Radiotherapy For Endometrial Cancer Research Articles

Retrospective Analysis of All Types of Adjuvant Radiotherapy in Endometrial Cancer: Single-Center Experiences in a Middle-Income Country.

We retrospectively analyzed the efficacy, focusing on overall survival (OS) and the patterns of failure, along with the toxicities of adjuvant radiotherapy (RT) in endometrial cancer patients. Two-hundred and nineteen patients with endometrial cancer patients who received adjuvant radiotherapy ± adjuvant chemotherapy (ACT) from January 2014 to December 2018 were investigated for overall survival (OS), local recurrence-free survival rate (LRFS), regional recurrence-free survival rate (RRFS), and distant metastasis-free survival rate (DMFS). Two-hundred and fourteen patients were evaluated. The numbers of VBT alone, EBRT plus VBT, and adjuvant chemotherapy (ACT) plus EBRT plus VBT were 65 (30.4%), 80 (37.4%), and 69 (32.2%) patients, respectively. Stage I (107 patients) was the most common followed by stage III (87 patients). With a median follow-up time of 67 months (IQR 56-78), the 5-year overall survival rates for VBT alone, EBRT plus VBT, and EBRT plus VBT plus ACT were 84.4%, 65%, and 57.4%, respectively. The most common severe (grade 3-4) acute toxicity was neutropenia (4.6%), followed by diarrhea (3.7%). Grade 3-4 late proctitis was found in only 1.9%. On multivariate analysis, advanced age (HR 6.15, p: 0.015), lymph node involvement (HR 6.66, p: 0.039), cervical involvement (HR 10.60, p: 0.029), and substantial LVSI (HR 21.46, p: 0.005) were associated with a higher risk of death. Advanced age (>65), substantial LVSI, lymph node involvement, and cervical stromal involvement were associated with poor overall survival. These findings here will help identifying high-risk patients and would make it possible to avoid unnecessary adjuvant treatment among patients with a good prognosis.

Abnormal preoperative haematological parameters in Endometrial cancer; reflecting tumour aggressiveness or reduced response to radiotherapy?

Background In endometrial cancer (EC), preoperative anaemia, thrombocytosis and leucocytosis appear to be associated with worse prognosis. It remains unclear whether these parameters solely reflect tumour aggressiveness, or also impact response to adjuvant treatment. Therefore, our primary aim is to evaluate the prognostic relevance of anaemia, thrombocytosis and leucocytosis on survival in EC. Secondary, to explore their predictive relevance in response to radiotherapy in EC. Methods A retrospective multicentre cohort study was performed within 10 hospitals. Preoperative haematological parameters were defined as: Anaemia – haemoglobin <7.45 mmol/L (<12 g/Dl), thrombocytosis – platelets >400 × 109 platelets/L, leucocytosis – leukocytes >10 × 109/L. The relationship of haematological parameters with clinicopathological characteristics, ESGO/ESTRO/ESP risk groups and survival were evaluated. Furthermore, the predictive value of haematological parameters was determined on the overall response to adjuvant radiotherapy and for the ESGO/ESTRO/ESP intermediate-risk group solely receiving radiotherapy. Results A total of 894 patients were included with a median follow-up of 4.5 years. Anaemia was present in 103 (11.5%), thrombocytosis in 79 (8.8%) and leucocytosis in 114 (12.7%) patients. The presence of anaemia or thrombocytosis was significantly associated with ESGO/ESTRO/ESP high-risk (respectively, P = 0.002 and P = 0.041). In the entire cohort, anaemia remained independently associated with decreased disease-specific survival (HR 2.31, 95% CI (1.19–4.50), P = 0.013) after adjusting for age, the abnormal haematological parameters and ESGO/ESTRO/ESP risk groups. In patients that were treated with adjuvant radiotherapy (n = 239), anaemia was associated with significant reduced 5-year disease-specific and recurrence-free survival (P = 0.005 and P = 0.025, respectively). In ESGO/ESTRO/ESP intermediate risk patients that received solely vaginal brachytherapy (n = 74), anaemia was associated with reduced disease-specific survival (P = 0.041). Conclusions Current data demonstrate the importance of preoperative anaemia as independent prognostic factor in patients with EC. Moreover, anaemia seems to be associated with reduced response to radiotherapy. Prospective validation in a larger study cohort is needed to verify anaemia as predictive biomarker for radiotherapy. What is already known on this subject? In endometrial cancer, preoperative abnormal haematological parameters like, anaemia, thrombocytosis and leucocytosis appears to be associated with FIGO advanced-stage and unfavourable outcome. What do the results of this study add? It remains unclear whether anaemia, thrombocytosis or leucocytosis solely reflecting worse prognosis by advanced tumour stage, or also impact response to adjuvant treatment. Current data demonstrate that anaemia is independent associated with decreased disease-specific survival and anaemia seems related with reduced response to radiotherapy and in specific to vaginal brachytherapy in ESGO/ESTRO/ESP intermediate risk patients. What are the implications of these findings for clinical practice and/or further research? Specific applied adjuvant treatment is needed if patients with anaemia have a reduced response to radiotherapy in EC. Prospective validation in a larger study cohort is required to verify anaemia as predictive biomarker for radiotherapy and to further evaluate the prognostic/predictive impact of anaemia in addition to the molecular subgroups.

Timing of Postoperative Radiation Therapy for Early-Stage Endometrial Carcinoma: A 20-Year Single-Center Retrospective Cohort Experience in China

To investigate the appropriate timing of radiotherapy (RT) after hysterectomy for women with early-stage endometrial carcinoma (EC). Between 1999 and 2020, 1080 patients with I and II endometrial cancer received postoperative RT at our hospital. All patients underwent hysterectomy followed by RT. The optimal cut-off values for the surgery-RT interval (SRI) based on overall survival (OS) were determined using the R software. The disease-free survival (DFS), OS, locoregional recurrence free survival (LRFS), and distant metastasis free survival (DMFS) rates were estimated using the Kaplan-Meier method. Multivariate analyses were performed using Cox proportional hazards regression. Median follow-up time was 52 months. Median SRI were 46 days. The optimal cut-off value for the surgery-RT interval (SRI) based on overall survival (OS) is 40 days. The group initiated RT within 40 days following surgery has higher OS (P = 0.004), higher LRFS (P = 0.002) and higher DMFS (P = 0.039). An SRI of ≤ 40 days was independently associated with higher OS (HR 0.454, 95% CI:0.261-0.788), higher LRFS (HR 0.487, 95% CI:0.304-0.779), and higher DMFS (HR 0.643, 95% CI:0.421-0.982) than SRI of >40 days. However, SRI had no significant effect on DFS. The surgery-RT interval affects the patients' survival endpoints. Based on this analysis, the timing of the initiation of RT after hysterectomy is crucial for patients with early-stage endometrial carcinoma (EC). The postoperative radiation therapy for endometrial cancer should be initiated within 40 days following surgery.

Changes in “don't eat me” signaling with radiotherapy in endometrial cancer (2301)

Changes in “don't eat me” signaling with radiotherapy in endometrial cancer (2301)

Change in vaginal length and sexual function in women who undergo surgery ± radiation therapy for endometrial cancer

PURPOSEEndometrial Cancer (EC) is the most common gynecologic malignancy in the United States. Standard treatment is TAH/BSO with radiation therapy (RT) and chemotherapy given based on risk. Treatment can cause significant vaginal changes, including shortening, narrowing, loss of elasticity, atrophy, and dryness. These are not life threatening, but affect a woman's physical, psychological, and social functioning. Adjuvant vaginal dilator use is often advised, but there are inconsistent recommendations on use. This prospective study compared vaginal length changes and sexual function in women compliant with dilation versus not after surgery and RT. METHODS AND MATERIALSEnrolled patients underwent surgery for Stage I-IIIC EC ±RT. Vaginal dilator use was recommended for women receiving RT (external beam or brachytherapy). Vaginal length was measured with a vaginal sound and the Female Sexual Function Index (FSFI) was used to assess sexual function. RESULTSForty-one enrolled patients had sufficient data for analysis. Dilation significantly increased FSFI scores (p = 0.02) while RT without dilation showed a significant decrease (p = 0.04). Dilation helped maintain vaginal length for all patients (0 cm vs. 1.8 cm loss (p = 0.03)). Individual arms did not show statistically significant changes in length with dilation, though the trend showed RT without dilation had an average loss of 2.3 cm as compared to only 0.2 cm for regular dilation. Notably, there was no difference in length change with dilation for surgery alone versus surgery and RT (p = 0.14). CONCLUSIONThis data provides novel, prospective evidence of the benefit of vaginal dilation for maintaining vaginal length and improving sexual health after any pelvic treatment for EC. This evidence also supports that the addition of RT after surgery does not appear to significantly worsen vaginal shortening. This study has important implications for providing a strong foundation for future studies and helping to establish solid clinical management criteria for the prevention of vaginal stenosis and promotion of female sexual health.

Is hospitalization within 6 months of completion of radiation therapy for endometrial cancer associated with decreased survival? (584)

<b>Objectives:</b> Radiation therapy (RT) is a core component in the management of women with locally advanced endometrial cancer (EC). For patients with early-stage (I and II), intermediate-risk disease, adjuvant RT is considered the standard of care. We hypothesized that hospitalization within six months of the completion of RT was associated with decreased overall survival (OS) and progression-free survival (PFS). We tried to identify factors predictive of a patients' likelihood of hospitalization within a short term of RT completion. <b>Methods:</b> An IRB-approved, retrospective cohort study included all patients who were diagnosed with EC and treated with radiation at our institution from January 2019 through December 2020. Data collected included functional status, disease stage, treatment course, hospitalizations, and demographics. Performance status was monitored via the Kamofsky Performance Scale. Common terminology criteria for adverse event (CTCAE) constipation and fatigue grades were gathered to provide insight into a patient's tolerance of RT. Statistical analysis was performed via Fisher's exact test. The Kaplan-Meier product estimator was utilized to derive survival curves, which were then compared via log-rank test. A critical value of p <0.05 was set for statistical significance. <b>Results:</b> Of 287 eligible patients, 27 (9.4%) were hospitalized within six months of RT. Of those patients, 13 of 27 (48%) were hospitalized within 30 days of completion of RT, and an additional five patients were hospitalized within 45 days of completion of radiation. The median length of hospitalization was six days, with hospital stays ranging from one to 20 days. Of patients who were hospitalized, 15 received EBRT alone, ten received vaginal brachytherapy alone, and two received a combination of EBRT + brachytherapy. The most common indications for hospitalization included disease progression, vaginal bleeding, altered mental status, failure to thrive, infection, and cardiovascular events. Most patients (21/27) did not undergo procedural intervention during their hospitalization, although two patients were admitted to the intensive care unit, and ultimately five of 27 patients expired during the hospitalization. Of the patients who expired, 40% of deaths were disease-related, while 60% were from other causes. Of the six patients who underwent procedural intervention during their admission, interventions included palliative RT, uterine artery embolization, biopsy, pleural catheter placement, and scheduled procedures unrelated to their disease process, inclusive of cholecystectomy and colonoscopy. Hospitalization within six months was associated with both decreased OS (p < 0.0001) and decreased PFS (p <0.0001). There was no significant variation in performance status, as indicated by Kamofsky's performance score, between patients who were and were not hospitalized within six months of completion of RT. BMI, age, constipation, and fatigue were not statistically significant predictors of a patients' likelihood of short interval hospitalization. <b>Conclusions:</b> Women with EC who received RT as part of their treatment and were hospitalized within six months had a statistically significant decreased OS and PFS. Age, BMI, race, and performance status were not found to be predictive of a patient's risk of short interval hospitalization.

Comparison of rates of vaginal brachytherapy vs. external beam radiation post-hysterectomy for endometrial cancer patients in rural vs. urban settings (459)

<b>Objectives:</b> The GOG-99 trial published in 2004 demonstrated that patients with high-intermediate risk endometrial cancer benefit from adjuvant external beam radiation therapy (EBRT) post-hysterectomy to decrease the risk of recurrence. The PORTEC-2 trial was then published in 2010, which was an open-label, non-inferiority randomized control trial that compared vaginal brachytherapy (VBT) to EBRT for patients with high-intermediate risk endometrial cancer. This trial demonstrated non-inferiority of VBT compared to EBRT with no significant difference in vaginal or locoregional recurrence, overall survival, and disease-free survival. However, it did show a significant decrease in grade 1-2 gastrointestinal toxicities in the VBT group. VBT is now the standard of care given its decreased toxicity but is also notably less time-consuming for patients. Our objective was to identify if there was a difference in the administration of VBT versus EBRT for endometrial cancer patients post-hysterectomy in rural versus urban locations. <b>Methods:</b> This is a retrospective cohort study based on the SEER 18 dataset of the US National Cancer Institute. Women with localized endometrial cancer post-hysterectomy were included in this study. The SEER dataset defines a localized tumor as a tumor confined to the organ of origin without extending beyond the primary organ. Data were collected from 2011 to 2018, given that PORTEC-2 was published in 2010. Urban versus rural population was defined by the rural-urban continuum codes. Women were excluded if they received both VBT and EBRT or if a rural-urban continuum code was not provided. Statistical analysis was completed with relative risk and confidence interval calculation. <b>Results:</b> In total, 10,840 women were included. There were 9813 women identified in metropolitan counties; 22% (<i>n</i>=2136) received EBRT post-hysterectomy for localized endometrial cancer, whereas 78% underwent VBT. There were 1027 women identified in nonmetropolitan counties, 22% (<i>n</i>=230) received EBRT and 78% (<i>n</i>=797) received VBT. When comparing metropolitan versus nonmetropolitan counties, there was no statistical difference between rates of EBRT versus VBT, with a relative risk of 1.16 (95% CI: 0.91-1.16, p=0.64). There were 125 women identified in completely rural counties, 21% (<i>n</i>=26) received EBRT and 79% (<i>n</i>=99) received VBT. There was no statistical difference in rates of radiation therapy between completely rural and metropolitan counties, with a relative risk of 0.95 (95% CI: 0.67-1.34, p=0.77). <b>Conclusions:</b> Living in a nonmetropolitan county or even a completely rural county was not associated with a difference in receiving EBRT versus VBT in patients with localized endometrial cancer status post-hysterectomy compared to rates in metropolitan counties. It could be inferred that even though rural counties may have fewer medical resources, patients are still receiving the standard of care in regard to radiation therapy for endometrial cancer.

Role of Brachytherapy in the Postoperative Management of Endometrial Cancer: Decision-Making Analysis among Experienced European Radiation Oncologists.

Simple SummaryThere are various society-specific guidelines addressing adjuvant brachytherapy (BT) after surgery for endometrial cancer (EC). However, these recommendations are not uniform. Against this background, clinicians need to make decisions despite gaps between best scientific evidence and clinical practice. We analysed decision criteria influencing the selection for adjuvant radiotherapy among European radiation oncology experts. For this, GEC-ESTRO provided 19 European radiation oncology experts on gynaecological brachytherapy for decision-making analyses. The manuscript presents patterns in decision-making among these experts and demonstrates areas of consensus/discrepancies. We also analysed dose prescription and techniques of brachytherapy. This analysis is of special value as the objective approach enabled us to obtain an unbiased description of decision-making among the specialists (the study was not aimed to create or enforce a consensus). The manuscript provides valuable insight into clinical decision-making with a high impact on treatment selection, as expected differences between experts were observed. With this manuscript we are able to visualize and quantify these. This information is relevant for interdisciplinary discussions.Background: There are various society-specific guidelines addressing adjuvant brachytherapy (BT) after surgery for endometrial cancer (EC). However, these recommendations are not uniform. Against this background, clinicians need to make decisions despite gaps between best scientific evidence and clinical practice. We explored factors influencing decision-making for adjuvant BT in clinical routine among experienced European radiation oncologists in the field of gynaecological radiotherapy (RT). We also investigated the dose and technique of BT. Methods: Nineteen European experts for gynaecological BT selected by the Groupe Européen de Curiethérapie and the European Society for Radiotherapy & Oncology provided their decision criteria and technique for postoperative RT in EC. The decision criteria were captured and converted into decision trees, and consensus and dissent were evaluated based on the objective consensus methodology. Results: The decision criteria used by the experts were tumour extension, grading, nodal status, lymphovascular invasion, and cervical stroma/vaginal invasion (yes/no). No expert recommended adjuvant BT for pT1a G1-2 EC without substantial LVSI. Eighty-four percent of experts recommended BT for pT1a G3 EC without substantial LVSI. Up to 74% of experts used adjuvant BT for pT1b LVSI-negative and pT2 G1–2 LVSI-negative disease. For 74–84% of experts, EBRT + BT was the treatment of choice for nodal-positive pT2 disease and for pT3 EC with cervical/vaginal invasion. For all other tumour stages, there was no clear consensus for adjuvant treatment. Four experts already used molecular markers for decision-making. Sixty-five percent of experts recommended fractionation regimens of 3 × 7 Gy or 4 × 5 Gy for BT as monotherapy and 2 × 5 Gy for combination with EBRT. The most commonly used applicator for BT was a vaginal cylinder; 82% recommended image-guided BT. Conclusions: There was a clear trend towards adjuvant BT for stage IA G3, stage IB, and stage II G1–2 LVSI-negative EC. Likewise, there was a non-uniform pattern for BT dose prescription but a clear trend towards 3D image-based BT. Finally, molecular characteristics were already used in daily decision-making by some experts under the pretext that upcoming trials will bring more clarity to this topic.

Increased risk of secondary bladder cancer after radiation therapy for endometrial cancer

To investigate the effect of radiation therapy (RT) after endometrial cancer (EC) diagnosis on the risk of occurring secondary bladder cancer (SBC) as well as on the survival outcome of those patients who suffered with SBC. Data was extracted from the Surveillance, Epidemiology, and End Results database between 1973 and 2015. Chi-squared test was utilized to compare clinicopathological characteristics among different groups. The Fine and Gray’s competing risk model was utilized to assess cumulative incidence and risk of occurring SBC in EC survivors. The Kaplan–Meier method and the Cox regression model were used for survival analysis. As a result, a total of 108,060 EC patients were included, among which 37,118 (34.3%) patients received RT while others did not. The incidence of SBC was 1.31%, 1.76% and 0.96% among patients who received prior brachytherapy, external-beam radiotherapy (EBRT) and others, respectively. Both of the EBRT (standardized incidence ratio (SIR) = 2.24, 95% CI [1.94–2.58]) and brachytherapy (SIR = 1.76, 95% CI [1.44–2.13]) group had a higher incidence of SBC than the general population in USA. The competing risk analysis demonstrated that receiving EBRT (HR = 1.97, 95% CI [1.64–2.36]) or brachytherapy (HR = 1.46, 95% CI [1.14–1.87]) were all independent risk factors for developing SBC. A survival detriment was only observed in SBC patients who received prior EBRT after EC diagnosis, but not for brachytherapy, when compared with those who did not undergo RT. Additionally, there were no significant survival differences between primary bladder cancer and SBC with or without prior RT history. Patients who underwent RT after EC had an increased risk of developing bladder cancer as secondary primary cancer. The prognosis of these SBC patients varied depending on types of RT that received after EC diagnosis.

Overall and cancer specific survival following radical or adjuvant (chemo)radiotherapy in a retrospective cohort of elderly patients with endometrial cancer

To report the overall survival and cancer specific survival outcomes of elderly women aged ≥70 years who received radical or adjuvant (chemo)radiotherapy for endometrial cancer, we conducted a retrospective review of 93 patients from the West of Scotland Cancer Network (WoSCAN) who received pelvic (+/− para-aortic) radiotherapy over a 5-year period (January 2011 to December 2015, inclusive). Association of treatment type and other variables with overall survival (OS) and cancer specific survival (CSS) were analysed using log rank tests and Cox proportional hazards models. Median age of the study population was 74 years (range 70–90 years); over 50% of patients were aged ≥75 years, and over 25% were ≥80 years. The majority of patients had endometrioid endometrial cancer (75.3%), and 24.7% had a high-risk histological subtype. Stage distribution was as follows: I/II (40.9%); III/IV (41.9%); recurrent disease (17.2%). Radiotherapy was predominantly delivered in the adjuvant setting (61.3%); intent was primary (22.6%) or salvage (16.1%) in the remaining patients. Chemotherapy was administered to almost 50% of the cohort, mainly in conjunction with adjuvant radiotherapy. After median follow up of 96 months, 5-year OS and CSS were 50.5%and CSS 59.3% for the entire series, 57.9% and 62.8% in the adjuvant group, 23.8% and 35.7% in the primary group, and 60.0% and 80.0% in the salvage group, respectively. Age ≥80 years and primary radiotherapy were statistically significant predictors of poorer survival, adjusting for pathology, stage and grade (hazard ratio (HR) 2.06, 95%Confidence Interval (CI) (1.11–3.80), p = 0.021; and HR 2.42 (CI 1.28–4.57), p = 0.006 respectively). In summary, poorer OS was associated with use of (chemo)radiotherapy as primary treatment of endometrial cancer and/or in women aged ≥80 years, suggesting that careful risk/benefit analysis is required in these two groups.

Patterns of Practice for Adjuvant Treatment of FIGO 1B Grade 3 Endometrial Adenocarcinoma Following Publication of ASTRO 2014 Guidelines for Postoperative Treatment in Women With Early Stage High Risk Endometrial Cancer

In 2014, the American Society for Radiation Oncology (ASTRO) published evidence-based guidelines for the role of postoperative radiation therapy in endometrial cancer. These guidelines were also endorsed by the Society of Gynecologic Oncology (SGO). They strongly recommended that women with grade 3 endometrioid endometrial cancer with deep myometrial invasion) receive pelvic radiation (EBRT) and not vaginal cuff brachytherapy (VCBT) given their increased risk of pelvic recurrence based on high quality evidence. We analyzed patterns of practice before and after this consensus guideline was published.We queried the National Cancer Database to identify all women with either FIGO 1C grade 3 disease from 2004-2009 and FIGO 1B grade 3 disease from 2009-2017 with endometrioid histology who were treated surgically. Patients were then stratified to treatment between 2004-2014 (prior to ASTRO guideline updates) and 2015-2017. Patients were excluded from final analysis if they were metastatic at diagnosis, received palliative-intent radiation, treatment parameters were unknown, or age < 18. Multivariable logistic regression was performed to evaluate for factors associated with receipt of VCBT using clinical and sociodemographic covariates.We identified 6,792 patients with grade 3 endometrioid endometrial carcinoma meeting current FIGO 1B disease classification, diagnosed between 2004 and 2017. Adjuvant radiation was not delivered to 38% of patients identified in the study period, and 26% received both EBRT and VCBT. From 2004-2014, of the patients that received single modality adjuvant radiation, 1168 patients received VCBT only (56%) and 908 received EBRT only (44%). The corresponding numbers for 2015 to 2017 for VCBT and EBRT were 347 (62%) and 217 (38%), respectively. The increase in VCBT utilization in 2015-2017 was statistically significant (P = 0.025). Patients who received VCBT were more likely to receive chemotherapy, be treated at a community cancer center or academic cancer center, or live within 50 miles of the treatment center (all P < 0.01). Racial and sociodemographic factors were not associated with likelihood of receipt of VCBT.Based on ASTRO 2014 guidelines, EBRT is strongly recommended in patients with FIGO 1B/ grade 3 endometrioid endometrial carcinoma. However, the rate of EBRT paradoxically declined in the period after the publication of the guideline. This may be in part due to conflicting data from ongoing trials during that time such as GOG 249 and PORTEC 3. Further investigation is warranted to investigate reasons for these variations in practice.C. Weil: None. F. Lew: None. D.K. Gaffney: Research Grant; NCI. Consultant; NCI. run meetings; NCI.G. Suneja: Research Grant; National Institutes of Health. Honoraria; National Comprehensive Cancer Network. Travel Expenses; National Comprehensive Cancer Network, Radiation Oncology Institute, American Board of Radiology; Radiation Oncology Institute, National Comprehensive Cancer Network, ASTRO.V.M. Williams: Involved in planning the mission and activities for the subcommittee; ARRO Equity and Inclusion Subcommittee.

PP05 Presentation Time: 10:40 AM: Change in Vaginal Length and Sexual Function in Women Who Undergo Surgery ± Radiation Therapy for Endometrial Cancer

Purpose: Over 65,000 women were diagnosed with endometrial cancer (EC) in 2020. Standard treatment is TAH/BSO with radiation therapy (RT) and chemotherapy given based on risk factors. These can cause significant changes in the vagina, including shortening, narrowing, loss of elasticity, atrophy, and dryness. These complications are not life threatening, but can affect a woman's physical, psychological, and social functioning. Adjuvant vaginal dilator use is often advised, but there are currently inconsistent recommendations on use and no prospective data to support its efficacy.

PP05 Presentation Time: 10:40 AM: Change in Vaginal Length and Sexual Function in Women Who Undergo Surgery ± Radiation Therapy for Endometrial Cancer

PP05 Presentation Time: 10:40 AM: Change in Vaginal Length and Sexual Function in Women Who Undergo Surgery ± Radiation Therapy for Endometrial Cancer

PO25: Is Adjuvant Brachytherapy Adequate after Surgical Staging of FIGO IB Grade 3 Endometrioid Adenocarcinoma?

Purpose: The Post-Operative Radiation Therapy in Endometrial Cancer (PORTEC) 1 trial excluded women with FIGO 1B (previous FIGO IC) grade 3 endometrioid adenocarcinoma and delivered adjuvant pelvic external beam radiation therapy (EBRT) on prospective protocol. The National Comprehensive Cancer Network recommends EBRT, with chemotherapy being a category 2B recommendation. GOG249 failed to show a survival advantage in a population that included FIGO IB grade 3 women and otherwise, no randomized data exist comparing adjuvant EBRT and vaginal brachytherapy (VBT) with or without chemotherapy in this population.

Toxicity and outcomes associated with high-dose rate brachytherapy for medically inoperable endometrial cancer

PurposeTo evaluate toxicity in inoperable endometrial cancer (EC) treated with definitive radiation therapy (RT). Materials and MethodsPatients treated with definitive RT for EC were retrospectively reviewed. EQD2 values were calculated for bladder, rectum, and sigmoid. Acute and late toxicities were retrospectively graded. Descriptive statistical analysis was performed. ResultsFifty-one patients were included. The majority of patients had endometrioid histology (N = 46, 90.2%) and Grade 1 disease (N = 32, 62.75%). Thirty-seven patients (72.5%) were treated with image-guided BT (IGBT) and 14 (27.5%) with two-dimensional BT. Forty patients (78.4%) received EBRT + BT and 11 (21.57%) received BT alone. No grade 2 (G2) or higher toxicities were reported with BT alone. G2 or higher acute toxicities with EBRT + BT were G2 proctitis (N = 2, 5.0%) and G3 proctitis (N = 1, 2.5%). Late toxicities included G3 vaginal stenosis (N = 1, 2.5%), proctitis (N = 1, 2.5%), enteritis (N = 1, 2.5%), and one G4 gastrointestinal bleed. One- and 2-year local control were 100% with BT alone and 93% and 89%, respectively, with EBRT + BT. One- and 2-year locoregional control were 100% with BT and 97% and 93%, respectively, with EBRT + BT. Recurrence-free survival was 89% at 1 and 2 years with BT alone compared to 87% and 80% with EBRT + BT. One- and 2-year overall survival were 88% and 72% with BT alone compared to 94% and 84% with EBRT + BT. There were no statistically significant differences in cancer control between the two groups. ConclusionsWomen with inoperable EC treated with definitive RT have low toxicity rates and durable local control.

PO-1124: Impact of lymph node dissection on adjuvant radiotherapy in endometrial cancer.

PO-1124: Impact of lymph node dissection on adjuvant radiotherapy in endometrial cancer.

Adjuvant radiotherapy for endometrial cancer with cervical stromal involvement: A patterns of practice survey in Australia and New Zealand.

The purpose of this study is to describe the patterns of practice in Australia and New Zealand for post-operative radiotherapy in endometrial cancer with cervical stromal involvement. A ten-item survey including five clinical case scenarios in endometrial cancer with cervical stromal invasion was emailed to Royal Australian and New Zealand College of Radiologists (RANZCR) radiation oncologists in 2018. Responses were analysed to determine relative frequency distributions and preferred adjuvant treatment modalities for the clinical case scenarios. A total of 65 respondents initiated the survey with 27 respondents treating more than 11 endometrial cancer cases annually. Only 31 respondents answered all five clinical case scenarios. Preferred adjuvant radiotherapy modalities varied for the Stage II cases between vault brachytherapy (VB), pelvic external beam radiotherapy (EBRT) or a combination. For the stage IIIA and IIIC1 cases, the majority recommended pelvic EBRT with or without VB boost (79% and 77%), and of these, most combined with chemotherapy (61% and 88%). For 4 of the 5 case scenarios, when pelvic EBRT was offered, most recommended a VB boost. This patterns of practice survey suggests variability in adjuvant radiotherapy recommendations in endometrial cancer with cervical involvement, particularly in cases where there is lack of randomised data and discrepancies in consensus guidelines.

From prognostication to prediction: Copy-number alterations predict poor response to radiotherapy in endometrial cancer

Objective: Endometrial cancers with high levels of somatic copy-number alterations (SCNA) represent a poor prognostic group, frequently comprising high-grade carcinomas. To date, no studies have demonstrated a correlation between SCNA burden and response to genotoxic therapies. Herein, we examine whether high SCNA status is associated with significantly worse outcomes after radiotherapy compared to an unirradiated population, potentially indicating that SCNA is predictive of radiotherapeutic efficacy.

Definitive Radiation Therapy for Medically Inoperable Endometrial Cancer

The standard of care for patients with endometrial cancer typically involves upfront surgery. External beam radiotherapy, brachytherapy, and/or chemotherapy are implemented in the adjuvant setting based on individual risk factors. In the subset of women who are unable to receive surgery due to medical comorbidities or tumor-related factors, external beam radiation and/or uterine brachytherapy can be employed in the definitive setting. To evaluate the clinical outcomes from definitive radiation therapy in women with newly diagnosed, medically inoperable, endometrial cancer. We used an institutional endometrial cancer database to identify medically inoperable patients who received definitive radiation therapy from 1999-2018. Kaplan-Meier method was used to calculate overall survival, cause-specific survival, and locoregional recurrence free survival. Cox regression analysis was used to assess variables associated with these outcomes. Forty-four patients were identified, with a median follow up of 29.1 months. Median age was 68 years (R: 40-90) and the median body mass index (BMI) was 43 (R:23-88). Ten patients (22.7%) had FIGO grade 3 disease. One patient received external beam radiation to the pelvis alone, twenty-seven patients underwent brachytherapy alone, and sixteen patients received combined external beam radiation to the pelvis followed by consolidative uterine brachytherapy. Chemotherapy was delivered in the neoadjuvant setting in two patients, adjuvant in one patient, and concurrently in two patients. 55% of patients had PET/CT and/or MRI based treatment planning. Four patients were unable to complete their intended treatment course due to exacerbation of medical comorbidities (2), progression of disease during treatment (1), or uterine perforation (1). Locoregional recurrence free survival was 92% (95% C.I. 83.7-100%) at 2 years. Cause-specific survival and overall survival were 79.3% (95% C.I. 65.8-95.7%) and 62% (95% C.I. 48.8-78.7%) respectively at 2 years. On univariate analysis, Grade 3 disease, age, and the presence of lymphadenopathy were associated with decreased overall survival, while surprisingly, BMI was associated with improved OS. KPS less than 80, radiotherapy technique, and smoking status were not associated with OS. On multivariate analysis, only the presence of lymphadenopathy remained significant. No variables were significantly associated with locoregional recurrence. There were no acute grade 3 toxicities observed in this cohort. Grade 3 toxicity was seen in 7.8% of patients with sufficient long term follow up. Definitive radiation therapy for endometrial cancer in medically inoperable patients is associated with excellent locoregional control and cause-specific survival. Cause-specific survival was considerably longer than overall survival in this cohort, suggesting that these patients frequently succumb to other medical conditions.

Determinants of Sensitivity to Radiotherapy in Endometrial Cancer.

Radiotherapy is one of the cornerstone treatments for endometrial cancer and has successfully diminished the risk of local recurrences after surgery. However, a considerable percentage of patients suffers tumor relapse due to radioresistance mechanisms. Knowledge about the molecular determinants that confer radioresistance or radiosensitivity in endometrial cancer is still partial, as opposed to other cancers. In this review, we have highlighted different central cellular signaling pathways and processes that are known to modulate response to radiotherapy in endometrial cancer such as PI3K/AKT, MAPK and NF-κB pathways, growth factor receptor signaling, DNA damage repair mechanisms and the immune system. Moreover, we have listed different clinical trials employing targeted therapies against some of the aforementioned signaling pathways and members with radiotherapy. Finally, we have identified the latest advances in radiotherapy that have started being utilized in endometrial cancer, which include modern radiotherapy and radiogenomics. New molecular and genetic studies in association with the analysis of radiation responses in endometrial cancer will assist clinicians in taking suitable decisions for each individual patient and pave the path for personalized radiotherapy.