Diapositiva 1

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How to evaluate results in skull base
malignancies? Giulio Cantù M.D. National Cancer
Institute Milano, Italy
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• Many papers on anterior cranio
• facial resections have been
• published after the first of
• Ketcham (1963).
• Many different approaches have
• been recommended.
• Many complications have been
• reported.

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Advances in skull base surgery coupled with
advances in reconstructive techniques (free
microvascular flaps) have enabled skill surgeons
to safely resect nearly all types of malignant
tumors involving the skull base that would have
been considered inoperable in the past.
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Complication rates ranging from 26 to 63 have
been reported in the literature (wound infection,
meningitis, CSF leakage, hematoma,
pneumocephalus, delayed return of neurological
function, ocular complications). Operative
mortality is generally under 5.
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• However, what about oncologic long term results?
• I performed five queries on Med-Line using some
  key words
• Malignant tumors, skull base surgery 318
  papers
• Malignant tumors, craniofacial resection 92
• Malignant tumors, anterior craniofacial
  resection 59
• Malignant tumors, anterior craniofacial
  resection, results 33
• Malignant tumors, anterior craniofacial
  resection, long-term results 11

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• Moreover, long-term results reported in the
  literature are difficult to interpret. This is
  due to many factors
• Small number of patients treated
• by each author.
• A variety of histologies.
• A variety of locations or origin of
• the primary tumor and the extent
• of local invasion.

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• A variety of surgical approaches.
• Combinations of untreated and
• previously treated patients.
• Long time frame of the experience
• being reported.
• Insufficient length of time of
• follow-up.

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In the attempt to overcome these difficulties,
Jatin Shah in 1999 was the promoter of an
International Collaborative Study between 17
Institutions with a good experience in anterior
craniofacial resections. The study collected 1307
patients.
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After the first general paper, using the
collected data-base, two other papers have been
published
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The conclusion of this International
Collaborative Study was
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However, two out of these three prognostic
factors are pathologic post operative rather than
clinical pre-operative staging characteristics.
In my 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 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.
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In the paper of the International Collaborative
Study we may find this sentence The majority of
patients in the current study did not have
information available on the exact anatomic
subsite of origin and the TNM stage grouping was
not reported in 35 of patients
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• The reasons for this fact may be
• The population collected in a multi- institutiona
  l study is unavoidably heterogenous
• The absence of a universally accepted staging
  system

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My Institution (National Cancer Institute of
Milan) is in a lucky situation, as it has become
the national landmark for malignant tumors
involving the skull base. So, we have collected
the largest series of cranio-facial resections in
the world (330 anterior and 60 lateral skull base
resections) Our large series of ethmoid
malignant tumors allowed us to develop in 1993 a
prognostic classification of these rare tumors,
in the absence, as far as 1997, of an AJCC-UICC
classification.
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INT Classification of ethmoid tumors T1 Tumor
involving the ethmoid and nasal cavity sparing
the most superior ethmoidal cells T2 Tumor with
extension to or erosion of the cribriform plate,
with or without erosion of the lamina papyracea
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
antero-inferior 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
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AJCC-UICC Classification of Ethmoid Sinus Cancers
(1997) T1 Tumor confined to ethmoid with or
without bone erosion T2 Tumor extends
into nasal cavity T3 Tumor extends to anterior
orbit and/or maxillary sinus T4 Tumor
with intracranial extension, orbital extension
including apex, involving sphenoid and/or
frontal sinus and/or skin of nose
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In 1999, we successfully demonstrated the better
prognostic value of our classification for
ethmoidal cancer against the 5th Edition
AJCC-UICC classification (1997).
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AJCC-UICC-2002 Classification of Nasal Cavity and
Ethmoid Sinus Cancers T1 Tumor restricted to any
one subsite, with or without bony invasion T2
Tumor invading two subsites in a single region or
extending to involve an adjacent region within
the nasoethmoidal complex, with or without bony
erosion. T3 Tumor extends to invade the medial
wall or floor of the orbit, maxillary sinus,
palate, or cribriform plate T4a Tumor invades any
of the following anterior orbital contents, skin
of nose or cheek, minimal extension to anterior
cranial fossa, pterygoid plates, sphenoid or
frontal sinuses T4b Tumor invades any of the
following orbital apex, dura, brain, middle
cranial fossa, cranial nerves other than (V2),
nasopharynx, or clivus
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After the publication of the sixth AJCC-UICC
classification in 2002 we staged 241 patients
treated between 1987 and 2001 with an anterior
craniofacial resection for ethmoid malignant
tumors with AJCC-UICC-1997, AJCC-UICC-2002 and
INT classifications. These cases are a
homogeneous series, allowing clear conclusions.
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DFS according to INT Classification
Survival CI 95
T2 0.592 0.434-0.718
T3 0.446 0.292-0.589
T4 0.187 0.069-0.349
T2 T3 T4 Recurrence
25 25 41 Primary 58 46 46
Years
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DFS according to INT Classification
T2 T3 T4 Recurrence
25 25 41 Primary 58 46 46
Survival CI 95
T2 0.343
0.155-0.541 T3 0.204
0.065-0.397 T4 0.080
0.017-0.209
Years
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• Why a so better overall performance of INT
  classification versus both AJCC-UICC 1997 and
  2002 classifications?
• I think that AJCC-UICC 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 walls of ethmoidal
  cells, approaching the cribriform plate, so
  requiring a cranio-facial resection.

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• T2 is a tumor invading two subsites in a single
  region or extending to involve an adjacent region
  within the nasoethmoidal complex.
• This means that a tumor vegetating in the nasal
  cavity is a T2.
• I see no reasons why neoplastic vegetations in
  the empty space of this cavity may worsen the
  prognosis. Also the possible involvement of
  inferior turbinates and/or nasal septum may be
  easily cured with a medial maxillectomy.

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T3 is a tumor invading the medial wall or floor
of the orbit, maxillary sinus, palate, or
cribriform plate. Actually, a tumor involving the
medial wall of the orbit, even if without orbital
extension, is very different from that invading
the maxillary sinus and destroying the palate
(also T3).
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In the AJCC-UICC stage T4a we may find tumors
with minimal extension to anterior cranial
fossa, pterygoid plates, sphenoid or frontal
sinuses. First of all, it is not easy to
understand what minimal extension to anterior
cranial fossa means. A tumor with intracranial
extension at least is attached to the dura. But
involvement of the dura makes a tumor to be in
the stage T4b.
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Moreover, sphenoid involvement is not clearly
defined, because a detailed description of its
extent is lacking. Actually, a tumor eroding the
anterior-inferior wall of the sphenoid sinus is
quite easily resectable. On the contrary, when
the tumor involves or destroys the
superior-posterior-lateral walls and spreads to
the cavernous sinus, the sella turcica and the
clivus, it is impossible to achieve its complete
removal.
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Tumors invading the dura, orbital apex, brain,
middle cranial fossa, cranial nerves other than
(V2), nasopharynx or clivus, are classified as
T4b. In my opinion, these tumors are very
different 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.
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Moreover, some authors demonstrated a different
prognosis between patients with dural involvement
and those with brain invasion. In the same paper
of the International Collaborative Study there is
this sentence For recurrence-free survival,
only brain invasion was significant, presumably
because a resection margin can still be achieved
when either bone or dura is involved, but this is
less likely when brain parenchyma is involved
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All these biases are overcome by INT
classification. Its better performance finds
explanation in a series of resons First of all,
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.
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Third, it satisfies one of the main goals of
tumor staging, namely, the progressive worsening
of prognosis for different classes. Finally,
INT 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.
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Staging according to INT classification 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.
Actually, in our study the T
stage 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 over-staging or
down-staging of the tumor.
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As regards histology, there is a general
consensus about a better prognosis for patients
with esthesioneuroblastoma, whereas patients with
undifferentiated tumors fare worse.
Squamous cell carcinoma
Years
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However, we must remember that tumors like
esthesioneuroblastoma and ethmoid Intestinal Type
Adeno Carcinoma need a very long follow-up. Two
relapses of esthesioneuroblastoma after 12 and 14
years from a craniofacial resection and
radiotherapy occurred in our patients. Two more
patients treated for an ITAC presented with a
local relapse (or new tumour with the same
histology) after 15 and 18 years respectively. A
very long follow-up is mandatory to state the
real prognosis of these tumors
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In conclusion, it is difficult to interpret long
term results reported in the literature for the
small number of patients and the heterogeneous
composition of the series. The adoption of a
universally accepted prognostic clinical
classification like INT may allow comparison of
results among homogeneous series treated not only
with surgery, but also with radiotherapy,
chemotherapy, and therapeutic combinations.
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In conclusion, the clinical and not pathological
characteristics of INT classification, and its
capability to divide tumors in prognostic
different stages allow comparison of results
among homogeneous series treated not only with
surgery, but also with radiotherapy,
chemotherapy, and therapeutic combinations.
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