Sitting is not good

Sedentary behaviour in relation to ovarian cancer risk: a systematic review and meta-analysis

https://tinyurl.com/2eb2g28v

 

         Inactivity is a health hazard. As a potential risk factor for ovarian cancer, which can be modified, there is little understanding of the increased risk due to a sedentary lifestyle.

         Databases at PubMed and Web of Science were accessed and seven studies had suitable data for meta-analysis, with information for just over 2000 women with ovarian cancer.

         Retrospective analysis of the data shows an increase in the relative risk of ovarian cancer to 1.29 due to prolonged sitting. This relates to an increase of approximately 3 cases/100,000 women in Australia, each year.

         Sedentary behaviour is defined as spending more than half of waking hours sitting or reclining. Interestingly this does not necessarily imply a lack of exercise, as the usual recommendations of physical activity can be completed and still have a sedentary lifestyle.

Futile screening

Motivators of Inappropriate Ovarian Cancer Screening: A Survey of Women and Their Clinicians

https://tinyurl.com/ipft7e6a

 

         Multiple clinical trials have shown no value in screening for ovarian cancer (OC). This study looked at the prevalence of OC screening for Australian women. The Cancer Australia position statement of 2019 does not support OC screening, even for those deemed at high risk. Despite this, women continue to be sent for OC screening, with more than half of physicians doing so.

         For the study 832 women were recruited from multiple-case breast cancer families, only 4% were BRCA1/2 positive. There was misplaced enthusiasm for OC screening, with about 75% of the women thinking that screening was likely to detect OC.

         The results showed that the higher a woman’s enthusiasm the more likely it was that OC screening would be performed. A majority of women who had OC screening previously said they would request more despite contrary advice from their physician.

         Survey of clinicians showed that most agreed with the statement, “There is a chance that these tests will detect cancer early…” Most gynaecologists agreed that screening is ineffective but still, almost half ordered the tests. When questioned the reason given for the futile testing was usually patient pressure. The authors state that changing women’s and physician’s belief will be challenging.

 

Centres of excellence

 

Clinical auditing as an instrument to improve care for patients with ovarian cancer: The Dutch Gynecological Oncology Audit (DGOA)

https://tinyurl.com/kzzntc7r

 

         Unless quality is measured there can be no improvement. Without information the management of ovarian cancer may be a best guess.

         The Dutch Institute of Clinical Auditing has a responsibility to determine quality indicators and provide feedback of verified information. In 2010 ovarian cancer care in Holland was rationalised, with surgical staging and primary treatment performed only at centres of excellence as defined by a minimum number of cytoreductive surgery procedures; being more than 20 annually.

         As a result Hospitals performing ovarian cancer surgery decreased from 90 to 23. There has been a significant delay in the onset of treatment and chemo but the number of patients who have complete primary resection of the cancer has increased.

         During the 5-year period 2013-18, 93% of all cases were included in the Audit. This is the first report and feedback will seek to address the issues identified. No significant change in staging or mortality was recorded.

More about PARPi

 

Alternate therapeutic pathways for PARP inhibitors and potential mechanisms of resistance

tinyurl.com/ozbdt3cv

         PARP inhibitors (PARPi) have the potential to revolutionise the treatment of ovarian cancers. These drugs are the first clinical application of a concept called synthetic lethality; this is a combination of 2 or more gene expression alterations leading to cell death.

         PARPi act on two separate pathways; firstly they inhibit DNA repair via the PARP1 enzyme and second they protect the cell from homologous recombination deficiency (HRD), which causes DNA instability.

         Many clinical trials have demonstrated the efficacy of 4 different PARPi drugs either alone or in combination. Initially the trials showed survival advantages for patients with germ-line or somatic mutations, recent evidence shows the advantages are more widespread with benefits to patients outside these groups.

         Unfortunately drug resistance to PARPi is becoming commonplace. It seems that the most likely cause is mutation to normal HR status. The high cost of these drugs will be a barrier to approval for routine first-line therapy.