Abstract
Objective
This study investigated the analgesic effects in patients with cervical cancer during brachytherapy.
Methods
In this prospective study, 100 patients with cervical cancer who were admitted to Chongqing University Cancer Hospital between July 2021 and April 2022 were randomly divided into an analgesia group (n = 50) and a control group (n = 50). The visual analog scale (VAS) scores at applicator placement‐T1, CT‐scan‐T2, and removal ‐T3, self‐rating anxiety scale (SAS) and self‐rating depression scale (SDS) scores before brachytherapy, short‐term clinical efficacy, and patient satisfaction were compared between the two groups.
Results
The VAS score of the analgesia group was significantly different at T1 (0 vs. 4.34±1.02, t = 67.40, p < 0.001), but not in the control group; however, there was no significant difference between the two groups at T2 (t = ‐0.49, p = 0.623) and T3 (t = ‐0.12, p = 0.912). The SAS and SDS scores first decreased and then increased in the analgesic group and increased in the control group with increasing brachytherapy time. Except for the first measurement, the differences between the two groups were statistically significant (all p < 0.001). The application of interstitial implantation (p = 0.027), local efficacy (p = 0.047), and patient satisfaction rates (p = 0.025) were higher in the analgesic group than in the control group.
Conclusion
Analgesia can relieve pain, maintain physical and mental health, and improve outcomes and patient satisfaction rates for cervical cancer.
Keywords: analgesia, cervical cancer, physical and mental health, satisfaction rate, three‐dimensional brachytherapy
1. INTRODUCTION
Cervical cancer is a common malignant gynecological tumor, and it is the fourth most common gynecological tumor. 1 It is expected that 111,820 new cases of cervical cancer and 61,579 related deaths occurred in China by 2022. 2 Brachytherapy is an important component of radical radiotherapy used for cervical cancer. 3 During brachytherapy for cervical cancer, the patient must undergo a series of processes in sequence: applicator placement and fixation, simulated positioning scanning, waiting for treatment (gynecological radiation oncologists outline the target area and organs at risk, and physicians design the brachytherapy plan), treatment, and removal of the applicator. The pain that may occur during applicator placement, removal, and transport is usually underestimated. 4 Based on the fact that the patient's pain is the most obvious when the applicator is placed, removed and simulated positioning, the patient's anxiety and depression are the most serious before brachytherapy, 5 and there is a correlation between the anxiety before brachytherapy and the pain during the treatment. 6 This study aimed to investigate the effect of analgesia on the physical and mental health and the clinical efficacy of three‐dimensional (3D) brachytherapy in patients with cervical cancer.
2. MATERIALS AND METHODS
2.1. Patient selection
In this prospective clinical study, 100 patients with cervical squamous cell carcinoma who were diagnosed and treated with concurrent chemoradiotherapy at Chongqing University Cancer Hospital between July 2021 and April 2022 were selected as research subjects. The inclusion criteria were as follows: pathologically confirmed cervical squamous cell carcinoma according to the 2018 FIGO of staging system, classified as stage IVA or earlier, and not receiving antineoplastic therapy. Patients with stage IVB or later; a history of pelvic radiotherapy combined with contraindications to radiotherapy and anesthesia; and serious dysfunction of other organs, such as the heart, lung, liver, and kidney. This study was approved by the Ethics Committee of the Chongqing University Cancer Hospital (approval number: CALS2022109‐A), and all patients provided signed informed consent.
2.2. Concurrent Chemoradiotherapy
All patients received intensity‐modulated radiation therapy with a dose of 45 Gy/1.8 Gy/25 F. A simultaneous boost or late boost was performed according to the patient's parametric and lymph node involvement. The total parametrial was 50–60 Gy, and the contribution of brachytherapy to the total number of enlarged lymph nodes was 55–63 Gy. During external beam radiotherapy, single‐agent cisplatin was administered weekly (40 mg/m2), for 5–6 cycles.
2.3. Three‐dimensional brachytherapy
After 25 fractions of external radiotherapy, pelvic MRI was performed before 3D brachytherapy, with 6 Gy per fraction, one to two fractions per week, and five fractions in total. self‐rating anxiety scale (SAS) and self‐rating depression scale (SDS) were scored before each brachytherapy, and visual analog scale (VAS) was used to evaluate pain during brachytherapy. During 3D brachytherapy, the patients must empty their bladders and rectum. The patient was placed in the bladder lithotomy position on the transfer bed and a urinary catheter was placed after perineal disinfection was completed. Patients in the analgesic group were administered intravenous anesthesia, and the sedative propofol (1–1.5 mg/kg) was injected intravenously. The patients were considered to be in the anesthesia state owing to the disappearance of the eyelash reflex, and then the applicator was placed. The respiratory movement and vital signs of the patients were monitored using a ventilator and an electrocardiogram. After placement, anesthesia was terminated (if the patient had limb agitation due to intraoperative stimulation, an appropriate amount of propofol or fentanyl was added to maintain anesthesia), and the applicator was fixed. After the patient had fully recovered autonomous consciousness, the VAS score was evaluated at the time of applicator placement (T1). The bladder was injected with 50 mL of normal saline, the catheter was clamped, and the patient was transferred to the CT room for localization scanning. The VAS score during the simulation (T2) was evaluated after scanning. The catheter was opened to maintain patency, and CT images were transferred to the Oncentra Brachy Therapy system. The gynecological‐oncologic radiation therapist delineated the target volume and organs at risk, and the physicist designed the plan according to the prescription. After the plan was approved, the catheter was occluded, and the bladder was reinjected with 50 mL of normal saline. The patients were transferred to the treatment room for brachytherapy and, upon completion of treatment, to the operating room. The VAS score was evaluated at the time of the applicator removal (T3). Patients in the control group underwent the same procedure, except that they did not receive intravenous anesthesia.
2.4. Evaluation parameter
The VAS is a well‐validated instrument for assessing pain intensity, which is easy to use and preferred by patients, and intensity on a verbal rating scale as mild (1–3), moderate (4–6), severe (7–9), and very severe (10). VAS scores were recorded at T1, T2, and T3 during each brachytherapy session in both patient groups. The SAS and SDS are self‐rating scales containing 20 questions each and are divided into four scores, which help individuals understand themselves and assess whether they are experiencing anxiety or depression. SAS scores are defined as: normal state < 50, mild anxiety 50–59, moderate anxiety 60–70, severe anxiety >70; SDS scores are classified as: normal state < 53, mild depression 53–62, moderate depression 63–72, severe depression > 72. SAS and SDS scores were assessed before each brachytherapy session, and the higher the total score, the higher the degree of anxiety and depression. 7 The application of the interstitial needle, short‐term local efficacy, and patient satisfaction rates were analyzed. RECIST1.1 criteria were used to evaluate short‐term local efficacy, such as complete response (CR) and partial response (PR).
2.5. Statistical analyses
The SPSS software (version 23.0) was used to analyze the data. Data were tested using the t‐test and multivariate analysis of variance, and statistical significance was set at p < 0.05. Graphpad prism7.0 was used for mapping.
3. RESULTS
There were no significant differences in the demographic and general data between the two groups (all p>0.05, Table 1).
TABLE 1.
Comparison of demographic and clinical data for both groups of patients.
| Analgesic group (n, %) | Control group (n, %) | χ 2 | p | |
|---|---|---|---|---|
| Age (years) | 2.22 | 0.137 | ||
| ≥60 | 13 (26.00%) | 20 (40.00%) | ||
| <60 | 37 (74.00%) | 30 (60.00%) | ||
| Clinical Stages (2018FIGO) | 0.54 | 0.793 | ||
| II | 17 (34.00%) | 19 (38.00%) | ||
| III | 31 (62.00%) | 28 (56.00%) | ||
| IV | 2 (4.00%) | 3 (6.00%) | ||
| Maximum Initial Tumor Diameter (cm) | 0.65 | 0.420 | ||
| ≥4 | 30 (60.00%) | 26 (52.00%) | ||
| <4 | 20 (40.00%) | 24 (48.00%) | ||
All patients underwent concurrent chemoradiotherapy. A total of 500 sessions of brachytherapy sessions were completed, and the VAS scores were evaluated 1,500 times. Table 2 shows the trend of the VAS scores for pain in the two groups. There was a significant difference in the VAS score at T1 (0 vs. 4.34 ± 1.02, P < 0.001), but no significant difference was observed in the VAS score at T2 and T3 (both P > 0.05) between the analgesic and control groups, as shown in Table 2.
TABLE 2.
Comparison of visual analog scale scores of pain at different time points between two groups.
| Different time | Analgesic group (n = 50) | Control group (n = 50) | t | p |
|---|---|---|---|---|
| T1 | 0 | 4.34±1.02 | 67.40 | <0.001 |
| T2 | 1.69±0.72 | 1.66±0.73 | ‐0.49 | 0.623 |
| T3 | 2.78±0.75 | 2.77±0.77 | ‐0.12 | 0.912 |
T1: The applicator was being implanted; T2: The applicator was being simulated positioning; T3: The applicator was being removed.
All the patients completed 500 SAS and SDS questionnaires. As shown in Figure 1, the SAS and SDS scores in the analgesic group showed an overall downward trend with an increase in the number of brachytherapy sessions, but increased in the last session. The SAS and SDS scores in the control group showed upward trends with increasing brachytherapy frequency. The SAS and SDS scores were significantly different between the two groups (all P < 0.001), except for the first time (SAS: t = 0.16, P = 0.875; SDS: t = 0.16, P = 0.871).
FIGURE 1.
The correlation between the trend of the self‐rating anxiety scale (SAS) and self‐rating depression scale (SDS) scores and the number of brachytherapy in the two groups (A, SAS score; B, SDS score).
Note: abc indicates the letter marking method and shows the differences in the number of brachytherapies (intra‐group comparisons); ▲ indicates significant differences compared to the normal controls (between‐group comparisons); BTx: Before X brachytherapy.
No serious adverse reactions related to anesthesia were observed in the analgesic group. The application of interstitial brachytherapy, CR, and patient satisfaction rate during brachytherapy were significantly higher in the analgesic group than in the control group (all p <0.05), as shown in Table 3.
TABLE 3.
The proportion of interstitial brachytherapy, efficacy, and patient satisfaction rate between two groups.
| Analgesic Group (n, %) | Control Group (n, %) | χ 2 | p | |
|---|---|---|---|---|
| Interstitial Brachytherapy | 4.89 | 0.027 | ||
| YES | 28 (56.00%) | 17 (34.00%) | ||
| NO | 22(44.00%) | 33 (66.00%) | ||
| Local Outcome | 4.03 | 0.047 | ||
| CR | 32 (64.00%) | 22 (44.00%) | ||
| PR | 18 (36.00%) | 28 (56.00%) | ||
| Patient Satisfaction Rate | 48 (96.00%) | 42 (84.00%) | 5.01 | 0.025 |
CR, complete response; PR, partial response.
4. DISCUSSION
Increasing attention has been paid to pain management in patients with cancer, including pain caused by antitumor therapy. Brachytherapy cannot be replaced with external radiotherapy in radical radiotherapy and chemotherapy for cervical cancer. 3 However, the pain during brachytherapy is a distressing and intractable problem. 7 , 8 , 9 Most patients with cervical cancer experience negative emotions, such as anxiety and fear, before brachytherapy. Additionally, pain during brachytherapy leads to resistance to or even refusal of subsequent treatment. 10 , 11 Therefore, developing an ideal analgesic for brachytherapy is important. To date, no consensus has been reached on the most effective analgesic modality for brachytherapy, which varies between centers. In addition to drugs, music and relaxation videos have provided significant relief in women undergoing prolonged brachytherapy. 12 , 13 Intravenous anesthesia was administered in this study. It is widely used because of its advantages, such as good muscle relaxation, few complications, rapid effect and recovery, and good tolerance in the Chinese population. 14 , 15
The VAS pain score at T1 was the highest in the control group, consistent with previous reports, 5 while the VAS pain score at T1 was 0 in the control group, and the difference between the two groups was significant, indicating that intravenous anesthesia could effectively inhibit pain at T1. There was no significant difference in VAS pain scores between the two groups at T2 and T3, indicating that intravenous anesthesia had no significant effect on subsequent analgesia, which was also in line with the characteristics of rapid onset and rapid recovery of intravenous anesthesia. After the implantation of the applicator, patients may still be in pain and need to be transported for many times and immobilized for a long time, which increases the probability of applicator displacement or even falling off. Therefore, for patients with pain sensitivity, other analgesic treatments are recommended in the subsequent process. 4 , 16
In a systematic review, nine out of ten studies on psychological problems reported that brachytherapy caused anxiety and pain in most women, 17 pain easily induced anxiety and depression in patients, and all patients who received brachytherapy in our study had different levels of anxiety and depression. The study of pain and anxiety levels in patients during brachytherapy for cervical cancer in Morocco conducted by Kenza and Benali found that up to 25% and 64% of patients experienced moderate and severe anxiety and pain, respectively. 18 Before brachytherapy, 85% (17/20) of the patients reported anxiety and depression according to Rollison et al. Anxiety and depression occur at different stages during brachytherapy, as reported by Wiebe et al., 5 with the highest scores being observed before brachytherapy; therefore, anxiety and depression scores before each brachytherapy session were evaluated in this study. Previous reports have shown that patients' anxiety and depression scores increased with an increase in brachytherapy time. Our study showed that the SAS and SDS scores in the experimental group decreased, while those in the control group increased with an increase in brachytherapy time, indicating that analgesia can effectively reduce patients' anxiety and depression caused by brachytherapy pain. However, the score in the fifth session was higher than that in the fourth session in the experimental group, which may be related to the patient's concerns regarding the final treatment effect.
Whether analgesic intervention in cancer patients can help prevent disease recurrence and improve overall survival is controversial. 19 , 20 Our study showed that analgesia provided more opportunities for interstitial implantation; that is, the application of interstitial implantation in the analgesic group was higher than in the control group, and the local efficacy was better. Follow‐up will be continued in the later stages of this study to further investigate the overall survival of the patients.
In conclusion, intravenous anesthesia can reduce pain associated with applicator insertion during brachytherapy, relieve negative emotions, such as anxiety and depression, and improve clinical efficacy and patient satisfaction rates; however, it has no analgesic effect on subsequent pain. Follow‐up pain management should also be given sufficient attention to patients with poor pain tolerance, anxiety, and depression.
CONFLICT OF INTEREST STATEMENT
The authors declare no conflicts of interest.
FOUNDATION PROJECT
General Program of Chongqing Science‐Health Joint Medical Research Program (No. 2021MSXM172); New technology and new project in Chongqing University Cancer Hospital in 2021 (No. 63); Chongqing Shapingba District Decision‐making Consultation and Management Innovation Project (No. Jcd2022101, No. Jcd202140); The Municipal Social Science Planning Doctor and Training Project (No. 2021PY31), the Chongqing Technical Innovation and Application Development Special‐Key Project (No. CSTB2022TIAD‐KPX0152)
ETHICAL STATEMENT
This study was approved by the Ethics Committee of the Chongqing University Cancer Hospital (approval number: CALS2022109‐A), and all patients provided signed informed consent.
Liu M, Wu H‐Y, Li J, et al. Clinical study of analgesia in brachytherapy for cervical cancer. Prec Radiat Oncol. 2023;7:137–141. 10.1002/pro6.1194
REFERENCES
- 1. Clinton SK, Giovannucci EL, Hursting SD. The world cancer research fund/american institute for cancer research third expert report on diet, nutrition, physical activity, and cancer: impact and future directions. J Nutr. 2020;150(4):663‐671. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2. Xia C, Dong X, Li H, et al. Cancer statistics in china and united states,2022: profiles, trends, and determinants. Chin Med J (Engl). 2022;135(5):584‐590. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3. Nadeem R, Catheryn M, Kristin, et al. NCCN Clinical Practice Guidelines in Oncology (NCCN GuidelinesⓇ) Cervical Cancer. [2021‐10‐26]. https://www.nccn.org/professionals/physician_gls/pdf/cervical.pdf
- 4. Wilson JM, Davies E, Tan X, et al. Demographic and clinical factors associated with variations in opioid administration using conscious sedation during HDR brachytherapy for cervical cancer. Brachytherapy. 2021;20(6):1164‐1171. [DOI] [PubMed] [Google Scholar]
- 5. Wiebe E, Surry K, Derrah L, et al. Pain and symptom assessment during multiple fractions of gynecologic high‐dose‐rate brachytherapy. Brachytherapy. 2011;10(5):352‐356. [DOI] [PubMed] [Google Scholar]
- 6. Warnock C. Patients' experiences of intracavity brachytherapy treatment for gynaecological cancer. Eur J Oncol Nurs. 2005;9(1):44‐55. [DOI] [PubMed] [Google Scholar]
- 7. Dunstan DA, Scott N, Todd AK. Screening for anxiety and depression: reassessing the utility of the Zung scales. BMC Psychiatry. 2017;17(1):329. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8. Sommat K, Lin JYX, Chew MML, et al. Non‐anesthetist‐administered moderate sedation with midazolam and fentanyl for outpatient MRI‐aided hybrid intracavitary and interstitial brachytherapy in cervix cancer: a single‐institution experience. J Contemp Brachytherapy. 2021;13(3):286‐293. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9. Humphrey P, Dures E, Hoskin P, et al. Brachytherapy for locally advanced cervical cancer: A survey of UK provision of care and support. Radiother Oncol. 2021;159(9):60‐66. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10. Bansal R, Khan Joad AS, Saxena M, et al. Oral midazolam is a safe and effective premedication in adult outpatients undergoing brachytherapy for cancer cervix under general anaesthesia: a prospective randomised, double blind placebo‐controlled study. Indian J Anaesth. 2015;59(7):437‐439. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11. Chen J, Zhang N, Liu Y, et al. Analysis of applicator insertion related acute side effects for cervical cancer treated with brachytherapy. Front Oncol. 2021;7(11):677052. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12. Sinha MK, Barman A, Goyal M, et al. Progressive muscle relaxation and guided imagery in breast cancer: a systematic review and meta‐analysis of randomised controlled trials. Indian J Palliat Care. 2021;27(2):336‐344. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13. Chi GC, Young A, McFarlane J, et al. Effects of music relaxation video on pain and anxiety for women with gynaecological cancer receiving intracavitary brachytherapy: a randomised controlled trial[J]. J Res Nurs. 2015;20(2):129‐144. [Google Scholar]
- 14. Wang F,Zhao YY, Guan M, et al. Application of intravenous sedation in 2582 cases of oral and maxillofacial surgery[J]. J Peking Univ, Health sci. 2020;52(1):181‐186. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15. Tang Qi, Wu Yu, Wan Qi, et al. Progress in the study of the mechanisms in propofol s rewarding effect[J]. J Clin Anesth. 2021;37(11):1217‐1220. [Google Scholar]
- 16. Mendez LC, Choi S, D'Alimonte L, et al. Opioid consumption and pain in gynecological cancer patients treated with interstitial brachytherapy. Brachytherapy. 2017;16(4):870‐876. [DOI] [PubMed] [Google Scholar]
- 17. Humphrey P, Bennett C, Cramp F. The experiences of women receiving brachytherapy for cervical cancer: A systematic literature review. Radiography. 2018;24(4):396‐403. [DOI] [PubMed] [Google Scholar]
- 18. Benali K, Tazi MA, Kietga G, et al. The Experience of pain and anxiety in cervical cancer patients undergoing multiple fraction high‐dose rate brachytherapy: a prospective observational study. J Cancer Ther. 2022;13(7):405‐416. [Google Scholar]
- 19. Bhang YL, Pei LJ, Sun C, et al. Regional anesthesia and cancer recurrence in patients with late‐stage cancer: a systematic review and meta‐analysis. Chin Med J (Engl). 2021;134(20):2403‐2411. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20. Yap A, Lopez‐Olivo MA, Dubowitz J, et al. Global onco‐anesthesia research collaboration group. Anesthetic technique and cancer outcomes: a meta‐analysis of total intravenous versus volatile anesthesia. Can J Anesth. 2019;66(8):546‐561. [DOI] [PubMed] [Google Scholar]