Lechner M, Takahashi Y, Turri-Zanoni M, Liu J, Counsell N, Hermsen M, Kaur RP, Zhao T, Ramanathan M Jr, Schartinger VH, Emanuel O, Helman S, Varghese J, Dudas J, Riechelmann H, Sprung S, Haybaeck J, Howard D, Engel NW, Stewart S, Brooks L, Pickles JC, Jacques TS, Fenton TR, Williams L, Vaz FM, O'Flynn P, Stimpson P, Wang S, Hannan SA, Unadkat S, Hughes J, Dwivedi R, Forde CT, Randhawa P, Gane S, Joseph J, Andrews PJ, Royle G, Franchi A, Maragliano R, Battocchio S, Bewicke-Copley H, Pipinikas C, Webster A, Thirlwell C, Ho D, Teschendorff A, Zhu T, Steele CD, Pillay N, Vanhaesebroeck B, Mohyeldin A, Fernandez-Miranda J, Park KW, Le QT, West RB, Saade R, Manes RP, Omay SB, Vining EM, Judson BL, Yarbrough WG, Sansovini M, Silvia N, Grassi I, Bongiovanni A, Capper D, Schüller U, Thavaraj S, Sandison A, Surda P, Hopkins C, Ferrari M, Mattavelli D, Rampinelli V, Facchetti F, Nicolai P, Bossi P, Henriquez OA, Magliocca K, Solares CA, Wise SK, Llorente JL, Patel ZM, Nayak JV, Hwang PH, Lacy PD, Woods R, O'Neill JP, Jay A, Carnell D, Forster MD, Ishii M, London NR Jr, Bell DM, Gallia GL, Castelnuovo P, Severi S, Lund VJ, and Hanna EY
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]( 177 Lu-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., Competing Interests: Conflict of interest statement NL receives research funding from Merck Inc., not related to this manuscript, and was a consultant for CoolTech Inc. and holds stock in Navigen Pharmaceuticals, both of which are unrelated to this manuscript. SW is on the advisory board of ALK, Genentech, OptiNose, SinopSys and a Consultant to NeurENT, Stryker, all of which are unrelated to this manuscript. All other authors declare no potential relevant conflicts of interest., (Copyright © 2021 Elsevier Ltd. All rights reserved.)