Patrice Wendling

CHICAGO — Recent events surrounding selective cyclooxygenase-2 inhibitors will have far-reaching implications for future drug trials, Gary S. Hoffman, M.D., said at a symposium sponsored by the American College of Rheumatology.

Drugs that are under investigation for chronic diseases such as arthritis will require longer trials and follow-up than they required in the past, in part because of their likely long-term use among the patients who need them.

“We can no longer endorse or not endorse these drugs based upon short-term studies, some of which have been as short as 6 weeks or 12 weeks and usually, certainly, less than a year,” said Dr. Hoffman, a member of the Food and Drug Administration's arthritis advisory committee.

NSAID trials now will include cardiovascular and thrombotic events among the adverse events they monitor.

But this raises a number of questions, including whether there are other adverse events such as cancer, autoimmune effects, or neurocognitive dysfunction that are beyond our current knowledge, said Dr. Hoffman, professor of medicine and chair of rheumatic and immunologic diseases at the Cleveland Clinic Foundation.

“Are we looking at this with blinders on because of recent events, or are there other important AEs that we should also be casting a broader net for?” Dr. Hoffman asked.

“Perhaps there are increases in malignancies if you follow patients who take drug x, y, or z long enough,” he continued. “How long should those patients be studied in the context of randomized trials?”

Although answers to these questions are lacking, it's obvious that closer premarket drug scrutiny will come at a greater cost, he said.

A number of forces, such as the market, consumers, and the medical community, will need to determine how cost-effectiveness will be measured, and they also will need to determine who will ultimately pay.

New strategies must be developed to make new drug studies cost effective, he said.

Ironically, it was adverse events associated with non-selective NSAIDs that drove the COX-2 market in the first place, he noted. Research suggests that as much as one-third of every dollar spent on NSAIDs goes to managing adverse events.

CHICAGO — Recent events surrounding selective cyclooxygenase-2 inhibitors will have far-reaching implications for future drug trials, Gary S. Hoffman, M.D., said at a symposium sponsored by the American College of Rheumatology.

Drugs that are under investigation for chronic diseases such as arthritis will require longer trials and follow-up than they required in the past, in part because of their likely long-term use among the patients who need them.

“We can no longer endorse or not endorse these drugs based upon short-term studies, some of which have been as short as 6 weeks or 12 weeks and usually, certainly, less than a year,” said Dr. Hoffman, a member of the Food and Drug Administration's arthritis advisory committee.

NSAID trials now will include cardiovascular and thrombotic events among the adverse events they monitor.

But this raises a number of questions, including whether there are other adverse events such as cancer, autoimmune effects, or neurocognitive dysfunction that are beyond our current knowledge, said Dr. Hoffman, professor of medicine and chair of rheumatic and immunologic diseases at the Cleveland Clinic Foundation.

“Are we looking at this with blinders on because of recent events, or are there other important AEs that we should also be casting a broader net for?” Dr. Hoffman asked.

“Perhaps there are increases in malignancies if you follow patients who take drug x, y, or z long enough,” he continued. “How long should those patients be studied in the context of randomized trials?”

Although answers to these questions are lacking, it's obvious that closer premarket drug scrutiny will come at a greater cost, he said.

A number of forces, such as the market, consumers, and the medical community, will need to determine how cost-effectiveness will be measured, and they also will need to determine who will ultimately pay.

New strategies must be developed to make new drug studies cost effective, he said.

Ironically, it was adverse events associated with non-selective NSAIDs that drove the COX-2 market in the first place, he noted. Research suggests that as much as one-third of every dollar spent on NSAIDs goes to managing adverse events.

CHICAGO — Recent events surrounding selective cyclooxygenase-2 inhibitors will have far-reaching implications for future drug trials, Gary S. Hoffman, M.D., said at a symposium sponsored by the American College of Rheumatology.

Drugs that are under investigation for chronic diseases such as arthritis will require longer trials and follow-up than they required in the past, in part because of their likely long-term use among the patients who need them.

“We can no longer endorse or not endorse these drugs based upon short-term studies, some of which have been as short as 6 weeks or 12 weeks and usually, certainly, less than a year,” said Dr. Hoffman, a member of the Food and Drug Administration's arthritis advisory committee.

NSAID trials now will include cardiovascular and thrombotic events among the adverse events they monitor.

But this raises a number of questions, including whether there are other adverse events such as cancer, autoimmune effects, or neurocognitive dysfunction that are beyond our current knowledge, said Dr. Hoffman, professor of medicine and chair of rheumatic and immunologic diseases at the Cleveland Clinic Foundation.

“Are we looking at this with blinders on because of recent events, or are there other important AEs that we should also be casting a broader net for?” Dr. Hoffman asked.

“Perhaps there are increases in malignancies if you follow patients who take drug x, y, or z long enough,” he continued. “How long should those patients be studied in the context of randomized trials?”

Although answers to these questions are lacking, it's obvious that closer premarket drug scrutiny will come at a greater cost, he said.

A number of forces, such as the market, consumers, and the medical community, will need to determine how cost-effectiveness will be measured, and they also will need to determine who will ultimately pay.

New strategies must be developed to make new drug studies cost effective, he said.

Ironically, it was adverse events associated with non-selective NSAIDs that drove the COX-2 market in the first place, he noted. Research suggests that as much as one-third of every dollar spent on NSAIDs goes to managing adverse events.

NEW ORLEANS — Psoriatic arthritis patients receiving etanercept reported sustained clinical benefits for up to 2 years, according to data from an open-label extension study.

Patients treated with the drug reported inhibition of disease as well as significant improvements in physical functioning and quality of life, Philip J. Mease, M.D., reported at the annual meeting of the American Academy of Dermatology.

After an initial 24-week blinded phase of the study, 169 patients received 25 mg of etanercept (Enbrel) twice weekly for an additional 48 weeks during the open-label extension phase.

Patient-reported outcomes included the physical and mental components of the Short-Form (SF-36) Health Survey and the Health Assessment Questionnaire-Disability Index (HAQ-DI). During the placebo-controlled phase, etanercept-treated patients had a mean improvement of 9.3 points on the SF-36 physical component summary scale, whereas placebo patients improved only 0.7 on the scale.

In the open-label phase, patients originally randomized to etanercept maintained their improvements (mean 12.6 points), and patients switched to etanercept from placebo improved almost to the same level as those on continuous etanercept, said Dr. Mease, a rheumatologist at the Swedish Medical Center, the University of Washington, Seattle. Both groups had normal mental health at baseline and maintained it throughout the industry-sponsored trial.

In the placebo-controlled phase, the HAQ-DI improved from 1.1 to 0.5 in the etanercept group and from 1.1 to 1 in the placebo group. At 48 weeks, 40 (53%) of 75 patients originally randomized to etanercept had an HAQ-DI of zero, indicating no disability in performing activities of daily living. The mean HAQ-DI score at 48 weeks was 0.4 for patients continuously treated with etanercept and 0.6 for 70 patients switched from placebo to the drug.

Eleven patients originally randomized to placebo and 10 patients on continuous etanercept dropped out of the open-label phase.

A change of 0.3 in the HAQ score is considered a minimal clinically important difference. Thus a change of 0.6 in the etanercept group “clearly was highly clinically meaningful to the patients,” said Dr. Mease, who receives grant support and is a consultant and member of the speaker's bureau for Amgen, which manufactures Enbrel.

NEW ORLEANS — Psoriatic arthritis patients receiving etanercept reported sustained clinical benefits for up to 2 years, according to data from an open-label extension study.

Patients treated with the drug reported inhibition of disease as well as significant improvements in physical functioning and quality of life, Philip J. Mease, M.D., reported at the annual meeting of the American Academy of Dermatology.

After an initial 24-week blinded phase of the study, 169 patients received 25 mg of etanercept (Enbrel) twice weekly for an additional 48 weeks during the open-label extension phase.

Patient-reported outcomes included the physical and mental components of the Short-Form (SF-36) Health Survey and the Health Assessment Questionnaire-Disability Index (HAQ-DI). During the placebo-controlled phase, etanercept-treated patients had a mean improvement of 9.3 points on the SF-36 physical component summary scale, whereas placebo patients improved only 0.7 on the scale.

In the open-label phase, patients originally randomized to etanercept maintained their improvements (mean 12.6 points), and patients switched to etanercept from placebo improved almost to the same level as those on continuous etanercept, said Dr. Mease, a rheumatologist at the Swedish Medical Center, the University of Washington, Seattle. Both groups had normal mental health at baseline and maintained it throughout the industry-sponsored trial.

In the placebo-controlled phase, the HAQ-DI improved from 1.1 to 0.5 in the etanercept group and from 1.1 to 1 in the placebo group. At 48 weeks, 40 (53%) of 75 patients originally randomized to etanercept had an HAQ-DI of zero, indicating no disability in performing activities of daily living. The mean HAQ-DI score at 48 weeks was 0.4 for patients continuously treated with etanercept and 0.6 for 70 patients switched from placebo to the drug.

Eleven patients originally randomized to placebo and 10 patients on continuous etanercept dropped out of the open-label phase.

A change of 0.3 in the HAQ score is considered a minimal clinically important difference. Thus a change of 0.6 in the etanercept group “clearly was highly clinically meaningful to the patients,” said Dr. Mease, who receives grant support and is a consultant and member of the speaker's bureau for Amgen, which manufactures Enbrel.

NEW ORLEANS — Psoriatic arthritis patients receiving etanercept reported sustained clinical benefits for up to 2 years, according to data from an open-label extension study.

Patients treated with the drug reported inhibition of disease as well as significant improvements in physical functioning and quality of life, Philip J. Mease, M.D., reported at the annual meeting of the American Academy of Dermatology.

After an initial 24-week blinded phase of the study, 169 patients received 25 mg of etanercept (Enbrel) twice weekly for an additional 48 weeks during the open-label extension phase.

Patient-reported outcomes included the physical and mental components of the Short-Form (SF-36) Health Survey and the Health Assessment Questionnaire-Disability Index (HAQ-DI). During the placebo-controlled phase, etanercept-treated patients had a mean improvement of 9.3 points on the SF-36 physical component summary scale, whereas placebo patients improved only 0.7 on the scale.

In the open-label phase, patients originally randomized to etanercept maintained their improvements (mean 12.6 points), and patients switched to etanercept from placebo improved almost to the same level as those on continuous etanercept, said Dr. Mease, a rheumatologist at the Swedish Medical Center, the University of Washington, Seattle. Both groups had normal mental health at baseline and maintained it throughout the industry-sponsored trial.

In the placebo-controlled phase, the HAQ-DI improved from 1.1 to 0.5 in the etanercept group and from 1.1 to 1 in the placebo group. At 48 weeks, 40 (53%) of 75 patients originally randomized to etanercept had an HAQ-DI of zero, indicating no disability in performing activities of daily living. The mean HAQ-DI score at 48 weeks was 0.4 for patients continuously treated with etanercept and 0.6 for 70 patients switched from placebo to the drug.

Eleven patients originally randomized to placebo and 10 patients on continuous etanercept dropped out of the open-label phase.

A change of 0.3 in the HAQ score is considered a minimal clinically important difference. Thus a change of 0.6 in the etanercept group “clearly was highly clinically meaningful to the patients,” said Dr. Mease, who receives grant support and is a consultant and member of the speaker's bureau for Amgen, which manufactures Enbrel.

ATLANTA — Endoscopic ultrasound may not be as accurate a diagnostic tool for preoperative staging of gastric cancer as currently thought, a new study suggests.

Findings from preoperative endoscopic ultrasound (EUS) had a lower-than-expected concordance with those from postoperative pathologic assessment in a large series of patients undergoing a complete resection for gastric cancer, David J. Bentrem, M.D., reported at a symposium sponsored by the Society of Surgical Oncology.

For example, only 49% of patients with an EUS stage II lesion had a T2 lesion present on a traditional pathology report.

Overall accuracy was 57% for individual EUS T stage lesions and 50% for N stage lesions. The main reason for error was overstaging of the primary tumor, said Dr. Bentrem of Memorial Sloan-Kettering Cancer Center, New York.

The results are important because staging is used to define the eligibility of high-risk patients for neoadjuvant trials and is routinely used by clinicians to stratify risk and guide treatment planning, he said. Hence, physicians “need to know what they're getting with a test,” said Dr. Bentrem.

At present, EUS remains the best test for establishing the extent of locoregional disease, Dr. Bentrem said, adding that most patients with gastric cancer undergo EUS prior to enrollment in a neoadjuvant chemotherapy protocol at Memorial Sloan-Kettering.

The findings contradict an earlier study conducted at the same institution that found preoperative EUS T stage correlated with pathologic T stage in 89% of 43 patients with gastric carcinoma (J. Clin. Oncol. 1993;11:2380–5).

As for how the results could be so disparate—particularly with more than 10 years of additional experience using EUS—Dr. Bentrem told this newspaper that the earlier study included the institution's first 50 patients who underwent EUS followed by resection, and thus there was a “higher degree of scrutiny for these first patients.” The studies also had other methodologic differences.

The current study included 296 patients who underwent a preoperative clinical assessment of T and N stage with EUS and subsequent resection for gastric adenocarcinoma between 1993 and 2003. Patients who had received neoadjuvant therapy were excluded from analysis.

Of the 223 patients evaluated with EUS for T stage lesions, 127 patients (57%) were correctly staged, 25 (11%) were understaged, and 71 (32%) were overstaged.

Of the 218 patients evaluated with EUS for N stage lesions, 110 patients (50%) were correctly staged, 54 (25%) were understaged, and 54 (25%) were overstaged.

The overall accuracy of EUS for assessing the presence or absence of nodal disease was 71%.

The highest agreement between the two methods was in distinguishing high-risk patients from low-risk patients. Of the 150 patients deemed high risk or showing evidence of either serosal invasion or nodal disease on preoperative EUS, 76% were found to be high risk on traditional pathologic assessment.

EUS did not distinguish among individual T stages based on outcome, particularly between T2 and T3 lesions, Dr. Bentrem said. Many of the pathologic T2 lesions were overstaged and identified as T3 on EUS. Patients with EUS-identified T2 and T3 lesions had similar outcomes, with a median survival rate of about 36 months.

ATLANTA — Endoscopic ultrasound may not be as accurate a diagnostic tool for preoperative staging of gastric cancer as currently thought, a new study suggests.

Findings from preoperative endoscopic ultrasound (EUS) had a lower-than-expected concordance with those from postoperative pathologic assessment in a large series of patients undergoing a complete resection for gastric cancer, David J. Bentrem, M.D., reported at a symposium sponsored by the Society of Surgical Oncology.

For example, only 49% of patients with an EUS stage II lesion had a T2 lesion present on a traditional pathology report.

Overall accuracy was 57% for individual EUS T stage lesions and 50% for N stage lesions. The main reason for error was overstaging of the primary tumor, said Dr. Bentrem of Memorial Sloan-Kettering Cancer Center, New York.

The results are important because staging is used to define the eligibility of high-risk patients for neoadjuvant trials and is routinely used by clinicians to stratify risk and guide treatment planning, he said. Hence, physicians “need to know what they're getting with a test,” said Dr. Bentrem.

At present, EUS remains the best test for establishing the extent of locoregional disease, Dr. Bentrem said, adding that most patients with gastric cancer undergo EUS prior to enrollment in a neoadjuvant chemotherapy protocol at Memorial Sloan-Kettering.

The findings contradict an earlier study conducted at the same institution that found preoperative EUS T stage correlated with pathologic T stage in 89% of 43 patients with gastric carcinoma (J. Clin. Oncol. 1993;11:2380–5).

As for how the results could be so disparate—particularly with more than 10 years of additional experience using EUS—Dr. Bentrem told this newspaper that the earlier study included the institution's first 50 patients who underwent EUS followed by resection, and thus there was a “higher degree of scrutiny for these first patients.” The studies also had other methodologic differences.

The current study included 296 patients who underwent a preoperative clinical assessment of T and N stage with EUS and subsequent resection for gastric adenocarcinoma between 1993 and 2003. Patients who had received neoadjuvant therapy were excluded from analysis.

Of the 223 patients evaluated with EUS for T stage lesions, 127 patients (57%) were correctly staged, 25 (11%) were understaged, and 71 (32%) were overstaged.

Of the 218 patients evaluated with EUS for N stage lesions, 110 patients (50%) were correctly staged, 54 (25%) were understaged, and 54 (25%) were overstaged.

The overall accuracy of EUS for assessing the presence or absence of nodal disease was 71%.

The highest agreement between the two methods was in distinguishing high-risk patients from low-risk patients. Of the 150 patients deemed high risk or showing evidence of either serosal invasion or nodal disease on preoperative EUS, 76% were found to be high risk on traditional pathologic assessment.

EUS did not distinguish among individual T stages based on outcome, particularly between T2 and T3 lesions, Dr. Bentrem said. Many of the pathologic T2 lesions were overstaged and identified as T3 on EUS. Patients with EUS-identified T2 and T3 lesions had similar outcomes, with a median survival rate of about 36 months.

ATLANTA — Endoscopic ultrasound may not be as accurate a diagnostic tool for preoperative staging of gastric cancer as currently thought, a new study suggests.

Findings from preoperative endoscopic ultrasound (EUS) had a lower-than-expected concordance with those from postoperative pathologic assessment in a large series of patients undergoing a complete resection for gastric cancer, David J. Bentrem, M.D., reported at a symposium sponsored by the Society of Surgical Oncology.

For example, only 49% of patients with an EUS stage II lesion had a T2 lesion present on a traditional pathology report.

Overall accuracy was 57% for individual EUS T stage lesions and 50% for N stage lesions. The main reason for error was overstaging of the primary tumor, said Dr. Bentrem of Memorial Sloan-Kettering Cancer Center, New York.

The results are important because staging is used to define the eligibility of high-risk patients for neoadjuvant trials and is routinely used by clinicians to stratify risk and guide treatment planning, he said. Hence, physicians “need to know what they're getting with a test,” said Dr. Bentrem.

At present, EUS remains the best test for establishing the extent of locoregional disease, Dr. Bentrem said, adding that most patients with gastric cancer undergo EUS prior to enrollment in a neoadjuvant chemotherapy protocol at Memorial Sloan-Kettering.

The findings contradict an earlier study conducted at the same institution that found preoperative EUS T stage correlated with pathologic T stage in 89% of 43 patients with gastric carcinoma (J. Clin. Oncol. 1993;11:2380–5).

As for how the results could be so disparate—particularly with more than 10 years of additional experience using EUS—Dr. Bentrem told this newspaper that the earlier study included the institution's first 50 patients who underwent EUS followed by resection, and thus there was a “higher degree of scrutiny for these first patients.” The studies also had other methodologic differences.

The current study included 296 patients who underwent a preoperative clinical assessment of T and N stage with EUS and subsequent resection for gastric adenocarcinoma between 1993 and 2003. Patients who had received neoadjuvant therapy were excluded from analysis.

Of the 223 patients evaluated with EUS for T stage lesions, 127 patients (57%) were correctly staged, 25 (11%) were understaged, and 71 (32%) were overstaged.

Of the 218 patients evaluated with EUS for N stage lesions, 110 patients (50%) were correctly staged, 54 (25%) were understaged, and 54 (25%) were overstaged.

The overall accuracy of EUS for assessing the presence or absence of nodal disease was 71%.

The highest agreement between the two methods was in distinguishing high-risk patients from low-risk patients. Of the 150 patients deemed high risk or showing evidence of either serosal invasion or nodal disease on preoperative EUS, 76% were found to be high risk on traditional pathologic assessment.

EUS did not distinguish among individual T stages based on outcome, particularly between T2 and T3 lesions, Dr. Bentrem said. Many of the pathologic T2 lesions were overstaged and identified as T3 on EUS. Patients with EUS-identified T2 and T3 lesions had similar outcomes, with a median survival rate of about 36 months.

CHICAGO — Recent events surrounding selective cyclooxygenase-2 inhibitors will have far-reaching implications for future drug trials, Gary S. Hoffman, M.D., said at a symposium sponsored by the American College of Rheumatology.

Drugs under investigation for chronic diseases such as arthritis will require longer trials and follow-up than in the past, in part because of their likely long-term use among the patients who need them. "We can no longer endorse or not endorse these drugs based upon short-term studies, some of which have been as short as 6 weeks or 12 weeks and usually, certainly, less than a year," said Dr. Hoffman, a member of the Food and Drug Administration's arthritis advisory committee.

NSAID trials now will include cardiovascular and thrombotic events among the adverse events they monitor.

But this raises questions as to whether there are other adverse events (AEs) such as cancer, autoimmune effects, or neurocognitive dysfunction that are beyond our current knowledge, said Dr. Hoffman, professor of medicine and chair of rheumatic and immunologic diseases at the Cleveland Clinic Foundation.

"Are we looking at this with blinders on because of recent events or are there other important AEs that we should also be casting a broader net for?" Dr. Hoffman asked. "Perhaps there are increases in malignancies if you follow patients who take drug x, y, or z long enough. How long should those patients be studied in the context of randomized trials?"

Although answers to these questions are lacking, it's obvious that closer premarket drug scrutiny will come at a greater cost, he said.

Forces such as the market, consumers, and the medical community will need to determine how cost-effectiveness will be measured, and ultimately who will pay.

New strategies need to be developed to make new drug studies cost-effective.

Ironically, it was adverse events associated with non-selective NSAIDs that drove the COX-2 market in the first place, he noted. Research suggests that as much as one-third of every dollar spent on NSAIDs goes to managing adverse events.

CHICAGO — Recent events surrounding selective cyclooxygenase-2 inhibitors will have far-reaching implications for future drug trials, Gary S. Hoffman, M.D., said at a symposium sponsored by the American College of Rheumatology.

Drugs under investigation for chronic diseases such as arthritis will require longer trials and follow-up than in the past, in part because of their likely long-term use among the patients who need them. "We can no longer endorse or not endorse these drugs based upon short-term studies, some of which have been as short as 6 weeks or 12 weeks and usually, certainly, less than a year," said Dr. Hoffman, a member of the Food and Drug Administration's arthritis advisory committee.

NSAID trials now will include cardiovascular and thrombotic events among the adverse events they monitor.

But this raises questions as to whether there are other adverse events (AEs) such as cancer, autoimmune effects, or neurocognitive dysfunction that are beyond our current knowledge, said Dr. Hoffman, professor of medicine and chair of rheumatic and immunologic diseases at the Cleveland Clinic Foundation.

"Are we looking at this with blinders on because of recent events or are there other important AEs that we should also be casting a broader net for?" Dr. Hoffman asked. "Perhaps there are increases in malignancies if you follow patients who take drug x, y, or z long enough. How long should those patients be studied in the context of randomized trials?"

Although answers to these questions are lacking, it's obvious that closer premarket drug scrutiny will come at a greater cost, he said.

Forces such as the market, consumers, and the medical community will need to determine how cost-effectiveness will be measured, and ultimately who will pay.

New strategies need to be developed to make new drug studies cost-effective.

Ironically, it was adverse events associated with non-selective NSAIDs that drove the COX-2 market in the first place, he noted. Research suggests that as much as one-third of every dollar spent on NSAIDs goes to managing adverse events.

CHICAGO — Recent events surrounding selective cyclooxygenase-2 inhibitors will have far-reaching implications for future drug trials, Gary S. Hoffman, M.D., said at a symposium sponsored by the American College of Rheumatology.

Drugs under investigation for chronic diseases such as arthritis will require longer trials and follow-up than in the past, in part because of their likely long-term use among the patients who need them. "We can no longer endorse or not endorse these drugs based upon short-term studies, some of which have been as short as 6 weeks or 12 weeks and usually, certainly, less than a year," said Dr. Hoffman, a member of the Food and Drug Administration's arthritis advisory committee.

NSAID trials now will include cardiovascular and thrombotic events among the adverse events they monitor.

But this raises questions as to whether there are other adverse events (AEs) such as cancer, autoimmune effects, or neurocognitive dysfunction that are beyond our current knowledge, said Dr. Hoffman, professor of medicine and chair of rheumatic and immunologic diseases at the Cleveland Clinic Foundation.

"Are we looking at this with blinders on because of recent events or are there other important AEs that we should also be casting a broader net for?" Dr. Hoffman asked. "Perhaps there are increases in malignancies if you follow patients who take drug x, y, or z long enough. How long should those patients be studied in the context of randomized trials?"

Although answers to these questions are lacking, it's obvious that closer premarket drug scrutiny will come at a greater cost, he said.

Forces such as the market, consumers, and the medical community will need to determine how cost-effectiveness will be measured, and ultimately who will pay.

New strategies need to be developed to make new drug studies cost-effective.

Ironically, it was adverse events associated with non-selective NSAIDs that drove the COX-2 market in the first place, he noted. Research suggests that as much as one-third of every dollar spent on NSAIDs goes to managing adverse events.

ATLANTA — Contrary to conventional belief, results of a new study suggest that surgical removal of the primary tumor can benefit women with stage IV breast cancer.

Although overall survival was unchanged at 5 years, there was a better progression-free survival for women who underwent local therapy of the primary tumor when initially presenting with metastatic disease, Roshni S. Rao, M.D., reported at a symposium sponsored by the Society of Surgical Oncology.

“This is important, because any time you can slow down the progression of the disease, it potentially gives other therapies a better chance at working,” Dr. Rao told this newspaper. “It's entirely possible that as medical therapy improves, the metastatic progression-free survival seen in these patients will translate into a survival benefit.”

The study joins a growing body of evidence that challenges traditional beliefs by suggesting that aggressive local therapy may prolong survival, said Dr. Rao, a breast-surgery fellow at the University of Texas M.D. Anderson Cancer Center, Houston.

Current treatment is generally directed at the sites of metastases, and the primary tumor is left intact. Surgery is undertaken only for palliation.

Only 3%-6% of American women diagnosed with breast cancer will be stage IV at presentation, but a staggering 50% of women internationally will present with metastatic disease, Dr. Rao said.

The retrospective, single-institution chart analysis included 224 women with stage IV breast cancer, including 142 patients who received systemic treatment without surgery and 82 who had surgery to remove the primary tumor and systemic therapy.

Of the surgical patients, 43 underwent mastectomies, and 39 had segmental resection.

All of the patients received hormonal therapy or chemotherapy within 3 months of diagnosis.

Both groups were similar in race, family and personal history of cancer, histology, tumor size, and estrogen- or progesterone-receptor status.

The surgical group was slightly younger than the nonsurgical group (49 years vs. 54 years); had one metastatic site (generally the liver); was more likely to receive chemotherapy than hormonal therapy as a first-line treatment; had a lower nodal stage (59 N0/N1 patients vs. 100); and was more likely to be Her2/neu positive (24 vs. 28 patients).

Initially, surgical patients demonstrated better survival than women who received systemic therapy alone. But this was not significant on final analysis, Dr. Rao said.

At 3 years, 119 of the 142 women (84%) in the nonsurgical group were alive, compared with 78 of the 82 women (95%) in the surgical group.

At final follow-up, there were 27 deaths in the nonsurgical group and 11 in the surgical group. Eleven patients who had surgical intervention at their primary site as well as their metastatic site had no evidence of disease during follow-up.

The only independent predictors of overall survival were having a single metastatic site and Her2/neu-negative status (hazard ratio 2.43 and 2.52, respectively).

Surgery and estrogen-negative status were the only independent predictors of metastatic progression-free survival (hazard ratio 0.47 and 0.6, respectively).

ATLANTA — Contrary to conventional belief, results of a new study suggest that surgical removal of the primary tumor can benefit women with stage IV breast cancer.

Although overall survival was unchanged at 5 years, there was a better progression-free survival for women who underwent local therapy of the primary tumor when initially presenting with metastatic disease, Roshni S. Rao, M.D., reported at a symposium sponsored by the Society of Surgical Oncology.

“This is important, because any time you can slow down the progression of the disease, it potentially gives other therapies a better chance at working,” Dr. Rao told this newspaper. “It's entirely possible that as medical therapy improves, the metastatic progression-free survival seen in these patients will translate into a survival benefit.”

The study joins a growing body of evidence that challenges traditional beliefs by suggesting that aggressive local therapy may prolong survival, said Dr. Rao, a breast-surgery fellow at the University of Texas M.D. Anderson Cancer Center, Houston.

Current treatment is generally directed at the sites of metastases, and the primary tumor is left intact. Surgery is undertaken only for palliation.

Only 3%-6% of American women diagnosed with breast cancer will be stage IV at presentation, but a staggering 50% of women internationally will present with metastatic disease, Dr. Rao said.

The retrospective, single-institution chart analysis included 224 women with stage IV breast cancer, including 142 patients who received systemic treatment without surgery and 82 who had surgery to remove the primary tumor and systemic therapy.

Of the surgical patients, 43 underwent mastectomies, and 39 had segmental resection.

All of the patients received hormonal therapy or chemotherapy within 3 months of diagnosis.

Both groups were similar in race, family and personal history of cancer, histology, tumor size, and estrogen- or progesterone-receptor status.

The surgical group was slightly younger than the nonsurgical group (49 years vs. 54 years); had one metastatic site (generally the liver); was more likely to receive chemotherapy than hormonal therapy as a first-line treatment; had a lower nodal stage (59 N0/N1 patients vs. 100); and was more likely to be Her2/neu positive (24 vs. 28 patients).

Initially, surgical patients demonstrated better survival than women who received systemic therapy alone. But this was not significant on final analysis, Dr. Rao said.

At 3 years, 119 of the 142 women (84%) in the nonsurgical group were alive, compared with 78 of the 82 women (95%) in the surgical group.

At final follow-up, there were 27 deaths in the nonsurgical group and 11 in the surgical group. Eleven patients who had surgical intervention at their primary site as well as their metastatic site had no evidence of disease during follow-up.

The only independent predictors of overall survival were having a single metastatic site and Her2/neu-negative status (hazard ratio 2.43 and 2.52, respectively).

Surgery and estrogen-negative status were the only independent predictors of metastatic progression-free survival (hazard ratio 0.47 and 0.6, respectively).

ATLANTA — Contrary to conventional belief, results of a new study suggest that surgical removal of the primary tumor can benefit women with stage IV breast cancer.

Although overall survival was unchanged at 5 years, there was a better progression-free survival for women who underwent local therapy of the primary tumor when initially presenting with metastatic disease, Roshni S. Rao, M.D., reported at a symposium sponsored by the Society of Surgical Oncology.

“This is important, because any time you can slow down the progression of the disease, it potentially gives other therapies a better chance at working,” Dr. Rao told this newspaper. “It's entirely possible that as medical therapy improves, the metastatic progression-free survival seen in these patients will translate into a survival benefit.”

The study joins a growing body of evidence that challenges traditional beliefs by suggesting that aggressive local therapy may prolong survival, said Dr. Rao, a breast-surgery fellow at the University of Texas M.D. Anderson Cancer Center, Houston.

Current treatment is generally directed at the sites of metastases, and the primary tumor is left intact. Surgery is undertaken only for palliation.

Only 3%-6% of American women diagnosed with breast cancer will be stage IV at presentation, but a staggering 50% of women internationally will present with metastatic disease, Dr. Rao said.

The retrospective, single-institution chart analysis included 224 women with stage IV breast cancer, including 142 patients who received systemic treatment without surgery and 82 who had surgery to remove the primary tumor and systemic therapy.

Of the surgical patients, 43 underwent mastectomies, and 39 had segmental resection.

All of the patients received hormonal therapy or chemotherapy within 3 months of diagnosis.

Both groups were similar in race, family and personal history of cancer, histology, tumor size, and estrogen- or progesterone-receptor status.

The surgical group was slightly younger than the nonsurgical group (49 years vs. 54 years); had one metastatic site (generally the liver); was more likely to receive chemotherapy than hormonal therapy as a first-line treatment; had a lower nodal stage (59 N0/N1 patients vs. 100); and was more likely to be Her2/neu positive (24 vs. 28 patients).

Initially, surgical patients demonstrated better survival than women who received systemic therapy alone. But this was not significant on final analysis, Dr. Rao said.

At 3 years, 119 of the 142 women (84%) in the nonsurgical group were alive, compared with 78 of the 82 women (95%) in the surgical group.

At final follow-up, there were 27 deaths in the nonsurgical group and 11 in the surgical group. Eleven patients who had surgical intervention at their primary site as well as their metastatic site had no evidence of disease during follow-up.

The only independent predictors of overall survival were having a single metastatic site and Her2/neu-negative status (hazard ratio 2.43 and 2.52, respectively).

Surgery and estrogen-negative status were the only independent predictors of metastatic progression-free survival (hazard ratio 0.47 and 0.6, respectively).

TORONTO — A retrospective analysis has shown no adverse effects of thiazolidinediones on clinical outcomes in heart failure patients with diabetes.

In fact, thiazolidinedione (TZD) use was associated with reductions in all-cause hospitalizations, heart failure hospitalizations, and total hospital days. The reduction in hospital days also was noted in patients treated with TZD plus insulin.

These findings challenge current recommendations against the use of TZDs in heart failure that are based on concerns regarding fluid retention, particularly when used in combination with insulin. To date, there have been no trials assessing the impact of TZD therapy on heart failure outcomes.

“These findings support the concept that perhaps the nonhypoglycemic cardiovascular effects of TZDs may have favorable clinical impact in heart failure patients,” investigator John S. Golden, M.D., said during a poster presentation at the annual meeting of the Heart Failure Society of America.

Ultimately, clinical trials will determine the specific effects of TZDs in heart failure, and the extent to which an observational study can be extrapolated to a larger population.

“I can't tell you on the basis of this study that it is something we ought to be doing as a therapeutic intervention at this point,” said Dr. Golden of Mid-Atlantic Permanente Medical Group, Fairfax, Va. “I'm certainly not putting that much stock in hospital day reductions based on a small study like this. But, again, it lends some clinical support to the biochemical mechanisms supporting not only the safety, but efficacy, of TZDs in this population.”

Consecutively, 97 diabetic patients were referred to the heart failure treatment program at Mid-Atlantic with left ventricular ejection fractions of 35% or less and New York Heart Association (NYHA) class II-IV; 37% were treated with a TZD and 15% received a TZD plus insulin.

Patients treated with TZD and those not treated with the drug were well matched with regard to baseline left ventricular ejection fraction, glycosylated hemoglobin, and NYHA class. All patients were treated with ACE inhibitors or angiotensin receptor blockers, and 97% received β-blockers.

Clinical outcomes were measured at 1 year evaluating TZD use both alone and in combination with insulin.

Improvements in ejection fractions did not differ significantly between patients treated with TZDs and those who were not. Patients treated with a TZD, compared with those not treated, had significantly reduced all-cause hospitalizations per patient (0.19 vs. 0.71), heart failure hospitalizations per patient (0.03 vs. 0.16), and total hospital days (0.67 vs. 2.72), he said.

In the subpopulation treated with TZD plus insulin, there was a significant reduction in total hospital days per patient (0.07 vs. 2.30), compared with those not on the combination therapy. There was a trend toward increased diuretic usage in the TZD plus insulin group (69.3 mg vs. 45.5 mg furosemide/day). This was not seen in patients treated with TZD alone.

TORONTO — A retrospective analysis has shown no adverse effects of thiazolidinediones on clinical outcomes in heart failure patients with diabetes.

In fact, thiazolidinedione (TZD) use was associated with reductions in all-cause hospitalizations, heart failure hospitalizations, and total hospital days. The reduction in hospital days also was noted in patients treated with TZD plus insulin.

These findings challenge current recommendations against the use of TZDs in heart failure that are based on concerns regarding fluid retention, particularly when used in combination with insulin. To date, there have been no trials assessing the impact of TZD therapy on heart failure outcomes.

“These findings support the concept that perhaps the nonhypoglycemic cardiovascular effects of TZDs may have favorable clinical impact in heart failure patients,” investigator John S. Golden, M.D., said during a poster presentation at the annual meeting of the Heart Failure Society of America.

Ultimately, clinical trials will determine the specific effects of TZDs in heart failure, and the extent to which an observational study can be extrapolated to a larger population.

“I can't tell you on the basis of this study that it is something we ought to be doing as a therapeutic intervention at this point,” said Dr. Golden of Mid-Atlantic Permanente Medical Group, Fairfax, Va. “I'm certainly not putting that much stock in hospital day reductions based on a small study like this. But, again, it lends some clinical support to the biochemical mechanisms supporting not only the safety, but efficacy, of TZDs in this population.”

Consecutively, 97 diabetic patients were referred to the heart failure treatment program at Mid-Atlantic with left ventricular ejection fractions of 35% or less and New York Heart Association (NYHA) class II-IV; 37% were treated with a TZD and 15% received a TZD plus insulin.

Patients treated with TZD and those not treated with the drug were well matched with regard to baseline left ventricular ejection fraction, glycosylated hemoglobin, and NYHA class. All patients were treated with ACE inhibitors or angiotensin receptor blockers, and 97% received β-blockers.

Clinical outcomes were measured at 1 year evaluating TZD use both alone and in combination with insulin.

Improvements in ejection fractions did not differ significantly between patients treated with TZDs and those who were not. Patients treated with a TZD, compared with those not treated, had significantly reduced all-cause hospitalizations per patient (0.19 vs. 0.71), heart failure hospitalizations per patient (0.03 vs. 0.16), and total hospital days (0.67 vs. 2.72), he said.

In the subpopulation treated with TZD plus insulin, there was a significant reduction in total hospital days per patient (0.07 vs. 2.30), compared with those not on the combination therapy. There was a trend toward increased diuretic usage in the TZD plus insulin group (69.3 mg vs. 45.5 mg furosemide/day). This was not seen in patients treated with TZD alone.

TORONTO — A retrospective analysis has shown no adverse effects of thiazolidinediones on clinical outcomes in heart failure patients with diabetes.

In fact, thiazolidinedione (TZD) use was associated with reductions in all-cause hospitalizations, heart failure hospitalizations, and total hospital days. The reduction in hospital days also was noted in patients treated with TZD plus insulin.

These findings challenge current recommendations against the use of TZDs in heart failure that are based on concerns regarding fluid retention, particularly when used in combination with insulin. To date, there have been no trials assessing the impact of TZD therapy on heart failure outcomes.

“These findings support the concept that perhaps the nonhypoglycemic cardiovascular effects of TZDs may have favorable clinical impact in heart failure patients,” investigator John S. Golden, M.D., said during a poster presentation at the annual meeting of the Heart Failure Society of America.

Ultimately, clinical trials will determine the specific effects of TZDs in heart failure, and the extent to which an observational study can be extrapolated to a larger population.

“I can't tell you on the basis of this study that it is something we ought to be doing as a therapeutic intervention at this point,” said Dr. Golden of Mid-Atlantic Permanente Medical Group, Fairfax, Va. “I'm certainly not putting that much stock in hospital day reductions based on a small study like this. But, again, it lends some clinical support to the biochemical mechanisms supporting not only the safety, but efficacy, of TZDs in this population.”

Consecutively, 97 diabetic patients were referred to the heart failure treatment program at Mid-Atlantic with left ventricular ejection fractions of 35% or less and New York Heart Association (NYHA) class II-IV; 37% were treated with a TZD and 15% received a TZD plus insulin.

Patients treated with TZD and those not treated with the drug were well matched with regard to baseline left ventricular ejection fraction, glycosylated hemoglobin, and NYHA class. All patients were treated with ACE inhibitors or angiotensin receptor blockers, and 97% received β-blockers.

Clinical outcomes were measured at 1 year evaluating TZD use both alone and in combination with insulin.

Improvements in ejection fractions did not differ significantly between patients treated with TZDs and those who were not. Patients treated with a TZD, compared with those not treated, had significantly reduced all-cause hospitalizations per patient (0.19 vs. 0.71), heart failure hospitalizations per patient (0.03 vs. 0.16), and total hospital days (0.67 vs. 2.72), he said.

In the subpopulation treated with TZD plus insulin, there was a significant reduction in total hospital days per patient (0.07 vs. 2.30), compared with those not on the combination therapy. There was a trend toward increased diuretic usage in the TZD plus insulin group (69.3 mg vs. 45.5 mg furosemide/day). This was not seen in patients treated with TZD alone.

NEW ORLEANS — Oral contraceptives are a safe and effective treatment for acne but are best used as adjunct therapy, Julie C. Harper, M.D., reported at the annual meeting of the American Academy of Dermatology.

Topical retinoids such as adapalene, tazarotene, and tretinoin remain the first-line treatment for all grades of acne, followed by oral or topical antibiotics, and then hormonal therapy.

“They [oral contraceptives] are fabulous to add to your acne treatment, but they aren't stand-alone medications or first-line treatments,” Dr. Harper said.

Ortho Tri-Cyclen (norgestimate/ethinyl estradiol) and Estrostep (norethindrone acetate/ethinyl estradiol) have been approved by the Food and Drug Administration for the treatment of acne.

Newer contraceptives such as Yasmin, which contains the novel progestin drospirenone also are effective, said Dr. Harper of the department of dermatology at the University of Alabama, Birmingham.

A recent study showed that Yasmin was superior to Ortho Tri-Cyclen in reducing the total number of skin lesions in women with mild to moderate acne vulgaris after 6 months, and was rated superior by investigators for its therapeutic effect (Cutis. 2004;74:123-30).

Yasmin “tops” the other OCs in treating acne, but the difference is not dramatic, Dr. Harper said. It may take several months to see an improvement in acne on Yasmin, and she recommends a minimum of 3 months of treatment.

Yasmin combines ethinyl estradiol and 3 mg of drospirenone, a spironolactone analogue that has antimineralocorticoid and antiandrogenic activity. Androgens stimulate sebaceous epithelial cell (sebocyte) differentiation and sebum production. Excess sebum is a key factor in the development of acne.

All combined oral contraceptives have the potential to improve acne because they increase sex hormone-binding globulin, thereby decreasing serum androgen. This is true even when a woman's serum levels are in the normal range.

Most women with acne have normal circulating levels of androgen hormones, she said, adding that scientists now suspect an end-organ hyperresponsiveness to androgens in patients with acne.

OCs are used most safely to treat acne in younger women who don't smoke, do not have a history of migraines, and are normotensive. Dr. Harper will not prescribe OCs to women who smoke, are aged 35 years or older, or on rifampin.

Spironolactone 50-100 mg is recommended for women who aren't candidates for OCs and have failed conservative treatments.

The relative risk of breast cancer is 1.24 times higher in current OC users, she said.

The relative risk of stroke is 2.5 times higher in current contraceptive users, although there has been no evidence that Yasmin significantly increases thrombolytic events, compared with other OCs, Dr. Harper said.

NEW ORLEANS — Oral contraceptives are a safe and effective treatment for acne but are best used as adjunct therapy, Julie C. Harper, M.D., reported at the annual meeting of the American Academy of Dermatology.

Topical retinoids such as adapalene, tazarotene, and tretinoin remain the first-line treatment for all grades of acne, followed by oral or topical antibiotics, and then hormonal therapy.

“They [oral contraceptives] are fabulous to add to your acne treatment, but they aren't stand-alone medications or first-line treatments,” Dr. Harper said.

Ortho Tri-Cyclen (norgestimate/ethinyl estradiol) and Estrostep (norethindrone acetate/ethinyl estradiol) have been approved by the Food and Drug Administration for the treatment of acne.

Newer contraceptives such as Yasmin, which contains the novel progestin drospirenone also are effective, said Dr. Harper of the department of dermatology at the University of Alabama, Birmingham.

A recent study showed that Yasmin was superior to Ortho Tri-Cyclen in reducing the total number of skin lesions in women with mild to moderate acne vulgaris after 6 months, and was rated superior by investigators for its therapeutic effect (Cutis. 2004;74:123-30).

Yasmin “tops” the other OCs in treating acne, but the difference is not dramatic, Dr. Harper said. It may take several months to see an improvement in acne on Yasmin, and she recommends a minimum of 3 months of treatment.

Yasmin combines ethinyl estradiol and 3 mg of drospirenone, a spironolactone analogue that has antimineralocorticoid and antiandrogenic activity. Androgens stimulate sebaceous epithelial cell (sebocyte) differentiation and sebum production. Excess sebum is a key factor in the development of acne.

All combined oral contraceptives have the potential to improve acne because they increase sex hormone-binding globulin, thereby decreasing serum androgen. This is true even when a woman's serum levels are in the normal range.

Most women with acne have normal circulating levels of androgen hormones, she said, adding that scientists now suspect an end-organ hyperresponsiveness to androgens in patients with acne.

OCs are used most safely to treat acne in younger women who don't smoke, do not have a history of migraines, and are normotensive. Dr. Harper will not prescribe OCs to women who smoke, are aged 35 years or older, or on rifampin.

Spironolactone 50-100 mg is recommended for women who aren't candidates for OCs and have failed conservative treatments.

The relative risk of breast cancer is 1.24 times higher in current OC users, she said.

The relative risk of stroke is 2.5 times higher in current contraceptive users, although there has been no evidence that Yasmin significantly increases thrombolytic events, compared with other OCs, Dr. Harper said.

NEW ORLEANS — Oral contraceptives are a safe and effective treatment for acne but are best used as adjunct therapy, Julie C. Harper, M.D., reported at the annual meeting of the American Academy of Dermatology.

Topical retinoids such as adapalene, tazarotene, and tretinoin remain the first-line treatment for all grades of acne, followed by oral or topical antibiotics, and then hormonal therapy.

“They [oral contraceptives] are fabulous to add to your acne treatment, but they aren't stand-alone medications or first-line treatments,” Dr. Harper said.

Ortho Tri-Cyclen (norgestimate/ethinyl estradiol) and Estrostep (norethindrone acetate/ethinyl estradiol) have been approved by the Food and Drug Administration for the treatment of acne.

Newer contraceptives such as Yasmin, which contains the novel progestin drospirenone also are effective, said Dr. Harper of the department of dermatology at the University of Alabama, Birmingham.

A recent study showed that Yasmin was superior to Ortho Tri-Cyclen in reducing the total number of skin lesions in women with mild to moderate acne vulgaris after 6 months, and was rated superior by investigators for its therapeutic effect (Cutis. 2004;74:123-30).

Yasmin “tops” the other OCs in treating acne, but the difference is not dramatic, Dr. Harper said. It may take several months to see an improvement in acne on Yasmin, and she recommends a minimum of 3 months of treatment.

Yasmin combines ethinyl estradiol and 3 mg of drospirenone, a spironolactone analogue that has antimineralocorticoid and antiandrogenic activity. Androgens stimulate sebaceous epithelial cell (sebocyte) differentiation and sebum production. Excess sebum is a key factor in the development of acne.

All combined oral contraceptives have the potential to improve acne because they increase sex hormone-binding globulin, thereby decreasing serum androgen. This is true even when a woman's serum levels are in the normal range.

Most women with acne have normal circulating levels of androgen hormones, she said, adding that scientists now suspect an end-organ hyperresponsiveness to androgens in patients with acne.

OCs are used most safely to treat acne in younger women who don't smoke, do not have a history of migraines, and are normotensive. Dr. Harper will not prescribe OCs to women who smoke, are aged 35 years or older, or on rifampin.

Spironolactone 50-100 mg is recommended for women who aren't candidates for OCs and have failed conservative treatments.

The relative risk of breast cancer is 1.24 times higher in current OC users, she said.

The relative risk of stroke is 2.5 times higher in current contraceptive users, although there has been no evidence that Yasmin significantly increases thrombolytic events, compared with other OCs, Dr. Harper said.

ATLANTA — When partial-breast irradiation was delivered with the MammoSite balloon catheter system after lumpectomy, the majority of patients showed good to excellent cosmetic results and had no local recurrences of cancer at 2 years, according to the first analysis of MammoSite Registry Trial data, presented at a symposium that was sponsored by the Society of Surgical Oncology.

Partial-breast irradiation (PBI) offers women the convenience of shortening their course of radiation treatment from 6 weeks for standard whole-breast radiation to a week. It also has the potential to substantially improve the documented underutilization of breast-conserving therapy in the United States, Peter D. Beitsch, M.D., told this newspaper.

The trial enrolled 1,419 women to receive PBI instead of a mastectomy.

The best cosmetic results were seen in women with larger breasts or with at least 7 mm of breast tissue between the skin and the balloon catheter, which is inflated inside the lumpectomy cavity. The average skin spacing was 10 mm.

Less than 10% of the women who enrolled (139) could not be treated because of a lack of skin spacing, balloon failure, lack of cavity conformity, or positive nodes. PBI is contraindicated in patients who are very young or who are node positive.

Of the 1,280 women treated, only 1% had positive margins and 91% had tumor margins greater than 2 mm. About 80% of the women had T1 tumors, 6.3% had T2 tumors, and 13.3% had ductal carcinoma in situ.

Only 3% of the patients had positive lymph nodes. Two percent of patients had breast size A, compared with 20% B, 33% C, 23% D, and 22% not reported.

About 98% of the women received a radiation dose of 34 Gy in 10 fractions over 5 days, Dr. Beitsch said during the meeting.

Analysis of the results showed that good to excellent cosmesis was achieved in 1,030 (95%) of 1,084 women overall, 229 (92%) of 248 patients at 1 year, and 18 (94.7%) of 19 patients at 2 years. Fair to poor cosmesis was reported in 54 (5%) women overall, 19 (7.7%) of 248 patients at 1 year, and 1 (5.3%) of 19 patients at 2 years.

Good to excellent cosmetic results were reported in 89% of women when the skin spacing was 7 mm or more.

Surgeons can improve skin spacing by proper preoperative planning to determine who is a candidate for the therapy prior to surgery and performing the lumpectomy accordingly, Dr. Beitsch said during an interview with this newspaper.

“The surgeon [also] must make sure the margins of the lumpectomy are free of tumor, since partial breast radiation does not make up for inferior surgery,” added Dr. Beitsch, who is the director of the Dallas Surgical Group.

Data available on 1,140 women showed that there were 92 infections (8%), of which 60 were device related.

A total of 28% of patients reported radiation dermatitis, 20% had subcutaneous tissue changes, and 9% had late radiation skin changes.

The question of long-term radiation-related complications remains to be addressed, Dr. Beitsch said, adding that the 5-day radiation treatment is radiobiologically equivalent to about 54 Gy of whole-breast radiation.

There were no local recurrences, and one death was unrelated to treatment, Dr. Beitsch said.

No women in the study had augmented breasts. Dr. Beitsch suggested such patients would be better candidates for PBI with multiple catheters due to the inability to obtain enough skin spacing.

The MammoSite balloon catheter-based brachytherapy system is designed for inflation inside the lumpectomy cavity. Proxima Therapeutics, Inc.

ATLANTA — When partial-breast irradiation was delivered with the MammoSite balloon catheter system after lumpectomy, the majority of patients showed good to excellent cosmetic results and had no local recurrences of cancer at 2 years, according to the first analysis of MammoSite Registry Trial data, presented at a symposium that was sponsored by the Society of Surgical Oncology.

Partial-breast irradiation (PBI) offers women the convenience of shortening their course of radiation treatment from 6 weeks for standard whole-breast radiation to a week. It also has the potential to substantially improve the documented underutilization of breast-conserving therapy in the United States, Peter D. Beitsch, M.D., told this newspaper.

The trial enrolled 1,419 women to receive PBI instead of a mastectomy.

The best cosmetic results were seen in women with larger breasts or with at least 7 mm of breast tissue between the skin and the balloon catheter, which is inflated inside the lumpectomy cavity. The average skin spacing was 10 mm.

Less than 10% of the women who enrolled (139) could not be treated because of a lack of skin spacing, balloon failure, lack of cavity conformity, or positive nodes. PBI is contraindicated in patients who are very young or who are node positive.

Of the 1,280 women treated, only 1% had positive margins and 91% had tumor margins greater than 2 mm. About 80% of the women had T1 tumors, 6.3% had T2 tumors, and 13.3% had ductal carcinoma in situ.

Only 3% of the patients had positive lymph nodes. Two percent of patients had breast size A, compared with 20% B, 33% C, 23% D, and 22% not reported.

About 98% of the women received a radiation dose of 34 Gy in 10 fractions over 5 days, Dr. Beitsch said during the meeting.

Analysis of the results showed that good to excellent cosmesis was achieved in 1,030 (95%) of 1,084 women overall, 229 (92%) of 248 patients at 1 year, and 18 (94.7%) of 19 patients at 2 years. Fair to poor cosmesis was reported in 54 (5%) women overall, 19 (7.7%) of 248 patients at 1 year, and 1 (5.3%) of 19 patients at 2 years.

Good to excellent cosmetic results were reported in 89% of women when the skin spacing was 7 mm or more.

Surgeons can improve skin spacing by proper preoperative planning to determine who is a candidate for the therapy prior to surgery and performing the lumpectomy accordingly, Dr. Beitsch said during an interview with this newspaper.

“The surgeon [also] must make sure the margins of the lumpectomy are free of tumor, since partial breast radiation does not make up for inferior surgery,” added Dr. Beitsch, who is the director of the Dallas Surgical Group.

Data available on 1,140 women showed that there were 92 infections (8%), of which 60 were device related.

A total of 28% of patients reported radiation dermatitis, 20% had subcutaneous tissue changes, and 9% had late radiation skin changes.

The question of long-term radiation-related complications remains to be addressed, Dr. Beitsch said, adding that the 5-day radiation treatment is radiobiologically equivalent to about 54 Gy of whole-breast radiation.

There were no local recurrences, and one death was unrelated to treatment, Dr. Beitsch said.

No women in the study had augmented breasts. Dr. Beitsch suggested such patients would be better candidates for PBI with multiple catheters due to the inability to obtain enough skin spacing.

The MammoSite balloon catheter-based brachytherapy system is designed for inflation inside the lumpectomy cavity. Proxima Therapeutics, Inc.

ATLANTA — When partial-breast irradiation was delivered with the MammoSite balloon catheter system after lumpectomy, the majority of patients showed good to excellent cosmetic results and had no local recurrences of cancer at 2 years, according to the first analysis of MammoSite Registry Trial data, presented at a symposium that was sponsored by the Society of Surgical Oncology.

Partial-breast irradiation (PBI) offers women the convenience of shortening their course of radiation treatment from 6 weeks for standard whole-breast radiation to a week. It also has the potential to substantially improve the documented underutilization of breast-conserving therapy in the United States, Peter D. Beitsch, M.D., told this newspaper.

The trial enrolled 1,419 women to receive PBI instead of a mastectomy.

The best cosmetic results were seen in women with larger breasts or with at least 7 mm of breast tissue between the skin and the balloon catheter, which is inflated inside the lumpectomy cavity. The average skin spacing was 10 mm.

Less than 10% of the women who enrolled (139) could not be treated because of a lack of skin spacing, balloon failure, lack of cavity conformity, or positive nodes. PBI is contraindicated in patients who are very young or who are node positive.

Of the 1,280 women treated, only 1% had positive margins and 91% had tumor margins greater than 2 mm. About 80% of the women had T1 tumors, 6.3% had T2 tumors, and 13.3% had ductal carcinoma in situ.

Only 3% of the patients had positive lymph nodes. Two percent of patients had breast size A, compared with 20% B, 33% C, 23% D, and 22% not reported.

About 98% of the women received a radiation dose of 34 Gy in 10 fractions over 5 days, Dr. Beitsch said during the meeting.

Analysis of the results showed that good to excellent cosmesis was achieved in 1,030 (95%) of 1,084 women overall, 229 (92%) of 248 patients at 1 year, and 18 (94.7%) of 19 patients at 2 years. Fair to poor cosmesis was reported in 54 (5%) women overall, 19 (7.7%) of 248 patients at 1 year, and 1 (5.3%) of 19 patients at 2 years.

Good to excellent cosmetic results were reported in 89% of women when the skin spacing was 7 mm or more.

Surgeons can improve skin spacing by proper preoperative planning to determine who is a candidate for the therapy prior to surgery and performing the lumpectomy accordingly, Dr. Beitsch said during an interview with this newspaper.

“The surgeon [also] must make sure the margins of the lumpectomy are free of tumor, since partial breast radiation does not make up for inferior surgery,” added Dr. Beitsch, who is the director of the Dallas Surgical Group.

Data available on 1,140 women showed that there were 92 infections (8%), of which 60 were device related.

A total of 28% of patients reported radiation dermatitis, 20% had subcutaneous tissue changes, and 9% had late radiation skin changes.

The question of long-term radiation-related complications remains to be addressed, Dr. Beitsch said, adding that the 5-day radiation treatment is radiobiologically equivalent to about 54 Gy of whole-breast radiation.

There were no local recurrences, and one death was unrelated to treatment, Dr. Beitsch said.

No women in the study had augmented breasts. Dr. Beitsch suggested such patients would be better candidates for PBI with multiple catheters due to the inability to obtain enough skin spacing.

The MammoSite balloon catheter-based brachytherapy system is designed for inflation inside the lumpectomy cavity. Proxima Therapeutics, Inc.

ATLANTA — New data suggest that the Notch signaling genes—Notch1 and Jagged1—are potential novel prognostic markers for breast cancer, Michael Reedijk, M.D., FACS, reported at a symposium sponsored by the Society of Surgical Oncology.

“Patients expressing high levels of Jagged1 or Notch1 demonstrated significantly poorer overall survival than patients expressing low levels,” said Dr. Reedijk of University Health Network, Princess Margaret Hospital in Toronto.

Abnormal Notch signaling has been observed in a number of malignancies, but this is the first report of direct evidence linking high-level Notch1 and Jagged1 expression with poorer outcomes in women with breast cancer.

The data also suggest a mechanism by which Notch is activated in aggressive breast cancer that may be targeted with drugs currently under development for Alzheimer's disease, Dr. Reedijk said.

Dr. Reedijk and colleagues at Toronto's Hospital for Sick Children and the University Health Network analyzed tumor samples from 184 breast cancers using in situ hybridization. One-third of the cancers were node-positive, one-third were node-negative, and one-third had metastasized at presentation. Notch2 was expressed at high levels in most tumors.

In contrast, high levels of Notch1,Jagged1, and Notch3 were found in the tumors of a subset of patients with poor prognostic pathological features.

Patients with tumors expressing high levels of these genes showed lower overall survival than those expressing low levels of these genes, although the association was not statistically significant for Notch3.

The 5-year survival rate for women expressing high levels of Jagged1 was 42%, with a median survival of 50 months, compared with 65% and 83 months for patients with low levels of Jagged1.

The 5-year survival rate was 49% for women expressing high levels of Notch1, with a median survival of 53 months, compared with 64% and 91 months for patients with low levels of Notch1, he said at the meeting.

For patients coexpressing high levels of both Jagged1 and Notch1, the 5-year survival rate and median survival time were approximately half of those seen for tumors without Jagged1 and/or Notch1 expression. The 5-year survival rate was just 34%, with a median survival of 43 months.

“This suggests that there is a ligand and receptor circuit that is functioning in these tumors and may identify a signaling pathway that can be therapeutically targeted using newly developed γ-secretase inhibitors, which block Notch signaling,” Dr. Reedijk said.

ATLANTA — New data suggest that the Notch signaling genes—Notch1 and Jagged1—are potential novel prognostic markers for breast cancer, Michael Reedijk, M.D., FACS, reported at a symposium sponsored by the Society of Surgical Oncology.

“Patients expressing high levels of Jagged1 or Notch1 demonstrated significantly poorer overall survival than patients expressing low levels,” said Dr. Reedijk of University Health Network, Princess Margaret Hospital in Toronto.

Abnormal Notch signaling has been observed in a number of malignancies, but this is the first report of direct evidence linking high-level Notch1 and Jagged1 expression with poorer outcomes in women with breast cancer.

The data also suggest a mechanism by which Notch is activated in aggressive breast cancer that may be targeted with drugs currently under development for Alzheimer's disease, Dr. Reedijk said.

Dr. Reedijk and colleagues at Toronto's Hospital for Sick Children and the University Health Network analyzed tumor samples from 184 breast cancers using in situ hybridization. One-third of the cancers were node-positive, one-third were node-negative, and one-third had metastasized at presentation. Notch2 was expressed at high levels in most tumors.

In contrast, high levels of Notch1,Jagged1, and Notch3 were found in the tumors of a subset of patients with poor prognostic pathological features.

Patients with tumors expressing high levels of these genes showed lower overall survival than those expressing low levels of these genes, although the association was not statistically significant for Notch3.

The 5-year survival rate for women expressing high levels of Jagged1 was 42%, with a median survival of 50 months, compared with 65% and 83 months for patients with low levels of Jagged1.

The 5-year survival rate was 49% for women expressing high levels of Notch1, with a median survival of 53 months, compared with 64% and 91 months for patients with low levels of Notch1, he said at the meeting.

For patients coexpressing high levels of both Jagged1 and Notch1, the 5-year survival rate and median survival time were approximately half of those seen for tumors without Jagged1 and/or Notch1 expression. The 5-year survival rate was just 34%, with a median survival of 43 months.

“This suggests that there is a ligand and receptor circuit that is functioning in these tumors and may identify a signaling pathway that can be therapeutically targeted using newly developed γ-secretase inhibitors, which block Notch signaling,” Dr. Reedijk said.

ATLANTA — New data suggest that the Notch signaling genes—Notch1 and Jagged1—are potential novel prognostic markers for breast cancer, Michael Reedijk, M.D., FACS, reported at a symposium sponsored by the Society of Surgical Oncology.

“Patients expressing high levels of Jagged1 or Notch1 demonstrated significantly poorer overall survival than patients expressing low levels,” said Dr. Reedijk of University Health Network, Princess Margaret Hospital in Toronto.

Abnormal Notch signaling has been observed in a number of malignancies, but this is the first report of direct evidence linking high-level Notch1 and Jagged1 expression with poorer outcomes in women with breast cancer.

The data also suggest a mechanism by which Notch is activated in aggressive breast cancer that may be targeted with drugs currently under development for Alzheimer's disease, Dr. Reedijk said.

Dr. Reedijk and colleagues at Toronto's Hospital for Sick Children and the University Health Network analyzed tumor samples from 184 breast cancers using in situ hybridization. One-third of the cancers were node-positive, one-third were node-negative, and one-third had metastasized at presentation. Notch2 was expressed at high levels in most tumors.

In contrast, high levels of Notch1,Jagged1, and Notch3 were found in the tumors of a subset of patients with poor prognostic pathological features.

Patients with tumors expressing high levels of these genes showed lower overall survival than those expressing low levels of these genes, although the association was not statistically significant for Notch3.

The 5-year survival rate for women expressing high levels of Jagged1 was 42%, with a median survival of 50 months, compared with 65% and 83 months for patients with low levels of Jagged1.

The 5-year survival rate was 49% for women expressing high levels of Notch1, with a median survival of 53 months, compared with 64% and 91 months for patients with low levels of Notch1, he said at the meeting.

For patients coexpressing high levels of both Jagged1 and Notch1, the 5-year survival rate and median survival time were approximately half of those seen for tumors without Jagged1 and/or Notch1 expression. The 5-year survival rate was just 34%, with a median survival of 43 months.

“This suggests that there is a ligand and receptor circuit that is functioning in these tumors and may identify a signaling pathway that can be therapeutically targeted using newly developed γ-secretase inhibitors, which block Notch signaling,” Dr. Reedijk said.

As the number of children taking to the links has steadily risen, so too has the number of pediatric golf-related head injuries.

Golf-related accidents were the second most common cause of sports-related injury, after bicycle use, among 2,546 patients younger than 19 years who were evaluated by neurosurgeons for any cause at the Medical College of Georgia in Augusta between 1996 and 2002. A chart review revealed 64 sports-related injuries, 15 (23%) of which were golf-related, according to Scott Y. Rahimi, M.D., lead author and neurosurgery resident at the medical college.

Seven of the golf injuries were caused by golf cart accidents, seven by golf clubs, and one by a golf ball (J. Neurosurg. [Pediatrics 2] 2005;102:163–6).

The mean age of the children in the study was 7 years, and the youngest was 9 months.

The most common injury was depressed skull fractures, which occurred in 7 (47%) of the 15 cases, followed by nondisplaced skull fractures in 3 (20%), subarachnoid hemorrhage in 2 (13%), epidural hematoma in 2 (13%), and subdural hematoma in 1 (6%).

Six children required neurosurgical procedures for their injuries. Twelve patients made full recoveries, including nine patients who were managed conservatively.

One child developed chronic headaches after a 3-year follow-up. Another child required permanent shunt placement and underwent multiple shunt revisions due to device malfunction. One child died due to uncontrollable cerebral edema following a golf-cart accident.

A review of the literature by the investigators found that not only are golf-related injuries increasing, but they are the leading type of sports injury in regions where golf is popular, Dr. Rahimi and his colleagues wrote. Augusta, where this research was conducted, is home of the Masters Golf Tournament and a hotbed of golf enthusiasm.

The authors cite a 1997 review of head injuries at the Westchester Medical Center in New York in the 3-month period following Tiger Woods' first Masters championship. The review showed that of the eight children who required surgery for their head injury, half had a depressed skull fracture from a golf club. No similar golf injuries were seen in the 12 months prior to Mr. Woods' win (Surg. Neurol. 1998;50:608).

A report by the Consumer Product Safety Commission identified 19 deaths between 1973 and 1996 that were a direct consequence of children playing with golf clubs (Percept. Mot. Skills 1998;86:747–53).

Golf-related injuries most often involve golf clubs and balls and occur at parks and homes, rather than at golf courses.

Still, the author noted, the more widespread use of golf carts also contributes to the increase in accidents.

As a way to prevent or reduce injuries, Dr. Rahimi and his colleagues recommended precautionary guidelines and safety training programs, proper storage of golf clubs, adult supervision of golf-club and golf-cart use, and the requirement of a minimum legal age to drive a golf cart. In Georgia and many other states, it is illegal to drive a golf cart without a valid driver's license.

As the number of children taking to the links has steadily risen, so too has the number of pediatric golf-related head injuries.

Golf-related accidents were the second most common cause of sports-related injury, after bicycle use, among 2,546 patients younger than 19 years who were evaluated by neurosurgeons for any cause at the Medical College of Georgia in Augusta between 1996 and 2002. A chart review revealed 64 sports-related injuries, 15 (23%) of which were golf-related, according to Scott Y. Rahimi, M.D., lead author and neurosurgery resident at the medical college.

Seven of the golf injuries were caused by golf cart accidents, seven by golf clubs, and one by a golf ball (J. Neurosurg. [Pediatrics 2] 2005;102:163–6).

The mean age of the children in the study was 7 years, and the youngest was 9 months.

The most common injury was depressed skull fractures, which occurred in 7 (47%) of the 15 cases, followed by nondisplaced skull fractures in 3 (20%), subarachnoid hemorrhage in 2 (13%), epidural hematoma in 2 (13%), and subdural hematoma in 1 (6%).

Six children required neurosurgical procedures for their injuries. Twelve patients made full recoveries, including nine patients who were managed conservatively.

One child developed chronic headaches after a 3-year follow-up. Another child required permanent shunt placement and underwent multiple shunt revisions due to device malfunction. One child died due to uncontrollable cerebral edema following a golf-cart accident.

A review of the literature by the investigators found that not only are golf-related injuries increasing, but they are the leading type of sports injury in regions where golf is popular, Dr. Rahimi and his colleagues wrote. Augusta, where this research was conducted, is home of the Masters Golf Tournament and a hotbed of golf enthusiasm.

The authors cite a 1997 review of head injuries at the Westchester Medical Center in New York in the 3-month period following Tiger Woods' first Masters championship. The review showed that of the eight children who required surgery for their head injury, half had a depressed skull fracture from a golf club. No similar golf injuries were seen in the 12 months prior to Mr. Woods' win (Surg. Neurol. 1998;50:608).

A report by the Consumer Product Safety Commission identified 19 deaths between 1973 and 1996 that were a direct consequence of children playing with golf clubs (Percept. Mot. Skills 1998;86:747–53).

Golf-related injuries most often involve golf clubs and balls and occur at parks and homes, rather than at golf courses.

Still, the author noted, the more widespread use of golf carts also contributes to the increase in accidents.

As a way to prevent or reduce injuries, Dr. Rahimi and his colleagues recommended precautionary guidelines and safety training programs, proper storage of golf clubs, adult supervision of golf-club and golf-cart use, and the requirement of a minimum legal age to drive a golf cart. In Georgia and many other states, it is illegal to drive a golf cart without a valid driver's license.

As the number of children taking to the links has steadily risen, so too has the number of pediatric golf-related head injuries.

Golf-related accidents were the second most common cause of sports-related injury, after bicycle use, among 2,546 patients younger than 19 years who were evaluated by neurosurgeons for any cause at the Medical College of Georgia in Augusta between 1996 and 2002. A chart review revealed 64 sports-related injuries, 15 (23%) of which were golf-related, according to Scott Y. Rahimi, M.D., lead author and neurosurgery resident at the medical college.

Seven of the golf injuries were caused by golf cart accidents, seven by golf clubs, and one by a golf ball (J. Neurosurg. [Pediatrics 2] 2005;102:163–6).

The mean age of the children in the study was 7 years, and the youngest was 9 months.

The most common injury was depressed skull fractures, which occurred in 7 (47%) of the 15 cases, followed by nondisplaced skull fractures in 3 (20%), subarachnoid hemorrhage in 2 (13%), epidural hematoma in 2 (13%), and subdural hematoma in 1 (6%).

Six children required neurosurgical procedures for their injuries. Twelve patients made full recoveries, including nine patients who were managed conservatively.

One child developed chronic headaches after a 3-year follow-up. Another child required permanent shunt placement and underwent multiple shunt revisions due to device malfunction. One child died due to uncontrollable cerebral edema following a golf-cart accident.

A review of the literature by the investigators found that not only are golf-related injuries increasing, but they are the leading type of sports injury in regions where golf is popular, Dr. Rahimi and his colleagues wrote. Augusta, where this research was conducted, is home of the Masters Golf Tournament and a hotbed of golf enthusiasm.

The authors cite a 1997 review of head injuries at the Westchester Medical Center in New York in the 3-month period following Tiger Woods' first Masters championship. The review showed that of the eight children who required surgery for their head injury, half had a depressed skull fracture from a golf club. No similar golf injuries were seen in the 12 months prior to Mr. Woods' win (Surg. Neurol. 1998;50:608).

A report by the Consumer Product Safety Commission identified 19 deaths between 1973 and 1996 that were a direct consequence of children playing with golf clubs (Percept. Mot. Skills 1998;86:747–53).

Golf-related injuries most often involve golf clubs and balls and occur at parks and homes, rather than at golf courses.

Still, the author noted, the more widespread use of golf carts also contributes to the increase in accidents.

As a way to prevent or reduce injuries, Dr. Rahimi and his colleagues recommended precautionary guidelines and safety training programs, proper storage of golf clubs, adult supervision of golf-club and golf-cart use, and the requirement of a minimum legal age to drive a golf cart. In Georgia and many other states, it is illegal to drive a golf cart without a valid driver's license.