Ascites near death

Uptake of lipids from ascites drives NK cell metabolic dysfunction in ovarian cancer

https://tinyurl.com/yc4ssp65

Free fluid in the abdominal cavity is called ascites. When ascites occurs in patients with ovarian cancer it has always been recognised as an ominous sign of near death. Some understanding of why is now becoming clear. Previously it was thought that the loss of protein and general debility that occurs with ascites was responsible. This research suggests that the immune response to cancer is suppressed by fat content in the fluid.

The immune response to ovarian cancer is generated by a cellular mechanism via lymphocytes. There are two main types; T cells which are specific to the cancer cell antigen and Natural Killer (NK) cells which are non-specific and have a protective function by reducing metastasis of cancer and causing cell death.

In the presence of ascites, the immune response is suppressed. Using an experimental model with NK cells in ascitic fluid, the protection was impaired. This damage to lymphocyte function was not seen when the NK cells were placed in peritoneal fluid obtained from subjects who did not have cancer.

Further analysis of the components of ascites showed the active component causing impairment is the presence of phospho-lipids. These fats surround the NK cells, attaching to the cell membrane and preventing the normal cytotoxic action.

Sometimes size doesn’t matter

Ovarian cancer survival by residual disease following cytoreductive surgery: a nationwide study in Norway

https://tinyurl.com/59v8kavu

It is well known that one of the most important predictors of cure with ovarian cancer is the completeness of the initial surgery. This retrospective survey of 2608 women with ovarian cancer from the Norwegian Cancer registry looked at survival after surgery compared to the amount of residual tumour left behind.

Unsurprisingly those women who had apparently complete removal with no residual tumour did best. When only a small fragment of tumour remained (1-4 mm diameter) survival decreased two-fold. 

For those women with larger residual tumour the risk of death was three times greater. This level of risk was constant for all tumours larger than 4mm, with some measuring 20mm or more. Whether or not women with no residual cancer had neoadjuvant therapy did not change the chance of survival.

Risk management

Large-scale analysis to identify risk factors for ovarian cancer

https://tinyurl.com/2sfbv5nw

The UK Biobank recruited 500,000 participants during the period 2006-2010. A questionnaire and blood and urine tests together with physical exam provide base-line information looking for biomarkers of subsequent disease.

During the follow up 1441 cases of ovarian cancer were detected. Data from the initialsurvey was collected and compared retrospectively with the other 220,201 women who did not have ovarian cancer. There is a huge amount of data with 2920 items for everyone involved.  Statistical adjustment attempted to separate cause from effect.

Results from the survey supported the known association with obesity and the protective effect of hormonal contraception and childbirth. Some blood factors suggest causal effects. The authors conclude avoiding obesity and limiting the number of menstrual cycles should be promoted. To this extent, the risk of ovarian cancer may be reduced by lifestyle modification.

Adverse visual effects with Elahere

Ocular Events with Mirvetuximab Show No Impact on QoL in Ovarian Cancer

https://tinyurl.com/4zbpp67k

One of the more exciting developments in ovarian cancer treatment has been the FDA approval of an antibody drug combination called Elahere in the treatment of platinum resistant ovarian cancer. This group of patients are especially difficult to treat with a poor disease-free survival of around 4 months. Results from the MIRASOL trial suggest an increase to 6 months.

Elahere is a targeted treatment for women with ovarian cancer which demonstrate Folate Receptor 𝛂 expression (about 80%). One of the important adverse effects is loss of visual acuity. This is seen in 50% of patients, it develops within 4 to 5 weeks of commencing treatment. The cause is inflammatory change due to local action of the drug and subsequent chronic formation of microcysts in the cornea, usually this adverse effect is reversible.

This prospective study of the Quality of Life for women participants in the MIRASOL trial showed no deterioration for those women who experienced eye complications. The suggestion is that the use of Elahere extends life and does not decrease the enjoyment, meaning the benefit is greater than the risk.

Not for everyone

Risk-Reduction Surgery Benefit in Non-BRCA Ovarian Cancer

https://tinyurl.com/2mnd5c9y

Risk reduction surgery has been promoted as a means of avoiding ovarian cancer. Most studies have concentrated on removal of fallopian tubes for women who are at high risk, especially those who carry the BRCA or Lynch mutation. Some centres have extended this for all women and suggested that additional surgery, to remove the fallopian tubes, be added to other abdominal surgical procedures. Any extra intervention will increase operative risk.

This prospective study of 142 non-BRCA women at low risk, looks at the surgical specimen, and compares the evidence, of pre-cancer change with a similar control group of 388 women, who had the same surgery for risk reduction, in the presence of a hazardous mutation.

Results from the study show similar rates of normal appearance at about 95%. No evidence of pre-cancer change was found in non BRCA women whereas 3% of specimen removed from BRCA +ve women did show abnormality which might lead to subsequent ovarian cancer.

The author states that the number of cases  suggest that the procedure is commonly being performed on low-risk women, and that though the benefit is yet to be established the potential for harm is great.

Putting cancer to sleep

Scientists Discover How To Reactivate Cancer’s Dormant “Kill Switch”

https://tinyurl.com/yeytv4es

Ovarian cancer presents late. The peak incidence is at age 75 which is about 10 years later than most cancers.  Theories about why this is so suggested that there is a period of dormancy, and that the cancer becomes overt because of some unexplained change.

This research suggests that many aggressive and hard to treat cancers including ovarian cancer hijack normal protective functions that would otherwise limit cancer invasion. This protective mechanism limits cellular metabolism by blocking DNA and RNA transcription,with consequent reduction in enzyme and protein activity which would otherwise promote cancer growth.

When this process is hijacked, the protection is lost. This research suggests that the protective mechanism can be restored using synthetic RNA fragments to alter cellular metabolism.

This discovery has the potential to provide a new target for precision therapy by restoring cancer dormancy.

We’ve been looking in the wrong place

Aged and BRCA mutated stromal cells drive epithelial cell transformation

https://tinyurl.com/mxs7nz32

Ovarian cancer is different, the commonest type called serous cancer presents late with metastasis. It has been known for some time that the most likely site of origin for this cancer is the fallopian tube as a precursor abnormality of the epithelium occurs known as a serous tubal intraepithelial cancer (STIC) lesion.

These lesions have a high risk of conversion to invasive cancer with subsequent spread to ovary, meaning that ovarian cancer is always advanced at the time of presentation.

It seemed logical that STIC lesions would develop in the epithelium as a result of conversion from adaptable stem cells. This research from the US suggests that the initial change occurs in cells from the sub-epithelial layer known as the stroma. The responsible cells are called mesenchymal stem cells (MSC). Usually, these cells assist in repair of tubal tissues. Women with known increased risk of ovarian cancer such as those with the BRCA mutation have increased numbers of MSC, which are present before ovarian cancer develops.

Further understanding of the role of the fallopian tube in the cause of ovarian cancer supports the role of preventative surgery for high-risk women.