PARPi, who benefits?

Homologous Recombination Deficiency Assays in Epithelial Ovarian Cancer: Current Status and Future Direction

https://tinyurl.com/2pbwkmxm

         Sometimes progress in the care of patients with ovarian cancer seems painfully slow. Then new understanding begins to show a way forward. One such innovation was the appreciation that much cancer starts due to a failure of repair in the DNA that makes up the cell nucleus. Cellular DNA is under constant attack from within and without. If DNA is not repaired cells will usually die but sometimes the cell line continues as a cancer.

          Faulty DNA repair, known as Homologous Recombination Deficiency (HRD) is seen with BRCA1/2 mutation and sometimes with other acquired mutations, being present in about 50% of all ovarian cancer. As a consequence another enzyme; Polyadenosine Ribonucleotide Polymerase (PARP) becomes more important in DNA repair. Repair by PARP is less exact and sometimes may  prolong cancer, a concept known as synthetic lethality.

         This understanding of the biology of ovarian cancer has led to new treatment with drugs that inhibit PARP (PARPi). Up to 40% of patients with BRCA mutation do not respond to PARPi. So, better testing for HRD is needed. Currently the HRD status of individuals is inferred from the mutation. Unfortunately this does not predict PARPi response. An HRD test hopefully will better show who will benefit from PARPi

Embryo Selection

Pre-implantation genetic testing for BRCA gene mutation carriers: a cost effectiveness analysis

https://tinyurl.com/evhm49d2

 

         For some communities ovarian cancer is a real and constant threat, none more so than for the Ashkenazi in Israel. Ovarian cancer is related to an inherited condition in about 25% of cases. The Ashkenazi have a high incidence of BRCA1/2 mutation, which increases the likelihood of developing ovarian cancer compared to the general population.

         One strategy for avoiding ovarian cancer and the common fatal consequence is by prevention through pre-implantation genetic screening and selection of embryos, as part of In Vitro Fertilisation (IVF). This study seeks to determine the cost-effectiveness of doing this for parents who carry the BRCA1/2 gene.

         Cost-effectiveness is routinely determined as a measure known as the Quality Affected Year (QALY), meaning the value of a year without disease. Most advanced economies put the acceptable cost at a QALY of around $US 40,000. Results from the study suggest a QALY cost for the IVF embryo screening strategy at $US 44,000. This may be acceptable for small high-risk communities such as the Ashkenazi.

 

Neo facts

Association Between Overall Survival and the Tendency for Cancer Programs to Administer Neoadjuvant Chemotherapy for Patients With Advanced Ovarian Cancer

https://tinyurl.com/6cmpxrby

         Any treatment protocol needs constant reappraisal. Neoadjuvant chemotherapy (Neo) is the use of chemo for ovarian cancer patients before surgery, at the time of initial presentation. First used for patients who were either too frail or had too big a tumour for surgery, Neo has become more frequent.

         Previous studies in 2010 showed no disadvantage in survival. Neo is often preferred because the subsequent surgery is more straightforward with fewer complications. Also logistically it make scheduling surgery simpler. Although generally there has been an increase in the use of Neo, some treatment centres have not done so.

         This retrospective study looks at 20,000+ patients from 300+  centres during the period 2004-2015. No difference was seen in overall survival between centres which increased Neo compared to those that did not. The mortality at one year was less in centres where Neo use increased.

 

Choice of surgeon

Impact of Surgeon Type and Rurality on Treatment and Survival of Ovarian Cancer Patients

https://tinyurl.com/7y2arz8j

 

         Choose your surgeon carefully. Any woman unlucky enough to have ovarian cancer requires surgical removal. This is best done in a centre of excellence, preferably by a surgical oncologist. Unfortunately this is not always possible.

         675 women with advanced ovarian cancer from Iowa were included in this study. Of these women, those living in non-urban locations were less likely to have their surgery by a surgical oncologist and also less likely to have complete surgical clearance and to follow the usual chemotherapy regime.

         Not surprisingly women who did receive care in a centre of excellence had better outcomes. Survival for these women was increased, being 40% more likely to survive 3 years, compared to women from non-urban environment that did not access the best care. Although not mandatory, surgical oncology medical care does confer an advantage.

Take the tubes

Ovarian Cancer Incidence and Death in Average-Risk Women Undergoing Bilateral Salpingo-Oophorectomy at Benign Hysterectomy

https://tinyurl.com/y3t5jkj8         

         “Prevention is better than a cure”. This certainly seems to be the case for ovarian cancer, which despite progress in therapy remains a highly lethal condition. One suggestion for prevention of ovarian cancer is that any woman who has a hysterectomy should have removal of the fallopian tubes and ovaries at the same time.

         It is thought that most ovarian cancer starts in the tubes.  One in five women will have a hysterectomy during their lifetime. Previously there has been little hard evidence about the benefit from tube and ovary removal. 

         This retrospective review of almost 200,000 women who had a hysterectomy, in Ontario, during the period 1996-2010, looked at the incidence of and death from ovarian cancer.  25% of those women had tube and ovary removal at the time of hysterectomy. Results from the review confirmed that the women who had the tubes and ovaries removed had about 70% reduction in the risk of developing and dying from ovarian cancer, with even better outcomes when done before the age of 50.