64 Can chemotherapy change tumor BRCA status and affect susceptibility to treatment?

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Ectopic pregnancy in women with recurrent miscarriage

The aim of this study was to investigate the possible association between recurrent miscarriage (RM) and ectopic pregnancy (EP)

Comparison of minimally invasive surgery with laparotomic approach in the treatment of high risk endometrial cancer: A systematic review

Objective: To analyze all published studies comparing minimally invasive surgery (MIS) with laparotomic one in the surgical treatment of high-risk endometrial cancer (EC) in term of operative, peri-operative and oncological outcomes. Data sources: We conducted a systematic literature search in PubMed between January 1995–March 2019. Methods of study selection: Titles and abstracts were analyzed by two reviewers. A set of explicit criteria was used for selection of literature: 1) randomized controlled trials (RCT), prospective or retrospective cohort studies, given the rarity of this tumor and the concomitant lack of data in the form of large trials, all reviewed original report publications with an appropriate number of subjects were considered and included; 2) participants of interest being patients who have suffered from high risk EC 3) the outcome measures including overall survival (OS), disease-free survival (DFS) and recurrence, (4) English language, (5) abstract available. Results: Thirty relevant articles were selected for full reading. For final analysis 20 studies were selected. Then, as second step, the full articles were evaluated to determine whether full inclusion criteria were met. In total, 9 papers were identified and included. Conclusion: MIS appears to be safe in the management of high-risk EC patients, showing better perioperative and postoperative outcomes and comparable oncological outcomes than open surgery. Prospective randomized trial would be needed to confirm this data

Letrozole in the management of advanced ovarian cancer: An old drug as a new targeted therapy

At present, there is no standard of care on the use of letrozole in ovarian cancer management. We performed a systematic review of the available literature addressing this issue. Data demonstrated a role for letrozole in ovarian cancer, in both the primary and recurrent setting. Letrozole, which has a favorable toxicity profile, seems to assure a prolonged recurrence-free interval, particularly when used as maintenance treatment, in low grade serous ovarian cancer; in recurrent cases it had also led to prolonged disease control. However, the optimal setting and biologically relevant patient population needs to be defined in larger trials

Secondary cytoreductive surgery in platinum-sensitive recurrent ovarian cancer before olaparib maintenance: Still getting any benefit? A case-control study

Objective: The role of secondary cytoreductive surgery (SCS) in platinum-sensitive recurrent ovarian cancer (PSROC) is still controversial. We investigated the role of SCS in PSROC patients with BRCA1/2 mutation (BRCAmut) who received platinum-based chemotherapy followed by olaparib maintenance. Methods: This is a case-control study. Patients with first PSROC admitted to our Gynecologic Oncology Unit between 2014 and 2018 were identified. Main eligibility criteria: positive BRCA1/2 germline or somatic mutation status and olaparib maintenance at primary recurrence after response to platinum-based chemotherapy. Cases were those who received SCS followed by medical treatment (SCS-CT-OLA, group 1), controls were those who received medical treatment alone (CT-OLA, group 2). Results: Overall, 46 patients were identified; 23 (50%) BRCAmut women undergoing SCS followed by platinum-based chemotherapy and olaparib maintenance were matched with 23 (50%) BRCAmut women who only received medical treatment. Groups were well balanced: no statistical differences were found with regard of age, mutational status, treatment's approach at diagnosis, timing and patterns of disease presentation at recurrence. Median time to first subsequent therapy (TFST) was significantly longer in the SCS-CT-OLA than in the CT-OLA group (42 months vs 16 months; p = 0.05). Also, SCS-CT-OLA patients had the best post-recurrence survival (PRS), with a 3-year PRS of 79% in SCS-CT-OLA group versus 42% in CT-OLA group (p = 0.02). Conclusions: SCS increases TFST and PRS in PSROC patients with BRCAmut candidate for olaparib maintenance after platinum-based chemotherapy. Prospective studies are needed. In the era of personalized medicine, indication to SCS should be individualized

BRCA status and platinum sensitivity in advanced ovarian cancer according to Chemotherapy Response Score

Objective To evaluate a relation between BRCA1/2 status and the Chemotherapy Response Score in patients with epithelial ovarian cancer undergoing neoadjuvant chemotherapy and interval debulking surgery. Methods Data were retrospectively collected on patients with unresectable disease undergoing three or four cycles of neoadjuvant chemotherapy and interval debulking surgery at the Gynecologic Oncology Unit of the Catholic University of the Sacred Heart from January 2016 to December 2020. All patients were assessed for BRCA1/2 somatic mutation at diagnosis. The omental specimens obtained at the interval surgery were evaluated according to Bohm's Chemotherapy Response Score System. Results A total of 172 patients were included in the analysis, 69 (40%) patients were BRCA1/2 mutation carriers and 103 (60%) patients were wild type. In the wild-type group (BRCAwt), 73 (70.9%) patients had a Chemotherapy Response Score of 1 or 2 and 30 (29.1%) patients had a score of 3. In the BRCA1/2 carriers group (BRCAmut), 39 (56.5%) patients had a score of 1 or 2 and 30 (43.5%) patients had a score of 3. Among the BRCAwt group, those with a Chemotherapy Response Score of 3 had a prolonged median progression-free survival (22 vs 15 months, p=0.003). Among the BRCAmut carriers group, no differences were found (30 vs 27 months, p=0.55). No difference in overall survival was observed in either the BRCAmut carriers population (p=0.23) or the BRCAwt population (60 vs 44 months, p=0.06). Conclusions Patients with BRCA1/2mut seem to achieve a score of 1, 2 or 3 with the same frequency. In contrast, patients with BRCAwt seem to have a score of 1 or 2 more frequently than a score of 3. In patients with BRCA1/2mut, this score may not be an indicator of chemosensitivity

A Laparoscopic Adjusted Model Able to Predict the Risk of Intraoperative Capsule Rupture in Early-stage Ovarian Cancer: Laparoscopic Ovarian Cancer Spillage Score (LOChneSS Study)

Study Objective: To identify preoperative/intraoperative patient and tumor characteristics associated with an increased risk of tumor spillage during minimally invasive surgery (MIS) for early-stage ovarian cancer (OC). The secondary end point was to develop a score system able to estimate the risk of tumor rupture during MIS. Design: Retrospective observational study. Setting: Patients with International Federation of Gynecology and Obstetrics stage I OC. Patients: Patients aged ≥18 years old, with International Federation of Gynecology and Obstetrics stage IA to IC1 OC of any histology. Interventions: Preoperative and intraoperative characteristics of patients treated with MIS for early-stage OC at Policlinico Universitario Agostino Gemelli, IRCCS in Rome, Italy, from January 1, 2001, to December 31, 2017, were collected. Measurements and Main Results: A total of 151 patients were included. Previous pelvic surgery was more represented in patients with nonruptured tumors (46.0% vs 63.4%; p = .042). In addition, a larger tumor diameter (p <.001), a higher body mass index (p = .032), ultrasound characteristics (p = .029), and adhesions to large bowel (14% vs 2.0%; p = .003), uterus (44% vs 6.9%; p <.001), contralateral ovary (8.0% vs 0%; p = .004), ovarian fossa (64% vs 14.9%; p <.001), and pouch of Douglas peritoneum (32% vs 4.0%; p <.001) increased rupture rate. At multivariate analysis, a larger tumor diameter (p <.001) and adhesions to ovarian fossa peritoneum (p = .007) were independently associated with intraoperative cancer spillage and included in the score calculation. A disease-free survival (DFS) difference between the rupture group and the no-rupture group was detected (5-year DFS, 74.9% vs 94.4%; p = .011), with superimposable overall survival (5-year overall survival, 91.2% vs 97.9%; p = .089). Conclusion: Some preoperative/intraoperative characteristics increase the risk of tumor rupture during MIS for early-stage OC. A laparoscopic predictive model of capsule disruption could be considered to intraoperatively tailor surgical approach to prevent tumor spillage and avoid affecting patient's DFS

Sexual Function following Laparoscopic versus Transvaginal Closure of the Vaginal Vault after Laparoscopic Hysterectomy: Secondary Analysis of a Randomized Trial by the Italian Society of Gynecological Endoscopy Using a Validated Questionnaire

Study Objective: The effect of the different types of vaginal cuff closures on posthysterectomy sexual function has not been investigated in depth. We evaluated if there is a difference between transvaginal versus a laparoscopic closure after total laparoscopic hysterectomy (TLH) on female sexual function, using a validated questionnaire. Design: Secondary analysis of a prospective randomized controlled trial. Setting: Three academic research centers. Patients: Women consenting to telephone interviews on their sexual life before and after undergoing TLH were included. Interventions: Patients were randomly assigned to a laparoscopic or transvaginal approach for vaginal cuff closure at the end of TLH for benign indications. Measurements and Main Results: A validated questionnaire (the Female Sexual Function Index [FSFI]) was used to explore sexuality before and after the operation. Of the 1408 patients enrolled in the primary study, 400 patients were asked to complete the questionnaire. Of them, 182 (41.4%) were eligible and accepted enrollment in the present analysis. No difference was found in terms of pre- and postoperative FSFI scores between groups. Patients with a low preoperative FSFI score (<26.55) had a significantly higher likelihood of having a postoperative sexual disorder (p <.001). Women who received bilateral adnexectomy before menopause and those with postoperative vaginal cuff hematoma had a significantly lower postoperative FSFI score (p = .001 and p = .04, respectively). After multivariable analysis, both variables maintained at least a tendency toward an association with a lower postoperative FSFI score (odds ratio, 2.696; 95% confidence interval, 1.010\u20137.194; p = 0.048 and p = 0.053; odds ratio, 13.2; 95% confidence interval, .966\u2013180.5, respectively). Conclusion: Transvaginal and laparoscopic cuff closures after TLH have similar sexual postoperative outcomes. A patient with sexual problems before TLH is more likely to have a low FSFI score postoperatively. Premenopausal patients undergoing bilateral ovariectomy and those with postoperative vaginal cuff hematoma have a worse postoperative sexual life. (Clinicaltrials.gov, protocol number NCT02453165, registration date May 25, 2015.

Evolution of Clinical Trials in Ovarian Cancer Management over the Past 20 Years: Never Settle Down, Always Go beyond

Purpose. A practice synthesis of available evidence-based medicine data in ovarian cancer (OC), aiming to provide directions for future research. Materials and Methods. We performed a systematic review. PubMed was searched for relevant OC trials between January 2000 and December 2019. Results. Out of 865 references screened, 199 trials were found eligible for inclusion. Most trials were multicenter (83.9%). There was a trend reduction in the number of patients enrolled/per study over the years. Studies testing targeted/biological therapies dominated the second decade (60 trials in 2010-2019 versus 2 trials in 2000-2009). The proportion of trials with positive survival and clinical outcomes significantly increased from 23.8% in early 2000s to 54.1% in the last 5 years. Trials with histology/molecular biomarker criteria were more likely to meet progression-free survival endpoint than those without these selection criteria (69.2% versus 32.6%). Conclusion. This systematic review suggests a trend of increased positive studies, mainly linked to precision medicine

Comparison of minimally invasive surgery with laparotomic approach in the treatment of high risk endometrial cancer: A systematic review

Objective: To analyze all published studies comparing minimally invasive surgery (MIS) with laparotomic one in the surgical treatment of high-risk endometrial cancer (EC) in term of operative, peri-operative and oncological outcomes. Data sources: We conducted a systematic literature search in PubMed between January 1995\u2013March 2019. Methods of study selection: Titles and abstracts were analyzed by two reviewers. A set of explicit criteria was used for selection of literature: 1) randomized controlled trials (RCT), prospective or retrospective cohort studies, given the rarity of this tumor and the concomitant lack of data in the form of large trials, all reviewed original report publications with an appropriate number of subjects were considered and included; 2) participants of interest being patients who have suffered from high risk EC 3) the outcome measures including overall survival (OS), disease-free survival (DFS) and recurrence, (4) English language, (5) abstract available. Results: Thirty relevant articles were selected for full reading. For final analysis 20 studies were selected. Then, as second step, the full articles were evaluated to determine whether full inclusion criteria were met. In total, 9 papers were identified and included. Conclusion: MIS appears to be safe in the management of high-risk EC patients, showing better perioperative and postoperative outcomes and comparable oncological outcomes than open surgery. Prospective randomized trial would be needed to confirm this data