Innovative Follow-up Strategies for Endometrial Cancer

Increasing recognition of the heterogeneous nature of endometrial cancer, the excellent prognosis of low-risk cases and improvements in risk stratification offer opportunities for innovative, personalised follow-up strategies. This review article outlines the evidence base for alternative follow-up strategies in the different risk categories of endometrial cancer, cancer survivorship programmes and considers future directions in endometrial cancer follow-up, including emerging new techniques, such as the liquid biopsy, and opportunities for combining molecular and clinicopathological features to personalise endometrial cancer follow-up

Attitudes and barriers to participation in window-of-opportunity trials reported by White and Asian/Asian British ethnicity patients who have undergone treatment for endometrial cancer

Abstract Purpose Window-of-opportunity trials (WOT) are a study design that have been used to investigate drug activity in endometrial cancer (EC). Recruitment to cancer clinical trials by patients from ethnic minority groups is reported to be lower than for patients of White ethnicity. Methods A verbal questionnaire was conducted with White and Asian/Asian British ethnicity patients who had undergone treatment for EC. Strategic purposeful sampling was used to recruit patients from diverse social/educational backgrounds. Questions explored: background knowledge of clinical research, WOT study design, and views on medications that might be investigated. Thematic analysis was used to explore motivations for WOT participation and perceived barriers. Results In total, 21 patients were recruited to the study (15 White and 6 Asian/Asian British). Views on optimum time to receive trial information differed, preferences ranging from 'at the time of diagnosis' to 'a few days after diagnosis'. The choice of medication under investigation had a strong influence on potential willingness to participate, with greater interest reported in medications derived from vitamins or food supplements rather than hormone-based drugs. Potential barriers to participation included concern over potential side-effects and the emotional/physical burden of a cancer diagnosis prior to major surgery. Discussion This study provides important insights into patients’ views on WOT participation in EC and raises issues that need to be considered for future trial design and participant recruitment materials. The timing and format of study information and type of substance under investigation were factors influencing potential participation. Future studies should consider using multi-lingual visual information videos to address information needs, as this may encourage participation by ethnic minority patients

Patient acceptability of circulating tumour DNA testing in endometrial cancer follow-up

ObjectiveCirculating tumour DNA (ctDNA) is emerging as a potential option to detect disease recurrence in many cancer types, however, ensuring patient acceptability of changing clinical practice and the introduction of new technology is paramount.MethodsPatients enrolled in a non‐intervention cohort study determining the ability of ctDNA to detect recurrent endometrial cancer (EC) were invited to participate in a semi‐structured interview. Analysis was performed by Template Analysis.ResultsEighteen patients were interviewed. A ctDNA blood test was viewed by participants as more physically and psychologically acceptable than clinical examination to monitor for EC recurrence. In particular, participants expressed overwhelming preference for a blood test rather than pelvic examination. Although participants acknowledged that an abnormal ctDNA result could cause anxiety, they expressed a preference to be informed of their results, even if a recurrence was too small to detect radiologically. Explanations for these opinions were a desire for certainty whether their cancer would recur or not, and knowledge would help them be more aware of symptoms that should be reported to their clinician.ConclusionsctDNA monitoring to identify EC recurrence appears to be acceptable to patients, and for many, it may be preferable to clinical examination.</div

Patient acceptability of ctDNA testing in endometrial cancer follow-up

Objective: Circulating tumour DNA (ctDNA) is emerging as a potential option to detect disease recurrence in many cancer types however, ensuring patient acceptability of changing clinical practice and the introduction of new technology is paramount. This study aimed to explore women’s opinions on the acceptability of ctDNA to monitor for endometrial cancer (EC) recurrence. Methods: Women enrolled on a non-intervention cohort study determining the ability of ctDNA to detect recurrent endometrial cancer were invited to participate in a semi-structured interview. Data was analysed using Template Analysis. Results: Eighteen women were interviewed. Participants represented a mix of cases, including early stage high-risk EC, metastatic disease at diagnosis and EC recurrence, to ensure a wide range of participant experiences were captured. A ctDNA blood test was viewed by participants as more physically and psychologically acceptable than clinical examination to monitor for EC recurrence. In particular, participants expressed overwhelming preference for a blood test rather than pelvic examination. Although participants acknowledged that an abnormal ctDNA result could cause anxiety, they expressed a preference to be informed of their results, even if a recurrence was too small to detect radiologically. Explanations for these opinions were a desire for certainty whether their cancer would recur or not, and knowledge would help them be more aware of symptoms that should be reported to their clinician. Conclusions: ctDNA monitoring to identify EC recurrence appears to be acceptable to patients, and for many, may be preferable to clinical examination

Acceptability and utilisation of patient-initiated follow-up for endometrial cancer amongst women from diverse ethnic and social backgrounds: A mixed methods study

INTRODUCTION: A shift in focus towards risk stratification and survivorship in early stage endometrial cancer (EC) has led to the replacement of hospital follow-up (HFU) with patient-initiated follow-up (PIFU) schemes. METHODS: A mixed methods study was undertaken prospectively to investigate utility and patient satisfaction with a newly introduced PIFU scheme. RESULTS: Two hundred and twenty-eight women were enrolled onto PIFU in the first 18 months, median age 65 years (range 42-90 years). Twenty-four (10.5%) women were non-British White ethnicity. Forty-five women contacted the Clinical Nurse Specialist (CNS) at least once (19.7%), the primary reason being vaginal bleeding/discharge (42%). Contact was greater in first six months on the scheme compared to the second 6 months, and women who made contact were significantly younger than those who did not (57 years vs. 65 years, p < 0.001). CONCLUSIONS: PIFU appears to be well received by the majority of women. Although many of the CNS contacts were due to physical symptoms, a number were for psychological support or reassurance. Younger women had greater CNS contact indicating that they may benefit from a greater level support. Patient feedback of the PIFU scheme was positive, with many women reporting that it enabled them to have more control over their own health

Differences in the molecular profile of endometrial cancers from British White and British South Asian women

OBJECTIVES: To identify differences in the mutational profile of endometrial tumours between British White (BW) and South Asian (BSA) women. METHODS: We analysed primary tumours from matched cohorts of British White (BW) and British South Asian (BSA) women resident in Leicestershire diagnosed with EC. Next Generation Sequencing was performed to investigate mutational differences in a panel of 10 genes previously identified as being commonly mutated in EC. The presence of somatic Mismatch Repair (MMR) gene deficiencies was determined by immunohistochemistry. RESULTS: In total, 57 tumours (27 BSA and 30 BW) were sequenced. There was no significant difference in the overall mutation frequency of the 10 genes analysed; however, numerous differences were observed between the groups. There was a positive association between PIK3CA and PTEN mutations in the BSA group, with 78% of PIK3CA-mutant tumours harbouring a PTEN mutation, whereas only 11% of PIK3CA wild-type (wt) tumours were PTEN mutant positive (p = 0.0012). In BW women, 90% of ARID1A mutant tumours had co-existent PI3K pathway mutations versus 50% of wild-type (wt) ARID1A patients (p = 0.0485). This trend was not significant in the BSA group (p = 0.66). The age at diagnosis was significantly higher in the BW group with a somatic MMR gene deficiency compared to those with no deficiency (72.8 years versus 59.6 years, p = 0.007), whereas this difference was not seen in the BSA group (64 years versus 60 years, p = 0.37). CONCLUSION: We have identified differences in the mutational profile of primary EC tumours from BW and BSA women. Further research is needed to confirm these findings and to explore their potential implications for early detection, treatment response and prognosis.</div

Development of a patient-derived explant model for prediction of drug responses in endometrial cancer

ObjectiveTo undertake a pilot study to develop a novel Patient-Derived-Explant (PDE) model system for use in endometrial cancer (EC) that is capable of monitoring differential drug responses in a pre-clinical setting.MethodsFresh tumour was obtained post-hysterectomy from 27 patients with EC. Tumours were cut into 1–3 mm3 explants that were cultured at the air-liquid interface for 16–24 h in culture media. Explants were cultured in different media conditions to optimise viability. Explants were also treated with carboplatin/paclitaxel or pembrolizumab for 24 h and processed into histology slides. Multiplexed immunofluorescence for Ki67 (proliferation marker), cPARP (apoptosis marker) and CAM 5.2 (tumour mask) was performed followed by image analysis and quantitation of biomarker expression.ResultsEC samples are amenable to PDE culture with preserved histological architecture and PDE viability for up to 48 h, with the addition of autologous serum in culture media facilitating EC-PDE viability. Our PDE platform provides evidence of differential drug-response to conventional chemotherapeutics and immune checkpoint inhibition, and these responses can be assessed in the context of a preserved tumour microenvironment.ConclusionsOur PDE platform represents a rapid, low-cost pre-clinical model which can be easily integrated into drug development pipelines. PDE culture preserves original tumour architecture and enables evaluation of spatial relationships in the tumour microenvironment. PDE culture has the potential for personalised drug-testing in a pre-clinical setting which is increasingly important in an era of personalised medicine in the treatment of EC.</div

Peri-operative variables associated with prolonged intensive care stay following cytoreductive surgery for ovarian cancer

Background: Peri-operative variables associated with prolonged Intensive Care Unit (ICU) admission following cytoreductive surgery for ovarian cancer were investigated. Patients and Methods: A retrospective review was carried out of patients admitted to the ICU following cytoreductive surgery for ovarian cancer in a single tertiary referral centre from 2015-2019. Patients were categorized according to length of ICU stay (<48 h and ≥48 h), and peri-operative variables were compared across the two groups. Results: A total of 56 patients were admitted to the ICU post-operatively, 37 for <48 h and 19 for ≥48 h (range=3-11 days). Greater duration of procedure and estimated blood loss, bowel resection, higher post-operative lactate level, lower post-operative albumin level and requirement for post-operative blood products were associated with prolonged ICU stay. Increased intraoperative fluid requirement was an independent predictor of extended ICU stay. Conclusion: Utilizing identified intra-operative risk factors to perform individualized risk assessments might improve planning of ICU resources. Optimizing intraoperative fluid management may improve short-term patient outcomes