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.

A Combined Hypofractionated Volumetric Modulated Arc Radiotherapy, Radio-Sensitising and Adjuvant Metronomic Chemotherapy Treatment for Canine Stage IV Nasal Tumours With Intracranial Extension.

Radiation therapy has become the standard of care in the treatment of canine intranasal neoplasia, but because of the poor prognosis associated with stage IV nasal tumours and the proximity of the brain to the irradiation target, few data regarding the treatment of very advanced neoplasms are available. The aim of this pilot study was to evaluate the feasibility, safety and effectiveness of a combined treatment composed of definitive high-dose hypofractionated volumetric modulated arc radiotherapy on tumours with concurrent treatment of regional lymph nodes if positive or as prophylaxis, carboplatin radio-sensitising, and adjuvant metronomic chemotherapy for stage IV canine nasal tumours with intracranial extension. A pilot observational study was conducted in 7 dogs. Magnetic resonance imaging follow-up examinations revealed complete responses in 5 dogs and partial responses in 2. The median overall survival time, evaluated via Kaplan-Meier survival analysis, was 310 days with a 95% confidence interval of 210-400 days, whereas the median progression-free survival was 240 days with a 95% confidence interval of 190-290 days. Despite the proximity of highly sensitive organs at risk, no grade III or IV toxicities were observed, and volumetric modulated arc radiotherapy seemed to be a feasible treatment option for stage IV canine nasal tumours where conformal 3D radiotherapy has proven to give higher doses with severe damage to the surrounding unaffected tissues. Further studies are needed on the role of the sphenoid bone microscopic infiltration and regional lymph node involvement. The absence of severe toxicity could also lead to a dose escalation study and chemotherapy scheme.

Single-modality palliative radiotherapy versus palliative radiotherapy after chemotherapy failure for cats with nasal lymphoma.

Published studies describing outcomes for cats with nasal lymphoma (NLSA) receiving first-line palliative radiation (PRT) versus PRT after chemotherapy failure are currently lacking. The aims of this retrospective observational study were to compare outcomes for cats with NLSA that were treated with these two methods. A total of 48 cats were included in analyses; 32 receiving PRT alone and 16 receiving PRT after chemotherapy failure. The treatment response, progression-free survival (PFS), disease-specific survival (DSS), overall survival (OS), and incidence rate of systemic disease were compared between the two groups. The overall response rate (ORR) was calculated from the same target lesions between pre-RT (within a week before starting PRT) and post-RT (on date of PRT completion) by computed tomography (CT) imaging. The ORR was 94% in cats that received PRT alone, 13 had a complete response (CR) and 17 had a partial response (PR). The ORR was 88% in cats that received PRT after chemotherapy failure, with five having CR and nine with PR. There were no significant differences in the ORR between the two groups. The PFS, DSS, and OS significantly increased in the cats that received PRT alone compared to the cats that received PRT after chemotherapy failure (median PFS: 336 vs 228 days, P = 0.0012, median DSS: 360 vs 242 days, P = 0.0025, median OS: 346 vs 242 days, P = 0.0036, respectively). The incidence rate of systemic disease significantly increased in 75% (12/16) of cats receiving PRT after chemotherapy failure compared to 41% (13/32) of cats receiving PRT alone. The results suggested that clinical outcomes may improve in cats with NLSA with first-line PRT compared to PRT after chemotherapy failure.

Heterotopia glial nasal: a propósito de un caso / Nasal glial heterotopia:: case report

Las tumoraciones congénitas de la cara son motivo frecuente de consulta al cirujano plástico pediátrico. La gran mayoría son benignas pero llamativas por su localización. Dentro de éstas, las tumoraciones de la línea media nasal cobran especial importancia por la posibilidad de presentar comunicaciones intracraneanas, porque pueden generar obstrucción al flujo de aire del neonato y porque la demora en su diagnóstico y tratamiento adecuados puede determinar secuelas a largo plazo. Nos centraremos en el diagnóstico y tratamiento de la heterotopia glial nasal a propósito de un caso en paciente de 2 años de edad. (AU)

Congenital face tumors are frequently referred to the pediatric plastic surgeon. Most of them are benign lesions, but they are striking because of their localization. The nasal midline masses are especially important because they may have intracranial connections, they can cause airway obstruction and because the delay in correct diagnosis and treatment may cause long term sequelae. We will focus on the diagnosis and treatment of nasal glial heterotopia: regarding a two-year-old patient. (AU)

A prospective, multi-centre, Veterinary Radiation Therapy Oncology Group study reveals potential efficacy of toceranib phosphate (Palladia) as a primary or adjuvant agent in the treatment of canine nasal carcinoma.

Radiation is the standard of care for dogs with nasal tumours. The addition of another therapy that could improve outcome without increasing toxicity is attractive. Medical therapy that could offer better outcome than maximally tolerated dose chemotherapy when radiation therapy (RT) is not possible or is declined is also attractive. This article reports the findings from a prospective, multi-centre, non-randomized, Veterinary Radiation Therapy Oncology Group clinical trial designed to evaluate whether toceranib phosphate (toceranib) has primary activity and if the addition of toceranib to RT could positively impact outcome. Owner's discretion determined enrolment in toceranib alone or toceranib + RT arm. Historical controls for radiation alone were selected from patients treated with identical RT and imaging protocols. Responses were evaluated with pre-treatment and week-16 CT scans. RT total dose of 42 Gy was completed in 10 fractions. Sixty-three dogs enrolled from 10 study sites. Overall response rates (CR + PR) were significantly improved in the toceranib + RT (79.4%) and RT alone (68.9%) arms over toceranib alone (22%) (p = .011). Clinical benefit rates (CR + PR + SD) were significantly improved in the toceranib + RT arm over the RT alone arm at 97.3% and 79.2% respectively (p = .036). Treatment with toceranib alone, toceranib + RT and RT alone resulted in median survival times of 298, 615 and 368 days respectively, but were not statistically significantly different (p = .0502). Adverse events associated with toceranib administration did not potentiate the RT side effect profile. Toceranib appears to have primary activity against nasal carcinoma.

Treatment of advanced-stage canine nasal carcinomas with toceranib phosphate: 23 cases (2015-2020).

OBJECTIVE: To determine the median survival time (MST) of dogs with nasal carcinoma treated with toceranib phosphate. MATERIAL AND METHODS: The databases of four Spanish referral hospitals were retrospectively searched for dogs with a diagnosis of nasal tumours presented between January 2015 and October 2020. Dogs treated with radiotherapy or other chemotherapies prior toceranib were excluded. RESULTS: Twenty-three dogs with a confirmed nasal carcinoma treated with toceranib phosphate and with a CT scan for initial staging according to Adams Modified Staging System were included. Nine dogs had a stage III nasal carcinoma whereas 14 dogs had a stage IV nasal carcinoma. No dog had stages I and II nasal carcinoma. The median overall survival time was 139 days. The difference between the MST between dogs with stages III and IV was not statistically significant [P = 0.6, 140 days for stage III (range 46-401) vs 120 days for stage IV (range 23-600)]. Overall, dogs with epistaxis achieved a longer median survival (166 days) than dogs without epistaxis (83 days). Toceranib phosphate was generally well tolerated. Most dogs had an initial clinical benefit followed by progressive disease. SIGNIFICANCE: This is the first study to report the MST in dogs with stages III and IV nasal carcinoma treated with toceranib phosphate. This retrospective study showed that toceranib phosphate decreases the clinical signs associated with nasal carcinomas.

Sustained remission of multi-line relapsed extranodal NK/T-cell lymphoma, nasal type, following sintilimab and chidamide: A case report.

INTRODUCTION: There is currently no optimal treatment modality for refractory or relapsed Extranodal NK/T-cell lymphoma, nasal type (ENKTL). In recent years, programmed cell death protein 1 (PD-1)/programmed cell - ligand 1 pathway blockade and histone deacetylase inhibitors have emerged as promising strategies for refractory or relapsed ENKTL. Accumulating evidence has shown that therapeutic effects of anti-PD-1 antibody could be enhanced by histone deacetylase inhibitors. PATIENT CONCERNS: A 52-year-old male patient was diagnosed with stage I ENKTL by biopsy on February 2010. DIAGNOSIS: positron emission tomography-computed tomography (PET-CT) and biopsy were used to diagnose relapsed ENKTL in 2014. INTERVENTIONS: The patient was treated with radiotherapy and six cycles of etoposide, prednisone, vincristine (Oncovin), cyclophosphamide and doxorubicin hydrochloride and achieved complete remission (CR) by PET-CT in August 2010. In November 2014, the patient was diagnosed with relapsed stage IV ENKTL and was treated with six cycles of alternative chemotherapy with the regimen of steroid (dexamethasone), methotrexate, ifosfamide, L-asparaginase, and etoposide and pegaspargase plus Gemcitabine, Oxaliplatin along with radiotherapy. The patient achieved remission and was placed on thalidomide maintenance treatment. Upon suspicion of relapse suggested by PET-CT, Autologous stem cell transplant was performed after BCNU, etoposide, Ara-C, and melphalan preconditioning on February 2016. Following relapse again in December 2016, the lesions of left femur were treated with radiotherapy and he received anti-PD-1 antibody. He was treated with 4 cycles of pegaspargase plus Gemcitabine, Oxaliplatin on August 2017. The patient's condition improved. He received maintenance and consolidation therapy including lenalidomide, radiotherapy of the right nasal cavity and paranasal sinuses and antigen-specific reactive T cell infusions. PET-CT imaging showed there was high metabolic activity signal in the distal end of right femoral on August 2018 and the treatment regimen was adjusted to radiotherapy of the distal end of right femoral and systemic treatment of PD-1 antibody Sintilimab and chidamide 30 mg. After 5 months post-treatment, biopsy of nasopharynx showed no lymphoma cells. The patient continued the treatment of Sintilimab and chidamide 20 mg. OUTCOMES: PET-CT imaging showed his lesions obtained remission after 8 months post-treatment. CONCLUSION: Thus, combination of sintilimab and chidamide can be used to treat relapsed ENKTL following treatment failure from chemo-, radio-, and immuno-therapy. A clinical trial has been launched.

A five-year retrospective study of treatment outcomes using the L-asparaginase-based regimen as a first-line chemotherapy protocol for patients diagnosed with extranodal NK/T-cell lymphoma, nasal-type, in Thailand.

OBJECTIVE: To assess clinical outcomes of newly diagnosed extranodal NK/T-cell lymphoma nasal-type (ENKTL) patients treated with L-asparaginase-containing chemotherapy as first-line chemotherapy. MATERIALS AND METHODS: We retrospectively reviewed data of new ENKTL patients in Siriraj Hospital, Thailand during 2012-2016. RESULTS: Among 27 patients, 16 were men and 11 were women, and their median age was 52 (range, 25-83) years. The primary sites were the aero-nasal area (23) and skin (4). Clinical stages of ENKTL were I, II, III and IV in 10, 8, 1 and 8 patients, respectively. Patients classified according to the NK cell-lymphoma prognostic index with PINK (27) and PINK-E (19) as low, intermediate, and high were 14, 8, 5, respectively and 11, 4, and 4, respectively. Chemotherapy regimens used were SMILE (24) and AspaMetDex (3). Fourteen patients received post- chemotherapy local radiation. The overall response rate for 26 assessable patients was 69%, with complete response in 14 patients (52%). Median progression-free and overall survival were 32 and 33 months, respectively. The most common L-asparaginase regimen related complications were hypofibrinogenemia (24) and hypersensitivity (9). The overall mortality at follow-up was 14/27 (52%) owing to sepsis (11) and disease progression (3). DISCUSSION: L-asparaginase-based regimens showed similar results as other study results. including those in which hematopoietic stem cell transplantation was performed, suggesting that transplantation can be avoided if it is unaffordable. Thrombosis or bleeding, the regimen side effects, should be carefully monitored during treatment. CONCLUSIONS: L-asparaginase-based regimens offer a good outcome as a front-line treatment for ENKTL.

Efficacy of chemotherapy and palliative hypofractionated radiotherapy for cats with nasal lymphoma.

Nasal lymphoma (NL) is the most common nasal tumor in cats, and radiotherapy, chemotherapy, or a combination of these treatments have been described as the treatment for this disease. However, the previous studies included various machines and protocols of radiotherapy. Therefore, we aimed to retrospectively compare the prognosis among cases treated with palliative hypofractionated radiotherapy, chemotherapy, and a combination of them with united machine and protocol of radiotherapy. When compared overall survival and progression free survival, there was no significant difference among these three groups. The data of this study suggested that similar efficacy could be achieved by palliative hypofractionated radiotherapy, chemotherapy, or a combination of them.

m6A methyltransferase Wilms' tumor 1-associated protein facilitates cell proliferation and cisplatin resistance in NK/T cell lymphoma by regulating dual-specificity phosphatases 6 expression via m6A RNA methylation.

Nasal-type natural killer/T-cell lymphoma (NKTCL) is an aggressive malignancy with poor survival outcomes that is relatively resistant to chemotherapy. N6-Methyladenosine (m6A) modification, the most prevalent modification of eukaryotic messenger RNA, is involved in the progression of various tumors. However, it is unclear whether it has a physiological role in NKTCL development. To address this question, we probed its function and molecular mechanisms in NKTCL. Initially, we demonstrated that Wilms' tumor 1-associated protein (WTAP), a major RNA N6-adenosine methyltransferase, was obviously upregulated in human NKTCL cell lines (YTS and SNK-6 cells), compared with normal NK cells. Functionally, depletion of WTAP noticeably repressed proliferation and facilitated apoptosis in YTS and SNK-6 cells. Moreover, intervention of WTAP evidently prohibited NKTCL cell chemotherapy resistance to cisplatin, as reflected by a lower inhibition of cell viability and decreased expression of drug resistance-associated protein expression MRP-1 and P-gp in YTS and SNK-6 cells. With regard to the mechanism, we revealed that WTAP enhanced dual-specificity phosphatases 6 (DUSP6) expression by increasing m6A levels of DUSP6 mRNA transcript, leading to oncogenic functions in NKTCL. Interestingly, WTAP contributed to the progression and chemotherapy sensitivity of NKTCL by stabilizing DUSP6 mRNA in an m6A-dependent manner. Taken together, these findings uncovered a critical function for WTAP-guided m6A methylation and identified DUSP6 as an important target of m6A modification in the regulation of chemotherapy resistance in NKTCL oncogenesis. This study highlights WTAP as a potential therapeutic target of NKTCL treatment.

Rhinoscopic Appearance and Clinical Features of a Nasal Transmissible Venereal Tumor in a Dog.

A 2-year-old male neutered mixed breed dog was referred for evaluation of left-sided unilateral epistaxis and mucoid discharge following adoption from Mexico 2 months prior to presentation. Computed tomography (CT) showed soft tissue that filled the entirety of the left nasal passage with mild turbinate loss. Subsequent rhinoscopy revealed multifocal patches of discrete, white, wispy, vascularized abnormal tissue in the left nasal cavity. Cytology and histopathology procured with rhinoscopic-guidance were suspicious for transmissible venereal tumor (TVT). Confirmation of a TVT diagnosis was made with polymerase chain reaction for the long interspersed element inserted upstream of the c-myc gene. The dog was treated with 4 cycles of vincristine (0.5 mg/m2, IV, once every 7 days) with complete and sustained resolution of clinical signs shortly after the third cycle. Nasal TVT in dogs is an uncommon presentation of a neoplasm that primarily results in genital or oral lesions. There is a void in the veterinary literature regarding the rhinoscopic appearance, as well as limited clinical descriptions of nasal TVT. Therefore, the objectives of this report were to provide a detailed description of the rhinoscopic appearance of a canine nasal TVT, in addition to clinical features, diagnostic findings, CT imaging, and successful therapeutic management.

Primary nasal-ethmoid choriocarcinoma detected by 18F-FDG PET/CT: a rare tumor with complete remission.

Choriocarcinoma is a highly malignant and rare tumor characterized by secretion of the beta-subunit-of-humanchoriogonadotropin (ß-HCG). We report a case of primary nasal choriocarcinoma with good response to chemotherapy. A 36-years-old woman gravida 0 and with history of 4 spontaneous abortion, in December 2018 referred to Otorhinolaryngology Department for repeated episodes of epistaxis. Cervical Magnetic Resonance Imaging (MRI) revealed a tumor mass involving right nasal cavity, right ethmoid, sphenoidal and maxillary sinuses. For a differential diagnosis between metastatic gestational choriocarcinoma and primary choriocarcinoma in January 2019 she underwent 18Fluorine-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (18F-FDG-PET/CT) scan that demonstrated intense uptake only in the nasal-ethmoid tumor mass showed by MRI. This was suggestive of primary nasal-ethmoid choriocarcinoma she received 3 courses of BEP - regimen and after ß-HCG was reduced to 500 mIU/mL and 18F-FDG-PET/CT scan showed a decreased uptake in tumor mass but the appearance of a new uptake in cervical lymph node which was analysed and reported as metastatic localization of choriocarcinoma. Therefore she was treated with 2 cycles of TIP-regimen. Subsequents 18F-FDG-PET/CT and MRI showed a complete tumor remission. This case proved the fundamental role of PET/CT to make diagnosis of primitive choriocarcinoma and to exclude the hypothesis of distant metastasis.

Outcomes of patients treated with SVILE vs. P-GemOx for extranodal natural killer/T-cell lymphoma, nasal type: a prospective, randomized controlled study.

Objective: To compare the efficacy and safety of the novel SVILE regimen with the P-GemOx regimen in patients with newly diagnosed extranodal natural killer/T-cell lymphoma, nasal type (ND-ENKTL). Methods: From April 2015 to July 2018, 103 patients with ND-ENKTL were randomly assigned to SVILE (experimental group) or P-GemOx (control group) chemotherapy followed by radiotherapy and consolidation chemotherapy. The primary endpoint was the overall response rate after 3 cycles of chemotherapy, and secondary study endpoints were complete response (CR), progression-free survival (PFS), and overall survival (OS). Safety was also evaluated. Results: There were no significant differences in baseline characteristics in the experimental vs. control groups. In experimental and control groups, respectively, the overall response rates were 91.7% vs. 97.0% for stage I/II and 75.0% vs. 72.2% for stage III/IV. The CR rates were 83.4% vs. 97.0% for stage I/II and 68.8% vs. 61.1% for stage III/IV. None of those differences were significant. There was no significant difference in PFS and OS between groups and between patients in stage I/II and stage III/IV. The 3-year PFS and OS in stage I/II were 88.3% vs. 93.3% and 88.8% vs. 97.0%, respectively. The 3-year PFS and OS in stage III/IV were 46.2% vs. 65.7% and 68.8% vs. 72.2%, respectively. The common adverse events were hematological toxicity, hepatotoxicity, and coagulation abnormalities, which were found to be reversible with supportive therapy. Conclusions: The novel SVILE regimen has comparable effects to those of P-GemOx in patients with ND-ENKTL and is well tolerated. SVILE is a therapeutic option for ND-ENKTL.

SVILE regimen, a combination of dexamethasone, vindesine, ifosfamide, pegaspargase, and etoposide, for treating relapsed/refractory extranodal natural killer/T-cell lymphoma, nasal type.

OBJECTIVE: To explore the effectiveness and safety of dexamethasone, vindesine, ifosfamide, pegaspargase, and etoposide combination (SVILE regimen) in the treatment of relapsed/refractory extranodal natural killer/T-cell lymphoma, nasal type (R/R-ENKTL). METHODS: This descriptive, retrospective medical chart review assessed data from 20 R/R-ENKTL patients treated with the SVILE regimen between November 2014 and August 2019. Complete response (CR) rate, overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) since SVILE treatment were analysed. RESULTS: After receiving 1-5 SVILE regimen chemotherapy cycles (median 2 cycles), patients had ORR and CR rates of 70.0 % and 45.0 %, respectively. Stage Ⅰ/Ⅱ patients had CR rate of 100.0 % and stage Ⅲ/Ⅳ patients had ORR and CR rates of 60.0 % and 26.7 %, respectively. Three-year PFS and OS rates of the 20 patients were 43.8 % and 54.2 %, respectively. Three-year PFS and OS rates of stage Ⅰ/Ⅱ patients and stage Ⅲ/Ⅳ patients were 100.0 % vs. 26.7 % and 100.0 % vs. 40.0 % (P ＜ 0.05), respectively. The PFS and OS of patients who achieved CR after SVILE chemotherapy were significantly better than those of non-CR patients. The main adverse events were reversible haematological toxicity. CONCLUSIONS: The SVILE regimen is a new treatment option that is effective and safe for R/R-ENKTL patients.

Surgeons reaching satisfying outcomes without surgery: nasal dorsum skin cancer recurrence treated with electrochemotherapy.

Cutaneous squamous cell carcinoma of the head and neck district are generally treated with surgery. Surgery is the standard treatment in early stages and local advanced tumors, followed by adjuvant therapy, radiation or concurrent chemoradiation therapy. Local recurrence treatment depends on previous therapies, though radical surgery is often the first choice at the expense of anatomy preservation. We present the case of a patient with cutaneous squamous cell carcinoma of the nasal dorsum which relapsed after surgery and radiation therapy. The patient refused radical surgery and electrochemotherapy under general anesthesia was administered. After 6 months from treatment, the patient showed a complete clinical response. Electrochemotherapy could be considered as an alternative to surgery in small lesion when other approaches are refused.