Matt Lechner1, Yoko Takahashi2, Mario Turri-Zanoni3, Jacklyn Liu4, Nicholas Counsell5, Mario Hermsen6, Raman Preet Kaur7, Tianna Zhao8, Murugappan Ramanathan7, Volker H Schartinger9, Oscar Emanuel4, Sam Helman10, Jordan Varghese10, Jozsef Dudas9, Herbert Riechelmann9, Susanne Sprung11, Johannes Haybaeck12, David Howard13, Nils Wolfgang Engel14, Sarah Stewart15, Laura Brooks15, Jessica C Pickles16, Thomas S Jacques16, Tim R Fenton17, Luke Williams18, Francis M Vaz19, Paul O'Flynn19, Paul Stimpson19, Simon Wang20, S Alam Hannan19, Samit Unadkat19, Jonathan Hughes15, Raghav Dwivedi15, Cillian T Forde19, Premjit Randhawa19, Simon Gane19, Jonathan Joseph19, Peter J Andrews19, Gary Royle4, Alessandro Franchi21, Roberta Maragliano22, Simonetta Battocchio23, Helen Bewicke-Copley4, Christodoulos Pipinikas4, Amy Webster4, Chrissie Thirlwell24, Debbie Ho25, Andrew Teschendorff26, Tianyu Zhu26, Christopher D Steele8, Nischalan Pillay4, Bart Vanhaesebroeck4, Ahmed Mohyeldin27, Juan Fernandez-Miranda27, Ki Wan Park28, Quynh-Thu Le29, Robert B West29, Rami Saade2, R Peter Manes30, Sacit Bulent Omay30, Eugenia M Vining30, Benjamin L Judson30, Wendell G Yarbrough31, Maddalena Sansovini32, Nicolini Silvia32, Ilaria Grassi32, Alberto Bongiovanni33, David Capper34, Ulrich Schüller35, Selvam Thavaraj36, Ann Sandison37, Pavol Surda38, Claire Hopkins38, Marco Ferrari39, Davide Mattavelli40, Vittorio Rampinelli40, Fabio Facchetti23, Piero Nicolai39, Paolo Bossi41, Oswaldo A Henriquez10, Kelly Magliocca42, C Arturo Solares10, Sarah K Wise10, Jose L Llorente43, Zara M Patel28, Jayakar V Nayak28, Peter H Hwang28, Peter D Lacy44, Robbie Woods44, James P O'Neill45, Amrita Jay46, Dawn Carnell15, Martin D Forster47, Masaru Ishii7, Nyall R London48, Diana M Bell49, Gary L Gallia50, Paolo Castelnuovo3, Stefano Severi32, Valerie J Lund51, Ehab Y Hanna52. 1. UCL Cancer Institute, University College London, London, UK; Academic Head and Neck Centre, UCL Division of Surgery and Interventional Science, University College London, London, UK; ENT Department, Barts Health NHS Trust, London, United Kingdom; Rhinology & Endoscopic Skull Base Surgery, Department of Otolaryngology-H&N Surgery, Stanford University School of Medicine, Palo Alto, USA. Electronic address: m.lechner@ucl.ac.uk. 2. Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, USA. 3. Unit of Otorhinolaryngology and Head & Neck Surgery, Department of Biotechnology and Life Sciences, ASST Sette Laghi, University of Insubria, Varese, Italy. 4. UCL Cancer Institute, University College London, London, UK. 5. Cancer Research UK & UCL Cancer Trials Centre, University College London, London, UK. 6. Department of Head and Neck Oncology, Instituto de Investigacio´n Sanitaria Del Principado de Asturias (ISPA), Instituto Universitario de Oncologı´a Del Principado de Asturias (IUOPA), Centro de Investigacio´n Biome´dica en Red (CIBER-ONC), Oviedo, Spain. 7. Department of Otolaryngology - Head and Neck Surgery, Johns Hopkins School of Medicine, Baltimore, USA. 8. Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, USA. 9. Department of Otorhinolaryngology, Medical University of Innsbruck, Innsbruck, Austria. 10. Department of Otolaryngology-Head and Neck Surgery, Emory University School of Medicine, Atlanta, USA. 11. Institute of Pathology, Neuropathology and Molecular Pathology, Medical University of Innsbruck, Innsbruck, Austria. 12. Institute of Pathology, Neuropathology and Molecular Pathology, Medical University of Innsbruck, Innsbruck, Austria; Diagnostic & Research Center for Molecular BioMedicine, Institute of Pathology, Medical University Graz, Graz, Austria. 13. Head and Neck Cancer Unit, Imperial College Healthcare NHS Trust, London, UK. 14. Department of Oncology, Haematology and Bone Marrow Transplantation with Section Pneumology, Hubertus Wald Tumorzentrum, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. 15. Head and Neck Centre, University College London Hospitals NHS Trust, London, UK. 16. Department of Developmental Biology and Cancer & Teaching Department, UCL Great Ormond Street Institute of Child Health, London, UK; Department of Histopathology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK. 17. School of Biosciences, University of Kent, Canterbury, UK; School of Cancer Sciences, Faculty of Medicine, University of Southampton, Southampton, UK. 18. UCL Division of Surgery and Interventional Science, University College London, London, UK. 19. Royal National Ear, Nose and Throat Hospital and Head and Neck Centre, University College London Hospitals NHS Trust, London, UK. 20. Institute of Nuclear Medicine, University College London, London, UK. 21. Department of Translational Research, University of Pisa, Pisa, Italy. 22. Department of Medicine and Surgery, Unit of Pathology, University of Insubria, Varese, Italy. 23. Pathology Unit, Department of Molecular and Translational Medicine, University of Brescia, ASST Spedali Civili, Brescia, Italy. 24. UCL Cancer Institute, University College London, London, UK; College of Medicine and Health and Institute of Biomedical and Clinical Science, University of Exeter, Exeter, UK. 25. Stem Cell Institute, University of Cambridge, Cambridge, UK. 26. CAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Shanghai, China. 27. Department of Neurosurgery, Stanford University School of Medicine, Palo Alto, USA. 28. Rhinology & Endoscopic Skull Base Surgery, Department of Otolaryngology-H&N Surgery, Stanford University School of Medicine, Palo Alto, USA. 29. Department of Radiation Oncology, Stanford University School of Medicine, Palo Alto, USA. 30. Department of Neurosurgery, Yale School of Medicine, New Haven, USA. 31. Department of Otolaryngology/Head and Neck Surgery, UNC School of Medicine, Chapel Hill, NC, USA. 32. Therapeutic Nuclear Medicine, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy. 33. Osteoncology and Rare Tumors Center (CDO-TR), IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy. 34. Department of Neuropathology, Charite - Universitatsmedizin Berlin, Corporate Member of Freie Universitat Berlin and Humboldt-Universitat zu Berlin, Berlin, Germany; German Cancer Consortium (DKTK), Partner Site Berlin, German Cancer Research Center (DKFZ), Heidelberg, Germany. 35. Department of Pediatric Hematology and Oncology, Institute of Neuropathology, And Research Institute Children's Cancer Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. 36. Centre for Clinical, Oral & Translational Science, King's College London, Department of Head and Neck Pathology, Guy's Hospital, London, UK. 37. Department of Head and Neck Pathology, Guy's Hospital, London, UK. 38. Guy's Hospital, King's College, London, UK. 39. Section of Otorhinolaryngology - Head and Neck Surgery, Department of Neurosciences, University of Padova, Italy. 40. Unit of Otorhinolaryngology - Head and Neck Surgery, Department of Medical and Surgical Specialities, Radiological Sciences, and Public Health, University of Brescia, Brescia, Italy. 41. Medical Oncology, Department of Medical and Surgical Specialities, Radiological Sciences, and Public Health, University of Brescia, Brescia, Italy. 42. Department of Pathology, Emory University School of Medicine, Atlanta, USA. 43. Dept Otolaryngology, Hospital Universitario Central de Asturias, Oviedo, Spain. 44. Department of Otolaryngology, Head and Neck Surgery, Beaumont Hospital, Dublin, Ireland. 45. Department of Otolaryngology, Head and Neck Surgery, Beaumont Hospital, Dublin, Ireland; The Royal College of Surgeons in Ireland, Dublin, Ireland. 46. Department of Histopathology, University College London Hospitals NHS Trust, London, UK. 47. UCL Cancer Institute, University College London, London, UK; Academic Head and Neck Centre, UCL Division of Surgery and Interventional Science, University College London, London, UK; Department of Oncology, Haematology and Bone Marrow Transplantation with Section Pneumology, Hubertus Wald Tumorzentrum, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. 48. Department of Otolaryngology - Head and Neck Surgery, Johns Hopkins School of Medicine, Baltimore, USA; Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, USA; Sinonasal and Skull Base Tumor Program, Head and Neck Surgery Branch, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD, USA. 49. Department of Pathology, The University of Texas MD Anderson Cancer Center Houston, USA; Division of Anatomic Pathology, City of Hope Comprehensive Cancer Center, Duarte, CA, United States. 50. Department of Otolaryngology - Head and Neck Surgery, Johns Hopkins School of Medicine, Baltimore, USA; Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, USA. 51. Royal National Ear, Nose and Throat Hospital and Head and Neck Centre, University College London Hospitals NHS Trust, London, UK. Electronic address: v.lund@ucl.ac.uk. 52. Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, USA. Electronic address: EYHanna@mdanderson.org.
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.
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.
Authors: John P Marinelli; Jeffrey R Janus; Jamie J Van Gompel; Michael J Link; Eric J Moore; Kathryn M Van Abel; Brandon W Peck; Christine M Lohse; Daniel L Price Journal: J Neurol Surg B Skull Base Date: 2018-02-22
Authors: Kevin C Miller; John P Marinelli; Jamie J Van Gompel; Michael J Link; Jeffrey R Janus; Robert L Foote; Katharine A Price; Joaquin Garcia; Michael Rivera; Ashish V Chintakuntlawar Journal: Head Neck Date: 2018-12-10 Impact factor: 3.147
Authors: Diana Bell; Rami Saade; Dianna Roberts; Thomas J Ow; Michael Kupferman; Franco DeMonte; Ehab Y Hanna Journal: Head Neck Pathol Date: 2014-05-08
Authors: John P Marinelli; Jeffrey R Janus; Jamie J Van Gompel; Michael J Link; Robert L Foote; Christine M Lohse; Katharine A Price; Ashish V Chintakuntlawar Journal: Head Neck Date: 2018-05-13 Impact factor: 3.147
Authors: Khodayar Goshtasbi; Arash Abiri; Mehdi Abouzari; Ronald Sahyouni; Beverly Y Wang; Bobby A Tajudeen; Frank P K Hsu; Gilbert Cadena; Edward C Kuan Journal: Int Forum Allergy Rhinol Date: 2019-06-28 Impact factor: 3.858
Authors: Waleed M Abuzeid; Changeun Song; Judd H Fastenberg; Christina H Fang; Noel Ayoub; Elina Jerschow; Paul K Mohabir; Peter H Hwang Journal: Laryngoscope Date: 2017-11-29 Impact factor: 3.325
Authors: Jamie J Van Gompel; Caterina Giannini; Kerry D Olsen; Eric Moore; Manolo Piccirilli; Robert L Foote; Jan C Buckner; Michael J Link Journal: J Neurol Surg B Skull Base Date: 2012-10
Authors: Christodoulos P Pipinikas; Harpreet Dibra; Anna Karpathakis; Andrew Feber; Marco Novelli; Dahmane Oukrif; Guiseppe Fusai; Roberto Valente; Martyn Caplin; Tim Meyer; Andrew Teschendorff; Christopher Bell; Tiffany J Morris; Paolo Salomoni; Tu-Vinh Luong; Brian Davidson; Stephan Beck; Christina Thirlwell Journal: Endocr Relat Cancer Date: 2015-04-21 Impact factor: 5.678