Clinical outcomes, Kadish-INSICA staging and therapeutic targeting of somatostatin receptor 2 in olfactory neuroblastoma.
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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, Brooks Laura, 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, Hughes Jonathan, 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, Hanna Ehab Y
Аннотация
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.