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Clinical Trial Predictors

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Perceived Burdens Predict Patients’ Withdrawal From Cancer Trials https://tinyurl.com/yd2h5dnc            Part and parcel of the search for improved treatment of cancer is the Clinical Trial. Recruiting suitable patients for trials and retaining them is problematic. This study looks at why recruits join trials and seeks to predict which of these will leave the trial early.          The result showed that the likelihood of completing the trial depended on a balance between the benefits of the trial compared to the burden of participation. The benefits reported included access to medication not otherwise available, better interaction with carers, feeling good about helping others, and possible cure. The burdens of clinical trials were listed as; possible placebo treatment, lifestyle disruption, and drug side effects.          When asked prior to trial...

Super survivors

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The genomic and immune landscape of long-term survivors of high-grade serous ovarian cancer   https://tinyurl.com/mvn36kwe            It is somewhat of a paradox that the BRCA1/2 gene, which increases the risk of ovarian cancer also is found to be protective, in that women who carry this gene sometimes are super survivors.          This study looked at the genome of 60 women with advanced ovarian cancer who had survived 10 years or more. Whole genome sequencing showed that these women were more likely to have genetic mutation resulting in DNA repair deficiency.          Other genetic differences included amplification of cyclin E1 and suppression of a gene; RB1.  Normally both these genetic changes would have adverse effects, however in combination with BRCA positive status survival is sometimes enhanced. Reasons as to why this is so ...

Cost of cancer

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Societal costs of ovarian cancer in a population-based cohort – a cost of illness analysis   https://tinyurl.com/5n89v4zm             It is often forgotten that the impact of ovarian cancer is greater than the immediate consequences of the disease. This population-based study looked at the direct and indirect costs to society resulting from ovarian cancer, for 283 women with ovarian cancer.          Direct costs are the price of medical care. Indirect costs are the result of loss of earnings and opportunity for the patient and their carer.          Results from the survey showed that during the 6 year period after diagnosis the total cost per patient was about €200,000 or €30,000 each year. The cost per year decreased with longer survival. These patients pre-dated the development of precision therapy with PARPi. It is encouraging to realise tha...

Predicting Survival

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Validation of the KELIM score as a predictor of response to neoadjuvant treatment in patients with advanced high grade serous ovarian cancer https://tinyurl.com/4vebw3w8            One of the many unresolved questions about ovarian cancer is; why do some women survive better than others? This study suggests that an objective measurement of the rapidity of response to chemo may provide a guide as to who will do well.          As part of the standard care for high-grade ovarian cancer, most women have chemotherapy before surgery, known as neoadjuvant therapy (NACT). . The response to NACT is measured by the reduction of the CA125 antigen; this is elevated in about 90% of epithelial ovarian cancers.          A retrospective trial for 217 patients with ovarian cancer showed that the rate of elimination of CA125 (KELIM) from serum is related to survival....

Care for all

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Improving LGBTQ+ Inclusivity in Ovarian Cancer Care https://tinyurl.com/yx5schcr            Equity and inclusion are fundamental for good health care. It is clear that there is bias against the diverse LGBTQ+ community in cancer care and also a perception by members of the community that they will be discriminated against when they seek medical assistance.          This article by the CEO of the world ovarian cancer coalition seeks to address these issues. Education is needed to explain that the use of oral contraceptives, pregnancy and breast-feeding are protective against ovarian cancer. Non-heterosexual women are therefore disadvantaged. Risk reduction surgery may be appropriate, but needs careful discussion and understanding.          Failure to include diverse minority groups in cancer research, most notably in the design of clinical trials, is...

Recurrence pre-determined

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DNA methylation and transcriptomic features are preserved throughout disease recurrence and chemoresistance in high grade serous ovarian cancers https://tinyurl.com/4yvhprf7            Progress in the treatment of ovarian cancer is slow and often occurs in small steps. This study uses whole genome data to show the genetic signature of ovarian cancer is unchanged after recurrence.          Previously it was thought that recurrence of ovarian cancer is due to resistance to chemotherapy, as a result of a yet to be described genetic mutation. This small study suggests that this is not the case.          Whole genome sequencing was obtained from 28 women, with data before treatment and after recurrence.. No change likely to cause resistance was detected; suggesting that resistance and recurrence of ovarian cancer is pre-determined at presentation. As who...

Pumping iron, dubious benefit

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Independent and joint associations of weightlifting and aerobic activity with all-cause, cardiovascular disease and cancer mortality in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial   https://tinyurl.com/bdzkstr9            Often data obtained from one trial has other uses. The Prostate, Lung, Colorectal and Ovarian Cancer screening trial (PLCO) involved 1.5 million people, over a period of 13 years, with the aim of demonstrating the benefit of screening. No survival benefit for ovarian cancer was found.          Analysis of the data continues, it is seen that moderate to vigorous physical exercise is associated with a significant (32%) lower risk of all-cause mortality. Adding weight training to the exercise routine did not significantly improve the benefit.          Although the exercise routines improved overall mortality...

Maybe no surgery?

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  Measure of CA-125 Elimination May Guide Interval Debulking Surgery Selection in High-Grade Serous Ovarian Cancer https://tinyurl.com/mpwbajh2            Change in treatment for cancer often occurs when conventional treatment protocols are challenged. Ovarian cancer survival is  determined by the completeness of initial surgical excision. It is now usual for this surgery to be preceded by chemo in a procedure called neoadjuvant therapy (neo).          This article looks at whether all patients who have neo need to have surgery, measuring the speed at which the marker; CA125 is eliminated, shown by testing blood serum. The rate of elimination is called KELIM, the patient group (254 women), fell into two groups those who had high KELIM (90 women, i.e. good responders), and those who did not.          For patients with high KELIM, debulking ...

Chemo makes you deaf

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Common Chemotherapy Drugs Seem to Increase Hearing Loss in Adults https://tinyurl.com/mr48a9jd            One of the more significant side effects of chemo is neuropathy. Peripheral neuropathy with loss of function and pain is well recognised and may be an inevitable consequence of chemotherapy as part of the initial treatment of ovarian cancer.          Less well recognised and often not considered is cranial neuropathy, where the cranial nerves are damaged. For the auditory nerve this damage presents as hearing loss and often tinnitus.           Data from a study looking at survivors of cancer who had chemo found that 70% had significant hearing loss, with hearing below the 50 th  percentile for any frequency. Similarly 40% reported tinnitus with ringing in the ears for longer than 10 minutes. Despite the high incidence of hearing loss o...

Drug resistance

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Genomic and epigenomic BRCA alterations predict adaptive resistance and response to platinum-based therapy in patients with triple-negative breast and ovarian carcinomas https://tinyurl.com/5xw4248z            One of the unsolved issues in ovarian cancer is why some patients are resistant to the normal chemotherapy regime. This article suggests that epigenetic alteration may be a cause.          Epigenetic change occurs when chemical effects such as methylation cause structural deformity to DNA. The effects of this change to the BRCA gene are similar to mutation. Both groups with BRCA alteration, either due to mutation or epigenetics, have a good response to chemo.          Exposure of the epigenetically changed BRCA gene to platinum chemo may cause reversal to normal BRCA status. It is suggested that adaption to the effects of chemo in this way can...

Does side matter?

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Exploring the prognostic impact of tumor sidedness in ovarian cancer: A population-based survival analysis of over 10,000 patients   https://tinyurl.com/247uyffd            For some cancers the side of origin makes a difference in survival. The side of presentation for instance, affects Colon cancer, with left sided tumours having better survival. Differences in genetic and physical factors account for the side variation in colon cancer.          This study looks at a large number of women who have ovarian cancer and explores the impact of which side of the abdomen is affected. Data from the SEER public database provided information about more than 10,000 women who had ovarian cancer during the period, 2004 through to 2017.          Of these women about 26% had bilateral cancer at presentation, the remainder had an equal distribution between ri...

Leak prediction

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OVA-LEAK: Prognostic score for colo-rectal anastomotic leakage in patients undergoing ovarian cancer surgery   https://tinyurl.com/2apaxd4t            One of the more devastating consequences of surgery for ovarian cancer is post-operative leakage of bowel content from an anastomotic site. This complication has a mortality of about 3%.          A strategy for avoiding this complication of difficult surgery is to perform a bowel diversion in the form of an ileostomy as part of the initial surgery. It is however difficult to predict which patients will be liable to post-operative leak. An application; OVA-LEAK, accessible via the web has been developed to predict which patients should be managed in this way*.          This study looked at the value of the OVA-LEAK score with a comparison to the standard clinical assessment of those patients requi...

Could COVID increase ovarian cancer risk?

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Are female-specific cancers long-term sequelae of COVID-19? Evidence from a large-scale genome-wide cross-trait analysis https://tinyurl.com/mvdfnx9r             Could the pandemic result in more ovarian cancer in the future?  Previously an association of cancer with viral infections has been noted especially involving the liver cervix and lymphomas. It is suspected that up to 10% of all cancer is associated with a previous viral infection.          This begs the question, “Will COVID-19 infection do the same”? Obviously the pandemic is too recent for long-term effects to be apparent. However, it is possible to look at the genetic variants resulting from the infection and speculate about the consequences.          One of the commonest genetic variations is a Single Nucleotide Polymorphism (SNP), where a single change in the DNA code has oc...

Good intentions

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Patient and Clinician Decision Support to Increase Genetic Counseling for Hereditary Breast and Ovarian Cancer Syndrome in Primary Care   https://tinyurl.com/3rznxyer            Much ovarian cancer occurs as a consequence of an inherited genetic mutation, with about 20% being associated with BRCA1/2 variants. Screening for this mutation has the potential to reduce the prevalence of ovarian cancer through risk reduction surgery. It is recommended in the US that asymptomatic women should be screened. Many women especially in minority ethnic and racial groups are not screened with resultant health disparity and poor clinical outcomes.          This prospective Randomised Clinical Trial looked at the benefit or not of providing a Decision Aid to women and a Navigation Tool to clinicians regarding genetic screening as an attempt to increase the number of women receiving screening. 190 women we...

Gloomy facts

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The global burden and associated factors of ovarian cancer in 1990–2019: findings from the Global Burden of Disease Study 2019   https://tinyurl.com/4ceyypnr            Starting in 1990, the Global Burden of Disease Study (GBD) aims to understand the epidemiology of health challenges to people across the world in the 21 st  Century. This article looks at the data obtained about ovarian cancer during the most recent GBD 2019 with correlation to known risk factors.          Findings from the GBD show ovarian cancer is increasing worldwide with the number of new cases and deaths from ovarian cancer increasing by more than 100% when compared to the first GBD in 1990.          Age-standardised rates of disease however did not change suggesting the increase may be due to population growth and ageing. More ovarian cancer is seen in high Social De...

Aspirin protects

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Modification of the Association Between Frequent Aspirin Use and Ovarian Cancer Risk: A Meta-Analysis Using Individual-Level Data From Two Ovarian Cancer Consortia https://tinyurl.com/yc3ec597            Previously it has been thought that regular aspirin use would reduce the risk of developing ovarian cancer by reducing inflammation. Through the databases of the Ovarian Cancer Association Consortium and the Ovarian Cancer Cohort association it has been possible to assess the aspirin usage for 8326 women with ovarian cancer and compare to normal women.          Findings from the analysis showed frequent aspirin use (6 days or more each week) was protective. Those women had a 13% less risk of ovarian cancer.          Protection with aspirin use was seen for all women with varying known risk factors except for endometriosis associated cancer, which wa...

Covid impact

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The Impact of COVID-19 Infection During the Postoperative Period After Surgery for Ovarian Cancer https://tinyurl.com/3ntra3r6            During the worst period of the pandemic the demand for hospital care caused other medical procedures to be delayed. Also, ovarian cancer patients who contracted Covid-19 infection could not be admitted to acute care hospitals due to concern about cross infection.          This small study looks at the immediate post-operative status of 12 women with ovarian cancer who had the misfortune to have been infected with Covid-19 and had their surgery delayed. The outcomes for this group were compared with a similar number of women who had ovarian cancer but not Covid-19.          There were no pre-operative differences seen between the two groups. Women who had Covid-19 on average waited 6 weeks longer after becoming vir...

Bugs everywhere

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An evaluation of the microbiota of the upper reproductive tract of women with and without epithelial ovarian cancer   https://tinyurl.com/2y75pnry            In the quest for knowledge about the cause of ovarian cancer there is great interest in the role of inflammation and infection. Previously it has been supposed that the ovaries and tubes were sterile. It is now known that there is a normal bacterial population (microbiota) and the importance of this is becoming clear.          For this prospective study 25 women who were scheduled to have resection of the ovaries and tubes gave consent for microbiological examination of the specimens. Women were excluded from the study if they had received antibiotics or were known to have cervical or uterine cancer. Contamination was avoided.          Results from the study showed two women with previousl...

More MMR

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The prevalence of mismatch repair deficiency in ovarian cancer: a systematic review and meta-analysis   https://tinyurl.com/2jn8v8ar            One of the many disappointments in the treatment of ovarian cancer has been the failure of immunotherapy.  For other cancers, most significantly melanoma, immune therapy in the form of checkpoint inhibition with drugs such as Keytruda has been game changing.  Thus far this has not been true for ovarian cancer.          Checkpoint inhibition is most effective for cancers with defective DNA repair mediated through a process called Mismatch Repair deficiency (MMR).  Some ovarian cancer demonstrates MMR.          This study looks at all the available published information to determine the prevalence of MMR.  Results from the review show MMR to be most likely for women...

Case closed

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Weekly Dose-Dense Chemotherapy as First-Line for Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer https://tinyurl.com/4863ea92             The final report of the ICON-8 trial closes the debate as to whether weekly chemo is more effective than the standard chemo.          A clinical trial in 2008 involving Japanese women (JGOC 3016) reported a survival benefit for women with ovarian cancer whose chemo frequency was increased from the normal one dose every three weeks to a weekly dose regimen.      Some doubt about the benefit for the general population remained and a large clinical  trial involving 1566 patients (ICON-8) began in 2011, with random allocation to either standard or weekly chemo. The final results are now available. There is no survival benefit for non-Japanese women. Adverse side effects were commoner with weekly chemo.

Salvage issue

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Hematological disorders after salvage PARPi treatment for ovarian cancer: cytogenetic and molecular defects and clinical outcomes https://tinyurl.com/2e84hn5 p          When ovarian cancers recur in the first 6 months after standard treatment it is generally accepted that there is a need for exceptional or salvage therapy. Usually the salvage treatment course involves repeat chemotherapy, with PARP inhibitors being added or recommenced.          It is becoming clear that this approach to platinum resistant ovarian cancer is simplistic and that these patients have special needs and are liable to significant adverse effects from therapy, meaning platinum chemo and enzyme inhibition may be harmful.          This study looks at 182 women who commenced salvage therapy and recorded the high risk of hematological disorders. 16 of the women developed marrow canc...

Crossed lines

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  Locomotive syndrome in cancer patients: a new role of orthopaedic surgeons as a part of comprehensive cancer care https://tinyurl.com/2nyunrzp            Sub-specialisation in medical care has lead to great benefits for patients but also causes problems when loss of skills and litigation anxiety results in non-availability of essential care. This is especially true for orthopaedic surgeons who have almost completely removed themselves from cancer care with all patients being referred to a small group of sub-specialists.               Cancer patients frequently have need of orthopaedic surgery when fractures occur either as a result of bone metastasis or osteoporosis. There are far too many cases for sub-specialty referral but many general orthopaedic surgeons are loath to accept cancer patients.          This article ...

Vitamin D might help

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Peritoneal restoration by repurposing vitamin D inhibits ovarian cancer dissemination https://tinyurl.com/5n7uc2ve            Much attention is currently centred on the changes that occur when ovarian cancer metastasises to the peritoneum. A process called epithelial-mesenchymal transition is involved; this results in loss of organisation of the cancer, with consequent escape of primitive cells into the peritoneal space. From these primitive cells metastases occur.          Research such as this in vitro study looks at possible causes for and possible restoration of the transition. It has previously been shown that Vitamin D therapy reduces cancer mortality. One of the effects of vitamin D is to promote cell adhesion and thereby limit escape. Also, Vitamin D acts through gene regulation to reduce transition.          This small research project on t...

Synchronous cancer

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Co-existence of breast and ovarian cancers in BRCA germ-line mutation carriers   https://tinyurl.com/2f5hy6aj            Mutation of the BRCA genes is known to predispose to women having either breast or ovarian cancer, sometimes both. There is limited previous information about the cause and effect of synchronous breast and ovarian cancers, one study suggesting about two thirds of those women affected are BRCA positive.*          This small retrospective study looks at 6 women with both cancers, with greater detail about one case suggesting the possibility that the ovarian cancer could be a distant metastasis of a primary breast cancer.          It is apparent that women unfortunate enough to have both ovarian cancer and breast cancer during their lifetime should prompt genetic screening of close relatives. *   https://tinyurl.com/msn2jyb...