Comparison of the Efficacy of adjuvant External Beam Radiotherapy, Vaginal Brachytherapy, and External Beam Radiotherapy with Vaginal Brachytherapy in Patients with FIGO Stage IB Endometrioid carcinoma: A Meta-Analysis

Comparison of the Efficacy of adjuvant External Beam Radiotherapy, Vaginal Brachytherapy, and External Beam Radiotherapy with Vaginal Brachytherapy in Patients with FIGO Stage IB Endometrioid carcinoma: A Meta-Analysis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Comparison of the Efficacy of adjuvant External Beam Radiotherapy, Vaginal Brachytherapy, and External Beam Radiotherapy with Vaginal Brachytherapy in Patients with FIGO Stage IB Endometrioid carcinoma: A Meta-Analysis Hai-Na Qu This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4252806/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Objective: Currently, there is debate surrounding the selection of adjuvant treatment for FIGO IB endometrioid carcinoma.The aim of this study is to compare the efficacy of postoperative adjuvant external beam radiotherapy (EBRT), vaginal brachytherapy (VBT), and the combination therapy of EBRT with VBT (EBRT+VBT) in patients with stage IB endometrioid carcinoma. Methods: We selected randomized controlled trials comparing postoperative adjuvant EBRT, VBT, and EBRT+VBT in patients with stage IB endometrioid carcinoma. Data analysis was performed using Review Manager 5.4.1. The primary study endpoints included 5-year overall survival (OS), 5-year disease-free survival (DFS), rates of distant metastasis, and rates of local recurrence. Secondary endpoints encompassed post-radiotherapy toxicities such as gastrointestinal toxicity, urinary toxicity, vaginal toxicity, and health-related quality of life scores (HRQL). Result: Survival findings: ①There were no statistically significant differences observed between the EBRT group and the VBT group in terms of 5-year OS (RR=1.02, 95% CI: 0.98-1.06, P=0.42), 5-year DFS (RR=1.05, 95% CI: 0.94-1.18, P=0.40), and 5-year distant metastasis rate (RR=0.69, 95% CI: 0.44-1.07, P=0.09). ②Compared to the VBT group, the EBRT+VBT group exhibited a significantly prolonged 5-year DFS (RR=1.16, 95% CI: 1.06-1.27, P=0.0010), reduced rates of local recurrence (RR=0.32, 95% CI: 0.13-0.75, P=0.009), and distant metastasis (RR=0.56, 95% CI: 0.32-0.96, P=0.03), but did not show improvement of 5-year OS in patients(RR=1.01, 95% CI: 0.97-1.05, P=0.73). ③There was no statistically significant difference observed in 5-year OS between the EBRT group and the EBRT+VBT group (RR=0.98, 95% CI: 0.93-1.03, P=0.46). Toxic outcomes: ①At 12 months, the diarrhea score in the VBT group was significantly lower than that in the EBRT group (RR=8.56, 95% CI: 5.38-11.91, P＜0.00001); the social function score in the VBT group was significantly higher than that in the EBRT group (RR=-5.60, 95% CI: -8.33--2.88, P＜0.0001). There were no statistically significant differences in the global health status score (RR=-1.80, 95% CI: -4.36-0.75, P=0.17) and urinary urgency score (RR=4.04, 95% CI: -0.81-8.90, P=0.10). ②Compared to the EBRT+VBT group, the VBT group had a lower incidence rate of gastrointestinal toxicity at 5 years, with statistically significant differences (RR=3.90, 95% CI: 2.18-7.00, P＜0.00001); there were no statistically significant differences in the rates of genitourinary toxicity (RR=1.68, 95% CI: 0.65-4.34, P=0.28) and vaginal toxicity (RR=1.76, 95% CI: 0.56-5.53, P=0.33). Conclusion: 1.There was no significant difference in 5-year OS in patients with stage IB endometrial carcinoma treated with VBT, EBRT and EBRT+VBT after surgery. Compared with VBT and EBRT, EBRT+VBT significantly extended DFS for 5 years and reduced the incidence of local recurrence and distant metastasis. 2.Although there was no significant difference between VBT and EBRT in overall health status score and urgency of urination score, VBT was superior to EBRT in diarrhea score, other gastrointestinal toxicity and social function score. Stage IB endometrioid carcinoma EBRT VBT OS toxicity Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 Figure 12 Figure 13 Figure 14 Figure 15 Introduction Endometrial carcinoma is a prevalent malignancy among women, with its global incidence showing an upward trend in recent years. Statistical data indicates an annual occurrence of approximately 320,000 new cases worldwide, resulting in 76,000 fatalities [ 1 ]. More than 90% of diagnoses occur during the perimenopausal period, with 25% before menopause and 75% after menopause [ 2 ].Vaginal bleeding commonly presents as the initial symptom, facilitating early detection of endometrioid carcinoma [ 3 ]. Consequently, a significant portion of patients are typically diagnosed at stages I to II, with approximately 80% at stage I, leading to favorable treatment outcomes and a five-year survival rate exceeding 95% [ 4 ]. Studies have shown that around 15–20% of women present with high-risk factors for recurrence, warranting postoperative adjuvant radiotherapy [ 5 ]. As per the NCCN guidelines, some patients with FIGO stage I endometrioid carcinoma may require postoperative targeted radiation therapy. Adjuvant radiation therapy options encompass EBRT, VBT, and EBRT + VBT [ 6 ]. Postoperative adjuvant therapy for patients with FIGO stage IB endometrioid carcinoma should be tailored based on tumor differentiation and the presence of recurrence risk factors, such as age ≥ 60 years and lymphovascular space invasion (LVSI) [ 6 ]. According to the NCCN guidelines, high/intermediate differentiation at FIGO stage IB warrants consideration of VBT as the primary approach. Observation may be an option for those without accompanying risk factors, while EBRT may be considered if risk factors are present. In cases of FIGO stage IB endometrioid carcinoma with low differentiation, both EBRT and/or VBT are recommended [ 6 ]. However, there is ongoing controversy surrounding the selection of optimal adjuvant radiotherapy approaches. Onsrud et al. has observed that EBRT lacks survival benefits for early-stage endometrial carcinoma and should be used cautiously, particularly in women with a longer life expectancy. Trials such as PORTEC-1, PORTEC-2, and others [ 8 , 9 ] have consistently shown the notable advantage of postoperative EBRT in achieving local regional control. Nevertheless, none of these trials have revealed a significant improvement in overall survival rates. Consequently, our research was undertaken to determine a more effective postoperative adjuvant treatment strategy for stage IB endometrioid carcinoma patients. The utilization of postoperative EBRT and VBT may entail acute toxicity and long-term complications. The toxic reactions associated with EBRT typically include pain, genitourinary reactions (e.g., urinary frequency, urinary incontinence, and cystitis), and gastrointestinal reactions (such as nausea, diarrhea, intestinal obstruction, and fecal incontinence) [ 5 , 10 – 12 ]. In contrast, The toxicities associated with VBT mainly consist of vaginal mucosal atrophy leading to vaginal dryness, dyspareunia, and vaginal fibrosis resulting in vaginal stenosis or shortening.This could potentially reduce the quality of life for certain patients [ 13 ]. Consequently, decisions regarding postoperative adjuvant radiotherapy must be grounded in genuine clinical benefits. Yet, whether different adjuvant radiotherapy modalities following surgery for stage IB endometrioid carcinoma yield distinct treatment effects remains inconclusive in current research [ 8 , 9 , 12 ]. To explore which radiotherapy modality can optimize local recurrence control, mitigate toxicity, and enhance the quality of life for patients, we undertook this meta-analysis.This meta-analysis retrieved 10 randomized controlled trials focusing on adjuvant radiotherapy in patients with stage IB endometrioid carcinoma post-surgery. The aim was to compare the clinical utility of EBRT, VBT, and EBRT + VBT, aiming to guide the clinical management of adjuvant radiotherapy in women with stage IB endometrioid carcinoma post-surgery. Studies and methods Literature search: We conducted searches in the following databases: PubMed, EMBASE, and CENTRAL (Cochrane Library), using the following main search terms: “Endometrial Neoplasm”, “Neoplasm,Endometrial”, “Neoplasms,Endometrial”, “Endometrial Carcinoma”, “Carcinoma,Endometrial”, “Carcinomas,Endometrial”, “Endometrial Carcinomas”, “Endometrial Cancer”, “Cancer,Endometrial”, “Cancers,Endometrial”, “Endometrial Cancers”, “Endometrium Cancer”, “Cancer, Endometrium”, “Cancers,Endometrium”, “Cancer of the Endometrium”, “Carcinoma of Endometrium”, “Endometrium Carcinoma”, “Endometrium Carcinomas”, “Cancer of Endometrium”, “Endometrium Cancers”, “Radiotherapies”, “Radiation Therapy”, “Radiation Therapies ”, “Therapies, Radiation”, “Therapy,Radiation”, “Radiation Treatment”, “Radiation Treatments”, “Treatment,Radiation”, “Radiotherapy,Targeted”, “Radiotherapies,Targeted”, “Targeted Radiotherapies”, “Targeted Radiotherapy”, “Targeted Radiation Therapy”, “Radiation Therapies,Targeted”, “Targeted Radiation Therapies”, “Therapies,Targeted Radiation”, “Therapy,Targeted Radiation”, “Radiation Therapy,Targeted”, “randomized controlled trial”, “randomized”, "placebo". The searches were not restricted by date or language. Selection criteria: Inclusion criteria 1. The patient met the diagnostic criteria based on pathology, and was eventually diagnosed with stage IB endometrioid carcinoma; 2. The research objectives are not restricted by nationality, age, gender, income, race, or any other factors; 3. All included patients underwent a laparoscopic total hysterectomy with salpingo-oophorectomy, and gynecologists performed pelvic and paraaortic lymph node dissection according to the NCCN guidelines; 4. Patients were randomly assigned to either the EBRT group, the VBT group, or the EBRT + VBT group post-surgery; 5. The study design employed a randomized controlled trial; 6. Complete clinical raw data was available. Exclusion criteria 1. The patients were confirmed to neither have stage IB endometrioid carcinoma nor a recurrence or metastasis of endometrial carcinoma following pathological diagnoses; 2.Patients who had undergone radiotherapy or chemotherapy prior to surgery; 3.Animal experiments; 4.Irrelevant to the research topic; 5. Conference summaries, meta-analyses, reviews, case reports. Data extraction and quality assessment The first reviewer extracted data from the included studies.The second reviewer re-confirmed the data to minimize potential errors.The data extracted from each study include the first author, the year of publication, the type of study, the number of patients, the method of adjuvant radiotherapy used, and the outcomes. The methods of adjuvant radiotherapy include VBT, EBRT, and EBRT + VBT. The primary study outcomes include the 5-year OS rate, the 5-year DFS rate, the incidence of distant metastases, and the rate of local recurrence. Secondary outcomes include toxicological reactions following radiotherapy, such as gastrointestinal toxicity, urological toxicity, and vaginal toxicity, as well as health-related quality of life scores. If the original literature provides the necessary data, it is directly extracted. If not provided, data are indirectly extracted from the figures or tables mentioned in the literature and subsequently processed using Review Manager 5.4.1 software to calculate the required data. Data analysis We conducted the meta-analysis using the Review Manager version 5.4.1 software. Binary variables were presented as risk ratios with 95% confidence intervals. Continuous variables were displayed as weighted mean differences with 95% CI, calculated based on the mean, standard deviation, p-value, and sample size of each study.Heterogeneity was assessed using the I2 test. If the I2 value exceeded 50%, a random-effects model was applied to each variable; otherwise, a fixed-effects model was utilized for meta-analysis [ 14 , 15 , 16 ]. A two-sided P value less than 0.05 was considered statistically significant. We used the Cochrane Risk of Bias Assessment Tool to evaluate the methodological quality of randomized controlled trials [ 17 ]. This tool involves a per-study assessment based on seven main criteria: 1. Random sequence generation (selection bias); 2. Allocation concealment (selection bias); 3. Implementation bias (blinding of researchers and participants); 4. Measurement bias (blinding of outcome assessment); 5. Follow-up bias (completeness of outcome data); 6. Reporting bias; 7. Other biases. Each criterion can be rated as "low risk," "unclear" (lack of information or uncertainty about the likelihood of bias), or "high risk." Result Literature search and included studies After conducting the database search according to the retrieval strategy, a total of 796 articles were retrieved. Following the establishment of inclusion and exclusion criteria, 118 studies were excluded due to duplication and animal experiments. Upon screening titles and abstracts, 560 studies were further excluded. Subsequently, 118 full-text articles were reviewed, resulting in the final inclusion of 10 articles. Among these, 79 were literature reviews, 14 were incomplete articles, 7 lacked appropriate control groups, and 8 had insufficient data. The flowchart detailing this process can be found in Fig. 1 . Quality evaluation All 10 selected literature were systematically evaluated using the Cochrane Risk of Bias Assessment Tool. They provided detailed explanations of their randomization methods, which were deemed appropriate. The assessment of publication bias indicated a low risk of bias in the included studies. The results of the methodological quality assessment are depicted in Fig. 2 Included study characteristics Seven randomized controlled studies [ 7 , 18 – 23 ] reported on 4,468 patients, with 1,563 patients receiving EBRT, 1,623 patients receiving VBT, and 1,282 patients receiving EBRT + VBT. The details of the authors’ names, publication years, treatment regimens, study duration, follow-up duration, number of patients, and data sources are included in the literature. The basic characteristics of the selected studies are presented in Table 1 . Table 1 Study characteristics Study Data source Period EBRT(n) VBT(n) EBRT + VBT(n) Follow up Result 2018 G.Wortman PORTEC-2 2002–2006 214 213 -- 116m (18–163) 5 year overall survival; Disease-free survival; Distant recurrence;Vaginal recurrence; Pelvic recurrence 2010 Nout RA 19 radiation oncology centres, Dutch 2002–2006 214 213 -- 5-10y Vaginal recurrence; Locoregional recurrence (pelvic or vaginal, or both); Distant metastases;Overall; Disease-free survival;Treatment-related toxic 2016 Vishal Gupta, MD NCDB 1998–2012 1084 744 718 66.1m 5 year overall survival 2021 Wenhui Wang 13 Chinese radiation oncology centers of grade A tertiary hospitals 1999–2015 51 25 142 42m (3-237) 5 year overall survival; Disease-free survival;Distant recurrence;Toxicity; Local-regional failure-free survival BENGT SORBE, M.D., PH.D. 2011 5 cancer centers, Swedish 1997–2008 -- 263 264 62m (12–138) Locoregional recurrences ; Overall survival; Recurrence-free survival; Recurrence-free interval; Cancer-specific survival; Toxicity Mathias Onsrud 2013 4 different university hosptials 1968–1974 -- 140 133 20.5y (0-43.4) Overall survival;Secondary Cancer Sunil R.A., MBBS, MD 2018 Gujarat Cancer Research Institute (GCRI) 2011–2016 -- 25 25 60m 5 year overall survival;Toxicity; Three articles [ 24 , 25 , 26 ] reported on the health-related quality of life (HRQL) scores of patients who underwent adjuvant radiotherapy postoperatively (including patients with stage IB-II). Cancer-specific HRQL was measured using the European Organisation for Research and Treatment of Cancer (EORTC) Core Questionnaire (QLQ-C30 version 3.0) [ 27 ]. The EORTC QLQ-C30 is a multidimensional cancer-specific quality of life questionnaire. The QLQ-C30 questionnaire comprises 5 functional scales (physical functioning, role functioning, emotional functioning, cognitive functioning, social functioning), 9 symptom scales (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, financial difficulties), and 1 global health status scale [ 28 , 29 ]. Higher scores on the functional and global health status scales indicate higher levels of functioning. Conversely, higher scores on the symptom scales reflect higher levels of symptoms and lower quality of life. Baseline quality of life questionnaires are typically administered 3 to 4 weeks after surgery and must be returned before the start of radiotherapy. The summary of HRQL scores from the selected studies is presented in Table 2 . Table 2 Health related quality of life (HRQL) after EBRT and VBT Study Groups Global Health Status M ± SD Social Functioning Scores M ± SD Diarrhea Scores M ± SD Urinary Urgency M ± SD 2015 de Boer SM EBRT Baseline 69.6 ± 20.78 77.5 ± 22.26 8 ± 25.23 24 ± 34.14 12m 75 ± 14.84 87.8 ± 20.78 16 ± 29.69 31.4 ± 40.08 VBT Baseline 70.5 ± 18.51 77.8 ± 17.77 5 ± 22.21 24 ± 34.06 12m 76.6 ± 20.73 93.2 ± 22.21 7 ± 23.69 27.5 ± 33.32 2009 Nout RA EBRT Baseline 69 ± 29.69 77.8 ± 31.91 7.5 ± 25.97 22.6 ± 48.98 12m 75 ± 25.97 87.7 ± 31.17 15.2 ± 46.01 31.8 ± 57.89 VBT Baseline 70.5 ± 25.91 78 ± 31.10 4.9 ± 21.47 24 ± 44.42 12m 78 ± 29.62 93.6 ± 19.25 6 ± 29.62 27.3 ± 46.64 2012 Nout RA EBRT Baseline 69.2 ± 20.88 77.5 ± 22.84 8 ± 26.10 23 ± 45.68 12m 76 ± 26.10 88 ± 26.10 15 ± 26.10 31.5 ± 45.68 VBT Baseline 70.6 ± 24.61 78 ± 20.51 5 ± 23.25 24 ± 47.86 12m 77 ± 27.35 93.6 ± 25.98 7 ± 23.25 27.6 ± 41.02 EBRT: External Beam Radiation Therapy VBT: Vaginal Brachytherapy Survival findings We conducted comparative analyses of the three radiotherapy modalities. Seven studies compared the EBRT group with the VBT group, among which four studies analyzed 5-year OS, 5-year DFS, and 5-year distant metastasis rates. Five studies compared the EBRT + VBT group with the VBT group, analyzing 5-year OS, 5-year DFS, 5-year local recurrence rates, and 5-year distant metastasis rates. Two studies compared the EBRT + VBT group with the EBRT group, analyzing 5-year OS in both groups. The EBRT group and the VBT group Four studies reported the 5-year OS outcomes for stage IB endometrioid carcinoma patients who received adjuvant EBRT or adjuvant VBT postoperatively. The EBRT group included 1563 individuals, and the VBT group contained 1195 individuals. With an I2 of 24%, a fixed effects model was employed. The results revealed no statistically significant difference in 5-year OS between the adjuvant EBRT and adjuvant VBT groups (RR = 1.02, 95% CI: 0.98–1.06, P = 0.42) (Fig. 3 ). Three studies investigated the 5-year DFS of patients who received adjuvant EBRT and adjuvant VBT postoperatively. The EBRT group comprised 479 individuals, while the VBT group consisted of 451 individuals. With an I2 greater than 50%, a random effects model was employed. The results revealed no significant statistical difference in 5-year DFS between the adjuvant EBRT and adjuvant VBT groups (RR = 1.05, 95% CI: 0.94–1.18, P = 0.40) (Fig. 4 ). Three studies analyzed the 5-year incidence of distant metastasis after adjuvant EBRT and adjuvant VBT, with 479 participants in the EBRT group and 451 participants in the VBT group. With an I2 of 0%, and a fixed effects model was employed. The results revealed no significant statistical difference in the 5-year incidence of distant metastasis between the adjuvant EBRT and adjuvant VBT groups, although the adjuvant EBRT group had a tendency to reduce the incidence of distant metastasis (RR = 0.69, 95% CI: 0.44–1.07, P = 0.09) (Fig. 5 ). The EBRT + VBT group and the VBT group Five studies reported the 5-year OS of patients with stage IB endometrioid adenocarcinoma who received either adjuvant EBRT + VBT or adjuvant VBT postoperatively. The EBRT + VBT group included 1437 individuals, and the VBT group included 1337 individuals. With an I2 of 15%, a fixed effects model was employed. The results revealed no significant statistical difference in the 5-year OS between the adjuvant EBRT + VBT and adjuvant VBT groups (RR = 1.01, 95% CI: 0.97–1.05, P = 0.73) (Fig. 10 ). Three studies reported the 5-year DFS of patients with stage IB endometrioid carcinoma who underwent adjuvant EBRT + VBT and adjuvant VBT postoperatively. The EBRT + VBT group comprised 431 individuals, while the VBT group included 313 individuals. With an I2 of 35%, a fixed effects model was employed. The results revealed that the 5-year DFS was significantly superior in the adjuvant EBRT + VBT group compared to the adjuvant VBT group, with a statistically significant difference (RR = 1.16, 95% CI: 1.06–1.27, P = 0.0010) (Fig. 11 ). Two studies reported the 5-year local recurrence rates of patients with stage IB endometrioid carcinoma who underwent adjuvant EBRT + VBT and adjuvant VBT postoperatively. The EBRT + VBT group comprised 289 individuals, while the VBT group included 288 individuals. With an I2 of 0%, and a fixed effects model was used. The results revealed that the 5-year local recurrence rate was significantly reduced in the adjuvant EBRT + VBT group compared to the adjuvant VBT group, with a statistically significant difference (RR = 0.32, 95% CI: 0.13–0.75, P = 0.009) (Fig. 12 ). Three studies reported the 5-year distant metastasis rates of patients with stage IB endometrioid carcinoma who underwent adjuvant EBRT + VBT and adjuvant VBT postoperatively. The EBRT + VBT group comprised 431 individuals, while the VBT group included 313 individuals. With an I2 of 0%, a fixed effects model was employed. The results indicated that the 5-year incidence of distant metastasis was significantly lower in the adjuvant EBRT + VBT group compared to the adjuvant VBT group, with a statistically significant difference (RR = 0.56, 95% CI: 0.32–0.96, P = 0.03) (Fig. 13 ). The EBRT + VBT group and the EBRT group Two articles described the 5-year OS rates of patients with stage IB endometrioid carcinoma who received either adjuvant EBRT + VBT or adjuvant EBRT postoperatively. The EBRT + VBT group had 860 individuals, and the EBRT group had 1135 individuals. With an I2 of 0%, a fixed effects model was employed. The results indicated that there was no significant statistical difference in the 5-year OS rates between the adjuvant EBRT + VBT and adjuvant EBRT groups (RR = 0.98, 95% CI: 0.93–1.03, P = 0.46) (Fig. 15 ). Toxicities Among the studies we included, three conducted comparative analyses of the HRQL scores between the EBRT group and the VBT group. These scores included overall health status and social functioning, where higher scores indicate higher levels of functioning or activity, and scores for urgency and diarrhea, where higher scores indicate more severe symptoms. Additionally, three studies, which included both the EBRT + VBT group and the VBT group, performed comparative analyses on toxic reactions, specifically gastrointestinal toxicity, urinary toxicity, and vaginal toxicity. The health-related quality of life scores between the EBRT group and the VBT group Three articles compared the health-related quality of life scores between two groups of patients receiving adjuvant EBRT and adjuvant VBT postoperatively. The EBRT group comprised 594 individuals, while the VBT group included 608 individuals. The results indicated that both the EBRT and VBT groups had relatively low overall health status scores at baseline, with no significant statistical difference observed (RR=-1.19, 95% CI:-3.76-1.38, P = 0.37, I2 = 0%), indicating comparability between the two groups. At 12 months post-radiotherapy, both the EBRT and VBT groups showed improvement in overall health status scores, but no significant statistical difference was found (RR=-1.80, 95% CI:-4.36-0.75, P = 0.17, I2 = 0%). However, the VBT group exhibited a more favorable overall health status compared to the EBRT group (see Fig. 6 ). The social functioning scores in both the EBRT and VBT groups were relatively low at baseline, with no statistically significant differences between the two groups (RR = -0.35, 95% CI: -2.98 to 2.29, P = 0.8, I2 = 0%), indicating comparability. At 12 months post-radiotherapy, the social function scores of both groups increased, and the VBT group had a markedly higher social function score at 12 months than the EBRT group, with a P value that signified a statistically significant difference (RR = -5.60, 95% CI: -8.33 to -2.88, P < 0.0001, I2 = 0%) (refer to Fig. 7 ). The diarrhea scores in both the EBRT and VBT groups showed no significant statistical difference at baseline (RR = 2.85, 95% CI:0.13–5.58, P = 0.04, I2 = 0%), indicating comparability between the two groups. At 12 months post-radiotherapy, the diarrhea scores of both groups increased, with higher scores indicating greater symptom severity. The VBT group had a significantly lower diarrhea score at 12 months compared to the EBRT group (RR = 8.56, 95% CI: 5.38–11.91, P < 0.00001, I2 = 0%), with a P value that was statistically significant (refer to Fig. 8 ). The urgency scores in both the EBRT and VBT groups showed no significant statistical difference at baseline (RR=-0.60, 95% CI:-5.21-4.01, P = 0.80, I2 = 0%), indicating comparability between the two groups. At 12 months post-radiotherapy, the urgency scores for both groups increased, with higher scores reflecting more severe symptoms. However, there was no significant statistical difference in the urgency of urination scores between the VBT and EBRT groups one year post-radiotherapy (RR = 4.04, 95% CI: -0.81 to 8.90, P = 0.10, I2 = 0%), although the VBT group demonstrated a relative advantage over the EBRT group (see Fig. 9 ). The EBRT + VBT group and the VBT group The main observation was the occurrence rates of gastrointestinal toxicity, genitourinary toxicity, and vaginal toxicity following adjuvant radiotherapy. Gastrointestinal toxicity reactions included nausea, diarrhea, intestinal obstruction, and fecal incontinence. Genitourinary toxicity reactions included urinary frequency, urinary incontinence, and cystitis. Vaginal toxicity reactions included vaginal stenosis and vaginal dryness. Three studies reported the 5-year occurrence rates of gastrointestinal toxicity following adjuvant EBRT + VBT and adjuvant VBT in patients with stage IB endometrioid carcinoma, comprising 431 individuals in the EBRT + VBT group and 313 individuals in the VBT group. With an I2 of 0%, a fixed-effects model was applied. Compared to the EBRT + VBT group, the 5-year occurrence rate of gastrointestinal toxicity was significantly lower in the adjuvant VBT group (RR = 3.90, 95% CI:2.18-7.00, P<0.00001). Three studies investigated the 5-year occurrence rates of genitourinary toxicity, involving 431 individuals in the EBRT + VBT group and 306 individuals in the VBT group, with an I2 of 0% and a fixed-effects model was applied. The results showed no significant difference in the occurrence rates of genitourinary toxicity between the two groups (RR = 1.68, 95% CI:0.65–4.34, P = 0.28). Two studies reported the 5-year occurrence rates of vaginal toxicity following adjuvant EBRT + VBT and adjuvant VBT, comprising 289 individuals in the EBRT + VBT group and 288 individuals in the VBT group. With an I2 of 83%, a random-effects model was applied. The results demonstrated no significant difference in the 5-year occurrence rates of vaginal toxicity between the two groups (RR = 1.76, 95% CI:0.56–5.53, P = 0.33). (See Fig. 14 ) Discussion This meta-analysis suggests that there are no significant statistical differences in 5-year OS, 5-year DFS, and the incidence of distant metastasis between patients with stage IB endometrioid carcinoma who receive postoperative adjuvant EBRT and those who receive postoperative adjuvant VBT. However, the VBT group exhibits significantly better social function scores and diarrhea scores compared to the EBRT group. Compared to postoperative adjuvant VBT, postoperative adjuvant EBRT + VBT significantly prolongs the 5-year DFS, reduces the incidence of local recurrence and distant metastasis, but does not improve the 5-year OS. The incidence of gastrointestinal toxicities is significantly lower in the postoperative adjuvant VBT group than in the EBRT + VBT group. Compared to postoperative adjuvant EBRT, the EBRT + VBT group does not improve the 5-year OS of patients. In conclusion, adjuvant VBT may represent an ideal strategy for treating stage IB endometrioid carcinoma. Currently, it remains unclear whether adjuvant VBT alone is sufficient as a treatment for stage IB endometrioid carcinoma patients or if EBRT treatment is necessary. To address this question, the Norwegian Radium Hospital conducted a study where stage I endometrial carcinoma patients were randomly assigned to either the VBT group or the VBT ± EBRT group [ 7 , 30 ]. They found that while EBRT improved local control, it was associated with a significantly lower survival rate (HR 1.36, p = 0.013) in patients under the age of 60, which the authors attributed to an increased risk of second malignant neoplasm associated with EBRT. This is consistent with the conclusions from Professor Sorbe[ 19 ] and some randomized trial data that emphasize the importance of EBRT for local-regional control[ 8 , 31 – 33 ]. The PORTEC-2 trial [ 8 ] compared patients with high to intermediate-risk disease receiving either VBT alone or EBRT treatment. While the VBT treatment group had a slightly higher risk of pelvic recurrence, there was no significant difference in vaginal recurrence or overall survival rates between the two treatment groups. Previous randomized trials, including PORTEC-1 and GOG-99, have demonstrated a significant advantage of postoperative EBRT in local-regional control, but none of these trials have shown a significant benefit for overall survival. It is unclear why the improvement in local control has not translated into an improvement in overall survival. Our study also showed that postoperative adjuvant EBRT did significantly reduce the rates of local recurrence and distant metastasis, but the 5-year survival rate of patients was not improved. The reasons for this may be related to increased adverse reactions associated with EBRT or an increased risk of second malignant neoplasm. Professor Chino conducted a study analyzing data from the SEER database and found that in patients with FIGO stage IB endometrioid carcinoma who underwent lymph node dissection, all three radiation therapy modalities (EBRT, EBRT + VBT, and VBT alone) were superior to no adjuvant treatment, but there was no significant difference among the three radiation therapy modalities [ 34 ]. Professor Andrew T. Wong’s research on patients with IB stage endometrioid carcinoma found that postoperative adjuvant EBRT treatment (HR 0.83, 95%CI 0.74–0.93, p = 0.002) and adjuvant VBT treatment (HR 0.82, 95%CI 0.74–0.93, p = 0.002) both improved patient survival rates[ 35 ]. These studies all indicate that adjuvant radiation therapy after surgery is superior to no adjuvant radiation therapy for patients with stage IB endometrioid carcinoma. However, there was no significant difference in improving patient survival rates among different radiation therapy modalities. This is consistent with our study results, which may be attributed to the inherently favorable prognosis of patients with stage IB endometrioid carcinoma. In patients with stage I endometrioid carcinoma, as the risk factors increase and individual differences emerge, the rates of local recurrence and distant metastasis also increase. For instance, in patients with risk factors, such as age ≥ 60 years, deep myometrial invasion, lymphovascular space invasion (LVSI), and poor histological differentiation, the rates of local recurrence and distant metastasis tend to rise [ 6 ]. This indicates the necessity for individualized postoperative adjuvant treatment. The risk factors include: 1) age ≥ 60 years; 2) deep myometrial invasion; 3) lymphovascular space invasion (LVSI); 4) poor histological differentiation [ 6 ]. The PORTEC-1 trial compared postoperative EBRT treatment with observation in patients with stage I endometrial carcinoma, while the PORTEC-2 trial compared postoperative EBRT treatment with VBT treatment in these patients. Professor Tjalling Bosse and colleagues [ 36 ], through a pooled analysis of the PORTEC-1 and PORTEC-2 trials, found that LVSI was the strongest independent prognostic factor for pelvic recurrence, distant metastasis, and overall survival. Treatment decisions should be based on the presence of risk factors such as LVSI and histological differentiation. Unfortunately, in the studies included in our meta-analysis, there were no detailed data on tumor differentiation, patient age, LVSI, and other risk factors in the VBT group, EBRT group, or EBRT + VBT group. Therefore, we were unable to conduct further stratified analysis based on these risk factors, which may have had an impact on the results. Both EBRT and VBT treatments can lead to the occurrence of acute toxicity and long-term complications. Published literature indicates that the toxic reactions of EBRT mainly include pain, fatigue, hearing impairment, dermoreaction, genitourinary reactions (thamuria, urinary incontinence, cystitis), gastrointestinal reactions (nausea, diarrhea, intestinal obstruction, fecal incontinence), neurological complications (motor neuropathy, sensory neuropathy), soft tissue reactions, and pelvic insufficiency fractures [ 5 , 10 – 12 ]. Research by Professor Ta M-H and colleagues [ 37 ] revealed that the most common toxic reactions are gastrointestinal and genitourinary reactions. Professor Stephanie M. de Boer reported that patients undergoing EBRT treatment experience more intestinal symptoms, which affect daily activities [ 26 ].Professor Nout RA found through HRQL analysis that patients receiving EBRT treatment are more likely to need to be close to the toilet due to intestinal issues, which severely restrict their daily activities [ 24 ]. HRQL analysis of survivors 15 years after the PORTEC-1 trial found that patients treated with EBRT continue to experience intestinal symptoms over time [ 10 , 24 , 25 ]. This is consistent with our research results. Professor Stephanie M. de Boer also reported that patients receiving EBRT treatment are more likely to experience late-stage genitourinary symptoms, which may be due to the long-term effects of EBRT treatment on the normal aging changes of pelvic floor muscles but do not affect overall quality of life [ 26 ]. Compared with EBRT treatment, VBT treatment is mainly used for the vaginal stump and part of the upper vagina, and the radiation range usually includes the upper 1/2 of the vagina, which results in lower doses to surrounding normal tissues. Therefore, the incidence of bladder, intestinal tract, skeleton, and bone marrow toxicity with VBT is lower. The toxic reactions of VBT mainly include vaginal mucosal atrophy leading to vaginal dryness, dyspareunia, and vaginal fibrosis leading to vaginal stenosis or shortening. In our meta-analysis, there was no significant statistical difference in the incidence of vaginal toxicity between the EBRT + VBT group and the VBT group, which may be due to the small number of studies included and high heterogeneity, which significantly influenced the results of this study. The PORTEC-2 trial reported that the rates of sexual activity and symptom scores were similar to the long-term scores of survivors in the PORTEC-1 trial and were similar to those of patients undergoing surgery alone, indicating that cancer diagnosis and treatment have an impact on the sexual aspect of HRQL [ 10 ]. Limitations of any conclusion include lower rates of sexual activity in the elderly and lower completion rates of sexual dysfunction surveys. In this study, although the dosage regimens for the three radiation therapy modalities (EBRT, EBRT + VBT, and VBT) varied among individuals, they were mostly controlled within certain ranges. The dosage range for EBRT was generally between 44.0 Gy and 54.0 Gy; in combined therapy, the range for EBRT use was mostly between 39.6 Gy and 50.4 Gy, with VBT serving as a booster, featuring various dosage fractionation schemes mostly ranging from 4–6 Gy * 2–3 times; while for standalone VBT treatment, different dosage regimens schemes were mostly 7 Gy * 3 times or 6 Gy * 5 times. The specific dosage regimens schemes were determined by the treating physician based on comprehensive evaluations of individual patient differences. The strength of our study includes its focused examination on the choice of adjuvant radiotherapy for stage IB endometrioid carcinoma patients after surgery, representing a single stage of endometrial carcinoma and thus reducing heterogeneity. Another advantage is that the included studies are all randomized controlled trials, which provide a high level of evidence in evidence-based medicine. However, there are limitations to our study. Firstly, the included literature did not classify patients according to risk factors, thus preventing further stratified analysis based on these factors. Additionally, the specific dosage regimens for radiation therapy in the studies were determined subjectively by the treating physicians based on individual patient assessments, introducing some degree of subjectivity. Despite these limitations, the majority of studies included in our analysis were of high quality. Currently, there is a lack of research on the targeted selection of adjuvant treatment modalities based on risk factors in patients with stage IB endometrioid carcinoma. To better elucidate the decision-making process for adjuvant radiotherapy, larger sample sizes and multicenter randomized controlled trials are needed to obtain higher-quality data and further clarify which adjuvant radiotherapy modality can provide greater survival benefits and improve quality of life for patients. Conclusion There was no significant difference in 5-year OS in patients with stage IB endometrial carcinoma treated with VBT, EBRT and EBRT + VBT after surgery. Compared with VBT and EBRT, EBRT + VBT significantly extended DFS for 5 years and reduced the incidence of local recurrence and distant metastasis. Although there was no significant difference between VBT and EBRT in overall health status score and urgency of urination score, VBT was superior to EBRT in diarrhea score, other gastrointestinal toxicity and social function score. References CROSBIE E J, KITSON S J, MCALPINE J N, et al. Endometrial cancer[J]. Lancet, 2022, 399(10333): 1412–1428. Trojano Giuseppe et al. Conservative treatment in early stage endometrial cancer: a review.[J]. Acta bio-medica: Atenei Parmensis, 2019, 90(4) : 405–410. Braun MM,Overbeek-Wager EA,Grumbo RJ.Diagnosis and management of endometrial cancer[J].Am Fam Physician,2016,93(6):468–474. 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Long-Term Impact of Endometrial Cancer Diagnosis and Treatment on Health-Related Quality of Life and Cancer Survivorship: Results From the Randomized PORTEC-2 Trial. Int J Radiat Oncol Biol Phys. 2015;93(4):797–809. doi: 10.1016/j.ijrobp.2015.08.023 . van Andel G, Bottomley A, Fosså SD, et al. An international field study of the EORTC QLQ-PR25: a questionnaire for assessing the health-related quality of life of patients with prostate cancer. Eur J Cancer. 2008;44(16):2418–2424. doi: 10.1016/j.ejca.2008.07.030 . Greimel E, Bottomley A, Cull A, et al. An international field study of the reliability and validity of a disease-specific questionnaire module (the QLQ-OV28) in assessing the quality of life of patients with ovarian cancer [published correction appears in Eur J Cancer. 2003;39(17):2570]. Eur J Cancer. 2003;39(10):1402–1408. doi: 10.1016/s0959-8049(03)00307-1 . van de Poll-Franse LV, Mols F, Gundy CM, et al. Normative data for the EORTC QLQ-C30 and EORTC-sexuality items in the general Dutch population. Eur J Cancer. 2011;47(5):667–675. doi: 10.1016/j.ejca.2010.11.004 . Aalders J, Abeler V, Kolstad P, Onsrud M. Postoperative external irradiation and prognostic parameters in stage I endometrial carcinoma: clinical and histopathologic study of 540 patients. Obstet Gynecol. 1980;56(4):419–427. Keys HM, Roberts JA, Brunetto VL, et al. A phase III trial of surgery with or without adjunctive external pelvic radiation therapy in intermediate risk endometrial adenocarcinoma: a Gynecologic Oncology Group study [published correction appears in Gynecol Oncol. 2004;94(1):241-2]. Gynecol Oncol. 2004;92(3):744–751. doi: 10.1016/j.ygyno.2003.11.048 . Creutzberg CL, van Putten WL, Koper PC, et al. Surgery and postoperative radiotherapy versus surgery alone for patients with stage-1 endometrial carcinoma: multicentre randomised trial. PORTEC Study Group. Post Operative Radiation Therapy in Endometrial Carcinoma. Lancet. 2000;355(9213):1404–1411. doi: 10.1016/s0140-6736(00)02139-5 . Matei D, Filiaci V, Randall ME, et al. Adjuvant Chemotherapy plus Radiation for Locally Advanced Endometrial Cancer. N Engl J Med. 2019;380(24):2317–2326. doi: 10.1056/NEJMoa1813181 . Chino JP, Jones E, Berchuck A, Secord AA, Havrilesky LJ. The influence of radiation modality and lymph node dissection on survival in early-stage endometrial cancer. Int J Radiat Oncol Biol Phys. 2012;82(5):1872–1879. doi: 10.1016/j.ijrobp.2011.03.054 . Wong AT, Rineer J, Schwartz D, et al. Patterns of adjuvant radiation usage and Survival findings for stage I endometrial carcinoma in a large hospital-based cohort. Gynecol Oncol. 2017;144(1):113–118. doi: 10.1016/j.ygyno.2016.11.003 . Bosse T, Peters EE, Creutzberg CL, et al. Substantial lymph-vascular space invasion (LVSI) is a significant risk factor for recurrence in endometrial cancer–A pooled analysis of PORTEC 1 and 2 trials. Eur J Cancer. 2015;51(13):1742–1750. doi: 10.1016/j.ejca.2015.05.015 . Ta MH, Schernberg A, Giraud P, et al. Comparison of 3D conformal radiation therapy and intensity-modulated radiation therapy in patients with endometrial cancer: efficacy, safety and prognostic analysis. Acta Oncol. 2019;58(8):1127–1134. doi: 10.1080/0284186X.2019.1599136 . Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4252806","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":290570342,"identity":"0823d148-4ea3-4cc8-8299-c35db7fe5e13","order_by":0,"name":"Hai-Na Qu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA00lEQVRIiWNgGAWjYBACeYbjBx9+MKixY2xvPkCcFsPGM8nGEhXHkpl7jiUQac3hA2YSPGeYGdtn5BgQp4Ox7UCChGQbGzNvQ87HG28Y7OR0GwhoYec5eMCgsE2GT7Lh7GbLOQzJxmYHCNky40BCAsgWw8bebdI8DAcStxHSwnD/gcEB3jZmxv2HeZ4RqeXAAcMGkPcb23jYiNNi2HAmmRkUyIw9bMaWcwyI8AswKo//BEfl/McPb7ypsJMjqAUFSPAQGTXIWkjVMQpGwSgYBSMCAABjo0dCC2u/KwAAAABJRU5ErkJggg==","orcid":"","institution":"","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Hai-Na","middleName":"","lastName":"Qu","suffix":""}],"badges":[],"createdAt":"2024-04-11 13:38:47","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4252806/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4252806/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":54861183,"identity":"91e5c45c-852d-4e98-91f7-faefda95e723","added_by":"auto","created_at":"2024-04-17 19:44:12","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":428753,"visible":true,"origin":"","legend":"\u003cp\u003eFlow diagram of the study selection procedure.\u003c/p\u003e","description":"","filename":"Fig.1.tif.png","url":"https://assets-eu.researchsquare.com/files/rs-4252806/v1/5bb572fa8d5b2d59fd5ba1ac.png"},{"id":54861632,"identity":"9f583413-93be-48ae-b504-a2fff6457427","added_by":"auto","created_at":"2024-04-17 19:52:12","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":1034685,"visible":true,"origin":"","legend":"\u003cp\u003e(A)The risk of bias graph displays the assessment of bias risk for each included study;(B)risk of bias summary displays the assessment of bias risk, representing all included studies in percentage form.\u003c/p\u003e","description":"","filename":"Fig.2.tif.png","url":"https://assets-eu.researchsquare.com/files/rs-4252806/v1/494ea7365b6f3742f066e57d.png"},{"id":54861182,"identity":"3664d9a8-7a6b-42f0-bb4a-fcd8ee07f6ff","added_by":"auto","created_at":"2024-04-17 19:44:12","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":32435,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of 5-year OS for EBRT Group versus VBT Group.\u003c/p\u003e","description":"","filename":"Fig.3.tif.png","url":"https://assets-eu.researchsquare.com/files/rs-4252806/v1/86a5778e9805a568284c062b.png"},{"id":54861184,"identity":"fc459093-9539-48f0-843e-fcda3f194c52","added_by":"auto","created_at":"2024-04-17 19:44:12","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":31920,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of 5-year DFS for EBRT Group versus VBT 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score; (B) Global Health Status score at 12 months after radiotherapy.\u003c/p\u003e\n\u003cp\u003eNote: The higher the score, the higher the level of function or activity.\u003c/p\u003e","description":"","filename":"Fig.6.Tif.png","url":"https://assets-eu.researchsquare.com/files/rs-4252806/v1/b9e1b93ea6ac1e21878a29d3.png"},{"id":54861633,"identity":"280ffaf9-5ad2-47eb-bacf-5007ef3e4b3c","added_by":"auto","created_at":"2024-04-17 19:52:12","extension":"png","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":87327,"visible":true,"origin":"","legend":"\u003cp\u003e(A) Baseline value of Social Functioning Scores; (B) Social Functioning Scores at 12 months after radiotherapy.\u003c/p\u003e","description":"","filename":"Fig.7.tif.png","url":"https://assets-eu.researchsquare.com/files/rs-4252806/v1/1ccd997c47272ec58b81f6f3.png"},{"id":54861188,"identity":"e0e7270c-358f-4e83-bebc-324129344aae","added_by":"auto","created_at":"2024-04-17 19:44:12","extension":"png","order_by":8,"title":"Figure 8","display":"","copyAsset":false,"role":"figure","size":64113,"visible":true,"origin":"","legend":"\u003cp\u003e(A) Baseline value of Diarrhea Scores; (B) Diarrhea Scores at 12 months after radiotherapy.\u003c/p\u003e\n\u003cp\u003eNote: A higher score reflects a higher level of symptoms.\u003c/p\u003e","description":"","filename":"Fig.8.tif.png","url":"https://assets-eu.researchsquare.com/files/rs-4252806/v1/b16cdb715aed20bc96f0ad37.png"},{"id":54861193,"identity":"dfef9fd8-4ef4-41ea-bfaa-89257594c936","added_by":"auto","created_at":"2024-04-17 19:44:12","extension":"png","order_by":9,"title":"Figure 9","display":"","copyAsset":false,"role":"figure","size":63903,"visible":true,"origin":"","legend":"\u003cp\u003e(A) Baseline value of Urinary urgency scores ; (B) Urinary urgency scores at 12 months after radiotherapy.\u003c/p\u003e\n\u003cp\u003eNote: A higher score reflects a higher level of 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Group.\u003c/p\u003e","description":"","filename":"Fig.11.png","url":"https://assets-eu.researchsquare.com/files/rs-4252806/v1/7edb9facb11941123cbe9acf.png"},{"id":54861191,"identity":"de346708-2f8d-44bb-8dc6-ca88b3e4ac3e","added_by":"auto","created_at":"2024-04-17 19:44:12","extension":"png","order_by":12,"title":"Figure 12","display":"","copyAsset":false,"role":"figure","size":592046,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of 5-year local recurrence rate for EBRT+VBT Group versus VBT Group.\u003c/p\u003e","description":"","filename":"Fig.12.tif.png","url":"https://assets-eu.researchsquare.com/files/rs-4252806/v1/5d885e9429b915c1cede08db.png"},{"id":54861189,"identity":"e340bb67-d37b-48f8-9818-3de9dc66ca78","added_by":"auto","created_at":"2024-04-17 19:44:12","extension":"png","order_by":13,"title":"Figure 13","display":"","copyAsset":false,"role":"figure","size":4493,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of 5-year incidence of distant metastasis for EBRT+VBT Group versus VBT Group.\u003c/p\u003e","description":"","filename":"Fig.13.png","url":"https://assets-eu.researchsquare.com/files/rs-4252806/v1/7946ef83495a2db96b069253.png"},{"id":54861195,"identity":"e393daac-5593-44a6-b821-175e2aae8c97","added_by":"auto","created_at":"2024-04-17 19:44:12","extension":"png","order_by":14,"title":"Figure 14","display":"","copyAsset":false,"role":"figure","size":506532,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of 5-year incidence of toxic reactions for EBRT+VBT Group versus VBT Group.\u003c/p\u003e\n\u003cp\u003e(A)The incidence of gastrointestinal toxicity reactions;(B)The incidence of urinary system toxicity reactions;(C)The incidence of vaginal toxic reactions.\u003c/p\u003e","description":"","filename":"Fig.14.tif.png","url":"https://assets-eu.researchsquare.com/files/rs-4252806/v1/6b7cbcca93d1bebbad82ae08.png"},{"id":54861197,"identity":"2febc0bc-f821-4f03-9488-9e0e8b144952","added_by":"auto","created_at":"2024-04-17 19:44:12","extension":"png","order_by":15,"title":"Figure 15","display":"","copyAsset":false,"role":"figure","size":30482,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of 5-year OS for EBRT+VBT Group versus EBRT Group.\u003c/p\u003e","description":"","filename":"Fig.15.tif.png","url":"https://assets-eu.researchsquare.com/files/rs-4252806/v1/d70f1eaa3be43a91652ba446.png"},{"id":55264510,"identity":"b472be19-5071-41ea-aa64-bdc8604e70c8","added_by":"auto","created_at":"2024-04-25 01:45:18","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2626265,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4252806/v1/286fdba9-b5b3-41c3-98be-4be4fa9af160.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Comparison of the Efficacy of adjuvant External Beam Radiotherapy, Vaginal Brachytherapy, and External Beam Radiotherapy with Vaginal Brachytherapy in Patients with FIGO Stage IB Endometrioid carcinoma: A Meta-Analysis","fulltext":[{"header":"Introduction","content":"\u003cp\u003eEndometrial carcinoma is a prevalent malignancy among women, with its global incidence showing an upward trend in recent years. Statistical data indicates an annual occurrence of approximately 320,000 new cases worldwide, resulting in 76,000 fatalities [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. More than 90% of diagnoses occur during the perimenopausal period, with 25% before menopause and 75% after menopause [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].Vaginal bleeding commonly presents as the initial symptom, facilitating early detection of endometrioid carcinoma [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Consequently, a significant portion of patients are typically diagnosed at stages I to II, with approximately 80% at stage I, leading to favorable treatment outcomes and a five-year survival rate exceeding 95% [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Studies have shown that around 15\u0026ndash;20% of women present with high-risk factors for recurrence, warranting postoperative adjuvant radiotherapy [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. As per the NCCN guidelines, some patients with FIGO stage I endometrioid carcinoma may require postoperative targeted radiation therapy. Adjuvant radiation therapy options encompass EBRT, VBT, and EBRT\u0026thinsp;+\u0026thinsp;VBT [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003cp\u003ePostoperative adjuvant therapy for patients with FIGO stage IB endometrioid carcinoma should be tailored based on tumor differentiation and the presence of recurrence risk factors, such as age\u0026thinsp;\u0026ge;\u0026thinsp;60 years and lymphovascular space invasion (LVSI) [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. According to the NCCN guidelines, high/intermediate differentiation at FIGO stage IB warrants consideration of VBT as the primary approach. Observation may be an option for those without accompanying risk factors, while EBRT may be considered if risk factors are present. In cases of FIGO stage IB endometrioid carcinoma with low differentiation, both EBRT and/or VBT are recommended [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. However, there is ongoing controversy surrounding the selection of optimal adjuvant radiotherapy approaches. Onsrud et al. has observed that EBRT lacks survival benefits for early-stage endometrial carcinoma and should be used cautiously, particularly in women with a longer life expectancy. Trials such as PORTEC-1, PORTEC-2, and others [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] have consistently shown the notable advantage of postoperative EBRT in achieving local regional control. Nevertheless, none of these trials have revealed a significant improvement in overall survival rates. Consequently, our research was undertaken to determine a more effective postoperative adjuvant treatment strategy for stage IB endometrioid carcinoma patients.\u003c/p\u003e \u003cp\u003eThe utilization of postoperative EBRT and VBT may entail acute toxicity and long-term complications. The toxic reactions associated with EBRT typically include pain, genitourinary reactions (e.g., urinary frequency, urinary incontinence, and cystitis), and gastrointestinal reactions (such as nausea, diarrhea, intestinal obstruction, and fecal incontinence) [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan additionalcitationids=\"CR11\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. In contrast, The toxicities associated with VBT mainly consist of vaginal mucosal atrophy leading to vaginal dryness, dyspareunia, and vaginal fibrosis resulting in vaginal stenosis or shortening.This could potentially reduce the quality of life for certain patients [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Consequently, decisions regarding postoperative adjuvant radiotherapy must be grounded in genuine clinical benefits. Yet, whether different adjuvant radiotherapy modalities following surgery for stage IB endometrioid carcinoma yield distinct treatment effects remains inconclusive in current research [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. To explore which radiotherapy modality can optimize local recurrence control, mitigate toxicity, and enhance the quality of life for patients, we undertook this meta-analysis.This meta-analysis retrieved 10 randomized controlled trials focusing on adjuvant radiotherapy in patients with stage IB endometrioid carcinoma post-surgery. The aim was to compare the clinical utility of EBRT, VBT, and EBRT\u0026thinsp;+\u0026thinsp;VBT, aiming to guide the clinical management of adjuvant radiotherapy in women with stage IB endometrioid carcinoma post-surgery.\u003c/p\u003e"},{"header":"Studies and methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eLiterature search:\u003c/h2\u003e \u003cp\u003eWe conducted searches in the following databases: PubMed, EMBASE, and CENTRAL (Cochrane Library), using the following main search terms: \u0026ldquo;Endometrial Neoplasm\u0026rdquo;, \u0026ldquo;Neoplasm,Endometrial\u0026rdquo;, \u0026ldquo;Neoplasms,Endometrial\u0026rdquo;, \u0026ldquo;Endometrial Carcinoma\u0026rdquo;, \u0026ldquo;Carcinoma,Endometrial\u0026rdquo;, \u0026ldquo;Carcinomas,Endometrial\u0026rdquo;, \u0026ldquo;Endometrial Carcinomas\u0026rdquo;, \u0026ldquo;Endometrial Cancer\u0026rdquo;, \u0026ldquo;Cancer,Endometrial\u0026rdquo;, \u0026ldquo;Cancers,Endometrial\u0026rdquo;, \u0026ldquo;Endometrial Cancers\u0026rdquo;, \u0026ldquo;Endometrium Cancer\u0026rdquo;, \u0026ldquo;Cancer, Endometrium\u0026rdquo;, \u0026ldquo;Cancers,Endometrium\u0026rdquo;, \u0026ldquo;Cancer of the Endometrium\u0026rdquo;, \u0026ldquo;Carcinoma of Endometrium\u0026rdquo;, \u0026ldquo;Endometrium Carcinoma\u0026rdquo;, \u0026ldquo;Endometrium Carcinomas\u0026rdquo;, \u0026ldquo;Cancer of Endometrium\u0026rdquo;, \u0026ldquo;Endometrium Cancers\u0026rdquo;, \u0026ldquo;Radiotherapies\u0026rdquo;, \u0026ldquo;Radiation Therapy\u0026rdquo;, \u0026ldquo;Radiation Therapies \u0026rdquo;, \u0026ldquo;Therapies, Radiation\u0026rdquo;, \u0026ldquo;Therapy,Radiation\u0026rdquo;, \u0026ldquo;Radiation Treatment\u0026rdquo;, \u0026ldquo;Radiation Treatments\u0026rdquo;, \u0026ldquo;Treatment,Radiation\u0026rdquo;, \u0026ldquo;Radiotherapy,Targeted\u0026rdquo;, \u0026ldquo;Radiotherapies,Targeted\u0026rdquo;, \u0026ldquo;Targeted Radiotherapies\u0026rdquo;, \u0026ldquo;Targeted Radiotherapy\u0026rdquo;, \u0026ldquo;Targeted Radiation Therapy\u0026rdquo;, \u0026ldquo;Radiation Therapies,Targeted\u0026rdquo;, \u0026ldquo;Targeted Radiation Therapies\u0026rdquo;, \u0026ldquo;Therapies,Targeted Radiation\u0026rdquo;, \u0026ldquo;Therapy,Targeted Radiation\u0026rdquo;, \u0026ldquo;Radiation Therapy,Targeted\u0026rdquo;, \u0026ldquo;randomized controlled trial\u0026rdquo;, \u0026ldquo;randomized\u0026rdquo;, \"placebo\". The searches were not restricted by date or language.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eSelection criteria:\u003c/h2\u003e \u003cp\u003e \u003cstrong\u003eInclusion criteria\u003c/strong\u003e \u003cp\u003e1. The patient met the diagnostic criteria based on pathology, and was eventually diagnosed with stage IB endometrioid carcinoma; 2. The research objectives are not restricted by nationality, age, gender, income, race, or any other factors; 3. All included patients underwent a laparoscopic total hysterectomy with salpingo-oophorectomy, and gynecologists performed pelvic and paraaortic lymph node dissection according to the NCCN guidelines; 4. Patients were randomly assigned to either the EBRT group, the VBT group, or the EBRT\u0026thinsp;+\u0026thinsp;VBT group post-surgery; 5. The study design employed a randomized controlled trial; 6. Complete clinical raw data was available.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eExclusion criteria\u003c/strong\u003e \u003cp\u003e1. The patients were confirmed to neither have stage IB endometrioid carcinoma nor a recurrence or metastasis of endometrial carcinoma following pathological diagnoses; 2.Patients who had undergone radiotherapy or chemotherapy prior to surgery; 3.Animal experiments; 4.Irrelevant to the research topic; 5. Conference summaries, meta-analyses, reviews, case reports.\u003c/p\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eData extraction and quality assessment\u003c/h2\u003e \u003cp\u003e The first reviewer extracted data from the included studies.The second reviewer re-confirmed the data to minimize potential errors.The data extracted from each study include the first author, the year of publication, the type of study, the number of patients, the method of adjuvant radiotherapy used, and the outcomes. The methods of adjuvant radiotherapy include VBT, EBRT, and EBRT\u0026thinsp;+\u0026thinsp;VBT. The primary study outcomes include the 5-year OS rate, the 5-year DFS rate, the incidence of distant metastases, and the rate of local recurrence. Secondary outcomes include toxicological reactions following radiotherapy, such as gastrointestinal toxicity, urological toxicity, and vaginal toxicity, as well as health-related quality of life scores. If the original literature provides the necessary data, it is directly extracted. If not provided, data are indirectly extracted from the figures or tables mentioned in the literature and subsequently processed using Review Manager 5.4.1 software to calculate the required data.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eData analysis\u003c/h2\u003e \u003cp\u003e We conducted the meta-analysis using the Review Manager version 5.4.1 software. Binary variables were presented as risk ratios with 95% confidence intervals. Continuous variables were displayed as weighted mean differences with 95% CI, calculated based on the mean, standard deviation, p-value, and sample size of each study.Heterogeneity was assessed using the I2 test. If the I2 value exceeded 50%, a random-effects model was applied to each variable; otherwise, a fixed-effects model was utilized for meta-analysis [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. A two-sided P value less than 0.05 was considered statistically significant. We used the Cochrane Risk of Bias Assessment Tool to evaluate the methodological quality of randomized controlled trials [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. This tool involves a per-study assessment based on seven main criteria: 1. Random sequence generation (selection bias); 2. Allocation concealment (selection bias); 3. Implementation bias (blinding of researchers and participants); 4. Measurement bias (blinding of outcome assessment); 5. Follow-up bias (completeness of outcome data); 6. Reporting bias; 7. Other biases. Each criterion can be rated as \"low risk,\" \"unclear\" (lack of information or uncertainty about the likelihood of bias), or \"high risk.\"\u003c/p\u003e \u003c/div\u003e"},{"header":"Result","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eLiterature search and included studies\u003c/h2\u003e \u003cp\u003eAfter conducting the database search according to the retrieval strategy, a total of 796 articles were retrieved. Following the establishment of inclusion and exclusion criteria, 118 studies were excluded due to duplication and animal experiments. Upon screening titles and abstracts, 560 studies were further excluded. Subsequently, 118 full-text articles were reviewed, resulting in the final inclusion of 10 articles. Among these, 79 were literature reviews, 14 were incomplete articles, 7 lacked appropriate control groups, and 8 had insufficient data. The flowchart detailing this process can be found in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eQuality evaluation\u003c/h2\u003e \u003cp\u003eAll 10 selected literature were systematically evaluated using the Cochrane Risk of Bias Assessment Tool. They provided detailed explanations of their randomization methods, which were deemed appropriate. The assessment of publication bias indicated a low risk of bias in the included studies. The results of the methodological quality assessment are depicted in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eIncluded study characteristics\u003c/h2\u003e \u003cp\u003eSeven randomized controlled studies [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan additionalcitationids=\"CR19 CR20 CR21 CR22\" citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e] reported on 4,468 patients, with 1,563 patients receiving EBRT, 1,623 patients receiving VBT, and 1,282 patients receiving EBRT\u0026thinsp;+\u0026thinsp;VBT. The details of the authors\u0026rsquo; names, publication years, treatment regimens, study duration, follow-up duration, number of patients, and data sources are included in the literature. The basic characteristics of the selected studies are presented in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eStudy characteristics\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStudy\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eData source\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePeriod\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eEBRT(n)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eVBT(n)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eEBRT\u0026thinsp;+\u0026thinsp;VBT(n)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eFollow up\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eResult\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2018\u003c/p\u003e \u003cp\u003eG.Wortman\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePORTEC-2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2002\u0026ndash;2006\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e214\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e213\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e--\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e116m\u003c/p\u003e \u003cp\u003e(18\u0026ndash;163)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e5 year overall survival;\u003c/p\u003e \u003cp\u003eDisease-free survival;\u003c/p\u003e \u003cp\u003eDistant recurrence;Vaginal recurrence;\u003c/p\u003e \u003cp\u003ePelvic recurrence\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2010\u003c/p\u003e \u003cp\u003eNout RA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19 radiation oncology centres,\u003c/p\u003e \u003cp\u003eDutch\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2002\u0026ndash;2006\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e214\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e213\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e--\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e5-10y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eVaginal recurrence;\u003c/p\u003e \u003cp\u003eLocoregional recurrence (pelvic or vaginal, or both);\u003c/p\u003e \u003cp\u003eDistant metastases;Overall;\u003c/p\u003e \u003cp\u003eDisease-free survival;Treatment-related toxic\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2016\u003c/p\u003e \u003cp\u003eVishal Gupta,\u003c/p\u003e \u003cp\u003eMD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNCDB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1998\u0026ndash;2012\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1084\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e744\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e718\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e66.1m\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e5 year overall survival\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2021\u003c/p\u003e \u003cp\u003eWenhui Wang\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13 Chinese radiation oncology centers of grade A tertiary hospitals\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1999\u0026ndash;2015\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e142\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e42m\u003c/p\u003e \u003cp\u003e(3-237)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e5 year overall survival;\u003c/p\u003e \u003cp\u003eDisease-free survival;Distant recurrence;Toxicity;\u003c/p\u003e \u003cp\u003eLocal-regional failure-free survival\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBENGT SORBE, M.D., PH.D.\u003c/p\u003e \u003cp\u003e2011\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 cancer centers,\u003c/p\u003e \u003cp\u003eSwedish\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1997\u0026ndash;2008\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e--\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e263\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e264\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e62m\u003c/p\u003e \u003cp\u003e(12\u0026ndash;138)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eLocoregional recurrences ;\u003c/p\u003e \u003cp\u003eOverall survival; Recurrence-free survival;\u003c/p\u003e \u003cp\u003eRecurrence-free interval;\u003c/p\u003e \u003cp\u003eCancer-specific survival; Toxicity\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMathias Onsrud\u003c/p\u003e \u003cp\u003e2013\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 different university hosptials\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1968\u0026ndash;1974\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e--\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e140\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e133\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e20.5y\u003c/p\u003e \u003cp\u003e(0-43.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eOverall survival;Secondary Cancer\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSunil R.A., MBBS, MD\u003c/p\u003e \u003cp\u003e2018\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGujarat Cancer Research Institute (GCRI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2011\u0026ndash;2016\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e--\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e60m\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e5 year overall survival;Toxicity;\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThree articles [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e] reported on the health-related quality of life (HRQL) scores of patients who underwent adjuvant radiotherapy postoperatively (including patients with stage IB-II). Cancer-specific HRQL was measured using the European Organisation for Research and Treatment of Cancer (EORTC) Core Questionnaire (QLQ-C30 version 3.0) [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. The EORTC QLQ-C30 is a multidimensional cancer-specific quality of life questionnaire. The QLQ-C30 questionnaire comprises 5 functional scales (physical functioning, role functioning, emotional functioning, cognitive functioning, social functioning), 9 symptom scales (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, financial difficulties), and 1 global health status scale [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. Higher scores on the functional and global health status scales indicate higher levels of functioning. Conversely, higher scores on the symptom scales reflect higher levels of symptoms and lower quality of life. Baseline quality of life questionnaires are typically administered 3 to 4 weeks after surgery and must be returned before the start of radiotherapy. The summary of HRQL scores from the selected studies is presented in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eHealth related quality of life (HRQL) after EBRT and VBT\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStudy\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eGroups\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGlobal Health Status\u003c/p\u003e \u003cp\u003eM\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSocial Functioning Scores\u003c/p\u003e \u003cp\u003eM\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eDiarrhea Scores\u003c/p\u003e \u003cp\u003eM\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eUrinary Urgency\u003c/p\u003e \u003cp\u003eM\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003e2015\u003c/p\u003e \u003cp\u003ede Boer SM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eEBRT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBaseline\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e69.6\u0026thinsp;\u0026plusmn;\u0026thinsp;20.78\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e77.5\u0026thinsp;\u0026plusmn;\u0026thinsp;22.26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e8\u0026thinsp;\u0026plusmn;\u0026thinsp;25.23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e \u003cp\u003e24\u0026thinsp;\u0026plusmn;\u0026thinsp;34.14\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12m\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e75\u0026thinsp;\u0026plusmn;\u0026thinsp;14.84\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e87.8\u0026thinsp;\u0026plusmn;\u0026thinsp;20.78\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e16\u0026thinsp;\u0026plusmn;\u0026thinsp;29.69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e \u003cp\u003e31.4\u0026thinsp;\u0026plusmn;\u0026thinsp;40.08\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eVBT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBaseline\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e70.5\u0026thinsp;\u0026plusmn;\u0026thinsp;18.51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e77.8\u0026thinsp;\u0026plusmn;\u0026thinsp;17.77\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e5\u0026thinsp;\u0026plusmn;\u0026thinsp;22.21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e \u003cp\u003e24\u0026thinsp;\u0026plusmn;\u0026thinsp;34.06\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12m\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e76.6\u0026thinsp;\u0026plusmn;\u0026thinsp;20.73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e93.2\u0026thinsp;\u0026plusmn;\u0026thinsp;22.21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e7\u0026thinsp;\u0026plusmn;\u0026thinsp;23.69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e \u003cp\u003e27.5\u0026thinsp;\u0026plusmn;\u0026thinsp;33.32\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003e2009\u003c/p\u003e \u003cp\u003eNout RA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eEBRT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBaseline\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e69\u0026thinsp;\u0026plusmn;\u0026thinsp;29.69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e77.8\u0026thinsp;\u0026plusmn;\u0026thinsp;31.91\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e7.5\u0026thinsp;\u0026plusmn;\u0026thinsp;25.97\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e \u003cp\u003e22.6\u0026thinsp;\u0026plusmn;\u0026thinsp;48.98\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12m\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e75\u0026thinsp;\u0026plusmn;\u0026thinsp;25.97\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e87.7\u0026thinsp;\u0026plusmn;\u0026thinsp;31.17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e15.2\u0026thinsp;\u0026plusmn;\u0026thinsp;46.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e \u003cp\u003e31.8\u0026thinsp;\u0026plusmn;\u0026thinsp;57.89\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eVBT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBaseline\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e70.5\u0026thinsp;\u0026plusmn;\u0026thinsp;25.91\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e78\u0026thinsp;\u0026plusmn;\u0026thinsp;31.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e4.9\u0026thinsp;\u0026plusmn;\u0026thinsp;21.47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e \u003cp\u003e24\u0026thinsp;\u0026plusmn;\u0026thinsp;44.42\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12m\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e78\u0026thinsp;\u0026plusmn;\u0026thinsp;29.62\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e93.6\u0026thinsp;\u0026plusmn;\u0026thinsp;19.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e6\u0026thinsp;\u0026plusmn;\u0026thinsp;29.62\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e \u003cp\u003e27.3\u0026thinsp;\u0026plusmn;\u0026thinsp;46.64\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003e2012\u003c/p\u003e \u003cp\u003eNout RA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eEBRT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBaseline\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e69.2\u0026thinsp;\u0026plusmn;\u0026thinsp;20.88\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e77.5\u0026thinsp;\u0026plusmn;\u0026thinsp;22.84\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e8\u0026thinsp;\u0026plusmn;\u0026thinsp;26.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e \u003cp\u003e23\u0026thinsp;\u0026plusmn;\u0026thinsp;45.68\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12m\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e76\u0026thinsp;\u0026plusmn;\u0026thinsp;26.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e88\u0026thinsp;\u0026plusmn;\u0026thinsp;26.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e15\u0026thinsp;\u0026plusmn;\u0026thinsp;26.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e \u003cp\u003e31.5\u0026thinsp;\u0026plusmn;\u0026thinsp;45.68\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eVBT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBaseline\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e70.6\u0026thinsp;\u0026plusmn;\u0026thinsp;24.61\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e78\u0026thinsp;\u0026plusmn;\u0026thinsp;20.51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e5\u0026thinsp;\u0026plusmn;\u0026thinsp;23.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e \u003cp\u003e24\u0026thinsp;\u0026plusmn;\u0026thinsp;47.86\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12m\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e77\u0026thinsp;\u0026plusmn;\u0026thinsp;27.35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e93.6\u0026thinsp;\u0026plusmn;\u0026thinsp;25.98\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e7\u0026thinsp;\u0026plusmn;\u0026thinsp;23.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e \u003cp\u003e27.6\u0026thinsp;\u0026plusmn;\u0026thinsp;41.02\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003eEBRT: External Beam Radiation Therapy\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003eVBT: Vaginal Brachytherapy\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eSurvival findings\u003c/h2\u003e \u003cp\u003eWe conducted comparative analyses of the three radiotherapy modalities. Seven studies compared the EBRT group with the VBT group, among which four studies analyzed 5-year OS, 5-year DFS, and 5-year distant metastasis rates. Five studies compared the EBRT\u0026thinsp;+\u0026thinsp;VBT group with the VBT group, analyzing 5-year OS, 5-year DFS, 5-year local recurrence rates, and 5-year distant metastasis rates. Two studies compared the EBRT\u0026thinsp;+\u0026thinsp;VBT group with the EBRT group, analyzing 5-year OS in both groups.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eThe EBRT group and the VBT group\u003c/h2\u003e \u003cp\u003eFour studies reported the 5-year OS outcomes for stage IB endometrioid carcinoma patients who received adjuvant EBRT or adjuvant VBT postoperatively. The EBRT group included 1563 individuals, and the VBT group contained 1195 individuals. With an I2 of 24%, a fixed effects model was employed. The results revealed no statistically significant difference in 5-year OS between the adjuvant EBRT and adjuvant VBT groups (RR\u0026thinsp;=\u0026thinsp;1.02, 95% CI: 0.98\u0026ndash;1.06, P\u0026thinsp;=\u0026thinsp;0.42) (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThree studies investigated the 5-year DFS of patients who received adjuvant EBRT and adjuvant VBT postoperatively. The EBRT group comprised 479 individuals, while the VBT group consisted of 451 individuals. With an I2 greater than 50%, a random effects model was employed. The results revealed no significant statistical difference in 5-year DFS between the adjuvant EBRT and adjuvant VBT groups (RR\u0026thinsp;=\u0026thinsp;1.05, 95% CI: 0.94\u0026ndash;1.18, P\u0026thinsp;=\u0026thinsp;0.40) (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThree studies analyzed the 5-year incidence of distant metastasis after adjuvant EBRT and adjuvant VBT, with 479 participants in the EBRT group and 451 participants in the VBT group. With an I2 of 0%, and a fixed effects model was employed. The results revealed no significant statistical difference in the 5-year incidence of distant metastasis between the adjuvant EBRT and adjuvant VBT groups, although the adjuvant EBRT group had a tendency to reduce the incidence of distant metastasis (RR\u0026thinsp;=\u0026thinsp;0.69, 95% CI: 0.44\u0026ndash;1.07, P\u0026thinsp;=\u0026thinsp;0.09) (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eThe EBRT\u0026thinsp;+\u0026thinsp;VBT group and the VBT group\u003c/h2\u003e \u003cp\u003eFive studies reported the 5-year OS of patients with stage IB endometrioid adenocarcinoma who received either adjuvant EBRT\u0026thinsp;+\u0026thinsp;VBT or adjuvant VBT postoperatively. The EBRT\u0026thinsp;+\u0026thinsp;VBT group included 1437 individuals, and the VBT group included 1337 individuals. With an I2 of 15%, a fixed effects model was employed. The results revealed no significant statistical difference in the 5-year OS between the adjuvant EBRT\u0026thinsp;+\u0026thinsp;VBT and adjuvant VBT groups (RR\u0026thinsp;=\u0026thinsp;1.01, 95% CI: 0.97\u0026ndash;1.05, P\u0026thinsp;=\u0026thinsp;0.73) (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e10\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThree studies reported the 5-year DFS of patients with stage IB endometrioid carcinoma who underwent adjuvant EBRT\u0026thinsp;+\u0026thinsp;VBT and adjuvant VBT postoperatively. The EBRT\u0026thinsp;+\u0026thinsp;VBT group comprised 431 individuals, while the VBT group included 313 individuals. With an I2 of 35%, a fixed effects model was employed. The results revealed that the 5-year DFS was significantly superior in the adjuvant EBRT\u0026thinsp;+\u0026thinsp;VBT group compared to the adjuvant VBT group, with a statistically significant difference (RR\u0026thinsp;=\u0026thinsp;1.16, 95% CI: 1.06\u0026ndash;1.27, P\u0026thinsp;=\u0026thinsp;0.0010) (Fig.\u0026nbsp;\u003cspan refid=\"Fig7\" class=\"InternalRef\"\u003e11\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eTwo studies reported the 5-year local recurrence rates of patients with stage IB endometrioid carcinoma who underwent adjuvant EBRT\u0026thinsp;+\u0026thinsp;VBT and adjuvant VBT postoperatively. The EBRT\u0026thinsp;+\u0026thinsp;VBT group comprised 289 individuals, while the VBT group included 288 individuals. With an I2 of 0%, and a fixed effects model was used. The results revealed that the 5-year local recurrence rate was significantly reduced in the adjuvant EBRT\u0026thinsp;+\u0026thinsp;VBT group compared to the adjuvant VBT group, with a statistically significant difference (RR\u0026thinsp;=\u0026thinsp;0.32, 95% CI: 0.13\u0026ndash;0.75, P\u0026thinsp;=\u0026thinsp;0.009) (Fig.\u0026nbsp;\u003cspan refid=\"Fig8\" class=\"InternalRef\"\u003e12\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThree studies reported the 5-year distant metastasis rates of patients with stage IB endometrioid carcinoma who underwent adjuvant EBRT\u0026thinsp;+\u0026thinsp;VBT and adjuvant VBT postoperatively. The EBRT\u0026thinsp;+\u0026thinsp;VBT group comprised 431 individuals, while the VBT group included 313 individuals. With an I2 of 0%, a fixed effects model was employed. The results indicated that the 5-year incidence of distant metastasis was significantly lower in the adjuvant EBRT\u0026thinsp;+\u0026thinsp;VBT group compared to the adjuvant VBT group, with a statistically significant difference (RR\u0026thinsp;=\u0026thinsp;0.56, 95% CI: 0.32\u0026ndash;0.96, P\u0026thinsp;=\u0026thinsp;0.03) (Fig.\u0026nbsp;\u003cspan refid=\"Fig9\" class=\"InternalRef\"\u003e13\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eThe EBRT\u0026thinsp;+\u0026thinsp;VBT group and the EBRT group\u003c/h2\u003e \u003cp\u003eTwo articles described the 5-year OS rates of patients with stage IB endometrioid carcinoma who received either adjuvant EBRT\u0026thinsp;+\u0026thinsp;VBT or adjuvant EBRT postoperatively. The EBRT\u0026thinsp;+\u0026thinsp;VBT group had 860 individuals, and the EBRT group had 1135 individuals. With an I2 of 0%, a fixed effects model was employed. The results indicated that there was no significant statistical difference in the 5-year OS rates between the adjuvant EBRT\u0026thinsp;+\u0026thinsp;VBT and adjuvant EBRT groups (RR\u0026thinsp;=\u0026thinsp;0.98, 95% CI: 0.93\u0026ndash;1.03, P\u0026thinsp;=\u0026thinsp;0.46) (Fig.\u0026nbsp;\u003cspan refid=\"Fig10\" class=\"InternalRef\"\u003e15\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003eToxicities\u003c/h2\u003e \u003cp\u003eAmong the studies we included, three conducted comparative analyses of the HRQL scores between the EBRT group and the VBT group. These scores included overall health status and social functioning, where higher scores indicate higher levels of functioning or activity, and scores for urgency and diarrhea, where higher scores indicate more severe symptoms. Additionally, three studies, which included both the EBRT\u0026thinsp;+\u0026thinsp;VBT group and the VBT group, performed comparative analyses on toxic reactions, specifically gastrointestinal toxicity, urinary toxicity, and vaginal toxicity.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003eThe health-related quality of life scores between the EBRT group and the VBT group\u003c/h2\u003e \u003cp\u003eThree articles compared the health-related quality of life scores between two groups of patients receiving adjuvant EBRT and adjuvant VBT postoperatively. The EBRT group comprised 594 individuals, while the VBT group included 608 individuals. The results indicated that both the EBRT and VBT groups had relatively low overall health status scores at baseline, with no significant statistical difference observed (RR=-1.19, 95% CI:-3.76-1.38, P\u0026thinsp;=\u0026thinsp;0.37, I2\u0026thinsp;=\u0026thinsp;0%), indicating comparability between the two groups. At 12 months post-radiotherapy, both the EBRT and VBT groups showed improvement in overall health status scores, but no significant statistical difference was found (RR=-1.80, 95% CI:-4.36-0.75, P\u0026thinsp;=\u0026thinsp;0.17, I2\u0026thinsp;=\u0026thinsp;0%). However, the VBT group exhibited a more favorable overall health status compared to the EBRT group (see Fig.\u0026nbsp;\u003cspan refid=\"Fig11\" class=\"InternalRef\"\u003e6\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe social functioning scores in both the EBRT and VBT groups were relatively low at baseline, with no statistically significant differences between the two groups (RR = -0.35, 95% CI: -2.98 to 2.29, P\u0026thinsp;=\u0026thinsp;0.8, I2\u0026thinsp;=\u0026thinsp;0%), indicating comparability. At 12 months post-radiotherapy, the social function scores of both groups increased, and the VBT group had a markedly higher social function score at 12 months than the EBRT group, with a P value that signified a statistically significant difference (RR = -5.60, 95% CI: -8.33 to -2.88, P\u0026thinsp;\u0026lt;\u0026thinsp;0.0001, I2\u0026thinsp;=\u0026thinsp;0%) (refer to Fig.\u0026nbsp;\u003cspan refid=\"Fig12\" class=\"InternalRef\"\u003e7\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe diarrhea scores in both the EBRT and VBT groups showed no significant statistical difference at baseline (RR\u0026thinsp;=\u0026thinsp;2.85, 95% CI:0.13\u0026ndash;5.58, P\u0026thinsp;=\u0026thinsp;0.04, I2\u0026thinsp;=\u0026thinsp;0%), indicating comparability between the two groups. At 12 months post-radiotherapy, the diarrhea scores of both groups increased, with higher scores indicating greater symptom severity. The VBT group had a significantly lower diarrhea score at 12 months compared to the EBRT group (RR\u0026thinsp;=\u0026thinsp;8.56, 95% CI: 5.38\u0026ndash;11.91, P\u0026thinsp;\u0026lt;\u0026thinsp;0.00001, I2\u0026thinsp;=\u0026thinsp;0%), with a P value that was statistically significant (refer to Fig.\u0026nbsp;\u003cspan refid=\"Fig13\" class=\"InternalRef\"\u003e8\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe urgency scores in both the EBRT and VBT groups showed no significant statistical difference at baseline (RR=-0.60, 95% CI:-5.21-4.01, P\u0026thinsp;=\u0026thinsp;0.80, I2\u0026thinsp;=\u0026thinsp;0%), indicating comparability between the two groups. At 12 months post-radiotherapy, the urgency scores for both groups increased, with higher scores reflecting more severe symptoms. However, there was no significant statistical difference in the urgency of urination scores between the VBT and EBRT groups one year post-radiotherapy (RR\u0026thinsp;=\u0026thinsp;4.04, 95% CI: -0.81 to 8.90, P\u0026thinsp;=\u0026thinsp;0.10, I2\u0026thinsp;=\u0026thinsp;0%), although the VBT group demonstrated a relative advantage over the EBRT group (see Fig.\u0026nbsp;\u003cspan refid=\"Fig14\" class=\"InternalRef\"\u003e9\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec17\" class=\"Section2\"\u003e \u003ch2\u003eThe EBRT\u0026thinsp;+\u0026thinsp;VBT group and the VBT group\u003c/h2\u003e \u003cp\u003eThe main observation was the occurrence rates of gastrointestinal toxicity, genitourinary toxicity, and vaginal toxicity following adjuvant radiotherapy. Gastrointestinal toxicity reactions included nausea, diarrhea, intestinal obstruction, and fecal incontinence. Genitourinary toxicity reactions included urinary frequency, urinary incontinence, and cystitis. Vaginal toxicity reactions included vaginal stenosis and vaginal dryness. Three studies reported the 5-year occurrence rates of gastrointestinal toxicity following adjuvant EBRT\u0026thinsp;+\u0026thinsp;VBT and adjuvant VBT in patients with stage IB endometrioid carcinoma, comprising 431 individuals in the EBRT\u0026thinsp;+\u0026thinsp;VBT group and 313 individuals in the VBT group. With an I2 of 0%, a fixed-effects model was applied. Compared to the EBRT\u0026thinsp;+\u0026thinsp;VBT group, the 5-year occurrence rate of gastrointestinal toxicity was significantly lower in the adjuvant VBT group (RR\u0026thinsp;=\u0026thinsp;3.90, 95% CI:2.18-7.00, P\u0026lt;0.00001). Three studies investigated the 5-year occurrence rates of genitourinary toxicity, involving 431 individuals in the EBRT\u0026thinsp;+\u0026thinsp;VBT group and 306 individuals in the VBT group, with an I2 of 0% and a fixed-effects model was applied. The results showed no significant difference in the occurrence rates of genitourinary toxicity between the two groups (RR\u0026thinsp;=\u0026thinsp;1.68, 95% CI:0.65\u0026ndash;4.34, P\u0026thinsp;=\u0026thinsp;0.28). Two studies reported the 5-year occurrence rates of vaginal toxicity following adjuvant EBRT\u0026thinsp;+\u0026thinsp;VBT and adjuvant VBT, comprising 289 individuals in the EBRT\u0026thinsp;+\u0026thinsp;VBT group and 288 individuals in the VBT group. With an I2 of 83%, a random-effects model was applied. The results demonstrated no significant difference in the 5-year occurrence rates of vaginal toxicity between the two groups (RR\u0026thinsp;=\u0026thinsp;1.76, 95% CI:0.56\u0026ndash;5.53, P\u0026thinsp;=\u0026thinsp;0.33). (See Fig.\u0026nbsp;\u003cspan refid=\"Fig15\" class=\"InternalRef\"\u003e14\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis meta-analysis suggests that there are no significant statistical differences in 5-year OS, 5-year DFS, and the incidence of distant metastasis between patients with stage IB endometrioid carcinoma who receive postoperative adjuvant EBRT and those who receive postoperative adjuvant VBT. However, the VBT group exhibits significantly better social function scores and diarrhea scores compared to the EBRT group. Compared to postoperative adjuvant VBT, postoperative adjuvant EBRT\u0026thinsp;+\u0026thinsp;VBT significantly prolongs the 5-year DFS, reduces the incidence of local recurrence and distant metastasis, but does not improve the 5-year OS. The incidence of gastrointestinal toxicities is significantly lower in the postoperative adjuvant VBT group than in the EBRT\u0026thinsp;+\u0026thinsp;VBT group. Compared to postoperative adjuvant EBRT, the EBRT\u0026thinsp;+\u0026thinsp;VBT group does not improve the 5-year OS of patients. In conclusion, adjuvant VBT may represent an ideal strategy for treating stage IB endometrioid carcinoma.\u003c/p\u003e \u003cp\u003eCurrently, it remains unclear whether adjuvant VBT alone is sufficient as a treatment for stage IB endometrioid carcinoma patients or if EBRT treatment is necessary. To address this question, the Norwegian Radium Hospital conducted a study where stage I endometrial carcinoma patients were randomly assigned to either the VBT group or the VBT\u0026thinsp;\u0026plusmn;\u0026thinsp;EBRT group [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. They found that while EBRT improved local control, it was associated with a significantly lower survival rate (HR 1.36, p\u0026thinsp;=\u0026thinsp;0.013) in patients under the age of 60, which the authors attributed to an increased risk of second malignant neoplasm associated with EBRT. This is consistent with the conclusions from Professor Sorbe[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e] and some randomized trial data that emphasize the importance of EBRT for local-regional control[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan additionalcitationids=\"CR32\" citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. The PORTEC-2 trial [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e] compared patients with high to intermediate-risk disease receiving either VBT alone or EBRT treatment. While the VBT treatment group had a slightly higher risk of pelvic recurrence, there was no significant difference in vaginal recurrence or overall survival rates between the two treatment groups. Previous randomized trials, including PORTEC-1 and GOG-99, have demonstrated a significant advantage of postoperative EBRT in local-regional control, but none of these trials have shown a significant benefit for overall survival. It is unclear why the improvement in local control has not translated into an improvement in overall survival. Our study also showed that postoperative adjuvant EBRT did significantly reduce the rates of local recurrence and distant metastasis, but the 5-year survival rate of patients was not improved. The reasons for this may be related to increased adverse reactions associated with EBRT or an increased risk of second malignant neoplasm.\u003c/p\u003e \u003cp\u003eProfessor Chino conducted a study analyzing data from the SEER database and found that in patients with FIGO stage IB endometrioid carcinoma who underwent lymph node dissection, all three radiation therapy modalities (EBRT, EBRT\u0026thinsp;+\u0026thinsp;VBT, and VBT alone) were superior to no adjuvant treatment, but there was no significant difference among the three radiation therapy modalities [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. Professor Andrew T. Wong\u0026rsquo;s research on patients with IB stage endometrioid carcinoma found that postoperative adjuvant EBRT treatment (HR 0.83, 95%CI 0.74\u0026ndash;0.93, p\u0026thinsp;=\u0026thinsp;0.002) and adjuvant VBT treatment (HR 0.82, 95%CI 0.74\u0026ndash;0.93, p\u0026thinsp;=\u0026thinsp;0.002) both improved patient survival rates[\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. These studies all indicate that adjuvant radiation therapy after surgery is superior to no adjuvant radiation therapy for patients with stage IB endometrioid carcinoma. However, there was no significant difference in improving patient survival rates among different radiation therapy modalities. This is consistent with our study results, which may be attributed to the inherently favorable prognosis of patients with stage IB endometrioid carcinoma.\u003c/p\u003e \u003cp\u003eIn patients with stage I endometrioid carcinoma, as the risk factors increase and individual differences emerge, the rates of local recurrence and distant metastasis also increase. For instance, in patients with risk factors, such as age\u0026thinsp;\u0026ge;\u0026thinsp;60 years, deep myometrial invasion, lymphovascular space invasion (LVSI), and poor histological differentiation, the rates of local recurrence and distant metastasis tend to rise [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. This indicates the necessity for individualized postoperative adjuvant treatment. The risk factors include: 1) age\u0026thinsp;\u0026ge;\u0026thinsp;60 years; 2) deep myometrial invasion; 3) lymphovascular space invasion (LVSI); 4) poor histological differentiation [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. The PORTEC-1 trial compared postoperative EBRT treatment with observation in patients with stage I endometrial carcinoma, while the PORTEC-2 trial compared postoperative EBRT treatment with VBT treatment in these patients. Professor Tjalling Bosse and colleagues [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e], through a pooled analysis of the PORTEC-1 and PORTEC-2 trials, found that LVSI was the strongest independent prognostic factor for pelvic recurrence, distant metastasis, and overall survival. Treatment decisions should be based on the presence of risk factors such as LVSI and histological differentiation. Unfortunately, in the studies included in our meta-analysis, there were no detailed data on tumor differentiation, patient age, LVSI, and other risk factors in the VBT group, EBRT group, or EBRT\u0026thinsp;+\u0026thinsp;VBT group. Therefore, we were unable to conduct further stratified analysis based on these risk factors, which may have had an impact on the results.\u003c/p\u003e \u003cp\u003eBoth EBRT and VBT treatments can lead to the occurrence of acute toxicity and long-term complications. Published literature indicates that the toxic reactions of EBRT mainly include pain, fatigue, hearing impairment, dermoreaction, genitourinary reactions (thamuria, urinary incontinence, cystitis), gastrointestinal reactions (nausea, diarrhea, intestinal obstruction, fecal incontinence), neurological complications (motor neuropathy, sensory neuropathy), soft tissue reactions, and pelvic insufficiency fractures [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan additionalcitationids=\"CR11\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Research by Professor Ta M-H and colleagues [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e] revealed that the most common toxic reactions are gastrointestinal and genitourinary reactions. Professor Stephanie M. de Boer reported that patients undergoing EBRT treatment experience more intestinal symptoms, which affect daily activities [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e].Professor Nout RA found through HRQL analysis that patients receiving EBRT treatment are more likely to need to be close to the toilet due to intestinal issues, which severely restrict their daily activities [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. HRQL analysis of survivors 15 years after the PORTEC-1 trial found that patients treated with EBRT continue to experience intestinal symptoms over time [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. This is consistent with our research results. Professor Stephanie M. de Boer also reported that patients receiving EBRT treatment are more likely to experience late-stage genitourinary symptoms, which may be due to the long-term effects of EBRT treatment on the normal aging changes of pelvic floor muscles but do not affect overall quality of life [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Compared with EBRT treatment, VBT treatment is mainly used for the vaginal stump and part of the upper vagina, and the radiation range usually includes the upper 1/2 of the vagina, which results in lower doses to surrounding normal tissues. Therefore, the incidence of bladder, intestinal tract, skeleton, and bone marrow toxicity with VBT is lower. The toxic reactions of VBT mainly include vaginal mucosal atrophy leading to vaginal dryness, dyspareunia, and vaginal fibrosis leading to vaginal stenosis or shortening. In our meta-analysis, there was no significant statistical difference in the incidence of vaginal toxicity between the EBRT\u0026thinsp;+\u0026thinsp;VBT group and the VBT group, which may be due to the small number of studies included and high heterogeneity, which significantly influenced the results of this study. The PORTEC-2 trial reported that the rates of sexual activity and symptom scores were similar to the long-term scores of survivors in the PORTEC-1 trial and were similar to those of patients undergoing surgery alone, indicating that cancer diagnosis and treatment have an impact on the sexual aspect of HRQL [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Limitations of any conclusion include lower rates of sexual activity in the elderly and lower completion rates of sexual dysfunction surveys.\u003c/p\u003e \u003cp\u003eIn this study, although the dosage regimens for the three radiation therapy modalities (EBRT, EBRT\u0026thinsp;+\u0026thinsp;VBT, and VBT) varied among individuals, they were mostly controlled within certain ranges. The dosage range for EBRT was generally between 44.0 Gy and 54.0 Gy; in combined therapy, the range for EBRT use was mostly between 39.6 Gy and 50.4 Gy, with VBT serving as a booster, featuring various dosage fractionation schemes mostly ranging from 4\u0026ndash;6 Gy * 2\u0026ndash;3 times; while for standalone VBT treatment, different dosage regimens schemes were mostly 7 Gy * 3 times or 6 Gy * 5 times. The specific dosage regimens schemes were determined by the treating physician based on comprehensive evaluations of individual patient differences.\u003c/p\u003e \u003cp\u003eThe strength of our study includes its focused examination on the choice of adjuvant radiotherapy for stage IB endometrioid carcinoma patients after surgery, representing a single stage of endometrial carcinoma and thus reducing heterogeneity. Another advantage is that the included studies are all randomized controlled trials, which provide a high level of evidence in evidence-based medicine. However, there are limitations to our study. Firstly, the included literature did not classify patients according to risk factors, thus preventing further stratified analysis based on these factors. Additionally, the specific dosage regimens for radiation therapy in the studies were determined subjectively by the treating physicians based on individual patient assessments, introducing some degree of subjectivity. Despite these limitations, the majority of studies included in our analysis were of high quality. Currently, there is a lack of research on the targeted selection of adjuvant treatment modalities based on risk factors in patients with stage IB endometrioid carcinoma. To better elucidate the decision-making process for adjuvant radiotherapy, larger sample sizes and multicenter randomized controlled trials are needed to obtain higher-quality data and further clarify which adjuvant radiotherapy modality can provide greater survival benefits and improve quality of life for patients.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003e \u003col\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eThere was no significant difference in 5-year OS in patients with stage IB endometrial carcinoma treated with VBT, EBRT and EBRT\u0026thinsp;+\u0026thinsp;VBT after surgery. Compared with VBT and EBRT, EBRT\u0026thinsp;+\u0026thinsp;VBT significantly extended DFS for 5 years and reduced the incidence of local recurrence and distant metastasis.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eAlthough there was no significant difference between VBT and EBRT in overall health status score and urgency of urination score, VBT was superior to EBRT in diarrhea score, other gastrointestinal toxicity and social function score.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003c/ol\u003e \u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eCROSBIE E J, KITSON S J, MCALPINE J N, et al. Endometrial cancer[J]. Lancet, 2022, 399(10333): 1412\u0026ndash;1428.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTrojano Giuseppe et al. Conservative treatment in early stage endometrial cancer: a review.[J]. 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Acta Oncol. 2019;58(8):1127\u0026ndash;1134. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1080/0284186X.2019.1599136\u003c/span\u003e\u003cspan address=\"10.1080/0284186X.2019.1599136\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Stage IB endometrioid carcinoma, EBRT, VBT, OS, toxicity","lastPublishedDoi":"10.21203/rs.3.rs-4252806/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4252806/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eObjective: \u003c/strong\u003eCurrently, there is debate surrounding the selection of adjuvant treatment for FIGO IB endometrioid carcinoma.The aim of this study is to compare the efficacy of postoperative adjuvant external beam radiotherapy (EBRT), vaginal brachytherapy (VBT), and the combination therapy of EBRT with VBT (EBRT+VBT) in patients with stage IB endometrioid carcinoma.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e We selected randomized controlled trials comparing postoperative adjuvant EBRT, VBT, and EBRT+VBT in patients with stage IB endometrioid carcinoma. Data analysis was performed using Review Manager 5.4.1. The primary study endpoints included 5-year overall survival (OS), 5-year disease-free survival (DFS), rates of distant metastasis, and rates of local recurrence. Secondary endpoints encompassed post-radiotherapy toxicities such as gastrointestinal toxicity, urinary toxicity, vaginal toxicity, and health-related quality of life scores (HRQL).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResult:\u003c/strong\u003e Survival findings: ①There were no statistically significant differences observed between the EBRT group and the VBT group in terms of 5-year OS (RR=1.02, 95% CI: 0.98-1.06, P=0.42), 5-year DFS (RR=1.05, 95% CI: 0.94-1.18, P=0.40), and 5-year distant metastasis rate (RR=0.69, 95% CI: 0.44-1.07, P=0.09). ②Compared to the VBT group, the EBRT+VBT group exhibited a significantly prolonged 5-year DFS (RR=1.16, 95% CI: 1.06-1.27, P=0.0010), reduced rates of local recurrence (RR=0.32, 95% CI: 0.13-0.75, P=0.009), and distant metastasis (RR=0.56, 95% CI: 0.32-0.96, P=0.03), but did not show improvement of 5-year OS in patients(RR=1.01, 95% CI: 0.97-1.05, P=0.73). ③There was no statistically significant difference observed in 5-year OS between the EBRT group and the EBRT+VBT group (RR=0.98, 95% CI: 0.93-1.03, P=0.46).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eToxic outcomes: \u003c/strong\u003e①At 12 months, the diarrhea score in the VBT group was significantly lower than that in the EBRT group (RR=8.56, 95% CI: 5.38-11.91, P＜0.00001); the social function score in the VBT group was significantly higher than that in the EBRT group (RR=-5.60, 95% CI: -8.33--2.88, P＜0.0001). There were no statistically significant differences in the global health status score (RR=-1.80, 95% CI: -4.36-0.75, P=0.17) and urinary urgency score (RR=4.04, 95% CI: -0.81-8.90, P=0.10). ②Compared to the EBRT+VBT group, the VBT group had a lower incidence rate of gastrointestinal toxicity at 5 years, with statistically significant differences (RR=3.90, 95% CI: 2.18-7.00, P＜0.00001); there were no statistically significant differences in the rates of genitourinary toxicity (RR=1.68, 95% CI: 0.65-4.34, P=0.28) and vaginal toxicity (RR=1.76, 95% CI: 0.56-5.53, P=0.33).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e1.There was no significant difference in 5-year OS in patients with stage IB endometrial carcinoma treated with VBT, EBRT and EBRT+VBT after surgery. Compared with VBT and EBRT, EBRT+VBT significantly extended DFS for 5 years and reduced the incidence of local recurrence and distant metastasis.\u003c/p\u003e\n\u003cp\u003e2.Although there was no significant difference between VBT and EBRT in overall health status score and urgency of urination score, VBT was superior to EBRT in diarrhea score, other gastrointestinal toxicity and social function score.\u003c/p\u003e","manuscriptTitle":"Comparison of the Efficacy of adjuvant External Beam Radiotherapy, Vaginal Brachytherapy, and External Beam Radiotherapy with Vaginal Brachytherapy in Patients with FIGO Stage IB Endometrioid carcinoma: A Meta-Analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-04-17 19:44:07","doi":"10.21203/rs.3.rs-4252806/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"295b6aa9-63f9-4663-8ae0-0b3879577fb5","owner":[],"postedDate":"April 17th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-04-21T13:20:06+00:00","versionOfRecord":[],"versionCreatedAt":"2024-04-17 19:44:07","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4252806","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4252806","identity":"rs-4252806","version":["v1"]},"buildId":"GqpaHPwrfC8PjnIFayRh5","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}