PARPi for whom

Deleterious somatic variants in 473 consecutive individuals with ovarian cancer: results of the observational AGO-TR1 study (NCT02222883)

https://tinyurl.com/26f5s3dz

 

         Personalised or precision therapy for ovarian cancer is becoming more common, with some genetic mutations being responsive to new treatments such as PARP inhibitors. 

         There is pressure to make these new drugs available to a larger group of patients. Unfortunately the cost means that a “try it and see” approach is not feasible. This prospective review of 473 non-selected ovarian cancer patients looks at their genetic status seeking to determine the real incidence of these mutations.

         Of these women, who presented consecutively at one centre of excellence with ovarian cancer, 26.4% were suitable for precision drug treatment. Most (20% of the total) were BRCA1/2 positive; the remainder usually non-epithelial subtype ovarian cancers had other susceptible ovarian cancer predisposition genetic mutations. The commonest mutation; P53 which is seen in up to 90% of all ovarian cancer was excluded from the study as no precision therapy is currently available for this group.

Biome matters

Ovarian cancer and the microbiome: a complex relationship

https://tinyurl.com/2p96bvwj

 

         Ecological causes for cancer and other diseases are big news. Discoveries of peptic ulceration following bacterial infection (H. pylori) and the possible elimination of cervical cancer by immunization against papilloma virus were groundbreaking. Maybe ovarian cancer will be next?

         Bacterial colonization of the body is known as the biome. Normally the biome of the vagina is very stable with predominance of lactobacillus species (usually L. crispatus). Previous studies have shown that when the bacterial population is changed, premature labour is more likely.

         Cervical smear samples from young women with BRCA mutation are less likely to show a stable lactobacillus biome. Current research is looking at the biome as a marker for increased ovarian cancer risk, and also to determine whether infection of the fallopian tube may be a stimulus for pre-cancerous change.

Surgeon/Patient mismatch

Association of Surgeon-Patient Sex Concordance With Postoperative Outcomes

https://tinyurl.com/yvsywx4k

 

         Sometimes research is astonishing. This study, which looks at the outcomes after surgery for women who have a male surgeon, is one such. Outcomes for those women are worse than for similar operations performed by female surgeons.

         Data was obtained from a large number of patients (more than 1 million), who had one of the common surgical procedures during the period 2007-2019. Of those patients, about half had surgeons of the opposite sex. Criteria for adverse results from surgery included death, readmission, or complication within a 30-day period following the surgery.

         Results from the data analysis show significantly increased risk of death or complication for those women who had a male surgeon. Interestingly there was no increased risk for men treated by female surgeons. As the authors say,  “Further work should seek to understand the underlying mechanism”.

Coffee and cancer

Lifetime caffeine intake and the risk of epithelial ovarian cancer

https://tinyurl.com/2p8zbvbd

         Caffeine has bad press. Studies have suggested that caffeine may exacerbate various conditions including, diabetes, osteoporosis, hypertension, bleeding disorders, and schizophrenia. Previously a link with ovarian cancer has been suggested. This retrospective study seems to disprove the suggestion.

         Total lifetime caffeine consumption was calculated for 497 women with ovarian cancer and compared to 904 women who did not. Only a very few of each group did not consume caffeine either in coffee, tea or cola. Patterns of caffeine consumption were similar for both groups.

         Risk assessment showed that overall; those women who had the highest caffeine intake did not have any increased risk. It was noted that pre-menopausal women who were high caffeine consumers did have an increased risk. However, this is a small number of women and may be a coincidence.

BRCA +ve screening

The challenging screen detection of ovarian cancer in BRCA mutation carriers adhering to a 6-month follow-up program: results from a 6-years surveillance

https://tinyurl.com/2p84ht3d

 

         For many women who discover they carry either the BRCA1 or BRCA2 mutation, risk reduction surgery is appropriate. For others a screening program aimed at early detection of ovarian cancer is the best course. It is not known how effective these screening programs are.

         This prospective study records the six-year outcomes for 191 women who were found, in 2015, to carry the BRCA mutation. Screening tests done were, 6 monthly CA125 serology and pelvic ultrasound investigation. 58 of the women chose to have risk reduction surgery and were excluded from follow up.

         From the remaining 138 women, 9 cancers were diagnosed, all screen detected, mostly in BRCA1 individuals. All but one of the cancers were early, (stage I/II). CA125 serology alone was not sufficient to detect all these cancers. Screening of women who are BRCA +ve may be expensive but it is essential.

Ultimate fate

Long-Term Survival Among Histological Subtypes in Advanced Epithelial Ovarian Cancer: Population-Based Study Using the Surveillance, Epidemiology, and End Results Database

https://tinyurl.com/8udkpevw

 

         Information about the ultimate fate of long-term survivors after ovarian cancer is scarce. This retrospective study looks at a large number of women and matches their outcome to the type of ovarian cancer

         Data for more than 8000 women with stage III/IV ovarian cancer was collected from the SEER database. All these women were diagnosed during the period 2000-2014 and had survived 5 years or more after initial diagnosis.

         Despite their long-term survival, most of these women (80%) died from ovarian cancer, particularly the serous epithelial subtypes. For other subtypes it is less likely that women will die from ovarian cancer, with mucinous, endometrioid and clear cell cancer patients being half as likely to die from ovarian cancer. Other causes such as different cancers or cardiac disease become more important.

Live long

Conditional Relative Survival of Ovarian Cancer: A Korean National Cancer Registry Study

 

https://tinyurl.com/8t4h8eht

 

         It has been long thought that the chances of survival with ovarian cancer increase with time after initial diagnosis. This study, from Korea, provides an objective measure of how significant this improvement is.

         Retrospective review of almost 300 thousand women with ovarian cancer, of whom about two thirds died, showed that the most dangerous period was the first year; when about 12% of patients die. All the women were diagnosed during the period 1997-2016 .

         For each year after the first the odds of 5 years survival increase; from 61% initially to 84% after 5 years. Survival is longer in Korea than Australia due to the different mix of ovarian cancer, with endometrioid and clear cell cancer being more common. Knowing this will be useful in counselling women with ovarian cancer that, “Yes, things do get better”. 

A quiet death

Physician Variation in End-of-Life Care Among Women With Ovarian Cancer

https://tinyurl.com/2sydhrrz

 

         Ovarian cancer patients who are terminal should have access to a dignified and controlled death. So, why is this rarely the case? Sometimes the patient is unwilling to accept the inevitable and wishes to continue active treatment. More often this is physician driven.

         This retrospective study looked at Medicare benefits for more than 6,000 women during the period 2000-2016. These women were all aged more than 66; they had end-stage ovarian cancer.

         More than half of these women had aggressive end-of life treatment, with failure to start Palliative Care, admission to an ICU, an invasive procedure and chemotherapy during the last two weeks of life being the commonest. Analysis of the data showed a cluster of inappropriate care limited to some physicians. It is suggested that education of treating physicians would be the most effective means of improving end-of-life care.

A survivor. Why?

Attributions of survival and methods of coping of long-term ovarian cancer survivors: a qualitative study

https://tinyurl.com/4336wckr

 

         Surviving ovarian cancer is the exception, not the rule.  Which means that those who do survive are worthy of study, looking for practical and emotional routines that may be helpful to others.

         Ten-year survival is even more exceptional, with about 8% of Stage IV ovarian cancer patients living this long after diagnosis. This study looked at 22 women, trying to establish common strategies or tactics. Because of the scarcity of long-term survivors, the study is small and biased towards the white and wealthy.

         Unsurprisingly there was no feature common to all the women. A small number (5 of the 22) thought they were just lucky, none felt guilty. For those who had faith, it usually strengthened. A large majority (19 of the 22) attributed their survival to expert medical care. Many adopted a positive attitude to their adversity and made life-affirming choices, with changes to diet and exercise, to exclude negative feedback and seek control through greater knowledge.

 

PARPi, who benefits?

Homologous Recombination Deficiency Assays in Epithelial Ovarian Cancer: Current Status and Future Direction

https://tinyurl.com/2pbwkmxm

         Sometimes progress in the care of patients with ovarian cancer seems painfully slow. Then new understanding begins to show a way forward. One such innovation was the appreciation that much cancer starts due to a failure of repair in the DNA that makes up the cell nucleus. Cellular DNA is under constant attack from within and without. If DNA is not repaired cells will usually die but sometimes the cell line continues as a cancer.

          Faulty DNA repair, known as Homologous Recombination Deficiency (HRD) is seen with BRCA1/2 mutation and sometimes with other acquired mutations, being present in about 50% of all ovarian cancer. As a consequence another enzyme; Polyadenosine Ribonucleotide Polymerase (PARP) becomes more important in DNA repair. Repair by PARP is less exact and sometimes may  prolong cancer, a concept known as synthetic lethality.

         This understanding of the biology of ovarian cancer has led to new treatment with drugs that inhibit PARP (PARPi). Up to 40% of patients with BRCA mutation do not respond to PARPi. So, better testing for HRD is needed. Currently the HRD status of individuals is inferred from the mutation. Unfortunately this does not predict PARPi response. An HRD test hopefully will better show who will benefit from PARPi

Embryo Selection

Pre-implantation genetic testing for BRCA gene mutation carriers: a cost effectiveness analysis

https://tinyurl.com/evhm49d2

 

         For some communities ovarian cancer is a real and constant threat, none more so than for the Ashkenazi in Israel. Ovarian cancer is related to an inherited condition in about 25% of cases. The Ashkenazi have a high incidence of BRCA1/2 mutation, which increases the likelihood of developing ovarian cancer compared to the general population.

         One strategy for avoiding ovarian cancer and the common fatal consequence is by prevention through pre-implantation genetic screening and selection of embryos, as part of In Vitro Fertilisation (IVF). This study seeks to determine the cost-effectiveness of doing this for parents who carry the BRCA1/2 gene.

         Cost-effectiveness is routinely determined as a measure known as the Quality Affected Year (QALY), meaning the value of a year without disease. Most advanced economies put the acceptable cost at a QALY of around $US 40,000. Results from the study suggest a QALY cost for the IVF embryo screening strategy at $US 44,000. This may be acceptable for small high-risk communities such as the Ashkenazi.

 

Neo facts

Association Between Overall Survival and the Tendency for Cancer Programs to Administer Neoadjuvant Chemotherapy for Patients With Advanced Ovarian Cancer

https://tinyurl.com/6cmpxrby

         Any treatment protocol needs constant reappraisal. Neoadjuvant chemotherapy (Neo) is the use of chemo for ovarian cancer patients before surgery, at the time of initial presentation. First used for patients who were either too frail or had too big a tumour for surgery, Neo has become more frequent.

         Previous studies in 2010 showed no disadvantage in survival. Neo is often preferred because the subsequent surgery is more straightforward with fewer complications. Also logistically it make scheduling surgery simpler. Although generally there has been an increase in the use of Neo, some treatment centres have not done so.

         This retrospective study looks at 20,000+ patients from 300+  centres during the period 2004-2015. No difference was seen in overall survival between centres which increased Neo compared to those that did not. The mortality at one year was less in centres where Neo use increased.

 

Choice of surgeon

Impact of Surgeon Type and Rurality on Treatment and Survival of Ovarian Cancer Patients

https://tinyurl.com/7y2arz8j

 

         Choose your surgeon carefully. Any woman unlucky enough to have ovarian cancer requires surgical removal. This is best done in a centre of excellence, preferably by a surgical oncologist. Unfortunately this is not always possible.

         675 women with advanced ovarian cancer from Iowa were included in this study. Of these women, those living in non-urban locations were less likely to have their surgery by a surgical oncologist and also less likely to have complete surgical clearance and to follow the usual chemotherapy regime.

         Not surprisingly women who did receive care in a centre of excellence had better outcomes. Survival for these women was increased, being 40% more likely to survive 3 years, compared to women from non-urban environment that did not access the best care. Although not mandatory, surgical oncology medical care does confer an advantage.

Take the tubes

Ovarian Cancer Incidence and Death in Average-Risk Women Undergoing Bilateral Salpingo-Oophorectomy at Benign Hysterectomy

https://tinyurl.com/y3t5jkj8         

         “Prevention is better than a cure”. This certainly seems to be the case for ovarian cancer, which despite progress in therapy remains a highly lethal condition. One suggestion for prevention of ovarian cancer is that any woman who has a hysterectomy should have removal of the fallopian tubes and ovaries at the same time.

         It is thought that most ovarian cancer starts in the tubes.  One in five women will have a hysterectomy during their lifetime. Previously there has been little hard evidence about the benefit from tube and ovary removal. 

         This retrospective review of almost 200,000 women who had a hysterectomy, in Ontario, during the period 1996-2010, looked at the incidence of and death from ovarian cancer.  25% of those women had tube and ovary removal at the time of hysterectomy. Results from the review confirmed that the women who had the tubes and ovaries removed had about 70% reduction in the risk of developing and dying from ovarian cancer, with even better outcomes when done before the age of 50.

Emergencies best avoided

Patients with low socio-economic status are more likely to present for non-elective Ovarian Cancer surgery

https://tinyurl.com/j2dv32a7

         Survival for women with ovarian cancer is dependent on the quality of care provided. One of the most significant markers of better care is the completeness of surgical clearance at the initial surgery. Obviously there will be a better chance of this when the surgery follows careful pre-operative planning.

         Sometimes this is not possible and many women present with complications of ovarian cancer requiring immediate emergency surgery. This retrospective survey looked at about 100,000 women in the US who had surgery for ovarian cancer during the period 2010-2015. Of these women, 19% were emergencies.

         Those women who needed emergency care had higher mortality (2.7% vs. 0.6%), longer hospital stays, and more post-operative complications. The non-elective surgery group had lower incomes, were younger, with more co-existing disease shown as marked weight loss, diabetes and cardiac failure. Surgery for urgent cases was often incomplete without pelvic clearance or lymph node sampling.

Toxic means effective

Adverse Events as a Potential Clinical Marker of Antitumor Efficacy in Ovarian Cancer Patients Treated With Poly ADP-Ribose Polymerase Inhibitor

https://tinyurl.com/vcwbxxn4

 

         For cancer patients undergoing chemotherapy adverse reactions are part and parcel of the treatment. Previous studies have shown that patients who have adverse effects early on (within one week) have better response to the treatment. This study looks at PARPi treatment for ovarian cancer and notes a similar outcome.

         PARPi drugs are a targeted chemotherapy for ovarian cancer patients. Most if not all patients taking PARPi drugs have adverse effects. 10-15% of the patients cannot complete the course due to significant toxicity, with marrow suppression, nausea, and fatigue being common.

         Results from this small prospective study (78 women) confirmed that an early adverse response did improve the outcome. In addition those women who developed anaemia during the first 4 weeks of treatment, suggesting marrow suppression, had better progress free survival, with a median of 30 weeks compared to 20 weeks for those not anaemic.

Hidden benefits

Clinical and pathological outcomes of risk-reducing salpingo-oophorectomy for Japanese women with hereditary breast and ovarian cancer

https://tinyurl.com/jyusbsvx

 

         Increasingly women with a greater genetic risk of developing ovarian cancer are encouraged to have risk reduction surgery. For these women it is important to understand the risk-benefit ratio. Another benefit apart from prevention is early detection of cancer.

         In the study 117 women with either BRCA1 (72) or BRCA2 (45) mutations had MRI scan followed by elective surgery one month later. The surgical specimens were examined for cancerous change. Most ovarian cancer arises from the fallopian tube with a precursor condition known as Serous Tubular Intraepithelial Carcinoma (STIC).

         At surgery three STIC lesions were found and three stage I invasive carcinomas. All pre-operative MRI scans were normal. It is suggested that the study shows another benefit of risk-reduction surgery; enabling early diagnosis of malignancy in 5% not otherwise detectable.

 

False hopes

Immune checkpoint inhibitors in ovarian cancer: where do we stand?

https://tinyurl.com/hrcvufkb

 

         When a new treatment for cancer is found, women with lethal ovarian cancer often have their hopes raised. Checkpoint inhibition is one of these new forms of treatment. First used in the management of melanoma, Pembrolizumab (Keytruda) has radically changed the outcomes for many melanoma and lung cancer patients by “curing the incurable”.

         Unfortunately despite multiple trials of Keytruda and similar formulations, both alone and in combination, no benefit in terms of improved survival for ovarian cancer has been shown. This review looks at how checkpoint inhibition works and what the prospects are.

         All cells die. Some cancer cells slow the rate of cell death by blocking the T cell immune response, through a checkpoint. It seems that ovarian cancers do not induce T cell checkpoints. The authors conclude that there is likely to be no benefit in using checkpoint inhibition for ovarian cancer.

Don't forget the diet

The Effect of Nutrition Intervention With Oral Nutritional Supplements on Ovarian Cancer Patients Undergoing Chemotherapy

https://tinyurl.com/3c4crv6w

 

         Women unlucky enough to have ovarian cancer are frequently mal-nourished. Previous studies have shown that at the time of diagnosis only about 10% are well nourished. Reasons for this include, peritoneal metastases with leak of protein to ascitic fluid, loss of appetite, nausea and vomiting, and sub acute bowel obstruction.

         This study looks at whether oral food supplement can improve the nutritional status of these women. By random allocation, a group of 60 women with ovarian cancer were divided into two groups; those who received supplement and those who did not. Assessment of nutritional health used the Patient Generated Subjective Global Assessment format, which records weight, function, intake and symptoms. 

         Results from the study were linked to biochemical and haematological data. It shows that a simple intervention with oral food supplement can have a significant beneficial effect. Further investigation, to determine whether improved nutrition results in improved outcomes, is warranted.

Male partner issues

Fear, worry and sadness: an exploratory study of psychological wellbeing in men caring for their partner with ovarian cancer

https://tinyurl.com/nh9dbxc

 

         It is often forgotten that ovarian cancer is not just a disease for the patient. Family, friends, and caregivers for women with ovarian cancer all are affected to a lesser or greater degree. For many women their male partner becomes the caregiver.

         That women with ovarian cancer frequently develop psychological stress is well known. There is little information about how men, whose partners have become patients, are affected. This small study sought responses from 36 male caregivers, with assessment of anxiety and depression. 

         Results from the study suggest excessive anxiety about the future, the relationship, and recurrence, with many caregivers being clinical depressed due to seemingly inevitable progression. The authors suggest that psychological damage is common with ovarian cancer. Health care providers should be aware of this and look to support the extended contact group.

Is diagnosis delayed?

Factors impacting the time to ovarian cancer diagnosis based on classic symptom presentation in the United States

https://tinyurl.com/4wwbbaxe

 

         Delay in diagnosis is said to be common in ovarian cancer. There is little scientific evidence for this claim. One factor, said to be implicated in the delay, is the vague nature of symptoms. 

         This retrospective study looked at almost 14,000 women with ovarian cancer. Data obtained from Medicare claims history showed the interval from presenting with any initial typical symptom to diagnosis. Classic symptoms of possible ovarian cancer are pain, distension, early satiety, and urinary dysfunction.

         Results from the study showed the delay after initial presentation, with a mean of three months and a median of one month. Black women, those with multiple symptoms, and those whose first Medicare claim was through an emergency centre, did worse. Improvement is shown with a reduction in delay of about 13% in the last five year period (2011-15) when compared to the initial one (1992-99).

 

My brother died of ovarian cancer

My brother died of ovarian cancer: Why Deputy Lords Speaker Ian Duncan is campaigning for trans health

https://tinyurl.com/43bryw4j

         Rather than my version of this story, I encourage everyone to click on the link above and read the original article from “i news”.

         Ian Duncan writes of the problems his brother Sean had when he transitioned to male. He takes the opportunity to campaign for equitable medical care for transgender men. He says, “ The whole community has become a football for different political, moral factions who are using it as a means to tell a story.” 

         Transgender men frequently receive suboptimal medical care, sometimes due to prejudice but more often neglect. If surgical pelvic clearance is performed as part of the transition, ovaries may be left in situ. This can further complicate proper surveillance.

ICON8, final report

Weekly platinum-based chemotherapy versus 3-weekly platinum-based chemotherapy for newly diagnosed ovarian cancer (ICON8): quality-of-life results of a phase 3, randomised, controlled trial

https://tinyurl.com/3sndxv8f

 

         In 2013 a phase III trial In Japan (JGOG 3016) showed a survival advantage when the normal chemotherapy after initial surgery for ovarian cancer was altered. Usually chemo is given as at 3-weekly intervals with 6 doses as a minimum, more if serum markers show the need. Instead of this the frequency was changed to weekly.

         Because of reported increase in toxicity and in order to replicate the findings a prospective randomly allocated phase III trial (ICON8) began in 2011. 1566 women with ovarian cancer were allocated into two groups; either 3-weekly or weekly chemotherapy commenced, with both groups having the same chemotherapeutic agents.

         Parameters measured in the trial were quality of life, survival and neuropathy. Results showed no improvement in survival with more frequent dose regimes. Quality of life measurements at 9 months were similar for both groups, though the weekly dose group reported adverse effects during chemo more often. Both groups had neuropathy, with a later onset for those having extended chemo suggesting it may be related to total dose received.

Reality check

Real-world progression-free survival among patients with newly diagnosed advanced ovarian cancer: Does maintenance therapy work?

https://tinyurl.com/yf5nkc3a

 

         In an ideal world every patient with ovarian cancer would have optimal treatment. However, there is often a difference between the rhetoric and reality.

         Personalised cancer therapy is becoming more frequent including maintenance treatment following surgery and chemo, with monoclonal antibodies or enzyme inhibitors. This study looked at the real experiences of women with advanced ovarian cancer.

         463 women were included in this retrospective study, all ovarian cancer patients at the same centre of excellence. Treatment began during the period 2016-2020. Only 21% of the women received maintenance therapy. Those patients who did had a 29% lower risk of progression, with a median improvement in progression free survival of 4 months compared to those who did not.

 

Early palliative care

Acceptability and Feasibility of Early Palliative Care Among Women with Advanced Epithelial Ovarian Cancer: A Randomized Controlled Pilot Study

https://tinyurl.com/2ndw9xhj

 

         Women with advanced ovarian cancer are usually aware of the probable outcome. Beginning Palliative care is often delayed. Sometimes by patients but also due to hesitation by medical care providers.

         This small study of 32 women all of whom had advanced ovarian cancer, with recurrence after initial treatment, looked at the acceptance of early palliative care.  Of the group, 23 women joined the study with half being allocated to palliative care and the others having standard oncology treatment.

         Prior to commencement all the women had poor wellbeing, many being clinically depressed. Most (87%) knew their disease to be incurable. Acceptance of the offer for early palliative care, which precludes active treatment, was high. Unfortunately because of the high death rate for these women in both groups, no meaningful information about any change in quality of life could be obtained from this small study.