How common is complete clearance?

Surgical and blood-based minimal residual disease in patients with ovarian cancer after frontline therapy: Clinical outcomes and translational opportunities

https://tinyurl.com/4698cc7c

In the treatment of ovarian cancer, the most important determinant of survival is the effectiveness of the initial surgical procedure. The aim is complete clearance and for about 80% of women no residual cancer can be detected either by CT scan or plasma CA 125 levels. Despite this only about 20% of women will have been cured suggesting that residual cancer is present despite evidence to the contrary.

This study shows the true rate of minimal residual disease (MRD), by measuring circulating tumour DNA (CT DNA), and by repeat “second look” laparoscopy after completion of surgery and chemo.

Findings from the study showed that of 95 patients thought to have had a complete clearance at initial surgery almost half had MRD with abnormal CT DNA or second look laparoscopy. These women had worse survival and earlier recurrent disease. The authors suggest that searching for occult MRD should be part of standard treatment to enable correct management.

Nausea and Vomiting, when and why

Time-Trend Analysis and Risk Factors for Niraparib-Induced Nausea and Vomiting in Ovarian Cancer: A Prospective Study

https://tinyurl.com/6wauzndb

Niraparib (zejula) is one of two PARP inhibitor drugs approved by the TGA in Australia for maintenance therapy of ovarian cancer. A common side effect affecting up to 60% of patients is nausea and vomiting. Occasionally this may be so severe as to be life-threatening.

This prospective survey looked at the treatment course for 53 patients who underwent maintenance therapy with niraparib. 31 had treatment induced nausea and vomiting, for 3 of them this was severe with weight loss, dehydration, and malnutrition.

The adverse effect was greatest 8 hours after taking the oral medication, which is when the plasma concentration is greatest. The severity of the reaction decreased over time with less severe reactions being reported after 8 weeks. This may be due to dose manipulation which is common.

The authors note that nausea and vomiting are often causes for patients to cease treatment. Monitoring this side effect and correct timing for anti-emetic treatment with dose modification may avoid discontinuation.

Delay not always harmful

Earlier is not always better: Optimal time to initiate adjuvant chemotherapy after surgery for ovarian cancer

https://tinyurl.com/4y2kpmrr

Standard treatment of ovarian cancer includes chemo after surgery, either with or without neoadjuvant chemo beforehand. There has always been an imperative to begin chemo as soon as possible, hoping to reduce the risk of recurrence.

For some women with ovarian cancer, it is not possible to start chemo early. Either because of debility infection or circumstance. This study looks at outcomes for women who start chemo late and compares them to other women whose chemo is not delayed.

The retrospective study looked at the outcomes of 1700 women who had surgery for ovarian cancer at 5 German Hospitals during the period 2020-2021. They were divided into 3 groups; those who had chemo early (less than 3 weeks post-surgery), intermediate (3-5 weeks post-surgery), and late (greater than 5 weeks). The outcomes measured were progress free survival (PFS),
and overall survival (OS).

Results from this study showed both early and late groups had worse OS than those women who started their chemo in the intermediate time frame of 3-5 weeks post-surgery. Previous studies have shown more post-op complications for the early group and women who start chemo late often have more complex disease. Of interest is that PFS was similar for all 3 groups. The authors suggest that women whose chemo is delayed can be reassured that the delay will not cause immediate harm.

Limited understanding

Shared decision making for ovarian cancer survivors with different levels of health literacy: a qualitative interview study on knowledge and comprehension

https://tinyurl.com/n8ubvxhz

Management of ovarian cancer is best when the patient and the carer can share decision making. For this to occur both parties need to be fully informed and able to understand the process.

This shared decision making involves choice of therapy and detection of recurrence. A small retrospective study shows that many women have a limited understanding of medical terms and jargon, making decisions difficult.

A group of 17 women with ovarian cancer were asked about their understanding of the care they had received. They also answered a questionnaire aiming to determine their basic medical knowledge and confidence about sharing decisions.

Results from the study showed limited understanding about the course of their illness with false confidence in physical examination as a means of detecting recurrence. In general, there is a low level of medical literacy which makes shared decisions difficult.

Cataract and Ovarian Cancer

Ovarian Cancer and the Risk of Cataract Episodes: A Nationwide Cohort Study 

https://tinyurl.com/449xa994

Both cataracts and ovarian cancer are found in the elderly. It has been known that cataracts may develop in patients with cancer who have therapy, most often due to radiation but also as a side-effect of chemo.

One of the important causes of cataract is high oxidative stress, which is an imbalance of free oxygen and antioxidants. This is also linked to many cancers including ovarian cancer.A retrospective survey looks at the incidence of cataract in patients with ovarian cancer compared to the general population.

Using data from the Taiwan National Health Insurance database, 5000 women with ovarian cancer were matched with 20,000 women who were cancer free. About 10% of the cancer group had cataract, of whom less than half required surgery. Comparison with the control group showed a slight increase in cataract diagnosis of about 7%, for those women with cancer.

This study is limited by the small ethnic variation with most of the women being Han Taiwanese. However, the authors suggest that routine eye examination should be part of standard care for women with ovarian cancer.

Improvement, slow but real

Demographic trends in mortality due to ovarian cancer in the United States, 1999-2020

https://tinyurl.com/2py9489j

Progress in care for patients with ovarian cancer can be slow. It often seems that a cure is impossible and that there has been no improvement in the outcomes for women who face this great challenge.

However, it is important to recognise that change is occurring and that survival has significantly increased over recent times. This survey looks at mortality due to ovarian cancer and the trend of improvement in the US over the current century.

Using data from the CDC epidemiological database the decrease in deaths from ovarian cancer is shown with a reduction from the initial rate of 14.6/100,000 in 1999 to 10.2/100,000 in 2020. This dramatic change no doubt reflects better care and earlier detection of disease.

Sadly, the data also shows that this improvement is not universal. Somewhat surprisingly the death rate is highest in non-Hispanic white women at 13.5/100,000, whereas Asian women deaths from ovarian cancer declined to 7.5/100,000 over this time interval.

This disparity may be due to differences in BRCA mutation and age. Overall, it is encouraging to note the changing prognosis for ovarian cancer.

Ovarian cancer during pregnancy

Epithelial ovarian cancer and borderline tumours during pregnancy: a report from the International Network on Cancer, Infertility, and Pregnancy

https://tinyurl.com/4fbdzz6w

Any cancer found during pregnancy causes great concern, with possible damage to the foetus and mother being the main worry, although change in the progression of disease due to altered immunology also is a factor.

Fortunately, ovarian cancer is not common during pregnancy. This article looks at the available information with respect to maternal and foetal outcomes. 

About 1% of all pregnancies have an incidental finding of an adnexal mass. This is more often found now that ultrasound examination is part of the normal standard of care. There is a very low incidence of these masses being found to be malignant (0.2 -3/100,000). Of the malignant masses, three quarters are due to borderline tumours and one quarter invasive ovarian cancer usually epithelial.

Using the INCIP database 129 women were identified as having ovarian cancer discovered prior to childbirth. About half had invasive cancer the others, borderline tumours. 64% of these women had standard care with resection and chemo, the others had treatment deferred.

Birth weights of infants whose mother had received chemo were significantly reduced. Women who had standard treatment for ovarian cancer had better survival. Most cancers were early-stage, overall survival of 80% at 5 years was good. The numbers of cases are small but support active treatment of ovarian cancer during pregnancy.

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.