HIPEC dubious benefit

Hyperthermic intraperitoneal chemotherapy in recurrent ovarian cancer: An updated systematic review and meta-analysis. 

https://tinyurl.com/5n6ujj6a

As knowledge increases there is more understanding of the treatment of ovarian cancer. One of the special characteristics of ovarian cancer is the early metastasis especially to the peritoneal lining of the abdomen. As an attempt to treat this spread, which is often microscopic, an invasive and painful therapy called Hyperthermic intraperitoneal chemotherapy. (HIPEC) has been promoted. 

This article is a review of all the available data relating to clinical trials of HIPEC when compared to standard chemo without HIPEC. The endpoints for the study are progression free survival (PFS), overall survival (OS) and post operative complications.

Only 4 trials were shown to fit the criteria with 801 participants of whom 398 received HIPEC in addition to standard care. The results were discouraging with no improvement in OS or PFS. Post operative complications were significantly increased for the treatment group, especially infection and anaemia.

Obviously, these are small numbers of cases with significant exclusions and possible bias. However, there is doubt that such an invasive procedure is warranted.

New Targeted therapy

The antibody–drug conjugate targeting ROR1, NBE-002, is active in high-grade serous ovarian cancer preclinical models

https://tinyurl.com/2h8jthp9

New pre-clinical research from Sydney Australia has shown a possible new therapy for ovarian cancer. The research identifies the effectiveness of inhibition of a cell membrane receptor named the receptor tyrosine kinase orphan receptor 1 (ROR1). This receptor becomes more active with ovarian cancer. Usually, ROR1 has an important part in early embryonic development and is suppressed later. In the presence of cancer increased ROR1 activity promotes cancer growth and spread.

An antibody/drug combination labelled NBE 002 has been shown to block the receptor with restriction of cell metabolism causing cell death. This early study showed about half the cell types used which had been previously grown from human ovarian cancer had increased ROR1 activity.

If the therapeutic effect can be reproduced in human clinical trials, this drug combination may be yet another example of the possible benefits of targeted cancer treatment.

Biosynthetic Taxol

New method of Taxol production has the potential to greatly reduce the cost

https://tinyurl.com/3hrrx7x4

Since 1996 Taxol, a growth suppressant has been used, together with carboplatin, a cytotoxic, in the initial chemo treatment of ovarian cancer. Originally extracted from the bark of the Pacific Yew tree, Taxol is the most expensive in terms of raw ingredients of any drug in common use.

The original process required the bark from two trees for each individual treatment killing the tree which took 100 years to mature. Subsequently it has been extracted from the harvested Yew needles at a cost of US$20000/ Kg. These too are in short supply.

Now a biosynthetic process using cloned yeast cells has been developed, thereby ensuring an adequate supply at much less cost. Hopefully this will make this essential treatment more readily available, especially in third world countries.

FDA approval

FDA Approves New Treatment for KRAS-Mutated Recurrent Low-Grade Serous Ovarian Cancer

https://tinyurl.com/4t7up48w

Low Grade Serous Ovarian Cancer (LGSOC) is rare, comprising about 5% of all ovariancancer and difficult to treat. Usually, patients with LGSOC have better survival than other forms of ovarian cancer. However, recurrence is common, eight out of ten women with LGSOC will have a recurrence of the cancer.

Recurrent LGSOC is resistant, meaning chemo used as the first-line treatment is no longer effective. Women with LGSOC are often younger than the usual ovarian cancer patients, the opportunity cost is greater when recurrence occurs.

The new targeted therapy using the antibody drug combination Avutometinib plus Defactinib is a welcome addition to LGSOC recurrence management. FDA approval for this drug follows encouraging results from the RAMP-201 clinical trial. 

The target for this new therapy is mutation of the KRAS gene with consequent damage to DNA repair. About 50% of women with LGSOC carry this mutation. This is the second FDA approval of an antibody drug combination for ovarian cancer, suggesting these drugs will have an important role in the future.

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.