Development of a dual energy CT based model to assess response to treatment in patients with high grade serous ovarian cancer: a pilot cohort study

Availability of data and materials: Datasets and material analysed are available on reasonable request from the corresponding author.Supplementary Information: The online version contains supplementary material available at https://doi. org/10.1186/s40644-023-00579-2.Copyright © The Author(s) 2023. Background: In patients with cancer, the current gold standard for assessing response to treatment involves measuring cancer lesions on computed tomography (CT) imaging. The percentage change in size of specific lesions determines whether patients have had a complete/partial response or progressive disease, according to RECIST criteria. Dual Energy CT (DECT) permits additional measurements of iodine concentration, a surrogate marker of vascularity. Here we explore the role of changes in iodine concentration within cancer tissue on CT scans to assess its suitability for determining treatment response in patients with high grade serous ovarian cancer (HGSOC). Methods: Suitable RECIST measurable lesions were identified from the CT images of HGSOC patients, taken at 2 different time points (pre and post treatment). Changes in size and iodine concentration were measured for each lesion. PR/SD were classified as responders, PD was classified as non-responder. Radiological responses were correlated with clinical and CA125 outcomes. Results: 62 patients had appropriate imaging for assessment. 22 were excluded as they only had one DECT scan. 32/40 patients assessed (113 lesions) had received treatment for relapsed HGSOC. RECIST and GCIG (Gynaecologic Cancer Inter Group) CA125 criteria / clinical assessment of response for patients was correlated with changes in iodine concentration, before and after treatment. The prediction of median progression free survival was significantly better associated with changes in iodine concentration (p = 0.0001) and GCIG Ca125 / clinical assessment (p = 0.0028) in comparison to RECIST criteria (p = 0.43). Conclusion: Changes in iodine concentration from dual energy CT imaging may be more suitable than RECIST in assessing response to treatment in patients with HGSOC. Trial Registration: CICATRIx IRAS number 198179, 14 Dec 2015, https://www.myresearchproject.org.uk/.John Bush Academic Fund, Mount Vernon Cancer Centre and the Cancer Treatment Research Trust

Preclinical Studies on the Effect of Rucaparib in Ovarian Cancer: Impact of Brca2 Status

Copyright: © 2021 by the authors. Background: Approximately 50% of ovarian cancer patients harbour homologous recombination repair deficiencies. These deficiencies have been successfully targeted using poly (ADP-ribose) polymerase inhibitors (PARPi) particularly for patients harbouring BRCA1/2 mutations. The aim of this study is to assess the effects of the PARPi rucaparib in vitro using cell lines with BRCA2 mutations in comparison to those with BRCA2 wild type. Methods: Cell proliferation assays, RT-qPCR, immunofluorescence, annexin V/PI assays were used to assess the effects of rucaparib in vitro. Results: The BRCA2 mutant ovarian cancer cell line PEO1 exhibited higher PARP1 activity when treated with H2O2 compared to wild type cell lines. The migratory and proliferative capacity of PEO1 cells was compromised following treatment with rucaparib 10 µM compared to BRCA2 wild-type cell lines via a mechanism involving the mTOR pathway. Rucaparib treatment significantly increased DNA damage primarily in PEO1 cells and SKOV3 cells compared with wild type. Conclusions: Appropriate identification of robust predictive biomarkers for homologous recombination deficiency using ‘liquid’ biopsies would facilitate the identification of patients suitable for PARPi therapy. Preliminary efforts to undertake such testing are described here. This study also demonstrates the mechanisms of action of rucaparib (PARPi) which may involve elements of the mTOR pathway.Cancer Treatment & Research Trust (CTRT Charity Number 29909)

Identification of RAD51 foci in cancer-associated circulating cells of patients with high-grade serous ovarian cancer: Association with treatment outcomes

Data availability statement: Data are available upon reasonable request. Datasets will be made available on reasonable request from the corresponding author.Supplementary Data are available online at https://ijgc.bmj.com/content/33/9/1427#supplementary-materials .Objective Fifty percent of patients with high-grade serous ovarian cancer harbor defects in the homologous recombination repair pathway. RAD51 foci form where DNA is damaged, indicating its involvement in repairing double-stranded breaks. High levels of RAD51 in ovarian cancer tissue have been associated with a poorer prognosis. Objective To demonstrate RAD51 foci in circulating cancer-associated cells of patients with ovarian cancer and their association with clinical outcomes. Methods One hundred and twenty-four patients with high-grade serous ovarian cancer had blood samples taken at strategic points during treatment and follow-up. Cells were stained using WT1 and RAD51 antibodies with immunofluorescence and reviewed under Leica camera microscopy; RAD51 foci were counted. Correlations were made between numbers of RAD51 foci and treatment response, BRCA status, and progression-free survival. Results RAD51 foci were identified in all patients (n=42) with wild-type BRCA. BRCA mutant/homologous recombination deficiency-positive patients (n=8) had significantly lower numbers of RAD51 foci (p=0.009). Responders to treatment (n=32) had a reduction in circulating cells (p=0.02) and RAD51 foci (p=0.0007). Numbers of RAD51 foci were significantly higher in the platinum-resistant population throughout treatment: At the start of treatment, in 56 platinum-sensitive patients there was a mean of 3.6 RAD51 foci versus 6.2 in 15 platinum-resistant patients (p=0.02). Patients with a high number of RAD51 foci had worse median progression-free survival: in 39 patients with a mean of 3 RAD51 foci whose progression-free survival was 13 months (p=0.04). Conclusions Levels of RAD51 foci in circulating cancer-associated cells of patients with high-grade serous ovarian cancer are associated with clinical outcomes and may be a more pragmatic method of determining a homologous repair-deficient population.John Bush Academic Fund, Mount Vernon Cancer Centre, and the Cancer Treatment Research Trust

Description of a Retrospective Cohort of Epithelial Ovarian Cancer Patients with Brain Metastases: Evaluation of the Role of PARP Inhibitors in this Setting

Data Availability Statement: Data will be available upon reasonable request.Copyright © 2023 by the authors. Background: The incidence of brain metastases (BM) in patients with epithelial ovarian cancer (EOC) is low: 0.3–11%. The onset of BM has been regarded as a late event with limited treatment options and poor prognosis. This retrospective case series aims to explore the current management strategies with particular emphasis on the use of PARP inhibitors and outcomes, as well as identification of other prognostic indicators. Methods: A total of 39 ovarian cancer patients with brain metastases were identified from eight cancer centres in the UK. Clinical characteristics, details of management, and survival data were collected. Results: A total of 14/39 had BM as their first site of relapse. The majority (29 patients) received systemic treatments in addition to local radiotherapy (RT)/surgery. Nineteen patients had BRCA mutations (one somatic), one had a RAD51C mutation, and eighteen were BRCA wild type; one was unknown. A total of 14/39 patients received maintenance PARP inhibitors. As is well known, patients who received PARPi had consistently better outcomes. This was no different for those who received PARPi as part of the management of their BM. Platinum sensitivity and receiving more than one modality of therapy (e.g., radiation +/− chemotherapy and PARPi) for BM were also good prognostic indicators. Median PFS/OS for those treated with chemotherapy and either RT or surgery, then PARP inhibitor maintenance, have not been reached after a median of 33 months follow up. Conclusions: As with abdominal relapse, maintenance treatment with PARP inhibitors also has a valuable role in managing BMs in EOC patients.This research received no extra funding

Flora of Iraq. Volume 5, part 2. Lythraceae to Campanulaceae.

Families treaed in volume 5, part 2. Lythraceae / S. A. Ghazanfar. Onagraceae / P.H. Raven. Haloragaceae / C.C. Townsend. Gentianaceae / P. Taylor †. Menyanthaceae / P. Taylor. Primulaceae / P. Taylor. Plumbaginaceae / S. Mobayen. Plantaginaceae / Z. Chalabi-Ka’bi †. Crassulaceae / M. Bywater. Saxifragaceae / C.C. Townsend. Vahliaceae / C.C. Townsend. Parnassiaceae / J.R. Edmondson. Umbelliferae / C.C. Townsend. Valerianaceae / E. Hadač. Dipsacaceae / I.K. Ferguson. Campanulaceae / H.A. Alizzi †

A review of valve surgery for rheumatic heart disease in Australia

Background: Globally, rheumatic heart disease (RHD) remains an important cause of heart disease. In Australia it particularly affects older non-Indigenous Australians and Aboriginal Australians and/or Torres Strait Islander peoples. Factors associated with the choice of treatment for advanced RHD remain variable and poorly understood. Methods: The Australian and New Zealand Society of Cardiac and Thoracic Surgeons Cardiac Surgery Database was analysed. Demographics, co-morbidities, pre-operative status and valve(s) affected were collated and associations with management assessed. Results: Surgical management of 1384 RHD and 15843 non-RHD valve procedures was analysed. RHD patients were younger, more likely to be female and Indigenous Australian, to have atrial fibrillation (AF) and previous percutaneous balloon valvuloplasty (PBV). Surgery was performed on one valve in 64.5%, two valves in 30.0% and three valves in 5.5%. Factors associated with receipt of mechanical valves in RHD were AF (OR 2.69) and previous PBV (OR 1.98) and valve surgery (OR 3.12). Predictors of valve repair included being Indigenous (OR 3.84) and having fewer valves requiring surgery (OR 0.10). Overall there was a significant increase in the use of mitral bioprosthetic valves over time. Conclusions: RHD valve surgery is more common in young, female and Indigenous patients. The use of bioprosthetic valves in RHD is increasing. Given many patients are female and younger, the choice of valve surgery and need for anticoagulation has implications for future management of RHD and related morbidity, pregnancy and lifestyle plans

Proceedings Of The 23Rd Paediatric Rheumatology European Society Congress: Part Two

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