Radiation Oncology/Esthesioneuroblastoma

Esthesioneuroblastoma

Overview

• Also known as olofactory neuroblastoma
• Originating from the olofactory epithelium in the roof of the nasal cavity
  • Exact cell of origin controversial
  • Data suggest ENB is derived from immature olofactory neurons of neuroectodermal origin
• Lines superior one third of nasal septum, cribriform plate, and superior turbinate
  • Tumor typically occurs in the vault of nasal cavity or lateral wall adjacent to ethymoid sinuses
• Estimated to be 3-5% of nasal malignant tumors
• Bimodal age distribution
  • 10-20 years
  • 40-60 years
• Clinical presentation
  • Unilateral symptoms: nasal obstruction, epistaxis
• Nodal spread
  • Rare in early stage (<10%)
  • More common in advanced stage (30-50%)

Staging

Kadish System

• Kadish A: confined to nasal cavity (18%)
• Kadish B: extends to paranasal sinuses (32%)
• Kadish C: extends beyond nasal cavity and paranasal sinuses (49%)
• Kadish D: lymph node or distant metastases

TNM Staging

• As per Nasal Cavity and Paranasal Sinuses staging

Outcome

• Survival
  • Kadish A: 83%
  • Kadish B: 49%
  • Kadish C: 39%
  • Kadish D: 13%
• Predictors of survival
  • Kadish stage
  • Treatment modality
  • Age at diagnosis

Treatment

• Rare disease, so most studies are small, single institution, retrospective
• Surgery frequently primary modality
• Some evidence that postop RT improves local control, particularly for more advanced disease
• Some evidence that concurrent chemo-RT may be beneficial
• Elective nodal irradiation controversial, particularly if chemo-RT used for primary disease
• Treatment recommendations (Hansen, 2nd ed)
  • Small, low grade tumors: surgery or RT alone (65-70 Gy)
  • Large tumors: consider preop RT (50 Gy), surgery, or postop chemo-RT (60 Gy)

• Ulsan University, Korea; 2011 (1996-2007) PMID 20421144 -- "Radiotherapy for esthesioneuroblastoma: is elective nodal irradiation warranted in the multimodality treatment approach?" (Noh OK, Int J Radiat Oncol Biol Phys. 2011 Feb 1;79(2):443-9. Epub 2010 Apr 24.)
  • Retrospective. 14 patients, various combinations of modalities, elective nodal irradiation 4 patients. Median F/U 2.2 years
  • Outcome: 3-year OS 73%. LR 21%, regional recurrence 21%, distant failure 14%. No nodal failure in patients treated with chemo-RT, regardless of ENI
  • Conclusion: Elective nodal irradiation may play a limited role, if patients treated with chemo-RT

• Chiba; 2007 (1999-2005) PMID 17398027 -- "Proton-beam therapy for olfactory neuroblastoma." (Nishimura H, Int J Radiat Oncol Biol Phys. 2007 Jul 1;68(3):758-62. Epub 2007 Mar 29.)
  • Retrospective. 14 patients (Kadish A 2/14, Kadish B 5/14, Kadish C 7/14). Dose 65 GyE in 2.5 Gy/fx. Median F/U 3.3 years
  • Outcome: 5-year LC 84%, 5-year RFS 71%, 5-year OS 93%
  • Toxicity: Liquorrhea 1 patient, no other Grade 3+
  • Conclusion: Excellent local control and survival outcome, without serious side effects

• Harvard; 2002 (1992-1998) PMID 12173330 -- "Neuroendocrine tumors of the sinonasal tract. Results of a prospective study incorporating chemotherapy, surgery, and combined proton-photon radiotherapy." (Fitzek MM, Cancer. 2002 May 15;94(10):2623-34.)
  • Prospective. 19 patients with olofactory neuroblastoma or neuroendocrine carcinoma. Kadish Stage B 4/19, Kadish Stage C 15/19. Induction cisplatin/etoposide x2 cycles, then proton/photon RT to 69.2 CGE concomitant boost. If response, further 2 cycles of chemo. Median F/U 3.7 years
  • Outcome: 5-year OS 74%; 5-year LC 88%
  • Toxicity: 1 patient unilateral vision loss after induction chemo. 4 patients frontal/temporal lobe damage by MRI. 2 patients soft tissue/bone necrosis. No radiation-induced visual loss
  • Conclusion: This approach is successful, with radical surgery reserved for nonresponders