ORLANDO, May 31 — A test widely used to monitor ovarian cancer patients for recurrence did not improve survival despite allowing patients to begin second- and third-line therapy earlier, a large European study showed.

• Explain to interested patients that serial CA125 testing allowed ovarian cancer patients to begin therapy for recurrence earlier than they would have without the testing.
• Note, however, that the earlier therapy based upon testing did not improve survival.
• Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

Patients followed with serial CA125 testing began therapy for recurrence about five months sooner than did patients whose treatment was delayed until symptomatic recurrence, Gordon T. Rustin, M.D., reported at the American Society of Clinical Oncology meeting.

Yet, after four years of follow-up, essentially the same proportion of patients had died in each group, Dr. Rustin, of Mount Vernon Cancer Center in Middlesex, England, said.

“Early treatment does not improve survival, and in fact, if anything, slightly decreases quality of life; this is because women who are treated early receive far more chemotherapy,” said Dr. Rustin.

In women with ovarian cancer, serum levels of the cancer antigen CA125 often rise several months before signs or symptoms of recurrent disease. Many oncologists routinely monitor ovarian cancer patients with CA125 testing, although the benefits of monitoring had never been demonstrated in a large prospective clinical study.

So Dr. Tustin and investigators in 10 countries performed a trial to determine whether early treatment based on CA125 test results improved survival in these patients.

The study involved 527 patients who were in complete remission after first-line platinum-based chemotherapy. All the women had a normal CA125 level at study entry.

They underwent CA125 testing every three months, but neither the patients nor their physicians knew the results.

Randomization was triggered if a patient’s CA125 level exceeded two times the upper limit of normal. The patients were assigned to immediate chemotherapy or to delayed treatment based on clinical or symptomatic evidence of recurrence.

The primary outcome was overall survival. After a median follow-up of 49 months, 351 patients (66%) had died.

Patients randomized to immediate chemotherapy started second-line treatment 4.8 months sooner and third-line treatment 4.6 months sooner than did the delayed-therapy group.

Nonetheless, the mortality hazard ratio for early versus delayed treatment was 1.00, reflecting no difference in survival.

“Earlier institution of chemotherapy did not induce a longer remission; this is what so many people out there have been treating patients for,” said Dr. Rustin.

Although the study was negative, the results should allow physicians and patients to make more informed decisions regarding ovarian cancer recurrence and initiation of chemotherapy, he said.

“For the first time women can be reassured that there is no benefit from early detection by routine CA125 testing. They can be told that even if CA125 rises, chemotherapy can be safely delayed until they have signs or symptoms of recurrence. For the first time ever, women now have informed choices to be able to decide.”

In his own clinical practice, most women choose not to have routine CA125 testing. However, Dr. Rustin informs patients about the clinical signs and symptoms of recurrence and encourages them to seek a consultation at the first hint of recurrence.

The study clearly showed that starting therapy early does not make a difference in survival, said Maurie Markman, M.D., a gynecologic oncology specialist at the University of Texas M.D. Anderson Cancer Center in Houston.

However, he believes the study is notable for what the results do not say, as well as for what they do say.

“The study doesn’t say that these women who received therapy either earlier or later did not benefit from that therapy,” said Dr. Markman, who was not involved in the study. “It says that there wasn’t a difference in outcome.”

“The fact that therapy was initiated could very well have had a substantial impact on how long those women lived,” he continued. “It doesn’t say there is no benefit of therapy. It says there is no benefit of starting therapy based solely on this tumor marker.”

The results also do not say that a surveillance strategy for ovarian cancer recurrence, which is routine in the U.S., would be wrong, said Dr. Markman, adding that “there is no evidence that women were harmed by this.”

Dr. Rustin and colleagues reported no competing interests. Dr. Markman disclosed relationships with Bristol-Myers Squibb, Celgene, CTI, Eli Lilly, Genentech, GlaxoSmithKline , Hana Pharmaceuticals, and Ortho Biotech.

Primary source: Journal of Clinical Oncology

Source reference:
Rustin GJ et al. “A randomized trial in ovarian cancer of early treatment of relapse based on CA125 level alone versus delayed treatment based on conventional clinical indicators” J Clin Oncol 2009; 27(15S): Abstract 1.

ORLANDO, May 31 — A drug commonly used to treat breast cancer improves survival in some cases of stomach cancer by about 26%, a Belgian researcher said here.

• Explain to interested patients that trastuzumab (Herceptin) has long been used to treat a specific subtype of breast cancer.
• Note that this study finds a similar subtype in some cases of stomach cancer and shows that the drug is also effective in that setting.
• Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

In a randomized phase III trial, the combination of the monoclonal antibody trastuzumab (Herceptin) and standard chemotherapy outperformed chemotherapy alone, according to Eric Van Cutsem, M.D., Ph.D., of the University Hospital Gasthuisberg in Leuven, Belgium.

It’s the first time the drug — which targets the HER2/neu receptor — has been shown to improve survival in disease other than breast cancer, Dr. Van Cutsem told attendees at the annual meeting of the American Society of Clinical Oncology.

It’s also the “first phase III study to report improved overall survival with a personalized, targeted treatment for gastric cancer,” Dr. Van Cutsem said in a statement.

In the so-called ToGA trial, tumors from 3,807 patients with advanced gastric cancer were tested for HER2, and 22.1% were positive for the receptor, Dr. Van Cutsem reported.

The researchers randomized 594 patients to get standard chemotherapy with or without trastuzumab.

They said median overall survival with the combination was 13.5 months compared with 11.1 months for chemo alone, a difference that was significant at P=0.0048.

After a median of 17.1 months of follow-up the hazard ratio for death was 0.74, with a 95% confidence interval from 0.60 to 0.91, the researchers said.

The overall response rate was 47.3% in the combination arm and 34.5% in the chemo-alone arm, a difference that was significant at P=0.0017.

Safety profiles were similar between the arms, the researchers found, including the rate of symptomatic congestive heart failure. Asymptomatic left ventricular ejection fraction decreases were reported in 4.6% of patients in the combination arm and 1.1% in the chemotherapy alone arm.

Although it’s difficult to make such comparisons, the “gastric data is clearly as strong as in breast cancer,” according to David Schenkein, M.D., of Genentech, a subsidiary of Roche, which makes the drug.

In advanced HER2-positive breast cancer, he said, the pivotal trial showed improved median survival of 25.1 months, compared with 20.3 months for the chemotherapy arm, a 25% improvement in overall survival.

ASCO President Richard Schilsky, M.D., of the University of Chicago Medical Center, said the study is a “great example of the whole concept of personalized medicine.”

“Until these data came out,” he said, “we didn’t know we had to think about two different molecular subtypes of stomach cancer — HER2-positive and HER2-negative.”

The finding is important and may herald clinical use of the drug in HER2/neu-positive gastric cancer, according to Leonard Saltz, M.D., of Memorial Sloan-Kettering Cancer Center in New York City.

“It would not make sense to expose every gastric cancer patient to trastuzumab,” he said. “However, for those whose tumors express the target for trastuzumab, adding that drug to the treatment regimen makes sense.”

But, Dr. Saltz said, there are “a few caveats to keep in mind.”

He noted that the study regimen does not involve replacing chemotherapy, so that trastuzumab “adds, albeit modestly, to the side effects that patients must endure.”

Also, he said, “we must be careful not to confuse the term ’significant’ with ’substantial’.” The survival improvement is 2.7 months or 81 days — “modest progress, not ’substantial’ progress, from a clinical perspective,” Dr. Saltz said.

Other caveats, he said, include the cost of the drug and HER2 testing, which mean the “cost of this modest progress is going to be quite substantial.”

Len Lichtenfeld, M.D., of the American Cancer Society, said the study is “interesting” but agreed that the “gain is modest in terms of the number of months of increased survival.”

On the other hand, he said, “it is important to remember that gastric cancer is difficult to treat, with currently available therapies providing limited success.”

The study was supported by Roche. Dr. Van Cutsem reported financial links with Roche. Some members of the research team are employed by the company. Dr. Saltz reported financial links with Amgen, Bayer, Bristol-Myers Squibb, Genentech, ImClone, Merck, Pfizer, Roche, Taiho Pharmaceuticals, and YM BioSciences. Dr. Lichtenfeld is an employee of the American Cancer Society.

This article was developed in collaboration with ABC News.

Primary source: Journal of Clinical Oncology

ORLANDO, May 31 — A vaccine that uses cancer cells against themselves significantly slows the progress of a deadly form of blood cancer, a researcher said here.

• Explain to interested patients that despite advances in therapy, follicular non-Hodgkin’s lymphoma remains almost invariably fatal.
• Note that this study found that a therapeutic vaccine administered after chemotherapy-induced remission can prolong the period before disease recurs.
• Note, too, that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

In patients with follicular non-Hodgkin’s lymphoma, the vaccine — dubbed BiovaxID — nearly doubled the time before the disease recurred, compared with a control drug, according to Stephen Schuster, M.D., of the University of Pennsylvania School of Medicine in Philadelphia.

The therapeutic vaccine is tailored to each patient’s cancer and given with a drug that stimulates the immune system, Dr. Schuster said at the annual meeting of the American Society of Clinical Oncology.

“We’ve now moved into an era where we can safely use a patient’s immune system to effectively fight follicular lymphoma and enhance the response to conventional chemotherapy,” Dr. Schuster said in a statement.

There are about 65,000 new cases of non-Hodgkin’s lymphoma diagnosed each year in the U.S., and even with aggressive chemotherapy and recent advances in therapy, the disease is almost uniformly fatal.

In the follicular form of the disease, 90% of patients die within seven years of diagnosis.

The vaccine itself is made by extracting cells from lymph nodes and identifying a cancer marker — an “idiotype” — that is unique to each patient, Dr. Schuster said.

The idiotype is then fused with an immune stimulant called keyhole limpet hemocyanin, or KLH. Finally, the combination is administered along with another immune stimulant, granulocyte-macrophage colony-stimulating factor, or GM-CSF.

In this study, the researchers studied 117 patients who had been treated with standard chemotherapy, achieved a complete response, and then maintained that response for at least six months.

They were randomized to get the therapeutic vaccine or the KLH immune stimulant alone, acting as a control drug. Both were administered with GM-CSF.

All told, 76 patients got the vaccine and 41 got the control drug, Dr. Schuster said.

After a median follow-up of 56 months, the median time to relapse for patients getting the vaccine was 44.2 months, compared with 30.6 for those in the control group. The difference was significant at P=0.045 and yielded a hazard ratio of 1.6, the researchers found.

No serious adverse events were associated with the vaccine, Dr. Schuster said.

“The problem with that kind of lymphoma is that chemotherapy doesn’t actually cure anybody,” said ASCO President Richard Schilsky, M.D., of the University of Chicago Medical Center, who was not involved in the study.

“They all go into remission with chemotherapy but they all relapse,” Dr. Schilsky said. “Each time you use chemotherapy, the remission lasts less time and eventually they just become refractory.”

So, he said, “the longer you can keep them in remission the better.”

The researchers commented that the approach might also be useful in other forms of B cell cancer, such as chronic lymphocytic leukemia. Dr. Schilsky noted that — unlike other forms of cancer — the B cell cancers display a range of cell surface proteins that are distinctive.

“That’s what makes this a feasible approach, because you can use that to develop a unique vaccine for each kind of lymphoma,” he said.

The study was supported by Biovest International. The researchers reported financial links with Accentia Biopharmaceuticals, Biovest International, Antigenics, Biogen Idec, Genentech, and Xeme Biopharma.

Primary source: Journal of Clinical Oncology

Source reference:
Schuster SJ et al. “Idiotype vaccine therapy (BiovaxID) in follicular lymphoma in first complete remission: Phase III clinical trial results” J Clin Oncol 2009; 27(15S): Abstract P2.

Gloucester Pharmaceuticals announced that results from two studies of romidepsin, its novel, cyclic peptide, histone deacetylase inhibitor under investigation for the treatment of hematologic malignancies, will be presented at the American Society of Clinical Oncology (ASCO) Annual Meeting in Orlando, Florida on Saturday, May 30, 2009.

Poster Q11 #8546 entitled “Pooled analyses of 2 international, multicenter clinical studies of romidepsin in 167 patients with cutaneous T-cell lymphoma (CTCL)” by M Demierre, S Whittaker, Y Kim, E Kim, R Piekarz, M Prince, J Nichols, J Balser, A Prentice and S Bates, describes clinical results from a pooled analysis of two Phase 2 international studies of romidepsin in cutaneous T-cell lymphoma (CTCL).

Poster S13 #8584 entitled “Histone deacetylase inhibitors potently synergize the antineoplastic effects of the proteasome inhibitor bortezomib in mantle cell lymphoma (MCL)” by L Paoluzzi, L Scotto, Seshan and O O’Connor, describes data from a preclinical study of romidepsin in combination with Velcade® (bortezomib) in mantle cell lymphoma (MCL). This study was conducted in collaboration with researchers from the Herbert Irving Comprehensive Cancer Center, College of Physicians and Surgeons, The New York Presbyterian Hospital and Columbia University.

Both posters will be presented during the General Poster Sessions Saturday, May 30, 2009 from 8:00am - 12:00pm ET on Level 2 of West Hall C at the Orlando Convention Center.

About Romidepsin

Romidepsin is a late-stage oncology drug candidate being studied across a range of hematologic malignancies. A registration trial in cutaneous T-cell lymphoma (CTCL) has recently been completed, successfully exceeding its primary endpoint based on overall response rate. A registration trial in a second indication, peripheral T-cell lymphoma (PTCL), is currently enrolling patients. Complete and durable responses were observed in a previous National Cancer Institute trial including both patients with CTCL and PTCL. Numerous other trials are ongoing in additional indications including multiple myeloma. Over 750 patients, to date, have received romidepsin in clinical trials with the most common adverse effects including fatigue, gastrointestinal disturbances and hematologic toxicities. Romidepsin’s cyclic peptide structure is novel among members of a new class of cancer drugs known as histone deacetylase (HDAC) inhibitors. HDAC inhibition has been shown to increase acetylation of histones and other proteins. The downstream effects of HDAC inhibition include growth inhibition, apoptosis, inhibition of angiogenesis and differentiation. Preclinical studies suggest that romidepsin is a pan-HDAC inhibitor and is a potent inhibitor of Class I, Class II and Class IV HDACs. Gloucester Pharmaceuticals retains worldwide rights to romidepsin which received Orphan Drug Designation from the U.S. Food and Drug Administration (FDA) for the treatment of non-Hodgkin’s T-cell lymphomas, including CTCL and PTCL, and Orphan status from the European Medicines Agency (EMEA) for the treatment of both CTCL and PTCL. The FDA has also granted Fast Track status for CTCL and PTCL. A New Drug Application submission for romidepsin in CTCL was accepted by the FDA and a PDUFA is scheduled in November of 2009.

Source
Gloucester Pharmaceuticals

View drug information on Velcade.

CHICAGO, June 1 — More precancerous polyps were found in colonoscopies performed with deep sedation than with milder sedation in which patients remained conscious, a researcher reported here.

• Explain to interested patients that colonoscopies may be performed either with deep sedation or with milder sedation in which the patient remains conscious and able to communicate.
• Explain that this study was retrospective analysis of medical records and therefore a weaker form of evidence than a prospective, randomized trial.
• Note that this study was published as an abstract and presented orally at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

Doctors found polyps larger than 9 mm or suspected colorectal tumors found at a 25% higher rate (95% CI 9% to 42%) in patients examined under deep sedation, said Katherine Hoda, M.D., of Oregon Health and Science University in Portland, Ore.

The differences persisted after controlling for age, gender, race, American Society of Anesthesiologists (ASA) class, and clinical site type, Dr. Hoda told colleagues at Digestive Disease Week here.

At a press briefing in advance of her formal presentation, Dr. Hoda said colonoscopists may encounter fewer distractions when patients are deeply sedated and hence do a better job of finding polyps.

But the study design — a retrospective review of nearly 105,000 patient records — could not fully exclude the possibility that patients with higher polyp counts were more likely to receive deep sedation, she pointed out.

She said prospective studies are needed to settle the issue.

Dr. Hoda and colleagues at OHSU analyzed data from the Clinical Outcomes Research Initiative, which collects information on colonoscopies performed at 61 U.S. practice sites.

From 2002 through 2007, the database yielded 101,367 procedures conducted with moderate conscious sedation — typically induced with a benzodiazepine plus fentanyl or another opioid — and 3,501 performed under deep sedation, most commonly with propofol.

Dr. Hoda said these proportions reflect the fact that conscious sedation is the predominant U.S. standard.

Large polyps were found more frequently in patients with deep sedation: 7.2% of such patients had large polyps identified, compared with 6.0% of those with conscious sedation (P=0.01).

The difference remained significant after adjusting for several potential confounding factors available in the database records (OR 1.25, 95% CI 1.09 to 1.42).

But Dr. Hoda said the choice of deep versus conscious sedation is not random in clinical practice.

Patients more likely to pose problems during colonoscopy would preferentially receive deep sedation, and it’s conceivable that such patients would be at higher risk for advanced polyps.

She said the analysis showed ASA scores were higher in patients who received deep sedation, reflecting a greater burden of systemic disease.

But she said the likelihood is that deep sedation genuinely allows better polyp detection.

Patients who remain conscious sometimes report discomfort or otherwise interact with the colonoscopist during the procedure, she said. Time and attention spent on making a conscious patient comfortable may detract from the clinician’s ability to focus on the colonoscopy monitor.

She added that recovery times following deep sedation are typically the same or shorter than after conscious sedation. “Propofol is cleared from the body very quickly,” she said.

A downside, though, is that some centers require that deep sedation be delivered by an anesthesiologist, increasing the procedure’s cost.

The database used in the study did not contain cost information.

Kenneth Wang, M.D., of the Mayo Clinic in Rochester, Minn., said the study provided the first hard data on sedation level as an influence on the effectiveness of detection.

“Nobody has ever really looked at [whether] deep sedation can aid in detecting more polyps,” he said, although clinician efficiency and patient satisfaction has been well documented.

“This will really need to be verified in studies to see if this is actually true. I suspect it probably is,” Dr. Wang said.

“Awake or conscious sedation is exactly that — the patient feels things,” he added. “If you’re trying to remove a polyp and the patient is having some issue with discomfort, you tend not to want to do too much more. Whereas if you have the patient under deep sedation, it wouldn’t surprise me that you could look more carefully around folds, for example, or come in and out of a rather tricky turn.”

No external funding for the study was reported. Dr. Hoda reported no potential conflicts of interest. Dr. Wang reported research funding from AstraZeneca Pharmaceuticals, BARRX Medical, Fujinon, Olympus America, and Spectra Science.

Primary source: Digestive Disease Week

Source reference:
Hoda K, et al “More large polyps are seen on screening colonoscopy with deep sedation compared with moderate conscious sedation” DDW 2009; Abstract 722.

LITTLE FALLS, N.J., June 1 — Taking a break from hormone replacement therapy doesn’t reduce a woman’s chances of having to return for a second screening mammogram, researchers say.

• Explain that brief hormone therapy suspension was associated with small changes in breast density but did not affect overall mammography rescreening rates.

Hormone therapy increases breast density, and abnormal screening mammograms are more common among women with denser breasts, but recall rates were not significantly different between women who didn’t take a break from hormone therapy and those who took one or two months off prior to screening, according to Diana S. M. Buist, Ph.D., M.P.H., and colleagues.

“No evidence supports short-term hormone therapy suspension before mammography,” they reported in the June 2 issue of the Annals of Internal Medicine.

To prevent false positives and avoid recalls, some women take short breaks from using postmenopausal hormone therapy before having mammography.

However, no evidence exists for the efficacy of this practice.

So to test whether one or two months off the hormones decreases mammography recall rates, the researchers looked at 1,704 women ages 45 to 80 who had used hormone therapy at their most recent screening in the Radiological Evaluation and Breast Density (READ) trial.

All of the women were due for mammography and were still using hormones when they were included in the study.

About a third of the women suspended their hormones for one month, and another third for two months before getting a mammogram. The rest, who continued on their hormone regimen, served as the control group.

The researchers found no significant differences between recall rates among the three groups — 11.3% in the continuous-hormone group, 12.3% in the one-month suspension group, and 9.8% in the two-month suspension group.

They also found that decreases in percentage of breast density were not statistically significant, although they trended downward — 0.1% for no suspension, ­-0.9% for one-month suspension, and -1.5% for two-month suspension.

However, women in the groups who stopped hormone treatment experienced increased menopause symptoms.

The linear trends of increased recall were seen with increasing percentage of density, signaling that “density is still an important factor influencing recall rates, but it is likely that change in density needs to be large to have any clinical effect on recall rates,” the researchers said.

“We really hoped to find that a brief break in hormone therapy would lower false-positives and remove unnecessary costs and anxiety by improving mammography,” Dr. Buist said. “We were disappointed to find that it didn’t, but we’ll keep trying to find ways to reduce recall rates for women.”

The researchers noted that their study is limited in that it can only be generalized to women ages 45 to 80 who have used hormone therapy for at least one year.

TThe study was supported by a grant from the National Cancer Institute. The researchers reported no conflicts of interest.

Primary source: Annals of Internal Medicine

Source reference:

Buist DSM, et al “Short-term hormone therapy suspension and mammography recall” Ann Intern Med 2009; 150: 752-65.

ORLANDO, June 1 — How small is too small to treat? That’s always a tough question, but findings reviewed in this MedPage Today InFocus discussion suggest that regardless of size, micrometastases in sentinel node biopsy should not be ignored.

Julie Gralow, M.D., an associate professor in the oncology division of the University of Washington School of Medicine in Seattle, said that she and other oncologists have struggled with the issue of when to treat axillary nodes in women with early stage breast cancer who have micrometastases of 2 mm or less discovered by analysis of the sentinel node.

Now, however, evidence from a Dutch study reported at the American Society of Clinical Oncology meeting indicates that the “no treatment” approach may increase the five-year risk of recurrence.

Also, in this installment of InFocus, Dr. Gralow and Peggy Peck, MedPage Today executive editor discuss conflicting data on the efficacy of tamoxifen when used concurrently with some antidepressants.

LITTLE FALLS, N.J., June 16 — CT colonography may be just as accurate as colonoscopy in high-risk colorectal cancer patients, a new study shows.

• Explain that in patients at high risk of colorectal cancer, CT colonography had a negative predictive value of 96.3% overall — a figure comparable to regular colonoscopy.
• Note, however, that the negative predictive value fell to 84.9% for those who had a positive fecal occult blood test.

The so-called “virtual colonoscopy” had a negative predictive value of 96.3% overall, a figure comparable to regular colonoscopy, according to Cristiana Laudi, M.D., of the Institute for Cancer Research and Treatment in Torino, Italy, and colleagues.

“Our values . . . suggest a potentially effective use of CT colonography as an alternative to colonoscopy for screening individuals with family history of advanced colorectal neoplasia,” the researchers reported in the June 17 Journal of the American Medical Association.

Virtual colonoscopy has been recognized as an alternative to traditional colonoscopy for colorectal cancer screening in average-risk patients.

Since it is less invasive and more tolerable, advocates say it may increase adherence to screening, the researchers said.

However, less information comparing the two procedures is available when it comes to patients at an increased risk of colorectal cancer.

So to assess the accuracy of CT colonography in detecting advanced colorectal neoplasia in patients at increased risk, the researchers conducted a multicenter cross-sectional study of 937 patients. All had a family history of advanced neoplasia in first-degree relatives, personal history of colorectal adenomas, or positive results from fecal occult blood tests.

Patients were recruited in 11 Italian centers and one Belgian center between December 2004 and May 2007.

Each underwent CT colonography and colonoscopy on the same day.

The researchers used unblinded colonoscopy as the reference standard.

Overall, they found that CT colonography identified 151 of 177 patients with advanced neoplasia 6 mm or larger for a sensitivity of 85.3% (95% CI 79% to 90%).

It correctly classified results as negative for 667 of 760 participants without such lesions for a specificity of 87.8% (95% CI 85.2% to 90%).

Positive and negative predictive values were 61.9% and 96.3%, respectively.

For disease-positive patients with neoplasia that were 10 mm or larger, the test identified them with a sensitivity of 90.8% and a specificity of 84.5%. Positive and negative predictive values were 48.8% and 98.3%, respectively.

The researchers said the sensitivity measurements for 6 mm and 10 mm are “comparable with figures reported in two large trials on average-risk individuals but higher than those of two previous multicenter studies that included patients with clinical indication for colonoscopy or those with family history of CRC.”

They noted that CT colonography can only classify a lesion by its size, so large hyperplastic polyps or rare, low-risk adenomas can generate false-positives.

However, when the results were stratified, the negative predictive value in the positive fecal occult blood test group dropped to 84.9% (95% CI 76.2% to 91.3%, P<0.001).

“Our results do not support using CT colonography as a first-line strategy in fecal occult blood test-positive subjects,” the researchers said.

“Because of the high prevalence of advanced neoplasia in this group of participants, colonoscopy would have been performed in 55% of the cases if CT colonography had been used as a screening test, making such a strategy not as cost-effective as using colonoscopy as a first-line screening test.”

The researchers said their study was limited in that protocols and radiologist experience were not uniform across the centers where the study was conducted.

Also, colonoscopy was used as a reference standard, and the test may miss some lesions. The researchers said longer-term follow-up is needed to determine whether clinically significant lesions were missed.

The study was supported by grants from the Italian Association for Cancer Research, Progetti di Ricerca Finalizzata from Region Piemonte, the Fondazione Cassa di Risparmio di Torino, and the Compagnia di San Paolo. The researchers reported no conflicts of interest.

Primary source: Journal of the American Medical Association

Source reference:

Regge D, et al “Diagnostic accuracy of computed tomographic colonography for the detection of advanced neoplasia in individuals at increased risk of colorectal cancer” JAMA 2009; 301(23) 2453-61.

A low cellular level of a tiny fragment of RNA appears to increase the spread of breast cancer in mouse models of the disease, according to researchers at Whitehead Institute for Biomedical Research.

Measuring levels of this so-called microRNA, which is also associated with metastatic breast cancer in humans, may more accurately predict the likelihood of metastasis (which accounts for 90% of cancer-related deaths) and ultimately help determine patient prognoses.

In the study, whose results are reported in the June 12 issue of Cell, Scott Valastyan, a graduate student in Whitehead Member Robert Weinberg’s laboratory, screened patient breast cancer samples for microRNAs with potential roles in metastasis. MicroRNAs are single strands of RNA about 21-23 nucleotides long. Within a cell, a single microRNA can fine-tune the expression of dozens of genes simultaneously. This capability could be particularly important in metastasis, a multi-step process that could be influenced by a single microRNA at several points.

The screened samples were classified as either metastatic cancer or non-metastatic cancer. After analysis, the microRNA miR-31 stood out because of its inverse correlation with metastasis. In samples where a patient’s original tumor had not metastasized, the cancer cells retained high levels of the microRNA. But where the tumor had metastasized, the cancer cells came to possess lower levels of miR-31.

The functional role of miR-31 in metastasis regulation was then confirmed in mice. When Valastyan removed miR-31 from normally non-aggressive breast cancer cells and implanted those cells into mice, the cells formed highly aggressive tumors. Mice injected with the cancer cells lacking miR-31 had 6 to 10 times more cancer cells that metastasized to their lungs than did their counterparts implanted with unmodified cancer cells.

To see how increasing miR-31 levels could affect metastasis, Valastyan introduced miR-31 into breast cancer cells that readily metastasize. After injecting these altered cells into mice, the mice had four to 40 times fewer metastases than mice injected with the unaltered cells.

Valastyan says that quantifying miR-31 levels in a patient’s cancer cells could one day support a more accurate prognosis. Currently, breast cancers are divided into three major categories, two of which are typically associated with poor prognoses.

“This microRNA seems to be quite unique, in that it seems to provide some prognostic utility across these existing subclassifications [of cancers],” says Valastyan. A better-defined prognosis could help patients determine whether they might benefit from poorly tolerated cancer therapies.

In addition, miR-31 could be a useful target for cancer therapy. Weinberg, who is also a professor of biology at MIT, is cautiously optimistic. “At present, it’s quite difficult to inhibit the action or promote the actions of a microRNA in a whole organism,” he says, “but in the future, microRNAs like this one might prove to be very important in altering the clinical progression of a tumor or causing it to revert to a more benign state.”

This research was supported by the National Institutes of Health (NIH), MIT Ludwig Center for Molecular Oncology, U.S. Department of Defense (DoD), Breast Cancer Research Foundation, Harvard Breast Cancer Specialized Program of Research Excellence (SPORE), and a DoD Breast Cancer Research Program (BCRP) Idea Award.

Robert Weinberg’s primary affiliation is with Whitehead Institute for Biomedical Research, where his laboratory is located and all his research is conducted. He is also a professor of biology at Massachusetts Institute of Technology.

Full Citation:

“A Pleiotropically Acting microRNA, miR-31, Inhibits Breast Cancer Metastasis”
Cell, June 12, 2009
Scott Valastyan (1,2), Ferenc Reinhardt (1), Nathan Benaich (1,3), Diana Calogrias (4), Attila M. Szász (4), Zhigang C. Wang (5,6), Jane E. Brock (4), Andrea L. Richardson (4), and Robert A. Weinberg (1,2,7).

References

1.Whitehead Institute, 9 Cambridge Center, Cambridge, MA 02142, USA
2. Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
3. Department of Biology, Williams College, Williamstown, MA 01267, USA
4. Department of Pathology, Brigham and Women’s Hospital, Boston, MA 02115, USA
5. Department of Surgery, Brigham and Women’s Hospital, Boston, MA 02115, USA
6. Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA
7. MIT Ludwig Center for Molecular Oncology, Cambridge, MA 02139, USA

Source
Whitehead Institute for Biomedical Research

Healthcare professionals can now order a number of Macmillan Cancer Support’s free, high-quality cancer information booklets in CD format.

Macmillan has produced 37 audio CDs for people living with cancer who have any disability or visual impairment which may make reading difficult, or who simply prefer information in audio format.

Sue Green, Senior Information Development Nurse at Macmillan Cancer Support, says:

“Following a diagnosis of cancer, people often feel confused, anxious and afraid. High-quality information can help people affected by cancer to feel more in control and able to plan their lives, and can take away some of the fear and isolation they may feel.

“People may struggle to take in everything they’re told about their treatment and the side-effects it may cause so information to have at home is really important. They can take information away and listen to it in their own time, in the comfort of their own home.”

The CDs give information and advice about specific types of cancer, different types of treatment and possible side-effects, and the emotional effects of cancer.

Cynthia Higgins, a retired nurse, has had difficulty reading since being treated for Ocular Melanoma in 1997. She says:

“Macmillan’s new CDs give people with visual impairment a degree of independence and a sense of privacy. It’s very difficult to ask, even a loving relative, to continually go over a passage they are reading to you, or to find a section you want to hear again. It also allows people the opportunity to react to the information in private.”

To order from Macmillan’s range of audio CDs, visit be.macmillan.org.uk

Source
Macmillan Cancer Support

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