Age alone not a barrier

The functional trajectories of older women having surgery for gynae-oncology cancer: A single site prospective observational study

http://tinyurl.com/49sebad9

Whether to put elderly women through the challenge of clearance surgery for ovarian cancer is a difficult choice. There has previously been a reluctance to treat older women with the same extensive surgical resection which is the standard of care for younger fitter women.

This prospective review looked at about 100 previously self-reliant women with cancer, who were 65 years old or older and measured their postoperative functional recovery, with correlation to their independence before diagnosis.

Results from the survey showed that 70% of the women were able to function normally with full independence at 12 months post-surgery. Some of the women had impairment of function at six months with subsequent recovery. Those women who had cognitive impairment prior to surgery were unchanged at the 12-month review. 

None of the parameters used in assessment which included measurements of cognition, function, and frailty proved useful in determining the outcome. The authors suggest that age and incapacity should not be criteria for incomplete treatment.

Immune status OC

Unveiling the Immunogenicity of Ovarian Tumours as the Crucial Catalyst for Therapeutic Success

https://tinyurl.com/bd4ke3sx

Ovarian cancer is resistant to immune therapy. Because of this less than 15% will respond to treatments such as checkpoint inhibition or T Cell infusion which are effective as treatment for many other cancers.

Immune resistance occurs in ovarian cancer by various processes which include, downwards regulation of otherwise protective genes, and change of surface proteins on cancer cells that act as targets for immune response. This leads to platinum resistance and early recurrence.

Understanding of this altered immune status results in new classifications of cancer types,with separation of ovarian cancer into homologous recombination deficiency, (about 40%),and epithelial mesenchymal transition, (the rest). The latter group are the most immune resistant and have worse survival.

With this knowledge will come improved targeted therapy, probably in combination, looking to counter immune resistance and enable cytotoxic effect.

Virus RNA predicts survival

Prevalence of viral DNA in high-grade serous epithelial ovarian cancer and correlation with clinical outcomes

https://tinyurl.com/e6e9vaer

It becomes clear with new understanding that many cancers including ovarian cancer show evidence of viral infection. This retrospective study looks at tissue samples from 98 patients with ovarian cancer. Using a polymerase chain reaction, the presence or absence of viral DNA in these samples were measured and compared to the survival outcomes.

46 of the patients showed evidence of viral infection with one or more virus signatures detected. The viruses found included known carcinogens such as the human papilloma virus and Epstein-Barr virus.

Cancers containing viral DNA were more likely to be platinum resistant and had worse survival. This was especially true for younger women, (<70). It is not clear whether the virus infection is a cause of the cancer or an effect of the disease, but the study suggests virus infection is a negative survival predictor.

OC in the young, a different disease

Early-Onset Ovarian Cancer <30 Years: What Do We Know about Its Genetic Predisposition?

https://tinyurl.com/2x6p5jhj

Ovarian cancer in young women (age 18-30) is rare being about 5% of the total. It was assumed that most ovarian cancer in women of this age was due to inherited genetic mutations. Usually, ovarian cancer is a disease of the elderly. Of whom about 20% have a genetic mutation, which causes the disease. This retrospective survey of more than 300 young women from four different data sets found much less genetic mutation; about 3%.

A different spectrum of disease is seen in the young, with about half of ovarian cancer arising from embryonal germ cells. Serous Ovarian Cancer is much less common in young women, being about 40% of all cases compared to 90% overall. Low Grade disease is more likely in the young. However, survival is almost 50% worse for the young, (HR0.53) despite these seemingly favourable pathology types. This is another example of the different nature of ovarian cancer in young women.

The reason why some young women develop ovarian cancer is unknown. It seems to be a random misfortune not associated with any genetic or environmental predisposition. The poor outcomes for these women are also unexplained.

IPEC yes or no

Should We Abandon Intraperitoneal Chemotherapy in the Treatment of Advanced Ovarian Cancer? A Meta-Analysis 

https://tinyurl.com/3drtt9jb

Use of intra peritoneal chemotherapy (IPEC) is low in Australia. The reasons for this include adverse effect with pain and toxicity. Logistic issues such as access and expertise also limit its use.

There has previously been little evidence of the potential benefit. This study, a retrospective analysis of all available data looked at the survival benefits of IPEC.

Six studies, with results for more than 4500 patients were shown to fit the selection criteria. Both overall survival and progress free survival were improved with IPEC, by almost 20%,(HR 0.81).

The implication of the study is that the IPEC therapy should be re-evaluated, and greater use would be beneficial.

Endometrial biopsy of limited value

A retrospective study of Pipelle endometrial biopsy for ovarian, fallopian tube, and peritoneal cancers

https://tinyurl.com/3jc3my57

Although well established in the diagnosis of endometrial cancer, the value of endometrial biopsy for ovarian and fallopian tube cancer is not well understood. Much ovarian cancer starts in the fallopian tube, it has been suggested that endometrial biopsy could be a low-invasive means to obtain a tissue diagnosis.

This retrospective study reviewed biopsies obtained from 99 women who had endometrial biopsy as part of their workup for ovarian cancer. Findings from the review showed that the biopsy had a low specificity, with high false negative results for early-stage ovarian cancer but the sensitivity for a positive test was acceptable at 44% for late-stage disease.

The tissue type found at biopsy was confirmed in the resected ovarian cancer specimen in 74% of cases.

A negative result therefore does not exclude ovarian cancer especially early-stage disease. However, as a minimally invasive test endometrial biopsy has the potential to speed access to personalised therapy.It is unlikely due to cost and resource issues that endometrial biopsy will become part of standard care for ovarian cancer.

PID and cancer

Pelvic inflammatory disease and risk of epithelial ovarian cancer: a national population-based case-control study in Sweden

https://tinyurl.com/2mk66bpe

Once again, the large data base of clinical information in Sweden gives further insight into the epidemiology of ovarian cancer. This study compares the risk of developing ovarian cancer after previous pelvic inflammatory disease. (PID) It is becoming increasingly obvious that infection is an important cause for much cancer.

The retrospective review compared the incidence of PID in 1000 women who developed ovarian cancer with 10000 women who did not have cancer. PID may occur as salpingitis possibly sexually transmitted, be associated with endometriosis, urinary tract infection or inflammatory bowel disease.

Results from the study showed that women with a past history of PID were 39% more likely to develop epithelial ovarian cancer and 46% more likely to develop serous ovarian cancer. The greater the number of PID events the more likely subsequent ovarian cancer occurred.

The authors suggest the increased cancer risk may be due to inflammatory change or persisting bacterial effect and that women with a history of PID should be more actively screened for subsequent ovarian cancer.

Brain Fog possibly infective

Prevalence of active cytomegalovirus infection at diagnosis of ovarian cancer and during chemotherapy and subsequent changes in cognitive functioning

https://tinyurl.com/yc5mfuf9

Cytomegalovirus (CMV) is a herpes type virus found in 50% of the population. It lies dormant after initial infection and can recur causing various symptoms which include fatigue and decreased cognitive function.

This prospective study looked at the CMV status of 89 women with ovarian cancer and reviewed their cognitive function before and following chemotherapy.

At the time of initial presentation 30% of the women had blood levels of antibodies suggested active CMV infection. This increased to 60% following chemo. The infection rate reverted to 30% once chemo was ceased. 

Those women with active CMV disease at the onset had significantly worse cognitive function than the uninfected. The authors suggest that “brain fog”, which is a complication of chemo for ovarian cancer may be in part be due to the presence of active CMV infection, and that women should be screened for CMV as part of the diagnostic workup.

BRCA maybe not relevant

Causality and functional relevance of BRCA1 and BRCA2 pathogenic variants in non-high-grade serous ovarian carcinomas

https://tinyurl.com/e5859f7b

With increased availability more and more patients with ovarian cancer have genetic screening with the BRCA variants being the primary target. Is this a suitable use of resources?

This paper; a prospective review of almost 1000 ovarian cancer cases looked at the incidence of BRCA variants for patients who had the commonest type being high-grade serous ovarian cancer versus the less common non-high-grade types.

BRCA variants were found in 13% of the high-grade cancers and 3% of the non-high-grade cancers. Further review showed that some of the less common cancers had incorrect pathology, the others had faulty BRCA genotyping or that the variation was only partial with incomplete penetration.

The authors suggest that BRCA genotyping for non-high-grade serousovarian cancer has no value

Wine and cancer

Association between wine consumption and cancer: a systematic review and meta-analysis

https://tinyurl.com/2jaz8hu6

    High alcohol consumption has been shown to be associated with an increased risk for many cancers including breast and ovarian cancer. However, it has been suggested that low to moderate wine consumption (less than 2 glasses of wine daily for women) may be protective.

    This review; a meta-analysis of all the available data looked at 454 reports which conformed with the criteria for inclusion. The relative risk of developing breast or ovarian cancer for moderate drinkers was the same as the normal population (RR 1.03).

    Moderate drinking is protective against gastric cancer. The authors suggest this may be due to antibacterial activity of alcohol against H. Pylori. Low to moderate consumption of alcohol does not increase ovarian cancer risk.

Who is platinum resistant?

Proteogenomic analysis of chemo-refractory high-grade serous ovarian cancer

https://tinyurl.com/2p9bdrwk

One of the many problems with ovarian cancer is that many women (about 15%) do not respond to standard therapy. These women are termed as platinum resistant, have a recurrence before six months after initial treatment, with very poor outcomes.

This study looks at identifying those women so that alternative personalised treatment might be considered. It is a retrospective review of pretreatment biopsy obtained from 242 women with high grade ovarian cancer. Of them, 97 were platinum resistant.

Using proteogenomic analysis, which combines information from whole of genome sequencing and spectroscopic data about protein and RNA transcription, different subgroups were identified. In particular a protein signature common to all the platinum resistant cancers may assist in early diagnosis.

As of now there is no alternative effective treatment. However, the authors suggest that early identification may mean that the adverse side effects of platinum chemo can be avoided, with more palliative care being appropriate for these women.

Borderline tumours and cancer

Risks of non-ovarian cancers in women with borderline ovarian tumour: a national cohort study in Sweden

https://tinyurl.com/uchdbbnk

One of the great advantages of medical research from Scandinavia is the quality of the epidemiology data. This paper is an example of the large numbers of the sample group which can be obtained from the Swedish Cancer Registry.

Almost 5000 women were diagnosed to have a borderline ovarian tumour during the period 1995-2018. Follow up of those women showed an increased risk of non-ovarian cancer when compared to the general population.

The types of cancer included bowel, uterine, renal, lung, thyroid and pancreas. There was no association shown with breast cancer or leukaemia. The authors speculate that the presence of a borderline tumour may be a marker for increased cancer risk possibly due to a shared cause or predisposition.

FDA & PARGi

IDEAYA Receives Fast Track Designation for Potential First-in-Class PARG Inhibitor, IDE161, for Treatment of Pretreated, Platinum-Resistant Advanced or Metastatic Ovarian Cancer Patients having tumours with BRCA1/2 Mutations

https://tinyurl.com/bdhy2uuj

Defective DNA repair is important as a cause for ovarian cancer and the prevention of cancer elimination once established. Personalised treatment using PARP inhibitors acts by blocking alternative repair pathways through a process called synthetic lethality. 

Unfortunately resistance to PARPi is inevitable. Often this occurs because another repair process becomes active. One such process is Poly (ADP-ribose) Glycohydralase (PARG). A new Drug IDE161 has been developed to inhibit this repair process in a similar manner to PARPi.

The FDA has given Fast Track approval for this drug as a preliminary to full access. Usually this implies the FDA has confidence that the new treatment for those women with ovarian cancer, who have become resistant, will have a good outcome. With time it may be that the role of PARGi expands to become an alternative to PARPi as maintenance therapy.

One size doesn’t fit all

Uptake and Outcomes of Neoadjuvant Chemotherapy Among US Patients with Less Common Epithelial Ovarian Carcinomas

https://tinyurl.com/5xvnykwb

Sometimes there is a temptation to use a treatment protocol, which has shown to be successful for one type of cancer more widely. An example of this is the application of Neoadjuvant chemo (Neo) prior to surgery for rarer types of ovarian cancer. Although Neo is beneficial for High Grade Serous Ovarian Cancer, it seems to be ineffective for other types.

This retrospective review looked at about 1000 cases of Low Grade Serous Ovarian Cancer in women who presented with advanced disease (stage III-IV), during the period 2006-2019. There was a gradual increase in the number receiving Neo, with 15% having delayed surgery with Neo beforehand.

When the data was reviewed in 2022, no benefit was shown with survival worse for those who had Neo, and larger residual volumes after initial surgery. Similar failed Neo, with worse outcomes, were seen for women with Clear Cell Ovarian Cancer and Mucinous Ovarian cancer.

HIPEC benefit confirmed

Cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy in patients with advanced ovarian cancer (OVHIPEC-1): final survival analysis of a randomised, controlled, phase 3 trial

 

https://tinyurl.com/3kparpnm

    For cancer research it is important to consider the longer term. It is often many years before a conclusion about the merit of a new procedure can be reached. 

    This study looked at the long-term benefits of hyperthermic intraperitoneal chemo (HIPEC) by revisiting the subjects of the OVHIPEC-1 trial 7 years after the trial ceased. The initial trial showed improved progression free survival and overall survival for those women who received HIPEC as part of their therapy in addition to normal chemo for ovarian cancer.

 

    Review of the data has enabled the determination of 10-year survival for the first time, which shows that HIPEC benefit is prolonged. More patients survive with better quality of life due to longer intervals between recurrence and less platinum resistance making repeat treatment easier. 

Another look at UKCTOCS

Tumour stage, treatment, and survival of women with high-grade serous Tubo-ovarian cancer in UKCTOCS: an exploratory analysis of a randomised controlled trial 

https://tinyurl.com/dr7z7sr9 

    Screening of ovarian cancer has been shown to be ineffectual. The UKCTOCS trial over 15 years, which had more than 200,000 participants proved that there was no benefit in terms of long-term survival for women who received comprehensive ovarian cancer screening when compared to women who did not. 

    This review of the data looked at the staging for those women who developed ovarian cancer either during the trial or in the 9 years since the trial finished. Of the participants 0.5% had ovarian cancer, the incidence is the same in the screened and non-screened group. 

    A significant difference is noted in the staging of the cancers detected, with fewer women from the screened group presenting with advanced (III-IV stage) ovarian cancer. Survival after diagnosis with advanced disease was longer for those women who had been screened.  

    Screening does detect advanced disease sooner, and women who have been screened are less likely to have advanced stage ovarian cancer. Maybe the criteria for success need to change?