Outcomes and relapse patterns of stage IB grade 2 or 3 endometrial cancer treated with adjuvant vaginal brachytherapy.

Risk factors for pelvic recurrence in early stage endometrial cancer are poorly understood. We sought to describe outcomes, patterns of failure, and risk factors for recurrence among patients with grade 2-3 endometrial cancer with deep myometrial invasion who were treated with vaginal brachytherapy as sole adjuvant therapy after hysterectomy and lymph node dissection. We retrospectively reviewed the records of stage I patients with grade 2-3 endometrioid histology and ≥50% myometrial invasion treated at an academic institution from January 2005 to December 2017. Only patients with endometrioid histology were included. Mixed histologies, including papillary serous or clear cell components, were excluded. Further exclusion criteria were International Federation of Gynecology and Obstetrics stage IB grade 1 patients, follow-up time less than 3 months, receipt of pelvic irradiation or any form of systemic therapy (chemotherapy, aromatase inhibitor). Overall survival, disease-free survival, and pelvic recurrence-free survival were calculated with Kaplan-Meier methods. Multivariable Cox proportional hazards regression was used to analyze factors associated with overall survival and disease-free survival. Among 131 consecutive patients identified, 111 (85%) patients met the inclusion criteria. The majority (98.2%) underwent lymph node dissection with ≥10 lymph nodes removed in 78.9%. With a median follow-up of 36 months (IQR 12-70 months), the 3-year overall survival, disease-free survival, and pelvic recurrence-free survival were 89.6%, 90.1%, and 92.8%, respectively. Histologic grade 3, older age, and lymphovascular invasion were not associated with inferior outcomes; however, lower uterine segment involvement (p=0.031), tumor size >4 cm (p=0.024), and <10 lymph nodes removed (p=0.032) were associated with reduced disease-free survival on multivariable analysis. Pelvic recurrence occurred in 12 (11%) patients, most often in the setting of synchronous distant disease (n=9), and was significantly more likely with lower uterine segment involvement. Among patients with stage IB grade 2-3 endometrial cancer treated with vaginal brachytherapy, the risk factors for recurrence (larger tumor size and lower uterine segment involvement) in conjunction with established risk factors (high grade, ≥50% myometrial invasion, and lymphovascular invasion) may identify a group of high-risk patients who might benefit from pelvic radiotherapy.

Hochreiter A ，Kelly JR ，Young MR ，Litkouhi B ，Black JD ，Stromberger C ，Higgins S ，Schwartz PE ，Damast S ... -  《-》

Low-dose adjuvant vaginal cylinder brachytherapy for early-stage non-endometrioid endometrial cancer: recurrence risk and survival outcomes.

The aim of this study was to evaluate recurrence patterns and survival outcomes for patients with early-stage non-endometrioid endometrial adenocarcinoma treated with adjuvant high-dose rate vaginal brachytherapy with a low-dose scheme. A retrospective review was performed of patients with International Federation of Gynecology and Obstetrics (FIGO) stage I-II non-endometrioid endometrial cancer who received adjuvant vaginal brachytherapy with a low-dose regimen of 24 Gy in six fractions from November 2005 to May 2017. All patients had >6 months of follow-up. Rates of recurrence-free survival, overall survival, vaginal, pelvic, and distant recurrence were calculated by the Kaplan-Meier method. Prognostic factors for recurrence and survival were evaluated by Cox proportional hazards modeling. A total of 106 patients were analyzed. Median follow-up was 49 months (range 9-119). Histologic subtypes were serous (47%, n=50), clear cell (10%, n=11), mixed (27%, n=29), and carcinosarcoma (15%, n=16). Most patients (79%) had stage IA disease, 94% had surgical nodal assessment, and 13% had lymphovascular invasion. Adjuvant chemotherapy was delivered to 75%. The 5-year recurrence-free and overall survival rates were 74% and 83%, respectively. By histology, 5-year recurrence-free/overall survival rates were: serous 73%/78%, clear cell 68%/88%, mixed 88%/100%, and carcinosarcoma 56%/60% (p=0.046 and p<0.01). On multivariate analysis, lymphovascular invasion was significantly associated with recurrence (HR 3.3, p<0.01). The 5-year vaginal, pelvic, and distant recurrence rates were 7%, 8%, and 21%, respectively. Vaginal and pelvic recurrence rates were highest for patients with carcinosarcoma, lymphovascular invasion and/or FIGO stage IB/II disease. At 5 years, vaginal and pelvic recurrence rates for patients with lymphovascular invasion were 33% and 40%, respectively. Patients with stage IA disease or no lymphovascular invasion had 5-year vaginal recurrence rates of 4% and pelvic recurrence rates of 6% and 3%, respectively. Adjuvant high-dose rate brachytherapy with a low-dose scheme is effective for most patients with early-stage non-endometrioid endometrial cancer, particularly stage IA disease and no lymphovascular invasion. Pelvic radiation therapy should be considered for those with carcinosarcoma, lymphovascular invasion and/or stage IB/II disease.

Smart A ，Buscariollo D ，Alban G ，Buzurovic I ，Cheng T ，Pretz J ，Krechmer B ，King M ，Lee L ... -  《-》

Patterns of recurrence in stage I endometrioid endometrial adenocarcinoma with lymphovascular space invasion.

Simpkins F ，Papadia A ，Kunos C ，Michener C ，Frasure H ，AbuShahin F ，Mariani A ，Bakkum-Gamez JN ，Landrum L ，Moore K ，Thomas SG ，Windhorn A ，Rose PG ... -  《-》

How deep is too deep? Assessing myometrial invasion as a predictor of distant recurrence in stage I endometrioid endometrial cancer.

The goal of this study was to evaluate the depth of myometrial invasion as a predictor of distant recurrence in patients with node-negative stage IB endometrioid endometrial cancer. A retrospective multicenter study, including surgically staged endometrial cancer patients at Mayo Clinic, Rochester (MN, USA) between January 1999 and December 2017, and Fondazione Policlinico Universitario A. Gemelli (Rome, Italy) between March 2002 and March 2017, was conducted. Patients without lymph node assessment were excluded. The follow-up was restricted to the first 5 years following surgery. Recurrence-free survival was estimated using the Kaplan-Meier method. Cox proportional hazards models were fit to evaluate the association of clinical and pathologic characteristics with the risk of recurrence. Of 386 patients, the mean (SD) depth of myometrial invasion was 70.4 (13.2)%. We identified 51 recurrences (14 isolated vaginal, 37 non-vaginal); the median follow-up of the remaining patients was 4.5 (IQR 2.3-7.0) years. At univariate analysis, the risk of non-vaginal recurrence increased by 64% (95% CI 1.28 to 2.12) for every 10-unit increase in the depth of myometrial invasion. International Federation of Gynecology and Obstetrics (FIGO) grade and myometrial invasion were independent predictors of non-vaginal recurrence. The 5-year non-vaginal recurrence-free survival was 95.2% (95% CI 92.0% to 98.6%), 84.0% (95% CI 76.6% to 92.1%), and 67.1% (95% CI 54.2% to 83.0%) for subsets of patients with myometrial invasion <71% (n=207), myometrial invasion ≥71% and grade 1-2 (n=132), and myometrial invasion ≥71% and grade 3 (n=47), respectively. A total of 256 (66.3%) patients received either vaginal brachytherapy only or no adjuvant therapy. Patients who received adjuvant chemotherapy, regardless of receipt of external beam radiotherapy or vaginal brachytherapy, had an approximately 70% lower risk of any recurrence (HR adjusted for age, grade, myometrial invasion 0.31, 95% CI 0.12 to 0.85) and of non-vaginal recurrence (adjusted HR 0.32, 95% CI 0.10 to 0.99). The invasion of the outer third of the myometrium and histologic grade were found to be independent predictors of distant recurrence among patients with endometrioid, node-negative stage IB endometrial cancer. Future studies should investigate if systemic adjuvant therapy for patients with myometrial invasion of the outer third would improve outcomes.

Dinoi G ，Garzon S ，Weaver A ，McGree M ，Glaser G ，Langstraat C ，Kumar A ，Weroha J ，Garda AE ，Shahi M ，Palmieri E ，Scambia G ，Fanfani F ，Mariani A ... -  《-》

Impact of different adjuvant radiotherapy modalities on women with early-stage intermediate- to high-risk endometrial cancer.

Vaginal brachytherapy was recommended for patients with intermediate-risk endometrial cancer, however, optimal radiotherapy modalities for intermediate-high- or high-risk patients remains controversial. Previous studies have mainly focused on survival outcomes and have seldom taken cost issues into consideration, especially for high-risk patients. The purpose of this study is to compare the survival outcomes and costs associated with two adjuvant radiotherapy modalities in the management of patients with early-stage, intermediate- to high-risk endometrial cancer. According to ESMO-ESCO-ESTRO criteria, 238 patients with stage I/II, intermediate- to high-risk endometrial cancer who underwent radiotherapy from January 2003 to December 2015 at our institution were reviewed. The vaginal brachytherapy group and external beam radiation therapy combined with the vaginal brachytherapy group were propensity score-matched at a 1:1 ratio. The Kaplan-Meier method and Cox proportional hazards regression model were used. A total of 361 patients met our inclusion criteria, the median age of the patients was 58 years (range, 28-85). All were diagnosed with stage I-II endometrial cancer (324 with stage I and 37 with stage II; 350 with endometrioid adenocarcinoma; and 10 with mucinous carcinoma). The median follow-up time was 60.5 months (range, 3-177). Among 119 matched pairs, no significant differences were found in overall (10.9% vs 8.4%, P=0.51), locoregional (4.2% vs 1.7%, P=0.45), or distant recurrence rates (6.7% vs 6.7%, P=1.0) between the two groups. There were also no differences in the 5-year overall (94.8% vs 93.9%, P=0.78) or progression-free survival (90.0% vs 84.4%, P=0.23) between the two groups. The rates of acute and late toxicity were significantly higher in the external beam radiation therapy combined with vaginal brachytherapy vs the vaginal brachytherapy group (all P<0.05), except for the acute hematological toxicity rate (17.6% vs 9.2%, P=0.06). External beam radiation therapy combined with vaginal brachytherapy had a higher median cost ($2759 vs $937, P<0.001) and longer median radiotherapy duration (41 days vs 17 days, P<0.001) than vaginal brachytherapy. Vaginal brachytherapy was associated with similar local control and long-term survival outcomes relative to the combination of external beam radiotherapy and vaginal brachytherapy and it also minimizes radiation-related complications, reduces medical costs, and shortens radiotherapy duration. Vaginal brachytherapy may be the optimal radiation modality for patients with early-stage endometrial cancer at intermediate to high risk.

Jin M ，Hou X ，Sun X ，Zhang Y ，Hu K ，Zhang F ... -  《-》