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Treatment of Intracranial Metastatic Esthesioneuroblastoma

University of Southern California/Norris Cancer Center, Los Angeles, CA

To the Editor:Esthesioneuroblastoma (ENB), also called an olfactory neuroblastoma, is an uncommon sinonasal tumor arising from the sensory epithelium in the nasal cavity.¹ Metastatic disease occurs in 25% to 50% of patients with ENB.^1-5 In patients with metastatic disease, 20% to 30% will involve the CNS. ENB invades the CNS by growth of tumor through the cribriform plate and invasion into the anterior cranial base. Upon entering the CNS, ENB metastasizes to either the brain parenchyma or leptomeninges. Few data are available regarding either treatment or outcome of patients with ENB and CNS metastases.

This was an open-label, nonrandomized, single-institution trial in which patients with ENB metastatic to the CNS and no prior CNS-directed therapies were treated with a single systemic chemotherapy regimen in conjunction with radiotherapy and regional chemotherapy as clinically appropriate.

Six patients (two men; four women) ranging in age from 47 to 61 years (median, 53.5 years) with ENB had clinical and neuroradiographic evidence of CNS metastases (brain parenchyma, n = 6; leptomeningeal, n = 3). CNS-directed therapy included radiotherapy (to the brain in three patients and to the spine in two) and chemotherapy (systemic in six patients and regional in three). Systemic chemotherapy consisted of carboplatin, lomustine, and vincristine administered every 2 months. Patients were evaluated by neuroradiographic and neurologic examination every other month.

One to six cycles of systemic chemotherapy were administered (median, 4.5 cycles). Six to 19 cycles of regional chemotherapy were administered (median, 17 cycles). Toxicity included aseptic meningitis (n = 3), radiation enteritis (n = 1), and grade 3 myelosuppression.⁴ Two patients required hospitalization for neutropenic fever, and two patients required a transfusion (platelets in two; RBCs in one). No treatment-related death occurred. Partial response was seen in four patients; two patients demonstrated progressive disease. Median duration of response was 9 months (range, 2 to 12 months). Overall survival ranged from 3 to 13 months (median, 10.5 months). Cause of death was progressive parenchymal brain disease (three patients), systemic disease (two patients), and leptomeningeal disease (one patient).

All patients in the present series had CNS metastases and therefore would be classified as having Kadish stage C recurrent ENB. As is customary, all patients were treated with curative intent initially, with craniofacial surgery followed by adjuvant radiotherapy.

Furthermore, four patients had a previous extraneural locoregional recurrence treated with reoperation (four patients) and systemic chemotherapy (three patients). Because of extensive CNS disease at the time of study entry, no patient was considered a candidate for reoperation. In addition, prior sinonasal radiotherapy limited the application of CNS-directed radiotherapy. Therefore, chemotherapy was the primary palliative therapy administered. The Packer chemotherapy protocol was used for two reasons.⁶ First, ENB is considered a subtype of primitive neuroectodermal tumors (PNETs), for which the Packer protocol has demonstrated efficacy.⁶ Second, platinum-based regimens are commonly used for recurrent ENB in which the largest experience was reported from the Mayo clinic.^2,4,7,8 In that study, 10 patients were reported, of whom half responded to salvage chemotherapy, with a median duration of response of 9.5 months.⁸ This experience is similar to the present study and suggests meaningful palliation is possible in patients with ENB and CNS metastases by using a combined-modality approach. Whether other chemotherapy regimens used for the treatment of PNETs (such as chronic oral etoposide or autologous bone marrow transplantation) may prove useful for recurrent ENB involving the CNS is uncertain but warrants investigation.^9,10

In conclusion, recurrent ENB with metastases to the CNS are treatable, and treatment is associated with acceptable toxicity and reasonable disease palliation using an approach similar to that of recurrent PNETs.

REFERENCES

1. Kadish S, Goodman M, Wang CC: Olfactory neuroblastoma: A clinical analysis of 17 cases. Cancer 37: 1571-1576, 1976[CrossRef][Medline]

2. Levine PA, Gallagher R, Cantrell RW: Esthesioneuroblastoma: Reflections of a 21-year experience. Laryngoscope 109: 1539-1543, 1999[CrossRef][Medline]

3. Miyamoto CR, Gleich LL, Biddinger PW, et al: Esthesioneuroblastoma and sinonasal undifferentiated carcinoma: Impact of histological grading and clinical staging on survival and prognosis. Laryngoscope 110: 1262-1265, 2000[CrossRef][Medline]

4. Simon JH, Zhen W, McCulloch TM, et al: Esthesioneuroblastoma: The University of Iowa experience 1978-1998. Laryngoscope 111: 488-493, 2000

5. Rodas RA, Erkman-Balis B, Cahill DW: Late intracranial metastasis from esthesioneuroblastoma: Case report and review of the literature. Neurosurgery 19: 622-627, 1986[Medline]

6. Packer RJ, Sutton LN, Goldwein JW, et al: Improved survival with the use of adjuvant chemotherapy in the treatment of medulloblastoma. J Neurosurg 74: 433-440, 1991[CrossRef][Medline]

7. Polin RS, Sheehan JP, Chenelle AG, et al: The role of preoperative adjuvant treatment in the management of esthesioneuroblastoma: The University of Virginia experience. Neurosurgery 42: 1029-1037, 1998[CrossRef][Medline]

8. McElroy EAJr, Buckner J, Lewis JE: Chemotherapy for advanced esthesioneuroblastoma: The Mayo Clinic experience. Neurosurgery 42: 1023-1027, 1998[Medline]

9. Ashley DM, Meier L, Kerby T, et al: Response of recurrent medulloblastoma to low dose oral etoposide. J Clin Oncol 14: 1922-1927, 1996[Abstract/Free Full Text]

10. Dunkel IJ, Bayett JM, Yates A, et al: High-dose carboplatin, thiotepa, and etoposide with autologous stem-cell rescue for patients with recurrent medulloblastoma. J Clin Oncol 16: 222-228, 1998[Abstract/Free Full Text]

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This Article Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Chamberlain, M. C. Search for Related Content PubMed PubMed Citation Articles by Chamberlain, M. C. Social Bookmarking                            What's this?