The University of Southampton
University of Southampton Institutional Repository

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

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

Introduction: olfactory neuroblastoma (ONB) is a rare cancer of the sinonasal region. We provide a comprehensive analysis of this malignancy with molecular and clinical trial data on a subset of our cohort to report on the potential efficacy of somatostatin receptor 2 (SSTR2)-targeting imaging and therapy.

Methods: we conducted a retrospective analysis of 404 primary, locally recurrent, and metastatic olfactory neuroblastoma (ONB) patients from 12 institutions in the United States of America, United Kingdom and Europe. Clinicopathological characteristics and treatment approach were evaluated. SSTR2 expression, SSTR2-targeted imaging and the efficacy of peptide receptor radionuclide therapy [PRRT](177Lu-DOTATATE) were reported in a subset of our cohort (LUTHREE trial; NCT03454763).

Results: dural infiltration at presentation was a significant predictor of overall survival (OS) and disease-free survival (DFS) in primary cases (n = 278). Kadish-Morita staging and Dulguerov T-stage both had limitations regarding their prognostic value. Multivariable survival analysis demonstrated improved outcomes with lower stage and receipt of adjuvant radiotherapy. Prophylactic neck irradiation significantly reduces the rate of nodal recurrence. 82.4% of the cohort were positive for SSTR2; treatment of three metastatic cases with SSTR2-targeted peptide-radionuclide receptor therapy (PRRT) in the LUTHREE trial was well-tolerated and resulted in stable disease (SD).

Conclusions: this study presents pertinent clinical data from the largest dataset, to date, on ONB. We identify key prognostic markers and integrate these into an updated staging system, highlight the importance of adjuvant radiotherapy across all disease stages, the utility of prophylactic neck irradiation and the potential efficacy of targeting SSTR2 to manage disease.

Adjuvant, Diagnostic imaging, Esthesioneuroblastoma, Human, Olfactory, Prognosis, Radiotherapy, Receptors, SSTR2 protein, Somatostatin
0959-8049
221-236
Lechner, Matt
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Takahashi, Yoko
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Turri-Zanoni, Mario
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Liu, Jacklyn
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Counsell, Nicholas
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Hermsen, Mario
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Kaur, Raman Preet
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Zhao, Tianna
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Ramanathan, Murugappan
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Schartinger, Volker H
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Emanuel, Oscar
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Helman, Sam
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Varghese, Jordan
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Dudas, Jozsef
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Stewart, Sarah
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Pickles, Jessica C
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Jacques, Thomas S
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Fenton, Tim R
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Williams, Luke
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Vaz, Francis M
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O'Flynn, Paul
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Stimpson, Paul
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Wang, Simon
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Zhu, Tianyu
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Judson, Benjamin L
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Hanna, Ehab Y
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Takahashi, Yoko
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Counsell, Nicholas
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Hermsen, Mario
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Zhao, Tianna
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Magliocca, Kelly
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Solares, C Arturo
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Hwang, Peter H
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O'Neill, James P
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Bell, Diana M
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Gallia, Gary L
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Castelnuovo, Paolo
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Severi, Stefano
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Lund, Valerie J
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Hanna, Ehab Y
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Lechner, Matt, Takahashi, Yoko, Turri-Zanoni, Mario, Liu, Jacklyn, Counsell, Nicholas, Hermsen, Mario, Kaur, Raman Preet, Zhao, Tianna, Ramanathan, Murugappan, Schartinger, Volker H, Emanuel, Oscar, Helman, Sam, Varghese, Jordan, Dudas, Jozsef, Riechelmann, Herbert, Sprung, Susanne, Haybaeck, Johannes, Howard, David, Engel, Nils Wolfgang, Stewart, Sarah, Pickles, Jessica C, Jacques, Thomas S, Fenton, Tim R, Williams, Luke, Vaz, Francis M, O'Flynn, Paul, Stimpson, Paul, Wang, Simon, Hannan, S Alam, Unadkat, Samit, Dwivedi, Raghav, Forde, Cillian T, Randhawa, Premjit, Gane, Simon, Joseph, Jonathan, Andrews, Peter J, Royle, Gary, Franchi, Alessandro, Maragliano, Roberta, Battocchio, Simonetta, Bewicke-Copley, Helen, Pipinikas, Christodoulos, Webster, Amy, Thirlwell, Chrissie, Ho, Debbie, Teschendorff, Andrew, Zhu, Tianyu, Steele, Christopher D, Pillay, Nischalan, Vanhaesebroeck, Bart, Mohyeldin, Ahmed, Fernandez-Miranda, Juan, Park, Ki Wan, Le, Quynh-Thu, West, Robert B, Saade, Rami, Manes, R Peter, Omay, Sacit Bulent, Vining, Eugenia M, Judson, Benjamin L, Yarbrough, Wendell G, Sansovini, Maddalena, Silvia, Nicolini, Grassi, Ilaria, Bongiovanni, Alberto, Capper, David, Schüller, Ulrich, Thavaraj, Selvam, Sandison, Ann, Surda, Pavol, Hopkins, Claire, Ferrari, Marco, Mattavelli, Davide, Rampinelli, Vittorio, Facchetti, Fabio, Nicolai, Piero, Bossi, Paolo, Henriquez, Oswaldo A, Magliocca, Kelly, Solares, C Arturo, Wise, Sarah K, Llorente, Jose L, Patel, Zara M, Nayak, Jayakar V, Hwang, Peter H, Lacy, Peter D, Woods, Robbie, O'Neill, James P, Jay, Amrita, Carnell, Dawn, Forster, Martin D, Ishii, Masaru, London, Nyall R, Bell, Diana M, Gallia, Gary L, Castelnuovo, Paolo, Severi, Stefano, Lund, Valerie J and Hanna, Ehab Y (2022) Clinical outcomes, Kadish-INSICA staging and therapeutic targeting of somatostatin receptor 2 in olfactory neuroblastoma. European Journal of Cancer, 162, 221-236. (doi:10.1016/j.ejca.2021.09.046).

Record type: Article

Abstract

Introduction: olfactory neuroblastoma (ONB) is a rare cancer of the sinonasal region. We provide a comprehensive analysis of this malignancy with molecular and clinical trial data on a subset of our cohort to report on the potential efficacy of somatostatin receptor 2 (SSTR2)-targeting imaging and therapy.

Methods: we conducted a retrospective analysis of 404 primary, locally recurrent, and metastatic olfactory neuroblastoma (ONB) patients from 12 institutions in the United States of America, United Kingdom and Europe. Clinicopathological characteristics and treatment approach were evaluated. SSTR2 expression, SSTR2-targeted imaging and the efficacy of peptide receptor radionuclide therapy [PRRT](177Lu-DOTATATE) were reported in a subset of our cohort (LUTHREE trial; NCT03454763).

Results: dural infiltration at presentation was a significant predictor of overall survival (OS) and disease-free survival (DFS) in primary cases (n = 278). Kadish-Morita staging and Dulguerov T-stage both had limitations regarding their prognostic value. Multivariable survival analysis demonstrated improved outcomes with lower stage and receipt of adjuvant radiotherapy. Prophylactic neck irradiation significantly reduces the rate of nodal recurrence. 82.4% of the cohort were positive for SSTR2; treatment of three metastatic cases with SSTR2-targeted peptide-radionuclide receptor therapy (PRRT) in the LUTHREE trial was well-tolerated and resulted in stable disease (SD).

Conclusions: this study presents pertinent clinical data from the largest dataset, to date, on ONB. We identify key prognostic markers and integrate these into an updated staging system, highlight the importance of adjuvant radiotherapy across all disease stages, the utility of prophylactic neck irradiation and the potential efficacy of targeting SSTR2 to manage disease.

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Accepted/In Press date: 28 September 2021
e-pub ahead of print date: 31 December 2021
Published date: 1 February 2022
Additional Information: Funding Information: We would like to acknowledge the invaluable support from Prof. Tariq Enver and the UCL Cancer Institute. We would also like to thank Josep Linares, Dr. Naomi Guppy and David Allan from HSL Labs/UCL Advanced Diagnostics. TJ and his team are grateful for funding from the Brain Tumour Charity , Children with Cancer UK , Great Ormond Street Hospital Children’s Charity, Olivia Hodson Cancer Fund, Cancer Research UK and the National Institute of Health Research. All research at Great Ormond Street Hospital NHS Foundation Trust and UCL Great Ormond Street Institute of Child Health is made possible by the NIHR Great Ormond Street Hospital Biomedical Research Centre. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. Funding Information: This work was supported by the Rhinology and Laryngology Research Fund, Royal College of Surgeons (Lionel Colledge Family Research Grant) and the UCL / UCLH Biomedical Research Centre (BRC). Additional support was provided by the Intramural Research Program of the National Institutes of Health / National Institute on Deafness and Other Communication Disorders . Funding Information: This work was supported by the Rhinology and Laryngology Research Fund, Royal College of Surgeons (Lionel Colledge Family Research Grant) and the UCL/UCLH Biomedical Research Centre (BRC). Additional support was provided by the Intramural Research Program of the National Institutes of Health/National Institute on Deafness and Other Communication Disorders.We would like to acknowledge the invaluable support from Prof. Tariq Enver and the UCL Cancer Institute. We would also like to thank Josep Linares, Dr. Naomi Guppy and David Allan from HSL Labs/UCL Advanced Diagnostics. TJ and his team are grateful for funding from the Brain Tumour Charity, Children with Cancer UK, Great Ormond Street Hospital Children's Charity, Olivia Hodson Cancer Fund, Cancer Research UK and the National Institute of Health Research. All research at Great Ormond Street Hospital NHS Foundation Trust and UCL Great Ormond Street Institute of Child Health is made possible by the NIHR Great Ormond Street Hospital Biomedical Research Centre. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. Publisher Copyright: © 2021 Elsevier Ltd Copyright: Copyright 2022 Elsevier B.V., All rights reserved.
Keywords: Adjuvant, Diagnostic imaging, Esthesioneuroblastoma, Human, Olfactory, Prognosis, Radiotherapy, Receptors, SSTR2 protein, Somatostatin

Identifiers

Local EPrints ID: 455983
URI: http://eprints.soton.ac.uk/id/eprint/455983
ISSN: 0959-8049
PURE UUID: b5d9dc13-411c-4605-b609-a38003a731f7
ORCID for Tim R Fenton: ORCID iD orcid.org/0000-0002-4737-8233

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Date deposited: 11 Apr 2022 17:20
Last modified: 01 Jul 2022 16:50

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Contributors

Author: Matt Lechner
Author: Yoko Takahashi
Author: Mario Turri-Zanoni
Author: Jacklyn Liu
Author: Nicholas Counsell
Author: Mario Hermsen
Author: Raman Preet Kaur
Author: Tianna Zhao
Author: Murugappan Ramanathan
Author: Volker H Schartinger
Author: Oscar Emanuel
Author: Sam Helman
Author: Jordan Varghese
Author: Jozsef Dudas
Author: Herbert Riechelmann
Author: Susanne Sprung
Author: Johannes Haybaeck
Author: David Howard
Author: Nils Wolfgang Engel
Author: Sarah Stewart
Author: Jessica C Pickles
Author: Thomas S Jacques
Author: Tim R Fenton ORCID iD
Author: Luke Williams
Author: Francis M Vaz
Author: Paul O'Flynn
Author: Paul Stimpson
Author: Simon Wang
Author: S Alam Hannan
Author: Samit Unadkat
Author: Raghav Dwivedi
Author: Cillian T Forde
Author: Premjit Randhawa
Author: Simon Gane
Author: Jonathan Joseph
Author: Peter J Andrews
Author: Gary Royle
Author: Alessandro Franchi
Author: Roberta Maragliano
Author: Simonetta Battocchio
Author: Helen Bewicke-Copley
Author: Christodoulos Pipinikas
Author: Amy Webster
Author: Chrissie Thirlwell
Author: Debbie Ho
Author: Andrew Teschendorff
Author: Tianyu Zhu
Author: Christopher D Steele
Author: Nischalan Pillay
Author: Bart Vanhaesebroeck
Author: Ahmed Mohyeldin
Author: Juan Fernandez-Miranda
Author: Ki Wan Park
Author: Quynh-Thu Le
Author: Robert B West
Author: Rami Saade
Author: R Peter Manes
Author: Sacit Bulent Omay
Author: Eugenia M Vining
Author: Benjamin L Judson
Author: Wendell G Yarbrough
Author: Maddalena Sansovini
Author: Nicolini Silvia
Author: Ilaria Grassi
Author: Alberto Bongiovanni
Author: David Capper
Author: Ulrich Schüller
Author: Selvam Thavaraj
Author: Ann Sandison
Author: Pavol Surda
Author: Claire Hopkins
Author: Marco Ferrari
Author: Davide Mattavelli
Author: Vittorio Rampinelli
Author: Fabio Facchetti
Author: Piero Nicolai
Author: Paolo Bossi
Author: Oswaldo A Henriquez
Author: Kelly Magliocca
Author: C Arturo Solares
Author: Sarah K Wise
Author: Jose L Llorente
Author: Zara M Patel
Author: Jayakar V Nayak
Author: Peter H Hwang
Author: Peter D Lacy
Author: Robbie Woods
Author: James P O'Neill
Author: Amrita Jay
Author: Dawn Carnell
Author: Martin D Forster
Author: Masaru Ishii
Author: Nyall R London
Author: Diana M Bell
Author: Gary L Gallia
Author: Paolo Castelnuovo
Author: Stefano Severi
Author: Valerie J Lund
Author: Ehab Y Hanna

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