Ovarian Cancer: Are We Choosing Wisely?

Choosing Wisely is a campaign by medicine’s specialty societies to identify and reduce the use of ineffective tests and procedures by physicians. A study by Rustin et al. demonstrated that in women in remission after initial chemotherapy for ovarian cancer CA-125 surveillance was ineffective – their median survival did not improve. In fact, monitoring was harmful to the extent that chemotherapy, with its immediate, deleterious effects on patients was initiated sooner – women managed by CA-125 surveillance had five fewer months of chemotherapy-free “remission.” This study provided evidenced-based medicine that CA-125 surveillance was ineffective.

Esselen et al. in last week’s JAMA Oncology on-line examined the impact of Rustin’s evidence-based recommendation on physician behavior. Using the National Comprehensive Cancer Network database on ovarian cancer, drawn from six large academic medical centers, they looked at the use of CA-125 testing before and after the publication of Rustin’s study. There findings:

• “there was no change in the use of CA-125 tests or computed tomographic scans.”
• “the study by Rustin et al. did not change practice at 6 NCCN academic centers despite widespread discussion.”
• There was “an estimated mean population cost for one year of ovarian cancer surveillance testing of $16,194,647.”

A simultaneous commentary by James Goodwin asks “why was there no change in practice in response to good evidence?” He suggests several reasons:

• That Ruskin’s study was characterized as early versus delayed treatment not as routine surveillance – thus the results confused physicians. But as he notes elsewhere “the six centers studied by Esselen et al. were leading academic medical centers, populated by clinicians who also sit on the committees that write the guidelines.”
• That it’s hard to tell physicians they are wrong or harmful in their behavior. Physicians typically respond that they are the exception – they do it differently, their patients are different, or even, times have changed.
• That medical economics, while not irrelevant, “muddies the issue.” This is an argument about physician’s primary duty to their patient’s well-being, not to society. “It is difficult enough helping patients decide on what is best for them without introducing the concept of what is best for society.”

And while all of these contentions are true, I believe that another of Goodwin’s arguments drives all of the physicians’ behavior:

• Medical practitioners practice and patients live in “a sea of uncertainty.” That the stress of not knowing drives us “to seek more information through testing” to increase our certainty. But more information was not necessarily helpful. The discomfort with uncertainty extends to our patients – “While physicians may be challenged dealing with uncertainty, many of our patients refuse absolutely to tolerate it.”

The drive to reduce risk especially in a life or death situation is greater than economic issues or evidence-based medicine. The behavior physicians demonstrated in Esselen’s paper is the territory of Tversky and Kahneman’s Nobel prize winning Prospect theory – how we make judgments when uncertain. We might do better at improving medical care and reducing unnecessary testing to look to their work and the field of behavioral economics they founded rather than to simply continue Choosing Wisely.

To read the full article on ACSH.org, please click here.

Ovarian Cancer Test On Horizon As Scientists Find Earliest Signs Of Disease

Ovarian cancer could be detected years before any symptoms emerge after scientists at Oxford University found a way to spot the first signs of the disease.

Cancer of the ovaries is the fifth most common cancer for women in the UK, with about 7100 new cases each year but it is difficult to diagnose because it grows virtually unseen into the abdominal cavity.

Now a new study has found that levels of a protein called SOX2 are much higher in the fallopian tubes of women with ovarian cancer and those genetically predisposed to the disease.

The breakthrough could lead to early screening for the disease in a similar way to a cervical smear test.

Professor Ahmed Ahmed, from the MRC Weatherall Institute of Molecular Medicine at Oxford University, said: ‘Ovarian cancer can be undetectable for up to four years and only a third of people with the cancer get an early diagnosis.

“A test for SOX2 could not only help detect cancers early but in some cases would enable us to detect a tumour before it becomes cancerous.

“Early treatment hugely improves the odds for patients, so early detection is essential. However, there is still a lot of work to be done because detecting SOX2 in the fallopian tubes is not an easy task.

“We are hoping that a test that is based on this discovery would detect the tumour at the pre-cancer state. A bit similar to what the cervical smear test does.”

The team identified an enzyme that enables ovarian cancer to spread and are hoping that it could be targeted with drugs.

Katherine Taylor, Chief Executive at research charity Ovarian Cancer Action, one of the study’s funders, said: “We need to save the lives of more women by making ovarian cancer treatment more effective.

“There has been little progress in ovarian cancer treatment in the past 30 years so these findings are promising, and have provided two areas of focus for scientists working on ovarian cancer.

“Early detection and effective treatment are vital, and these discoveries will hopefully being us closer to both.”

To read this entire article on Telegraph.co.uk, click here.

Uncle Sam Wants You — Or at Least Your Genetic and Lifestyle Information

Government scientists are seeking a million volunteers willing to share the innermost secrets of their genes and daily lives as part of an ambitious 10-year research project to understand the causes and cures of disease.

Those selected to be members of the “precision medicine cohort” will be asked to provide a detailed medical history and blood samples so researchers can extract DNA. They will also be asked to report information about themselves — including their age, race, income, education, sexual orientation and gender identity, officials said.

But the project involves much more than statistics and laboratory work.

The government plans to collect information about a person’s lifestyle — diet, exercise, smoking, drinking, sleep patterns and other behavior — and the environment in which a person lives, so researchers can identify possible risk factors, including air pollution or high lead levels in drinking water.

Those wishing to participate will be able to sign up by computer or smartphone, and even by using an ordinary telephone to contact a traditional call center. The project, begun as part of President Obama’sPrecision Medicine Initiative, seeks to develop treatments tailored to the characteristics of individual patients.

“Anybody anywhere can raise their hand and say they want to participate,” said Kathy L. Hudson, deputy director of the National Institutes of Health, which is leading the effort.

Health care providers, including a number of hospitals and community health centers, will invite their patients to participate. Enrollment is scheduled to begin in November or December, with a goal of signing up a million or more people within four years.

“There are a lot of enticing reasons to participate,” said Mark Masselli, president and chief executive of the Community Health Center in Middletown, Conn., one of a half-dozen clinics chosen by the government to recruit patients. “Perched on your shoulders will be the best and brightest researchers, working on your behalf.”

The project is being orchestrated by Dr. Francis S. Collins, director of the National Institutes of Health, who in a previous job led the government’s successful effort to map the human genome.

Congress in December provided $130 million to the National Institutes of Health for the million-person research cohort. Mr. Obama has requested $230 million for the fiscal year that starts Oct. 1, and the appropriations committees in both houses of Congress have approved the request as part of a spending bill for 2017. That bipartisan support strongly suggests that the project will continue after Mr. Obama leaves office.

The scale of the project dwarfs most other population-based health research in the United States, such as the Framingham Heart Study, which has produced valuable insights on heart disease by following about 15,500 people enrolled at different times since the late 1940s.

“In the Precision Medicine Initiative,” Dr. Hudson said, “we hope to follow people for at least a decade. The longer it lasts, the more value it will have.”

People can sign up through academic medical centers at Columbia University, Northwestern University in Illinois, the University of Arizona and the University of Pittsburgh, each of which is working with local partners. Columbia, for example, is collaborating with NewYork-Presbyterian Hospital, Harlem Hospital and Weill Cornell Medicine.

Participants will be recruited to reflect the geographic, racial, ethnic and socioeconomic diversity of the nation. To help achieve that goal, officials have enlisted community health centers, where more than 90 percent of patients have annual incomes less than twice the poverty level (less than $23,760 for an individual). About one-third of health center patients are Latinos, and about one-fourth are African-Americans.

Officials said they wanted patients to be partners in the research, not just “human subjects.” To that end, patients will have access to all the information about themselves, including laboratory and genetic test results. Doctors could eventually use the data to shape treatment for an individual patient, rather than using standard treatments that may not work for everyone. Patients will help guide the research, sitting on its steering committee and advisory board.

The government intends to collect data from online questionnaires, physical exams, electronic health records and activity-tracking devices like Fitbit. Using smartphone apps and wearable sensors, participants could report information on their blood pressure, heart rate and other vital signs.

Officials hope to recruit 150,000 patients from community health centers. Anne Kauffman Nolon, president and chief executive of Hudson River HealthCare, a community health center serving 10 counties of New York, said her patients would need help to overcome several obstacles. The patients, she said, include homeless people, migrant seasonal farm workers, people with low literacy skills and people who have neither computers nor smartphones.

Dr. Carmen Chinea, the chief medical officer of the Hudson River health center, said that participants would not receive instant gratification, but could eventually receive “more precise treatments” for conditions including diabetes, cancer and depression.

The Mayo Clinic will create a huge biobank to collect, analyze and store 35 million samples of blood, DNA and other materials from participants. Vanderbilt University will operate a data center to store information. Some of the data will be made available, without personal identifiers, to researchers and “citizen scientists,” officials said.

Cancer doctors already choose drugs for certain types of cancer based in part on genetic characteristics of tumors. Dr. Joshua C. Denny, the principal investigator for the project at Vanderbilt, said his research had identified genetic mutations that increase the risk of heart attack or stroke for people taking a certain blood-thinning medication.

Dr. Rhonda K. Trousdale, chief of endocrinology at Harlem Hospital, said she was reaching out to church and community leaders to seek their help in publicizing the project and enrolling volunteers.

“A big motivation for researchers is to use this data to find correlations between people’s lifestyle, family history, environment and genomic data — to figure out what factors contribute to disease and if they affect different populations in different ways,” Dr. Trousdale said. “That’s what precision medicine is about.”

To read this entire article, published online by The New York Times, please click here.

Liquid Biopsies Offer Hope For Earlier Treatment, Better Tracking Of Ovarian Cancer

Researchers at the Mayo Clinic Center for Individualized Medicine have found a promising new way to monitor and treat recurrence of ovarian cancer — a hard-to-detect disease that claims many lives. New research from George Vasmatzis, Ph.D., of the Department of Laboratory Medicine and Pathology at Mayo Clinic, finds liquid biopsies from blood tests and DNA sequencing can detect a return of ovarian cancer long before a tumor reappears. That could lead to earlier intervention and more effective, individualized treatment. Dr. Vasmatzis’ research on the “Quantification of Somatic Chromosomal Rearrangements in Circulating Cell-free DNA From Ovarian Cancers” is published in the July 20 edition ofScientific Reports.

“With liquid biopsies, we don’t have to wait for tumor growth to get a DNA sample,” says Dr. Vasmatzis. “This important discovery makes it possible for us detect recurrence of the disease earlier than other diagnostic methods. We can repeat liquid biopsies to monitor the progression of the cancer. That gives hope of a better treatment plan over time.”

The study was done on 10 patients in advanced stages of ovarian cancer. Blood was drawn before and after surgery. Investigators compared DNA from the liquid blood biopsies to DNA tissue samples from the tumor, using mate-pair sequencing — an inexpensive whole exome sequencing that can reveal genetic changes that contribute to tumor growth.

“In this study, the blood drawn before and after surgery and the surgical tissue was used to identify DNA fragments with abnormal junctions that can only be seen in this patient’s tumor DNA,” explains Dr. Vasmatzis. “Next-generation mate-pair sequencing was used to identify specific DNA changes of the tumor to create an individualized monitoring panel for liquid biopsy. This allows us to shape treatment to the individual patient rather than using a standard treatment that may not work for everyone.”

When post-surgery DNA matched that of the tumor, patients were later found to have had a recurrence of ovarian cancer. However, when the post-surgery DNA did not match the DNA of the tumor, patients were found to be in remission.

Ovarian cancer has one of the highest death rates of all gynecological cancers, because the tumor often cannot be detected until the late stages. Most patients go into remission after initial treatment, but the tumor returns 75 percent of the time. The next stage of ovarian cancer that develops typically does not respond to chemotherapy. More than 21,000 women in the U.S. were diagnosed with ovarian cancer, and 14,000 women died of the disease in 2015.

To read this full article, published online by ScienceDaily, click here.

Women With Ovarian Cancer Wait Over A Month To Start Treatment

Women diagnosed with ovarian cancer waited about 38 days, on average, from the initial concerning imaging test to initiation of treatment, according to a study analyzing health care transit times at a single community hospital.

“Ovarian cancer is such a hard disease to diagnose early,” Christopher J. LaFargue, MD, lead study author, said in an interview at the annual meeting of the Society of Gynecologic Oncology. “Once it’s diagnosed, it’s imperative that women get in to see the gynecologic oncologist [and] make sure their treatment care isn’t lagged for any reason.”

In an effort to characterize the length of time between critical points in the care of women with ovarian cancer and determine the impact of patient demographics, Dr. LaFargue and his associates retrospectively evaluated the medical records of 45 women who were diagnosed with ovarian cancer at Long Beach (Calif.) Memorial Medical Center between January 2012 and May 2015.

They examined patient demographics, including preoperative CA-125. Time points of interest were first concerning imaging test, first gynecologic oncology appointment, initiation of treatment, and adjuvant therapy. They used univariate analyses to determine associations between specific patient demographics and the time intervals of interest.

Dr. LaFargue, a resident in the department of obstetrics and gynecology at the University of California, Irvine, reported that the mean age of patients was 61 years, and the mean driving distance to the hospital from the patients’ home was 11 miles. More than half of the patients were white (58%) and 62% of patients were diagnosed with stage III or IV disease. Preoperative CA-125 exceeded 200 U/mL in 62% of patients. Medicare enrollees with supplemental insurance made up less than half of the group (44%).

The researchers found that the average time from initial concerning imaging to start of treatment was about 38 days. The average time from initial imaging to the first office visit with a gynecologic oncologist was about 18 days. The time from that appointment to initial treatment was 19 days, on average. The time from the start of neoadjuvant chemotherapy to interval cytoreductive surgery was 103 days, on average.

The only factor that significantly impacted transit time was a patient’s CA-125 level. Those who had a level of 200 U/mL or greater were more likely to receive surgery or treatment quicker, compared with those who had a CA-125 level less than 200 U/mL. No other statistically significant associations between patient demographics and length of time intervals were observed.

“It would have been nice to have seen a correlation with insurance status,” Dr. LaFargue said. “That’s kind of what we were hoping for, because then you can make an argument with insurance payers that patients who have Medicare aren’t getting treated as quickly as those who have a PPO, for example.”

He acknowledged certain limitations of the study, including its small sample size, lack of outcomes data, and the fact that it was conducted in a community hospital setting.

Dr. LaFargue reported having no financial disclosures.

To read this entire article on OncologyPractice.com, please click here.

Use of CA-125 Tests and Computed Tomographic Scans for Surveillance in Ovarian Cancer

Importance  A 2009 randomized clinical trial demonstrated that using cancer antigen 125 (CA-125) tests for routine surveillance in ovarian cancer increases the use of chemotherapy and decreases patients’ quality of life without improving survival, compared with clinical observation. The Society of Gynecologic Oncology guidelines categorize CA-125 testing as optional and discourage the use of radiographic imaging for routine surveillance. To date, few studies have examined the use of CA-125 tests in clinical practice.

Objectives  To examine the use of CA-125 tests and computed tomographic (CT) scans in clinical practice before and after the 2009 randomized clinical trial and to estimate the economic effect of surveillance testing.

Design, Setting, and Participants  A prospective cohort of 1241 women with ovarian cancer in clinical remission after completion of primary cytoreductive surgery and chemotherapy at 6 National Cancer Institute–designated cancer centers between January 1, 2004, and December 31, 2011, was followed up through December 31, 2012, to study the use of CA-125 tests and CT scans before and after 2009. Data analysis was conducted from April 9, 2014, to March 28, 2016.

Main Outcomes and Measures  The use of CA-125 tests and CT scans before and after 2009. Secondary outcomes included the time from CA-125 markers doubling to retreatment among women who experienced a rise in CA-125 markers before and after 2009, and the costs associated with surveillance testing using 2015 Medicare reimbursement rates.

Results  Among 1241 women (mean [SD] age 59 [12] years; 1112 white [89.6%]), the use of CA-125 testing and CT scans was similar during the study period. During 12 months of surveillance, the cumulative incidence of patients undergoing 3 or more CA-125 tests was 86% in 2004-2009 vs 91% in 2010-2012 (P = .95), and the cumulative incidence of patients undergoing more than 1 CT scan was 81% in 2004-2009 vs 78% in 2010-2012 (P = .50). Among women whose CA-125 markers doubled (n = 511), there was no significant difference in the time to retreatment with chemotherapy before and after 2009 (median, 2.8 vs 3.5 months; P = .40). During a 12-month period, there was a mean of 4.6 CA-125 tests and 1.7 CT scans performed per patient, resulting in a US population surveillance cost estimate of $1 999 029 per year for CA-125 tests alone and $16 194 647 per year with CT scans added.

Conclusions and Relevance  CA-125 tests and CT scans are still routinely used for surveillance testing in patients with ovarian cancer, although their benefit has not been proven and their use may have significant implications for patients’ quality of life as well as costs.

To read this entire study on JAMA Oncology, click here.

Benefit Strongly Suggested With Hormonal Maintenance in Low-Grade Serous Carcinoma

In patients with low-grade serous carcinoma, maintenance hormonal therapy reduced the risk of recurrence by 77%, compared with surveillance, in a retrospective cohort from The University of Texas MD Anderson Cancer Center. The study was reported by David Marc Gershenson, MD, at the 2016 ASCO Annual Meeting.¹ Dr. ­Gershenson acknowledged that, as a retrospective study conducted over a long period, the study has some limitations; however, the findings “are potentially practice-changing,” he maintained.

“Women with stage II–IV low-grade serous carcinoma who received hormonal maintenance therapy following primary treatment had a significantly better outcome, compared with women who underwent surveillance,” reported Dr. Gershenson. They had superior median progression-free survival and, for the subgroup with no evidence of disease following primary treatment, superior progression-free and overall survival. For the entire subset with no evidence of disease, median overall survival was 115.7 months (median overall survival = 106.8 months for the surveillance group and 191.3 months for the hormonal maintenance therapy group).

Rare Subtype Not Chemosensitive

Low-grade serous carcinoma is a rare subtype of cancer of the ovaries/peritoneum. It may arise de novo or following a diagnosis of serous borderline tumor. Relative to high-grade serous carcinoma, low-grade serous carcinoma is characterized by young age at diagnosis, chemoresistance, prolonged overall survival, and aberrations within the MAP kinase-signaling pathway, Dr. Gershenson shared. “There have been no prospective clinical trials in the front-line setting, but data from the MD Anderson low-grade serous carcinoma database have suggested relative chemoresistance in multiple settings,” he added.

A recent report from the Arbeitsgemeinschaft Gynaekologische Onkologie (AGO) Study Group database of 5,114 patients, for example, found that among patients with low-grade serous carcinoma who were suboptimally debulked, the response rate to platinum/taxane chemotherapy was 23%, compared with 90% for patients with high-grade serous carcinoma who were also suboptimally debulked.² The conclusion was that low-grade serous carcinoma is not as responsive to standard chemotherapy as high-grade tumors.

Without other more active treatments, according to the 2015 Gynecologic Cancer Intergroup Ovarian Cancer Consensus Conference, “Platinum-based chemotherapy is a standard for high-risk, early or advanced-stage, rare epithelial ovarian cancers and should remain the control arm” for trials of new approaches, according to Dr. Gershenson.

Based on reports of the promising activity of hormonal therapy in the recurrent setting, there has been increasing interest in integrating this modality into the primary treatment setting. The purpose of this study was to evaluate the effect of hormonal maintenance therapy compared with surveillance after primary treatment in a retrospective cohort.

Study Details

The study included 204 patients diagnosed with stage II–IV low-grade serous carcinoma between 1981 and 2013. Patients’ median age was 47.7 years; 75% had primary ovarian low-grade serous carcinoma, and 25% had primary peritoneal low-grade serous carcinoma; 30% had no gross residual disease, and 70% had residual disease, with no differences between the arms.

At the completion of chemotherapy, however, the groups differed in terms of disease status, with 60.9% of the hormonal maintenance group demonstrating persistent disease, compared with only 8.3% of the surveillance group, revealed Dr. Gershenson.

All patients who had not recurred had been followed for at least 2 years after primary cytoreductive surgery and platinum-based chemotherapy. Following chemotherapy, patients started on hormonal maintenance (n = 70) or underwent surveillance only (n = 134). Hormonal therapy consisted primarily of letrozole (54.3%) and tamoxifen (28.5%); in the entire cohort, 13% of patients switched to another hormonal therapy due to toxicity. The median duration of hormonal therapy was 33.3 months (range, 1–223 months).

Risk of Progression Reduced by 77%

Despite a much greater frequency of persistent disease after primary treatment, patients in the hormonal therapy maintenance group experienced significantly less disease progression, Dr. Gershenson reported. For the entire cohort of 204 women, median progression-free survival was 27.3 months in the surveillance group and 64.9 months in the hormonal therapy group, representing a 77% reduction in risk, according to the multivariate analysis (P < .001). The proportion of patients who were recurrence-free was 23% vs 40%, respectively. Median overall survival was numerically but not statistically significantly improved, from 98.8 months with surveillance to 115.7 months with maintenance (P = .36).

In patients with no evidence of disease at the completion of chemotherapy, median progression-free survival was 29.9 months with surveillance and 81.1 months with maintenance therapy (P < .001), and median overall survival was 106.8 months vs 191.3 months, respectively (P = .04).

Disclosure: Dr. Gershenson has consulted for Clovis Oncology and owns stock in AbbVie, Biogen Idec, Celgene, GlaxoSmithKline, Johnson & Johnson, Merck, and Pfizer.

To read this entire article on The ASCO Post, please click here.

No Clinical Benefit With Novel Treatment for Ovarian CCC

The first randomized phase III clinical trial to compare irinotecan (Camptosar, Camptothecin-11, CPT-11) and cisplatin (Platinol, Platinol-AQ, CDDP) with standard of care — paclitaxel (Taxol, Onxal) plus carboplatin (Paraplatin) — in patients with clear cell carcinoma (CCC) of the ovary found no significant survival benefit between the groups.

With a median follow-up of 44.3 months, 2-year progression-free survival rates were 73.0% in the irinotecan-plus-cisplatin (CPT-P) group and 77.6% in the paclitaxel-plus-carboplatin (TC) group (HR 1.17; 95% CI 0.87 to 1.58). Two-year overall survival rates were 85.5% with CPT-P and 87.4% with TC (HR 1.13; 95% CI 0.80 to 1.61).

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Both regimens were well tolerated, although the toxicity profiles differed significantly, Aikou Okamoto, MD, of Jikei University School of Medicine in Tokyo and colleagues in the Japanese Gynecologic Oncology Group reported online in the Journal of Clinical Oncology.

“The previous randomized phase II study [JGOG3014] showed a tendency of progression-free survival superiority of the CPT-P arm in a subset analysis of patients without residual disease or with residual disease of less than 2 cm,” the researchers wrote. “However, we could not identify the survival advantage of CPT-P in any subgroup analyses by region, stage, and size of the residual disease in the current phase III randomized trial.”

The study also revealed the limitations of existing anticancer agents to improve prognosis in patients with ovarian CCC. Identification of driver mutations “is a crucial first step toward personalizing treatment of CCC,” Okamoto and colleagues emphasized.

Studies of metastatic clear cell renal cancer have demonstrated the effectiveness of using a combination of targeted treatments such as a PI3K-Akt-mTOR pathway inhibitor as well as anti-angiogenic agents and new immunotherapy drugs, the researchers said. “Therefore, we emphasize that therapeutic regimens should consider such combinations and/or target drugs to improve the prognosis of CCC of the ovary.”

The negative results of this trial highlight two major challenges in cancer research, Emese Zsiros, MD, PhD, of Roswell Park Cancer Institute in Buffalo, NY, said in an interview.

“In vitro studies on cancer cell lines often do not translate to clinical benefit in patients given the heterogeneity and complexity of cancer in real life,” she explained. “Also, if a phase II study does not show significant activity of a new drug or drug combination, it is unlikely to detect a significant clinical benefit in a large phase III study.”

Zsiros, who was not affiliated with the study, also noted that while CCC accounts for only 4-12% of all ovarian cancers in the U.S. and Europe, it is much more common in Japan, accounting for more than 20% of all ovarian cancers.

Unlike serous ovarian cancer, CCC is often associated with a large one-sided pelvic mass and an increased incidence of hypercalcemia and vascular thromboembolic complications such as deep venous thrombosis and/or pulmonary embolism, she pointed out. The lower proliferation rate and increased resistance to traditional chemotherapeutic agents make CCC “a much more difficult disease to treat.”

Given the relatively poor prognosis and similarity to clear cell renal cancer, patients with CCC of the ovary are best treated as part of a clinical trial exploring alternative or novel agents, Zsiros suggested.

In the international, multi-institutional study, 667 patients were recruited at 129 centers in Japan, Korea, France, and the U.K., from September 2006 to February 2011. Japanese women made up 93.5% of the study population.

The median age in both the experimental and standard-of-care groups was 53. A total of 411 patients (66.4%) had stage I disease, and 33.6% had stage II to IV disease. Of the latter group, 23% had stage III/IV disease.

Patients were randomly assigned to receive either:

• irinotecan at 60 mg/m² on days 1, 8, and 15 plus cisplatin at 60 mg/m² on day 1 every 4 weeks for six cycles (CPT-P group); or
• paclitaxel at 175 mg/m² plus carboplatin at an area under the curve of 6.0 mg/mL/min on day 1 every 3 weeks for six cycles (TC group).

Of the 619 patients eligible for evaluation, the 332 in the CPT-P group experienced more grade 3/4 anorexia, diarrhea, nausea, vomiting, and febrile neutropenia. The 335 patients in the TC group had grade 3/4 leukopenia, neutropenia, thrombocytopenia, peripheral sensory neuropathy, and joint pain more frequently, the study showed.

No deaths related to treatment were reported, the researchers said.

Read this full article on MedPageToday.com by clicking here.

Simpler Ovarian Cancer Testing ‘Saves Lives’

Simplifying the way ovarian patients are tested is a “win-win” that saves both lives and money, a study shows.

Testing their DNA should identify the most effective drugs and finds out if other family members are at risk.

Fewer than a third of patients are currently tested, but the team at the Institute of Cancer Research (ICR) in London made it easier for women and increased uptake to 100%.

Experts said the findings were an important step.

The focus of testing is a set of genetic mutations which run in families called BRCA – they cause 15% of the 7,100 ovarian cancers detected in the UK each year.

Knowing if the patient is in the 15% helps improve treatment as some chemotherapy drugs are more effective against tumours caused by BRCA mutations.

And cancer drugs such as PARP inhibitors work only in women with BRCA mutations.

A tumour that is positive for BRCA is also an early warning to other family members that they may be at risk of developing ovarian, breast or prostate cancers.

Testing currently involves getting an appointment with a separate genetics team after being diagnosed by a cancer doctor. The average wait is 12-15 weeks, the researchers say, and only a minority of women go for it.

The ICR team used advances in genetics testing – which is getting faster and cheaper – to offer screening with the original cancer doctor.

Prof Nazneen Rahman, who led the trial, told the BBC News website: “It cuts off all that time on a waiting list and extra consultation. The feedback from patients has been overwhelmingly positive.”

The results of the trial, published in the journal Scientific Reports, showed all patients had screening and got their results in a quarter of the time. It also estimated the National Health Service would save £2.6m a year if it changed the way testing was offered.

Prof Rahman added: “There would be 283 fewer cancers and 77 fewer deaths a year – it really does save lives and money.

“It’s very unusual to get a win-win all round that allows us to help more people but doesn’t cost more.”

It is likely the approach would also work for other cancers, such as those in the breast.

Prof Paul Workman, the chief executive of ICR, said: “Twenty years ago the BRCA2 gene was identified at the ICR. This study is an excellent example of how science such as this can be turned into something very practical that can improve the patient care and save lives. We hope the new model for genetic testing will be rolled out across the NHS.”

Alexandra Holden, from the charity Target Ovarian Cancer, commented: “Any improved access to genetic testing for all women with ovarian cancer is an important step.

“It is essential that all women with ovarian cancer get genetic counselling, as we know from the women with ovarian cancer we support that there can be numerous, complex implications of a test, for all the family.”

To read this article, published online by BBC News, click here.

Promising Screening Research For Ovarian Cancer

Dorianne Short had been feeling uncomfortable chronic abdominal and back pain consistently for 18 months.

By the time she turned 50, doctors finally had diagnosed her with uterine fibroids, growths that develop from uterine tissue, and scheduled surgery to remove them.

But when her doctor began the surgery, her physician immediately stopped when she saw that the root of the problem was not fibroids, but stage two ovarian cancer.

“I waited four hours on the table for the gynecological oncologist to do the surgery,” Short recalled. She had to have a hysterectomy to remove her ovaries and uterus and later had eight five-hour chemotherapy treatments.

“I’m lucky,” said Short, now 64 and cancer-free for more than 10 years. “Mine conceivably could have progressed to stage four by the time I was diagnosed.”

Ovarian cancer is the most deadly of the female reproductive system cancers, according to the American Cancer Society. It’s also relatively uncommon.

The most recent state data shows that in Delaware from 2005 to 2009, 314 women were diagnosed with the disease and 217 died from it. But that number only represents 2.7 percent of all cancers diagnosed in women at that time.

The disease begins in a woman’s egg-producing ovaries and often spreads throughout the entire reproductive system and pelvis.

There is no specific test to screen for the disease, but area scientists and clinicians are now studying the genetic mutations that cause cancer with the hope that the research will lead to a way to detect tumors earlier.

In collaboration with the Wistar Institute, a freestanding National Cancer Institute-designated center in Philadelphia, Christiana Care Health System is studying cancer-causing proteins in tissues collected from patients.

Bolstered by a $100,000 grant from the Delaware Ovarian Cancer Foundation, the goal is to build a robust ovarian tissue database, said Dr. Stephanie Jean, director of gynecologic oncology research at Christiana Care.

“It’s a real need,” Jean said. “But there isn’t anything right now that I’m aware of that makes a big difference in screening.”

Due to lack of early detection and misdiagnosed symptoms, only about 20 percent of ovarian cancers are found at stage one or two.  If the cancer is found later, the five-year survival rate can be below 30 percent.

Unlike ways to detect breast cancer, which can include a breast exam, mammography or biopsy, there is no simple physical screening test for ovarian cancer. An ultrasound can uncover cancer spots, but not well enough to be guaranteed. A pap test, which can detect abnormal cervical cancers cells, cannot show ovarian cancer.

Currently there are two approved tests that show cancerous proteins, CA 124 and HE4, in ovarian cancer patients, but David Speicher, a scientists with the Wistar Institute, said they are not reliable enough for early diagnosis.

Speicher said there is a “one in a billion type of difference between your high abundance proteins and your proteins that are going to be good biomarkers.”

Scientists want to create new biomarker tests that can be used in combination with the current models to improve early diagnosis rates

Ideally a simple blood test could be used in screening or perhaps a Pap smear could expand to test for ovarian cancer cells. Ovarian cancer tumor cells can be shed into the vaginal canal, Jean explained.

“It’s all so very new. It’s a very exciting area of research now, but too early to say what it will actually produce in the end,” she said.

Challenges In Detecting 

The American Cancer Society estimates that in 2016 22,280 women in the United States will be diagnosed with ovarian cancer and 14,240 will die from it.

Even though about 15 percent of ovarian cancers are related to the BRCA 1 and 2 breast cancer genes, there are four different subtypes of ovarian cancer and each differ genetically.

“I think part of it is these are very smart tumors,” Jean said. The cancer’s major symptoms often are not seen as indicating a serious illness.

Dorianne Short often felt tired and had trouble eating meals, but she chalked it up to being on a Weight Watchers program.

“It wasn’t something I could definitely pinpoint.” she said. Now president of the Delaware Ovarian Cancer Foundation, she tries to raise awareness of the symptoms and new initiatives through 5Ks, fundraisers and health fairs and by turning towns teal in September for ovarian cancer education.

Sherry Pollex, girlfriend of NASCAR driver Martin Truex Jr., also turned her diagnosis into an awareness platform.  Pollex was diagnosed with stage 3 ovarian cancer in August of 2014 at age 35.

She felt bloated and had severe pelvic pain, but doctors could not locate the cause, diagnosing her with conditions such as ovarian cysts, celiac disease or irritable bowel syndrome.

Finally the pain was so bad, a friend who was a gastroenterologist offered to do a CT scan on her entire body to see if there was an underlying issue. Thirty minutes later her friend was in tears, she said, as he explained that ovarian cancer had spread to her pelvic area. He gave her until Christmas.

“Cancer never even crossed my mind,” she said from Dover when Truex was competing at the Dover International Speedway in May. “That day my life changed forever. It’s so shocking. I was trying to get pregnant.”

She has a 13-inch scar from her rib cage to pubic bone where doctors removed her ovaries, uterus and scrapped cancer cells off her spleen and diaphragm. Then she had 17 straight months of chemotherapy.

“You know when something is wrong with your body,” Pollex said. “I can’t emphasize that enough. Do your research and ask questions.”

Now Pollex advocates for a test called the Ova1.

Though not a screening test, it can detect whether a pelvic mass is benign or cancerous. It is covered by Medicare and some insurance companies, but patients would have to pay $295 if it is not approved.

The test helps refer women to a gynecological oncologist for surgery if the mass is cancerous, said Dr. Judy Wolf, chief medical officer of Vermillion, the manufactor of the Ova1 test.

Wolf, formerly a professor of gynecologic oncology at The University of Texas MD Anderson Cancer Center, added that being seen by a gynecological oncologist will improve a woman’s survival rate by 40 percent. Tumors are not always easily found and it is difficult to discern normal tissue from a malignant mass.

“Unfortunately there’s many places along the path to diagnosis and treatment when women with ovarian cancer are failed,” she said.

To read this entire article on DelawareOnline.com, click here.