures than previously reported.

Intensity-modulated particle beam radiation therapy in the management of olfactory neuroblastoma.

BackgroundTo report the clinical experience and short-term efficacy in the management of olfactory neuroblastoma (ONB).MethodsWe performed a retrospective analysis of 12 ONB patients treated with particle beam radiation therapy (PBRT) between 12/2015 and 5/2019 at the Shanghai Proton and Heavy Ion Center. Four (33.3%) patients presented with Kadish B ONB, and 8 (66.7%) presented with Kadish C or D disease. Eleven patients received proton radiotherapy (PRT) followed by a carbon ion radiotherapy (CIRT) boost, one patient received CIRT only. The 2-year survival rates were calculated using the Kaplan-Meier method. Acute and late adverse events were summarized and scored according to the CTCAE (version 4.03).ResultsWith a median follow-up of 17.5 (range, 2.53–49.9) months, all patients but 1 were alive. Eight patients were alive without evidence of disease, and 2 additional patients achieved partial response and remained alive with residual disease. One patient died of toxicity associated with salvage chemotherapy for distant metastasis and local failure. Another patient developed distant metastasis only and was alive at the time of the last follow-up. The 2-year OS, PFS, LRPFS, and DMFS rates were 83.3%, 75.8%, 87.5%, and 79.5%, respectively. No acute or late toxicities of ≥ grade 3 was observed.ConclusionsIntensity modulated PBRT of ONB is well tolerated. While longer follow-up is needed, early outcomes suggested that PBRT is safe and effective for the treatment of ONB with minimal adverse events.

Clinical Outcomes and Multidisciplinary Patterns of Failure for Olfactory Neuroblastoma: The Ohio State Experience.

Purpose Olfactory neuroblastoma (ONB) is a rare head and neck cancer believed to be originated from neural crest cells of the olfactory membrane located in the roof of the nasal fossa. This study evaluates clinical outcomes and failure patterns in ONB patients of those patients treated with surgical resection at a high-volume tertiary cancer center. Methods and Materials Thirty-nine ONB patients who underwent surgical resection at our institution from 1996 to 2017 were retrospectively identified. Univariate, multivariate, and survival analysis were calculated using Cox regression analysis and Kaplan-Meier log-rank. Results Median follow-up time was 59 months (range: 5.2-236 months). The median overall survival (OS) and disease-free survival (DFS) for the entire cohort were 15 and 7.6 years, respectively. The 5-year cumulative OS and DFS were 83 and 72%, respectively. The 5-year OS for low Hyams grade (LHG) versus high Hyams grade (HHG) was 95 versus 61% ( p = 0.041). LHG was found in 66% of the early Kadish stage patients compared with 28% in the advanced Kadish stage patients ( p = 0.057). On multivariate analysis, HHG and positive node status predicted for worse OS and only HHG predicted for worse DFS. Of note, five patients (all Kadish stage A) who received surgical resection alone had no observed deaths or recurrences with a median follow-up of 44 months (range: 5-235 months). Conclusion In this retrospective cohort, patients with positive nodes or HHG have significantly worse clinical outcomes. Future studies should explore treatment intensification for HHG or positive nodes.

The Impact of Adjuvant Radiation Therapy and Elective Nodal Irradiation in Early Stage/Low Grade versus Advanced Stage/High Grade Olfactory Neuroblastoma

Olfactory neuroblastoma (ONB) is a rare head and neck cancer originating from neural crest cells of the olfactory membrane located in the roof of the nasal fossa. Several retrospective studies have shown surgical resection, followed by adjuvant radiotherapy, to be superior to either modality alone. However, even with bi-modality or even tri-modality therapy ONB patients with high Hyams grade (HHG) and advanced Kadish stages (AKS), C or D, have worse clinical outcomes compared to low Hyams grade (LHG) and early Kadish stages (EKS), A or B. This study evaluates clinical outcomes in ONB patients, comparing adjuvant radiation therapy versus surgery alone in EKS. In addition we evaluated the impact of adjuvant radiotherapy including elective nodal irradiation (ENI). Forty-one ONB patients treated with surgical resection at our institution from 1996 to 2017 were identified. Two patients died following surgery and were excluded from the analysis. Univariate, multivariate, and survival analysis was performed with comparative analysis between radiation of the primary site and ENI. Median follow-up time in this cohort was 59 months (range 5.2-236). The median overall survival (OS) and disease free survival (DFS) for the entire cohort was 15 years and 7.6 years, respectively. The five-year cumulative OS and DFS was 83% and 72%, respectively. Ten patients (26%) had ONBs classified as EKS and 29 patients (75%) had AKS tumors. The 5 year OS for ONBs with LHG was 100% compared to 65% for those with ONBs with HHG (p=.017). 66% of the EKS patients were also LHG compared to only 28% LHG in AKS patients (p=.057). The 5 year OS/DFS was 100%/100%, 100%/66%, 100%/75%, and 59%/47% for EKS/LHG, EKS/HHG, AKS/LHG, and AKS/HHG, respectively (p=0.07). Five patients in the EKS group received surgical resection alone, and there were no observed deaths or recurrences with a median follow up of 44 months (range 5-235 months). 31 (79%) patients in the entire cohort presented with node-negative disease. 13 (56%) of the node-negative patients received ENI. There were six nodal-failures in the entire cohort, with one failure 16 years following treatment (median 59 months, range 6-165 months). In node-negative patients the 10 year nodal-failure rate was reduced from 38% (3/8) in patients treated with primary site radiation alone to 0% (0/9) with the addition of ENI (p=.04). In this retrospective review, patients with both AKS and HHG have significant worse clinical outcomes compared to EKS and LHG. In EKS patients, surgery alone resulted in long term OS and DFS. For patients with node negative disease at presentation (other than those with EKS who did not undergo radiation), ENI resulted in significant reduction in the regional failure. In select patients presenting EKS and LHG ONB, surgical resection alone can be considered. Furthermore ENI should be standard of radiation therapy and long term follow up is recommended.

Clinical features and the molecular biomarkers of olfactory neuroblastoma

Olfactory neuroblastoma (ONB) is a kind of rare and complex head and neck tumor. The reports on this field are very scarce due to the low morbidity. Here, we summarized the clinical features and prognosis of ONB through analysis of 10 cases, and determined the phosphorylation status of some molecules known to be involved in carcinogesis such as Akt, Erk, Stat3 and Stat5 in ONB tissue. Ten ONB patients were recruited in this study, 6 male and 4 female, ranging from 26 to 66 years old. In the 10 cases, 6 were diagnosed as late T stage (T3/T4), 6 were at late Kadish stage (C/D) and 3 were at high Hyams grade (Ⅲ), which indicated a poorer prognosis. Patient characteristics–gender and tumor features were evaluated with respect to the overall survival (OS) through univariate analysis. The result indicated that the OS of male is obviously higher than that of female after a series of combined treatment. The OS of ONB patients in the late stage or high grade is lower than those in early stages or low grade. Moreover, p-Akt, p-Erk, p-Stat3 and p-Stat5 was detected in 5 (50%), 9 (90%), 7 (70%) and 0 patients (0%), respectively, suggesting the former 3 molecules might be potential biomarkers for diagnosis of ONB.

Role of 18F‐FDG PET/CT differentiating olfactory neuroblastoma from sinonasal undifferentiated carcinoma

The purpose of this study is to demonstrate the potential contribution of positron emission tomography (PET)/computed tomography (CT) to help differentiate olfactory neuroblastoma (ONB) from sinonasal undifferentiated carcinoma (SNUC). Following approval by the institutional review board at the Wexner Medical Center at the Ohio State University, Columbus, Ohio, a pilot study with retrospective review of patients with biopsy-proven diagnosis of ONB s and SNUC s was conducted. Staging PET/CT scans were reviewed to document the maximum standardized uptake value (SUVmax). A statistical comparison of SUVmax was performed. We identified 13 patients (7 with ONBs and 6 with SNUCs) with mean age 60.2 years who had undergone staging F-18 fluorodeoxyglucose (18 F-FDG) PET/CT of the primary tumor at the time of their diagnosis. Mean SUVmax was found to be five-fold higher in SNUC patients (35.63, range 10.8-77.9) than in ONB patients (7.24, range 4.6-10.7) (P ≤ 0.00169). Maximum standardized uptake value of 18 F-FDG PET/CT can be used to initially discriminate between ONB and SNUC. This finding may prove helpful to guide diagnostic and treatment planning when the histopathologic diagnosis is inconclusive. 4. Laryngoscope, 2016 127:321-324, 2017.