Kadish Stage Research Articles

Abstract 4706: Multispectral immunofluorescence analysis of the olfactory neuroblastoma tumor immune microenvironment reveals macrophage and polymorphonuclear leukocyte stroma localization and tumor parenchyma exclusion

Abstract Background: Olfactory neuroblastoma (ONB), also known as esthesioneuroblastoma, is a rare malignancy of the nasal cavity and anterior skull base. Multispectral immunofluorescence (mxIF), allows for comprehensive evaluation of tumor immune cell spatial relationships and thorough characterization of the tumor immune microenvironment (TIME). The objective of this study was to comprehensively define the ONB myeloid cell TIME with mxIF. Methods: A tissue microarray including 47 clinically annotated human ONB samples was obtained, in addition to IRB approval, from our tertiary care hospital. A myeloid specific panel was validated in ONB tissue as well as controls. The panel stained for CD15, CD68, CD11b, CD14, HLA-DR, synaptophysin, and DAPI. Phenotypes of interest included CD11b+/CD15+/CD14−/HLA-DRlow/− polymorphonuclear leukocytes (PMNs), CD11b+/CD14+/CD15−/HLA-DR low/−monocytes, and CD68+ Pan Macrophages. HALO image analysis v3.4 was used to objectively quantify immune cell spatial relationships. A retrospective chart review was performed from these clinically annotated specimens with collection of patient demographics, stage, Hyams grade, dural infiltration status, and outcomes. Results: Three samples were excluded based on too little available tissue for meaningful analysis. Of the remaining 44, 38 were primary and 6 were recurrent tumors. PMNs, monocytes, and macrophages are present in the TIME of ONB at 22 cells per mm2, 2.0 cells per mm2, and 34 cells per mm2 respectively. Increased PMN and macrophage cell densities were noted in the stroma when compared to the tumor parenchyma (28 cells per mm2 vs 14 cells per mm2, p<0.0001 and 46 cells per mm2 vs 21 cells per mm2, p<0.0001). A similar trend was seen in monocytes (3.5 cells per mm2 vs 0.80 cells per mm2, p=0.0588) but it did not reach statistical significance. When we compared by Kadish Stage, higher stage (C/D) had more tumor infiltrating PMNs than low stage (A/B) (median of 1.3 cells per mm2 vs median 0 cells per mm2, p=0.0011). No further differences in cell distributions were noted when comparing for Hyams grade, stage, dural infiltration, recurrent disease, or other clinical factors. Nearest neighbor analysis demonstrates that macrophages are closer to tumor cells than PMNs or monocytes (19.68 µm vs 27.78 µm, p<0.0001, and 25.77 µm, p=0.0026, respectively). Conclusion: This study is the first to comprehensively define the ONB myeloid TIME using mxIF. Our study demonstrates the ONB TIME contains abundant myeloid populations. As these cells have been shown to be immunosuppressive, thereby fostering tumor cell escape and host evasion, in other human malignancies we posit they play a similar role in ONB. The functional study of myeloid populations in ONB, and whether they represent targets for therapeutic intervention, is warranted. Citation Format: Riley Larkin, Diana Lopez, Yvette Robbins, Wiem Lassoued, Gary Gallia, Clint T. Allen, Nyall R. London. Multispectral immunofluorescence analysis of the olfactory neuroblastoma tumor immune microenvironment reveals macrophage and polymorphonuclear leukocyte stroma localization and tumor parenchyma exclusion. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4706.

Prognostic significance of PD-1, CTLA-4, CD4, and CD8 expression in olfactory neuroblastoma.

There are limited data regarding immune surveillance mechanisms in olfactory neuroblastoma. We investigated the expression of programmed cell death protein 1 (PD-1), cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), CD4, and CD8 in olfactory neuroblastoma to identify potential therapeutic targets. Immunohistochemistry was used to detect PD-1 and CTLA-4 and measure the numbers of CD4+ and CD8+ T cells in 56 patients with olfactory neuroblastoma. The relationships between these molecules in tumor microenvironment, clinicopathological features, and survival were analyzed. The prevalence of PD-1 in Kadish C stage was 24.14%, significantly greater than in Kadish A and B stage. CD4+ T-cell and CD8+ T-cell levels correlated with higher Hyams histological grade and Kadish stage. In addition, PD-1 was related positively with CTLA-4, CD4+ T cells, and CD8+ T cells in olfactory neuroblastoma. Univariate survival analysis showed that higher PD-1 positivity, CD8+ T cells, and Hyams grade correlated with worse clinical outcome. Multivariate analysis showed that the expression of PD-1 was an independent parameter for poor prognosis. In conclusion, olfactory neuroblastoma with PD-1 expression had more aggressive clinicopathological features and worse prognosis. PD-1 may potentially predict the outcome of olfactory neuroblastoma patients.

Recurrent Esthesioneuroblastoma: Long-Term Outcomes of Salvage Therapy

Esthesioneuroblastoma (ENB) is a rare malignant neoplasm arising from the olfactory epithelium of the cribriform plate. Although survival is excellent with a reported 5-year overall survival (OS) of 82%, recurrence is frequent and occurs in 40-50% of cases. This study investigates the characteristics of ENB recurrence and the subsequent prognosis of patients with recurrence. The clinical records of all patients diagnosed as having ENB with subsequent recurrence at a tertiary hospital from 1 January 1960 to 1 January 2020 were retrospectively reviewed. Overall survival (OS) and progression-free survival (PFS) were reported. A total of 64 out of 143 ENB patients had recurrences. In total, 45 out of 64 recurrences met the inclusion criteria and were included in this study. From these, 10 (22%) had a sinonasal recurrence, 14 (31%) had an intracranial recurrence, 15 (33%) had a regional recurrence, and 6 (13%) had a distal recurrence. The average interval from initial treatment to recurrence was 4.74 years. There were no differences in rates of recurrence with respect to age, sex, or types of surgery (endoscopic, transcranial, lateral rhinotomy, and combined). The time to recurrence was shorter for Hyams grades 3 and 4 compared to Hyams grades 1 and 2 (3.75 years vs. 5.70 years, p < 0.05). Patients with recurrence limited to the sinonasal region had a lower overall primary Kadish stage compared to recurrences beyond the sinonasal region (2.60 vs. 3.03, p < 0.05). A total of 9 (20%) out of 45 patients developed secondary recurrence. Following recurrence, the subsequent 5-year OS and PFS were 63 and 56%, respectively. The mean time to secondary recurrence after treatment of the primary recurrence was 32 months, which was significantly shorter than the time to primary recurrence (32 months vs. 57 months, p = 0.048). The mean age of the secondary recurrence group is significantly older than the primary recurrence group (59.78 years vs. 50.31 years, p = 0.02). No statistically significant differences were observed between the secondary recurrence group and the recurrence group in terms of their overall Kadish stages or Hyams grades. Following an ENB recurrence, salvage therapy appears to be an effective therapeutic option with a subsequent 5-year OS of 63%. However, subsequent recurrences are not infrequent and may require additional therapy.

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.

Surgical Resection and Intensity Modulated Proton Therapy for Esthesioneuroblastoma

<h3>Purpose/Objective(s)</h3> Esthesioneuroblastoma (ENB) is a rare locally aggressive neuroendocrine sinonasal malignancy commonly presenting with skull base and intracranial invasion, which is often managed using multimodality therapy with surgery and radiotherapy (RT). Advances in surgical techniques as well as RT have improved outcomes for these complex tumors. Proton therapy has dosimetric advantages over conventional X-ray based approaches and may further improve the therapeutic ratio. We report our early experience with intensity modulated proton therapy (IMPT) in the management of ENB. <h3>Materials/Methods</h3> We retrospectively reviewed treatment records of patients with ENB treated at our center with IMPT from 2015-2021. IMPT was delivered with a 2 to 5 field pencil-beam scanning plan, initially with single-field optimization, then multi-field optimization after 2018. All pathology was internally reviewed. Event outcomes were calculated from date of biopsy to time of locoregional recurrence or death. Survival statistics were calculated using the Kaplan-Meier (KM) method using a scientific 2-D graphing and statistics software. <h3>Results</h3> 15 patients were identified, median age 52 (range 32-78), gender (male 12, female 3), Kadish stage (B – 2; C – 12; D – 1), AJCC T classification (T3 – 3, T4b – 12), 2 had nodal metastasis at diagnosis, Hyams (grade 2 – 10; grade 3-4 – 5). Local disease extent included: anterior cranial fossa – 11, middle cranial fossa – 2, dura – 12, brain parenchyma 1, nasopharynx – 2, orbit – 6. The majority (n=14) were managed with surgical resection followed by postoperative RT, and one underwent primary chemoradiation. Surgery included bifrontal craniotomy + extended endoscopic resection (n=7) and extended endoscopic resection alone (n=7). IMPT was delivered in conventional fractionation (n=12) or hyperfractionated accelerated course (n=3), median dose 68 CGE (range 60-72), neck coverage (n=11). Four received concurrent platinum-based chemotherapy. At median follow up of 20 months (IQR 16-51), 2 patients have died, unrelated to disease progression. Three patients have recurred including 1 local, 1 regional, and 1 distant metastasis (out of field dural metastases). Both patients with locoregional recurrence have undergone surgical salvage and have no evidence of disease. IMPT was well tolerated with expected acute toxicities. One patient developed frontal lobe brain necrosis at 3 years post-treatment managed conservatively, and one underwent functional sinus surgery for sinus obstruction. No de novo high grade visual toxicity was observed. KM 2-year locoregional recurrence-free survival was 83% and OS 88%. <h3>Conclusion</h3> IMPT is feasible in ENB with early outcomes demonstrating excellent local control and favorable toxicity profile in this cohort of patients with very locally advanced disease. IMPT may allow for improved coverage of tumor volumes in close proximity to numerous critical structures. Additional follow up is needed to track long term disease control outcomes and late toxicities.

Clinical Outcomes and Patterns of Failure in Esthesioneuroblatoma: A Single Institutional Experience.

Esthesioneuroblastoma (ENB) is a rare sinonasal malignancy that is typically managed with a combination of surgical resection, radiotherapy and chemotherapy. Data used to guide therapeutic decision making are scant and typically obtained from small retrospective series due to the relative infrequency of the diagnosis. Here, we report our own institutional experience in the management of patients with ENB to help compliment these prior single institutional reports. Records from patients receiving treatment for ENB at the University of Minnesota Medical Center were obtained from 1994 to 2019. A total of 17 patients were identified from our retrospective review. Kadish stage at initial presentation was A in 2 (12%), B in 5 (29%), C in 9 (53%) and D in 1 (6%). All patients underwent surgical resection. Adjuvant radiotherapy was utilized in 12 (71%) patients with concurrent chemotherapy administered in 3 (18%) patients. One patient received neoadjuvant chemoradiotherapy followed by surgical resection. Four patients developed recurrent disease with locoregional failure presenting as the most common site of initial relapse within our study population. Isolated local recurrence occurred in 2 patients, one patient developed combined local and regional failure, while another had combined regional and distant failure with osseous metastases. Recurrent disease was managed by either combined salvage surgery and radiotherapy (RT) or RT alone. Three of the 4 patients who developed recurrence eventually succumbed to their disease. Estimates for 5-year DFS and OS were 65% and 90%, respectively, for the entire cohort.

Experiences and Outcomes in Olfactory Neuroblastoma Over A Decade at a Tertiary Cancer Center.

Background Olfactory neuroblastoma is a rare epithelial malignancy arising from the odorant receptors in the nasal mucosa or along the cribriform plate of the ethmoid bone. Clinical presentation includes nasal stuffiness, local pain, epistaxis, anosmia, visual impairment, proptosis, headache, and seizures. Radiologic imaging with CT or MRI, an ophthalmic evaluation, and histopathologic confirmation with immunohistochemistry are parts of the initial diagnostic workup. Although surgery, chemotherapy, and radiation have an equally important role in the management, earlier stages may preferably be treated with surgery or radiotherapy and the later stages with a multimodality approach. Materials and Methods We conducted a retrospective review of 13 patients diagnosed with olfactory neuroblastoma, registered at Mehdi Nawaz Jung Regional Cancer Center over a decade (2010-2019). We analyzed the age and sex distribution, performance status at presentation, clinical symptomatology, and the Kadish stage. In addition, the therapeutic aspects of patients were studied. Results The most common presentation noted was nasal stuffiness, followed by epistaxis and proptosis. The majority of patients had good performance status at presentation. Ten patients presented with a Kadish stage C, while the remaining patients presented with Kadish stage B. Cervical nodal metastasis was seen in three patients, four patients received multimodality treatment with neoadjuvant chemoradiotherapy followed by surgery, two patients received neoadjuvant chemotherapy followed by radiation, two patients received only surgery, and one patient received surgery followed by adjuvant radiation. Conformal radiation techniques were used to deliver doses as high as 50 to 66 Gy in 2 Gy per fraction. Two patients presented with distant metastasis during follow-up, one with bone metastasis, and the other with retroperitoneal nodal metastasis; they received palliative chemotherapy and conformal radiation to the primary site. Conclusion This study concludes that neoadjuvant chemotherapy followed by radiation gives the best outcomes. It has been observed that in multi-modality treatment, radiotherapy played a significant role in improving overall survival and better outcomes. Multidisciplinary discussions provide a better sequencing of management.

The prognostic value of S-100 protein and Ki-67 index in olfactory neuroblastoma.

To evaluate the prognostic value of S-100 protein and Ki-67 labeling index in olfactory neuroblastomas. A retrospective study was conducted on a cohort of 85 patients with olfactory neuroblastomas. The immunohistochemical expression of S-100 and Ki-67 was assessed, and the predictive value of S-100 and Ki-67 was further evaluated. The optimal cutoff value of Ki-67 labeling index was determined using time-dependent receiver operating characteristic curve analysis. Overall survival and progression-free survival were assessed using the Kaplan-Meier method. A cut-off Ki-67 labeling index value of 67.5% was determined for prognosis in patients with olfactory neuroblastomas. There was a significant correlation between Ki-67 expression and cervical lymph node metastasis (P=0.049). Compared with S-100 (+), S-100 (-) was associated with a higher rate of lymph node metastasis and a higher level of Ki-67 (P=0.007,<0.001, respectively), as well as an advanced Kadish stage (P=0.037). Survival analyses showed that patients with S-100 (+) had better 5-year overall survival than those with S-100 (-) (P=0.028), and patients with both S-100 (+) and Ki-67 (<67.5%) had superior 5-year overall survival compared with all the other patients (P=0.0225). Our findings suggest that S-100 combined with Ki-67 labeling index are reliable prognostic factors in patients with olfactory neuroblastomas.

Esthesioneuroblastoma (Olfactory Neuroblastoma): Overview and Extent of Surgical Approach and Skull Base Resection.

Esthesioneuroblastoma is a rare malignancy originating from the olfactory epithelium. Treatment consists of surgical resection with strong consideration for adjuvant treatment in advanced Kadish stage and high Hyams grade. In the modern era, overall outcomes for esthesioneuroblastoma are favorable compared with many other sinonasal malignancies with 5-year overall survival estimated to be 80%. When selecting the optimal surgical approach, the surgeon must consider the approach that will allow for a negative margin resection and adequate reconstruction. In appropriately selected patients, endoscopic outcomes appear at least equivalent to open approaches and unilateral endoscopic approach may be used in select olfactory preservation cases.

Prognostic value of microvessel density and its correlation with clinicopathological features in human olfactory neuroblastoma.

Although angiogenesis plays an important role in tumor growth and invasion, its role in the progression of olfactory neuroblastoma (ONB) has rarely been published. The aim of the present research was to analyze the prognostic role of microvessel density (MVD) in ONB and its association with clinicopathological parameters. 70 ONB cases were assessed for immunohistochemical expression of CD31, CD34, CD105, VEGF, and VEGFR2. The expression of CD105-MVD was negatively associated with histological grade and tumor Kadish stage, and its expression was positively correlated with the expression of VEGF/VEGFR2. Low expression of CD105-MVD and high tumor histological grade were strongly associated with poor survival. Thus, CD105-MVD was demonstrated to be a valuable independent prognostic indicator for ONB. MVD is expected to be useful as an important marker to distinguish tumor histological grade.

Long-term oncologic outcomes in esthesioneuroblastoma: An institutional experience of 143 patients.

Esthesioneuroblastoma (ENB) is a rare malignant neoplasm arising from the olfactory epithelium of the cribriform plate. The goal of this study was to update our oncologic outcomes for this disease and explore prognostic factors associated with survival. We performed a retrospective analysis of patients with ENB treated at a single tertiary care institution from January 1, 1960, to January 1, 2020. Univariate and multivariate analysis was performed. Overall survival (OS), progression-free survival (PFS), and distant metastasis-free survival (DMFS) were reported. Among 143 included patients, the 5-year OS was 82.3% and the 5-year PFS was 51.6%; 5-year OS and PFS have improved in the modern era (2005-present). Delayed regional nodal metastasis was the most common site of recurrence in 22% of patients (median, 57 months). On univariate analysis, modified Kadish staging (mKadish) had a negative effect on OS, PFS, and DMFS (p<0.05). Higher Hyams grade had a negative effect on PFS and DMFS (p<0.05). Positive margin status had a negative effect on PFS (p<0.05). Orbital invasion demonstrated worsening OS (hazard ratio, 3.1; p<0.05). On multivariable analysis, high Hyams grade (3 or 4), high mKadish stage (C+D), and increasing age were independent negative prognostic factors for OS (p<0.05). High Hyams grade (3+4), high mKadish stage (C+D), age, and positive margin status were independent negative prognostic factors for PFS (p<0.05). High Hyams grade (3+4) was an independent negative prognostic factor for DMFS (p<0.05). Patients with low Hyams grade and mKadish stage have favorable 5-year OS, PFS, and DMFS.

Impact of esthesioneuroblastoma treatment delays on overall patient survival.

To characterize clinical factors associated with esthesioneuroblastoma treatment delays and determine the impact of these delays on overall survival. Retrospective database analysis. The 2004-2016 National Cancer Database was queried for patients with esthesioneuroblastoma managed by primary surgery and adjuvant radiation. Durations of diagnosis-to-treatment initiation (DTI), diagnosis-to-treatment end (DTE), surgery-to-RT initiation (SRT), radiotherapy treatment (RTD), and total treatment package (TTP) were analyzed. The cohort was split into two groups for each delay interval using the median time as the threshold. A total of 814 patients (39.6% female, 88.5% white) with mean ± SD age of 52.6 ± 15.1 years who underwent both esthesioneuroblastoma surgery and adjuvant radiotherapy were queried. Median DTI, DTE, SRT, RTD, and TTP were 34, 140, 55, 45, and 101 days, respectively. A significant association was identified between increased regional radiation dose above 66 Gy and decreased DTI (OR=0.54, 95% CI 0.35-0.83, p=0.01) and increased RTD (OR=3.94, 95% CI 2.36-6.58, p < 0.001) durations. Chemotherapy administration was linked with decreased SRT (OR=0.64, 95% CI 0.47-0.89, p=0.01) and TTP (OR=0.59, 95% CI 0.43-0.82, p=0.001) durations. Cox proportional-hazards analysis revealed that increased RTD was associated with decreased survival (HR=1.80, 95% CI 1.26-2.57, p < 0.005), independent of age, sex, race, regional radiation dose, facility volume, facility type, insurance status, modified Kadish stage, chemotherapy status, Charlson-Deyo comorbidity index, and surgical margins. Delays during, and prolongation of radiotherapy for esthesioneuroblastoma appears to be associated with decreased survival. 4 Laryngoscope, 133:764-772, 2023.

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.

Exclusively endoscopic surgical resection of esthesioneuroblastoma: A systematic review.

BackgroundHistorically sinonasal malignancies were always addressed via open craniofacial surgery for an oncologic resection. Increasingly esthesioneuroblastomas are excised using an exclusively endoscopic approach, however, the rarity of this disease limits the availability of long‐term and large scale outcomes data.ObjectiveThe primary objective is to evaluate the treatment modalities used and the overall survival of patients with esthesioneuroblastoma managed with exclusively endoscopic surgery.MethodsIn accordance with PRISMA guidelines, PubMed was queried to identify studies describing outcomes associated with endoscopic management of esthesioneuroblastomas.ResultsForty‐four out of 2462 articles met inclusion criteria, totaling 399 patients with esthesioneuroblastoma treated with an exclusively endoscopic approach. Seventy‐two patients (18.0%) received adjuvant chemotherapy and 331 patients (83.0%) received postoperative radiation therapy. The average age was 50.6 years old (range 6–83). Of the 399 patients, 57 (16.6%) were Kadish stage A, 121 (35.2%) were Kadish stage B, 145 (42.2%) were Kadish stage C, and 21 (6.1%) were Kadish stage D. Pooled analysis demonstrated that 66.0% of patients had Hyams histologic Grade Ⅰ or Ⅱ, while 34.0% of patients had Grade Ⅲ or Ⅳ disease. Negative surgical margins were achieved in 86.9% of patients, and recurrence was identified in 10.3% of patients. Of those with 5‐year follow‐up, reported overall survival was 91.1%.ConclusionExclusively endoscopic surgery for esthesioneuroblastoma is performed for a wide range of disease stages and grades, and the majority of these patients are also treated with adjuvant chemotherapy or radiation therapy. Reported overall recurrence rate is 10.3% and 5‐year survival is 91.1%.

Olfactory Neuroblastoma: Surgical Treatment Experience of 42 Cases.

ObjectiveOur purpose was to estimate the safety and effectiveness of the endoscopic endonasal approach (EEA) in olfactory neuroblastoma (ONB) and determine whether preservation of the dura and olfactory bulb could be considered in selected patients.MethodsWe retrospectively reviewed patients diagnosed with ONBs between July 2010 and June 2021 at our institution, and collected data on demographic, disease stage, surgical approach, overall survival (OS), disease-free survival (DFS), and postoperative complications.ResultsThe study sample included 42 patients (8 treated for recurrence and 34 initial cases), 28 of which were men and 14 were women with a median age of 47.19 years. The mean duration from the beginning of treatment and follow-up time was 8.91 and 51 months, respectively. Among the 42 patients, 32 had unilateral lesions, and the rest had bilateral lesions. Patient symptoms were predominantly nasal, and four patients presented without any symptoms. The modified Kadish staging was A in three patients, B in 14 patients, C in 17 patients, and D in 8 patients. According to the preoperative examinations, five patients had cervical lymph node metastasis, and no patients had distant metastases. EEA was used in 38 patients, cranioendoscopic approach in 3, and open craniofacial approach in 1. The 5-year OS and DFS rates were 89.1 and 79.2%, respectively. The 2-year OS and DFS rates were both 89.1%. The overall surgical complication incidence was 9.52% (one cerebrospinal fluid rhinorrhea, one cervical hematoma, and two epileptic seizures).ConclusionThe present results support the importance of earlier treatment for advanced ONB and the fact that it is safe and efficacious to treat ONBs via EEA. The preservation of the dura can be considered for select patients—specifically those without skull base involvement and who underwent postoperative comprehensive therapy.

Computed Tomography and Magnetic Resonance Imaging of Preoperative Cases of Esthesioneuroblastoma (Olfactory Neuroblastoma): A Case Series

Esthesioneuroblastoma is an uncommon aggressive tumour arising from the olfactory epithelium of superior nasal cavity, frequently invading the base of cranium, cranial vault and orbit. Contrast enhanced Computed Tomography (CT) and contrast enhanced Magnetic Resonance Imaging (MRI) were done for three patients which showed modified Kadish stage C tumour. Biopsy was done to confirm the diagnosis and patients were subjected to surgery and radiotherapy. The purpose of this case series was to report the radiological features of esthesioneuroblastoma. This is a report on three cases of different age groups who presented tumour with intracranial extension which were histopathologically proven as esthesioneuroblastoma.

Clinicopathologic Features and Prognosis of Olfactory Neuroblastoma with Isocitrate Dehydrogenase 2 Mutations

Because of their rarity, it is not known whether isocitrate dehydrogenase 2 (IDH2) mutations are related to the occurrence of olfactory neuroblastoma (ONB). We investigated the relationships between IDH2 mutations, clinicopathological parameters, and the prognosis for ONB to establish a molecular classification using IDH2 mutations. An 82-patient cohort was retrospectively screened using immunohistochemistry with a mutation-specific IDH2 antibody and real-time polymerase chain reactions for IDH2 mutations. We also immunohistochemically determined the expression of chromogranin A, synaptophysin, neuron-specific enolase, CD56, S100, and Ki-67. The 2 methods used for the detection of IDH2 mutations had high consistency. Mutation of IDH2 detected by real-time polymerase chain reaction correlated with higher Kadish stage, Hyams grade, and Ki-67 proliferation index. Mutation of IDH2 correlated negatively with the expression of chromogranin A, synaptophysin, CD56, and S100. Kaplan-Meier analysis showed that an IDH2 mutation, a high Hyams grade, and high Ki-67 proliferation index were associated with poor overall survival. The Hyams grade and IDH2 mutation were independent prognostic factors on multivariable analysis. Immunohistochemistry was a reliable method to assess the mutation status of IDH2. Tumors with IDH2 mutations represented a distinct subset with aggressive behavior and conferred a poor prognosis. The gene status of IDH2 could be a major molecular classification criterion in ONB.

Long-Term Outcomes of Olfactory Neuroblastoma: MD Anderson Cancer Center Experience and Review of the Literature.

Olfactory neuroblastoma (ONB) is a rare sinonasal malignant neoplasm that is known to develop late recurrence. The aim of this study is to evaluate the long-term outcomes of patients with ONB and to determine the factors associated with prognosis. Retrospective study. A retrospective review of the medical records of 139 patients diagnosed with ONB at MD Anderson Cancer Center was performed between 1991 and 2016. Descriptive statistics were calculated, and Kaplan-Meier curves were utilized to assess survival. Median follow-up time was 75 months. Overall, 129 patients (92.8%) had surgery as part of their treatment and 82 (58.9%) patients received postoperative radiation therapy (PORT) or concurrent chemoradiotherapy. Endoscopic approaches were utilized for 72 patients, 69.4% of whom had pure endoscopic endonasal approaches. Five-year overall survival and disease-specific survival were 85.6% and 93.4%, respectively. Recurrence rate was 39.6% with a median time to recurrence of 42 months. Among the 31 patients who received elective nodal irradiation (ENI), two patients developed neck recurrence (6.4%) compared with 20 who developed neck recurrence when ENI was omitted (34.4%) (P=.003). Advanced Kadish stage, orbital invasion, intracranial invasion, and presence of cervical lymphadenopathy at the time of presentation were significantly associated with poor survival. ONB has an excellent survival. Surgical resection with PORT when indicated is the mainstay of treatment. Endoscopic approaches can be used as a good tool. Elective neck irradiation reduces the risk of nodal recurrence among patients with clinically N0 neck. Despite the excellent survival, recurrence rate remains high and delayed, highlighting the need for long-term surveillance. Level 4 Laryngoscope, 132:290-297, 2022.

Primary experience and discussion on the treatment of esthesioneuroblastoma

Objective: To summarize the preliminary experience in the treatment of esthesioneuroblastoma (ENB) and to explore the effect of age, chemotherapy, modified Kadish stage and pathological grade on the prognosis of ENB. Methods: The clinical data of 87 ENB patients from the First Affiliated Hospital of Sun Yat-sen University and Sun Yat-sen University Cancer Center between June 2002 and November 2017 were retrospectively analyzed. The modified Kadish stage was used to evaluate the extent of the lesions, and the Hyams grading system was used for pathological grading. The patients were followed up regularly to evaluate the recurrence and metastasis of the tumor. Cox proportional hazard model was used for univariate and multivariate analyses. Prognostic factors with P<0.05 in univariate analysis were included in multivariate analysis. After controlling the confounding factors, the model coefficients were used to calculate the hazard ratio (HR) and 95% confidence interval (CI). Results: The median follow-up time of ENB patients was 29 months, and the 5-year overall survival rate was 39.3%. In univariate analysis, age, chemotherapy, modified Kadish stage and pathology grade were independent predictors of overall survival, while gender, radiotherapy and surgery were not prognostic factors. Multivariate analysis showed that modified Kadish stage and pathology grade were independent predictors of overall survival rate after excluding confounding factors. Conclusions: Age, chemotherapy, modified Kadish stage and pathological grade are taking important role in the overall survival rate of patients with ENB. Modified Kadish stage and pathological grade are independent predictors of overall survival rate.

Elective neck irradiation in the management of esthesioneuroblastoma: a systematic review and meta-analysis

There is no consensus about the optimal management of the neck in clinically node negative esthesioneuroblastoma (ENB). The aim of this study is to assess the impact of elective neck irradiation (ENI) in terms of regional disease control and survival. The study was performed according to the PRISMA guidelines searching on Scopus, PubMed/MEDLINE, and Google Scholar databases. The primary outcome was the regional recurrence rate (RRR), that was reported as odds ratio (OR) and 95% confidence interval (CI). Secondary outcomes were the overall survival (OS), and the distant-metastases free survival (DMFS), that were reported as logarithm of the hazard ratios (logHRs) and 95% confidence intervals (CIs). A total of 489 clinically node negative patients were included from 9 retrospective studies. ENI significantly reduced the risk of regional recurrence compared to no treatment. No difference was measured between ENI and observation, according to both OS and DMFS. No stratified analysis could be performed based on Kadish stage and Hyams grade. ENI should be recommended to improve the regional disease control. No advantage was measured in terms of survival or distant metastases with a low quality of evidence. Further prospective studies should be designed to understand if ENI could be avoided in early stage and low-grade tumors.