ORIGINAL ARTICLE
Optimization of long-term outcomes for patients with esthesioneuroblastoma
Thomas J. Ow, MD,1 Ehab Y. Hanna, MD,1 Dianna B. Roberts, PhD,1 Nicholas B. Levine, MD,2 Adel K. El-Naggar, MD, PhD,3 David I. Rosenthal, MD,4
Franco DeMonte, MD, FRCS(C),2 Michael E. Kupferman, MD1*
1
Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, 2Department of Neurosurgery, The University of Texas MD
Anderson Cancer Center, Houston, Texas, 3Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, 4Department of Radiation Oncology,
The University of Texas MD Anderson Cancer Center, Houston, Texas.
Accepted 8 February 2013
Published online 18 June 2013 in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/hed.23327
ABSTRACT: Background. Esthesioneuroblastoma is a rare cancer of the
anterior cranial base that arises in the region of the olfactory rootlets.
The purpose of this study was to review the long-term outcomes of
patients diagnosed with esthesioneuroblastoma (ENB) treated at a single
institution to determine factors associated with improved disease control
and survival.
Methods. A retrospective review of 70 patients with ENB treated at
the University of Texas MD Anderson Cancer Center between 1992
and 2007 was undertaken. Survival and recurrence was analyzed
and compared using the Kaplan–Meier method and log-rank
statistics.
Results. Seventy patients were reviewed. The majority (77%) had T3 or
T4 disease at presentation, 38% identified as modified Kadish stage C
or D. Ninety percent of patients received surgical resection as part of
their treatment, and 66% received postoperative radiation or
chemoradiation. The median follow-up was 91.4 months (7.6 years).
Forty-eight percent of patients developed recurrent disease and the
median time to recurrence was 6.9 years. Overall and disease-specific
median survival was 10.5 and 11.6 years, respectively. Patients who
were treated with surgery alone had a median disease-specific survival
of 87.9 months, whereas those who were treated with surgery and
postoperative radiation had a median disease-specific survival of 218.5
months (p ¼ .047).
Conclusion. Patients with ENB can achieve favorable long-term survival,
even if disease is locally advanced. Survival is improved considerably
when surgical resection is followed by postoperative radiation. However,
recurrence rates and mortality remain high, and therefore long-term
C 2013 Wiley Periodicals,
observation in these patients is warranted. V
Inc. Head Neck 36: 524–530, 2014
INTRODUCTION
emphasizing the prognostic significance of local invasion
of vital structures (ie, orbit, cranium) and the presence of
regional and distant metastasis. Generally, it seems that
surgical resection and adjuvant radiation provides the
optimal management strategy for ENB.4,12–14 New techniques and therapies have become available for the management of ENB, including endoscopic surgery, advances in
the delivery of radiation, and novel chemotherapeutics.
Current standards of care and outcomes must be critically
appraised for comparison and quality control for these
new treatment modalities.
In the current study, we have reviewed all of the
patients evaluated for treatment or follow-up for ENB at
our tertiary cancer center during a 15-year period. Our
objective was to describe long-term recurrence and survival outcomes for our large cohort of patients with ENB,
and to determine clinicopathologic features or treatment
factors that were associated with the most favorable
outcomes.
Esthesioneuroblastoma (ENB), also called olfactory neuroblastoma, is a neuroectodermal tumor that arises in
the region of the superior nasal cavity and the cribriform plate of the anterior skull base.1 Since the first
description of this neoplasm in 1924 by Berger and
Richard,2 the diagnosis and management of these
tumors has progressed remarkably. ENB accounts for
roughly 3% of all intranasal tumors.3 Despite its rarity,
this disease has received considerable attention in the
literature. Approximately 1200 cases have been reported
to date.3,4
The anatomic location, the natural history, and the low
incidence of ENB limit the ability to determine the optimal diagnosis and treatment strategies for this disease.
Despite these challenges, several retrospective reviews5–7
and meta-analyses4,8 have yielded some fundamental principles in the management of this neoplasm. Several classification systems for ENB have been proposed,9–11 each
KEY WORDS: esthesioneuroblastoma, olfactory, surgical procedures,
operative, radiotherapy, survival
MATERIALS AND METHODS
*Corresponding author: M. E. Kupferman, 1400 Pressler Drive, Unit 1445,
Houston, TX 77030-4008. E-mail: MEKupfer@mdanderson.org
Ehab Y. Hanna, MD, editor, was recused from consideration of this manuscript.
524
HEAD & NECK—DOI 10.1002/HED
APRIL 2014
Patient data
A retrospective review of all patients with the diagnosis
of ENB at The University of Texas MD Anderson Cancer
TREATMENT
FOR ESTHESIONEUROBLASTOMA
TABLE 1. Patient characteristics.
Characteristics
FIGURE 1. Distribution of age at diagnosis among patients
reviewed in this study (n ¼ 70).
Center (MD Anderson) was undertaken. Data was gathered
as part of an Institutional Review Board–approved clinical
database for patients with tumors of the paranasal sinuses.
The study was approved by the Institutional Review Board
and informed consent was waived. Patients treated or followed for ENB at MD Anderson between the years of
1992 to 2007 were included. The records for these patients
were last reviewed for this study in March 2011.
Several clinicopathologic factors were recorded, including patient demographic information, date of diagnosis,
and date that treatments were rendered. Dates of diagnosis, treatment, recurrence, and death were extracted from
the records or deduced from clinical notes. Disease stage
was either recorded from the patient charts or determined
from imaging reports. Both American Joint Committee on
Cancer (AJCC) stage and Kadish score, as modified by
Morita,11 was recorded. All pathological specimens were
evaluated by an experienced head and neck pathologist at
the time of presentation to MD Anderson if treatment was
rendered at our institution.
The following outcomes were evaluated: local recurrence, regional recurrence, distant metastasis, and death.
The date of last contact in the record and the presence of
disease at this time point were also noted.
Statistical analysis
Overall survival was defined as the period from the last
date of initial treatment to the time of death or last contact. Patients alive at last contact were censored. Diseasespecific survival was defined as the last date of initial
treatment to the time of death with active disease.
Patients who were lost to follow-up or who died without
recurrence were censored. Time to recurrence was defined
as the last date of initial treatment to the time of first recurrence. Patients who died or who were lost to followup before recurrence were censored. Median follow-up
was calculated according to the method of Schemper and
Smith.15 Survival analyses were performed using the
Kaplan–Meier method. Survival between groups was
compared using the log-rank test.
RESULTS
Seventy patients were identified and had adequate
records for analysis in this study. The median age of
patients at the time of diagnosis was 51.9 years. The distribution of the age at diagnosis among patients in the
study is presented in Figure 1. The majority of patients
No. of patients
Total
Age
Median age at diagnosis
Range
<50 y
>50 y
Sex
Male
Female
Staging
T classification
T1 or T2
T3 or T4
Unknown
N classification
N0
Nþ
Unknown
Kadish/Morita stage
A or B
B or C, unclear
C
D
Unknown
Orbital invasion
Intracranial extension
Range or %
70
37
33
51.9 y
9.0–78.7 y
53
47
42
28
60
40
12
54
4
17
77
6
66
3
1
94
4
2
29
1
24
3†
13
6*
25*
41
1
34
4
19
9*
36*
* Five patients with orbital invasion had concurrent intracranial extension and 1 patient had
orbital extension alone.
†
Two of the 3 patients with neck metastases (therefore Kadish D) had concurrent intracranial
extension and orbital invasion.
were men (60%). In 13 patients, the modified Kadish
stage at presentation was not evident from the records.
Among the remaining patients, 29 had stage A or B disease according to the classification system described by
Morita et al.11 Twenty-four had stage C, and only 3
patients presented with metastasis to cervical lymph
nodes (stage D). Demographic and staging information
are summarized in Table 1.
Forty-six patients (66%) received definitive treatment at
MD Anderson. Twenty-four patients (34%) presented to
MD Anderson with recurrent disease or transferred care
to the center for surveillance after definitive treatment
elsewhere. Thirty-six patients (52%) underwent open craniofacial resection, and 5 (7%) underwent endoscopicassisted craniofacial resection. Forty-five patients (66%)
received postoperative radiation treatment. Eleven patients
(16%) received chemotherapy in the neoadjuvant setting.
A summary of the treatments rendered in this study is
summarized in Table 2.
The median follow-up for this cohort was 91.4 months
(range, 1.61 months–440 months). Five patients had less
than 6 months follow-up available for review, and were
thus excluded from analysis for recurrent disease. Four
patients had no disease-free interval. Twenty-eight
patients (46%) had recurrence, and the median time to recurrence was 82.9 months (6.9 years). First recurrence
was local in 11 patients (18%), regional in 11 patients
(18%), and distant in 6 patients (10%). Sixty-five patients
were evaluable for the development of distant metastasis.
Overall, a total of 10 patients (15%) developed distant
HEAD & NECK—DOI 10.1002/HED
APRIL 2014
525
OW ET AL.
TABLE 2. Treatments rendered.
Treatments
Treated definitively at MD Anderson
Seen at MD Anderson after definitive Rx
Surgery
Open craniofacial resection
Endoscopic –
Assisted craniofacial resection
Open approach, other
Endoscopic –
Definitive surgery
Endoscopic –
Not definitive surgery
Procedure unclear
No surgery
Radiation treatment
None
Postoperative
Preoperative
Definitive
Unclear
Chemotherapy
No
Yes
Before definitive Rx
Concurrent with definitive Rx
After definitive Rx
No. of
patients
%
46
24
66
34
36
52
5
6
7
9
3
4
9
4
7
13
6
10
12
45
4
7
2
18
66
6
10
55
15
11
1
5
79
21
16
1
7
Abbreviation: Rx, treatment.
metastasis. Recurrence patterns and patterns of metastasis
are summarized in Table 3.
Figure 2 presents the overall survival and disease-specific survival for the entire cohort. Median overall survival was 126.3 months (10.5 years), and median diseasespecific survival was 139 months (11.6 years). Diseasespecific survival stratified by AJCC T and N classification, as well as by Morita (modified Kadish) stage, is pre-
TABLE 3. Patterns of recurrence.
Pattern
No. of
patients
%
28
33
46
54
11
11
6
18
18
10
10
55
15
85
Recurred
Yes
No
Site of first recurrence
Local
Regional
Distant
Distant metastasis
Yes
No
Sites of distant metastasis
Spine
Parietal lobe, brain
Leptomeningeal
Breast
Lung
Skull
Dura
526
HEAD & NECK—DOI 10.1002/HED
4
2
2
1
1
1
1
APRIL 2014
sented in Figure 3. The disease-specific survival of
patients with T3 or T4 disease (54 patients) was analyzed
after these patients were stratified by treatment (Figure
4A). Patients with T3 or T4 disease who received surgery
and postoperative radiation had a median disease-specific
survival of 218.5 months (18.2 years) compared to 87.9
months (7.3 years) for those who received surgery alone,
log-rank p ¼ .04 (Figure 4B).
DISCUSSION
In the current study, we present the outcomes after
extensive follow-up (median 7.6 years) for a large cohort
of patient with ENB who were treated and/or followed at
our institution. Our findings confirm and emphasize several important characteristics of this disease.
In our study, patients with locally advanced (T3 and
T4) disease clearly benefited from postoperative radiation.
The median disease-specific survival after resection followed by radiation for patients with T3 and T4 disease
was excellent (18.2 years in our analysis). The difference
in disease-specific survival between those treated with
surgery and radiation versus surgery alone reached statistical significance. Our findings are in keeping with other
reports and reviews. Although craniofacial resection with
postoperative radiation is generally held as the gold standard for advanced ENB, few reports have been able to
definitively show that this approach is optimal. Several
single-institution reports have favored the addition of
postoperative radiation to surgery.10,14,16,17 Dulguerov and
Calcaterra10 reported a dramatic difference in recurrencefree status among those treated with surgery or radiation
alone (14% and 40%, respectively, compared to 92% for
surgery and radiation). Chao et al18 found that multimodality therapy was associated with improved survival
compared to single modality treatment. In the study by
Foote et al,14 it was suggested that adjuvant radiation
improved local control. Diaz et al16 reported a 10-year
survival of 75% among patients with Kadish C disease
treated with surgery and postoperative radiation. In the
meta-analysis by Dulguerov et al,4 multimodality therapy,
particularly surgery combined with radiation, yielded the
highest survival rates. This finding was supported by 2
separate analyses of the Surveillance, Epidemiology, and
End Results database,13,19 both of which showed that surgery combined with radiation is superior to radiation
alone. Surgery and radiation compared to surgery alone
did not reach a statistically significant difference in these
reports, however. A meta-analysis by Kane et al20 also
did not find a significant difference in survival between
those patients that received surgery alone versus those
that received postoperative radiation. Our study, evaluating a large cohort of patients with extended follow-up,
supports the use of postoperative radiation for patients
with locally advanced disease.
It is important to emphasize the importance of establishing the correct diagnosis when a patient presents with
a sinonasal neuroendocrine tumor. At our institution, all
pathological diagnoses are confirmed after careful review
of pathologic specimens obtained from outside institutions. Poorly differentiated ENB can easily be confused
with other neuroendocrine tumors of the head and neck,
including
sinonasal
undifferentiated
carcinoma,
TREATMENT
FOR ESTHESIONEUROBLASTOMA
FIGURE 2. Overall (A) and disease-specific (B) survival.
neuroendocrine carcinoma, and small cell carcinoma. The
disparity in the natural history as well as the local and
distant control rates between ENB and these more aggressive non-ENB entities has been previously reported.21 For
non-ENB neuroendocrine tumors, the high rates of systemic failure warrants a multimodality treatment approach
that includes systemic chemotherapy, whereas ENB can
often be treated with local therapy alone. Thus, accurate
pathologic diagnosis is crucial to select the appropriate
treatment and optimize outcome among these patients.
It is clear from our study that long-term follow-up is
mandatory for patients with ENB, a finding which is supported by previous publications. Despite excellent survival outcomes (disease-specific survival of 11.6 years),
46% of the patients developed recurrent disease in our
study with a median time to recurrence of 6.9 years. The
median follow-up was 7.6 years in this study, so we
believe we have captured the majority of recurrences for
this patient set. Ozsahin et al12 reported a median time to
local-regional progression of 110 months (9.2 years).
Bachar et al5 reported a median time to recurrence of 57
months. The study by de Gabory et al,22 described a
cohort of patients with a median follow-up of 99.1
months (8.3 years), and found that the disease-free survival rate was 71.5% at 10 years. In the meta-analysis by
Dulguerov et al,4 24 publications reported a 5-year disease-free survival rate (average 41% disease-free at 5
years), whereas only 5 studies were identified that
reported a 10-year disease-free survival (average 52% disease-free at 10 years). It seems that despite good longterm overall survival, recurrences are relatively high
(approximately 50%), and can be most often expected to
occur between 5 and 10 years after treatment. The authors
of this study propose that a period of 7 to 10 years is necessary for adequate patient follow-up, as well as for optimal measurement of recurrence and survival outcomes in
future studies.
The patterns of treatment failure are important to
review in order to examine how treatment for ENB
might best be improved. In our study, the site of first
recurrence was local in 11 patients (18%), regional in
11 patients (18%), and distant in 6 patients (10%).
Four additional patients failed at distant sites after local
or regional recurrence. Interestingly, distant failure was
intracranial, pericranial, or spinal in 10 of 12 sites
recorded (some patients failed at multiple distant sites).
Bachar et al5 reported on 39 patients, and found local,
regional, and distant failure rates of 15%, 18%, and
8%, respectively. In their meta-analysis, Dulguerov et
al4 reported that local, regional, and distant failure was
29%, 16%, and 17%, respectively. Ozsahin et al,12 in
their series, reported higher overall local, regional, and
distant failure rates, reporting 31%, 26%, and 19%,
respectively. It seems that patients are at relatively high
FIGURE 3. Disease-specific survival stratified by American Joint Committee on Cancer (AJCC) T and N classification (A) and modified Kadish score
(B).
HEAD & NECK—DOI 10.1002/HED
APRIL 2014
527
OW ET AL.
FIGURE 4. Disease-specific survival of patients with T3 or T4 esthesioneuroblastoma (ENB) when stratified by treatment (A) and stratified by those
who received surgery versus surgery and postoperative radiation (B).
risk for local-regional failure (perhaps 30% to 40%)
when followed for an extended period, however, distant
failure also remains a concern.
Although it has been difficult to establish the true benefit of chemotherapy for ENB, chemotherapy may theoretically improve both local-regional and distant control. In
our study, 15 patients received chemotherapy. The regimens and strategies in which chemotherapy was used
were variable among the patients we reviewed, so it is
difficult to draw definitive conclusions about the effect of
chemotherapy on disease control and survival from our
patient cohort. The small number of patients who were
treated with concurrent chemoradiation in the postoperative setting had advanced disease and did seem to have
an outcome comparable to those that received radiation
alone. Chemotherapy was most often utilized in the neoadjuvant setting in our cohort, but the overall impact of
this modality is unclear. At our institution, neoadjuvant
regimens including cisplatin and etoposide are typically
advocated for those with advanced disease with intracranial or orbital invasion.23 Platinum-based treatment concurrently with radiation is also advocated postoperatively
for those at high risk of local-regional recurrence. Evidence supporting multimodality treatment is summarized
above, but data specific to the utility of chemotherapy for
ENB is limited to case reports and small series. Chao et
al18 reported on 8 patients who received neoadjuvant
chemotherapy, 6 of whom showed no evidence of disease
at the time the study was completed. Two cases of preoperative chemoradiation with cisplatin and etoposide were
detailed by Sohrabi et al24 offering another potential treatment strategy using chemotherapy for patients with
advanced ENB. Neoadjuvant chemotherapy was also supported in a study of ifosfamide, cisplatin, and etoposide, a
report in which 9 of 11 patients achieved an objective
response.25 A case of a durable response to sunitinib in
the palliative setting has also been published, offering
another intriguing option for study in the era of targeted
therapy.26
Three patients in our study presented with nodal metastasis, and clearly these 3 patients had a very poor
outcome compared to most others in our cohort. The
528
HEAD & NECK—DOI 10.1002/HED
APRIL 2014
Surveillance, Epidemiology, and End Results database
study by Jethanamest et al19 showed that the presence of
lymph node metastasis was clearly associated with
decreased survival. Eleven patients in our study went on
to develop regional recurrence as their first site of disease
progression. No patients in our study underwent elective
neck dissection, and the exact number of patients who
received elective radiation to the neck was unclear from
the records we reviewed. With long-term follow-up, it
seems that regional failure among patients with ENB
approaches 20%. In the report by Howell et al27 examining 48 patients with ENB, 5 patients presented with cervical metastasis, and 9 others developed nodal disease during follow-up. Nodal metastases were easily identifiable
on CT scan, MRI, and fluorodeoxyglucose-positron emission tomography scan, and metastases most commonly
occurred in level II, followed by levels I, III, and the retropharyngeal nodes.27 A meta-analysis of the published
cases of patients with ENB and neck metastasis reported
an overall (combined early and late) cervical metastasis
rate of 20%, and the literature suggested surgical resection with postoperative radiation was the best salvage
treatment for patients with regional failure.28 In a comprehensive review of the literature, regional spread seemed
to be higher among patients with Kadish C disease.29
There exist some data to suggest that elective neck irradiation improves regional control, however, definitive evidence is lacking.29 A study by Noh et al,30 identified
nodal recurrences in 3 of 4 patients despite elective treatment of the neck. The authors went on to suggest that
perhaps chemotherapy was more effective in limiting regional spread, however, the study was not powered to
definitively answer these questions. It is reasonable to
recommend elective irradiation of the first echelon lymph
nodes for patients with advanced local disease; however,
there are very limited data for this. At our institution, we
now favor elective neck nodal irradiation for most
patients. Currently, elective surgical treatment of the N0
neck is not the standard of care for those who will not
undergo adjuvant irradiation.
The overall local control rate in our cohort was 82%.
Sixty-two patients (90%) received surgical resection as
TREATMENT
part of their treatment. The standard approach to treatment for ENB at our institution traditionally has been
open craniofacial resection, but, more recently, we have
used endoscopic or combined craniotomy-endoscopic
approaches. Forty-one of the patients (61%) in our series
received 1 of these surgical approaches. Endoscopic surgery without craniotomy was used as a definitive modality of treatment in only 3 patients in our series. Our group
has recently adopted this technique for patients with early
stage ENB. Our recent publication of a large series of
patients with sinonasal tumors who were treated endoscopically shows that this procedure is safe with acceptable rates of disease control.31 The efficacy of the endoscopic approach for ENB has been examined in recent
publications. Castelnuovo et al32 reported 10 patients with
ENB who received endoscopic resection, 9 of whom
received postoperative radiation. All of the patients were
disease-free at the time of the report; however, the median follow-up was only 39 months. Another recent publication reported on 8 patients who received an endoscopic
resection followed by adjuvant radiation, all of whom
were with no evidence of disease with a mean follow-up
of 27 months.33 The meta-analysis by Devaiah and
Andreoli8 reported a survival advantage among those who
received an endoscopic or endoscopic-assisted approach.
There is an obvious selection bias in this analysis, as
noted by the authors, because smaller tumors are more
amenable to endoscopic resection, however, the data does
suggest comparable survival rates with these procedures.8
From these limited reports, endoscopic resection seems to
be a safe and effective procedure for carefully selected
patients with ENB. Because of excellent local control
reported with standard techniques, and the proclivity for
this tumor to recur after an extended period, careful study
with long-term follow-up will be required to definitively
support endoscopic resection as an acceptable treatment
option for ENB.
Our study is limited by all of the usual biases of a retrospective analysis, however, to our knowledge this is the
largest single-institution series reported to date. In our
study, it did seem that the AJCC staging system stratified
for outcome better than the modified Kadish (Morita11)
system, however, the overwhelming clinicopathologic
prognosticator was node status at presentation. We did
not evaluate pathologic grade of tumor according to the
classification by Hyams,34 as this information was not
available for the majority of our patients. Despite these
flaws, our review helps solidify several important factors
that contribute to the management strategy for ENB.
CONCLUSIONS
Our review suggests that patients with ENB, even when
locally advanced, can expect excellent survival if treated
with surgical resection and postoperative radiation. However, recurrence rates remain relatively high and commonly occur after a prolonged disease-free interval.
Chemotherapy may further improve local, regional, and
distant control. Endoscopic surgical techniques may be an
option that offers comparable rates of local control with
reduced morbidity in carefully selected patients. The roles
of both chemotherapy and endoscopic surgery in the management of ENB remain to be further evaluated.
FOR ESTHESIONEUROBLASTOMA
REFERENCES
1. Iezzoni JC, Mills SE. "Undifferentiated’’ small round cell tumors of the
sinonasal tract: differential diagnosis update. Am J Clin Pathol 2005;124
Suppl:S110–S121.
2. Berger LLG, Richard D. L’esthesioneuroepitheliome olfactif. L’esthesioneuroepitheliome olfactif. Bull Assoc Franc Etude Cancer 1924;13:
410–412.
3. Broich G, Pagliari A, Ottaviani F. Esthesioneuroblastoma: a general
review of the cases published since the discovery of the tumour in 1924.
Anticancer Res 1997;17:2683–2706.
4. Dulguerov P, Allal AS, Calcaterra TC. Esthesioneuroblastoma: a metaanalysis and review. Lancet Oncol 2001;2:683–690.
5. Bachar G, Goldstein DP, Shah M, et al. Esthesioneuroblastoma: The Princess Margaret Hospital experience. Head Neck 2008;30:1607–1614.
6. Zafereo ME, Fakhri S, Prayson R, et al. Esthesioneuroblastoma: 25-year
experience at a single institution. Otolaryngol Head Neck Surg 2008;138:
452–458.
7. Resto VA, Eisele DW, Forastiere A, Zahurak M, Lee DJ, Westra WH.
Esthesioneuroblastoma: the Johns Hopkins experience. Head Neck 2000;
22:550–558.
8. Devaiah AK, Andreoli MT. Treatment of esthesioneuroblastoma: a 16year meta-analysis of 361 patients. Laryngoscope 2009;119:1412–1416.
9. Kadish S, Goodman M, Wang CC. Olfactory neuroblastoma. A clinical
analysis of 17 cases. Cancer 1976;37:1571–1576.
10. Dulguerov P, Calcaterra T. Esthesioneuroblastoma: the UCLA experience
1970–1990. Laryngoscope 1992;102:843–849.
11. Morita A, Ebersold MJ, Olsen KD, Foote RL, Lewis JE, Quast LM. Esthesioneuroblastoma: prognosis and management. Neurosurgery 1993;32:
706–714; discussion 714–715.
12. Ozsahin M, Gruber G, Olszyk O, et al. Outcome and prognostic factors in
olfactory neuroblastoma: a rare cancer network study. Int J Radiat Oncol
Biol Phys 2010;78:992–997.
13. Platek ME, Merzianu M, Mashtare TL, et al. Improved survival following
surgery and radiation therapy for olfactory neuroblastoma: analysis of the
SEER database. Radiat Oncol 2011;6:41.
14. Foote RL, Morita A, Ebersold MJ, et al. Esthesioneuroblastoma: the role
of adjuvant radiation therapy. Int J Radiat Oncol Biol Phys 1993;27:
835–842.
15. Schemper M, Smith TL. A note on quantifying follow-up in studies of failure time. Control Clin Trials 1996;17:343–346.
16. Diaz EM Jr, Johnigan RH III, Pero C, et al. Olfactory neuroblastoma: the
22-year experience at one comprehensive cancer center. Head Neck 2005;
27:138–149.
17. Ward PD, Heth JA, Thompson BG, Marentette LJ. Esthesioneuroblastoma:
results and outcomes of a single institution’s experience. Skull Base 2009;
19:133–140.
18. Chao KS, Kaplan C, Simpson JR, et al. Esthesioneuroblastoma: the impact
of treatment modality. Head Neck 2001;23:749–757.
19. Jethanamest D, Morris LG, Sikora AG, Kutler DI. Esthesioneuroblastoma:
a population-based analysis of survival and prognostic factors. Arch Otolaryngol Head Neck Surg 2007;133:276–280.
20. Kane AJ, Sughrue ME, Rutkowski MJ, et al. Posttreatment prognosis of
patients with esthesioneuroblastoma. J Neurosurg 2010;113:340–351.
21. Rosenthal DI, Barker JL Jr, El-Naggar AK, et al. Sinonasal malignancies
with neuroendocrine differentiation: patterns of failure according to histologic phenotype. Cancer 2004;101:2567–2573.
22. de Gabory L, Abdulkhaleq HM, Darrouzet V, Bebear JP, Stoll D. Longterm results of 28 esthesioneuroblastomas managed over 35 years. Head
Neck 2011;33:82–86.
23. Diaz EM Jr, Kies MS. Chemotherapy for skull base cancers. Otolaryngol
Clin North Am 2001;34:1079–1085.
24. Sohrabi S, Drabick JJ, Crist H, Goldenberg D, Sheehan JM, Mackley HB.
Neoadjuvant concurrent chemoradiation for advanced esthesioneuroblastoma: a case series and review of the literature. J Clin Oncol 2011;29:
e358–e361.
25. Kim DW, Jo YH, Kim JH, et al. Neoadjuvant etoposide, ifosfamide, and
cisplatin for the treatment of olfactory neuroblastoma. Cancer 2004;101:
2257–2260.
26. Preusser M, Hutterer M, Sohm M, et al. Disease stabilization of progressive olfactory neuroblastoma (esthesioneuroblastoma) under treatment
with sunitinib mesylate. J Neurooncol 2010;97:305–308.
27. Howell MC, Branstetter BF IV, Snyderman CH. Patterns of regional
spread for esthesioneuroblastoma. AJNR Am J Neuroradiol 2011;32:
929–933.
28. Gore MR, Zanation AM. Salvage treatment of late neck metastasis in
esthesioneuroblastoma: a meta-analysis. Arch Otolaryngol Head Neck
Surg 2009;135:1030–1034.
29. Zanation AM, Ferlito A, Rinaldo A, et al. When, how and why to treat the
neck in patients with esthesioneuroblastoma: a review. Eur Arch Otorhinolaryngol 2010;267:1667–1671.
30. Noh OK, Lee SW, Yoon SM, et al. Radiotherapy for esthesioneuroblastoma: is elective nodal irradiation warranted in the multimodality treatment approach? Int J Radiat Oncol Biol Phys 2011;79:443–449.
HEAD & NECK—DOI 10.1002/HED
APRIL 2014
529
OW ET AL.
31. Hanna E, DeMonte F, Ibrahim S, Roberts D, Levine N, Kupferman M. Endoscopic resection of sinonasal cancers with and without craniotomy:
oncologic results. Arch Otolaryngol Head Neck Surg 2009;135:
1219–1224.
32. Castelnuovo PG, Delù G, Sberze F, et al. Esthesioneuroblastoma: endonasal endoscopic treatment. Skull Base 2006;16:25–30.
530
HEAD & NECK—DOI 10.1002/HED
APRIL 2014
33. Gallia GL, Reh DD, Salmasi V, Blitz AM, Koch W, Ishii M. Endonasal endoscopic resection of esthesioneuroblastoma: the Johns Hopkins Hospital
experience and review of the literature. Neurosurg Rev 2011;34:465–475.
34. Hyams VJ. Olfactory neuroblastoma. In: Hyams VJ, Batsakis JG, Michaels
L, editors. Tumors of the upper respiratory tract and ear. Washington
D.C.: Armed Forces Institute of Pathology; 1988. pp 240–248.