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Figure 1.
Disease-free survival curves according to the Istituto Nazionale per lo Studio e la Cura dei Tumori (INT) and American Joint Committee on Cancer–Union Internationale Contre le Cancer (AJCC-UICC) tumor classification stages.

Disease-free survival curves according to the Istituto Nazionale per lo Studio e la Cura dei Tumori (INT) and American Joint Committee on Cancer–Union Internationale Contre le Cancer (AJCC-UICC) tumor classification stages.

Figure 2.
Disease-free survival curves for patients with adenocarcinoma only according to the Istituto Nazionale per lo Studio e la Cura dei Tumori (INT) and American Joint Committee on Cancer–Union Internationale Contre le Cancer (AJCC-UICC) tumor classification stages.

Disease-free survival curves for patients with adenocarcinoma only according to the Istituto Nazionale per lo Studio e la Cura dei Tumori (INT) and American Joint Committee on Cancer–Union Internationale Contre le Cancer (AJCC-UICC) tumor classification stages.

Figure 3.
Overall survival curves according to the Istituto Nazionale per lo Studio e la Cura dei Tumori (INT) and American Joint Committee on Cancer–Union Internationale Contre le Cancer (AJCC-UICC) tumor classification stages.

Overall survival curves according to the Istituto Nazionale per lo Studio e la Cura dei Tumori (INT) and American Joint Committee on Cancer–Union Internationale Contre le Cancer (AJCC-UICC) tumor classification stages.

Figure 4.
Overall survival curves for patients with adenocarcinoma only according to the Istituto Nazionale per lo Studio e la Cura dei Tumori (INT) and American Joint Committee on Cancer–Union Internationale Contre le Cancer (AJCC-UICC) tumor classification stages.

Overall survival curves for patients with adenocarcinoma only according to the Istituto Nazionale per lo Studio e la Cura dei Tumori (INT) and American Joint Committee on Cancer–Union Internationale Contre le Cancer (AJCC-UICC) tumor classification stages.

Table 1. 
Istituto Nazionale per lo Studio e la Cura dei Tumori Classification of Malignant Ethmoid Tumors
Istituto Nazionale per lo Studio e la Cura dei Tumori Classification of Malignant Ethmoid Tumors
Table 2. 
Disease Characteristics*
Disease Characteristics*
Table 3. 
Disease-Free and Overall Survival Rates*
Disease-Free and Overall Survival Rates*
Table 4. 
Estimates of Disease-Free and Overall Survival by Prior Treatment and Istituto Nazionale per lo Studio e la Cura dei Tumori (INT) Tumor Stage Classification*
Estimates of Disease-Free and Overall Survival by Prior Treatment and Istituto Nazionale per lo Studio e la Cura dei Tumori (INT) Tumor Stage Classification*
1.
Hermanek  PedSobin  LHed TNM Classification of Malignant Tumours. 4th ed. Berlin, Germany Springer-Verlag1987;
2.
American Joint Committee on Cancer, AJCC Manual for Staging of Cancer. 4th ed. Philadelphia, Pa Lippincott-Raven1992;
3.
American Joint Committee on Cancer, AJCC Cancer Staging Manual. 5th ed. Philadelphia, Pa Lippincott-Raven1997;
4.
Sobin  LHedWettekind  Ced TNM Classification of Malignant Tumors. 5th ed. New York, NY John Wiley & Sons Inc1997;
5.
Sisson  GAToriumi  DMAtiyah  RA Paranasal sinus malignancy: a comprehensive update. Laryngoscope. 1989;99143- 150
6.
Spiro  JDSoo  KCSpiro  RH Nonsquamous cell malignant neoplasms of the nasal cavities and paranasal sinuses. Head Neck. 1995;17114- 118Article
7.
Kadish  SGoodman  MWang  CC Olfactory neuroblastoma: a clinical analysis of 17 cases. Cancer. 1976;371571- 1576Article
8.
Biller  HFLawson  WSachdev  VPSom  P Esthesioneuroblastoma: surgical treatment without radiation. Laryngoscope. 1990;1001199- 1201Article
9.
Dulguerov  PCalcaterra  T Esthesioneuroblastoma: the UCLA experience 1970-1990. Laryngoscope. 1992;102843- 849Article
10.
Austin  JRCebrun  HKershisnik  MM  et al.  Olfactory neuroblastoma and neuroendocrine carcinoma of the anterior skull base: treatment results at the M. D. Anderson Cancer Center. Skull Base Surg. 1996;61- 8Article
11.
Ellingwood  KEMillion  RR Cancer of the nasal cavity and ethmoid/sphenoid sinuses. Cancer. 1979;431517- 1526Article
12.
Roux  FXBrasnu  DMenard  M  et al.  Les abords combinés des tumeurs malignes de l'ethmoïde et autres sinus paranasaux: principes et résultats. Ann Otolaryngol Chir Cervicofac. 1991;108292- 297
13.
Cantù  GSolero  CLSalvatori  PMattavelli  FPizzi  NLicitra  L A new classification of malignant ethmoid tumors: 3rd European Skull Base Congress, London, 9-11 April 1997. Skull Base Surg. 1997;7 (suppl 2) 33
14.
Cantù  GSolero  CLMariani  L  et al.  Anterior craniofacial resection for malignant ethmoid tumors: a series of 91 patients. Head Neck. 1999;21185- 191Article
15.
Kaplan  ELMeier  P Nonparametric estimation from incomplete observations. J Am Stat Assoc. 1958;53457- 481Article
16.
Cox  DR Regression models and life tables. J R Stat Soc. 1972;34187- 220
17.
Shah  JPKraus  DHBilsky  MHGutin  PHHarrison  LHStrong  EW Craniofacial resection for malignant tumors involving the anterior skull base. Arch Otolaryngol Head Neck Surg. 1997;1231312- 1317Article
18.
Schwaab  GMicheau  CLe Guillou  C Olfactory esthesioneuroma: a report of 40 cases. Laryngoscope. 1988;98872- 876Article
19.
Zappia  JJCarroll  WRWolf  GTThornton  AFHo  LKrause  CJ Olfactory neuroblastoma: the results of modern treatment approaches at the University of Michigan. Head Neck. 1993;15190- 196Article
Original Article
November 1999

A New Classification for Malignant Tumors Involving the Anterior Skull Base

Author Affiliations

From the Unit of Cranio-maxillo-facial Surgery (Drs Cantù, Mattavelli, and Pizzi), Division of Medical Statistics and Biometrics (Dr Mariani), and Unit of Medical Oncology A (Dr Licitra), Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy, and the Second Division of Neurosurgery, Istituto Nazionale Neurologico "C Besta" (Dr Lazzaro Solero), Milan, Italy.

Arch Otolaryngol Head Neck Surg. 1999;125(11):1252-1257. doi:10.1001/archotol.125.11.1252
Abstract

Objectives  To propose our clinical classification of malignant ethmoid tumors and to compare it with the last American Joint Committee on Cancer (AJCC)–Union Internationale Contre le Cancer (UICC) classification, published in 1997.

Design  Retrospective review.

Setting  Tertiary cancer facility.

Patients  We evaluated 123 consecutive patients undergoing craniofacial resection for malignant ethmoid tumors involving the anterior skull base. The mean follow-up was 60 months. Fifty-nine patients (48%) presented with recurrent disease after prior therapy. We classified them with a new classification system (Istituto Nazionale per lo Studio e la Cura dei Tumori) based on the most commonly accepted unfavorable prognostic factors (involvement of dura mater; intradural extension; involvement of the orbit and, in particular, of its apex; invasion of maxillary, frontal, and/or sphenoid sinuses; and invasion of the infratemporal fossa and skin. We also classified patients with the AJCC classification published in 1997.

Main Outcome Measures  Disease-free status and overall survival rate. To study a possible association with tumor stage, the Cox regression model was adopted.

Results  According to our classification, patient distribution by tumor type was T2, n=46; T3, n=29; and T4, n=48 (no T1 tumors were present in the series). For previously untreated patients, 5-year disease-free survival estimates were T2, 57%; T3, 50%; and T4, 13%. For relapses, corresponding figures were T2, 31%; T3, 23%; and T4, 1%. The prognostic difference among stages was statistically significant (P<.001). Similar results were obtained for overall survival. In contrast, patient distribution among different AJCC stages was less balanced, and we failed to detect a significant association with the clinical outcome using this classification.

Conclusion  We propose the use of our staging system by all those specialists in the field willing to validate the classification and possibly apply it for clinical and investigational purposes.

WHILE A classification of maxillary sinus carcinomas has been available since the publication of the first edition of the AJCC Manual for Staging of Cancer of the American Joint Committee on Cancer (AJCC), carcinomas of the paranasal sinuses were not considered in the first 3 editions of the TNM Classification of Malignant Tumours of the Union Internationale Contre le Cancer (UICC). Only in the fourth edition of the TNM Classification of Malignant Tumours, published in 1987,1 did a classification of maxillary sinus carcinomas appear—the same as that reported in the fourth edition of the AJCC Manual for Staging of Cancer.2 Ethmoid carcinomas were finally staged in the fifth editions of both the AJCC Cancer Staging Manual3 and the UICC's TNM Classification of Malignant Tumours.4

Some of the authors who have published articles on nasal and paranasal tumors admitted that without a classification of ethmoid tumors, the cases presented had not been staged. Sisson et al5 wrote that "The ethmoid cancers were not staged because there is no generally accepted staging system for this site." Spiro et al,6 after having staged tumors of the maxillary sinuses, wrote that "As there is no widely accepted staging system for the remaining sinuses or the nasal cavity, no attempt was made to stage tumors arising in these sites." This was the case even though the fourth edition of the AJCC Manual for Staging Cancer states that a

proper classification and staging of cancer will allow the physician to determine treatment for the patient more appropriately, to evaluate results of management more reliably, and to compare statistics reported from various institutions on a local, regional, and national basis more confidently.2

Nevertheless, some attempts to stage nasoethmoid tumors have been made. Kadish et al7 and later Biller et al8 proposed a classification for esthesioblastomas. Dulguerov and Calcaterra9 of the University of California, Los Angeles, Medical Center proposed another classification in 1992; this was once again for esthesioblastomas, and the authors of the M. D. Anderson Cancer Center study10 referred to it to stage their cases.

Ellingwood and Million11 published a classification for cancers of the nasal cavity and ethmoid/sphenoidal sinuses in 1979. Finally, Roux et al12 adopted a staging system they called modified TNM.

It is evident that there is a lot of confusion in the classification of malignant ethmoid tumors. If we look into the various classifications presented, it is easy to see, as stated by Dulguerov and Calcaterra,9 that some of them, despite their historical significance as first attempts at staging, are clearly inadequate.

In the absence of a universally accepted staging system and on the basis of our experience with anterior craniofacial resections, we developed in 1993 and presented in 1995 an original classification for malignant ethmoid tumors13 based on the most commonly accepted unfavorable prognostic factors (involvement of dura mater; intradural extension; involvement of the orbit and, in particular, of its apex; invasion of maxillary, frontal, and/or sphenoidal sinus; and invasion of the infratemporal fossa and skin) (Table 1). We applied this classification to all consecutive malignant nasoethmoid tumors that were treated at our institution.14

The aims of this article are to verify the prognostic effectiveness of our staging system (Istituto Nazionale per lo Studio e la Cura dei Tumori [INT]) in patients with nasoethmoid tumors who underwent an anterior craniofacial resection and to compare it with the recently published AJCC-UICC classification.

PATIENTS AND METHODS
PATIENTS

From 1987 through 1996, 130 patients underwent an anterior craniofacial resection for ethmoid malignant tumor at the INT of Milan. Seven of the subjects were excluded from the analyses because they died postoperatively. Our surgical technique has already been published.14 Patient charts, operative notes, follow-up clinic notes, radiographic study results, and pathologic reports were analyzed for each patient. In particular, radiographic study results and pathologic reports were used to assess the clinical and pathologic T stage.

Patient ages varied from 22 to 79 years (mean age, 54 years), and the male-female ratio was 2.2 (84/39). The main disease characteristics are described in Table 2.

Sixty-four patients were previously untreated (52%), whereas 59 (48%) presented with a recurrence after prior treatments performed elsewhere. Eight untreated patients underwent 3 to 5 cycles of primary chemotherapy with cisplatin, fluorouracil, and leucovorin according to a treatment protocol that began in 1996. The prior treatments were surgery (n=17), surgery followed by radiotherapy (n=16), radiotherapy followed by surgery (n=8), radiotherapy (n=6), chemotherapy followed by radiotherapy (n=9), and chemotherapy (n=3). The ethmoid was involved in all cases and was the most probable site of origin of the tumor in all the patients.

Histological diagnosis was always based on a transnasal biopsy specimen or on a specimen from previous surgery performed elsewhere. The extent of the tumor was always assessed with a computed tomographic (CT) scan in axial and coronal projections, whereas magnetic resonance imaging (MRI) scans were obtained for patients who were unable to achieve a proper position for CT scan coronal sections. Magnetic resonance imaging was also used for patients with intracranial and intraorbital extension (documented by CT scan) to assess the infiltration of dura mater and periorbita.

Fifty-six patients underwent planned postoperative radiotherapy with a dose of 50 to 66 Gy. Therefore, 95 patients (77%) received radiotherapy either preoperatively or postoperatively.

According to the INT staging system, the tumors of 46 patients were classified as T2, 29 as T3, and 48 as T4. Of course, no T1 tumors were present in the series, since these rare small tumors are not treated with craniofacial resection. According to the AJCC-UICC staging system, the tumors of 15 patients were classified as T1, 8 as T2, 38 as T3, and 62 as T4. Only 1 patient initially presented with cervical node metastasis; 5 patients had cervical node metastasis after a few months.

STATISTICAL METHODS

The disease-free and overall survival rates were measured from the date of surgery to the date of disease recurrence or death; in the absence of any event, these rates were measured from the date of surgery to the last follow-up assessment available. Disease-free and overall survival curves were estimated with the Kaplan-Meier method.15 After carefully checking the underlying proportional hazard assumption, the Cox regression model16 was adopted to study a possible association between tumor stage and clinical outcome in terms of disease-free or overall survival rates. The analyses were adjusted for prior treatment, a factor shown to be an important predictor in our previous article.14 The tumor stage and prior treatment were entered into the Cox models by means of 0 vs 1 indicator variables. Histological findings turned out to be of negligible importance in the present study and were therefore disregarded. In all of the analyses, the conventional 5% significance level was adopted.

RESULTS

In 121 (98%) of the 123 patients considered, a correspondence was found between clinical and pathologic staging using both the INT and AJCC-UICC classification systems. Only 1 clinically diagnosed T4 tumor turned out to be a pT3 tumor, and 1 diagnosed T2 tumor was really a pT3 tumor.

The median follow-up time was 60 months. Seventy-five patients had disease recurrence. These recurrences were mainly local, either isolated (n=65) or in combination with other types (n=5); recurrences only rarely occurred at distant sites (n=3) or only in the lymphatic nodes (n=2). Sixty-five deaths were recorded, caused by ethmoid tumor recurrence (n=59), other primary tumors (n=2), nonneoplastic causes (n=3), or unknown causes (n=1).

Figure 1 shows the disease-free survival curves in the whole series according to the INT and AJCC-UICC tumor classification stages. The same curves are plotted in Figure 2, considering only patients with adenocarcinoma, the most frequent type of malignant neoplasm identified with histological testing. It is apparent that a clear separation among the curves was evident only for the INT system of tumor staging. For the AJCC-UICC staging, patients with T2 tumors had a good prognosis, whereas for patients with T1, T3, and T4 tumors, the clinical outcome was almost the same.

Overall survival curves are shown in Figure 3 for the whole series and for patients with adenocarcinoma in Figure 4. The findings were in accordance with those previously described for disease-free survival.

Significant results were achieved by the INT classification system among different T stages for disease-free and overall survival rates (Table 3). Significant results were also obtained for prior treatment, which confirmed that this is a prognostic factor not only for disease-free survival, as already shown,14 but also for overall survival. By including suitable interaction terms in the Cox models, the prognostic role of the INT tumor stage classification was shown not to be affected by prior treatment. When applying the AJCC-UICC staging system to the Cox models, statistical results among different T stages were not significant for either disease-free (P=.14) or overall (P=.40) survival rates.

Table 4 reports 3- and 5-year estimates (and corresponding 95% confidence intervals) that were obtained with the Cox models for disease-free and overall survival rates according to prior treatment and the INT tumor stage classification.

COMMENT

The precise identification of the site of origin of some nasoethmoid tumors may be difficult. Shah et al17 have distinguished ethmoid tumors from nasal tumors. Ellingwood and Million11 wrote that "An effort was made to specify a single site of origin, but it was sometimes a moot point whether the tumor originated in the nasal cavity or the ethmoid sinus." Moreover, many authors have suggested that "the olfactory neuroblastoma is a malignant neoplasm originating in the upper nasal vault in the region of the cribriform plate."710,1719 Dulguerov and Calcaterra9 stated that "Esthesioneuroblastomas either arise in, or spread very rapidly to, the ethmoid sinuses." In the introduction of their historical article, Kadish et al7 wrote that "The sense of smell is located in a specialized sensory neuroepithelium that covers the superior nasal turbinates and the upper portion of the nasal septum." Since the superior turbinates, the cribriform plate, and the upper portion of the nasal septum belong to the ethmoid, it seems appropriate to include esthesioneuroblastomas in the classification of ethmoid tumors.

Nodal and distant metastases of malignant ethmoid tumors are uncommon. Therefore, if we perform a radical resection of the tumor, we have a chance to cure the patient. Anterior craniofacial resection is now recognized as the treatment of choice for ethmoid tumors involving the cribriform plate with or without invasion of the anterior cranial fossa. However, it is sometimes difficult to achieve radical resection with this procedure. A clinical classification of a tumor should be able to identify, through a simple and reproducible characterization, the extensions where radical resection is difficult, allowing patients to be divided into prognostic groups accordingly.

Looking into the various staging systems presented, we think that only the classification of Dulguerov and Calcaterra9 is appropriate, mainly because it introduces a distinction between tumors that do not involve the most superior ethmoid cells (T1) and those that extend to or erode the cribriform plate (T2). The T1 tumors might be excised through a facial approach, whereas the others require craniofacial resection to achieve radical resection. However, it is our opinion that the classification of Dulguerov and Calcaterra is limited by the generic inclusion in the T3 category of tumors invading the orbit. We believe a distinction should be made between tumors with invasion in the anterior two thirds of the orbit and those with orbit apex involvement. In fact, it is possible to achieve radical resection with orbital exenteration for tumor invasion in the anterior two thirds of the orbit, but this is not the case for tumors with orbit apex involvement. Furthermore, their classification for the involvement of the sphenoidal sinus is far too general. A tumor that has eroded the anterior-inferior wall of the sphenoidal sinus is very different from a tumor that has largely destroyed the superior-posterior-lateral walls and spread to the cavernous sinuses, the sella turcica, and the clivus. It is easy to achieve radical resection in the first instance, but not in the second. Finally, the classification of Dulguerov and Calcaterra was proposed only for esthesioneuroblastomas.

The UICC-AJCC classification system3,4 introduces the concept, already used by us,13 that different prognostic values should be applied for tumor involvement of the anterior orbit and the apex. However, we believe that the UICC-AJCC classification system has some important discrepancies. A T1 tumor may be small, low, and resectable via rhinotomy or endoscopy, but it may also be rather large, eroding the lamina papyracea, even without orbital involvement, and/or eroding the cribriform plate without intracranial extension. In the latter instance, a craniofacial resection is required. Tumor extension into the nasal cavity is the peculiarity of a T2 lesion. We see no reason why neoplastic vegetations in the empty space of the cavity may worsen the prognosis. Also, the possible involvement of turbinates and/or septum may be easily cured with medial maxillectomy. In addition, the UICC-AJCC T4 tumor classification stage is too broad. It includes tumors with little intracranial extension without dural involvement, tumors attached to the outer face of the dura, and tumors with brain infiltration. In the INT classification system, the first 2 situations would be classified as T3 and the third as T4. We believe it is easy to achieve radical resection with a dural resection in the first 2 cases but not when the tumor involves the brain. Moreover, sphenoid involvement is not clearly defined in the AJCC-UICC classification system because a detailed description of its extent is lacking. Finally, a tumor involving the frontal sinus may be resected more easily and radically than a tumor that extends to the pterygoid plate or infratemporal fossa; this is not mentioned in the AJCC-UICC classification system.

Our analyses clearly identified all these problems. According to the AJCC-UICC classification system, no trend was observed in terms of disease-free or overall survival rates among the different tumor stages. Oddly, only the patients with T2 tumors showed a relatively good outcome. Considering the small number of patients with tumors in this category, we believe that a plausible explanation may be the fortuitous selection of less aggressive tumors. Perhaps a tumor fungating in the nasal cavity is less malignant than a tumor confined in the ethmoid cells but eroding the bone.

In contrast, our classification system turned out to have prognostic value. A progressive worsening of the prognosis was shown to occur from T2 to T4. Because our series included many histological types and this might bring into question the validity of the results, we also verified the prognostic value of our classification system for adenocarcinoma, the most frequent type of malignant neoplasm identified with histological testing. Similar results were obtained. However, no conclusions can be drawn for melanomas and undifferentiated carcinomas because of the small number of these histological types.

All features of tumor extension that were used in our classification system to distinguish one stage from another can be easily assessed with clinical examination, CT scan, and MRI. In particular, MRI is able to reveal the involvement of the dura and the periorbita. The clinical classification of T stage changed after surgical resection in only 2 cases.

The only limitation of our series is that we did not include patients with T1 tumors because they did not undergo craniofacial resection. From 1987 through 1996, we saw only 3 patients with T1 tumors—too small a subgroup to warrant statistical analysis. The T1 tumors were resected with a paranasal approach, the patients were treated with postoperative radiotherapy, and all were alive and well at the time of this report.

CONCLUSIONS

Based on our findings, we believe our new system for the classification of malignant tumors involving the anterior skull is valid for a number of reasons. First, it is based on anatomical and not just histological criteria. In fact, we apply our system of classification to all malignant tumors of the ethmoid. Second, it takes into account the possibilities and limitations of the most modern surgical treatment for ethmoid tumors (ie, craniofacial resection) to achieve radical resection. Third, it satisfies one of the main goals of tumor staging, namely the progressive worsening of prognosis for different classes. Finally, our system of tumor classification proved to be valid not only for the overall study but also when applied separately to untreated and recurring cases. Staging can be done clinically by means of CT scans and MRI examinations, which accurately reveal tumor extension and involvement of those anatomical structures that determine a change of stage. This permits confrontation between homogeneous series treated with surgery, radiotherapy, chemotherapy, and therapeutic combinations.

Therefore, we recommend the INT staging system for malignant tumors of the ethmoid to all specialists in the field who are willing to validate tumor classification and possibly apply it for clinical and investigational purposes.

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Article Information

Accepted for publication May 20, 1999.

This study was sponsored by the Associazione Italiana per la Ricerca sul Cancro (AIRC), Milan, Italy.

The authors thank Betty Johnston for editing the manuscript.

Corresponding author: Giulio Cantù, MD, Istituto Nazionale Tumori, Via Venezian 1, 20133 Milan, Italy (e-mail: licitra@istitutotumori.mi.it).

References
1.
Hermanek  PedSobin  LHed TNM Classification of Malignant Tumours. 4th ed. Berlin, Germany Springer-Verlag1987;
2.
American Joint Committee on Cancer, AJCC Manual for Staging of Cancer. 4th ed. Philadelphia, Pa Lippincott-Raven1992;
3.
American Joint Committee on Cancer, AJCC Cancer Staging Manual. 5th ed. Philadelphia, Pa Lippincott-Raven1997;
4.
Sobin  LHedWettekind  Ced TNM Classification of Malignant Tumors. 5th ed. New York, NY John Wiley & Sons Inc1997;
5.
Sisson  GAToriumi  DMAtiyah  RA Paranasal sinus malignancy: a comprehensive update. Laryngoscope. 1989;99143- 150
6.
Spiro  JDSoo  KCSpiro  RH Nonsquamous cell malignant neoplasms of the nasal cavities and paranasal sinuses. Head Neck. 1995;17114- 118Article
7.
Kadish  SGoodman  MWang  CC Olfactory neuroblastoma: a clinical analysis of 17 cases. Cancer. 1976;371571- 1576Article
8.
Biller  HFLawson  WSachdev  VPSom  P Esthesioneuroblastoma: surgical treatment without radiation. Laryngoscope. 1990;1001199- 1201Article
9.
Dulguerov  PCalcaterra  T Esthesioneuroblastoma: the UCLA experience 1970-1990. Laryngoscope. 1992;102843- 849Article
10.
Austin  JRCebrun  HKershisnik  MM  et al.  Olfactory neuroblastoma and neuroendocrine carcinoma of the anterior skull base: treatment results at the M. D. Anderson Cancer Center. Skull Base Surg. 1996;61- 8Article
11.
Ellingwood  KEMillion  RR Cancer of the nasal cavity and ethmoid/sphenoid sinuses. Cancer. 1979;431517- 1526Article
12.
Roux  FXBrasnu  DMenard  M  et al.  Les abords combinés des tumeurs malignes de l'ethmoïde et autres sinus paranasaux: principes et résultats. Ann Otolaryngol Chir Cervicofac. 1991;108292- 297
13.
Cantù  GSolero  CLSalvatori  PMattavelli  FPizzi  NLicitra  L A new classification of malignant ethmoid tumors: 3rd European Skull Base Congress, London, 9-11 April 1997. Skull Base Surg. 1997;7 (suppl 2) 33
14.
Cantù  GSolero  CLMariani  L  et al.  Anterior craniofacial resection for malignant ethmoid tumors: a series of 91 patients. Head Neck. 1999;21185- 191Article
15.
Kaplan  ELMeier  P Nonparametric estimation from incomplete observations. J Am Stat Assoc. 1958;53457- 481Article
16.
Cox  DR Regression models and life tables. J R Stat Soc. 1972;34187- 220
17.
Shah  JPKraus  DHBilsky  MHGutin  PHHarrison  LHStrong  EW Craniofacial resection for malignant tumors involving the anterior skull base. Arch Otolaryngol Head Neck Surg. 1997;1231312- 1317Article
18.
Schwaab  GMicheau  CLe Guillou  C Olfactory esthesioneuroma: a report of 40 cases. Laryngoscope. 1988;98872- 876Article
19.
Zappia  JJCarroll  WRWolf  GTThornton  AFHo  LKrause  CJ Olfactory neuroblastoma: the results of modern treatment approaches at the University of Michigan. Head Neck. 1993;15190- 196Article
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