Sharon O’Toole

The value of human epididymis 4, D‐dimer, and fibrinogen compared with CA 125 alone in triaging women presenting with pelvic masses: a retrospective cohort study

AbstractIntroductionCA 125, the biomarker in common clinical use for ovarian cancer, is limited by low sensitivity for early disease and high false positives. The aim of this study was to evaluate several candidate biomarkers, alone or in combination, compared with CA 125 in the prediction of malignant/borderline vs benign tumor status in premenopausal and postmenopausal women with pelvic masses.Material and methodsThis was a retrospective observational cohort study set in St James’s Hospital, a tertiary referral center for gynecological malignancy in Dublin, Ireland. Women undergoing surgery for pelvic masses between 2012 and 2018 were included. Preoperative human epididymis protein 4 (HE4), the Risk of Ovarian Malignancy Algorithm, the Risk of Malignancy Index I and II, D‐dimer, and fibrinogen were assessed. Logistic regression models were fitted for each biomarker alone and in combination. Receiver operating characteristics‐area under the curve (ROC‐AUC) and partial AUCs in the 90%‐100% specificity range were determined.ResultsIn all, 89 premenopausal and 185 postmenopausal women were included. In premenopausal women, no biomarker(s) outperformed CA 125 (AUC 0.73; 95% CI 0.63–0.84). In postmenopausal women, HE4 had a partial AUC (pAUC) of 0.71 (95% CI 0.64–0.79) compared with 0.57 (95% CI 0.51–0.69) for CA 125 (p = 0.009). HE4 + D‐dimer had an improved pAUC of 0.74 (95% CI 0.68–0.81, p < 0.001) and HE4 + D‐dimer + fibrinogen had a pAUC of 0.75 (95% CI 0.68–0.82).ConclusionsA novel biomarker panel of HE4 ± D‐dimer ± fibrinogen outperformed CA 125 alone as a high‐specificity biomarker in postmenopausal women and could aid in the preoperative triaging of pelvic masses. No biomarker(s) outperformed CA 125 in premenopausal women.

A pilot study evaluating the feasibility of enriching and detecting circulating tumour cells from peripheral and ovarian veins in rare epithelial ovarian carcinomas.

Studies on circulating tumour cells (CTCs) in rare epithelial ovarian carcinomas (EOC) are limited, despite their potential as a minimally invasive biomarker for monitoring cancer progression and predicting outcomes. This pilot study aimed to assess the feasibility of enriching and detecting CTCs from both peripheral and ovarian vein blood samples in rare EOC subtypes. Blood samples were collected from the peripheral and ovarian veins of 20 patients with rare EOC. Among the 20 patients, 12 had early-stage disease (I-II), while 8 had advanced disease (III-IV). CTCs were enriched using the Parsortix® system and immunophenotyped via immunofluorescence targeting epithelial markers (EpCAM/pan-cytokeratin) and Hoechst for positive selection, and CD45 for negative selection. CTC status (positive versus negative) was correlated with clinicopathological data. CTCs were successfully detected in 45 % (1-19 CTCs) of baseline peripheral samples and 55 % (1-4776 CTCs) of ovarian vein samples. CTC doublets and clusters were detected in ovarian vein samples (3/11), but not in peripheral samples (0/20). A higher proportion of deaths were observed in CTC+ patients compared to CTC- patients (p = 0.0088). Here we demonstrate the feasibility of enriching and detecting CTCs from both peripheral and ovarian vein blood in patients with rare EOC. The higher CTC yield in ovarian vein blood suggests that tumour-draining blood may play a role in improving CTC detection. This pilot study paves the way for larger studies to investigate the prognostic utility of CTCs and refine their clinical value in these rare understudied EOC.

Rare gynaecological cancers in Malta – An analysis of incidence between 2010 and 2021

Whilst about 18 % of all cancers in females are gynaecological cancers, more than 50 % of these can be classified as rare tumours (defined as an annual incidence of <6 per 100,000). Such cancers represent an important challenge for small countries like Malta where the small caseload may limit the expertise of clinicians in the diagnosis and treatment of such cancers. The study uses data from the Maltese population-based cancer registry to examine trends in incidence rate of the rare gynaecological cancers for the 12-year period between 2010 and 2021. It employs the RARECAREnet list to identify the rare gynaecological cancers by major rare gynaecological cancer categories and histological types and analyses the number of cases and incidence rates in Malta to monitor trends and provide an insight of the burden of such cancers. A total of 709 new cases of rare gynaecological cancers were discovered during the 12-year period. Globally, these rare gynae cancers, constituted 42.6 % of all the gynae cancers that occurred during this period. Most of these rare cancers were ovarian (399 cases, 56.3 %), followed by rare cancers of the vulva and vagina (122 cases, 17.21 %), rare cancers of the corpus uteri (93 cases, 13.12 %) and rare cancers of the cervix uteri (73 cases, 10.3 %). Other rare gynaecological cancers (10 cases, 1.41 %) and cancers of the placenta (2 cases, 0.04 %) were much rarer. The outcomes in terms of 5-year survival was worse for the rare cancers compared with the commoner types of gynae cancers with an overall 5-year survival of 45.10 % and 45.48 % for rare gynae cancers for the 2010-2014 and 2015-2019 cohorts respectively and an overall 5-year survival of 69.94 % and 73.44 % for the common gynae cancers for the 2010-2014 and 2015-2019 cohorts respectively. The study shows that globally rare gynaecological cancers in a small state like Malta are in fact not so rare - with a total of 709 rare gynaecological cancers in 12 years for Malta. These cases are however few when considering that they are divided into over 30 different histopathological groups. Numbers are also small when it comes to accumulating statistical power for analysis. The caseload for the individual sub-categories is small and will often be shared amongst the different individual gynaecologists and/or their clinical team. Thus, it might be difficult for these specialists to gather enough technical expertise that is crucial for early diagnosis and the treatment of these rare cancers. This study provides a rationale for international collaboration where there is scope for joint research and sharing of expertise. Establishment of common databases for the various types of rare gynaecological tumours will provide statistical power, enabling analysis of outcomes for these rare cancers and establishment of guidelines.

Unravelling the biological and clinical challenges of circulating tumour cells in epithelial ovarian carcinoma

Epithelial ovarian carcinoma (EOC) is the eighth most common cancer in women and the leading cause of gynaecological cancer death, predominantly due to the absence of effective screening tools, advanced stage at diagnosis, and high rates of recurrence. Circulating tumour cells (CTCs), a rare subset of tumour cells that disseminate from a tumour and migrate into the circulation, play a pivotal role in the metastatic cascade, and therefore hold promise as biomarkers for disease monitoring and prognostication. Exploring CTCs from liquid biopsies is an appealing approach for research and clinical practice, given it is minimally invasive, facilitates serial sampling and enables the capture of the entire spectrum of cancer cells circulating in the blood. The prognostic utility of CTC enumeration has been FDA-approved for clinical use in metastatic breast, prostate, and colorectal cancers. However, the unique biology of EOC, discussed herein, compounds the detection and characterisation complexities already inherent in CTC research, consequently hindering progress towards clinical applications. The aim of this review is to provide an overview of both the biological and clinical challenges encountered in harnessing the power of CTCs in EOC.