Factors Affecting Survival in Cervical Cancer Stage IIIB Treated with Radiation Therapy

Background: To evaluate the factors affecting overall survival (OS) and local control (LC) rates in patients with uterine cervical cancer FIGO stage IIIB treated with radiation therapy (RT). Methods: A retrospective study was conducted on 229 patients diagnosed with FIGO stage IIIB cervical cancer who received external beam RT (EBRT) followed by high-dose rate intracavitary brachytherapy (HDR-ICBT) at the Division of Radiation Oncology, Srinagarind Hospital, Khon Kaen University, Thailand, between January 1, 2009, and December 31, 2011. Key prognostic factors, including age, pre-treatment hemoglobin level, tumor size, histology, pelvic side wall involvement, concurrent chemoradiation (CCRT), equivalent dose in 2 Gy (EQD2) at point A, parametrial boost, and overall treatment time (OTT), were analyzed. Survival and local control rates were estimated using the Kaplan-Meier method; hazard ratios (HR) were calculated via Cox proportional hazards regression. Toxicities were recorded per CTCAE v4.03 and RTOG/EORTC criteria. Results: A total of 229 patients were analyzed. The median age was 55 years (range 33-79). The 5-year OS rate was 41.9% and the 5-year LC rate was 71.4%. Multivariate analysis identified pre-treatment hemoglobin <10 vs. ≥10 g/dL (HR=1.565, p=0.017), tumor size<5 vs. ≥5 cm (HR=0.621, p=0.008), squamous cell carcinoma (SCCA) histology vs. non-SCCA (HR=0.62, p=0.035), unilateral vs. bilateral pelvic side wall involvement (HR=0.691, p=0.049), and RT alone vs. CCRT (HR=1.852, p=0.001) as significant prognostic factors for OS. For LC, significant factors included age ≥50 years, higher hemoglobin, squamous histology, and smaller tumor size. Grade 3-4 gastrointestinal toxicities were most common; no grade 4 hematologic toxicity was seen. Conclusion: Pre-treatment hemoglobin level, tumor size, pelvic side wall involvement, histology, and CCRT were significant predictors of survival in FIGO stage IIIB cervical cancer treated with EBRT plus HDR-ICBT. Optimizing these factors may improve outcomes.

 Introduction

Cervical cancer remains a key public health issue worldwide, including in Thailand, where it is among the most prevalent cancers in women, with an estimated 8,662 new cases and 4,567 deaths per year, ranking 5th in cancer incidence and mortality [1-3]. The International Federation of Gynecology and Obstetrics (FIGO) defined cervical cancer stage IIIB as the tumor extending into the pelvic wall and/or causing hydronephrosis or non- functioning kidney [4, 5]. The National Comprehensive Cancer Network (NCCN) recommends external beam radiation therapy (EBRT) concurrent with platinum- based chemotherapy (CCRT) followed by high-dose rate intracavitary brachytherapy (HDR-ICBT) with or without immunotherapy as the standard treatment of choice [6]. However, the 5-year overall survival (OS) in cervical cancer stage IIIB was only 34 - 54.8%, which remains inferior to stage IIB at 61 - 80.3% [7-11]. This study aimed to clarify the factors influencing OS and local control (LC) in locally advanced cervical cancer FIGO stage IIIB treated at our institution, contributing evidence for optimizing treatment strategies.

Materials and Methods <italic id="italic-1">Study Design and Population<italic id="italic-2"/></italic>

A retrospective cohort of female patients with pathologically confirmed cervical cancer, the 2009 FIGO clinical stage IIIB, treated with EBRT with or without concurrent chemotherapy plus HDR-ICBT between January 2009 and December 2011 at the Division of Radiation Oncology, Srinagarind Hospital, Khon Kaen University, was collected and analyzed. Patients with prior pelvic radiation therapy (RT), other concurrent malignancies, recurrent disease, incomplete data, or unstaged disease were excluded from the study.

<italic id="italic-3">Data Collection<italic id="italic-4"/></italic>

Patient demographics, clinical, and treatment characteristics were extracted from medical records, including age (<50 vs. ≥50 years), pre-treatment hemoglobin (<10 vs. ≥10 g/dL), tumor size (<5 vs. ≥5 cm), histology (Squamous cell carcinoma [SCCA] vs non-SCCA), pelvic side wall involvement (one vs. both sides), treatment modality (RT alone vs. CCRT), point A dose (<85 vs. ≥85 Gy EQD2), parametrial EBRT boost (yes/no), and overall treatment time (OTT) (<56 vs. ≥56 days). All patients were staged according to the 2009 FIGO clinical staging by per vaginal, per rectal examinations, intravenous pyelogram, cystoscope, and proctoscope in the tumor clinic of the multidisciplinary team, which consisted of radiation oncologists, gynecologic oncologists, and urologists. Routine pre-treatment cross-sectional imaging was not available due to the limitations of hospital facilities at the time of the study.

<italic id="italic-5">Treatment<italic id="italic-6"/></italic>

All patients received whole pelvis EBRT (50-50.4 Gy, 1.8-2 Gy per fraction), with or without parametrial EBRT boost. HDR-ICBT (Ir-192, 6 Gy × 4 fractions at point A) was performed weekly after the completion of EBRT. Prescribing to point A was used as a surrogate in the absence of 3D planning under the limited-resource circumstances. Chemotherapy (cisplatin 40 mg/m² IV weekly × 5–6 cycles) was offered unless contraindicated. The RT alone group was defined as patients receiving whole pelvis EBRT followed by HDR-ICBT. Patients receiving whole pelvis EBRT concurrent with chemotherapy, followed by HDR-ICBT, were categorized as the CCRT group.

<italic id="italic-7">Outcomes<italic id="italic-8"/></italic>

The primary endpoint was 5-year OS, which was defined as the time from diagnosis to death/last follow-up. The secondary endpoint was 5-year LC, which was defined as the time from the end of primary treatment to local recurrence. Tumor recurrence was assessed by clinical examination, pap smear, and biopsy of the suspected lesions. Toxicities were reported according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 and toxicity criteria from the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC).

<italic id="italic-8dce15814cc2b5aea28aaa0d0fbf5344">Statistical Analysis<italic id="italic-d59b12f309afaca67bb9f2a73c16f7a2"/></italic>

Baseline characteristics were described using frequencies with percentages for categorical data and means with standard deviations (SD) or medians with interquartile ranges (IQR) for continuous data. OS and LC rates were estimated using Kaplan-Meier analysis. The log-rank test was used to compare the Kaplan-Meier curves. The Cox proportional hazard model was used to perform the multivariable analysis to find the factors affecting OS and LC. Statistical significance was indicated by a p-value ≤ 0.05. Data analysis was performed with IBM SPSS Statistics Version 19 (IBM Inc., New York, NY).

Results <italic id="italic-2ae79f7ca6345267816597ac373047e9">Patient and Treatment Characteristics<italic id="italic-c05be39a126364f3da2a54fc39514e67"/></italic>

The medical records of 232 patients with the 2009 FIGO clinical stage IIIB cervical cancer were reviewed. Of these, 3 patients were excluded according to the exclusion criteria. Therefore, a total of 229 patients were included in the analysis. The median age was 55 years (range 33- 79). The median follow-up time was 20.7 months (range 1-86.5). Most patients (67.7%) had pre-treatment Hb ≥10 g/dL; 58.5% had tumor size ≥5 cm; SCCA comprised 83.4%; 62% had bilateral pelvic side wall involvement; 51.1% received CCRT; 82.1% received point A dose ≥85 Gy; 59% received parametrial EBRT boost. OTT ≥56 days occurred in 95.2%. Almost all patients were clinically assessed as stage IIIB by pelvic side wall involvement (99.6%) (Table 1).

Patient factors     Percentage
1. Age (years)   median = 55 (range 33-79)  
< 50 84   36.70
≥ 50 145   63.30
2. Pre-treatment Hb (g/dL)   mean = 10.6 (range 5.7-15.4)  
< 10 74   32.30
≥ 10 155   67.70
Disease factors      
3. Tumor size (cm.)   median = 5 (range 2-10)  
< 5 91   39.70
≥ 5 134   58.50
N/A 4   1.80
4. Histology      
Squamous cell carcinoma 191   83.40
Adenocarcinoma 32   14.00
Adenosquamous cell carcinoma 3   1.30
Small cell carcinoma 2   0.90
Sarcoma 1   0.40
5. Pelvic side wall involvement      
One side 86   37.60
Both sides 142   62.00
N/A 1   0.40
Treatment factors      
6. Treatment modality      
CCRT 117   51.10
RT alone 111   48.50
N/A 1   0.40
7. Point A dose (Gy)   median = 90.85 (range 55.4-98.4)  
< 85 41   17.90
≥ 85 188   82.10
8. Parametrial boost      
Yes 135   59.00
No 94   41.00
9. Overall treatment time (days)   median = 79 (range 35-164)  
< 56 11   4.80
≥ 56 218   95.20

<italic id="italic-5f446ebc9ac32eaf01f8829c57f37259">Survival, Local Control, and Prognostic Factors<italic id="italic-7cf516db5218a6bb7d31ce005921ffd6"/></italic>

The 5-year OS rate was 41.9%. The Kaplan-Meier univariable analysis showed that the survival was statistically significant better in pre-treatment Hb ≥10 vs.<10 g/dL (5-year OS 50.0% vs. 24.7%, median survival 59.8 mo. vs. 25.4 mo., p-value <0.001), histology of SCCA vs. non-SCCA (5-year OS 45.5% vs. 27.3%, median survival 52.2 mo. vs 29.6 mo., p-value=0.006), tumor size <5 vs. ≥5 cm (5-year OS 52.7% vs. 34.3%, median survival 65.4 vs. 31.7 mo., p-value=0.003), and CCRT vs. RT alone (5-year OS 51.8% vs. 31.7%, median survival 66.9 vs. 33.9 mo., p-value <0.001), respectively (Fig.1 & Table 2).

Factors N 5-year survival (%) Median survival (mo.) p-value
1. Age (years) < 50 84 41.7 36.2 (25.2-47.2) 0.936
≥ 50 145 42 48.0 (33.8-62.2)
2. Pre-treatment Hb (g/dL) < 10 74 24.7 25.4 (17.3-33.5) <0.001*
≥ 10 155 50 59.8 (43.6-76.0)
3. Tumor size (cm.) < 5 91 52.7 65.4 (35.0-95.8) 0.003*
≥ 5 134 34.3 31.7 (24.8-38.6)
4. Histology SCCA 191 45.5 52.2 (37.0-67.4) 0.006*
Non-SCCA 38 27.3 29.6 (16.5-42.7)
5. PSW involvement One side 86 48.3 58.4 (45.2-71.6) 0.053
Both sides 142 38.3 34.1 (26.6-41.6)
6. Treatment modality RT alone 111 31.7 33.9 (25.8-42.0) <0.001*
CCRT 117 51.8 66.9 (46.4-77.2)
7. Point A dose (Gy) < 85 41 43.6 37.6 (8.0-67.2) 0.742
≥ 85 188 41.7 43.3 (31.9-54.7)
8. Parametrial boost No 94 37.5 38.7 (27.7-49.7) 0.542
Yes 135 44.8 44.5 (23.8-65.2)
9. OTT (days) < 56 11 45.5 44.5 (14.1-75.0) 0.628
≥ 56 218 41.9 40.9 (28.7-53.1)

For the multivariable analysis using the Cox proportional hazard model, all 4 factors above remained statistically significant for OS. The adjusted hazard ratio (HR) was 1.565 for pre-treatment Hb <10 g/dL (95%CI 1.090-2.247, p-value = 0.017), 0.620 for histology of SCCA (95%CI 0.408-0.968, p-value = 0.035), 0.621 for tumor size <5 cm. (95%CI 0.410-0.875, p-value= 0.008) and 1.852 for RT alone (95%CI 1.290-2.725,p-value = 0.001). One-sided pelvic side wall extension was the only factor that showed no statistical difference in univariable analysis (p-value = 0.053), but in the multivariable analysis, when adjusting with other factors, one-sided pelvic side wall extension was a significant positive prognostic factor for OS compared to both pelvic side wall extension with HR of 0.691 (95%CI 0.478-0.998, p-value = 0.049) (Table 3).

Factors Adjusted HR 95% CI p-value
Pre-treatment Hb (g/dL)
< 10 vs. ≥ 10 1.565 1.090 - 2.247 0.017*
Tumor size (cm.)
< 5 vs. ≥ 5 0.621 0.410 - 0.875 0.008*
Histology
SCCA vs. non-SCCA 0.62 0.408 - 0.968 0.035*
PSW involvement
One side vs. Both sides 0.691 0.478 - 0.998 0.049*
Treatment modality
RT alone vs. CCRT 1.852 1.290 - 2.725 0.001*

Abbreviations: HR = hazard ratio, CI = confidence interval

For the secondary endpoint, the 5-year LC was 71.4%. Predictive factors for better LC from the univariable analysis were age ≥50 vs. <50 years (78.3% vs. 58.5%, p-value = 0.002), pre-treatment Hb ≥10 vs. <10 g/dL (79.5% vs. 46.0%, p-value <0.001), histology of SCCA vs. non-SCCA (76.8% vs.45.6%, p-value <0.001), and tumor size <5 vs. ≥5 cm (85.8% vs.60.2%, p-value<0.001) (Figure 2 and Table 4).

Factors N 5-year local control (%) Median time to recurrence (mo.) p-value
1. Age (years) < 50 84 58.5 - 0.002*
≥ 50 145 78.3 -
2. Pre-treatment Hb (g/dL) < 10 74 46 58.2 <0.001*
≥ 10 155 79.5 -
3. Tumor size (cm.) < 5 91 85.8 - <0.001*
≥ 5 134 60.2 -
4. Histology SCCA 191 76.8 - <0.001*
Non-SCCA 38 45.6 16.5
5. PSW involvement One side 86 74.7 - 0.098
Both sides 142 70.5 -
6. Treatment modality RT alone 111 66 - 0.43
CCRT 117 75.7 -
7. Point A dose (Gy) < 85 41 73.4 - 0.72
≥ 85 188 70.9 -
8. Parametrial boost No 94 70.8 - 0.834
Yes 135 71.4 -
9. OTT (days) < 56 11 88.9 - 0.216
≥ 56 218 70.5 -

The Cox proportional hazard model for multivariable analysis showed that all previously mentioned factors were significant predictors for better LC with the adjusted HR of 2.379 (age <50 vs.≥50 years; 95%CI 1.230-4.602, p-value =0.010), 1.896 (pre-treatment Hb <10 vs. ≥10 g/dL; 95%CI 1.054-3.408, p-value=0.033), 0.398 (tumor size <5 vs. ≥5 cm; 95%CI 0.194-0.817, p-value = 0.012) and 0.313 (histology of SCCA vs. non-SCCA; 95%CI 0.170-0.576, p-value=<0.001), respectively (Table 5).

Factors Adjusted HR 95% CI p-value
Age (years)
< 50 vs. ≥ 50 2.379 1.230 - 4.602 0.010*
Pre-treatment Hb (g/dL)
< 10 vs. ≥ 10 1.896 1.054 - 3.408 0.033*
Tumor size (cm.)
< 5 vs. ≥ 5 0.398 0.194 - 0.817 0.012*
Histology
SCCA vs. non-SCCA 0.313 0.170 - 0.576 <0.001*

Abbreviations: HR = hazard ratio, CI = confidence interval

<italic id="italic-62b42f4798df4b6b2326cd112fb6d3fd">Toxicity<italic id="italic-ab27da117dde6a08445e2e6883d81eb3"/></italic>

The most common grade 3-4 complications were gastrointestinal toxicities (11.35%), such as diarrhea and radiation proctitis. No grade 4 hematologic toxicity occurred in CCRT patients. One patient had a severe urinary tract infection. Small bowel obstruction occurred in one patient who received CCRT with bilateral parametrial EBRT boost. Grade 4 radiation proctitis happened in one patient who received CCRT (EQD2 radiation dose at point A was 93.2 Gy) (Table 6).

Toxicity Grade
3 4 5
Gastrointestinal toxicity 24 2 0
Genitourinary toxicity 4 1 0
Skin toxicity 4 0 0
Hematologic toxicity 4 0 0

Remark: Toxicities stratified by grading from both CCRT and RT alone groups

Discussion

This single-institution retrospective study of exclusive FIGO stage IIIB cervical cancer provided evidence that pre-treatment Hb, tumor size, histology, pelvic wall involvement, and CCRT were key predictors for overall survival. As for local control, age, pre-treatment Hb, tumor size, and histology were predictive factors.

The 5-year OS rate in this study was 41.9%, which was similar to the literature [7-11]. This study used the 2009 FIGO clinical staging at the time of the study, which may include stage IIIC patients as of the 2018 FIGO staging in the analysis. However, the survival in this study was almost identical to the study by Wright et al., which performed a prognostic performance comparing the 2009 and 2018 FIGO clinical staging. The literature found that the 2009 FIGO stage IIIB had a 5-year OS rate of 38.4% (37.2–39.6%) while the 2018 FIGO stage IIIB, IIIC1, and IIIC2 were 41.4% (39.9–42.9%), 60.8% (58.7–62.8%), and 37.5% (33.3–41.7%), respectively [10].

Young patients were associated with poor tumor response and higher local recurrence, which may be due to aggressive tumor biology, which was mostly found in the younger age group [12, 13]. Hong et al. documented that the age group of less than forty years correlated with lower tumor response [14]. Similarly, Saibishkumar et al. studied exclusive FIGO stage IIIB cervical cancer and found that an age of more than 50 years was associated with no residual tumor after whole pelvis EBRT [15]. This study also demonstrated poorer local control in the younger age group (<50 years) with an adjusted HR of 2.379, even after adjusting for the CCRT factor. Many studies have demonstrated a correlation between pre-treatment Hb level and overall survival, with the optimal cut point ranging from 10 to 12 g/dL [14, 16-19]. In this study, we demonstrated that a pre-treatment Hb level lower than 10 g/dL was a poor prognostic factor for overall survival (HR = 1.565, 95% CI 1.090 – 2.247, p-value = 0.017).

The larger tumor size was a poor prognostic factor for local control and overall survival in uterine cervical cancer at any stage [17–20]. Kudaka et al. found that squamous cell cervical cancer stage IIIB-IVA (92% IIIB) receiving CCRT had poorer overall survival when the tumor size was greater than 5.5 cm [17]. Similarly, this study found that tumor size less than 5 cm was associated with better overall survival (HR = 0.621, 95% CI 0.410 - 0.875, p-value = 0.008) and local control (HR = 0.398, 95%CI 0.194-0.817, p-value = 0.012).

Regarding pelvic side wall involvement, unilateral invasion was a better prognostic factor for overall survival compared to bilateral invasion (HR = 0.691, 95% CI 0.478-0.998, p-value = 0.049), which was similar to previous literature reporting that bilateral PSW extension had poorer OS than one side in uterine cervical cancer stage IIIB [19, 21]. This finding offered valuable clinical insight, which was often overlooked even in the current staging system.

Several trials showed better survival of SCCA than adenocarcinoma only in early-stage cervical cancer [13, 22, 23]. However, the number of patients with stage IIIB in those trials was very few (5.3% and 16.0% of patients in Kilgore et al. and Kleine et al. studies respectively). A study from Katanyoo et al. analyzing stage IIIB/IVA uterine cervical cancer (168 patients) also showed no survival difference between SCCA and adenocarcinoma in subgroup of stage IIIB/IVA [24]. Rose PG et al. retrospectively analyzed cervical cancer stage IB2-IVA demonstrating that adenocarcinoma and adenosquamous cell carcinoma had worse OS and PFS in RT alone group but similar in the platinum-based CCRT compared to SCCA group [25]. A recent retrospective study of Yokoi et al. in IB-IVA cervical cancer treated with both RT alone and CCRT with weekly nedaplatin showed that adenocarcinoma group had worse OS and PFS [26]. In this study, only stage IIIB was analyzed and the result showed statistically significant poorer OS and LC in non- SCCA group (mostly adenocarcinoma).

As for the overall survival, we found that only CCRT had statistically significant impact. This study showed that RT alone was a negative prognostic factor for OS with HR 1.852 (95%CI 1.290 – 2.725, p-value = 0.001).

In contrast to the subgroup analysis in stage III – IVA from Eifel et al., which reported that OS, local failure, and DFS were not different in CCRT compared to RT alone group [27]. However, a retrospective analysis of stage IIIB cervical cancer from Kuroda et al. reported that receiving CCRT was a good significant prognostic factor [28]. CCRT remains the standard of care in stage IIIB unless contraindicated. Prior literature had shown that the survival and local control outcomes would decrease if the OTT was more than 56 days [29-32]. Nevertheless, we found that the OS and LC rates were not statistically different between the 2 groups of OTT (p-value = 0.628 for OS and 0.216 for LC). However, this study could not effectively evaluate the impact of treatment delay due to most patients had prolonged OTT (N = 218), and only 11 patients had achieved OTT less than 56 days. The major cause of prolonged OTT in this study was the limitation in brachytherapy resources and the long waiting list. Therefore, this study could not evaluate the OTT impact effectively. Completion of EBRT plus ICBT within 56 days remains the standard of care.

The radiation dose at point A of 85-90 Gy (EQD2) was recommended in NCCN, ABS, and ASTRO guidelines for advanced-stage cervical cancer [6, 33, 34]. We used the cut point of 85 Gy and found that escalating point A dose over 85Gy did not show OS and LC benefit similar to the retrospective study from Saibishkumar et al. showing no survival difference even escalated point A dose more than 80 Gy [15].

According to parametrial boost, we found no benefit of LC with external beam parametrial boost, which was similar to Rajasooriyar et al. study documenting that parametrial boost after EBRT did not add benefit in pelvic control [35]. However, to define pelvic recurrence, the follow-up diagnostic imagings were not routinely done due to limited resource circumstances. We performed routine post-treatment per vaginal examination, per rectal examination, and pap smear. Cross-sectional imagings would only be done in selected patients in whom recurrence was clinically suspected.

Limitations of this study included inherent selection and information bias due to its retrospective design. Performance status could not be assessed properly. Lymph node involvement could not be systematically evaluated in the absence of routine pre-treatment cross-sectional imaging. The OTT could not be prospectively controlled. Recurrence was primarily monitored via clinical examination, cytology, and confirmed with pathology, without routine cross-sectional imaging, which may have potentially underestimated subclinical relapse and reflected real-world resource constraints.

In conclusion, in FIGO stage IIIB cervical cancer treated with EBRT plus HDR-ICBT, higher pre-treatment hemoglobin, smaller tumor size, squamous histology, unilateral pelvic wall involvement, and receipt of CCRT independently predict better survival. Optimizing these factors, where possible, should be the focus of clinical efforts to improve patient outcomes.

Declarations

Clinical trial registration

Not applicable

Conflicts of interest/Competing interests

The authors declared no conflict of interest.

Availability of data and material

The data used for this study are not available due to patient confidentiality.

Code availability

Not applicable

Authors’ contributions

SK and MP contributed to the conception and supervision. NK contributed to data collection and primary drafting of the manuscript. NS, KT, CS, and SL contributed to formal analysis, data visualization, and resources. YN contributed to project administration. All authors approved the final version for submission.

Ethics approval

The protocol of this study was approved by the Center for Ethics in Human Research, Khon Kaen University (Ref. No: HE601019).

Consent to participate

Not applicable.

Consent for publication

Not applicable

Originality Declaration for Figures

All figures included in this manuscript are original and have been created by the authors specifically for the purposes of this study. No previously published or copyrighted images have been used. The authors confirm that all graphical elements, illustrations, and visual materials were generated from the data obtained in the course of this research or designed uniquely for this manuscript.

Acknowledgments

The author would like to express sincere gratitude to all our staff for their support and share the cases that made this study possible.

Declaration on generative AI and AI-assisted technologies in the writing process

This article was edited with the assistance of a generative AI tool for proofreading and grammatical corrections. All original content, research, and conclusions are the work of the authors.

References 05 04 2021 10.1002/ijc.33588 Ferlay J Colombet M Soerjomataram I Parkin DM Piñeros M Znaor A Bray F International Journal of Cancer Cancer statistics for the year 2020: An overview 3 05 209-249 71 2021 10.3322/caac.21660 Sung H Ferlay J Siegel RL Laversanne M Soerjomataram I Jemal A Bray F CA: a cancer journal for clinicians Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries 3 06 322-329 5 2025 10.1016/j.jncc.2024.11.006 Wu J Jin Q Zhang Y Ji Y Li J Liu X Duan H et al Journal of the National Cancer Center Global burden of cervical cancer: current estimates, temporal trend and future projections based on the GLOBOCAN 2022 2 05 97-98 125 2014 10.1016/j.ijgo.2014.02.003 FIGO Committee on Gynecologic Oncology International Journal of Gynaecology and Obstetrics: The Official Organ of the International Federation of Gynaecology and Obstetrics FIGO staging for carcinoma of the vulva, cervix, and corpus uteri 1 04 129-135 145 2019 10.1002/ijgo.12749 Bhatla N Berek JS Cuello Fredes M Denny LA Grenman S Karunaratne K Kehoe ST et al International Journal of Gynaecology and Obstetrics: The Official Organ of the International Federation of Gynaecology and Obstetrics Revised FIGO staging for carcinoma of the cervix uteri National Comprehensive Cancer Network. Cervical Cancer (Version 4.2025) [Internet]. [cited 2025 Aug 16]. Available from: https://www.nccn.org/professionals/physician_gls/ pdf/cervical.pdf 4 CD002225 2001 10.1002/14651858.CD002225 Green J. Kirwan J. Tierney J. Symonds P. Fresco L. Williams C. Collingwood M. The Cochrane Database of Systematic Reviews Concomitant chemotherapy and radiation therapy for cancer of the uterine cervix 3 06 203-212 14 2002 10.1053/clon.2002.0076 Lukka H. Hirte H. Fyles A. Thomas G. Elit L. Johnston M. Fung MFK Browman G. Clinical Oncology (Royal College of Radiologists (Great Britain)) Concurrent cisplatin-based chemotherapy plus radiotherapy for cervical cancer--a meta-analysis 22 2 (May-August) 08 72-82 45 2025 Ratanasrithong P Khomphaiboonkij U Thai cancer journal Five years survival rate in cervical cancer patients by stages (FIGO 2018) in National cancer institute of Thailand 1 07 49-57 134 2019 10.1097/AOG.0000000000003311 Wright JD Matsuo K Huang Y Tergas AI Hou JY Khoury-Collado F St Clair CM et al Obstetrics and Gynecology Prognostic Performance of the 2018 International Federation of Gynecology and Obstetrics Cervical Cancer Staging Guidelines 6 1469-1471 11 2010 Pesee M Krusun S Padoongcharoen P Asian Pacific journal of cancer prevention: APJCP High dose rate cobalt-60 afterloading intracavitary therapy for cervical carcinoma in Srinagarind hospital - analysis of survival 6 Pt 1 06 1464-1467 180 1999 10.1016/s0002-9378(99)70038-4 Brewster W. R. DiSaia P. J. Monk B. J. Ziogas A. Yamada S. D. Anton-Culver H. American Journal of Obstetrics and Gynecology Young age as a prognostic factor in cervical cancer: results of a population-based study 2 05 184-190 73 1999 10.1006/gyno.1999.5364 Chen R. J. Lin Y. H. Chen C. A. Huang S. C. Chow S. N. Hsieh C. Y. Gynecologic Oncology Influence of histologic type and age on survival rates for invasive cervical carcinoma in Taiwan 5 913-917 22 1992 10.1016/0360-3016(92)90787-i Hong J. H. Chen M. S. Lin F. J. Tang S. G. International Journal of Radiation Oncology, Biology, Physics Prognostic assessment of tumor regression after external irradiation for cervical cancer 2 05 142-146 79 2006 10.1016/j.radonc.2006.03.016 Saibishkumar EP Patel FD Sharma SC Karunanidhi G Ghoshal S Kumar V Kapoor R Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology Prognostic value of response to external radiation in stage IIIB cancer cervix in predicting clinical outcomes: a retrospective analysis of 556 patients from India 22 12 234 7 2007 10.1186/1471-2407-7-234 Grigiene R Valuckas KP Aleknavicius E Kurtinaitis J Letautiene SR BMC cancer The value of prognostic factors for uterine cervical cancer patients treated with irradiation alone 5 10 916-921 18 2013 10.1007/s10147-012-0457-x Kudaka W Nagai Y Toita T Inamine M Asato K Nakamoto T Wakayama A et al International Journal of Clinical Oncology Long-term results and prognostic factors in patients with stage III-IVA squamous cell carcinoma of the cervix treated with concurrent chemoradiotherapy from a single institution study 2 297-300 8 2007 Pomros P Sriamporn S Tangvoraphonkchai V Kamsa-Ard S Poomphakwaen K Asian Pacific journal of cancer prevention: APJCP Factors affecting survival of cervical cancer patients treated at the radiation unit of Srinagarind Hospital, Khon Kaen University, Thailand 6 695-701 45 2006 10.1080/02841860600833160 Serkies K Badzio A Jassem J Acta Oncologica (Stockholm, Sweden) Clinical relevance of hemoglobin level in cervical cancer patients administered definitive radiotherapy 1 01 12-18 26 2015 10.3802/jgo.2015.26.1.12 Endo D Todo Y Okamoto K Minobe S Kato H Nishiyama N Journal of Gynecologic Oncology Prognostic factors for patients with cervical cancer treated with concurrent chemoradiotherapy: a retrospective analysis in a Japanese cohort 2 298-307 22 Lee HS Moon SR Kim BS Suh CO Kim GE Loh JK Kim DW Cancer Research and Treatment Treatment Results and Prognostic Factors of Radical Radiotherapy in FIGO Stage 3B Cervical Cnacer 1 09 137-153 31 1988 10.1016/0090-8258(88)90281-8 Kilgore L. C. Soong S. J. Gore H. Shingleton H. M. Hatch K. D. Partridge E. E. Gynecologic Oncology Analysis of prognostic features in adenocarcinoma of the cervix 2 11 145-149 35 1989 10.1016/0090-8258(89)90032-2 Kleine W. Rau K. Schwoeorer D. Pfleiderer A. Gynecologic Oncology Prognosis of the adenocarcinoma of the cervix uteri: a comparative study 2 05 292-296 125 2012 10.1016/j.ygyno.2012.01.034 Katanyoo K Sanguanrungsirikul S Manusirivithaya S Gynecologic Oncology Comparison of treatment outcomes between squamous cell carcinoma and adenocarcinoma in locally advanced cervical cancer 2 11 208-212 135 2014 10.1016/j.ygyno.2014.08.018 Rose PG Java JJ Whitney CW Stehman FB Lanciano R Thomas GM Gynecologic Oncology Locally advanced adenocarcinoma and adenosquamous carcinomas of the cervix compared to squamous cell carcinomas of the cervix in gynecologic oncology group trials of cisplatin-based chemoradiation 2 03 e19 28 2017 10.3802/jgo.2017.28.e19 Yokoi E Mabuchi S Takahashi R Matsumoto Y Kuroda H Kozasa K Kimura T Journal of Gynecologic Oncology Impact of histological subtype on survival in patients with locally advanced cervical cancer that were treated with definitive radiotherapy: adenocarcinoma/adenosquamous carcinoma versus squamous cell carcinoma 01 5 03 872-880 22 2004 10.1200/JCO.2004.07.197 Eifel PJ Winter K Morris M Levenback C Grigsby PW Cooper J Rotman M Gershenson D Mutch DG Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology Pelvic irradiation with concurrent chemotherapy versus pelvic and para-aortic irradiation for high-risk cervical cancer: an update of radiation therapy oncology group trial (RTOG) 90-01 4 07 588-593 53 2012 10.1093/jrr/rrs010 Kuroda Y Murakami N Morota M Sekii S Takahashi K Inaba K Mayahara H et al Journal of Radiation Research Impact of concurrent chemotherapy on definitive radiotherapy for women with FIGO IIIb cervical cancer 1 04 69-76 67 2003 10.1016/s0167-8140(02)00439-5 Chen SW Liang JA Yang SN Ko HL Lin FJ Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology The adverse effect of treatment prolongation in cervical cancer by high-dose-rate intracavitary brachytherapy 1 01 36-43 10 2000 10.1016/s1053-4296(00)80019-3 Lanciano R. Seminars in Radiation Oncology Optimizing radiation parameters for cervical cancer 01 1 01 33-48 52 2002 10.1016/s0360-3016(01)01755-2 Nag S Chao C Erickson B Fowler J Gupta N Martinez A Thomadsen B International Journal of Radiation Oncology, Biology, Physics The American Brachytherapy Society recommendations for low-dose-rate brachytherapy for carcinoma of the cervix 30 5 07 1275-1288 32 1995 10.1016/0360-3016(95)00220-S Perez C. A. Grigsby P. W. Castro-Vita H. Lockett M. A. International Journal of Radiation Oncology, Biology, Physics Carcinoma of the uterine cervix. I. Impact of prolongation of overall treatment time and timing of brachytherapy on outcome of radiation therapy 3 12 607-610 159 2020 10.1016/j.ygyno.2020.09.015 Chino J Annunziata CM Beriwal S Bradfield L Erickson BA Fields EC Fitch J et al Gynecologic Oncology The ASTRO clinical practice guidelines in cervical cancer: Optimizing radiation therapy for improved outcomes 1 47-52 11 2012 10.1016/j.brachy.2011.07.002 Viswanathan AN Beriwal S De Los Santos JF Demanes DJ Gaffney D Hansen J Jones E et al Brachytherapy American Brachytherapy Society consensus guidelines for locally advanced carcinoma of the cervix. Part II: high-dose-rate brachytherapy 9 11 1532-1537 22 2012 10.1097/IGC.0b013e31826c4dee Rajasooriyar C Van Dyk S Lindawati M Bernshaw D Kondalsamy-Chennakesavan S Narayan K International Journal of Gynecological Cancer: Official Journal of the International Gynecological Cancer Society Reviewing the role of parametrial boost in patients with cervical cancer with clinically involved parametria and staged with positron emission tomography