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.