ABBREVIATIONS
AJCC American Joint Committee on Cancer
ASCO American Society of Clinical Oncology
CTV Clinical Target Volume
CR Completed Respon
EBRT External Beam Radiation Therapy
FIGO Fédération Internationale de Gynécologie et d'Obstétrique
GTV Gross Tumor Volume
HDR High Dose Rate
HPV Human Papilloma Virus
IHC Immunohistochemistry
IV Irradiated Volume
LDR Low Dose Rate
PR Partial Respon
PTV Planning Target Volume
TV Treatment Volume
UICC Union for International Cancer ControL
WHO World Health Organization
1
INTRODUCTION
1. Scientific aims
Cervical cancer is one of the most common cancers in women. It is the
first leading cause of death in women in the world. In 2008, there are 529 800
new cases of cervical cancer worldwide (accounting for 9% of total newly
cancer patients) and an estimated 275.100 women die of this disease (8% of
total cancer deaths). According to a cancer registry in Hanoi from 1998 to 2007
in Vietnam, there are 2.093 new cases of cervical cancer, accounted for 7.3% of
total cancers in women, with age-standardized incidence rate of 6.8 / 100.000.
Although the screening program of cervical cancer has been deployed but
the rate of inoperable stage (IIB, III) cervical cancer is still account for over
50% of new cases. For early stages, cervical cancer has high cure rate with

97.8%, 90.7%, 80% and 40.4%. Average survival time of the patients was 42.1
± 1.2 (months). The 4-year overall survival rate of the response patients were
higher than the not response patients were (42.0% compared with 14.9%), p
<0.01. The 4-year overall survival rate of anemia patients were lower than those
who were not anemia (14.5% compared with 47.5%), p <0.01. The local
recurrence rate was 8.2%. The metastasis rate was 16.6% which is the most
common location of lung metastases (5%).
To assess the hematological toxicities, the hepatic and renal toxicities of
the regimen. Leukopenia, neutropenia, anemia are the most common toxicity,
higher rates in the last cycles of chemotherapy.
Evaluating the late toxicities of the gastrointestinal tract and the urinary
tract showed that gastrointestinal complications were 74.4%, bleeding proctitis
accounted for the highest percentage (40.8%), followed by diarrhea (31.2%),
rectovaginal fistula (0.6%), intestinal necrosis (0.6%). Urinary complications
were 10.1%, including dysuria (5.7%), irritation during urination (3.8%),
hematuria (0.6%). The rate of late complications in the first year was 69.3%, the
second year was 14.0%, the third year was 1.2%, no patients had the late
toxicities in the fourth year. Average time of post-treatment late toxicities was
7.9 ± 5.5 months.
4. The structure of the thesis
The thesis consists of 108 pages, with 4 main chapters: Introduction 2
pages , Chapter 1 (Overview) 35 pages 35, Chapter 2 (Patients and Methods) 17
pages, Chapter 3 (results) 24 pages, Chapter 4 (discussion) 27 pages,
Conclusion and recommendation 3 pages.
The thesis has 28 tables, 6 pictures and photos and 15 diagrams, 128
references (102 Vietnamese and 26 English).
CHAPTER 1: OVERVIEW
1.1. The burden of cervical cancer
1.2. Anatomy and histology of the cervix
1.3. Risk factors

Tumor involves lower third of the vagina, no
extension to pelvic wall
T
3B
III
B
Tumor extends to pelvic wall and/or causes of
hydronephrosis or nonfunctioning kidney
N (Regional lymph node):
Nx Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
N1 Regional lymph node metastasis
M (Distant Metastasis)
M0 No distant metastasis
M1 Distant metastasis
Stage T N M
IIB T2b N0 M0
III T3 N0 M0
IIIA T3a N0 M0
IIIB
T3b Any N M0
T1-3 N1 M0
AJCC (2010). Cancer staging manual, seventh edition.
1.7. Treatment of cervical cancer
1.7.1. The treatment of carcinoma in situ
1.7.2. The treatment of stage IA
1.7.3. The treatment of stage IB-IIA
4
1.7.4. The treatment of stage IIB-III
Chemoradiation

small intestine was 1.1%. Author Nakato T et al [83] did the study in 210 stage
IIIB cervical cancer patients, the results showed the rate of late toxicities in
HDR and LDR groups were respectively 6% and 10%.
Vietnamese studies:
Bui Dieu studied on 226 stage IB-IIA cervical cancer patients at Hospital
K from 1992 to 2003, the 5-year overall survival rates of the Caesium 137
brachytherapy group and Radium 226 brachytherapy group were respectively
65.5% and 50.8%. The study by Nguyen Van Tuyen on 331 patients with stage
IB-II cervical cancer treated with surgery in combined with radiotherapy in
5
from 1999 to 2002, the recurrence rate after 5 years was 11.7%, metastasis rate
was 15.0%, the 5-year overall survival rate was 76.4% , the 5-years disease-free
survival rate was 74.3%. The results from study of Thi Tuyet Anh Cung et al on
45 patients with stage IIB-IIIB cervical cancer treated with chemoradiation
showed the response rate was 88.9%.
Chapter 2: PATIENTS AND METHODS
2.1. Patients
157 patients with stage IIB-IIIB cervical cancer were treated with cisplatin
in combined with high-dose rate brachytherapy and external beam radiation
therapy from 8/2008 to 8/2011 at K hospital.
2.1.1. Patient criteria
- The patients with stage IIB - IIIB cervical cancer according to TNM and
FIGO classification are eligible for this study.
- Histopathology was carcinoma of the cervix
- No prior chemotherapy or radiotherapy
- The patients must have a performance status of 0, 1 and 2 ECOG score
(Eastern Cooperative Oncology Group).
- Blood counts are in the normal range (granulocytes> 2000/ml, platelets>
100.000/ml, Hb> 9g/dl).
- Total serum bilirubin < 1.5 mg/dL and SGOT, SGPT <2.5 x normal.

2.2.3.1. Clinical and test characteristics before treatment
• The clinical features:
+ Age, sex, time from first symptoms on admission (in months), the
symptoms: abnormal vaginal bleeding, back pain
+ Clinical examination: To evaluate tumor location, size, shape (warts,
sores, infection ), and bleeding, extensive surrounding tissue
• Laboratory tests
+ Complete blood count
+ Blood chemistries
+ SCC-Ag serum for monitoring during and after treatment.
• Radiologic tests
+ All patients underwent MRI to evaluate the spread of the tumor.
+ CT sim plan radiation therapy.
+ Abdominal ultrasound: assessment of other organs, abdominal lymph
nodes.
+ Chest X-ray: detecting metastatic lung lesions. Chest- CT if required for
better disease evaluation.
+ Bone- scan: detecting metastatic bone lesions.
• Histopathology: Histopathological classification according to WHO.
• Confirmed diagnosis is based on clinical and histopathology.
• Staging of the disease is based on clinical and MRI.
2.2.3.2. Treatment plan
• Intravenous cisplatin
- Cisplatin 40 mg/m
2
IV weekly x 5 weeks in concurrent with EBRT
- Cisplatin does not use in the day of brachytherapy.
- External radiation is started 2-2.5 hours after cisplatin injection.
Administration:
- Before the drug infusion: 1.5-2 liters Glucose 5% or 0.9% Natriclorid IV

+ The lower limit: including vaginal and orifice of ureter with stage II,
III.
+ The lateral limits: Head of the femur.
The body turns 180 degrees.
- Lateral pelvic radiation fields.
+ Body turns 90 degrees to the left or 270 degrees to the right.
+ The goal is increasing the pelvic lymph nodes dosage and decreasing
surface dosage.
+ The front limit: pubic bone.
+ The behind limit: sacrum bone.
+ The lower and upper limits are the same as interior- posterior fields.
Dose and fractionation:
+ Fractionation of 1,8-2 Gy/ day, 5 days/ week.
+ Total dose: 50 Gy
+ Increase dose 10 Gy for patients with large lesions in pelvic lymph
nodes parameter.
• High- dose rate brachytherapy
- Prepare the patient:
+ Patients enema before treatment.
+ Used prophylactic antibiotics.
8
+ Injection premedication before 10-15 minutes.
+ Foley bladder sonde during treatment.
- Brachytherapy is usually delivered using afterloading applicators that are
placed in the uterine cavity and vagina. Vaginal packing is used to hold
the tandem and colpostats in place and to maximize the distance between
the sources and the bladder and rectum. Radiographs should be obtained
at the time of insertion to verify accurate placement, and the system
should be repositioned if positioning can be improved.
- Radioactive sources: Iridum use 192 (HDR)

- Status of patients: Alive, death, healthy, recurrence or metastasis.
9
- The overall disease-free survival was defined as the time from
randomization until loco regional recurrence, metastasis, or death by any
cause.
B. Common toxicities
∗ Hematological toxicities, hepatic toxicities and renal toxicities
Common Toxicity Criteria for Anticancer Drugs (WHO)
Adverse Event Grade 0 Grade I GradeII GradeIII Grade
IV
Leukocytes
(x 10
3
)
≥ 4 3 - 3,9 2 - 2,9 1-1,9 < 1
Neutrophils
(x 10
3
)
≥ 2 1,5 - 1,9 1 - 1,4 0,5-0,9 < 0,5
Hemoglobin
(g/L)
≥ 125 100-24,9 80- 99,9 65-79,9 < 65
Platelets (x 10
3
) 150-450 75 - 149 50- 74,9 25-49,9 < 25
SGOT and/or
SGPT
≤ 40 40,1-100 100,1-200 200,1-800 ≥ 800,1
Creatinin

n % n % n % n %
Complete response 76 75,2 9 90,0 30 65,2 115 73,2
>0,05
Partial response 16 15,8 0 0,0 11 23,9 27 17,3
Stable disease 6 6,0 1 10,0 1 2,2 8 5,0
Progressive disease 3 3,0 0 0,0 4 8,7 7 4,5
Total 101 100,0 10 100,0 46 100,0 157 100,0
Table 3.2.1.1 Response rates according to stage
Response rates according to ages
Results Response Not response
P
n % n %
< 50 38 26,8 8 53,3
< 0,05
≥ 50 104 73,2 7 46,7
Total 142 100,0 15 100,0
Table 3.2.1.2 Response rates according to ages
Response rates according to anemia status
Result Response Not response
P
n % n %
Anemia 45 91,8 4 8,2
> 0,05
11
Not anemia
97 89,8 11 10,2
Table 3.2.1.3 Response rates according to anemia status
Response rates according to histopathology
Result Response Not response
P

Overall survival according to response characteristics
Response Not response
Number of patients 142 15
Death patients 23 8
Survival ratio (%) 42,0 14,9
Median survival time ± standard
deviation (years)
3,6 ± 0,1 2,4 ± 0,3
LogRank Test: χ
2
= 17,18; degrees of freedom 1; P < 0,01
Table 3.2.2.3. Overall survival according to response characteristics
Overall survival according to anemia status
Anemia Not anemia
Number of patients 108 49
Death patients 20 11
Survival ratio (%) 14,5 47,5
Median survival time ±
standard deviation (months)
36,3 ± 1,7 43,2 ± 1,3
LogRank Test: χ
2
= 6,9; degrees of freedom 1; P < 0,01
Table 3.2.2.4. Overall survival according to anemia status
13
Local- recurrences and metastases
Organs n Tỷ lệ (%)
Metastasis Liver metastases
2 1,3
Supraclavicular metastases 6 3,8

Comment: Anemia is mainly grade 1 and 2. Anemia increases in the last cycles
Platelet toxicities
Figue 3.3.1.3. Platelet toxicities
Comment: Platelet toxicities are mainly grade 1. Platelet toxicities increases in
the last cycles
Liver toxicities
15
Figue 3.3.1.4. Liver toxicities
Comment: Liver toxicities are mainly grade 1. Liver toxicities increase in the
last cycles.
Renal toxicities
Table 3.3.1.2. The change in serum creatinine after treatment
Before
treament
After
1 week
After
2 weeks
After
3 weeks
After
4 weeks
After
5 weeks
n % n % n % n % n % n %
Gr 0 157 100,0 157 100,0 156 99,3 157 100,0 153 97,2 152 96,5
Gr 1 0 0,0 0 0,0 1 0,7 0 0,0 2 1,4 4 2,8
Gr 2 0 0,0 0 0,0 0 0,0 0 0,0 2 1,4 0 0,0
Gr 3 0 0,0 0 0,0 0 0,0 0 0,0 0 0,0 1 0,7
Gr 4 0 0,0 0 0,0 0 0,0 0 0,0 0 0,0 0 0,0

In total of 157 patients, stage IIB patients have highest rate (64.3%),
followed by patients with stage IIIB (29.3%), only 6.4% of patients in stage
IIIA. According to Cung Thi Tuyet Anh, 45 patients were treated with
concurrent chemotherapy and HDR brachytherapy, the stage IIB rate was
55.6% and the stage IIIB rate was 44.4%.
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Table 4.1.1 Staging characteristics of patients
Researcher n Stage
IIB
StageIII
A
Stage
IIIB
Le Phuc Thinh (2005) 999 66,96% - 32,03%
Ngo Thi Tinh (2005) 243 52,8% 2,6% 45,3%
Nguyen Ba Duc et al (2005) 30 20% - 80%
Cung Thi Tuyet Anh (2007) 45 55,6% - 44,4%
Rose et al (1999) 526 52,28% 2,8% 41,82%
Nguyen Tien Quang (2012) 157 64,3% 6,4% 29,3%
The results of our study similar to Le Phuc Thinh’s study about staging
rates, however, differ from the results of Ngo Thi Tinh, Cung Thi Tuyet Anh.
4.2. Results
Response rates

Numbe
r of
patients
Stage
Overall
respons

Tuyet Anh (2007) did the study on 45 cases of stage IIB-IIIB cervical cancer,
the response rate was 88.9%. The research of Watanabe (2006) showed overall
response rates of stage IIB-IVA patients were 96%.
18
According to those results, the response rates of cervical cancer patients
were treated with concurrent chemoradition are very high. The results of our
study are the same as other studies.
Response rate according to ages
When comparing the response rates in 2 groups of patients over 50 years
of age and under 50 years of age, response rates of patients ≥ 50 years of age
was 73.2%, higher than patients <50 years of age (26, 8%). This difference is
statistically significant with P <0.05. Of the patients <50 years old, the not
response group was 53.3%, nearly 2 times higher than the response group. This
difference is statistically significant with P <0.05.
Response rate according to anemia status
When studying the relationship between response and anemia, we found a
complete response rate of patients without anemia group was 91.8%, higher
than the anemia group (89.8%). However, this difference was not statistically
significant (P> .05). According to Gillian Thomas (2002), the 5-year overall
survival in the over hemoglobin 120g / L group was 74%, in the hemoglobin
110-119 g / L group was 52% and the hemoglobin upper 110 g / L group was
only 45%. The relationship between anemia and hypoxia are still controversial,
but scientists have demonstrated hypoxia causes irradiation and chemotherapy
resistance of the cancer cells.
Response rate according to histopathology
Our results showed the response rates of squamous cells carcinoma group
was 91.4%, higher than the adenocarcinoma group (76.9%). However, this
difference was not statistically significant (P> 0.05).
Hong JH did the research histopathology of cervical cancer; he found that
adenocarcinoma type and adenosquamous carcinoma type have a worse

same as the results of Kim JC (5-year survival was 37.5%).
Overall survival according to staging characteristics
Staging is a important prognostic factor for survival. According to Hee-
Chul Park et al, 233 patients stage IIIA-IIIB cervical cancer stage IIIA-IIIB had
5-year overall survival rate of 60.6%. Demanes DJ et al did the study in 62
cervical cancer patients from stage I-IVA, the 5-year overall survival rates of
patients with stage IIB and IIIB were respectively 47% and 39%. In our study,
the analysis of survival rates according disease stage results showed overall
survival of patients was 44.2% stage II, stage III is higher than 40.0%. This
difference was not statistically significant with P> 0.05.
Overall survival according to response rate
The results showed the overall survival rates of patients with response
group is 42.0%, higher than that of non-response (14,9%). This difference is
statistically significant with P <0.01. Classe JM studied on 175 patients with
stage IB2-IVA cervical cancer; the results showed that patients with complete
20
response had a better disease-free survival and overall survival compared to
partial response patients.
4-year overall survival according to anemia status
Many studies have shown that there is a close association between
anemia, hypoxia response with response rate and survival rate in the treatment
of cervical cancer. According to Gillian Thomas (2002), the 5-year overall
survival in the over hemoglobin 120g / L group was 74%, in the hemoglobin
110-119 g / L group was 52% and the hemoglobin upper 110 g / L group was
only 45%. The relationship between anemia and hypoxia are still controversial,
but scientists have demonstrated hypoxia causes irradiation and chemotherapy
resistance of the cancer cells. This difference is statistically significant with P
<0.01. Thus, the result of our study was similar to results of Gillian Thomas.
Local-recurrence and metastases
In our study, there were 26 metastatic patients accounted for 16.6%. The

lower mainly grade 1 and 2. Thus, hepatotoxicity in our study is acceptable.
Nephrotoxicity occurs during treatment (assessed through serum creatinine) in
our study was very low with only 7 cases (4.9%).
4.3.2. Late complications
133/157 patients had side effects from radiation therapy (84.5%),
gastrointestinal tract complications was 117 patients (74.4 %) and urinary tract
complications was 16 patients (10.1%). In patients with gastrointestinal
complications the bleeding proctitis accounted for the highest rate 40.8%,
followed by diarrhea (31.2%), rectovaginal fistula (0.6%), intestinal necrosis
(0.6%). Urinary tract complications were 16 patients (10.1%), of which dysuria
was 5.7%, irritation during urination was 3.8% and hematuria was 1 patient. In
total 133 patients had complications (Table 3:25), the patients with
complications occurring in the first year accounted for the highest percentage
(69.3%), followed by the 2nd year (14%), only 2 patients had complications in
the first 3 years, no patient had any complications in the 4
th
. In the study of
Toita T et al, bleeding proctitis rate was 9% and interitis was 15%. According
to research by Ngo Thi Tinh, urinary tract complications was 10.5%, diarrhea
was 60.5%, bleeding proctitis was 54.4%, rectal stenosis was 3.4% Thus, the
late complications in the digestive system and the urinary tract of our results are
higher than the results of studies abroad.
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CONCLUSION
1. Treatment results
1.1. Near results
- The overall response rate was high (90.5%), complete response rate was
73.2%, partial response rate was 17.3%, stable disease was 5% and progress
disease was 4.5%.
- Response rates in patients ≥ 50 years of age group are higher than patients <50

- The rate of platelets toxicities was 14.8%, mainly grade 1, no cases of grade 3
and 4. Platelets toxicities increased in the last cycles.
- The rate of high GOT and/or GPT patients was only 7.1% , no cases of grade
3 and 4. Hepatic toxicities increased in the last cycles
- Percentage of high creatinine serum patients was 4.9%.
2.2. Late complications
- Complications in the gastrointestinal tract were 74.4%, the bleeding proctitis
accounted for the highest rate 40.8%, followed by diarrhea (31.2%),
rectovaginal fistula (0.6%), intestinal necrosis (0.6%).
- Urinary tract complications were 16 patients (10.1%), of which dysuria was
5.7%, irritation during urination was 3.8% and hematuria was 1 patient.
- The patients with complications occurring in the first year accounted for the
highest percentage (69.3%), followed by the 2nd year (14%), only 2 patients
had complications in the first 3 years, no patient had any complications in the
4
th
year. The average time post-treatment of late complications was 7.9 ± 5.5
months.
RECOMMENDATIONS
The high-dose rate brachytherapy in combined with external beam
radiation therapy and cisplatin regimen in the treatment of stage IIB-IIIB
cervical cancer should be widely used to improve the response rates and
survivals for patients.
24