Understanding HRD

Limitations of homologous recombination status testing and poly (ADP-ribose) polymerase inhibitor treatment in the current management of ovarian cancer

https://tinyurl.com/ca67pusw

Recognition of the importance of defective DNA repair (DDR) as the cause for most ovarian cancer has radically changed the prospects for survival. Initially demonstrated as the basis for hereditary breast and ovarian cancer through the BRCA genetic mutation, DDR is the target for personalised therapy with enzyme inhibition using PARPi.

It is now realised that DDR is much more common and the basic defect is described as homologous recombination deficiency (HRD), which is not confined to the BRCA mutation. It is possible to test directly for HRD and this has increased the number of women who have been assigned personalised therapy.

However, there are problems; not all HRD women respond to PARPi, many develop resistance to the drug and it is unclear whether overall survival is improved. 

Partly this is due to the inaccuracies of HRD testing, the current test produces a score for homologous proficiency (HRP). It seems that HRP is complex with partial genetic penetration. There is more to learn about HRD.

What reduces OC risk?

Prospective analysis of circulating biomarkers and ovarian cancer risk in the UK Biobank

https://tinyurl.com/4p825ens

As an interesting variation of the use of biomarkers in the prediction of ovarian cancer, this article looks at the serum biomarkers which make ovarian cancer less likely.

The data for this analysis is taken from the UK Biobank. This is a remarkable source of information. Established in 2013, there are 500,000 participants in the UK, who underwent genetic and phenotypic testing, looking for strategies to reduce cancer and other diseases.

For this study, the presence of 20 biomarkers was compared to the risk of later development of ovarian cancer for more than 230,000 women. From the analysis it is shown that high levels of three of these markers (IGF-1, HbA1-c, and alanine aminotransferase) are protective in that the incidence of ovarian cancer is reduced for these women.

Once again, the value of the Biobank is demonstrated. The foresight and preparedness to allocate resources to this valuable project is commendable and will show valuable insight into disease as the years go by.

Basic, better, best

Accuracy of ultrasound, magnetic resonance imaging and

intraoperative frozen section in the diagnosis of ovarian

tumors: data from a London tertiary centre

https://tinyurl.com/4f74v2sa

Sometimes it can be difficult to differentiate between benign and malignant masses found in the ovary. For best management of ovarian tumors, it is crucial to identify cancer before surgery so that the correct technique can be used.

This study looked at 156 ovarian masses which were surgically removed. The final diagnosis, obtained by pathological examination was compared to the pre-operative diagnosis obtained by ultrasound MRI or intraoperative frozen section.

Results from the study showed that frozen section was the best at determining the presence of borderline and malignant tumors. Ultrasound and MRI have high specificity at diagnosing benign tumors but both these modalities have low predictive values when diagnosing borderline or malignant pathology.

The inference from this study is that pre-operative diagnosis is unreliable and that frozen section tissue analysis is required for best management.

Predicting blood transfusion needs

A pre-operative scoring model to estimate the risk of blood transfusion over an ovarian cancer debulking surgery (BLOODS score)

https://tinyurl.com/y37f76dh

Surgical procedures required for the initial treatment of ovarian cancer are complex and lengthy, frequently involving blood loss. Meaning transfusion of donated blood is necessary. Previous studies have shown that blood transfusion occurs in 40 –70% of initial ovarian cancer debulking surgical procedures.

Blood transfusion is not without hazard. Those patients who require blood have increased risk of infection, altered immunity, and higher mortality, and morbidity. This article tests a scoring system which can assist by identifying patients likely to require transfusion prior to surgery. With this knowledge, it may be possible to reduce the need for transfusion by the use of blood-saving techniques.

The score is calculated using serum levels of CA125, albumen and hemoglobin, with clinical assessment of tumour size and spread. Retrospective assessment showed that the score predicts transfusion in three quarters of women who will require it as part of the operative clearance of ovarian cancer.