Adjuvant Treatment Of Endometrial Cancer Research Articles

A novel multi-channel applicator with a U-shaped channel for vaginal intracavity brachytherapy.

Endometrial cancer is one of the most common gynecological malignancies in the world. Vaginal brachytherapy is an important postoperative adjuvant treatment for endometrial cancer. However, a common problem with existing applicators is insufficient dose at the vaginal apex. This study describes the Hangzhou (HZ) cylinder, a novel 3D printed vaginal intracavity brachytherapy applicator, detailing its characteristics, dose distribution, and clinical applications. The HZ cylinder is distinguished by its unique structure: a U-shaped channel with a 2mm diameter, a straight central axis channel of the same diameter, and 10 parallel straight channels. For comparison, standard plans were employed, designed to ensure that a minimum of 95% of the prescribed dose reached 5mm beneath the mucosal surface. We conducted comparative analyses of mucosal surface doses and doses at a 5mm depth below the mucosa between the HZ cylinder and a conventional single-channel cylinder across various treatment schemes. Additionally, the study examined dose differences in target volume and organs at risk (OARs) between actual HZ cylinder plans and hypothetical single-channel plans. In the standard plans, mucosal surface doses at the apex of the vagina were 209.32% and 200.61% of the prescribed dose with the HZ and single-channel cylinders, respectively. The doses on the left and right wall mucosal surfaces varied from 149.26% to 178.13% and 142.98% to 180.75% of the prescribed dose, and on the anterior and posterior wall mucosal surfaces varied from 128.87% to 138.50% and 142.98% to 180.75% of the prescribed dose. Analysis of 24 actual treatment plans revealed that when the vaginal tissue volume dose covering 98% (vaginal D98%) was comparable between the HZ cylinder and virtual single-channel plans (6.74±0.07Gy vs. 6.69±0.10Gy, p=0.24), rectum doses of HZ cylinder plans were significantly lower than those of single-channel plans (D1cc, 5.96±0.56Gy vs. 6.26±0.71Gy, p=0.02 and D2cc, 5.26±0.52Gy vs. 5.56±0.62Gy, p=0.02). The HZ cylinder demonstrates a reduction in dose to the rectum and bladder while maintaining adequate target volume coverage. Its mucosal surface dose is comparable to that of the traditional single-channel cylinder. These findings suggest that the HZ cylinder is a viable and potentially safer alternative for vaginal brachytherapy, warranting further investigation with larger sample sizes.

Nomogram for predicting pathology upstaging in patients with EIN: is sentinel lymph node assessment useful in these patients?

The objective of this study was to identify the risk factors for postoperative pathological escalation of endometrial cancer in patients with a pathologic diagnosis of endometrial intraepithelial neoplasia (EIN) before surgery. Some of the clues from the preoperative assessment were used to build a nomogram to predict the likely pathological escalation after surgery, and to explore the feasibility of sentinel lymph node biopsy in these patients with possible pathological escalation. This was a retrospective analysis of patients who underwent surgical treatment for EIN diagnosed before surgery between 2018 and 2023 in The Obstetrics and Gynecology Hospital of Fudan University. parameters including clinical, radiological and histopathological factors were analyzed by univariate and multivariate logistic regression to determine the correlation with pathology upstaging. A nomogram based on the multivariate results was developed to predict the probability of pathology upstaging. A total of 729 patients were included, divided into training set and validation set. 484 patients were used to build the model. This nomogram was subsequently validated using 245 patients. Upstaging to endometrial carcinoma occurred in 115 (23.8 percent) of 484 women treated between 2018 and 2023 in training set. A lager endometrial thickness (at least 15 mm), menopause, hypertension, HE4, and endometrial blood were significantly associated with upstaging. A nomogram developed using these factors demonstrated good predictive performance (area under the receiver operating characteristic curve (AUC)=0.6808; 95% confidence interval [CI]=0.6246-0.7369). The nomogram showed similar predictive performance in the validation data set, based on another 245 women (AUC=0.7821; 95% CI=0.7076-0.8567). This study developed a novel nomogram based on the 5 most important factors, which can accurately predict invasive cancer. It is common for women with preoperative diagnosis of EIN to experience pathological progression to endometrial cancer. For some patients with postoperative pathological escalation, we found lymph node metastasis. This nomogram may be useful to help doctor decide whether to perform sentinel lymph node biopsy for surgical staging in these EIN patients. According to the nomogram, simultaneous sentinel lymph node biopsy in patients with high probability of postoperative pathological upgrading can provide better guidance for postoperative adjuvant treatment of endometrial cancer and avoid the occurrence of secondary surgery.

Nodal staging in high and high-intermediate risk endometrial cancer surgery: Which role in the molecular classification era?

ObjectivesNodal staging contributes to risk group definition and the indication to adjuvant treatment in endometrial cancer (EC) patients. However, the role of nodal assessment evolved and requires redefinition.Primary outcome of the study was to assess the impact of surgical nodal staging in defining high-risk (HR) EC. Secondary outcome was to evaluate the contribution of nodal assessment to the decision for adjuvant treatment in both high-risk and high-intermediate risk (HIR) patients submitted to surgery. MethodsClinical stage I-II EC patients with postoperative diagnosis of HR and HIR disease were included. The contribution of nodal staging in prognostic groups allocation was assessed by reviewing HR patients to identify those without any other feature of such class (non-endometrioid histology, p53abn immunohistochemistry, post-operative T3-T4 disease) and HIR cases to assess how nodal staging affected adjuvant treatment indication. Descriptive statistics were conducted to describe the two populations. ResultsFifty-seven patients were included, 46 with HR and 11 with HIR disease. Chemotherapy and external-beam radiotherapy (EBRT) were proposed in 40 HR patients. Considering histology, immunohistochemical profile and FIGO stage, high risk classification was exclusively relied on nodal involvement in 2/46 cases (4.3 %). Omitting retroperitoneal staging, one of them would have been classified in the intermediate risk group and the other as HIR: without nodal staging, chemotherapy and EBRT would have been omitted in 1/40 (2.5 %) case.Among HIR patients, chemotherapy was proposed in 7/11 cases and EBRT in all cases. Adjuvant chemotherapy was indicated in 5/6 (83.3 %) and omitted in 1/6 (16.7 %) pN0 patient (stage Ib G2, substantial LVSI). In HIRpN0 patients, omitting nodal staging could have changed adjuvant treatment indication in 1/6 (16.7 %) case. In HIRpNx patients, adjuvant chemotherapy was omitted in one patient (stage II, grade 2 and LVSI negative): nodal staging unavailability might have changed indication to chemotherapy in 1/5 (20 %) case, without changing indication to EBRT.Unavailable nodal staging could globally be related to omission of chemotherapy in 2/57 (3.5 %) patients and of EBRT in 1/57 (1.8 %) patient. ConclusionsIn this series, nodal staging had limited impact on definition of HR class and on the choice of adjuvant treatment in HR and HIR EC patients.

Where Morphological and Molecular Classifications Meet: The Role of p53 Immunohistochemistry in the Prognosis of Low-Risk Endometrial Carcinoma (GLAMOUR Study).

No prospective study has validated molecular classification to guide adjuvant treatment in endometrial cancer (EC), and not even retrospective data are present for patients with morphological low-risk EC. We conducted a retrospective, multicenter, observational study including 370 patients with low-risk endometrioid EC to evaluate the incidence and prognostic role of p53 abnormal expression (p53abn) in this specific subgroup. Among 370 patients, 18 had abnormal expressions of p53 (4.9%). In 13 out of 370 patients (3.6%), recurrences were observed and two were p53abn. When adjusting for median follow-up time, the odds ratio (OR) for recurrence among those with p53abn versus p53 wild type (p53wt) was 5.23-CI 95% 0.98-27.95, p = 0.053. The most common site of recurrence was the vaginal cuff (46.2%). One recurrence occurred within the first year of follow-up, and the patient exhibited p53abn. Both 1-year and 2-year DFS rates were 94.4% and 100% in the p53abn and p53wt groups, respectively. One patient died from the disease and comprised p53wt. No difference in OS was registered between the two groups; the median OS was 21.9 months (16.4-30.1). Larger multicenter studies are needed to tailor the treatment of low-risk EC patients with p53abn. Performing molecular classification on all EC patients might be cost-effective, and despite the limits of our relatively small sample, p53abn patients seem to be at greater risk of recurrence, especially locally and after two years since diagnosis.

Abstract IA014: Personalized adjuvant treatment in endometrial cancer

Abstract The majority of endometrial cancer patients are cured by surgical removal of the uterus. Adjuvant treatment is recommended for a subset of patients with tumor characteristics associated with increased risk of recurrence. Historically pathologists have played a central role in defining histopathological factors that together make-up a risk profile which directs the type of adjuvant treatment. This traditional approach suffers from interobserver variability and lacks a biological basis. With the advance of molecular pathology, we have been able to define molecularly distinct endometrial cancer subsets which also carry distinct prognostic information and may form a basis for targeted adjuvant treatment. The RAINBO program exploits this concept by running 4 molecular subclass specific clinical trials. During my talk I will go over the past, the present and the future of adjuvant treatment in endometrial cancer with an emphasis on the role of pathology. Citation Format: Tjalling Bosse. Personalized adjuvant treatment in endometrial cancer [abstract]. In: Proceedings of the AACR Special Conference on Endometrial Cancer: Transforming Care through Science; 2023 Nov 16-18; Boston, Massachusetts. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(5_Suppl):Abstract nr IA014.

The progress and prospect of sentinel lymph node mapping in endometrial carcinoma

Sentinel lymph node (SLN) refers to the initial site of the lymphatic drainage from a primary tumor area. Identifying the SLN and analyzing tumor involvement can predict the status of the remaining lymph nodes. Accordingly, sentinel lymph node mapping (SLN mapping) has been brought up and widely applied to cancer therapy for its illuminating role in clinical lymph node resection. Sufficient information to guide surgical pathological staging and adjuvant treatment in endometrial cancer can be rendered by SLN mapping, hence minimizing surgery injury and reducing the incidence of complications. Evidence suggests that using SLN mapping does not affect progression-free survival (PFS) and overall survival (OS) of endometrial cancer patients. Furthermore, there is increasing evidence that using SLN mapping has a high detection rate (DR), sensitivity, and negative predictive value (NPV) for patients with early-stage lower-risk endometrial cancer. This review aims to systematically summarize the advances and application prospects of SLN mapping in endometrial cancer, with an expectation of furnishing reference for the clinical application.

Efficacy and prognosis of adjuvant treatment of endometrial cancer with medroxyprogesterone acetate COX regression analysis.

Endometrial cancer is one of the most commonly diagnosed gynecological cancers worldwide, and early-stage high-risk endometrial cancer has a poor prognosis. Adjuvant treatments after surgery, such as chemotherapy and radiotherapy, have been widely used in clinical practice to improve patient survival. Medroxyprogesterone acetate is a synthetic progestogen that has been reported to have potential anticancer effects in endometrial cancer. However, its efficacy, safety, and long-term prognostic benefits as an adjuvant treatment for endometrial cancer remain controversial. Therefore, this study aimed to observe the efficacy and prognostic impact of adjuvant medroxyprogesterone acetate treatment in patients with early-stage high-risk endometrial cancer and evaluate its safety. To observe the efficacy and prognosis of adjuvant treatment of endometrial cancer with medroxyprogesterone acetate and to evaluate its safety. We collected the clinical data of 200 patients with early-stage high-risk endometrial cancer who were admitted to the Department of Obstetrics and Gynecology of our hospital from January 2018 to December 2022. The control group (100 patients) underwent conventional surgical treatment, and the study group (100 patients) was administered adjuvant medroxyprogesterone acetate tablets on top of the control group. The Kaplan-Meier curve analysis and log-rank test were performed to determine the possible factors influencing the 5-year cumulative survival rate in the patients. The Cox regression analysis was performed to identify the factors influencing the survival prognosis of endometrial cancer. According to the Cox regression analysis, age [hazard ratio (HR) = 4.636, 95% confidence interval (95%CI): 1.411-15.237], pathological type (HR = 6.943, 95%CI: 2.299-20.977), molecular typing (HR = 5.789, 95%CI: 3.305-10.141), and myometrial infiltration (HR = 5.768, 95%CI: 1.898-17.520) were factors influencing the prognosis of patients with early-stage high-risk endometrial cancer. Age, pathological type, molecular typing, and myometrial infiltration were all relevant factors affecting the prognosis of early-stage high-risk endometrial cancer. The potential long-term prognostic benefit of adjuvant postoperative radiotherapy in patients with early-stage high-risk endometrial cancer is worthy of clinical consideration.

Molecular subtypes of endometrial cancer: Implications for adjuvant treatment strategies.

When determining adjuvant treatment for endometrial cancer, the decision typically relies on factors such as cancer stage, histologic grade, subtype, and a few histopathologic markers. The Cancer Genome Atlas revealed molecular subtyping of endometrial cancer, which can provide more accurate prognostic information and guide personalized treatment plans. To summarize the expression and molecular basis of the main biomarkers of endometrial cancer. PubMed was searched from January 2000 to March 2023. Studies evaluating molecular subtypes of endometrial cancer and implications for adjuvant treatment strategies. Three authors independently performed a comprehensive literature search, collected and extracted data, and assessed the methodological quality of the included studies. We summarized the molecular subtyping of endometrial cancer, including mismatch repair deficient, high microsatellite instability, polymerase epsilon (POLE) exonuclease domain mutated, TP53 gene mutation, and non-specific molecular spectrum. We also summarized planned and ongoing clinical trials and common therapy methods in endometrial cancer. POLE mutated endometrial cancer consistently exhibits favorable patient outcomes, regardless of adjuvant therapy. Genomic similarities between p53 abnormality endometrial cancer and high-grade serous ovarian cancer suggested possible overlapping treatment strategies. High levels of immune checkpoint molecules, such as programmed cell death 1 and programmed cell death 1 ligand 1 can counterbalance mismatch repair deficient endometrial cancer immune phenotype. Hormonal treatment is an appealing option for high-risk non-specific molecular spectrum endometrial cancers, which are typically endometrioid and hormone receptor positive. Combining clinical and pathologic characteristics to guide treatment decisions for patients, including concurrent radiochemotherapy, chemotherapy, inhibitor therapy, endocrine therapy, and immunotherapy, might improve the management of endometrial cancer and provide more effective treatment options for patients. We have characterized the molecular subtypes of endometrial cancer and discuss their value in terms of a patient-tailored therapy in order to prevent significant under- or overtreatment.

Pattern of practice for postoperative management of endometrial cancer in Korea: a survey by the Korean Gynecologic Oncology Group and the Korean Radiation Oncology Group (KGOG 2028-KROG 2104).

This study aimed to investigate the current status of postoperative management of uterine endometrial cancer (EC) in Korea. A mail survey was administered to members of the Korean Gynecologic Oncology Group and Korean Radiation Oncology Group. A total of 38 gynecologic cancer surgeons (GYNs) and 31 radiation oncologists (RO) in 43 institutions was responded. The questionnaire consisted of general questions for clinical decision and clinical case questions. The GYN and RO responses were compared using chi-square statistics. The 2 expert groups had similar responses for clinical decision based on the results of the Gynecologic Oncology Group (GOG)-249 and Postoperative Radiation Therapy for Endometrial Carcinoma-III trials in the early-stage EC. In contrast, the responses based on GOG-258 results differed, as GYNs most frequently opted for sequential chemotherapy (CTx) and radiotherapy (RT), while ROs preferred concurrent chemoradiotherapy in locally advanced stage (p<0.05). Based on the GOG-258, GYNs preferred CTx alone for adjuvant treatment of serous or clear cell adenocarcinoma histology, whereas ROs advocated for combined CTx and RT (sequential or concurrent). Among the clinical case questions, GYNs were more likely than ROs to choose CTx alone rather than the combination of CTx and RT (sequential or concurrent) as the answers to case questions representing patients with locally advanced stage or unfavorable histology (all p<0.05). The present study showed several different opinions of GYNs and ROs regarding adjuvant treatment for EC, particularly for adjuvant RT in advanced stage or unfavorable histology.

Early endometrial carcinoma: Experience and outcomes.

Endometrial carcinoma (EC) data from India are very sparse. We did a retrospective analysis of our patients registered at this peripheral cancer center based in rural Punjab and studied their outcome. Ninety-eight Stage I and II EC patients with endometroid histology registered at our institute from January 2015 to April 2020 were studied for demography, histopathology, treatment received, and outcomes. FIGO 2009 staging and new European Society for Medical Oncology (ESMO) risk group classification was used. Our patients had a median age of 60 years (range 32-93 years). There were 39 (39.8%), 41 (42.0%), 4 (4.1%), 12 (12.2%) patients in the low risk, intermediate risk (IR), high intermediate risk, and high risk groups, respectively, as per new ESMO risk classification. Two (2.0%) patients had incomplete information to assign them to a particular risk group. Fifty (46.7%) patients underwent complete surgical staging and 54 (50.5%) patients received adjuvant RT. With a median follow-up of 27.0 months, there were 1 locoregional and 2 distant recurrences. There were 8 deaths in total. Three-year overall survival for the entire group is 90.6%. The risk group determines adjuvant treatment in endometrial cancer. Patients operated at dedicated cancer center tend to have better surgical staging and thus better outcome because of better risk stratification and grouping for adjuvant therapy. IR histology was more common in our group of patients, which is variable as compared to available literature.

Refining adjuvant treatment in endometrial cancer based on molecular features: the RAINBO clinical trial program

BackgroundThe endometrial cancer molecular classification has been integrated into the 2020 World Health Organization (WHO) diagnostic classification and European treatment guidelines, and provides direction towards more effective and less toxic...

Applications and Safety of Sentinel Lymph Node Biopsy in Endometrial Cancer.

Lymph node status is important in predicting the prognosis and guiding adjuvant treatment in endometrial cancer. However, previous studies showed that systematic lymphadenectomy conferred no therapeutic values in clinically early-stage endometrial cancer but might lead to substantial morbidity and impact on the quality of life of the patients. The sentinel lymph node is the first lymph node that tumor cells drain to, and sentinel lymph node biopsy has emerged as an acceptable alternative to full lymphadenectomy in both low-risk and high-risk endometrial cancer. Evidence has demonstrated a high detection rate, sensitivity and negative predictive value of sentinel lymph node biopsy. It can also reduce surgical morbidity and improve the detection of lymph node metastases compared with systematic lymphadenectomy. This review summarizes the current techniques of sentinel lymph node mapping, the applications and oncological outcomes of sentinel lymph node biopsy in low-risk and high-risk endometrial cancer, and the management of isolated tumor cells in sentinel lymph nodes. We also illustrate a revised sentinel lymph node biopsy algorithm and advocate to repeat the tracer injection and explore the presacral and paraaortic areas if sentinel lymph nodes are not found in the hemipelvis.

Serum miRNA-204-5p as a potential non-invasive biomarker for the diagnosis of endometrial cancer with sentinel lymph node mapping.

The lymph node status is one of the most critical prognostic factors used in determining adjuvant treatment in endometrial cancer (EC). Lymphadenectomy is associated significant surgical and postoperative risks. The use of sentinel lymph node mapping (SLNM) has emerged as an alternative method to complete lymphadenectomy in EC. However, there remains controversy surrounding the use of SLNM in high-risk disease and its false-negative rate (3%). The authors previously identified miR-204-5p as a tumor-suppressor miRNA associated with lymph node metastasis in EC tissues. The present study demonstrated that serum miR-204-5p in patients with EC has the potential for use as an early diagnostic biomarker combined with SLNM to assess the lymph node status prior to surgery. The present study also aimed to identify the optimal cut-off value of serum miR-204-5p. The relative expression levels of miR-204-5p were detected using reverse transcription-quantitative PCR in the serum of 52 patients with EC (total SLNM). A total of 20 patients diagnosed with ovarian cysts, 20 patients diagnosed with myoma, and 20 participants diagnosed with endometrial polyps or endometrial hyperplasia were included as the control group. miR-204-5p expression was also detected in lymph node tissues using in situ hybridization. The results revealed that serum miR-204-5p expression was downregulated in patients with EC compared with its expression in patients with benign ovarian cysts, myoma and endometrial hyperplasia/polyps (P<0.01). In accordance with the final pathological evaluation, patients with EC with a positive SLN status had a significantly lower level of miR-204-5p compared with those with a negative SLN status (P<0.01). The area under the ROC curve of miR-204-5p was 0.923, 95% CI (0.847-1.000), and the diagnostic value had a sensitivity of 87.2% and specificity of 80.0%, with an optimal cut-off value of 0.253. On the whole, it was demonstrated that a lower miR-204-5p expression is associated with lymph node metastasis in these SLN(+) EC tissues, indicating that the downregulation of serum miR-204-5p in patients with EC has potential for use as an early diagnostic biomarker combined with SLNM. In addition, with a cut-off value of 0.253, it appeared optimal for the prediction of lymph node metastasis in EC.

PO-1339 Long- term outcomes after electronic brachytherapy in the adjuvant treatment of endometrial cancer.

PO-1339 Long- term outcomes after electronic brachytherapy in the adjuvant treatment of endometrial cancer.

Adjuvant treatment in endometrial cancer: when and what to choose

Endometrial cancer is the most common gynecological malignancy in developed countries. The management is primarily surgical, but adjuvant treatment may be indicated after surgery, according to the risk of recurrence. This review will focus on the prognostic risk groups presented in the 2020 ESGO/ESTRO/ESP guidelines and the ongoing trials based on new molecular markers that will help to get a more personalized cancer medicine.

Role of adjuvant and post-surgical treatment in gynaecological cancer.

Adjuvant and post-operative therapy aimed at reducing the risk of disease recurrence and improving potential for cure can be broadly categorised into systemic and locoregional treatment. For epithelial ovarian cancer, cytoreductive surgery and platinum-based chemotherapy is the mainstay management. Maintenance therapy with PARPi is a state-of-the-art option for women with advanced disease following complete or partial response to first-line platinum-based chemotherapy, particularly those with BRCA mutations. Adjuvant treatment for endometrial cancer depends mostly on FIGO staging and histopathological risk factors. For cervical cancer, adjuvant chemoradiation is indicated after surgery in women with close or positive resection margins and positive nodes. Generally, recommendations for adjuvant therapy should be individualised and reviewed at the multidisciplinary tumour board meeting, and the decision for adjuvant therapy should be balanced with treatment toxicity. The overview of the role of adjuvant and post-surgical treatment in gynaecological cancers will be discussed in this chapter.

Factors influencing treatment decision and guideline conformity in high-grade endometrial cancer patients: a population-based study.

Treatment according to guidelines has been demonstrated to improve survival in a number of different cancer entities. Deviations from guidelines depend on several factors, including the patient's preferences, age and comorbidities. The aim of this study was to assess the adherence to guideline recommendations concerning surgical and adjuvant treatment in endometrial cancer. Furthermore, we sought to evaluate the reasons for non-adherence to guidelines by further examining the influence of comorbidities and age. The influence of age, comorbidities, tumor stage and histological subtype on guideline adherence was evaluated by multivariable logistic regression in a cohort of 353 high-grade endometrial cancer patients. High-grade endometrial cancer was defined as carcinosarcoma, Type II (serous, clear cell, mixed cell carcinoma) and Type I G3 histology. Extensive surgical procedures, particularly systematic LNE, were less frequently applied in patients with comorbidities (p = 0.015) or higher age (p < 0.01). Guideline adherence was not affected by comorbidities (p = 0.563), but was significantly reduced with higher age (p < 0.01). In a multivariable model, higher age (p < 0.01), obesity (p = 0.011), higher FIGO Stage (p < 0.01) and histologic subtype (p < 0.01) significantly decreased OS. Surgery (p < 0.001), chemotherapy (p < 0.01) and systematic LNE (p = 0.011) were associated with higher OS. Age seems to be the strongest independent factor leading to guideline deviation. Comorbidities were associated with less aggressive treatment, but not with deviations from guidelines.

Maintained survival outcome after reducing lymphadenectomy rates and optimizing adjuvant treatment in endometrial cancer

ObjectiveMain controversies in endometrial cancer treatment include the role of lymphadenectomy and optimal adjuvant treatment. We assessed clinical outcome in a population-based endometrial cancer cohort in relation to changes in treatment management over two decades. MethodsAll consenting endometrial cancer patients receiving primary treatment at Haukeland University Hospital from 2001 to 2019 were included (n = 1308). Clinicopathological variables were evaluated for year-to-year changes. Clinical outcome before and after discontinuing adjuvant radiotherapy and individualizing extent of lymphadenectomy was analyzed. ResultsThe rate of lymphadenectomy was reduced from 78% in 2001–2012 to 53% in 2013–2019. The rate of patients with verified lymph node metastases was maintained (9% vs 8%, p = 0.58) and FIGO stage I patients who did not undergo lymphadenectomy had stable 3-year recurrence-free survival (88% vs 90%, p = 0.67). Adjuvant chemotherapy for completely resected FIGO stage III patients increased from 27% to 97% from 2001 to 2009 to 2010–2019, while adjuvant radiotherapy declined from 57% to 0% (p < 0.001). These patients had improved 5-year overall- and recurrence-free survival; 0.49 [95% CI: 0.37–0.65] in 2001–2009 compared to 0.61 [0.45–0.83] in 2010–2019, p = 0.04 and 0.51 [0.39–0.68] to 0.71 [0.60–0.85], p = 0.03, respectively. For stage I, II and IV, survival rates were unchanged. ConclusionsOur study demonstrates that preoperative stratification by imaging and histological assessments permits a reduction in lymphadenectomy to around 50%, and is achievable without an increase in recurrences at 3 years. In addition, our findings support that adjuvant chemotherapy alone performs equally to adjuvant radiotherapy with regard to survival, and is likely superior in advanced stage patients.

Brachytherapy quality assurance in the PORTEC-4a trial for molecular-integrated risk profile guided adjuvant treatment of endometrial cancer

ObjectiveThe PORTEC-4a trial investigates molecular-integrated risk profile guided adjuvant treatment for endometrial cancer. The quality assurance programme included a dummy run for vaginal brachytherapy prior to site activation, and annual quality assurance to verify protocol adherence. Aims of this study were to evaluate vaginal brachytherapy quality and protocol adherence. MethodsFor the dummy run, institutes were invited to create a brachytherapy plan on a provided CT-scan with the applicator in situ. For annual quality assurance, institutes provided data of one randomly selected brachytherapy case. A brachytherapy panel reviewed and scored the brachytherapy plans according to a checklist. ResultsAt the dummy run, 15 out of 21 (71.4%) institutes needed adjustments of delineation or planning. After adjustments, the mean dose at the vaginal apex (protocol: 100%; 7 Gy) decreased from 100.7% to 99.9% and range and standard deviation (SD) narrowed from 83.6–135.1 to 96.4–101.4 and 8.8 to 1.1, respectively. At annual quality assurance, 22 out of 27 (81.5%) cases had no or minor and 5 out of 27 (18.5%) major deviations. Most deviations were related to delineation, mean dose at the vaginal apex (98.0%, 74.7–114.2, SD 7.6) or reference volume length. ConclusionsMost feedback during the brachytherapy quality assurance procedure of the PORTEC-4a trial was related to delineation, dose at the vaginal apex and the reference volume length. Annual quality assurance is essential to promote protocol compliance, ensuring high quality vaginal brachytherapy in all participating institutes.

Adjuvant Electronic Brachytherapy For Patients With Endometrial Cancer

Brachytherapy plays a fundamental role in the adjuvant treatment of endometrial cancer (EC) to decrease vaginal cuff recurrence. Traditionally high dose rate (HDR) brachytherapy with Iridium 192 (Ir-192) had been used, but the recent development of electronic brachytherapy (eBT) based on X-ray emissions could be an alternative. Our objectives are to analyze the local recurrence in EC treated with eBT, toxicity profile and to compare with series from the literature with HDR Ir-192 brachytherapy. From September 2015 to January 2019, 271 patients with endometrial cancer were treated with vaginal eBT at our institution. 117 patients received vaginal eBT as monotherapy and 154 as a boost after external beam radiation therapy (EBRT). We used different dose-fractionation schedules: total dose was 15 Gy in 3 fractions or 14 Gy in 2 for eBT as a boost to EBRT; and 25 Gy in 5 fractions or 21 Gy in 3 fractions for exclusive eBT. Acute and late toxicities were recorded using Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Data was collected retrospectively. The median follow-up was 24 months. The average age was 66 years. 70% were diagnosed as endometrioid carcinoma (Type I). According to the International Federation of Gynaecology and Obstetrics (FIGO) classification: 30% FIGO IA; 39% FIGO IB and 31% FIGO ≥IIA. Acute toxicity: 33% had vaginal toxicity; 10% had urinary toxicity; 8% had rectal toxicity and all of them were ≤Grade 1 (G1) or G2. G1-G2 chronic toxicity was observed: 10% vaginal toxicity; 1% urinary toxicity; 8% rectal toxicity; 3 patients (1.5%) had G3 rectal late toxicity. A statistically significant difference was found in the rectal toxicity observed at the patients treated with EBRT plus eBT versus eBT as monotherapy (p = 0.008). 8 patients had locoregional recurrence, 8 had systemic recurrence and 12 had both recurrences. Only 1 vaginal cuff relapse was observed. Our series, shows an increase in acute G1 vaginal mucosa toxicity with respect to HDR Ir-192 brachytherapy (33% vs 15.8%), but reduction of late vaginal mucosal toxicity (10% eBT vs. 23% Ir-192). Vaginal cuff recurrence results were better than the literature (0.36% eBT vs. 0.7-1.4% Ir-192). eBT at endometrial cancer is a feasible alternative to HDR brachytherapy with Ir-192 in effectiveness with an acceptable grade 1 acute toxicity. It has given long-term benefits for patients, providing the same dosimetric coverage in the area of treatment as HDR brachytherapy with reduction in the dose of organs at risk, benefits for staff and health system as mobility, versatility and ease of installation of the equipment. Further research is needed to establish eBT as an alternative to high dose rate brachytherapy.