Patrice Wendling

CHICAGO — Delivery of a lower total radiation dose in fewer but more intense fractions improved control of high-risk prostate cancer without increasing toxicity in a multicenter, phase III trial of 168 men.

After a median follow-up of 3 years, the freedom from biochemical failure rate was 87% with hypofractionated radiotherapy vs. 79% with conventional radiation.

The difference in this co-primary end point was significant (P = .035).

In a multivariate Cox analysis, hypofractionated radiation therapy reduced the risk of biochemical failure by roughly 70% (hazard ratio 0.35), said lead author Dr. Giorgio Arcangeli, a radiation oncologist at the Regina Elena National Cancer Institute in Rome. Metastasis-free survival was similar in both groups.

Men in the hypofractionated arm received 62 Gy of radiation in 20 fractions of 3.1 Gy over 5 weeks, compared with 80 Gy of radiation in 40 fractions of 2 Gy over 8 weeks in the conventional arm.

New data suggest that prostate cancer may have a unique biology that makes it more sensitive than other tumors and normal tissue to higher daily doses of radiation, potentially allowing clinicians to complete radiation treatment in a shorter time.

Dr. Arcangeli acknowledged that longer follow-up is required to definitively validate this treatment strategy, but suggested there are important up-front benefits for patients.

“It offers convenience to patients by halving the number of visits to radiotherapy departments, an important benefit for these patients, who are typically an older, less mobile group,” Dr. Arcangeli said.

The investigators hypothesized that the two treatment schedules would be equally effective because they have the same biological equivalent dose and same tumor control probability, but that late complications would be reduced with hypofractionation.

So far, no significant differences between the two groups have been observed in the other primary end point of late side effects in urinary and bowel function, Dr. Arcangeli said at the annual meeting of the American Society for Radiation Oncology, where the findings were presented.

Three-year rates of grade 2 or higher toxicity were 15% in the hypofractionation arm and 17% in the conventional arm for gastrointestinal side effects, and 11% vs. 15% for genitourinary toxicity.

The severity of toxicity scores did not differ between groups, but acute toxicity in the hypofractionation arm developed and ended earlier than in the conventional arm, he said.

Men were eligible for the study if they had a prostate-specific antigen (PSA) level of more than 20 ng/mL, a Gleason score of 7, T3 or higher disease, or at least two of the follow characteristics: Gleason score of 7, PSA level of 11-20 ng/mL, and T2c disease.

Overall, 83 men received hypofractionated and 85 men conventional fractionated schedules of 3-D conformal radiotherapy to the prostate and seminal vesicles, beginning 2 months after initiation of a 9-month course of total androgen blockade.

They had no distant metastases, previous pelvic irradiation, or previous prostate surgery other than transurethral resection of the prostate. Their median age was 75 years.

Studies are in progress to test the benefits of even shorter treatment schedules, Dr. Arcangeli commented in a statement.

The authors reported no conflicts of interest related to their study.

CHICAGO — Delivery of a lower total radiation dose in fewer but more intense fractions improved control of high-risk prostate cancer without increasing toxicity in a multicenter, phase III trial of 168 men.

After a median follow-up of 3 years, the freedom from biochemical failure rate was 87% with hypofractionated radiotherapy vs. 79% with conventional radiation.

The difference in this co-primary end point was significant (P = .035).

In a multivariate Cox analysis, hypofractionated radiation therapy reduced the risk of biochemical failure by roughly 70% (hazard ratio 0.35), said lead author Dr. Giorgio Arcangeli, a radiation oncologist at the Regina Elena National Cancer Institute in Rome. Metastasis-free survival was similar in both groups.

Men in the hypofractionated arm received 62 Gy of radiation in 20 fractions of 3.1 Gy over 5 weeks, compared with 80 Gy of radiation in 40 fractions of 2 Gy over 8 weeks in the conventional arm.

New data suggest that prostate cancer may have a unique biology that makes it more sensitive than other tumors and normal tissue to higher daily doses of radiation, potentially allowing clinicians to complete radiation treatment in a shorter time.

Dr. Arcangeli acknowledged that longer follow-up is required to definitively validate this treatment strategy, but suggested there are important up-front benefits for patients.

“It offers convenience to patients by halving the number of visits to radiotherapy departments, an important benefit for these patients, who are typically an older, less mobile group,” Dr. Arcangeli said.

The investigators hypothesized that the two treatment schedules would be equally effective because they have the same biological equivalent dose and same tumor control probability, but that late complications would be reduced with hypofractionation.

So far, no significant differences between the two groups have been observed in the other primary end point of late side effects in urinary and bowel function, Dr. Arcangeli said at the annual meeting of the American Society for Radiation Oncology, where the findings were presented.

Three-year rates of grade 2 or higher toxicity were 15% in the hypofractionation arm and 17% in the conventional arm for gastrointestinal side effects, and 11% vs. 15% for genitourinary toxicity.

The severity of toxicity scores did not differ between groups, but acute toxicity in the hypofractionation arm developed and ended earlier than in the conventional arm, he said.

Men were eligible for the study if they had a prostate-specific antigen (PSA) level of more than 20 ng/mL, a Gleason score of 7, T3 or higher disease, or at least two of the follow characteristics: Gleason score of 7, PSA level of 11-20 ng/mL, and T2c disease.

Overall, 83 men received hypofractionated and 85 men conventional fractionated schedules of 3-D conformal radiotherapy to the prostate and seminal vesicles, beginning 2 months after initiation of a 9-month course of total androgen blockade.

They had no distant metastases, previous pelvic irradiation, or previous prostate surgery other than transurethral resection of the prostate. Their median age was 75 years.

Studies are in progress to test the benefits of even shorter treatment schedules, Dr. Arcangeli commented in a statement.

The authors reported no conflicts of interest related to their study.

CHICAGO — Delivery of a lower total radiation dose in fewer but more intense fractions improved control of high-risk prostate cancer without increasing toxicity in a multicenter, phase III trial of 168 men.

After a median follow-up of 3 years, the freedom from biochemical failure rate was 87% with hypofractionated radiotherapy vs. 79% with conventional radiation.

The difference in this co-primary end point was significant (P = .035).

In a multivariate Cox analysis, hypofractionated radiation therapy reduced the risk of biochemical failure by roughly 70% (hazard ratio 0.35), said lead author Dr. Giorgio Arcangeli, a radiation oncologist at the Regina Elena National Cancer Institute in Rome. Metastasis-free survival was similar in both groups.

Men in the hypofractionated arm received 62 Gy of radiation in 20 fractions of 3.1 Gy over 5 weeks, compared with 80 Gy of radiation in 40 fractions of 2 Gy over 8 weeks in the conventional arm.

New data suggest that prostate cancer may have a unique biology that makes it more sensitive than other tumors and normal tissue to higher daily doses of radiation, potentially allowing clinicians to complete radiation treatment in a shorter time.

Dr. Arcangeli acknowledged that longer follow-up is required to definitively validate this treatment strategy, but suggested there are important up-front benefits for patients.

“It offers convenience to patients by halving the number of visits to radiotherapy departments, an important benefit for these patients, who are typically an older, less mobile group,” Dr. Arcangeli said.

The investigators hypothesized that the two treatment schedules would be equally effective because they have the same biological equivalent dose and same tumor control probability, but that late complications would be reduced with hypofractionation.

So far, no significant differences between the two groups have been observed in the other primary end point of late side effects in urinary and bowel function, Dr. Arcangeli said at the annual meeting of the American Society for Radiation Oncology, where the findings were presented.

Three-year rates of grade 2 or higher toxicity were 15% in the hypofractionation arm and 17% in the conventional arm for gastrointestinal side effects, and 11% vs. 15% for genitourinary toxicity.

The severity of toxicity scores did not differ between groups, but acute toxicity in the hypofractionation arm developed and ended earlier than in the conventional arm, he said.

Men were eligible for the study if they had a prostate-specific antigen (PSA) level of more than 20 ng/mL, a Gleason score of 7, T3 or higher disease, or at least two of the follow characteristics: Gleason score of 7, PSA level of 11-20 ng/mL, and T2c disease.

Overall, 83 men received hypofractionated and 85 men conventional fractionated schedules of 3-D conformal radiotherapy to the prostate and seminal vesicles, beginning 2 months after initiation of a 9-month course of total androgen blockade.

They had no distant metastases, previous pelvic irradiation, or previous prostate surgery other than transurethral resection of the prostate. Their median age was 75 years.

Studies are in progress to test the benefits of even shorter treatment schedules, Dr. Arcangeli commented in a statement.

The authors reported no conflicts of interest related to their study.

CHICAGO — Along with its known cardiovascular benefits, anticoagulation therapy may improve biochemical control of localized prostate cancer treated with radiotherapy.

In a retrospective study of 662 patients, the biochemical control rate at 48 months was significantly better (at 91%) in men taking warfarin, clopidogrel, and/or aspirin, compared with 78% in men not taking blood-thinning therapy. Distant metastases were also significantly reduced in the anticoagulant group, compared with the nonanticoagulant group (1% vs. 5%).

The overall survival rates were 92% and 90%, respectively, which did not reach statistical significance, Dr. Kevin S. Choe and his colleagues reported in a poster at the annual meeting of the American Society for Radiation Oncology.

Previous clinical trials have produced limited and inconsistent data in metastatic prostate disease, although epidemiologic studies have shown that men on anticoagulants develop prostate cancer less frequently. There is also substantial evidence from preclinical models suggesting that anticoagulants may influence multiple tumor processes including tumor growth, angiogenesis, and the metastatic pathway, Dr. Choe of the University of Chicago said at a press briefing.

“According to our data, we think that the most plausible path [by which an anticoagulant influences prostate cancer patients] … is by limiting metastases, because we see the biggest effect among patients who have very aggressive types of prostate cancer that tend to spread,” he said.

In subgroup analysis, the improvement in biochemical control was statistically significant only for patients with high-risk disease as defined by National Comprehensive Cancer Network criteria.

The 4-year, freedom-from-biochemical-failure rate using the Phoenix definition (prostate-specific antigen greater than nadir plus 2 ng/mL) was 82.4% in high-risk men on anticoagulants vs. 57.6% in high-risk controls. The biochemical failure rate for patients both on and off anticoagulants was 92.5% vs. 83% in intermediate-risk men and 95% vs. 90.5% in low-risk men.

In multivariate analysis, anticoagulant use was independently associated with improved biochemical control, lowering the risk of biochemical failure by almost half (hazard ratio, 0.54). The type of anticoagulant did not significantly influence biochemical failure rates, nor was the combination of two agents better than a single agent.

The current study grew out of another study in the same cohort by Dr. Choe and his colleagues showing that warfarin and clopidogrel use during external-beam radiotherapy substantially increasesd the risk of grade 3 or higher rectal bleeding (Int. J. Radiat. Oncol. Biol. Phys. 2009 May 20 [doi:10.1016/j.ijrobp.2009.02.026]).

Although aspirin and other less potent blood-thinning agents such as enoxaparin may lessen the risk of this bleeding toxicity, Dr. Choe balked at recommending anticoagulation for all prostate cancer patients.

“In patients already taking anticoagulants for cardiovascular risks, there may be additional benefits in prostate cancer,” he said, adding that if an anticoagulant were ever to be recommended, “it would need to be planned out very carefully” and will require larger prospective studies to determine whether the benefit is worth the risk.

The median dosage used by patients at consult or during follow-up was warfarin 5 mg/day and clopidogrel 75 mg/day. Aspirin dosage was not recorded. All patients were treated with external-beam radiotherapy, permanent seed implant, or both. No patients underwent surgery. Their median age was 69 years, and median initial PSA was 8.4 ng/mL.

Dr. Choe plans to conduct a prospective database analysis of prostate cancer patients who had surgery instead of radiotherapy to test the hypothesis that the benefit results from an effect on the cancer itself and not an interaction between the anticoagulants and radiotherapy.

The investigators reported no study sponsorship or conflicts of interest.

CHICAGO — Along with its known cardiovascular benefits, anticoagulation therapy may improve biochemical control of localized prostate cancer treated with radiotherapy.

In a retrospective study of 662 patients, the biochemical control rate at 48 months was significantly better (at 91%) in men taking warfarin, clopidogrel, and/or aspirin, compared with 78% in men not taking blood-thinning therapy. Distant metastases were also significantly reduced in the anticoagulant group, compared with the nonanticoagulant group (1% vs. 5%).

The overall survival rates were 92% and 90%, respectively, which did not reach statistical significance, Dr. Kevin S. Choe and his colleagues reported in a poster at the annual meeting of the American Society for Radiation Oncology.

Previous clinical trials have produced limited and inconsistent data in metastatic prostate disease, although epidemiologic studies have shown that men on anticoagulants develop prostate cancer less frequently. There is also substantial evidence from preclinical models suggesting that anticoagulants may influence multiple tumor processes including tumor growth, angiogenesis, and the metastatic pathway, Dr. Choe of the University of Chicago said at a press briefing.

“According to our data, we think that the most plausible path [by which an anticoagulant influences prostate cancer patients] … is by limiting metastases, because we see the biggest effect among patients who have very aggressive types of prostate cancer that tend to spread,” he said.

In subgroup analysis, the improvement in biochemical control was statistically significant only for patients with high-risk disease as defined by National Comprehensive Cancer Network criteria.

The 4-year, freedom-from-biochemical-failure rate using the Phoenix definition (prostate-specific antigen greater than nadir plus 2 ng/mL) was 82.4% in high-risk men on anticoagulants vs. 57.6% in high-risk controls. The biochemical failure rate for patients both on and off anticoagulants was 92.5% vs. 83% in intermediate-risk men and 95% vs. 90.5% in low-risk men.

In multivariate analysis, anticoagulant use was independently associated with improved biochemical control, lowering the risk of biochemical failure by almost half (hazard ratio, 0.54). The type of anticoagulant did not significantly influence biochemical failure rates, nor was the combination of two agents better than a single agent.

The current study grew out of another study in the same cohort by Dr. Choe and his colleagues showing that warfarin and clopidogrel use during external-beam radiotherapy substantially increasesd the risk of grade 3 or higher rectal bleeding (Int. J. Radiat. Oncol. Biol. Phys. 2009 May 20 [doi:10.1016/j.ijrobp.2009.02.026]).

Although aspirin and other less potent blood-thinning agents such as enoxaparin may lessen the risk of this bleeding toxicity, Dr. Choe balked at recommending anticoagulation for all prostate cancer patients.

“In patients already taking anticoagulants for cardiovascular risks, there may be additional benefits in prostate cancer,” he said, adding that if an anticoagulant were ever to be recommended, “it would need to be planned out very carefully” and will require larger prospective studies to determine whether the benefit is worth the risk.

The median dosage used by patients at consult or during follow-up was warfarin 5 mg/day and clopidogrel 75 mg/day. Aspirin dosage was not recorded. All patients were treated with external-beam radiotherapy, permanent seed implant, or both. No patients underwent surgery. Their median age was 69 years, and median initial PSA was 8.4 ng/mL.

Dr. Choe plans to conduct a prospective database analysis of prostate cancer patients who had surgery instead of radiotherapy to test the hypothesis that the benefit results from an effect on the cancer itself and not an interaction between the anticoagulants and radiotherapy.

The investigators reported no study sponsorship or conflicts of interest.

CHICAGO — Along with its known cardiovascular benefits, anticoagulation therapy may improve biochemical control of localized prostate cancer treated with radiotherapy.

In a retrospective study of 662 patients, the biochemical control rate at 48 months was significantly better (at 91%) in men taking warfarin, clopidogrel, and/or aspirin, compared with 78% in men not taking blood-thinning therapy. Distant metastases were also significantly reduced in the anticoagulant group, compared with the nonanticoagulant group (1% vs. 5%).

The overall survival rates were 92% and 90%, respectively, which did not reach statistical significance, Dr. Kevin S. Choe and his colleagues reported in a poster at the annual meeting of the American Society for Radiation Oncology.

Previous clinical trials have produced limited and inconsistent data in metastatic prostate disease, although epidemiologic studies have shown that men on anticoagulants develop prostate cancer less frequently. There is also substantial evidence from preclinical models suggesting that anticoagulants may influence multiple tumor processes including tumor growth, angiogenesis, and the metastatic pathway, Dr. Choe of the University of Chicago said at a press briefing.

“According to our data, we think that the most plausible path [by which an anticoagulant influences prostate cancer patients] … is by limiting metastases, because we see the biggest effect among patients who have very aggressive types of prostate cancer that tend to spread,” he said.

In subgroup analysis, the improvement in biochemical control was statistically significant only for patients with high-risk disease as defined by National Comprehensive Cancer Network criteria.

The 4-year, freedom-from-biochemical-failure rate using the Phoenix definition (prostate-specific antigen greater than nadir plus 2 ng/mL) was 82.4% in high-risk men on anticoagulants vs. 57.6% in high-risk controls. The biochemical failure rate for patients both on and off anticoagulants was 92.5% vs. 83% in intermediate-risk men and 95% vs. 90.5% in low-risk men.

In multivariate analysis, anticoagulant use was independently associated with improved biochemical control, lowering the risk of biochemical failure by almost half (hazard ratio, 0.54). The type of anticoagulant did not significantly influence biochemical failure rates, nor was the combination of two agents better than a single agent.

The current study grew out of another study in the same cohort by Dr. Choe and his colleagues showing that warfarin and clopidogrel use during external-beam radiotherapy substantially increasesd the risk of grade 3 or higher rectal bleeding (Int. J. Radiat. Oncol. Biol. Phys. 2009 May 20 [doi:10.1016/j.ijrobp.2009.02.026]).

Although aspirin and other less potent blood-thinning agents such as enoxaparin may lessen the risk of this bleeding toxicity, Dr. Choe balked at recommending anticoagulation for all prostate cancer patients.

“In patients already taking anticoagulants for cardiovascular risks, there may be additional benefits in prostate cancer,” he said, adding that if an anticoagulant were ever to be recommended, “it would need to be planned out very carefully” and will require larger prospective studies to determine whether the benefit is worth the risk.

The median dosage used by patients at consult or during follow-up was warfarin 5 mg/day and clopidogrel 75 mg/day. Aspirin dosage was not recorded. All patients were treated with external-beam radiotherapy, permanent seed implant, or both. No patients underwent surgery. Their median age was 69 years, and median initial PSA was 8.4 ng/mL.

Dr. Choe plans to conduct a prospective database analysis of prostate cancer patients who had surgery instead of radiotherapy to test the hypothesis that the benefit results from an effect on the cancer itself and not an interaction between the anticoagulants and radiotherapy.

The investigators reported no study sponsorship or conflicts of interest.

Soldiers and their families are being offered free access to psychotherapy across the country for as long as they want.

The Soldiers Project is providing confidential psychotherapy to address the growing need for comprehensive mental health care for military personnel and their families and to stop the transmission of trauma to future generations, according to project founder and director Dr. Judith Broder.

“We know that when people are traumatized and it's not treated that the trauma gets carried on to their children and their children's children, but if there's early intervention and treatment then the traumatized person is less likely to be a transmitter,” said Dr. Broder, a psychiatrist and psychoanalyst. “That's the basic impetus—to get in there early and as intensive as possible, and that's a fundamental difference from the services the VA [Veterans Administration] can provide.”

Started in 2004 under the aegis of the Los Angeles Institute and Society of Psychoanalytic Studies, Tthe Soldiers Project now has chapters in the cities of Chicago, Seattle, and Sacramento, and in New York, New Jersey, and southern California. At least 350 soldiers or veterans have been treated. Patients access services via the project's Web site (www.thesoldiersproject.org

Soldiers returning home may be changed by combat-related medical conditions or become impatient or withdrawn, while family dynamics can change as children and spouses adapt to fill the void of the missing parent. The uncertainty of whether a soldier will be redeployed is unique to this war.

If the slow, painstaking work of psychoanalysis, which Sigmund Freud once likened to archaeological excavation, sounds like an odd match for tight-lipped, action-oriented soldiers, Dr. Broder said the approach is actually well-suited. In some fundamental way, the basic character of many of the young men and women who have served has been shattered, and that this type of wound may be difficult to reach by the more widely used cognitive-behavioral therapy with its systematic, goal-oriented approach to influencing dysfunctional behaviors and emotions.

“This isn't just about reaching the triggers of anxiety, but it's about rebuilding a shattered structure of the self,” she said. “In most cases, it has very little to do with the excavation of the past, even though the stereotype is that we're going to talk about their mothers.”

The volunteer physicians may opt to prescribe medication to the returning soldiers in addition to providing psychotherapy, she said. They try to help the soldiers obtain medications through the VA, since the soldiers must pay out of pocket otherwise.

Patients are matched with a local therapist who has had specific training in PTSD and the military culture.

Source DR. BRODER

Soldiers and their families are being offered free access to psychotherapy across the country for as long as they want.

The Soldiers Project is providing confidential psychotherapy to address the growing need for comprehensive mental health care for military personnel and their families and to stop the transmission of trauma to future generations, according to project founder and director Dr. Judith Broder.

“We know that when people are traumatized and it's not treated that the trauma gets carried on to their children and their children's children, but if there's early intervention and treatment then the traumatized person is less likely to be a transmitter,” said Dr. Broder, a psychiatrist and psychoanalyst. “That's the basic impetus—to get in there early and as intensive as possible, and that's a fundamental difference from the services the VA [Veterans Administration] can provide.”

Started in 2004 under the aegis of the Los Angeles Institute and Society of Psychoanalytic Studies, Tthe Soldiers Project now has chapters in the cities of Chicago, Seattle, and Sacramento, and in New York, New Jersey, and southern California. At least 350 soldiers or veterans have been treated. Patients access services via the project's Web site (www.thesoldiersproject.org

Soldiers returning home may be changed by combat-related medical conditions or become impatient or withdrawn, while family dynamics can change as children and spouses adapt to fill the void of the missing parent. The uncertainty of whether a soldier will be redeployed is unique to this war.

If the slow, painstaking work of psychoanalysis, which Sigmund Freud once likened to archaeological excavation, sounds like an odd match for tight-lipped, action-oriented soldiers, Dr. Broder said the approach is actually well-suited. In some fundamental way, the basic character of many of the young men and women who have served has been shattered, and that this type of wound may be difficult to reach by the more widely used cognitive-behavioral therapy with its systematic, goal-oriented approach to influencing dysfunctional behaviors and emotions.

“This isn't just about reaching the triggers of anxiety, but it's about rebuilding a shattered structure of the self,” she said. “In most cases, it has very little to do with the excavation of the past, even though the stereotype is that we're going to talk about their mothers.”

The volunteer physicians may opt to prescribe medication to the returning soldiers in addition to providing psychotherapy, she said. They try to help the soldiers obtain medications through the VA, since the soldiers must pay out of pocket otherwise.

Patients are matched with a local therapist who has had specific training in PTSD and the military culture.

Source DR. BRODER

Soldiers and their families are being offered free access to psychotherapy across the country for as long as they want.

The Soldiers Project is providing confidential psychotherapy to address the growing need for comprehensive mental health care for military personnel and their families and to stop the transmission of trauma to future generations, according to project founder and director Dr. Judith Broder.

“We know that when people are traumatized and it's not treated that the trauma gets carried on to their children and their children's children, but if there's early intervention and treatment then the traumatized person is less likely to be a transmitter,” said Dr. Broder, a psychiatrist and psychoanalyst. “That's the basic impetus—to get in there early and as intensive as possible, and that's a fundamental difference from the services the VA [Veterans Administration] can provide.”

Started in 2004 under the aegis of the Los Angeles Institute and Society of Psychoanalytic Studies, Tthe Soldiers Project now has chapters in the cities of Chicago, Seattle, and Sacramento, and in New York, New Jersey, and southern California. At least 350 soldiers or veterans have been treated. Patients access services via the project's Web site (www.thesoldiersproject.org

Soldiers returning home may be changed by combat-related medical conditions or become impatient or withdrawn, while family dynamics can change as children and spouses adapt to fill the void of the missing parent. The uncertainty of whether a soldier will be redeployed is unique to this war.

If the slow, painstaking work of psychoanalysis, which Sigmund Freud once likened to archaeological excavation, sounds like an odd match for tight-lipped, action-oriented soldiers, Dr. Broder said the approach is actually well-suited. In some fundamental way, the basic character of many of the young men and women who have served has been shattered, and that this type of wound may be difficult to reach by the more widely used cognitive-behavioral therapy with its systematic, goal-oriented approach to influencing dysfunctional behaviors and emotions.

“This isn't just about reaching the triggers of anxiety, but it's about rebuilding a shattered structure of the self,” she said. “In most cases, it has very little to do with the excavation of the past, even though the stereotype is that we're going to talk about their mothers.”

The volunteer physicians may opt to prescribe medication to the returning soldiers in addition to providing psychotherapy, she said. They try to help the soldiers obtain medications through the VA, since the soldiers must pay out of pocket otherwise.

Patients are matched with a local therapist who has had specific training in PTSD and the military culture.

Source DR. BRODER

BERLIN — The addition of bevacizumab to chemotherapy failed to significantly improve progression-free or overall survival in previously untreated advanced melanoma in the phase II BEAM trial.

Median progression-free survival was 5.6 months for bevacizumab (Avastin) plus carboplatin and paclitaxel-based chemotherapy, and 4.2 months for chemotherapy alone. Despite a hazard ratio of 0.78, the difference was not statistically significant (P = .14), Dr. Steven O'Day reported at a joint congress of the European Cancer Organization and the European Society for Medical Oncology.

Overall survival was widely reported before the congress as having been significantly increased by 4 months with bevacizumab, but an unplanned post hoc analysis performed just before the formal data presentation showed that the survival benefit had narrowed and had taken the statistical advantage with it.

Median overall survival went from 12.3 months in the bevacizumab arm and 8.6 months in the chemotherapy arm at a median follow-up of 13 months in the initial analysis (HR, 0.67; P = .04) to 12.3 months and 9.2 months, respectively, at a median follow-up of 18 months in the post hoc analysis (HR, 0.79; P = .19).

Response rates also favored bevacizumab over chemotherapy (25.5% vs. 16.4%), but were not significantly different (P =.16) in the Roche Pharmaceuticals–sponsored study.

Although the revised data sent stock analysts and journalists scrambling, the findings are still cause for optimism in a disease with few treatment options and a 5-year survival of less than 5%, according to Dr. O'Day, chief of research and director of the melanoma program at the Angeles Clinic and Research Institute in Santa Monica, Calif.

“I am optimistic because strong trends of improvement were seen across all efficacy parameters” (progression-free survival, overall survival, and response), he said in an interview. “This was a randomized, phase II with 2:1 randomization, so it wasn't powered for overall survival to be significantly different. I'm also optimistic because even the worse prognosis patients with M1c disease and elevated [lactate dehydrogenase] seemed to benefit from this treatment.”

Based on the current data, Roche plans to go forward with a larger, randomized phase III trial that is adequately powered to detect a significant survival benefit, he said.

BEAM (A Study of Bevacizumab With Carboplatin and Paclitaxel Chemotherapy for the First-Line Treatment of Patients With Metastatic Melanoma) included 214 patients (mean age, 60 years) with stage IV M1a/b, M1c disease, of which 73% was M1c disease and 54% of M1c patients had abnormal lactate dehydrogenase levels. Patients received chemotherapy with or without bevacizumab 15 mg/kg administered intravenously on day 1 every 3 weeks.

Bevacizumab, an anti–vascular endothelial growth factor (VEGF)–specific inhibitor, was evaluated because melanoma is a very vascular tumor, and elevated VEGF levels correlate with tumor progression and worse prognosis. The addition of bevacizumab to chemotherapy has improved outcomes in other cancers, including metastatic colorectal cancer and non–small cell lung cancer.

No new safety events were observed in the trial. Grade 3/4 treatment-related adverse events that occurred with 2% or more increased incidence in the bevacizumab arm included febrile neutropenia, neutropenia, peripheral neuropathy, pulmonary embolism, hypertension, anorexia, and musculoskeletal pain. There were two deaths in the bevacizumab arm and none in the chemotherapy arm, Dr. O'Day said.

He has served an advisory/consultant role and received research funds from Genentech Inc. and Roche for clinical trials.

BERLIN — The addition of bevacizumab to chemotherapy failed to significantly improve progression-free or overall survival in previously untreated advanced melanoma in the phase II BEAM trial.

Median progression-free survival was 5.6 months for bevacizumab (Avastin) plus carboplatin and paclitaxel-based chemotherapy, and 4.2 months for chemotherapy alone. Despite a hazard ratio of 0.78, the difference was not statistically significant (P = .14), Dr. Steven O'Day reported at a joint congress of the European Cancer Organization and the European Society for Medical Oncology.

Overall survival was widely reported before the congress as having been significantly increased by 4 months with bevacizumab, but an unplanned post hoc analysis performed just before the formal data presentation showed that the survival benefit had narrowed and had taken the statistical advantage with it.

Median overall survival went from 12.3 months in the bevacizumab arm and 8.6 months in the chemotherapy arm at a median follow-up of 13 months in the initial analysis (HR, 0.67; P = .04) to 12.3 months and 9.2 months, respectively, at a median follow-up of 18 months in the post hoc analysis (HR, 0.79; P = .19).

Response rates also favored bevacizumab over chemotherapy (25.5% vs. 16.4%), but were not significantly different (P =.16) in the Roche Pharmaceuticals–sponsored study.

Although the revised data sent stock analysts and journalists scrambling, the findings are still cause for optimism in a disease with few treatment options and a 5-year survival of less than 5%, according to Dr. O'Day, chief of research and director of the melanoma program at the Angeles Clinic and Research Institute in Santa Monica, Calif.

“I am optimistic because strong trends of improvement were seen across all efficacy parameters” (progression-free survival, overall survival, and response), he said in an interview. “This was a randomized, phase II with 2:1 randomization, so it wasn't powered for overall survival to be significantly different. I'm also optimistic because even the worse prognosis patients with M1c disease and elevated [lactate dehydrogenase] seemed to benefit from this treatment.”

Based on the current data, Roche plans to go forward with a larger, randomized phase III trial that is adequately powered to detect a significant survival benefit, he said.

BEAM (A Study of Bevacizumab With Carboplatin and Paclitaxel Chemotherapy for the First-Line Treatment of Patients With Metastatic Melanoma) included 214 patients (mean age, 60 years) with stage IV M1a/b, M1c disease, of which 73% was M1c disease and 54% of M1c patients had abnormal lactate dehydrogenase levels. Patients received chemotherapy with or without bevacizumab 15 mg/kg administered intravenously on day 1 every 3 weeks.

Bevacizumab, an anti–vascular endothelial growth factor (VEGF)–specific inhibitor, was evaluated because melanoma is a very vascular tumor, and elevated VEGF levels correlate with tumor progression and worse prognosis. The addition of bevacizumab to chemotherapy has improved outcomes in other cancers, including metastatic colorectal cancer and non–small cell lung cancer.

No new safety events were observed in the trial. Grade 3/4 treatment-related adverse events that occurred with 2% or more increased incidence in the bevacizumab arm included febrile neutropenia, neutropenia, peripheral neuropathy, pulmonary embolism, hypertension, anorexia, and musculoskeletal pain. There were two deaths in the bevacizumab arm and none in the chemotherapy arm, Dr. O'Day said.

He has served an advisory/consultant role and received research funds from Genentech Inc. and Roche for clinical trials.

BERLIN — The addition of bevacizumab to chemotherapy failed to significantly improve progression-free or overall survival in previously untreated advanced melanoma in the phase II BEAM trial.

Median progression-free survival was 5.6 months for bevacizumab (Avastin) plus carboplatin and paclitaxel-based chemotherapy, and 4.2 months for chemotherapy alone. Despite a hazard ratio of 0.78, the difference was not statistically significant (P = .14), Dr. Steven O'Day reported at a joint congress of the European Cancer Organization and the European Society for Medical Oncology.

Overall survival was widely reported before the congress as having been significantly increased by 4 months with bevacizumab, but an unplanned post hoc analysis performed just before the formal data presentation showed that the survival benefit had narrowed and had taken the statistical advantage with it.

Median overall survival went from 12.3 months in the bevacizumab arm and 8.6 months in the chemotherapy arm at a median follow-up of 13 months in the initial analysis (HR, 0.67; P = .04) to 12.3 months and 9.2 months, respectively, at a median follow-up of 18 months in the post hoc analysis (HR, 0.79; P = .19).

Response rates also favored bevacizumab over chemotherapy (25.5% vs. 16.4%), but were not significantly different (P =.16) in the Roche Pharmaceuticals–sponsored study.

Although the revised data sent stock analysts and journalists scrambling, the findings are still cause for optimism in a disease with few treatment options and a 5-year survival of less than 5%, according to Dr. O'Day, chief of research and director of the melanoma program at the Angeles Clinic and Research Institute in Santa Monica, Calif.

“I am optimistic because strong trends of improvement were seen across all efficacy parameters” (progression-free survival, overall survival, and response), he said in an interview. “This was a randomized, phase II with 2:1 randomization, so it wasn't powered for overall survival to be significantly different. I'm also optimistic because even the worse prognosis patients with M1c disease and elevated [lactate dehydrogenase] seemed to benefit from this treatment.”

Based on the current data, Roche plans to go forward with a larger, randomized phase III trial that is adequately powered to detect a significant survival benefit, he said.

BEAM (A Study of Bevacizumab With Carboplatin and Paclitaxel Chemotherapy for the First-Line Treatment of Patients With Metastatic Melanoma) included 214 patients (mean age, 60 years) with stage IV M1a/b, M1c disease, of which 73% was M1c disease and 54% of M1c patients had abnormal lactate dehydrogenase levels. Patients received chemotherapy with or without bevacizumab 15 mg/kg administered intravenously on day 1 every 3 weeks.

Bevacizumab, an anti–vascular endothelial growth factor (VEGF)–specific inhibitor, was evaluated because melanoma is a very vascular tumor, and elevated VEGF levels correlate with tumor progression and worse prognosis. The addition of bevacizumab to chemotherapy has improved outcomes in other cancers, including metastatic colorectal cancer and non–small cell lung cancer.

No new safety events were observed in the trial. Grade 3/4 treatment-related adverse events that occurred with 2% or more increased incidence in the bevacizumab arm included febrile neutropenia, neutropenia, peripheral neuropathy, pulmonary embolism, hypertension, anorexia, and musculoskeletal pain. There were two deaths in the bevacizumab arm and none in the chemotherapy arm, Dr. O'Day said.

He has served an advisory/consultant role and received research funds from Genentech Inc. and Roche for clinical trials.

CHICAGO — Lower levels of health literacy among Hispanics may be associated with poorer blood pressure and glycemic control, based on the results of a cohort study.

A cross-sectional analysis of 327 Hispanics with mild to moderate chronic kidney disease enrolled in the Hispanic Chronic Renal Insufficiency Cohort (HCRIC) study showed that 127 (39%) could not read in English or Spanish and 86 (26%) had low health literacy based on a score of 22 or less on the Short Test of Functional Health Literacy in Adults. Spanish language preference was reported by 268 (82%) of the participants.

Spanish language preference as compared with English language preference was significantly associated with a higher mean systolic BP (138.8 mm Hg vs. 131.4 mm Hg) and decreased use of an ACE inhibitor or angiotensin II receptor blocker (67% vs. 81%), Dr. Claudia Lora reported on behalf of the study group in a poster at a meeting sponsored by the International Society on Hypertension in Blacks. Participants with a Spanish language preference were older, were less educated, and had a lower income, compared with those who preferred English.

An inability to read and low health literacy were significantly associated with poorer self-reported health and poorer blood pressure control, defined by a reading of 130/80 mm Hg or higher.

After adjustment for sociodemographic factors, language preference, and clinical factors, the inability to read remained independently associated with poor BP control, reported Dr. Lora of the nephrology section at the University of Illinois at Chicago. Neither health literacy nor language preference was associated with estimated glomerular filtration rate, control of diabetes, or dyslipidemia in adjusted analyses.

“Subjects with low health literacy and a Spanish language preference represent a particularly vulnerable segment of the chronic kidney disease population,” Dr. Lora wrote in the poster. “The long-term impact of these patient-centered factors on the progression of [chronic kidney disease] is being evaluated in the HCRIC study.”

In a second poster at the meeting, preliminary results from the first 64 diabetic participants in the Paso del Norte Kidney Disease Study showed that health literacy was inadequate in 34%, marginal in 7%, and adequate in 59%.

Participants were predominantly Mexican American (59 patients) with stages 2-4 chronic kidney disease (61) and a mean body mass index of 33 kg/m

Poor glycemic control, defined by a hemoglobin A_1c level of 7% or more, was reported in 59% of participants, noted Dr. Patrick Ragland, formerly with Texas Tech University Health Sciences Center at El Paso and now a resident at Tulane University in New Orleans.

In a logistic regression analysis that adjusted for sex, age, insurance, education, income, birthplace, language preference, hypertension, and current smoking, participants with inadequate health literacy were more likely to have poor glycemic control than were those with marginal or adequate health literacy (odds ratio, 6.34; P = .083). The investigators suggested that the small number of patients could account for the lack of statistical significance

The researchers noted that the prevalence of diabetes is higher in Hispanics than in whites and that Hispanics with diabetes have a two- to threefold higher risk of developing end-stage renal disease than do whites.

The authors reported no conflicts of interest. Dr. Ragland's study was sponsored by grants from the Paso del Norte Health Foundation, the Manuel and Guadalupe Soto Memorial Research Fund, and Texas Tech.

CHICAGO — Lower levels of health literacy among Hispanics may be associated with poorer blood pressure and glycemic control, based on the results of a cohort study.

A cross-sectional analysis of 327 Hispanics with mild to moderate chronic kidney disease enrolled in the Hispanic Chronic Renal Insufficiency Cohort (HCRIC) study showed that 127 (39%) could not read in English or Spanish and 86 (26%) had low health literacy based on a score of 22 or less on the Short Test of Functional Health Literacy in Adults. Spanish language preference was reported by 268 (82%) of the participants.

Spanish language preference as compared with English language preference was significantly associated with a higher mean systolic BP (138.8 mm Hg vs. 131.4 mm Hg) and decreased use of an ACE inhibitor or angiotensin II receptor blocker (67% vs. 81%), Dr. Claudia Lora reported on behalf of the study group in a poster at a meeting sponsored by the International Society on Hypertension in Blacks. Participants with a Spanish language preference were older, were less educated, and had a lower income, compared with those who preferred English.

An inability to read and low health literacy were significantly associated with poorer self-reported health and poorer blood pressure control, defined by a reading of 130/80 mm Hg or higher.

After adjustment for sociodemographic factors, language preference, and clinical factors, the inability to read remained independently associated with poor BP control, reported Dr. Lora of the nephrology section at the University of Illinois at Chicago. Neither health literacy nor language preference was associated with estimated glomerular filtration rate, control of diabetes, or dyslipidemia in adjusted analyses.

“Subjects with low health literacy and a Spanish language preference represent a particularly vulnerable segment of the chronic kidney disease population,” Dr. Lora wrote in the poster. “The long-term impact of these patient-centered factors on the progression of [chronic kidney disease] is being evaluated in the HCRIC study.”

In a second poster at the meeting, preliminary results from the first 64 diabetic participants in the Paso del Norte Kidney Disease Study showed that health literacy was inadequate in 34%, marginal in 7%, and adequate in 59%.

Participants were predominantly Mexican American (59 patients) with stages 2-4 chronic kidney disease (61) and a mean body mass index of 33 kg/m

Poor glycemic control, defined by a hemoglobin A_1c level of 7% or more, was reported in 59% of participants, noted Dr. Patrick Ragland, formerly with Texas Tech University Health Sciences Center at El Paso and now a resident at Tulane University in New Orleans.

In a logistic regression analysis that adjusted for sex, age, insurance, education, income, birthplace, language preference, hypertension, and current smoking, participants with inadequate health literacy were more likely to have poor glycemic control than were those with marginal or adequate health literacy (odds ratio, 6.34; P = .083). The investigators suggested that the small number of patients could account for the lack of statistical significance

The researchers noted that the prevalence of diabetes is higher in Hispanics than in whites and that Hispanics with diabetes have a two- to threefold higher risk of developing end-stage renal disease than do whites.

The authors reported no conflicts of interest. Dr. Ragland's study was sponsored by grants from the Paso del Norte Health Foundation, the Manuel and Guadalupe Soto Memorial Research Fund, and Texas Tech.

CHICAGO — Lower levels of health literacy among Hispanics may be associated with poorer blood pressure and glycemic control, based on the results of a cohort study.

A cross-sectional analysis of 327 Hispanics with mild to moderate chronic kidney disease enrolled in the Hispanic Chronic Renal Insufficiency Cohort (HCRIC) study showed that 127 (39%) could not read in English or Spanish and 86 (26%) had low health literacy based on a score of 22 or less on the Short Test of Functional Health Literacy in Adults. Spanish language preference was reported by 268 (82%) of the participants.

Spanish language preference as compared with English language preference was significantly associated with a higher mean systolic BP (138.8 mm Hg vs. 131.4 mm Hg) and decreased use of an ACE inhibitor or angiotensin II receptor blocker (67% vs. 81%), Dr. Claudia Lora reported on behalf of the study group in a poster at a meeting sponsored by the International Society on Hypertension in Blacks. Participants with a Spanish language preference were older, were less educated, and had a lower income, compared with those who preferred English.

An inability to read and low health literacy were significantly associated with poorer self-reported health and poorer blood pressure control, defined by a reading of 130/80 mm Hg or higher.

After adjustment for sociodemographic factors, language preference, and clinical factors, the inability to read remained independently associated with poor BP control, reported Dr. Lora of the nephrology section at the University of Illinois at Chicago. Neither health literacy nor language preference was associated with estimated glomerular filtration rate, control of diabetes, or dyslipidemia in adjusted analyses.

“Subjects with low health literacy and a Spanish language preference represent a particularly vulnerable segment of the chronic kidney disease population,” Dr. Lora wrote in the poster. “The long-term impact of these patient-centered factors on the progression of [chronic kidney disease] is being evaluated in the HCRIC study.”

In a second poster at the meeting, preliminary results from the first 64 diabetic participants in the Paso del Norte Kidney Disease Study showed that health literacy was inadequate in 34%, marginal in 7%, and adequate in 59%.

Participants were predominantly Mexican American (59 patients) with stages 2-4 chronic kidney disease (61) and a mean body mass index of 33 kg/m

Poor glycemic control, defined by a hemoglobin A_1c level of 7% or more, was reported in 59% of participants, noted Dr. Patrick Ragland, formerly with Texas Tech University Health Sciences Center at El Paso and now a resident at Tulane University in New Orleans.

In a logistic regression analysis that adjusted for sex, age, insurance, education, income, birthplace, language preference, hypertension, and current smoking, participants with inadequate health literacy were more likely to have poor glycemic control than were those with marginal or adequate health literacy (odds ratio, 6.34; P = .083). The investigators suggested that the small number of patients could account for the lack of statistical significance

The researchers noted that the prevalence of diabetes is higher in Hispanics than in whites and that Hispanics with diabetes have a two- to threefold higher risk of developing end-stage renal disease than do whites.

The authors reported no conflicts of interest. Dr. Ragland's study was sponsored by grants from the Paso del Norte Health Foundation, the Manuel and Guadalupe Soto Memorial Research Fund, and Texas Tech.

BERLIN — The perseverance of researchers has led to the preliminary finding that aspirin helps prevent cancers in Lynch syndrome, a genetic condition that accounts for about 5% of all colon cancers.

A daily 600-mg dose of aspirin reduces the cancer burden in this high-risk group by about half, with the effect becoming apparent after about 3 years, Dr. John Burn said at a joint congress of the European Cancer Organization and European Society for Medical Oncology.

This preliminary finding is surprising, given that a report last year of the main trial results showed no difference in the number of colonic adenomas, after a mean of 29 months, between those taking aspirin and those taking 30 g of the resistant maize starch Novelose and placebo (N. Engl. J. Med. 2008;359:2567-78).

“The results were profoundly disappointing,” Dr. Burn said of the original trial. “There was absolutely no effect. If anything, the aspirin group had slightly more adenomas.”

The results were, however, in line with a series of randomized trials that have not found a convincing benefit with aspirin use. The difference with the current analysis is that follow-up extended up to 10 years after randomization, and it focused directly on cancers rather than on using adenomas as a surrogate for cancer prevention, said Dr. Burn, head of the Institute of Human Genetics at Newcastle University, Newcastle upon Tyne, England.

“We are working hard to fill in some of the missing data,” Dr. Burn said in an interview. “We can then begin to explore making treatment of Lynch syndrome a new official indication for aspirin.”

The follow-up analysis almost didn't happen: The original negative results dashed two attempts to secure funding for it, the study manager retired, and the statistician went on maternity leave. Dr. Burn and his coinvestigators D. Timothy Bishop, Ph.D., of Leeds (England) University and John Mathers, Ph.D., of Newcastle University pressed on, buoyed by a systematic review of the original cardiovascular trials showing that regular use of at least 300 mg of aspirin reduced the incidence of colorectal cancer, but only after a latency of about 10 years (Lancet 2007;369:1603-13).

With the help of a visiting fellow, the team tracked down and analyzed 711 of the original 937 patients for whom follow-up extended beyond the end of the trial.

An analysis of the still-blinded data revealed 17 colorectal cancers in the aspirin group vs. 29 in the placebo group, Dr. Burn reported. The difference between the aspirin and placebo groups did not achieve statistical significance (P = .08), but did so when the two groups were compared at least 24 months after randomization (P = .03). Six patients among a small group randomized to the starch limb also developed colorectal cancers.

The number of endometrial cancers was significantly reduced, with only 5 occurring in the aspirin group and 13 in the placebo group (P = .05). There was no impact of aspirin on breast (seven vs. five cases), ovarian (five vs. three), or pancreatic (two vs. two) cancers.

The benefit of aspirin was most obvious in those who used it for more than 2 years, and was seen about 3 years after randomization when most or all patients would have discontinued their aspirin, Dr. Burn said. “The effect takes 3 years to begin, but persists for 5 more years,” he said at a press briefing held during the meeting.

Surprisingly, the study did not demonstrate an effect of aspirin on adenoma formation, despite the decrease in cancers. Of the 100 participants with adenomas who were identified during long-term follow-up, 48% were in the aspirin group and 52% were in the placebo group.

Dr. Burn said that these data are still preliminary, and hypothesized that salicylate could induce apoptosis in aberrant stem cells, much as it does in plants as a defense against infection. Thus, adenomas may still form in patients on aspirin, but the reduced number of aberrant stem cells makes them less likely to progress to cancer.

The regular use of aspirin reduced cardiovascular events, but did not significantly increase bleeding events. This is likely because the cohort was relatively young (mean age, 45 years), said Dr. Burn, who noted that 600 mg is actually a subanalgesic dose.

The investigators are keen to initiate a large-scale, dose-inferiority study to determine if similar levels of protection can be achieved with a lower dose.

“We need large-scale international collaboration, but it can be done,” Dr. Burn said. “If we can reduce the hereditary cancer burden with an over-the-counter cheap drug, the long-term benefits will be wonderful.”

The initial CAPP2 (Colorectal Adenoma/Carcinoma Prevention Programme 2) trial was funded by multiple sources, including Bayer Pharmaceuticals, which provided administrative support for the follow-up analysis. The authors reported no conflicts of interest.

A daily 600-mg dose of aspirin reduces the cancer burden by about half in these high-risk patients.

Source © jimdeli/Fotolia.com

BERLIN — The perseverance of researchers has led to the preliminary finding that aspirin helps prevent cancers in Lynch syndrome, a genetic condition that accounts for about 5% of all colon cancers.

A daily 600-mg dose of aspirin reduces the cancer burden in this high-risk group by about half, with the effect becoming apparent after about 3 years, Dr. John Burn said at a joint congress of the European Cancer Organization and European Society for Medical Oncology.

This preliminary finding is surprising, given that a report last year of the main trial results showed no difference in the number of colonic adenomas, after a mean of 29 months, between those taking aspirin and those taking 30 g of the resistant maize starch Novelose and placebo (N. Engl. J. Med. 2008;359:2567-78).

“The results were profoundly disappointing,” Dr. Burn said of the original trial. “There was absolutely no effect. If anything, the aspirin group had slightly more adenomas.”

The results were, however, in line with a series of randomized trials that have not found a convincing benefit with aspirin use. The difference with the current analysis is that follow-up extended up to 10 years after randomization, and it focused directly on cancers rather than on using adenomas as a surrogate for cancer prevention, said Dr. Burn, head of the Institute of Human Genetics at Newcastle University, Newcastle upon Tyne, England.

“We are working hard to fill in some of the missing data,” Dr. Burn said in an interview. “We can then begin to explore making treatment of Lynch syndrome a new official indication for aspirin.”

The follow-up analysis almost didn't happen: The original negative results dashed two attempts to secure funding for it, the study manager retired, and the statistician went on maternity leave. Dr. Burn and his coinvestigators D. Timothy Bishop, Ph.D., of Leeds (England) University and John Mathers, Ph.D., of Newcastle University pressed on, buoyed by a systematic review of the original cardiovascular trials showing that regular use of at least 300 mg of aspirin reduced the incidence of colorectal cancer, but only after a latency of about 10 years (Lancet 2007;369:1603-13).

With the help of a visiting fellow, the team tracked down and analyzed 711 of the original 937 patients for whom follow-up extended beyond the end of the trial.

An analysis of the still-blinded data revealed 17 colorectal cancers in the aspirin group vs. 29 in the placebo group, Dr. Burn reported. The difference between the aspirin and placebo groups did not achieve statistical significance (P = .08), but did so when the two groups were compared at least 24 months after randomization (P = .03). Six patients among a small group randomized to the starch limb also developed colorectal cancers.

The number of endometrial cancers was significantly reduced, with only 5 occurring in the aspirin group and 13 in the placebo group (P = .05). There was no impact of aspirin on breast (seven vs. five cases), ovarian (five vs. three), or pancreatic (two vs. two) cancers.

The benefit of aspirin was most obvious in those who used it for more than 2 years, and was seen about 3 years after randomization when most or all patients would have discontinued their aspirin, Dr. Burn said. “The effect takes 3 years to begin, but persists for 5 more years,” he said at a press briefing held during the meeting.

Surprisingly, the study did not demonstrate an effect of aspirin on adenoma formation, despite the decrease in cancers. Of the 100 participants with adenomas who were identified during long-term follow-up, 48% were in the aspirin group and 52% were in the placebo group.

Dr. Burn said that these data are still preliminary, and hypothesized that salicylate could induce apoptosis in aberrant stem cells, much as it does in plants as a defense against infection. Thus, adenomas may still form in patients on aspirin, but the reduced number of aberrant stem cells makes them less likely to progress to cancer.

The regular use of aspirin reduced cardiovascular events, but did not significantly increase bleeding events. This is likely because the cohort was relatively young (mean age, 45 years), said Dr. Burn, who noted that 600 mg is actually a subanalgesic dose.

The investigators are keen to initiate a large-scale, dose-inferiority study to determine if similar levels of protection can be achieved with a lower dose.

“We need large-scale international collaboration, but it can be done,” Dr. Burn said. “If we can reduce the hereditary cancer burden with an over-the-counter cheap drug, the long-term benefits will be wonderful.”

The initial CAPP2 (Colorectal Adenoma/Carcinoma Prevention Programme 2) trial was funded by multiple sources, including Bayer Pharmaceuticals, which provided administrative support for the follow-up analysis. The authors reported no conflicts of interest.

A daily 600-mg dose of aspirin reduces the cancer burden by about half in these high-risk patients.

Source © jimdeli/Fotolia.com

BERLIN — The perseverance of researchers has led to the preliminary finding that aspirin helps prevent cancers in Lynch syndrome, a genetic condition that accounts for about 5% of all colon cancers.

A daily 600-mg dose of aspirin reduces the cancer burden in this high-risk group by about half, with the effect becoming apparent after about 3 years, Dr. John Burn said at a joint congress of the European Cancer Organization and European Society for Medical Oncology.

This preliminary finding is surprising, given that a report last year of the main trial results showed no difference in the number of colonic adenomas, after a mean of 29 months, between those taking aspirin and those taking 30 g of the resistant maize starch Novelose and placebo (N. Engl. J. Med. 2008;359:2567-78).

“The results were profoundly disappointing,” Dr. Burn said of the original trial. “There was absolutely no effect. If anything, the aspirin group had slightly more adenomas.”

The results were, however, in line with a series of randomized trials that have not found a convincing benefit with aspirin use. The difference with the current analysis is that follow-up extended up to 10 years after randomization, and it focused directly on cancers rather than on using adenomas as a surrogate for cancer prevention, said Dr. Burn, head of the Institute of Human Genetics at Newcastle University, Newcastle upon Tyne, England.

“We are working hard to fill in some of the missing data,” Dr. Burn said in an interview. “We can then begin to explore making treatment of Lynch syndrome a new official indication for aspirin.”

The follow-up analysis almost didn't happen: The original negative results dashed two attempts to secure funding for it, the study manager retired, and the statistician went on maternity leave. Dr. Burn and his coinvestigators D. Timothy Bishop, Ph.D., of Leeds (England) University and John Mathers, Ph.D., of Newcastle University pressed on, buoyed by a systematic review of the original cardiovascular trials showing that regular use of at least 300 mg of aspirin reduced the incidence of colorectal cancer, but only after a latency of about 10 years (Lancet 2007;369:1603-13).

With the help of a visiting fellow, the team tracked down and analyzed 711 of the original 937 patients for whom follow-up extended beyond the end of the trial.

An analysis of the still-blinded data revealed 17 colorectal cancers in the aspirin group vs. 29 in the placebo group, Dr. Burn reported. The difference between the aspirin and placebo groups did not achieve statistical significance (P = .08), but did so when the two groups were compared at least 24 months after randomization (P = .03). Six patients among a small group randomized to the starch limb also developed colorectal cancers.

The number of endometrial cancers was significantly reduced, with only 5 occurring in the aspirin group and 13 in the placebo group (P = .05). There was no impact of aspirin on breast (seven vs. five cases), ovarian (five vs. three), or pancreatic (two vs. two) cancers.

The benefit of aspirin was most obvious in those who used it for more than 2 years, and was seen about 3 years after randomization when most or all patients would have discontinued their aspirin, Dr. Burn said. “The effect takes 3 years to begin, but persists for 5 more years,” he said at a press briefing held during the meeting.

Surprisingly, the study did not demonstrate an effect of aspirin on adenoma formation, despite the decrease in cancers. Of the 100 participants with adenomas who were identified during long-term follow-up, 48% were in the aspirin group and 52% were in the placebo group.

Dr. Burn said that these data are still preliminary, and hypothesized that salicylate could induce apoptosis in aberrant stem cells, much as it does in plants as a defense against infection. Thus, adenomas may still form in patients on aspirin, but the reduced number of aberrant stem cells makes them less likely to progress to cancer.

The regular use of aspirin reduced cardiovascular events, but did not significantly increase bleeding events. This is likely because the cohort was relatively young (mean age, 45 years), said Dr. Burn, who noted that 600 mg is actually a subanalgesic dose.

The investigators are keen to initiate a large-scale, dose-inferiority study to determine if similar levels of protection can be achieved with a lower dose.

“We need large-scale international collaboration, but it can be done,” Dr. Burn said. “If we can reduce the hereditary cancer burden with an over-the-counter cheap drug, the long-term benefits will be wonderful.”

The initial CAPP2 (Colorectal Adenoma/Carcinoma Prevention Programme 2) trial was funded by multiple sources, including Bayer Pharmaceuticals, which provided administrative support for the follow-up analysis. The authors reported no conflicts of interest.

A daily 600-mg dose of aspirin reduces the cancer burden by about half in these high-risk patients.

Source © jimdeli/Fotolia.com

HAMBURG, GERMANY — The combination of four new serum biomarkers did not improve differentiation of adnexal malignancies from benign disease in a study of 83 women, a finding that differs from those of previous studies.

Median concentrations of osteopontin, insulinlike growth factor (IGF)–II, leptin, and prolactin in preoperative serum samples were not significantly different between women with benign ovarian neoplasm and those with ovarian cancer, Dr. Stefano Guerriero said at the World Congress on Ultrasound in Obstetrics and Gynecology.

Ten women were found to have ovarian cancer, and 73 had benign neoplasm.

The diagnostic performance of the biomarkers was also evaluated using a split-point scoring method in which a score of 1 or lower was required for a benign mass and a score of 2 or more indicated cancer.

With this method, the simultaneous evaluation of the four serum protein markers had a sensitivity of 80% and a specificity of just 10%, he said.

The sensitivity was 68% and specificity 40% with the use of only CA 125, a serum biomarker that is widely used to screen women at increased risk for ovarian cancer and to indicate treatment response in those with ovarian cancer.

Transvaginal ultrasonography showed a sensitivity of 80% but a specificity of 92%, reported Dr. Guerriero and his colleagues at the University of Cagliari (Italy).

“Although previously proposed with encouraging results in the screening of ovarian cancer, the preliminary evaluation of these new biomarkers does not seem to be useful in the preoperative evaluation of patients with an adnexal mass when compared with CA 125 and transvaginal ultrasonography,” he said.

In a 2005 blind, cross-validation study, no single marker could completely distinguish women with ovarian cancer from healthy controls, but the combination of the four proteins achieved a striking 95% sensitivity, specificity, and positive predictive value and a negative predictive value of 94% (Proc. Natl. Acad. Sci. USA 2005;102:7677–82). In a more recent study evaluating an ovarian cancer marker panel that included leptin, prolactin, osteopontin, IGF-II, macrophage migration inhibitory factor, and CA 125, only CA 125, osteopontin, and IGF-II levels differed significantly between ovarian cancer patients and controls with benign ovarian disease (Anticancer Res. 2009;29:573–6).

When asked how the studies' findings could be so different, Dr. Guerriero responded that he did not know, adding that his study took considerable time and money to conduct. “It's incredible to me,” he said.

The 10 malignancies in the study included 4 primary invasive tumors (2 stage III and 2 stage IV), 3 borderline tumors, and 3 metastatic cancers (2 breast and 1 stomach). The majority of the benign masses were endometriomas (29), serous masses (15), and dermoid masses (13). The mean age of the cohort was 41 years, and 18% were postmenopausal.

The study was supported by Assessorato Igiene e Sanità, Regione Autonoma della Sardegna.

HAMBURG, GERMANY — The combination of four new serum biomarkers did not improve differentiation of adnexal malignancies from benign disease in a study of 83 women, a finding that differs from those of previous studies.

Median concentrations of osteopontin, insulinlike growth factor (IGF)–II, leptin, and prolactin in preoperative serum samples were not significantly different between women with benign ovarian neoplasm and those with ovarian cancer, Dr. Stefano Guerriero said at the World Congress on Ultrasound in Obstetrics and Gynecology.

Ten women were found to have ovarian cancer, and 73 had benign neoplasm.

The diagnostic performance of the biomarkers was also evaluated using a split-point scoring method in which a score of 1 or lower was required for a benign mass and a score of 2 or more indicated cancer.

With this method, the simultaneous evaluation of the four serum protein markers had a sensitivity of 80% and a specificity of just 10%, he said.

The sensitivity was 68% and specificity 40% with the use of only CA 125, a serum biomarker that is widely used to screen women at increased risk for ovarian cancer and to indicate treatment response in those with ovarian cancer.

Transvaginal ultrasonography showed a sensitivity of 80% but a specificity of 92%, reported Dr. Guerriero and his colleagues at the University of Cagliari (Italy).

“Although previously proposed with encouraging results in the screening of ovarian cancer, the preliminary evaluation of these new biomarkers does not seem to be useful in the preoperative evaluation of patients with an adnexal mass when compared with CA 125 and transvaginal ultrasonography,” he said.

In a 2005 blind, cross-validation study, no single marker could completely distinguish women with ovarian cancer from healthy controls, but the combination of the four proteins achieved a striking 95% sensitivity, specificity, and positive predictive value and a negative predictive value of 94% (Proc. Natl. Acad. Sci. USA 2005;102:7677–82). In a more recent study evaluating an ovarian cancer marker panel that included leptin, prolactin, osteopontin, IGF-II, macrophage migration inhibitory factor, and CA 125, only CA 125, osteopontin, and IGF-II levels differed significantly between ovarian cancer patients and controls with benign ovarian disease (Anticancer Res. 2009;29:573–6).

When asked how the studies' findings could be so different, Dr. Guerriero responded that he did not know, adding that his study took considerable time and money to conduct. “It's incredible to me,” he said.

The 10 malignancies in the study included 4 primary invasive tumors (2 stage III and 2 stage IV), 3 borderline tumors, and 3 metastatic cancers (2 breast and 1 stomach). The majority of the benign masses were endometriomas (29), serous masses (15), and dermoid masses (13). The mean age of the cohort was 41 years, and 18% were postmenopausal.

The study was supported by Assessorato Igiene e Sanità, Regione Autonoma della Sardegna.

HAMBURG, GERMANY — The combination of four new serum biomarkers did not improve differentiation of adnexal malignancies from benign disease in a study of 83 women, a finding that differs from those of previous studies.

Median concentrations of osteopontin, insulinlike growth factor (IGF)–II, leptin, and prolactin in preoperative serum samples were not significantly different between women with benign ovarian neoplasm and those with ovarian cancer, Dr. Stefano Guerriero said at the World Congress on Ultrasound in Obstetrics and Gynecology.

Ten women were found to have ovarian cancer, and 73 had benign neoplasm.

The diagnostic performance of the biomarkers was also evaluated using a split-point scoring method in which a score of 1 or lower was required for a benign mass and a score of 2 or more indicated cancer.

With this method, the simultaneous evaluation of the four serum protein markers had a sensitivity of 80% and a specificity of just 10%, he said.

The sensitivity was 68% and specificity 40% with the use of only CA 125, a serum biomarker that is widely used to screen women at increased risk for ovarian cancer and to indicate treatment response in those with ovarian cancer.

Transvaginal ultrasonography showed a sensitivity of 80% but a specificity of 92%, reported Dr. Guerriero and his colleagues at the University of Cagliari (Italy).

“Although previously proposed with encouraging results in the screening of ovarian cancer, the preliminary evaluation of these new biomarkers does not seem to be useful in the preoperative evaluation of patients with an adnexal mass when compared with CA 125 and transvaginal ultrasonography,” he said.

In a 2005 blind, cross-validation study, no single marker could completely distinguish women with ovarian cancer from healthy controls, but the combination of the four proteins achieved a striking 95% sensitivity, specificity, and positive predictive value and a negative predictive value of 94% (Proc. Natl. Acad. Sci. USA 2005;102:7677–82). In a more recent study evaluating an ovarian cancer marker panel that included leptin, prolactin, osteopontin, IGF-II, macrophage migration inhibitory factor, and CA 125, only CA 125, osteopontin, and IGF-II levels differed significantly between ovarian cancer patients and controls with benign ovarian disease (Anticancer Res. 2009;29:573–6).

When asked how the studies' findings could be so different, Dr. Guerriero responded that he did not know, adding that his study took considerable time and money to conduct. “It's incredible to me,” he said.

The 10 malignancies in the study included 4 primary invasive tumors (2 stage III and 2 stage IV), 3 borderline tumors, and 3 metastatic cancers (2 breast and 1 stomach). The majority of the benign masses were endometriomas (29), serous masses (15), and dermoid masses (13). The mean age of the cohort was 41 years, and 18% were postmenopausal.

The study was supported by Assessorato Igiene e Sanità, Regione Autonoma della Sardegna.

HAMBURG, GERMANY — The presence of small antral follicles measuring 2.1–4.0 mm predicted pregnancy and ovarian response in a prospective cohort of 142 women who underwent in vitro fertilization.

The study took advantage of a novel software program called sonography-based automated volume count (SonoAVC) that can automatically identify and measure the dimensions of hypoechogenic areas such as ovarian follicles observed on 3-D ultrasonography. In this instance, the program was used to calculate the number of antral follicles measuring 9 mm or less in diameter in the early follicular phase (days 2–5) in subfertile women (aged 40 years or less) who were due to undergo their first cycle of assisted reproductive technology.

In all, 73 viable pregnancies were confirmed on ultrasound 7 weeks following embryo transfer.

Women who conceived had significantly more antral follicles measuring 2.1–4.0 mm than did those who had unsuccessful treatment, Nick Raine-Fenning, Ph.D., and his colleagues reported at the World Congress on Ultrasound in Obstetrics and Gynecology. There were no significant differences among women with antral follicles measuring 4.1–6.0 mm, 6.1–8.0 mm, or 8.1–9.0 mm.

On multiple logistic regression analysis, the number of antral follicles measuring 2.1–4.0 mm was a significant independent predictor of pregnancy (odds ratio, 1.23), said Dr. Raine-Fenning of the University of Nottingham (England). The total number of antral follicles and younger age also were significant predictors, while other antral follicle subgroups and type of treatment were not.

“These early results are encouraging, as very few studies have shown a link [between the number of these small follicles and] eventual pregnancy outcome,” they said.

Larger follicles are more likely to be atretic and of poorer quality, while smaller antral follicles relate more closely to serum levels of anti-Müllerian hormone and may better reflect the quality of the oocyte, Dr. Raine-Fenning said in an interview.

Current tests of ovarian reserve are considered quantitative, in that they give an idea of how many oocytes one can expect during in vitro fertilization (IVF) treatment, but are not qualitative, as they cannot predict pregnancy, he noted.

Among women who conceived in the current study versus those who did not, there were more mature oocytes (10.73 vs. 9.04), fertilized oocytes (7.26 vs. 5.81), and cleaved embryos (6.89 vs. 5.53). The number of small antral follicles 2.1–4.0 mm in size was a significant predictor for all three of these secondary outcomes both in univariate and multivariate analyses, Dr. Raine-Fenning reported.

Earlier this year, the investigators reported that SonoAVC identified a comparable number of follicles to real-time 2-D ultrasound in a preliminary study of 72 women undergoing their first cycle of assisted reproductive technology. Follicle tracking with SonoAVC did not significantly improve the number of mature oocytes retrieved, however, when compared with conventional ultrasound (11.43 vs. 10.70) or clinical pregnancy rates (43% vs. 42%).

The SonoAVC software is available only with a few General Electric ultrasound machines, but the additional cost of the software should be reclaimed in improved efficiency in the IVF unit, Dr. Raine-Fenning said.

He reported no relevant financial conflicts of interest.

HAMBURG, GERMANY — The presence of small antral follicles measuring 2.1–4.0 mm predicted pregnancy and ovarian response in a prospective cohort of 142 women who underwent in vitro fertilization.

The study took advantage of a novel software program called sonography-based automated volume count (SonoAVC) that can automatically identify and measure the dimensions of hypoechogenic areas such as ovarian follicles observed on 3-D ultrasonography. In this instance, the program was used to calculate the number of antral follicles measuring 9 mm or less in diameter in the early follicular phase (days 2–5) in subfertile women (aged 40 years or less) who were due to undergo their first cycle of assisted reproductive technology.

In all, 73 viable pregnancies were confirmed on ultrasound 7 weeks following embryo transfer.

Women who conceived had significantly more antral follicles measuring 2.1–4.0 mm than did those who had unsuccessful treatment, Nick Raine-Fenning, Ph.D., and his colleagues reported at the World Congress on Ultrasound in Obstetrics and Gynecology. There were no significant differences among women with antral follicles measuring 4.1–6.0 mm, 6.1–8.0 mm, or 8.1–9.0 mm.

On multiple logistic regression analysis, the number of antral follicles measuring 2.1–4.0 mm was a significant independent predictor of pregnancy (odds ratio, 1.23), said Dr. Raine-Fenning of the University of Nottingham (England). The total number of antral follicles and younger age also were significant predictors, while other antral follicle subgroups and type of treatment were not.

“These early results are encouraging, as very few studies have shown a link [between the number of these small follicles and] eventual pregnancy outcome,” they said.

Larger follicles are more likely to be atretic and of poorer quality, while smaller antral follicles relate more closely to serum levels of anti-Müllerian hormone and may better reflect the quality of the oocyte, Dr. Raine-Fenning said in an interview.

Current tests of ovarian reserve are considered quantitative, in that they give an idea of how many oocytes one can expect during in vitro fertilization (IVF) treatment, but are not qualitative, as they cannot predict pregnancy, he noted.

Among women who conceived in the current study versus those who did not, there were more mature oocytes (10.73 vs. 9.04), fertilized oocytes (7.26 vs. 5.81), and cleaved embryos (6.89 vs. 5.53). The number of small antral follicles 2.1–4.0 mm in size was a significant predictor for all three of these secondary outcomes both in univariate and multivariate analyses, Dr. Raine-Fenning reported.

Earlier this year, the investigators reported that SonoAVC identified a comparable number of follicles to real-time 2-D ultrasound in a preliminary study of 72 women undergoing their first cycle of assisted reproductive technology. Follicle tracking with SonoAVC did not significantly improve the number of mature oocytes retrieved, however, when compared with conventional ultrasound (11.43 vs. 10.70) or clinical pregnancy rates (43% vs. 42%).

The SonoAVC software is available only with a few General Electric ultrasound machines, but the additional cost of the software should be reclaimed in improved efficiency in the IVF unit, Dr. Raine-Fenning said.

He reported no relevant financial conflicts of interest.

HAMBURG, GERMANY — The presence of small antral follicles measuring 2.1–4.0 mm predicted pregnancy and ovarian response in a prospective cohort of 142 women who underwent in vitro fertilization.

The study took advantage of a novel software program called sonography-based automated volume count (SonoAVC) that can automatically identify and measure the dimensions of hypoechogenic areas such as ovarian follicles observed on 3-D ultrasonography. In this instance, the program was used to calculate the number of antral follicles measuring 9 mm or less in diameter in the early follicular phase (days 2–5) in subfertile women (aged 40 years or less) who were due to undergo their first cycle of assisted reproductive technology.

In all, 73 viable pregnancies were confirmed on ultrasound 7 weeks following embryo transfer.

Women who conceived had significantly more antral follicles measuring 2.1–4.0 mm than did those who had unsuccessful treatment, Nick Raine-Fenning, Ph.D., and his colleagues reported at the World Congress on Ultrasound in Obstetrics and Gynecology. There were no significant differences among women with antral follicles measuring 4.1–6.0 mm, 6.1–8.0 mm, or 8.1–9.0 mm.

On multiple logistic regression analysis, the number of antral follicles measuring 2.1–4.0 mm was a significant independent predictor of pregnancy (odds ratio, 1.23), said Dr. Raine-Fenning of the University of Nottingham (England). The total number of antral follicles and younger age also were significant predictors, while other antral follicle subgroups and type of treatment were not.

“These early results are encouraging, as very few studies have shown a link [between the number of these small follicles and] eventual pregnancy outcome,” they said.

Larger follicles are more likely to be atretic and of poorer quality, while smaller antral follicles relate more closely to serum levels of anti-Müllerian hormone and may better reflect the quality of the oocyte, Dr. Raine-Fenning said in an interview.

Current tests of ovarian reserve are considered quantitative, in that they give an idea of how many oocytes one can expect during in vitro fertilization (IVF) treatment, but are not qualitative, as they cannot predict pregnancy, he noted.

Among women who conceived in the current study versus those who did not, there were more mature oocytes (10.73 vs. 9.04), fertilized oocytes (7.26 vs. 5.81), and cleaved embryos (6.89 vs. 5.53). The number of small antral follicles 2.1–4.0 mm in size was a significant predictor for all three of these secondary outcomes both in univariate and multivariate analyses, Dr. Raine-Fenning reported.

Earlier this year, the investigators reported that SonoAVC identified a comparable number of follicles to real-time 2-D ultrasound in a preliminary study of 72 women undergoing their first cycle of assisted reproductive technology. Follicle tracking with SonoAVC did not significantly improve the number of mature oocytes retrieved, however, when compared with conventional ultrasound (11.43 vs. 10.70) or clinical pregnancy rates (43% vs. 42%).

The SonoAVC software is available only with a few General Electric ultrasound machines, but the additional cost of the software should be reclaimed in improved efficiency in the IVF unit, Dr. Raine-Fenning said.

He reported no relevant financial conflicts of interest.

CHICAGO — Despite the underrepresentation of Hispanics in heart failure trials, evidence has emerged suggesting that they have unique risk factors and outcomes that must be taken into clinical consideration.

The evidence also underscores the need to recognize the vast heterogeneity of Hispanics, Dr. Ileana Piña said at a meeting sponsored by the International Society on Hypertension in Blacks.

“Hispanics represent a cultural group, not a racially identifiable group,” said the Cuban-born cardiologist. “You can't lump them all together.”

But that's exactly what has happened. It wasn't until the 2000 U.S. census that the term “Hispanic” was changed to “Spanish, Hispanic, or Latino” to describe persons of Cuban, Mexican, Puerto Rican, South or Central American, or other Spanish culture or origin, regardless of race.

Several studies have made the observation—coined the “Hispanic paradox”—that Hispanics have lower all-cause and cardiovascular mortality, despite increased obesity and diabetes, and lower socioeconomic status, said Dr. Piña, professor of medicine at Case Western Reserve University, Cleveland.

A study of Medicare enrollees found that Hispanics were 1.2 times more likely to be hospitalized for heart failure than were whites, while blacks were 1.5 times more likely. But after adjustment for sex and age, in-hospital mortality was significantly lower in Hispanics and blacks than in whites. A California study also showed that blacks and “Latinos” initially hospitalized with heart failure in 1991 or 1992 were more likely to be rehospitalized than were Asians and whites, but were less likely to die during the following year.

Sociocultural factors are often used to explain the Hispanic paradox, but more recent data are causing some to rethink the paradox or at least to differentiate Hispanics by birthplace. Among diabetics in the San Antonio Heart Study, age- and sex-adjusted hazard ratios indicated that U.S.-born Mexican-Americans have a 66% greater risk of all-cause and CV mortality, compared with non-Hispanic whites, while Mexico-born Mexican-Americans appeared to be at similar risk.

Greater representation in patient registries, research studies, and clinical trials is needed Dr. Piña said. Only one major heart failure trial, HF-ACTION, has specifically differentiated Hispanics, and those patients made up just 3%.

Greater elucidation of heart failure risk factors and outcomes in Hispanic populations could lead to more targeted therapies and risk modification. With one in three U.S. residents expected to be Hispanic by 2050, there is great urgency to act, said Dr. Piña, who disclosed serving as a speaker for AstraZeneca, Novartis, and Merck.

CHICAGO — Despite the underrepresentation of Hispanics in heart failure trials, evidence has emerged suggesting that they have unique risk factors and outcomes that must be taken into clinical consideration.

The evidence also underscores the need to recognize the vast heterogeneity of Hispanics, Dr. Ileana Piña said at a meeting sponsored by the International Society on Hypertension in Blacks.

“Hispanics represent a cultural group, not a racially identifiable group,” said the Cuban-born cardiologist. “You can't lump them all together.”

But that's exactly what has happened. It wasn't until the 2000 U.S. census that the term “Hispanic” was changed to “Spanish, Hispanic, or Latino” to describe persons of Cuban, Mexican, Puerto Rican, South or Central American, or other Spanish culture or origin, regardless of race.

Several studies have made the observation—coined the “Hispanic paradox”—that Hispanics have lower all-cause and cardiovascular mortality, despite increased obesity and diabetes, and lower socioeconomic status, said Dr. Piña, professor of medicine at Case Western Reserve University, Cleveland.

A study of Medicare enrollees found that Hispanics were 1.2 times more likely to be hospitalized for heart failure than were whites, while blacks were 1.5 times more likely. But after adjustment for sex and age, in-hospital mortality was significantly lower in Hispanics and blacks than in whites. A California study also showed that blacks and “Latinos” initially hospitalized with heart failure in 1991 or 1992 were more likely to be rehospitalized than were Asians and whites, but were less likely to die during the following year.

Sociocultural factors are often used to explain the Hispanic paradox, but more recent data are causing some to rethink the paradox or at least to differentiate Hispanics by birthplace. Among diabetics in the San Antonio Heart Study, age- and sex-adjusted hazard ratios indicated that U.S.-born Mexican-Americans have a 66% greater risk of all-cause and CV mortality, compared with non-Hispanic whites, while Mexico-born Mexican-Americans appeared to be at similar risk.

Greater representation in patient registries, research studies, and clinical trials is needed Dr. Piña said. Only one major heart failure trial, HF-ACTION, has specifically differentiated Hispanics, and those patients made up just 3%.

Greater elucidation of heart failure risk factors and outcomes in Hispanic populations could lead to more targeted therapies and risk modification. With one in three U.S. residents expected to be Hispanic by 2050, there is great urgency to act, said Dr. Piña, who disclosed serving as a speaker for AstraZeneca, Novartis, and Merck.

CHICAGO — Despite the underrepresentation of Hispanics in heart failure trials, evidence has emerged suggesting that they have unique risk factors and outcomes that must be taken into clinical consideration.

The evidence also underscores the need to recognize the vast heterogeneity of Hispanics, Dr. Ileana Piña said at a meeting sponsored by the International Society on Hypertension in Blacks.

“Hispanics represent a cultural group, not a racially identifiable group,” said the Cuban-born cardiologist. “You can't lump them all together.”

But that's exactly what has happened. It wasn't until the 2000 U.S. census that the term “Hispanic” was changed to “Spanish, Hispanic, or Latino” to describe persons of Cuban, Mexican, Puerto Rican, South or Central American, or other Spanish culture or origin, regardless of race.

Several studies have made the observation—coined the “Hispanic paradox”—that Hispanics have lower all-cause and cardiovascular mortality, despite increased obesity and diabetes, and lower socioeconomic status, said Dr. Piña, professor of medicine at Case Western Reserve University, Cleveland.

A study of Medicare enrollees found that Hispanics were 1.2 times more likely to be hospitalized for heart failure than were whites, while blacks were 1.5 times more likely. But after adjustment for sex and age, in-hospital mortality was significantly lower in Hispanics and blacks than in whites. A California study also showed that blacks and “Latinos” initially hospitalized with heart failure in 1991 or 1992 were more likely to be rehospitalized than were Asians and whites, but were less likely to die during the following year.

Sociocultural factors are often used to explain the Hispanic paradox, but more recent data are causing some to rethink the paradox or at least to differentiate Hispanics by birthplace. Among diabetics in the San Antonio Heart Study, age- and sex-adjusted hazard ratios indicated that U.S.-born Mexican-Americans have a 66% greater risk of all-cause and CV mortality, compared with non-Hispanic whites, while Mexico-born Mexican-Americans appeared to be at similar risk.

Greater representation in patient registries, research studies, and clinical trials is needed Dr. Piña said. Only one major heart failure trial, HF-ACTION, has specifically differentiated Hispanics, and those patients made up just 3%.

Greater elucidation of heart failure risk factors and outcomes in Hispanic populations could lead to more targeted therapies and risk modification. With one in three U.S. residents expected to be Hispanic by 2050, there is great urgency to act, said Dr. Piña, who disclosed serving as a speaker for AstraZeneca, Novartis, and Merck.

CHICAGO – Screening patients with irritable bowel syndrome for restless legs syndrome may lead to greater identification of RLS and improved treatment for both conditions.

In a single, community-based gastroenterology center, 29% of 90 patients with irritable bowel syndrome (IBS) based on Rome III criteria were also diagnosed with RLS. The prevalence of RLS in the general population is 1%-10%.

All patients with both IBS and RLS had alterations in the initiation and maintenance of sleep, lead author Dr. P. Patrick Basu and his associates reported in a poster at a meeting on neurogastroenterology and motility. Involuntary jerks and wakefulness during more than 30% of sleep time occurred in 75% and 63% of patients, respectively. The mean age of the cohort was 33 years; 60 were female, 38 were Hispanic, 26 white, 24 Asian, and 2 black.

Of the 26 patients with RLS, 62% had diarrhea-predominant IBS, 4% had constipation-predominant IBS, and 33% had mixed IBS, suggesting the specific pathophysiology of diarrhea-predominant IBS may contribute to or relate to RLS. Previous research has identified a link between small intestinal bacterial overgrowth, which may contribute to IBS, and several sensory disorders including fibromyalgia, interstitial cystitis, and RLS.

“Diagnosis of simultaneous IBS and RLS may provide enhanced therapeutic efficacy for these patients, as some medications [that is,] rifaximin, may provide relief for both conditions,” wrote Dr. Basu, director of gastroenterology, North Shore–Long Island Jewish Health System at Forest Hills, N.Y., and his associates.

Although the data were not included in the poster, 19 of the 26 IBS patients with RLS were treated with the antibiotic rifaximin, with 9 reporting relief of their RLS symptoms, Dr. Basu said in an interview. The diagnosis of RLS was made using a standard questionnaire formulated by the International Restless Legs Syndrome Study Group and was confirmed by polysomnography.

Dr. Basu's decision to use rifaximin was prompted by an independent study in 13 patients with IBS and a positive lactulose breath test, an indicator of small intestinal bacterial overgrowth, in which rifaximin 1,200 mg/day for 10 days was associated with at least an 80% improvement from baseline in RLS symptoms in 10 patients and a “great” or “moderate” global GI symptom improvement in 11 patients (Dig. Dis. Sci. 2008;53:1252-6). Five of the 10 patients followed long term (mean 139 days) maintained complete resolution of their RLS symptoms.

Dr. Basu uses rifaximin plus probiotics in his own practice for patients with both RLS and IBS, and is planning to evaluate its efficacy at doses up to 1,400 mg/day in combination with probiotics in 75 IBS patients with RLS. Further investigations to determine the underlying mechanisms in IBS and RLS are needed to address the causality and possible concomitant nature of both disorders, he said.

Two studies from Washington University School of Medicine, St. Louis, examined whether RLS is associated with celiac disease and Crohn's disease, because all three conditions are associated with iron deficiency. The incidence of RLS was 35% in 85 patients with celiac disease (Dig. Dis. Sci. 2009 Sept. 3 [Epub ahead of print] and 43% in 272 consecutive patients with Crohn's disease (Inflammatory Bowel Dis. 2009 July 2 [doi: 10.1002/ibd.21001]). The rate of iron deficiency was significantly higher in celiac patients with active RLS than in those with no RLS, but there was no difference between Crohn's patients with and without RLS with respect to current iron deficiency.

Dr. Basu noted that screening IBS patients for RLS may allow greater identification and subsequent treatment of RLS, which is thought to be underdiagnosed, even in the general population.

Dr. Basu and associates reported no conflicts of interest. Support for preparation of the poster was provided by Salix Pharmaceuticals, which markets rifaximin as Xifaxan.

CHICAGO – Screening patients with irritable bowel syndrome for restless legs syndrome may lead to greater identification of RLS and improved treatment for both conditions.

In a single, community-based gastroenterology center, 29% of 90 patients with irritable bowel syndrome (IBS) based on Rome III criteria were also diagnosed with RLS. The prevalence of RLS in the general population is 1%-10%.

All patients with both IBS and RLS had alterations in the initiation and maintenance of sleep, lead author Dr. P. Patrick Basu and his associates reported in a poster at a meeting on neurogastroenterology and motility. Involuntary jerks and wakefulness during more than 30% of sleep time occurred in 75% and 63% of patients, respectively. The mean age of the cohort was 33 years; 60 were female, 38 were Hispanic, 26 white, 24 Asian, and 2 black.

Of the 26 patients with RLS, 62% had diarrhea-predominant IBS, 4% had constipation-predominant IBS, and 33% had mixed IBS, suggesting the specific pathophysiology of diarrhea-predominant IBS may contribute to or relate to RLS. Previous research has identified a link between small intestinal bacterial overgrowth, which may contribute to IBS, and several sensory disorders including fibromyalgia, interstitial cystitis, and RLS.

“Diagnosis of simultaneous IBS and RLS may provide enhanced therapeutic efficacy for these patients, as some medications [that is,] rifaximin, may provide relief for both conditions,” wrote Dr. Basu, director of gastroenterology, North Shore–Long Island Jewish Health System at Forest Hills, N.Y., and his associates.

Although the data were not included in the poster, 19 of the 26 IBS patients with RLS were treated with the antibiotic rifaximin, with 9 reporting relief of their RLS symptoms, Dr. Basu said in an interview. The diagnosis of RLS was made using a standard questionnaire formulated by the International Restless Legs Syndrome Study Group and was confirmed by polysomnography.

Dr. Basu's decision to use rifaximin was prompted by an independent study in 13 patients with IBS and a positive lactulose breath test, an indicator of small intestinal bacterial overgrowth, in which rifaximin 1,200 mg/day for 10 days was associated with at least an 80% improvement from baseline in RLS symptoms in 10 patients and a “great” or “moderate” global GI symptom improvement in 11 patients (Dig. Dis. Sci. 2008;53:1252-6). Five of the 10 patients followed long term (mean 139 days) maintained complete resolution of their RLS symptoms.

Dr. Basu uses rifaximin plus probiotics in his own practice for patients with both RLS and IBS, and is planning to evaluate its efficacy at doses up to 1,400 mg/day in combination with probiotics in 75 IBS patients with RLS. Further investigations to determine the underlying mechanisms in IBS and RLS are needed to address the causality and possible concomitant nature of both disorders, he said.

Two studies from Washington University School of Medicine, St. Louis, examined whether RLS is associated with celiac disease and Crohn's disease, because all three conditions are associated with iron deficiency. The incidence of RLS was 35% in 85 patients with celiac disease (Dig. Dis. Sci. 2009 Sept. 3 [Epub ahead of print] and 43% in 272 consecutive patients with Crohn's disease (Inflammatory Bowel Dis. 2009 July 2 [doi: 10.1002/ibd.21001]). The rate of iron deficiency was significantly higher in celiac patients with active RLS than in those with no RLS, but there was no difference between Crohn's patients with and without RLS with respect to current iron deficiency.

Dr. Basu noted that screening IBS patients for RLS may allow greater identification and subsequent treatment of RLS, which is thought to be underdiagnosed, even in the general population.

Dr. Basu and associates reported no conflicts of interest. Support for preparation of the poster was provided by Salix Pharmaceuticals, which markets rifaximin as Xifaxan.

CHICAGO – Screening patients with irritable bowel syndrome for restless legs syndrome may lead to greater identification of RLS and improved treatment for both conditions.

In a single, community-based gastroenterology center, 29% of 90 patients with irritable bowel syndrome (IBS) based on Rome III criteria were also diagnosed with RLS. The prevalence of RLS in the general population is 1%-10%.

All patients with both IBS and RLS had alterations in the initiation and maintenance of sleep, lead author Dr. P. Patrick Basu and his associates reported in a poster at a meeting on neurogastroenterology and motility. Involuntary jerks and wakefulness during more than 30% of sleep time occurred in 75% and 63% of patients, respectively. The mean age of the cohort was 33 years; 60 were female, 38 were Hispanic, 26 white, 24 Asian, and 2 black.

Of the 26 patients with RLS, 62% had diarrhea-predominant IBS, 4% had constipation-predominant IBS, and 33% had mixed IBS, suggesting the specific pathophysiology of diarrhea-predominant IBS may contribute to or relate to RLS. Previous research has identified a link between small intestinal bacterial overgrowth, which may contribute to IBS, and several sensory disorders including fibromyalgia, interstitial cystitis, and RLS.

“Diagnosis of simultaneous IBS and RLS may provide enhanced therapeutic efficacy for these patients, as some medications [that is,] rifaximin, may provide relief for both conditions,” wrote Dr. Basu, director of gastroenterology, North Shore–Long Island Jewish Health System at Forest Hills, N.Y., and his associates.

Although the data were not included in the poster, 19 of the 26 IBS patients with RLS were treated with the antibiotic rifaximin, with 9 reporting relief of their RLS symptoms, Dr. Basu said in an interview. The diagnosis of RLS was made using a standard questionnaire formulated by the International Restless Legs Syndrome Study Group and was confirmed by polysomnography.

Dr. Basu's decision to use rifaximin was prompted by an independent study in 13 patients with IBS and a positive lactulose breath test, an indicator of small intestinal bacterial overgrowth, in which rifaximin 1,200 mg/day for 10 days was associated with at least an 80% improvement from baseline in RLS symptoms in 10 patients and a “great” or “moderate” global GI symptom improvement in 11 patients (Dig. Dis. Sci. 2008;53:1252-6). Five of the 10 patients followed long term (mean 139 days) maintained complete resolution of their RLS symptoms.

Dr. Basu uses rifaximin plus probiotics in his own practice for patients with both RLS and IBS, and is planning to evaluate its efficacy at doses up to 1,400 mg/day in combination with probiotics in 75 IBS patients with RLS. Further investigations to determine the underlying mechanisms in IBS and RLS are needed to address the causality and possible concomitant nature of both disorders, he said.

Two studies from Washington University School of Medicine, St. Louis, examined whether RLS is associated with celiac disease and Crohn's disease, because all three conditions are associated with iron deficiency. The incidence of RLS was 35% in 85 patients with celiac disease (Dig. Dis. Sci. 2009 Sept. 3 [Epub ahead of print] and 43% in 272 consecutive patients with Crohn's disease (Inflammatory Bowel Dis. 2009 July 2 [doi: 10.1002/ibd.21001]). The rate of iron deficiency was significantly higher in celiac patients with active RLS than in those with no RLS, but there was no difference between Crohn's patients with and without RLS with respect to current iron deficiency.

Dr. Basu noted that screening IBS patients for RLS may allow greater identification and subsequent treatment of RLS, which is thought to be underdiagnosed, even in the general population.

Dr. Basu and associates reported no conflicts of interest. Support for preparation of the poster was provided by Salix Pharmaceuticals, which markets rifaximin as Xifaxan.