Real world data on long term outcome of neoadjuvant chemotherapy in locally advanced esthesioneuroblastoma and sinonasal tumor with neuroendocrine differentiation - Results from a single centre study.

INTRODUCTION: Esthesioneuroblastoma and sinonasal neuroendocrine carcinoma (SNEC) are the most common histological subtypes of non-squamous Sinonasal Tumors. A multidisciplinary approach is preferred for locally advanced unresectable esthesioneuroblastoma and SNEC. METHODS: From June 2010 to October 2021, 59 patients with esthesioneuroblastoma and SNEC received NACT. NACT consists of 2-3 cycles of Etoposide-Platinum based chemotherapy. Depending upon response and performance status, subsequent therapy was planned. SPSS descriptive statistics were performed for analysis. Kaplan Meir methods were used for the estimation of Progression Free Survival (PFS) and Overall Survival (OS). RESULTS: 45 (76.3 %) Esthesioneuroblastoma and 14 (23.7 %) SNEC patients received NACT. The median age of the population was 45 years (range 20-81 years). The majority of patients received 2-3 cycles of Platinum (Cisplatin or Carboplatin) + Etoposide as NACT. 28 patients (47.5%) underwent surgery and 20 patients (33.9%) received definitive chemoradiotherapy after NACT. The most common grade 3 or above adverse events were anemia (13.6%), neutropenia (27.1), and hyponatremia (45.8%). At the time of analysis, the median PFS was 56 months (95% CI 31 months to 77 months), and the median OS was 70 months (95% CI 56 months to 86 months). The most common late toxicities noticed were metabolic syndrome (42.4%), hyperglycemia (39%), nasal bleeding (33.9%), hypertension (17%), dyslipidemia (8.5%), and hypothyroidism (5.1%). CONCLUSION: The study shows that NACT is safe, and can be easily delivered without any life-threatening toxicities, with a favorable response and improved survival in this subset of patients.

An exceptionally rare case of Cushing's syndrome caused by ectopic ACTH syndrome due to olfactory neuroblastoma in childhood.

OBJECTIVES: Ectopic adrenocorticotropic hormone secretion/syndrome (EAS) is caused by excess secretion of ACTH leading to hypercortisolism by non-pituitary, commonly malignant origins. We present a rare case of esthesioneuroblastoma (ENB) complicated by EAS in the follow-up period. CASE PRESENTATION: A child presented with nasal obstruction at the age of 10 months. Polypoid mass obstructing the right nasal passage was detected. Magnetic resonance imaging (MRI) showed a lesion limited within the nasal cavity. The lesion was completely removed by nasal endoscopic surgery. The pathologic examination revealed a diagnosis of esthesioneuroblastoma. It was confined to the nasal cavity so chemotherapy/radiotherapy was not administered and began to follow up. At 28 months of age, he presented with rapid weight gain. Laboratory data were consistent with Cushing's syndrome (CS). High-dose dexamethasone suppression test and imaging studies led us to think of ectopic ACTH syndrome originated from ENB relapse. After partial resection of the tumor, ketoconazole treatment was started along with chemotherapy. Hypercortisolemia was kept under control with ketoconazole treatment as long as the treatment was maintained. CONCLUSIONS: Cushing syndrome is a rare endocrine disorder. Adrenal sources of hypercortisolism and ectopic sources of ACTH overproduction should be investigated especially in young children.

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

OBJECTIVES: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: The pretreatment ADCmean value, Ki-67 index and Kadish stage have the potential to predict the response to NACT in advanced ONB patients. ADVANCES IN KNOWLEDGE: 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.

Electrochemotherapy for the palliative management of non-skin-origin head and neck cancer: case series and UK national survey.

OBJECTIVES: Electrochemotherapy uses electric fields to facilitate the influx of chemotherapy into cancer cells, producing a targeted effect. For head and neck cancer, it is mainly used for palliation of non-skin-origin metastases. It is used infrequently in the UK. This paper presents our experience and a UK survey to identify its frequency of use. METHODS: Between 2016 and 2019, a prospective database was created and reviewed. Only patients with non-skin-origin metastatic head and neck cancer, with no other palliative options, were included. Survival length, complications and symptomatic benefit were assessed. The survey was conducted via e-mail. RESULTS: Five patients were included: three with squamous cell carcinoma, one with esthesioneuroblastoma and one with hepatocellular carcinoma. Survival ranged from 1 month to over 20 months. Minor complications were seen. Only 15 out of 69 UK head and neck multidisciplinary teams offer electrochemotherapy. CONCLUSION: Electrochemotherapy is a well-tolerated adjunct to standard palliation of metastatic head and neck cancer, and is offered by a limited number of UK multidisciplinary teams.

Characteristics and overall survival in pediatric versus adult esthesioneuroblastoma: A population-based study.

BACKGROUND: Esthesioneuroblastoma (ENB) is an uncommon sinonasal malignancy and is even less common in the pediatric population. OBJECTIVE: The purpose of this study is to compare characteristics and outcomes of ENB between adult and pediatric patients. METHODS: The National Cancer Database was queried for patients with histologically proven ENB of the nasal cavity and paranasal sinuses, and then baseline characteristics, treatment, and survival data compared between the pediatric (age < 18 years) and adult (age ≥ 18 years) populations. RESULTS: 1411 patients were identified, with 45 in the pediatric cohort and 1366 in the adult cohort. Ten-year overall survival (OS) in the pediatric cohort was improved compared to the adult cohort, 87% and 66%, respectively (p < 0.05). Adjuvant chemotherapy was more commonly utilized in the pediatric cohort (p < 0.001). Race was associated with decreased OS in the pediatric cohort (p = 0.013). Pediatric patients had shorter length of stay (p = 0.009) and lived closer to their provider (p = 0.044) than adult ENB patients. CONCLUSION: Treatment of ENB in pediatric patients more commonly includes chemotherapy and more commonly occurs at academic medical centers. OS is improved in pediatric ENB compared to adults as well, but larger studies are necessary.

Prognostic factors and outcomes of multimodality treatment in olfactory neuroblastoma.

OBJECTIVE: The clinical data on olfactory neuroblastomas (ONBs) are scarce owing to their rarity. This study aimed to assess the potential prognostic factors, outcomes, and optimal treatment strategies in patients with ONB. METHODS AND MATERIALS: The data of 217 patients with ONB between 1991 and 2019 were retrospectively reviewed. Long-term survival, potential prognostic factors, and outcomes with combined treatment strategies were analyzed. RESULTS: All patients received radiotherapy (RT); 185 patients underwent surgery, and 139 patients received chemotherapy. The 5-year overall survival (OS), progression-free survival (PFS), locoregional failure-free survival (LRFS), and distant metastasis-free survival (DMFS) of the entire cohort were 80.0%, 79.0%, 79.3%, and 80%, respectively. On univariate analyses, R0/R1 resection, early Kadish stage, negative lymph nodes, absence of orbital invasion, and administration of surgery with RT were found to be favorable factors. Conversely, combined sequential treatment with surgery, RT, and chemotherapy was not associated with survival. Multivariate analysis demonstrated lymph node status, orbital invasion, and the combination of surgery and RT to be independent prognostic factors. CONCLUSIONS: Patients with ONB, who had lymph node metastases, orbital invasion diseases, advanced Kadish stages, R2 resection margins, and received RT alone, had poor outcomes. Combined administration of surgery and RT may be a potentially useful strategy in patients with advanced Kadish stages; the role of chemotherapy in these stages requires further evaluation.

Extensive tumor calcification in response to pre-operative reductive chemotherapy in pediatric esthesioneuroblastoma: a case report.

Esthesioneuroblastomas are uncommon tumors in pediatric patients and are typically treated with multimodal therapy. Changes in gross tumor quality and character in response to adjuvant treatment have not been clearly reported. We report the case of a 15-year-old female with a diagnosis of Kadish stage C esthesioneuroblastoma who was treated with neoadjuvant chemotherapy and surgical resection. The patient's tumor demonstrated cytoreduction after chemotherapy but also was found to have calcified. A combined trans-frontal sinus craniotomy with endoscopic endonasal resection was performed and resulted in negative margins and good clinical outcome.

Chemotherapy in Esthesioneuroblastoma/Olfactory Neuroblastoma: An Analysis of the Surveillance Epidemiology and End Results (SEER) 1973-2015 Database.

OBJECTIVE: Chemotherapy has been proposed as an adjunct to primary local therapy in esthesioneuroblastoma (ENB)/olfactory neuroblastoma (ON), but its role has not been precisely defined. Here, we evaluated its role in ENB treatment. MATERIALS AND METHODS: The Surveillance Epidemiology and End Results (SEER) database was queried for ENB/ON (International Classification of Diseases-3 9522). Cases met criteria for inclusion if they were unique, had a primary location in the nasal cavity, and had adequate information for Kadish staging derivation. Univariable and multivariable Cox analyses assessed chemotherapy treatment effect on disease-specific survival (DSS) and overall survival (OS). Multiple imputation addressed missing data. A P<0.05 was designated for statistical significance. RESULTS: In adjusted multivariable analyses, chemotherapy treatment was associated with inferior DSS (hazard ratio [HR], 1.74; 95% confidence interval [CI], 1.21-2.51; P=0.003) and OS (HR, 1.71; 95% CI, 1.26-2.32; P=0.001). Among the subset with local or regional disease treated with surgery and/or radiation therapy, chemotherapy remained associated with inferior outcomes DSS (HR, 2.78; 95% CI, 1.63-4.74; P<0.001) and OS (HR, 2.18; 95% CI, 1.45-3.27; P<0.001). Chemotherapy treatment misclassification did not explain these findings. CONCLUSIONS: This analysis does not support chemotherapy to improve either DSS or OS in primary ENB/ON treatment, after controlling for known ENB prognostic factors available from SEER. Other prognostic and treatment selection factors could exist which were not controlled in these analyses. Chemotherapy could beneficially affect outcomes other than DSS or OS. Although the concerns have been expressed regarding chemotherapy treatment misclassification in SEER, their analyses did not identify such misclassification as an explanation for our findings.

Utility of adjuvant chemotherapy in patients receiving surgery and adjuvant radiotherapy for primary treatment of esthesioneuroblastoma.

BACKGROUND: Past research established that surgery plus adjuvant radiotherapy (S + AR) improves overall survival (OS) in esthesioneuroblastoma (ENB). However, it is unknown if the addition of adjuvant chemotherapy (AC) further improves survival. The primary objective of this study was to compare survival among patients treated with S + AR alone to patients who underwent S + AR + AC. METHODS: Retrospective review of patient records. RESULTS: Thirty-eight patients met inclusion criteria for either S + AR or S + AR + AC treatment groups. The S + AR + AC group contained more patients with Kadish stage D disease, dural invasion, and positive histologic margins postsurgery. All S + AR + AC patients received platinum-based regimens, combined with etoposide in 67%. OS and recurrence-free survival did not differ between the two groups, even when restricting the analysis to patients with Kadish stages B and C disease. CONCLUSION: Patients who received platinum-based AC did not exhibit improved survival compared to S + AR alone. Further investigation, preferably prospective, into the optimal use of systemic therapy in ENB is warranted.

Ectopic adrenocorticotropic hormone syndrome associated with olfactory neuroblastoma: acquirement of adrenocorticotropic hormone expression during disease course as shown by serial immunohistochemistry examinations.

Ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS) is a condition of endogenous hypercortisolism sustained by an extrapituitary ACTH-secreting tumor. Olfactory neuroblastoma (ONB) is a rare malignant neoplasm of the sinonasal tract and is derived from the olfactory epithelium. Because the paranasal sinus is not a common site of EAS, the development of ONB in patients with EAS is rare. We herein report the first known case of ONB with acquirement of ACTH production during the clinical course as proven by immunohistochemistry. A 50-year-old man diagnosed with ONB was referred to our department in July 2015 because of hypokalemia, hyperglycemia, decreased eosinophil and granulocyte counts, and elevated serum levels of ACTH and cortisol. Although two previous ONB biopsy specimens (2011 and 2014) showed no ACTH immunoreactivity, a newly obtained specimen in August 2015 clearly showed ACTH immunoreactivity. This is the first case of ectopic ACTH syndrome associated with an ONB that acquired the ability to express ACTH during its clinical course as shown by serial immunohistochemical examinations.

Importance of neoadjuvant chemotherapy in olfactory neuroblastoma treatment: Series report and literature review / Importancia de la quimioterapia neoadyuvante en el tratamiento del neuroblastoma olfatorio: serie de casos y revisión de la literatura

INTRODUCTION AND OBJECTIVES: Olfactory neuroblastoma (ONB) is a rare entity that constitutes less than 5% of nasosinusal malignancies. Mainstream treatment consists in surgical resection+/-adjuvant radiotherapy. By exposing results observed with apparition of new therapeutic options as neoadjuvant chemotherapy, the objective is to evaluate a series and a review of the current literature. METHODS: A retrospective review was conducted including patients diagnosed and followed-up for ONB from 2008 to 2015 in our institution. RESULTS: 9 patients were included. Mean follow-up of 52.5 months (range 10-107). Kadish stage: A, 1 patient (11.1%) treated with endoscopic surgery; B, 2 patients (22.2%) treated with endoscopic surgery (one of them received adjuvant radiotherapy); C, 6 patients (66.7%), 4 patients presented intracranial extension and were treated with neoadjuvant chemotherapy followed by surgery and radiotherapy. The other 2 patients presented isolated orbital extension, treated with radical surgery (endoscopic or craniofacial resection) plus radiotherapy. The 5-year disease free and overall survival observed was 88.9%. CONCLUSION: Neoadjuvant chemotherapy could be an effective treatment for tumor reduction, improving surgical resection and reducing its complications

INTRODUCCIÓN Y OBJETIVOS: Elneuroblastoma olfatorio es una entidad rara que se corresponde con menos del 5% de las neoplasias nasosinusales. El tratamiento principal consiste en la resección quirúrgica ± radioterapia adyuvante. El objetivo es evaluar la sobrevida en una serie de casos y la literatura actual, mostrando resultados observados con la aparición de nuevas opciones terapéuticas como la quimioterapia neoadyuvante. MÉTODOS: Se realizó un estudio retrospectivo incluyendo pacientes tratados y seguidos en nuestro centro desde 2008 a 2015. RESULTADOS: Dentro del estudio fueron incluidos 9 pacientes. El seguimiento medio fue de 52,5 meses (rango 10-107). Estadio Kadish: A) un paciente (11,1%) fue tratado con resección endoscópica; B) 2 pacientes (22,2%) tratados con resección endoscópica (uno de ellos recibió radioterapia adyuvante); C) 6 pacientes (66,7%), de los cuales 4 presentaron extensión intracraneal y fueron tratados con quimioterapia neoadyuvante, cirugía y radioterapia adyuvante. Los otros 2 pacientes presentaron invasión intraorbitaria aislada, tratados con cirugía radical y radioterapia adyuvante. La sobrevida y periodo libre de enfermedad a 5 años fue del 88,9%. CONCLUSIÓN: La quimioterapia neoadyuvante puede ser un tratamiento efectivo para la reducción del tamaño tumoral, mejorando la resección quirúrgica y reduciendo sus complicaciones

Importance of neoadjuvant chemotherapy in olfactory neuroblastoma treatment: Series report and literature review.

INTRODUCTION AND OBJECTIVES: Olfactory neuroblastoma (ONB) is a rare entity that constitutes less than 5% of nasosinusal malignancies. Mainstream treatment consists in surgical resection+/-adjuvant radiotherapy. By exposing results observed with apparition of new therapeutic options as neoadjuvant chemotherapy, the objective is to evaluate a series and a review of the current literature. METHODS: A retrospective review was conducted including patients diagnosed and followed-up for ONB from 2008 to 2015 in our institution. RESULTS: 9 patients were included. Mean follow-up of 52.5 months (range 10-107). Kadish stage: A, 1 patient (11.1%) treated with endoscopic surgery; B, 2 patients (22.2%) treated with endoscopic surgery (one of them received adjuvant radiotherapy); C, 6 patients (66.7%), 4 patients presented intracranial extension and were treated with neoadjuvant chemotherapy followed by surgery and radiotherapy. The other 2 patients presented isolated orbital extension, treated with radical surgery (endoscopic or craniofacial resection) plus radiotherapy. The 5-year disease free and overall survival observed was 88.9%. CONCLUSION: Neoadjuvant chemotherapy could be an effective treatment for tumor reduction, improving surgical resection and reducing its complications.

Outcomes for olfactory neuroblastoma treated with induction chemotherapy.

BACKGROUND: Oncologic outcomes for induction chemotherapy and its role in patients with advanced olfactory neuroblastoma (ONB) remain unclear. METHODS: 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. RESULTS: 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. CONCLUSION: 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: A single institution's experience and general literature review]. / Esthésioneuroblastome : étude rétrospective et revue de la littérature.

PURPOSE: Olfactory neuroblastoma or esthesioneuroblastoma is a rare entity among head and neck neoplasms. In this paper, we report the experience of our institution and compare it with a comprehensive review of the literature. PATIENTS AND METHODS: We retrospectively analysed clinical and treatment data of patients referred to the Lyon Sud University Hospital (France) for histologically proven olfactive esthesioneuroblastoma. RESULTS: Ten patients treated between 1993 and 2015 have been analysed. Disease stage at diagnosis, according to the Kadish staging system, was C in 90% of cases. Median follow-up was 136 months. Ten-year overall survival was 90%. Five- and ten-year progression-free survival were 70% and 50%. Nine patients (90%) underwent surgical resection first. Seven of the nine patients who underwent resection (77%) received adjuvant three-dimensional (3D)-conformal radiotherapy (n=7), intensity-modulated radiotherapy (n=1), or volumetric arctherapy (n=1). The mean dose to the tumour volume was 61Gy. None of the patients received elective nodal irradiation. Two patients received concurrent chemotherapy. Five patients (50%) presented with disease recurrence, which was local (n=1), nodal (n=2) and cerebral (n=2). CONCLUSION: Our results are consistent with the literature. Because of the lack of prospective study and the low number of cases in the literature, each institution's experience is of the utmost important to improve standardised management of these tumours.

Outcomes of Sinonasal Cancer Treated With Proton Therapy.

PURPOSE: To report disease outcomes after proton therapy (PT) for sinonasal cancer. METHODS AND MATERIALS: Eighty-four adult patients without metastases received primary (13%) or adjuvant (87%) PT for sinonasal cancers (excluding melanoma, sarcoma, and lymphoma). Common histologies were olfactory neuroblastoma (23%), squamous cell carcinoma (22%), and adenoid cystic carcinoma (17%). Advanced stage (T3 in 25% and T4 in 69%) and high-grade histology (51%) were common. Surgical procedures included endoscopic resection alone (45%), endoscopic resection with craniotomy (12%), or open resection (30%). Gross residual disease was present in 26% of patients. Most patients received hyperfractionated PT (1.2 Gy [relative biological effectiveness (RBE)] twice daily, 99%) and chemotherapy (75%). The median PT dose was 73.8 Gy (RBE), with 85% of patients receiving more than 70 Gy (RBE). Prognostic factors were analyzed using Kaplan-Meier analysis and proportional hazards regression for multiple regression. Dosimetric parameters were evaluated using logistic regression. Serious, late grade 3 or higher toxicity was reported using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4. The median follow-up was 2.4 years for all patients and 2.7 years among living patients. RESULTS: The local control (LC), neck control, freedom from distant metastasis, disease-free survival, cause-specific survival, and overall survival rates were 83%, 94%, 73%, 63%, 70%, and 68%, respectively, at 3 years. Gross total resection and PT resulted in a 90% 3-year LC rate. The 3-year LC rate was 61% for primary radiation therapy and 59% for patients with gross disease. Gross disease was the only significant factor for LC on multivariate analysis, whereas grade and continuous LC were prognostic for overall survival. Six of 12 local recurrences were marginal. Dural dissemination represented 26% of distant recurrences. Late toxicity occurred in 24% of patients (with grade 3 or higher unilateral vision loss in 2%). CONCLUSIONS: Dose-intensified, hyperfractionated PT with or without concurrent chemotherapy results in excellent LC after gross total resection, and results in patients with gross disease are encouraging. Patients with high-grade histology are at greater risk of death from distant dissemination. Continuous LC is a major determinant of survival justifying aggressive local therapy in nearly all cases.

Multimodality Treatment of Pediatric Esthesioneuroblastoma.

BACKGROUND: Esthesioneuroblastoma (ENB) is a rare cancer of the nasal cavity in children. Radical surgery followed by postoperative radiation is considered the standard of care in adults. A similar approach in children can lead to significant long-term morbidity. PROCEDURE: A retrospective multi-institutional review of patients less than 21 years of age diagnosed with ENB between 1990 and 2014 was performed. Clinical features, treatment, and outcome were obtained from the medical records. RESULTS: Twenty-four patients were identified with a median age of 14 years (range 0.6-20 years) at diagnosis. The majority (75%) were females. Headache was the most common presenting symptom, followed by nasal obstruction and epistaxis. Eight patients had Kadish stage B tumors and 16 had Kadish stage C tumors. Nine patients had metastatic disease. Gross total resection was achieved at diagnosis in eight patients and after neoadjuvant chemotherapy in four patients. Twenty-one patients received radiation therapy (45-68.4 Gy). Thirteen patients received neoadjuvant chemotherapy with 84% objective response rate. Seven patients experienced disease progression or relapse-five in central nervous system, one local, and one in cervical lymph node. Fifteen patients were alive at the last follow-up. The 5-year disease-free survival and overall survival were 74% and 73%, respectively. Late effects were observed in 78% of long-term survivors. Four patients developed subsequent malignant neoplasms. CONCLUSIONS: Pediatric ENB is a chemosensitive disease. Preoperative chemotherapy-based multimodal approach should be used in patients with advanced stage disease. Radiation therapy is effective for local control, but lower doses should be considered in children.

The role of systemic therapy in the management of sinonasal cancer: A critical review.

PURPOSE: Due to the rarity and the variety of histological types of sinonasal cancers, there is a paucity of data regarding strategy for their optimal treatment. Generally, outcomes of advanced and higher grade tumors remain unsatisfactory, despite the employment of sophisticated surgical approaches, technical advances in radiation techniques and the use of heavy ion particles. In this context, we critically evaluated the role of systemic therapy as part of a multidisciplinary approach to locally advanced disease. RESULTS: Induction chemotherapy has shown encouraging activity and could have a role in the multimodal treatment of patients with advanced sinonasal tumors. For epithelial tumors, the most frequently employed chemotherapy is cisplatin, in combination with either 5-fluorouracil, taxane, ifosfamide, or vincristine. Only limited experiences with concurrent chemoradiation exist with sinonasal cancer. The role of systemic treatment for each histological type (intestinal-type adenocarcinoma, sinonasal undifferentiated carcinoma, sinonasal neuroendocrine carcinoma, olfactory neuroblastoma, sinonasal primary mucosal melanoma, sarcoma) is discussed. CONCLUSIONS: The treatment of SNC requires a multimodal approach. Employment of systemic therapy for locally advanced disease could result in better outcomes, and optimize the therapeutic armamentarium. Further studies are needed to precisely define the role of systemic therapy and identify the optimal sequencing for its administration in relation to local therapies.

Proton therapy for pediatric and adolescent esthesioneuroblastoma.

BACKGROUND: Esthesioneuroblastoma (EN) of the paranasal sinus comprises less than 3% of tumors of in pediatric and adolescent patients [1]. The collective adult literature indicates a critical role for radiotherapy in attaining cure [2], yet pediatric outcome data is limited. Radiation in pediatric patients with EN can cause significant morbidity due to the proximity of critical structures. Proton radiotherapy offers a potential dosimetric benefit that may improve long-term survival and toxicity outcomes in the pediatric population [3]. METHODS: We retrospectively identified eight patients treated for EN with proton radiotherapy from 2000-2013. Times to event clinical endpoints are summarized using the Kaplan-Meier methods and are from the date of radiotherapy completion. Toxicities are reviewed and graded according to CTCAE v. 4.0. RESULTS: Median follow up was 4.6 years for survivors (range 0.8-9.4 years). The 4 year overall survival was 87.5%. Four of eight patients (one elective) had comprehensive neck radiotherapy. No local or regional failures were observed. Two patients failed distantly with diffuse leptomeningeal disease and intraparenchymal brain metastases, at 0.6 and 1.3 months respectively. Four patients developed radiation related late toxicities including endocrine dysfunction, two cases of grade 2 retinopathy and one case of grade 3 optic neuropathy. CONCLUSIONS: In a limited cohort, proton radiotherapy appears to provide excellent locoregional disease control even in those patients with locally advanced disease and intracranial extension. Distant failure determined overall survival in our cohort. Toxicities were acceptable given disease location and extent.