The Falling; Ovarian Cancer Neuropathy

The Falling, Wandering and Crashing Business of Cancer Treatment Side Effects

https://tinyurl.com/tjn58ke

Neuropathy is a common and often unexpected side effect of platinum chemotherapy for ovarian cancer. Some studies suggest up to 100% of patients will develop nerve damage, sensory, autonomic and motor*. The damage is usually reversible but long lasting, frequently for several years.

The effects are little discussed, probably because they are so distressing.  This article by Sherry Hanson in “Cure” is brilliant. She talks of the “twitch” causing breakages, weakness, can’t open the wine bottle and falls, giving up roller blading at the age of 75!

The story should be compulsory reading for those about to enter the world of platinum chemo. She writes well, tells it as it is, with black humour - “But I’m still here”.

*     https://tinyurl.com/vtr86yg

Ovarian Christmas Cheer

Blue Monday? Not for Ovarian cancer

https://tinyurl.com/on3l7m8

         Do you know about Blue Monday? It was news for me; it’s an invention by advertisers (of course), aimed at selling more stuff (of course), mostly cruising in the Caribbean. The third Monday in January, Blue Monday is the day when the end of good feelings after Christmas and the reality of failure to honour New Year’s resolutions kick in.

         This year Blue Monday is on January 13, 2020, but there will be no reason for those of us involved with ovarian cancer to be gloomy. 2019 has been a momentous year with signs of light: -

·      The mortality from ovarian cancer is decreasing at around 2.5% per annum

·      Australia has the best outcomes for ovarian cancer with 55% survival for patients<60 after 5 years

·      Radical change in drug treatment with PARP inhibitors helps to stop recurrence

·      Understanding the genetics of ovarian cancer means more patients receive targeted therapy

·      Commercial opportunity is driving research

·      Federal Government funding is at an all-time high

         So, enjoy Christmas, a time for hope and optimism, do not allow the January blues to happen. “Yes we can!”

P.S. Maybe we should hijack “Teal Blue Monday?”

Paul Kelly; how to make gravy

Ovarian cancer RCTs biased

Biased by design? Clinical trials and patient benefit in oncology

https://tinyurl.com/w2jq5zg

         A recent study examined the risk of bias and standard of reporting of clinical trials which resulted in the approval of new drugs for cancer treatment, in Europe, during the period 2014-2016 *.

         Almost half of these trials were assessed as biased. Only about a quarter measured overall survival as an end point. There was often disparity between the results reported when compared to the stated purpose of the trials.

         For many new cancer drug approvals a single pivotal drug trial was deemed sufficient, whereas for other medical conditions multiple supporting trials are required before approval is granted. Pivotal trials tend to be non-randomised, not double blind and usually incomplete. 

         In many cases, subsequent confirmatory trials, after approval, have shown no improvement in overall survival and frequently the initial findings are not replicated. This study suggests there is a major weakness in the approval process with often little patient benefit.

*  https://tinyurl.com/yxqy2qkq

Toxic dense-dose therapy for ovarian cancer not justified

Weekly dose-dense chemotherapy in first-line epithelial ovarian, fallopian tube, or primary peritoneal carcinoma treatment (ICON8): primary progression free survival analysis results from a GCIG phase 3 randomised controlled trial

https://tinyurl.com/uc9w7vt

The current chemotherapy treatment regime for ovarian cancer is single dose every three weeks. In 2013 a Japanese clinical trial* showed increased survival with a dose-dense regime where a double dose of the same chemotherapy is administered weekly.

There is a significant increase in side effects and toxicity with this dose-dense regime. A repeat randomised clinical trial has been completed comparing dose-dense therapy with conventional less toxic treatment regimes.

The findings of this large study with 1566 participants shows no improvement of progression free survival with the dose-dense therapy. Most side effects from treatment were greater with the dose-dense regime. The incidence of nerve injury and decreased white blood cell count was similar for all groups.

*      https://tinyurl.com/qpko65c

Ovarian cancer researcher’s generosity

Scientist donates £865,000 to establish charitable fund

https://tinyurl.com/thkl25o

Professor Nicola Curtin of Newcastle University was involved in the creation of Rubraca, a drug used in treatment of ovarian cancer. She has donated her share of the proceeds to a Community Foundation, which will help people to develop the skills, talents and confidence to overcome barriers to employment or education

The fund is named “The Curtin PARP Fund” after the drug a PARP Inhibitor and as an abbreviation of  “Passionate About Realising your Potential”.

Professor Curtin said, “I feel very privileged to have such a great career, I want to leave a lasting legacy that will change lives for the better. Like most scientists it's not the money that drives me, it's the intellectual challenge and the buzz I get from finding something out before anyone else knows it”.

No repeat surgery for ovarian cancer

Secondary Surgical Cytoreduction for Recurrent Ovarian Cancer

https://tinyurl.com/slqtvjs

Primary treatment for advanced ovarian cancer is with surgery and chemotherapy. The completeness of the initial surgical resection correlates to the overall survival. 

Intuitively it has been thought that, for recurrent ovarian cancer, further surgery would be beneficial.

In this clinical trial treatment for 485 patients was randomly selected, 240 for repeat surgery before chemotherapy and 245, chemotherapy alone. 

No increase in survival was noted following surgery. Patients’ quality of life deteriorated in the immediate post-operative period

So, why do it?

When evidence says no: gynaecologists’ reasons for (not) recommending ineffective ovarian cancer screening

https://tinyurl.com/y4q2cyhn

Clinical trials have repeatedly shown screening for ovarian cancer to be futile and potentially harmful due to the risk of over diagnosis*. Despite this, in the USA, large numbers of gynaecologists continue to recommend screening to their patients.

This survey of 401 currently practising US gynaecologists showed about 60% advised screening. The criteria tested were knowledge of appropriate practice, understanding of statistics, what they thought their colleagues did and whether they thought financial conflict of interest might be a cause for other doctors' choices.

The results were that screeners justified their decision, saying their colleagues supported screening and they were responding to patient pressure. Most thought wrongly that clinical evidence supported their choice. Non-screeners thought financial interest was a cause for inappropriate screening and had a better understanding of approved practice. Of significance was the difference in knowledge of statistical concepts with most screeners failing the test and non-screeners usually being statistically literate.

*https://tinyurl.com/yxmuhb9s

Ovarian cancer and commerce

New Hope in the Battle Against Ovarian Cancer

https://tinyurl.com/yy86894h

There is commercial interest in developing personalised medical care. Ovarian cancer is a possibly lucrative opportunity. AI predictive models are using  large data sets of patient drug-treatment protocols, genetic information and historical outcomes to develop targeted therapeutics.

In collaboration with the UK 100,000 Genomes Project, which is an NHS project collecting genetic material from cancer patients, a US biotechnology company; Helomics currently has data from 38,000 cases of ovarian cancer. 

Helomics is looking at genetic variations and expression together with its data set of drug-response profiles to build an AI-driven predictive model of ovarian cancer. This will guide clinicians, as to which drug or drug combinations to use for ovarian cancer treatments.

Metformin and ovarian cancer

Metformin plus first-line chemotherapy versus chemotherapy alone in the treatment of epithelial ovarian cancer: a prospective open-label pilot trial

https://tinyurl.com/y4wg6hpy

This small study; looking at non-diabetic patients with ovarian cancer, half of whom received metformin in addition to normal platinum based chemo, the others chemo alone; showed no progression free survival benefit. 

Type two diabetic patients have a lower incidence of tumour development than healthy controls and those diabetic patients, treated with metformin, who are diagnosed with cancer, have a lower mortality.

https://tinyurl.com/y3dnkc2s

A recent hypothesis proposes that primary non-hereditary ovarian cancer risk factors are increased through the development of ovarian fibrosis. Metformin, which reduces fibrosis, may be protective. 

https://tinyurl.com/yy4ytghy

PFS don’t be fooled

How one bit of medical jargon fuels public confusion about cancer treatments

https://tinyurl.com/y2x728q8

Most new cancer treatments haven’t been proved to help patients live longer or feel better. Instead they delay the growth of tumors, which is measured as an improvement in Progression Free Survival (PFS). In the last decade it’s become the norm in cancer trials.

Patients have no idea what PFS means; it is often a poor marker for outcomes that are most important to them, such as living longer or a better quality of life during and after treatment. 

Of the 42 fast-tracked cancer drugs the FDA approved in 2015-18, only 8 significantly prolonged overall survival. A recent review showed no link between a longer PFS and improved quality of life.

https://tinyurl.com/y3ljfhwa

Reports on trials should include cost, adverse effects, conflicts of interest and whether a drug improves overall survival. 

Lessons learned

Ovarian cancer survivor: 4 lessons I learned from treatment

https://tinyurl.com/y475pqfj

“I believe staying positive is just as important as the drugs that are administered. Except for the days on which I had chemotherapy infusions, I worked the entire time. I didn’t discuss my treatment. I didn’t want the fact that I had cancer to be the first thing people focused on when they saw or talked to me.

I had to be OK with letting others help me. I was taken aback by how many people stepped up. Having others share in this experience helped me to heal mentally and emotionally. Allowing others to assist me helped them cope with the situation, too, since my diagnosis had been so sudden and shocking.

Cancer treatment side effects are real. I had terrible chemo brain and exhaustion during my ovarian cancer treatment. It was incredibly frustrating, especially when I was working, because it felt like everything I did took twice as long.

I’ve always been a positive person, but since finishing my treatment, I’ve really tried to take everything in stride. Life can change in an instant, so I’ve learned to say “yes” to more things and step out of my comfort zone more often, don’t let cancer define you. It’s a bad thing that has happened to you, but it’s not you”.

Angela Hernandez

HRT and ovarian cancer

Menopausal hormone therapy treatment options and ovarian cancer risk: A Swedish prospective population‐based matched‐cohort study

https://doi.org/10.1002/ijc.32706

 Menopausal hormone replacement therapy (HRT) influences ovarian cancer. This survey of all Swedish women who received HRT between 2005-2012 looks at risk. HRT can be oestrogen only or combined oestrogen/progesterone, cutaneous administration is available. Some HRT is continuous some sequential. 

The incidence of ovarian cancer was obtained from the Swedish Cancer Register. The therapy group was compared with a larger control group of women who did not receive HRT.

Current users of continuous combined HRT have a small increased risk being 1.4 times more likely to develop ovarian cancer. This risk is reduced by cutaneous therapy. Oestrogen only HRT is protective with a reduced incidence of ovarian cancer. There is no increased risk with sequential therapy. Once HRT is discontinued there is no increased risk.

Old and vulnerable

Geriatric Vulnerability Score Validated for Use in Managing Care of Older Patients With Ovarian Cancer

https://tinyurl.com/y2s3hgkf

It is well known that elderly patients have worse survival outcomes from ovarian cancer. In Australia patients aged 75 or over have a 5 years survival rate of 21% compared to 52% for the young.

A measure of vulnerability; the geriatric vulnerability score (GVS) has been identified. This measures serum protein, circulating lymphocytes, physical activity and depression and assigns a score of 0 for normal 1 for abnormal, giving a maximum GVS of 4.

With a score of 3 or more the overall survival hazard ratio is 2.94 meaning that these patients are three times more likely than patients of the same age to die of the disease. This may be a significant consideration when choosing appropriate therapy.

Good news

Progress in cancer survival, mortality, and incidence in seven high-income countries 1995–2014 (ICBP SURVMARK-2): a population-based study

https://tinyurl.com/y2a7vpn3

This population-based study of cancer survival in seven countries provides information from 4 million patients comparing survival at 1 and 5 years post diagnosis. During the period 1995 to 2014 improved survival was recorded for all cancer types, especially in younger patients.

Comparison between different countries showed Australia to be the country with the best survival for every cancer type other than ovary and lung, for which Australia had the second best outcomes.  

Cancer incidence

https://tinyurl.com/y6nmmgzq

The annual review of cancer incidence in Australia shows an increase greater in remote areas, for indigenous Australians and those of lower socio-economic status.

However, the age-standardised incidence of ovarian cancer has decreased from 12.4/100,000 in 1982 to 9.8/100,000 now.

Ovary preservation? It’s OK

Fertility-sparing surgery for treatment of non-epithelial ovarian cancer: Oncological and reproductive outcomes in a prospective nationwide population-based cohort study

https://tinyurl.com/y2xjqd54

For young women with early stage ovarian cancer the decision as to the extent of surgery to undergo is difficult. Preservation of fertility is important, the concern is; does this mean an increased risk of recurrence?

This survey of the Swedish Quality Register for Gynecological Cancer identified 73 women, aged 18-40, with stage I ovarian cancer during the period 2008-2015. Most (78%) had ovary-sparing surgery, the others opted for full pelvic clearance.

The outcomes were good for both groups; the 5 years overall survival rate was 98%. There was no statistical difference in outcomes; the fertility of those women who had limited surgery was preserved, only 12% requiring IVF therapy.

Immunotherapy

How Immunotherapy Is Making an Impact in Ovarian Cancer

https://tinyurl.com/y6dvx8xb

In Australia 5 women in 1000 will develop advanced ovarian cancer by the age of 60. Progression free survival is improving, but overall survival is unchanged for the last 20 years. A need for alternate therapy has led to much clinical research. Immunotherapy is promoted as a great prospect for change.  Recently Dmitriy Zamarin, M.D. from Sloane Kettering spoke about various approaches: -

Check point inhibition; cancer develops when normal mutated cell death is prevented. Inhibition of this is good therapy in other cancers such as Keytruda for melanoma. Clinical trials have failed to show any benefit for ovarian cancer. 

Oncolytic virus therapy; vaccination with genetically modified adenovirus makes cancer cells vulnerable to killer T cells, these form in the patient’s thymus gland in response to disease. This is subject to clinical trial.

CAR T therapy; this process involves in vitro genetic modification of killer T cells. Although shown to be good for cancers of the blood, such as Kymriah for acute lymphoblastic leukaemia, no benefit is yet proved for solid tumours such as ovarian cancer. This too is subject to clinical trial.

It is early in a new field of research. What is clear is that each patient is different, the environment in which cancer exists is just as important as the tumour cell genetic type; targeted therapy is essential to change the current grim prospect.

T vs. C

Napping is OK

Cancer Survivors and the Art of Napping

https://tinyurl.com/y8xlcpvx

“Sita (my service dog) is around 14 years old. I also have a cat, named Cesar, who is 10. I tell them that we are all getting older together. 

I have been battling cancer for over eight years now. For someone with an incurable cancer on chemo, the tiredness never leaves. When the fatigue hits, I go to my bedroom. Cesar curls up between my legs, Sita lies on her bed and we all nap together.  

They obviously feel no guilt that they should be doing stuff, unlike me. Animals can be smarter than people and we can learn from them.”

Enough

The EOLO (End-of-Life Ovarian Cancer) Study: Approach to Ovarian Cancer Patients at the End of Life.

https://www.ncbi.nlm.nih.gov/pubmed/31437848

End-of-life chemotherapy is a thorny problem. This review of ovarian cancer patients, who died in the period between 2007 and 2017, recorded the frequency of chemo; the toxicity, mortality, and the most frequent palliative care measure adopted.

Of the 110 patients, 85 had undergone chemo in the last 3 months of life and 42 even had chemo during the last month.

The median overall patient survival was 52.8 months. The majority died at home, the quality of life decreased dramatically in the last 30 days.