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Anticancer Research Dec 2023Peputide receptor radionuclide therapy with 177Lu for midgut neuroendocrine metastasis has been clinically approved as a safe treatment. Unresectable metastases of...
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.
Topics: Female; Humans; Middle Aged; Esthesioneuroblastoma, Olfactory; Nose Neoplasms; Nasal Cavity; Treatment Outcome; Receptors, Peptide
PubMed: 38030203
DOI: 10.21873/anticanres.16778 -
Frontiers in Oncology 2023Olfactory neuroblastoma (ONB) is a rare malignant neoplasm of the olfactory mucosa. The paucity of genomic data has prevented the development of individualized ONB...
BACKGROUND
Olfactory neuroblastoma (ONB) is a rare malignant neoplasm of the olfactory mucosa. The paucity of genomic data has prevented the development of individualized ONB treatments. Here, we investigated the genomic and immune landscape of ONB in Chinese patients.
METHODS
Whole exome sequencing (WES) and multiplex immunofluorescence (MIF) analysis were performed on tissue samples from 19 Chinese ONB patients. Patients were divided into low- and high-grade groups.
RESULTS
Overall, 929 nonsynonymous alterations were identified in 18 (94.74%) ONB cases. The most prevalent altered cancer-related genes were (16%) and (16%). The most mutated oncogenic pathways were the WNT and RAS pathways. The median tumor mutation burden (TMB) was 0.45, ranging from 0 to 3.25. Only one case expressed PD-L1 (> 1%) in the tumor region. The percentage of CD8+ tumor-infiltrating lymphocytes (TILs) in the tumor region ranged from 0.03% to 84.9%, with a median of 1.08%. No significant differences were observed between the low- and high-grade groups for clinicopathological features, mutant genes, mutant pathways, TMB, tumor neoantigen burden (TNB), mutant-allele tumor heterogeneity (MATH), PD-L1 expression levels, or CD8+ TIL percentage. However, the low-grade group showed significantly more CD68+ macrophages in both the tumor and total region than the high-grade group. Notably, CD68+CD163- macrophages accounted for an average of 80.5% of CD68+ macrophages.
CONCLUSION
This study presents data on the genomic and immune landscape of ONB cases in China. and were the most prevalent altered cancer-related genes. The results of TMB, PD-L1, and CD8+ Tils suggest that ONB may be insensitive to immunotherapy. M1 macrophages may be positively associated with the prognosis of ONB.
IMPLICATIONS FOR PRACTICE
In this study, the most prevalent altered cancer-related genes were (16%) and (16%). The most mutated oncogenic pathways were the WNT and RAS pathways. The median tumor mutation burden (TMB) was 0.45, ranging from 0 to 3.25. Only one (1/15) case expressed PD-L1 (> 1%) in the tumor region. However, the low-grade group showed significantly more CD68+ macrophages in both the tumor and total region than the high-grade group. The higher level of CD68-related macrophages indicates that M1 macrophages potentially play an important role in ONB development that is possibly associated with prognosis.
PubMed: 38023213
DOI: 10.3389/fonc.2023.1226494 -
Pediatric Blood & Cancer Feb 2024Pediatric esthesioneuroblastoma (EN) can infiltrate skull base anatomy, presenting challenges due to high radiation doses and pediatric tissue sensitivity. This study...
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.
Topics: Humans; Child; Adolescent; Proton Therapy; Esthesioneuroblastoma, Olfactory; Prospective Studies; Nose Neoplasms; Nasal Cavity; Radiotherapy Dosage
PubMed: 38018357
DOI: 10.1002/pbc.30793 -
Pharmaceutics Nov 2023Tomato by-products represent a good source of phytochemical compounds with health properties, such as the steroidal glycoalkaloid α-tomatine (α-TM) and its aglycone...
Tomato by-products represent a good source of phytochemical compounds with health properties, such as the steroidal glycoalkaloid α-tomatine (α-TM) and its aglycone tomatidine (TD). Both molecules have numerous beneficial properties, such as potential anticancer activity. Unfortunately, their therapeutic application is limited due to stability and bioavailability issues. Therefore, a valid strategy seems to be their encapsulation into Solid Lipid Nanoparticles (SLN). The nanoformulations containing α-TM (α-TM-SLN) and TD (TD-SLN) were prepared by technique and subsequently characterized in terms of technological parameters (particle size, polydispersity index, zeta potential, microscopy, and calorimetric studies). To assess the effect of α-TM and TD on the percentage of cellular viability in Olfactory Ensheathing Cells (OECs), a peculiar glial cell type of the olfactory system used as normal cells, and in SH-SY5Y, a neuroblastoma cancer cell line, an MTT test was performed. In addition, the effects of empty, α-TM-SLN, and TD-SLN were tested. Our results show that the treatment of OECs with blank-SLN, free α-TM (0.25 µg/mL), and TD (0.50 µg/mL) did not induce any significant change in the percentage of cell viability when compared with the control. In contrast, in SH-SY5Y-treated cells, a significant decrease in the percentage of cell viability when compared with the control was found. In particular, the effect appeared more evident when SH-SY5Y cells were exposed to α-TM-SLN and TD-SLN. No significant effect in blank-SLN-treated SH-SY5T cells was observed. Therefore, SLN is a promising approach for the delivery of α-TM and TD.
PubMed: 38004552
DOI: 10.3390/pharmaceutics15112573 -
JAMA Otolaryngology-- Head & Neck... Jan 2024
Topics: Humans; Esthesioneuroblastoma, Olfactory; Nose Neoplasms; Nasal Cavity; Neoplasm Staging
PubMed: 37971766
DOI: 10.1001/jamaoto.2023.3635 -
JAMA Otolaryngology-- Head & Neck... Jan 2024
Topics: Humans; Esthesioneuroblastoma, Olfactory; Nose Neoplasms; Nasal Cavity; Neoplasm Staging
PubMed: 37971764
DOI: 10.1001/jamaoto.2023.3634 -
Cureus Oct 2023Esthesioneuroblastoma (ENB), a rare malignancy arising from the olfactory epithelium, poses clinical challenges owing to its propensity for local invasion and...
BACKGROUND
Esthesioneuroblastoma (ENB), a rare malignancy arising from the olfactory epithelium, poses clinical challenges owing to its propensity for local invasion and recurrence. Its management typically involves surgical resection and adjuvant radiotherapy. However, debate persists regarding the optimal treatment strategy, particularly the use of elective nodal irradiation (ENI). This study aimed to investigate recurrence patterns in patients with localized ENB treated with surgery and adjuvant radiotherapy without ENI.
METHODS
Our retrospective analysis included patients who underwent surgery followed by adjuvant radiotherapy for treatment of ENB between January 2011 and November 2022. Patients with incomplete data or who had received neoadjuvant radiotherapy were excluded. Patient characteristics, radiotherapy data (type, dose, and duration), and follow-up data were collected. Recurrence patterns were evaluated, and overall survival (OS), disease-free survival (DFS), and local control rates were determined using the Kaplan-Meier method.
RESULTS
Twelve patients with ENB (median age, 56 years) were included. Most had stage C disease. The median radiation dose was 60 Gy, and the median treatment duration was six weeks. Only one death was confirmed during the observation period, and the five-year DFS rates were 64.3%. Local control was achieved in 11 patients, with only one experiencing local recurrence. Regional lymph node recurrence occurred in three patients and was successfully managed via neck dissection. The timing of recurrence varied, emphasizing the importance of long-term surveillance.
CONCLUSION
Adjuvant radiotherapy without ENI is a viable treatment option for ENB, resulting in favorable local control and OS outcomes. Regional lymph node metastases were observed but effectively managed via salvage therapy. Prospective studies with larger cohorts are warranted to confirm the effectiveness of this treatment strategy and to define optimal radiotherapy fields.
PubMed: 37927675
DOI: 10.7759/cureus.46523 -
Environmental Research Jan 2024PM exposure represents a risk factor for the public health. PM is able to cross the blood-alveolar and blood-brain barriers and reach the brain through three routes:...
PM exposure represents a risk factor for the public health. PM is able to cross the blood-alveolar and blood-brain barriers and reach the brain through three routes: nasal olfactory pathway, nose-brain pathway, blood-brain barrier pathway. We evaluated the effect of PM to induce cytotoxicity and reduced viability on in vitro cultures of OECs (Olfactory Ensheathing Cells) and SH-SY5Y cells. PM samples were collected in the metropolitan area of Catania, and the gravimetric determination of PM, characterization of 10 trace elements and 16 polycyclic aromatic hydrocarbons (PAHs) were carried out for each sample. PM extracts were exposed to cultures of OECs and SH-SY5Y cells for 24-48-72 h, and the cell viability assay (MTT) was evaluated. Assessment of mitochondrial and cytoskeleton damage, and the assessment of apoptotic process were performed in the samples that showed lower cell viability. We have found an annual average value of PM = 16.9 μg/m and a maximum value of PM = 27.6 μg/m during the winter season. PM samples collected during the winter season also showed higher concentrations of PAHs and trace elements. The MTT assay showed a reduction in cell viability for both OECs (44%, 62%, 64%) and SH-SY5Y cells (16%, 17%, 28%) after 24-48-72 h of PM exposure. Furthermore, samples with lower cell viability showed a decrease in mitochondrial membrane potential, increased cytotoxicity, and also impaired cellular integrity and induction of the apoptotic process after increased expression of vimentin and caspase-3 activity, respectively. These events are involved in neurodegenerative processes and could be triggered not only by the concentration and time of exposure to PM, but also by the presence of trace elements and PAHs on the PM substrate. The identification of more sensitive cell lines could be the key to understanding how exposure to PM can contribute to the onset of neurodegenerative processes.
Topics: Humans; Trace Elements; Neuroblastoma; Cell Line; Mitochondria; Polycyclic Aromatic Hydrocarbons; Particulate Matter; Air Pollutants
PubMed: 37925127
DOI: 10.1016/j.envres.2023.117575 -
Frontiers in Oncology 2023Olfactory neuroblastoma (ONB) is a rare neoplasm originating from the olfactory neuroepithelium representing 3-6% of tumors of the sinonasal tract. ONB require... (Review)
Review
Olfactory neuroblastoma (ONB) is a rare neoplasm originating from the olfactory neuroepithelium representing 3-6% of tumors of the sinonasal tract. ONB require multi-disciplinary care. Historically, the gold standard surgical procedure for ONB has been open craniofacial resection. In the last years, endoscopic endonasal approaches have been largely introduced with lower complication rates, shorter hospital stay, and similar clinical outcome. Radiotherapy plays an important role in the management of ONB, however there are not generally accepted recommendations for its application. Although there is agreement that multimodal therapy is needed, the optimal use of chemotherapy is still unknown. The rarity of the disease, makes difficult to draw definitive conclusions about the role of systemic treatment in induction and concomitant setting.
PubMed: 37909011
DOI: 10.3389/fonc.2023.1242453 -
JCEM Case Reports Jul 2023Olfactory neuroblastomas, or esthesioneuroblastomas, are rare and aggressive malignant tumors that typically arise from the olfactory neuroepithelium in the upper nasal...
Olfactory neuroblastomas, or esthesioneuroblastomas, are rare and aggressive malignant tumors that typically arise from the olfactory neuroepithelium in the upper nasal cavity. In rare instances, they can be ectopic originating from areas outside the upper nasal cavity such as the sellar region. These tumors, also known as primary sellar neuroblastomas, may be mistaken for pituitary macroadenomas. We present a rare case of a primary sellar neuroblastoma in a 30-year-old woman with a prior diagnosis of presumed prolactinoma, status post transsphenoidal resection, with residual visual deficits, who presented with worsening vision and headaches. Pituitary magnetic resonance imaging showed a large sellar mass causing compression of the optic chiasm, and invasion of the right cavernous sinus and bilateral cavernous internal carotid arteries. The patient underwent a second transsphenoidal resection. Postoperatively, she developed central adrenal insufficiency, central hypothyroidism, central hypogonadism, and transient syndrome of inappropriate antidiuretic hormone secretion. Owing to rapid tumor regrowth, she underwent a craniotomy with plans for radiation treatment. This condition is challenging to diagnose and has poorly defined clinical management guidelines. An early, aggressive approach with surgical intervention is recommended.
PubMed: 37908997
DOI: 10.1210/jcemcr/luad081