Screening for Ovarian Cancer


US Preventive Services Task Force Recommendation Statement

Abstract

Importance  With approximately 14 000 deaths per year, ovarian cancer is the fifth most common cause of cancer death among US women and the leading cause of death from gynecologic cancer. More than 95% of ovarian cancer deaths occur among women 45 years and older.

Objective  To update the 2012 US Preventive Services Task Force (USPSTF) recommendation on screening for ovarian cancer.

Evidence Review  The USPSTF reviewed the evidence on the benefits and harms of screening for ovarian cancer in asymptomatic women not known to be at high risk for ovarian cancer (ie, high risk includes women with certain hereditary cancer syndromes that increase their risk for ovarian cancer). Outcomes of interest included ovarian cancer mortality, quality of life, false-positive rate, surgery and surgical complication rates, and psychological effects of screening.

Findings  The USPSTF found adequate evidence that screening for ovarian cancer does not reduce ovarian cancer mortality. The USPSTF found adequate evidence that the harms from screening for ovarian cancer are at least moderate and may be substantial in some cases, and include unnecessary surgery for women who do not have cancer. Given the lack of mortality benefit of screening, and the moderate to substantial harms that could result from false-positive screening test results and subsequent surgery, the USPSTF concludes with moderate certainty that the harms of screening for ovarian cancer outweigh the benefit, and the net balance of the benefit and harms of screening is negative.

Conclusions and Recommendation  The USPSTF recommends against screening for ovarian cancer in asymptomatic women. (D recommendation) This recommendation applies to asymptomatic women who are not known to have a high-risk hereditary cancer syndrome.

Introduction

The US Preventive Services Task Force (USPSTF) makes recommendations about the effectiveness of specific preventive care services for patients without obvious related signs or symptoms.

It bases its recommendations on the evidence of both the benefits and harms of the service and an assessment of the balance. The USPSTF does not consider the costs of providing a service in this assessment.

The USPSTF recognizes that clinical decisions involve more considerations than evidence alone. Clinicians should understand the evidence but individualize decision making to the specific patient or situation. Similarly, the USPSTF notes that policy and coverage decisions involve considerations in addition to the evidence of clinical benefits and harms.

Summary of Recommendation and Evidence

The USPSTF recommends against screening for ovarian cancer in asymptomatic women (D recommendation) (Figure 1).

This recommendation applies to asymptomatic women who are not known to have a high-risk hereditary cancer syndrome.

Rationale
Importance

The age-adjusted incidence of ovarian cancer from 2010 to 2014 was 11.4 cases per 100 000 women per year.1 Ovarian cancer is the fifth most common cause of cancer death among US women and the leading cause of death from gynecologic cancer, despite its low incidence.1 Approximately 14 000 women die of ovarian cancer each year in the United States. More than 95% of ovarian cancer deaths occur among women 45 years and older.2

Detection

The positive predictive value of screening tests for ovarian cancer is low, and most women with a positive screening test result do not have ovarian cancer (ie, many women without ovarian cancer will have a false-positive result on screening tests).

Benefits of Screening

The USPSTF found adequate evidence that screening with transvaginal ultrasound, testing for the serum tumor marker cancer antigen 125 (CA-125), or a combination of both does not reduce ovarian cancer mortality.

Harms of Screening

The USPSTF found adequate evidence that screening for ovarian cancer can result in important harms, including many false-positive results, which can lead to unnecessary surgical interventions in women who do not have cancer. Depending on the type of screening test used, the magnitude of harm ranges from moderate to substantial and reflects the risk for unnecessary diagnostic surgery. The USPSTF found inadequate evidence on the psychological harms of screening for ovarian cancer.

USPSTF Assessment

The USPSTF concludes that there is at least moderate certainty that the harms of screening for ovarian cancer outweigh the benefits.

Clinical Considerations
Patient Population Under Consideration

This recommendation applies to asymptomatic women who are not known to have a high-risk hereditary cancer syndrome (Figure 2). A hereditary cancer syndrome occurs when a genetic mutation is passed from parent to child that increases risk for developing cancers or can cause earlier onset of cancers. Women who have a hereditary cancer syndrome that puts them at high risk for ovarian cancer are excluded from this recommendation.

Risk Assessment

Women with certain hereditary cancer syndromes are at high risk for ovarian cancer. For example, women with BRCA1 or BRCA2 genetic mutations associated with hereditary breast and ovarian cancer syndrome are at high risk for ovarian cancer. Numerous genetic mutations and hereditary cancer syndromes may be associated with ovarian cancer, each with a different constellation of associated cancers and family history pattern.35 Women with a family history of ovarian or breast cancer may be at risk for a hereditary cancer syndrome and should discuss their family history with their health care professional. Management of a diagnosed hereditary cancer syndrome and prevention of ovarian cancer in these women is beyond the scope of this recommendation statement.

The clinical symptoms of ovarian cancer (eg, abdominal pain or pressure, bloating, constipation, urinary symptoms, back pain, or fatigue) are nonspecific and may be present in both healthy women and women with late-stage ovarian cancer; therefore, use of clinical symptoms for risk stratification for the early detection of disease is difficult.

Screening Tests

The USPSTF does not recommend routine screening for ovarian cancer using any method. Transvaginal ultrasound and serum CA-125 testing are readily available procedures that are commonly used to evaluate women with signs or symptoms of ovarian cancer, and both have been evaluated in screening studies. Pelvic examination is also commonly performed to evaluate women with lower abdominal symptoms, and although many clinicians perceive that pelvic examination with bimanual palpation of the ovaries is useful for screening for ovarian cancer,6 there is a lack of evidence to support this.7 Furthermore, the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial included bimanual palpation of the ovaries in its initial screening protocol, but this screening component was discontinued 5 years into the study because no cases of ovarian cancer were detected solely with bimanual palpation of the ovaries.8,9

The evaluation of abnormal test results consists of repeat testing with the same or a different test and often surgical removal (by laparoscopy or laparotomy) of 1 or both of the ovaries and fallopian tubes to determine whether a woman has ovarian cancer. Diagnostic guidelines recommend surgical removal of the complete ovary or ovaries, rather than tissue biopsy, to determine whether ovarian cancer is present.

Treatment

Treatment of ovarian cancer typically includes surgical treatment (staging or debulking) and intraperitoneal, intravenous, or combined chemotherapy.

Useful Resources

In a separate recommendation statement, the USPSTF recommends that women with a family history indicating they are at risk for a deleterious gene mutation (BRCA1 or BRCA2) be referred for genetic counseling and, if indicated, genetic testing.10 The National Cancer Institute provides additional information on ovarian cancer risk and hereditary cancer syndromes.11 The USPSTF also concluded in a separate recommendation statement that the current evidence was insufficient to assess the balance of benefits and harms of screening with pelvic examination to detect a range of gynecologic conditions in asymptomatic, nonpregnant women.7

Other Considerations
Research Needs and Gaps

Given that most cases of ovarian cancer are diagnosed at later stages, when associated mortality is high, further research is needed to identify new screening strategies that could accurately detect ovarian cancer early, at a point when outcomes could be improved. There is a need for more sensitive and specific serologic tests, as well as better imaging techniques. Because of the potential for serious harms from diagnostic workup of positive screening results (ie, surgical removal of the ovary to determine whether ovarian cancer is present), new screening strategies should minimize false-positive results and be highly specific. In addition, studies evaluating the benefits and harms of these screening strategies in asymptomatic women not at high risk for ovarian cancer are needed. Study outcomes should include ovarian cancer mortality, quality of life, false-positive rate, surgery rate, surgical complication rate, and psychological harms. Further research is also needed on primary prevention of ovarian cancer.

Discussion
Burden of Disease

Based on United States Cancer Statistics data on invasive cancer rates from 2010 to 2014, the average annual age-adjusted incidence of ovarian cancer was 11.4 cases per 100 000 women per year, with a mortality rate of 7.4 deaths per 100 000 women.1 In 2017, it is estimated that 22 440 new cases of ovarian cancer will have been diagnosed in the United States and 14 080 deaths will have occurred.12 Early stages of the disease are often asymptomatic. Symptoms are usually nonspecific and can include abdominal pain or pressure, bloating, constipation, urinary symptoms, back pain, or fatigue.13 The majority of women (88%) diagnosed with ovarian cancer are 45 years and older, with a median age at diagnosis of 63 years.2 Most women with ovarian cancer are diagnosed at later stages; approximately 60% of women have distant spread of disease at the time of diagnosis.2 From 2010 to 2014, white women had the highest age-adjusted incidence rate (11.8 cases per 100 000 women), followed by Hispanic women (10.3 cases per 100 000 women), black women (9.2 cases per 100 000 women), Asian/Pacific Islander women (9.1 cases per 100 000 women), and American Indian/Alaska Native women (8.3 cases per 100 000 women). White women are most likely to die of ovarian cancer, followed by black, Hispanic, American Indian/Alaska Native women, and Asian/Pacific Islander women.1

Mortality rates from ovarian cancer vary by stage at diagnosis; 5-year survival rates range from 92.5% for localized cancer to 28.9% for cancer with distant spread.14

Scope of Review

The USPSTF commissioned a review of the evidence on screening for ovarian cancer to update its 2012 recommendation. The evidence review evaluated the benefits and harms of screening for ovarian cancer in asymptomatic women not known to be at high risk for ovarian cancer. Outcomes of interest included ovarian cancer mortality, quality of life, false-positive rate, surgery and surgical complication rates, and psychological effects of screening. The USPSTF included primary peritoneal cancer in its ascertainment of ovarian cancer outcomes, even if it was not the primary end point of the study, because clinically, both types of cancer are diagnosed and treated as 1 disease. The USPSTF also considered ascertainment of ovarian cancer outcomes that included both incident and prevalent cases of cancer, since screening programs would detect both. The review included any screening approach evaluated by clinical trial design. The USPSTF considered the initial screening test (eg, transvaginal ultrasound or CA-125 testing interpreted using a single cutoff or the risk of ovarian cancer algorithm [ROCA; Abcodia Inc]) as the screening intervention. Further testing that subsequently occurred based on initial screening test results was considered follow-up testing and evaluation, rather than part of screening.

Effectiveness of Screening

The USPSTF reviewed direct evidence evaluating the benefits of screening for ovarian cancer on mortality.3 The USPSTF identified 3 good-quality studies evaluating the effect of annual screening in asymptomatic women not known to be at high risk for ovarian cancer. None of the studies found that screening significantly reduced ovarian cancer mortality. The largest and most recent trial, the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS), was a randomized clinical trial of 202 638 postmenopausal women aged 50 to 74 years not known to be at high risk for ovarian cancer.15 More than 95% of trial participants were white, and 1.6% reported a maternal history of ovarian cancer and 6.4% reported a maternal history of breast cancer; however, women with a family history considered “high risk” for familial ovarian cancer were explicitly excluded.16 The UKCTOCS trial had 2 intervention groups and a no-screening control group. Women were randomized to screening with CA-125 serum testing, with triage and follow-up determined by ROCA, or to yearly transvaginal ultrasound. The CA-125 ROCA screening intervention group was described as multimodal screening in the trial publications and included a standard protocol for all additional evaluation. ROCA evaluates changes in CA-125 values over time, following a baseline age-adjusted measurement. Women randomized to the control group received no screening. After a median follow-up of 11.1 years, ovarian cancer mortality (which includes mortality from primary peritoneal and fallopian tube cancer) was not significantly different among the control group and 2 intervention groups (0.35% in the control group, 0.32% in the transvaginal ultrasound group, and 0.32% in the CA-125 ROCA group). There was also no significant difference in mortality risk in the transvaginal ultrasound and CA-125 ROCA groups (hazard ratio, 0.91 [95% CI, 0.76-1.09] and 0.89 [95% CI, 0.74-1.08], respectively).3,15 Exploratory analyses of UKCTOCS trial data suggest the potential for emergence of a delayed mortality benefit of screening appearing beyond 10 years from randomization. However, this finding was not statistically significant unless cases of primary peritoneal cancer were excluded. Extended follow-up data may help clarify this potential finding in the future; however, given the aggressive nature (ie, low 5-year survival rate) of ovarian cancer, the mechanism behind a delayed benefit from screening and early detection would be unclear, especially because the trial discontinued screening after 7 to 11 years.

The pilot trial for the UKCTOCS trial, UK Pilot, was much smaller (n = 21 955 randomized). It evaluated the use of a single cutoff value for CA-125 testing and found no significant difference in ovarian cancer mortality (excluding cases of primary peritoneal cancer, which were not reported) between women who were screened vs not screened (0.08% vs 0.16%; relative risk, 0.50 [95% CI, 0.22-1.11]).3,17

The only trial conducted in the United States was the PLCO trial. In that trial, 68 557 women who had at least 1 ovary at baseline were randomized to either annual screening (both CA-125 testing and transvaginal ultrasound for the first 4 rounds of screening, then 2 rounds of CA-125 testing only) or usual care; median follow-up was 12.4 years. Eligible participants were women aged 55 to 74 years without a previous diagnosis of lung, colorectal, or ovarian cancer. Trial recruitment targeted women from the general population; the trial did not actively exclude women based on risk for hereditary ovarian cancer syndromes (based on reported family history), and 17.4% of participants reported a family history of ovarian or breast cancer. Nearly 90% of participants were white. Abnormal test results were managed by the participant’s personal health care practitioner. No difference was found in ovarian cancer mortality, which includes primary peritoneal cancer mortality, with 0.34% in the screening group and 0.29% in the usual care group (relative risk, 1.18 [95% CI, 0.82-1.71]).3,8 Recent analyses of PLCO trial data that add up to 6 more years of posttrial mortality data also did not find evidence of a longer-term benefit of screening.18

Potential Harms of Screening

The USPSTF reviewed evidence on harms of screening for ovarian cancer from the 3 studies described above, as well as a fourth study of fair quality reporting on quality of life and psychological harms of screening (Quality of life, Education, and Screening Trial [QUEST]) (n = 549 analyzed).19 Based on data from the 3 studies, the calculated false-positive rates (ie, the number of women without cancer who had a positive screening test result) were 11.9% in the first screening round in the UKCTOCS transvaginal ultrasound group and 9.0% in the first screening round in the UKCTOCS CA-125 ROCA group.3 These rates exclude cases of primary peritoneal cancer because this information was not reported. Cumulatively, in all subsequent screening rounds (ie, rounds 2 to 11) in the UKCTOCS CA-125 ROCA group, 44.2% of women who did not have ovarian cancer (including primary peritoneal cancer) had a positive CA-125 ROCA result at some point during the trial screening period.3 The false-positive rate for subsequent screening rounds in the UKCTOCS transvaginal ultrasound group was not reported. In the UK Pilot trial, the calculated false-positive rate (excluding cases of primary peritoneal cancer, which were not reported) of CA-125 testing using a single cutoff value was 4.2% across 3 screening rounds. In the PLCO trial, the calculated false-positive rate (including cases of primary peritoneal cancer) of transvaginal ultrasound and CA-125 testing was 9.6% across all 6 screening rounds.3 Surgery to investigate positive screening test results among women who ultimately did not have ovarian cancer occurred in 0.2% of participants in the UK Pilot CA-125 group, 0.97% of participants in the UKCTOCS CA-125 ROCA group, 3.25% of participants in the UKCTOCS ultrasound group, and 3.17% of participants in the PLCO CA-125 plus ultrasound group.3 Up to 15% of these women had major surgical complications.3

The USPSTF identified limited evidence on the psychological harms of screening for ovarian cancer from the UKCTOCS and QUEST trials.3,19,20 The UKCTOCS trial measured anxiety in a subgroup of participants. Although no significant differences were found between the intervention and control groups, there was a greater odds of psychological morbidity among women who were referred to higher levels of screening.20 The QUEST trial evaluated the effect of screening for ovarian cancer on cancer worry and quality of life among average-risk US women 30 years and older. Cancer screening consisted of alternating CA-125 testing and transvaginal ultrasound every 6 months, for a maximum of 4 screening rounds. Although no statistically significant difference in cancer worry was found between study groups, the trial found that women with abnormal test results were more likely to report cancer worry at 2 years of follow-up (odds ratio, 2.8 [95% CI, 1.1-7.2]) than women without abnormal results.19

Estimate of Magnitude of Net Benefit

The USPSTF found adequate evidence that screening for ovarian cancer does not reduce ovarian cancer mortality. Three large good-quality studies all found no benefit in ovarian cancer mortality from annual screening in asymptomatic women not known to be at high risk for ovarian cancer. The USPSTF also found adequate evidence from these 3 studies that the harms from screening for ovarian cancer are at least moderate and may be substantial in some cases. Harms from screening for ovarian cancer include false-positive results, which may lead to unnecessary diagnostic surgery to determine whether ovarian cancer is present, often resulting in removal of 1 or both of the ovaries and fallopian tubes. Serious surgical complications can also result. The USPSTF found the evidence on psychological harms of screening to be inadequate and could not draw any definitive conclusion on whether ovarian cancer screening causes psychological harms. Given the lack of mortality benefit of screening, and the moderate to substantial harms that could result from false-positive screening test results and subsequent surgery, the USPSTF concludes with moderate certainty that the harms of screening for ovarian cancer with CA-125 testing (using a single cutoff value or the ROCA), transvaginal ultrasound, or both outweigh the benefit, and the net balance of the benefit and harms of screening is negative.

Response to Public Comment

A draft version of this recommendation statement was posted for public comment on the USPSTF website from July 18, 2017, to August 14, 2017. Many comments voiced concern that given the aggressive nature of ovarian cancer and that symptoms often only appear at later stages, any screening test that can detect ovarian cancer early should be recommended. The USPSTF agrees that screening tests are needed that can accurately detect ovarian cancer earlier to prevent deaths from ovarian cancer; however, the evidence shows that currently available tests are not able to do so and can lead to harm by causing healthy women to undergo surgical removal of their ovaries when no cancer is present. The USPSTF issued its recommendation against screening based on this evidence, not on the costs of screening. Additional comments sought clarification on which women are at high risk for ovarian cancer and to whom the recommendation applies. The USPSTF revised the recommendation statement to clarify the role of family history in ovarian cancer risk and to describe symptoms of ovarian cancer. Women with a family history of ovarian or breast cancer or symptoms should discuss this with their health care provider. The USPSTF also provided more information on how it considered evidence from specific studies. The USPSTF considered study results that included cases of primary peritoneal cancer in the ascertainment of ovarian cancer because clinically, both types of cancer are diagnosed and treated as 1 disease. Similarly, the USPSTF considered study results that included reporting of both prevalent and incident cases of ovarian cancer, because screening would detect both.

Update of Previous USPSTF Recommendation

This recommendation statement is consistent with the 2012 USPSTF recommendation.21 Since 2012, the large UKCTOCS trial was published, and much like the PLCO trial, it did not find that screening for ovarian cancer reduces ovarian cancer mortality in asymptomatic women not known to be at high risk for ovarian cancer.

Recommendations of Others

There is consensus among major medical and public health organizations that screening for ovarian cancer in the general population is not recommended. The American College of Obstetricians and Gynecologists does not recommend screening for ovarian cancer in low-risk, asymptomatic women; evaluation of high-risk women may include transvaginal ultrasound and CA-125 testing, in addition to physical examination.22 The American Cancer Society states that there is no screening test proven to be effective and sufficiently accurate in the early detection of ovarian cancer and does not recommend screening for ovarian cancer in average-risk women.23 The American College of Radiology does not recommend screening for ovarian cancer in average-risk women.24 Consistent with the USPSTF, the American Academy of Family Physicians recommends against screening for ovarian cancer in asymptomatic women.25 Although it is beyond the scope of the USPSTF recommendation, other organizations, such as the National Comprehensive Cancer Network, have issued guidelines for the prevention of ovarian cancer in women with hereditary cancer syndromes.26

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Ovarian Cancer: Making the Case for Screening Those at High-Risk


30-year study suggests transvaginal ultrasound is a viable option for some high-risk women

Results of the 30-year prospective University of Kentucky Ovarian Cancer Screening Trial are adding to a body of evidence suggesting that an annual transvaginal ultrasound can detect early-stage ovarian cancer and improve survival rates for this patient population.

The cohort study by John van Nagell, MD, of the University of Kentucky Markey Cancer Center, and colleagues found that annual ultrasound screening of at-risk asymptomatic women was associated with early detection of lower-stage ovarian cancer and increased disease-free survival for types I and II epithelial ovarian cancer.

The study, published in Obstetrics & Gynecology, enrolled 46,101 women from January 1987 to June 2017 who met the eligibility criteria — women asymptomatic for ovarian cancer ages 50 or older and asymptomatic women ages 25 or older with a documented family history of ovarian cancer in at least one primary or secondary relative. Participants did not get genetic testing, but the women all completed a questionnaire that included medical history, surgical history, menopausal status, hormonal use, and family history of cancer.

The researchers documented a family history of ovarian cancer in 23.2% (20,195) of the participants and a family history of breast cancer in 43.8% (20,195). The women underwent 298,418 scans (mean of 6.5 scans per participant), with 246,275 scans (82.4%) visualizing one or both ovaries. Those women (699 or 1.5%) who had persisting ovarian tumors with transvaginal ultrasound underwent diagnostic surgery. This group was compared with 921 unscreened women with clinically detected epithelial ovarian cancer referred to the cancer center for treatment from 1995 to 2017.

The annual screenings found 71 invasive epithelial ovarian cancers and 17 epithelial ovarian tumors of low malignancy; of those with invasive epithelial ovarian cancer, 30 had stage I disease (42%), 15 had stage II (21%), 26 had stage III (37%), and no one had stage IV. These patients were followed from 9.2 months to 27 years. Looking at 5-, 10-, and 20-year disease-specific survival, the researchers found that the screened group had a significant survival benefit of 30% higher than the unscreened group.

“Sixty-three percent of women whose invasive ovarian cancer was detected by screening had stage I or II disease as opposed to 30% in unscreened women from the same geographic area diagnosed clinically during the same time period,” van Nagell and co-authors wrote. “That there was a substage shift within stage III in the screening group also is important, because there is a 5-year survival advantage of 20% in patients with stage IIIA compared with stage IIIC disease in the era of platinum+ taxane chemotherapy.”

Current Screening Guidelines

Survival for women with ovarian cancer, the leading cause of gynecologic cancer death in the U.S., remains dismally low. The U.S. Preventive Services Task Force (USPSTF) earlier this year reiterated their firm stance that average-risk, asymptomatic women should not be screened for ovarian cancer, citing the harms of screening — false-positive results, leading to unnecessary surgical interventions — and noting that research has not shown a reduction in mortality. The task force does recommend screening with CA-125 and transvaginal ultrasound in women who have genetic mutations and are considered very high-risk.

Asked for her perspective, Veena John, MD, system head of gynecologic cancer at Northwell Health Cancer Institute in New Hyde Park, N.Y., said she is not yet ready to change her clinical practice based on the trial by van Nagell et al., but noted that she follows the USPSTF’s recommendations that yearly screens are only for those women who carry genetic mutations. However, she added, “if the patient has a risk more than the average, it would benefit them to have sonograms.”

Still, she said that the issue of false positives is one of the main reasons for not jumping on the bandwagon of yearly screening considering the anxiety such testing can cause.

The University of Kentucky study acknowledged these concerns, particularly false-positive results from screening. The study authors noted that “in the United Kingdom Collaborative Trial of Ovarian Cancer Screening multimodal screening arm, only 15 of 488 screen-positive women with benign ovarian tumors at surgery (3.1%) experienced a postoperative complication, and 80% of these were minor.” In the Kentucky trial the authors noted that tumor removal via laparoscopy was their standard approach and if benign disease was detected, there was usually no further surgery.

“Surgical complications occurred in only 6.6% of these cases, and 97% of these complications were minor,” the researchers wrote.

Writing in an accompanying editorial, Sharon Robertson MD, MPH, and Jeffrey Peipert, MD, PhD, both of Indiana University School of Medicine in Indianapolis, called the effort of van Nagell and colleagues, “impressive,” but suggested caution interpreting the results for the general population. They pointed out several weaknesses of the study – the higher incidence of ovarian cancer in the study population vs the general population, the lack of genetic testing, and the fact that this was not a randomized controlled study.

Van Nagell, told the Reading Room that he does not dispute these observations and certainly agrees that a randomized controlled study would be warranted, but in a disease where the control group would be women who did not get screened and who would have to wait for clinical diagnosis, he asked, “Who would volunteer to be in that group?” He noted that women understand that ovarian cancer is considered a silent disease with at best, extremely subtle symptoms – for example, a feeling of fullness, abdominal bloating, a change in bowel habits, or urinary problems – and is often not found at its early stages.

Robertson and Peipert wrote that while the study did not reflect the general population they agreed with the authors’ conclusion that ultrasound screening in women at high risk for ovarian cancer may lead to earlier detection of the disease.

Van Nagell said he agreed with the recommendations from the British study for screening women with a lifetime risk of ovarian cancer of 3-10%, which includes women over age 50 or those over 25 with a family history of ovarian cancer.

John said that until there is an established screening guideline, it is important for physicians to understand the extremely subtle symptoms of ovarian cancer: “I tell my colleagues and those who refer patients to me to listen to the patients’ symptoms… please listen to them.” If transvaginal ultrasound screening or even prophylactic salpingo-oophorectomy is the recommended option, physicians and patients will need to discuss all the pros and cons of these options, she noted.

The Question of Mortality

In the Prostate, Lung, Colorectal, and Ovarian Trial conducted by Claire Zhu, PhD, and colleagues, the one trial often pointed to that dismisses routine screening for ovarian cancer, a reduction in mortality was not evident. “However, there was no standard evaluation algorithm for screen-detected ovarian tumors and no uniform treatment protocol for newly diagnosed ovarian cancers in this trial,” van Nagell and co-authors wrote. “As a result there was significant variation in the detection-treatment interval and type of treatment in both the screening and control arms of this trial.”

On the other hand, the U.K. trial did show an association with a reduction in mortality. And, with the University of Kentucky trial the association with reduced mortality was similar to the British study: “The 10-year ovarian cancer mortality was reduced in women receiving screening by 31% and produced 416 life years gained at a cost of $40,851 per life year gained.”

Van Nagell said he doesn’t dispute any of the opinions expressed by the USPSTF, the editorialists, or Veena John, but his ongoing work is erecting some pillars of care that may start to gain the attention of the wider community. While not calling for universal screening of women, establishing algorithms for screening protocols and surgeries certainly would help zero in on a devastating cancer, he said.

“We know if we can detect women with stage I or II cancer of the ovary, we can cure them,” van Nagell said. “We need to be defining a population that benefits from screening. Why on earth aren’t we focusing more on early detection methodology in at-risk women? Why on earth wouldn’t you want to focus on that risk group to try to detect cancer at an earlier and more curable stage?”

Newer Hormonal Contraceptives ‘Protect Against Ovarian Cancer’


Women who use newer hormonal contraceptives, which often have lower oestrogen doses, have a significantly reduced risk of developing ovarian cancer versus never users, which becomes more pronounced over time, say UK and Danish researchers.

Previous studies had demonstrated that older products, with higher levels of oestrogen and older progestogen formulations, reduced ovarian cancer risk but this is believed to be the first time it has been shown in contemporary products in a large-scale prospective analysis.

New Study

For the study, Lisa Iversen, PhD, research fellow, Institute of Applied Health Sciences, University of Aberdeen, examined prospective data on almost 1.9 million Danish women aged 15–49 years.

They found that women who were current or former users of hormonal contraceptives had a 34% reduced risk of developing any form of ovarian cancer, rising to a 74% reduced risk after more than 10 years of use.

The research, which was published in the BMJ on September 26th, suggested that, across the whole study population, hormonal contraceptive use had prevented 21% of ovarian cancers.

The team says that their findings indicate that “contemporary combined hormonal contraceptives are still associated with a reduced risk of ovarian cancer in women of reproductive age, with patterns similar to those seen with older combined oral products”.

They note, however, that while the beneficial effect appears to continue after stopping them, “it is not known how long for”.

The authors add: “It has been suggested that recent downward trends in ovarian cancer mortality rates in North America and Europe can be partly attributed to the use of combined oral contraceptives.

“We found a population prevented fraction of 21% with use of hormonal contraception, which supports the notion that these ovarian cancer mortality benefits are likely to continue.”

Past Research

Previous studies have demonstrated that women who use combined contraceptives have a reduced risk of developing ovarian cancer, and the effect persists many years after stopping use.

However, the majority of the evidence refers to older and higher dose oestrogen preparations that contain older progestogens, and there have been “substantial changes” in hormonal contraception in recent years, the team notes.

These include combined formulations with lower oestrogen doses, the introduction of newer progestogens, alterations in the patterns of administration, the introduction of non-oral administration, and the increased use of progestogen-only preparations.

Study Details

To examine the association between contemporary combined hormonal contraceptives and rates of ovarian cancer, the researchers conducted a prospective study of all Danish women aged 15–49 who were enrolled on the Danish Sex Hormone Register Study between 1995 and 2014.

After excluding women who had cancer or venous thrombosis or who were treated for fertility before study entry, the final population was 1,879,227 women.

The women were categorised as never users of contraceptive, current or recent users (defined as ≤1 year after stopping use), and former users (defined as >1 year since stopping use).

During the study period, 1249 women developed incident ovarian cancer during more than 21.4 million person-years of observation, or an average of 11.4 years of follow-up per woman.

Among women who had ever used hormonal contraceptives, 478 ovarian cancers were diagnosed during approximately 13.3 million person-years of follow-up. A further 771 ovarian cancers were diagnosed during approximately 8.2 million person-years of follow-up among never users.

The median age at ovarian cancer diagnosis was 44.4 years.

Adjusting for a range of factors, including parity, age group, education, polycystic ovary syndrome, and family history of breast or ovarian cancer, the team found that, overall, ever hormonal contraceptive users had a reduced risk of ovarian cancer versus never users, at a relative risk of 0.66.

This translated into a reduction in the age standardised absolute rate of ovarian cancer from 7.5 per 100,000 person years with never use to 3.2 per 100,000 years with ever use.

For current or recent users of hormonal contraceptives, the relative risk of developing ovarian cancer versus never users was 0.58, while that for former users was 0.77.

The risk of ovarian cancer decreased with increasing hormonal contraceptive use, from a relative risk of 0.82 with ≤1 year of use to 0.62 for >1 to ≤5 years, 0.57 for <5 to ≤10 years, and 0.26 for >10 years of use (p<0.001 for trend).

Findings

Analysis indicated that the results were similar when restricting the population to the period up to the first switch in contraceptive type, and there was little evidence of a substantial difference in risk by tumour type or progestogen content in the contraceptive.

However, the team found that progestogen-only hormonal contraceptives were not associated with a reduction in the risk of ovarian cancer, although relatively few women used these products exclusively.

The team calculates that, overall, the use of hormonal contraception, whether current or former, was associated with a 21% reduction in the incidence of ovarian cancer versus never use.

Noting the similar effect across ovarian cancer types, they write: “Recent understanding suggests that although ovarian cancer is clinically considered to be one disease, it is in fact a heterogeneous group of neoplasms with different pathogenesis pathways.

“Combined hormonal contraceptives suppress ovulation so protection against neoplastic development is feasible, but the exact mechanisms by which hormonal contraceptives reduce ovarian cancer risk are unclear.

“Whatever the biological mechanisms, the epidemiological evidence suggests a long-lasting protection against most types of ovarian cancer from combined oral contraception.”

Applying Precision Medicine to Ovarian Cancer: Proof-of-Principle for a “Molecular Second Look”


Objectives The objectives of this study were to assess if targeted investigation for tumor-specific mutations by ultradeep DNA sequencing of peritoneal washes of ovarian cancer patients after primary surgical debulking and chemotherapy, and clinically diagnosed as disease free, provides a more sensitive and specific method to assess actual treatment response and tailor future therapy and to compare this “molecular second look” with conventional cytology and histopathology-based findings.

Methods/Materials We identified 10 patients with advanced-stage, high-grade serous ovarian cancer who had undergone second-look laparoscopy and for whom DNA could be isolated from biobanked paired blood, primary and recurrent tumor, and second-look peritoneal washes. A targeted 56 gene cancer-relevant panel was used for next-generation sequencing (average coverage, >6500×). Mutations were validated using either digital droplet polymerase chain reaction (ddPCR) or Sanger sequencing.

Results A total of 25 tumor-specific mutations were identified (median, 2/patient; range, 1–8). TP53 mutations were identified in at least 1 sample from all patients. All 5 pathology-based second-look positive patients were confirmed positive by molecular second look. Genetic analysis revealed that 3 of the 5 pathology-based negative second looks were actually positive. In the 2 patients, the second-look mutations were present in either the original primary or recurrent tumors. In the third, 2 high-frequency, novel frameshift mutations in MSH6 and HNF1A were identified.

Conclusions The molecular second look detects tumor-specific evidence of residual disease and provides genetic insight into tumor evolution and future recurrences beyond standard pathology. In the precision medicine era, detecting and genetically characterizing residual disease after standard treatment will be invaluable for improving patient outcomes.

Ovarian Cancer and Immunotherapy: An Update


Immunotherapy has revolutionized the treatment of many types of cancer and is now undergoing testing in ovarian cancer. Clinical trials of drugs known as immune checkpoint inhibitors, which can unleash a potent immune system attack on cancer cells, have produced remissions in about 10-15 percent of patients with advanced and recurrent ovarian cancer – somewhat of a respectable figure, but given these modest response rates, the side effects of these agents, and the sometimes short remission periods, new approaches for the use of these agents need to be explored.

Ursula Matulonis, MD, says this is a very exciting time in research into immunotherapy for ovarian cancer.

Perhaps one of the keys to achieving greater success with these agents is using them in combination with other therapies. Laboratory studies have provided an abundance of evidence that combinations of immunotherapy agents plus other biologic therapies may prove significantly more effective in ovarian cancer than immune checkpoint inhibitors alone.

Immune Checkpoint Inhibitors

Ovarian cancer is a heterogenous disease, firstly meaning that several different types, or “histologies,” exist, each with its own unique genetic make-up. It also means that within an individual patient, different sites of cancer are likely comprised of several, genetically distinct, subtypes of cancer cells. This is one reason why it can be so difficult to treat with chemotherapy or targeted therapies: while the drugs are lethal to some cancer cell subtypes, they may leave others largely untouched, allowing the surviving cells to grow and proliferate. Immune checkpoint inhibitors, by contrast, have the potential to eliminate a broader range of tumor cell subtypes, sharply reducing the potential for drug resistance.

One of the advantages of combination regimens is that the second drug has the potential to make tumor cells more vulnerable to the immune checkpoint inhibitor. Before such approaches can become standard therapy, however, a variety of questions need to be answered: Which combinations work best in individual tumors? Are combinations more effective as front-line or follow-up treatment? Is it possible to pre-select patients based on the specific genetic profile identified in the cancer, the number of prior therapies, the histology of the cancer, etc.? The number of potential combinations of checkpoint inhibitors and other treatments is rather large, so sorting out these questions will inevitably take time. But we’ve already made a great start.

Immunotherapy Clinical Trials

Recognizing the exceptional promise of immunotherapies for ovarian cancer, my colleagues and I in the Gynecology Oncology Program at Dana-Farber have made a concerted effort to lead and participate in clinical trials of immunotherapies in combination with other types of drugs. These drugs include targeted therapies, which block cancer-related proteins in tumor cells; PARP inhibitors, which interfere with tumor cells’ ability to repair certain types of DNA damage; standard chemotherapy agents; and anti-angiogenic drugs, which pinch off tumors’ access to circulating blood. More than half a dozen such trials are now open or are about to open. Most of these are phase 1 trials, small-enrollment trials that are primarily concerned with the safety of potential new treatments, but which also track their effectiveness. One of the trials is a phase 3 study, the final stage before a therapy can be submitted to the Food and Drug Administration for consideration as a standard therapy.

An array of other immunotherapy trials for ovarian cancer is in the planning stages in the Gynecologic Oncology Program. These include a trial of a “neoantigen vaccine,” a treatment designed to spur a powerful, very precise immune system attack on tumor cells, in patients already treated with chemotherapy. Another will investigate a combination of the checkpoint inhibitors tremelimumab, durvalumab, and radiation therapy.

In addition, several immunotherapy trials led by researchers within the Center for Immuno-Oncology at Dana-Farber are also open to patients with ovarian cancer and other gynecologic cancers. A full list of ovarian cancer treatment trials is available on the Dana-Farber website.

This is a very exciting time in research into immunotherapy for ovarian cancer. There’s every reason to expect that immunotherapy will prove as effective in the treatment of this disease as it already has in cancers such a melanoma, Hodgkin lymphoma, lung cancer, kidney cancer, and others. Today’s clinical trials are where the revolution in treatment will take place.

By Ursula Matulonis, MD, Director, Gynecologic Oncology, Susan F. Smith Center for Women’s Cancers.

Onions – A Powerful Anti-Cancer Food Staple


onions anti cancer food

Story at-a-glance

  • People with the highest consumption of onions have a lower risk of several types of cancer, including ovarian, endometrial, liver, colon, kidney, esophageal, laryngeal, prostate, colorectal and breast cancer
  • Onions contain several anti-cancer compounds, including quercetin, anthocyanins, organosulfur compounds such as diallyl disulfide (DDS), S-allylcysteine (SAC) and S-methylcysteine (SMC) and onionin A (ONA)
  • ONA may offer protection against epithelial ovarian cancer, the most common type of ovarian cancer; quercetin helps protect against ovarian, breast, colon, brain and lung cancer

If you’re interested in using food to lower your risk of cancer, remember to eat lots of onions. Research shows that people with the highest consumption of onions (as well as other allium vegetables) have a lower risk of several types of cancer, including:1,2,3,4

  • Liver, colon5 and renal cell (kidney)
  • Esophageal and laryngeal
  • Prostate6 and colorectal
  • Breast7
  • Ovarian and endometrial

Onions contain several anti-cancer compounds, including quercetin, anthocyanins, organosulfur compounds such as diallyl disulfide (DDS), S-allylcysteine (SAC) and S-methylcysteine (SMC) and onionin A (ONA).

Onion Compound Suppresses Ovarian Cancer

Starting with the latter, ONA was recently found to offer protection against epithelial ovarian cancer (EOC),8 the most common type of ovarian cancer. As noted by Medical News Today:9

“With a [five]-year survival rate of approximately 40 percent, effective treatments for the illness are needed.

Although new cases of EOC ranks 10th among female malignancies, the team says the number of deaths due to this type of ovarian cancer ranks fifth in the United States.

About 80 percent of patients with EOC have a relapse after initial chemotherapy treatment.”

ONA, it turns out, slowed growth of EOC. The compound also inhibited other cancerous activities, and enhanced the effects of anti-cancer drugs. Mice fed ONA also lived longer. According to the authors:

“We found that ONA reduced the extent of ovarian cancer cell proliferation induced by co-culture with human macrophages. In addition, we found that ONA directly suppressed cancer cell proliferation.

Thus, ONA is considered useful for the additional treatment of patients with ovarian cancer owing to its suppression of the pro-tumor activation of [tumor-associated macrophages] and direct cytotoxicity against cancer cells.”

The Stronger an Onion’s Flavor, the More Effective Its Anti-Cancer Effects

Previous research has revealed that the stronger the flavor of the onion, the better its cancer-fighting potential. A 2004 study, in which food scientists analyzed 10 different varieties of onion, the following were found to be particularly effective against liver and colon cancer:10,11

  • Liver cancer: shallots, Western yellow onion and pungent yellow onion
  • Colon cancer: pungent yellow onion, Western yellow onion

Northern red onions were also found to be high in anti-cancer chemicals, just not quite as potent as the others listed.

Mild-flavored onions, such as Empire Sweet, Western white, Peruvian sweet and Vidalia had the lowest antioxidant activity, making them less potent in terms of anti-cancer benefits. According to lead author, Dr. Rui Hai Liu, an associate professor of food science:

“Onions are one of the richest sources of flavonoids in the human diet, and flavonoid consumption has been associated with a reduced risk of cancer, heart disease and diabetes.

Flavonoids are not only anti-cancer but also are known to be anti-bacterial, anti-viral, anti-allergenic and anti-inflammatory …

Our study of 10 onion varieties and shallots clearly shows that onions and shallots have potent antioxidant and antiproliferation activities and that the more total phenolic and flavonoid content an onion has, the stronger its antioxidant activity and protective effect.”

Quercetin — Another Potent Anti-Cancer Compound

Quercetin, another anti-cancer compound found in onions, has been shown to decrease cancer tumor initiation and inhibit the proliferation of cultured ovarian, breast and colon cancer cells. It’s also associated with a decreased risk for brain cancer,12 and a lower risk of lung cancer if you’re a smoker.13

Quercetin has also been shown to help lower blood pressure in hypertensive patients,14 and helps prevent histamine release, making quercetin-rich foods such as onions “natural antihistamines.”

Quercetin is available in supplement form, but getting this flavonoid naturally from onions makes more sense for a couple of reasons:15

  • One animal study found that animals received greater protection against oxidative stress when they consumed yellow onion in their diet, as opposed to consuming quercetin extracts.16
  • Quercetin is not degraded by low-heat cooking, such as simmering, making onion soup an easy-to-make superfood.

Other Beneficial Compounds Found in Onions

The organosulfur compounds DDS, SAC and SMC have also been found to inhibit colon and kidney cancer, in part by inducing cancer cell apoptosis (cell death), but also by inhibiting gene transcription and protecting against ultraviolet-induced immunosuppression.17 Onions are also a good source of:

Fiber, which can help lower your cancer risk, especially colon cancer

Vitamin C18

Anthocyanins (red, purple and blue plant pigments found in red onions). Research has linked anthocyanins to a reduced risk for a number of diseases, including cancer, cardiovascular disease and neurological dysfunction and decline.

They also help prevent obesity and diabetes, in part by inhibiting certain enzymes in your digestive tract, and by supporting healthy blood sugar control. They have potent anti-inflammatory effects, which helps explain their protective effects against chronic disease

The Many Health Benefits of Onions

While onions are gaining a reputation for their anti-cancer properties, the more we learn about onions, the more it becomes clear they offer whole body benefits.

That is the beauty of eating whole foods, after all, because they typically contain many beneficial phytochemicals that enhance your health in numerous synergistic ways. As for onions, research has shown that including onions in your diet may offer the following benefits:19

Prevent inflammatory processes associated with asthma Reduce symptoms associated with diabetes
Lower levels of cholesterol and triglycerides Reduce symptoms associated with osteoporosis and improve bone health
Maintain gastrointestinal health by sustaining beneficial bacteria Diminish replication of HIV
Reduce risk of neurodegenerative disorders Lower your risk of cataract formation
Antimicrobial properties that may help reduce the rate of food-borne illness Improvement of intestinal flora, improved absorption of calcium and magnesium due to the fructans they contain
Antibacterial, antifungal, antioxidant and anti-inflammatory properties Improved heart health. The sulfur compounds have anti-clotting properties and help improve blood lipid profiles.

The allium and allyl disulphide in onions also help decrease blood vessel stiffness by enhancing nitric oxide release.

This may reduce blood pressure, inhibit platelet clot formation, and help decrease the risk of coronary artery disease, peripheral vascular diseases, and stroke

Tips for Storing and Preparing Onions

If learning about their health benefits has inspired you to eat more onions, you’re in luck as they are incredibly versatile and come in a variety of colors and flavors. Keep in mind that the antioxidants tend to be most concentrated in the OUTER layers of the onion, so avoid overpeeling.

Ideally, peel off only the outermost paper-like layer. Peeling too many layers can reduce the onion’s quercetin and anthocyanin content by as much as 20 percent and 75 percent respectively.20 One piece of good news is that quercetin does not degrade when cooked over low heat, so when you’re making soup, for example, it simply transfers into the broth.

As for storing your onions, do NOT keep them in plastic. Whole, dry bulbs should be stored in a cool, dry and dark place with plenty of air movement to maximize shelf life.

To extend shelf life of sweet or mild onion varieties, which have a higher water content, you can store the whole bulbs in the fridge. Once an onion has been cut or peeled, it can be refrigerated in a sealed container for about a week before it starts going bad. Leaving a cut onion in room temperature can significantly reduce its antibacterial properties.21

Cooking With Onions

The video above demonstrates the best way to peel and dice an onion, while the chart below, both from the National Onion Association (NOA),22 provides a helpful summary of which types of onions are best used for various dishes.

Color Variety or Type Availability Raw Flavor/Texture Best Usage
Yellow Onion:

All-purpose and most popular. The most well-known sweet onions are yellow.

The best type of onion for caramelizing is a yellow storage variety.

Cooking brings out this variety’s nutty, mellow, often sweet, quality when caramelized.

Sweet March to September Crisp, juicy, mild flavor with a slightly sweet ending with little to no after-taste Raw, lightly cooked, sautéed or grilled
Fresh, Mild March to August Crisp, juicy, mild to slightly pungent with a faint after-taste Raw, lightly cooked, sautéed or grilled
Storage August to May Strong onion flavor, mild after-taste Grilled, sautéed, caramelized, baked or roasted
Red Onion:

Red onions have gained popularity in the past decade, especially in foodservice on saladsand sandwiches because of their color.

Sweet March to September Crisp, very mild onion flavor Raw, grilled or roasted
Fresh, Mild March to September Bright tones, slightly less water content than yellow with a slightly pungent ending Raw, grilled or roasted
Storage August to May Sharp, spicy and moderate to very pungent Raw, grilled or roasted
White Onion:

White onions are commonly used in white sauces, potato and pasta salads and in Mexican or Southwest cuisine.

Due to the compact nature of their cell structure, white onions do not store quite as long as other varieties.

Fresh, Mild March to August Moderately pungent and clean finish, very little after-taste Raw, grilled, sautéed or lightly cooked
Storage August to May Moderately pungent to very pungent and full flavored, but finishes with a cleaner and crisper flavor in comparison to yellow and red storage varieties Raw, grilled, sautéed or lightly cooked

Source:.mercola.com

Is Toxoplasma Gondii Deadly? Parasite Found In Cat Poop May Actually Help Treat Ovarian Cancer


You may know that Toxoplasma gondii, the parasite commonly found in cat feces, is linked to a number of adverse health consequences, such as rage disorder and even schizophrenia. However, new research suggests that the parasite may actually have a use in the medical world, and could play a role in research to find the elusive cure for cancer.

Scientists from Dartmouth’s Geisel School of Medicine found that a specific protein secreted by T. gondii causes the immune system in mice to attack ovarian tumors, ultimately increasing their chances of survival. The scientists hope they can replicate these results and eventually use the protein in the immunotherapy treatments currently administered to human ovarian cancer patients.

Past research has shown that a safe vaccine strain of T. gondii could cure several types of tumors in mice; however, in this recent study, the Dartmouth team wanted to understand why. To do this, the teamsystematically deleted genes in the parasite and then injected these altered parasites into mice with aggressive ovarian cancer to see what would happen. Eventually, through this trial and error process, they were able to identify the specific protein excreted by the parasite that was responsible for the cancer-fighting effect.

Although the research is still in its infancy, the study shows promise in treating ovarian cancer, a serious condition that accounts for about three percent of all cancers among women. According to the American Cancer Society, about 22,280 women will receive a new diagnosis of ovarian cancer in 2016, and about 14,240 women will die from ovarian cancer — the fifth in cancer deaths among women.

CatCatCat

Could our favorite four-legged friends lend a paw in the fight against cancer?

Immunotherapy itself relies on utilizing the patient’s own immune system to combat cancer. Part of what makes cancer so deadly is its ability to evade the body’s immune system. This ability to hide, also called immune tolerance, makes it difficult for the immune system cells to know which cells to attack. As a result, cancer is allowed to grow and spread.

However, in mice, T. gondii helps to break the ovarian cancer cell’s immune tolerance, making it easier for the mice’s immune system to effectively detect and destroy aggressive ovarian cancer cells. There are already clinical trials underway to explore the usefulness of bacterium Listeria monocytogenes in breaking the immune tolerance of pancreatic tumors.

Intraperitoneal Chemo for Ovarian Cancer Revisited?


Intraperitoneal (IP) chemotherapy is now an alternative to intravenous (IV) administration that “must be discussed” for women with cytoreduced ovarian cancer, several experts said here at the American Society of Clinical Oncology (ASCO) 2016 Annual Meeting.

But the phase 2 data that prompted those comments “will do nothing to settle the controversy” surrounding the choice of IP or IV therapy, Richard Schilsky, MD, ASCO chief medical officer, told Medscape Medical News.

As previously reported by Medscape, despite better outcomes with IP chemo, reported as far back as 2001, this approach is underutilized largely because of toxicities and difficulties with administration.

But now two prospective studies suggest that a switch from a cisplatin- to a carboplatin-based IP regimen might overcome some barriers.

The findings demonstrate “the potential clinical utility of this route of drug delivery…both in routine clinical care and in the development of innovative clinical trial concepts in ovarian cancer,” Maurie Markham, MD, the discussant for both studies, told Medscape Medical News. “These were both small studies and one always needs to wait for the peer-reviewed publications,” he added.

But, he concluded in his presentation, “the IP strategy may be appropriately considered one potential approach…rather than either a mandated or discarded concept…in the evolving management of ovarian cancer.”

“IP chemotherapy is an effective yet underused treatment,” added Don Dizon, MD, ASCO expert in ovarian cancer. “For women with optimally cytoreduced or completely resected ovarian cancer, whether or not they received neoadjuvant chemotherapy, intraperitoneal chemotherapy must be an option that is discussed,” he said at a press briefing.

New Studies With Carboplatin

The two new studies used different combinations of IV paclitaxel combined with IP carboplatin in different populations with advanced disease.

The OV21/PETROC study, which was selected as a late-breaking abstract and highlighted in the press program, randomized women with epithelial ovarian cancer after neoadjuvant IV chemotherapy and debulking surgery, reported Helen Mackay, MD, head of medical oncology and hematology at Sunnybrook Odette Cancer Centre in Toronto.

All patients received IV paclitaxel, but women in group 1 (n = 101) also received IV carboplatin, and those in group 3 (n = 102) received IP carboplatin. (However, the group in which patients received IV cisplatin was abandoned on the basis of efficacy advice from an independent data safety monitoring committee).

For the primary end point of the trial, progressive disease rate at 9 months, the per protocol results showed that IP-treated patients fared significantly better than IV-treated patients (23.3% vs 42.2%; P value unstratified = .01).

And although the trial was not powered to detect a difference in overall survival, “the hazard ratio was similar to what we’ve seen in other intraperitoneal trials,” said Dr Mackay, showing a median overall survival (defined as time from randomization to disease progression) of 38.1 months in IV patients and 59.3 months in IP patients (hazard ratio [HR], 0.8; P = .40).

 In terms of toxicity, “IP carboplatin was well tolerated; quality-of-life data did not differ between the arms and improved with time,” she said.

“I would say at this time, for the upfront cytoreduced patient, and also for the neoadjuvant patient, that intraperitoneal chemotherapy remains an option for discussion,” she said. “We need to learn more about the biology and the potential predictive signatures.”

“This study provides reassurance for patients and providers that the carboplatin-based IP regimen is both effective and well tolerated with maintenance of quality of life,” Dr Dizon said in statement. “That said, we need to further define those who derive the greatest benefit from this approach,” he added.

The second study presented at the meeting was unrandomized and evaluated 71 women with stage II to IV ovarian or primary peritoneal carcinoma who completed at least one cycle of IV dose-dense paclitaxel and IP carboplatin (ddTCip) after primary cytoreductive surgery.

A total of 46 patients (60.5%) completed six or more cycles, but with many interruptions because of toxicity, reported Kosei Hasegawa, MD, PhD, from Saitama Medical University International Medical Center in Hidaka, Japan.

Overall, 83.1% of patients had an objective response, including complete response (12.7%), partial response (70.4%), and stable disease (14.1%), he said.

Median progression-free survival was 18.3 months, and median overall survival was 55.5 months.

With the exception of the port-related adverse events rate (11.8%), the regimen’s toxicity profile was similar to that seen in the dose-dense group of a previous trial (JGOG3016), said Dr Hasegawa.

Grade 3/4 toxicities included neutropenia (84.2%), anemia (56.5%), and thrombocytopenia (22.4%). “We suggest that the frontline chemotherapy with ddTCip therapy is safe and effective, even for suboptimal residual ovarian carcinoma patients,” he concluded.

Molecular Imaging of Ovarian Cancer


Ovarian cancer is the most lethal gynecologic malignancy and the fifth leading cause of cancer-related death in women. Over the past decade, medical imaging has played an increasingly valuable role in the diagnosis, staging, and treatment planning of the disease. In this “Focus on Molecular Imaging” review, we seek to provide a brief yet informative survey of the current state of the molecular imaging of ovarian cancer. The article is divided into sections according to modality, covering recent advances in the MR, PET, SPECT, ultrasound, and optical imaging of ovarian cancer. Although primary emphasis is given to clinical studies, preclinical investigations that are particularly innovative and promising are discussed as well. Ultimately, we are hopeful that the combination of technologic innovations, novel imaging probes, and further integration of imaging into clinical protocols will lead to significant improvements in the survival rate for ovarian cancer.

Johnson & Johnson Pays $55M In Second Lawsuit Claiming Talcum Powder Products Cause Ovarian Cancer


ohnson & Johnson was ordered to pay $55 million in damages to a South Dakota woman who claimed the use of their talc-based powder products resulted in her ovarian cancer.

Baby powder

Last Monday, a woman from South Dakota was granted $5 million in compensatory damages and $50 million in punitive damages after she claimed Johnson & Johnson’s talcum powder-based products caused her ovarian cancer, The New York Daily News reported. This is thesecond lawsuit the company has lost this year.

Gloria Ristesund used the company’s talc-based powder products, including Baby Powder and Shower-to-Shower Powder, on her genitals as a part of her hygienic routine for decades. According to her lawyers, she was diagnosed with ovarian cancer after undergoing hysterectomy and other related surgeries, something she believed to be related to her use of talc-based products. Her cancer is currently in remission, Reuters reported.

Ovarian cancer is the eighth most common cancer and the fifth leading cause of cancer death in the U.S., with 20,000 women being diagnosed with the illness each year, according to theCenters for Disease Control and Prevention. It accounts for 3 percent of all cancers in women.

The verdict adds to the ongoing debate about the safety of talc-based cosmetic products, and comes just three months after Johnson & Johnson was ordered to pay $72 million in damages to the family of an Alabama woman who died from the same type of cancer. Despite these two losses, the company maintains that their products are safe and plan to appeal the recent decision.

“Unfortunately, the jury’s decision goes against 30 years of studies by medical experts around the world that continue to support the safety of cosmetic talc,” Johnson & Johnson spokeswoman Carol Goodrich said in a statement. “For over 100 years, Johnson & Johnson has provided consumers with a safe choice for cosmetic powder products and we will continue to work hard to exceed consumer expectations and evolving product preferences.”

Talcum powder is widely used in cosmetic products, including adult body and facial powders. The powder — made from talc, a mineral that consists of the elements magnesium, silicon, and oxygen — is used to keep skin dry and protect against rashes. Some talc contains asbestos, a substance that has been linked to cancers in and around the lungs when inhaled, according to the American Cancer Society; however, this type of talc is not used in modern consumer products.

Dr. Daniel Cramer first suggested there was a link between using talcum powder on genitals and ovarian cancer in 1982. After this finding, he was reportedly called by companies for help putting warning labels on these kinds of products. A more recent study, released shortly after the February verdict, supported Cramer’s finding, that applying the product to genitals, underwear, and sanitary napkins could increase the risk of developing ovarian cancer risk by a third.

Jim Onder, who served as an attorney for the plaintiffs in the two recent cases, said internal documents show that Johnson & Johnson was aware of the studies linking their products to ovarian cancer.

“The evidence is real clear that Johnson & Johnson has known about the dangers associated with talcum powder for over 30 years,” said Onder, according to the New York Daily News. “Instead of giving a warning, what they did was targeted the groups most at risk for developing ovarian cancer.” The groups Onder is referring to are overweight women, black and Latino people.

Johnson & Johnson is reportedly facing more than 1,200 talcum-powder lawsuits accusing the company of not adequately warning consumers about their products cancer risks.