WHICH CLASSIFICATION FOR ETHMOID MALIGNANT TUMORS
INVOLVING THE ANTERIOR SKULL BASE?
Giulio Cantù, MD,1 Carlo L. Solero, MD,5 Rosalba Miceli, PhD,2 Luigi Mariani, MD,2
Franco Mattavelli, MD,1 Massimo Squadrelli-Saraceno, MD,1 Gabriella Bimbi, MD,1
Stefano Riccio, MD,1 Sarah Colombo, MD,1 Laura Locati, MD,3 Patrizia Olmi, MD,4
Lisa Licitra, MD3
1
Department of Head and Neck Surgery, Istituto Nazionale per lo Studio e la Cura dei Tumori, Via Venezian 1,
20133 Milan, Italy. E-mail: [email protected]
2
Division of Medical Statistics and Biometrics, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy
3
Unit of Medical Oncology of the Department of Head and Neck Surgery, Istituto Nazionale per lo Studio e la Cura
dei Tumori, Milan, Italy
4
Department of Radiotherapy, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy
5
Second Division of Neurosurgery, Istituto Nazionale Neurologico ‘‘C. Besta,’’ Milan, Italy
Accepted 19 August 2004
Published online 30 December 2004 in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/hed.20136
Abstract: Background. The purpose of this study was to
compare three systems of classification for malignant ethmoidal
tumors in patients undergoing anterior craniofacial resection.
Methods. A radiologic locoregional evaluation of 241 patients with malignant ethmoid tumors was performed before
patients underwent an anterior craniofacial resection. Disease in
each case was staged according to the American Joint
Committee on Cancer – Union Internationale Contre le Cancer
(AJCC-UICC) 1997 classification, the AJCC-UICC 2002 classification, and the Istituto Nazionale Tumori (INT) classification.
Kaplan – Meier curves and Cox models were used to investigate
the prognostic value of each classification system on diseasefree survival (DFS) and overall survival (OS). The classifications
were compared in terms of prognostic discrimination capability,
measured by use of an index of agreement between each
classification and DFS or OS time.
Correspondence to: G. Cantù
Partially presented at the 15th Annual Meeting of the North American Skull
Base Society, February 11 – 17, 2004, New Orleans, Louisiana.
B 2004 Wiley Periodicals, Inc.
224
Classification of Ethmoid Tumors
Results. All three classification systems yielded statistically
significant results in the Cox analysis, both for DFS and OS. In
the AJCC-UICC 2002 system, minor differences were observed
between T1 and T3 tumors. The INT classification showed a
progressive worsening of the prognosis with increasing stage.
The index of prognostic discrimination favored the INT classification over both the 1997 and 2002 AJCC-UICC classifications.
Conclusions. Both the 1997 and 2002 AJCC-UICC classifications seemed to have limited prognostic value. By contrast,
the INT classification satisfied one of the main goals of tumor
staging, demonstrating the progressive worsening of prognosis with different tumor classes. A 2004 Wiley Periodicals, Inc.
Head Neck 27: 224 – 231, 2005
Keywords: ethmoid tumors; tumor staging; craniofacial resection; paranasal sinuses; prognostic factors
After the paramount work of Ketcham et al,1 a
large number of articles on anterior craniofacial
resection for malignant tumors involving the anterior skull base have been published, and now
HEAD & NECK
March 2005
this type of surgery is widely recognized as the
‘‘gold standard’’ for tumors approaching or involving the cribriform plate. However, few studies
have examined prognostic factors in this tumor
type. Tumor extension represents one of the
most important and recognized factors impacting
long-term outcome, implying that optimal tumor
staging classification is critical for accurate prognostic assessment.2 – 4
Before 1997, many different staging classifications based on disparate criteria were adopted
for malignant tumors arising in the ethmoid.
In 1999, we successfully validated an original
classification (the Istituto Nazionale per lo Studio
e la Cura dei Tumori [INT] classification, Table 1)
for ethmoidal cancer5 against the 5th Edition of
the American Joint Committee on Cancer – Union
Internationle Contre le Cancer (AJCC-UICC) classification.6,7 The INT classification relies on the
most commonly accepted prognostic factors.
On the basis of these encouraging results, in
this study we tested the 6th AJCC-UICC8,9 2002
classification in terms of prognostic performance
versus the 1997 AJCC-UICC and the INT classifications. This article is based on the evaluation
of 241 patients with malignant tumors involving
the ethmoid, all undergoing anterior craniofacial
resection. Results of this comparative analysis
are reported.
involving the ethmoid). Ten patients (4%) were
excluded from the analysis because of postoperative death. Therefore, 241 cases were considered
in this study. Eight patients with small tumors
(T1 according to the INT classification) did
not require craniofacial resection and, therefore,
were not included in the analysis. Since 1997, we
have no longer operated on patients with either
melanoma (n = 2) or deep involvement of the
brain (n = 4).
The adopted surgical technique has already
been published.10,11 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 classification.
Patients’ ages varied from 11 to 79 years (median age, 55.3 years), and the male/female ratio
was 2.5 (173/68). Disease characteristics are reported in Table 2, together with the tumor distribution according to all the three staging systems.
One hundred fifty patients (62%) were initially
seen with primary disease; of these, 59 (39%)
underwent primary chemotherapy with cisplatin,
Table 2. Disease characteristics.
No. (%)
PATIENTS AND METHODS
From 1987 through June 2002, 251 patients
underwent an anterior craniofacial resection for
malignant tumors involving the anterior skull
base at the INT. The ethmoid was always involved, and it was the site of origin of the tumor
in all but 11 patients (maxillary sinus tumors
Table 1. INT classification of malignant ethmoid tumors.
T1 Tumor involving the ethmoid and nasal cavity sparing the
most superior ethmoid cells
T2 Tumor with extension to or erosion of the cribriform plate,
with or without erosion of the lamina papiracea and without
extension into the orbit
T3 Tumor extending into the anterior cranial fossa extradurally
and/or into the anterior two thirds of the orbit, with or without
erosion of the anteroinferior wall of the sphenoid sinus,
and/or involvement of the maxillary and frontal sinus
T4 Tumor with intradural extension, or involving the orbital apex,
the sphenoid sinus, the pterygoid plate, the infratemporal
fossa or the skin
Abbreviation: INT, Istituto Nazionale per lo Studio e la Cura dei Tumori.
Classification of Ethmoid Tumors
Type of disease
Primary
Recurrence
Tumor histology
Adenocarcinoma
Squamous cell carcinoma
Esthesioneuroblastoma
Adenoid cystic carcinoma
Melanoma
Other
INT classification
T2
T3
T4
AJCC-UICC 1997 classification
T1
T2
T3
T4
AJCC-UICC 2002 classification
T1
T2
T3
T4A
T4B
150 (62.2)
91 (37.8)
113 (46.9)
25 (10.4)
24 (9.9)
21 (8.7)
11 (4.6)
47 (19.5)
83 (34.4)
71 (29.5)
87 (36.1)
32 (13.3)
22 (9.1)
69 (28.6)
118 (49.0)
21 (8.7)
21 (8.7)
62 (25.7)
64 (26.6)
73 (30.3)
Abbreviations: INT, Istituto Nazionale per lo Studio e la Cura dei Tumori;
AJCC-UICC, American Joint Committee on Cancer – Union Internationale
Contre le Cancer.
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March 2005
225
fluorouracil, and leucovorin according to a treatment protocol in use at our institution since 1996.
The remaining 91 patients (38%) were initially
seen with a recurrence after previous treatment
performed elsewhere. Such treatments, either
alone or in combination, were as follows: surgery
in 67 cases (74%), radiotherapy in 58 cases (64%),
and chemotherapy in 30 cases (33%). In patients
with recurrent disease, the tumors were classified according to their extension on presentation
at our institute. After surgery performed at our
institute, 132 patients (55%) overall underwent
planned postoperative radiotherapy with a dose
of 50 to 66 Gy. Histologic diagnosis was based on
either a transnasal biopsy or the specimen analysis from previous surgery performed elsewhere.
The extent of the tumor was always assessed with
at least a CT scan in axial and coronal projections.
In cases with intracranial and/or intraorbital extension documented by CT scan, an MRI was
added to assess the infiltration of dura mater
and periorbita.
Only four patients were initially seen with
cervical node metastases (three with undifferentiated carcinomas and one with melanoma).
Disease-free survival (DFS)
and overall survival (OS) times were measured
from the date of surgery to the date of disease recurrence or death; in the absence of either event,
the time was measured from the date of surgery
to the date of last follow-up available. DFS and
OS curves were estimated with the Kaplan –
Meier method according to each classification
Statistical Methods.
system. The prognostic effect of the latter was
also investigated by means of Cox regression
models,12 after checking the underlying proportional-hazard assumption. The Cox analyses were
adjusted for the type of disease (primary or recurrent), a factor shown to be an important predictor in our previous study.5,10 The tumor stage
classifications and the type of disease were entered into the models by means of 0/1 indicator
variables. Suitable interaction terms were also
included for testing whether the individual classifications had different prognostic effects depending on the type of disease.
The prognostic discrimination of each classification (ie, the agreement between each classification and OS or DFS time) was estimated by
use of the probability of concordance K,13 with
rescaling on the maximum concordance theoretically achievable with each classification in the
available sample. The higher the probability (up
to a maximum of 1), the better the quality of the
classification system. To evaluate the performance of the AJCC-UICC 2002 classification compared with either the INT or AJCC-UICC 1997
classification, we calculated the difference between the estimates of K, together with the corresponding bias-corrected accelerated percentile
interval (BCa) bootstrap 95% confidence intervals (CIs).14
In all of the analyses, the conventional twosided 5% significance level was adopted. We used
SAS (SAS Institute Inc., SAS/STAT User’s Guide,
version 6. 4th ed, vol 1, Cary, NC: SAS Institute
Inc., 1989) and the S-Plus software (S-PLUS 2000
FIGURE 1. Disease-free survival (DFS, left panel) and overall survival (OS, right panel) curves according to the American Joint Committee
on Cancer – Union Internationale Contre le Cancer 1997 tumor classification.
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Classification of Ethmoid Tumors
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March 2005
FIGURE 2. Disease-free survival (DFS, left panel) and overall survival (OS, right panel) curves according to the American Joint Committee
on Cancer – Union Internationale Contre le Cancer 2002 tumor classification.
Guide to Statistics, vol 1 and 2, Data Analysis
Products Division, MathSoft, Seattle, WA) to perform modeling and statistical calculations.
RESULTS
The median follow-up time was 61 months. One
hundred forty-two patients (59%) had a disease
recurrence. These recurrences were mainly local,
either isolated (n = 117) or in combination with
other sites (n = 14); they rarely occurred at
distant sites (n = 9) or only in the lymphatic
nodes (n = 2). One hundred twenty-one deaths
were recorded, caused by tumor recurrence (n =
110), other primary tumors (n = 2), or nonneoplastic causes (n = 9). A correspondence between
clinical and pathologic staging for the INT classification was found in 236 (98%) of 241 patients.
Four of the five unmatched patients had a relapse
after prior surgery and radiotherapy performed
elsewhere. In three cases, the pathologic stage
was superior to the clinical one; and in two cases,
vice versa. Clinical staging missed the presence
of disease in the following sites: skin, intradural
extension, infratemporal fossa, maxillary sinus,
and orbital apex (one case each).
Relevant survival
curves are shown in Figure 1. The 5-year DFS
probability (95% CI) was 0.44 (0.24 – 0.62) for
patients with T1 tumors, 0.62 (0.32– 0.82) for pa-
AJCC-UICC 1997 Classification.
FIGURE 3. Disease-free survival (DFS, left panel) and overall survival (OS, right panel) curves according to the Istituto Nazionale per lo
Studio e la Cura dei Tumori tumor classification system.
Classification of Ethmoid Tumors
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227
FIGURE 4. Disease-free survival (DFS, left panel) and overall survival (OS, right panel) curves for patients with adenocarcinoma only
according to the Istituto Nazionale per lo Studio e la Cura dei Tumori tumor classification system.
tients with T2 tumors, 0.32 (0.21 – 0.44) for patients with T3 tumors, and 0.27 (0.18 –0.36) for
patients with T4 tumors; the corresponding
figures for OS were 0.40 (0.19 – 0.60), 0.72 (0.39 –
0.89), 0.45 (0.32 – 0.57), and 0.41 (0.31 – 0.51).
According to this classification, T2 tumors had a
relatively favorable prognosis, whereas a less
favorable prognosis was shown for T3 and T4,
and the prognosis for T1 tumors was in between.
Cox model analysis showed a significant prognostic effect of the classification on DFS ( p = .005)
but not OS ( p = .061). The agreement between
AJCC-UICC 1997 classification and clinical outcome was K = 0.68 for DFS and K = 0.66 for OS.
Survival curves
are shown in Figure 2. The 5-year DFS probability (95% CI) was 0.46 (0.21 – 0.68) for patients
with T1 tumors, 0.40 (0.15 – 0.65) for patients with
T2 tumors, 0.46 (0.32 – 0.58) for patients with T3
AJCC-UICC 2002 Classification.
tumors, 0.34 (0.22 – 0.46) for patients with T4a
tumors, and 0.18 (0.10 – 0.29) for patients with
T4b tumors; the corresponding figures for OS
were 0.38 (0.14 – 0.63), 0.52 (0.21 – 0.76), 0.60
(0.47 – 0.72), 0.37 (0.21 – 0.53), and 0.35 (0.23 – 0.47).
Patients with T2 tumors showed the most favorable prognosis, as seen with the AJCC-UICC
1997 classification. For the remaining stages, a
trend toward an unfavorable prognosis with increasing stage was apparent. Cox model analysis
showed a significant prognostic effect of the
classification on DFS ( p = .001) and OS ( p = .013).
The agreement with the clinical outcome was
K = 0.67 for DFS and K = 0.65 for OS. The preceding values are similar to those reported for the
AJCC-UICC 1997 classification.
Figure 3 shows the DFS (left
panel) and OS (right panel) curves of the whole
series according to the INT classification. A clear
INT Classification.
Table 3. Results of Cox model analysis of the INT classification.
Disease-free survival
INT classification
Type of disease
Overall survival
INT classification
Type of disease
Tumor characteristic
Hazard ratio (95% CI)
Wald’s p value
T3 vs T2
T4 vs T2
Recurrent vs primary
1.87 (1.22 – 2.88)
3.21 (2.14 – 4.81)
1.83 (1.33 – 2.53)
<.001*
T3 vs T2
T4 vs T2
Recurrent vs primary
2.05 (1.24 – 3.38)
3.25 (2.04 – 5.18)
2.18 (1.52 – 3.13)
<.001*
<.001
<.001
Abbreviations: INT, Istituto Nazionale per lo Studio e la Cura dei Tumori; CI, confidence interval.
*P for the 2-degrees of freedom test for the overall association.
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Classification of Ethmoid Tumors
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separation among the curves for both endpoints is
shown. The 5-year DFS probability (95% CI) was
0.51 (0.38 – 0.62) for patients with T2 tumors, 0.37
(0.25 –0.49) for patients with T3 tumors, and 0.13
(0.05 –0.24) for patients with T4 tumors; the corresponding figures for OS were 0.65 (0.52 – 0.76),
0.45 (0.32 –0.57), and 0.24 (0.14 – 0.36). Similar
patterns were observed by plotting the DFS and
OS curves of patients with adenocarcinoma
(Figure 4). Significant results ( p < .001) were
achieved in the Cox model for both DFS and OS
(Table 3). Type of disease (primary vs recurrent)
was confirmed as a prognostic factor both for
DFS and OS ( p < .001).5,10,11 The test on the interaction between INT classification and type of
disease failed to achieve statistical significance,
suggesting that the prognostic role of the INT
classification might not differ in primary and
recurrent tumors. The agreement between the
INT classification and clinical outcome was K =
0.75 for DFS and K = 0.74 for OS.
The difference in terms of agreement between INT and AJCC-UICC 2002 classifications was 0.082 (95% CI, 0.053 –0.113) for DFS
and 0.086 (95% CI, 0.052 –0.115) for OS. The
confidence limits excluded a zero difference, thus
providing statistical support to the evidence of
a better overall performance of the INT classification compared with the AJCC-UICC 2002
staging system.
DISCUSSION
Nowadays anterior craniofacial resection is the
‘‘gold standard’’ for the surgical treatment of
tumors involving the anterior skull base. Although the surgical techniques have been extensively described, few articles have focused on the
oncologic prognostic factors.15 – 17 All authors emphasize the fact that the prognosis for these patients is dictated by the primary tumor, whereas
the problems of lymph node and distant metastases are of minor importance.
Two recent retrospective analyses concluded
that dural and/or orbit involvement, histologic
type, and positive margins are indicative of a poor
prognosis.18,19 However, in neither study was a
clinical classification used to stage the disease
preoperatively. The identified prognostic factors
were pathologic rather than clinical.
However, in our opinion, the real problem is a
clinical one. Faced with a patient with a tumor
involving the anterior skull base, what are the
clinical criteria that indicate the likelihood of
Classification of Ethmoid Tumors
curing him or her with a craniofacial resection? In
addition to histologic findings, can we relate these
criteria to T classification? In short, we need a clinical prognostic classification.
In their review on nasal and paranasal sinus
carcinoma, Dulguerov et al20 wrote: ‘‘Articles that
employed a staging system for patients with nasal and ethmoid carcinoma were sparse and the
classification systems used varied and sometimes
were arbitrary.’’ A lot of original classifications
have been published in the past, but some of them
were only used for esthesioneuroblastomas.21,22
Roux et al23 used a classification quite similar to
the AJCC-UICC 2002 system.
The UICC-AJCC 1997 staging system6,7 introduced the concept, which we had already adopted,24 that different prognostic values should be
applied in cases of tumor involvement of either
the anterior orbit or its apex. In the former case,
we may achieve a radical resection with orbital
cleaning, but this is not the case for tumors with
orbit apex involvement. However, we believe that
the UICC-AJCC 1997 classification has some discrepancies. A T1 tumor may be small, low, and
resectable by means of 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, thus requiring a craniofacial
resection. Nasal cavity extension is the peculiarity
of a T2 lesion. We see no reason why neoplastic
vegetations in the empty space of this cavity may
worsen the prognosis. The possible involvement of
turbinates and/or nasal septum may be easily
cured with a medial maxillectomy. In addition, T4
tumor classification is too broad. In fact, 49% of our
patients have T4 disease. This classification includes tumors with little intracranial extension
without dural involvement, tumors attached to the
outer surface of the dura, and tumors with brain
infiltration. In the INT classification system, the
first two tumor presentations would be classified
as T3 and the third as T4. We believe it is possible
to achieve clean margins with a dural resection
in the first two cases but not when the tumor
involves the brain. Furthermore, the definition of
sphenoid sinus involvement is far too general. A
tumor eroding the anteroinferior wall of the sphenoid sinus is quite easily resectable; whereas, when
the tumor involves and destroys the superiorposterior-lateral walls and spreads to the cavernous sinuses, the sella turcica, and the clivus, it is
impossible to achieve complete removal. Finally, a
tumor involving the frontal sinus may be resected
HEAD & NECK
March 2005
229
more easily and radically than a tumor that
extends to the pterygoid plate or infratemporal
fossa; this latter extension was not reported in the
AJCC-UICC 1997 classification system.
The AJCC-UICC 2002 classification8,9 uses a
different definition of T categories and includes
nasal cavity and ethmoid sinus in a nasoethmoid
complex, thus finding a solution for the difficult distinction of the site of origin of tumors of
this region.
The new AJCC-UICC classification introduces
a subdivision of the T4 classification, with T4a
and T4b defining the tumor under these categories as resectable and unresectable, respectively.
By use of the last classification for our patients
and by comparing it with the 1997 classification,
the number of T1 tumors is smaller (21 vs 32)
and the number of T2 tumors is the same, but
three T1 tumors (1997) are reclassified as T2
(2002), and eight T1 tumors are reclassified as
T3. Actually, involvement of the medial wall of
the orbit, even if without orbital extension, makes
what was previously a T1 tumor become a T3
tumor. But such a tumor is very different from
that invading the maxillary sinus and destroying
the palate (also T3). The T4a classification includes tumors with minimal extension to the
anterior cranial fossa, or involving the skin, the
sphenoid, or frontal sinuses (T4 in the old classification) and tumors involving the anterior
orbital contents (previous T3). Also, in this case,
we find a migration of cases to an upper stage (26
T3 tumors [1997] are reclassified as T4a [2002]).
In fact, no less than 56% of our patients have T4a
and T4b disease.
The adoption of the new classification will by
itself be responsible for the improved results of
future studies, at least with T3 tumors. Actually,
the prognostic discriminative effect of T1 versus
T3 was lost in the latest classification compared
with the 1997 classification (Figures 1 and 2). One
must be aware that by adopting the latest AJCCUICC classification, along with the most recent
widespread application of modern imaging methods, there will be a shift in classification from
lower to upper stages, which is the basis of the
well-known Will Rogers phenomenon. This implies that the results from upcoming studies
should be carefully interpreted, especially when
assessing therapeutic improvements.
Tumors invading the dura, orbital apex, brain,
middle cranial fossa, cranial nerves other than
(V2), nasopharynx, or clivus, are classified as T4b.
In our opinion, these tumors are very different
230
Classification of Ethmoid Tumors
from one another, and not all of them are unresectable. Actually, many surgeons dealing with
skull base surgery usually operate on tumors involving the dura of the anterior cranial fossa.
Moreover, some authors demonstrated a different
prognosis between patients with dural involvement and those with brain invasion.10,25
All the preceding discrepancies are illustrated
in Figures 3 and 4.
According to the AJCC-UICC 1997 classification, no trend was observed in terms of DFS or
OS rates among T1, T3, and T4 tumor classifications. Oddly, only the patients with T2 tumors
showed a better outcome. We believe that a plausible explanation may rest on the fortuitous
selection in T2 stage of fungating and probably
less-aggressive tumors.
According to the AJCC-UICC 2002 classification, patients with T2 disease again showed the
most favorable prognosis; minor differences were
observed between T1 and T3, whereas a trend
toward the most unfavorable prognosis was apparent only for T4a and T4b. The preceding results affect the prognostic capability of both the
1997 and 2002 AJCC-UICC classifications.
The INT classification system turned out to
have the best overall performance. The distribution of the tumors into each T classification is balanced, without grouping a large number of cases
in one stage or another. A progressive worsening
of the prognosis was shown to occur from T2 to T4
classifications. Such findings were confirmed for
both primary tumors and recurrences, as well as
for a specific histotype such as adenocarcinoma.
All features of tumor extension that are used
in the INT classification system to distinguish one
stage from another can be easily assessed with
clinical examination, CT scan, and MRI. MRI is
able to detect the grade of dura and/or orbital
involvement, as well as intradural extension. Actually, in our study, the T classification changed
after surgical resection in only five cases; four of
them involved relapses after prior surgery and
radiotherapy. In these cases, the cicatricial tissues
may simulate tumor (or vice versa), so allowing an
overstaging or downstaging of the tumor.
The INT classification does not include N
status, which might seem a limitation. However,
although nodal involvement is recognized as a
weak prognostic indicator, its rare occurrence in
ethmoid tumors would add little information to
prognostic classification based on T classification
only. In our database we use the AJCC-UICC
stages for lymph nodes.
HEAD & NECK
March 2005
CONCLUSIONS
The latest AJCC-UICC classification correctly
merges nasal cavity and ethmoid tumors in a
nasoethmoid complex, avoiding the moot question
about the site of origin of these tumors. However,
such classification does not offer clear advantages
over the AJCC-UICC 1997 classification in terms
of prognostic ability, because in each stage it
includes tumor extensions that are very different
in terms of curability. Moreover, the AJCC-UICC
2002 classification considers T4b tumors unresectable, whereas in many cases they are quite
easily resectable.
The validity of the INT classification was
confirmed on this large series of patients, and it
was shown to achieve the best prognostic discrimination among T classifications. We believe
that the INT system for malignant ethmoid tumors is valid for a number of reasons. First,
it is based on anatomic and not just pathologic
criteria. Second, it takes into account the possibilities and limitations of the ‘‘gold standard’’
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 series but also when applied separately to untreated and recurring cases and to
adenocarcinomas, the most frequent histologic
type in our series.
Staging can be carried out clinically by means
of CT scans and MRI, which accurately reveal
tumor extensions and involvement of those
anatomic structures that determine any modification of stage. This allows comparison of results among homogeneous series treated with
surgery, radiotherapy, chemotherapy, and therapeutic combinations.
Acknowledgments. Dr Cantù acknowledges
the valuable support of the nurses of Head and
Neck Surgery Unit at Istituto Nazionale per lo
Studio e la Cura dei Tumori, Milan, Italy. This
study was sponsored in part by Associazione
Italiana per la Ricerca sul Cancro (AIRC).
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Classification of Ethmoid Tumors
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