ORIGINAL RESEARCH

published: 23 May 2022

doi: 10.3389/fsurg.2022.906117

Intensity-Modulated Radiotherapy
and Three-Dimensional Conformal
Radiotherapy Combined with
Intracavitary Posterior Radiotherapy
for the Treatment of Medium-Term
and Advanced Cervical Cancer:
Efficacy, Safety and Prognostic Factors
Kewen Yu1 and Liping Zhou2*
1
Department of gynecology, Ningbo Women and Children’s Hospital, Ningbo, China, 2Department of gynecology, Zhuji
Edited by:
People’s Hospital of Zhejiang Province, Zhuji, China
Songwen Tan,
Central South University, China
Reviewed by: Objective: To explore the efficacy, safety, and prognostic factors of intensity modulated
Li Genlin,
radiation therapy (IMRT) and three dimensional conformal radiation therapy (3D-CRT)
The First Affiliated Hospital, University
of South China, China combined with intracavitary posterior radiotherapy for medium-term and advanced
Lihong Chen, cervical cancer.
The First Affiliated Hospital of Fujian
Medical University, China
Methods: Retrospectively analyze the clinical data of 104 patients with medium-term and
*Correspondence:
advanced cervical cancer who were treated in the radiotherapy department of our
Liping Zhou hospital from September 2015 to March 2017. According to the different radiotherapy
eternalzlp@163.com
techniques, they were divided into the IMRT combined with intracavitary posterior
radiotherapy group (n = 52) and the 3D-CRT combined with intracavitary posterior
Specialty section:
This article was submitted to Visceral radiotherapy group (n = 52). Observe and compare the short-term efficacy, occurrence
Surgery, a section of the journal of adverse reactions and overall survival rate of the two groups. The clinicopathological
Frontiers in Surgery
characteristics of the survival group and the death group were compared, and
Received: 28 March 2022
Accepted: 20 April 2022 univariate analysis and multiple logistic regression models were used to analyze the
Published: 23 May 2022 relationship between the clinicopathological characteristics and the patient’s prognosis.
Citation: Results: The total effective rate of IMRT combined with intracavitary posterior
Yu K and Zhou L (2022) Intensity-
radiotherapy group was 96.15%, which was higher than that of 3D-CRT combined
Modulated Radiotherapy and Three-
Dimensional Conformal Radiotherapy with intracavitary posterior radiotherapy group (88.46%), but the difference was not
Combined with Intracavitary Posterior statistically significant ( p > 0.05). The incidence of digestive system injury,
Radiotherapy for the Treatment of
Medium-Term and Advanced Cervical thrombocytopenia, and radiation proctitis in the IMRT combined intracavitary posterior
Cancer: Efficacy, Safety and radiotherapy group was lower than that of the 3D-CRT combined intracavitary
Prognostic Factors. Front. Surg.
posterior radiotherapy group, and the differences were statistically significant ( p <
9:906117.
doi: 10.3389/fsurg.2022.906117 0.05). The prognosis and survival of the two groups of patients were similar, and the

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Yu and Zhou Treatment of Cervical Cancer

difference was not statistically significant ( p > 0.05). Pathological classification, clinical
stage, and lymph node metastasis are independent influencing factors of 3-year
prognosis in patients with medium-term and advanced cervical cancer ( p < 0.05).
Conclusion: IMRT combined with intracavitary posterior radiotherapy is equivalent to
3D-CRT combined with intracavitary posterior radiotherapy, but it can reduce the incidence
of adverse reactions in patients with medium-term and advanced cervical cancer, and has
higher safety. Pathological typing, clinical staging, Lymph node metastasis were
independent factor affecting the prognosis of patients. In clinical treatment, IMRT combined
with intracavitary posterior radiotherapy is more recommended as a treatment plan for
patients with medium-term and advanced cervical cancer.
Keywords: medium-term and advanced cervical cancer, intensity modulated radiation therapy, three-dimensional
conformal radiotherapy, efficacy, prognosis

INTRODUCTION Diagnosed by pathological and imaging examinations; tumor

FIGO stage was IIB–IVA; Bian’s score was ≥70 points; expected
Cervical cancer is one of the most common malignant tumors in survival >3 months; abnormal liver and kidney function and
women. Early stage cervical cancer is usually treated with other organ diseases were excluded. According to the treatment
surgery, while radiotherapy and chemotherapy are the main method, the patients were divided into IMRT and 3D-CRT
treatments in the medium-term and advanced stages (1). At combined with intracavitary posterior radiotherapy groups, with
present, external irradiation combined with intracavitary 52 patients in each group. The age of IMRT combined with
posterior radiotherapy and concurrent chemotherapy is the intracavitary posterior radiotherapy group was 32–77 years old,
standard method for the treatment of medium-term and with an average age of (55.03 ± 7.14) years; 32 cases of IIB, 10
advanced cervical cancer. Traditional radiotherapy methods cases of IIIA, 9 cases of IIIB, and 1 case of IVA; 49 cases of
such as four-field box-type and front-to-back penetrating squamous cell carcinoma and 3 cases of adenocarcinoma; 30
irradiation have been used earlier and are widely used, but patients had tumor diameter ≥4 cm, and 22 patients had tumor
their damage to the digestive tract, urinary tract and diameter <4 cm. The age of 3D-CRT combined with
hematopoietic systems is relatively serious (2, 3). Intensity intracavitary posterior radiotherapy group was 33–78 years old,
modulated radiation therapy (IMRT) and three dimensional with an average of (54.86 ± 7.25) years old; 34 cases of IIB, 9
conformal radiation therapy (3D-CRT) are new radiotherapy cases of IIIA, 8 cases of IIIB, and 1 case of IVA; 50 cases of
techniques, and there is no unified understanding on the squamous cell carcinoma and 2 cases of adenocarcinoma; 29
specific effects of these two techniques. However, studies have patients had tumor diameter ≥4 cm, and 23 patients had tumor
confirmed that these two techniques can increase the diameter <4 cm. There was no statistical difference in general
irradiation dose of target area and effectively reduce the clinical data such as age, FIGO stage, pathological classification
irradiation dose of surrounding normal tissues and organs, and tumor diameter between the two groups (p > 0.05), which
effectively control tumors and reduce damage to the body were comparable.
(4, 5). Whether IMRT and 3D-CRT can replace traditional
radiotherapy in the treatment of medium-term and advanced
cervical cancer is worth looking forward to. Therefore, in this Research Methods
study, IMRT combined with intracavitary radiotherapy was In terms of the IMRT combined with intracavitary posterior
used to treat patients with medium-term and advanced radiotherapy group: One day before localization, the patients
cervical cancer, and compared with 3D-CRT combined with underwent bowel preparation by oral administration of
intracavitary posterior radiotherapy, in order to provide Meglumine. Before localization, the patients’ bladder was filled
theoretical support for the efficient treatment of patients with and the rectum was emptied. The joints were fixed with
medium-term and advanced cervical cancer. The specific vacuum pad and thermoplastic film, and CT scan was
research is shown as follows. performed. Clinical target volume (CTV): including the
primary area of cervical tumor (parametrial triangle, cervix,
vagina, etc.) and pelvic metastatic area (parametrium,
MATERIALS AND METHODS paravaginal tissue, pelvic lymphatic area, etc.). Planned target
volume (PTV): CTV was expanded by 5 mm in the S/I, A/P,
General Information and R/L directions, respectively. Gross tumor target volume
A total of 104 patients with medium-term and advanced cervical (GTV): the cervical mass and lymph node metastases that
cancer who were admitted to our hospital from September 2015 have been diagnosed by imaging or definite diagnosis. Lymph
to March 2017 were selected. All patients met the diagnostic node area delineation: The lymph node area and
criteria for medium-term and advanced cervical cancer (6); corresponding blood vessel area were delineated along the

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Yu and Zhou Treatment of Cervical Cancer

lymph node area and the corresponding blood vessel area in survival time and adverse reactions. Survival time was
patients diagnosed with lymph node metastasis, followed by calculated from the time of diagnosis to the date of death or
delineation of the para-aortic lymph nodes, anterior iliac, the end of follow-up.
external iliac, internal iliac, common iliac and obturator
foramen. The range was from the fifth lumbar vertebra to the Statistical Methods
obturator foramen. The PTV dose was 1.8 Gy/time, and the SPSS 22.0 software was used for processing. The measurement
total dose was 48.60–50.40 Gy/27–28, 5 times a week. PTV data conforming to normal distribution were expressed as
adopted 7-field intensity-modulated irradiation, and was mean ± standard deviation, and t test was used for
irradiated with an isodose curve of 95% of PTV, and the comparison. Count data were expressed as (%), and χ2 test
minimum and maximum doses of the target area were within was used for comparison. Survival curves were drawn by using
the range of ±10% of the prescribed dose. After 25 times of the Kaplan-Meier method. The test level was α = 0.05, and
external irradiation, the irradiation was stopped, intracavitary p < 0.05 was considered statistically significant.
posterior radiotherapy was performed once a week, 6–7 Gy/
time, with a total dose of 30–36 Gy/5–6 f. The radiation doses
of the small intestine, rectum and bladder were V45 < 20%, RESULTS
V45 < 40% and V45 < 30%, respectively.
In terms of the 3D-CRT combined with intracavitary posterior Comparison of Short-Term Curative Effect
radiotherapy group: the positioning and target delineation between Two Groups of Patients
methods were the same as above. The target area was irradiated The results showed that the total effective rate of IMRT
by four-field box type, 6MV-X-ray, 180–200 cGy/time, the total combined with intracavitary posterior radiotherapy group was
dose was 4,500–5,000 cGy. Conventional segmentation 96.15%, which was higher than that of 3D-CRT combined
irradiation, 5 times a week. The method of intracavitary with intracavitary posterior radiotherapy group (88.46%), but
posterior radiotherapy was the same as above. the difference was not statistically significant (p > 0.05), as
Observation indicators: The short-term efficacy and adverse shown in Table 1.
reactions of the two groups of patients were recorded, analyzed
and compared, and the adverse reactions included acute and Comparison of Adverse Reactions of the
chronic radiation injury. Acute and chronic radiation injuries Two Groups of Patients
were divided into grades I, II, III, and IV. The higher the grade, The results showed that the incidence of digestive system injury,
the more severe the adverse reaction. Acute radiation injury thrombocytopenia, and radiation proctitis in the IMRT
included digestive tract, blood, and urinary system injury; combined with intracavitary posterior radiotherapy group
chronic radiation injury was mainly intestinal and urinary were 28.85%, 9.62%, and 19.23%, respectively, which were
system injury, including radiation cystitis and proctitis. After lower than those in the 3D-CRT combined with intracavitary
radiotherapy, consolidation chemotherapy was performed posterior radiotherapy group (55.77%, 40.38%, 48.08%), the
according to the specific conditions of the patients. During differences were statistically significant (p < 0.05). There was
hospitalization, the patients were regularly checked for blood no significant difference in the incidence of hemoglobin
routine every week. In the event of an acute chemoradiotherapy reduction, leukopenia, urinary system injury and radiation
reaction, medical staff need to timely treat the symptoms cystitis between the two groups (p > 0.05), as shown in
according to the specific conditions of the patient. Table 2.
Efficacy evaluation: The changes in tumor size were observed
by CT or MRI, and graded according to the WHO efficacy Comparison of Prognosis and Survival
evaluation criteria. including disease progression (PD): the between the Two Groups of Patients
product of the largest vertical diameter and the largest The results showed that during the 3-year follow-up, the total
diameter of the lesion (the product of the two diameters) number of deaths was 32 cases. Among them, the mortality
increased by more than 25% compared with that before rate of IMRT combined with intracavitary posterior
radiotherapy, and time continued more than 30 days; stable radiotherapy was 25.00% (13/52) lower than that of 3D-CRT
disease (SD): the two-dimensional product of the lesion
decreased by less than 50% or increased by less than 25%
compared with that before radiotherapy, and lasted for more TABLE 1 | Comparison of effective rates between the two groups of patients
than 30 days; partial remission (PR): the two-dimensional (n, %).
product of the lesion decreased by at least 50% compared with Group PD SD PR CR PR + CR
that before radiotherapy, duration of more than 30 days;
complete remission (CR): the lesions completely disappeared, IMRT combined with intracavitary 0 2 27 23 50 (96.15)
the duration of more than 30 days. Total effective rate = (PR + posterior radiotherapy group

CR) / total number of cases × 100%. 3D-CRT combined with intracavitary 0 5 26 20 46 (88.46)
Follow-up: Patients were regularly followed up every 3 posterior radiotherapy group

months by outpatient or telephone, all patients were followed χ2 – – – – 2.167

up for 3 years. The follow-up contents included patient p – – – – 0.141

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Yu and Zhou Treatment of Cervical Cancer

TABLE 2 | Comparison of the occurrence of adverse reactions of the two groups of patients (n, %).

Classification Adverse reaction IMRT combined with intracavitary 3D-CRT combined with intracavitary χ2 p
posterior radiotherapy group posterior radiotherapy group

Acute Digestive damage 15 (28.85) 29 (55.77) 7.721 0.005

Thrombocytopenia 5 (9.62) 21 (40.38) 13.128 0.001
Decreased hemoglobin 24 (46.15) 26 (50.00) 0.154 0.695
Leukopenia 35 (67.31) 34 (65.38) 0.043 0.836
Urinary system damage 8 (15.38) 11 (21.15) 0.580 0.446
Chronic Radiation proctitis 10 (19.23) 25 (48.08) 9.689 0.002
Radiation cystitis 3 (5.77) 6 (11.54) 1.095 0.295

DISCUSSION
The incidence of cervical cancer is increasing year by year, and
the patients tend to be younger. Therefore, it is particularly
important to reduce the mortality rate of cervical cancer and
control the development of cervical cancer (7). External beam
radiation combined with intracavitary radiotherapy and
concurrent chemotherapy in the treatment of medium-term and
advanced cervical cancer can prevent tumor metastasis and local
recurrence. The scope of external irradiation not only includes
the uterus, paracyngeal tissues, cervix and vagina, but also needs
to cover the pelvic lymphatic drainage area (8, 9). Traditional
external irradiation techniques are relatively backward, and the
incidence of various complications has increased, which has
been gradually replaced by IMRT, 3D-CRT and other new
FIGURE 1 | Comparison of prognosis and survival between the two groups radiotherapy technologies (10).
of patients.
3D-CRT is based on the reconstruction of three-dimensional
image of human body structure, and can accurately distinguish
normal tissue and tumor tissue. The radiation dose of the
rectum, bladder and other organs at risk can be reduced by
combined with intracavitary posterior radiotherapy group, adjusting the radiation direction and changing the radiation
which was 36.54% (19/52), and the median survival time of dose (11). IMRT is an in vitro three-dimensional irradiation
both groups was 36 months. The difference was not method developed through improved 3D-CRT technology. By
statistically significant (p > 0.05), as shown in Figure 1. adjusting the output dose, the radiation shape in all three-
dimensional directions can be kept consistent with the target
area, and the radiation dose of organs at risk and normal
Analysis of Prognostic Factors of Patients tissues around the target area can be reduced. so as to
with Medium-Term and Advanced Cervical effectively treat and control tumors (12). Compared with
Cancer 3D-CRT technology, IMRT technology can better adapt to
The results showed that there were significant differences in case irregularly shaped tumors, and at the same time, by controlling
type, clinical stage, tumor diameter, and lymph node metastasis the dose intensity, a high-dose target area can be concentrated
between the survival group and the death group (p < 0.05). in the target area (13). IMRT can reduce the acute
There was no statistically significant difference in age (p > myelosuppression and other reactions caused by concurrent
0.05) as shown in Table 3. chemotherapy, which can reduce the harm to surrounding
tissues and reduce the occurrence of various complications.
IMRT and 3D-CRT are widely used in cancer treatment.
Multivariate Analysis of Prognosis of Guillemin et al. (14) used IMRT and 3D-CRT in the treatment
Patients with Medium-Term and Advanced of non-small cell lung cancer and found that IMRT can more
Cervical Cancer effectively reduce the radiation dose to the surrounding organs
Logistic regression analysis showed that pathological type, at risk of patients. In cervical cancer, Contreras’ team (15)
clinical stage and lymph node metastasis were independent found that IMRT can reduce the amount of rectal and bladder
influencing factors of 3-year prognosis of patients with tissue around the tumor, ensure the coverage of tumor tissue,
medium-term and advanced cervical cancer (p < 0.05), while and alleviate complications caused by radiotherapy. This study
tumor diameter had no significant effect on 3-year prognosis found that the total effective rate of IMRT combined with
of patients (p > 0.05), as shown in Tables 4 and 5. intracavitary posterior radiotherapy was higher than that of 3D-

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Yu and Zhou Treatment of Cervical Cancer

TABLE 3 | Analysis of prognostic factors of patients with medium-term and advanced cervical cancer (n, %).

Influencing factors Survival group (n = 72) Death group (n = 32) χ2 p

Age (Years)
≥55 35 (48.61) 14 (43.75) 0.210 0.647
<55 37 (51.39) 18 (56.25)
Pathological typing
Squamous cell carcinoma 71 (98.61) 28 (87.50) 5.976 0.015
Adenocarcinoma 1 (1.39) 4 (12.50)
Clinical stage
II B 41 (56.94) 25 (78.12) 4.286 0.038
III–IV 31 (43.06) 7 (21.88)
Tumor diameter (cm)
≥4 46 (63.89) 13 (40.62) 4.85 0.027
<4 26 (36.11) 19 (59.38)
Lymph node metastasis
Yes 32 (44.44) 26 (81.25) 12.166 0.001
No 40 (55.56) 6 (18.75)

TABLE 4 | Assignment table. advanced cervical cancer. Among them, patients with
squamous cell carcinoma, late clinical stage, and lymph node
Influencing factors Assignment
metastasis have higher mortality rates. This may be related to
Pathological typing Squamous cell carcinoma = 1, Adenocarcinoma = 2 the fact that the cancer cells of squamous cell carcinoma
Clinical stage II B = 1, III ∼ IV = 2 patients have invaded into the muscle layer, the distance from
Tumor diameter ≥4 cm = 1, <4 cm = 2
the radiation source is far, patients with advanced staging
have increased tumor uncontrollability, and patients with
Lymph node metastasis Yes = 1, No = 2
lymph node metastasis have wider tumor distribution (16, 17).
Yüksel et al. (18), Ramlov et al. (19) found that case typing,
TABLE 5 | Multivariate analysis of prognosis of patients with medium-term and tumor size, lymph node metastasis, etc. are all risk factors for
advanced cervical cancer. the prognosis of patients with medium-term and advanced
Influencing factors B SE Walds df Sig. Exp(B)
cervical cancer. However, this study showed that tumor size was
not a prognostic factor for patients with medium-term and
Pathological typing 2.615 1.034 6.398 1 0.027 5.492 advanced cervical cancer, which was partially deviated from
Clinical stage 1.569 0.523 8.741 1 0.015 6.937 previous studies. This may be related to the small sample size
Tumor diameter 1.037 0.594 3.317 1 0.0145 2.459 and short follow-up time in this study. It is necessary to expand
Lymph node metastasis 1.375 0.509 7.321 1 0.023 6.558
the sample size and extend the follow-up time in the future to
improve the credibility of the research results.
In conclusion, IMRT combined with intracavitary posterior
radiotherapy has the same curative effect as 3D-CRT combined
CRT combined with intracavitary posterior radiotherapy, but the
with intracavitary posterior radiotherapy, but it can reduce the
difference was not statistically significant. There was no
incidence of adverse reactions of patients with medium-term
significant difference in the overall survival rate and median
and advanced cervical cancer and has higher safety. Pathological
survival time between the two groups. The results showed that
type, clinical stage, and lymph node metastasis are independent
the treatment efficacy of the two regimens were equivalent.
factors affecting the prognosis of patients. In clinical treatment,
However, the incidences of gastrointestinal tract injury,
IMRT combined with intracavitary posterior radiotherapy is
thrombocytopenia and subsequent radiation proctitis in the
more recommended as the treatment plan for patients with
IMRT combined with intracavitary posterior radiotherapy
medium-term and advanced cervical cancer.
group were significantly lower than those in the 3D-CRT
combined with intracavitary posterior radiotherapy group. This
suggested that when all conditions of intracavitary posterior
radiotherapy were the same, IMRT can relieve gastrointestinal DATA AVAILABILITY STATEMENT
and hematological injury, with higher safety.
The results of this study showed that pathological type, The original contributions presented in the study are included in
clinical stage and lymph node metastasis were independent the article/Supplementary Material, further inquiries can be
prognostic factors for patients with medium-term and directed to the corresponding author/s.

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Yu and Zhou Treatment of Cervical Cancer

ETHICS STATEMENT AUTHOR CONTRIBUTIONS

The studies involving human participants were reviewed and The first author is KY, he is responsible for the writing, research
approved by This study was approved by the ethics committee design, data analysis of the article. LZ is responsible for the
of our hospital. The patients/participants provided their guidance of the entire research. All authors contributed to the
written informed consent to participate in this study. article and approved the submitted version.

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