Journal of Cancer Therapy, 2013, 4, 1-9
Published Online December 2013 (http://www.scirp.org/journal/jct)
http://dx.doi.org/10.4236/jct.2013.411A001
Open Access JCT
1
Impact of Postoperative Radiotherapy and Chemotherapy
on Survival for Patients with Node Positive Oral Cancer
Mohamed Mahmoud1, Tarek Shouman1, Hesham Elhosseny1, Mona Aboelenin2, Mohamed Amin1
1Radiation Oncology Department, National Cancer Institute, Cairo University, Cairo, Egypt; 2Clinical Oncology Department, Faculty
of Medicine, Cairo University, Cairo, Egypt.
Received August 25th, 2013; revised September 22nd, 2013; accepted September 30th, 2013
Copyright © 2013 Mohamed Mahmoud et al. This is an open access article distributed under the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
ABSTRACT
Purpose: The aim of the present study is to compare between the use of post-operative concurrent chemotherapy and
radiotherapy alone on survival for patients with high risk oral cavity tumors at the National cancer Institute of Egypt,
undergoing surgery and receiving adjuvant treatment. Patients and Methods: This is a retrospective study, which was
carried out at the National Cancer Institute (Cairo University) on patients with node positive oral cavity cancer diag-
nosed between the year 2000 and 2008. The study included 60 patients (45 males and 15 females) with median age 57
years old. The patients underwent surgery, followed by postoperative radiotherapy 60 Gy/6 weeks versus postoperative
radiotherapy 60 Gy/6 weeks with concurrent cisplatin 100 mg/m2 at day 1, day 22 and day 43. Results: Regarding use
of concurrent chemotherapy, there was a significant difference in overall survival rate and locoregional control favoring
patients who received concurrent chemotherapy and radiotherapy, 3 years and 5 years overall survival rates respectively
were 53.8% and 40.4% compared to 37.5% and 26.3% for patients who didn’t receive any chemotherapy with (p <
0.038) for 5 years. Regarding age, there was a significant difference in overall survival rate favoring patients ≤57 years
in both arm groups, 3 years and 5 years overall survival rates respectively were 51.6% and 38.9% compared to 28.3%
and 18.9% for patients >57 years with (p < 0.028) for 5 years. Conclusion: We recommend for oral cavity tumor pa-
tients at the NCI of Egypt who have positive neck nodes to be treated with concurrent chemo-radiotherapy rather than
radiotherapy alone especially by using the new techniques as intensity modulated radiotherapy (IMRT) and image guid-
ed radiotherapy (IGRT).
Keywords: Concurrent Radiotherapy and Chemotherapy; Intensity Modulated Radiotherapy; Image Guided
Radiotherapy
1. Introduction
It is generally accepted that oral cavity squamous cell
carcinoma (OSCC) patients with positive lymph nodes,
Stage pT4 disease, or positive/close surgical margins re-
quire adjuvant radiotherapy (RT).
The application of chemotherapy to the treatment of
head and neck cancer dates back to the 1960s. Over the
decades, the role of chemotherapy has advanced from
initial use only in the recurrent or metastatic setting to
active current use in the definitive treatment setting. Coo-
per et al. 2004 [1] reported the results of a randomized
study in North America comparing radiation alone (60 to
66 Gy) to chemoradiation (same radiation dose plus three
cycles of 100 mg/m2 cisplatin) in patients with head and
neck carcinoma demonstrating high-risk features after
gross total resection.
This study demonstrated a benefit in loco-regional
control and disease-free survival for the chemoradiation
arm, but no overall survival benefit was appreciated. Ber-
nier et al. 2005 [2] randomized patients to essentially
equivalent treatment arms following head and neck can-
cer surgery. Eligibility criteria included patients with pa-
thologic T3 or T4 disease (except T3/N0), or patients with
any T-stage disease with two or more involved lymph
nodes, or patients with T1-2 and N0-1 disease with unfa-
vorable pathologic findings (extranodal spread, positive
margins, perineural involvement, or vascular embolism).
Local control, progression-free survival, and overall sur-
vival were superior for patients on the chemoradiation

Impact of Postoperative Radiotherapy and Chemotherapy on Survival
for Patients with Node Positive Oral Cancer
2
arm. These studies suggest that the addition of chemo-
radiation following surgery may be beneficial in selected
patients with high-risk head and neck cancer, although
with increased toxicity profiles.
The aim of the present study is to detect whether the
use of post-operative concurrent chemotherapy and radi-
otherapy has an impact on survival than post-operative ra-
diotherapy alone on patients who underwent surgery and
received adjuvant treatment, with high risk oral cavity tu-
mors treatment at the National Cancer Institute of Egypt.
2. Patients and Methods
This is a retrospective study, which includes 60 patients
with node positive squamous cell carcinoma of the oral
cavity. The patients underwent surgery, followed by pos-
toperative radiotherapy or postoperative radio-chemothe-
rapy at the radiotherapy department, National Cancer In-
stitute, Cairo University during the period between 2000
and 2008.
Data obtained from the patients’ files included, patients
serial number, age, sex, history of smoking, date of bi-
opsy, date of surgery, type of neck dissection, tumor site,
size, histological type, grade, surgical margin, lymph node
state, TNM, dose of chemotherapy, all data of radiother-
apy, time of occurrence of relapse whether locoregional
or distant as well as date of the patients in last visit.
All the patients were planned through 2-D simulator
planning using isocentric technique; thirty-seven patients
(33%) received unilateral treatment while seventy-five
patients (67%) received bilateral treatment.
The treated volume was either irradiated by two op-
posing fields in which its lower border was matched with
the upper border of a separate anterior direct field to co-
ver the neck nodes or by 2 laterals opposed fields which
included the neck nodes. All patients received a dose of
60 Gy/6 weeks.
As regarding chemotherapy, 30 patients received Con-
current Chemotherapy after checking of CBC, liver &
kidney functions, serum calcium & magnesium together
with proper hydration Patients received 3 cycles of che-
motherapy (100 mg/m2 on D1, D22, D43).
The median follow up was for 3 years. In each visit
complete physical examination was performed and inves-
tigations (in the form of CBC, liver functions, kidney
functions, local CT and pan endoscopy) were done every
6 months, some other investigations (chest X-ray, abdo-
minal ultrasound and bone scan) were selectively ordered
on suspicion.
Any abnormal finding was well documented and re-
lapse was confirmed radiologically (e.g. lung, liver, bone,
brain secondaries), and/or histopathologically (e.g. loco-
regional relapse or soft tissue secondaries).
Statistical Analysis
● Quantitative data were statistically described in terms
of mean standard deviation and range, while discrete
data were described using frequencies (number of
cases) and percentages when appropriate.
● Comparison of numerical variables between the study
groups was done using Student t test for independent
samples in comparing 2 groups when normally dis-
tributed and Mann Whitney U test for independent
samples when not normally distributed.
● For comparing categorical data, Chi square test was
performed. Exact test was used instead when the ex-
pected frequency was less than 5.
● Kaplan-Meier method was used to estimate overall
survival as a function of time since start of treatment.
● Comparisons between survival functions were per-
formed by using the log rank statistic.
● A probability value (p value) less than 0.05 is consid-
ered statistically significant. All statistical calculations
were done using SPSS (Statistical Package for the So-
cial Science; SPSS Inc., Chicago, IL, USA) version
17 for Microsoft Windows.
● Overall survival was calculated from the time of di-
agnosis to the time of death or last follow-up.
3. Results
This is a retrospective study was carried out at the Na-
tional Cancer Institute (Cairo University) on patients with
node positive oral cavity cancer diagnosed between the
year 2000 and 2008. The study included 60 patients. The
patients underwent surgery, followed by postoperative
radiotherapy or postoperative radio-chemotherapy.
The median patients age at diagnosis was 57.1 years
(range 29 - 78 years), 30 patients received post-operative
radiotherapy alone by a dose 60 Gy/30 fractions over 6
weeks, 2 Gy/fraction and 30 patients received the same
schedule of radiation with concurrent cisplatin 100 mg/m2
at D1, D22 and D43.
The follow up period ranged between 2 - 92 months
with a median follow up of 28 months. As shown in Fig-
ure 1 the overall survival rate at 3 years was 43%, 5 year
rate was 32% and median overall survival was 29 months
(95% CI 23.3 - 34.6).
3.1. Univariate Analysis
The 3 years overall survival and 5 years overall survival
was calculated for all patients in both arm groups and
shown in Table 1.
Regarding Nodal stage as shown in Figure 2, for pa-
tients with N1 disease the 3-year overall survival rate was
40%. Whereas for N2 disease was 22.2% while the 5-year
overall survival rate for patients with N1 disease was
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Impact of Postoperative Radiotherapy and Chemotherapy on Survival
for Patients with Node Positive Oral Cancer
Open Access JCT
3
Figure 1. Overall survival for all patients.
36.6% and for patients with N2 disease survival rate was
13.9% with (p < 0.006) for 5 years. In Figure 8, regarding Nodal stage, for patients with N1 disease the 3-year recurrence free survival was 48.6
%.where as for N2 disease was 22.2% while the 5-year
recurrence free survival for patients with N1 disease was
33.6% and for patients with N2 disease survival was
13.9% with (p < 0.013) for the 5 years.
Regarding the stage of the disease there was a signifi-
cant difference in overall survival rate favoring patients
with stage III; 3 years overall survival and 5 years survi-
val rates respectively were 51.8% and 41.3% compared
to 25.5% and 15.4% for patients with stage IV (p < 0.007)
for 5 years as shown in Figure 3.
Regarding use of concurrent chemotherapy as shown
in Figure 9, there was a significant difference in recur-
rence free survival rate favoring patients who received
concurrent chemotherapy, 3 years and 5 years recurrence
free survival respectively were 53.8% and 40.4% com-
pared to 36.4% and 24% for patients who didn’t receive
any chemotherapy, with median survival 39.9 and 23.4
months respectively with (p < 0.026) for the 5 years.
In Figure 4, regarding use of concurrent chemother-
apy, there was a significant difference in overall survival
rate favoring patients who received concurrent chemothe-
rapy, 3 years and 5 years overall survival rates respec-
tively were 53.8% and 40.4% compared to 37.5% and
26.3% for patients who didn’t receive any chemotherapy
with (p < 0.038) for 5 years.
Regarding age as shown in Figure 5, there was a sig-
nificant difference in overall survival rate favoring pa-
tients ≤57 years, 3 years and 5 years overall survival rates
respectively were 51.6% and 38.9% compared to 28.3%
and 18.9% for patients >57 years with (p < 0.028) for 5
years.
3.2. Multivariate Analysis
● Multivariate analysis was done for different prognos-
tic factors affecting Overall Survival.
It was shown that the following is independent prog-
nostic factor:
1) N-Stage of the tumor: survival for patients with N1
tumors was
Better than those of N2 (p < 0.005).
Regarding surgical margin as shown in Figure 6, there
wasn’t a significant difference in overall survival. For pa-
tients with negative margin 3 years and 5 years overall
survival rates respectively were 45.6% and 29.4% com-
pared to 33.8% and 29% for patients with positive or
closer margin with (p < 0.623) for 5 years.
● Multivariate analysis was done for different prognos-
tic factors affecting Recurrence free Survival.
It was shown that the following are independent prog-
nostic factors:
1) Recurrence free Survival for patients with N1 tu-
mors was better than those of N2 (p < 0.05).
The recurrence free survival rate at 3 years was 40.1%
and at 5 years was 27.3% and Median recurrence free
survival was 26 months as shown in Figure 7.

Impact of Postoperative Radiotherapy and Chemotherapy on Survival
for Patients with Node Positive Oral Cancer
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Table 1. 3 years overall survival and 5 years overall survival.
Overall survival rate
Factors Number of cases 3 years (%) 5 years (%) Median (months)P-value* 95% CI
All 60 43 32 29 23.3 - 34.6
Age
≤57yrs 40 51.6 38.9 39 17.5 - 42.2
>57yrs 20 28.3 18.9 25 0.028 18.5 - 32.6
Sex
Male 45 42.6 28.1 23 24.6 - 41.3
Female 15 38.4 30.2 26 0.820 19.2 - 34.3
PS
1 41 40.4 30.1 29 23.1 - 34.2
2 19 39.8 21.9 26 0.972 14.2 - 34.6
Smoking
No 47 41.6 33.7 28 19.6 - 36.2
Yes 13 40 26.1 30 0.69 22.8 - 32.2
Site
Tongue 45 36.9 25.9 26 17.2 - 36.1
Other Sites 15 45.3 23.4 33 0.139 21.2 - 34.3
Overall survival rate
Factors Number of cases 3 years (%) 5 years (%) Median (months)P-value* 95% CI
Grade
1 and 2 48 43 29.9 30 24.5 - 36.2
2 12 35.2 23.5 23 0.792 12.6 - 34.1
Margin
Negative 39 45.6 29.4 33 23.6 - 42.4
Positive/close 21 33.8 29.0 23 0.623 14.1 - 32.6
T-stage (tumor size)
T1 & 2 35 40 25 33.5 19.9 - 47
T3 & 4 25 41.1 30 28.5 0.89 22.3 - 44.6
N-stage
N1 45 51.2 40 36.6 24.7 - 47.8
N2 15 22.2 13.9 23.5 0.006 19.6 - 27.3
Stage
3 31 51.8 41.3 39 25.4 - 54.0
4 29 25.5 15.4 24 0.007 21.1 - 28.2
Type of neck dissection
RND 25 35.4 26.1 28 20.1 - 39.2
MRND 20 48.4 38.6 33 11.9 - 54.3
SND 15 41.1 23.6 30 0.635 17.8 - 42.2
Chemotherapy
NO 30 37.5 26.3 26 19.8 - 35.5
Yes 30 53.8 40.4 39 0.038 12.9 - 65.1
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Impact of Postoperative Radiotherapy and Chemotherapy on Survival
for Patients with Node Positive Oral Cancer
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Figure 2. Overall survival according to nodal stage.
Figure 3. Overall survival according to tumor stage.
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Impact of Postoperative Radiotherapy and Chemotherapy on Survival
for Patients with Node Positive Oral Cancer
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Figure 4. Overall survival according to concurrent chemotherapy.
Figure 5. Overall survival according to age.
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Impact of Postoperative Radiotherapy and Chemotherapy on Survival
for Patients with Node Positive Oral Cancer
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Figure 6. Overall survival according to surgical margin.
Figure 7. Locoregional control to all patients in months.
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Impact of Postoperative Radiotherapy and Chemotherapy on Survival
for Patients with Node Positive Oral Cancer
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Figure 8. Recurrence free survival in months according to nodal stage.
Figure 9. Recurrence free survival in months according to concurrent chemotherapy.
3.4. Discussion Regarding overall survival, in our study the 3 years &
5 years overall survival rates were 43% & 32% respec-
tively. Confirmatory results were reported by Bernier et
al. [3] who reported that overall survival rates of patients
with lymph node positive oral cavity tumors treated with
surgery and adjuvant RT at 3 years and 5 years were 42%
& 31.5% respectively. In another series [4] reported that
the 3 year and 5 years overall survivals rates were 45%
and 33.9% respectively.
Oral cavity tumors remain a challenging issue for onco-
logists despite the great advances in the multimodality
approach; surgery, chemotherapy and radiation. Adjuvant
radiotherapy could contribute to improved survival by im-
proving local control of the dissected neck, primary site,
pathways of perineural spread, or the undissected contra-
lateral neck and retropharyngeal nodes.

Impact of Postoperative Radiotherapy and Chemotherapy on Survival
for Patients with Node Positive Oral Cancer
9
In our study there was significant correlation between
nodal stage and overall survival (OAS), the 5-year over-
all survival for patients with N1 disease was 36.6% and
for patients with N2 disease survival was 13.9%. (p <
0.006).
Kao et al., 2008 [4] also reported that survival rates
were affected by nodal stage and reported that N1, 2, 3
five years survival was 50.7%, 33.2%, 31.5% respectively.
In our study there was a significant correlation be-
tween concurrent chemotherapy and survival rates, 5 years
overall survival for chemo-radiotherapy group was 40.4%,
while 5 years overall survival rates for radiotherapy alone
was 26.3% (P < 0.038). Bernier et al., 2004 [2] reported
that 5 years OAS for chemo-radiotherapy group was 56%
while for radiotherapy alone 40% (P < 0.01).
In our study surgical margin status didn’t affect OAS
and local control rates, which is comparable to that re-
ported by Hinerman et al., 2004 [5] who showed no sig-
nificant correlation between surgical margin and overall
survival rates (p < 0.88).
Sandro et al. 2004 [6] treated 47 patients by postop-
erative cisplatin and carboplatin concomitant with radio-
therapy 60 Gy, the estimated 2-year locoregional control,
progression-free survival, and overall survival rate was
73%, 56%, and 62%, respectively.
Another study conducted by Fietkau et al. 2006 [7],
comparing PORT alone 66 Gy/6.6 weeks with the same
regimen and concurrent cisplatin and 5-FU (5-Flurou-
racil). The 5 years LCR was 72%, for PORT and 88.6%
for concurrent chemoradiotherapy (p = 0.002), with im-
provement in OAS 48% for PORT versus 58% for com-
bined modality treatment.
Branko et al. 2007 [8] subjected 114 pateints with
stage III and IV SCHNC were randomized after surgery
to postoperative radiotherapy alone or concomitant che-
moradiotherapy. Patients in both groups were postopera-
tively irradiated to the total dose of 56 - 70 Gy. Chemo-
therapy included Mitomycin C 15 mg/rn2 after 10 Gy
and 5 mg of Bleomvcin twice weekly during irradiation.
Median follow-up was 76 months (48 - 103 months). At
5 years in the RT and CRT arms, the locoregional control
was 65% and 88% (p = 0.026), Disease-free survival
33% and 53% (p = 0.035), and overall survival 37% and
55% (p = 0.091) respectively.
4. Conclusions
In summary, we have demonstrated better overall sur-
vival rates in oral cavity tumor patients having positive
neck nodes when treated with adjuvant concurrent che-
motherapy and radiotherapy rather than adjuvant radio-
therapy alone.
So we recommend for oral cavity tumor patients at the
CI of Egypt who have positive neck nodes to be treated
with concurrent chemo-radiotherapy rather than radiothe-
rapy alone specially by using the new techniques as in-
tensity modulated radiotherapy (IMRT) and image guid-
ed radiotherapy (IGRT).
N
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