Adherence to ESGO guidelines and impact on survival in obese patients with endometrial cancer: a multicentric retrospective study.

OBJECTIVES: Obesity is known to be both a major risk factor for endometrial cancer and associated with surgical complexity. Therefore, the management of patients with obesity is a challenge for surgeons and oncologists. The aim of this study is to assess the adherence to European Society of Gynaecological Oncology (ESGO) guidelines in morbidly obese patients (body mass index (BMI) >40 kg/m2). The secondary objectives were the impact on overall survival and recurrence-free survival. METHODS: All the patients who were treated for an endometrial cancer in the 11 cancer institutes of the FRANCOGYN group were included and classified into three weight groups: morbid (BMI >40 kg/m2), obese (BMI 30-40), and normal or overweight (BMI <30). Adherence to guidelines was evaluated for surgical management, lymph node staging, and adjuvant therapies. RESULTS: In total, 2375 patients were included: 1330 in the normal or overweight group, 763 in the obese group, and 282 in the morbid group. The surgical management of the morbid group was in accordance with the guidelines in only 30% of cases, compared with 44% for the obese group and 48% for the normal or overweight group (p<0.001); this was largely because of a lack of lymph node staging. Morbid group patients were more likely to receive the recommended adjuvant therapy (61%) than the obese group (52%) or the normal or overweight group (46%) (p<0.001). Weight had no impact on overall survival (p=0.6) and morbid group patients had better recurrence-free survival (p=0.04). CONCLUSION: Adherence to international guidelines for surgical management is significantly lower in morbid group patients, especially for lymph node staging. However, morbidly obese patients had more often the adequate adjuvant therapies. Morbid group patients had a better recurrence-free survival likely because of better prognosis tumors.

Operative Hysteroscopy vs Vacuum Aspiration for Incomplete Spontaneous Abortion: A Randomized Clinical Trial.

Importance: Vacuum aspiration is commonly used to remove retained products of conception in patients with incomplete spontaneous abortion. Scarring of the uterine cavity may occur, potentially impairing future fertility. A procedural alternative, operative hysteroscopy, has gained popularity with a presumption of better future fertility. Objective: To assess the superiority of hysteroscopy to vacuum aspiration for subsequent pregnancy in patients with incomplete spontaneous abortion who intend to have future pregnancy. Design, Setting, and Participants: The HY-PER randomized, controlled, single-blind trial included 574 patients between November 6, 2014, and May 3, 2017, with a 2-year duration of follow-up. This multicenter trial recruited patients in 15 French hospitals. Individuals aged 18 to 44 years and planned for surgery for an incomplete spontaneous abortion with plans to subsequently conceive were randomized in a 1:1 ratio. Interventions: Surgical treatment by hysteroscopy (n = 288) or vacuum aspiration (n = 286). Main Outcomes and Measures: The primary outcome was a pregnancy of at least 22 weeks' duration during 2-year follow-up. Results: The intention-to-treat analyses included 563 women (mean [SD] age, 32.6 [5.4] years). All aspiration procedures were completed. The hysteroscopic procedure could not be completed for 19 patients (7%), 18 of which were converted to vacuum aspiration (8 with inability to completely resect, 7 with insufficient visualization, 2 with anesthetic complications that required a shortened procedure, 1 with equipment failure). One hysteroscopy failed due to a false passage during cervical dilatation. During the 2-year follow-up, 177 patients (62.8%) in the hysteroscopy group and 190 (67.6%) in the vacuum aspiration (control) group achieved the primary outcome (difference, -4.8% [95% CI, -13% to 3.0%]; P = .23). The time-to-event analyses showed no statistically significant difference between groups for the primary outcome (hazard ratio, 0.87 [95% CI, 0.71 to 1.07]). Duration of surgery and hospitalization were significantly longer for hysteroscopy. Rates of new miscarriages, ectopic pregnancies, Clavien-Dindo surgical complications of grade 3 or above (requiring surgical, endoscopic, or radiological intervention or life-threatening event or death), and reinterventions to remove remaining products of conception did not differ between groups. Conclusions and Relevance: Surgical management by hysteroscopy of incomplete spontaneous abortions in patients intending to conceive again was not associated with more subsequent births or a better safety profile than vacuum aspiration. Moreover, operative hysteroscopy was not feasible in all cases. Trial Registration: ClinicalTrials.gov Identifier: NCT02201732.

Impact of vulvar reconstruction on the accuracy of a nomogram for predicting local recurrence after surgery for vulvar cancer.

BACKGROUND DATA: Vulvar carcinoma is a rare disease accounting for 3%-5% of all gynaecological cancers. Although surgery is the standard treatment at an early stage, the outcomes are highly correlated with clear resection margins. Therefore, surgical defects can be important and require reconstruction. The aim of this study was to evaluate vulvar reconstructions using a previously validated nomogram predicting the risk of local recurrence at 2 years. METHODS: Patients who underwent surgery for vulvar cancer between 1998 and 2017 were extracted from eight FRANCOGYN centres. We estimated the probability of local recurrence at 2 years using a previously validated nomogram and compared it with actual relapse in patients with or without vulvar reconstruction. Patients were clustered into tiertiles according to their nomogram score: low-, intermediate-, and high-risk for local relapse probability. RESULTS: We reviewed 254 patients, of whom 49 underwent immediate vulvar reconstruction. The predicted and actual probability of two-year local relapse were 20.1% and 15.7%, respectively, with a concordance index of 0.75. In the low- and intermediate-risk groups, the difference between predicted and observed recurrence was less than 10% in patients with or without vulvar reconstruction. For the high-risk group, the difference reached 25% and observed recurrence probability was lower in patients who underwent vulvar plasty compared with those who did not (20.0% vs. 36.2%, respectively). Local recurrence-free survival rates following vulvar reconstruction were comparable at two years (82.1% vs. 84.8%, respectively, p = 0.26). CONCLUSION: Vulvar reconstruction after surgical resection for vulvar cancer is safe. Vulvar reconstruction should be considered in aggressive cases to decrease local recurrence.

Utility values and its time to deterioration in breast cancer patients after diagnosis and during treatments.

BACKGROUND: The potential effects of breast cancer (BC) on health-related quality of life (HRQoL) should be considered in clinical and policy decision-making, as the economic burden of BC management is currently assessed. In the last decades, time-to-HRQoL score deterioration (TTD) has been proposed as an approach to the analysis of longitudinal HRQoL in oncology. The main objectives of the current study were to investigate the evolution of the utility values in BC patients after diagnosis and during follow-ups and to evaluate the TTD in utility values among women in all stages of BC. METHODS: Health-state utility values (HSUV) were assessed using the EuroQol 5-Dimension 3-Level at diagnosis, at the end of the first hospitalization and 3 and 6 months after the first hospitalization. For a given baseline score, HSUV was considered to have deteriorated if this score decreased by ≥ 0.08 points of the EQ-5D utility index score and ≥ 7 points of the EQ visual analogue scale. TTD curves were calculated using the Kaplan-Meier estimation method. RESULTS: Overall 381 patients were enrolled between February 2006 and February 2008. The highest proportions of respondents at the baseline and all follow-ups reporting some and extreme problems were in pain discomfort and anxiety/depression dimensions; more than 80% of patients experienced a deterioration in EQ-5D utility index score and EQ VAS score with a median TTD of 3.15 months and 6.24 Months, respectively. CONCLUSIONS: BC patients undergoing therapy need psychological support to cope with their discomfort, pain, depression, anxiety, and fear during the process of diagnosis and treatment to improve their QoL.

Inguino-femoral radiotherapy in vulvar squamous cell carcinoma: clues to revised indications in patients with only one intracapsular lymph node metastasis.

Background and objectives: The aim was to review the clinical impact of groin metastatic nodal disease in women with vulvar squamous cell carcinoma (VSCC) and to evaluate the impact of adjuvant radiotherapy on women with single intracapsular lymph node metastasis (SILNM).Methods: Cohort study of women with vulvar squamous cell carcinoma (VSCC) managed between January 2005 and December 2015 in five institutions in France with prospectively maintained databases (French multicentre tertiary care centres). We evaluated Impact of SILNM on outcome.Results: A total of 176 women (34.6%) had at least one positive lymph node (LN). There were no significant differences for the 5-year overall survival rates between women with one extracapsular LN metastasis and women with one intracapsular LN metastasis, or with two node metastases (p = .62, p = .63 respectively). In women with a SILNM: (1) lymphovascular invasion (LVSI) was an independent negative predictive factor recurrence-free survival (RFS) (HR = 0.10 (95%CI, 0.01-0.90), p = .04) and (2) Adjuvant inguino-femoral radiotherapy was a positive independent factor associated with RFS (HR = 5.87 (95%CI 1.21-28.5), p = .02).Conclusion: A potential positive effect of adjuvant radiotherapy in node positive VSCC, irrespective of the number of affected LN, should be considered especially in the case of LVSI.

Does lymphadenectomy improve survival in patients with intermediate risk endometrial cancer? A multicentric study from the FRANCOGYN Research Group.

OBJECTIVE: The role of lymphadenectomy in intermediate risk endometrial cancer remains uncertain. We evaluated the impact of lymphadenectomy on overall survival and relapse-free survival for patients with intermediate risk endometrial cancer. METHODS: We retrospectively reviewed patients from the FRANCOGYN database with intermediate risk endometrial cancer, based on pre-operative and post-operative criteria (type 1, grade 1-2 tumors with deep (> 50%) myometrial invasion and no lymphovascular space invasion), who received primary surgical treatment between November 2002 and August 2013. We compared overall survival and relapse-free survival between staged and unstaged patients. RESULTS: From 1235 screened patients, we selected 108 patients with intermediate risk endometrial cancer. Eighty-two (75.9%) patients underwent nodal staging (consisting of pelvic +/- para-aortic lymphadenectomy). Among them, 35 (32.4%) had lymph node disease. The median follow-up was 25 months (range 0.4 to 155.0). The overall survival rates were 82.5% for patients staged (CI 64.2 to 91.9) vs 77.9 % for unstaged patients (CI 35.4 to 94.2) (P = 0.73). The relapse-free survival rates were 68.9% for staged patients (CI 51.2 to 81.3) vs 68.8% for unstaged patients (CI 29.1 to 89.3) (P=0.67). CONCLUSION: Systematic nodal staging does not appear to improve overall survival and relapse-free survival for patients with IR EC but could provide information to tailor adjuvant therapy. Sentinel lymph node dissection may be an effective and less invasive alternative staging technique and should provide a future alternative for this population.

Melatonin Levels in Preterm and Term Infants and Their Mothers.

The prevention of perinatal brain damage following preterm birth remains a public health priority. Melatonin has been shown to be a promising neuroprotectant in neonatal preclinical models of brain damage, but few studies have investigated melatonin secretion in newborns. We hypothesized that melatonin circulating levels would be lower in preterm compared to term infants. We conducted a prospective, longitudinal, multicenter study to assess melatonin, and 6-sulfatoxy-melatonin (aMT6s) concentrations, measured by radioimmunoassay. Among 209 neonates recruited, 110 were born before 34 gestational weeks (GW) and 99 born after 34 GW. Plasma melatonin concentrations, measured at birth and on Day 3 were below detectable levels (≤7 pg/mL) in 78% and 81%, respectively, of infants born before 34 GW compared to 57% and 34%, respectively, of infants born after 34 GW. The distribution of plasma melatonin concentrations was found to be correlated with gestational age at both time-points (p < 0.001). Median urine aMT6s concentrations were significantly lower in infants born before 34 GW, both on Day 1 (230 ng/L vs. 533 ng/L, p < 0.0001) and on Day 3 (197 ng/L vs. 359 ng/L, p < 0.0001). In conclusion, melatonin secretion appears very low in preterm infants, providing the rationale for testing supplemental melatonin as a neuroprotectant in clinical trials.

Therapeutic value of surgical paraaortic staging in locally advanced cervical cancer: a multicenter cohort analysis from the FRANCOGYN study group.

BACKGROUND: The prognostic impact of surgical paraaortic staging remains unclear in patients with locally advanced cervical cancer (LACC). The objective of our study was to evaluate the survival impact of surgical staging in patients with LACC and no evidence of paraaortic lymph node (PALN) metastasis on pre-operative imaging work-up. METHODS: Data of 1447 patients with cervical cancer treated between 1996 and 2016 were extracted from maintained databases of 10 French University hospitals. Patients with locally advanced disease (IB2 or more) treated by concurrent chemoradiation therapy (CRT) and no evidence of paraaortic metastasis on pre-operative imaging work-up were selected for further analysis. The Kaplan-Meier method was used to estimate the survival distribution. A Cox proportional hazards model was used to account for the influence of multiple variables. RESULTS: Six hundred and forty-seven patients were included, 377 (58.3%) with surgical staging and 270 (41.7%) without, with a mean follow up of 38.1 months (QI 13.0-56.0). Pathologic analysis revealed positive lymph nodes in 47 patients (12.5%). In multivariate model analysis, surgical staging remained an independent prognostic factor for DFS (OR 0.64, CI 95% 0.46-0.89, p = 0.008) and OS (OR 0.43, CI 95% 0.27-0.68, p < 0.001). The other significant parameter in multivariate analysis for both DFS and OS was treatment by intracavitary brachytherapy (OR respectively of 0.7 (0.5-1.0) and 0.6 (0.4-0.9), p < 0.05). CONCLUSION: Nodal surgical staging had an independent positive impact on survival in patients with LACC treated with CRT with no evidence of metastatic PALN on imaging.

Identification of a low risk population for parametrial invasion in patients with early-stage cervical cancer.

BACKGROUND: Recent studies have challenged radical procedures for less extensive surgery in selected patients with early-stage cervical cancer at low risk of parametrial invasion. Our objective was to identify a subgroup of patients at low risk of parametrial invasion among women having undergone surgical treatment. METHODS: Data of 1447 patients with cervical cancer treated between 1996 and 2016 were extracted from maintained databases of 10 French University hospitals. Patients with early-stage (IA2-IIA) disease treated by radical surgery including hysterectomy and trachelectomy, were selected for further analysis. The Kaplan-Meier method was used to estimate the survival distribution. A Cox proportional hazards model including all the parameters statistically significant in univariate analysis, was used to account for the influence of multiple variables. RESULTS: Out of the 263 patients included for analysis, on final pathology analysis 28 (10.6%) had parametrial invasion and 235 (89.4%) did not. Factors significantly associated with parametrial invasion on multivariate analysis were: age > 65 years, tumor > 30 mm in diameter measured by MRI, lymphovascular space invasion (LVSI) on pathologic analysis. Among the 235 patients with negative pelvic lymph nodes, parametrial disease was seen in only 7.6% compared with 30.8% of those with positive pelvic nodes (p < 0.001). In a subgroup of patients presenting tumors < 30 mm, negative pelvic status and no LVSI, the risk of parametrial invasion fell to 0.6% (1/173 patients). CONCLUSION: Our analysis suggests that there is a subgroup of patients at very low risk of parametrial invasion, potentially eligible for less radical procedures.

A Proposal for a Classification for Recurrent Endometrial Cancer: Analysis of a French Multicenter Database From the FRANCOGYN Study Group.

OBJECTIVE: Endometrial cancer (EC) recurrences are relatively common with no standardized way of describing them. We propose a new classification for them called locoregional, nodal, metastasis, carcinomatosis recurrences (rLMNC). PATIENTS AND METHODS: The data of 1230 women with EC who were initially treated by primary surgery were included in this French multicenter retrospective study. Recurrences were classified based on dissemination pathways: (1) locoregional recurrence (rL); (2) nodal recurrence (rN) for lymphatic pathway; (3) distant organ recurrence (rM) for hematogenous pathway; and (4) carcinomatosis recurrence (rC) for peritoneal pathway. These pathways were further divided into subgroups. We compared recurrence free survival and overall survival (OS) between the 4 groups (rL/rN/rM/rC). RESULTS: The median follow-up was 35.6 months (range, 1.70-167.60). One hundred ninety-eight women (18.2%) experienced a recurrence: 150 (75.8%) experienced a single-pathway recurrence and 48 (24.2%) a multiple-pathway recurrence. The 5-year OS was 34.1% (95% confidence interval [CI], 27.02%-43.1%), and the median time to first recurrence was 18.9 months (range, 0-152 months). The median survival after recurrence was 14.8 months (95% CI, 11.7-18.8). Among women with single pathway of recurrence, a difference in 5-year OS (P < 0.001) and survival after recurrence (P < 0.01) was found between the 4 rLNMC groups. The carcinomatosis group had the worst prognosis compared with other single recurrence pathways. Women with multiple recurrences had poorer 5-year OS (P < 0.001) and survival after recurrence (P < 0.01) than those with single metastasis recurrence, other than women with peritoneal carcinomatosis. CONCLUSIONS: This easy-to-use and intuitive classification may be helpful to define EC recurrence risk groups and develop guidelines for the management of recurrence. Its prognosis value could also be a tool to select homogenous populations for further trials.

Management and Survival of Elderly and Very Elderly Patients with Endometrial Cancer: An Age-Stratified Study of 1228 Women from the FRANCOGYN Group.

BACKGROUND: Little data exist about the clinical management and survival of elderly patients with endometrial cancer. This study aimed to evaluate the management of elderly and very elderly patients with endometrial cancer as well as the overall survival (OS) rate, disease-free survival (DFS) rate, and cancer-specific survival (CSS) rate in a multicenter cohort. METHODS: Data from 1228 patients with endometrial cancer who received primary treatment between January 2001 and December 2012 were collected from a multicenter database. Clinical management, DFS, CSS, and OS were analyzed. RESULTS: Based on the international endometrial cancer risk classification, 36% (212/582) of women age 65 years or younger, 42% (220/526) of women ages 65-80 years, and 48% (58/120) of women older than 80 years showed high-risk endometrial cancer (p < 0.001). Pelvic lymphadenectomy was performed for 85% (230/271) of the women age 65 years or younger and 46% (33/71) of the women older than 80 years (p < 0.001). Radiotherapy was performed for 27% (33/120) of the very elderly and 40% (233/582) of the young patients (p = 0.009). The 3-year CSS rates were 95% (95% confidence interval [CI], 93-97%) for the women age 65 years or younger, 90% (95% CI, 87-94%) for the women ages 65-80 years, and 82% (95% CI, 73-93%) for the women older than 80 years (p < 0.001). CONCLUSIONS: The elderly and very elderly patients with endometrial cancer showed poorer prognosis than young patients. The significant lower CSS rate for the elderly patients could have be due to both the higher rate of high-risk endometrial cancer and undertreatment. Specific guidelines for the management of elderly and very elderly patients with endometrial cancer are needed to improve their prognosis.

Patterns of recurrence and outcomes in surgically treated women with endometrial cancer according to ESMO-ESGO-ESTRO Consensus Conference risk groups: Results from the FRANCOGYN study Group.

OBJECTIVES: The purpose of this study was to analyse the endometrial cancer (EC) patterns of recurrence based on a large French multicentre database according to ESMO-ESGO-ESTRO classification. METHODS: Data of women with histologically proven EC who received primary surgical treatment between January 2001 and December 2012 were retrospectively abstracted from seven institutions with prospectively maintained databases. The endpoints were recurrence, recurrence free survival (RFS) and overall survival (OS). Time to the first EC recurrence in a specific site was evaluated by using cumulative incidence analysis (Gray's test). RESULTS: Data from 829 women were analysed in whom recurrences were observed in 176 (21%) with a median and mean time to recurrence of 13 and 19.5months, respectively. High (35%) and high-intermediate risk groups (16%) were associated with higher recurrence rates compared with low (9%) and intermediate (9%) risk patients (p<0.0001). Women with high risk EC had a higher 5-year cumulative incidence of distant recurrence (20.7%) than women with high-intermediate, intermediate and low risk EC (5.6%, 3.5%, 3.3%), (p<0.001), respectively. Women with high risk and high-intermediate risk EC had a higher 5-year cumulative incidence of loco-regional recurrence (24.3% and 16.6%, respectively) than women with intermediate and low risk EC (6.6% and 6.5%, respectively), (p<0.001). CONCLUSIONS: We report specific time and site patterns of first recurrence according to the ESMO/ESGO/ESTRO classification. Sites and hazard rates for recurrence differ widely between subgroups over time. Defining patterns of EC recurrence may provide useful information for developing follow-up recommendations and designing therapeutic approaches.

Predicting poor prognosis recurrence in women with endometrial cancer: a nomogram developed by the FRANCOGYN study group.

BACKGROUND: The purpose of this study was to develop a nomogram to predict 'poor prognosis recurrence' (PPR) in women treated for endometrial cancer (EC). METHODS: The data of 861 women who received primary surgical treatment between January 2001 and December 2013 were abstracted from a prospective multicenter database. Data were randomly split into two sets: training and validation with a predefined 2/3 ratio. A Cox proportional hazards multivariate model of selected prognostic features was performed in the training cohort (n=574) to develop a nomogram predicting PPRs. The nomogram was validated in the validation cohort of 287 patients. RESULTS: In the training cohort, 82 (14.3%) developed subsequent PPR. Age, histologic type and grade, lymphovascular space invasion status, FIGO stage, and nodal staging (SLN±pelvic and/or para-aortic lymphadenectomy) were independently associated with subsequent PPR. The nomogram showed an area under the receiver operating characteristic curve (AUC) of 0.82 (95% confidence interval (CI), 0.73-0.89) in the training set. The validation set showed a good discrimination with an AUC of 0.75 (95% CI, 0.65-0.83). CONCLUSIONS: We have developed a robust tool that is able to predict subsequent PPRs in women with FIGO I-III EC.

Tumor Size, an Additional Prognostic Factor to Include in Low-Risk Endometrial Cancer: Results of a French Multicenter Study.

BACKGROUND: Additional tools are needed to improve the selection of women with early-stage endometrial cancer (EC) at increased risk of nodal metastases and/or recurrence to adapt surgical staging and adjuvant therapies. The aim of this study was to assess the impact of EC tumor size on nodal status and recurrence-free survival (RFS) according to European risk groups for recurrence. METHODS: Data of 633 women with early-stage EC who received primary surgical treatment between 2001 and 2012 were abstracted from a multicenter database. Optimal tumor size cut-offs were determined by a minimal p value approach according to final nodal status. Logistic regression was used to determine the impact of defined tumor size on nodal involvement, and the Kaplan-Meier method was used to estimate the survival distribution. RESULTS: The number of women with final low-, intermediate-, and high-risk EC was 302, 204, and 127, respectively. Tumor size was correlated with nodal status and RFS in women with low-risk EC, while no correlation was found for women with intermediate/high-risk EC. Tumor size ≥35 mm emerged as the optimal threshold for a higher rate of nodal involvement (odds ratio 4.318, 95 % CI 1.13-16.51, p = 0.03) and a lower RFS (p = 0.005) in women with low-risk EC. CONCLUSION: Tumor size is an independent prognostic factor of lymph node involvement in women with low-risk EC and could be a valuable additional histological criterion for selecting women at increased risk of lymph node metastases to better adapt surgical staging.

Impact of the occurrence of a response shift on the determination of the minimal important difference in a health-related quality of life score over time.

BACKGROUND: An important challenge of the longitudinal analysis of health-related quality of life (HRQOL) is the potential occurrence of a Response Shift (RS) effect. While the impact of RS effect on the longitudinal analysis of HRQOL has already been studied, few studies have been conducted on its impact on the determination of the Minimal Important Difference (MID). This study aims to investigate the impact of the RS effect on the determination of the MID over time for each scale of both EORTC QLQ-C30 and QLQ-BR23 questionnaires in breast cancer patients. METHODS: Patients with breast cancer completed the EORTC QLQ-C30 and the EORTC QLQ-BR23 questionnaires at baseline (time of diagnosis; T0), three months (T1) and six months after surgery (T2). Four hospitals and care centers participated in this study: cancer centers of Dijon and Nancy, the university hospitals of Reims and Strasbourg At T1 and T2, patients were asked to evaluate their HRQOL change during the last 3 months using the Jaeschke transition question. They were also asked to assess retrospectively their HRQOL level of three months ago. The occurrence of the RS effect was explored using the then-test method and its impact on the determination of the MID by using the Anchor-based method. RESULTS: Between February 2006 and February 2008, 381 patients were included of mean age 58 years old (SD = 11). For patients who reported a deterioration of their HRQOL level at each follow-up, an increase of RS effect has been detected between T1 and T2 in 13/15 dimensions of QLQ-C30 questionnaire, and 4/7 dimensions of QLQ-BR23 questionnaire. In contrast, a decrease of the RS effect was observed in 8/15 dimensions of QLQ-C30 questionnaire and in 5/7 dimensions of QLQ-BR23 questionnaire in case of improvement. At T2, the MID became ≥ 5 points when taking into account the RS effect in 10/15 dimensions of QLQ-C30 questionnaire and in 5/7 dimensions of QLQ-BR23 questionnaire. CONCLUSIONS: This study highlights that the RS effect increases over time in case of deterioration and decreases in case of improvement. Moreover, taking the RS into account produces a reliable and significant MID.

Severe Obesity Impacts Recurrence-Free Survival of Women with High-Risk Endometrial Cancer: Results of a French Multicenter Study.

BACKGROUND: Studies focusing on the impact of obesity on survival in endometrial cancer (EC) have reported controversial results and few data exist on the impact of obesity on recurrence rate and recurrence-free survival (RFS). The aim of this study was to assess the impact of obesity on surgical staging and RFS in EC according to the European Society of Medical Oncology (ESMO) risk groups. METHODS: Data of 729 women with EC who received primary surgical treatment between January 2000 and December 2012 were abstracted from a multicenter database. RFS distributions according to body mass index (BMI) in each ESMO risk group were estimated using the Kaplan-Meier method. Survival was evaluated using the log-rank test, and the Cox proportional hazards model was used to determine influence of multiple variables. RESULTS: Distribution of the 729 women with EC according to BMI was BMI < 30 (n = 442; 60.6 %), 30 ≤ BMI < 35 (n = 146; 20 %) and BMI ≥ 35 (n = 141; 19.4 %). Nodal staging was less likely to be performed in women with a BMI ≥ 35 (72 %) than for those with a BMI < 30 (90 %) (p < 0.0001). With a median follow-up of 27 months (interquartile range 13-52), the 3-year RFS was 84.5 %. BMI had no impact on RFS in obese women in the low-/intermediate-risk groups, but a BMI ≥ 35 was independently correlated to a poorer RFS (hazard ratio 12.5; 95 % confidence interval 3.1-51.3) for women in the high-risk group. CONCLUSION: Severe obesity negatively impacts RFS in women with high-risk EC, underlining the importance of complete surgical staging and adapted adjuvant therapies in this subgroup of women.

French Multicenter Study Evaluating the Risk of Lymph Node Metastases in Early-Stage Endometrial Cancer: Contribution of a Risk Scoring System.

BACKGROUND: This study was designed to develop a risk scoring system (RSS) for predicting lymph node (LN) metastases in patients with early-stage endometrial cancer (EC). METHODS: Data of 457 patients with early-stage EC who received primary surgical treatment between January 2001 and December 2012 were abstracted from a prospective, multicentre database (training set). A risk model based on factors impacting LN metastases was developed. To assess the discrimination of the RSS, both internal by the bootstrap approach and external validation (validation set) were adopted. RESULTS: Overall the LN metastasis rate was 11.8 % (54/457). LN metastases were associated with five variables: age ≥60 years, histological grade 3 and/or type 2, primary tumor diameter ≥1.5 cm, depth of myometrial invasion ≥50 %, and the positive lymphovascular space involvement status. These variables were included in the RSS and assigned scores ranging from 0 to 9. The discrimination of the RSS was 0.81 [95 % confidence interval (CI) 0.78-0.84] in the training set. The area under the curve of the receiver-operating characteristics for predicting LN metastases after internal and external validation was 0.80 (95 % CI 0.77-0.83) and 0.85 (95 % CI 0.81-0.89), respectively. A total score of 6 points corresponded to the optimal threshold of the RSS with a rate of LN metastases of 7.5 % (29/385) and 34.7 % (25/72) for low-risk (≤6 points) and high-risk patients (>6 points), respectively. At this threshold, the diagnostic accuracy was 83 %. CONCLUSIONS: This RSS could be useful in clinical practice to determine which patients with early-stage EC should benefit from secondary surgical staging including complete lymphadenectomy.

A Predictive Model Using Histopathologic Characteristics of Early-Stage Type 1 Endometrial Cancer to Identify Patients at High Risk for Lymph Node Metastasis.

BACKGROUND: This study aimed to develop a predictive model using histopathologic characteristics of early-stage type 1 endometrial cancer (EC) to identify patients at high risk for lymph node (LN) metastases. METHODS: The data of 523 patients who received primary surgical treatment between January 2001 and December 2012 were abstracted from a prospective multicenter database (training set). A multivariate logistic regression analysis of selected prognostic features was performed to develop a nomogram predicting LN metastases. To assess its accuracy, an internal validation technique with a bootstrap approach was adopted. The optimal threshold in terms of clinical utility, sensitivity, specificity, negative predictive values (NPVs), and positive predictive values (PPVs) was evaluated by the receiver-operating characteristics (ROC) curve area and the Youden Index. RESULTS: Overall, the LN metastasis rate was 12.4 % (65/523). Lymph node metastases were associated with histologic grade, tumor diameter, depth of myometrial invasion, and lymphovascular space involvement status. These variables were included in the nomogram. Discrimination of the model was 0.83 [95 % confidence interval (CI) 0.80-0.85] in the training set. The area under the curve ROC for predicting LN metastases after internal validation was 0.82 (95 % CI 0.80-0.84). The Youden Index provided a value of 0.2, corresponding to a cutoff of 140 points (total score in the algorithm). At this threshold, the model had a sensitivity of 0.73 (95 % CI 0.62-0.83), a specificity of 0.84 (95 % CI 0.82-0.85), a PPV of 0.40 (95 % CI 0.34-0.45), and an NPV of 0.95 (95 % CI 0.94-0.97). CONCLUSION: The results show that the risk of LN metastases can be predicted correctly so that patients at high risk can benefit from adapted surgical treatment.

External validation of nomograms designed to predict lymphatic dissemination in patients with early-stage endometrioid endometrial cancer: a multicenter study.

OBJECTIVE: The objective of the study was to externally validate and assess the robustness of 2 nomograms designed to predict the probability of lymphatic dissemination (LD) for patients with early-stage endometrioid endometrial cancer. STUDY DESIGN: Using a prospective multicenter database, we assessed the discrimination, calibration, and clinical utility of 2 nomograms in patients with surgically treated early-stage endometrioid endometrial cancer. RESULTS: Among the 322 eligible patients identified, the overall LD rate was 9.9% (32 of 322). Predictive accuracy according to discrimination was 0.65 (95% confidence interval, 0.61-0.69) for the full nomogram and 0.71 (95% confidence interval, 0.68-0.74) for the alternative nomogram. The correspondence between observed recurrence rate and the nomogram predictions suggests a moderate calibration of the nomograms in the validation cohort. CONCLUSION: The nomograms were externally validated and shown to be partly generalizable to a new and independent patient population. Although these tools provide a more individualized estimation of LD, additional parameters are needed to allow higher accuracy for counseling patients in clinical practice.

Direct Comparison of Logistic Regression and Recursive Partitioning to Predict Lymph Node Metastasis in Endometrial Cancer.

OBJECTIVE: The purpose was to compare logistic regression model (LRM) and recursive partitioning (RP) to predict lymph node metastasis in early-stage endometrial cancer. METHODS/MATERIALS: Three models (1 LRM and 2 RP, a simple and a complex) were built in a same training set extracted from the Surveillance, Epidemiology, and End Results database for 18,294 patients who underwent hysterectomy and lymphadenectomy for stage I or II endometrial cancer. The 3 models were validated in a same validation set of 499 patients. Model performance was quantified with respect to discrimination (evaluated by the areas under the receiver operating characteristics curves) and calibration. RESULTS: In the training set, the areas under the receiver operating characteristics curves were similar for LRM (0.80 [95% confidence interval [CI], 0.79-0.81]) and the complex RP model (0.79 [95% CI, 0.78-0.80]) and higher when compared with the simple RP model (0.75 [95% CI, 0.74-0.76]). In the validation set, LRM (0.77 [95% CI, 0.75-0.79]) outperformed the simple RP model (0.72 [95% CI, 0.70-0.74]). The complex RP model had good discriminative performances (0.75 [95% CI, 0.73-0.77]). Logistic regression model also outperformed the simple RP model in terms of calibration. CONCLUSIONS: In these real data sets, LRM outperformed the simple RP model to predict lymph node metastasis in early-stage endometrial cancer. It is therefore more suitable for clinical use considering the complexity of an RP complex model with similar performances.