Research - updated regularly
Ovarian Cancer
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Uterine Cancer
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Vulval Cancer
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Cervical Cancer
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Research Selection Criteria
Studies about gynaecological cancer diagnosis, treatment, or epidemiology are selected based on validity, study phase and methods, journal status, and likely interest to women with gynaecological cancers, and their friends and family.
Ovarian Cancer Research Update
December 2010
Personalised ovarian cancer treatment 'on the way'
Researchers have discovered a technique, called OncoMap, which can be used to detect point mutations which drive the onset and growth of ovarian cancer cells, paving the way for personalised treatment.
The scientists hope this could lead to women having their tumour screened, specific point mutations - misspellings in a single letter of the genetic code - identified and the appropriate treatment being prescribed to target the mutation and halt the cancer growth.
OncoMap can determine, using mass spectrometry, the point mutations in more than 100 known cancer-causing genes present in tumours.
Dr Ursula Matulonis, director/programme leader in medical gynaecologic oncology at the Dana Farber Cancer Institute in Boston, US, and associate professor of medicine at Harvard Medical School, said: "The success of conventional chemotherapy has reached a plateau, and new means of characterising ovarian cancer so that treatment can be personalised are needed."
She added: "This study shows that it's feasible to use OncoMap to identify whether a patient's tumour has a mutation in an oncogene for which a known drug is available to target that specific gene, so as to enable us to place her on a clinical study of that drug."
According to Cancer Research UK, ovarian cancer is the fifth most common type to affect women in the UK.
November 2010
Dad's Family History of Breast, Ovarian Cancer Matters, Too
By Kathleen Doheny, HealthDay Reporter, October 28 (HealthDay News) --
But study found women with paternal family history 5 times less likely to be referred to counseling
Women with female relatives who have had breast or ovarian cancer are often acutely aware of their own increased risk and may seek genetic counseling.
But they should also pay attention to their father's family history, one genetic counselor warns.
The inherited genetic predisposition to breast and ovarian cancer is mostly caused by a mutation in one or both of the BRCA1 or BRCA2 tumor suppressor genes, said Jeanna McCuaig, a genetic counselor at Princess Margaret Hospital in Toronto. And, she pointed out, "if your mom or your dad has a BRCA1 or BRCA2 mutation, you would have a 50 percent chance of inheriting it from either one."
That explains why a father's family history is as important to consider as a mother's, she said.
"Anecdotally, I've had patients come in and say, 'I never thought about my dad's side,'" McCuaig said. She decided to do some research into the implications of that statement. "We took two years of patient charts referred to our clinic, referred as new patients, and looked to see how many had relatives [with breast or ovarian cancers] on the mom's side versus the dad," she said.
She found that patients who came to her Familial Breast and Ovarian Cancer Clinic at the hospital were more than five times more likely to be referred with a maternal family history of breast or ovarian cancer than a paternal history of such cancers.
To get the word out, she wrote a commentary on the subject, published online in The Lancet Oncology.
The lack of awareness that women may inherit a mutated gene from their fathers is also present among many health-care providers, McCuaig suspects. This is problematic, she noted in her study, because they often serve as gatekeepers for referrals to specialized clinics, including those that do genetic testing.
If a woman tests positive for a BRCA1 or BRCA2 mutation, she has about a 50 percent to 85 percent risk of breast cancer in her lifetime, said McCuaig, citing various studies, and about a 20 percent to 44 percent risk of ovarian cancer.
In contrast, the lifetime risk of developing ovarian cancer in the general population is 1.4 percent, according to the National Cancer Institute, which also states that women who inherit a BRCA1 or BRCA2 mutation are about five times as likely to develop breast cancer as women without such a mutation.
Men with the BRCA 2 mutation have a 6 percent risk of breast cancer, McCuaig said, compared to less than 1 percent in the general male population. Men with BRCA1 or BRCA2 mutation also have a higher prostate cancer risk than other men, she said.
According to the study, about 20 percent to 30 percent of the more than 690,000 women diagnosed with breast cancer and nearly 190,000 diagnosed with ovarian cancer in developed countries have a family history of cancer, the study noted, and between 5 percent and 10 percent are due mostly to an inherited mutation in one of the BRCA1 and BRCA2 genes.
Women and men should take into account the cancer history on both their parents' sides of the family, McCuaig said, and health-care providers should ask about both sides when taking a medical history.
"It's an important point," said Dr. Len Lichtenfeld, deputy chief medical officer for the American Cancer Society. "For those of us in cancer treatment, it's not new information, but it's very important for patients and family to be aware of this and not forget" to consider the father's history.
"The bottom line? The family history [of breast and ovarian cancer] in the women in your father's family is every bit as important as the family history of the women on your mother's side," he said.
More information
To learn about BRCA1 and BRCA2 mutations, visit the U.S. National Cancer Institute.
SOURCES: Jeanna McCuaig, M.Sc., genetic counselor, Familial Breast and Ovarian Cancer Clinic, Princess Margaret Hospital, Toronto; Len Lichtenfeld, M.D., deputy medical officer, American Cancer Society, Atlanta; Oct. 24, 2010, The Lancet Oncology
October 2010
Experimental drug shrinks tumours in women with hereditary breast and ovarian cancers
Monday 16 August 2010
An experimental drug called olaparib has been shown to shrink tumours in women whose advanced cancers were caused by faults in their BRCA genes.
The international phase-II studies, both published in the Lancet, looked at women with advanced ovarian or breast tumours.
Their results add further weight to the idea that the key to treating certain types of cancer may be to target their underlying genetic weaknesses, rather than the organ in which the cancer originated.
First author on the ovarian trial Dr William Audeh, a cancer expert specialising in cancer genetics at Cedars-Sinai Medical Centre in the US, described the findings as "significant".
He revealed: "Olaparib is the first single-agent, non-chemotherapy treatment to show benefit to patients with cancers that result from BRCA1 or BRCA2 gene mutations.
"Until now, treatments for cancer have been selected based upon where in the body the cancer originated. [This study suggests] that it is the underlying genetic weakness of a cancer, not the organ of origin, that is the key to selecting effective therapy."
The investigational drug olaparib is a poly-ADP-ribose phosphorylase (PARP) inhibitor.
It is designed to interfere with an enzyme called poly-ADP ribose-phosphorylase, or PARP, which helps to repair DNA damage caused to cancer cells.
Tumours which are caused by faults in BRCA genes already have difficulty repairing their DNA, for example when given chemotherapy.
By blocking the activity of PARP, olaparib in theory makes the chemotherapy much more effective.
The ovarian cancer study, which was coordinated by researchers at the Breakthrough Breast Cancer Research Unit at King's College London, as well as researchers in the US and Australia, involved 57 patients, 33 of whom were given a high dose of olaparib.
Eleven of these women saw a significant reduction in the size of their tumours. Three out of 24 women given a lower dose also benefited.
In the breast cancer trial, 27 women received the higher dose, of whom 11 responded, while six out of a further 27 women given a lower dose also responded.
Side-effects tended to be relatively mild and included nausea, fatigue and anaemia.
Dr Audeh noted that many women with advanced BRCA-mutated cancer have limited treatment options, as they will have already tried several different chemotherapy drugs.
He revealed: "PARP inhibitors may be a promising new option for this heavily 'pre-treated' population."
Dr Claire Knight, health information officer at Cancer Research UK, said: "PARP inhibitors have been showing excellent promise in early clinical trials and these results are also encouraging.
"Cancer Research UK scientists have been key players in developing this new generation of cancer drugs. We look forward to the results of larger clinical trials to determine if these drugs could be an effective way to treat cancers caused by faults in the BRCA genes."
References:
Tutt, A. et al (2010). Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and advanced breast cancer: a proof-of-concept trial The Lancet, 376 (9737), 235-244 DOI: 10.1016/S0140-6736(10)60892-6
Audeh, M.et al (2010). Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and recurrent ovarian cancer: a proof-of-concept trial The Lancet, 376 (9737), 245-251 DOI: 10.1016/S0140-6736(10)60893-8
September 2010
Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and recurrent ovarian cancer: a proof-of-concept trial
Original Text
Dr M William Audeh MD a , Prof James Carmichael MD b, Richard T Penson MD c, Prof Michael Friedlander PhD d, Prof Bethan Powell MD e, Katherine M Bell-McGuinn PhD f, Clare Scott MD g, Prof Jeffrey N Weitzel MD h, Ana Oaknin MD i, Niklas Loman MD j, Prof Karen Lu MD k, Prof Rita K Schmutzler MD l, Ursula Matulonis MD c, Mark Wickens BSc b, Andrew Tutt PhD m
Summary: Background
Olaparib is a novel, orally active poly(ADP-ribose) polymerase (PARP) inhibitor that induces synthetic lethality in homozygous BRCA-deficient cells. We aimed to assess the efficacy and safety of olaparib for treatment of advanced ovarian cancer in patients with BRCA1 or BRCA2 mutations.
Methods
In this international, multicentre, phase 2 study, we enrolled two sequential cohorts of women (aged ≥18 years) with confirmed genetic BRCA1 or BRCA2 mutations, and recurrent, measurable disease. The study was undertaken in 12 centres in Australia, Germany, Spain, Sweden, and the USA. The first cohort (n=33) was given continuous oral olaparib at the maximum tolerated dose of 400 mg twice daily, and the second cohort (n=24) was given continuous oral olaparib at 100 mg twice daily. The primary efficacy endpoint was objective response rate (ORR). This study is registered with ClinicalTrials.gov, number NCT00494442.
Findings
Patients had been given a median of three (range 1—16) previous chemotherapy regimens. ORR was 11 (33%) of 33 patients (95% CI 20—51) in the cohort assigned to olaparib 400 mg twice daily, and three (13%) of 24 (4—31) in the cohort assigned to 100 mg twice daily. In patients given olaparib 400 mg twice daily, the most frequent causally related adverse events were nausea (grade 1 or 2, 14 [42%]; grade 3 or 4, two [6%]), fatigue (grade 1 or 2, ten [30%]; grade 3 or 4, one [3%]), and anaemia (grade 1 or two, five [15%]; grade 3 or 4, one [3%]). The most frequent causally related adverse events in the cohort given 100 mg twice daily were nausea (grade 1 or 2, seven [29%]; grade 3 or 4, two [8%]) and fatigue (grade 1 or 2, nine [38%]; none grade 3 or 4).
Interpretation
Findings from this phase 2 study provide positive proof of concept of the efficacy and tolerability of genetically targeted treatment with olaparib in BRCA-mutated advanced ovarian cancer.
Funding AstraZeneca.
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(10)60893-8/fulltext
August 2010
Women With Hereditary Ovarian Cancer Are More Likely to Get Liver and Spleen Cancers
Women with ovarian cancer and hereditary BRCA1 or BRCA2 mutations are more likely to develop metastases in the liver, spleen or lung, compared with women non-hereditary ovarian cancer.
A study conducted in 19 women with BRCA1/2 deficient epithelial ovarian cancer of primary peritoneal cancer
http://jco.ascopubs.org/cgi/content/abstract/28/15/2505
Gourley C, Michie CO, Roxburgh V, et al. Increased Incidence of Visceral Metastases in Scottish Patients With BRCA1/2-Defective Ovarian Cancer: An Extension of the Ovarian BRCAness Phenotype. J Clin Oncol.2010; 28: 2505-2511
Some Ovarian Cancer Cells are ‘Shielded’ From Platinum Chemotherapy
A new study helps to explain the reason for resistance to platinum-based chemotherapy in women with ovarian cancer. The researchers examined cells from three patients with high-grade serous carcinoma of the ovary, before and after platinum resistance developed. The analysis showed that some cells have special characteristics that allow them to remain shielded from the platinum-based therapy. These cells can then go on to cause resistance and promote tumour re-growth.
This research helps to explain platinum-resistant ovarian cancer, and provides information for the future of drugs that target cells that are resistant to current therapies.
Reference:
Cooke SL, Ng CKY, Melnyk N, et al. Genomic analysis of genetic heterogeneity and evolution in high-grade serous ovarian carcinoma. Oncogene 2010; advance online publication 28 June 2010; doi: 10.1038/onc.2010.245
http://www.nature.com/onc/journal/vaop/ncurrent/abs/onc2010245a.html
New Blood Test for Ovarian Cancer Approved in the US
A new blood test is available in the US to help diagnose ovarian cancer. The ARCHITECT HE4 (human epididymis protein 4) assay, made by Abbott, is an automated assay to test for HE4, a biomarker that has been detected in high levels of the blood of some ovarian cancer patients.
The HE4 test is to be used in conjunction with the current CA-125 test. CA-125 is a protein expressed by approximately 80% of ovarian cancers. HE4 will be useful for monitoring ovarian cancer recurrence in women for whom CA-125 is not a disease marker.
References:
http://www.medicalnewstoday.com/articles/190945.php
http://www.ovariancancer.org/2010/06/04/abbott-receives-fda-clearance-for-new-ovarian-cancer-test/
Promising New Drug for Recurrent Ovarian Cancer
A new drug made by Amgen, known as AMG 386, has shown promising results in patients with recurrent ovarian cancer when administered in combination with paclitaxel. AMG 386 is an angiogenesis inhibitor; it blocks the formation of new blood vessels that supply nutrients for the tumour to grow.
A randomised Phase 2 trial was conducted in 161 patients with recurrent ovarian cancer.
Women in the study were allocated into one of three treatment groups: intravenous paclitaxel weekly (three weeks on and one week off) plus AMG 386 at 10 mg/kg (n=53), AMG 386 at 3 mg/kg (n=53), or placebo (n=55).
Women receiving AMG 386 10 mg/kg had the longest progression-free survival time of 7.2 months, compared with 5.7 months in the 3 mg/kg group and 4.6 months in the placebo group (80% CI, 0.59 - 0.98; p=0.17). The most common adverse events were hypokalemia, peripheral neuropathy, neutropenia, dyspnea, and thromboembolic events.
The next step will be to investigate the efficacy and safety of AMG 386 in a larger, phase III study.
Reference:
http://www.medicalnewstoday.com/articles/191082.php
http://abstract.asco.org/AbstView_74_50835.html
Longer-Term Bevacizumab Treatment May Extend Progression-Free Survival of Ovarian Cancer
Data presented at the 2010 annual meeting of the American Society of Clinical Oncology (ASCO) show that long-term use of bevacizumab (Avastin) may be beneficial in ovarian cancer. Bevacizumab is a monoclonal antibody that works by acting to inhibit angiogenesis (the formation of new blood vessels that supply the tumour with nutrients to grow).
A randomised, double-blind, placebo-controlled, multicentre trial was conducted in 1,873 women with newly diagnosed Stage 3 or Stage 4 ovarian cancer. They all underwent surgery then were randomised to receive either standard chemotherapy and a placebo, standard chemotherapy and bevacizumab, or standard chemotherapy and bevacizumab then up to 10 months of bevacizumab alone.
Patients who received long-term bevacizumab experienced cancer worsening after a median of 14.1 months, versus 10.3 months for patients treated with standard chemotherapy and placebo. The short-term use of bevacizumab did not lead to significantly better results than the standard chemotherapy alone.
http://www.nytimes.com/2010/06/07/health/research/07oncology.html
http://www.medicalnewstoday.com/articles/191026.php
Early Research Indicates a Potential New Protein Marker for Ovarian Cancer
Researchers in the US using a new technique known as NAPPA (nucleic acid programmable protein array) may have found a new protein biomarker for ovarian cancer. They plan to undertake further research to determine whether the presence of the protein in blood is predictive of ovarian cancer.
http://www.medicalnewstoday.com/articles/192089.php
July 2010
New Treatment Regimen Shown Effective Against Advanced Ovarian Cancer, Study Suggests
ScienceDaily (June 7, 2010) — Newly reported results from a major clinical trial show that adding bevacizumab (Avastin) to standard frontline chemotherapy for women with advanced ovarian cancer and then continuing a maintenance dose of the drug afterwards significantly extends progression-free survival. Women receiving the new treatment regimen saw no worsening of their disease for 14.1 months, compared to 10.3 months for women receiving standard therapy.
The international, multi-center, randomized, double-blind, placebo-controlled Phase III clinical trial was conducted by a network of researchers known as the Gynecologic Oncology Group (GOG) and sponsored by the U.S. National Cancer Institute. The trial results were presented at the 46th Annual Meeting of the American Society of Clinical Oncology (ASCO).
The trial marked the first time a molecularly targeted agent has been part of a validated strategy for treating advanced ovarian cancer. It was also the first time a maintenance dosing approach involving any therapy has been outlined for the disease. Additionally, ongoing analysis of the trial data may offer insights into genetically defined subgroups of patients who benefited more than others, pointing to the possibility of more personalized, even more effective treatment for ovarian cancer in the future.
"Ovarian cancer remains one of the most deadly cancers in women, so this clinical advance is particularly welcome," says Robert A. Burger, M.D., lead investigator on the GOG trial and director of the Women's Cancer Center at Fox Chase Cancer Center. "Before this, we could treat ovarian cancer patients only with surgery and chemotherapy involving relatively toxic agents. Now, we have a third type of more targeted therapy to offer these patients, potentially opening the way to even greater progress in years to come."
According to the American Cancer Society, approximately 22,000 new cases of ovarian cancer will be diagnosed this year, and about 15,000 women will die from their disease. Ovarian cancer is the eighth most common cancer among women, excluding non-melanoma skin cancers. It ranks fifth in cancer deaths among women, accounting for more deaths than any other cancer of the female reproductive system.
The trial, dubbed GOG-0218, enrolled 1,873 previously untreated women with advanced disease from 336 sites in four countries (U.S., Canada, South Korea, and Japan). The women were randomly assigned to one of three treatment protocols: standard chemotherapy (carboplatin and paclitaxel) plus placebo, followed by placebo maintenance for an up to 10 additional months; standard chemotherapy plus bevacizumab followed by placebo maintenance; and standard chemotherapy plus bevacizumab followed by bevacizumab maintenance. The type and frequency of bevacizumab-associated side effects were similar to those seen in previous cancer studies involving the drug.
Bevacizumab, a humanized monoclonal antibody, is an angiogenesis inhibitor, meaning that the drug limits tumor growth by interfering with the formation of new blood vessels to supply the tumor with needed nutrients. It acts by inhibiting the function of a naturally occurring protein called vascular endothelial growth factor, or VEGF, which is overproduced in many cancers and stimulates new blood vessel formation.
Burger is the lead investigator on the GOG-0218 study presented at ASCO, which was launched in September 2005 while he was at the University of California, Irvine; he moved to Fox Chase Cancer Center in September 2008. The co-authors on the study are: M.F. Brady, Roswell Park Cancer Institute; M.A. Bookman, University of Arizona Cancer Center; J.L. Walker, University of Oklahoma Health Sciences Center; H.D. Homesley, Brody School of Medicine; J. Fowler, James Cancer Hospital at the Ohio State University; B.J. Monk, University of California, Irvine, Medical Center; B.E. Greer, Seattle Cancer Care Alliance; M. Boente, Minnesota Oncology and Hematology; and S.X. Liang, State University of New York at Stony Brook.
Story Source: The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by Fox Chase Cancer Center.
June 2010
Flaxseed and Ovarian Cancer
A U.S. researcher says a flaxseed diet helped lessen the severity of ovarian cancer in hens.
Janice Bahr of the University of Illinois said flaxseed -- a rich source of alpha-linolenic acid -- has already been shown to inhibit colon, breast, skin and lung cancers. She is a co-author of a study that linked flaxseed added to the diet to increased survival times in chickens with ovarian cancer.
"The chicken is the only animal that spontaneously develops ovarian cancer on the surface of the ovaries like humans," Bahr said in a statement.
The study, published in Gynecologic Oncology, found hens fed the flaxseed-enriched diet for 1 year had a significant reduction in late-stage ovarian tumors. The hens fed the control diet had more late-stage tumors and the cancer was more likely to spread.
The researchers also found hens fed flaxseed were more likely to maintain a healthy weight. Both diets had equal caloric content, but the flaxseed-fed hens weighed less at six months than the control-fed hens, the study said.
http://www.upi.com/Health_News
May 2010
Ovarian Cancer Patients Have Lower Death Risk When Treated By Experts
Article Date: 18 Oct 2009 - 0:00 PDT
Women with ovarian cancer are less likely to die from their disease if they are treated by specialist gynaecological oncologists than if they are cared for by general gynaecologists, according to the results of a study carried out in Scotland, UK, and reported at this week's 16th International Meeting of the European Society of Gynaecological Oncology (ESGO) in Belgrade, Serbia.
An analysis of survival data from a cohort of 912 ovarian cancer patients treated in the West of Scotland Managed Clinical Network showed a 24% lower risk of death in women treated by gynaecological oncologists who specialise in the treatment of gynaecological cancer than by general gynaecologists who treat the full range of gynaecological problems that women can experience.
Reporting her findings at a late breaker session of the congress, Dr Alex Stirling, from the West of Scotland Cancer Surveillance Unit, explained that recent reorganisation of cancer services in Scotland was designed to provide equal standards of care for patients wherever they lived. However, some women continue to be treated away from larger cancer centres, and do not therefore have access to gynaecological oncologists.
Dr Stirling added that, by the end of the year, cancer services in the area will be centralised, and selection of cases for surgery will be decided by a specialist multidisciplinary team - hopefully helping to reduce remaining inequalities of care and ensuring that more difficult cases are treated by gynaecological oncologists.
Source: European Society of Gynaecological Oncology
April 2010
Avastin Increases Progression-Free Survival in Women with Advanced Ovarian Cancer
Results from the Gynecologic Oncology Group (GOG) 0218 study show that women with previously untreated advanced ovarian cancer had progression-free survival (time without the disease worsening) after treatment with bevacizumab (Avastin®) plus chemotherapy followed by maintenance use of bevacizumab alone, compared with women receiving chemotherapy alone.
GOG 0218 is a three-arm study in which women with newly diagnosed advanced ovarian cancer who already had surgery to remove as much of the tumor as possible were randomized to receive one of the following:
- Arm 1: Placebo in combination with carboplatin and paclitaxel chemotherapy followed by placebo alone, for a total of up to 15 months of therapy;
- Arm 2: Bevacizumab in combination with carboplatin and paclitaxel chemotherapy followed by placebo alone, for a total of up to 15 months of therapy;
- Arm 3: Bevacizumab in combination with carboplatin and paclitaxel chemotherapy followed by the maintenance use of bevacizumab alone, for a total of up to 15 months of therapy.
Women in Arm 3 had longer progression-free survival compared to those who received chemotherapy alone. Women in Arm 2, who did not continue maintenance use of bevacizumab, did not live longer without the disease worsening compared to chemotherapy alone.
The results of this study will be presented in June at the American Society of Clinical Oncology (ASCO) meeting.
Reference: http://www.medicalnewstoday.com/articles/180406.php
Delays in Referring Older Women With Ovarian Cancer
A study published in the British Journal of Cancer has discovered that older women with suspected ovarian cancer may be referred by their GPs for investigation later than younger women.
Reference: http://www.medicalnewstoday.com/articles/181061.php
Link Between Diet and Ovarian Cancer Survival
Higher total fruit and vegetable consumption, and higher vegetable consumption alone led to a survival advantage for women with epithelial ovarian cancer.
Reference: http://www.medicalnewstoday.com/articles/180738.php
March 2010
A New Combination Test Might Improve Detection of Early-Stage Ovarian Cancer
A combination of contrast-enhanced ultrasound imaging plus proteomic blood sample analyses may help physicians detect early-stage ovarian cancer, according to study published in the American Journal of Roentgenology.
Proteomic analysis of blood samples detects unique proteins that serve as biomarkers for ovarian cancer. However, information from proteomic analysis must be verified using imaging. Contrast-enhanced ultrasound is an inexpensive, noninvasive imaging technique that can verify information from proteomic analysis and may help identify early microvascular changes known to be associated with early ovarian cancer.
References:
Dutta S, Wang F, Fleischer AC, Fishman DA. (2010). New Frontiers for Ovarian Cancer Risk Evaluation: Proteomics and Contrast-Enhanced Ultrasound. Am J Roentgenology 194:349-354
http://www.ajronline.org/cgi/content/abstract/194/2/349?maxtoshow=&hits=10&RESULTFORMAT=1&title=ovarian+cancer&andorexacttitle=
and&andorexacttitleabs=and&andorexactfulltext=and&searchid=1&FIRSTINDEX=0&sortspec=relevance&fdate=1/1/2010&resourcetype=HWCIT
http://www.medicalnewstoday.com/articles/176827.php
Symptoms Are Not Useful For Detecting Ovarian Cancer
Medical evaluation triggered by symptoms suggestive of ovarian cancer does not appear to detect early-stage ovarian cancer earlier, according to a recent case-control study published in the Journal of the National Cancer Institute.
The researchers conducted interviews with 812 patients aged 35-74 years with epithelial ovarian cancer and with 1313 control subjects. The symptom index was considered positive when pelvic or abdominal pain or bloating or feeling full was reported at least daily for at least 1 week, with an onset of less than 12 months before diagnosis or a reference date (for control subjects). The consensus criteria were considered fulfilled when any symptom above or urinary urgency or frequency was reported for at least 1 month, with an onset of less than 12 months before diagnosis or a reference date.
Results revealed that ovarian cancer patients with a positive index or who met consensus criteria did so only within 5 months before diagnosis. The estimated positive predictive value of the symptom index or symptoms meeting the consensus criteria was 0.6%–1.1% overall and less than 0.5% for early-stage disease.
The authors conclude that medical evaluation based on symptoms is likely to result in diagnosis of ovarian cancer in only 1 of 100 women with such symptoms.
Reference:
Rossing MA, Wicklund KG, Cushing-Haugen KL, Weiss NS. (2010). Predictive Value of Symptoms for Early Detection of Ovarian Cancer. J Natl Cancer Inst. Advance Access published on January 28, 2010; doi:10.1093/jnci/djp500
Two New Treatment Regimens for Ovarian Cancer Added to NCCN Guidelines
The US National Comprehensive Cancer Network (NCCN) recently added two combination chemotherapy regimens to the NCCN Clinical Practice Guidelines for Oncology for Ovarian Cancer.
The newly added regimens are carboplatin (Paraplatin)/weekly paclitaxel (Taxol) and carboplatin/liposomal doxorubicin (Doxil) for cytotoxic therapy for patients with platinum-sensitive epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer that has recurred. The addition of these regimens is based on data from studies published in The Lancet and The Journal of Clinical Oncology showing that both combination regimens improved median progression-free survival in women with specific types of recurring ovarian cancer, compared with conventional regimens. In addition, the carboplatin/weekly paclitaxel regimen improved overall survival.
Reference: http://www.nccn.org/about/news/newsinfo.asp?NewsID=237
February 2010
Potential New Treatment Target for Papillary Serous Ovarian Cancer
A gene called MAGP2 may be a new target for treatment of ovarian cancer. A large US study found that expression of microfibril-associated glycoprotein 2 (MAGP2) was correlated with reduced patient survival among women with papillary serous ovarian cancer. It appears that MAGP2 may assist the growth of tumour blood supply.
Reference:
Mok SC, Bonome T, Vathipadiekal V, et al. (2009). A Gene Signature Predictive for Outcome in Advanced Ovarian Cancer Identifies a Survival Factor: Microfibril-Associated Glycoprotein 2. Cancer Cell 16(6): 521-532
http://www.sciencedaily.com/releases/2009/12/091208181128.htm
New Diagnostic Test for Ovarian Cancer Approved in Europe
A new diagnostic blood test made by Abbott, called the ARCHITECT HE4 test, is now available in Europe. The test can help determine the risk of whether a pelvic mass is benign or malignant, and can be used in the assessment of epithelial ovarian cancer.
Reference: http://www.medicalnewstoday.com/articles/176088.php
Phase III Study Begins for Oral Ovarian Cancer Treatment
An international study (the AGO-OVAR 12 or LUME-Ovar-1 trial) is underway to evaluate the efficacy and safety of an oral anti-cancer agent, called BIBF 1120 (planned brand name Vargatef™), as first-line treatment in combination with standard chemotherapy in patients with advanced ovarian cancer.
BIBF 1120 is a new oral compound known as an anti-angiogenic. It works by simultaneously inhibiting three receptors involved in the formation of blood vessels, a process also called angiogenesis, which is needed for tumours to grow and spread.
Data from a phase II study in women with ovarian cancer show that, at 36 weeks, more women receiving BIBF 1120 were progression-free compared to women receiving placebo (14.3% vs 5%).
Reference: http://www.medicalnewstoday.com/articles/174516.php
Ovarian Cancer Biomarkers CA125, HE4 and Mesothelin May Rise 3 Years Before Clinical Diagnosis
A new study reports that serum concentrations of the ovarian cancer biomarkers CA125, human epididymis protein 4 (HE4), and mesothelin began to rise 3 years before clinical diagnosis. However, the markers were substantially elevated only in the last year prior to diagnosis. The stage of the cancer at the time of marker elevation is unknown.
The study investigated serum specimens from 34 patients in a clinical trial who were diagnosed with ovarian cancer and had serum specimens available, as well as 70 matched control subjects.
These findings are unlikely to lead to a change in screening protocols, because the increases do not occur early enough to be used for screening.
Reference:
(2010). Assessing Lead Time of Selected Ovarian Cancer Biomarkers. Journal of the National Cancer Institute 102(1):NP; doi:10.1093/jnci/djp470
http://jnci.oxfordjournals.org/cgi/reprint/102/1/NP-a
December 2009/January 2010
New Targeted Radiotherapy Destroys Ovarian Tumour Cells
A Swedish study has found that a new radioactive therapy that seeks and destroys tumour cells appears safe in women with metastatic ovarian cancer.
This was a preliminary study in 9 women with ovarian cancer to determine the distribution of the substance in the body. The active substance is injected into the abdominal cavity. The study showed that the active substance reached the tumour cells in the abdomen without any measurable side-effects.
Reference: http://www.medicalnewstoday.com/articles/162510.php
PARP Inhibitors Show Good Results for Advanced Ovarian Cancer
A phase 1 study of olaparib - a new type of drug known as a PARP inhibitor – has shown promising results in patients with BRCA-positive ovarian cancer. The study was conducted by scientists from the Breakthrough Breast Cancer Research Centre at the Institute for Cancer Research in London, UK.
PARP (poly(ADP-ribose) polymerase) inhibitors work by blocking the synthesis of DNA and inducing apoptosis (cell suicide), causing tumours to stop growing or even shrink. The drug works in a targeted way and only affects cancer cells, so should have fewer side effects than other anti-cancer drugs.
In the study, over 50% of patients' tumors shrank or did not grow further after treatment with olaparib. One of the first patients to receive the treatment remained in remission two years later.
The next step is to trial the drug in a larger group of patients.
Reference:
Mendes-Pereira AM, Martin SA, Brough R, et al. (2009). Synthetic lethal targeting of PTEN mutant cells with PARP inhibitors. EMBO Molecular Medicine, Published Online: Sep 16 2009.
DOI: 10.1002/emmm.200900041
http://www.medicalnewstoday.com/articles/164196.php
BNC2 Gene May Indicate Increased Risk of Ovarian Cancer
A study published in Nature Genetics reports that the BNC2 gene may be associated with an increased risk of developing ovarian cancer. BNC2 is more common and less harmful than BRCA1 and BRCA2 but may significantly raise cancer risk when combined with other genes.
http://www.medicalnewstoday.com/articles/164062.php
More Sensitive Screening Needed to Detect Early Ovarian Tumours
An American study of tumours removed as a precaution in women with BRCA1 found that most tumours were under 1 centimetre diameter for about 4 years before metastasizing. Existing tests would have to be much more sensitive to detect tumours of this size.
http://www.medicalnewstoday.com/articles/164062.php
October 2009
Young, Premenopausal Women Can Retain Fertility After Epithelial Ovarian Cancer
Ovarian cancer treatment traditionally involves removing both ovaries and the uterus, which pushes younger women into menopause, resulting in a loss of reproductive function. However, a new study has shown that premenopausal women with Stage I ovarian cancer who have the cancerous ovary removed have the same five-year survival rates as women who have both ovaries removed.
This study investigated the safety of fertility-conserving surgery in 1186 premenopausal women aged 50 years with stage IA or IC epithelial ovarian cancers. Results were compared for women who underwent bilateral oophorectomy (n = 754; 64%) versus women who underwent ovarian conservation (n = 432; 36%).
Ovaries were more likely to be preserved among women who were younger, had a later year of diagnosis, or who lived in the United States (p < 0.05 for all). Ovarian preservation was less likely tin women with endometrioid or clear cell histologies, or stage IC disease (p < 0.05 for all). Similarly, uterine preservation was more likely in women who were younger, had a later year of diagnosis, lived in the United States, were single, and women who had mucinous tumors or stage IA disease (p < 0.05 for all).
Importantly, neither ovarian preservation not uterine preservation affected survival (hazard ratio [HR] for ovarian preservation = 0.69, 95% confidence interval [CI]: 0.39-1.20; HR for uterine preservation = 0.87, 95% CI: 0.62-1.22). The results showed similar survival rates for up to five years among women in whom one ovary was preserved and in women who had both ovaries removed.
Reference:
Wright JD, Shah M, Mathew L, et al. Fertility preservation in young women with epithelial ovarian cancer. Cancer; Published Online: August 10, 2009 (DOI: 10.1002/cncr.24461); Print Issue Date: September 15, 2009
http://www3.interscience.wiley.com/journal/122542472/abstract
Delays in Diagnosis of Ovarian Cancer Because of Poor Symptom Investigation
Ovarian cancer has often been termed the "silent killer" because it is thought to have few symptoms. However, a recent study published in the British Medical Journal found that symptoms of ovarian cancer are common and that their early identification has the potential to improve prognosis. The study also shows that women with ovarian cancer can go undiagnosed for months because their symptoms are not always being investigated promptly.
The key symptoms that could indicate ovarian cancer were investigated in 212 women presenting to primary care practices in England.
Seven symptoms were identified as indicating ovarian cancer, including abdominal distension, urinary frequency, abdominal pain, postmenopausal bleeding, loss of appetite, rectal bleeding, and abdominal bloating. Some women presenting with the first three of these symptoms waited at least six months before the diagnosis was made. All of these symptoms were associated of a <1% risk of ovarian cancer except abdominal distension, which had a positive predictive value of 2.5%. This means that it carries the highest risk of indicating ovarian cancer and warrants rapid investigation. Over a third of women reported this symptom and it was equally as common in stages I and II cancer as it was in advanced cancer.
Notably, abdominal distension is not included in current guidance for urgent investigation. If it was, say the authors, it would aid earlier diagnosis of ovarian cancer.
References:
Hamilton W, Peters TJ, Bankhead C, and Sharp D. Risk of ovarian cancer in women with symptoms in primary care: population based case-control study. BMJ 2009 339: b2998.
http://www.bmj.com/cgi/content/full/339/aug25_2/b2998
Austoker J. Diagnosis of ovarian cancer in primary care. BMJ 2009;339:b3286
http://www.bmj.com/cgi/content/full/339/aug25_2/b3286
Ovarian Tumours May Exist For Four Years Before Metastasising
Most ovarian cancer deaths are caused by tumours of the serous histological type (BRCA1 mutation), which are rarely diagnosed before the cancer has metastasised. Researchers in the US investigated the early natural history of serous ovarian cancers discovered in apparently healthy women who underwent prophylactic bilateral salpingo-oophorectomy (PBSO).
They found that these cancers exist in the body for about four years before they metastasise and become clinically apparent. During this time, the tumours are usually less than 1 cm in diameter, and not visible on gross examination of the ovaries and Fallopian tubes.
These results mean that there is a long window of opportunity for early detection of these cancers. However, early detection requires a test that is sufficiently sensitive and specific to detect very small tumours.
References: http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1000114
Mayo Clinic Awarded US$11.5 Million For Research Into Ovarian Cancer Treatments
Investigators at the Mayo Clinic Cancer Center in the US have received a five-year, $11.5 million grant to translate research into treatments for women with ovarian cancer.
The research consists of four projects that aim to:
- Combine a new enzyme inhibitor, a PARP inhibitor, with topotecan, an established chemotherapy drug for ovarian cancer. The PARP inhibitor is intended to augment topotecan's effectiveness.
- Determine inherited factors that control a woman's immune response to ovarian cancer.
- Advance new therapy, developed at Mayo, based on re-engineered viruses that invade and destroy ovarian cancer cells.
- Test the impact of a small molecule drug, flavopiridol, that prevents ovarian cancer resistance to platinum chemotherapy.
Reference: http://www.medicalnewstoday.com/articles/162177.php
August 2009
Hormone Replacement Therapy Is Associated with Increased Ovarian Cancer Risk
Women who currently take hormone replacement therapy (HRT) or who have taken it in the past have an increased risk of ovarian cancer, compared with women who have never taken HRT, according to a study published this month in the Journal of the American Medical Association.
The study followed 909,946 Danish women aged 50 – 79 years for an average of 8 years. During this time, 3,068 ovarian cancers were detected.
Current HRT users had a 38% greater risk of all ovarian cancers, and a 44% greater risk of epithelial ovarian cancer, compared with women who never used HRT. Women who had used HRT in the past had a 15% greater risk of epithelial ovarian cancers, compared with never users. The increased risk of ovarian cancer occurs regardless of the duration of use, the formulation, oestrogen dose, regimen or route of administration.
The level of increased risk reported in the study equates to approximately 1 extra ovarian cancer for around 8,300 women taking HRT each year, or around 140 extra cases of ovarian cancer in Denmark over the 8-year follow-up period.
Reference:
Steinrud L, Lokkegaard E, Helms Andreasen A, Kruger-Kjaer S, Lidegaard O. Hormone therapy and ovarian cancer. JAMA 2009; 302(3):298-305
http://www.medicalnewstoday.com/articles/157610.php
Women and GPs Lack Awareness About Ovarian Cancer – First Results of the Pathfinder Study
First results from the Target Ovarian Cancer Pathfinder Study show a widespread lack of awareness about ovarian cancer in the UK. This study, which is being conducted by the UK charity Target Ovarian Cancer, surveyed women in the general population, women with ovarian cancer, clinical nurse specialists, clinicians, researchers, and GPs about their experiences with ovarian cancer.
Of the 400 GPs surveyed:
• Only half of GPs knew that 'increased abdominal size' was the most important symptom of ovarian cancer, and fewer than 2% knew that 'difficulty eating' or 'feeling full' were possible signs of the disease.
• 61% of GPs did not realise that a woman's risk of ovarian cancer is increased if there is a history of the disease on her father's side of the family, and many thought that symptoms of ovarian cancer were more likely to indicate irritable bowel syndrome.
• Only 27% were aware of new UK guidance about ovarian cancer, which was published in February this year.
Of the 1,000 women surveyed:
• Only 4% were confident about naming a symptom of ovarian cancer
• Most women were unaware of the links with increasing age (63%) and childlessness (80%)
References:
http://info.cancerresearchuk.org/news/archive/newsarchive/2009/june/19242695
http://www.targetovarian.org.uk/page.asp?section=260§ionTitle=The+Target+Ovarian+Cancer+Pathfinder+Study+First+Results
July 2009
Recurrent Ovarian Cancer
Symptoms Are Just as Good as CA125 Levels for Determining When to Begin Chemotherapy
New research presented at the American Society of Clinical Oncology meeting in Orlando showed that treating ovarian cancer recurrence based on an increase in CA125 alone has no benefit on survival, compared with waiting for clinical symptoms of recurrence to occur.
The study was conducted in 529 women with remission from ovarian cancer after first-line platinum-based chemotherapy. Overall survival was compared for 265 women who started second-line chemotherapy based on elevated CA125 levels versus 264 women who had increased CA125 but delayed starting second-line chemotherapy until relapse symptoms such as pelvic pain and bloating appeared (an average of 4.8 months delay).
Overall survival was the same for each group, averaging at 41 months since completion of first-line chemotherapy, regardless of when second-line chemotherapy was started.
The lead investigator, Dr Ruskin, commented, "there is no benefit from early detection of recurrence by routine CA125 measurements. Even if CA125 rises, if they are well, chemotherapy can be delayed until signs or symptoms of tumour recurrence."
Reference:
http://www.curetoday.com/index.cfm/fuseaction/news.showNewsArticle/id/13/news_id/1270
Ovarian Cancer Screening
Combined Screening with CA125 Plus Ultrasound is Effective
There are promising results from a large trial of screening for ovarian cancer in 200,000 postmenopausal women in the UK.
Post-menopausal women aged 50–74 were randomly allocated to no treatment, vaginal ultrasound, or vaginal ultrasound plus serum CA125 screening. Sensitivity was generally higher with combined screening than with ultrasound only for all primary ovarian and tubal cancers (89% vs 85%) and for primary invasive epithelial ovarian and tubal cancers (90% vs 75%).
Specificity was significantly higher (p<0.0001) with combined screening versus ultrasound alone for both primary ovarian and tubal cancers, as well as primary epithelial invasive ovarian and tubal cancers (99.8% vs 98.2% and 99.8% and 98.2%, respectively). This resulted in lower rates of repeat testing and surgery, reflecting that combined screening offered better detection of benign abnormalities and borderline tumours.
These preliminary results demonstrate that screening strategies for ovarian cancer are feasible. Final results (due in 5 years time) are awaited to determine the outcomes of screening on mortality.
Reference:
Menon et al. Sensitivity and specificity of multimodal and ultrasound screening for ovarian cancer, and stage distribution of detected cancers: results of the prevalence screen of the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS). The Lancet Oncology 2009; 10(4): 327-340
Highly Sensitive New Screening Method Detects 96% of Early-Stage Ovarian Cancer
A new screening method for ovarian cancer based on serum CA125 levels plus levels 3 serum proteins appears to be the most sensitive screening method discovered so far for detecting early-stage ovarian cancer.
This study analysed 358 serum samples available at the National Cancer Institute from 4 groups of patients (healthy controls; patients with benign adnexal masses; patients with stage I or II ovarian cancer; and patients with stage III or IV ovarian cancer). Samples were tested for levels of CA125 plus the biomarker proteins apolipoprotein A-1 (ApoA-1), transthyretin (TTR), and transferrin (TF).
The sensitivity and specificity of screening for CA125 plus the 3 biomarker proteins was 96% for early-stage ovarian cancer. This is the highest sensitivity of an ovarian cancer screening test reported to date. Serous and endometrioid early-stage cancers were detected with sensitivities of 94% and 98%, respectively.
The next step is to evaluate this screening method in a prospective study of healthy volunteers.
Reference:
Nosov V, Su F, Anmeus M, et al. Validation of serum biomarkers for detection of early-stage ovarian cancer. Am J Obstet Gynecol 2009; 200(639): 639.e1-639.e5
Ovarian Cancer Gene Breakthrough
Canadian researches have discovered a single mutation in the genetic code that causes granulosa cell tumours, a rare and often untreatable form of ovarian cancer. This information will eventually be used to identify granulosa cell tumours and to develop news ways to treat them.
http://www.medicalnewstoday.com/articles/153560.php
May 2009
Promising New Drugs for Ovarian Cancer
Dasatinib and Lpathomab Show Good Preclinical Results
Two preclinical studies (conducted on ovarian cancer cells in lab dishes) showed good results for new drugs for ovarian cancer.
Dasatinib Enhances the Activity of Ovarian Cancer Chemotherapy
Dasatinib, a drug used in the treatment of leukaemia, enhanced the activity of a standard regimen of carboplatin and paclitaxel against four types of ovarian cancer cells.
This study tested the effects of various combinations of dasatinib, carboplatin and paclitaxel on four ovarian cancer cell lines in lab dishes (IGROV1, SKOV3, OVAR3 and A2780). The findings showed that the addition of dasatinib was effective in cell lines with high expression of the SRC pathway, which is involved in cell proliferation in ovarian cancer. It is hoped that in the future therapy may be able to be targeted according to patients’ individual gene expression pathways. For example, patients with high SRC expression may benefit from the addition of dasatinib. Further study is required to determine the safety and effectiveness of dasatinib in patients.
Reference:
http://www.sciencedaily.com/releases/2009/04/090419133837.htm
Lpathomab Slowed Tumour Cell Progression
Lpathomab is a monoclonal antibody that acts as a ‘molecular sponge’ to absorb a lipid lysophosphatidic acid (LPA) and eliminate the activity of LPA on tumour grown, the growth of new tumour blood vessels (neovascularisation) and tumour metastasis.
In recent studies in SKOV3 ovarian cancer cells, lpathomab blocked LPA-triggerd migration of tumour cells, decreased neovascularisation and showed anti-metastatic activity.
These results are promising but they are very early-stage and further studies in ovarian cancer patients are required to determine whether lpathomab is safe and effective.
Reference: http://www.medicalnewstoday.com/articles/146872.php
Genetic Variations in the Risk of Developing Ovarian Cancer and Survival
The risk of developing ovarian cancer and survival time may depend on the number of variations a women has in the micro-RNA (mi-RNA) processing pathway and mi-RNA binding sites.
Researchers in the US examined genetic data from 417 cancer patients and 417 healthy controls. They found that median survival was up to 151 months for women with few mi-RNA variations compared with 24 months for women with the most unfavourable variations. Women with 8 or more variations were 4.5 times more likely to develop ovarian cancer than women with 5 or less variations.
This information might help the development of targeted therapy in the future.
Reference: http://www.medicalnewstoday.com/articles/146660.php
Combination Treatment in Gynaecological Cancers
Treatment with Combination Topotecan and Docetaxel is Effective Against Recurrent Uterine, Ovarian, Fallopian or Peritoneal Cancers
Recurrent gynaecological cancers can be very difficult to treat because of spread to other organs, resistance to chemotherapy, or the patient may have already had heavy chemotherapy and be unable to withstand further treatment.
Topotecan and docetaxel are effective when used separately against recurrent gynaecological cancers. This study was the first to assess the effect of combination topotecan and docetaxel in recurrent uterine, ovarian, fallopian or peritoneal cancers. Twenty-four women received a total of six treatments with combination therapy (once weekly for 3 weeks, then a 1-week rest, then once weekly for 3 weeks).
The results showed that almost 40% of these women experienced clinical benefit (what outcome?) after combination treatment. The median overall survival was 18.5 months and there were relatively few side effects compared with toxicities in similar studies.
The next step is to conduct a larger trial in more women to determine whether the effect is reproducible.
Reference: http://www.sciencedaily.com/releases/2009/04/090421181039.htm
April 2009
New Drug Shows Encouraging Results for Women with Recurrent Ovarian Cancer
A recent study has shown that a new drug, currently named CNTO328, stabilised or shrank ovarian cancers in 8 out of 18 women in the UK. The rate of survival was “unusually high”, given that these women had recurrent tumours and were not expected to live for more than a year after they began the study.
If the drug continues to get good results in future trials, it could be available for patients within 5 years.
Reference: http://www.hindu.com/thehindu/holnus/099200904070940.htm
The Screening Debate Continues
Ovarian cancers detected early may be less aggressive
A new study raises questions about the benefits of screening for ovarian cancer, because screening is most likely to detect those types of cancer that are slow-growing (or indolent), not the aggressive types that are likely to be fatal. Scientists from the Duke Comprehensive Cancer Centre found that 39 of 40 ovarian cancers detected at an early stage had a genetic profile predicting long-term survival.
These results are consistent with studies in breast cancer showing that about one quarter of breast cancers detected early on mammograms disappear spontaneously. Andrew Berchuck, who led the Duke University study, explains that: “what you tend to find with screening is the cancer equivalent of a cold virus, not HIV”.
References:
http://www.sciencedaily.com/releases/2009/03/090324131452.htm
Mutch, David G. (2009). “To Screen or Not To Screen”. Obstetrics & Gynecology;113(4):772-774
Screening may cause women to have unnecessary tests
A study comparing the only two available screening tests for ovarian cancer has found that neither of them are great at picking up early tumours. Furthermore, they may cause women to have unnecessary surgery.
These tests compared in the study were the CA125 test and the transvaginal ultrasonography (TU). CA125 is a protein found on the surface of the ovaries and some other normal tissues that may be higher in patients with ovarian cancer. TU is when an ultrasound operator looks for any odd growths on the ovaries. Women with positive results on either test usually have a biopsy to check whether the cells of the ovary are cancerous.
The study looked at information from 35,000 aged between 55 and 74 years who had had CA125 and TU screening tests every year for 4 years. The results were:
- Out of 87 women diagnosed with ovarian cancer during the study period, screening picked up cancer in only 60 women, meaning that screening detected only 67% of cancers.
- Only one cancer was detected for every 20 biopsies; 19 out of 20 women underwent an unnecessary biopsy, with all the associated stress that this brings.
- Most cancers (72%) detected by screening were late stage.
References:
http://www.medicalnewstoday.com/articles/144679.php
Partridge E, Kreimer AR, Greenlee RT, et al. (2009). “Results from four rounds of ovarian cancer screening in a randomized trial.” Obstetrics & Gynecology:113(4):775-782
Obesity and Ovarian Cancer – A link?
There may be a link between obesity and ovarian cancer. The study followed almost 95,000 women in the US for 7 years and found that:
- Obese women (BMI ?30 kg/m2) who had never used hormone replacement therapy (HRT) had an almost 80% greater risk of ovarian cancer compared with women who were normal weight.
- There was no increased risk among obese women who had used HRT.
The authors suggested that obese women may be more likely to have hormonal changes that lead to ovarian cancer. However, it’s too early to make any conclusions and more studies showing an association between obesity and ovarian cancer are required before any conclusions can be drawn.
Reference: Leitzmann MF et al. Body mass index and risk of ovarian cancer. Cancer 2009; 115; 812-22
2008
Anassuya Ramachandran, Doctor of Philosophy in Obstetrics and Gynaecology, Auckland
Dissecting the Role of Activin in Ovarian Cancer
The role of activin had been proposed in the development of ovarian cancer, but the mechanism of action was unclear. Her early experiments were to assess the role of activin on the growth of 16 ovarian cancer cell lines. To her surprise, it had the opposite action to what had previously been described in the literature. The rest of her PhD project was to unravel this seeming contradiction, and to provide experimental evidence for the exact role of activin in the growth of these cells. Anassuya’s project was the first research to confirm the involvement of activin as a growth suppressor of ovarian cancer cells. Her project provided some important understanding of the mechanism of action of activin, and identified many of the key genes that regulate growth suppression in ovarian cancer. Annasuya’s project will change the way that cancer researchers understand the development of ovarian cancer. This information will be valuable in the design of new therapies, as new therapeutic targets are required to treat this deadly cancer.
Uterine Cancer Research Update
May 2009
Combination Treatment in Gynaecological Cancers
Treatment with Combination Topotecan and Docetaxel is Effective Against Recurrent Uterine, Ovarian, Fallopian or Peritoneal Cancers
Recurrent gynaecological cancers can be very difficult to treat because of spread to other organs, resistance to chemotherapy, or the patient may have already had heavy chemotherapy and be unable to withstand further treatment.
Topotecan and docetaxel are effective when used separately against recurrent gynaecological cancers. This study was the first to assess the effect of combination topotecan and docetaxel in recurrent uterine, ovarian, fallopian or peritoneal cancers. Twenty-four women received a total of six treatments with combination therapy (once weekly for 3 weeks, then a 1-week rest, then once weekly for 3 weeks).
The results showed that almost 40% of these women experienced clinical benefit (what outcome?) after combination treatment. The median overall survival was 18.5 months and there were relatively few side effects compared with toxicities in similar studies.
The next step is to conduct a larger trial in more women to determine whether the effect is reproducible.
Reference: http://www.sciencedaily.com/releases/2009/04/090421181039.htm
Vulval Cancer Research Update
December 2009 and January 2010
A New Vaccine Eliminates HPV Virus and May Cause Regression of VIN
A new therapeutic vaccine designed to eliminate infection with HPV may cause precancerous VIN lesions to regress.
This new vaccine differs from Gardasil and Cervarix, which prevent infection with HPV, because it is designed for use by people who have already been exposed to HPV but cannot clear the virus on their own. Chronic HPV infection is associated with a high risk of developing HPV-related cancer.
A study published in the New England Journal of Medicine reports that the new vaccine induced an HPV-specific immune response in 100% of patients with advance vulvar intraepithelial neoplasia (VIN3). The vaccine produced measurable regression of VIN3 lesions within 1 year of administration for 79% of women. In 9 women (47%), VIN3 lesions completely disappeared and the women remained free of symptoms two years after vaccination.
References:
http://www.medicalnewstoday.com/articles/170511.php
http://content.nejm.org/cgi/content/abstract/361/19/1838
Kenter GG, Welters MJP, Valentijn ARPM, et al. Vaccination against HPV-16 Oncoproteins for Vulvar Intraepithelial Neoplasia. NEJM 2009; 361(5): 1838-1847
May 2009
HPV Vaccine May Prevent Vulval and Vaginal Cancers
A review of medical literature suggests that the human papillomavirus (HPV) vaccine may be useful at preventing vulval and vaginal cancers. The researchers searched Medline, a medical database, for studies in which patients with vulval or vaginal cancers underwent a DNA test to determine if HPV was also present.
The reviewers found HPV (usually HPV16) was present in the 40% of vulvar cancer cases and in 65% of vaginal cancer cases. HPV was also found in over 75% of cases of pre-cancerous vulvar or vaginal intraepithelial neoplasia.
Even though HPV vaccines may not have as great an effect on these cancer as they do on cervical cancer, they may still reduce the number of HPV-related vulval and vaginal cancers.
Reference:
Smith JS, Backes DM, Hoots BE, Kurman RJ, Pimenta JM. (2009). “Human Papillomavirus Type-Distribution in Vulvar and Vaginal Cancers and Their Associated Precursors.” Obstetrics & Gynecology:113(4):917-924
April 2009
Excellent Survival Outcomes With Surgery for Stage I and Stage II Vulval Cancer
Almost all patients with FIGO (International Federation of Gynecology and Obstetrics) Stage I or Stage II squamous cell vulvar cancer survive to 5 years after their diagnosis if they are treated with vulvar-conserving surgery, according to a retrospective analysis of data from 121 women with vulvar cancer in the US. Five-year survival was 97% for Stage I patients and 95% for Stage II patients.
Vulva-conserving surgery was used to treat 96% of these women and did not impact on the likelihood of disease progression or survival.
Reference:
Tantipalakorn C, Robertson G, Marsden DE, Gebski V, Hacker NF. (2009). “Outcome and Patterns of Recurrence for International Federation of Gynecology and Obstetrics (FIGO) Stages I and II Squamous Cell Vulvar Cancer.” Obstetrics & Gynecology:113(4):895-901
HPV Vaccine May Prevent Vulval and Vaginal Cancers
A review of medical literature suggests that the human papillomavirus (HPV) vaccine may be useful at preventing vulval and vaginal cancers. The researchers searched Medline, a medical database, for studies in which patients with vulval or vaginal cancers underwent a DNA test to determine if HPV was also present.
The reviewers found HPV (usually HPV16) was present in the 40% of vulvar cancer cases and in 65% of vaginal cancer cases. HPV was also found in over 75% of cases of pre-cancerous vulvar or vaginal intraepithelial neoplasia.
Even though HPV vaccines may not have as great an effect on these cancer as they do on cervical cancer, they may still reduce the number of HPV-related vulval and vaginal cancers.
Reference:
Smith JS, Backes DM, Hoots BE, Kurman RJ, Pimenta JM. (2009). “Human Papillomavirus Type-Distribution in Vulvar and Vaginal Cancers and Their Associated Precursors.” Obstetrics & Gynecology:113(4):917-924
Cervical Cancer Research Update
August 2010
Trial Underway of a New Immunotherapy Drug for Cervical Intraepithelial Neoplasia
A new clinical trial has begun in the US to investigate the safety and efficacy of a new immunotherapy drug for grade 2 or 3 cervical intraepithelial neoplasia (CIN), also known as cervical dysplasia. CIN is a precursor to cervical cancer.
The study is a multicentre, randomised, placebo controlled, blinded clinical trial of a drug known as ADXS11-001 (made by Advaxis, Inc). Results of the first part of the study are expected in 15 months.
http://www.medicalnewstoday.com/articles/190501.php
Smoking Causes Molecular Changes Associated with Cervical Cancer
A recent study found that women who smoke are more likely to have molecular changes leading to cervical cancer. This study builds on previous evidence of an association between smoking and cervical cancer.
Cervical epithelium biopsy specimens were examined from 228 women, including 188 with cervical intraepithelial neoplasia (CIN) and 40 healthy controls. Women with CIN who smoked had underexpression of the tumour suppressors p53 and fragile histidine triad, and the immunologic marker interleukin-10, plus overexpression of the tumour markers cyclooxygenase-2 and Ki-67, compared with non-smoking women with CIN. These results indicate that smoking is associated with negative molecular changes in the cervical epithelium.
Reference:
Samir R, Asplund A, Tot T, et al. Tissue tumour marker expression in smokers, including serum cotinine concentrations, in women with cervical intraepithelial neoplasia or normal squamous cervical epithelium. Am J Obstet Gynecol 2010;202:579.e1-7.
http://download.journals.elsevierhealth.com/pdfs/journals/0002-9378/PIIS000293780902208X.main-abr.pdf?jid=ymob
March 2010
Combined Chemotherapy and Radiotherapy Achieves Better Survival
Cervical cancer survival is improved with combined chemotherapy and radiotherapy, compared to radiotherapy alone, according to a large analysis of data from 3.452 women in 15 clinical trials. A higher proportion of women who received combined chemotherapy (drug treatment) and x-ray treatment (radiotherapy) survived at 5 years after treatment, compared with women who received radiotherapy alone (66 out of 100 vs 60 out of 100).
Additionally, a sub-analysis found that continuing chemotherapy after combination chemo- and radiotherapy could improve survival rates even further, although more research is required to confirm this.
Reference: http://www.medicalnewstoday.com/articles/176572.php
HPV Testing Is More Effective Than Cytology (Pap) For Preventing Cervical Cancer
A randomised, controlled trial published in the Lancet Oncology reports that screening for HPV is more effective than cytology for prevention of invasive cervical cancer, because it allows detection of persistent high-grade lesions earlier and provides a longer low-risk period. These results were greatest among older women (aged 35-60 years); in younger women, HPV screening could lead to over-diagnosis of regressive CIN2.
In this two-phase study, women aged 25-60 years were randomised to conventional cytology (n = 47,001) or to HPV testing in combination with liquid-based cytology (first phase) or alone (second phase) (n = 47,369). In phase one, HPV-positive women aged 35-60 years were referred to colposcopy, whereas women aged 25-34 years were referred to colposcopy only if cytology was also abnormal or HPV testing was persistently positive. In phase two, women in the HPV group were referred for colposcopy if the HPV test was positive. Two rounds of screening occurred in each phase, and all women had cytology testing only at the second round; 33,851 women from the cytology group and 32,998 from the HPV-testing group had a second round of screening. The primary endpoint was the detection of grade 2 and 3 CIN (CIN2 and CIN3), and of invasive cervical cancers during the first and second screening rounds, in the intention-to-screen population.
There were a significantly lower number of cervical cancer cases in the HPV group compared with the cytology group over the two screening rounds, indicating that the HPV-based screening is more effective than cytology in preventing cervical cancer. Similar numbers of invasive cervical cancers were detected with each method in the first round of screening (9 with cytology vs 7 with HPV testing; p=0•62). There were no cases detected in the HPV group during round 2, compared with 9 in the cytology group (p=0•004). Overall, in the two rounds of screening, 18 invasive cancers were detected with cytology versus 7 with HPV testing (p=0•028).
HPV testing was superior to cytology for detection of grade 2 and 3 CIN and invasive cervical cancers. In round 1 in women aged 35-60 years, the relative detection values for HPV vs cytology for CIN2 and CIN3 were 2•00 (95% CI 1•44-2•77) and 2•08 (1•47-2•95) for CIN3; relative detection was 2•03 (1•60—2•57) for CIN2 and 3 together. For round 2, the relative detection was 0•54 (0•23-1•28) for CIN2, 0•48 (0•21-1•11) for CIN3, and 0•51 (0•28-0•93) for CIN2 and 3 together.
Among women aged 25—34 years, there was significant heterogeneity between phases in the relative detection of CIN3. At round one the relative detection was 0•93 (0•52—1•64) in phase one and 3•91 (2•02—7•57) in phase two. At round two the relative detection was 1•34 (0•46—3•84) in phase one and 0•20 (0•04—0•93) in phase two. Pooling both phases, the detection ratio of CIN2 for women aged 25—34 years was 4•09 (2•24—7•48) at round one and 0•64 (0•23—1•27) at round two.
Reference
Ronco G, Giorgi-Rossi P, Carozzi F, et al. (2010). Efficacy of human papillomavirus testing for the detection of invasive cervical cancers and cervical intraepithelial neoplasia: a randomised controlled trial. Lancet Oncology; Early Online Publication, 19 January 2010: doi:10.1016/S1470-2045(09)70360-2
http://www.medicalnewstoday.com/articles/176502.php
Other Interesting Links:
Triapine Shows Promising Results for Treatment of Advanced Cervical Cancer
A phase one Irish study reports that that a new chemotherapy agent, Triapine, was well tolerated in combination with cisplatin chemotherapy and radiation treatment in women with cervical cancer. This regimen provided both significant reduction in cancer disease and cancer control. Triapine works by suppressing tumour growth. A phase two follow-up study is ongoing at the Ireland Cancer Center.
http://www.medicalnewstoday.com/articles/178773.php
HPV Screening and Vaccination Have Minimal Benefits for Women Aged Over 41
A study reported in the Journal of the National Cancer Institute found that the rate of new infections preventable by HPV vaccination declines with age, suggesting that HPV vaccination and screening is of limited benefit in women aged over 41.
http://www.medicalnewstoday.com/articles/179269.php
Gardasil is Effective in Young Men
The HPV vaccine Gardasil has been shown to prevent anal cancer and precancerous anal lesions in young men who have sex with men, as well as precancerous cervical lesions and genital warts in women aged 25-45 years.
http://www.medicalnewstoday.com/articles/179507.php
February 2010
HPV Testing Better for Prevention of Invasive Cancers than Cytology Screening Alone
Results from a recent trial suggest that DNA testing for human papillomavirus (HPV) should be the main screening tool for cervical cancer in women aged 35 years and older.
The trial, known as The New Technologies for Cervical Cancer (NTCC) screening study, was a two-phase study in women aged 25 - 60 years who received conventional cytology only or HPV testing plus cytology (first phase), and HPV testing alone (second phase). HPV testing detected persistent high-grade lesions which lead to earlier cervical cancer, compared to cytology screening alone.
Although DNA testing for HPV is generally superior to cytology for detecting precancerous lesions cervical intraepithelial neoplasia (CIN2 and CIN3), it results in more false-positive tests than conventional Pap smears. In the study, HPV testing led to over-diagnosis and treatment among women aged 25-34 years. Therefore, the authors concluded that HPV testing should become the main screening tool for women aged 35 years or older at longer screening intervals, with cytology reserved for triage of women who test positive for HPV.
Reference:
Ronco G, Giorgi-Rossi P, Carozzi F, et al. (2010). Efficacy of human papillomavirus testing for the detection of invasive cervical cancers and cervical intraepithelial neoplasia: a randomised controlled trial. The Lancet Oncology. DOI: 10.1016/S1470-2045(09)70360-2
http://www.medicalnewstoday.com/articles/176397.php
November 2009
Hysterectomy is Better Than Radiotherapy For Cervical Tumours <6cm Diameter
Radical hysterectomy appears to be superior to radiation therapy for women with cervical tumours measuring less than 6 cm diameter.
A US study compared survival data for 4885 patients with stage IB1-IIA cervical cancer in the Surveillance, Epidemiology, and End Results database who had received either radical hysterectomy or primary combination external-beam and brachytherapy radiation.
There was a 59% improvement in survival rate with radical hysterectomy (hazard ratio [HR] 0.41; 95% confidence interval [CI] 0.35–0.50). When analysed by tumour size, survival rates improved by 62% for tumours <4cm diameter (HR 0.38; 95% CI 0.30–0.48) and by 49% for tumours 4-6cm diameter (HR 0.51; 95% CI 0.36–0.72). However, for women with tumours that were >6 cm in size, survival was similar radical hysterectomy and radiation.
Reference:
Bansal N, Herzog TJ, Shaw RE, et al. Primary therapy for early-stage cervical cancer: radical hysterectomy vs radiation. Am J Obstet Gynecol 2009; 201:485.e1-9
http://www.ajog.org/article/S0002-9378(09)00637-1/abstract
Why Aren’t Women Getting Gardasil? A New Study Investigates
An estimated 3 out of 4 women in the US remain unvaccinated three years after the introduction of the Gardasil vaccine for HPV, despite extensive advertising and government mandates.
A marketing study found that women aged 18-30 were more likely to consider getting the vaccine after participating in a survey than because of commercial advertising or a law requiring them to do so.
The researchers suggested that the survey was successful because it was least coercive and encouraged women to think about the risks of not being vaccinated. In contrast, there was a negative backlash against laws requiring vaccination, and women were sceptical about advertising of the vaccine.
The study was titled "The Influence of Different Types of Cues-to-Action on Vaccination Behaviour: An Exploratory Study," and it will be published in the next edition of the Journal of Marketing Theory and Practice.
Reference: http://www.medicalnewstoday.com/articles/163771.php
Information about the free Gardasil vaccine available to young women in NZ: www.cervicalcancervaccine.govt.nz
American Guidelines Recommend Fewer Screening Tests for Cervical Cancer
New evidence-based guidelines from the American College of Obstetricians and Gynecologists (ACOG) have downgraded the frequency of screening for cervical cancer. The new guidelines recommend that women have their first cervical cancer screening test at age 21. Screening should then occur every two years (instead of annually) for women aged under 30, and every three years for women aged 30 and over.
These guidelines bring the US closer to New Zealand’s cervical screening programme, which recommends screening every three years unless abnormalities have been detected.
Reference: http://www.medicalnewstoday.com/articles/171742.php
Practice Bulletin #109, "Cervical Cytology Screening," is published in the December 2009 issue of Obstetrics & Gynecology.
October 2009
The FDA Affirms that Gardasil is Safe
A study of adverse events occurring after administration of the Gardasil HPV vaccine since 2006 indicates that the vaccine is associated with similar rates of adverse events as other vaccines, with the exception of a higher proportion of reports of fainting and blood clots.
The Centers for Disease Control and Prevention (CDC) analysed adverse events reported to the Vaccine Adverse Event Reporting System (VAERS) between 1 June 2006 and 31 December 2008. VAERS is a national, voluntary, passive surveillance system.
There were 12,424 reports of adverse events following HPV administration, equating to 53.9 per 100,000 doses distributed. Of these, 772 (6.2%) were serious, including 32 deaths. The most common adverse events per 100,000 doses administered were syncope (8.2), local injection site reactions (7.5), nausea (5), headache (4.1), hypersensitivity reactions (3.1), urticaria (2.6), venous thromboembolic events (0.2), autoimmune disorders (0.2), Guillain-Barré syndrome (0.2); anaphylaxis (0.1) and death (0.1).
References:
Slade BA, Leidel L, Vellozzi C, et al. Postlicensure Safety Surveillance for Quadrivalent Human Papillomavirus Recombinant Vaccine. JAMA. 2009; 302(7):750-757
http://www.jama.ama-assn.org/cgi/content/abstract/302/7/750
http://www.medicalnewstoday.com/articles/161559.php
August 2009
Gardasil Highly Effective At Preventing Precancerous Cervical Lesions
The final analysis of the PATRICIA (PApilloma TRIal against Cancer In young Adults) study shows that the HPV vaccine Gardasil is highly effective against the precancerous cervical lesions that can eventually lead to cervical cancer. It was also cross-protective against other cancer-causing HPV types that are closely related to HPV-16/18.
Gardasil acts against HPV types 16/18, which account for around 70% of cervical cancers, while related HPV types account for the remainder of cervical cancers.
In this study, women aged 15 – 25 years were randomised to receive either the HPV vaccine at months 0, 1 and 6 (n=8093) or control (n=8069). The primary endpoint was the efficacy of the vaccine against cervical intraepithelial neoplasia 2+ (CIN2+), the precancerous lesions that can eventually lead to cervical cancer.
After a mean follow-up of 3 years, the vaccine had 93% efficacy against CIN2+ associated with HPV-16/18. The vaccine was also protective against other HPV-31 (related to HPV-16) and HPV-45 (related to HPV-18).
References:
Paavonen J, Naud P, Salmerón J, et al. Efficacy of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine against cervical infection and precancer caused by oncogenic HPV types (PATRICIA): final analysis of a double-blind, randomised study in young women. Lancet Early Online Publication, 7 July 2009; doi:10.1016/S0140-6736(09)61248-4
http://www.medicalnewstoday.com/articles/156609.php
July 2009
HPV Vaccine for Boys
Doctors at the British Medical Association conference in June are calling for boys to receive the HPV vaccine too, so they will not be able to pass on the virus to girls. This will help to reduce the 3,000 cervical cancer diagnoses and 1,000 deaths from the disease each year.
http://www.mirror.co.uk/news/top-stories/2009/06/21/jabs-for-boys-too-say-docs-115875-21458922/
May 2009
Landmark Study shows HPV Testing is Significantly Better than Pap and Visual Inspection for Reducing Deaths from Cervical Cancer
A new study shows that advanced cervical cancers and deaths from cervical cancer were significantly lower after a single round of HPV testing than with Pap (cytology) testing or visual inspection with acetic acid (VIA). The HPV test was the digene test made by Qiagen, which is approved for use together with Pap in women aged 30 years and older in Europe and the US.
This study is notable because it is the first randomised, controlled trial to assess the effects of different screening tools on cervical cancer incidence and death. It was an eight-year study in over 130,000 women in the world’s poorest countries, and was funded by Qiagen (a Netherlands company who make the digene HPV test), and the Bill and Melinda Gates Foundation, who are working together to make a version of this test available to public health programmes in developing countries.
Almost 300,000 women die of cervical cancer every year, with 80% of these deaths occurring in developing countries. The WHO estimates that only around 5% of women in the developing world are screened for cervical disease, compared with 40-50% of women in the developed world.
Reference: http://www.content.nejm.org/
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