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Original Article |

Salvage Treatment of Late Neck Metastasis in Esthesioneuroblastoma:  A Meta-analysis FREE

Mitchell R. Gore, MD, PhD; Adam M. Zanation, MD
[+] Author Affiliations

Author Affiliations: Department of Otolaryngology–Head and Neck Surgery, University of North Carolina at Chapel Hill School of Medicine.


Arch Otolaryngol Head Neck Surg. 2009;135(10):1030-1034. doi:10.1001/archoto.2009.143.
Text Size: A A A
Published online

Objective  Esthesioneuroblastoma (ENB) is an uncommon tumor of the sinonasal region with a 20% rate of neck metastases. To our knowledge, the rate of neck metastases occurring 6 or more months after diagnosis has not been well characterized. The rate of successful salvage of these late neck metastases, defined in this study as disease-free survival for at least 1 year, has not been previously reported.

Design  Meta-analysis examining 33 articles published since 1990.

Patients  A total of 678 patients with ENB with 79 patients with neck metastases occurring 6 or more months after the initial diagnosis.

Interventions  Patients were grouped according to treatment with surgery, radiotherapy, or combined surgery and radiotherapy.

Main Outcome Measures  The rate of successful salvage of late neck metastases, defined as disease-free survival for at least 1 year, was compared for the 3 treatment groups.

Results  The rate of cervical metastases was 20.2%, with a 12.4% rate of late neck metastases. The combined successful salvage rate for late neck metastases with surgery, radiation, or combined therapy was 31.2%. An odds ratio (OR) analysis revealed that surgery plus radiation provided a statistically significant increase in the rate of successful salvage in patients with late neck metastases, with an OR of 8.6 vs single modality therapy and a number-needed-to-treat of 3. We found no difference in the OR for successful salvage for surgery alone vs radiation alone (OR, 1.5).

Conclusion  Treatment of neck metastases occurring 6 or more months after an initial diagnosis of ENB with combined surgery and radiotherapy provides a statistically significant survival advantage vs single-modality therapy.

Esthesioneuroblastoma (ENB) is an uncommon tumor of the sinonasal region that accounts for approximately 3% to 6%1,2 of all primary malignant sinus tumors and less than 1% of all head and neck cancers.2 Esthesioneuroblastoma, sometimes referred to as olfactory neuroblastoma,3 was first described by Berger et al4 in 1924. There remains some controversy as to the cell of origin of ENB, although the most widely accepted opinion is that ENB arises from the olfactory epithelium,5 which would account for the intimate relationship of most in situ ENBs with the cribiform plate, the midline superior nasal structures, and the anterior skull base. Many authors have examined the rate of neck metastasis in patients with ENB, with larger series typically reporting a rate of neck metastasis of 15% through 30%.2 Ferlito and Micheau2 found an overall rate of 23.5% in a review of articles about ENB written from 1990 through 2003.

Many of these authors reported that a substantial proportion of these neck metastases occur late (ie, ≥6 months after diagnosis of the primary tumor). To our knowledge, no study has examined the overall rate of success in salvaging late neck metastases with surgery, radiotherapy, or combined surgery and radiation. There remains controversy regarding the treatment of neck metastases in ENB. Approximately 5% of patients with ENB present with evidence of disease in the neck,2 and it is generally accepted that treatment of the neck in these patients is indicated. Most centers do not routinely perform neck dissection or radiation treatment of the neck at the time of resection of the primary tumor unless there is evidence of cervical disease.

The difficulty in establishing the optimal approach to salvaging neck metastases in the patient with ENB stems from several factors, including the low incidence of the disease, which makes it difficult to perform randomized trials or to assemble retrospective cohorts with large numbers of patients, and the high proportion of late neck metastases, which can present several years after treatment of the primary tumor.

Given the significant rate of cervical metastases, particularly late neck metastasis, insight into the value of salvage therapy for late neck metastases is invaluable in developing a more standardized approach to the neck in the patient with ENB. There may be value to elective treatment of the neck with neck dissection, radiotherapy, or both, because cervical metastases have been shown to drastically reduce survival rates in ENB.

We reviewed the largest ENB series, to our knowledge, reported since 1990.1,2,537 The case series included patients in whom the diagnosis of ENB was supported by immunohistochemical, histochemical, or histologic analysis. Our inclusion criteria were patients with confirmed ENB with late neck metastases, which we defined as metastases occurring 6 or more months after diagnosis of the primary tumor, from studies since 1990 from which data were available on the rate of late neck metastases. We examined the rate of salvage of late neck failures with surgery, radiotherapy, or combined treatment with surgery and radiotherapy. Successful salvage therapy was defined as disease-free survival at 1 year after salvage therapy because follow-up data were available for patients with neck salvage failure from at least 12 months after salvage therapy. Cases of patients with late neck salvage failures treated exclusively with chemotherapy were not included in the salvage data. The rate of failure among patients treated with surgery, radiotherapy, and combined surgery and radiotherapy among patients in which late neck salvage failed vs successful late neck salvage was examined. We also examined the location of salvage failure for patients for whom these data were reported, as well as available data on the treatment of subsequent salvage failure following attempted salvage of late neck metastasis. The odds ratios (ORs) and confidence intervals (CIs) were calculated using OR = ad/bc, standard error (SE) of (log)e OR = √(1/a + 1/b + 1/c + 1/d), Y = loge OR − [N1-α/2 × SE (loge OR)], Z = loge OR + [N1-α/2 × SE (loge OR)] (where α = .05 to give the 95% CI), and CI = eY to eZ.38 The Fisher exact test was then used to calculate the P value for the association between groups and outcomes, with P ≤ .05 considered statistically significant.

A total of 32 studies, involving 687 patients (Table 1), published from 1990 through 2007 were examined.1,5,537 Ten studies did not include explicit data on salvage in patients with late neck metastases, leaving a total of 476 patients included in the remaining studies. The overall rate of neck metastases was 20.2% for all 678 patients (137 of 678). The rate of late neck metastases for the 637 patients for whom data on time of diagnosis of cervical metastasis were available was 12.4% (79 of 637). Of the total number of patients with cervical metastases for whom data on time of diagnosis of neck disease were available, 61.7% (79 of 128) of these cervical metastases occurred 6 or more months after diagnosis of the primary ENB. The rate of attempted neck salvage with surgery, radiotherapy, or both was similar among patients with early and late neck metastases, with 45 of 62 patients (70%) with late neck metastases undergoing attempted neck salvage compared with 36 of 49 patients (73%) with early neck metastases undergoing attempted salvage therapy. Of 36 patients with neck metastases diagnosed at less than 6 months from the time of diagnosis of the primary tumor, neck salvage failed in 25 patients (69%). This was similar to the failure rate of attempted neck salvage in 45 patients with late neck metastases, with salvage failure in 31 patients (a rate of 69%).

Table Graphic Jump LocationTable 1. Articles Used for Meta-analysis

Data on the specific type of salvage therapy used were available for each of the 45 patients with late neck metastases who underwent attempted salvage therapy (Table 2). Patients who underwent chemotherapy in addition to another modality were included with that modality (eg, patients who underwent salvage therapy with chemoradiation were included in the radiation treatment group). Patients who underwent chemotherapy alone were not included in the attempted salvage group. In patients with late neck metastases who underwent attempted salvage and failed treatment, most (16 of 31 [52%]) had undergone salvage therapy consisting of surgery alone. Treatment in the remaining patients was evenly divided between attempted salvage with radiation alone (8 of 31 [16%]) and surgery plus radiation (7 of 31 [23%]). For patients who underwent successful salvage of the neck (ie, experienced disease-free survival for at least 1 year), most had undergone salvage treatment with a combination of surgery and radiation (10 of 14 [71%]). Salvage therapy in 3 of 14 patients had been successful using surgery alone (21%), and salvage was successful in 1 of 14 patients treated with radiation to the neck alone (7%).

Table Graphic Jump LocationTable 2. Patients With Failure of Salvage Treatment by Modalitya

Table 3 shows the results of an OR analysis for combined surgery and radiotherapy vs surgery alone, radiotherapy alone, and the combined data for surgery alone plus radiotherapy alone. Because the incidence of ENB is much less than 10% in the general population, the OR is expected to approximate the relative risk well. The outcome was successful salvage therapy of late neck metastasis, with success defined as disease-free survival for at least 1 year. Combined surgery plus radiotherapy increased the rate of successful neck salvage over surgery alone (OR, 7.6; 95% CI, 1.1-24.2; 2-tailed Fisher exact test P = .01; NNT, 3; 95% CI of NNT, 1.4-6.9), radiotherapy alone (OR, 11.4; 95% CI, 1.2-113.2; 2-tailed Fisher exact test P = .04; NNT, 3; 95% CI of NNT, 1.3-6.0), and surgery alone plus radiotherapy alone (OR, 8.6; 95% CI, 2.0-35.9; 2-tailed Fisher exact test P = .003; NNT, 3; 95% CI of NNT, 1.4-5.6). The rate of successful salvage was equivalent for surgery alone and radiotherapy alone (OR, 1.5; 95% CI, 0.1-16.8; 2-tailed Fisher exact test P > .99; NNT, 22).

Table Graphic Jump LocationTable 3. Odds Ratio (ORs) and Fisher Exact Test Analysis of Combined Surgery and Radiotherapy vs Surgery Alone, Radiotherapy Alone, Surgery Alone+Radiotherapy Alone, and Surgery Alone vs Radiotherapy Alone

Owing to the relatively low incidence of ENB and the difficulty in assembling large case series or prospective trials, treatment of primary disease and regional spread remain controversial. In addition, the treatment of this disease has changed greatly over the years, meaning that patients included in case series can span several decades over which treatment modalities have changed greatly. One particular aspect of ENB that is potentially troublesome is the tendency of cervical metastases to present late. Although this pattern has been noted by several authors, to our knowledge, standardization of the evaluation and treatment of these late neck metastases has not been specifically addressed. The rate of cervical metastasis observed overall in this work, 20.2%, was similar to the rates reported previously in the literature. Interestingly, of all patients with cervical metastases, a slight majority, 61.4%, presented with neck disease at 6 or more months after diagnosis of the primary tumor. We found that the rate of attempted salvage (roughly 70% in both groups) as well as the rate of failed salvage of the neck with surgery, radiotherapy, or a combination of the 2 (roughly 69% in both groups) was similar between patients who presented with early and late neck metastases. The site of failure after neck salvage was specified in 17 patients, and most of these failures were locoregional,11 whereas 6 failures occurred in distant sites. Perhaps most interestingly, most patients (71%) who were alive and disease free for at least 1 year following attempted salvage of late neck metastases were treated with combined surgery and radiation therapy. This is in contrast to the group of patients who underwent failed salvage therapy, a small majority of whom (52%) had been treated with surgery alone, with similar numbers being treated with radiation alone or combined radiotherapy and surgery (26% and 23%, respectively). The OR analysis reveals that combined surgery and radiotherapy is clearly superior to surgery alone or radiotherapy alone, with the OR for successful salvage for combined surgery with radiotherapy vs surgery alone or radiotherapy alone being greater than 7.0 and statistically significant for each. In addition, the number of patients needed to treat (NNT) with combined therapy vs single modality therapy was only 3. The clear increase in the odds of successful salvage as well as the low NNT in order to benefit 1 patient illustrate that combined modality therapy clearly increases the odds of successful salvage and is superior to single modality therapy in providing disease-free survival for at least 1 year.

Although care must be taken when interpreting these numbers given the differences in use of chemotherapy, treatment of the original primary lesion, and the relatively large time span over which data were collected, there is a clear predominance in the use of surgery plus radiotherapy in the treatment of patients who experienced disease-free survival, whereas to a lesser degree there was a clear predominance of patients treated with surgery alone among those in whom salvage therapy failed. Although it is difficult to posit a causal relationship with retrospective data, it seems clear that surgery plus radiotherapy, with or without chemotherapy, is the treatment of choice in salvage of late neck metastases in patients with ENB. This finding is further strengthened by the low incidence of ENB in the general population, which predicts that the OR should approximate relative risk well. In addition, the rate of successful salvage of late neck metastases in this data set, approximately 30%, is greater than the rate of successful salvage for neck recurrence in patients with head and neck squamous cell carcinoma treated with surgery, radiotherapy, or combined modality treatment42 and similar to the rate of successful salvage of isolated neck recurrences in patients treated with definitive radiotherapy for node-positive head and neck cancer.43 Although late neck recurrence in ENB still carries a relatively poor prognosis, 30% is an encouraging rate of successful salvage for such advanced disease. Given the high rate of late neck metastases, it is reasonable to screen patients whose neck tumor is classified as N0 at the time of diagnosis of their primary ENB for recurrence 6 months to 1 year after diagnosis with computed tomographic scans of the neck. It is also reasonable to regularly examine the neck for clinical signs of metastasis when patients are seen in follow-up over the months to years following diagnosis, because patients have presented with regional spread many years after initial treatment.18 In addition, we recommend attempted neck salvage with a combination of radiotherapy and neck dissection in patients who present with late neck metastases and are both willing and sufficiently healthy to undergo salvage treatment of the neck.

Correspondence: Adam M. Zanation, MD, Department of Otolaryngology–Head and Neck Surgery, University of North Carolina at Chapel Hill School of Medicine, CB No. 7070, Chapel Hill, NC 27599-7070 (adam_zanation@med.unc.edu).

Submitted for Publication: January 19, 2009; final revision received March 29, 2009; accepted April 5, 2009.

Author Contributions: All authors had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Gore and Zanation. Acquisition of data: Gore and Zanation. Analysis and interpretation of data: Gore and Zanation. Drafting of the manuscript: Gore and Zanation. Critical revision of the manuscript for important intellectual content: Gore and Zanation. Statistical analysis: Gore. Administrative, technical, and material support: Zanation. Study supervision: Zanation.

Financial Disclosure: None reported.

Previous Presentation: This study was a poster presentation at the Seventh International Conference on Head and Neck Cancer; July 20, 2008; San Francisco, California.

Dias  FLSa  GMLima  RA  et al.  Patterns of failure and outcome in esthesioneuroblastoma. Arch Otolaryngol Head Neck Surg 2003;129 (11) 1186- 1192
PubMed Link to Article
Ferlito  AMicheau  C Infantile olfactory neuroblastoma: a clinicopathological study with review of the literature. ORL J Otorhinolaryngol Relat Spec 1979;41 (1) 40- 45
PubMed Link to Article
Bradley  PJJones  NSRobertson  I Diagnosis and management of esthesioneuroblastoma. Curr Opin Otolaryngol Head Neck Surg 2003;11 (2) 112- 118
PubMed Link to Article
Berger  LLuc  GRichard  D L’esthésioneuroépithéliome olfactif. Bull Assoc Fr Etud Cancer 1924;13410- 421
Unger  FHaselsberger  KWalch  CStammberger  HPapaefthymiou  G Combined endoscopic surgery and radiosurgery as treatment modality for olfactory neuroblastoma (esthesioneuroblastoma). Acta Neurochir (Wien) 2005;147 (6) 595- 601
PubMed Link to Article
Lund  VJHoward  DWei  WSpittle  M Olfactory neuroblastoma: past, present, and future? Laryngoscope 2003;113 (3) 502- 507
PubMed Link to Article
Morita  AEbersold  MJOlsen  KDFoote  RLLewis  JEQuast  LM Esthesioneuroblastoma: prognosis and management. Neurosurgery 1993;32 (5) 706- 714
PubMed Link to Article
Koka  VNJulieron  MBourhis  J  et al.  Aesthesioneuroblastoma. J Laryngol Otol 1998;112 (7) 628- 633
PubMed Link to Article
Theilgaard  SABuchwald  CIngeholm  PKornum Larsen  SEriksen  JGSand Hansen  H Esthesioneuroblastoma: a Danish demographic study of 40 patients registered between 1978 and 2000. Acta Otolaryngol 2003;123 (3) 433- 439
PubMed Link to Article
Skarsgard  DPGroome  PAMackillop  WJ  et al.  Cancers of the upper aerodigestive tract in Ontario, Canada, and the United States. Cancer 2000;88 (7) 1728- 1738
PubMed Link to Article
Foote  RLMorita  AEbersold  MJ  et al.  Esthesioneuroblastoma: the role of adjuvant radiation therapy. Int J Radiat Oncol Biol Phys 1993;27 (4) 835- 842
PubMed Link to Article
Beitler  JJFass  DEBrenner  HA  et al.  Esthesioneuroblastoma: is there a role for elective neck treatment? Head Neck 1991;13 (4) 321- 326
PubMed Link to Article
Davis  REWeissler  MC Esthesioneuroblastoma and neck metastasis. Head Neck 1992;14 (6) 477- 482
PubMed Link to Article
Bailey  BJBarton  S Olfactory neuroblastoma: management and prognosis. Arch Otolaryngol 1975;101 (1) 1- 5
PubMed Link to Article
Argiris  ADutra  JTseke  PHaines  K Esthesioneuroblastoma: the Northwestern University experience. Laryngoscope 2003;113 (1) 155- 160
PubMed Link to Article
Monroe  ATHinerman  RWAmdur  RJMorris  CGMendenhall  WM Radiation therapy for esthesioneuroblastoma: rationale for elective neck irradiation. Head Neck 2003;25 (7) 529- 534
PubMed Link to Article
Dulguerov  PAllal  ASCalcaterra  TC Esthesioneuroblastoma: a meta-analysis and review. Lancet Oncol 2001;2 (11) 683- 690
PubMed Link to Article
Schmidt  JLZarbo  RJClark  JL Olfactory neuroblastoma: clinicopathologic and immunohistochemical characterization of four representative cases. Laryngoscope 1990;100 (10, pt 1) 1052- 1058
PubMed Link to Article
Dulguerov  PCalcaterra  T Esthesioneuroblastoma: the UCLA experience 1970-1990. Laryngoscope 1992;102 (8) 843- 849
PubMed Link to Article
Sakata  KAoki  YKarasawa  K  et al.  Esthesioneuroblastoma: a report of seven cases. Acta Oncol 1993;32 (4) 399- 402
PubMed Link to Article
Zappia  JJCarroll  WRWolf  GTThornton  AFHo  LKrause  CJ Olfactory neuroblastoma: the results of modern treatment approaches at the University of Michigan. Head Neck 1993;15 (3) 190- 196
PubMed Link to Article
Guedea  FVan Limbergen  EVan den Bogaert  W High dose level radiation therapy for local tumour control in esthesioneuroblastoma. Eur J Cancer 1994;30A (12) 1757- 1760
PubMed Link to Article
Slevin  NJIrwin  CJRBanerjee  SSGupta  NKFarrington  WT Olfactory neural tumours: the role of external beam radiotherapy. J Laryngol Otol 1996;110 (11) 1012- 1016
PubMed Link to Article
Irish  JDasgupta  RFreeman  J  et al.  Outcome and analysis of the surgical management of esthesioneuroblastoma. J Otolaryngol 1997;26 (1) 1- 7
PubMed
Levine  PAGallagher  RCantrell  RW Esthesioneuroblastoma: reflections of a 21-year experience. Laryngoscope 1999;109 (10) 1539- 1543
PubMed Link to Article
Pickuth  DHeywang-Köbrunner  SHSpielmann  RP Computed tomography and magnetic resonance imaging features of olfactory neuroblastoma: an analysis of 22 cases. Clin Otolaryngol Allied Sci 1999;24 (5) 457- 461
PubMed Link to Article
Resto  VAEisele  DWForastiere  AZahurak  MLee  DJWestra  WH Esthesioneuroblastoma: the Johns Hopkins experience. Head Neck 2000;22 (6) 550- 558
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PubMed
Miyamoto  RCGleich  LLBiddinger  PWGluckman  JL Esthesioneuroblastoma and sinonasal undifferentiated carcinoma: impact of histological grading and clinical staging on survival and prognosis. Laryngoscope 2000;110 (8) 1262- 1265
PubMed Link to Article
Simon  JHZhen  WMcCulloch  TM  et al.  Esthesioneuroblastoma: the University of Iowa experience 1978-1998. Laryngoscope 2001;111 (3) 488- 493
PubMed Link to Article
Hwang  S-KPaek  S-HKim  DGJeon  YKChi  JGJung  HW Olfactory neuroblastomas: survival rate and prognostic factor. J Neurooncol 2002;59 (3) 217- 226
PubMed Link to Article
Iliades  TPrintza  AEleftheriades  NGeorgios  KPsifidis  AThomas  Z Olfactory neuroblastoma: a report of 3 cases. ORL J Otorhinolaryngol Relat Spec 2002;64 (6) 454- 456
PubMed Link to Article
McLean  JNNunley  SRKlass  CMoore  CMüller  SJohnstone  PA Combined modality therapy of esthesioneuroblastoma. Otolaryngol Head Neck Surg 2007;136 (6) 998- 1002
PubMed Link to Article
Loy  AHReibel  JFRead  PW  et al.  Esthesioneuroblastoma: continued follow-up of a single institution's experience. Arch Otolaryngol Head Neck Surg 2006;132 (2) 134- 138
PubMed Link to Article
Eich  HTMüller  RPMicke  OKocher  MBerthold  FHero  B Esthesioneuroblastoma in childhood and adolescence: better prognosis with multimodal treatment? Strahlenther Onkol 2005;181 (6) 378- 384
PubMed Link to Article
Devaiah  AKLarsen  CTawfik  OO'Boynick  PHoover  LA Esthesioneuroblastoma: endoscopic nasal and anterior craniotomy resection. Laryngoscope 2003;113 (12) 2086- 2090
PubMed Link to Article
Eden  BVDebo  RFLarner  JM  et al.  Esthesioneuroblastoma: long-term outcome and patterns of failure: the University of Virginia experience. Cancer 1994;73 (10) 2556- 2562
PubMed Link to Article
Morris  JAGardner  MJ Calculating confidence intervals for relative risks, odds ratios, and standardised ratios and rates. Br Med J (Clin Res Ed) 1988;296 (6632) 1313- 1316
PubMed Link to Article
Chao  KSKaplan  CSimpson  JR  et al.  Esthesioneuroblastoma: the impact of treatment modality. Head Neck 2001;23 (9) 749- 757
PubMed Link to Article
Kumar  MFallon  RJHill  JSDavis  MM Esthesioneuroblastoma in children. J Pediatr Hematol Oncol 2002;24 (6) 482- 487
PubMed Link to Article
Lund  VJHoward  DWei  WSpittle  M Olfactory neuroblastoma: past, present, and future? Laryngoscope 2003;113 (3) 502- 507
PubMed Link to Article
Mabanta  SRMendenhall  WMStringer  SPCassisi  NJ Salvage treatment for neck recurrence after irradiation alone for head and neck squamous cell carcinoma with clinically positive neck nodes. Head Neck 1999;21 (7) 591- 594
PubMed Link to Article
Liauw  SLAmdur  RJMorris  CGWerning  JWVillaret  DBMendenhall  WM Isolated neck recurrence after definitive radiotherapy for node-positive head and neck cancer: salvage in the dissected or undissected neck. Head Neck 2007;29 (8) 715- 719
PubMed Link to Article

Figures

Tables

Table Graphic Jump LocationTable 1. Articles Used for Meta-analysis
Table Graphic Jump LocationTable 2. Patients With Failure of Salvage Treatment by Modalitya
Table Graphic Jump LocationTable 3. Odds Ratio (ORs) and Fisher Exact Test Analysis of Combined Surgery and Radiotherapy vs Surgery Alone, Radiotherapy Alone, Surgery Alone+Radiotherapy Alone, and Surgery Alone vs Radiotherapy Alone

References

Dias  FLSa  GMLima  RA  et al.  Patterns of failure and outcome in esthesioneuroblastoma. Arch Otolaryngol Head Neck Surg 2003;129 (11) 1186- 1192
PubMed Link to Article
Ferlito  AMicheau  C Infantile olfactory neuroblastoma: a clinicopathological study with review of the literature. ORL J Otorhinolaryngol Relat Spec 1979;41 (1) 40- 45
PubMed Link to Article
Bradley  PJJones  NSRobertson  I Diagnosis and management of esthesioneuroblastoma. Curr Opin Otolaryngol Head Neck Surg 2003;11 (2) 112- 118
PubMed Link to Article
Berger  LLuc  GRichard  D L’esthésioneuroépithéliome olfactif. Bull Assoc Fr Etud Cancer 1924;13410- 421
Unger  FHaselsberger  KWalch  CStammberger  HPapaefthymiou  G Combined endoscopic surgery and radiosurgery as treatment modality for olfactory neuroblastoma (esthesioneuroblastoma). Acta Neurochir (Wien) 2005;147 (6) 595- 601
PubMed Link to Article
Lund  VJHoward  DWei  WSpittle  M Olfactory neuroblastoma: past, present, and future? Laryngoscope 2003;113 (3) 502- 507
PubMed Link to Article
Morita  AEbersold  MJOlsen  KDFoote  RLLewis  JEQuast  LM Esthesioneuroblastoma: prognosis and management. Neurosurgery 1993;32 (5) 706- 714
PubMed Link to Article
Koka  VNJulieron  MBourhis  J  et al.  Aesthesioneuroblastoma. J Laryngol Otol 1998;112 (7) 628- 633
PubMed Link to Article
Theilgaard  SABuchwald  CIngeholm  PKornum Larsen  SEriksen  JGSand Hansen  H Esthesioneuroblastoma: a Danish demographic study of 40 patients registered between 1978 and 2000. Acta Otolaryngol 2003;123 (3) 433- 439
PubMed Link to Article
Skarsgard  DPGroome  PAMackillop  WJ  et al.  Cancers of the upper aerodigestive tract in Ontario, Canada, and the United States. Cancer 2000;88 (7) 1728- 1738
PubMed Link to Article
Foote  RLMorita  AEbersold  MJ  et al.  Esthesioneuroblastoma: the role of adjuvant radiation therapy. Int J Radiat Oncol Biol Phys 1993;27 (4) 835- 842
PubMed Link to Article
Beitler  JJFass  DEBrenner  HA  et al.  Esthesioneuroblastoma: is there a role for elective neck treatment? Head Neck 1991;13 (4) 321- 326
PubMed Link to Article
Davis  REWeissler  MC Esthesioneuroblastoma and neck metastasis. Head Neck 1992;14 (6) 477- 482
PubMed Link to Article
Bailey  BJBarton  S Olfactory neuroblastoma: management and prognosis. Arch Otolaryngol 1975;101 (1) 1- 5
PubMed Link to Article
Argiris  ADutra  JTseke  PHaines  K Esthesioneuroblastoma: the Northwestern University experience. Laryngoscope 2003;113 (1) 155- 160
PubMed Link to Article
Monroe  ATHinerman  RWAmdur  RJMorris  CGMendenhall  WM Radiation therapy for esthesioneuroblastoma: rationale for elective neck irradiation. Head Neck 2003;25 (7) 529- 534
PubMed Link to Article
Dulguerov  PAllal  ASCalcaterra  TC Esthesioneuroblastoma: a meta-analysis and review. Lancet Oncol 2001;2 (11) 683- 690
PubMed Link to Article
Schmidt  JLZarbo  RJClark  JL Olfactory neuroblastoma: clinicopathologic and immunohistochemical characterization of four representative cases. Laryngoscope 1990;100 (10, pt 1) 1052- 1058
PubMed Link to Article
Dulguerov  PCalcaterra  T Esthesioneuroblastoma: the UCLA experience 1970-1990. Laryngoscope 1992;102 (8) 843- 849
PubMed Link to Article
Sakata  KAoki  YKarasawa  K  et al.  Esthesioneuroblastoma: a report of seven cases. Acta Oncol 1993;32 (4) 399- 402
PubMed Link to Article
Zappia  JJCarroll  WRWolf  GTThornton  AFHo  LKrause  CJ Olfactory neuroblastoma: the results of modern treatment approaches at the University of Michigan. Head Neck 1993;15 (3) 190- 196
PubMed Link to Article
Guedea  FVan Limbergen  EVan den Bogaert  W High dose level radiation therapy for local tumour control in esthesioneuroblastoma. Eur J Cancer 1994;30A (12) 1757- 1760
PubMed Link to Article
Slevin  NJIrwin  CJRBanerjee  SSGupta  NKFarrington  WT Olfactory neural tumours: the role of external beam radiotherapy. J Laryngol Otol 1996;110 (11) 1012- 1016
PubMed Link to Article
Irish  JDasgupta  RFreeman  J  et al.  Outcome and analysis of the surgical management of esthesioneuroblastoma. J Otolaryngol 1997;26 (1) 1- 7
PubMed
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