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.

Alarming weight loss

Adipose tissue loss during neoadjuvant chemotherapy: a key prognostic factor in advanced epithelial ovarian cancer

https://tinyurl.com/55ykwrm4

Early understanding of probable poor survival may be useful in planning the management of ovarian cancer. This study looks at changes in body composition that occur after chemo prior to surgery (neoadjuvant chemo).

This prospective study looked at 53 patients with advanced ovarian cancer who received three cycles of chemo before surgery. Using CT scans before and after chemo the muscle and fat volumes were measured. All patients showed loss of muscle and fat. This was greater for those women who were obese before treatment.

Loss of muscle volume did not alter survival. Loss of fat however was a marker of poor survival especially when the fat loss was visceral within the abdomen rather than subcutaneous. This was even more marked when the weight loss was rapid. The authors suggest that nutritional support to avoid weight loss may be beneficial for ovarian cancer patients undergoing neoadjuvant chemo.

A catchy title

Leader cells promote immunosuppression to drive ovarian cancer progression in vivo

https://tinyurl.com/myym6w6v

In medical research having a catchy name for any recent findings is a good tool to promote visibility and attract funding. A recent article from the Hudson Institute demonstrates this.

Ovarian cancer presents late with metastasis having already occurred for 75% of cases at the time of diagnosis. This study looks at a feature of aggressive ovarian cancer, whereby cells at the margins of the cancer known as “Leader cells”, develop invasive outgrowths formed of keratin-14, a protein similar to skin and hair proteins.

The presence of these leader cells promotes invasion of surrounding tissues, the exact nature of why this occurs is unclear but studies in mice ovarian cancer cells show immune suppression. As a result, the normal protective immune reaction to invasion, mediated by T cell lymphocytes is inactivated.

Caution about the significance of these results is expressed by the authors who suggest this study is limited and further investigation is warranted. Despite this caution the term “Leader cells” seems to have caught the attention of the popular press.

Robots are the future

Feasibility of Robotic Surgical Approach in Peritoneal Carcinomatosis

https://tinyurl.com/4h24fnfr

Complete clearance of ovarian cancer at the time of the first surgery remains the most important factor in a cure. Sometimes with advanced cancer the distant spread to the lining of the abdomen, (peritoneal carcinomatosis), makes clearance difficult if not impossible.

New surgical techniques using robotic assistance are becoming commonplace for some surgical procedures, notably prostate cancer. Robotic surgery is safer with less morbidity and mortality, there is better visualisation of small structures and is more likely to achieve complete clearance.

This retrospective study of 16 patients, 9 of whom had ovarian surgery, showed that robotic surgery is feasible and safe. Because of the cost and due to limited resources, randomised prospective clinical trials, looking for better outcomes will be required before this technique becomes more readily available.

Indicators of survival

The impact of preoperative immuno-nutritional status on prognosis in ovarian cancer: a multi-centre real-world study

https://tinyurl.com/yeyspm3c

Two relatively simple indices of health may be obtained prior to surgery for ovarian cancer. These are the Prognostic nutritional Index (PNI) which is measured using the serum albumen and the Systemic Immune-inflammation Index (SII) calculated as a ratio of platelets to white cells in circulating blood.

This prospective survey looked at survival after surgery for women with ovarian cancer and the correlation to pre-operative health.

Results obtained from the study showed that those women with good nutritional health (high PNI) had better progress free survival and overall survival. Women whose immune status was good before surgery (high SII) had good progress free survival but slightly worse overall survival.

For those women whose nutritional and immune status were not good there was more platinum resistance and poor outcomes. Use of these markers gives important prognostic information and may alter management.

Vigil, partial FDA approval

The US FDA grants RMAT Designation to Gradalis’ Vigil for Advanced Ovarian Cancer

https://tinyurl.com/46bdjj7v

For women with ovarian cancer who don’t respond to maintenance therapy using PARP inhibitors there is new hope. The FDA has enabled fast access through the Regenerative Medicine Advanced Therapy, (RMAT) designation to a targeted treatment called Vigil, which is intended for use in patients who do not have defective DNA repair.

RMAT designation is used to speed the approval process of drugs which have shown encouraging impact on otherwise untreatable illness. Vigil is a new form of immunotherapy whereby cells from the patient’s own cancer are infected with a bacterial DNA fragment (a plasmid), and then injected back in to the donor, to promote an immune reaction similar to a vaccine.

Although this drug is only in a phase II clinical trial, early responses have shown promising improvements in progress free and overall survival.

The clinical trial titled VITAL is not recruiting currently and there are no Australian candidates. Following the FDA approval, phase III trials are expected soon.

More about survival

Role of pre-diagnostic reproductive factors on long-term (10 years or greater) survival of epithelial ovarian cancer: The Extreme study

https://tinyurl.com/3hft7xmy

It is well known that the risk of ovarian cancer is reduced by reproductive factors such as, previous pregnancy, breast feeding, and oral contraception.

This retrospective study, using information from the Danish health system, looks at survival after ovarian cancer for almost 12,000 women and sought to relate the chance of survival to previous gynaecological history.

Results from the study suggest that a previous history of childbirth, endometriosis, and infertility are protective with between 8% and 17% better survival respectively.

A history of previous hysterectomy or salpingectomy showed no survival benefit. The authors make no suggestion as to why this is so but suggest further research may be indicated.

Hair Loss with Chemo

Chemotherapy-Induced Alopecia in Ovarian Cancer: Incidence, Mechanisms, and Impact Across Treatment Regimens

https://tinyurl.com/5n8wuaje

Hair loss caused by chemotherapy for ovarian cancer is common and has a major effect on quality of life and loss of self-respect. Standard treatment of ovarian cancer includes surgery and chemotherapy sometimes administered before and after surgery. Two drugs are usually part of the chemo; cytotoxics and growth inhibitors.

When the growth inhibitor Paclitaxel is used hair loss occurs for all patients with complete baldness (alopecia), usually reversible, for about 65%.

Despite being so frequent there is little understanding about hair loss. Chemotherapy unfortunately is non-selective with side effects caused by damage to normal cell division. This is greatest for structures which have rapid cell turnover, notably hair, gut and nerves. Cell death occurs and hair breaks with sometimes alopecia.

The psychological impact is significant and may result in patients resisting or absconding from treatment. For them alternative treatment with doxorubicin may be used, hair loss is reduced with this drug but not excluded.

Another good idea disproved.

Metabolism of Primary High-Grade Serous Ovarian Carcinoma (HGSOC) Cells under Limited Glutamine or Glucose Availability

https://tinyurl.com/2bxh2b4c

As understanding of ovarian cancer increases previous suggestions as to cause and effect are often disproved and need to be disregarded.

It is known that there are two groups of high grade serous ovarian, (HGSOC) cancer patients, one of which survive better. Formerly there was a theory that this division is due to difference in glucose metabolism. Two main pathways of glucose metabolism occur; glycolysis, which does not need oxygen and phosphorylation which does. It had been thought that chemo response was better for cells which use the second pathway as a priority.

This basic research using cancer cells from 45 patients with HGSOC showed no correlation between survival and glucose metabolism. There is however evidence shown that cancer cell proliferation is decreased in low glucose conditions, which supports anecdotal evidence of the benefit of anti-hyperglycaemic such as Metformin and maybe Ozempic.

What's New and Yet to Come?

Promising New Drugs and Therapeutic Approaches for Treatment of Ovarian Cancer—Targeting the Hallmarks of Cancer 

https://tinyurl.com/bdzu8nr5 

As we begin a new year, it's an opportune time to examine both current advances in ovarian cancer treatment and potential breakthroughs on the horizon. 

Recent progress in ovarian cancer treatment has been marked by the advent of personalised medicine, which targets specific genetic and molecular variations in individual patients. This approach has led to improved survival rates through the introduction of novel therapeutics, particularly PARP and angiogenesis inhibitors. 

Innovative drug delivery mechanisms are revolutionizing treatment, most notably through antibody-drug conjugates (ADCs). The latest example is MIRV (mirvetuximab soravtansine), which has shown promise in treating recurrent ovarian cancer. 

This article examines ongoing phase III clinical trials and evaluates their potential impact on patient care. Immunotherapy, while previously showing limited efficacy, is experiencing a renaissance through combination approaches. The DUO trial, which combines PARP inhibition with checkpoint inhibition, suggests a promising new direction in treatment. 

This year's basic research emphasizes tumour-specific characteristics rather than broader patient parameters, aiming to identify novel targets for personalised therapy. These developments offer renewed hope for improving outcomes in ovarian cancer treatment.

BRCA, even more worrisome

New tool puts reproductive risk for BRCA carriers into perspective

https://tinyurl.com/24hrpkzp

Ever since the 1960s, the familial risk of breast and ovarian cancer has been recognised as the hereditary breast and ovarian cancer syndrome (HBOC). The genetic mutations responsible were shown to be located on chromosomes 17 and 13 and labelled BRCA1 and 2.

These mutations are dominant, meaning only one copy of the gene needs to be affected. More recently the effect of both genes bearing the mutation causing childhood disease and early onset cancers is becoming clearer. Many women carrying one of the BRCA mutations are unaware of this additional risk.

What this means is that if both a child’s mother and father carry a BRCA mutation, that child has a 75% risk of both genes being affected and a 100% risk of being a carrier.

The major risk to the child with dual BRCA mutation is a bone marrow disorder, Fanconi’s Anaemia. This is an incurable condition with a limited lifespan of about 30 years and much associated cancer.

Obviously, the risk of this happening is much greater in populations where there is a high BRCA mutation, such as Ashkenazi Jews and the Shetlanders. Advice about possible dual inheritance should form part of genetic counselling.

Your gut biome affects ovarian cancer immune response

Integrative multi-omics analysis uncovers tumour-immune-gut axis influencing immunotherapy outcomes in ovarian cancer

https://tinyurl.com/3h5wuk33

About 50% of all ovarian cancer has an increased T cell infiltration suggesting a strong immune response. This is associated with good survival.

Targeted immune therapy which inhibits checkpoint activity unfortunately thus far has not been shown to be effective against ovarian cancer. This study looked at the impact of the faecal microbiome on immune checkpoint blockade (ICB).

Using data from another study, which tested the effect of ICB for recurrent ovarian cancer, a subgroup of patients showed a significant benefit (30%). These patients had a different microbiome when compared to those patients who did not have much benefit.

This information suggests that manipulation of the gut biome could be an aid to survival for patients with recurrent ovarian cancer.