TAREK K. SABER, M.D.; HESHAM A. HUSSEIN, M.D.; ALI H. MEBEED, M.D.; HESHAM I. EL SEBAI, M.D.; IHAB SAMI, M.D. and IMAN G. FARAHAT, M.D.* The Departments of Surgical Oncology and Pathology*, National Cancer Institute, Cairo University. Journal of the Egyptian Nat. Cancer Inst., Vol. 21, No. 3, September: 219-227, 2009

1. ABSTRACT
Aim of Work: The purpose of this study is to analyze
the causes of Loco-regional failure in 51 patients with
tumors of the oral cavity abutting the mandible.
Patients and Methods: This cross-sectional study (27
patients were operated upon in the retrospective section
and 24 patients in the prospective section of the study)
was done in the department of Surgical Oncology, National
Cancer Institute, Cairo University, from January 2003 to
January 2008. Fifty-one patients, with oral cavity cancerous
lesions abutting the mandible, were operated upon by
segmental mandibulectomy en-bloc with primary tumor
resection in addition to modified radical or selective neck
dissection according to the status of the cervical lymph
nodes.
Results: During a median follow-up of 2 years, 29
patients (56.8%) had local recurrences, the incidence of
nodal recurrence after neck dissection was detected in 4
patients (7.8%). On multivariate analysis, tumor depth,
tumor grade, oral mucosa, soft tissue and bone surgical
margins in addition to metastatic lymphadenopathy were
independent prognostic factors of loco-regional failure
and disease-free survival.
Conclusion: Oral cavity cancers abutting the mandible
should be treated with great caution by a multidisciplinary
oncology team (resection and reconstruction surgeons) as
it has a very aggressive biologic behavior. Negative
intraoperative pathological margins should be attempted
since this is the critical point for patients with cancers
abutting the mandible? Further research on the biologic
margin and genetic study is required.
Key Words: Oral cavity cancer abutting the mandible –
Predictors of loco-regional failure.
INTRODUCTION
Oral cancer is the sixth most common cancer
worldwide, with a high prevalence in south
Journal of the Egyptian Nat. Cancer Inst., Vol. 21, No. 3, September: 219-227, 2009
Cancer of Oral Cavity Abutting the Mandible;
Predictors of Loco-regional Failure
TAREK K. SABER, M.D.; HESHAM A. HUSSEIN, M.D.; ALI H. MEBEED, M.D.;
HESHAM I. EL SEBAI, M.D.; IHAB SAMI, M.D. and IMAN G. FARAHAT, M.D.*
The Departments of Surgical Oncology and Pathology*, National Cancer Institute, Cairo University.
219
Asia. Surgery is the most well established mode
of initial definitive treatment for a majority of
oral cancers. Primary site location, size, prox-
imity to bone, and depth of infiltration are
factors which influence a particular surgical
approach. Tumors that approach or involve the
mandible require specific understanding of the
mechanism of bone involvement. This facilitates
the employment of mandible sparing approaches
such as marginal mandibulectomy and mandib-
ulotomy [1,2].
Standard plain radiographs such as the or-
thopantomogram (OPG) are reasonably sensitive
in detecting mandibular invasion, but this should
be confirmed in doubtful cases with more sen-
sitive imaging techniques like CT and MRI [3].
It was found that a malignant tumor does
not extend directly through the intact periosteum
and cortical bone toward the cancellous part of
the mandible since the periosteum acts as a
significant protective barrier, instead the tumor
advances from the attached gingiva towards the
alveolus [4,5].
In patients with teeth, tumor extends through
the dental sockets into the cancellous part of
the bone and invades the mandible while in
edentulous patients the tumor extends up to the
alveolar crest and then infiltrates through the
dental pores in the alveolar process and extends
to the cancellous part of the mandible, Fig. (1)
shows the classification of mandible invasion
with oral cancer [6,7].
Thus in patients with very early invasion of
the alveolar process, marginal mandibulectomy
is feasible since the cortical part of the mandible
Correspondence: Dr Tarek K. Saber,
Department of Surgical Oncology, National Cancer
Institute, Cairo University, khairytarek@yahoo.com

2. 220
inferior to the roots of the teeth remains unin-
volved and can be safely spared [8,9].
In edentulous patients, the feasibility of
marginal mandibulectomy depends on the ver-
tical height of the body of the mandible which
is not visible with the age desorption process.
Segmental mandibulectomy must be performed
when there is extension of tumor to involve the
cancellous part of the mandible and may also
be required in patients who have massive pri-
mary tumors with extensive soft tissue disease
surrounding the mandible, and should not be
considered to simply gain access for resection
as mandibulotomy is a reasonable solution [10].
PATIENTS AND METHODS
This study was conducted in the National
Cancer Institute, Cairo University, a tertiary
cancer institution, from January 2003 to January
2008.
Statistical analysis was performed on 51
patients who fulfilled our inclusion criteria.
These criteria included patients with all T stages,
N0, N1 or N2 patients with exclusion of patients
with distant metastases.
The patients were staged according to the
American Joint Committee of Cancer (AJCC)
staging system.
Demographic data including clinical presen-
tation, relevant imaging findings, operative
details, histopathologic confirmation and follow-
up information is presented.
In addition to routine laboratory investiga-
tions, chest X-ray, cardiologic and anesthetic
consultations, pre-operative plain X-ray of the
mandible (Panorex) was done in 21 patients.
Pre-operative CT scan of the head and neck
was done in 38 patients.
All patients were operated upon as the pri-
mary definitive treatment (apart from two pa-
tients who received pre-operative neo-adjuvant
chemoradiation therapy due to advanced stage
of disease). Commando operation was per-
formed in the form by lateral segmental man-
dibulectomy en-bloc with excision of the pri-
mary tumor in addition to modified radical or
selective neck dissection in 45 patients. Central
mandibulectomy was performed in 4 patients
with appropriate mandibular reconstruction,
and two patients were operated upon by marginal
mandibulectomy with appropriate soft tissue
reconstruction.
In the majority of patients, a pectoralis major
myo-cutaneous flap was done for reconstruction
followed by a deltopectoral fascio-cutaneous
flap.
A free vascularized radial forearm flap was
done for three patients for reconstruction of
floor of mouth defects and a free vascularized
fibular graft was done for two patients for
mandibular reconstruction.
Pathologic examination of the resected speci-
men:
The surgical specimens submitted to the
Department of Pathology at the National Cancer
Institute, Cairo University, were processed in
standard fashion after orientation of the mucosal,
soft tissue, and bone margins of the resected
part of the mandible.
Lymph nodes were identified by visual in-
spection and palpation, and were dissected out
from the gross specimen. After fixation in 10%
neutral buffered formalin, decalcification of
bony sections was done utilizing a solution
containing 10% formic acid and 10% Hcl.
After decalcification, the specimen was sub-
sequently processed routinely for paraffin em-
bedding and staining by haematoxylin and eosin
(H&E).
After the sections were processed, slides
from each section containing the tumor were
assessed to determine the extent of mandibular
bone invasion, if present.
The sections from margins of resection,
including bone pathological margins, were eval-
uated and classified as negative if there was no
evidence of tumor at the margin, close if the
tumor was within 2mm distance from the margin
or positive if the margin was involved by tumor
tissue (microscopic cut-through).
Surgical and post-operative treatment done
to patients and their results were planned ac-
cording to the site of primary tumor and stage
of disease.
RESULTS
From a total of fifty-one patients with oral
cavity cancer, 31 (60.7%) were male patients
Cancer of Oral Cavity Abutting the Mandible

3. Tarek K. Saber, et al. 221
and 20 (39.3%) were females whose ages ranged
from 22 to 73 years. The median age of all
patients was 58 years, while the mean age was
56.3 years.
The commonest tumor was alveolar margin
carcinoma encountered in 19 patients (37.2%),
followed by 14 patients (27.4%) with retromolar
tumors, followed by other sites, as shown in
Table (1).
A.J.C .C staging is shown in Table (2), where
T3 was the commonest (31.3%), followed by
T2 (29.4%) and T4 (27.4%). Negative nodes
(N0) represented 52.94% of the cases followed
by N1 (43.13%) (Table 2).
Regarding the histology of tumors, squamous
cell carcinoma was the predominant histology
found in 47 patients (92.1%) (Table 3).
Regarding the grade of the tumor, Interme-
diate grade (grade 2) was the predominant grade
in 38 patients (80.8%) (Table 4). Table (5) shows
the number of patients at different primary sites,
their stage, tumor grade and histopathological
type.
The final pathological reports for the surgical
pathological margins in different sites came
with negative pathological margins in 9/19
patients of alveolar margin carcinoma, 7/14
patients of retromolar trigone, 3/8 buccal mucosa
patients, 2/6 patients of tongue carcinoma, 1/3
floor of mouth patient and one patient of basal
cell carcinoma.
Positive margins recorded high incidence in
9/19 patients with alveolar margin carcinoma,
3/14 patients with retromolar trigone, 4/7 in
buccal mucosa, 3/6 of tongue carcinoma patients
and 1/3 patients with floor of mouth carcinoma.
Close margins were reported in 1/19 patients
with carcinoma of the alveolar margin, 4/14 in
retromolar trigone patients, 1/8 of buccal mu-
cosa, 1/6 in tongue carcinoma and one case of
floor of mouth carcinoma. All results are sum-
marized in Table (6). Figs. (2-5) show radiolog-
ical and intraoperative photographs of oral
cavity cancer.
In this study, most cases of mandibular bone
invasion with tumor were in patients of alveolar
margin tumors, this was proved pathologically
in 14/19 patients. Bone invasion occurred next
in frequency in 8/14 patients with retromolar
tumors. Tumors of the buccal mucosa abutting
the mandible (gingivo-buccal sulcus tumors)
invaded the mandible in 2/8 patients, one of
these patients had a grade 2 squamous cell
carcinoma and the other one had muco-
epdermoid cancer of the gingivo-buccal sulcus
(GBC). Both patients had T 4 lesions, but this
was not observed in a patient with a locally
advanced GBC and another patient with grade
3 squamous cell carcinoma (Table 7).
As regards the incidence of local recurrence
in this study, the highest rate of local recurrence
was found in 5/6 patients (83.3%) with carci-
noma of the tongue (Table 8).
In this study, we had 4/50 patients (6%) who
underwent neck dissection and developed neck
recurrence in the neck dissection side. Details
of locoregional recurrence and distant metastases
according to primary site tumors are shown in
Table (9).
Results of treatment for the 51 patient with
oral cavity cancer abutting the mandible are
presented in Table (10).
Table (1): Oral cavity cancers abutting the mandible; sites
and number of cases.
Alveolar margin
Retromolar trigone
Buccal mucosa (gingivo-buccal complex)
Tongue
Floor of mouth
Skin of Chin
Total No. of cases
19 (37.25)
14 (27.45)
8 (15.6)
6 (11.7)
3 (5.8)
1 (1.9)
51
Site of primary tumor
No. of cases
(%)
Table (2): T. N. M stage of 51 patients.
T 1
T 2
T 3
T 4
Referred
recurrent
cases
Total no.
T stage
T = Tumor. N = Node. M = Metastasis.
M 0
M 0
M 0
M 0
0
M stage
27 (52.94)
22 (43.13)
2 (3.92)
0
None
51
No. of
cases (%)
N 0
N 1
N 2
N 3
Neck
Recurrence
after
treatment
N stage
3 (5.8)
15 (29.4)
16 (31.3)
14 (27.4)
3 (5.8)
51
No. of
cases (%)

4. 222 Cancer of Oral Cavity Abutting the Mandible
Table (3): Histological type of primary tumor.
1 (1.9%)
Basal cell
carcinoma
1 (1.9%)
Verrucous
carcinoma
2 (3.9%)
Muco-epedermoid
carcinoma
No. of cases
Type of
tumor
47 (92.1%)
Squamous cell
carcinoma
Table (6): Pathologic surgical margin according to the site of primary tumor.
Negative surgical margin
Positive surgical margin
Close margin
Margin status
1ry Tumor
9 (47.3%)
9 (47.3%)
1 (5.2%)
Alveolar
margin
N=19
7 (50%)
3 (21.4%)
4 (28.5%)
Retromolar
trigone
N=14
3 (37.5%)
4 (57.1%)
1 (12.5%)
Buccal mucosa
(GBC)
N=8
2 (33.3%)
3 (50%)
1 (16.6%)
Tongue
N=6
1 (33.3%)
1 33.3%
1 33.3%
Floor of mouth
N=3
1
0
0
Chin
N=1
Table (4): Grade of primary tumor.
No. of cases
Type of
tumor
4/47 (8.5%)
Squamous
cell Ca.
Grade 1
38/47 (80.8%)
Squamous
cell Ca.
Grade 2
8/47 (17%)
Squamous
cell Ca.
Grade 3
Gd1 1 case 1/51 (3.9%)
Gd3 1 case 1/51 (3.9%)
Muco-epedermoid
Grade 1,3
1/51 (1.9%)
Verrucous
carcinoma
1/51 (1.9%)
Basal cell
carcinoma
Table (5): Tumor and nodal stage, histopathology and grade in different sites of oral cavity cancer patients.
Alveolar margin (19)
31.5%
Retromolar trigone (14)
27.4%
Buccal mucosa (8)
Tongue (6)
Floor of mouth (3)
Chin mandible (1)
Primary site
G3=3
G2=14
G1=2
G3=2
G2=11
G1=1
G3=4
G2=3
G1=1
G3=1
G2=4
G1=1
G2=3
Grade
Squamous cell carcinoma.
Squamous cell
Carcinoma. (13)
Mucoepidermoid (1)
Verrucous carcinoma (1)
Squamous cell carcinoma (6)
Mucoepidermoid (1)
Squamous cell carcinoma
Squamous cell carcinoma
Basal cell carcinoma
Histopathology
N0=9
N1=8
N2=2
N0=7
N1=7
N0=4
N1=4
N0=5
N1=1
N0=3
N0=1
Node
T=0
T2=6
T3=6
T4=7
T1=1
T2=5
T3=6
T4=2
T1=0
T2=2
T3=2
T4=4
T1=0
T2=2
T3=4
T4=0
T1=2
T4=1
T4=1
Tumor
T = Tumor. N = Node. G = Grade.

5. Table (7): Incidence of mandible invasion in different sites of oral cavity cancer.
Invasion of Mandible
Percentage
Site of 1ry tumor
1/1
Chin
2/3
66.6%
F.O.M
0/6
0%
Tongue
2/8
14.2%
Buccal mucosa
(GBC)
8/14
57.1%
Retromolar trigone
14/19
73.6%
Alveolar margin
FOM: Floor of mouth.
Tarek K. Saber, et al. 223
Table (10): Results of treatment according to site of primary tumor.
11 cases
(57.8%)
7 cases
(50%)
5 cases
(62.5%)
5 cases
(83.3%)
1 case
No
29/51 cases of
locegional failure
56.8%
Local recurrence
Yes
Yes
Yes
Yes
Yes
Yes
Adjuvant
therapy
14 cases
8 cases
2 cases
No case of
mandibular
infiltration
2 cases
1 case
27/51 cases
mandibular
invasion with
tumor
52.9%
Positive invasion
of mandible
Commando
N=19 case
Commando
N=13 cases
Marg.mandibulectomy
N=1 case
Commando
N=8 cases
Commando
N=6 cases
Commando
N=2 cases
Wide excision=1 case
Central mandibulectomy
N=1 case
Primary treatment
Alveolar margin
Retromolar trigone
Buccal mucosa GBC
Tongue
Floor of mouth
Chin
Total no.
Percentage
Site of 1ry tumor
Table (8): Incidence of local recurrence in different sites of oral cavity cancer.
Local recurrence
Percentage
Site of 1ry tumor
0/1
0%
Chin
1/3
33.3%
F.O.M
5/6
83.3%
Tongue
5/8
62.5%
Buccal mucosa
(GBC)
7/14
50%
Retromolar trigone
11/19
57.8%
Alveolar margin
FOM: Floor of mouth.
Table (9): Details of loco-regional and distant metastases according to site of primary tumor.
Total cases of local recurrence
Positive mucosal margin
Positive soft tissue margin
Positive bone margin
Nodal recurrence
Distant metastases
Site of 1ry tumor
29/51 (56.8%)
16/51 (31.3%)
8/51 (15.6%)
3/51 (5.8%)
4/51 (7.8%)
1/51 (1.9%)
Total No. Local,
Nodal, Recurrence,
Distant metastases
1/3 (33.3%)
1/1
0
0
0
0
Floor of
Mouth
(F.O.M)
5/6 (83.3%)
2/5 (40%)
1/5 (20%)
0
1/5 (20%)
0
Tongue
5/8 (62.5%)
3/5 (60%)
1/5 (20%)
1/5 (20%)
0
0
Buccal
mucosa
(GBC)
7/14 (50%)
4/7 (57.1%)
2/7 (28.5%)
1/7 (14.2%)
1/7 (14.2%)
1/7 (14.2%)
Retromolar
trigone
11/19 (57.8%)
6/11 (54.5%)
4/11 (36.3%)
1/11 (9.1%)
2/11 (18.1%)
Alveolar
margin

6. No Bone
Invasion
T1
Invasion within
Alveolar Bone
T2
Invasion beyond
alveolar bone but
above the LMC
T3
Invasion including
the LMC
T4
224 Cancer of Oral Cavity Abutting the Mandible
DISCUSSION
In this study, we had considerable high rates
of loco-regional failure in patients with carci-
noma abutting the mandible in different sites
of the oral cavity. In comparison, a similar
study from Rapidis et al from the Greek Cancer
Institute in 2009 included 194 patients with
tumors abutting the mandible to whom a com-
posite mandibular resection in addition to the
appropriate type of neck dissection was carried
out.
Fig. (1): Classification of mandible invasion with oral
cancer.
T 1 No Bone Invasion.
T 2 Invasion within Alveolar Bone.
T 3 Invasion beyond alveolar bone but above the *LMC.
T 4 Invasion including the LMC.
*LMC: Level of Mandibular Canal (Alexander D.Rapidis) (12).
Fig. (2): Carcinoma of floor of mouth abutting the man-
dible.
Fig. (3): CT of tumor invading the alveolar bone on the
lt. side.
Fig. (4): Lip splitting, lower cheek flap, marginal man-
dibulectomy en-bloc with wide excision of tumor
of floor of mouth.
Fig. (5): Specimen, en- bloc resection of floor of mouth
tumor + marginal mandibulectomy + modified
radical neck dissection.

7. Tarek K. Saber, et al. 225
Local recurrence in alveolar margin carci-
noma was found in 61.9% (26/42 patients), in
50% of patients with retromolar carcinoma (5/10
patients), in 42.6% of patients with tongue
cancer (20/47 patients), in 41.9% of patients
with floor of mouth carcinoma (13/31 patients)
in a total of 64/194 patients (32.6%).
The overall rate of loco-regional failure in
our study was 29/51 patients (56.8%), where
alveolar margin cancer recurrence was detected
in 11/19 patients (57.6%), in carcinoma of the
tongue, in 5/6 patients (83.3%) with local re-
currence, retromolar trigone in 7/14 patients
(50%), carcinoma of the buccal mucosa or the
gingivo-buccal complex in 5/8 patients (62.5%),
while in floor of mouth carcinoma, we had 1/3
patient (33.3%) with local recurrence [12].
This high incidence of local recurrence in
our study could be explained by the high number
of positive resection margins which were exam-
ined pathologically after surgery, as presented
in Table (6).
Jones et al. [13], in an attempt to identify
those patients most at risk for recurrence, ret-
rospectively determined the clinical and histo-
logical factors that was associated with recur-
rence in 49 patients with stage I and II oral
cavity cancer. Multiple regression analysis re-
vealed that when various interactions between
variables were controlled for, only the presence
of a positive surgical margin or a tumor depth
greater than 5mm was significantly associated
with recurrence. Each-individually-increased
the likelihood of recurrence almost threefold
[14].
Again, this high rate of local recurrence in
our study could be explained by the high inci-
dence of positive margins, although most of
these cases were operated upon by segmental
mandibulectomy to be sure of negative margins
but results came with positive soft tissue margins
as shown in Table (6).
O`Brien et al. [15] prospectively documented
patients who were treated with marginal or
segmental resection for oral (n=110) and oropha-
ryngeal (n=17) cancers. Among patients with
bone invasion, the local control rate was higher
following segmental resection when compared
to marginal resections (87% Vs. 75%), but this
was not statistically significant. Survival was
significantly influenced by positive soft tissue
margins but not bone invasion or the type of
resection. They concluded that bone invasion
alone did not predict for local control or survival
rates among patients with oral and oropharyn-
geal cancers. Involved soft tissue margins were
highly predictive of local recurrence and de-
creased survival. Conservative resection of the
mandible is safe as long as marginal mandibulec-
tomy does not lead to compromise of soft tissue
margins. Segmental resection should be reserved
for patients with extensive bone invasion or
those with limited invasion in a thin atrophic
mandible.
The need for intra-operative frozen section
confirmation cannot be over-emphasized in
order to obtain adequate local control for these
potentially curable tumors which were inade-
quately treated.
However, despite apparently adequate local
resection of oral cancer,
recurrence rates of 25-48% have been re-
ported [16]. Recurrent oral cancer tends to appear
at the primary site, perhaps because of the
persistence of malignant cells within local lym-
phatics or field cancerization, and is usually
seen within 36 months after the initial treatment.
Surgery and radiotherapy may cause tissue
hypoxia, hypocellularity, and fibrosis, the last
of which can encase persistent malignant cells,
making detection difficult. These processes may
eventually result in local recurrence. One of the
most important causes of local recurrence is
the persistence of tumor cells at the resection
margin [17].
Slootweg et al. [18] examined the resection
margins of 394 patients who underwent tumor
resection and found a much lower incidence of
local recurrence in patients with negative (3.9%)
than positive (21.9%) margins.
Unfortunately, locally recurrent cancer de-
velops even when resection margins are histo-
logically tumor-free. It is believed that the
relatively small number of cancer cells that
remains in the patient at the margin is the main
source of local recurrence. This limited number
of cells has been designated local minimal
residual cancer (MRC) [19-22].

8. 226
Recent molecular genetic studies provide
evidence that the majority of, if not all, head
and neck squamous cell carcinomas (HNSCCs)
develop within a contiguous field of pre-
neoplastic cells and genetic alterations associ-
ated with the process of carcinogenesis. A sub-
clone in a field gives rise to an invasive carci-
noma. An important implication of this
knowledge is that, after surgery of the initial
carcinoma, part of the field may remain in the
patient.
A field with preneoplastic cells that share
genetic alterations with cells of the excised
tumor has been detected in the resection margins
of at least 25% of patients, indicating that this
frequently occurs. Fields can be much larger
than the actual carcinoma, sometimes having a
diameter >7cm [19].
Still further research is ongoing to accurately
predict and, therefore, have an implication on
early prediction and treatment of patients most
susceptible to have recurrences based on genetic
and biologic examination of the surgical margin
in patients with oral cavity squamous cell car-
cinoma.
Conclusion:
Oral cavity cancers abutting the mandible
should be treated with great caution by a mul-
tidisciplinary oncology team (resection and
reconstruction surgeons) as it has a very aggres-
sive biologic behavior. Negative intraoperative
pathological margins should be attempted since
this is the critical point for patients with cancers
abutting the mandible. Further research on the
biologic margin with genetic studies is required.
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