Kerri Wachter

BALTIMORE – Navigating the gluten-free world can be very challenging for patients with celiac disease and their families. Clinicians need to help them understand food labeling and other dietary concerns.

Fortunately there are some tips that can simplify finding gluten-free foods, according to one expert at a meeting on pediatric nutrition sponsored by Johns Hopkins University.

Photo: Marek Uliasz/iStock.com

"This is the good news. All that you have to teach your patients are six words ... to identify whether a product that is not labeled gluten-free is a gluten-containing item," said Pam Cureton, who is a registered dietician at the University of Maryland Center for Celiac Research in Baltimore.

Parents and patients should check the label for wheat, barley, malt, rye, oats (not specifically-labeled gluten-free), and brewer’s yeast.

"Teach your patients those six words and they are good to go," she said.

Some things – like modified food starch and maltodextrin – can trip parents up though. However, the Food Allergen Labeling and Consumer Protection Act of 2004 requires that if a product contains wheat (or a few other common food allergens), the label has to state this, Ms. Cureton said. So, modified food starch – without the word wheat next to it on a label – is derived from corn. "It is safe for your patients to eat."

She offered this tip for maltodextrin. "I always tell my patients that if it sounds like a food flavoring or food additive – malt flavoring, malt syrup, malt extract – if it sounds like a food, don’t eat it. If it sounds like a chemical – maltodextrin, isomalt, maltase – those are highly processed sugar alcohols, and they’re fine to eat."

In addition, some manufacturers will use statements such as "may contain wheat." This can be tricky. "The ‘may contain’ are allergen advisory statements. It could be something like ‘manufactured in a plant that contains wheat.’ " However, according to the Food Allergen Labeling and Consumer Protection Act, the product label must state "contains wheat," not "may contain wheat." The phrasing "may contain" is a voluntary statement that manufacturers may add to the label, when in doubt. "It’s not a reliable way to determine if this is a good product or not," said Ms. Cureton.

Sometimes products carry label statements such as "the manufacturer tests their products to 5 ppm or no detectable gluten." Other manufacturers may make the exact same product but don’t bother with this and don’t include it on their labels.

"Basically, I ignore these statements ... if it’s a product labeled gluten-free, you just ignore these statements and move on," she said.

"Hopefully, soon, the FDA will come up with a definition for the term gluten-free. There is none at this point. As long as it doesn’t contain wheat, rye, or barley, that’s all that matters." This is expected to be enacted in 2012. "Once that happens, you need to be prepared for the fallout."

While the labeling will be voluntary, for those manufacturers that choose to use the words ‘gluten-free’ on the label, the product can’t contain wheat, rye, or barley. To meet the proposed gluten-free definition, a product must have less than 20 ppm of wheat. But "what does that mean? Is it per serving, per day, per slice?" she asked.

Clinicians should be able to explain this to their patients. So, where does the number come from? Several studies have been done to determine how much wheat is safe for a patient with celiac disease – how much can be ingested before damage begins?

In one randomized control trial from Italy, researchers found that 10 mg gluten per day showed no signs of damage on repeat endoscopy, while with 50 mg per day, the beginning signs of intestinal damage could be seen (Am. J. Clin. Nutr. 2007;85:160-6).

The researchers also looked at how much gluten-free food was eaten in this Italian population per day – about 300 g per day. Given this, they calculated what level of contamination in a gluten-free product would result in less than 10 mg gluten per day if a person ate 300 g of gluten-free food per day – 20 ppm (approximately 6 mg gluten per day). "So in other words, they could eat a lot of gluten-free food without getting near that 10 mg, which is safe."

In other terms, 20 ppm is 20 mg gluten per 100 g gluten-free product. For perspective, a slice of bread has 2,500 mg of gluten (125,000 ppm). "They can have 500 g of gluten-free food per day without going over that 10 mg." This means: 18 slices of gluten-free bread or 18.5 cups of gluten-free rice cereal or 9.5 servings gluten-free pasta.

Once you’ve explained gluten-free labels, it’s important to explain good nutrition in general to your celiac patients and their parents. Ms. Cureton recommends using the new dietary guidelines that can be found at www.myplate.gov to help patients understand the other components of a healthy diet.

"Weight gain is a huge issue in this group. They have been malabsorbing calories for however long they were undiagnosed. Now they’re diagnosed, and the gut heals and they absorb those calories," she said.

For example, a patient might have been eating 3,000 calories a day and maintaining their weight because they were only absorbing half of that. "They need to look at their portion sizes. Just because it says gluten-free doesn’t mean that you get to eat a whole box of brownies."

Eating out at restaurants is another really important topic to go over because this is such a large part of American culture. "We like to eat out. Somebody with celiac disease is no different. They like eating out as well. However, this becomes quite a challenge ... people with celiac disease feel left out."

She suggested these simple tools for eating out:

• Ask if there is a gluten-free menu (or check the menu online).

• Tell the server that you have a "food allergy" to wheat (technically not correct, but people understand this term).

• Carry an ingredient card as a cheat sheet.

• Be very specific when ordering (no croutons, no meat marinades).

• Order simple dishes.

• Bring your own sauces or foods.

• Send back unsafe foods (don’t pick the croutons off your salad).

• Tip well, if you’ve been served well.

Some helpful resources include www.eatright.org, www.glutenfreediet.ca, and www.glutenfreedietitian.com.

Ms. Cureton reported that she had no relevant financial relationships.

BALTIMORE – Navigating the gluten-free world can be very challenging for patients with celiac disease and their families. Clinicians need to help them understand food labeling and other dietary concerns.

Fortunately there are some tips that can simplify finding gluten-free foods, according to one expert at a meeting on pediatric nutrition sponsored by Johns Hopkins University.

Photo: Marek Uliasz/iStock.com

"This is the good news. All that you have to teach your patients are six words ... to identify whether a product that is not labeled gluten-free is a gluten-containing item," said Pam Cureton, who is a registered dietician at the University of Maryland Center for Celiac Research in Baltimore.

Parents and patients should check the label for wheat, barley, malt, rye, oats (not specifically-labeled gluten-free), and brewer’s yeast.

"Teach your patients those six words and they are good to go," she said.

Some things – like modified food starch and maltodextrin – can trip parents up though. However, the Food Allergen Labeling and Consumer Protection Act of 2004 requires that if a product contains wheat (or a few other common food allergens), the label has to state this, Ms. Cureton said. So, modified food starch – without the word wheat next to it on a label – is derived from corn. "It is safe for your patients to eat."

She offered this tip for maltodextrin. "I always tell my patients that if it sounds like a food flavoring or food additive – malt flavoring, malt syrup, malt extract – if it sounds like a food, don’t eat it. If it sounds like a chemical – maltodextrin, isomalt, maltase – those are highly processed sugar alcohols, and they’re fine to eat."

In addition, some manufacturers will use statements such as "may contain wheat." This can be tricky. "The ‘may contain’ are allergen advisory statements. It could be something like ‘manufactured in a plant that contains wheat.’ " However, according to the Food Allergen Labeling and Consumer Protection Act, the product label must state "contains wheat," not "may contain wheat." The phrasing "may contain" is a voluntary statement that manufacturers may add to the label, when in doubt. "It’s not a reliable way to determine if this is a good product or not," said Ms. Cureton.

Sometimes products carry label statements such as "the manufacturer tests their products to 5 ppm or no detectable gluten." Other manufacturers may make the exact same product but don’t bother with this and don’t include it on their labels.

"Basically, I ignore these statements ... if it’s a product labeled gluten-free, you just ignore these statements and move on," she said.

"Hopefully, soon, the FDA will come up with a definition for the term gluten-free. There is none at this point. As long as it doesn’t contain wheat, rye, or barley, that’s all that matters." This is expected to be enacted in 2012. "Once that happens, you need to be prepared for the fallout."

While the labeling will be voluntary, for those manufacturers that choose to use the words ‘gluten-free’ on the label, the product can’t contain wheat, rye, or barley. To meet the proposed gluten-free definition, a product must have less than 20 ppm of wheat. But "what does that mean? Is it per serving, per day, per slice?" she asked.

Clinicians should be able to explain this to their patients. So, where does the number come from? Several studies have been done to determine how much wheat is safe for a patient with celiac disease – how much can be ingested before damage begins?

In one randomized control trial from Italy, researchers found that 10 mg gluten per day showed no signs of damage on repeat endoscopy, while with 50 mg per day, the beginning signs of intestinal damage could be seen (Am. J. Clin. Nutr. 2007;85:160-6).

The researchers also looked at how much gluten-free food was eaten in this Italian population per day – about 300 g per day. Given this, they calculated what level of contamination in a gluten-free product would result in less than 10 mg gluten per day if a person ate 300 g of gluten-free food per day – 20 ppm (approximately 6 mg gluten per day). "So in other words, they could eat a lot of gluten-free food without getting near that 10 mg, which is safe."

In other terms, 20 ppm is 20 mg gluten per 100 g gluten-free product. For perspective, a slice of bread has 2,500 mg of gluten (125,000 ppm). "They can have 500 g of gluten-free food per day without going over that 10 mg." This means: 18 slices of gluten-free bread or 18.5 cups of gluten-free rice cereal or 9.5 servings gluten-free pasta.

Once you’ve explained gluten-free labels, it’s important to explain good nutrition in general to your celiac patients and their parents. Ms. Cureton recommends using the new dietary guidelines that can be found at www.myplate.gov to help patients understand the other components of a healthy diet.

"Weight gain is a huge issue in this group. They have been malabsorbing calories for however long they were undiagnosed. Now they’re diagnosed, and the gut heals and they absorb those calories," she said.

For example, a patient might have been eating 3,000 calories a day and maintaining their weight because they were only absorbing half of that. "They need to look at their portion sizes. Just because it says gluten-free doesn’t mean that you get to eat a whole box of brownies."

Eating out at restaurants is another really important topic to go over because this is such a large part of American culture. "We like to eat out. Somebody with celiac disease is no different. They like eating out as well. However, this becomes quite a challenge ... people with celiac disease feel left out."

She suggested these simple tools for eating out:

• Ask if there is a gluten-free menu (or check the menu online).

• Tell the server that you have a "food allergy" to wheat (technically not correct, but people understand this term).

• Carry an ingredient card as a cheat sheet.

• Be very specific when ordering (no croutons, no meat marinades).

• Order simple dishes.

• Bring your own sauces or foods.

• Send back unsafe foods (don’t pick the croutons off your salad).

• Tip well, if you’ve been served well.

Some helpful resources include www.eatright.org, www.glutenfreediet.ca, and www.glutenfreedietitian.com.

Ms. Cureton reported that she had no relevant financial relationships.

BALTIMORE – Navigating the gluten-free world can be very challenging for patients with celiac disease and their families. Clinicians need to help them understand food labeling and other dietary concerns.

Fortunately there are some tips that can simplify finding gluten-free foods, according to one expert at a meeting on pediatric nutrition sponsored by Johns Hopkins University.

Photo: Marek Uliasz/iStock.com

"This is the good news. All that you have to teach your patients are six words ... to identify whether a product that is not labeled gluten-free is a gluten-containing item," said Pam Cureton, who is a registered dietician at the University of Maryland Center for Celiac Research in Baltimore.

Parents and patients should check the label for wheat, barley, malt, rye, oats (not specifically-labeled gluten-free), and brewer’s yeast.

"Teach your patients those six words and they are good to go," she said.

Some things – like modified food starch and maltodextrin – can trip parents up though. However, the Food Allergen Labeling and Consumer Protection Act of 2004 requires that if a product contains wheat (or a few other common food allergens), the label has to state this, Ms. Cureton said. So, modified food starch – without the word wheat next to it on a label – is derived from corn. "It is safe for your patients to eat."

She offered this tip for maltodextrin. "I always tell my patients that if it sounds like a food flavoring or food additive – malt flavoring, malt syrup, malt extract – if it sounds like a food, don’t eat it. If it sounds like a chemical – maltodextrin, isomalt, maltase – those are highly processed sugar alcohols, and they’re fine to eat."

In addition, some manufacturers will use statements such as "may contain wheat." This can be tricky. "The ‘may contain’ are allergen advisory statements. It could be something like ‘manufactured in a plant that contains wheat.’ " However, according to the Food Allergen Labeling and Consumer Protection Act, the product label must state "contains wheat," not "may contain wheat." The phrasing "may contain" is a voluntary statement that manufacturers may add to the label, when in doubt. "It’s not a reliable way to determine if this is a good product or not," said Ms. Cureton.

Sometimes products carry label statements such as "the manufacturer tests their products to 5 ppm or no detectable gluten." Other manufacturers may make the exact same product but don’t bother with this and don’t include it on their labels.

"Basically, I ignore these statements ... if it’s a product labeled gluten-free, you just ignore these statements and move on," she said.

"Hopefully, soon, the FDA will come up with a definition for the term gluten-free. There is none at this point. As long as it doesn’t contain wheat, rye, or barley, that’s all that matters." This is expected to be enacted in 2012. "Once that happens, you need to be prepared for the fallout."

While the labeling will be voluntary, for those manufacturers that choose to use the words ‘gluten-free’ on the label, the product can’t contain wheat, rye, or barley. To meet the proposed gluten-free definition, a product must have less than 20 ppm of wheat. But "what does that mean? Is it per serving, per day, per slice?" she asked.

Clinicians should be able to explain this to their patients. So, where does the number come from? Several studies have been done to determine how much wheat is safe for a patient with celiac disease – how much can be ingested before damage begins?

In one randomized control trial from Italy, researchers found that 10 mg gluten per day showed no signs of damage on repeat endoscopy, while with 50 mg per day, the beginning signs of intestinal damage could be seen (Am. J. Clin. Nutr. 2007;85:160-6).

The researchers also looked at how much gluten-free food was eaten in this Italian population per day – about 300 g per day. Given this, they calculated what level of contamination in a gluten-free product would result in less than 10 mg gluten per day if a person ate 300 g of gluten-free food per day – 20 ppm (approximately 6 mg gluten per day). "So in other words, they could eat a lot of gluten-free food without getting near that 10 mg, which is safe."

In other terms, 20 ppm is 20 mg gluten per 100 g gluten-free product. For perspective, a slice of bread has 2,500 mg of gluten (125,000 ppm). "They can have 500 g of gluten-free food per day without going over that 10 mg." This means: 18 slices of gluten-free bread or 18.5 cups of gluten-free rice cereal or 9.5 servings gluten-free pasta.

Once you’ve explained gluten-free labels, it’s important to explain good nutrition in general to your celiac patients and their parents. Ms. Cureton recommends using the new dietary guidelines that can be found at www.myplate.gov to help patients understand the other components of a healthy diet.

"Weight gain is a huge issue in this group. They have been malabsorbing calories for however long they were undiagnosed. Now they’re diagnosed, and the gut heals and they absorb those calories," she said.

For example, a patient might have been eating 3,000 calories a day and maintaining their weight because they were only absorbing half of that. "They need to look at their portion sizes. Just because it says gluten-free doesn’t mean that you get to eat a whole box of brownies."

Eating out at restaurants is another really important topic to go over because this is such a large part of American culture. "We like to eat out. Somebody with celiac disease is no different. They like eating out as well. However, this becomes quite a challenge ... people with celiac disease feel left out."

She suggested these simple tools for eating out:

• Ask if there is a gluten-free menu (or check the menu online).

• Tell the server that you have a "food allergy" to wheat (technically not correct, but people understand this term).

• Carry an ingredient card as a cheat sheet.

• Be very specific when ordering (no croutons, no meat marinades).

• Order simple dishes.

• Bring your own sauces or foods.

• Send back unsafe foods (don’t pick the croutons off your salad).

• Tip well, if you’ve been served well.

Some helpful resources include www.eatright.org, www.glutenfreediet.ca, and www.glutenfreedietitian.com.

Ms. Cureton reported that she had no relevant financial relationships.

CHICAGO – Tocilizumab alone may be sufficient to meet the clinical, structural, safety, and quality of life end points of combination tocilizumab/methotrexate therapy, based on the results of additional early analyses of a 2-year, phase IIIb study of more than 500 patients with moderate to severe rheumatoid arthritis.

"The primary end point, as presented at EULAR [the European League Against Rheumatism annual congress], was not statistically significant," Dr. Maxime Dougados said at the annual meeting of the American College of Rheumatology. The remission rate according to the DAS28 (Disease Activity Score based on a 28-joint count) was 40% for those on combination therapy and 37% for those on monotherapy. "For all of the secondary end points of the study, it was exactly the same thing," he said.

There were also no differences between the two groups in scores on ACR 20 (an evaluation reflecting a 20% improvement according to ACR criteria), ACR 50 (a 50% improvement), ACR 70, or ACR 90 assessments.

Dr. Dougados of Université René Descartes, Paris, presented new data on quality of life measures in the trial of tocilizumab, a humanized monoclonal antibody that blocks the interleukin-6 receptor.

There were no clinical or statistical differences between the two groups based on the HAQ-DI (Health Assessment Questionnaire–Disability Index) or the RAQoL (Rheumatoid Arthritis Quality of Life) questionnaire.

The results come from the ACT-RAY trial, which is a double-blind, phase IIIb study of the efficacy and safety of tocilizumab that is given with methotrexate, compared with tocilizumab in patients who did not have an adequate response to methotrexate and thus were switched from methotrexate to tocilizumab alone.

Patients had to be naive to biologics and have moderate to severe active RA (based on the 1987 ACR criteria) to be included in the ongoing 2-year trial. The disease had to be active (resulting in a DAS28 score greater than 4.4), severe (involving at least one radiologic erosion), and refractory (requiring the patient to take methotrexate).

The researchers enrolled 556 patients who did not have adequate responses to methotrexate; in all, 277 of the 279 patients in the combination therapy group and 276 of the 277 in the monotherapy group were included in the intention-to-treat and safety analyses. A total of 260 patients in the combination group and 252 in the monotherapy group completed 24 weeks of treatment.

Tocilizumab was given at 8 mg/kg every 4 weeks, and patients who had been randomized to the monotherapy group were also given a placebo.

The study’s primary end point was the percentage of patients with DAS28-based remission at week 24. The results presented at the EULAR congress showed that tocilizumab monotherapy was similar in efficacy to the combination therapy.

In terms of the structural evaluation, the researchers looked at mean changes from baseline of the Genant-modified Sharp Score (GmSS) over the first 24 weeks of the trial. The overall changes in total scores, joint space–narrowing scores, or erosion scores were considerably less than expected. The researchers expected an increase in mean GmSS of 3.5-4.0, but none of the measures was greater than 1.0 for either group. "This suggests or confirms that tocilizumab is able to prevent structural deterioration," said Dr. Dougados. However, "we have not discovered any new information" in terms of safety, he added.

Data are pending on both the sustainability of the symptomatic effect at 1 year and the progression of structural damage at 1 and 2 years.

Dr. Dougados reported that he receives consulting fees and research grants from F. Hoffmann-La Roche, which sponsored the study. Several coauthors reported significant financial relationships with pharmaceutical companies, including Hoffmann-La Roche.

*Correction, 12/20/2011: An earlier version of this story had a headline that misstated the study findings.

CHICAGO – Tocilizumab alone may be sufficient to meet the clinical, structural, safety, and quality of life end points of combination tocilizumab/methotrexate therapy, based on the results of additional early analyses of a 2-year, phase IIIb study of more than 500 patients with moderate to severe rheumatoid arthritis.

"The primary end point, as presented at EULAR [the European League Against Rheumatism annual congress], was not statistically significant," Dr. Maxime Dougados said at the annual meeting of the American College of Rheumatology. The remission rate according to the DAS28 (Disease Activity Score based on a 28-joint count) was 40% for those on combination therapy and 37% for those on monotherapy. "For all of the secondary end points of the study, it was exactly the same thing," he said.

There were also no differences between the two groups in scores on ACR 20 (an evaluation reflecting a 20% improvement according to ACR criteria), ACR 50 (a 50% improvement), ACR 70, or ACR 90 assessments.

Dr. Dougados of Université René Descartes, Paris, presented new data on quality of life measures in the trial of tocilizumab, a humanized monoclonal antibody that blocks the interleukin-6 receptor.

There were no clinical or statistical differences between the two groups based on the HAQ-DI (Health Assessment Questionnaire–Disability Index) or the RAQoL (Rheumatoid Arthritis Quality of Life) questionnaire.

The results come from the ACT-RAY trial, which is a double-blind, phase IIIb study of the efficacy and safety of tocilizumab that is given with methotrexate, compared with tocilizumab in patients who did not have an adequate response to methotrexate and thus were switched from methotrexate to tocilizumab alone.

Patients had to be naive to biologics and have moderate to severe active RA (based on the 1987 ACR criteria) to be included in the ongoing 2-year trial. The disease had to be active (resulting in a DAS28 score greater than 4.4), severe (involving at least one radiologic erosion), and refractory (requiring the patient to take methotrexate).

The researchers enrolled 556 patients who did not have adequate responses to methotrexate; in all, 277 of the 279 patients in the combination therapy group and 276 of the 277 in the monotherapy group were included in the intention-to-treat and safety analyses. A total of 260 patients in the combination group and 252 in the monotherapy group completed 24 weeks of treatment.

Tocilizumab was given at 8 mg/kg every 4 weeks, and patients who had been randomized to the monotherapy group were also given a placebo.

The study’s primary end point was the percentage of patients with DAS28-based remission at week 24. The results presented at the EULAR congress showed that tocilizumab monotherapy was similar in efficacy to the combination therapy.

In terms of the structural evaluation, the researchers looked at mean changes from baseline of the Genant-modified Sharp Score (GmSS) over the first 24 weeks of the trial. The overall changes in total scores, joint space–narrowing scores, or erosion scores were considerably less than expected. The researchers expected an increase in mean GmSS of 3.5-4.0, but none of the measures was greater than 1.0 for either group. "This suggests or confirms that tocilizumab is able to prevent structural deterioration," said Dr. Dougados. However, "we have not discovered any new information" in terms of safety, he added.

Data are pending on both the sustainability of the symptomatic effect at 1 year and the progression of structural damage at 1 and 2 years.

Dr. Dougados reported that he receives consulting fees and research grants from F. Hoffmann-La Roche, which sponsored the study. Several coauthors reported significant financial relationships with pharmaceutical companies, including Hoffmann-La Roche.

*Correction, 12/20/2011: An earlier version of this story had a headline that misstated the study findings.

CHICAGO – Tocilizumab alone may be sufficient to meet the clinical, structural, safety, and quality of life end points of combination tocilizumab/methotrexate therapy, based on the results of additional early analyses of a 2-year, phase IIIb study of more than 500 patients with moderate to severe rheumatoid arthritis.

"The primary end point, as presented at EULAR [the European League Against Rheumatism annual congress], was not statistically significant," Dr. Maxime Dougados said at the annual meeting of the American College of Rheumatology. The remission rate according to the DAS28 (Disease Activity Score based on a 28-joint count) was 40% for those on combination therapy and 37% for those on monotherapy. "For all of the secondary end points of the study, it was exactly the same thing," he said.

There were also no differences between the two groups in scores on ACR 20 (an evaluation reflecting a 20% improvement according to ACR criteria), ACR 50 (a 50% improvement), ACR 70, or ACR 90 assessments.

Dr. Dougados of Université René Descartes, Paris, presented new data on quality of life measures in the trial of tocilizumab, a humanized monoclonal antibody that blocks the interleukin-6 receptor.

There were no clinical or statistical differences between the two groups based on the HAQ-DI (Health Assessment Questionnaire–Disability Index) or the RAQoL (Rheumatoid Arthritis Quality of Life) questionnaire.

The results come from the ACT-RAY trial, which is a double-blind, phase IIIb study of the efficacy and safety of tocilizumab that is given with methotrexate, compared with tocilizumab in patients who did not have an adequate response to methotrexate and thus were switched from methotrexate to tocilizumab alone.

Patients had to be naive to biologics and have moderate to severe active RA (based on the 1987 ACR criteria) to be included in the ongoing 2-year trial. The disease had to be active (resulting in a DAS28 score greater than 4.4), severe (involving at least one radiologic erosion), and refractory (requiring the patient to take methotrexate).

The researchers enrolled 556 patients who did not have adequate responses to methotrexate; in all, 277 of the 279 patients in the combination therapy group and 276 of the 277 in the monotherapy group were included in the intention-to-treat and safety analyses. A total of 260 patients in the combination group and 252 in the monotherapy group completed 24 weeks of treatment.

Tocilizumab was given at 8 mg/kg every 4 weeks, and patients who had been randomized to the monotherapy group were also given a placebo.

The study’s primary end point was the percentage of patients with DAS28-based remission at week 24. The results presented at the EULAR congress showed that tocilizumab monotherapy was similar in efficacy to the combination therapy.

In terms of the structural evaluation, the researchers looked at mean changes from baseline of the Genant-modified Sharp Score (GmSS) over the first 24 weeks of the trial. The overall changes in total scores, joint space–narrowing scores, or erosion scores were considerably less than expected. The researchers expected an increase in mean GmSS of 3.5-4.0, but none of the measures was greater than 1.0 for either group. "This suggests or confirms that tocilizumab is able to prevent structural deterioration," said Dr. Dougados. However, "we have not discovered any new information" in terms of safety, he added.

Data are pending on both the sustainability of the symptomatic effect at 1 year and the progression of structural damage at 1 and 2 years.

Dr. Dougados reported that he receives consulting fees and research grants from F. Hoffmann-La Roche, which sponsored the study. Several coauthors reported significant financial relationships with pharmaceutical companies, including Hoffmann-La Roche.

*Correction, 12/20/2011: An earlier version of this story had a headline that misstated the study findings.

SAN ANTONIO – Treatment with atorvastatin did not significantly change mammographic density after 1 year in a small randomized phase III study of premenopausal women at high risk for breast cancer.

While statins are widely used to prevent cardiovascular disease, it has been suggested that these drugs also may have a role in breast cancer prevention. Statin users are estimated to have a 30%-70% lower incidence of breast cancer, compared with nonusers, according to Dr. Marie E. Wood, professor of medicine and director of the familial cancer program at the University of Vermont, Burlington, and her coinvestigators.

A total of 63 premenopausal women were randomized to receive either 40 mg of atorvastatin (Lipitor) or placebo daily for a year. At the end of that time the investigators found no association between change in breast density and atorvastatin use in a multivariable linear regression analysis adjusted for age and body mass index. The data were presented in poster form at the San Antonio Breast Cancer Symposium.

The women had a mean age of 44 years and a mean body mass index (BMI) of 26.4 kg/m². Mammographic density was assessed using the Breast Imaging Reporting and Data System (BI-RADS), which is a standardized qualitative assessment of mammographic breast density with four categories.

Four percent of women had fatty-replaced breast tissue, 29% had scattered fibroglandular densities, 56% had heterogeneously dense breasts, and 11% had extremely dense breast tissue.

A total of 26% of women withdrew from the study – four because of side effects (headache, back pain, joint pain), six because of abnormal laboratory values, and the remainder for other reasons.

Baseline to 12-month changes in breast density were measured in all patients on a continuous scale using the visual analog scale method. Mean density at study entry was 31.6% and 32.4% at the end of treatment. Because of the skewed distribution of breast density change, a Wilcoxon signed-rank test was performed to determine if the change in breast density varied with treatment. No statistically significant difference was observed between the two treatment groups (P = .89).

Premenopausal women with regular menstrual cycles (four cycles in past 6 months) were eligible if they were at least 35 years of age and at increased risk of developing breast cancer. Increased risk was defined as having at least one of the following: a prior biopsy demonstrating atypical hyperplasia or lobular carcinoma in situ; BRCA1/2 mutation carrier (or mutation is in a family member); 5-year Gail Model Risk of greater than1.66%; a strong family history of breast and/or ovarian cancer; a prior history of breast cancer (ductal carcinoma in situ and stage 0-IIIb) and at least 1 year off of all therapy; and a history of chemoradiotherapy treatment for Hodgkin’s disease.

Women were excluded if they had a history of stage IV breast cancer or ovarian cancer; were already taking statins; were taking HRT, tamoxifen, raloxifene, an aromatase inhibitor; or were participating in another chemoprevention trial.

The researchers urged caution in interpreting the data, given the small sample size, slow accrual, wide variation in the mammographic density in this population, and the fact that mammograms were done during the transition to digital mammography.

"While the primary aim of this study was not met, we have shown that biomarker studies can be done in a multi-institutional setting ... Additional biomarker evaluation may prove informative," they wrote

Dr. Wood and her associates are currently analyzing the effect of a daily statin vs. placebo on markers of breast cancer risk, including mammographic density, serum markers (IGF-1), and tissue markers (atypia and Ki67).

This study is sponsored by the Breast Cancer Research Foundation and the Cancer and Leukemia Group B. The researchers reported that they have no relevant disclosures.

SAN ANTONIO – Treatment with atorvastatin did not significantly change mammographic density after 1 year in a small randomized phase III study of premenopausal women at high risk for breast cancer.

While statins are widely used to prevent cardiovascular disease, it has been suggested that these drugs also may have a role in breast cancer prevention. Statin users are estimated to have a 30%-70% lower incidence of breast cancer, compared with nonusers, according to Dr. Marie E. Wood, professor of medicine and director of the familial cancer program at the University of Vermont, Burlington, and her coinvestigators.

A total of 63 premenopausal women were randomized to receive either 40 mg of atorvastatin (Lipitor) or placebo daily for a year. At the end of that time the investigators found no association between change in breast density and atorvastatin use in a multivariable linear regression analysis adjusted for age and body mass index. The data were presented in poster form at the San Antonio Breast Cancer Symposium.

The women had a mean age of 44 years and a mean body mass index (BMI) of 26.4 kg/m². Mammographic density was assessed using the Breast Imaging Reporting and Data System (BI-RADS), which is a standardized qualitative assessment of mammographic breast density with four categories.

Four percent of women had fatty-replaced breast tissue, 29% had scattered fibroglandular densities, 56% had heterogeneously dense breasts, and 11% had extremely dense breast tissue.

A total of 26% of women withdrew from the study – four because of side effects (headache, back pain, joint pain), six because of abnormal laboratory values, and the remainder for other reasons.

Baseline to 12-month changes in breast density were measured in all patients on a continuous scale using the visual analog scale method. Mean density at study entry was 31.6% and 32.4% at the end of treatment. Because of the skewed distribution of breast density change, a Wilcoxon signed-rank test was performed to determine if the change in breast density varied with treatment. No statistically significant difference was observed between the two treatment groups (P = .89).

Premenopausal women with regular menstrual cycles (four cycles in past 6 months) were eligible if they were at least 35 years of age and at increased risk of developing breast cancer. Increased risk was defined as having at least one of the following: a prior biopsy demonstrating atypical hyperplasia or lobular carcinoma in situ; BRCA1/2 mutation carrier (or mutation is in a family member); 5-year Gail Model Risk of greater than1.66%; a strong family history of breast and/or ovarian cancer; a prior history of breast cancer (ductal carcinoma in situ and stage 0-IIIb) and at least 1 year off of all therapy; and a history of chemoradiotherapy treatment for Hodgkin’s disease.

Women were excluded if they had a history of stage IV breast cancer or ovarian cancer; were already taking statins; were taking HRT, tamoxifen, raloxifene, an aromatase inhibitor; or were participating in another chemoprevention trial.

The researchers urged caution in interpreting the data, given the small sample size, slow accrual, wide variation in the mammographic density in this population, and the fact that mammograms were done during the transition to digital mammography.

"While the primary aim of this study was not met, we have shown that biomarker studies can be done in a multi-institutional setting ... Additional biomarker evaluation may prove informative," they wrote

Dr. Wood and her associates are currently analyzing the effect of a daily statin vs. placebo on markers of breast cancer risk, including mammographic density, serum markers (IGF-1), and tissue markers (atypia and Ki67).

This study is sponsored by the Breast Cancer Research Foundation and the Cancer and Leukemia Group B. The researchers reported that they have no relevant disclosures.

SAN ANTONIO – Treatment with atorvastatin did not significantly change mammographic density after 1 year in a small randomized phase III study of premenopausal women at high risk for breast cancer.

While statins are widely used to prevent cardiovascular disease, it has been suggested that these drugs also may have a role in breast cancer prevention. Statin users are estimated to have a 30%-70% lower incidence of breast cancer, compared with nonusers, according to Dr. Marie E. Wood, professor of medicine and director of the familial cancer program at the University of Vermont, Burlington, and her coinvestigators.

A total of 63 premenopausal women were randomized to receive either 40 mg of atorvastatin (Lipitor) or placebo daily for a year. At the end of that time the investigators found no association between change in breast density and atorvastatin use in a multivariable linear regression analysis adjusted for age and body mass index. The data were presented in poster form at the San Antonio Breast Cancer Symposium.

The women had a mean age of 44 years and a mean body mass index (BMI) of 26.4 kg/m². Mammographic density was assessed using the Breast Imaging Reporting and Data System (BI-RADS), which is a standardized qualitative assessment of mammographic breast density with four categories.

Four percent of women had fatty-replaced breast tissue, 29% had scattered fibroglandular densities, 56% had heterogeneously dense breasts, and 11% had extremely dense breast tissue.

A total of 26% of women withdrew from the study – four because of side effects (headache, back pain, joint pain), six because of abnormal laboratory values, and the remainder for other reasons.

Baseline to 12-month changes in breast density were measured in all patients on a continuous scale using the visual analog scale method. Mean density at study entry was 31.6% and 32.4% at the end of treatment. Because of the skewed distribution of breast density change, a Wilcoxon signed-rank test was performed to determine if the change in breast density varied with treatment. No statistically significant difference was observed between the two treatment groups (P = .89).

Premenopausal women with regular menstrual cycles (four cycles in past 6 months) were eligible if they were at least 35 years of age and at increased risk of developing breast cancer. Increased risk was defined as having at least one of the following: a prior biopsy demonstrating atypical hyperplasia or lobular carcinoma in situ; BRCA1/2 mutation carrier (or mutation is in a family member); 5-year Gail Model Risk of greater than1.66%; a strong family history of breast and/or ovarian cancer; a prior history of breast cancer (ductal carcinoma in situ and stage 0-IIIb) and at least 1 year off of all therapy; and a history of chemoradiotherapy treatment for Hodgkin’s disease.

Women were excluded if they had a history of stage IV breast cancer or ovarian cancer; were already taking statins; were taking HRT, tamoxifen, raloxifene, an aromatase inhibitor; or were participating in another chemoprevention trial.

The researchers urged caution in interpreting the data, given the small sample size, slow accrual, wide variation in the mammographic density in this population, and the fact that mammograms were done during the transition to digital mammography.

"While the primary aim of this study was not met, we have shown that biomarker studies can be done in a multi-institutional setting ... Additional biomarker evaluation may prove informative," they wrote

Dr. Wood and her associates are currently analyzing the effect of a daily statin vs. placebo on markers of breast cancer risk, including mammographic density, serum markers (IGF-1), and tissue markers (atypia and Ki67).

This study is sponsored by the Breast Cancer Research Foundation and the Cancer and Leukemia Group B. The researchers reported that they have no relevant disclosures.

SAN ANTONIO – Bevacizumab improved progression-free survival when added to standard treatment in a study of more than 400 women with HER2-positive locally recurrent or metastatic breast cancer.

That finding, which emerged from the AVEREL trial, adds another wrinkle in the ongoing controversy regarding use of bevacizumab (Avastin) in breast cancer treatment.

For the primary end point of investigator-assessed progression-free survival (PFS), conducted at a median follow-up of 26 months, the addition of bevacizumab resulted in a hazard ratio of 0.82 (P = .0775), compared with treatment with trastuzumab and docetaxel alone. This difference was not statistically significant. Median investigator-assessed PFS was 16.5 months with bevacizumab, compared with 13.7 months without it.

In an assessment by an independent review committee (IRC), however, a significant improvement in PFS was seen with the addition of bevacizumab (hazard ratio, 0.72; P = .0162). Median IRC-assessed PFS was 16.8 months with bevacizumab, compared with 13.9 months without it.

Lead investigator Dr. Luca Gianni reported the results at the San Antonio Breast Cancer Symposium. AVEREL is a randomized, placebo-controlled phase III trial designed to evaluate bevacizumab combined with trastuzumab (Herceptin) and docetaxel (Taxotere) as first-line therapy for HER2-positive, locally recurrent or metastatic breast cancer.

The findings add more data to support the effectiveness of the drug in particular subpopulations of patients with metastatic breast cancer.

In November 2011, the Food and Drug Administration announced it was revoking its approval of the metastatic breast cancer indication for bevacizumab after concluding the drug had not been shown safe and effective for that use.

Many in the breast cancer community consider the agency’s decision unwarranted. "Bevacizumab improves the response rate – about doubles it – which for my symptomatic patients is a clear benefit," said press conference moderator Dr. Lisa Carey, professor in the department of medicine at the University of North Carolina at Chapel Hill. "It improves the progression-free survival to a greater or lesser degree in every trial that it’s ever been studied."

She conceded that "it doesn’t do anything to overall survival." The FDA cited the lack of improvement in overall survival for metastatic breast cancer patients in its decision. Dr. Gianni noted, however, that "Survival is a very important end point, but it’s not the only end point in metastatic breast cancer."

Dr. Carey agreed. "I would love to have the availability of the drug routinely for my symptomatic patients, in whom I would like to have more than one agent given – particularly one that’s well-tolerated as [bevacizumab] is."

Patients were eligible for the AVEREL trial if they had measurable or evaluable HER2-positive locally recurrent or metastatic breast cancer with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. They could not have received prior chemotherapy for advanced disease. Patients with central nervous system metastases were excluded.

The researchers enrolled 424 women with previously untreated disease. The women were randomized to receive either trastuzumab plus docetaxel (n = 208) or the same regimen plus bevacizumab (n = 216). Intravenous trastuzumab was given with an 8-mg/kg loading dose that was followed by a dosage of 6 mg/kg given every 3 weeks. Docetaxel was given intravenously at a dosage of 100 mg/m² given every 3 weeks. Bevacizumab was given intravenously at a dosage of 15 mg/kg every 3 weeks.

Trastuzumab and bevacizumab were given until disease progression. Docetaxel was given for a planned minimum of six cycles or until progression or unacceptable toxicity occurred. The primary end point was investigator-assessed PFS. Secondary end points included overall survival (OS), overall response rate, duration of response, time to treatment failure, safety (including adverse events of special interest for bevacizumab), and quality of life. Exploratory analyses included PFS evaluated by an IRC (to comply with FDA recommendations) and biomarker assessment.

In terms of safety, "There were no new safety signals observed in this patient population with respect to what we really know from other patient populations exposed to Avastin," said Dr. Gianni, director of medical oncology at the San Raffaele Cancer Center in Milano, Italy.

The researchers also conducted an exploratory analyses of plasma vascular endothelial growth factor-alpha (VEGF-A). Their results suggest a potentially predictive effect – greater benefit with high VEGF-A levels – that are consistent with observations in HER2-negative locally recurrent or metastatic breast cancer.

The AVEREL trial was sponsored by Hoffman-La Roche. Dr. Gianni has disclosed that he is a consultant to Roche, Genentech, GSK, Wyeth, Novartis, Eisai, Pfizer, Millennium Takeda, Sanofi Aventis, Boehringer Ingelheim, Biogen Idec, AstraZeneca, Genomic Health, and Celgene. Dr. Carey reported that she has no relevant financial relationships to disclose.

*Correction, 12/9/11: An earlier version of this article incorrectly noted in the headline that Avastin improves breast cancer survival.

SAN ANTONIO – Bevacizumab improved progression-free survival when added to standard treatment in a study of more than 400 women with HER2-positive locally recurrent or metastatic breast cancer.

That finding, which emerged from the AVEREL trial, adds another wrinkle in the ongoing controversy regarding use of bevacizumab (Avastin) in breast cancer treatment.

For the primary end point of investigator-assessed progression-free survival (PFS), conducted at a median follow-up of 26 months, the addition of bevacizumab resulted in a hazard ratio of 0.82 (P = .0775), compared with treatment with trastuzumab and docetaxel alone. This difference was not statistically significant. Median investigator-assessed PFS was 16.5 months with bevacizumab, compared with 13.7 months without it.

In an assessment by an independent review committee (IRC), however, a significant improvement in PFS was seen with the addition of bevacizumab (hazard ratio, 0.72; P = .0162). Median IRC-assessed PFS was 16.8 months with bevacizumab, compared with 13.9 months without it.

Lead investigator Dr. Luca Gianni reported the results at the San Antonio Breast Cancer Symposium. AVEREL is a randomized, placebo-controlled phase III trial designed to evaluate bevacizumab combined with trastuzumab (Herceptin) and docetaxel (Taxotere) as first-line therapy for HER2-positive, locally recurrent or metastatic breast cancer.

The findings add more data to support the effectiveness of the drug in particular subpopulations of patients with metastatic breast cancer.

In November 2011, the Food and Drug Administration announced it was revoking its approval of the metastatic breast cancer indication for bevacizumab after concluding the drug had not been shown safe and effective for that use.

Many in the breast cancer community consider the agency’s decision unwarranted. "Bevacizumab improves the response rate – about doubles it – which for my symptomatic patients is a clear benefit," said press conference moderator Dr. Lisa Carey, professor in the department of medicine at the University of North Carolina at Chapel Hill. "It improves the progression-free survival to a greater or lesser degree in every trial that it’s ever been studied."

She conceded that "it doesn’t do anything to overall survival." The FDA cited the lack of improvement in overall survival for metastatic breast cancer patients in its decision. Dr. Gianni noted, however, that "Survival is a very important end point, but it’s not the only end point in metastatic breast cancer."

Dr. Carey agreed. "I would love to have the availability of the drug routinely for my symptomatic patients, in whom I would like to have more than one agent given – particularly one that’s well-tolerated as [bevacizumab] is."

Patients were eligible for the AVEREL trial if they had measurable or evaluable HER2-positive locally recurrent or metastatic breast cancer with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. They could not have received prior chemotherapy for advanced disease. Patients with central nervous system metastases were excluded.

The researchers enrolled 424 women with previously untreated disease. The women were randomized to receive either trastuzumab plus docetaxel (n = 208) or the same regimen plus bevacizumab (n = 216). Intravenous trastuzumab was given with an 8-mg/kg loading dose that was followed by a dosage of 6 mg/kg given every 3 weeks. Docetaxel was given intravenously at a dosage of 100 mg/m² given every 3 weeks. Bevacizumab was given intravenously at a dosage of 15 mg/kg every 3 weeks.

Trastuzumab and bevacizumab were given until disease progression. Docetaxel was given for a planned minimum of six cycles or until progression or unacceptable toxicity occurred. The primary end point was investigator-assessed PFS. Secondary end points included overall survival (OS), overall response rate, duration of response, time to treatment failure, safety (including adverse events of special interest for bevacizumab), and quality of life. Exploratory analyses included PFS evaluated by an IRC (to comply with FDA recommendations) and biomarker assessment.

In terms of safety, "There were no new safety signals observed in this patient population with respect to what we really know from other patient populations exposed to Avastin," said Dr. Gianni, director of medical oncology at the San Raffaele Cancer Center in Milano, Italy.

The researchers also conducted an exploratory analyses of plasma vascular endothelial growth factor-alpha (VEGF-A). Their results suggest a potentially predictive effect – greater benefit with high VEGF-A levels – that are consistent with observations in HER2-negative locally recurrent or metastatic breast cancer.

The AVEREL trial was sponsored by Hoffman-La Roche. Dr. Gianni has disclosed that he is a consultant to Roche, Genentech, GSK, Wyeth, Novartis, Eisai, Pfizer, Millennium Takeda, Sanofi Aventis, Boehringer Ingelheim, Biogen Idec, AstraZeneca, Genomic Health, and Celgene. Dr. Carey reported that she has no relevant financial relationships to disclose.

*Correction, 12/9/11: An earlier version of this article incorrectly noted in the headline that Avastin improves breast cancer survival.

SAN ANTONIO – Bevacizumab improved progression-free survival when added to standard treatment in a study of more than 400 women with HER2-positive locally recurrent or metastatic breast cancer.

That finding, which emerged from the AVEREL trial, adds another wrinkle in the ongoing controversy regarding use of bevacizumab (Avastin) in breast cancer treatment.

For the primary end point of investigator-assessed progression-free survival (PFS), conducted at a median follow-up of 26 months, the addition of bevacizumab resulted in a hazard ratio of 0.82 (P = .0775), compared with treatment with trastuzumab and docetaxel alone. This difference was not statistically significant. Median investigator-assessed PFS was 16.5 months with bevacizumab, compared with 13.7 months without it.

In an assessment by an independent review committee (IRC), however, a significant improvement in PFS was seen with the addition of bevacizumab (hazard ratio, 0.72; P = .0162). Median IRC-assessed PFS was 16.8 months with bevacizumab, compared with 13.9 months without it.

Lead investigator Dr. Luca Gianni reported the results at the San Antonio Breast Cancer Symposium. AVEREL is a randomized, placebo-controlled phase III trial designed to evaluate bevacizumab combined with trastuzumab (Herceptin) and docetaxel (Taxotere) as first-line therapy for HER2-positive, locally recurrent or metastatic breast cancer.

The findings add more data to support the effectiveness of the drug in particular subpopulations of patients with metastatic breast cancer.

In November 2011, the Food and Drug Administration announced it was revoking its approval of the metastatic breast cancer indication for bevacizumab after concluding the drug had not been shown safe and effective for that use.

Many in the breast cancer community consider the agency’s decision unwarranted. "Bevacizumab improves the response rate – about doubles it – which for my symptomatic patients is a clear benefit," said press conference moderator Dr. Lisa Carey, professor in the department of medicine at the University of North Carolina at Chapel Hill. "It improves the progression-free survival to a greater or lesser degree in every trial that it’s ever been studied."

She conceded that "it doesn’t do anything to overall survival." The FDA cited the lack of improvement in overall survival for metastatic breast cancer patients in its decision. Dr. Gianni noted, however, that "Survival is a very important end point, but it’s not the only end point in metastatic breast cancer."

Dr. Carey agreed. "I would love to have the availability of the drug routinely for my symptomatic patients, in whom I would like to have more than one agent given – particularly one that’s well-tolerated as [bevacizumab] is."

Patients were eligible for the AVEREL trial if they had measurable or evaluable HER2-positive locally recurrent or metastatic breast cancer with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. They could not have received prior chemotherapy for advanced disease. Patients with central nervous system metastases were excluded.

The researchers enrolled 424 women with previously untreated disease. The women were randomized to receive either trastuzumab plus docetaxel (n = 208) or the same regimen plus bevacizumab (n = 216). Intravenous trastuzumab was given with an 8-mg/kg loading dose that was followed by a dosage of 6 mg/kg given every 3 weeks. Docetaxel was given intravenously at a dosage of 100 mg/m² given every 3 weeks. Bevacizumab was given intravenously at a dosage of 15 mg/kg every 3 weeks.

Trastuzumab and bevacizumab were given until disease progression. Docetaxel was given for a planned minimum of six cycles or until progression or unacceptable toxicity occurred. The primary end point was investigator-assessed PFS. Secondary end points included overall survival (OS), overall response rate, duration of response, time to treatment failure, safety (including adverse events of special interest for bevacizumab), and quality of life. Exploratory analyses included PFS evaluated by an IRC (to comply with FDA recommendations) and biomarker assessment.

In terms of safety, "There were no new safety signals observed in this patient population with respect to what we really know from other patient populations exposed to Avastin," said Dr. Gianni, director of medical oncology at the San Raffaele Cancer Center in Milano, Italy.

The researchers also conducted an exploratory analyses of plasma vascular endothelial growth factor-alpha (VEGF-A). Their results suggest a potentially predictive effect – greater benefit with high VEGF-A levels – that are consistent with observations in HER2-negative locally recurrent or metastatic breast cancer.

The AVEREL trial was sponsored by Hoffman-La Roche. Dr. Gianni has disclosed that he is a consultant to Roche, Genentech, GSK, Wyeth, Novartis, Eisai, Pfizer, Millennium Takeda, Sanofi Aventis, Boehringer Ingelheim, Biogen Idec, AstraZeneca, Genomic Health, and Celgene. Dr. Carey reported that she has no relevant financial relationships to disclose.

*Correction, 12/9/11: An earlier version of this article incorrectly noted in the headline that Avastin improves breast cancer survival.

NEW YORK – Ultrasound-accelerated thrombolysis treatment of submassive pulmonary embolism reduced right ventricular dilatation and the risk of heart failure, according to the results of a retrospective study of 29 patients at one facility.

"My end point is not so much seeing 100% clot clearance. My main goal of therapy is to see that regression of the right ventricle. We want to see that [right ventricle/left ventricle] ratio go back to normal to prevent long-term sequelae," said Dr. Tod C. Engelhardt, who presented the study results at the Veith Symposium on Vascular Medicine sponsored by the Cleveland Clinic.

Dr. Engelhardt and his colleagues found that ultrasound-accelerated thrombolysis (USAT) significantly reduced the right ventricle/left ventricle (RV/LV) ratio from 1.37 to 1.02 following treatment. All patients survived to hospital discharge, with a median time to follow-up CT of less than 48 hours. Symptoms such as dyspnea and difficulty speaking resolved 2-3 hours after the initiation of treatment.

"This is an interesting group because when they present, they don’t look too bad on paper or clinically," he said. These patients usually have normal blood pressure with minimal oxygen supplementation, but more than 90% have some dyspnea with exertion. About 40% of patients with PE have the submassive type, which has a 90-day mortality of 22%, compared with 58% for massive PE.

"The thing that separates them is right ventricular enlargement. They have impending right heart failure because of the right ventricular dilatation." An RV/LV ratio greater than 0.9 is considered significant, noted Dr. Engelhardt, chair of cardiovascular and thoracic surgery at East Jefferson General Hospital in Metairie, La.

Patients with persistent RV dysfunction at discharge are approximately eight times more likely to have recurrent PE and four times more likely to die, compared with patients in whom RV dysfunction had regressed at discharge.

"There has to be a high index of suspicion of PE," he said in an interview. Usually the emergency physician will have chest computed tomographic angiography (CTA) done. "Once you get the scan, you can see the PE and the right heart size. Then I get an echocardiogram and a duplex scan of the lower extremities" to look for deep vein thrombosis.

However, "I have found that the CTA gives me everything that I need in order to make a decision and to proceed with therapy. The CTA does two things for me. I can see the extent of the involvement of the pulmonary embolism, and I can measure the relative sizes of the right and left ventricles to generate that ratio. This allows me to categorize the patient as a submassive PE patient and to move forward with therapy," he said.

"Patients with massive and submassive emboli can be treated with USAT."

Once the diagnosis of PE is made, the patient is started on anticoagulant therapy. "I don’t think that hinders what I do; in fact, it complements it."

With a submassive PE patient, "once I make the diagnosis and the patient is already anticoagulated, my next step is to move to the cath lab to place catheters and start [USAT] treatment."

With USAT, ultrasound energy causes fibrin strands to thin and loosen, exposing plasminogen receptor sites. Thrombus permeability and thrombolytic penetration are dramatically increased. Ultrasonic pressure waves force the thrombolytic deep into the clot, allowing the drug to work faster and clear the clot sooner with a lower drug dose and without hemolysis.

The goal of USAT is to accelerate thrombolysis and rapidly reverse right ventricular dilatation and reduce pulmonary clot burden. This improves pulmonary perfusion and reduces right heart load. Because a lower drug dose (no more than 20 mg of recombinant tissue plasminogen activator [TPA]) is used than with conventional treatment, the risk of bleeding is significantly lowered. Aggressive management of submassive PE can prevent more harmful consequences later, according to Dr. Engelhardt.

Dr. Engelhardt reported on the experience at his center, where surgeons treated 32 PE patients with ultrasound-accelerated thrombolysis between February 2009 and June 2011.

They performed retrospective data analysis on 29 consecutive patients with pre- and posttreatment contrast-enhanced CT imaging, clinical history, RV/LV ratio reduction, and clot burden reduction. They used this information to identify the optimum drug dose as a maximum of 20 mg recombinant TPA over 12 hours. This dose resulted in good clinical outcomes with no bleeding complications.

Adverse effects were limited. There were no intracranial hemorrhages or systemic bleeding complications. Four patients had puncture site bleeding that required transfusion. One patient had suspected recurrent PE.

Although there has been "trepidation in changing the status quo of anticoagulation alone," he said, "patients with massive and submassive emboli can be treated with USAT. Certainly patients who are in cardiogenic shock may have time for a catheter placement and can be treated with systemic TPA. Many massive PE patients can be resuscitated so that they do have time for catheter placement."

The catheters are inserted over a 0.35-inch guidewire through the femoral vein. "When I first started doing this – the first 10 or so patients – I did bilateral groin sticks because I’m placing bilateral pulmonary artery catheters," Dr. Engelhardt said.

He now uses a 10-French catheter that has two ports. "So I can now put catheters in each port and feed one into the right and one into the left." The catheter includes small ultrasound transducers and allows for thrombolytic drug delivery.

"I developed a protocol when I first started doing these cases. I was giving a bolus dose down each side – 4 mg each side – then I would run it for 12 hours at 0.5 mg per side. Since then, I’ve decided not to give a bolus dose but to run 0.5 mg per side for 20 hours." He now administers 20 mg total because he found that larger doses provide the same results as 20 mg but with complications such as groin hematomas.

"These catheters treat only what they’re in contact with, so I try to get these catheters as far into the periphery of the lung as I can. I’ve never had a perforation," he said.

Dr. Engelhardt is a consultant to EKOS Corp., which makes the ultrasound device.

NEW YORK – Ultrasound-accelerated thrombolysis treatment of submassive pulmonary embolism reduced right ventricular dilatation and the risk of heart failure, according to the results of a retrospective study of 29 patients at one facility.

"My end point is not so much seeing 100% clot clearance. My main goal of therapy is to see that regression of the right ventricle. We want to see that [right ventricle/left ventricle] ratio go back to normal to prevent long-term sequelae," said Dr. Tod C. Engelhardt, who presented the study results at the Veith Symposium on Vascular Medicine sponsored by the Cleveland Clinic.

Dr. Engelhardt and his colleagues found that ultrasound-accelerated thrombolysis (USAT) significantly reduced the right ventricle/left ventricle (RV/LV) ratio from 1.37 to 1.02 following treatment. All patients survived to hospital discharge, with a median time to follow-up CT of less than 48 hours. Symptoms such as dyspnea and difficulty speaking resolved 2-3 hours after the initiation of treatment.

"This is an interesting group because when they present, they don’t look too bad on paper or clinically," he said. These patients usually have normal blood pressure with minimal oxygen supplementation, but more than 90% have some dyspnea with exertion. About 40% of patients with PE have the submassive type, which has a 90-day mortality of 22%, compared with 58% for massive PE.

"The thing that separates them is right ventricular enlargement. They have impending right heart failure because of the right ventricular dilatation." An RV/LV ratio greater than 0.9 is considered significant, noted Dr. Engelhardt, chair of cardiovascular and thoracic surgery at East Jefferson General Hospital in Metairie, La.

Patients with persistent RV dysfunction at discharge are approximately eight times more likely to have recurrent PE and four times more likely to die, compared with patients in whom RV dysfunction had regressed at discharge.

"There has to be a high index of suspicion of PE," he said in an interview. Usually the emergency physician will have chest computed tomographic angiography (CTA) done. "Once you get the scan, you can see the PE and the right heart size. Then I get an echocardiogram and a duplex scan of the lower extremities" to look for deep vein thrombosis.

However, "I have found that the CTA gives me everything that I need in order to make a decision and to proceed with therapy. The CTA does two things for me. I can see the extent of the involvement of the pulmonary embolism, and I can measure the relative sizes of the right and left ventricles to generate that ratio. This allows me to categorize the patient as a submassive PE patient and to move forward with therapy," he said.

"Patients with massive and submassive emboli can be treated with USAT."

Once the diagnosis of PE is made, the patient is started on anticoagulant therapy. "I don’t think that hinders what I do; in fact, it complements it."

With a submassive PE patient, "once I make the diagnosis and the patient is already anticoagulated, my next step is to move to the cath lab to place catheters and start [USAT] treatment."

With USAT, ultrasound energy causes fibrin strands to thin and loosen, exposing plasminogen receptor sites. Thrombus permeability and thrombolytic penetration are dramatically increased. Ultrasonic pressure waves force the thrombolytic deep into the clot, allowing the drug to work faster and clear the clot sooner with a lower drug dose and without hemolysis.

The goal of USAT is to accelerate thrombolysis and rapidly reverse right ventricular dilatation and reduce pulmonary clot burden. This improves pulmonary perfusion and reduces right heart load. Because a lower drug dose (no more than 20 mg of recombinant tissue plasminogen activator [TPA]) is used than with conventional treatment, the risk of bleeding is significantly lowered. Aggressive management of submassive PE can prevent more harmful consequences later, according to Dr. Engelhardt.

Dr. Engelhardt reported on the experience at his center, where surgeons treated 32 PE patients with ultrasound-accelerated thrombolysis between February 2009 and June 2011.

They performed retrospective data analysis on 29 consecutive patients with pre- and posttreatment contrast-enhanced CT imaging, clinical history, RV/LV ratio reduction, and clot burden reduction. They used this information to identify the optimum drug dose as a maximum of 20 mg recombinant TPA over 12 hours. This dose resulted in good clinical outcomes with no bleeding complications.

Adverse effects were limited. There were no intracranial hemorrhages or systemic bleeding complications. Four patients had puncture site bleeding that required transfusion. One patient had suspected recurrent PE.

Although there has been "trepidation in changing the status quo of anticoagulation alone," he said, "patients with massive and submassive emboli can be treated with USAT. Certainly patients who are in cardiogenic shock may have time for a catheter placement and can be treated with systemic TPA. Many massive PE patients can be resuscitated so that they do have time for catheter placement."

The catheters are inserted over a 0.35-inch guidewire through the femoral vein. "When I first started doing this – the first 10 or so patients – I did bilateral groin sticks because I’m placing bilateral pulmonary artery catheters," Dr. Engelhardt said.

He now uses a 10-French catheter that has two ports. "So I can now put catheters in each port and feed one into the right and one into the left." The catheter includes small ultrasound transducers and allows for thrombolytic drug delivery.

"I developed a protocol when I first started doing these cases. I was giving a bolus dose down each side – 4 mg each side – then I would run it for 12 hours at 0.5 mg per side. Since then, I’ve decided not to give a bolus dose but to run 0.5 mg per side for 20 hours." He now administers 20 mg total because he found that larger doses provide the same results as 20 mg but with complications such as groin hematomas.

"These catheters treat only what they’re in contact with, so I try to get these catheters as far into the periphery of the lung as I can. I’ve never had a perforation," he said.

Dr. Engelhardt is a consultant to EKOS Corp., which makes the ultrasound device.

NEW YORK – Ultrasound-accelerated thrombolysis treatment of submassive pulmonary embolism reduced right ventricular dilatation and the risk of heart failure, according to the results of a retrospective study of 29 patients at one facility.

"My end point is not so much seeing 100% clot clearance. My main goal of therapy is to see that regression of the right ventricle. We want to see that [right ventricle/left ventricle] ratio go back to normal to prevent long-term sequelae," said Dr. Tod C. Engelhardt, who presented the study results at the Veith Symposium on Vascular Medicine sponsored by the Cleveland Clinic.

Dr. Engelhardt and his colleagues found that ultrasound-accelerated thrombolysis (USAT) significantly reduced the right ventricle/left ventricle (RV/LV) ratio from 1.37 to 1.02 following treatment. All patients survived to hospital discharge, with a median time to follow-up CT of less than 48 hours. Symptoms such as dyspnea and difficulty speaking resolved 2-3 hours after the initiation of treatment.

"This is an interesting group because when they present, they don’t look too bad on paper or clinically," he said. These patients usually have normal blood pressure with minimal oxygen supplementation, but more than 90% have some dyspnea with exertion. About 40% of patients with PE have the submassive type, which has a 90-day mortality of 22%, compared with 58% for massive PE.

"The thing that separates them is right ventricular enlargement. They have impending right heart failure because of the right ventricular dilatation." An RV/LV ratio greater than 0.9 is considered significant, noted Dr. Engelhardt, chair of cardiovascular and thoracic surgery at East Jefferson General Hospital in Metairie, La.

Patients with persistent RV dysfunction at discharge are approximately eight times more likely to have recurrent PE and four times more likely to die, compared with patients in whom RV dysfunction had regressed at discharge.

"There has to be a high index of suspicion of PE," he said in an interview. Usually the emergency physician will have chest computed tomographic angiography (CTA) done. "Once you get the scan, you can see the PE and the right heart size. Then I get an echocardiogram and a duplex scan of the lower extremities" to look for deep vein thrombosis.

However, "I have found that the CTA gives me everything that I need in order to make a decision and to proceed with therapy. The CTA does two things for me. I can see the extent of the involvement of the pulmonary embolism, and I can measure the relative sizes of the right and left ventricles to generate that ratio. This allows me to categorize the patient as a submassive PE patient and to move forward with therapy," he said.

"Patients with massive and submassive emboli can be treated with USAT."

Once the diagnosis of PE is made, the patient is started on anticoagulant therapy. "I don’t think that hinders what I do; in fact, it complements it."

With a submassive PE patient, "once I make the diagnosis and the patient is already anticoagulated, my next step is to move to the cath lab to place catheters and start [USAT] treatment."

With USAT, ultrasound energy causes fibrin strands to thin and loosen, exposing plasminogen receptor sites. Thrombus permeability and thrombolytic penetration are dramatically increased. Ultrasonic pressure waves force the thrombolytic deep into the clot, allowing the drug to work faster and clear the clot sooner with a lower drug dose and without hemolysis.

The goal of USAT is to accelerate thrombolysis and rapidly reverse right ventricular dilatation and reduce pulmonary clot burden. This improves pulmonary perfusion and reduces right heart load. Because a lower drug dose (no more than 20 mg of recombinant tissue plasminogen activator [TPA]) is used than with conventional treatment, the risk of bleeding is significantly lowered. Aggressive management of submassive PE can prevent more harmful consequences later, according to Dr. Engelhardt.

Dr. Engelhardt reported on the experience at his center, where surgeons treated 32 PE patients with ultrasound-accelerated thrombolysis between February 2009 and June 2011.

They performed retrospective data analysis on 29 consecutive patients with pre- and posttreatment contrast-enhanced CT imaging, clinical history, RV/LV ratio reduction, and clot burden reduction. They used this information to identify the optimum drug dose as a maximum of 20 mg recombinant TPA over 12 hours. This dose resulted in good clinical outcomes with no bleeding complications.

Adverse effects were limited. There were no intracranial hemorrhages or systemic bleeding complications. Four patients had puncture site bleeding that required transfusion. One patient had suspected recurrent PE.

Although there has been "trepidation in changing the status quo of anticoagulation alone," he said, "patients with massive and submassive emboli can be treated with USAT. Certainly patients who are in cardiogenic shock may have time for a catheter placement and can be treated with systemic TPA. Many massive PE patients can be resuscitated so that they do have time for catheter placement."

The catheters are inserted over a 0.35-inch guidewire through the femoral vein. "When I first started doing this – the first 10 or so patients – I did bilateral groin sticks because I’m placing bilateral pulmonary artery catheters," Dr. Engelhardt said.

He now uses a 10-French catheter that has two ports. "So I can now put catheters in each port and feed one into the right and one into the left." The catheter includes small ultrasound transducers and allows for thrombolytic drug delivery.

"I developed a protocol when I first started doing these cases. I was giving a bolus dose down each side – 4 mg each side – then I would run it for 12 hours at 0.5 mg per side. Since then, I’ve decided not to give a bolus dose but to run 0.5 mg per side for 20 hours." He now administers 20 mg total because he found that larger doses provide the same results as 20 mg but with complications such as groin hematomas.

"These catheters treat only what they’re in contact with, so I try to get these catheters as far into the periphery of the lung as I can. I’ve never had a perforation," he said.

Dr. Engelhardt is a consultant to EKOS Corp., which makes the ultrasound device.

 San Antonio – While treatment with the clodronate does not appear to affect disease-free survival among women with stages I-III breast cancer, the drug does appear to improve certain outcomes for women aged 50 years and older, according to the results of a phase III trial of more than 3,000 patients.

Disease-free survival (DFS) did not differ between women treated with clodronate and those given placebo (hazard ratio, 0.91; P = .27). However, women at least 50 years of age saw benefits in secondary protocol predefined end points, Dr. Alexander H.G. Paterson said at the San Antonio Breast Cancer Symposium.

"This is an easy treatment and it’s oral. It seems to have an effect in older women and low toxicity. We’ve now got four trials [pointing in] the same direction ... that is of a benefit in older patients," said Dr. Paterson, a professor in the departments of medicine and oncology at the University of Calgary in Canada.

In the double-blind, phase III National Surgical Adjuvant Breast and Bowel Project (NSABP) B-34 clinical trial, patients with stage I-III breast cancer were randomized to receive oral clodronate 1,600 mg daily for 3 years or placebo, given alone or in addition to adjuvant chemotherapy or hormone therapy. Patients also underwent surgery (lumpectomies or mastectomies) and received radiation therapy and chemotherapy or hormonal therapy.

The groups were stratified by age (younger than 50 years or at least 50 years), number of positive nodes and estrogen receptor/progesterone receptor (ER/PR) status. The primary end point was disease-free survival, which was defined to include all recurrences, deaths, and second primary cancers. Secondary end points are the incidence of skeletal metastases, overall survival, recurrence-free interval, bone metastasis–free interval, and nonbone metastasis–free interval.

The researchers reported on 3,311 patients (1,656 on placebo and 1,655 on clodronate) with a median of 8 years in the study. Of note, almost two-thirds of patients (64%) were at least 50 years old at the time of enrollment. Three-quarters had pathologically-negative axillary nodes and almost a quarter (22%) had ER-negative or PR-negative breast cancer.

"Compliance was an issue. The drop in compliance really occurred in the first 6 months, when patients were also receiving intravenous chemotherapy," said Dr. Paterson. A total of 40% of patients did not complete 3 years of study therapy.

Patients on clodronate had a slightly lower rate of treatment failure at distant sites (5.4% vs. 6.6%). The researchers suspect that the disease-free survival benefit was attenuated due to the equivalent event rates for second primary cancers, contralateral cancers and local/regional relapses.

Overall toxicity was low and comparable for the two groups. There was one case of osteonecrosis of the jaw in the clodronate group.

However, clodronate showed benefit regarding distant metastases in all protocol predefined secondary end points. Hazard reductions ranged from 15% for overall survival to 26% for nonbone metastasis–free interval.

Dr. Paterson noted that secondary protocol predefined end point reductions were even greater among women at least 50 years of age. For these women, there was a 24% reduction in breast cancer recurrence–free interval (P = .05), a 39% reduction in bone metastasis–free interval (P = .024), and a 37% reduction in nonbone metastasis–free interval (P = .015). In addition, women 50 years and older had a 20% reduction in overall survival, though this was not statistically significant (P = 0.1).

"Similar beneficial results in older postmenopausal women are seen in other studies involving bisphosphonates," he said.

Bisphosponates are thought to inhibit the growth of bone metastases by inhibiting osteoclast function and subsequent bone turnover. However, the role of bisphosphonates in preventing or delaying the development of bone (or other) metastases in patients with early breast cancer remains unclear.

The trial received support from the National Cancer Institute and Bayer Schering Pharma Oy. Dr. Paterson disclosed that he is a consultant for GlaxoSmithKline, Amgen, Roche Diagnostics, and Nicomed.

 San Antonio – While treatment with the clodronate does not appear to affect disease-free survival among women with stages I-III breast cancer, the drug does appear to improve certain outcomes for women aged 50 years and older, according to the results of a phase III trial of more than 3,000 patients.

Disease-free survival (DFS) did not differ between women treated with clodronate and those given placebo (hazard ratio, 0.91; P = .27). However, women at least 50 years of age saw benefits in secondary protocol predefined end points, Dr. Alexander H.G. Paterson said at the San Antonio Breast Cancer Symposium.

"This is an easy treatment and it’s oral. It seems to have an effect in older women and low toxicity. We’ve now got four trials [pointing in] the same direction ... that is of a benefit in older patients," said Dr. Paterson, a professor in the departments of medicine and oncology at the University of Calgary in Canada.

In the double-blind, phase III National Surgical Adjuvant Breast and Bowel Project (NSABP) B-34 clinical trial, patients with stage I-III breast cancer were randomized to receive oral clodronate 1,600 mg daily for 3 years or placebo, given alone or in addition to adjuvant chemotherapy or hormone therapy. Patients also underwent surgery (lumpectomies or mastectomies) and received radiation therapy and chemotherapy or hormonal therapy.

The groups were stratified by age (younger than 50 years or at least 50 years), number of positive nodes and estrogen receptor/progesterone receptor (ER/PR) status. The primary end point was disease-free survival, which was defined to include all recurrences, deaths, and second primary cancers. Secondary end points are the incidence of skeletal metastases, overall survival, recurrence-free interval, bone metastasis–free interval, and nonbone metastasis–free interval.

The researchers reported on 3,311 patients (1,656 on placebo and 1,655 on clodronate) with a median of 8 years in the study. Of note, almost two-thirds of patients (64%) were at least 50 years old at the time of enrollment. Three-quarters had pathologically-negative axillary nodes and almost a quarter (22%) had ER-negative or PR-negative breast cancer.

"Compliance was an issue. The drop in compliance really occurred in the first 6 months, when patients were also receiving intravenous chemotherapy," said Dr. Paterson. A total of 40% of patients did not complete 3 years of study therapy.

Patients on clodronate had a slightly lower rate of treatment failure at distant sites (5.4% vs. 6.6%). The researchers suspect that the disease-free survival benefit was attenuated due to the equivalent event rates for second primary cancers, contralateral cancers and local/regional relapses.

Overall toxicity was low and comparable for the two groups. There was one case of osteonecrosis of the jaw in the clodronate group.

However, clodronate showed benefit regarding distant metastases in all protocol predefined secondary end points. Hazard reductions ranged from 15% for overall survival to 26% for nonbone metastasis–free interval.

Dr. Paterson noted that secondary protocol predefined end point reductions were even greater among women at least 50 years of age. For these women, there was a 24% reduction in breast cancer recurrence–free interval (P = .05), a 39% reduction in bone metastasis–free interval (P = .024), and a 37% reduction in nonbone metastasis–free interval (P = .015). In addition, women 50 years and older had a 20% reduction in overall survival, though this was not statistically significant (P = 0.1).

"Similar beneficial results in older postmenopausal women are seen in other studies involving bisphosphonates," he said.

Bisphosponates are thought to inhibit the growth of bone metastases by inhibiting osteoclast function and subsequent bone turnover. However, the role of bisphosphonates in preventing or delaying the development of bone (or other) metastases in patients with early breast cancer remains unclear.

The trial received support from the National Cancer Institute and Bayer Schering Pharma Oy. Dr. Paterson disclosed that he is a consultant for GlaxoSmithKline, Amgen, Roche Diagnostics, and Nicomed.

 San Antonio – While treatment with the clodronate does not appear to affect disease-free survival among women with stages I-III breast cancer, the drug does appear to improve certain outcomes for women aged 50 years and older, according to the results of a phase III trial of more than 3,000 patients.

Disease-free survival (DFS) did not differ between women treated with clodronate and those given placebo (hazard ratio, 0.91; P = .27). However, women at least 50 years of age saw benefits in secondary protocol predefined end points, Dr. Alexander H.G. Paterson said at the San Antonio Breast Cancer Symposium.

"This is an easy treatment and it’s oral. It seems to have an effect in older women and low toxicity. We’ve now got four trials [pointing in] the same direction ... that is of a benefit in older patients," said Dr. Paterson, a professor in the departments of medicine and oncology at the University of Calgary in Canada.

In the double-blind, phase III National Surgical Adjuvant Breast and Bowel Project (NSABP) B-34 clinical trial, patients with stage I-III breast cancer were randomized to receive oral clodronate 1,600 mg daily for 3 years or placebo, given alone or in addition to adjuvant chemotherapy or hormone therapy. Patients also underwent surgery (lumpectomies or mastectomies) and received radiation therapy and chemotherapy or hormonal therapy.

The groups were stratified by age (younger than 50 years or at least 50 years), number of positive nodes and estrogen receptor/progesterone receptor (ER/PR) status. The primary end point was disease-free survival, which was defined to include all recurrences, deaths, and second primary cancers. Secondary end points are the incidence of skeletal metastases, overall survival, recurrence-free interval, bone metastasis–free interval, and nonbone metastasis–free interval.

The researchers reported on 3,311 patients (1,656 on placebo and 1,655 on clodronate) with a median of 8 years in the study. Of note, almost two-thirds of patients (64%) were at least 50 years old at the time of enrollment. Three-quarters had pathologically-negative axillary nodes and almost a quarter (22%) had ER-negative or PR-negative breast cancer.

"Compliance was an issue. The drop in compliance really occurred in the first 6 months, when patients were also receiving intravenous chemotherapy," said Dr. Paterson. A total of 40% of patients did not complete 3 years of study therapy.

Patients on clodronate had a slightly lower rate of treatment failure at distant sites (5.4% vs. 6.6%). The researchers suspect that the disease-free survival benefit was attenuated due to the equivalent event rates for second primary cancers, contralateral cancers and local/regional relapses.

Overall toxicity was low and comparable for the two groups. There was one case of osteonecrosis of the jaw in the clodronate group.

However, clodronate showed benefit regarding distant metastases in all protocol predefined secondary end points. Hazard reductions ranged from 15% for overall survival to 26% for nonbone metastasis–free interval.

Dr. Paterson noted that secondary protocol predefined end point reductions were even greater among women at least 50 years of age. For these women, there was a 24% reduction in breast cancer recurrence–free interval (P = .05), a 39% reduction in bone metastasis–free interval (P = .024), and a 37% reduction in nonbone metastasis–free interval (P = .015). In addition, women 50 years and older had a 20% reduction in overall survival, though this was not statistically significant (P = 0.1).

"Similar beneficial results in older postmenopausal women are seen in other studies involving bisphosphonates," he said.

Bisphosponates are thought to inhibit the growth of bone metastases by inhibiting osteoclast function and subsequent bone turnover. However, the role of bisphosphonates in preventing or delaying the development of bone (or other) metastases in patients with early breast cancer remains unclear.

The trial received support from the National Cancer Institute and Bayer Schering Pharma Oy. Dr. Paterson disclosed that he is a consultant for GlaxoSmithKline, Amgen, Roche Diagnostics, and Nicomed.

SAN ANTONIO – An investigational genetic test may not only be able to differentiate women likely to have early recurrence of estrogen receptor–positive breast cancer but also could lead to novel combinations of existing drugs to treat these patients earlier in the disease process, according to Dr. Minetta C. Liu.

Researchers developed a 91-gene classifier "that essentially separated those patients who were going to recur early [within 3 years] vs. those who were going to recur late [beyond 10 years]," Dr. Liu announced at a press briefing held during the San Antonio Breast Cancer Symposium.

"Our work is very much hypothesis generating. To be able to identify early vs. late recurrences at the time of diagnosis would be useful, but we actually need to be able to know what to do about it once we identify it," said Dr. Liu, director of translational breast cancer research at Georgetown Lombardi Comprehensive Cancer Center in Washington, D.C.

The ability to reliably predict early treatment failure may help to identify patients who require agents beyond endocrine therapy to prevent the early onset of distant metastases, she said. "We hope to exploit these molecular differences of early vs. later recurrences to help us guide novel drug combinations in ER–positive early-stage disease," Dr. Liu added.

Session moderator Dr. Jennifer A. Ligibel of Dana-Farber Cancer Institute, Boston, agreed: This type of analysis "will help us to give chemotherapy to fewer patients potentially, if they do not have tumors that are consistent with early relapse and to know which patients really require extended therapy beyond the initial 5 years of treatment of endocrine therapy for patients who are potentially destined for late relapse."

The researchers acquired snap-frozen, pretreatment tumor biopsies collected at the Edinburgh Breakthrough Research Unit in Scotland between 1982 and 1990. The samples were from patients with stages I-III estrogen receptor–positive breast cancer, starting tamoxifen-alone adjuvant treatment. These patients had to have at least a 10-year follow-up in the absence of distant release.

A histology review was performed of the samples and those that contained at least 50% tumor were cleared for RNA extraction for gene expression profiling.

This training data set included 111 samples, with 57 relapses. Tumors from patients with relapse were subdivided into early recurrence (within 3 years of diagnosis) and late recurrence (more than 10 years). A total of 25 patients had early recurrences and 22 had late recurrences. Median follow-up was 13 years.

The investigators selected a validation data set from the literature that met certain criteria, such as quality of data and follow-up (BMC Genomics 2008;9:239). This previously published data set included 255 samples from patients with stages I-II estrogen receptor–positive breast cancer with tamoxifen-alone adjuvant treatment. Of these, 67 had distant relapse – 25 patients had early recurrences and 7 had late recurrences. The median follow-up was 9 years.

Using this training data set, the researchers developed a 91-gene classifier "that essentially separated those patients, who were going to recur early vs. those who were going to recur late," Dr. Liu said. They optimized the classifier and applied it to a validation data set.

"We had very high accuracy, sensitivity, specificity, positive predictive value, and negative predictive value," said Dr. Liu. However, "we didn’t stop at developing a classifier. We wanted to understand what these genes are trying to tell us within the classifier. ... A novel computational method allowed us to look at [estrogen receptor]network topology – to create a map basically."

The investigators identified several genes that were overexpressed in patients with early recurrences: CALM1, CALM2, CALM3, SRC, CDK1, and MAPK1. They also identified genes that had increased expression in patients with late recurrences: ESR1, ESR2, EGFR, BCL2, and AR.

"Clearly there are robust molecular differences between those tumors that recur early versus those that recur much later despite adjuvant tamoxifen. The majority of the genes in our classifier relate to apoptosis and proliferation," said Dr. Liu.

"I want to emphasize that we’re not just about developing a score and identifying these patients. We actually want to do something about it and understand what the underlying mechanisms are behind these genetic differences."

Dr. Liu reported that she has no relevant financial disclosures.

SAN ANTONIO – An investigational genetic test may not only be able to differentiate women likely to have early recurrence of estrogen receptor–positive breast cancer but also could lead to novel combinations of existing drugs to treat these patients earlier in the disease process, according to Dr. Minetta C. Liu.

Researchers developed a 91-gene classifier "that essentially separated those patients who were going to recur early [within 3 years] vs. those who were going to recur late [beyond 10 years]," Dr. Liu announced at a press briefing held during the San Antonio Breast Cancer Symposium.

"Our work is very much hypothesis generating. To be able to identify early vs. late recurrences at the time of diagnosis would be useful, but we actually need to be able to know what to do about it once we identify it," said Dr. Liu, director of translational breast cancer research at Georgetown Lombardi Comprehensive Cancer Center in Washington, D.C.

The ability to reliably predict early treatment failure may help to identify patients who require agents beyond endocrine therapy to prevent the early onset of distant metastases, she said. "We hope to exploit these molecular differences of early vs. later recurrences to help us guide novel drug combinations in ER–positive early-stage disease," Dr. Liu added.

Session moderator Dr. Jennifer A. Ligibel of Dana-Farber Cancer Institute, Boston, agreed: This type of analysis "will help us to give chemotherapy to fewer patients potentially, if they do not have tumors that are consistent with early relapse and to know which patients really require extended therapy beyond the initial 5 years of treatment of endocrine therapy for patients who are potentially destined for late relapse."

The researchers acquired snap-frozen, pretreatment tumor biopsies collected at the Edinburgh Breakthrough Research Unit in Scotland between 1982 and 1990. The samples were from patients with stages I-III estrogen receptor–positive breast cancer, starting tamoxifen-alone adjuvant treatment. These patients had to have at least a 10-year follow-up in the absence of distant release.

A histology review was performed of the samples and those that contained at least 50% tumor were cleared for RNA extraction for gene expression profiling.

This training data set included 111 samples, with 57 relapses. Tumors from patients with relapse were subdivided into early recurrence (within 3 years of diagnosis) and late recurrence (more than 10 years). A total of 25 patients had early recurrences and 22 had late recurrences. Median follow-up was 13 years.

The investigators selected a validation data set from the literature that met certain criteria, such as quality of data and follow-up (BMC Genomics 2008;9:239). This previously published data set included 255 samples from patients with stages I-II estrogen receptor–positive breast cancer with tamoxifen-alone adjuvant treatment. Of these, 67 had distant relapse – 25 patients had early recurrences and 7 had late recurrences. The median follow-up was 9 years.

Using this training data set, the researchers developed a 91-gene classifier "that essentially separated those patients, who were going to recur early vs. those who were going to recur late," Dr. Liu said. They optimized the classifier and applied it to a validation data set.

"We had very high accuracy, sensitivity, specificity, positive predictive value, and negative predictive value," said Dr. Liu. However, "we didn’t stop at developing a classifier. We wanted to understand what these genes are trying to tell us within the classifier. ... A novel computational method allowed us to look at [estrogen receptor]network topology – to create a map basically."

The investigators identified several genes that were overexpressed in patients with early recurrences: CALM1, CALM2, CALM3, SRC, CDK1, and MAPK1. They also identified genes that had increased expression in patients with late recurrences: ESR1, ESR2, EGFR, BCL2, and AR.

"Clearly there are robust molecular differences between those tumors that recur early versus those that recur much later despite adjuvant tamoxifen. The majority of the genes in our classifier relate to apoptosis and proliferation," said Dr. Liu.

"I want to emphasize that we’re not just about developing a score and identifying these patients. We actually want to do something about it and understand what the underlying mechanisms are behind these genetic differences."

Dr. Liu reported that she has no relevant financial disclosures.

SAN ANTONIO – An investigational genetic test may not only be able to differentiate women likely to have early recurrence of estrogen receptor–positive breast cancer but also could lead to novel combinations of existing drugs to treat these patients earlier in the disease process, according to Dr. Minetta C. Liu.

Researchers developed a 91-gene classifier "that essentially separated those patients who were going to recur early [within 3 years] vs. those who were going to recur late [beyond 10 years]," Dr. Liu announced at a press briefing held during the San Antonio Breast Cancer Symposium.

"Our work is very much hypothesis generating. To be able to identify early vs. late recurrences at the time of diagnosis would be useful, but we actually need to be able to know what to do about it once we identify it," said Dr. Liu, director of translational breast cancer research at Georgetown Lombardi Comprehensive Cancer Center in Washington, D.C.

The ability to reliably predict early treatment failure may help to identify patients who require agents beyond endocrine therapy to prevent the early onset of distant metastases, she said. "We hope to exploit these molecular differences of early vs. later recurrences to help us guide novel drug combinations in ER–positive early-stage disease," Dr. Liu added.

Session moderator Dr. Jennifer A. Ligibel of Dana-Farber Cancer Institute, Boston, agreed: This type of analysis "will help us to give chemotherapy to fewer patients potentially, if they do not have tumors that are consistent with early relapse and to know which patients really require extended therapy beyond the initial 5 years of treatment of endocrine therapy for patients who are potentially destined for late relapse."

The researchers acquired snap-frozen, pretreatment tumor biopsies collected at the Edinburgh Breakthrough Research Unit in Scotland between 1982 and 1990. The samples were from patients with stages I-III estrogen receptor–positive breast cancer, starting tamoxifen-alone adjuvant treatment. These patients had to have at least a 10-year follow-up in the absence of distant release.

A histology review was performed of the samples and those that contained at least 50% tumor were cleared for RNA extraction for gene expression profiling.

This training data set included 111 samples, with 57 relapses. Tumors from patients with relapse were subdivided into early recurrence (within 3 years of diagnosis) and late recurrence (more than 10 years). A total of 25 patients had early recurrences and 22 had late recurrences. Median follow-up was 13 years.

The investigators selected a validation data set from the literature that met certain criteria, such as quality of data and follow-up (BMC Genomics 2008;9:239). This previously published data set included 255 samples from patients with stages I-II estrogen receptor–positive breast cancer with tamoxifen-alone adjuvant treatment. Of these, 67 had distant relapse – 25 patients had early recurrences and 7 had late recurrences. The median follow-up was 9 years.

Using this training data set, the researchers developed a 91-gene classifier "that essentially separated those patients, who were going to recur early vs. those who were going to recur late," Dr. Liu said. They optimized the classifier and applied it to a validation data set.

"We had very high accuracy, sensitivity, specificity, positive predictive value, and negative predictive value," said Dr. Liu. However, "we didn’t stop at developing a classifier. We wanted to understand what these genes are trying to tell us within the classifier. ... A novel computational method allowed us to look at [estrogen receptor]network topology – to create a map basically."

The investigators identified several genes that were overexpressed in patients with early recurrences: CALM1, CALM2, CALM3, SRC, CDK1, and MAPK1. They also identified genes that had increased expression in patients with late recurrences: ESR1, ESR2, EGFR, BCL2, and AR.

"Clearly there are robust molecular differences between those tumors that recur early versus those that recur much later despite adjuvant tamoxifen. The majority of the genes in our classifier relate to apoptosis and proliferation," said Dr. Liu.

"I want to emphasize that we’re not just about developing a score and identifying these patients. We actually want to do something about it and understand what the underlying mechanisms are behind these genetic differences."

Dr. Liu reported that she has no relevant financial disclosures.

Sexting among children and adolescents appears to be far more variable and less explicit than previously thought, based on the results of two studies published online Dec. 5 in Pediatrics. Sexting is defined broadly as the transmission via cell phone, the Internet, and other electronic media of sexual images.

In a survey, 149 of 1,560 young people (9.6%) reported appearing in, creating, or receiving nude or nearly nude images in the previous year.

© Mariusz Blach - Fotolia.com

"This study reveals that estimates of youth involved in sexting vary considerably depending on what activities are included in the concept of sexting. The percentage of youth who have, in the past year, appeared in or created sexually explicit sexual images that potentially violate child pornography laws is low (1%). But if sexting is defined as appearing in, creating, or receiving sexually suggestive rather than explicit images, the survey reveals 9.6% of youth who used the Internet in the past year [were] involved in this way," Kimberly J. Mitchell, Ph.D., and her coinvestigators wrote (Pediatrics 2011 Dec. 5 [doi: 10.1542/peds.2011-1730]).

Dr. Mitchell and her associates used data from the third Youth Internet Safety Survey (YISS-3) on sexting, among other technology-based problems. Data collection occurred between August 2010 and January 2011. YISS-3 was conducted via telephone surveys with a national sample of youth Internet users aged 10-17 years.

A national survey research firm conducted the sampling, screening, and telephone interviews. The main sample was drawn from a national sample of households with telephones developed by random digit dialing. At the end of data collection, 45 interviews had been completed by cell phone in addition to 1,515 landline interviews, resulting in a total sample size of 1,560. Eligible respondents were children and adolescents who had used the Internet at least once a month for the previous 6 months.

Interviewers first asked to speak with the adult who was most familiar with that child’s Internet use, and after receiving informed consent, interviewers asked a series of questions about Internet use. Then the interviewer requested permission to interview the child or teen. Interviewers told parents that the youth interview would be confidential and would include questions about "sexual material your child may have seen on the Internet."

Adolescents were asked five screener questions about three types of sexting involvement: receiving "nude or nearly nude" images; forwarding or posting such images; and appearing in or creating such images. Follow-up questions gathered details, including the content of the nude or nearly nude images. The screeners asked:

– Has anyone ever sent you nude or nearly nude pictures or videos of kids who were under the age of 18 years that someone else took?

– Have you ever forwarded or posted any nude or nearly nude pictures or videos of other kids who were under the age of 18 that someone else took?

– Have you ever taken nude or nearly nude pictures or videos of yourself?

– Has someone else ever taken nude or nearly nude pictures or videos of you?

– Have you ever taken nude or nearly nude pictures or videos of other kids who were under the age of 18?

When a young person responded positively to one of these questions, the interviewers asked if the incident occurred in the past year. Interviewers then asked extensive follow-up questions about up to two unique sexting episodes in the past year.

"Sexting may not indicate a dramatic change in ... youth sexual behavior. It may just make some of that behavior more visible."

Of those individuals who reported involvement in sexting, 39 (2.5%) appeared in or created images and 110 participants (7.1%) received images but did not appear in or create them. Of the 39 young people who appeared in or created images, 61% were girls, 72% were 16 or 17 years of age, and 6% were 10-12 years of age. Most adolescents created images of themselves (1.8% of total sample). Some were photographed by someone else (0.3%); and some photographed other young people (0.4%).

Of the 110 young people who received images but did not appear in or create them, 56% were girls, 55% were aged 16 or 17 years, and none were younger than 12 years.

One of the goals of this study was to determine how adolescents define "nude" or "nearly nude." Participants were asked whether the images "showed breasts, genitals, or someone’s bottom." Only 21 (54%) of the young people who appeared in or created images reported pictures that met these criteria; the same was true for 84% of the 110 youth who received images.

In most of the episodes, the person responsible – when it was not the respondent – was someone the young person knew. Adults were involved in a minority of the incidents, and they were all young adults aged 18-21 years. An aggravating component, such as alcohol or drug use, was involved in 31% of incidents. "The most commonly reported reason for incidents was ‘romance as part of an existing relationship’; pranks and jokes; or trying to start a relationship," wrote Dr. Mitchell and her associates at Crimes Against Children Research Center at the University of New Hampshire in Durham.

Twenty-one percent of the respondents who appeared in or created images said they were very or extremely upset, embarrassed or afraid, as did 25% who received sexting images.

"Our findings also raise the question of how sexting should be defined. As is often the case with popularly-inspired neologisms, the term sexting may be fatally compromised by its multiple and expansive colloquial use," the researchers noted. "Clearly, for many youth nude or nearly nude encompasses pictures that do not show naked breasts or genitals. Researchers and clinicians need to directly ask about the content of images."

Furthermore, "sexting may not indicate a dramatic change in youth risk taking or youth sexual behavior. It may just make some of that behavior more visible to adults and other authorities," they said.

In terms of disclosure, 28% of youth who appeared in or created sexting images and 28% who received images "either reported incidents to an authority (such as a parent, teacher, or police) or an authority found out in some other way," the researchers said.

Police Cases of Sexting

In the second study, Janis Wolak, J.D., and her coinvestigators at the Crimes Against Children Research Center empirically examined police-investigated sexting cases based on data gathered from interviews with investigators about a nationally representative sample of 675 sexting cases in 2008 and 2009 (Pediatrics 2011 Dec. 5 [doi: 10.1542/peds.2011-2242]).

The data about sexting cases were collected as part of the Third National Juvenile Online Victimization Study, which is a stratified national sample of 2,712 law enforcement agencies. The agencies were asked by mail if they had handled sexting cases from 2008 or 2009. Detailed telephone interviews were then conducted about specific cases. In addition, interviewers wrote narrative descriptions of cases.

Again, because the term "sexting" is imprecise in its meaning, the researchers used a more specific expression – youth-produced sexual images. Specifically, the agencies were asked if they handled any cases from 2008 or 2009 that involved sexual images created by minors (age 17 or younger) and if these images were or could have been considered child pornography under the statutes of the local jurisdiction.

U.S. law enforcement agencies handled an estimated 3,477 cases of youth-produced sexual images during this time period; approximately 2,291 law enforcement agencies saw at least one such case during that time.

Of cases known to police, 36% involved adults. In 50% of the cases, the offenders were young adults (aged 18-24 years). A total of 38% involved adults aged at least 25 years. In 10% of cases, the adults were 18- or 19-year-old high school students who legitimately belonged to adolescent peer groups that included minors. The remainder of cases were of a mixed nature.

"Estimates of youth involved in sexting vary considerably depending on what activities are included in the concept of sexting."

Thirty-one percent of youth-only cases involved nonconsensual, malicious, exploitative, or criminal behavior. Among these cases, 19% involved criminal behavior in addition to the creation, dissemination, or possession of sexual images – such as blackmail or sexually abusing a younger minor. The most prevalent factor in these cases was the distribution of images without consent (57%).

The remaining cases (33%) were termed experimental. Thirty-two percent of experimental cases occurred in romantic relationships (10% of total cases), while the majority (57%) of cases involved sexual attention-seeking (19% of total cases). The rest (11%) were incidents with no apparent sexual motivation.

When adults were involved, arrests occurred in 62% of cases. Arrests occurred in 36% of youth-only aggravated cases; 5% of youth-only aggravated offenders (n = 10) were subjected to sex offender registration. In the experimental cases, 18% involved an arrest.

"The diversity of cases identified in the study clearly undermines some reports that suggest sexting is relatively harmless or confined to dating behavior. Only 10% of cases involved images created for or sent to established adolescent girlfriends or boyfriends. At the other extreme, youth-produced sexual images played a role in criminal sexual relationships between adult sex offenders and minors. Such cases can be challenging to pediatricians, parents, and authorities because underage victims may have strong attachments to adult offenders and may not perceive themselves as having been victimized. To manage these cases effectively, clinicians must be sensitive to the perceptions of victims and not assume that youth will be eager to cooperate or see the situation as criminal," the authors wrote.

The authors from both studies have indicated they have no relevant disclosures. The studies were supported by grants awarded by the Office of Juvenile Justice and Delinquency Prevention, Office of Justice Programs, U.S. Department of Justice.

Sexting among children and adolescents appears to be far more variable and less explicit than previously thought, based on the results of two studies published online Dec. 5 in Pediatrics. Sexting is defined broadly as the transmission via cell phone, the Internet, and other electronic media of sexual images.

In a survey, 149 of 1,560 young people (9.6%) reported appearing in, creating, or receiving nude or nearly nude images in the previous year.

© Mariusz Blach - Fotolia.com

"This study reveals that estimates of youth involved in sexting vary considerably depending on what activities are included in the concept of sexting. The percentage of youth who have, in the past year, appeared in or created sexually explicit sexual images that potentially violate child pornography laws is low (1%). But if sexting is defined as appearing in, creating, or receiving sexually suggestive rather than explicit images, the survey reveals 9.6% of youth who used the Internet in the past year [were] involved in this way," Kimberly J. Mitchell, Ph.D., and her coinvestigators wrote (Pediatrics 2011 Dec. 5 [doi: 10.1542/peds.2011-1730]).

Dr. Mitchell and her associates used data from the third Youth Internet Safety Survey (YISS-3) on sexting, among other technology-based problems. Data collection occurred between August 2010 and January 2011. YISS-3 was conducted via telephone surveys with a national sample of youth Internet users aged 10-17 years.

A national survey research firm conducted the sampling, screening, and telephone interviews. The main sample was drawn from a national sample of households with telephones developed by random digit dialing. At the end of data collection, 45 interviews had been completed by cell phone in addition to 1,515 landline interviews, resulting in a total sample size of 1,560. Eligible respondents were children and adolescents who had used the Internet at least once a month for the previous 6 months.

Interviewers first asked to speak with the adult who was most familiar with that child’s Internet use, and after receiving informed consent, interviewers asked a series of questions about Internet use. Then the interviewer requested permission to interview the child or teen. Interviewers told parents that the youth interview would be confidential and would include questions about "sexual material your child may have seen on the Internet."

Adolescents were asked five screener questions about three types of sexting involvement: receiving "nude or nearly nude" images; forwarding or posting such images; and appearing in or creating such images. Follow-up questions gathered details, including the content of the nude or nearly nude images. The screeners asked:

– Has anyone ever sent you nude or nearly nude pictures or videos of kids who were under the age of 18 years that someone else took?

– Have you ever forwarded or posted any nude or nearly nude pictures or videos of other kids who were under the age of 18 that someone else took?

– Have you ever taken nude or nearly nude pictures or videos of yourself?

– Has someone else ever taken nude or nearly nude pictures or videos of you?

– Have you ever taken nude or nearly nude pictures or videos of other kids who were under the age of 18?

When a young person responded positively to one of these questions, the interviewers asked if the incident occurred in the past year. Interviewers then asked extensive follow-up questions about up to two unique sexting episodes in the past year.

"Sexting may not indicate a dramatic change in ... youth sexual behavior. It may just make some of that behavior more visible."

Of those individuals who reported involvement in sexting, 39 (2.5%) appeared in or created images and 110 participants (7.1%) received images but did not appear in or create them. Of the 39 young people who appeared in or created images, 61% were girls, 72% were 16 or 17 years of age, and 6% were 10-12 years of age. Most adolescents created images of themselves (1.8% of total sample). Some were photographed by someone else (0.3%); and some photographed other young people (0.4%).

Of the 110 young people who received images but did not appear in or create them, 56% were girls, 55% were aged 16 or 17 years, and none were younger than 12 years.

One of the goals of this study was to determine how adolescents define "nude" or "nearly nude." Participants were asked whether the images "showed breasts, genitals, or someone’s bottom." Only 21 (54%) of the young people who appeared in or created images reported pictures that met these criteria; the same was true for 84% of the 110 youth who received images.

In most of the episodes, the person responsible – when it was not the respondent – was someone the young person knew. Adults were involved in a minority of the incidents, and they were all young adults aged 18-21 years. An aggravating component, such as alcohol or drug use, was involved in 31% of incidents. "The most commonly reported reason for incidents was ‘romance as part of an existing relationship’; pranks and jokes; or trying to start a relationship," wrote Dr. Mitchell and her associates at Crimes Against Children Research Center at the University of New Hampshire in Durham.

Twenty-one percent of the respondents who appeared in or created images said they were very or extremely upset, embarrassed or afraid, as did 25% who received sexting images.

"Our findings also raise the question of how sexting should be defined. As is often the case with popularly-inspired neologisms, the term sexting may be fatally compromised by its multiple and expansive colloquial use," the researchers noted. "Clearly, for many youth nude or nearly nude encompasses pictures that do not show naked breasts or genitals. Researchers and clinicians need to directly ask about the content of images."

Furthermore, "sexting may not indicate a dramatic change in youth risk taking or youth sexual behavior. It may just make some of that behavior more visible to adults and other authorities," they said.

In terms of disclosure, 28% of youth who appeared in or created sexting images and 28% who received images "either reported incidents to an authority (such as a parent, teacher, or police) or an authority found out in some other way," the researchers said.

Police Cases of Sexting

In the second study, Janis Wolak, J.D., and her coinvestigators at the Crimes Against Children Research Center empirically examined police-investigated sexting cases based on data gathered from interviews with investigators about a nationally representative sample of 675 sexting cases in 2008 and 2009 (Pediatrics 2011 Dec. 5 [doi: 10.1542/peds.2011-2242]).

The data about sexting cases were collected as part of the Third National Juvenile Online Victimization Study, which is a stratified national sample of 2,712 law enforcement agencies. The agencies were asked by mail if they had handled sexting cases from 2008 or 2009. Detailed telephone interviews were then conducted about specific cases. In addition, interviewers wrote narrative descriptions of cases.

Again, because the term "sexting" is imprecise in its meaning, the researchers used a more specific expression – youth-produced sexual images. Specifically, the agencies were asked if they handled any cases from 2008 or 2009 that involved sexual images created by minors (age 17 or younger) and if these images were or could have been considered child pornography under the statutes of the local jurisdiction.

U.S. law enforcement agencies handled an estimated 3,477 cases of youth-produced sexual images during this time period; approximately 2,291 law enforcement agencies saw at least one such case during that time.

Of cases known to police, 36% involved adults. In 50% of the cases, the offenders were young adults (aged 18-24 years). A total of 38% involved adults aged at least 25 years. In 10% of cases, the adults were 18- or 19-year-old high school students who legitimately belonged to adolescent peer groups that included minors. The remainder of cases were of a mixed nature.

"Estimates of youth involved in sexting vary considerably depending on what activities are included in the concept of sexting."

Thirty-one percent of youth-only cases involved nonconsensual, malicious, exploitative, or criminal behavior. Among these cases, 19% involved criminal behavior in addition to the creation, dissemination, or possession of sexual images – such as blackmail or sexually abusing a younger minor. The most prevalent factor in these cases was the distribution of images without consent (57%).

The remaining cases (33%) were termed experimental. Thirty-two percent of experimental cases occurred in romantic relationships (10% of total cases), while the majority (57%) of cases involved sexual attention-seeking (19% of total cases). The rest (11%) were incidents with no apparent sexual motivation.

When adults were involved, arrests occurred in 62% of cases. Arrests occurred in 36% of youth-only aggravated cases; 5% of youth-only aggravated offenders (n = 10) were subjected to sex offender registration. In the experimental cases, 18% involved an arrest.

"The diversity of cases identified in the study clearly undermines some reports that suggest sexting is relatively harmless or confined to dating behavior. Only 10% of cases involved images created for or sent to established adolescent girlfriends or boyfriends. At the other extreme, youth-produced sexual images played a role in criminal sexual relationships between adult sex offenders and minors. Such cases can be challenging to pediatricians, parents, and authorities because underage victims may have strong attachments to adult offenders and may not perceive themselves as having been victimized. To manage these cases effectively, clinicians must be sensitive to the perceptions of victims and not assume that youth will be eager to cooperate or see the situation as criminal," the authors wrote.

The authors from both studies have indicated they have no relevant disclosures. The studies were supported by grants awarded by the Office of Juvenile Justice and Delinquency Prevention, Office of Justice Programs, U.S. Department of Justice.

Sexting among children and adolescents appears to be far more variable and less explicit than previously thought, based on the results of two studies published online Dec. 5 in Pediatrics. Sexting is defined broadly as the transmission via cell phone, the Internet, and other electronic media of sexual images.

In a survey, 149 of 1,560 young people (9.6%) reported appearing in, creating, or receiving nude or nearly nude images in the previous year.

© Mariusz Blach - Fotolia.com

"This study reveals that estimates of youth involved in sexting vary considerably depending on what activities are included in the concept of sexting. The percentage of youth who have, in the past year, appeared in or created sexually explicit sexual images that potentially violate child pornography laws is low (1%). But if sexting is defined as appearing in, creating, or receiving sexually suggestive rather than explicit images, the survey reveals 9.6% of youth who used the Internet in the past year [were] involved in this way," Kimberly J. Mitchell, Ph.D., and her coinvestigators wrote (Pediatrics 2011 Dec. 5 [doi: 10.1542/peds.2011-1730]).

Dr. Mitchell and her associates used data from the third Youth Internet Safety Survey (YISS-3) on sexting, among other technology-based problems. Data collection occurred between August 2010 and January 2011. YISS-3 was conducted via telephone surveys with a national sample of youth Internet users aged 10-17 years.

A national survey research firm conducted the sampling, screening, and telephone interviews. The main sample was drawn from a national sample of households with telephones developed by random digit dialing. At the end of data collection, 45 interviews had been completed by cell phone in addition to 1,515 landline interviews, resulting in a total sample size of 1,560. Eligible respondents were children and adolescents who had used the Internet at least once a month for the previous 6 months.

Interviewers first asked to speak with the adult who was most familiar with that child’s Internet use, and after receiving informed consent, interviewers asked a series of questions about Internet use. Then the interviewer requested permission to interview the child or teen. Interviewers told parents that the youth interview would be confidential and would include questions about "sexual material your child may have seen on the Internet."

Adolescents were asked five screener questions about three types of sexting involvement: receiving "nude or nearly nude" images; forwarding or posting such images; and appearing in or creating such images. Follow-up questions gathered details, including the content of the nude or nearly nude images. The screeners asked:

– Has anyone ever sent you nude or nearly nude pictures or videos of kids who were under the age of 18 years that someone else took?

– Have you ever forwarded or posted any nude or nearly nude pictures or videos of other kids who were under the age of 18 that someone else took?

– Have you ever taken nude or nearly nude pictures or videos of yourself?

– Has someone else ever taken nude or nearly nude pictures or videos of you?

– Have you ever taken nude or nearly nude pictures or videos of other kids who were under the age of 18?

When a young person responded positively to one of these questions, the interviewers asked if the incident occurred in the past year. Interviewers then asked extensive follow-up questions about up to two unique sexting episodes in the past year.

"Sexting may not indicate a dramatic change in ... youth sexual behavior. It may just make some of that behavior more visible."

Of those individuals who reported involvement in sexting, 39 (2.5%) appeared in or created images and 110 participants (7.1%) received images but did not appear in or create them. Of the 39 young people who appeared in or created images, 61% were girls, 72% were 16 or 17 years of age, and 6% were 10-12 years of age. Most adolescents created images of themselves (1.8% of total sample). Some were photographed by someone else (0.3%); and some photographed other young people (0.4%).

Of the 110 young people who received images but did not appear in or create them, 56% were girls, 55% were aged 16 or 17 years, and none were younger than 12 years.

One of the goals of this study was to determine how adolescents define "nude" or "nearly nude." Participants were asked whether the images "showed breasts, genitals, or someone’s bottom." Only 21 (54%) of the young people who appeared in or created images reported pictures that met these criteria; the same was true for 84% of the 110 youth who received images.

In most of the episodes, the person responsible – when it was not the respondent – was someone the young person knew. Adults were involved in a minority of the incidents, and they were all young adults aged 18-21 years. An aggravating component, such as alcohol or drug use, was involved in 31% of incidents. "The most commonly reported reason for incidents was ‘romance as part of an existing relationship’; pranks and jokes; or trying to start a relationship," wrote Dr. Mitchell and her associates at Crimes Against Children Research Center at the University of New Hampshire in Durham.

Twenty-one percent of the respondents who appeared in or created images said they were very or extremely upset, embarrassed or afraid, as did 25% who received sexting images.

"Our findings also raise the question of how sexting should be defined. As is often the case with popularly-inspired neologisms, the term sexting may be fatally compromised by its multiple and expansive colloquial use," the researchers noted. "Clearly, for many youth nude or nearly nude encompasses pictures that do not show naked breasts or genitals. Researchers and clinicians need to directly ask about the content of images."

Furthermore, "sexting may not indicate a dramatic change in youth risk taking or youth sexual behavior. It may just make some of that behavior more visible to adults and other authorities," they said.

In terms of disclosure, 28% of youth who appeared in or created sexting images and 28% who received images "either reported incidents to an authority (such as a parent, teacher, or police) or an authority found out in some other way," the researchers said.

Police Cases of Sexting

In the second study, Janis Wolak, J.D., and her coinvestigators at the Crimes Against Children Research Center empirically examined police-investigated sexting cases based on data gathered from interviews with investigators about a nationally representative sample of 675 sexting cases in 2008 and 2009 (Pediatrics 2011 Dec. 5 [doi: 10.1542/peds.2011-2242]).

The data about sexting cases were collected as part of the Third National Juvenile Online Victimization Study, which is a stratified national sample of 2,712 law enforcement agencies. The agencies were asked by mail if they had handled sexting cases from 2008 or 2009. Detailed telephone interviews were then conducted about specific cases. In addition, interviewers wrote narrative descriptions of cases.

Again, because the term "sexting" is imprecise in its meaning, the researchers used a more specific expression – youth-produced sexual images. Specifically, the agencies were asked if they handled any cases from 2008 or 2009 that involved sexual images created by minors (age 17 or younger) and if these images were or could have been considered child pornography under the statutes of the local jurisdiction.

U.S. law enforcement agencies handled an estimated 3,477 cases of youth-produced sexual images during this time period; approximately 2,291 law enforcement agencies saw at least one such case during that time.

Of cases known to police, 36% involved adults. In 50% of the cases, the offenders were young adults (aged 18-24 years). A total of 38% involved adults aged at least 25 years. In 10% of cases, the adults were 18- or 19-year-old high school students who legitimately belonged to adolescent peer groups that included minors. The remainder of cases were of a mixed nature.

"Estimates of youth involved in sexting vary considerably depending on what activities are included in the concept of sexting."

Thirty-one percent of youth-only cases involved nonconsensual, malicious, exploitative, or criminal behavior. Among these cases, 19% involved criminal behavior in addition to the creation, dissemination, or possession of sexual images – such as blackmail or sexually abusing a younger minor. The most prevalent factor in these cases was the distribution of images without consent (57%).

The remaining cases (33%) were termed experimental. Thirty-two percent of experimental cases occurred in romantic relationships (10% of total cases), while the majority (57%) of cases involved sexual attention-seeking (19% of total cases). The rest (11%) were incidents with no apparent sexual motivation.

When adults were involved, arrests occurred in 62% of cases. Arrests occurred in 36% of youth-only aggravated cases; 5% of youth-only aggravated offenders (n = 10) were subjected to sex offender registration. In the experimental cases, 18% involved an arrest.

"The diversity of cases identified in the study clearly undermines some reports that suggest sexting is relatively harmless or confined to dating behavior. Only 10% of cases involved images created for or sent to established adolescent girlfriends or boyfriends. At the other extreme, youth-produced sexual images played a role in criminal sexual relationships between adult sex offenders and minors. Such cases can be challenging to pediatricians, parents, and authorities because underage victims may have strong attachments to adult offenders and may not perceive themselves as having been victimized. To manage these cases effectively, clinicians must be sensitive to the perceptions of victims and not assume that youth will be eager to cooperate or see the situation as criminal," the authors wrote.

The authors from both studies have indicated they have no relevant disclosures. The studies were supported by grants awarded by the Office of Juvenile Justice and Delinquency Prevention, Office of Justice Programs, U.S. Department of Justice.

Bevacizumab improves survival in HER2-positive metastatic disease

Bevacizumab (Avastin) improved progression-free survival (PFS) when added to standard treatment in a study of more than 400 women with human epidermal growth factor receptor 2 (HER2)–positive locally recurrent or metastatic breast cancer.

That finding, which emerged from the AVEREL trial, adds another wrinkle in the ongoing controversy regarding use of bevacizumab in breast cancer treatment.

For the primary endpoint of investigator- assessed PFS, conducted at a median follow-up of 26 months, the addition of bevacizumab resulted in a hazard ratio (HR) of 0.82 (P = 0.0775), compared with treatment with trastuzumab (Herceptin) and docetaxel alone. This difference was not statistically significant. Median investigator-assessed PFS was 16.5 months with bevacizumab versus 13.7 months without it.

In an assessment by an independent review committee (IRC), however, a significant improvement in PFS was seen with the addition of bevacizumab (hazard ratio, 0.72; P = 0.0162). Median IRC-assessed PFS was 16.8 months with bevacizumab, compared with 13.9 months without the drug.

* For a PDF of the full article, click in the link to the left of this introduction.

Bevacizumab improves survival in HER2-positive metastatic disease

Bevacizumab (Avastin) improved progression-free survival (PFS) when added to standard treatment in a study of more than 400 women with human epidermal growth factor receptor 2 (HER2)–positive locally recurrent or metastatic breast cancer.

That finding, which emerged from the AVEREL trial, adds another wrinkle in the ongoing controversy regarding use of bevacizumab in breast cancer treatment.

For the primary endpoint of investigator- assessed PFS, conducted at a median follow-up of 26 months, the addition of bevacizumab resulted in a hazard ratio (HR) of 0.82 (P = 0.0775), compared with treatment with trastuzumab (Herceptin) and docetaxel alone. This difference was not statistically significant. Median investigator-assessed PFS was 16.5 months with bevacizumab versus 13.7 months without it.

In an assessment by an independent review committee (IRC), however, a significant improvement in PFS was seen with the addition of bevacizumab (hazard ratio, 0.72; P = 0.0162). Median IRC-assessed PFS was 16.8 months with bevacizumab, compared with 13.9 months without the drug.

* For a PDF of the full article, click in the link to the left of this introduction.

Bevacizumab improves survival in HER2-positive metastatic disease

Bevacizumab (Avastin) improved progression-free survival (PFS) when added to standard treatment in a study of more than 400 women with human epidermal growth factor receptor 2 (HER2)–positive locally recurrent or metastatic breast cancer.

That finding, which emerged from the AVEREL trial, adds another wrinkle in the ongoing controversy regarding use of bevacizumab in breast cancer treatment.

For the primary endpoint of investigator- assessed PFS, conducted at a median follow-up of 26 months, the addition of bevacizumab resulted in a hazard ratio (HR) of 0.82 (P = 0.0775), compared with treatment with trastuzumab (Herceptin) and docetaxel alone. This difference was not statistically significant. Median investigator-assessed PFS was 16.5 months with bevacizumab versus 13.7 months without it.

In an assessment by an independent review committee (IRC), however, a significant improvement in PFS was seen with the addition of bevacizumab (hazard ratio, 0.72; P = 0.0162). Median IRC-assessed PFS was 16.8 months with bevacizumab, compared with 13.9 months without the drug.

* For a PDF of the full article, click in the link to the left of this introduction.

BALTIMORE – Cystic fibrosis–related diabetes differs from type 1 and 2 diabetes and requires different management.

"Screening early and knowing which patients are at risk is really important," Amanda Leonard said at a meeting on pediatric nutrition sponsored by Johns Hopkins University.

Nutritional status and pulmonary function begin to decline in cystic fibrosis patients several years before diagnosis of cystic fibrosis–related diabetes (CFRD), so identifying and treating patients with CFRD can have a big impact on life expectancy, said Ms. Leonard, a senior pediatric clinical dietician at the Johns Hopkins Cystic Fibrosis Center.

Although CFRD is very different from type 1 and type 2 diabetes, "it does share some components," she said. She summarized the highlights of the clinical care guidelines for CFRD issued by the American Diabetes Association and the Cystic Fibrosis Foundation (Diabetes Care 2010;33:2697-708).

CFRD is associated with weight loss, protein catabolism, lung function decline, and increased mortality. There does not appear to be an autoimmune etiology for CFRD, and ketones are very rare.

For patients with cystic fibrosis, the incidence of related diabetes is more than 50% at age 40 years. The peak age of onset for CFRD is 20-24 years, whereas type 1 diabetes is more common in children and type 2 diabetes is more common in mid-to-late adulthood, she said.

"In CFRD there is a severe insulin deficiency, but it’s not as complete as in type 1," she said. CFRD is defined as the presence of at least two of the following on two occasions: a fasting glucose level of at least 126 mg/dL, a 2-hour oral glucose tolerance test (OGTT) of plasma glucose that is at least 200 mg/dL, or a hemoglobin A_1c of at least 6.5% (although an HbA_1c less than 6.5% does not exclude CFRD).

"Screening early and knowing which patients are at risk is really important."

In CFRD patients, fasting glucose can range from 100 to 125 mg/dL, and a 2-hour OGTT result can range from 140 to 199 mg/dL. "So it’s not quite diabetes, but it’s not quite right either," she said. CFRD is "not an all or nothing kind of thing. It’s not that either you have it or you don\'t. It can be transient in nature, and there’s a spectrum," she said.

An outpatient OGTT performed when the patient is clinically stable is the test of choice for routine screening. OGTT screening is recommended annually for cystic fibrosis patients who are not already known to have diabetes, and such screening should begin by the time the patient is 10 years old.

HbA_1c cannot be considered a screening test for CFRD because of the high prevalence of false negatives, but a low HbA_1c can be used to confirm diagnosis.

Hospitalized patients who are admitted for pulmonary exacerbation and/or treatment with corticosteroids should have both fasting and 2-hour postprandial blood glucose monitoring. CFRD is diagnosed when fasting or postprandial hyperglycemia persists longer than 48 hours.

Patients receiving overnight continuous drip feedings should have blood glucose monitoring midcycle to screen for CFRD. Diagnosis is based on a midcycle or immediate postfeeding glucose level of at least 200 mg/dL. This should be confirmed on two separate nights.

Insulin is the definitive treatment for all patients with CFRD (with or without fasting hyperglycemia). Other diabetes agents have not been shown to be of benefit in CFRD and cannot be recommended over insulin. "Insulin is the treatment of choice. Oral agents do not seem to work as well," Ms. Leonard said.

Blood glucose goals are the same as for all patients with diabetes but are adjusted for individual patient circumstances. In general, the HbA_1c goal is less than 7.0%.

Diet should be based on current guidelines for the nutritional management of all patients with cystic fibrosis. Counting carbohydrates to guide insulin therapy can help optimize glycemic control.

BALTIMORE – Cystic fibrosis–related diabetes differs from type 1 and 2 diabetes and requires different management.

"Screening early and knowing which patients are at risk is really important," Amanda Leonard said at a meeting on pediatric nutrition sponsored by Johns Hopkins University.

Nutritional status and pulmonary function begin to decline in cystic fibrosis patients several years before diagnosis of cystic fibrosis–related diabetes (CFRD), so identifying and treating patients with CFRD can have a big impact on life expectancy, said Ms. Leonard, a senior pediatric clinical dietician at the Johns Hopkins Cystic Fibrosis Center.

Although CFRD is very different from type 1 and type 2 diabetes, "it does share some components," she said. She summarized the highlights of the clinical care guidelines for CFRD issued by the American Diabetes Association and the Cystic Fibrosis Foundation (Diabetes Care 2010;33:2697-708).

CFRD is associated with weight loss, protein catabolism, lung function decline, and increased mortality. There does not appear to be an autoimmune etiology for CFRD, and ketones are very rare.

For patients with cystic fibrosis, the incidence of related diabetes is more than 50% at age 40 years. The peak age of onset for CFRD is 20-24 years, whereas type 1 diabetes is more common in children and type 2 diabetes is more common in mid-to-late adulthood, she said.

"In CFRD there is a severe insulin deficiency, but it’s not as complete as in type 1," she said. CFRD is defined as the presence of at least two of the following on two occasions: a fasting glucose level of at least 126 mg/dL, a 2-hour oral glucose tolerance test (OGTT) of plasma glucose that is at least 200 mg/dL, or a hemoglobin A_1c of at least 6.5% (although an HbA_1c less than 6.5% does not exclude CFRD).

"Screening early and knowing which patients are at risk is really important."

In CFRD patients, fasting glucose can range from 100 to 125 mg/dL, and a 2-hour OGTT result can range from 140 to 199 mg/dL. "So it’s not quite diabetes, but it’s not quite right either," she said. CFRD is "not an all or nothing kind of thing. It’s not that either you have it or you don\'t. It can be transient in nature, and there’s a spectrum," she said.

An outpatient OGTT performed when the patient is clinically stable is the test of choice for routine screening. OGTT screening is recommended annually for cystic fibrosis patients who are not already known to have diabetes, and such screening should begin by the time the patient is 10 years old.

HbA_1c cannot be considered a screening test for CFRD because of the high prevalence of false negatives, but a low HbA_1c can be used to confirm diagnosis.

Hospitalized patients who are admitted for pulmonary exacerbation and/or treatment with corticosteroids should have both fasting and 2-hour postprandial blood glucose monitoring. CFRD is diagnosed when fasting or postprandial hyperglycemia persists longer than 48 hours.

Patients receiving overnight continuous drip feedings should have blood glucose monitoring midcycle to screen for CFRD. Diagnosis is based on a midcycle or immediate postfeeding glucose level of at least 200 mg/dL. This should be confirmed on two separate nights.

Insulin is the definitive treatment for all patients with CFRD (with or without fasting hyperglycemia). Other diabetes agents have not been shown to be of benefit in CFRD and cannot be recommended over insulin. "Insulin is the treatment of choice. Oral agents do not seem to work as well," Ms. Leonard said.

Blood glucose goals are the same as for all patients with diabetes but are adjusted for individual patient circumstances. In general, the HbA_1c goal is less than 7.0%.

Diet should be based on current guidelines for the nutritional management of all patients with cystic fibrosis. Counting carbohydrates to guide insulin therapy can help optimize glycemic control.

BALTIMORE – Cystic fibrosis–related diabetes differs from type 1 and 2 diabetes and requires different management.

"Screening early and knowing which patients are at risk is really important," Amanda Leonard said at a meeting on pediatric nutrition sponsored by Johns Hopkins University.

Nutritional status and pulmonary function begin to decline in cystic fibrosis patients several years before diagnosis of cystic fibrosis–related diabetes (CFRD), so identifying and treating patients with CFRD can have a big impact on life expectancy, said Ms. Leonard, a senior pediatric clinical dietician at the Johns Hopkins Cystic Fibrosis Center.

Although CFRD is very different from type 1 and type 2 diabetes, "it does share some components," she said. She summarized the highlights of the clinical care guidelines for CFRD issued by the American Diabetes Association and the Cystic Fibrosis Foundation (Diabetes Care 2010;33:2697-708).

CFRD is associated with weight loss, protein catabolism, lung function decline, and increased mortality. There does not appear to be an autoimmune etiology for CFRD, and ketones are very rare.

For patients with cystic fibrosis, the incidence of related diabetes is more than 50% at age 40 years. The peak age of onset for CFRD is 20-24 years, whereas type 1 diabetes is more common in children and type 2 diabetes is more common in mid-to-late adulthood, she said.

"In CFRD there is a severe insulin deficiency, but it’s not as complete as in type 1," she said. CFRD is defined as the presence of at least two of the following on two occasions: a fasting glucose level of at least 126 mg/dL, a 2-hour oral glucose tolerance test (OGTT) of plasma glucose that is at least 200 mg/dL, or a hemoglobin A_1c of at least 6.5% (although an HbA_1c less than 6.5% does not exclude CFRD).

"Screening early and knowing which patients are at risk is really important."

In CFRD patients, fasting glucose can range from 100 to 125 mg/dL, and a 2-hour OGTT result can range from 140 to 199 mg/dL. "So it’s not quite diabetes, but it’s not quite right either," she said. CFRD is "not an all or nothing kind of thing. It’s not that either you have it or you don\'t. It can be transient in nature, and there’s a spectrum," she said.

An outpatient OGTT performed when the patient is clinically stable is the test of choice for routine screening. OGTT screening is recommended annually for cystic fibrosis patients who are not already known to have diabetes, and such screening should begin by the time the patient is 10 years old.

HbA_1c cannot be considered a screening test for CFRD because of the high prevalence of false negatives, but a low HbA_1c can be used to confirm diagnosis.

Hospitalized patients who are admitted for pulmonary exacerbation and/or treatment with corticosteroids should have both fasting and 2-hour postprandial blood glucose monitoring. CFRD is diagnosed when fasting or postprandial hyperglycemia persists longer than 48 hours.

Patients receiving overnight continuous drip feedings should have blood glucose monitoring midcycle to screen for CFRD. Diagnosis is based on a midcycle or immediate postfeeding glucose level of at least 200 mg/dL. This should be confirmed on two separate nights.

Insulin is the definitive treatment for all patients with CFRD (with or without fasting hyperglycemia). Other diabetes agents have not been shown to be of benefit in CFRD and cannot be recommended over insulin. "Insulin is the treatment of choice. Oral agents do not seem to work as well," Ms. Leonard said.

Blood glucose goals are the same as for all patients with diabetes but are adjusted for individual patient circumstances. In general, the HbA_1c goal is less than 7.0%.

Diet should be based on current guidelines for the nutritional management of all patients with cystic fibrosis. Counting carbohydrates to guide insulin therapy can help optimize glycemic control.