Tóm tắt tiếng anh: Đánh giá kết quả điều trị ung thư lưỡi giai đoạn T1-2N1M0 bằng phẫu thuật kết hợp hóa xạ trị đồng thời

MINISTRY OF EDUCATION
MINISTRY OF HEALTH
HANOI MEDICAL UNIVERSITY

DINH XUAN CUONG

RESEARCH THE RESULTS OF TREATMENT OF
T1-2N1M0 STAGE TONGUE CANCER BY SURGERY
COMBINED WITH CONCURRENT
CHEMORADIOTHERAPY

Specialty

: Oncology

Code

9720108

SUMMARY OF DOCTORAL DISSERTATION

HANOI - 2022


THE STUDY IS COMPLETED AT
HANOI MEDICAL UNIVERSITY

Supervisors:

Prof.PhD. Le Van Quang
PhD.Dr. Nguyen Phi Hung

Critic 1: Associate Prof. Pham Cam Phương, PhD
Critic 2: PhD.Dr. Bui Vinh Quang
Critic 3: Associate Prof. Le Ngoc Ha, PhD

The thesis will be defended before the Examining Board at

university level in Hanoi Medical University
At time on month date 2022

The thesis can be found at
- National Library of Vietnam
- Library of Hanoi Medical University


LIST OF PUBLICATION RELATED TO
THE THESIS
1.

Dinh Xuan Cuong, Le Van Quang. Survival results of T12N1M0 stage tongue cancer by surgery combined with
concurrent chemoradiotherapy, Journal of Medical Research, no
1 in 2021, 1-11.

2.

Dinh Xuan Cuong, Ma Chinh Lam, Le Van Quang. Evaluation
of lymph node metastasis of T1-2N0M0 stage anterior tongue
cancer at K hospital, Journal of Otolaryngology, no. 6, 2020,
556-561.

3.

Dinh Xuan Cuong. Results of treatment of tongue cancer stage
T1-2N0-1M0

with

surgery

combined

with

concurrent

chemoradiotherapy at K hospital, Vietnamese Journa of
Oncology, no. 1, 2020, 69-73.


INTRODUCTION
1. Reason to choose the thesis.
Tongue cancer is the most common cancer in the oral cavity,
accounting for 30-40%. According to GLOBOCAN 2020, it is
estimated that there are about 377,713 new cases of oral cancer
worldwide and about 177,757 deaths every year. According to records
in Vietnam in 2020, there are about 2152 new cases of oral cancer and
1099 deaths every year.
Treatment strategy for tongue cancer include surgery, radiation
and chemotherapy, in which the treatment regimen depends on the
stage of the disease and the patient's condition. For early-stage tongue

cancer, surgery alone or in combination with adjuvant therapy after
surgery has good results. Many studies around the world showed that
the combination of adjuvant treatment after surgery for early-stage
tongue cancer reduces the risk of local recurrence, prolongs diseasefree survival and overall survival. . The study of Yu et al. comparing
the group of patients receiving adjuvant radiotherapy after surgery
with the group of surgery alone showed that the adjuvant radiation
group had a longer survival time. A multicenter study evaluating the
role of adjuvant chemoradiotherapy for head and neck squamous cell
carcinoma found that chemoradiotherapy was effective in reducing
local recurrence (RR = 0.59, p < 0.0001) and improved survival (RR =
0.8, p = 0.0002). In Vietnam, the adjuvant treatment after surgery for
early-stage tongue cancer depends on the characteristics of tumor
lesions in surgery and histopathological results. However, currently,
there are no studies on tongue cancer in T1-2N1M0 stage in Vietnam
to provide clinical and subclinical characteristics as well as analyze
risk factors to guide treatment methods after surgery. Therefore, we
conduct the study on the topic: "Research the results of treatment of
T1-2N1M0 tongue cancer by surgery combined with concurrent
chemoradiotherapy" to aim at achieving two objectives:
1. Evaluation of the treatment results of T1-2N1M0 stage of tongue
cancer by surgery combined with concurrent chemoradiotherapy.
2. Analysis of some clinical and histopathological prognostic factors.
2. Contributions of the thesis:
Surgery combined with concurrent chemoradiotherapy is an
effective treatment method for T1-2N1M0 stage tongue cancer. The


mean disease-free survival time was 45.3±2.3 months, the 5-year
disease-free survival rate was 66.8%. The mean overall survival time
was 46.9±2.1 months, the 5-year overall survival rate reached 73.9%.

The recurrence rate is 25.7%, of which the majority of recurrences are
in the cervical nodes (63.2%). Common chemical toxicity was
vomiting and nausea accounted for 75.7%, in which grade III toxicity
only encountered 9.7%. The rate of leukopenia accounted for 66.2%,
no grade IV toxicity was recorded. Liver and kidney toxicity are rare.
Radiation toxicity is common in dermatitis and mucositis, mainly
grade II (dermatitis 58.1%; mucositis 60.8%). Most patients had
xerostomia complications (90.5%); in which grade 2 is the most
common (36.5%). Skin fibrosis occurs 48.6%; mainly grade I (32.4%),
cleft palate 16.2%, mostly grade I (10.8%). There is a correlation
between the recurrence rate and histological grade, depth of invasion
and lymph node rupture status. There was a correlation between
disease-free survival, 5-year overall survival and factors of histological
grade, depth of invasion and ruptured lymph node.
3. Structure of the thesis:
The thesis consists of 116 pages, with 4 main chapters:
Introduction 2 pages, Chapter 1 (Literature review) 29 pages, Chapter
2 (Study subjects and methodology) 16 pages, Chapter 3 (Findings) 31
pages, Chapter 4 (Discussion) 35 pages, Conclusions and
Recommendations 3 pages. The thesis includes 42 tables, 3 figures and
17 charts, 117 references (22 Vietnamese documents, 95 English
documents).
Chapter 1: OVERVIEW
Combination
treatment of surgery and concurrent
chemoradiotherapy for early stage tongue cancer.
1.1.1. Surgery
1.1.1.1. Primary tumor
- T1: wide tumor resection, margin > 1 cm from the edge of the tumor,
if possible, immediate biopsy of resection margin

- T2: Partial tongue resection and cervical lymphadenectomy.
1.1.1.2. Regional lymph node
* Indication:
- For lymph nodes that are not clinically palpable: only selective
lymphadenectomy is enough (group I, II, III lymph node dissection
because the rate of metastasis is common in groups I and II).

1.1.


- For clinically palpable lymph nodes:
+ Lymph node size ≤ 3 cm, functional cervical lymphadenectomy.
+ Lymph node size is > 3 cm, radical cervical lymphadenectomy
+ Fixed lymph nodes, attached to surrounding tissue,
chemotherapy or radiotherapy first, consider surgery later.
1.1.2. Concurrent chemoradiotherapy
- Radiotherapy
* Indication:
Postoperative adjuvant radiation therapy, with or without
concurrent chemotherapy, is indicated for patients with positive or
asymptotic resection margin, bone invasion, or lymph node metastasis
on postoperative pathology. Postoperative radiotherapy should be
considered if there is lymphatic or neurological invasion of the
primary tumor.
* Technique and indications for radiotherapy
Postoperative radiotherapy
Tumor:
+ With negative resection margin, radiation dose is 50 Gy at 1,8 –
2 Gy/fraction.
+ With positive resection margin, radiation dose is 70 Gy at 1,8 –

2 Gy/fraction
Lympho nodes:
+ Total neck lymph node radiotherapy with dose at 45 – 55 Gy
+ Ruptured lymph node: increase the dose from 10 – 15 Gy.
- Chemotherapy
Use symtemic or oral agents, can be used alone or in combination
with multiple chemicals. Studies have shown that multiple
chemotherapy regimens results in better response than monotherapy.
Through many clinical trials, cisplatin-containing regimens increased
survival rates in the treated group. After cervical lymphadenectomy, if
metastases on 2 lymph nodes or metastases break the envelope,
chemotherapy is also indicated in combination with postoperative
radiotherapy. The chemical used is Cisplatin with a dose of 100mg/m2
of skin alternately on the 1st, 15th and 30th day of radiation treatment.
There are many different regimens applied to head and neck cancer, in
which CF regimen is cheap, good response results but low toxicity.
1.1.3. Radiotherapy combined with chemotherapy regimens with
platinum group


At least three clinical trials have demonstrated the benefit of
improving overall or disease-free survival with a combination of
platinum-based chemotherapy and radiation compared with radiation
alone.
+ The EORTC study included 334 high-risk squamous cell
carcinoma patients of the oral cavity, oropharynx, larynx, and
hypopharynx. Intervention group: radiation combined with
chemotherapy (cisplatin 100 mg/m2, IV days 1, 22, 43 of radiation)
compared with the radiotherapy alone group with the same dose (66
Gy, 2 Gy/day). At the 60-month follow-up, concurrent

chemoradiotherapy had a higher 5-year disease-free survival (47% vs
36%), a higher overall survival (53% vs 23%). However, grade 3, 4
adverse events on mucosa were higher in the combination treatment
group (41% vs 21%).
+ The RTOG study included 459 patients with high-risk
squamous cell carcinoma of the oral cavity, oropharynx, larynx, and
hypopharynx: radiotherapy group with doses of 60-66 Gy in 30-33
fractions, combined with cisplatin days 1, 22, and 43 of radiation
compared with the radiotherapy alone group with the same dose. At
the 46-month follow-up, the intervention group had a higher 4-year
disease-free survival (40% vs 30%) and a lower local recurrence rate
(19% vs 30%). However, the difference in overall survival was not
statistically significant and grade 3 and 4 adverse events were higher
in the combination treatment group.
1.2. Several studies of T1-2N1M0 stage tongue cancer
Many research around the world, such as the studies of Yu,
Shrime, Tsai, Vanessa ... demonstrated that adjuvant radiotherapy
improves 5-year disease-free survival time and overall survival
compared with surgery alone for early-stage tongue cancer. Some
other studies such as the study of EORTC, RTOG, Cooper ... recorded
better local control rate, improved survival of concurrent
chemoradiotherapy compared with radiation alone. Histological grade,
tumor depth are factors related to the outcome of control and survival.
In Vietnam, surgery combined with adjuvant chemoradiotherapy
is also used to treat patients with early-stage tongue cancer with highrisk factors. A study by Vu Viet Anh (2014) evaluated 47 patients with
T1-2N0-1 stage tongue cancer who were treated surgically and then
combined with radiotherapy alone or chemoradiotherapy at Vietnam


National Cancer hospital, the average survival time overall is 43

months. The survival time with the radiation group alone was 42.1
months (74%), and the concurrent chemoradiation group was 43.7
months (82.9%).

-

-

Chapter 2: OBJECTIVES AND METHODOLOGY
2.1 Research subjects
Research subjects consist of 74 patients with pT1-2N1M0 stage
tongue cancer that has met the following selection criteria and
exclusion criteria:
Selection criteria
The patient was diagnosed with anterior tongue cancer by
histopathology as squamous cell carcinoma.
The stage of disease after surgery is: T1-2N1M0 in accordance with
AJCC 2010.
Performance status (PS): 0-1
Good bone marrow function, good liver and kidney function:
+ White blood cells ≥ 4 G/l
+ Hemoglobin ≥ 125 g/l
+ Platelets ≥ 150 G/l
+ AST/ALT ≤ 40 U/l
+ Creatinine ≤ 100 mmol/l
No serious acute and chronic diseases at risk of death, no cancer other.
Indication for postoperative concurrent chemoradiotherapy.
Have full archival records and have contact information of the patients
after treatment.
Exclusion criteria

Have a history of other cancer
The patient did not receive adjuvant chemoradiotherapy
The planned radiotherapy is not fully performed
Patients > 70 years old.
2.2. Time and place of the study
- Time of the study: from September 2015 to July 2021
- Place of the study: K Hospital
2.3. Study methodology
2.3.1. Design of the study


-

Study methodology: Clinical intervention without control group
Calculation of the sample size
p(1 – p)
n = Z21-α/2
d2
Where:
n : Minimum sample size in the study

Z1−α / 2

-

: confidence coefficient with a probability level of 95% (α
= 0,05)→Z = 1,96.
p: overall survival rate at the 5 year period of T1-2N0-1 stage
tongue cancer (p = 0.808) (Shim SJ- 2010).
d: deviation of p, select d = 0.1

Minimum sample size is 59 patients. Sampling is from 74
patients.
2.3.2. Research variables
Age: divided into age groups: 40, 41 -50, 51 – 60, > 60
Gender: Male, female
Performance status index: calculated according to the scale of the
Eastern Cooperation Oncology Group (ECOG: Eastern Cooperation
Oncology Group).
Time from symptom onset to treatment: in months.
Some risk factors: drinking alcohol, smoking, oral disease.
Clinical symptoms.
Subclinical symptoms: histopathology, imaging
Diagnosis of staging according to AJCC 2010
Surgical results:
postoperative
time, postoperative
complications.
Chemoradiotherapy outcomes.
Survival time: disease-free survival time, overall survival time.
The relationship between survival time and factors: age, sex, stage of
disease, histological grade, depth of invasion.
Side effects of the regimen
+ On the hematological system: leukopenia, thrombocytopenia,
anemia
+ Extra-hematological system: increased liver enzymes, increased
urea, increased creatinine
+ Adverse effects of radiation therapy: dermatitis, skin fibrosis,
jaw tightening.

-

•
•

-

Some clinical and histopathological prognostic factors: age, gender,
histological grade, deep invasion, tumor stage T1/T2.
2.3.3. Conducting method
2.3.3.1. Collecting information about patient characteristics
2.3.3.2. Surgery
2.3.3.3. Adjuvant chemoradiotherapy
The patient received concurrent chemoradiotherapy with the Cisplatin
regimen every 3 weeks. Conducted 2 to 6 weeks after surgery.
Chemical composition
Cisplatin 100mg/m2, IV, day 1, day 22, day 43
Radiotherapy techniques:
+ Implementation steps
Treatment
simulation: patient immobilization, computed
tomography simulation
Treatment planning: determination target volume according to ICRU
50 and IRCU 62 recommendations, indicate radiation doses
+ Monitoring and responding during radiotherapy
2.3.3.4. Follow up after treatment
After the end of treatment, patients were followed up every 3 months
for the first 2 years, every 6 months for the next 3 years and once a
year for the following years.
2.4. Data analysis:

- Information on patients participating in the study is collected
according to the pre-established research sample records.
- Using IT software SPSS 22.0 to analyze statistics:
- Descriptive statistics: Average, standard deviation.
- Rate comparison: Test χ2 (p < 0.05) or Fisher's exact test.
- Kaplan - Meier survival rate estimation method

CHAPTER 3: RESULTS
After doing a study on 74 patients from 2015 to 2021, we had
some following conclusions:
3.1. Some clinical and histopathological characteristics of studies
patient group
3.1.1. Age and gender
- Age: average age was 53.4 ± 8.2, max was 68 years old and
min was 34 years old.
- Gender: male / female was 44/30 = 1.47
3.1.2. Medical history and symptoms
- Medical history: a large number of patients had risk factors


(70.3%), there was both smoking and drinking accounted for 37.8%.
- The average duration of diagnosis: 6.1 ± 2.4 months.
- Clinical symptoms: ulcer (43.2%), palpable tumor (33.8%)
- Performance status at diagnosis: ECOG = 0 (59.5%) and ECOG
= 1 accounted for 40.5%.
- Disease stage: Among 74 patients, there were 65.5% patients stage-T2.
Average tumor size was 3.2 ± 0.9 cm, max was 4.0 cm, min was
1.5cm.
- Histopathological characteristics: Tumor grade II was 60.8%, tiếp then
grade I was 22.9%.

- Depth of invation: Most of patients presented with DOI > 5mm
(accounted for 66.2%).
- Lymph node metastasis: 59.5% patients at dignosis were presented
with lymph node metastasis and 40.5% patients were not detected
before surgery. 93.2% patients had one lymph node metastasis after
surgery and group I-II cervical lymph node was the most common
metastasis, accounted for 63.6%.
3.2. Treatment results
3.2.1. Characteristics of treatment
- Analysis the cervical lymph node metastasis, the rate of metastais in
group I was the highest, accounting for 60.8%; then group II (36.5%);
and group III (2.7%). No report of metastais in group IV, V of cervical
lymph nodes.
- Analysis of cervical lymph node dissection, average number of
dissection nodes was 13.3±3.4, Min was 8 nodes, Max was 31 nodes.
The number of dissection nodes from 10 to 15 nodes is the most
common, accounting for 59.4%.
- All patients received surgical inventions with resection margin and
there is no report of positive or close margin after surgery.
- The risk factors of tongue cancer patients after surgery were high
tumoral grade (16.2% for grade III), DOI >5mm (66.2%) and
extranodal extension (ENE) (22.9%).
- For adjuvant chemotherapy, 93.1% of patients received chemotherapy
at doses of more than 85% standard doses. Most of patints received 3
cycles of cisplatin chemotherapy, accounting for 90.6%.
- For adjuvant radiation, all patients received radiation at a dose of 60
Gy to the tumor bed and nodal metastasis, and a dose of 50 Gy to


the contralateral cervical nodes.

3.2.2. Characteristics of recurrent/metastatic diseases
- Among 74 patients in our study, there were 19 patients presented
metastatic/recurrent diseases during follow-up time between 09/2015
and 07/2021 (accounting for 25.7%). Among 19 patients, most of
patients had recurrent cervical nodes (accounting for 63.2%), then
recurrent tongue (15.7%). There were 2 patients presented with lung
metastasis during follow-up. Recurrence under 24 months from
terminal treatment was the most common, accounting for 79%.
Univariate analysis of risk factors for recurrence
Table 3.1: Univariate analysis of risk factors for recurrence
95% Confidence
Risk factors
Odd ratio
p
interval
Age (≤60, >60)
0,808
0,27-2,46
0,467
Gender (male, female)
0,596
0,2-1,78
0,259
Tumoral stage (T1, T2)
2,81
0,73-10,9
0,103
Tumor grade (I+II vs III)
5,83
1,91-22,5

0,009
DOI (≤5, >5mm)
6,56
1,91-22,5
0,001
Extranodal extension
12,92
5,73-25,1
0,001
Univariate analysis for comparison of patients with recurrent and
non-recurrent status, a statistically significant association was found
for high tumoral grade, DOI and ENE with p < 0.05. There was no
significant differences in 2 groups for age, gender and tumoral stage
T1/T2.
Multivariate analysis for of risk factors for recurrence
Table 3.2: Multivariate analysis for of risk factors for recurrence
Odd
95% Confidence
Risk factors
p
ratio
interval
0,68
0,11-4,22
0,68
Age (≤60, >60)
1,08
0,17-6,29
0,929
Gender (male, female)

Tumoral stage (T1, T2)
3,33
1,34-32,99
0,033
Tumor grade (I+II vs III)
4,26
2,79-23,11
0,015
DOI (≤5, >5mm)
9,52
4,12-25,33
0,002
Extranodal extension
Univariate analysis for comparison of patients with recurrent and
non-recurrent status, a statistically significant association was found
for high tumoral grade, DOI and ENE with p < 0.05.


3.3. Survival analysis
3.3.1. Disease-free survival
Disease-free survival

Chart 3.1: Graph of disease-free survival
During follow-up, there were 19 patients presented with
recurrent/metastatic status.
5-year DFS rate was 72.1%, mean DFS was 45.3±2.3 months.
Relation between disease-free survival and risk factors

Chart 3.2. Disease-free survival and age
5-year DFS rate with age ≤60 and >60 tuổi were 69.1% and

69.3%, respectively. There was no significant difference between these
2 groups, p=0.724.


Chart 3.3: Disease-free survival and gender
5-year DFS rate with gender male and female were 49.4% and
54.4%, respectively. There was no significant difference between these
2 groups with p=0.176.

Chart 3.4: Disease-free survival and tumoral stages
There was no significant difference for 5-year DFS rates with
tumoral stage T1 and T2, p = 0.320.


Chart 3.5: Disease-free survival and tumoral grades
5-year DFS rates with grades I, I and grade III were 71.4% and
34.6%, respectively. There was significant difference between these 2
groups with p = 0.003.

Chart 3.6: Disease-free survival and depth of invasion
Group of patients with DOI > 5mm had lower 5-year DFS 5 rate
than group of patients with DOI ≤ 5mm (47.0% vs 84.8%,
respectively). There was significant difference between these 2 groups
with p=0.002.


Chart 3.7: Disease-free survival and extranodal extension
Group of patients with EXE + had lower 5-year DFS 5 rate than
group of patients with EXE - (22.7% vs 76.6%, respectively). There
was statistically significant difference between these 2 groups

p=0.0001.
3.3.2. Overall survival
Overall survival

Chart 3.8: Overall survival
During average follow-up time of 35.3 ± 12.1 months (16 – 62
montsh), there was 17 death events.
5-year OS 5 rate was 73.9%, mean OS was 46.9±2.1 months.


Relation between overall survival and risk factors

Chart 3.9: Overall survival and age
5-year OS rate with age ≤ 60 was 78.3% compared with patients
aged > 60 (68.8%), there was no significant difference between these 2
groups with p=0.681.

Chart 3.10: Overall survival and gender
There was no significant difference for overall survival between
male and female patients (56.4% vs 74.8%, respectively), there was no
significant difference between these 2 groups with p=0.112.


Chart 3.11: Overall survival and tumoral stage
There was no significant difference for 5-year OS rates with stage
T1 and T2, p = 0.206.

Chart 3.12: Overall survival and tumoral grades
Patients with grades I, II had higher 5-year OS rates than patients
with grade, accounting for 78.7% and 31.4%, respectively. There was

significant difference between these 2 groups with p=0.012.


Chart 3.13: Overall survival and depth of invasion
5-year OS rates with DOI > 5mm and DOI ≤ 5mm were 87.4%
and 47.1%. there was significant difference between these 2 groups
with p=0.002.

Chart 3.14: Overall survival and extranodal extension
5-year OS rates of patients with ENE + and ENE – were 78.9%
and 27.3%, respectively. There was significant difference between
these 2 groups with p=0.0004.


3.3.3. Adverse events
3.3.3.1. Adverse events on hematology
Table 3.3. Adverse events on hematology
All
Grade
Grade Grade
Grade I
grades
II
III
IV
Adverse events
n
%
n
%

n
% n % n %
Leukopenia
49 66,2 20 27 22 29,7 7 9,4 0 0
Neutropenia
Thrombocytopenia
Anemia

43 58,1 28

36

7

9,5

7

6

8,1

0

0

0

0

0

0

27 36,5 25 33,8

2

2,8

0

0

0

0

8,1

6

9,5 1

1,4

For adverse events on hematology, leukopenia was the most
common, accounting for 66.2%; grade-III leukopenia occured in 9.4%
of cases. There was no report of grade-IV leukopenia.
Neutropenia was seen in more than 50% cases, but there was one

patient presented with grade-IV adverse events.
Low hemoglobin occured less often than other toxicities,
accounting for 36.5%, no report of grades III and IV.
Thrombocytopenia was not often seen in our study, accounting for
8.1% cases, only grade-I.
3.3.3.2. Adverse events on liver, kidneys and other
organs Table 3.4. Adverse events on liver,
kidneys
All
Grade
Grade
Grade
Grade I
Adverse
grades
II
III
IV
events
n
%
n
%
n
%
n
%
n
%
Elevated

liver
6 9,4 5 7,8 1 1,6 0
0
0
0
enzymes
Elevated ure
1 1,6 1 1,6 0
0
0
0
0
0
Elevated
5 6,7 4 5,4 1 1,6 0
0
0
0
creatinine
Toxicity on liver and kidneys was not often seen in our study,
elevated liver enzymes accounted 9.4%, elevated ure accounted for 1.6%
and elevated creatinine accounted for 6.7%. There was no patients with
grade-III and -IV adverse events.


Adverse
events

Table 3.5. Other toxicities
All

Grade I Grade II
grades
n
%
n
%
n
%

Grade
III
n
%

Grade
IV
n %

Vomitting,
56 75,7 18 24,3 31 41,9 7
9,4 0 0
nausea
Anorexia
37 50 36 48,6 1
1.4
0
0
0 0
Peripheral
6 8,1

5 6,8
1
1,4
0
0
0 0
nerve
Dermatologic
74 100 18 24,3 43 58,1 13 17,6 0 0
toxicity
Mucositis
74 100 11 14,9 45 60,8 18 24,3 0 0
Vomitting and nausea mainly occured, especially at grades I and
II. Grade III accounted for 9.4%.
50% of patients presented with anorexia, only grades I and II.
Peripheral nerve toxicity occured in 8 cases, accounted for 8.1%.
All of patients had dermatologic toxicities and mucositis after
chemoradiation, mostly grade-II (dermatologic toxicities accounted for
58.1%; mucositis accounted for 60.8%).
Table 3.6. Late toxicities after chemoradiation
All
Grade
Grade
Grade I Grade II
grades
III
IV
Toxicities
n
%

n
%
n
%
n
%
n %
Xerostomia 67 90,5 25 33,7 27 36,5 15 20,3 0
0
Skin fibrosis

36

48,6

24

32,4

12

16,2

0

0

0

0

Trismus
12 16,2 8 10,8 4 0,05 0
0
0
0
Most of patients presented with toxicities of mouth dry
(accounting for 90.5%); most of these patients presented with grade-II
xerostomia (accounting for 36.5%).
Dermatologic fibrosis was seen in 48.6% cases; mostly grade-I
(accounted for 32.4%).
Trismus was reported in 16,2% cases, mostly grade-I (accounted
for 10.8%).
There was no patient with grade-IV late toxicities.


CHAPTER 4: DISCUSSION
4.1. Clinical and sub-clinical characteristics
Age: in our study, 74.3% of patients were above 50 years olds,
mean age was 53.4±8.2. Ngo Xuan Quy’s study, mean age was 54.1,
Vu Viet Anh’s showed that 93.6% of patients were above 40 and mean
age was 57.49, Shabbir Akhtar’s study, mean age was 55. A study of
Sagheb (2016) showed that the average age was 59.
Gender: male/female ratio has changed depended on the
results of studies, Vu Viet Anh’s study was 1.76/1, Ngo Xuan Quy’s
study was 1.3/1, Kiyoto Shiga’s study was 1.52/1, Shabbir Akhtar’s
study was 1.6/1, Nguyen Quoc Bao’s was 1.2/1. In our study,
male/female ratio was 1.47/1. Male patient rate was higher that of
female, a possible reason was that men receive many negative
effects from many risks causing tongue cancer such as smoking,

drinking alcohol...
Medical history: smoking, drinking alcohol were risk factors
caused the oral cavity cancer, especially tongue cancer. In our study,
smoking was accounted for 44.5% and drinking alcohol was accounted
for 48.6%. This was similar to the results of others studies in our
country and in the world.
Time to diagnosis: average time to diagnosis was 6.1 ± 2.4
months. Our result was similar to those of other authors in our country
and in the world.
Clinical symptoms: Most of patients had tumor and ulcer in
the tongue at the time of diagnosis. Our result was similar to those of
other authors, including Tran Dang Ngoc Linh’s study (47.6% vs
40.7%, respectively), Tran Van Cong’s study (28.1% vs 42.9%,
respectively), Ngo Xuan Quy (46.2% vs 39.2%, respectively).
Performance status: In our study, all of patients had
performance status of ECOG 0-1 point, because the treatment
protocol included surgery, followed by chemoradiation, was similar
to the study design of clinical trials in the world. Our study showed
that most of patients had the performance status with ECOG 0 point,
accounting for 59.5%.
Systematic symptoms: most of patients in our study had weight
loss lower than 5% (accounting for 66.2%), and 33.8% of patients had
weight loss over 5%. Tongue cancer can affect daily nutrition of
patients, so that it could lead to weight loss.


Tumor stage: stage-T2 was the most common (65.5%), stage-T1
was accounted for 36.5%. Ngo Xuan Quy’s study giai đoạn II chiểm
63,8%, Anna Lee giai đoạn I chiếm 52,1%.
Anatomopathology: In our study, squamous cell carcinoma

grade-II was the most commom (accounted for 60.8%), followed by
grade-I (accounted for 22.9%), and grade-III was reported in 16.8%.
Our result was similar to result of Ngo Xuan Quy’s study, the rate of
grade I, grade II and grade III were 21.5%; 70% and 7.7%,
respectively. A study of Su Jung Shim, squamous cell carcinoma with
high differentiation and medium-low differentiation rates were 61%
and 39%, respectively; Tseng-Cheng Chen’s study showed that high
differentiation was the most common type of cancer, accounted for
87.1%
Depth of invation: one of risk factors related to high rate of
cervical node metastais and poor prognosis for survival of patients
with tongue cancer. In our study, rate of patients with DOI > 5mm
was 66.2%. Our result was similar to those of other authors in the
world.
Neck lymph node metastasis: In our study, among 74 patients
with postoperative diagnosis, there was 40.5% of patients that did not
present neck lymph node metastasis. A study of Nguyen Duc Huan,
rate of occult lymph node metastasis was 29.6%. Ngo Xuan Quy’s
study showed that there was 30.7% of tongue cancer patients presented
with lymph node metastasis. In our study, group-II metastasis was the
most common, then group-I, and group-III metastasis was rare. Our
result was similar to those of other authors in our country and in the
world.
4.2. Treatment results
4.2.1. Recurrence characteristics
During the follow-up, there were 19 patients presented with
recurrent diseases (accounting for 25.7%), among these 19 patients,
reccurent lymph node metastasis was the most common (accounting
for 63.2%), then at tongue (accounting for 15.7%), and both tongue
and cervical nodes were 10.5%, there were 2 patients have distant

metastasis (accounting for 10.5%). Our result was similar to those of
other authors, including Ngo Xuan Quy (24.6%), Ikram M (36.4%),
Chen T.C (27.1%).


Relation between recurrence and risk factors
Age, gender: In our study, there was a non-significant relation
between recurent diseases and age, gender. Our result was similar to
those of authors Bo Wang, Anne Lee.
Tumor grades: High tumor grade patients have high risk of
recurrence than low-middle grade patients (p < 0.05). Our result was
similar to those of author Bo Wang.
DOI: Rate of recurrent disease in group of > 5mm was higher than
those with DOI ≤ 5mm and there was a significant difference between two
groups with p = 0.001. Our result was similar to those of other authors.
Tumor stage: In our study, tumor stage-T2 has higher risk of
recurrence than stage-T1, but there was no significant difference.
4.2.2. Overall survival and disease-free survival
5-year disease-free survival rate (DFS) was 72.1% and mean DFS
was 45.3±2.3 months. 5-year overall survial rate (OS) was 73.9% with
mean OS of 46.9±2,.1 months. Our result was similar to those of ohter
authors: Nguyen Duc Loi (5-year OS: 62.7%), Vu Viet Anh (4-year OS:
80%), Ngo Xuan Quy (5-year OS: 65,4%), Su Jung Shim (5-year DFS:
74%, 5-year OS: 71%).
Relation between survival time and risk factors
Age: Our study showed that there was non-significant difference
about survival time. In the world, there were some studies showed
differences results. Studies of Ngo Xuan Quy, Richard J, Deniella
showed that there was a significant difference about survival time
between groups of ages, some studies showed non-significant

differences, including studies of Su Jung Shim, Anna Lee.
Gender: Our study showed that there was non-significant
difference about survival time between male/female genders. Our
result was similar to those of other authors in our country and in the
world (Vu Viet Anh, Kiyoto Shiga, Jefferey C. Liu).
Tumor stage: Our result showed that there was no difference for
survival between stage T1 and T2. Studies of Ngo Xuan Quy, Anna
Lee, Daniella… showed that 5-year DFS and 5-year OS 5 of stage-T1
were higher than those of stage-T2 (p < 0.05). In our study, all of
patients diagnosed of stage III (pN1), and cervical node metastasis is
one of strongly risk factors affected to survival time.


Tumor grade: There was a significant difference for survival
between tumor grade-III vs grade-I, II (p < 0.05). Our result was
similar to those of other authors, including Ngo Xuan Quy, Thomas
Mucke, Su Jung Shim, Daniella.
DOI: There was a significant difference for survival between
group of DOI > 5mm and of DOI ≤ 5mm (p < 0.05). Several studies
showed that DOI is one of risk factors for tongue cancer, increases the
risk of cervical node metastasis and affects survival rates (Su Jung
Shim, Ahmed S.Q, Daniella).
4.2.3. Toxicities of treatment
Toxicities on hematology
Evaluating the toxicities on hematology system, among 74
patients treated: Leukopenia was one of the most common toxicities
(accounted for 66.2%); grade-III leukopenia was reported in 9.4% of
cases, there was no patients presented with grade-IV leukopenia.
Neutropenia was reported in more than 50% cases, but only one
patient suffered from neutropenia grade-IV, and there was no

complications in all of cases. Anemia was reported less often than
others, accounted for 36.5%, and no report of grade-III, IV.
Thrombocytopenia was rarely occured in our study, accounted for
8.1%, and only presenting of grade-I. There.was no death or grade-V
related to toxicities of our treatment. When patients presented with
these toxicities, it could be interruption between cycles chemotherapy
or stopping both chemotherapy and radiotherapy, therefore several
patients did not receive enough doses of chemotherapy and
radiotherapy. Compared to results of other previous studies, our result
was similar to those of other authors.
Toxicites on non-hematology systems
In our study, vomitting and nausea was reported in most of
patients, and rate of grade-III vomitting was only 9.4%. Our result was
similar to those of other authors using chemotherapy of cisplatin every
3 weeks. This is one of particular characteristics of cisplatin-based
regimen chemotherapy. However, grade-I,II of vomiting and nausea in
our study were the most common.
Anorexia was common in 50% of cases in our study. This is also
one of common adverse events, however it is difficult to assess and
able to be affected by other factors, especially pschology.