Abstract
Objective
This study aimed to investigate the impact of bladder volume on dosimetric outcomes of organs at risk (OARs) in postoperative volumetric-modulated arc therapy (VMAT) for patients with cervical cancer.
Methods
The study included 71 cervical cancer patients who received radical hysterectomy and postoperative VMAT between January 2020 and January 2023. Patients were divided into 3 groups according to average bladder volume observed in computed tomography simulation positioning images: Group A (<300 mL), Group B (300–500 mL), and Group C (≥500 mL). The study compared dosimetric parameters(V30, V40, V45, and D2cc) for OARs like the bladder, rectum, small intestine, and sigmoid colon, as well as the incidence of radiation cystitis and proctitis among these groups.
Results
The median follow-up of the cohort was 33 months, with a median patient age of 48 years. Group A demonstrated the highest V40 and V45 values for the bladder (p<0.05). Conversely, Group C displayed the highest values for the V40 and V45 of the rectum, as well as the V45 and D2cc of the sigmoid colon (p<0.05). No statistically significant differences were observed in the incidence of acute radiation cystitis and radiation cystitis among the 3 groups. Significant difference was observed in the incidence rates of late radiation cystitis (p<0.05) and radiation proctitis (p<0.05) among the 3 groups. Group A exhibited the highest prevalence of late radiation cystitis, whereas Group C demonstrated the highest prevalence of late radiation proctitis.
Conclusion
Bladder volume significantly affects dosimetry of the bladder, rectum, and sigmoid colon in postoperative VMAT for cervical cancer patients. A recommended bladder volume of 300–500 mL helps reduce radiation-induced cystitis and proctitis.
Keywords: Cervical Cancer, Volumetric-Modulated Arc Therapy, Radiation injuries, Cystitis, Proctitis
Synopsis
Bladder volume significantly affects the dosimetric distribution to the bladder, rectum, and sigmoid colon during postoperative volumetric modulated arc therapy for cervical cancer patients. Maintaining an optimal bladder volume within the range of 300–500 mL could reduce the risk of radiation-induced cystitis and proctitis.
INTRODUCTION
Cervical cancer is a widely observed gynecological malignancy, ranking as the second most prevalent malignant tumor of the female reproductive system globally. Recent trends suggest a gradual decrease in the average age of onset of cervical cancer, highlighting a shift towards younger demographics and posing a substantial health risk for women [1]. Surgical intervention is primarily recommended for early-stage cervical cancer, specifically stages IA to IIA. After radical surgery, patients with pathological high-risk factors (such as positive surgical margins, parametrial invasion, and lymph node [LN] metastasis) or intermediate-risk factors (including large tumor size, deep stromal invasion, and lymphatic vascular space involvement) are recommended to undergo adjuvant radiotherapy [2]. This recommendation is further supported by the evolution of radiotherapy towards precision treatment, facilitated by rapid advancements in medical imaging and computer technology. Volumetric-modulated arc therapy (VMAT) represents a novel radiotherapy approach aimed at enhancing the precision of radiation delivery to the tumor site while minimizing radiation exposure to adjacent healthy tissues. This technique has been shown to improve local tumor control rates and decrease the occurrence of normal tissue complications [3]. Following radical surgery for cervical cancer, the proximity of critical organs such as the bladder, rectum, sigmoid colon, and small intestine to the clinical target volume (CTV) necessitates careful consideration to minimize radiation-induced damage during pelvic radiotherapy. This damage subsequently gives rise to radiation-induced complications that have a detrimental effect on patients’ quality of life and may necessitate interruptions in radiotherapy treatment [4].
Currently, regulating bladder volume to a moderate level is a controllable factor that effectively reduces radiation complications by minimizing exposure of organs at risk (OARs) to high-dose radiation. However, despite recommending patients to maintain a consistent bladder filling sensation as during positioning prior to radiotherapy, bladder volume demonstrates notable fluctuations during the treatment regimen. The fluctuation in bladder volume can lead to the positional shift of OARs, causing potential variability in the accurate delivery of radiation dosage to these structures [5]. The impact of bladder volume changes on the dosimetric distribution of OARs (bladder, rectum, sigmoid colon, and small intestine) in external beam radiotherapy for patients with cervical cancer following radical surgery incompletely elucidated.
This study utilized dose-volume histograms (DVHs) generated from volumetric VMAT plans for postoperative cervical cancer to evaluate dosimetric parameters of the bladder and surrounding OARs, and examined the influence of fluctuations in bladder volume on the dosimetric distribution of OARs.
MATERIALS AND METHODS
1. General information
A retrospective analysis was conducted on a cohort of patients who underwent radical surgery followed by radiotherapy at Beijing Obstetrics and Gynecology Hospital, Capital Medical University, between January 2020 and January 2023. The study protocol received approval from the Ethics Committee of Beijing Obstetrics and Gynecology Hospital, Capital Medical University (No. 2024-KY-014-01), and adhered to the principles outlined in the Declaration of Helsinki and Good Clinical Practice Guidelines. Informed consent forms were obtained from all patients who consented to the aforementioned treatment.
2. Inclusion and exclusion criteria
The inclusion criteria for the study consisted of histopathological confirmation of cervical squamous cell carcinoma (SCC), adenocarcinoma, or other types of carcinoma, a Karnofsky Performance Score (KPS) of ≥70, the presence of pathological high-risk factors such as positive surgical margins, parametrial invasion, and LN metastasis, the presence of intermediate-risk factors in postoperative pathology based on the Sedlis criteria for SCC [6] and the “4-factor model” for adenocarcinoma [7], and the availability of complete clinical data. The exclusion criteria included a history of previous pelvic radiotherapy, presence of distant metastasis, allergy to contrast agents, concomitant severe hepatic or renal dysfunction, and severe bone marrow suppression.
3. External beam radiotherapy
Computed tomography (CT) simulation
Before positioning the patient for the CT simulation scanning, the rectum and bladder were emptied one hour prior. Additionally, the patient orally consumed 1,000 mL of warm water mixed with 40 mL of a 60% diatrizoate meglumine solution. The patients were then placed in a supine position and immobilized using a thermoplastic membrane, with their hands placed above their head, while maintaining calm breathing. The CT scanning procedure covered the area from the superior margin of the third lumbar vertebra to a point 5 cm distal to the ischial tuberosity, with a slice thickness of 5 mm. The CT images were imported into the Varian Eclipse (Version 8.6) radiotherapy planning system workstation. Throughout subsequent radiation sessions, patients are advised to maintain a consistent bladder holding sensation similar to that experienced during CT simulation (Fig. S1).
Target volume and OAR delineation
The delineation of target volumes adhered to the Radiation Therapy Oncology Group consensus guidelines published in 2008 and 2021 for delineating the CTV for intensity-modulated pelvic radiation therapy in the postoperative treatment of cervical cancer [8,9]. The CTV included the vaginal cuff, partial vagina, paravaginal and parametrial soft tissues, as well as areas of pelvic LN drainage (common iliac, external iliac, internal iliac, presacral, and obturator), with the possibility of extending to the para-aortic LN drainage region in instances necessitating extended field irradiation. The delineation of LN drainage regions in the common iliac, external iliac, and internal iliac involved outlining a 7 mm perivascular space surrounding the pelvic vessels, while excluding muscle and bone structures. The boundaries of the obturator region were defined as a tissue strip extending 18 mm inward from the pelvic wall, connecting the soft tissue space between the internal and external iliac arteries. The presacral region was identified as a tissue strip extending at least 10 mm from the anterior border of the S1–S2 sacrum. The CTV for the vaginal cuff should encompass the posterior aspect of the anterior rectal wall, including approximately one-third of the mesorectum. The anterior boundary of the CTV for the vaginal cuff was specified as the posterior aspect of the bladder wall. If the CTV encompassed the small intestine or sigmoid colon, these structures would not be excluded in order to preserve a 7 mm margin around the blood vessels. Considering setup error and organ motion, the resulting planning target volume (PTV) demonstrated a 10 mm expansion superiorly and inferiorly, a 5mm expansion laterally, a 7 mm expansion posteriorly, and a 5 mm expansion anteriorly, with an additional 10 mm outward extension in the vaginal cuff region. OARs included in this study were the bladder, rectum, small intestine, sigmoid colon, pelvic bones, femoral heads, and spinal cord, with margins extending 10 mm above and below the PTV.
Treatment planning
All participants underwent VMAT planning using the Varian Eclipse radiotherapy planning system. This entailed the utilization of dual-arc plans, with one arc encompassing a counterclockwise rotation of 179° to 181° and the other arc covering a clockwise rotation of 181° to 179°. The X-ray energy utilized was 6 MV, and the maximum dose rate administered was 600 MU/min. Following the protocols established by the National Comprehensive Cancer Network, external beam radiation therapy (EBRT) was commonly prescribed at a dose of 45 Gy/25 fractions, administered daily over 5 days per week. The radiotherapy treatment plans were devised by a senior physicist using the Anisotropic Analytic Algorithm to enhance the precision of dose distribution. The planning criteria for VMAT were specified as follows: (1) Ensuring that 100% of the prescribed dose covers 95% of the PTV; (2) Limiting the volume of the PTV receiving doses exceeding 110% of the prescription dose to less than 1%; (3) Ensuring the absence of cold spots within the PTV and detecting no hot spots on the posterior wall of the rectum and anterior wall of the bladder. The dose constraints for OARs were defined as bladder V40 <50%, rectum V40 <50%, small intestine V30 <40%, sigmoid colon V40 <50%, femoral heads V45 <5%, and a maximum allowable dose to the spinal cord (Dmax) of less than 40 Gy.
Evaluation of dosage parameters
Patients were stratified into 3 cohorts based on their average bladder volume as observed in CT simulation positioning images: Group A (<300 mL), Group B (300–500 mL), and Group C (≥500 mL). Utilizing the Eclipse planning system, dose parameters were derived through the assessment of radiotherapy plans using DVHs and isodose curves. The investigation yielded dose parameters for OARs, encompassing bladder and rectum volumes, as well as V30, V40, V45, and D2cc values for the bladder, rectum, sigmoid colon, and small intestine. Fig. S1 displays a representative isodose distribution commonly observed in external beam radiotherapy treatments.
Concurrent chemoradiotherapy
All patients underwent treatment with a Varian linear accelerator (Varian, Palo Alto, CA, USA) and positional verification was conducted using cone-beam computed tomography (CBCT). Verification was initially performed continuously for the first 5 sessions and then weekly thereafter. Concurrent cisplatin chemotherapy was administered at a weekly dose of 30–40 mg/m2 during radiotherapy. Chemotherapy administration was temporarily halted if the white blood cell count dropped below 3.0×109/L or the platelet count fell below 100×109/L.
4. Intracavitary brachytherapy
Following EBRT, intracavitary brachytherapy was administered using image-guided 3-dimensional brachytherapy with high-dose rate 192Ir, delivering 10 Gy in 2 fractions to all patients.
Follow-up and assessment of toxicities
Patients were monitored at regular intervals following the completion of treatment, with follow-up appointments scheduled every 3 months during the initial 2 years, every 6 months from years 3 to 5, and annually thereafter. These follow-up assessments included gynecological examinations, measurement of SCC antigen, and enhanced chest and abdominal CT scans. Toxicities were evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE Version 5.0) [10].
5. Statistical analysis
Statistical analysis was conducted utilizing SPSS 22.0 software (IBM Corp., Armonk, NY, USA). Measurement data were expressed as mean ± standard deviation. Baseline characteristics, such as age, KPS, International Federation of Gynecology and Obstetrics (FIGO) stage, pelvic LN metastasis, and bladder volume, were assessed for intergroup variances utilizing t-tests or χ2 tests. The study analyzed doses to OARs, including the bladder, rectum, sigmoid colon, and small intestine, across various bladder volume groups through one-way analysis of variance (ANOVA), followed by pairwise comparisons utilizing the LSD-t method. Fisher’s exact test or χ2 test was employed to assess the incidence rates of radiation cystitis and radiation proctitis. A significance level of p<0.05 was deemed statistically significant.
RESULTS
1. Patient characteristics
A cohort of 71 patients who underwent radical hysterectomy for cervical cancer were enrolled in the study, with ages ranging from 29 to 73 years and a median age of 48 years. The distribution of staging was as follows: IB2 stage was present in 32 cases, IB3 stage in 13 cases, IIA1 stage in 10 cases, IIA2 stage in 7 cases, IIIC1p stage in 8 cases, and IIIC2p stage in 1 case. Pathological types included SCC in 55 cases, adenocarcinoma in 9 cases, and other types in 7 cases.
The cohort of 71 patients was stratified into 3 groups based on average bladder volume as determined from localization CT images: Group A (n=16) with <300 mL, Group B (n=39) with 300–500 mL, and Group C (n=16) with ≥500 mL. A statistically significant difference in bladder volume was observed among the 3 groups (p<0.001). However, no statistically significant differences were found in age, FIGO stage, pathological type, and pelvic LN metastasis among the groups (p>0.05), indicating comparability, as illustrated in Table S1.
2. Analysis of cumulative dose to OARs
Comparison of bladder dose distribution
An ANOVA was utilized to compare bladder dosimetric parameters (V30, V40, V45, and D2cc) across varying bladder volume cohorts. The findings revealed that there was no statistically significant discrepancy in bladder V30 among the 3 groups (p>0.05). Additionally, bladder V40 in Group A exhibited a significantly greater value compared to Group B (p<0.01), while bladder V45 in Group A surpassed the values observed in Groups B and C, with statistically significant variances (p<0.05); The bladder D2cc in Group A exhibited a statistically significant decrease compared to Group C, with a significance level of p<0.05. Detailed comparative dose distributions among the various groups can be found in Table S2 and Fig. 1.
Fig. 1. Comparison of bladder dose distribution in different bladder volume groups.
ns, no statistical difference.
*The p-value less than 0.05; **The p-value less than 0.01.
Comparison of rectum dose distribution
An ANOVA was employed to assess the variations in rectum dosimetric parameters (V30, V40, V45, and D2cc) across distinct bladder volume cohorts. The findings revealed that there was no statistically significant variance in rectum V30 among the 3 groups (p>0.05). Additionally, rectum V40 in Group A exhibited a statistically significant decrease compared to Group C (p<0.05), while rectum V45 in Groups A and B both demonstrated statistically significant reductions relative to Group C (p<0.05). The mean rectum D2cc in Group A was found to be significantly lower than that in Group C, with a statistical significance level of p<0.05. Detailed comparative dose distributions among the various groups can be observed in Table S3 and Fig. 2.
Fig. 2. Comparison of rectum dose distribution in different bladder volume groups.
ns, no statistical difference.
*The p-value less than 0.05; **The p-value less than 0.01.
Comparison of sigmoid colon dose distribution
An ANOVA analysis was utilized to compare the dosimetric parameters (V30, V40, V45, and D2cc) of the sigmoid colon across varying bladder volume groups. The findings revealed that there was no significant variance in sigmoid colon V30 and V40 among the groups (p>0.05). However, both sigmoid colon V45 and D2cc were significantly lower in Groups A and B compared to Group C (p<0.05). The comparative dose distributions among the various groups are displayed in Table S4 and Fig. 3.
Fig. 3. Comparison of sigmoid colon dose distribution in different bladder volume groups.
ns, no statistical difference.
*The p-value less than 0.05; **The p-value less than 0.01.
Comparison of small intestine dose distribution
An ANOVA was performed to assess the differences in small intestine dosimetric parameters (V30, V40, V45, and D2cc) across various bladder volume categories. The findings indicated that there were no statistically significant variances in small intestine V30, V40, V45, and D2cc among the 3 groups (p>0.05). The comparative dose distributions for the distinct groups are illustrated in Table S5 and Fig. 4.
Fig. 4. Comparison of small intestine dose distribution in different bladder volume groups.
ns, no statistical difference.
3. Analysis of the risk of radiation cystitis and radiation proctitis
There were no statistically significant differences observed among the 3 groups in the incidence of acute radiation cystitis and radiation cystitis (all p>0.05) (Table 1). To thoroughly evaluate the effects of different bladder filling volumes on late toxicity in OARs, all participants in this research were monitored for a minimum of one year. The study was concluded with a follow-up deadline of March 2024, with a median follow-up period of 33 months (range: 14–47 months) and a follow-up compliance rate of 100%. Group A displayed the highest occurrence of late radiation cystitis, while Group C exhibited the highest occurrence of late radiation proctitis. In contrast, Group B showed lower prevalence rates of both late radiation cystitis and proctitis compared to the other groups (all p<0.05) (Table 2).
Table 1. Acute toxicities among patients with different bladder volume groups.
| Group | No. | Radiation cystitis | Radiation proctitis | ||||
|---|---|---|---|---|---|---|---|
| Degree I | Degree II | Degree III | Degree I | Degree II | Degree III | ||
| A | 16 | 5 (31.25) | 1 (6.25) | 0 (0.00) | 7 (43.75) | 2 (12.50) | 0 (0.00) |
| B | 39 | 12 (30.76) | 3 (7.69) | 0 (0.00) | 16 (41.03) | 5 (12.82) | 0 (0.00) |
| C | 16 | 5 (31.25) | 1 (6.25) | 0 (0.00) | 6 (37.50) | 2 (12.50) | 0 (0.00) |
| p-value | 0.998 | 0.937 | |||||
Values are presented as number (%).
Table 2. Comparison of late toxicities among different bladder volume groups.
| Group | No. | Radiation cystitis | Radiation proctitis | ||||
|---|---|---|---|---|---|---|---|
| Degree I | Degree II | Degree III | Degree I | Degree II | Degree III | ||
| A | 16 | 6 (37.50) | 2 (12.50) | 0 (0.00) | 3 (18.75) | 1 (6.25) | 0 (0.00) |
| B | 39 | 4 (10.25) | 1 (2.56) | 0 (0.00) | 5 (12.82) | 1 (2.56) | 0 (0.00) |
| C | 16 | 5 (31.25) | 1 (2.56) | 0 (0.00) | 6 (37.50) | 2 (12.50) | 0 (0.00) |
| p-value (Fisher) | 0.010* | 0.026* | |||||
Values are presented as number (%).
*The p-value less than 0.05.
DISCUSSION
Radiotherapy is essential in the management of cervical cancer, particularly with the advent of advanced techniques such as intensity-modulated radiation therapy (IMRT), image-guided radiation therapy, and tomotherapy [11,12,13]. Several clinical studies have confirmed the effectiveness of IMRT technology in cervical cancer for improving the delivery of doses to target areas, reducing acute and chronic radiation-induced side effects, and improving long-term survival rates [13,14,15]. The successful implementation of precision radiotherapy requires strict adherence to consistent patient positioning, accurate alignment of target areas and OARs with the radiation treatment plan, and the maintenance of optimal bladder filling by patients before treatment to reduce bladder radiation exposure and protect the small intestine. This study demonstrates that bladder volume significantly influences the dosimetric distribution of the bladder, rectum, and sigmoid colon in VMAT in patients with cervical cancer after radical hysterectomy. A bladder volume ranging from 300–500 mL is correlated with a decreased risk of radiation-induced cystitis and proctitis, making it the recommended threshold for optimal outcomes in cervical cancer radiotherapy.
In the context of postoperative EBRT for cervical cancer, the anatomical proximity of the bladder and rectum to the vaginal stump in a specialized location results in the occurrence of radiation-induced cystitis and proctitis. The positioning of the bladder and rectum, as pelvic hollow organs, is subject to notable alteration based on the bladder’s filling status [16,17]. However, it remains difficult to consistently achieve optimal bladder filling prior to each pelvic radiotherapy session, even when following strict bladder training protocols, due to potential fluctuations in bladder volume resulting from individual patient physiology and health status [18]. Jhingran et al. [19] conducted a study on bladder volume variations in 24 cervical cancer patients undergoing IMRT, revealing a median difference of 247 cm3 between the maximum and minimum bladder volumes during treatment, highlighting the considerable variability in bladder volume. Chen et al. [20] utilized CBCT technology to examine variations in bladder volume throughout IMRT for cervical cancer. The study identified bladder volume ranges of 41–93 cm3, 48–134 cm3, and 100–208 cm3 for the empty bladder, non-empty bladder, and bladder filling indicator groups, respectively. Despite the administration of bladder filling instructions, the research results suggest that maintaining a consistent bladder volume during radiotherapy for cervical cancer remains a challenging. Furthermore, the increased frequency of radiotherapy treatments leads to higher bladder radiation doses, causing localized radiation-induced injury and the gradual development of symptoms associated with radiation cystitis, including urinary frequency, urgency, painful urination, and decreased bladder capacity, ultimately leading to a reduction in bladder volume [21]. Research on uncertainties in target volumes and OARs is currently a focal point in studies on IMRT.
The bladder is centrally located within the pelvis in terms of its anatomical position, forming a concave-shaped layout with CTV, and changes in bladder filling status can alter bladder position, thereby affecting the dose received by OARs [22]. A meta-analysis was conducted to examine the effects of various bladder filling states on the doses received by normal tissues during brachytherapy treatment for cervical cancer. The analysis incorporated data from 6 studies involving a total of 135 patients. The results suggest that bladder and rectal doses were lower with a filled bladder compared to an empty bladder, while the results for the rectum and sigmoid colon were the opposite [23]. Lv et al. [24] conducted a study to examine the impact of bladder filling status on bladder dose parameters in 16 cervical cancer patients undergoing external beam IMRT. The results showed that bladder V40 and V50 were significantly lower when the bladder was filled compared to when it was empty. The findings of our study indicate that bladder volumes of 300–500 mL have the least side effects on the rectum and bladder during external beam IMRT after radical hysterectomy for cervical cancer. As the volume of the bladder gradually increases, it shifts anteriorly, thereby moving further away from the targeted irradiation area. Therefore, when bladder volume is less than 300 mL, bladder V40 and V45 are higher. Conversely, as bladder volume increases, the position of the vaginal stump moves posteriorly, causing the rectum to be relatively closer to the high-dose area of the vaginal stump. Consequently, when bladder volume is more than 500 mL, rectal V40 and V45 are higher. With an increase in bladder filling, sigmoid colon V45 and D2cc are highest when bladder volume is more than 500 mL. One potential explanation for this phenomenon is that following radical surgery for cervical cancer, the removal of pelvic organ structures results in the bladder occupying a significant portion of the anterior space within the pelvic cavity. Consequently, the sigmoid colon may shift towards the posterior region of the pelvic cavity, leading to an increase in the volume of the sigmoid colon within the irradiation target area. The findings of our study suggest that the distribution of dose parameters in the small intestine is not affected by bladder filling status, which contradicts prior research indicating that bladder filling decreases small intestine doses [25,26]. Consequently, there is ongoing debate surrounding the impact of bladder filling status on OARs dose distribution in IMRT for cervical cancer.
This study investigates the delayed toxic effects of radiation-induced cystitis and proctitis, highlighting the impact of variations in bladder volume on rectal and bladder doses and functions, a common occurrence. The study found incidence rates of 26.76% for radiation cystitis and 25.35% for proctitis, with no occurrences of grade III or higher late toxicities, likely attributable to the utilization of advanced VMAT techniques. The study revealed a positive correlation between bladder volume less than 300 mL and the highest incidence of radiation cystitis, as evidenced by increased bladder V40 and V45. Conversely, bladder volume exceeding 500 mL was associated with the highest rates of radiation proctitis, indicated by elevated rectal V40 and V45. Within the range of 300 to 500 mL bladder volume, the occurrence of radiation-induced cystitis and proctitis was relatively low. Currently, there is a dearth of universally acknowledged guidelines regarding the most suitable bladder filling levels. The findings of this research suggest that maintaining a bladder volume of 300–500 mL is advisable for post-radical hysterectomy external beam radiotherapy, as it can improve patient comfort and adherence, as well as decrease doses to critical organs and the occurrence of radiation-induced toxicities.
However, it is important to acknowledge the limitations of this study, including its retrospective design and small sample size. Prospective clinical trials are needed to validate the findings of the results. Additionally, the study focuses solely on the relationship between bladder volume and the distribution of doses to OARs, indicating that bladder volume plays a significant role in the development of radiation-induced cystitis and/or proctitis. Due to the limitation of sample size, other factors such as rectum and sigmoid colon volumes were not examined in this study. During the study, patients were instructed to achieve rectal emptying prior to each radiotherapy session in order to promote a more consistent rectal volume. Further study is needed on this topic.
In conclusion, bladder volume significantly affects the dosimetric distribution of the bladder, rectum, and sigmoid colon in postoperative VMAT for patients with cervical cancer. A bladder volume range of 300–500 mL is recommended as the threshold for postoperative radiation in this population for a lower incidence of radiation-induced cystitis and proctitis.
Footnotes
Funding: The present study was supported by the Beijing Hospitals Authority Clinical Medicine Development of special funding support (Code: ZYLX201705), Beijing Municipal Science Technology and Commission (No. Z191100006619035), and Beijing Hospitals Authority’s Ascent Plan (Code: DFL20221201).
Conflict of Interest: No potential conflict of interest relevant to this article was reported.
- Conceptualization: W.M., Z.L.
- Data curation: W.Y.
- Formal analysis: W.Y.
- Methodology: W.Y., W.M.
- Supervision: Z.L.
- Writing - original draft: W.Y.
- Writing - review & editing: W.M., Z.L.
SUPPLEMENTARY MATERIALS
Comparison of baseline characteristics among 3 groups
Analysis of bladder dose distribution among different bladder volume groups
Analysis of rectum dose distribution among different bladder volume groups
Analysis of sigmoid colon dose distribution among different bladder volume groups
Analysis of small intestine dose distribution among different bladder volume groups
Computed tomography image showing isodose curves during external beam radiation therapy of a cervical cancer patient.
References
- 1.Guo M, Xu J, Du J. Trends in cervical cancer mortality in China from 1989 to 2018: an age-period-cohort study and Joinpoint analysis. BMC Public Health. 2021;21:1329. doi: 10.1186/s12889-021-11401-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Chargari C, Peignaux K, Escande A, Renard S, Lafond C, Petit A, et al. Radiotherapy of cervical cancer. Cancer Radiother. 2022;26:298–308. doi: 10.1016/j.canrad.2021.11.009. [DOI] [PubMed] [Google Scholar]
- 3.Thakur N, Kaur H, Kaur S, Lehal P, Sudan M, Jain N, et al. Comparative analysis of VMAT and IMRT techniques: evaluation of dose constraints and bone marrow sparing in cervical cancer patients undergoing chemoradiotherapy. Asian Pac J Cancer Prev. 2024;25:139–144. doi: 10.31557/APJCP.2024.25.1.139. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Mohamadian N, Nasseri S, Hosseini S, Molaie F, Zarifi S, Eskandari A, et al. Dosimetric impact of bladder volume on organs at risk during external beam radiotherapy of cervical cancer. Radiat Prot Dosimetry. 2023;199:1351–1356. doi: 10.1093/rpd/ncad183. [DOI] [PubMed] [Google Scholar]
- 5.Eminowicz G, Motlib J, Khan S, Perna C, McCormack M. Pelvic organ motion during radiotherapy for cervical cancer: understanding patterns and recommended patient preparation. Clin Oncol (R Coll Radiol) 2016;28:e85–e91. doi: 10.1016/j.clon.2016.04.044. [DOI] [PubMed] [Google Scholar]
- 6.Sedlis A, Bundy BN, Rotman MZ, Lentz SS, Muderspach LI, Zaino RJ. A randomized trial of pelvic radiation therapy versus no further therapy in selected patients with stage IB carcinoma of the cervix after radical hysterectomy and pelvic lymphadenectomy: a Gynecologic Oncology Group study. Gynecol Oncol. 1999;73:177–183. doi: 10.1006/gyno.1999.5387. [DOI] [PubMed] [Google Scholar]
- 7.Ryu SY, Kim MH, Nam BH, Lee TS, Song ES, Park CY, et al. Intermediate-risk grouping of cervical cancer patients treated with radical hysterectomy: a Korean Gynecologic Oncology Group study. Br J Cancer. 2014;110:278–285. doi: 10.1038/bjc.2013.716. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Small W, Jr, Bosch WR, Harkenrider MM, Strauss JB, Abu-Rustum N, Albuquerque KV, et al. NRG oncology/RTOG consensus guidelines for delineation of clinical target volume for intensity modulated pelvic radiation therapy in postoperative treatment of endometrial and cervical cancer: an update. Int J Radiat Oncol Biol Phys. 2021;109:413–424. doi: 10.1016/j.ijrobp.2020.08.061. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Small W, Jr, Mell LK, Anderson P, Creutzberg C, De Los Santos J, Gaffney D, et al. Consensus guidelines for delineation of clinical target volume for intensity-modulated pelvic radiotherapy in postoperative treatment of endometrial and cervical cancer. Int J Radiat Oncol Biol Phys. 2008;71:428–434. doi: 10.1016/j.ijrobp.2007.09.042. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Freites-Martinez A, Santana N, Arias-Santiago S, Viera A. Using the Common Terminology Criteria for Adverse Events (CTCAE - Version 5.0) to evaluate the severity of adverse events of anticancer therapies. Actas Dermosifiliogr (Engl Ed) 2021;112:90–92. doi: 10.1016/j.ad.2019.05.009. [DOI] [PubMed] [Google Scholar]
- 11.Faye MD, Alfieri J. Advances in radiation oncology for the treatment of cervical cancer. Curr Oncol. 2022;29:928–944. doi: 10.3390/curroncol29020079. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Cheng YK, Kuo SH, Yen HH, Wu JH, Chen YC, Huang MY. The prognostic significance of pretreatment squamous cell carcinoma antigen levels in cervical cancer patients treated by concurrent chemoradiation therapy and a comparison of dosimetric outcomes and clinical toxicities between tomotherapy and volumetric modulated arc therapy. Radiat Oncol. 2022;17:91. doi: 10.1186/s13014-022-02063-w. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Wang D, Yin Y, Zhou Q, Li Z, Ma X, Yin Y, et al. Dosimetric predictors and Lyman normal tissue complication probability model of hematological toxicity in cervical cancer patients with treated with pelvic irradiation. Med Phys. 2022;49:756–767. doi: 10.1002/mp.15365. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Chopra S, Gupta S, Kannan S, Dora T, Engineer R, Mangaj A, et al. Late toxicity after adjuvant conventional radiation versus image-guided intensity-modulated radiotherapy for cervical cancer (PARCER): a randomized controlled trial. J Clin Oncol. 2021;39:3682–3692. doi: 10.1200/JCO.20.02530. [DOI] [PubMed] [Google Scholar]
- 15.Raina P, Singh S. Comparison between three-dimensional conformal radiation therapy (3DCRT) and intensity-modulated radiation therapy (IMRT) for radiotherapy of cervical carcinoma: a heterogeneous phantom study. J Biomed Phys Eng. 2022;12:465–476. doi: 10.31661/jbpe.v0i0.2101-1257. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Figueredo Negron CI, Gamboa Garay O, Pabón Girón A, Esguerra Cantillo JA, Guerrero Lizcano E. A comparison of intensity-modulated radiotherapy with simultaneous integrated boost with three-dimensional conformal radiotherapy with sequential boost for locally advanced cervical cancer: a dosimetric study. Cureus. 2022;14:e32940. doi: 10.7759/cureus.32940. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Yang H, Zhao X, He Y, Tan X, Peng H, Zhong M, et al. Dosimetric impacts of cone-beam computed tomography (CBCT)-based anatomic changes in intensity-modulated radiotherapy for cervical cancer. Ann Transl Med. 2022;10:1381. doi: 10.21037/atm-22-6157. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Li X, Wang L, Cui Z, Li Y, Liu P, Wang Y, et al. Correction to: online MR evaluation of inter- and intra-fraction uterus motions and bladder volume changes during cervical cancer external beam radiotherapy. Radiat Oncol. 2021;16:200. doi: 10.1186/s13014-021-01922-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Jhingran A, Salehpour M, Sam M, Levy L, Eifel PJ. Vaginal motion and bladder and rectal volumes during pelvic intensity-modulated radiation therapy after hysterectomy. Int J Radiat Oncol Biol Phys. 2012;82:256–262. doi: 10.1016/j.ijrobp.2010.08.024. [DOI] [PubMed] [Google Scholar]
- 20.Chen VE, Gillespie EF, Manger RP, Skerritt LA, Tran JH, Proudfoot JA, et al. The impact of daily bladder filling on small bowel dose for intensity modulated radiation therapy for cervical cancer. Med Dosim. 2019;44:102–106. doi: 10.1016/j.meddos.2018.02.010. [DOI] [PubMed] [Google Scholar]
- 21.Wang Y, Zhu Y, Xu X. Advances in the management of radiation-induced cystitis in patients with pelvic malignancies. Int J Radiat Biol. 2023;99:1307–1319. doi: 10.1080/09553002.2023.2181996. [DOI] [PubMed] [Google Scholar]
- 22.Shah M, Agarwal S, Agarwal R, Subramanian B, Gupta S, De S, et al. Observational study of cone beam computed tomography based interfractional urinary bladder filling variation during image guided radiation therapy in pelvic malignancies. J Cancer Res Ther. 2021;17:152–156. doi: 10.4103/jcrt.JCRT_626_18. [DOI] [PubMed] [Google Scholar]
- 23.Fu T, Xu W, Xu S, Zhou J, Qin S, Wang L, et al. Effects of different status of the bladder on dosimetry to normal tissue in brachytherapy of cervix cancer: a meta-analysis. Chin J Radiat Oncol. 2016;25:718–723. [Google Scholar]
- 24.Lv Y, Wang F, Yang L, Sun G. Intensity-modulated whole pelvic radiotherapy provides effective dosimetric outcomes for cervical cancer treatment with lower toxicities. Cancer Radiother. 2014;18:745–752. doi: 10.1016/j.canrad.2014.08.005. [DOI] [PubMed] [Google Scholar]
- 25.Patel RB, Gururajachar JM, Revathy T. Implications of bladder volume on target coverage and dose to critical structures during high dose rate intracavitary brachytherapy for cervical cancer: a dosimetric study. J Cancer Res Ther. 2019;15:1207–1211. doi: 10.4103/jcrt.JCRT_253_19. [DOI] [PubMed] [Google Scholar]
- 26.Dutta S, Dewan A, Mitra S, Sharma MK, Aggarwal S, Barik S, et al. Dosimetric impact of variable bladder filling on IMRT planning for locally advanced carcinoma cervix. J Egypt Natl Canc Inst. 2020;32:31. doi: 10.1186/s43046-020-00033-5. [DOI] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Comparison of baseline characteristics among 3 groups
Analysis of bladder dose distribution among different bladder volume groups
Analysis of rectum dose distribution among different bladder volume groups
Analysis of sigmoid colon dose distribution among different bladder volume groups
Analysis of small intestine dose distribution among different bladder volume groups
Computed tomography image showing isodose curves during external beam radiation therapy of a cervical cancer patient.