Dosimetric Difference of Urinary Bladder and Rectum in Patients Undergoing Intracavitary Brachytherapy for Cervical Cancer under Procedural Sedation and General Anesthesia: A Survey at

ABSTRACT


INTRODUCTION
Cervical cancer (CC) is the fourth most frequent cancer in women worldwide and the primary cause of cancer death in women in sub-Saharan Africa, with an estimated 604,000 new cases and 342,000 deaths reported in 2020(1).Since they account for more than 80% of the worldwide burden of CC, low-and middle-income countries are disproportionately afflicted by the disease, with sub-Saharan Africa having the highest age-standardized incidence and mortality rates in 2021(1).The disease is worsened by the synergistic epidemic between HIV and human papillomaviruses (HPV).In Tanzania, Cervical cancer is the 1st most common disease among women, and 6525 women die from the disease each year while 10241 women were diagnosed with cervical cancer by 2023(2).Concurrent chemoradiation with high dose rate intracavitary brachytherapy (HDR-ICBT) is the standard of care in patients with locally advanced cervical cancer (3).Brachytherapy can be delivered using either low dose rate(LDR), pulsed dose rate(PDR) or high dose rate(HDR).HDR-ICBT is the type of radiation treatment used to treat cancer which involves the insertion of small radioactive source into or near the tumor to deliver high dose radiation 8Gy per session for 3 sessions(each application done at weekly intervals) for a specific period of time to the cancer cells while minimizing the radiation exposure to surrounding organs at risk(OAR), with imaging technique such as conventional x-ray, Computed tomography(CT), Magnetic Resonance Imaging(MRI) , Ultrasound, PET to guide the placement of applicator where the patient is given medication( GA or sedation) to help reduce discomfort(4).The American Brachytherapy Society(ABS) recommends a cumulative external beam and intracavitary(EBRT+ICBT) radiation dose of approximately 80-90Gy for definitive treatment of carcinoma of cervix and that HDR-ICRT to be performed under general anesthesia(4).In addition the overall treatment time of EBRT and brachytherapy should be less than 8 weeks, beyond which which local control and survival has been shown to decrease by 1% per day(5).Although examination under anaesthesia helps in better visualization of the diseased structure and delineation of parametrial extension of the disease, though chances of anaesthesiainduced complications are more (9).Moreover, there is long overall treatment time (OTT)(5).Using procedural sedation (PS)/ conscious sedation (CS) on patients can be a good alternative because longer overall treatment time (OTT) causes results to be subpar.Procedural sedation is a method of giving sedatives or dissociative substances along with or without analgesics to produce a condition that enables the patient to endure unpleasant operations while maintaining cardio-respiratory function.By lowering the degree of consciousness, it enables the patient to autonomously maintain oxygenation and airway control(5,9).
At BCC, brachytherapy is routinely performed under general anesthesia while procedural sedation being performed at ORCI.Although ICBT has received extensive research and is a crucial component of cervical cancer care, the anesthetic side of the procedure has received less attention (9,11,12).Comprehensive data correlating the use of GA or sedation that has influence on dose to the organs at risk(OAR) on 2D-BT is not available in our settings.Therefore this study to be focused on determining these dosimetric differences received by OAR in patients under sedation and GA at two medical facilities, BCC and ORCI.The study is likely to be of importance in the field of radiation oncology in reduction of urinary bladder and rectal toxicities among cervical cancer patients.Depending on the patient's comfort, several anesthetic formulations may be utilized, according to American Brachytherapy Society (ABS) recommendations (13,14).General anesthesia/spinal anesthesia (GA/SA), paracervical block, and conscious sedation (CS) are some of the anesthetic techniques that have been utilized to insert the HDR-ICBT applicator(3).Various institutions pick the anesthetic technique that works best for their patients and the facility.Despite offering effective analgesia and muscular relaxation GA has long overall treatment time.PS, on the other hand, is straightforward and practical to apply but may result in pain, discomfort, and insufficient muscle relaxation (7,9,12), this might result in inadequate vaginal packing and incorrect ICBT applicator positioning, which would increase doses to organs at risk (OAR) and compromise dosimetry.Though ICBT has been vastly studied and constitutes an integral portion of cervical cancer treatment, there are limited studies regarding its anesthetic perspective (9,11,12).To the best of our knowledge, there are limited information from Tanzania correlating the anesthesia and the ICBT dosimetry.In order to determine if GA or sedation have impact on the dosimetry, this study therefore aims to address this gap in knowledge and provide valuable insights of dosage received to the urinary bladder and rectum at the two setups that is Bugando Cancer Center North western Tanzania and Ocean Road Cancer Institute, Eastern Tanzania.

Study area
The study was conducted at Bugando Cancer Center, North-Western Tanzania and Ocean Road cancer Institute, Eastern Tanzania.Ocean Road Cancer Institute (ORCI) is located in Ilala District, in Dar es Salaam.It is the main referral center of the country for cancer patients.The institute receive approximately 7436 cancer patients annually.The center offers radiotherapy, screening programs and cancer prevention, nuclear medicine services, chemotherapy, palliative care, training and research.Corresponding Author: Francis .G. Kazoba Bugando Cancer Centre (BCC) is a tertiary care medical facility located in Nyamagana District, in Mwanza, along the southern shores of Lake Victoria.The cancer unit at Bugando is the second public cancer treatment center, with the capacity to attend 120 cancer patients on daily basis.

Study design and project duration
A hospital based analytical cross-sectional design with retrospective record review was utilized in this study, from May 2022 to December 2022.

Study population
The study included all patients' files that underwent HDRintracavitary Brachytherapy for cervical cancer at Bugando Cancer Center and Ocean Road Cancer Institute.Patients who received three intracavitary Brachytherapy sessions under sedation or general anesthesia and had complete dosimetry data available for urinary bladder and rectum in medical record system were included in the study.Patients who received HDR-ICBT for palliative care and oncological emergency.

Ethical consideration
Ethical approval for the study was sought from the Joint Catholic University of Health and Allied Sciences and Bugando Medical Centre Research and Ethics Committee and also permission to collect data was granted by Institutional Review Board of the Ocean Road Cancer Institute and Bugando Cancer Center.Confidentiality was maintained throughout the process from data collection, data analysis, and management.In the case a participant states identifying information accidentally say name or other personal identifiers, removal of this information from the checklist and other excel sheet was done prior analysis.Identification number was used instead of participant names.All participants' information was kept on a secure; password protected computer and was not be disclosed.

Characteristics of the study participants
The study involved 273 participants with carcinoma cervix, ranging in age from 28 to 87 years, with a mean age of 53.16 years (SD = 9.89).The age distribution was relatively diverse, covering a broad range of ages.Among these 273 participants, 143 (52.4%) received treatment at Bugando Cancer Center, while the remaining 130 (47.6%) were treated at Ocean Road Cancer Institute.The distribution of participants across the two facilities indicates a balanced representation of patients from both centers.Regarding the cancer stage of the participants, the study encompassed different stages of carcinoma cervix.Notably, the majority of participants were at stage IIB, accounting for 151 cases (55.3%).The next most common stage was IIIB, comprising 22.7% of the participants.Stages I and II together represented a significant portion of the cases, suggesting the study captured a diverse range of disease progression among the patient population.During the Intra-Cavitary Brachy-Therapy procedures, two different techniques were used: General Anesthesia (GA) and Conscious Sedation (CS).Among the 273 participants, 143 (52.4%) received treatment under General Anesthesia, and 130 (47.6%) were treated under Conscious Sedation.The use of different techniques in the study allowed for a comparison of dosimetric parameters under different anesthesia and sedation conditions .The dose per fraction for Intra-Cavitary Brachy-Therapy was consistent at 8.0 Gy per 3 Fraction for all participants.

Dosimetric Difference of Urinary Bladder and Rectum under General Anesthesia versus Sedation
The independent samples t-test was conducted to compare the dosimetric parameters of the urinary bladder and rectum between patients treated under General Anesthesia (GA) and Sedation (CS) during Intra-Cavitary Brachy-Therapy (ICBT).
For the urinary bladder dose, the assumption of equal variances was violated, as indicated by the Levene's test (F = 4.051, p = 0.045).Therefore, both equal and unequal variances were considered for the t-test.The results revealed a statistically significant difference in the mean urinary bladder dose between patients under GA and CS (t = -3.339,df = 271, p < 0.001).Patients treated under GA had a significantly lower mean urinary bladder dose (-5.01559) compared to those under CS.The 95% confidence interval for the difference in means ranged from -7.97276 to -2.05843 when assuming equal variances, and from -8.00281 to -2.02838 when not assuming equal variances.
Regarding the rectum dose, both equal and unequal variances were considered for the t-test.The Levene's test showed no significant difference in variances (F = 0.478, p = 0.490).The t-test results did not reveal a statistically significant difference in the mean rectum dose between patients under GA and SA (t = 0.400, df = 271, p = 0.690).The mean difference was small (0.53322), and the 95% confidence interval for the difference in means ranged from -2.09298 to 3.15941 when assuming equal variances and from -2.09032 to 3.15676 when not assuming equal variances.

CONCLUSION
Based on the findings of this study, it can be concluded that there is a statistically significant dosimetric difference in the urinary bladder dose between patients undergoing HDR-ICBT for cervical cancer under General Anesthesia (GA) and Conscious Sedation (CS).Specifically, patients treated under GA received a significantly lower mean urinary bladder dose compared to those under CS.However, no statistically significant difference was observed in the mean rectum dose between patients undergoing HDR-ICBT under GA and CS.This suggests that the choice of anesthesia technique may not have a significant impact on the mean rectum dose in this patient population.Based on this findings it is recommended that when planning HDR-ICBT treatment, healthcare providers should carefully consider the choice of anesthesia technique as it may impact the dose received by the urinary bladder.Although no significant difference was observed in the mean rectum dose between GA and CS groups in your study, it is essential to continue monitoring the rectum dose during HDR-ICBT.The rectum is a critical organ at risk, and its dose should be closely monitored to ensure patient safety and minimize potential side effects, and considering using 3D (three dimensional) Treatment Planning will help to show the urinary bladder and rectum for appropriate planning of the treatment dose each will receive.

Dosimetric Difference of Urinary Bladder and Rectum in Patients Undergoing Intracavitary Brachytherapy for Cervical Cancer under Procedural Sedation and General Anesthesia: A Survey at Bugando Cancer Center and Ocean Road Cancer Institute 1973 Volume 03 Issue 09 September 2023 Corresponding
Author: Francis .G. Kazoba

Table 2 : Doses of ICBT received and the Ovoid size and Tandem length used
The dosimetric parameters for the urinary bladder and rectum were analyzed.For the urinary bladder dose, the values ranged from 9.70% to 71.70%, with a mean of 32.0366% and a standard deviation of 12.62401%.In the case of the rectum dose, the values ranged from 5.80% to 61.30%, with a mean of 36.2678% and a standard deviation of 10.99061%.The relatively large standard deviations for both dosimetric parameters indicate variability in the data distribution, with wider spreads of values around the respective means.

Dosimetric Difference of Urinary Bladder and Rectum in Patients Undergoing Intracavitary Brachytherapy for Cervical Cancer under Procedural Sedation and General Anesthesia: A Survey at Bugando Cancer Center and Ocean Road Cancer Institute 1974 Volume 03 Issue 09 September 2023 Corresponding Author: Francis .G. Kazoba The Rectum Dose
Under GA, the mean was 36.5217 with a standard error of 0.92996.The 95% confidence interval ranged from 34.6833 to 38.3600.The dose ranged from 9.80 to 59.20, with a variance of 123.669 and a standard deviation of 11.12068.The distribution showed almost no skewness (skewness = -0.016)and a slightly negative kurtosis of -0.362.Under CS, the mean rectum dose was 35.9885 with a standard error of 0.95440.The 95% confidence interval ranged from 34.1002 to 37.8768.The dose ranged from 5.80 to 61.30, with a variance of 118.414 and a standard deviation of 10.88183.The distribution exhibited a slightly negative skewness of -0.312 and a positive kurtosis of 0.228.

Dosimetric Difference of Urinary Bladder and Rectum in Patients Undergoing Intracavitary Brachytherapy for Cervical Cancer under Procedural Sedation and General Anesthesia: A Survey at Bugando Cancer Center and Ocean Road Cancer Institute 1975 Volume 03 Issue 09 September 2023 Corresponding
the anesthesia group compared to 4.90 Gy (70% of point A dose) in patients without anesthesia (p value 0.6), and the mean dose to the rectal point was significantly higher in the anesthesia group compared to patients without anesthesia (5.09Gy) (3).Additionally, Chen et al.'s findings about local vaginal anesthesia align with our focus on comparing anesthesia techniques for patient comfort during HDR-ICBT.However, there are notable differences in the literature.Sharma et al. reported that the mean dose to the rectal point was significantly higher in the anesthesia group compared to patients without anesthesia (3), which contrasts with our study's finding of no significant difference in the mean rectum dose between GA and CS groups.These discrepancies may be attributed to variations in treatment protocols, patient populations, or anesthesia administration techniques employed across different studies.Furthermore, Lim et al. observed considerably greater complications associated with GA during HDR Brachytherapy (4), while our study did not analyze anesthesia-related complications, and none were reported.This discrepancy may stem from differences in patient selection, medical practices, or factors contributing to anesthesia-related complications.
Author: Francis .G. Kazoba support Sharma et al.'s results, as we observed no significant difference in the mean urinary bladder dose between GA and CS groups, resembling the lack of significant disparity in the mean dose to the bladder reference point reported in their research.Sharma et al revealed that the mean dose to the bladder reference point was 5.0 Gy (71.85% of point A dose) in