Clinical outcomes, Kadish-INSICA staging and therapeutic targeting of somatostatin receptor 2 in olfactory neuroblastoma

Purpose Olfactory neuroblastoma (ONB) is a rare head and neck cancer believed to be originated from neural crest cells of the olfactory membrane located in the roof of the nasal fossa. This study evaluates clinical outcomes and failure patterns in ONB patients of those patients treated with surgical resection at a high-volume tertiary cancer center. Methods and Materials Thirty-nine ONB patients who underwent surgical resection at our institution from 1996 to 2017 were retrospectively identified. Univariate, multivariate, and survival analysis were calculated using Cox regression analysis and Kaplan–Meier log-rank. Results Median follow-up time was 59 months (range: 5.2–236 months). The median overall survival (OS) and disease-free survival (DFS) for the entire cohort were 15 and 7.6 years, respectively. The 5-year cumulative OS and DFS were 83 and 72%, respectively. The 5-year OS for low Hyams grade (LHG) versus high Hyams grade (HHG) was 95 versus 61% (p = 0.041). LHG was found in 66% of the early Kadish stage patients compared with 28% in the advanced Kadish stage patients (p = 0.057). On multivariate analysis, HHG and positive node status predicted for worse OS and only HHG predicted for worse DFS. Of note, five patients (all Kadish stage A) who received surgical resection alone had no observed deaths or recurrences with a median follow-up of 44 months (range: 5–235 months). Conclusion In this retrospective cohort, patients with positive nodes or HHG have significantly worse clinical outcomes. Future studies should explore treatment intensification for HHG or positive nodes.

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Therapeutic targeting of HMGB1 during experimental sepsis modulates the inflammatory cytokine profile to one associated with improved clinical outcomes

Scientific Reports ◽

10.1038/s41598-017-06205-z ◽

2017 ◽

Vol 7 (1) ◽

Cited By ~ 37

Author(s):

Natalie E. Stevens ◽

Marianne J. Chapman ◽

Cara K. Fraser ◽

Tim R. Kuchel ◽

John D. Hayball ◽

...

Keyword(s):

Clinical Outcomes ◽

Inflammatory Cytokine ◽

Cytokine Profile ◽

Experimental Sepsis ◽

Therapeutic Targeting

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Neuroradiological and Neuropathological Changes After 177Lu-Octreotate Peptide Receptor Radionuclide Therapy of Refractory Esthesioneuroblastoma

Operative Neurosurgery ◽

10.1093/ons/opy028 ◽

2018 ◽

Vol 15 (6) ◽

pp. 100-109 ◽

Cited By ~ 2

Author(s):

Julia R Schneider ◽

Deborah R Shatzkes ◽

Stephen C Scharf ◽

Tristan M Tham ◽

Kay O Kulason ◽

...

Keyword(s):

Radionuclide Therapy ◽

Therapeutic Option ◽

Somatostatin Receptor ◽

Malignant Neoplasm ◽

Peptide Receptor Radionuclide Therapy ◽

Olfactory Neuroblastoma ◽

Somatostatin Analogues ◽

Symptomatic Improvement ◽

Peptide Receptor ◽

Molecular Alterations

Abstract BACKGROUND AND IMPORTANCE Olfactory neuroblastoma, also known as esthesioneuroblastoma (ENB), is a malignant neoplasm with an unpredictable behavior. Currently, the widely accepted treatment is inductive chemotherapy, with or without surgery, followed by radiotherapy. Since data on genetics and molecular alterations of ENB are lacking, there is no standard molecularly targeted therapy. However, ENB commonly expresses the somatostatin receptor (SSTR) that is also expressed by neuroendocrine tumors. Peptide receptor radionuclide therapy (PRRT) using radiolabeled somatostatin analogues, such as 177Lu-octreotate, is an effective treatment for the latter. We present the complex neuroradiological and neuropathological changes associated with 177Lu-octreotate treatment of a patient with a highly treatment-resistant ENB. CLINICAL PRESENTATION A 60-yr-old male presented with an ENB that recurred after chemotherapy, surgery, stereotactic radiosurgery, and immunotherapy. Pathology revealed a Hyams grade 3 ENB and the tumor had metastasized to lymph nodes. Tumor SSTR expression was seen on 68Ga-octreotate positron emission tomography (PET)/computed tomography (CT), suggesting that PRRT may be an option. He received 4 cycles of 177Lu-octreotate over 6 mo, with a partial response of all lesions and symptomatic improvement. Four months after the last PRRT cycle, 2 of the lesions rapidly relapsed and were successfully resected. Three months later, 68Ga-octreotate PET/CT and magnetic resonance imaging indicate no progression of the disease. CONCLUSION We describe imaging changes associated with 177Lu-octreotate PRRT of relapsing ENB. To our knowledge, this is the first report describing neuropathological changes associated with this treatment. PRRT is a promising therapeutic option to improve the disease control, and potentially, the survival of patients with refractory ENB.

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Therapeutic targeting of nitroglycerin-mediated trigeminovascular neuronal hypersensitivity predicts clinical outcomes of migraine abortives

Pain ◽

10.1097/j.pain.0000000000002142 ◽

2020 ◽

Vol Publish Ahead of Print ◽

Cited By ~ 1

Author(s):

Simon Akerman ◽

Marcela Romero-Reyes ◽

Nazia Karsan ◽

Pyari Bose ◽

Jan R. Hoffmann ◽

...

Keyword(s):

Clinical Outcomes ◽

Therapeutic Targeting

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Pre-therapy extrahepatic 68Ga-DOTATATE avid tumor burden is associated with shortterm clinical outcomes of 177Lu-DOTATATE in advanced metastatic gastroenteropancreatic neuroendocrine tumors

10.21203/rs.3.rs-463333/v1 ◽

2021 ◽

Author(s):

Hong Song ◽

Pamela L. Kunz ◽

Benjamin L. Franc ◽

Farshad Moradi ◽

Judy Nguyen ◽

...

Keyword(s):

Clinical Outcomes ◽

Prognostic Marker ◽

Neuroendocrine Tumors ◽

Tumor Volume ◽

Somatostatin Receptor ◽

Rank Test ◽

Gastroenteropancreatic Neuroendocrine Tumors ◽

Kaplan Meier ◽

Significant Difference

Abstract Lutetium-177 ( 177 Lu)-DOTATATE is an effective systemic therapy for metastatic somatostatin receptor positive neuroendocrine tumors (NETs). Here we report our experience with the use of pre-therapy 68 Ga-DOTATATE PET as prognostic marker for short-term clinical outcomes of 177 Lu-DOTATATE therapy in patients with advanced NETs. Materials and methods: We retrospectively reviewed patients who received at least one dose of 177 Lu-DOTATATE between Dec. 2016 and July 2019 at our institution. 50 patients (63.6 ± 10.0 years) with advanced gastroenteropancreatic neuroendocrine tumors (GEP-NETs) who had pre-therapy 68 Ga-DOTATATE PET were included in the analysis. 68 Ga-DOTATATE avid tumor volumes were determined automatically using an SUV thresholding approach. Total and extrahepatic 68 Ga-DOTATATE avid tumor volumes were measured and dichotomized into large and small tumor volume groups. Association with progression free survival (PFS) and overall survival (OS) were determined at median follow up of 32 months by Kaplan-Meier survival analysis with Log-Rank test. Results: During follow up, 38 patients (76%) had disease progression and 15 patients (30%) died. Kaplan-Meier analysis of PFS in GEP-NETs patients showed that smaller extrahepatic 68 Ga-DOTATATE avid tumor volume (<140 mL) is associated with significantly longer PFS (Median PFS 29.0 ± 6.7 months vs 9.0 ± 1.7 months, P = 0.0001). This trend in PFS is less prominent when total 68 Ga-DOTATATE avid tumor volume is analyzed. Similarly, Kaplan-Meier analysis of OS found that GEP-NETs patients with smaller extrahepatic 68 Ga-DOTATATE avid tumor volume (<150 mL) is associated with significantly longer OS (Median OS not reached vs 44.0 ± 12.3 months, P = 0.002). This association with OS is not statistically significant when total 68 Ga-DOTATATE avid tumor volume is analyzed. When 68 Ga-DOTATATE avid hepatic tumor volume is grouped into low (<500 mL), medium (500-1000mL) and large (> 1000 mL) tumor volumes, no statistically significant difference in PFS is observed, P = 0.19. The accuracy of extrahepatic 68 Ga-DOTATATE avid tumor volume as prognostic marker for PFS and OS at 32 months are moderate at 58% and 72%. Conclusions: Smaller extrahepatic 68 Ga-DOTATATE avid tumor volumes are associated with longer PFS and OS following 177 Lu-DOTATATE treatment in patients with advanced GEP-NETs. The accuracy of extrahepatic 68 Ga-DOTATATE avid tumor volume as prognostic marker for PFS and OS at 32 months are moderate, which may limit its clinical application.

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Erratum: Clinical Outcomes and Multidisciplinary Patterns of Failure for Olfactory Neuroblastoma: The Ohio State Experience

Journal of Neurological Surgery Part B Skull Base ◽

10.1055/s-0039-1694000 ◽

2019 ◽

Author(s):

Adam R. Wolfe ◽

Dukagjin Blakaj ◽

Nyall London ◽

Adriana Blakaj ◽

Brett Klamer ◽

...

Keyword(s):

Clinical Outcomes ◽

Olfactory Neuroblastoma ◽

Patterns Of Failure ◽

State Experience

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Somatostatin receptor imaging of olfactory neuroblastoma

The Journal of Laryngology & Otology ◽

10.1017/s0022215100136023 ◽

1996 ◽

Vol 110 (12) ◽

pp. 1161-1163 ◽

Cited By ~ 14

Author(s):

Hans A. Ramsay ◽

Kalevi J. A. Kairemo ◽

Antti P. Jekunen

Keyword(s):

Somatostatin Receptor ◽

Somatostatin Receptors ◽

Olfactory Neuroblastoma ◽

Receptor Expression ◽

Treatment Modalities ◽

Somatostatin Analogue ◽

Receptor Imaging ◽

Rare Tumour ◽

Recurrent Tumour ◽

Base Of The Skull

AbstractNeural-crest tumours, including neuroblastomas, express somatostatin receptors. This can be shown by radionuclide labelling of octreotide, a somatostatin analogue. Studies on imaging with this substance have dealt with childhood neuroblastomas. Olfactory neuroblastoma (aesthesioneuroblastoma) is a rare tumour in which somatostatin receptor content has not been analysed, nor have radionuclide methods for diagnostic purposes been described. We report a case of olfactory neuroblastoma, in which scanning with m In-labelled octreotide was performed. A strong uptake was seen at the base of the skull. This was confirmed as a recurrent tumour by magnetic resonance (MR) imaging. Uptake was also observed in the neck and chest, indicating extensive spread of the disease.Somatostatin receptor expression has been shown to correlate with prognosis in childhood neuroblastoma. The accuracy of labelled octreotide in the diagnosis of olfactory neuroblastoma indicates that it might be useful in radionuclide therapy of patients with advanced disease, when no other treatment modalities are available.

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