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Objective: To investigate whether patients with a history of placental abruption have an increased risk for subsequent maternal long-term morbidity. Study design: A population-based study compared the incidence of long-term renal morbidity in cohort of women with and without a history of placental abruption. Deliveries occurred during a 25-year period, with a mean follow-up duration of 11.2 years. Renal morbidity included kidney transplantation, chronic renal failure, hypertensive renal disease, etc. Results: During the study period 99 354 deliveries met the inclusion criteria; 1.8% (n = 1807) occurred in patients with a diagnosis of placental abruption. Patients with placental abruption did not have higher cumulative incidence of renal related hospitalizations, using Kaplan–Meier survival curve. During the follow-up period patients with a history of placental abruption did not have higher rate of renal morbidity (0.2% versus 0.1%; OR 1.8; 95% CI 0.6–4.8;p = 0.261). When performing a Cox proportional hazards model, adjusted for confounders such as parity and diabetes mellitus, a history of placental abruption was not associated with renal related hospitalizations (adjusted HR, 1.6; 95% CI, 0.6–4.2;p = 0.381). Conclusion: Placental abruption, even though considered a part of the “placental syndrome” with possible vascular etiology, is not a risk factor for long-term maternal renal complications. [ABSTRACT FROM PUBLISHER]

Objective: To evaluate the use of manipulators on the outcome of women who had minimally invasive surgery for endometrial cancer. Methods: Retrospective analysis of patients operated with or without an intrauterine manipulator. Results: Six hundred ninety-nine patients were included. The median follow-up was 44 months (range, 29-67). Nineteen (8.8%) patients had positive cytology in the manipulator group versus 21 (4.4%) in the comparison group ( p  = 0.02). Total recurrence rate was similar between the groups (12.3% vs. 11.9%; p  = 0.8). Vaginal vault recurrence was the most common site of recurrence with higher incidence in the manipulator group (4.5% vs. 1.3%; p  = 0.007). Subgroup analysis of low-risk patients who did not receive adjuvant treatment showed higher recurrence rate (8.3% vs. 3%; p  = 0.023) and worse disease-free survival ( p  = 0.01) for the manipulator group. After controlling for other variables, the use of a manipulator did not affect the risk of recurrence for the whole cohort (hazard ratio [HR], 1.28; confidence interval [95% CI], 0.7-2.1, p  = 0.3) and for the low-risk subgroup of patients who did not receive adjuvant treatment (HR, 2.47; 95% CI, 0.8-7, p  = 0.08). Conclusion: The use of a manipulator increases the risk of positive cytology as well as vaginal vault recurrences, but it does not reduce the overall survival of patients.

Background: Limited data suggests lower uterine segment involvement (LUSI) in endometrial cancer may be associated with other poor prognostic factors. We assessed the unclear impact of LUSI on prognosis in endometrial cancer., Method: ology: A revision of pathological samples following surgical staging between the years 2002-2022 was performed and clinical data collected from patients' records. Characteristics and outcomes of women with and without LUSI were compared and analysed. Kaplan Meyer survival curves compared overall survival (OS) and progression-free survival (PFS)., Results: 429 women were included, of which 45 (10.5%) had LUSI. No differences were found between the groups regarding demographic or clinical characteristics. LUSI was significantly associated with lympho-vascular space invasion (40% vs. 22% p = 0.01), lymph node involvement (6.4% vs. 9.1%, p = 0.05), shorter PFS (4 vs. 5.5 years, p = 0.01) and OS (5.6 vs. 11.5 years, p = 0.03). Multivariate analysis showed higher hazard ratios for OS and PFS (1.55 95%CI 0.79-3.04 and 1.29 95%CI 0.66-2.53, respectively) but these were insignificant even in a sub-analysis of endometrioid histology (1.76 95%CI 0.89-3.46 and 1.35 95%CI 0.69-2.65, respectively). A trend towards decreased PFS and OS was demonstrated in the Kaplan Meyer survival curves for all cases (log rank test p = 0.5 and 0.29 respectively), endometrioid histology (log rank test p = 0.06 and 0.51 respectively) and early-stage disease (log rank test p = 0.63 and 0.3 respectively)., Conclusion: LUSI may be related to poorer outcome of endometrial cancer and may represent an additional factor to consider when contemplating adjuvant treatment, especially in endometrioid-type and early-stage disease., (© 2024 Published by Elsevier Ltd.)

Background: Controversy exists in the literature regarding the possible association between infertility treatments in singleton pregnancies and long-term risk for childhood malignancy. Data regarding infertility treatments in twins and long-term childhood malignancies are scarce. Objective: We sought to investigate whether twins conceived following infertility treatments are at an increased risk for childhood malignancy. Study design: A population-based retrospective cohort study, comparing the risk for future childhood malignancy in twins conceived by infertility treatments (in vitro fertilization and ovulation induction) and those who were conceived spontaneously. Deliveries occurred between the years 1991 and 2021 in a tertiary medical center. A Kaplan-Meier survival curve was used to compare the cumulative incidence of childhood malignancies, and a Cox proportional hazards model was constructed to control for confounders. Results : During the study period, 11,986 twins met the inclusion criteria; 2910 (24.3%) were born following infertility treatments. No statistically significant differences were noted between the groups comparing the rate (per 1000) of childhood malignancies (2.0 in the infertility treatments group vs. 2.2 in the comparison group, OR 1.04, 95% CI 0.41-2.62; p = 0.93). Likewise, the cumulative incidence over time was comparable between the groups (log-rank test, p = 0.87). In a Cox regression model, controlling for maternal and gestational age, no significant differences in childhood malignancies were noted between the groups (adjusted HR = 0.82, 95% CI 0.49-1.39, p = 0.47). Conclusions: In our population, twins conceived following infertility treatments are not at an increased risk for childhood malignancies.

Objective: Pathological involvement of cervical conization margins is a risk factor for recurrence, although management of these patients is controversial. We aimed to define risk factors for positive margins and compare recurrence following additional surgical intervention compared to conservative management., Methods: A retrospective study of all conizations at our center between 2010 and 2019. Univariate analysis identified characteristics associated with positive margins. Women were stratified by mode of management comparing three groups (surveillance, repeat conization or hysterectomy) then two groups (surveillance vs. additional surgery). Kaplan Meyer survival curves compared cumulative recurrence stratified by mode of management. Pathological results of subsequent surgical procedures were examined for residual disease., Results: Of 448 conizations performed, 131 (29.2%) had positive margins which were associated with menopause, high-grade cytology and endocervical gland involvement. Women who underwent surveillance (n = 45) were more likely to be nulliparous, with low-grade histology and less endocervical gland involvement. Women who underwent hysterectomy (n = 61) were more likely to be postmenopausal and parous. Recurrence did not differ significantly in the three-group (p = 0.073) or two-group model (6.4% vs. 7.1% p = 0.869). Kaplan Meyer survival curves depicting cumulative recurrence did not differ significantly in either model (log rank test p = 0.642 for the three-group model, and p = 0.868 for the two-group model). Residual disease was found in 51.6% of hysterectomy specimens and 52.6% of repeat conizations., Conclusion: Surveillance is non-inferior to additional surgery in cases with positive conization margins and constitutes a valid option specifically for younger women at risk of future obstetric complications and those susceptible post-hysterectomy complications., Competing Interests: Declaration of competing interest The authors declare no potential conflict of interest., (Copyright © 2023 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

There is an emerging focus on the role of robotic surgery in ovarian cancer. To date, the operational and cost implications of the procedure remain unknown. The objective of the current study was to evaluate the impact of integrating minimally invasive robotic surgery on patient flow, resource utilization, and hospital costs associated with the treatment of ovarian cancer during the in-hospital and post-discharge processes. 261 patients operated for the primary treatment of ovarian cancer between January 2006 and November 2014 at a university-affiliated tertiary hospital were included in this study. Outcomes were compared by surgical approach (robotic vs. open surgery) as well as pre- and post-implementation of the robotics platform for use in ovarian cancer. The in-hospital patient flow and number of emergency room visits within 3 months of surgery were evaluated using multi-state Markov models and generalized linear regression models, respectively. Robotic surgery cases were associated with lower rates of postoperative complications, resulted in a more expedited postoperative patient flow (e.g., shorter time in the recovery room, ICU, and inpatient ward), and were between $10,376 and $7,421 less expensive than the average laparotomy, depending on whether or not depreciation and amortization of the robotic platform were included. After discharge, patients who underwent robotic surgery were less likely to return to the ER (IRR 0.42, p = 0.02, and IRR 0.47, p = 0.055, in the univariate and multivariable models, respectively). With appropriate use of the technology, the addition of robotics to the medical armamentarium for the management of ovarian cancer, when clinically feasible, can bring about operational efficiencies and entails cost savings., (© 2022. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

Background: The possible impact of interpregnancy interval (IPI) on perinatal outcomes has long been studied, however, a definition of the optimal interval is still not clear. Both short and long IPIs have been associated with obstetrical syndromes and short and long-term complications. In this study, we sought to explore the impact of IPI on the hazard for neoplasm of the offspring, thus contribute to the present literature in determining the preferred birth spacing., Objective: We aim to investigate the association between short and long IPIs and the hazard for childhood neoplasm of the offspring., Methods: A population-based retrospective cohort analysis comparing offspring neoplasm hazard following three different IPIs. Exposure was defined as short (<6 months), or long (>60 months) IPIs, whereas intermediate IPI (6 months - 60 months) served as the comparison group. The study included singleton live births in a tertiary regional hospital between 1991 and 2014. Offspring were followed for 18 years, and all hospitalization records for neoplasm diagnoses were collected. Kaplan-Meier survival curves were used for the cumulative incidence of neoplasm morbidity, and Cox proportional hazards models were used to control for confounders., Results: During the study period, 144,397 deliveries met the inclusion criteria. Of those, 18,947 (13.1%) occurred in women with short IPI, 114,012 (79%) in women with intermediate IPI, and 11,438 (7.9%) in women with long IPI. 61 benign neoplasms and 80 malignant neoplasms were registered in offspring born after long IPI. The total percentage of neoplasm were the highest in the long IPI group versus the intermediate and short IPI groups (malignant - 0.7%, 0.6%, 0.5% respectively, benign - 0.5%, 0.4%, 0.3% respectively). Controlling for maternal age, diabetes mellitus, preterm delivery, birth weight, smoking, cesarean section, and fertility treatments, long IPI was found to be independently associated with high hazard for long-term pediatric neoplasm related hospitalizations (adjusted HR 1.39, 95% CI 1.09, 1.77). Short IPI may be associated to decreased hazard for childhood neoplasms (adjusted HR 0.74, 95% Cl 0.59, 0.92)., Conclusions: Long IPI is associated with a high hazard for childhood neoplasms, compared with intermediate and short IPIs. Short IPI may be associated with decreased hazard for childhood neoplasms.

Objective: The aim of this study was to evaluate whether children that were born small for gestational age (SGA) have an increased risk for childhood neoplasm., Study Design: A population-based cohort analysis comparing the risk for long-term childhood neoplasms (benign and malignant) in children that were born SGA vs. those that were appropriate for gestational age (AGA), between the years1991-2014. Childhood neoplasms were predefined based on ICD-9 codes, as recorded in the hospital medical files. Kaplan-Meier survival curves were constructed to compare cumulative oncological morbidity in both groups over time. Cox proportional hazards model was used to control for confounders., Results: During the study period 231,973 infants met the inclusion criteria; out of those 10,998 were born with a diagnosis of SGA. Children that were SGA at birth had higher incidence of lymphoma (OR 2.50, 95% CI 1.06-5.82; p value = 0.036). In addition, cumulative incidence over time of total childhood lymphoma was significantly higher in SGA children (Log Rank = 0.030). In a Cox regression model controlling for other perinatal confounders; SGA at birth remained independently associated with an increased risk for childhood lymphoma (adjusted HR 2.41, 95% CI 1.03-5.56, p value = 0.043)., Conclusion: Being delivered SGA is associated with an increased long-term risk for childhood malignancy and specifically lymphoma., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Poly ADP-ribose glycohydrolase (PARG) is responsible for the catabolism of PARP-synthesized PAR to free ADP-ribose. Inhibition of PARG leads to DNA repair interruption and consequently induces cell death. This study aims to evaluate the effect of a PARG inhibitor (PARGi) on epithelial ovarian cancer (OC) cell lines, alone and in combination with a PARP inhibitor (PARPi) and/or Cisplatin., Methods: PARG mRNA levels were studied in three different OC datasets: TCGA, Hendrix, and Meyniel. PARG protein levels were assessed in 100 OC specimens from our bio-bank. The therapeutic efficacy of PARGi was assessed using cell migration and clonogenic formation assays. Flow cytometry was used to evaluate the cell apoptosis rate and the changes in the cell cycle., Results: PARG protein was highly expressed in 34% of the OC tumors and low expression was found in another 9%. Similarly, Hendrix, Meyneil and TCGA databases showed a significant up-regulation in PARG mRNA expression in OC samples as compared to normal tissue (P=0.001, P=0.005, P=0.005, respectively). The use of PARGi leads to decreased cell migration. PARGi in combination with PARPi or Cisplatin induced decreased survival of cells as compared to each drug alone. In the presence of PARPi and Cisplatin, PARG knockdown cell lines showed significant G2/M cell cycle arrest and cell death induction., Conclusions: PARG inhibition appears as a complementary strategy to PARP inhibition in the treatment of ovarian cancer, especially in the presence of homologous recombination defects., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Matanes, López-Ozuna, Octeau, Baloch, Racovitan, Dhillon, Kessous, Raban, Kogan, Salvador, Lau, Gotlieb and Yasmeen.)

Objective: We sought to explore whether maternal pre-pregnancy obesity is an independent risk factor for offspring respiratory morbidity during childhood., Methods: A population-based retrospective cohort analysis comparing childhood respiratory morbidity incidence in offspring to mothers with pre-pregnancy obesity (BMI ≥ 30 kg/m 2 ) and those who had lower BMI was conducted. Respiratory diagnoses were pre-defined based on ICD-9 codes. The study population comprises of all deliveries that took place at the Soroka University Medical Center (SUMC), the sole tertiary hospital in the Negev (Southern Israel), between the years 1991-2014. A Kaplan-Meier survival curve was used for cumulative respiratory morbidity incidences over time and a Cox proportional hazards model was constructed to control for confounders., Results: During the study period, 242,342 infants met the inclusion criteria; out of which 3290 were born to mothers with a diagnosis of pre-pregnancy obesity. Offspring to mothers with pre-pregnancy obesity had a significant higher risk for obstructive sleep apnea (OR 1.43, 95% CI 1.002-2.046) as well as a higher total risk for hospitalizations due to childhood respiratory morbidity (OR 1.21, 95% CI 1.041-1.398). The cumulative respiratory morbidity incidence over time was significantly higher in the maternal pre-pregnancy obesity group (p = 0.044). Controlling for maternal age, gestational diabetes mellitus, hypertensive disorders and gestational age, pre-pregnancy obesity remained an independent risk factor for offspring respiratory morbidity (adjusted HR = 1.175, 95% CI 1.018-1.357)., Conclusion: Maternal pre-pregnancy obesity may create an environment leading to an increased risk for long-term offspring respiratory morbidity, and specifically obstructive sleep apnea., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Guidelines for the treatment of tubo-ovarian cancer patients beyond third line are lacking. We aimed to evaluate the effect of response in each line on patient's outcome as well as identify variables that predict response for additional line of chemotherapy. A cohort study was performed including all patients with advanced high-grade ovarian cancer. Survival analysis was performed using Kaplan-Meier curves and log-rank tests. Odds ratios and hazard ratios were calculated using multilevel, mixed-effects logistic regression and Cox regression, adjusting for repeated measures within individual patients. Two-hundred thirty-eight patients were included and underwent up to 10 lines of chemotherapy. The median progression-free survival was 15.6 and overall survival (OS) was 55.6 months. Response rates dropped with each additional line and by line 5, most patients (61%) became refractory and only 16% had any type of response (complete 4% or partial 12%). By line 2, whether a patient had partial disease (PR), stable disease (SD) or progressive disease (PD) did not have an effect on the OS. From line 2, whether a patient had PR, SD or PD did not have an effect on chemotherapy-free interval. Number of previous lines and time from previous line were the only variables that significantly correlated with both outcome of patients and response to the next line. In conclusion, time interval from the previous line of chemotherapy is the major clinical factor that predicts beneficial effect of another line of treatment in patients with ovarian cancer., (© 2020 Union for International Cancer Control.)

Introduction: We compared oncologic and clinical outcomes in patients with advanced ovarian cancer who received dose-dense weekly paclitaxel with 3-weekly carboplatin with those who received standard 3-weekly chemotherapy., Material and Methods: Comparison of all consecutive patients with advanced (International Federation of Gynecology and Obstetrics stages III-IV) ovarian cancer who received a dose-dense protocol between 2010 and 2016 with an immediate historical cohort of consecutive patients who received standard chemotherapy. Patients who received less than three cycles of treatment were excluded., Results: In all, 246 patients were included in the study, of whom 128 received the dose-dense protocol and 118 were treated with the standard Q3-week protocol. Patients in the dose-dense group had significantly better progression-free survival than those receiving the standard protocol (median progression-free survival 22 vs 15 months; log rank = 0.026). The overall survival of patients in the dose-dense group was also better than that of the patients in the standard protocol group; however, this difference was not statistically significant (median overall survival 66 vs 54 months; log rank = 0.185). The dose-dense protocol remained significantly associated with favorable survival outcome in multivariable analysis adjusted for stage, histologic type, cytoreductive results and neoadjuvant chemotherapy. The use of the dose-dense protocol was associated with higher rates of gastrointestinal, dermatologic, neurologic and hematologic side effects., Conclusion: Despite the limitations associated with the comparison to a historical cohort, a dose-dense chemotherapy protocol resulted in a significantly improved progression-free survival and the overall survival tended to be better, but this difference did not reach statistical significance compared with the standard chemotherapy protocol, and may be considered as a treatment alternative, albeit with some increased side effects., (© 2020 Nordic Federation of Societies of Obstetrics and Gynecology.)

Objective: Infectious diseases account for up to 43% of childhood hospitalizations. Given the magnitude of infection-related hospitalizations, we aimed to evaluate the effect of maternal smoking during pregnancy on the risk for long-term childhood infectious morbidity., Study Design: This is a population-based cohort analysis comparing the long-term risk for infectious diseases, in children born to mothers who smoked during pregnancy versus those who did not. Infectious diseases were predefined based on International Classification of Diseases, Ninth Revision codes. Deliveries occurred between the years 1991 and 2014., Results: A total of 246,854 newborns met the inclusion criteria; 2,986 (1.2%) were born to mothers who smoked during pregnancy. Offspring of smokers had significantly higher risk for several infectious diseases during childhood (upper respiratory tract, otitis, viral infections, and bronchitis) as well as increased risk for total infection-related hospitalizations (odds ratio = 1.5, 95% confidence interval [CI]: 1.3-1.7; p  = 0.001). Cumulative incidence of infection-related hospitalizations was significantly higher in offspring of smokers (log-rank test, p  = 0.001). Controlling for maternal age, diabetes, hypertensive disorders, and gestational age at index delivery, smoking remained an independent risk factor for infectious diseases during childhood (adjusted hazard ratio = 1.5, 95% CI: 1.3-1.6; p  = 0.001)., Conclusion: Intrauterine exposure to maternal smoking may create an environment leading to an increased future risk for long-term pediatric infectious morbidity of the offspring., Competing Interests: None declared., (Thieme. All rights reserved.)

Objective: To perform a hypothesis-generating evaluation of patient outcomes following neoadjuvant chemotherapy (NACT) compared with those following primary debulking surgery (PDS) in patients over age 75 with high-grade ovarian cancer., Methods: This was a retrospective cohort study of consecutive patients aged 75 years and older, with high-grade ovarian cancer. Data were analyzed in SPSS 25.0 using descriptive statistics to characterize groups based on primary treatment modality, Kaplan-Meier survival curves to estimate overall and progression-free survival, and Cox proportional hazards to analyze confounders., Results: Of 429 patients with stages III and IV high-grade ovarian cancer (endometrioid and serous), 71 were aged older than 75 years and met our criteria for inclusion; 58 were treated with NACT while 13 underwent primary debulking. Sixteen patients did not undergo interval debulking following NACT. There were no significant differences in demographic characteristics between the groups. Following NACT, more patients were completely debulked-36.2% versus 21% (P = 0.000)-and had a shorter length of stay (5 vs. 7 d; P = 0.018). Overall survival was similar between the NACT and PDS groups (58.7 vs. 59.7 mo; LR -0.836; P = 0.361) despite lower progression-free survival in the NACT group (25.9 vs. 47.1 mo; P = 0.042; LR 4.31). Both progression-free and overall survival were significantly higher when patients undergoing NACT achieved complete debulking (21.7 and 102.3 mo, respectively) compared with suboptimal debulking (12.03 and 14.2 mo, respectively)., Conclusion: In this select group older patients with stage III and IV high-grade ovarian cancers, neoadjuvant chemotherapy may be considered without compromising outcomes and contributes to complete debulking., (Copyright © 2020 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.)

Introduction: The objective was to assess whether an early response to neoadjuvant chemotherapy in women with advanced ovarian cancer may predict short- and long-term clinical outcome., Material and Methods: This is a retrospective study of all women with stage III-IV tubo-ovarian cancer treated with neoadjuvant chemotherapy at a single center in Montreal between 2003 and 2014. Logistic regression models were used to evaluate the association between cancer antigen 125 (CA-125) levels during neoadjuvant chemotherapy and debulking success. Cox proportional hazard models were used to estimate hazard ratios and their respective 95% CI for death and recurrence. Harrell's concordance indices were calculated to evaluate which variables best predicted the chemotherapy-free interval and overall survival in our population., Results: In all, 105 women were included. Following the first, second, and third cycles of neoadjuvant chemotherapy, CA-125 levels had a median reduction of 43.2%, 85.4%, and 92.9%, respectively, compared with CA-125 levels at diagnosis. As early as the second cycle, CA-125 was associated with overall survival (hazard ratio 1.03, 95% CI 1.01-1.05, per 50 U/mL increment). By the third cycle, CA-125 did not only predict overall survival (hazard ratio 1.04, 95% CI 1.01-1.08), but it predicted overall survival better than the success of debulking surgery (Harrell's concordance index 0.646 vs 0.616). Both absolute CA-125 levels and relative reduction in CA-125 levels after 2 and 3 cycles predicted the chance to achieve complete debulking (P < .05)., Conclusions: Reduction of CA-125 levels during neoadjuvant chemotherapy provides an early predictive tool that strongly correlates with successful cytoreductive surgery and long-term clinical outcome in women with advanced high-grade serous and endometrioid ovarian cancer., (© 2020 Nordic Federation of Societies of Obstetrics and Gynecology.)

Objective: Exploring the effect of maternal obesity during pregnancy on the long-term health of offspring is of great importance. The aim of this study was to evaluate the association between maternal pre-pregnancy obesity and future risk of childhood malignancies., Study Design: A population-based cohort analysis comparing the risk for long-term childhood malignancies (up to the age of 18 years) in children born (1991-2014) to mothers with and without pre-pregnancy obesity (body mass index > 30) was conducted in July 2017. Childhood malignancies were predefined based on ICD-9 codes, as recorded in the hospital medical files. Children with congenital malformations and multiple gestations were excluded from the analysis. The Kaplan-Meier survival curve was constructed to compare cumulative oncological morbidity in both groups over time. The Cox proportional hazards model was used to control for confounders., Results: During the study period, 241 273 infants met the inclusion criteria; 3268 were born to mothers with pre-pregnancy obesity. Children of obese women had significantly increased risk for several childhood malignancies (including brain tumors) as well as increased risk for total hospitalizations with malignancy diagnoses, even after controlling for several confounders (adjusted HR 1.90, 95% CI 1.07-3.37, P = 0.028). Cumulative incidence of oncological morbidity was also significantly increased over time in the studied group (log-rank P = 0.023)., Conclusion: Maternal pre-pregnancy obesity is significantly associated with an increased long-term risk for general childhood malignancies, and specifically brain tumors in the offspring. These results are important when counseling mothers regarding potential future risks and recommended lifestyle modifications., (© 2020 Wiley Periodicals, Inc.)

Objective: Data regarding the effect of post-partum bilateral tubal ligation (BTL) on future risk for ovarian cancer (OC) is lacking. In the current study, we aimed to evaluate the effect of BTL during cesarean delivery (CD) on the long-term risk for OC., Study Design: A population-based cohort analysis of women above the age of 35 that underwent CD in their last delivery, comparing the long-term risk for OC between patients that had a Pomeroy excisional BTL and those that did not. OC diagnosis was pre-defined based on ICD-9 codes. Procedures occurred between the years 1991-2017. Kaplan-Meier survival curve was used to compare the cumulative incidence of OC over time and Cox proportional hazards model was constructed to control for confounders., Results: During the study period 13,124 women met the inclusion criteria; 9438 (71.9%) of which had only CD and 3686 (28.1%) underwent CD with BTL. Despite the significantly higher incidence of maternal factors that might increase the long-term risk for OC in the BTL group (advanced maternal age, obesity, hypertensive diseases during pregnancy and diabetes mellitus), the cumulative incidence of OC cases was not significantly different between the two groups (Log-rank test p = 0.199). Likewise, when performing a Cox regression model controlling for maternal age, obesity, hypertensive diseases and diabetes, OC risk was not significantly different between the groups (adjusted HR 2.36, 95% CI 0.73-7.62; p = 0.149)., Conclusion: Despite an increased incidence of known risk factors for OC, patients that underwent BTL during CD did not have increased long-term risk for OC.

Objective: The aim of this study was to evaluate the association between large for gestational age (LGA) at birth and future risk of childhood neoplasm., Study Design: a population-based cohort to compare the long-term risk (up to the age of 18 years) of childhood neoplasms (benign and malignant) in children that were born LGA vs. those that were appropriate for gestational age (AGA), between the years 1991-2014. Childhood neoplasms diagnosis were defined according to international classification of disease 9 (ICD-9) codes recorded medical files. Kaplan-Meier survival curves were used in order to compare cumulative incidence of oncological morbidity over the study period. The Cox proportional hazards model was used to control for confounders., Results: 231,344 infants met the inclusion criteria; out of those 10,369 were diagnosed LGA at birth. Children that were LGA at birth had a higher incidence of leukemia (OR 2.25, 95%CI 1.08-4.65, p = 0.025) as well as kidney tumors (OR = 4.7, 95%CI = 1.02-21.9, p = 0.028). In addition, cumulative incidence over time of childhood malignancies, leukemia, and kidney tumors were significantly higher in LGA children (Log Rank = 0.010, 0.021, and 0.028, respectively). In a Cox regression model controlling for other perinatal confounders, LGA at birth remained independently associated with an increased risk for childhood malignancy (adjusted HR 1.51, 95%CI 1.02-2.23, p = 0.039)., Conclusion: LGA at birth is associated with increased long-term risk for childhood malignancy and specifically leukemia and kidney tumors. This possible link may help to improve current knowledge regarding potential exposures that are associated with childhood cancer development.

Ovarian cancer is the most lethal gynecological malignancy. Currently, new chemotherapeutic strategies are required to improve patient outcome and survival. Biguanides, classic anti-diabetic drugs, have gained importance for theiri antitumor potency demonstrated by various studies. Olaparib is a PARP inhibitor approved for maintenance therapy following platinum-based chemotherapy. Furthermore, Snai1, a transcription factor that works as a master regulator of the epithelial/mesenchymal transition process (EMT) is involved in ovarian cancer resistance and progression. Here we aimed to demonstrate the possible cross talk between biguanides and Snail in response to olaparib combination therapy. In this study, we have shown that while in A2780CR cells biguanides reduced cell survival (single treatments ~20%; combined treatment ~44%) and cell migration (single treatments ~45%; biguanide-olaparib ~80%) significantly, A2780PAR exhibited superior efficacy with single (~60%) and combined treatments (~80%). Moreover, our results indicate that knock-down of Snail further enhances the attenuation of migration, inhibits EMT related-proteins (~90%) and induces a synergistic effect in biguanide-olaparib treatment. Altogether, this work suggests a novel treatment strategy against drug-resistant or recurrent ovarian cancer., (© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Large-scale genomic studies have detailed the molecular landscape of tumors from patients with high-grade serous ovarian cancers (HGSC) who underwent primary debulking surgery and correlated the identified subgroups to survival. In recent years, there is increased use of neoadjuvant chemotherapy (NACT) for patients with HGSC and while abundant data exist for patients who underwent primary debulking, little data are available on the cancer cells remaining after NACT that could lead to recurrences. We aimed to analyze gene expression profiles of NACT-treated HGSC tumor samples, and correlate them to treatment response and outcome. Tumor samples were collected from patients with stage III or IV HGSC (NACT cohort, N = 57) at the time of surgery and diagnosis (biopsy samples N = 8). Tumor content was validated by histologic examination and bioinformatics. Gene expression analysis was performed using a tailored NanoString-based assay, while sequencing was performed using MiSeq. A cross-validated survival classifier revealed patient clusters with either a "Better" or "Worse" prognostic outcome. The association with overall survival remained significant after controlling for clinical variables, and differential gene expression, gene set enrichment analyses, and the appropriate survival models were used to assess the associations between alterations in gene expression in cancer cells remaining after NACT and outcome. Pathway-based analysis of the differentially expressed genes revealed comparatively high levels of cell cycle and DNA repair gene expression in the poor outcome group. IMPLICATIONS: Our work suggests mRNA expression patterns in key genes following NACT may reflect response to treatment and outcome in patient with HGSC., (©2019 American Association for Cancer Research.)

The aim of this study was to evaluate the impact of discordant endometrial sampling on the prognosis of patients finally diagnosed with uterine papillary serous carcinoma (UPSC) and to analyze UPSC mutational profile. Retrospective cohort study comparing outcomes of patients post-operatively diagnosed with UPSC and preoperatively diagnosed with endometrioid endometrial cancer (EEC) or UPSC. Genes commonly implicated in carcinogenesis were analyzed in a subgroup of 40 patients post-operatively diagnosed with UPSC, using next generation sequencing. 61 patients with UPSC on post-surgical, final pathology were included in the study. Prior to surgery, 15 were diagnosed with EEC (discordant) and 46 were correctly diagnosed with UPSC (concordant). After a median follow-up of 41.6 months [5.4-106.7], a preoperative diagnosis of EEC was associated with better 3-year progression-free survival (100% vs. 60.9%, P = 0.003) and longer disease free interval (63.5 versus 15 months, P = 0.026) compared to patients with an initial diagnosis of UPSC. Patients with a concordant diagnosis of UPSC were 5 times more likely to progress or die compared to those with a discordant EEC diagnosis (P = 0.02, P = 0.03, respectively), and their tumors were associated with higher rates of TP53 (88.9% vs. 61.5%, P = 0.04), and a lower rate of PTEN (14.8% vs. 38.5%, P = 0.09) and ARID1A (3.7% vs. 23.1%, P = 0.05) mutations. A pre-surgical diagnosis of EEC is associated with improved prognosis in patients with UPSC. Some histologically defined UPSC tumors contain endometrioid-like molecular characteristics that may confer a survival advantage, suggesting a possible need for molecular approaches to better stratify patients into risk groups., Competing Interests: The authors report no conflict of interest., (© 2019 The Author(s).)

Introduction: With the rapid uptake of robotic surgery in surgical oncology, its use in the treatment of epithelial ovarian cancers is being evaluated. Complete cytoreduction represents the goal of surgery either at primary cytoreduction or after neoadjuvant chemotherapy in the setting of interval cytoreduction. In selected patients, the extent of disease would enable minimally invasive surgery. The objective of this study was to evaluate the impact of introducing robotic surgery for interval cytoreduction of selected patients with stage III-IV ovarian cancer., Methods: All patients who underwent surgery from November 2008 to 2014 (concurrent time period when robotic and open surgery were used simultaneously) after receiving neoadjuvant chemotherapy for advanced ovarian cancer (stage III-IV) were compared with all consecutive patients who underwent cytoreductive surgery by laparotomy after neoadjuvant chemotherapy between January 2006 and November 2008. Inclusion criteria included an interval cytoreductive surgery by laparotomy or robotic assistance for stage III-IV non-mucinous epithelial ovarian, fallopian tube, or primary peritoneal cancer. Exclusion criteria included patients treated concurrently for a non-gynecologic cancer, as well as secondary cytoreductive surgeries and diagnostic surgeries without an attempt at tumor reduction. Overall survival, progression-free survival, and peri-operative outcomes were compared for the entire patient cohort with those with advanced ovarian cancer who received neoadjuvant chemotherapy immediately before and after the introduction of robotic surgery., Results: A total of 91 patients were selected to undergo interval cytoreduction either via robotic surgery (n=57) or laparotomy (n=34) after the administration of neoadjuvant chemotherapy. The median age of the cohort was 65 years (range 24-88), 78% had stage III disease, and the median follow-up time was 37 months (5.6-91.4 months). The median survival was 42.8±3.1 months in the period where both robotic surgery and laparotomy were offered compared with 37.9±9.8 months in the time period preceding when only laparotomy was performed (p=0.6). All patients selected to undergo interval robotic cytoreduction following neoadjuvant chemotherapy had a reduction of cancer antigen 125 by at least 80%, resolution of ascites, and CT findings suggesting the potential to achieve optimal interval cytoreduction. All these patients achieved optimal cytoreduction with <1 cm residual disease, including 82% with no residual disease. The median blood loss was 100 mL (mean 135 mL, range 10-1250 mL), and the median hospital stay was 1 day., Conclusion: Robotic interval cytoreductive surgery is feasible in well-selected patients. Future studies should aim to define ideal patients for minimally invasive cytoreductive surgery., Competing Interests: Competing interests: WG and SL obtained partial travel support for proctoring robotic surgery., (© IGCS and ESGO 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To assess risk factors for lymph node involvement in patients with endometrial cancer and a body-mass index (BMI) ≥30 kg/m 2 ., Materials and Methods: A retrospective analysis was performed of obese patients diagnosed with endometrial carcinoma between 2007 and 2015, treated in a single center in Montreal. Preoperative variables evaluated were age, BMI, parity, and preoperative ASA score, grade, CA-125 and histology. Odds ratios (OR) and hazard ratios (HR) and their respective 95% confidence intervals (95%CI) were calculated using multivariable logistic regression and Cox proportional hazard models., Results: The study included 230 women with BMI ≥30, 223 (97.0%) had complete staging. Pelvic lymph node involvement was detected in 26 patients (11.3%). Sentinel node detection and pelvic lymph node dissection decreased with increasing BMI (adjusted OR 0.86, 95%CI 0.76-0.97 and 0.76, 95%CI 0.59-0.96, respectively, per 1 kg/m 2 increment). Pelvic lymph node involvement was inversely correlated with BMI (adjusted OR 0.88, 95%CI 0.79-0.99) and present in 16/85 (18.8%), 6/56 (10.7%), and 4/82 (4.9%) of patients with a BMI of 30.0-34.9, 35.0-39.9, and ≥40.0 kg/m 2 , respectively. Preoperative CA-125 was associated with lymph node involvement (adjusted OR 2.77, 95%CI 1.62-4.73, per quartile increment)., Conclusion: Pelvic lymph node dissection might be omitted in selected cases of morbidly obese patients with failed sentinel nodes mapping and a low CA-125., (Copyright © 2019. Published by Elsevier Inc.)

Objective: Sentinel lymph node (SLN) mapping is increasingly being used in the treatment of apparent early-stage endometrial cancer. The aim of this study was to evaluate whether three tracers (blue dye, indocyanine green (ICG), and technetium-99 (Tc99)) performed better than two (ICG and Tc99)., Study Design: Prospective study of all consecutive patients (n=163) diagnosed with clinical early-stage endometrial cancer from 2015 to 2017. All patients were randomly assigned to receive a mixture of ICG and Tc99 with or without blue dye. Subgroup analysis for detection rates was performed for each group (double versus triple tracer)., Results: One hundred and fifty-seven patients met the inclusion criteria. Eighty patients received ICG and Tc99 with unilateral and bilateral SLN detection rates of 97.5% and 81.3%, respectively. Seventy-seven patients received all three tracers with unilateral and bilateral detection rates of 93.5% and 80.5%, respectively. Only one patient in the triple tracer group was detected by blue dye alone. No significant differences were noticed in unilateral or bilateral detection rates between the two groups, nor in the detection of lymph node metastasis., Conclusion: The addition of blue dye to ICG and Tc99 did not demonstrate any improvement in SLN detection., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

The hyperglycemic intrauterine environment has been shown to have long-term effects on offspring. We aimed to evaluate its effect on the long-term risk of childhood malignancies. This was a population-based cohort analysis comparing the risk for long-term childhood malignancies (≤18 years) in children born to mothers with and without gestational diabetes mellitus (GDM). Childhood malignancies were diagnosed by physicians and recorded in hospital medical files according to predefined codes based on ICD-9. Deliveries occurred between the years 1991 and 2014 in a tertiary medical center. Children to mothers with pre-GDM, with fetal congenital malformations, and with benign tumors were excluded from the analysis. Kaplan-Meier survival curve was constructed to compare cumulative oncological morbidity in both groups over time. Cox proportional hazards model was used to control for confounders. During the study period, 236 893 infants met the inclusion criteria; 10 294 (4.3%) of whom were born to mothers with GDM. Hospitalizations involving malignancy diagnoses were comparable between the groups (0.11 vs. 0.12%; P=0.424), as were the cumulative incidences of total oncological morbidity using a Kaplan-Meier survival curve (log-rank P=0.820). In the Cox regression model, maternal GDM was not associated with increased childhood oncological hospitalizations while controlling for maternal age, gestational age, and hypertensive disorders (adjusted hazard ratio: 1.02, 95% confidence interval: 0.58-1.82, P=0.932). Exposure to intrauterine hyperglycemic environment due to maternal GDM does not increase the risk for childhood malignancies.

Objective: In view of the recent controversy concerning the use of minimally invasive radical hysterectomy as primary treatment for early stage cervical cancer, this study compared the survival and perioperative outcomes in a cohort of patients who underwent radical hysterectomy either by laparotomy or by robotics., Methods: This retrospective study compared all consecutive patients with early stage cervical cancer since the beginning of the Division of Gynecologic Oncology at the Jewish General Hospital in 2003, who underwent robotic radical hysterectomy (n = 74) with a cohort of all consecutive patients from the immediate past who underwent open radical hysterectomy (n = 24) for early stage cervical cancer. All patients were treated at the Jewish General Hospital in Montréal (Canadian Task Force Classification II-2)., Results: The median follow-up time for the robotic group was 46 months. During that time, 7% and 17% of patients in the robotic group and the laparotomy group had disease recurrence, respectively (P = 0.12). Cox multivariate regression showed no statistically significant effect of surgical approach on overall survival (hazard ratio 1.50, P = 0.63) or on progression-free survival (hazard ratio 0.29, P = 0.07). Patients in the robotic cohort had significantly shorter median hospital stays (1 day vs. 7 days, P < 0.001), and their overall incidence of postoperative complications was lower (13% vs. 50%, P < 0.001). Median estimated blood loss for robotics was also significantly lower (82 mL vs. 528 mL, P < 0.001)., Conclusion: Based on the data on a limited number of patients in a Canadian context, robotic radical hysterectomy did not lead to worse oncologic outcomes and was associated with improved short-term surgical outcomes. One might consider the evaluation of more personalized surgical decision making., (Copyright © 2018 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.)

Objective: The aim of this study was to evaluate the association between maternal smoking during pregnancy and future risk of childhood neoplasm risk., Study Design: A population based cohort analysis comparing the risk for long-term childhood neoplasms in children born (1991-2014) to mothers that smoked during pregnancy vs. those that did not. Childhood neoplasms were pre-defined based on ICD-9 codes, as recorded in the hospital medical files. Children with congenital malformations and multiple gestations were excluded from the analysis. Kaplan-Meier survival curves were constructed to compare cumulative oncological morbidity over time. Cox proportional hazards model was used to control for confounders., Results: 241,273 infants met the inclusion criteria; out of those 2841 were born to mothers that smoked during pregnancy. Offspring to smoking mothers had higher incidence of benign (OR 1.6, 95%CI 1.02-2.58; p value = .038) but not malignant tumors. Total cumulative neoplasm incidence was significantly higher in smoking women (Log Rank = 0.001) but no significant difference in the incidence of malignant tumors was noted (Log Rank = 0.834). In a Cox regression model controlling for maternal confounders; a history of maternal smoking during pregnancy remained independently associated only with increased risk for benign tumors (adjusted HR 2.5, 95%CI 1.57-3.83, p = .001)., Conclusion: Maternal smoking during pregnancy is associated with increased long-term risk for benign but not malignant tumors. This is important when counseling mothers regarding potential future risks and recommended lifestyle modifications. Despite this large population study with long follow-up, childhood malignancies are rare, and clarifying the possible association may require further studies., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Poly (ADP-ribose) polymerase inhibitors (PARPi) have become the first targeted therapies available in the treatment of patients with high-grade serous ovarian cancer (HGSOC). We recently described a significant reduction in PARP1 protein levels in vitro and in vivo in patients treated with standard carboplatinum-paclitaxel chemotherapy, raising the question whether the sequence of treatment used today with chemotherapy followed by PARPi is optimal. In this study, we aim to evaluate if the sequence of PARPi followed by chemotherapy could be more beneficial., Methods: BRCA1-mutated (UWB1.287, SNU-251), epigenetically-silenced (OVCAR8), and wild-type (SKOV3, A2780PAR & A2780CR) ovarian cancer cell lines were exposed to clinically relevant doses of PARPi followed by different doses of standard chemotherapy and compared to the inverse treatment. The therapeutic efficacy was assessed using colony formation assays. Flow cytometry was used to evaluate cell apoptosis rate and the changes in cell cycle. Finally, apoptotic and cell cycle protein expression was immunodetected using western blot., Results: Exposure to PARPi prior to standard chemotherapy sensitized BRCA1-mutated or epigenetically-silenced BRCA1 cell lines to lower doses of chemotherapy. Similar results were observed in BRCA1 wild-type and cell lines in which BRCA1 functionality was restored. Moreover, this treatment increased the apoptotic rate in these cell lines., Conclusion: Pre-treatment with PARPi followed by standard chemotherapy in vitro is more efficient in growth inhibition and induction of apoptosis compared to the administration of standard chemotherapy followed by PARPi.

Objective: This study sought to evaluate the incidence, risk factors, and estimated cost associated with venous thromboembolism (VTE) following robotic surgery for endometrial cancer., Methods: The study included all consecutive patients with newly diagnosed endometrial cancer who underwent robotic surgery, excluding patients with a previous history of VTE (3%), those taking long-term warfarin (3%), and patients with conversions to laparotomy (3%). The incidence of postoperative symptomatic VTE within 90 days was analyzed. Direct and indirect medical costs were estimated using a linked billing database for standardized, inflation-adjusted costs., Results: A total of 558 cases were identified. Median BMI was 29 kg/m 2 (range, 17-85 kg/m 2 ), median operative time was 227 minutes (range, 75-419 minutes), and median blood loss was 30 mL (range, 3-400 mL). All patients received thromboprophylaxis with intraoperative subcutaneous heparin and sequential pneumatic compression devices. Extended postoperative prophylaxis for 28 days was administered to 88 (17.2%) patients with high-risk factors. A total of eight patients (1.6%) developed symptomatic VTE, and all eight were in the group that did not receive extended prophylaxis. The number needed to treat to prevent one VTE was 52.8, with an absolute risk reduction 1.89% (95% CI 0.59% to 3.19%). The average cost for treatment of a VTE was $7653 (range, $4396-$12 211), equivalent to the cost of treating 21 patients with extended prophylaxis ($356 per patient)., Conclusion: The incidence of VTE in patients with endometrial cancer who underwent robotic-assisted surgery was low (1.6%), and none of the VTEs occurred in the cohort of high-risk patients who received extended thromboprophylaxis., (Copyright © 2018 Society of Obstetricians and Gynaecologists of Canada. Published by Elsevier Inc. All rights reserved.)

Purpose: To investigate whether patients with a history of recurrent pregnancy loss (RPL) have an increased risk for future female malignancies., Methods: A retrospective population-based study compared the incidence of long-term female malignancies in a cohort of women with and without a history of RPL (2 or more consecutive pregnancy losses). Deliveries occurred between the years 1988 and 2013, with a mean follow-up duration of 12 years. Women with known malignancies before the index pregnancy were excluded from the analysis. Female malignancies were divided according to specific type including ovary, breast, uterine and uterine cervix. Kaplan-Meier survival curve was used to estimate the cumulative incidence of malignancies. Cox proportional hazards model was used to determine the adjusted hazard ratios (HR) for female malignancy after controlling for confounders., Results: During the study period, 106,265 patients met the inclusion criteria; 6.6% (n = 7052) of patients had a diagnosis of RPL. During the follow-up period, patients with RPL had a significantly increased risk of being diagnosed with female malignancies as a group, while individually there was an increased risk of breast and uterine cervix cancer. Using a Kaplan-Meier survival curve, patients with a history of RPL had a significantly higher cumulative incidence of female malignancies. Using a Cox proportional hazards model, adjusted for confounders such as smoking, parity, and diabetes mellitus, a history of RPL remained independently associated with female malignancies (adjusted HR 1.4; P = 0.003)., Conclusions: RPL is independently associated with long-term female malignancies. Patients with a history of RPL may benefit from counseling and screening for breast and uterine cervix cancer in particular.

Objective: Evaluation of the impact of lower uterine segment involvement (LUSI) in type II endometrial cancer, and mutational profile of uterine papillary serous carcinomas (UPSC)., Methods: Retrospective cohort study comparing patients with type II endometrial cancer with LUSI to patients without LUSI. Genes commonly implicated in carcinogenesis were analyzed in a subgroup of 42 patients with UPSC using next generation sequencing., Results: 83 patients with type II endometrial cancer were included in the study, of these, LUSI was diagnosed in 31.3%. During a median follow-up of 45.5 months, patients with LUSI developed more local and distant recurrences (local: 19.2% vs. 3.5%, P  = .03; distant: 50% vs. 17.5%, P  = .004) and progression events (73.1% vs. 26.3%, P  < .001), with shorter mean progression-free survival (16 months compared to 26.5 months, P  < .01). In a multivariate analysis, LUSI was the only significant pathological factor, associated with a 2.9-fold increase in the risk of progression ( P  = .007), and a 2.6-fold increase in the risk of death ( P  = .02). In the subgroup of patients with UPSC, mutations were identified in 54 genes, including TP53 (80%), PPP2R1A (40%), and PTEN (22.5%). Frequent mutations in the PTEN-PI3K-AKT signaling pathway were found in patients with tumor in the upper uterine segment only ( P  = .04), with PTEN being mutated in 29% of the samples ( P  = .07)., Conclusion: Type II endometrial cancers presenting in the LUS have a significantly worse prognosis and this might be associated with a unique mutational profile.

Objective: The expression of homologous recombination (HR) genes in high grade ovarian cancer (HGOC) samples from debulking surgeries were correlated to outcomes in patients selected for chemotherapy treatment regimens., Study Design: RNA was extracted from 96 fresh frozen tumor samples from debulking surgeries from chemotherapy naïve patients with HGOC (primary derived surgeries (PDS), n = 55) or following neoadjuvant chemotherapy treatment (NACT), n = 41). The samples were selected for high tumor content by a gynecological pathologist, and cancer cell content was further confirmed using a percent tumor content covariate, and mutation score covariate analysis. Gene expression analysis was performed using a tailored NanoString-based Pancancer Pathway Panel. Cox proportional hazard regression models were used to assess the associations between the expression of 19 HR genes and survival., Results: In the PDS group, over-expression of six HR genes (C11orf30, NBN, FANCF, FANCC, FANCB, RAD50) was associated with improved outcome, in contrast to the NACT group where four HR genes (BRCA2, TP53, FANCB, RAD51) were associated with worse outcome. With the adding extent of debulking as a covariate, three HR genes (NBN, FANCF, RAD50), and only one HR gene (RAD51) remained significantly associated with survival in PDS and NACT groups, respectively., Conclusion: Distinct HR expression profiles define subgroups associated with overall outcome in patients that are exposed to neoadjuvant chemotherapy and not only chemotherapy-naïve patients., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: Pilot study to assess the value of weekly paclitaxel plus carboplatin every 3weeks (dose dense regimen, DD) compared to the standard 3-weekly protocol in the adjuvant setting for endometrial cancer., Methods: Retrospective cohort study comparing consecutive patients with high and intermediate-high risk endometrial cancer, undergoing DD protocol (from 2011 to 2015) to a non-overlapping historical cohort with similar characteristics who received treatment every three weeks (2008-2011)., Results: 122 patients with endometrial cancer were included in the study, of these, 61 patients received the dose dense protocol and 61 were treated with the standard 3-weekly protocol. After a median follow-up of 61.6months in the 3-weekly cohort, compared with 41.6months in the DD cohort, 40 progressions were recorded. 29 progressions were observed in women treated in the standard protocol, with a three years progression free survival (PFS) of 57.4%, compared to 11 progressions observed in patients in the DD schedule, with a three years PFS of 79.5% (P=0.03). Patients who were treated with the DD protocol were less likely to have progression events compared to the standard cohort with a hazard ratio of 0.4 on multivariate analysis (CI 95%, 0.2-0.8, P=0.01), had significantly less distant metastases (P=0.01), and had improved overall survival when diagnosed with advanced stage disease (P=0.02). Complaints of musculoskeletal pain were more frequent in the standard cohort (n=17, 27.9%) compared to the dose dense cohort (n=4, 6.6%), P=0.005., Conclusion: Preliminary data suggests that dose dense chemotherapy might be a reasonable and superior option for adjuvant treatment of endometrial cancer, compared to standard chemotherapy., (Copyright © 2017 Elsevier Inc. All rights reserved.)