Advanced Olfactory Neuroblastoma Research Articles

Survival Analysis and Prognostic Factors After Endonasal Resection of Advanced Olfactory Neuroblastomas: A Single Institution Experience.

To explore the prognostic factors in patients with advanced olfactory neuroblastoma (ONB) underwent endoscopic surgery. Retrospective medical records were reviewed of patients with pathologically proven ONB who underwent endoscopic surgical resection. Clinicopathological characteristics including patient demographics, treatment, complications, follow-up, and outcomes were analyzed. Kaplan-Meier overall survival (OS) and disease-free survival (DFS) curves were plotted. Univariate and multivariate Cox regression models were used to determine prognostic factors. Eighty-five patients with Kadish stage C ONB were examined. According to the various staging systems used, most patients harbored modified Kadish stage C (78.8%). Twenty-six patients (30.6%) underwent bony skull base resection, 11 (12.9%) underwent dura resection, and 24 (28.2%) underwent additional intracranial resection that included the olfactory bulb and duct. Median follow-up was 39 months. Five-year OS and DFS rates were 83.7% and 74.9%, respectively. Five-year OS was 100% in patients treated with bony skull base resection and 77.5% in those who were not (P = .052). Dura resection did not improve OS. Multivariate Cox regression analysis identified perioperative complications (P = .009), gross total resection (P = .004), orbital invasion (P = .014), postoperative radiotherapy (P = .030), and bony skull base resection (P = .019) as independent prognostic predictors. For patients with advanced ONB, endoscopic surgery in conjunction with radiotherapy and chemotherapy is effective and safe. Dura resection should be performed with caution in selected patients to balance survival and complications. Postoperative radiotherapy is important to improve OS and DFS.

Comparing the role of different treatment modalities in locoregionally advanced olfactory neuroblastoma: The 20-year clinical experience of a single institution.

The clinical value of different treatment modalities, especially systemic chemotherapy (CT) in patients with locoregionally advanced olfactory neuroblastoma (LA ONB) remains unclear. Patients with LA ONB from 2000 to 2020 at our center were collected retrospectively. The entire cohort was divided into combined systemic and local therapy (CSLT) versus local therapy (LT) groups (grouping method 1), and the same cohort was divided into neoadjuvant chemotherapy (NAC) versus non-NAC groups (grouping method 2). CSLT group included patients treated with CT + LT. LT group included patients treated with surgery (SG), radiotherapy (RT), concurrent chemoradiotherapy (CCRT), or any combination of the above methods. LT group was further divided into mono-modality local therapy (MOLT) group and multi-modality local therapy (MULT) group. MOLT group included patients treated with RT alone or SG alone. MULT group included patients treated with SG + RT/CCRT, or CCRT alone. NAC group included patients treated with NAC + LT ± adjuvant chemotherapy (ADC). Non-NAC group included patients who received LT ± ADC. A total of 111 patients with LA ONB were included. The median follow-up was 80.2 months (range, 2.1-254.9). The 5- and 10-year OS rates were 70.2% and 61.3%, respectively. In univariate analysis, patients treated with NAC (n = 43) had significantly better overall survival (OS) compared with those without NAC (n = 68) (p = 0.041). Patients in MULT group (n = 45) had significantly improved OS (p = 0.004) and PFS (p = 0.003) compared with those in MOLT group (n = 15). Multivariate analysis identified NAC and CSLT (n = 51) were independent prognostic factors for superior OS (p = 0.020, p = 0.046). Our study suggested that CSLT, especially a combination of NAC and LT, improved the survival of patients with LA ONB. Multiple treatment modalities yielded better PFS and OS compared to single-modality treatment.

Comparing the role of different treatment modalities in locoregionally advanced olfactory neuroblastoma: The 20-year clinical experience of a single institution.

e18055 Background: There are few studies on different treatment modalities, especially systemic chemotherapy (CT) for locoregionally advanced olfactory neuroblastoma (LA ONB) with only a few small-sample studies reported. We retrospectively analyzed the treatment patterns and explored the factors affecting the prognosis of patients with LA ONB at our center over the past 20 years in the present study. Methods: LA ONB patients from 2000 to 2020 at our center were collected retrospectively. The entire cohort was divided into combined systemic and local therapy (CSLT) vs. local therapy (LT) groups (grouping method 1), and the same cohort was divided into neoadjuvant chemotherapy (NAC) vs. non-NAC groups (grouping method 2). CSLT group included patients treated with CT + LT. LT group included patients treated with surgery (SG), radiotherapy (RT), concurrent chemoradiotherapy (CCRT), or any combination of the above methods. LT group was further divided into mono-modality local therapy (MOLT) group and multi-modality local therapy (MULT) group. MOLT group included patients treated with RT alone or SG alone. MULT group included patients treated with SG + RT/CCRT, or CCRT alone. NAC group included patients treated with NAC + LT ± adjuvant chemotherapy (ADC). Non-NAC group included patients who received LT ± ADC. Results: A total of 111 patients with LA ONB were included. The median age was 40 (range, 10–82) years old. The median follow-up duration for the entire cohort was 80.2 (range, 2.1-254.9) months, while 88.5 (range, 4.0-240.7) months for the CSLT group, 77.2 (range, 2.1-254.9) months for the LT group, 86.0 (range, 4.0-240.7) months for the NAC group, and 78.7 (range, 2.1-254.9) months for the non-NAC group. Thirty-five patients (31.5%) died, among which 30 patients died of tumor progression, 3 patients died of other diseases, and 2 patients’ causes of death were not available. The estimated 5-year overall survival (OS), progression-free survival (PFS), local recurrence-free survival (LRFS) and distant metastasis-free survival (DMFS) rates for the entire cohort (n = 111) were 70.2%, 53.1%, 73.6%, and 74.1%, respectively. The estimated 10-year OS, PFS, LRFS, and DMFS rates were 61.3%, 37.7%, 60.1%, and 68.0%, respectively. In univariate analysis, patients treated with NAC (n = 43) had significantly better overall survival (OS) compared with those without NAC (n = 68) ( P = 0.041). Patients in MULT group (n = 45) had significantly improved OS ( P = 0.004) and PFS ( P = 0.003) compared with those in MOLT group (n = 15). Multivariate analysis identified NAC and CSLT (n = 51) were independent prognostic factors for superior OS ( P = 0.020; P = 0.046). Conclusions: Our study suggested that CSLT, especially a combination of NAC and LT, improved the survival of patients with LA ONB. Multiple treatment modalities yielded better PFS and OS compared to single modality treatment.

Neoadjuvant chemotherapy in the treatment of locally advanced olfactory neuroblastoma in 25 cases

Objective: To evaluate the efficacy of neoadjuvant chemotherapy (NACT) in the treatment of locally advanced olfactory neuroblastoma (ONB), and to explore the factors related to the efficacy of NACT. Methods: A total of 25 patients with ONB who underwent NACT in Beijing TongRen Hospital from April 2017 to July 2022 were retrospectively analyzed. There were 16 males and 9 females, with an average age of 44.9 years (ranged 26-72 years). There were 22 cases of Kadish stage C and 3 cases of stage D. After multiple disciplinary team(MDT) discussion, all patients were treated sequentially with NACT-surgery-radiotherapy. Among them, 17 cases were treated with taxol, cis-platinum and etoposide (TEP), 4 cases with taxol, nedaplatin and ifosfamide (TPI), 3 cases with TP, while 1 case with EP. SPSS 25.0 software was used for statistical analysis, and survival analyses were calculated based on the Kaplan-Meier method. Results: The overall response rate of NACT was 32% (8/25). Subsequently, 21 patients underwent extended endoscopic surgery and 4 patients underwent combined cranial-nasal approach. Three patients with stage D disease underwent cervical lymph node dissection. All patients received postoperative radiotherapy. The mean follow-up time was 44.2 months (ranged 6-67 months). The 5-year overall survival rate was 100.0%, and the 5-year disease-free survival rates was 94.4%. Before NACT, Ki-67 index was 60% (50%, 90%), while Ki-67 index was 20% (3%, 30%) after chemotherapy [M (Q1, Q3)]. The change of Ki-67 before and after NACT was statistically significant (Z=-24.24, P<0.05). The effects of age, gender, history of surgery, Hyams grade, Ki-67 index and chemotherapy regimen to NACT were analyzed. Ki-67 index≥25% and high Hyams grade were related to the efficacy of NACT (all P<0.05). Conclusions: NACT could reduce Ki-67 index in ONBs. High Ki-67 index and Hyams grade are clinical indicators sensitive to the efficacy of NACT. NACT-surgery-radiotherapy is effective for patients with locally advanced ONB.

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.

Chemo-radiotherapy for olfactory neuroblastoma: cases report and literature review

A 48-year-old female patient diagnosed as olfactory neuroblastoma was treated by radiotherapy 70 Gy in 35 fractions (2 Gy per fraction) to right nasal mass, right ethmoid sinus mass, bilateral upper 2/3 neck lymphadenopathy in 2010, and concurrent intravenous Cisplatin 30 mg/m 2 for one course. Tumor was gradually decreased in size without recurrence for 9 years. The second case was a 38-year-old male patient treated with induction chemotherapy by intravenous Etoposide + carboplatin for 4 courses during March to May in 2011 and followed by radiotherapy 70 Gy in 35 fractions (2 Gy per fraction) to ethmoid mass & bilateral level IIa lymphadenopathy during June to August in 2011. He was disease free without recurrence for 8 years. These two cases demonstrated that definitive chemo-radiotherapy would be an alternative treatment option for locally advanced olfactory neuroblastoma. They received definitive chemo-radiotherapy and experienced good local control without recurrence for more than 8 years. However, the further study for optimal regimen of chemotherapy is warranted.

Outcomes for olfactory neuroblastoma treated with induction chemotherapy

Oncologic outcomes for induction chemotherapy and its role in patients with advanced olfactory neuroblastoma (ONB) remain unclear. A retrospective review of 15 consecutive patients with extensive local invasion and/or nodal disease treated with induction chemotherapy with curative intent followed by definitive local therapy. The majority of patients were treated with cisplatin and etoposide. The response to chemotherapy was 68% (10/15). Response was 78% (7/9) in the high Hyams high-grade group and 50% (3/6) in the Hyams low-grade group. Seven patients had complete response (CR) and 3 patients were able to avoid orbital exenteration. The 5-year disease-free survival (DFS) and overall survival (OS) were 71% and 78%, respectively, with a trend toward improved survival in patients with CR. ONB is a chemosensitive tumor and induction chemotherapy is an acceptable strategy for aggressive and locoregional advanced disease. Hyams grade may predict chemosensitivity and CR may be associated with improved survival.

Esthesioneuroblastoma chemotherapy and radiotherapy for extensive disease: a case report

Malignant tumors of the nasal cavity are rare. We report the case of a 48 years old man who consulted us with a 2-year history of progressive nasal obstruction, occasional epistaxis, facial pain, and watering of the eyes. A diagnosis of olfactory neuroblastoma was established by histopathology and confirmed by immunohistochemistry. On staging, the mass was classified as a Kadish stage C tumor with extensive involvement of the nasal cavities, nasopharynx, paranasal sinuses and orbit. Endoscopic excision of the mass was done. Traditionally the mainstay of treatment in such locally advanced patients is craniofacial resection followed by adjuvant radiotherapy. Our patient was treated with limited surgery and chemoradiation. Patient is free of recurrence at a follow-up of 5 years. This case report demonstrates the potential efficacy of planned combined modality therapy, including limited surgery and early chemoradiation in the control of locally advanced olfactory neuroblastoma.

Neoadjuvant chemotherapy in the setting of locally advanced olfactory neuroblastoma with intracranial extension

Olfactory neuroblastoma (esthesioneuroblastoma) is a rare malignant tumor of neuroectodermal origin. With only about 1,000 cases reported, there are no clear guidelines regarding management of this disease. Intracranial extension and orbital involvement have been shown to be independent risk factors associated with poorer outcomes. We hereby report a case of a 46-year old male presented with an 8-month history of progressive nasal obstruction and intermittent right-sided epistaxis associated with anosmia and increased pressure sensation in and around the right eye. Further evaluation revealed a large enhancing heterogeneous cystic and solid mass in the right nasal cavity measuring 5.0×5.3×4.6 cm with extension superiorly into the anterior cranial fossa and frontal lobes, ethmoid and sphenoid sinuses. A biopsy of this mass confirmed high grade olfactory neuroblastoma. Because of the intra-cranial extension, a decision was made to start neoadjuvant chemotherapy with cisplatin and etoposide. The patient had very good response to this treatment on a repeat imaging study and went on to have resection of this mass. Post-operatively, he received radiation therapy to the tumor bed and 2 more cycles of chemotherapy. He has been followed now for more than 8 months with no evidence of disease recurrence.

Advanced olfactory neuroblastoma treated with combined conventional and hypofractionated stereotactic radiotherapy

Three patients with olfactory neuroblastoma (ONB) of the nasal and/or paranasal cavity were treated with a combination of conventional radiotherapy (RT) and hypofractionated stereotactic radiation therapy (SRT). Radiation doses of 30 to 50 Gy were delivered in 12 to 25 fractions using conventional RT, and then an additional 20 to 25 Gy was delivered in 5 fractions using SRT. Follow-up time was 42, 53, 65 months, three patients were alive, and local control was obtained in all, complete response (CR) in 2 and partial response (PR) in 1. Two patients had recurrence out of the radiation field and received salvage therapy. According to the Radiation Therapy Oncology Group (RTOG) acute/late radiation morbidity scoring criteria, there were no adverse effects of grade 3 or higher. The combined treatment with conventional RT and hypofractionated SRT achieved excellent local control without serious adverse effects.

P.312 Craniofacial resection and immediate reconstruction in a young female with advanced olfactory neuroblastoma: a clinical case

P.312 Craniofacial resection and immediate reconstruction in a young female with advanced olfactory neuroblastoma: a clinical case

Nonplatinum‐based chemotherapy with irinotecan plus docetaxel for advanced or metastatic olfactory neuroblastoma

The efficacy and safety of chemotherapy with irinotecan plus docetaxel were retrospectively evaluated for olfactory neuroblastoma. Twelve patients with histologically proven advanced or metastatic olfactory neuroblastoma were treated with chemotherapy with irinotecan plus docetaxel at the study institution between 2001 and 2005. Of these, 7 patients with locoregional disease and no prior radiotherapy received irinotecan plus docetaxel followed by definitive radiotherapy, 1 with photon radiotherapy and 6 with proton radiotherapy, whereas 3 patients with distant metastases and 2 with locoregional disease who had received prior radiotherapy received irinotecan plus docetaxel only. The most common toxicities of >or=grade 3 among the 12 patients receiving irinotecan plus docetaxel were leukopenia (33%), neutropenia (50%), febrile neutropenia (8%), and diarrhea (25%), all of which were manageable. Partial response was achieved in 3 patients, giving an overall response rate of 25%. The response rate was higher in patients aged <50 years (3 of 4 patients) compared with those aged >50 years (0 of 8 patients) (P = .018). With a median follow-up period of 22.2 months, the median progression-free survival and overall survival were 13.6 months and 36.6 months, respectively. Of the 7 patients with locoregional disease also receiving definitive radiotherapy, the 2-year survival rate was 100% and 6 patients were alive at the time of last follow-up. Chemotherapy for olfactory neuroblastoma with irinotecan plus docetaxel is safe and manageable. Patients aged <50 years may be sensitive to chemotherapy. Induction chemotherapy followed by definitive radiotherapy may represent a promising option for patients with locally advanced olfactory neuroblastoma.

Results of salvage therapy after failure of initial treatment for advanced olfactory neuroblastoma

Olfactory neuroblastoma is a very aggressive tumour with high rates of locoregional recurrence and distant metastasis. Therefore, salvage therapy plays an important role in control of these neoplasms. In this study, we present our experience and treatment outcomes for salvage therapy in patients with recurrent olfactory neuroblastoma. We retrospectively analysed 17 patients treated for advanced olfactory neuroblastoma during the last 15 years. The disease-free 5-year survival rate was 48% in all patients and 42% in the 17 patients with recurrence or distant metastasis. Salvage therapy was performed in 6 of 8 patients with recurrence or metastasis and proved successful in 50% of them. In the patients with locoregional recurrence, the success rate of salvage radiotherapy plus neck dissection was superior to salvage chemotherapy alone. In addition, 17% of the patients with distant metastasis after initial treatment died after salvage therapy. In 15% of patients with a clinical stage N0 at initial diagnosis, nodal recurrence developed and was successfully treated with salvage therapy. Complete surgical resection, including craniofacial resection and postoperative radiotherapy without elective neck dissection, is the preferred approach in the treatment of advanced olfactory neuroblastoma. In locoregional recurrence, successful salvage therapy may include selective neck dissection and radiotherapy, but in cases of distant metastasis, the prognosis was poor.

Surgical treatment versus concurrent chemoradiotherapy as an initial treatment modality in advanced olfactory neuroblastoma

Objective Olfactory neuroblastomas are very aggressive tumors with a high locoregional recurrence rate and distant metastasis. Surgical treatment, including craniofacial resection, has been the main treatment modality, but treatment outcomes of concurrent chemoradiotherapy remain unclear. We present our experiences regarding the treatment outcome of patients with advanced olfactory neuroblastoma undergoing surgical treatment and concurrent chemoradiotherapy. Methods We retrospectively analyzed 16 patients treated for advanced olfactory neuroblastoma within the past 10 years. Results The disease-free 5-year survival rate of the patients ( n = 10) who underwent surgical treatment was 68%. The survival rate for patients ( n = 6) who received concurrent chemoradiotherapy was 42%. The difference in the survival rate was not statistically significant, and no difference in the recurrence rate between the two groups. In the group having surgical treatment, post-operative radiotherapy and salvage therapy were important to increase the survival rate. In the group having concurrent chemoradiotherapy, no patient experienced primary tumor progression. Conclusion Complete surgical resection, including craniofacial resection (CFR), and post-operative radiotherapy seem to be essential in the treatment of advanced olfactory neuroblastoma. However, concurrent chemoradiotherapy may be another primary treatment modality.