Faiza Gaba

Preventing Ovarian Cancer through early Excision of Tubes and late Ovarian Removal (PROTECTOR): protocol for a prospective non-randomised multi-center trial

Risk-reducing salpingo-oophorectomy is the 'gold standard' for preventing tubo-ovarian cancer in women at increased risk. However, when performed in pre-menopausal women, it results in premature menopause and associated detrimental health consequences. This, together with acceptance of the central role of the fallopian tube in etiopathogenesis of high-grade serous carcinoma, by far the most common type of tubo-ovarian cancer, has led to risk-reducing early salpingectomy with delayed oophorectomy being proposed as a two-step surgical alternative for pre-menopausal women declining/delaying oophorectomy. To evaluate the impact on sexual function of risk-reducing early salpingectomy, within a two-step, risk-reducing, early salpingectomy with delayed oophorectomy tubo-ovarian cancer prevention strategy in pre-menopausal women at increased risk of tubo-ovarian cancer. Risk-reducing early salpingectomy is non-inferior for sexual and endocrine function compared with controls; risk-reducing early salpingectomy is superior for sexual/endocrine function, non-inferior for quality-of-life, and equivalent in satisfaction to the standard risk-reducing salpingo-oophorectomy. Multi-center, observational cohort trial with three arms: risk-reducing early salpingectomy with delayed oophorectomy; risk-reducing salpingo-oophorectomy; controls (no surgery). Consenting individuals undergo an ultrasound, serum CA125, and follicle-stimulating hormone measurements and provide information on medical history, family history, quality-of-life, sexual function, cancer worry, psychological well-being, and satisfaction/regret. Follow-up by questionnaire takes place annually for 3 years. Women receiving risk-reducing early salpingectomy can undergo delayed oophorectomy at a later date of their choosing, or definitely by the menopause. Inclusion criteria: pre-menopausal; aged >30 years; at increased risk of tubo-ovarian cancer (mutation carriers or on the basis of a strong family history); completed their family (for surgical arms). post-menopausal; previous bilateral salpingectomy or bilateral oophorectomy; pregnancy; previous tubal/ovarian/peritoneal malignancy; <12 months after cancer treatment; clinical suspicion of tubal/ovarian cancer at baseline. Sexual function measured by validated questionnaires. 1000 (333 per arm). It is estimated recruitment will be completed by 2023 and results published by 2027. ISRCTN registry: 25 173 360 (https://doi.org/10.1186/ISRCTN25173360).

Attitudes towards risk‐reducing early salpingectomy with delayed oophorectomy for ovarian cancer prevention: a cohort study

ObjectiveTo determine risk‐reducing early salpingectomy and delayed oophorectomy (RRESDO) acceptability and effect of surgical prevention on menopausal sequelae/satisfaction/regret in women at increased ovarian cancer (OC) risk.DesignMulticentre, cohort, questionnaire study (IRSCTN:12310993).SettingUnited Kingdom (UK).PopulationUK women without OC ≥18 years, at increased OC risk, with/without previous RRSO, ascertained through specialist familial cancer/genetic clinics and BRCA support groups.MethodsParticipants completed a 39‐item questionnaire. Baseline characteristics were described using descriptive statistics. Logistic/linear regression models analysed the impact of variables on RRESDO acceptability and health outcomes.Main outcomesRRESDO acceptability, menopausal sequelae, satisfaction/regret.ResultsIn all, 346 of 683 participants underwent risk‐reducing salpingo‐oophorectomy (RRSO). Of premenopausal women who had not undergone RRSO, 69.1% (181/262) found it acceptable to participate in a research study offering RRESDO. Premenopausal women concerned about sexual dysfunction were more likely to find RRESDO acceptable (odds ratio [OR] = 2.9, 95% CI 1.2–7.7, P = 0.025). Women experiencing sexual dysfunction after premenopausal RRSO were more likely to find RRESDO acceptable in retrospect (OR = 5.3, 95% CI 1.2–27.5, P &lt; 0.031). In all, 88.8% (143/161) premenopausal and 95.2% (80/84) postmenopausal women who underwent RRSO, respectively, were satisfied with their decision, whereas 9.4% (15/160) premenopausal and 1.2% (1/81) postmenopausal women who underwent RRSO regretted their decision. HRT uptake in premenopausal individuals without breast cancer (BC) was 74.1% (80/108). HRT use did not significantly affect satisfaction/regret levels but did reduce symptoms of vaginal dryness (OR = 0.4, 95% CI 0.2–0.9, P = 0.025).ConclusionData show high RRESDO acceptability, particularly in women concerned about sexual dysfunction. Although RRSO satisfaction remains high, regret rates are much higher for premenopausal women than for postmenopausal women. HRT use following premenopausal RRSO does not increase satisfaction but does reduce vaginal dryness.Tweetable abstractRRESDO has high acceptability among premenopausal women at increased ovarian cancer risk, particularly those concerned about sexual dysfunction.

Patient outcomes following interval and delayed cytoreductive surgery in advanced ovarian cancer: protocol for a multicenter, international, cohort study (Global Gynaecological Oncology Surgical Outcomes Collaborative)

The Global Gynecological Oncology Surgical Outcomes Collaborative (GO SOAR) has developed a network of gynecological oncology surgeons, surgical departments, and other interested parties that have the long-term ability to collaborate on outcome studies. Presented is the protocol for the GO SOAR2 study. To compare survival following interval and delayed cytoreductive surgery, between delayed cytoreductive surgery and no surgery (chemotherapy alone); and international variations in access to cytoreductive surgery for women with stage III-IV epithelial ovarian cancer. There is no difference in survival following interval and delayed cytoreductive surgery; there is poorer survival with no surgery compared with delayed cytoreductive surgery; and there are international disparities in prevalent practice and access to cytoreductive surgery in women with stage III-IV epithelial ovarian cancer. International, multicenter, mixed-methods cohort study. Participating centers, will review medical charts/electronic records of patients who had been consecutively diagnosed with stage III-IV ovarian cancer between January 1, 2006 and December 31, 2021. Qualitative interviews will be conducted to identify factors determining international variations in prevalent practice and access to cytoreductive surgery. Inclusion criteria include women with stage III-IV epithelial ovarian cancer, undergoing interval (after 3-4 cycles of chemotherapy) or delayed (≥5 cycles of chemotherapy) cytoreductive surgeries or no cytoreductive surgery (≥5 cycles of chemotherapy alone). Overall survival (defined from date of diagnosis to date of death); progression-free survival (defined from date of diagnosis to date of first recurrence); facilitator/barriers to prevalent practice and access to cytoreductive surgery. In order to determine whether there is a difference in survival following interval and delayed cytoreductive surgery and no surgery, data will be abstracted from 1000 patients. It is estimated that recruitment will be completed by 2023, and results published by 2024. NCT05523804.

Randomised trial of population‐based BRCA testing in Ashkenazi Jews: long‐term secondary lifestyle behavioural outcomes

AbstractObjectiveAshkenazi‐Jewish (AJ) population‐based BRCA testing is acceptable, cost‐effective and amplifies primary prevention for breast &amp; ovarian cancer. However, data describing lifestyle impact are lacking. We report long‐term results of population‐based BRCA testing on lifestyle behaviour and cancer risk perception.DesignTwo‐arm randomised controlled trials (ISRCTN73338115, GCaPPS): (a) population‐screening (PS); (b) family history (FH)/clinical criteria testing.SettingNorth London AJ‐population.Population/SampleAJ women/men &gt;18 years. Exclusions: prior BRCA testing or first‐degree relatives of BRCA‐carriers.MethodsParticipants were recruited through self‐referral. All participants received informed pre‐test genetic counselling. The intervention included genetic testing for three AJ BRCA‐mutations: 185delAG(c.68_69delAG), 5382insC(c.5266dupC) and 6174delT(c.5946delT). This was undertaken for all participants in the PS arm and participants fulfilling FH/clinical criteria in the FH arm. Patients filled out customised/validated questionnaires at baseline/1‐year/2‐year/3‐year follow‐ups. Generalised linear‐mixed models adjusted for covariates and appropriate contrast tests were used for between‐group/within‐group analysis of lifestyle and behavioural outcomes along with evaluating factors associated with these outcomes. Outcomes are adjusted for multiple testing (Bonferroni method), with P &lt; 0.0039 considered significant.Outcome measuresLifestyle/behavioural outcomes at baseline/1‐year/2‐year/3‐year follow‐ups.Results1034 participants were randomised to PS (n = 530) or FH (n = 504) arms. No significant difference was identified between PS‐ and FH‐based BRCA testing approaches in terms of dietary fruit/vegetable/meat consumption, vitamin intake, alcohol quantity/ frequency, smoking behaviour (frequency/cessation), physical activity/exercise or routine breast mammogram screening behaviour, with outcomes not affected by BRCA test result. Cancer risk perception decreased with time following BRCA testing, with no difference between FH/PS approaches, and the perception of risk was lowest in BRCA‐negative participants. Men consumed fewer fruits/vegetables/vitamins and more meat/alcohol than women (P &lt; 0.001).ConclusionPopulation‐based and FH‐based AJ BRCA testing have similar long‐term lifestyle impacts on smoking, alcohol, dietary fruit/vegetable/meat/vitamin, exercise, breast screening participation and reduced cancer risk perception.

Survival after interval and delayed cytoreduction surgery in advanced ovarian cancer: a Global Gynaecological Oncology Surgical Outcomes Collaborative–Led Study (GO SOAR2)

Although trials of neoadjuvant chemotherapy for ovarian cancer use 3 cycles, real world practice varies. We evaluated the effect of higher order cycles of chemotherapy, followed by cytoreduction surgery or no surgery on survival, tumor resectability, and post-operative morbidity. For our international, retrospective cohort study, the inclusion criteria were women with stage III to IV ovarian cancer undergoing interval (after 3-4 cycles of chemotherapy) or delayed (≥5 cycles) cytoreduction surgery or no cytoreduction surgery with chemotherapy alone (≥5 cycles). Multivariate regression analyses were used to model the effect of impact variables on overall survival and tumor resectability. Data were collected from 2498 patients from 22 centers across 12 countries. In total, 60.2% (n = 1504) underwent interval cytoreduction surgery, 30.4% (n = 760) underwent delayed cytoreduction surgery, and 9.4% (n = 234) did not undergo surgery. In the interval, delayed, and no-surgery groups, the mean follow-up periods were 57, 69, and 39 months, respectively. Patients undergoing interval versus delayed cytoreduction were more likely to achieve no residual tumor mass (no macroscopic residual disease [R0] = 72.2%, 1072/1484; 64.6%, 490/758). Patients who underwent interval versus delayed cytoreduction surgery had a greater proportion of minor (Clavien-Dindo 1-2, 32%, 471/1473; 28%, 212/756) and major (Clavien-Dindo 3-5, 9.6%, 141/1473; 8.6%, 65/756) morbidities. Interval cytoreduction surgery was associated with statistically significant greater overall survival than delayed cytoreduction surgery (HR 0.81, p = .01). R0 at the time of delayed cytoreduction was not equivalent to R0 at the time of cytoreductive surgery. R0 in the interval setting was associated with better overall survival (HR 0.77, p = .01). Patients who did not undergo surgery had twice as poor overall survival compared with patients who underwent delayed cytoreduction surgery (HR 2.01, p 4 neoadjuvant chemotherapy cycles had poorer overall survival, despite achieving R0 at surgery. Early maximum effort cytoreduction surgery with R0 in high volume centers and appropriate surgical resources are critical for increasing overall survival.

Global survey on training and practice in sentinel lymph node mapping for endometrial and cervical cancer among early-career gynecologic oncologists

This survey was designed to evaluate exposure to sentinel mapping for cervical and endometrial cancers in addition to the quality and availability of surgical training in sentinel procedures around the world. Furthermore, we aimed to identify obstacles in surgical training in the sentinel procedure to support the adoption of this technique in clinical practice. A 52-item survey was developed and computed using Qualtrics XM and SurveyMonkey software. The target population were members of the European Society of Gynaecological Oncology and the International Gynecological Cancer Society aged ≤40 years. The study invitation was disseminated within both organizations' database. The survey hyperlink was active between September and December 2022. Respondents using the same Internet Protocol address were excluded to avoid duplication of responses. Responses to <50% questions were excluded. Overall, 238 respondents joined the survey, and 182 (76.5%) provided answers that met the inclusion criteria. Sentinel mapping was implemented for a longer period and used more frequently in endometrial than in cervical carcinoma; 55% of the responders were initially trained in systematic lymph node dissection, and 22% were not yet trained in any lymph node staging. The main challenges in applying sentinel procedure for early-career gynecologic oncologists were no access to hands-on training (n = 22, 12.1%) and no clinical routine in performing systematic pelvic (n = 15, 8.2%) and para-aortic (n = 35, 19.2%) lymph node dissection in case of failed mapping. Although sentinel lymph node biopsy is integrated in cervical and endometrial cancer guidelines, a significant number of institutions do not implement this procedure in clinical routine, and 22% of early-career gynecologic oncologists are not trained in any type of surgical lymph node staging. Support for sentinel mapping in national guidelines and guided training opportunities are needed to apply this method globally.

A 3D Bioprinted Hormone-producing Model for BRCA Mutated Patients After Risk Reducing Surgery: the DISC-OVARY Trial

Selecting theca and granulosa cells from removed ovaries of BRCA1/2mut patients undergoing Risk-reducing salpingo-oophorectomy (RRSO) and developing a 3D bioprinted hormone-producing bioprosthetic model. If efficacy and tolerability are confirmed in vivo, this bioprosthetic model might be used to replace hormones' production in BRCA mutated patients undergoing prophylactic surgery.

Patient Outcomes Following Interval and Delayed Cytoreductive Surgery in Advanced Ovarian Cancer

To compare patient outcomes following interval and delayed cytoreductive surgeries and no surgery (neoadjuvant chemotherapy alone) and international variations in access to cytoreductive surgeries in women with advanced stage ovarian cancer.