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Cancer. 2002 May 15;94(10):2623-34.

Neuroendocrine tumors of the sinonasal tract. Results of a prospective study incorporating chemotherapy, surgery, and combined proton-photon radiotherapy.

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Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.



The authors report the results of a prospective study of patients with malignant neuroendocrine tumors of the sinonasal tract who received multimodality treatment incorporating high-dose proton-photon radiotherapy.


Nineteen patients with olfactory neuroblastoma (ONB) or neuroendocrine carcinoma (NEC) were treated between 1992 and 1998 on a prospective study. Four patients had Kadish Stage B disease, and 15 patients had Kadish Stage C disease. The median patient age was 44 years. Patients received chemotherapy with 2 courses of cisplatin and etoposide followed by high-dose proton-photon radiotherapy to 69.2 cobalt-Gray equivalents (CGE) using 1.6-1.8 CGE per fraction twice daily in a concomitant boost schedule. Two further courses of chemotherapy were given to responders.


Of 19 patients, 15 patients were alive at the time of this report with a median follow-up of 45 months (range, 20-92 months). Four patients died from disseminated disease 8-47 months after their original diagnosis. The 5-year survival rate was 74%. There were two local recurrences, and both patients underwent salvage surgery. The 5-year local control rate of initial treatment was 88%. Acute toxicity of chemotherapy was tolerable, with no patient sustaining more than Grade 3 hematologic toxicity. Thirteen patients showed a partial or complete response to chemotherapy. One patient developed unilateral visual loss after the first course of chemotherapy; otherwise, visual preservation was achieved in all patients. Four patients who were clinically intact developed radiation-induced damage to the frontal or temporal lobe by magnetic resonance imaging criteria. Two patients showed soft tissue and/or bone necrosis, and one of these patients required surgical repair of a cerebrospinal fluid leak.


Neoadjuvant chemotherapy and high-dose proton-photon radiotherapy is a successful treatment approach for patients with ONB and NEC. Radical surgery is reserved for nonresponders. Due to the precision of delivery of radiation with stereotactic setup and protons, no radiation-induced visual loss was observed.

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