Reducing Radiation Target Volume in Radical Radiotherapy for Stage IIb Cervical Cancer: A Single-arm Exploratory Study
Phase: NA
Conditions: Stage IIb Cervical Cancer Radical Radiotherapy
Sponsor: Chongqing University Cancer Hospital

 
 
 
 
 
 
Reducing Radiation Target Volume in Radical 
Radiotherapy for Stage IIb Cervical Cancer: A 
Single-arm Exploratory Study 
 
 
 
 
 
document date: October 10, 2025 
 
 
 
 
 
 
 
 
 
 

I. Research Background 
Cervical cancer is one of the most common malignant tumors in the female 
reproductive system worldwide. According to the latest data, its incidence and mortality 
rates still rank among the top for female cancers, especially in developing countries, 
where 80% of patients are diagnosed at the local advanced stage [1]. As a high-
incidence area for cervical cancer in China, the data from the National Cancer Center 
shows that in 2022, there were approximately 151,000 new cases and 56,000 deaths, 
and the disease burden and treatment-related toxicities have a significant impact on 
patients' quality of life.  
According to relevant international and domestic guidelines [3,4], early-stage cervical 
cancer patients are mainly treated with surgical methods. Those who refuse surgery or 
are unable to undergo surgery due to concurrent internal medical conditions can adopt 
radical radiotherapy, while patients in the local advanced stage are primarily treated 
with concurrent chemoradiotherapy (CCRT). Radiotherapy is an important treatment 
strategy for cervical cancer, which can be involved in the treatment of all stages, 
especially for patients who have not undergone surgical treatment, radiotherapy is an 
important curative treatment method. The irradiation range of radical radiotherapy 
traditionally adopts a large pelvic irradiation, usually including the primary tumor and 
pelvic lymphatic drainage areas (such as internal iliac, external iliac, obturator and pre-
sacral), with the aim of covering potential metastasis-risk areas. However, the resulting 
toxicities such as radiation-induced colitis, radiation-induced bladder inflammation, 
bone marrow suppression [5] and sexual function impairment [6] have become 
increasingly prominent. The rate of pelvic lymph node metastasis in early-stage cervical 
cancer is relatively low, especially for patients with small tumors, no lymphatic vessel 
invasion and superficial stromal infiltration [7,8]. The LACC staging range is wide and 
heterogeneous, and there are many relatively low-risk stage IIIB cervical cancers that 
are earlier in stage and have smaller tumor volumes with relatively better prognosis. 
Sakuragi et al. [9] reported that the incidence of pelvic lymph node metastasis in IB, IIA 
and IIB cervical cancers was 12-22%, 10-27% and 34-43% respectively. However, this 
study used the 2009 FIGO staging. Our center's statistics for 2018-2022 of 2009 FIGO 
IIB stage patients showed that there were 116 patients with FIGO IIB stage in 2018, and 
only 10 cases had lymph node metastasis confirmed by pelvic lymph node resection 
pathology, with a low incidence of pelvic lymph node metastasis (10/116, 8.6%) in 2018 
FIGO IIB stage patients. A multicenter prospective cohort study EMBRACE-I showed that 
among LACC cervical cancer patients receiving standard treatment modes, low-risk 
cervical cancer patients had significantly better overall treatment effects than those with 
a later stage, with significantly higher 5-year local control rate and overall survival rate 

[10]. For low-risk patients, routine irradiation of the pelvic lymphatic drainage area may 
lead to over-treatment, increase acute and long-term toxicity, significantly affecting the 
quality of life without significantly improving survival. If the prophylactic irradiation of 
the pelvic lymphatic drainage area is not considered, the target volume of radical 
radiotherapy will be reduced by at least half, significantly reducing radiation damage to 
surrounding normal organs, especially the intestine and bone marrow. Especially for 
young patients or those with more comorbidities, reducing the irradiation range may 
significantly improve the quality of life and provide better bone marrow reserve 
protection for concurrent chemotherapy.  
Modern imaging techniques (such as high-resolution MRI, enhanced CT, PET-CT) have 
high sensitivity for lymph node metastasis, and the negative predictive value of lymph 
node metastasis can reach over 90% [11-13]. Combined with sentinel lymph node 
biopsy technology, it can more accurately screen patients with extremely low risk of 
lymph node metastasis. The PHENIX-I [14] study reported at the 2025 SGO conference 
showed that the rate of non-sentinel lymph node metastasis in patients with early-
stage cervical cancer who had negative sentinel lymph nodes was less than 1%. Patients 
with negative sentinel lymph nodes did not require systematic lymph node dissection, 
and their survival rate and complications were better than those of traditional surgery. 
This provided an analogy basis for the reduction of the radiation target area, suggesting 
the feasibility of similar strategies in the field of radiotherapy. If the lymph nodes are 
clearly negative on imaging (especially combined with clinical examination), the 
irradiation range can be selectively reduced. The popularization of intensity-modulated 
radiotherapy (IMRT) and image-guided radiotherapy (IGRT) has made the dose 
distribution of the target area more precise, reducing damage to normal tissues. At the 
same time, image-guided brachytherapy (such as MRI-guided brachytherapy [15]) can 
increase the dose to the primary lesion, compensating for the local control needs after 
the reduction of the external irradiation range. The core of radical radiotherapy for 
cervical cancer lies in the high-dose coverage of the primary lesion (through EBRT 
combined with brachytherapy). If the primary lesion is well controlled, the absolute risk 
of lymph node recurrence is generally low. Some retrospective studies have shown that 
the local control rate of early-stage patients treated with EBRT combined with 
brachytherapy can exceed 90%, and the lymph node recurrence rate is less than 10% 
[16]. Patients with locally advanced cervical cancer after radical radiotherapy have a 
recurrence pattern mainly of distant metastasis, with a significantly higher incidence 
than local recurrence (77.5% : 36.9%) [17]. Among the 877 patients with locally advanced 
cervical cancer in our center from 2016 to 2022, 286 cases were in FIGO stage IIb in 
2018, and 32 cases had recurrence. The majority were local recurrence or distant 
metastasis, and only 1 case (1/286, 0.35%) was pelvic lymph node recurrence. The 

INTERLACE study published in THE LANCET in October 2024 [18] added induction 
chemotherapy (carboplatin (AUC2) + paclitaxel (80mg/m2)) for 6 cycles before CCRT for 
cervical cancer patients (2008 FIGO stage Ib1 positive lymph nodes, Ib2, II, IIIb, IVa). This 
improved the progression-free survival and overall survival of patients without 
significantly increasing adverse reactions or delaying the treatment process. Thus, 
induction chemotherapy was recommended by the latest NCCN cervical cancer 
guidelines (2025.V4 version) [4]. The addition of various technical means has led to 
better treatment outcomes for cervical cancer. Therefore, improving the quality of life 
has become our further pursuit goal. We can attempt "subtraction exploration" under 
the guarantee of good therapeutic efficacy, trying to reduce the irradiation range when 
performing radical radiotherapy for cervical cancer with low lymph node metastasis risk 
to reduce damage to normal tissues.  
In recent years, with the advancement of imaging technology and precise radiotherapy 
techniques, the exploration of reducing the irradiation range has achieved positive 
progress in multiple tumor types. For example, in early-stage non-small cell lung cancer 
(NSCLC), the application of stereotactic body radiotherapy (SBRT) precisely focuses on 
the tumor target area, reducing the irradiation volume to the primary lesion, 
significantly reducing the radiation dose to normal lung tissue while maintaining a good 
local control rate [19]. Similarly, in prostate cancer, the application of precise target 
delineation based on MRI fusion technology and intensity-modulated radiotherapy 
(IMRT) has reduced the irradiation range from the entire pelvic cavity to the prostate 
and some surrounding tissues, significantly reducing radiation-induced damage to the 
gastrointestinal and urogenital systems [20]. These studies provide important analogical 
basis for reducing the irradiation range in radical radiotherapy for cervical cancer, 
suggesting that individualized radiotherapy strategies may reduce toxicity while 
maintaining tumor control effects. At present, immunotherapy is increasingly being 
used in the treatment of malignant tumors. With the application of immunotherapy, the 
adjustment of the radiation irradiation range may also affect the efficacy of 
immunotherapy. Animal models have shown that if radiotherapy does not irradiate the 
lymphatic drainage area, more immune cells, such as CD8+ T cells and dendritic cells, 
may be preserved in the lymph nodes, which are crucial for immune responses. Lymph 
nodes are also the sites where immune cells are activated and proliferated, and 
preserving them may enhance the efficacy of immunotherapy [21]. Moreover, extensive 
radiotherapy may lead to lymphopenia, reducing the response rate of immunotherapy 
[22]. Reducing the irradiation range can minimize this damage to lymphocytes. 
Additionally, radiotherapy may alter the tumor microenvironment, such as increasing 
PD-L1 expression, but extensive irradiation may simultaneously damage lymphatic 
structures, affecting the transportation and activation of immune cells. Precise 

radiotherapy that avoids lymph nodes may maintain the functions of these structures 
and make immunotherapy more effective. When radiotherapy causes tumor cell death, 
antigens are released, and if the draining lymph nodes are intact, antigen presentation 
may be more effective, activating systemic immune responses, and combining 
immunotherapy may produce a stronger distant effect in controlling metastatic lesions 
[23]. We have previously explored in depth the impact of surgical removal of lymph 
nodes on immunotherapy after cervical cancer recurrence, and found that the 
immunotherapy effect was better in patients with recurrent cervical cancer who did not 
undergo lymph node resection. This was confirmed from a clinical perspective, 
demonstrating that preserving lymph nodes can enhance the efficacy of 
immunotherapy. Therefore, low-risk cervical cancer radical radiotherapy can also 
consider reducing the irradiation range and preserving lymph nodes and lymphatic 
drainage areas, providing more guarantees for better efficacy of immunotherapy in 
subsequent disease changes.  
Although the NCCN and ESTRO guidelines recommend individualized reduction of the 
irradiation range for patients with imaging-negative lymph nodes in cervical cancer, 
specific implementation standards have not yet been unified. Part of the reason is the 
lack of prospective studies to verify their safety. In clinical practice, traditional large 
irradiation field radiotherapy is still widely used. Therefore, it is urgent to accumulate 
evidence through single-arm exploratory studies to clarify the indications and risk 
stratification criteria for reducing the irradiation range. This single-arm exploratory 
study aims to verify the safety and effectiveness of reducing the irradiation range in 
radical radiotherapy for stage IIb cervical cancer. By combining modern imaging, 
pathological staging, and precise radiotherapy techniques, we explore new strategies to 
reduce treatment-related toxicity while ensuring tumor control, providing high-level 
evidence for future guideline updates and clinical practice. The study will focus on local 
control rate, progression-free survival rate, acute and long-term toxic reactions, and 
changes in quality of life, laying the foundation for more optimized treatment strategies 
for cervical cancer patients. 
II. Research Objectives 
(1) To explore the effectiveness and safety of reducing the irradiation area in the radical 
radiotherapy for stage IIb cervical cancer, and to provide high-level evidence for future 
guideline updates and clinical practice. 
(2) To observe the radiotherapy toxic and side effects during CCRT, and to verify the 
benefits brought by reducing the irradiation area to the improvement of patients' 
quality of life. 

Main observation indicators: Bone marrow suppression during CCRT, objective response 
rate (ORR), disease control rate (DCR), 1-year and 2-year recurrence rates in the pelvic 
lymphatic drainage area. 
Secondary observation indicators: Gastrointestinal and urinary system toxic and side 
effects during CCRT, incidence of lymphedema, 2-year progression-free survival (PFS). 
III. Research Population 
Inclusion criteria: 
1. Patients voluntarily participate in this study and sign the informed consent form; 
2. 50-75 years old; 
3. Patients with cervical cancer who have not undergone surgery or chemotherapy and 
are diagnosed with squamous cell carcinoma by pathological tissue, and HPV high-risk 
positive; 
4. 2018 International Federation of Gynecology and Obstetrics (FIGO) stage IIb (tumor 
size < 4 cm); 
5. ECOG score 0-1, expected survival greater than 6 months; 
6. Pregnant women must undergo pregnancy test (serum or urine) 7 days before 
enrollment, and the result is negative, and are willing to use appropriate contraceptive 
methods during the trial; 
7. The investigator judges that there are no absolute contraindications to radiotherapy 
and surgery, and can comply with the trial protocol. 
Exclusion criteria: 
1. Active or uncontrolled severe infection; 
2. Liver cirrhosis, decompensated liver disease; 
3. History of immunodeficiency, including HIV positive or having other acquired 
congenital immune deficiency diseases; 
4. Chronic renal insufficiency and renal failure; 
5. Patients with other malignancies that need treatment and/or newly diagnosed within 
5 years; 
6. Myocardial infarction, severe arrhythmia, and ≥ 2 grade congestive heart failure 
(New York Heart Association (NYHA) classification); 

7. Patients who have received pelvic arterial embolization; 
8. Patients who have undergone partial or radical hysterectomy; 
9. Patients who have received partial or radical hysterectomy; 
10. Patients with a history of severe allergic reaction to platinum-based chemotherapy 
drugs; 
11. Patients with comorbidities, need to take drugs with high liver and kidney function 
impairment during treatment, such as tuberculosis, etc.; 
12. Patients who cannot understand the experimental content and cannot cooperate 
and refuse to sign the informed consent form; 
13. Patients with serious conditions that endanger the safety of the patient or affect the 
completion of the study. 
Criteria for discontinuation of treatment by subjects: 
1. The study physician considers it necessary to terminate the treatment from the 
perspective of the best benefit for the patient; 
2. Adverse reactions or serious adverse events that cannot be tolerated are confirmed 
by the investigator; 
3. Patients who fail to complete the treatment on schedule and time; 
4. Patients withdraw the informed consent; 
5. Patients receive other anti-tumor drug treatments (such as immunotherapy, targeted 
therapy) that affect the judgment of therapeutic efficacy. 
IV. Research Design 
This study is a single-center, prospective clinical trial in China, and it plans to enroll 60 
patients.  
1. Patients diagnosed with cervical squamous cell carcinoma through biopsy, before 
anti-tumor treatment, undergo comprehensive gynecological examinations and 
imaging evaluations (CT, MRI or PET/CT), and are diagnosed with stage IIb cervical 
cancer (tumor size < 4 cm) according to the FIGO 2018 staging principle;  
2. Induction chemotherapy for 6 times (carboplatin (AUC 2) + paclitaxel (80 mg/m2), 
q1w);  
3. Platinum-containing regimen for concurrent chemoradiotherapy (CCRT)  

⑴ Concurrent radiotherapy: external irradiation uses rotational intensity-modulated 
radiotherapy (VAMT), and internal irradiation uses three-dimensional brachytherapy.  
⑵ Radiotherapy plan:  
① The external irradiation range only covers the entire uterus (including the primary 
lesion of the cervical cancer), bilateral parametrium, and 3 cm below the cervical/vaginal 
lesions.  
② External irradiation dose: 45 Gy/25 fractions; total external irradiation + 
brachytherapy dose: HR-CTV D90 ≥ 80 Gy (+20%).  
③ Normal organ limits (EQD2): bladder D2cc ≤ 80-90 Gy, rectum D2cc ≤ 65-75 Gy, 
sigmoid colon D2cc ≤ 70-75 Gy.  
⑷ Concurrent platinum-containing chemotherapy for 5 times (cisplatin 40 mg/m2 
q1w, if cisplatin is intolerable, use carboplatin AUC = 2 q1w. Window period 1 week).  
⑤ CCRT time is controlled within 56 days. After completing CCRT according to the 
plan, efficacy is evaluated within 1 week and recorded for analysis.  
⑥ If cervical biopsy after CCRT indicates positive pathology, perform adjuvant 
chemotherapy for 3 courses (TP regimen: paclitaxel 135 mg/m2, cisplatin 50 mg/m2, 
q3w; if cisplatin is intolerable, TC regimen: paclitaxel 135 mg/m2, carboplatin AUC = 4, 
q3w; window period 2 weeks) ± three-dimensional brachytherapy (A point or HR-CTV 
D90 no more than 96 Gy).  
4. Short-term efficacy is evaluated according to the WHO's evaluation criteria for solid 
tumors (RECIST 1.1). All lesions are evaluated within 4 weeks after the end of treatment 
and every half year thereafter until disease progression, with a window period of 4 
weeks. 
References： 
[1] Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN 
estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA 
Cancer J Clin. 2024 May-Jun;74(3):229-263. 
[2] Zheng Rongshou, Chen Ru, Han Bingfeng, et al. Analysis of the Epidemiological 
Situation of Malignant Tumors in China in 2022. Chinese Journal of Oncology, 2024, 
46(3): 221-231.  
[3] CSCO Guidelines for the Diagnosis and Treatment of Cervical Cancer 2024. 
[4] NCCN Guideline. Cervical Cancer. 2025.V4. 

[5] Chen YY, Huang YT. Comparison of two platinum-containing chemotherapy 
regimens in the treatment of advanced cervical cancer with concurrent 
chemoradiotherapy. Ann Med, 2024, 56(1):2371008. 
[6] Xie S, Liu M, Li W. Impact of Radiotherapy on Endocrine Function and Gut 
Microbiota in Cervical Cancer Patients Undergoing Ovarian Transposition. Int J Womens 
Health, 2024, 27:16:2319-2331. 
[7] Gulseren V, Kocaer M, Gungorduk O, et al. Preoperative predictors of pelvic and 
para-aortic lymph node metastases in cervical cancer. J Cancer Res Ther, 
2019,15(6):1231–1234. 
[8] Wenzel HHB, Hardie AN, Moncada-Torres A, et al. A federated approach to identify 
women with early-stage cervical cancer at low risk of lymph node metastases. Eur J 
Cancer, 2023, 185:61-68. 
[9] Sakuragi N. Up-to-date management of lymph node metastasis and the role of 
tailored lymphadenectomy in cervical cancer. Int J Clin Oncol, 2007, 12(3):165–175. 
[10] Pötter R, Tanderup K, Schmid MP, et al. MRI-guided adaptive brachytherapy in 
locally advanced cervical cancer (EMBRACE-I): a multicentre prospective cohort study[J]. 
Lancet Oncol,2021,22(4):538-547. 
[11] S. Woo, R. Atun, Z.J. Ward, A.M. Scott, H. Hricak, H.A. Vargas, Diagnostic 
performance of conventional and advanced imaging modalities for assessing newly 
diagnosed cervical cancer: systematic review and meta-analysis. Eur Radiol, 2020, 30: 
5560–5577. 
[12] B. Liu, S. Gao, S. Li. A comprehensive comparison of CT, MRI, positron emission 
tomography or positron emission tomography/CT, and diffusion weighted imaging-MRI 
for detecting the lymph nodes metastases in patients with cervical cancer: a meta-
analysis based on 67 studies. Gynecol Obstet Invest, 2017, 82: 209–222. 
[13] Yu W, Kou C, Bai W, et al. The diagnostic performance of PET/CT scans for the 
detection of para-aortic metastatic lymph nodes in patients with cervical cancer: A 
meta-analysis. PLoS One, 2019,14(7): e0220080. 
[14] Hua Tu, He Huang, Bingna Xian, et al. Sentinel lymph node biopsy versus pelvic 
lymphadenectomy in early-stage cervical cancer: a multi-center randomized trial 
(PHENIX/CSEM 010). Int J Gynecol Cancer, 2020, 30(11):1829-1833. 
[15] Schmid MP, Lindegaard JC, Mahantshetty U, et al. Risk Factors for Local Failure 
Following Chemoradiation and Magnetic Resonance Image-Guided Brachytherapy in 
Locally Advanced Cervical Cancer: Results From the EMBRACE-I Study. J Clin Oncol. 

2023, 41(10): 1933-1942. 
[16] Ester P Olthof, Hans H B Wenzel, Marissa C van Maaren，et al. Radical 
hysterectomy or chemoradiotherapy for clinically early-stage cervical cancer with 
suspicious lymph nodes on imaging: a retrospective cohort study. J Gynecol Oncol, 
2025, 36(2): e16. 
[17] Wu Chu Fan, Feng Tao, Xu Qing, et al. Patterns and prognosis of recurrence and 
metastasis after radical radiotherapy for cervical cancer. Chinese Journal of Radiation 
Oncology, 2024, 33(3): 231-236. 
[18] McCormack M, Eminowicz G, Gallardo D，et al. Induction chemotherapy followed 
by standard chemoradiotherapy versus standard chemoradiotherapy alone in patients 
with locally advanced cervical cancer (GCIG INTERLACE): an international, multicentre, 
randomised phase3 trial. Lancet, 2024, 404(10462): 1525-1535. 
[19] Kita N, Tomita N, Takaoka T, et al. Stereotactic body radiotherapy for central non-
small cell lung cancer: risk analysis of radiation pneumonitis and bronchial dose 
constraints. J Radiat Res, 2025, 14: rraf016. 
[20] Houlihan OA, Redmond K, Fairmichael C, et al. A Randomized Feasibility Trial of 
Stereotactic Prostate Radiation Therapy With or Without Elective Nodal Irradiation in 
High-Risk Localized Prostate Cancer (SPORT Trial). Int J Radiat Oncol Biol Phys. 2023, 
117(3):594-609. 
[21] Ariel E Marciscano, Ali Ghasemzadeh, Thomas R Nirschl, et al. Elective nodal 
irradiation attenuates the combinatorial efficacy  
of stereotactic radiation therapy and immunotherapy. Clin Cancer Res 
, 2018, 24(20): 5058-5071. 
[22] Lambin P，Lieverse RIY，Eckert F，et al．Lymphocyte sparing radiotherapy: the 
rationale for protecting lymphocyte-rich organs when combining radiotherapy with 
immunotherapy． Semin Radiat Oncol，2020，30( 2): 187-193． 
[23] Zhaoyun Liu, Zhiyong Yu, Dawei Chen，et al. Pivotal roles of tumor-draining lymph 
nodes in the abscopal effects from combined immunotherapy and radiotherapy. Cancer 
Commun (Lond), 2022 , 42(10): 971-986.