Cancer Doesn’t Care it’s Christmas

 Cancer Doesn’t Care it’s Christmas

https://tinyurl.com/y6vjvkgt

 

         Data from YouGov a UK government website show that at Christmas this year, 24% of the population will be directly affected by cancer; either themselves or someone in their family will be coping with active cancer and it’s treatment.

         The COVID-19 pandemic has added to the normal difficulties with 40% having experienced delays in treatment or diagnosis.  It is important to remember the special needs for cancer patients at this time.

         An English charity has produced a series of videos seeking to raise awareness and increase donations. One of these features Alexandria Mitchell an ovarian cancer survivor. She talks about Christmas, what it means to her and how we could all make Christmas better for women facing the disease and the side effects of treatment. Worth a look….

 

Gene shears give hope

CRISPR-Cas9 genome editing using targeted lipid nanoparticles for cancer therapy

https://tinyurl.com/y9z5gbq3

 

         One of the more hopeful prospects for cure of ovarian cancer is the relatively new technique of “Gene Shears”. First described in 2017 this employs a natural body defense against infection and tumour called CRISPR editing. CRISPR is an abbreviation of “clusters of regularly interspaced short palindromic repeats”.

         The CRISPR location on chromosomal DNA of cancer cells is vulnerable to attack by a protein enzyme, in this case Cas9. After the attack or gene shear the cell is damaged and cell death occurs. A problem with this is the delivery of the enzyme to the right target.

         This report shows treatment with gene shears for two tumours in mice; brain and ovarian tumours. Both respond to the enzyme, which was delivered as micro RNA in lipid nanoparticles, similar to new COVID-19 vaccine technology. Early results are encouraging and will probably lead to clinical trials for human patients.

Diet does not make a difference

Pre- and Post-Diagnosis Diet Quality and Ovarian Cancer Survival

 

https://tinyurl.com/y5mrnmto

 

         A popular misconception is that diet manipulation can improve outcomes for patients with cancer. Advocates for diet change have profited from this unproven speculation, with best-selling books and multi-media presentations.

         This prospective study from Brisbane, Australia, looked at dietary habits for ovarian cancer patients before and following diagnosis with a record of survival. 650 completed surveys were obtained at the time of diagnosis, and a further 503 twelve month’s later.

         Results showed no survival advantage for those patients who had a good diet quality prior to diagnosis or for those women who changed their diet in response to the onset of ovarian cancer

MS & ovarian cancer

Cancer incidence and mortality rates in multiple sclerosis: A matched cohort study

https://tinyurl.com/y63oh8uw

 

         Previous reviews of patients with Multiple Sclerosis (MS) showed an increased risk of breast and colon cancer. One of the recently developed drugs used in the treatment of MS, (Ocrevus) has been shown in clinical trials to increase the risk of breast cancer.

         This large population based survey compares cancer risks in a group of 54,000 MS patients with a control group of 264,000 people without MS. Retrospective search of the Canadian cancer registry shows no increased risk for breast or colon cancer.

         Risk of bladder and ovarian cancer is increased for MS patients. Possible reasons for this are the nature of the disease, with altered immune state and effects of treatment. Bladder cancer may be related to in-dwelling catheter placement.

         Ovarian cancer is approximately 50% more likely in patients with MS, meaning an increase in incidence from the normal 10 cases per 100,000 per annum, to about 15. The authors recommend active surveillance of MS patients, looking to detect ovarian cancer at an earlier stage.

Coping with Covid

Adapting and avoiding coping strategies for women with ovarian cancer during the COVID-19 pandemic

https://tinyurl.com/yy95gmu5

 

         The impact of the Covid 19 pandemic on the physical and psychological well being of women with ovarian cancer has been dramatic. This study looks at coping strategies these women have used during this difficult time

         An online survey of 600 women with ovarian cancer during March and April of 2020 produced 400 responses with relevant information. Active cancer treatment was ongoing for 40% of the respondents, who had a median age of 58.

         Two different coping strategies were noted: adaptive, with acceptance, or dysfunctional, with self-harm. From the survey it seemed that 64% of the women used adaptive strategies such as spirituality, hobbies or exercise. 

          Dysfunctional coping strategies employed included substance abuse, binge eating, and inappropriate use of prescription medication. There was no report of denial.

         With the likelihood being that the pandemic will continue for the foreseeable future, it is important that support services for women with ovarian cancer recognise their special needs. 

Sex after ovarian cancer

Psychosexual morbidity in women with ovarian cancer

https://tinyurl.com/y3rge7z3

         Thanks to improved treatment, women with ovarian cancer are living longer. There is an increasing attention to the quality of life rather than a fixation on survival.

         One of the priorities for women, usually not fully appreciated by medical attendants, is the pleasure of intimate sexual activity. There has been a dearth of information about what women experience after ovarian cancer treatment and a failure to appreciate the inevitable changes that occur.

         This paper from the UK is revelatory; the study is a retrospective analysis of all available literature. The findings are that up to 65% of women before surgery were sexually active. After surgery 75% reported adverse effect, the reasons were both physical and psychological with pain and loss of pleasure.

         The paper is very important and I would encourage full study of the detail. The loss of body image, change in interpersonal relationships from partner to carer, together with the disability of surgery are important but misunderstood consequences of ovarian cancer care.

Incidental salpingectomy does not decrease cancer risk

Ovarian cancer risk after salpingectomy for ectopic pregnancy or hydrosalpinx: results of the OCASE nationwide population-based database study

https://tinyurl.com/yywquctm

 

         Most epithelial ovarian cancer (the commonest and most lethal) starts in the fallopian tube and spreads to the ovary. For those women with a pre-disposition to develop ovarian cancer, due to inherited genetic mutation, risk reduction surgery is being recommended with removal of the fallopian tubes (salpingectomy).

         There is another large group of women who have had at least one tube removed; these are women who developed an ectopic pregnancy and who had surgical therapy. It would seem likely that these women should have a subsequent decreased ovarian cancer risk.

         This retrospective study using the Dutch pathology dataset looked at more than 21,000 women who had salpingectomy, usually unilateral, and compared their cancer risk with a similar size control group. No significant reduction of cancer risk was noted, the authors note that this is a young population and ovarian cancer usually presents later in life.

Dutch Public Pathology Database

Osteoporosis and ovarian cancer

Effect of gynecological cancer and its treatment on bone mineral density and the risk of osteoporosis and osteoporotic fracture

https://tinyurl.com/y3bxbfu2

 

         243 women with ovarian and endometrial cancer had their bone density measured before and during treatment. Their bone density measurements were compared to a control group of healthy post-menopausal women without cancer.

         All women with ovarian cancer had low bone density before and continuing during therapy.  Osteoporosis, which is a bone density less than two standard deviations below the normal mean, is commonly associated with many types of cancer probably due to a hormonal effect.

         Osteoporosis often causes pain and fracture with loss of function and deformity. Appropriate testing and treatment for osteoporosis should be part of the management of ovarian cancer. Treatment such as with bisphosphonates or denosumab, does not affect chemotherapy. 

Fast track new drug trial

FDA Places PC14586, for Cancers with Mutant Protein, on Fast Track

https://tinyurl.com/y5kv3utz

 

         Of recent times there has been a concentration on the treatment of ovarian cancer resulting from inherited or germ line mutations. High Grade Serous Ovarian Cancer is the commonest and most lethal, this is associated with an acquired or somatic mutation (TP53) in about 97% of cases.

          Now for the first time, a recent determination, by the Federal Drug Agency to fast-track acceptance for investigation of a new drug; PC14586, raises the prospect of a remedy for this somatic mutation.

         This drug is to be tested through a Phase I/II trial looking to establish its safety and effectiveness.   As with all clinical trials, the likelihood of progression to standard treatment is less than 2%. 

Ovarian tissue preservation

Breaking down the barriers: a new collaborative model providing fertility care for young cancer patients

https://tinyurl.com/y6t5jhuu

 

         Loss of fertility is of great concern to young women who undergo surgery and chemotherapy for cancer. Risk reduction surgery is now offered to those women who have an increased risk of ovarian cancer due to genetic predisposition.

         For pre-pubertal girls cryopreservation of ovarian tissue may be the only way to preserve fertility. There has been difficulty in access for patients outside major centres.

         A long-standing Fertility Preservation Service has been available in Melbourne. This has now been expanded to provide a nation-wide tissue retrieval and transportation service.

         Fertility preservation should be mandatory in cancer care; this new service makes it possible for all young people who need it.

 

Dangerous misunderstanding

Tackling misconceptions about ovarian cancer 

https://tinyurl.com/y58cmcfu

 

         With ovarian cancer early detection is critical for better survival. Because there is no screening test a high index of suspicion by women is essential. Adequate education as to symptoms and signs is needed.

         This study performed in Melbourne, Australia was a telephone survey of almost 500 women looking at their understanding of ovarian cancer.

         The results were alarming; 65% thought there is an effective screening test and that a PAP smear was used to detect ovarian cancer, 50% thought that a vaccine is available to prevent ovarian cancer. All these assumptions are incorrect. 

         Confusion regarding the vaccine is thought to be a result of the high numbers of women who have been immunised against HPV to prevent cervical cancer (90% uptake in Australia).

Darwinian chemo

 

Preventing drug resistance to PARP inhibition in ovarian cancer through novel dosing regimens based on cancer evolutionary dynamics

https://tinyurl.com/yymjfer6

 

         The historical use of chemotherapy has been an attempt at elimination, looking to cure. However, for many tumours including ovarian cancer there is high recurrence rate often associated with resistance to the first-line drug therapy.

         The development of drug resistant cancer may be an evolutionary process with survival of the fittest, being the evolution of a cancer clone to resist chemo. This preliminary report of an on-going PhD project addresses the issue of resistance to PARP inhibition.

         Evolutionary dynamic theory aims to control rather than eliminate cancer, the idea being that stop-start intermittent treatment will prolong the effectiveness of the enzyme inhibition, which is the mechanism of PARPi maintenance, thereby delaying cancer recurrence.

Replicate & Confirm

Real-World Outcomes of Olaparib for Relapsed BRCA Ovarian Cancer Consistent with Previous Trials

https://tinyurl.com/y38jzscg

         

         

      With any new therapy or drug treatment there is a honeymoon period of great enthusiasm and hope. This can be exaggerated by the results of Clinical Trials, which may emphasise positive results and present them in a manner calculated to increase sales.

         Fortunately scientific method assists to determine the true impact of trials by replication and confirmation. This article looks at a real-world study of 128 women with relapsed ovarian cancer who were treated with Olaparib as part of normal therapy and compared the outcomes with the published trial results (SOLO III).

         The SOLO III trial examined the effect of Olaparib treatment for ovarian cancer patients who relapsed after initial chemo and surgery. Its main finding was an improved median Progress Free Survival (PFS) of 30 months compared to 5 months with placebo. For the real-world study the median PFS was 15.5 months.

         Significant side effects were noted with almost 12% of the patients having to discontinue the treatment. The authors suggest the outcomes are consistent with the results of SOLO III.

IVF data shows risk

Early ovarian ageing: are a low number of oocytes harvested in young women associated with an earlier and increased risk of age-related diseases?

https://tinyurl.com/y3xd2cxa

    

     IVF is big business in Australia; one in twenty of all live births are following IVF therapy. There were more than 84,000 IVF cycles in 2018. These cycles are providing data, which is available for other purposes.

         This study looked at the number of eggs harvested during an IVF cycle and determined that a low number (less than 5) was an indicator of early ovary ageing (EOA) and a warning of early menopause.

         Ovarian cancer is mostly a disease of menopausal women; why this is so is unknown. The authors suggest that women who shows signs of EOA should be counseled about increased risk of menopause related disease.

Insomnia changes ovarian cancer risk

Sleep characteristics and risk of ovarian cancer among postmenopausal women

https://tinyurl.com/yx977xa7

 

         This study of almost 110,000 women as part of the Women’s Health Initiative (WHI) looks at sleep patterns and the effect on ovarian cancer incidence. The WHI began in 1991 with a total enrollment of 160,000 women looking at health issues for post-menopausal women mainly cancer, cardiovascular disease, and osteoporosis.

         The findings from the review are that the overall risk of ovarian cancer is unaffected by sleep disturbance. However, the grade of cancer differs between those who describe their sleep as restful or very restful and those who don’t.

         Women with insomnia have a higher incidence of invasive or high-grade serous ovarian cancer. Good sleepers are more likely to have low invasive borderline or low-grade serous ovarian cancer.

WHI

CA-125 survival predictor

Nadir CA-125 level as prognosis indicator of high-grade serous ovarian cancer

https://tinyurl.com/y3c8hxdr

 

         Some patients with High Grade Serous Ovarian Cancer (HGSOC) do better than others. This study looked at whether the serum level of Cancer Antigen 125 (CA-125) post surgery could be a predictor of length of survival.

         CA-125 has been used since 1980 to monitor the progress of patients after initial treatment for ovarian cancer. The lowest measure of CA-125 (Nadir) was recorded for 876 patients and outcomes reviewed, this was a retrospective survey.

         In Australia a serum level of less than 45 units/milliliter (U/ml) is normal. Those patients with lowest serum levels of less than 10 U/ml. after initial surgery had significantly better progress free and overall survivals. This was only true for the initial treatment and did not hold for repeat surgery.

BRCA1/2 MBS & MSAC, alphabet soup

 

Public Summary Document MSAC consideration Application No. 1554

https://tinyurl.com/y6qxtgcn

         Universal health care in Australia is unique; it acts as a funder not a provider with partial rebate of the fee for medical services through the Medical Benefits Schedule (MBS). The funding is always a compromise between what is desirable and what is affordable.

         The eligibility is determined by advice from the Medical Services Advisory Committee (MSAC). There is constant pressure for new funding of advances in technology or therapeutics. Application 1554 relates to genetic testing of ovarian cancer patients. 

         Currently there is funding only for testing of germ line or inherited mutations of the BRCA1/2 gene for patients who have recurrent ovarian cancer. The application sought expansion of testing to include somatic or acquired mutations at the time of initial diagnosis.

         The recommendation is that somatic and germ line testing be combined in one cheaper and quicker new test at the time of diagnosis. This means there is a need to increase funding for PARP inhibitor therapy with more patients being eligible sooner.

Endometriosis is protective

Ovarian cancer prognosis in women with endometriosis. A retrospective nationwide cohort study of 32,419 women.

https://tinyurl.com/y376m5jz

 

         Endometriosis is associated with ovarian cancer; the risk of developing ovarian cancer is put at between 5 and 10%. Often the cancer is of the subtypes endometrioid or clear cell cancer. These cancers present earlier and are commonly unilateral.

         It was thought that women who develop ovarian cancer having previously been diagnosed with endometriosis had better survival rates. This study of the Dutch cancer population revealed 32,000 case of ovarian cancer, 6% had suffered from endometriosis prior to diagnosis.

         Those women who had been endometriosis patients were younger and had more easily resected cancer on presentation. Even after allowing for the bias due to the more easily treated disease, having been diagnosed with endometriosis was protective, with survival being two times better than that of other patients who had not.

Smarter risk reduction

Attitudes towards risk‐reducing early salpingectomy with delayed oophorectomy for ovarian cancer prevention: a cohort study

https://tinyurl.com/yyk5q4k4

 

         Risk reduction surgery is being offered more often to reduce the risk of developing ovarian cancer for women who have a genetic predisposition. The level of risk had been set at 10%, meaning that one in ten women would develop ovarian cancer before the age of 60, now women with only a 5% risk are being encouraged to consider surgery.

         Traditionally the operation performed was bilateral resection of ovaries and fallopian tubes. Because of the loss of fertility and premature menopause there has been a move to a two-stage procedure with initial tube resection and delayed removal of the ovaries.

         This study looked at 683 women all of whom had an increased genetic risk of ovarian cancer and half of them had agreed to risk reduction surgery. Of those who did not have operative therapy approximately 50% said they would find the two-stage procedure acceptable.

         Amongst those women who had agreed to have risk reduction surgery almost 10% of premenopausal women, who had initial complete resection, regretted that choice. 

 

Old technology, new purpose

Detection of TP53 Clonal Variants in Papanicolaou Test Samples Collected up to 6 Years Prior to High-Grade Serous Epithelial Ovarian Cancer Diagnosis

https://tinyurl.com/y2oddycf

 

         The cervical or Pap smear was first described in 1928; the ability to detect pre-cancerous change revolutionized the management of cervical cancer preventing millions of deaths. Now DNA testing of Pap smear cells is being promoted as an aid to early diagnosis for ovarian cancer.

         High Grade Serous Ovarian Cancer (HGSOC) is highly lethal, especially because it presents late.  Most HGSOC develops first in the Fallopian tube. A DNA sequence; TP53 clone is a marker for cancer and the precursor.

         This small study of 17 women with HGSOC looked at Pap smears obtained on presentation and in the years prior to diagnosis. 64% (11) of these patients showed the TP53 clone at presentation. 2 of these women had serial Pap smears prior to diagnosis; the clonal marker was present on all the smears, in one case up to 68 months prior to diagnosis.

 

What price a year of life?

 

 

Economic Evaluation of Population-Based BRCA1/BRCA2 Mutation Testing across Multiple Countries and Health Systems

https://tinyurl.com/y3xjl36s

 

         This recent paper, an analysis of the economic value of BRCA genetic screening of the whole population used the Quality Adjusted Life Year (QALY) as a measure of cost. The QALY measures what price is reasonable for an extra year of life without disease. The amount is indeterminate and varies in different countries.

         Society values a QALY less than an individual; Drug companies when promoting their product usually apply a QALY of about $45,000. Non-commercial health interventions may have two QALYs; the social value at about $20,000, the individual payer $25,000.

         The study used the non-commercial criteria and found that in advanced economies the result from whole of population genetic screening for BRCA was cost saving, meaning the economic justification is sound. 

NHS criteria of cost effectiveness

Trans Man ovarian cancer

Trans social worker promotes gender awareness during virtual cancer care conference in St. John's

https://tinyurl.com/y6bxcw4f

         It is important for health care providers to understand the special challenges faced by trans patients who develop ovarian cancer. As with all patients there are individual requirements with regard to privacy and respect.

         Fortunately there has been great improvement in appreciation of the special needs for these patients, who often have stressful interactions with health care, resulting from their gender dysphoria.

         This article describes the experience of a trans man ovarian cancer patient and his coping strategies and tactics, with a link to his blog site.

https://tinyurl.com/y6g4xqbh

Tall women greater risk

Ovarian Cancer and Body Size

https://tinyurl.com/y4nfatfg

         This review looked at body size and height of women compared to their risk of ovarian cancer. All available literature was examined with more than 25,000 women who had ovarian cancer compared to more than 81,000 women who did not.

         The risk of developing ovarian cancer increased significantly with height and body mass index (BMI) changes. The elevated relative risk was 1.07 for each 5cm increase in height above 160cm.

         The effect of a rise in BMI was different for women who had previously had hormone replacement therapy (HRT) compared to those who had not. For women who had not had HRT,  the increased risk of ovarian cancer for every 5kg/m² above normal in BMI, was 1.10. Those women who had previously had HRT showed no change in risk of ovarian cancer despite elevation of the BMI.

         The authors note that because of better nutrition, women everywhere are growing taller, this could increase ovarian cancer incidence by 3% per decade.

HRT improves survival

Menopausal hormone therapy prior to the diagnosis of ovarian cancer is associated with improved survival

https://tinyurl.com/y945wwo6

         This multi-centric study from Europe, North America and Australasia looked at more than 6000 women who had been diagnosed with ovarian cancer. The use of hormone replacement therapy prior to diagnosis and the survival were measured.

         The type of hormone therapy; whether oestrogen only or combined oestrogen/progesterone was recorded. The duration of the hormone replacement was also available.

         The results show that taking both oestrogen only or combined therapy, for 5 years or more before diagnosis, improved survival by 20%.

Exercise is good

Physical activity and exercise in women with ovarian cancer: A systematic review

https://tinyurl.com/y9pb2va8

         The evidence is that exercise and physical activity is beneficial for cancer patients. This review from Queensland Australia looked at the amount of physical activity women took after diagnosis of ovarian cancer and the outcomes. 

         The available literature was reviewed; most women reduced the amount of exercise after diagnosis. Those women who returned to pre-diagnosis levels of exercise, or increased their activity, reported higher quality of life and less anxiety and depression.

         The authors suggested that measures to improve physical activity and encourage participation would result in better outcomes for ovarian cancer patients. A controlled trial is appropriate to confirm this.

A logical fallacy

Statins could reduce ovarian cancer risk by 40 per cent

https://tinyurl.com/y9u2l7xr

         There has been a recent beat-up in the media with a suggestion that statins drugs may reduce ovarian cancer. This statement appears to be a false premise or logical fallacy.

         Statins are one of the most commonly prescribed drugs, with almost 30% of the American adult population taking statins to reduce the risk of coronary artery disease. Statins reduce circulating lipoproteins by inhibition of a co-enzyme; in addition there is a side effect of increased cell death, which may have some protective effect against cancer.

         A recent article* states that women who have a genetic deficiency of the same co-enzyme have a 40% decreased risk of developing ovarian cancer. The study has been misinterpreted in that taking oral statins would have the same effect. This is yet to be proved.

*  https://tinyurl.com/ycbh2goe