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1.
Cancer Med ; 13(5): e6943, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38497548

RESUMEN

BACKGROUND: We investigated the outcomes of postoperative radiation therapy for olfactory neuroblastoma (ONB) and our cross-departmental collaboration to enhance the effectiveness of cancer treatment. METHODS: We retrospectively evaluated 22 patients with ONB who underwent postoperative radiotherapy after tumor resection. En bloc resection was performed; pathology specimens were prepared in coronal sections; and irradiation fields were determined after discussion with radiation oncologists, head and neck surgeons, and pathologists. RESULTS: The overall survival and local control rates were 95.5% and 100%, respectively, at a median 37-month follow-up. The 3- and 5-year disease-free survival (DFS) rates were 64.4% and 56.3%, respectively. Of the 22 patients, 9 (8 Kadish C and 1 Kadish B) had disease recurrence. Of the nine patients, five had positive margins and two had closed margins; cervical lymph node recurrence occurred in six, and distant metastasis with or without cervical lymph node recurrence occurred in three. DFS analysis of risk factors showed no statistically significant differences, but positive margins were a significant recurrence factor in multivariate analysis. CONCLUSIONS: The local control rate of ONB treated with postoperative radiation therapy was 100%. This may be attributed to cross-departmental cooperation between head and neck surgeons, pathologists, and radiation oncologists, which resulted in accurate matching of CT images for treatment planning with the location of the tumor and positive margins. Longer follow-up periods are required to evaluate the effectiveness of our strategy.


Asunto(s)
Estesioneuroblastoma Olfatorio , Neoplasias Nasales , Humanos , Estudios Retrospectivos , Estesioneuroblastoma Olfatorio/radioterapia , Estesioneuroblastoma Olfatorio/cirugía , Estesioneuroblastoma Olfatorio/patología , Recurrencia Local de Neoplasia , Neoplasias Nasales/patología , Cavidad Nasal/patología , Cavidad Nasal/cirugía
2.
Pathol Res Pract ; 253: 155040, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38171083

RESUMEN

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


Asunto(s)
Estesioneuroblastoma Olfatorio , Insulinoma , Neoplasias Nasales , Neoplasias Pancreáticas , Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Lactante , Biomarcadores de Tumor/análisis , Proteínas Represoras/metabolismo , Pronóstico , Neoplasias Pancreáticas/patología , Cavidad Nasal/patología
3.
Eur Arch Otorhinolaryngol ; 281(3): 1443-1448, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38163817

RESUMEN

PURPOSE: To investigate the clinical characteristics of the syndrome of inappropriate antidiuretic hormone (SIADH) associated with nasal and paranasal malignant tumors. METHODS: Patients with locally advanced or recurrence/metastatic malignant tumors of the nasal and paranasal sinuses were included. The SIADH was diagnosed according to the diagnostic criteria. The clinical characteristics of SIADH patients were retrospectively analyzed. RESULTS: Six patients (6/188, 3.2%) met the diagnostic criteria of SIADH, including four olfactory neuroblastoma (4/26, 15.4%), one neuroendocrine carcinoma (1/9, 11.1%), and one squamous cell carcinoma (1/63, 1.6%). Five patients (83.3%) had severe hyponatremia; however, the hyponatremia could be improved by fluid restriction or tolvaptan. Three patients' SIADH were recovered during the chemotherapy and the other three were recovered after the surgery. CONCLUSION: The incidence of SIADH associated with nasal and paranasal malignant tumors is relatively more common in olfactory neuroblastoma and neuroendocrine carcinoma. The hyponatremia caused by SIADH may be corrected by fluid restriction or tolvaptan, and the SIADH may be recovered through anti-tumor therapy.


Asunto(s)
Carcinoma Neuroendocrino , Estesioneuroblastoma Olfatorio , Hiponatremia , Síndrome de Secreción Inadecuada de ADH , Neoplasias Nasales , Humanos , Síndrome de Secreción Inadecuada de ADH/complicaciones , Síndrome de Secreción Inadecuada de ADH/diagnóstico , Hiponatremia/etiología , Hiponatremia/complicaciones , Tolvaptán/uso terapéutico , Estesioneuroblastoma Olfatorio/complicaciones , Estudios Retrospectivos , Carcinoma Neuroendocrino/complicaciones , Neoplasias Nasales/complicaciones , Cavidad Nasal
4.
World Neurosurg ; 183: e928-e935, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38246527

RESUMEN

BACKGROUND: Esthesioneuroblastoma (ENB) is a rare cancer deriving from the olfactory mucosa. Among the basal or neural genomic subtypes, the basal subtype is associated with poorer survival, poor differentiation, and higher levels of tumor-infiltrating immune cells (TIICs). The immune microenvironment of these ENB subtypes remains unclear. We used an established machine learning algorithm on ENB transcriptomic profiles. METHODS: The authors characterized 22 immune cell populations using the CIBERSORTx deconvolutional machine learning pipeline on RNA sequencing data from 18 ENB cases. The characterization aimed to elucidate differences in relative proportions and populations of TIICs between basal and neural ENB. RESULTS: No differences in age, Hyams, Dulguerov, IDH2 mutation, or PD-L1 expression were seen between basal and neural subtypes of ENB (P > 0.05). Also, no difference in median overall survival was appreciated (52.0 ± 13.1 months vs. 50.0 ± 43.2 months, P = 0.5). As a cohort, M2 macrophages were the most abundant subpopulation (14%) followed by naïve B cells (13%) and CD4 memory resting T cells (12%). No gross differences in CD20, CD4, or CD8 cells/mm2 were apparent on gross histology (P > 0.05). However, further analysis showed that activated CD4 memory T cells were significantly increased in the basal ENBs, whereas resting dendritic cells were increased in the neural ENB subtype. The TIIC profiles alone could not differentiate between basal and neural ENB, but did suggest immunoprofile differences. CONCLUSIONS: Basal and neural subtypes display distinct TIIC involvement, which may impact their difference in outcome. These findings provide the framework for further investigation in novel immunomodulation strategies for ENB.


Asunto(s)
Estesioneuroblastoma Olfatorio , Neoplasias Nasales , Humanos , Estesioneuroblastoma Olfatorio/genética , Mutación , Neoplasias Nasales/patología , Cavidad Nasal/patología , Expresión Génica , Pronóstico , Microambiente Tumoral
5.
Head Neck ; 46(2): 439-446, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38041523

RESUMEN

A critical procedure in the transcribriform approach is the resection of the crista galli. However, the standard technique for crista galli resection has several disadvantages. We reviewed the cases of patients with olfactory neuroblastomas who underwent an endoscopic endonasal transcribriform approach using a newly developed technique for crista galli resection. We performed a cadaveric study to measure the superior accessibility limits using the proposed method. We included 38 patients with olfactory neuroblastomas in this study. The tumor invaded the posterior crista galli in four patients. The anterior end of the crista galli was not invaded by the tumor. Our cadaveric study showed that the dura was approachable to the point that was 7.4 ± 1.3 mm superior and 23.2 ± 7.2 mm lateral to the foramen cecum following crista galli removal. By resecting the crista galli in advance, manipulation of the superior dura became feasible.


Asunto(s)
Estesioneuroblastoma Olfatorio , Neoplasias Nasales , Humanos , Cadáver , Hueso Etmoides , Cavidad Nasal/cirugía
8.
Pediatr Blood Cancer ; 71(2): e30793, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38018357

RESUMEN

BACKGROUND: Pediatric esthesioneuroblastoma (EN) can infiltrate skull base anatomy, presenting challenges due to high radiation doses and pediatric tissue sensitivity. This study reports outcomes of pediatric EN treated with proton radiotherapy (PT). PROCEDURE: Using an IRB-approved prospective outcomes registry, we evaluated patient, tumor, and treatment-related variables impacting disease control and toxicity in pediatric nonmetastatic EN treated with modern multimodality therapy, including PT. RESULTS: Fifteen consecutive patients (median age 16) comprising Kadish stage B (n = 2), C (n = 9), and D (n = 4) tumors were assessed, including six with intracranial involvement, four with cranial nerve deficits, and four with cervical lymphadenopathy. Before radiation, two had subtotal and 13 had gross total resections (endoscopic or craniofacial). Two underwent neck dissection. Eleven received chemotherapy before radiation (n = 5), concurrent with radiation (n = 4), or both (n = 2). Median total radiation dose (primary site) was 66 Gy/CGE for gross disease and 54 Gy/CGE (cobalt Gray equivalent) for microscopic disease. Median follow-up was 4.8 years. No patients were lost to follow-up. Five-year disease-free and overall survival rates were 86% (no local or regional recurrences). Two patients developed vertebral metastases and died. Two required a temporary feeding tube for oral mucositis/dysphagia. Late toxicities included symptomatic retinopathy, major reconstructive surgery, cataracts, chronic otitis media, chronic keratoconjunctivitis, hypothyroidism, and in-field basal cell skin cancer. CONCLUSIONS: A multimodality approach for pediatric EN results in excellent local control. Despite the moderate-dose PT, serious radiation toxicity was observed; further dose and target volume reductions may benefit select patients. Longer follow-up and comparative data from modern photon series are necessary to fully characterize any relative PT advantage.


Asunto(s)
Estesioneuroblastoma Olfatorio , Neoplasias Nasales , Terapia de Protones , Humanos , Niño , Adolescente , Terapia de Protones/métodos , Estesioneuroblastoma Olfatorio/radioterapia , Estudios Prospectivos , Neoplasias Nasales/radioterapia , Cavidad Nasal , Dosificación Radioterapéutica
9.
Anticancer Res ; 43(12): 5723-5728, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38030203

RESUMEN

BACKGROUND: Peputide receptor radionuclide therapy with 177Lu for midgut neuroendocrine metastasis has been clinically approved as a safe treatment. Unresectable metastases of olfactory neuroblastoma have shorter survival due to insufficient effective systemic treatment. CASE REPORT: Herein, we report a patient treated with peputide receptor radionuclide therapy for unresectable recurrent olfactory neusroblastoma following a rare cranial metastasectomy infection. A 50-year-old female patient with olfactory neuroblastoma of Kadish C was initially treated by skull base surgery plus postoperative radiotherapy following chemotherapy. Recurrent disease with neck and intracranial metastases was treated by four salvage surgeries. Surgical site infection following intracranial metastasectomy was treated with debridement and delayed cranioplasty. Peputide receptor radionuclide therapy was performed for unresectable multiple metastases after cranioplasty. Successful therapy using four cycles of peputide receptor radionuclide had neither grade 3 nor grade 4 adverse events. The patient was followed at an outpatient clinic. CONCLUSION: Further case accrual of peputide receptor radionuclide therapy is required to develop a treatment for unresectable olfactory neuroblastoma.


Asunto(s)
Estesioneuroblastoma Olfatorio , Neoplasias Nasales , Femenino , Humanos , Persona de Mediana Edad , Estesioneuroblastoma Olfatorio/radioterapia , Estesioneuroblastoma Olfatorio/cirugía , Neoplasias Nasales/radioterapia , Neoplasias Nasales/cirugía , Neoplasias Nasales/patología , Cavidad Nasal/patología , Resultado del Tratamiento , Receptores de Péptidos
13.
JAMA Otolaryngol Head Neck Surg ; 149(9): 837-844, 2023 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-37535372

RESUMEN

Importance: Current olfactory neuroblastoma (ONB) staging systems inadequately delineate locally advanced tumors, do not incorporate tumor grade, and poorly estimate survival and recurrence. Objective: The primary aims of this study were to (1) examine the clinical covariates associated with survival and recurrence of ONB in a modern-era multicenter cohort and (2) incorporate Hyams tumor grade into existing staging systems to assess its ability to estimate survival and recurrence. Design, Setting, and Participants: This retrospective, multicenter, case-control study included patients with ONB who underwent treatment between January 1, 2005, and December 31, 2021, at 9 North American academic medical centers. Intervention: Standard-of-care ONB treatment. Main Outcome and Measures: The main outcomes were overall survival (OS), disease-free survival (DFS), and disease-specific survival (DSS) as C statistics for model prediction. Results: A total of 256 patients with ONB (mean [SD] age, 52.0 [15.6] years; 115 female [44.9%]; 141 male [55.1%]) were included. The 5-year rate for OS was 83.5% (95% CI, 78.3%-89.1%); for DFS, 70.8% (95% CI, 64.3%-78.0%); and for DSS, 94.1% (95% CI, 90.5%-97.8%). On multivariable analysis, age, American Joint Committee on Cancer (AJCC) stage, involvement of bilateral maxillary sinuses, and positive margins were associated with OS. Only AJCC stage was associated with DFS. Only N stage was associated with DSS. When assessing the ability of staging systems to estimate OS, the best-performing model was the novel modification of the Dulguerov system (C statistic, 0.66; 95% CI, 0.59-0.76), and the Kadish system performed most poorly (C statistic, 0.57; 95% CI, 0.50-0.63). Regarding estimation of DFS, the modified Kadish system performed most poorly (C statistic, 0.55; 95% CI, 0.51-0.66), while the novel modification of the AJCC system performed the best (C statistic, 0.70; 95% CI, 0.66-0.80). Regarding estimation of DSS, the modified Kadish system was the best-performing model (C statistic, 0.79; 95% CI, 0.70-0.94), and the unmodified Kadish performed the worst (C statistic, 0.56; 95% CI, 0.51-0.68). The ability for novel ONB staging systems to estimate disease progression across stages was also assessed. In the novel Kadish staging system, patients with stage VI disease were approximately 7 times as likely to experience disease progression as patients with stage I disease (hazard ratio [HR], 6.84; 95% CI, 1.60-29.20). Results were similar for the novel modified Kadish system (HR, 8.99; 95% CI, 1.62-49.85) and the novel Dulguerov system (HR, 6.86; 95% CI, 2.74-17.18). Conclusions and Relevance: The study findings indicate that 5-year OS for ONB is favorable and that incorporation of Hyams grade into traditional ONB staging systems is associated with improved estimation of disease progression.


Asunto(s)
Estesioneuroblastoma Olfatorio , Neoplasias Nasales , Humanos , Masculino , Femenino , Persona de Mediana Edad , Estesioneuroblastoma Olfatorio/terapia , Estesioneuroblastoma Olfatorio/mortalidad , Estesioneuroblastoma Olfatorio/patología , Estudios Retrospectivos , Estudios de Casos y Controles , Neoplasias Nasales/patología , Cavidad Nasal , Análisis de Supervivencia , Estadificación de Neoplasias , Progresión de la Enfermedad
15.
Neurosurg Focus ; 55(2): E6, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37527675

RESUMEN

OBJECTIVE: Esthesioneuroblastoma (ENB), also known as olfactory neuroblastoma, is a rare, malignant tumor of neuroectodermal origin that arises from the olfactory neuroepithelium. In this study the authors present the first series in the literature on distant brain metastases (BMs) secondary to ENB that were treated with stereotactic radiosurgery (SRS), to evaluate the safety and effectiveness of SRS for this indication. METHODS: A retrospective analysis of clinical and radiological outcomes of patients with ENB who underwent CyberKnife (CK) SRS at a single center was conducted. The clinical and radiological outcomes of patients, including progression-free survival, overall survival, and local tumor control (LTC) were reported. RESULTS: Between 2003 and 2022, 32 distant BMs in 8 patients were treated with CK SRS at Stanford University. The median patient age at BM diagnosis was 62 years (range 47-75 years). Among 32 lesions, 2 (6%) had previously been treated with surgery, whereas for all other lesions (30 [94%]), CK SRS was used as their primary treatment modality. The median target volume was 1.5 cm3 (range 0.09-21.54 cm3). CK SRS was delivered by a median marginal dose of 23 Gy (range 15-30 Gy) and a median of 3 fractions (range 1-5 fractions) to a median isodose line of 77% (range 70%-88%). The median biologically effective dose was 48 Gy (range 21-99.9 Gy) and the median follow-up was 30 months (range 3-95 months). The LTC at 1-, 2-, and 3-year follow-up was 86%, 65%, and 50%, respectively. The median progression-free survival and overall survival were 29 months (range 11-79 months) and 51 months (range 15-79 months), respectively. None of the patients presented adverse radiation effects. CONCLUSIONS: In the authors' experience, SRS provided excellent LTC without any adverse radiation effects for BMs secondary to ENB.


Asunto(s)
Neoplasias Encefálicas , Estesioneuroblastoma Olfatorio , Neoplasias Nasales , Radiocirugia , Humanos , Persona de Mediana Edad , Anciano , Radiocirugia/efectos adversos , Estesioneuroblastoma Olfatorio/radioterapia , Estesioneuroblastoma Olfatorio/cirugía , Estesioneuroblastoma Olfatorio/etiología , Estudios Retrospectivos , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/cirugía , Neoplasias Encefálicas/patología , Cavidad Nasal/cirugía , Neoplasias Nasales/radioterapia , Neoplasias Nasales/cirugía , Neoplasias Nasales/etiología , Resultado del Tratamiento
16.
Vet Clin Pathol ; 52(3): 521-526, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37468966

RESUMEN

Nasal tumors account for less than 10% of all feline neoplasms, with lymphoma, followed by adenocarcinoma, and squamous cell carcinoma, the most commonly reported. Nasal neuroectodermal tumors, including olfactory neuroblastoma (ONB), are scarcely described, and their tumorigenesis is largely unknown. Here we report the cytological, histological, and immunohistochemical features of a feline ONB. We also provide a pathological review of nasal neuroendocrine neoplasms in cats. A 7-year-old Burmese cat was evaluated for sneezing, occasional epistaxis, and upper respiratory noise for 8 months. Computed tomography (CT) imaging revealed a 7 × 5 × 3 mm irregular mass effacing and expanding the nasal cavity, which extended to the nasopharynx. Cytologically, neoplastic cells were round to polygonal and had a round nucleus with finely stippled chromatin, a single small nucleolus, and abundant pale blue cytoplasm, which contained abundant fine pale pink granules. They exhibited mild cellular atypia, anisocytosis, and mild to occasionally moderate anisokaryosis. Rhinoscopic biopsies revealed a densely cellular, malignant neuroepithelial neoplasm. Cells were arranged in densely packed trabeculae and formed Homer Wright and Flexner-Wintersteiner-like rosettes, with rare mitotic figures and scant supportive fibrovascular stroma. Immunohistochemically, neoplastic cells were positive for vimentin, cytokeratin AE1/AE3, COX-2, and beta-tubulin and negative for S-100, chromogranin A, CD117, and epithelial membrane antigen (EMA). An ONB was diagnosed based on histological and immunohistochemical findings. Interestingly, and similar to nasal carcinomas, neoplastic cells diffusely neo-expressed COX-2. To the authors' knowledge, there is no previous evidence of COX-2 in feline ONB. Histopathology and immunohistochemistry are required for a definitive diagnosis of ONB.


Asunto(s)
Carcinoma , Enfermedades de los Gatos , Estesioneuroblastoma Olfatorio , Neoplasias Nasales , Gatos , Animales , Estesioneuroblastoma Olfatorio/diagnóstico , Estesioneuroblastoma Olfatorio/veterinaria , Ciclooxigenasa 2 , Neoplasias Nasales/diagnóstico , Neoplasias Nasales/veterinaria , Cavidad Nasal/patología , Carcinoma/patología , Carcinoma/veterinaria , Enfermedades de los Gatos/diagnóstico por imagen , Enfermedades de los Gatos/patología
17.
Oral Oncol ; 144: 106486, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37413771

RESUMEN

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.


Asunto(s)
Carcinoma Neuroendocrino , Estesioneuroblastoma Olfatorio , Neoplasias Nasales , Neoplasias de los Senos Paranasales , Humanos , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Terapia Neoadyuvante/métodos , Estesioneuroblastoma Olfatorio/tratamiento farmacológico , Etopósido/uso terapéutico , Estudios Retrospectivos , Cisplatino , Carcinoma Neuroendocrino/tratamiento farmacológico , Neoplasias de los Senos Paranasales/patología , Cavidad Nasal/patología , Neoplasias Nasales/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico
18.
Cancer Res Commun ; 3(6): 980-990, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-37377616

RESUMEN

Olfactory neuroblastoma is a rare tumor arising from the olfactory cleft region of the nasal cavity. Because of the low incidence of this tumor, as well as an absence of established cell lines and murine models, understanding the mechanisms driving olfactory neuroblastoma pathobiology has been challenging. Here, we sought to apply advances from research on the human olfactory epithelial neurogenic niche, along with new biocomputational approaches, to better understand the cellular and molecular factors in low- and high-grade olfactory neuroblastoma and how specific transcriptomic markers may predict prognosis. We analyzed a total of 19 olfactory neuroblastoma samples with available bulk RNA-sequencing and survival data, along with 10 samples from normal olfactory epithelium. A bulk RNA-sequencing deconvolution model identified a significant increase in globose basal cell (GBC) and CD8 T-cell identities in high-grade tumors (GBC from ∼0% to 8%, CD8 T cell from 0.7% to 2.2%), and significant decreases in mature neuronal, Bowman's gland, and olfactory ensheathing programs, in high-grade tumors (mature neuronal from 3.7% to ∼0%, Bowman's gland from 18.6% to 10.5%, olfactory ensheathing from 3.4% to 1.1%). Trajectory analysis identified potential regulatory pathways in proliferative olfactory neuroblastoma cells, including PRC2, which was validated by immunofluorescence staining. Survival analysis guided by gene expression in bulk RNA-sequencing data identified favorable prognostic markers such as SOX9, S100B, and PLP1 expression. Significance: Our analyses provide a basis for additional research on olfactory neuroblastoma management, as well as identification of potential new prognostic markers.


Asunto(s)
Estesioneuroblastoma Olfatorio , Neoplasias Nasales , Ratones , Humanos , Animales , Estesioneuroblastoma Olfatorio/genética , Mucosa Olfatoria/metabolismo , Vías Olfatorias/patología , Neoplasias Nasales/genética , ARN/metabolismo
19.
Head Neck ; 45(8): 1986-1999, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37306376

RESUMEN

BACKGROUND: The clinical value of different treatment modalities, especially systemic chemotherapy (CT) in patients with locoregionally advanced olfactory neuroblastoma (LA ONB) remains unclear. METHODS: 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. RESULTS: 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). 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.


Asunto(s)
Estesioneuroblastoma Olfatorio , Neoplasias Nasofaríngeas , Neoplasias Nasales , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioradioterapia/métodos , Estesioneuroblastoma Olfatorio/terapia , Fluorouracilo , Cavidad Nasal , Neoplasias Nasofaríngeas/terapia , Neoplasias Nasales/terapia , Estudios Retrospectivos
20.
Head Neck Pathol ; 17(2): 299-312, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37184733

RESUMEN

Although the definitions of sinonasal neuroendocrine and neuroectodermal neoplasms did not change substantially in the 5th edition WHO Classification of Head and Neck Tumours, the diagnosis of olfactory neuroblastoma (ONB), small cell neuroendocrine carcinoma, and large cell neuroendocrine carcinoma remains quite challenging in practice. Ambiguities surrounding the amount of keratin expression allowable in ONB and the amount of neuroendocrine differentiation seen in sinonasal undifferentiated carcinoma (SNUC) lead to significant diagnostic discrepancies at the high grade end of this tumor spectrum. Furthermore, a group of problematic neuroepithelial tumors that show overlapping features of ONB and neuroendocrine carcinoma have never been recognized in formal classification schemes. Since publication of the 5th edition WHO, two new tumor entities have been proposed that help resolve these problems. Olfactory carcinoma is defined by high grade keratin-positive neuroectodermal cells with frequent intermixed glands and shows recurrent Wnt pathway, ARID1A, and RUNX1 alterations. IDH2-mutant sinonasal carcinoma is a molecularly-defined category that encompasses tumors with undifferentiated (SNUC), large cell neuroendocrine, and neuroepithelial phenotypes. This review will provide a practical overview of these emerging entities and their application to diagnostic challenges in the post-WHO sinonasal neuroendocrine and neuroectodermal tumor classification.


Asunto(s)
Carcinoma Neuroendocrino , Estesioneuroblastoma Olfatorio , Neoplasias del Seno Maxilar , Neoplasias Nasales , Neoplasias de los Senos Paranasales , Humanos , Nueva Orleans , Carcinoma Neuroendocrino/patología , Neoplasias de los Senos Paranasales/patología , Neoplasias del Seno Maxilar/patología , Estesioneuroblastoma Olfatorio/diagnóstico , Estesioneuroblastoma Olfatorio/patología , Queratinas , Neoplasias Nasales/patología , Cavidad Nasal/patología
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