Surgical Oncology

SAN FRANCISCO – Postoperative complications are prognostic for poor outcomes in patients undergoing resection of gastric cancer, researchers reported at the annual Gastrointestinal Cancers Symposium sponsored by the American Society of Clinical Oncology.

The team retrospectively analyzed data collected in the U.S. Gastric Cancer Collaborative, a joint effort of seven moderate- to high-volume academic institutions across the United States. Analyses were based on 850 patients who underwent curative resection of gastric or gastroesophageal junction adenocarcinoma by abdominal approach from 2000 to 2012.

Complications occurred within a month of surgery in 40% of the patients, reported coauthor Dr. Ryan C. Fields of Washington University in St. Louis. These patients were 20% less likely to receive adjuvant therapy than were their peers with an uncomplicated postoperative course. And during a median follow-up of almost 3 years, those with postop complications were 60% more likely to die after potential confounding factors were taken into account.

"The particular strength of this data set is the cross-section of real-world treatments and outcomes that it represents," Dr. Fields noted.

Patients who had complications were older, had higher levels of comorbidity and complexity, underwent more extensive surgery, and had more advanced disease. "We could potentially identify preoperatively [these patients] in an attempt to reduce the chance of complications," he said.

Not included in this analysis was "the finding of muscular sarcopenia as measured from the psoas muscle on a preoperative CT scan. There are ongoing studies using this measure to identify patients who may benefit from a short course of intensive physical therapy and nutritional supplementation prior to surgery in an attempt to reduce complications," he added.

The study was limited by its retrospective and nonrandomized design, and factors such as selection bias and missing data may have affected outcomes, Dr. Fields acknowledged. The researchers are therefore conducting further analyses using propensity matching and imputation.

The data set "may not be representative of (patients in) other countries or importantly of the nearly 40% of patients with gastric cancer that are treated at non-university, community-based hospitals in the United States," he added. "I would argue, however, that if we accept the relationship between volume and outcomes that has been shown to be significant in gastrectomy, the effect of complications on outcomes would be expected to be even more significant in these settings."

Groups stratified by Clavien-Dindo score were too small to draw definitive conclusions, but there were trends whereby worse complications had a greater negative impact on outcome, Dr. Fields said.

"One of the problems that we have – as an oncologic community –is there is no real consistent definition of complications in a lot of this literature," he added, which may be generating some of the disparate findings. For example, the severity of a wound infection can range widely, with more severe infections affecting decisions about whether to delay or even withhold adjuvant therapy.

In the study, there were a total of 699 complications in 342 patients, "highlighting the ... observation that often complications can beget further complications," according to Dr. Fields.

More than one-third of the complications (37%) were of Clavien-Dindo grade III or IV, requiring care more invasive than simple treatment at the bedside or with intravenous medications.

The most common were anemia/bleeding (12%), wound infections (8%), pneumonia (6%), and respiratory failure requiring reintubation (6%).

Relative to counterparts without complications, patients who had complications were on average significantly older and had significantly higher American Society of Anesthesiologists scores (reflecting greater preoperative comorbidity and complexity), more extensive and complex surgery, and more advanced cancer.

"Importantly, we did not find neoadjuvant therapy to be associated with an increase in postoperative complications, and this is consistent with literature in other solid tumor types, such as pancreatic cancer and rectal cancer," noted Dr. Fields, who disclosed no conflicts of interest related to the study. Also, the extent of lymphadenectomy was not associated with this outcome.

A minority of patients had a laparoscopic surgery, and the number was too small to say whether this factor influenced complication rate, he said.

"What we can surmise, one, from the literature, and two, is that the specific complications that are oftentimes reduced with laparoscopy and minimally invasive surgery certainly relate to wound infection and wound problems for sure," Dr. Fields commented. "So I think if we can do anything to achieve the same oncologic goals and reduce the morbidity of an operation, and improve the ability of patients to get on adjuvant therapy, that’s going to be critical. And laparoscopy may be a way to do that in gastric cancer. It may be more challenging in some of the bulkier, more advanced tumors to apply it globally, but I think it certainly holds promise for that exact point."

Overall, 60% of patients without complications received adjuvant therapy, compared with 48% of patients with complications (P = .001).

In multivariate analyses conducted after a median follow-up of 35 months, patients who experienced postoperative complications still had shorter median survival (25 vs. 45 months) and were more likely to die (hazard ratio, 1.6; P = .004).

Other significant risk factors were receipt of neoadjuvant therapy, perineural invasion, and stage III or IV disease.

Dr. Fields disclosed no relevant conflicts of interest.

SAN FRANCISCO – Postoperative complications are prognostic for poor outcomes in patients undergoing resection of gastric cancer, researchers reported at the annual Gastrointestinal Cancers Symposium sponsored by the American Society of Clinical Oncology.

The team retrospectively analyzed data collected in the U.S. Gastric Cancer Collaborative, a joint effort of seven moderate- to high-volume academic institutions across the United States. Analyses were based on 850 patients who underwent curative resection of gastric or gastroesophageal junction adenocarcinoma by abdominal approach from 2000 to 2012.

Complications occurred within a month of surgery in 40% of the patients, reported coauthor Dr. Ryan C. Fields of Washington University in St. Louis. These patients were 20% less likely to receive adjuvant therapy than were their peers with an uncomplicated postoperative course. And during a median follow-up of almost 3 years, those with postop complications were 60% more likely to die after potential confounding factors were taken into account.

"The particular strength of this data set is the cross-section of real-world treatments and outcomes that it represents," Dr. Fields noted.

Patients who had complications were older, had higher levels of comorbidity and complexity, underwent more extensive surgery, and had more advanced disease. "We could potentially identify preoperatively [these patients] in an attempt to reduce the chance of complications," he said.

Not included in this analysis was "the finding of muscular sarcopenia as measured from the psoas muscle on a preoperative CT scan. There are ongoing studies using this measure to identify patients who may benefit from a short course of intensive physical therapy and nutritional supplementation prior to surgery in an attempt to reduce complications," he added.

The study was limited by its retrospective and nonrandomized design, and factors such as selection bias and missing data may have affected outcomes, Dr. Fields acknowledged. The researchers are therefore conducting further analyses using propensity matching and imputation.

The data set "may not be representative of (patients in) other countries or importantly of the nearly 40% of patients with gastric cancer that are treated at non-university, community-based hospitals in the United States," he added. "I would argue, however, that if we accept the relationship between volume and outcomes that has been shown to be significant in gastrectomy, the effect of complications on outcomes would be expected to be even more significant in these settings."

Groups stratified by Clavien-Dindo score were too small to draw definitive conclusions, but there were trends whereby worse complications had a greater negative impact on outcome, Dr. Fields said.

"One of the problems that we have – as an oncologic community –is there is no real consistent definition of complications in a lot of this literature," he added, which may be generating some of the disparate findings. For example, the severity of a wound infection can range widely, with more severe infections affecting decisions about whether to delay or even withhold adjuvant therapy.

In the study, there were a total of 699 complications in 342 patients, "highlighting the ... observation that often complications can beget further complications," according to Dr. Fields.

More than one-third of the complications (37%) were of Clavien-Dindo grade III or IV, requiring care more invasive than simple treatment at the bedside or with intravenous medications.

The most common were anemia/bleeding (12%), wound infections (8%), pneumonia (6%), and respiratory failure requiring reintubation (6%).

Relative to counterparts without complications, patients who had complications were on average significantly older and had significantly higher American Society of Anesthesiologists scores (reflecting greater preoperative comorbidity and complexity), more extensive and complex surgery, and more advanced cancer.

"Importantly, we did not find neoadjuvant therapy to be associated with an increase in postoperative complications, and this is consistent with literature in other solid tumor types, such as pancreatic cancer and rectal cancer," noted Dr. Fields, who disclosed no conflicts of interest related to the study. Also, the extent of lymphadenectomy was not associated with this outcome.

A minority of patients had a laparoscopic surgery, and the number was too small to say whether this factor influenced complication rate, he said.

"What we can surmise, one, from the literature, and two, is that the specific complications that are oftentimes reduced with laparoscopy and minimally invasive surgery certainly relate to wound infection and wound problems for sure," Dr. Fields commented. "So I think if we can do anything to achieve the same oncologic goals and reduce the morbidity of an operation, and improve the ability of patients to get on adjuvant therapy, that’s going to be critical. And laparoscopy may be a way to do that in gastric cancer. It may be more challenging in some of the bulkier, more advanced tumors to apply it globally, but I think it certainly holds promise for that exact point."

Overall, 60% of patients without complications received adjuvant therapy, compared with 48% of patients with complications (P = .001).

In multivariate analyses conducted after a median follow-up of 35 months, patients who experienced postoperative complications still had shorter median survival (25 vs. 45 months) and were more likely to die (hazard ratio, 1.6; P = .004).

Other significant risk factors were receipt of neoadjuvant therapy, perineural invasion, and stage III or IV disease.

Dr. Fields disclosed no relevant conflicts of interest.

SAN FRANCISCO – Postoperative complications are prognostic for poor outcomes in patients undergoing resection of gastric cancer, researchers reported at the annual Gastrointestinal Cancers Symposium sponsored by the American Society of Clinical Oncology.

The team retrospectively analyzed data collected in the U.S. Gastric Cancer Collaborative, a joint effort of seven moderate- to high-volume academic institutions across the United States. Analyses were based on 850 patients who underwent curative resection of gastric or gastroesophageal junction adenocarcinoma by abdominal approach from 2000 to 2012.

Complications occurred within a month of surgery in 40% of the patients, reported coauthor Dr. Ryan C. Fields of Washington University in St. Louis. These patients were 20% less likely to receive adjuvant therapy than were their peers with an uncomplicated postoperative course. And during a median follow-up of almost 3 years, those with postop complications were 60% more likely to die after potential confounding factors were taken into account.

"The particular strength of this data set is the cross-section of real-world treatments and outcomes that it represents," Dr. Fields noted.

Patients who had complications were older, had higher levels of comorbidity and complexity, underwent more extensive surgery, and had more advanced disease. "We could potentially identify preoperatively [these patients] in an attempt to reduce the chance of complications," he said.

Not included in this analysis was "the finding of muscular sarcopenia as measured from the psoas muscle on a preoperative CT scan. There are ongoing studies using this measure to identify patients who may benefit from a short course of intensive physical therapy and nutritional supplementation prior to surgery in an attempt to reduce complications," he added.

The study was limited by its retrospective and nonrandomized design, and factors such as selection bias and missing data may have affected outcomes, Dr. Fields acknowledged. The researchers are therefore conducting further analyses using propensity matching and imputation.

The data set "may not be representative of (patients in) other countries or importantly of the nearly 40% of patients with gastric cancer that are treated at non-university, community-based hospitals in the United States," he added. "I would argue, however, that if we accept the relationship between volume and outcomes that has been shown to be significant in gastrectomy, the effect of complications on outcomes would be expected to be even more significant in these settings."

Groups stratified by Clavien-Dindo score were too small to draw definitive conclusions, but there were trends whereby worse complications had a greater negative impact on outcome, Dr. Fields said.

"One of the problems that we have – as an oncologic community –is there is no real consistent definition of complications in a lot of this literature," he added, which may be generating some of the disparate findings. For example, the severity of a wound infection can range widely, with more severe infections affecting decisions about whether to delay or even withhold adjuvant therapy.

In the study, there were a total of 699 complications in 342 patients, "highlighting the ... observation that often complications can beget further complications," according to Dr. Fields.

More than one-third of the complications (37%) were of Clavien-Dindo grade III or IV, requiring care more invasive than simple treatment at the bedside or with intravenous medications.

The most common were anemia/bleeding (12%), wound infections (8%), pneumonia (6%), and respiratory failure requiring reintubation (6%).

Relative to counterparts without complications, patients who had complications were on average significantly older and had significantly higher American Society of Anesthesiologists scores (reflecting greater preoperative comorbidity and complexity), more extensive and complex surgery, and more advanced cancer.

"Importantly, we did not find neoadjuvant therapy to be associated with an increase in postoperative complications, and this is consistent with literature in other solid tumor types, such as pancreatic cancer and rectal cancer," noted Dr. Fields, who disclosed no conflicts of interest related to the study. Also, the extent of lymphadenectomy was not associated with this outcome.

A minority of patients had a laparoscopic surgery, and the number was too small to say whether this factor influenced complication rate, he said.

"What we can surmise, one, from the literature, and two, is that the specific complications that are oftentimes reduced with laparoscopy and minimally invasive surgery certainly relate to wound infection and wound problems for sure," Dr. Fields commented. "So I think if we can do anything to achieve the same oncologic goals and reduce the morbidity of an operation, and improve the ability of patients to get on adjuvant therapy, that’s going to be critical. And laparoscopy may be a way to do that in gastric cancer. It may be more challenging in some of the bulkier, more advanced tumors to apply it globally, but I think it certainly holds promise for that exact point."

Overall, 60% of patients without complications received adjuvant therapy, compared with 48% of patients with complications (P = .001).

In multivariate analyses conducted after a median follow-up of 35 months, patients who experienced postoperative complications still had shorter median survival (25 vs. 45 months) and were more likely to die (hazard ratio, 1.6; P = .004).

Other significant risk factors were receipt of neoadjuvant therapy, perineural invasion, and stage III or IV disease.

Dr. Fields disclosed no relevant conflicts of interest.

SAN DIEGO – About 30% of nodules detected by CT screening fit the criteria for an indeterminate pulmonary nodule. Very few of those nodules represent cancer, and the question is, what do you recommend for those patients in terms of follow-up?

"We’re encountering more and more patients with lung nodules in the clinic, and with the advance of screening, it will become even more of a problem. The numbers are tremendous," Dr. Pierre P. Massion stated at the Joint Conference on the Molecular Origins of Lung Cancer, sponsored by the American Association for Cancer Research and the International Association for the Study of Lung Cancer.

Dr. Massion, the Ingram Professor of Cancer Research at Vanderbilt-Ingram Cancer Center in Nashville, Tenn., said it’s important to differentiate – early, accurately, and noninvasively – benign lesions from cancer. "There is a race for early diagnosis, because surgery is the best chance for cure ... but we also need to decrease the number of thoracotomies performed for benign disease."

Data from eight large trials of lung cancer screening examined the relationship between lesion size and the probability of lung cancer (Chest 2007;132[3 Suppl]:94S-107S). The probability of cancer was 0-1% for lesions less than 5 mm in diameter; 6%-28% for those 5-10 mm, 33%-60% for those 11-20 mm, and 64%-82% for those 21-30 mm.

"The bigger the nodule, the greater the probability of cancer. In fact, however, the number of large nodules is very small," Dr. Massion said. "The indeterminate ones are between 5 and 15 mm in diameter, and these are the ones we struggle with how best to handle." The probability of cancer from indeterminate pulmonary nodules ranges from 6% to 60%, which is a large range.

The shape of the nodule provides additional information, Dr. Massion said. Triangular shape abutting a fissure and central calcification are generally indicators of benign disease and typically do not require follow-up. Alternatively, solid, noncalcified spiculated nodules have a high likelihood of being cancer. Part solid nodules are "very worrisome," he said. "These are most likely to contain malignancy. Nonsolid lesions, also called ground-glass opacities, are troublesome and difficult to assess. They represent about a 20% probability of disease."

The rate of growth of small nodules over time "is probably one of the best imaging markers, [but] for small nodules such as those 5 mm in diameter, the volumetric analysis has a large coefficient of variance," he said.

Prediction models are important to the evaluation of lung nodules, yet even with existing tools "we’re wrong about 30% of the time," he said. The best three prediction models come from studies of patients at the Mayo Clinic (Arch. Intern. Med. 1997;157:849-55) and the Veterans Affairs department (Chest 2007;131:383-88), and from patients enrolled in the PLCO (Prostate, Lung, Colorectal, and Ovarian) Cancer Screening Trial (N. Engl. J. Med. 2013;368:728-36). These prediction models are now recommended for use on nodules greater than 8 mm in diameter in the ACCP 2013 guidelines for evaluation of lung nodules (Chest 2013;143[5 Suppl]:e93S-120S).

"We have no models for never-smokers, which is a huge problem in the community at the moment."

Dr. Massion predicted that serum biomarkers might "come to the rescue" for deciding which patients with indeterminate pulmonary nodules might need to go for a biopsy or resection and which can be carefully watched over time.

In a separate study of 62 lung nodules that integrated clinical, imaging, and protein biomarker findings, clinical information alone resulted in about 50% sensitivity for predicting disease, "which is not great," said Dr. Massion, who was the principal investigator (Cancer Epidemiol. Biomarkers Prev. 2012;21:786-92). The addition of CT imaging increased the area under the curve to about 61%. Adding biomarkers in the blood raised the bar to about 69%.

"It’s not a panacea, but we show a trend toward improvement of classification of these nodules, which is where I think this field is going – integrating information from the clinic, imaging, and the discriminatory power of biomarkers."

Dr. Massion said that he had no relevant financial conflicts to disclose.

[email protected]

SAN DIEGO – About 30% of nodules detected by CT screening fit the criteria for an indeterminate pulmonary nodule. Very few of those nodules represent cancer, and the question is, what do you recommend for those patients in terms of follow-up?

"We’re encountering more and more patients with lung nodules in the clinic, and with the advance of screening, it will become even more of a problem. The numbers are tremendous," Dr. Pierre P. Massion stated at the Joint Conference on the Molecular Origins of Lung Cancer, sponsored by the American Association for Cancer Research and the International Association for the Study of Lung Cancer.

Dr. Massion, the Ingram Professor of Cancer Research at Vanderbilt-Ingram Cancer Center in Nashville, Tenn., said it’s important to differentiate – early, accurately, and noninvasively – benign lesions from cancer. "There is a race for early diagnosis, because surgery is the best chance for cure ... but we also need to decrease the number of thoracotomies performed for benign disease."

Data from eight large trials of lung cancer screening examined the relationship between lesion size and the probability of lung cancer (Chest 2007;132[3 Suppl]:94S-107S). The probability of cancer was 0-1% for lesions less than 5 mm in diameter; 6%-28% for those 5-10 mm, 33%-60% for those 11-20 mm, and 64%-82% for those 21-30 mm.

"The bigger the nodule, the greater the probability of cancer. In fact, however, the number of large nodules is very small," Dr. Massion said. "The indeterminate ones are between 5 and 15 mm in diameter, and these are the ones we struggle with how best to handle." The probability of cancer from indeterminate pulmonary nodules ranges from 6% to 60%, which is a large range.

The shape of the nodule provides additional information, Dr. Massion said. Triangular shape abutting a fissure and central calcification are generally indicators of benign disease and typically do not require follow-up. Alternatively, solid, noncalcified spiculated nodules have a high likelihood of being cancer. Part solid nodules are "very worrisome," he said. "These are most likely to contain malignancy. Nonsolid lesions, also called ground-glass opacities, are troublesome and difficult to assess. They represent about a 20% probability of disease."

The rate of growth of small nodules over time "is probably one of the best imaging markers, [but] for small nodules such as those 5 mm in diameter, the volumetric analysis has a large coefficient of variance," he said.

Prediction models are important to the evaluation of lung nodules, yet even with existing tools "we’re wrong about 30% of the time," he said. The best three prediction models come from studies of patients at the Mayo Clinic (Arch. Intern. Med. 1997;157:849-55) and the Veterans Affairs department (Chest 2007;131:383-88), and from patients enrolled in the PLCO (Prostate, Lung, Colorectal, and Ovarian) Cancer Screening Trial (N. Engl. J. Med. 2013;368:728-36). These prediction models are now recommended for use on nodules greater than 8 mm in diameter in the ACCP 2013 guidelines for evaluation of lung nodules (Chest 2013;143[5 Suppl]:e93S-120S).

"We have no models for never-smokers, which is a huge problem in the community at the moment."

Dr. Massion predicted that serum biomarkers might "come to the rescue" for deciding which patients with indeterminate pulmonary nodules might need to go for a biopsy or resection and which can be carefully watched over time.

In a separate study of 62 lung nodules that integrated clinical, imaging, and protein biomarker findings, clinical information alone resulted in about 50% sensitivity for predicting disease, "which is not great," said Dr. Massion, who was the principal investigator (Cancer Epidemiol. Biomarkers Prev. 2012;21:786-92). The addition of CT imaging increased the area under the curve to about 61%. Adding biomarkers in the blood raised the bar to about 69%.

"It’s not a panacea, but we show a trend toward improvement of classification of these nodules, which is where I think this field is going – integrating information from the clinic, imaging, and the discriminatory power of biomarkers."

Dr. Massion said that he had no relevant financial conflicts to disclose.

[email protected]

SAN DIEGO – About 30% of nodules detected by CT screening fit the criteria for an indeterminate pulmonary nodule. Very few of those nodules represent cancer, and the question is, what do you recommend for those patients in terms of follow-up?

"We’re encountering more and more patients with lung nodules in the clinic, and with the advance of screening, it will become even more of a problem. The numbers are tremendous," Dr. Pierre P. Massion stated at the Joint Conference on the Molecular Origins of Lung Cancer, sponsored by the American Association for Cancer Research and the International Association for the Study of Lung Cancer.

Dr. Massion, the Ingram Professor of Cancer Research at Vanderbilt-Ingram Cancer Center in Nashville, Tenn., said it’s important to differentiate – early, accurately, and noninvasively – benign lesions from cancer. "There is a race for early diagnosis, because surgery is the best chance for cure ... but we also need to decrease the number of thoracotomies performed for benign disease."

Data from eight large trials of lung cancer screening examined the relationship between lesion size and the probability of lung cancer (Chest 2007;132[3 Suppl]:94S-107S). The probability of cancer was 0-1% for lesions less than 5 mm in diameter; 6%-28% for those 5-10 mm, 33%-60% for those 11-20 mm, and 64%-82% for those 21-30 mm.

"The bigger the nodule, the greater the probability of cancer. In fact, however, the number of large nodules is very small," Dr. Massion said. "The indeterminate ones are between 5 and 15 mm in diameter, and these are the ones we struggle with how best to handle." The probability of cancer from indeterminate pulmonary nodules ranges from 6% to 60%, which is a large range.

The shape of the nodule provides additional information, Dr. Massion said. Triangular shape abutting a fissure and central calcification are generally indicators of benign disease and typically do not require follow-up. Alternatively, solid, noncalcified spiculated nodules have a high likelihood of being cancer. Part solid nodules are "very worrisome," he said. "These are most likely to contain malignancy. Nonsolid lesions, also called ground-glass opacities, are troublesome and difficult to assess. They represent about a 20% probability of disease."

The rate of growth of small nodules over time "is probably one of the best imaging markers, [but] for small nodules such as those 5 mm in diameter, the volumetric analysis has a large coefficient of variance," he said.

Prediction models are important to the evaluation of lung nodules, yet even with existing tools "we’re wrong about 30% of the time," he said. The best three prediction models come from studies of patients at the Mayo Clinic (Arch. Intern. Med. 1997;157:849-55) and the Veterans Affairs department (Chest 2007;131:383-88), and from patients enrolled in the PLCO (Prostate, Lung, Colorectal, and Ovarian) Cancer Screening Trial (N. Engl. J. Med. 2013;368:728-36). These prediction models are now recommended for use on nodules greater than 8 mm in diameter in the ACCP 2013 guidelines for evaluation of lung nodules (Chest 2013;143[5 Suppl]:e93S-120S).

"We have no models for never-smokers, which is a huge problem in the community at the moment."

Dr. Massion predicted that serum biomarkers might "come to the rescue" for deciding which patients with indeterminate pulmonary nodules might need to go for a biopsy or resection and which can be carefully watched over time.

In a separate study of 62 lung nodules that integrated clinical, imaging, and protein biomarker findings, clinical information alone resulted in about 50% sensitivity for predicting disease, "which is not great," said Dr. Massion, who was the principal investigator (Cancer Epidemiol. Biomarkers Prev. 2012;21:786-92). The addition of CT imaging increased the area under the curve to about 61%. Adding biomarkers in the blood raised the bar to about 69%.

"It’s not a panacea, but we show a trend toward improvement of classification of these nodules, which is where I think this field is going – integrating information from the clinic, imaging, and the discriminatory power of biomarkers."

Dr. Massion said that he had no relevant financial conflicts to disclose.

[email protected]

As C-reactive protein levels and erythrocyte sedimentation rates go up in patients with inflammatory bowel disease, the risk of colorectal cancer goes up, too, a finding that suggests a role for both as markers of colon cancer risk, Boston investigators reported in a prospective study published online Jan. 6 in Clinical Gastroenterology and Hepatology.

The team divided 3,145 IBD patients into quartiles based on median C-reactive protein (CRP) levels, and 4,008 others into quartiles based on median erythrocyte sedimentation rates (ESR), then followed them for a median of 6 years.

On multivariate analysis, there was a significant increase in the risk of colorectal cancer (CRC) across quartiles of CRP elevation (P for trend = .017). Higher median ESR was also independently associated with higher risk of CRC across quartiles (P for trend = .007) (Clin. Gastroenterol. Hepatol. 2014 Jan. 6 [doi: 10.1016/j.cgh.2013.12.030]).

"This association adds another clinical variable to help stratify patients into risk categories. There is an important need to identify high-risk subgroups that may benefit from continued intensive surveillance strategies while allowing for less frequent colonoscopies in patients at low risk of CRC. We believe that our findings ... suggest that an individual patient’s severity of inflammation may be helpful in further personalizing surveillance recommendations," and might even help monitor other outcomes, including treatment response, said the authors, led by Dr. Ashwin Ananthakrishnan, a gastroenterologist at Massachusetts General Hospital, Boston.

After adjustment for age, sex, race, IBD type, and other factors, the patients in the highest CRP quartile had more than double the risk of colorectal cancer compared with those in the lowest quartile (OR 2.72, 95% CI 0.95-7.76). The strength of association was similar in men and women, and in Crohn’s disease and ulcerative colitis.

Similarly, patients in the highest ESR quartile had double the risk compared with those in the lowest (OR 2.06, 95% CI 1.14-3.74). The correlation was strongest in ulcerative colitis patients and men.

The median CRP values in each of the quartiles were 0.8, 2.7, 7.5, and 32.8 mg/L. In the ESR group, the median quartile values were 7, 14, 25, and 50 mm/hr.

Overall, 33 patients in the CRP cohort and 102 patients in the ESR cohort developed colorectal cancer at a median age of 55 years. The median number of CRP measurements was three, and median number of ESR measurements six. More than half the subjects were women, most were white, and ulcerative colitis was slightly more common than was Crohn’s disease.

Adjusting for number of colonoscopies, intensity of health care utilization, use of corticosteroids, and other factors did not change results for either the CRP or ESR cohorts.

The National Institutes of Health funded the work. The investigators have no disclosures.

[email protected]

As C-reactive protein levels and erythrocyte sedimentation rates go up in patients with inflammatory bowel disease, the risk of colorectal cancer goes up, too, a finding that suggests a role for both as markers of colon cancer risk, Boston investigators reported in a prospective study published online Jan. 6 in Clinical Gastroenterology and Hepatology.

The team divided 3,145 IBD patients into quartiles based on median C-reactive protein (CRP) levels, and 4,008 others into quartiles based on median erythrocyte sedimentation rates (ESR), then followed them for a median of 6 years.

On multivariate analysis, there was a significant increase in the risk of colorectal cancer (CRC) across quartiles of CRP elevation (P for trend = .017). Higher median ESR was also independently associated with higher risk of CRC across quartiles (P for trend = .007) (Clin. Gastroenterol. Hepatol. 2014 Jan. 6 [doi: 10.1016/j.cgh.2013.12.030]).

"This association adds another clinical variable to help stratify patients into risk categories. There is an important need to identify high-risk subgroups that may benefit from continued intensive surveillance strategies while allowing for less frequent colonoscopies in patients at low risk of CRC. We believe that our findings ... suggest that an individual patient’s severity of inflammation may be helpful in further personalizing surveillance recommendations," and might even help monitor other outcomes, including treatment response, said the authors, led by Dr. Ashwin Ananthakrishnan, a gastroenterologist at Massachusetts General Hospital, Boston.

After adjustment for age, sex, race, IBD type, and other factors, the patients in the highest CRP quartile had more than double the risk of colorectal cancer compared with those in the lowest quartile (OR 2.72, 95% CI 0.95-7.76). The strength of association was similar in men and women, and in Crohn’s disease and ulcerative colitis.

Similarly, patients in the highest ESR quartile had double the risk compared with those in the lowest (OR 2.06, 95% CI 1.14-3.74). The correlation was strongest in ulcerative colitis patients and men.

The median CRP values in each of the quartiles were 0.8, 2.7, 7.5, and 32.8 mg/L. In the ESR group, the median quartile values were 7, 14, 25, and 50 mm/hr.

Overall, 33 patients in the CRP cohort and 102 patients in the ESR cohort developed colorectal cancer at a median age of 55 years. The median number of CRP measurements was three, and median number of ESR measurements six. More than half the subjects were women, most were white, and ulcerative colitis was slightly more common than was Crohn’s disease.

Adjusting for number of colonoscopies, intensity of health care utilization, use of corticosteroids, and other factors did not change results for either the CRP or ESR cohorts.

The National Institutes of Health funded the work. The investigators have no disclosures.

[email protected]

As C-reactive protein levels and erythrocyte sedimentation rates go up in patients with inflammatory bowel disease, the risk of colorectal cancer goes up, too, a finding that suggests a role for both as markers of colon cancer risk, Boston investigators reported in a prospective study published online Jan. 6 in Clinical Gastroenterology and Hepatology.

The team divided 3,145 IBD patients into quartiles based on median C-reactive protein (CRP) levels, and 4,008 others into quartiles based on median erythrocyte sedimentation rates (ESR), then followed them for a median of 6 years.

On multivariate analysis, there was a significant increase in the risk of colorectal cancer (CRC) across quartiles of CRP elevation (P for trend = .017). Higher median ESR was also independently associated with higher risk of CRC across quartiles (P for trend = .007) (Clin. Gastroenterol. Hepatol. 2014 Jan. 6 [doi: 10.1016/j.cgh.2013.12.030]).

"This association adds another clinical variable to help stratify patients into risk categories. There is an important need to identify high-risk subgroups that may benefit from continued intensive surveillance strategies while allowing for less frequent colonoscopies in patients at low risk of CRC. We believe that our findings ... suggest that an individual patient’s severity of inflammation may be helpful in further personalizing surveillance recommendations," and might even help monitor other outcomes, including treatment response, said the authors, led by Dr. Ashwin Ananthakrishnan, a gastroenterologist at Massachusetts General Hospital, Boston.

After adjustment for age, sex, race, IBD type, and other factors, the patients in the highest CRP quartile had more than double the risk of colorectal cancer compared with those in the lowest quartile (OR 2.72, 95% CI 0.95-7.76). The strength of association was similar in men and women, and in Crohn’s disease and ulcerative colitis.

Similarly, patients in the highest ESR quartile had double the risk compared with those in the lowest (OR 2.06, 95% CI 1.14-3.74). The correlation was strongest in ulcerative colitis patients and men.

The median CRP values in each of the quartiles were 0.8, 2.7, 7.5, and 32.8 mg/L. In the ESR group, the median quartile values were 7, 14, 25, and 50 mm/hr.

Overall, 33 patients in the CRP cohort and 102 patients in the ESR cohort developed colorectal cancer at a median age of 55 years. The median number of CRP measurements was three, and median number of ESR measurements six. More than half the subjects were women, most were white, and ulcerative colitis was slightly more common than was Crohn’s disease.

Adjusting for number of colonoscopies, intensity of health care utilization, use of corticosteroids, and other factors did not change results for either the CRP or ESR cohorts.

The National Institutes of Health funded the work. The investigators have no disclosures.

[email protected]

SAN ANTONIO – Extracorporeal shock wave therapy shows early promise for limiting the often-vexing problem of lymphedema arising after axillary lymphadenectomy.

In the first 10 affected patients treated in an ongoing randomized, sham-controlled clinical trial, lymphedema, as measured by median whole-arm water displacement, dropped from 4,200 mL at baseline by 192.5 mL after 10 once-weekly extracorporeal shock wave (ECSW) sessions. Patients who received sham sessions had a 12.5-mL decline from baseline measures, Dr. Sara Imboden reported at the San Antonio Breast Cancer Symposium.

Quantitative CT measures indicated the mean total cross-sectional area of the most swollen part of the arm decreased by 3% in the ECSW group, compared with 1.4% in the control group, added Dr. Imboden of the University of Bern (Switzerland).

A mean of 22 axillary lymph nodes had been removed from the breast cancer patients in the study. The ECSW therapy was performed over the length of the edematous arm at an energy density of 0.25-0.69 mJ/mm² once per week for 10 weeks. The control group followed the same treatment schedule, but the shock waves were contained inside the probe during their sessions.

None of the patients had to interrupt ECSW therapy due to complications.

The researchers plan to expand the randomized trial to include 30 patients, and to augment the results with patient reports of symptoms based on questionnaires assessing body image and with extended follow-up to evaluate functioning and recurrences.

The likely mechanism of benefit in patients with lymphedema involves ECSW-induced stimulation of angiogenesis and lymphatic vessel regeneration. These results have been demonstrated in animal studies.

No medications have been shown effective in treating lymphedema. Conventional therapy entails repeated manual lymph drainage and compression bandages.

Dr. Imboden reported having no financial conflicts of interest with regard to this university-funded study.

[email protected]

SAN ANTONIO – Extracorporeal shock wave therapy shows early promise for limiting the often-vexing problem of lymphedema arising after axillary lymphadenectomy.

In the first 10 affected patients treated in an ongoing randomized, sham-controlled clinical trial, lymphedema, as measured by median whole-arm water displacement, dropped from 4,200 mL at baseline by 192.5 mL after 10 once-weekly extracorporeal shock wave (ECSW) sessions. Patients who received sham sessions had a 12.5-mL decline from baseline measures, Dr. Sara Imboden reported at the San Antonio Breast Cancer Symposium.

Quantitative CT measures indicated the mean total cross-sectional area of the most swollen part of the arm decreased by 3% in the ECSW group, compared with 1.4% in the control group, added Dr. Imboden of the University of Bern (Switzerland).

A mean of 22 axillary lymph nodes had been removed from the breast cancer patients in the study. The ECSW therapy was performed over the length of the edematous arm at an energy density of 0.25-0.69 mJ/mm² once per week for 10 weeks. The control group followed the same treatment schedule, but the shock waves were contained inside the probe during their sessions.

None of the patients had to interrupt ECSW therapy due to complications.

The researchers plan to expand the randomized trial to include 30 patients, and to augment the results with patient reports of symptoms based on questionnaires assessing body image and with extended follow-up to evaluate functioning and recurrences.

The likely mechanism of benefit in patients with lymphedema involves ECSW-induced stimulation of angiogenesis and lymphatic vessel regeneration. These results have been demonstrated in animal studies.

No medications have been shown effective in treating lymphedema. Conventional therapy entails repeated manual lymph drainage and compression bandages.

Dr. Imboden reported having no financial conflicts of interest with regard to this university-funded study.

[email protected]

SAN ANTONIO – Extracorporeal shock wave therapy shows early promise for limiting the often-vexing problem of lymphedema arising after axillary lymphadenectomy.

In the first 10 affected patients treated in an ongoing randomized, sham-controlled clinical trial, lymphedema, as measured by median whole-arm water displacement, dropped from 4,200 mL at baseline by 192.5 mL after 10 once-weekly extracorporeal shock wave (ECSW) sessions. Patients who received sham sessions had a 12.5-mL decline from baseline measures, Dr. Sara Imboden reported at the San Antonio Breast Cancer Symposium.

Quantitative CT measures indicated the mean total cross-sectional area of the most swollen part of the arm decreased by 3% in the ECSW group, compared with 1.4% in the control group, added Dr. Imboden of the University of Bern (Switzerland).

A mean of 22 axillary lymph nodes had been removed from the breast cancer patients in the study. The ECSW therapy was performed over the length of the edematous arm at an energy density of 0.25-0.69 mJ/mm² once per week for 10 weeks. The control group followed the same treatment schedule, but the shock waves were contained inside the probe during their sessions.

None of the patients had to interrupt ECSW therapy due to complications.

The researchers plan to expand the randomized trial to include 30 patients, and to augment the results with patient reports of symptoms based on questionnaires assessing body image and with extended follow-up to evaluate functioning and recurrences.

The likely mechanism of benefit in patients with lymphedema involves ECSW-induced stimulation of angiogenesis and lymphatic vessel regeneration. These results have been demonstrated in animal studies.

No medications have been shown effective in treating lymphedema. Conventional therapy entails repeated manual lymph drainage and compression bandages.

Dr. Imboden reported having no financial conflicts of interest with regard to this university-funded study.

[email protected]

A combination of two targeted, orally administered drug therapies – trametinib and dabrafenib – has been approved by the Food and Drug Administration for treating patients with unresectable melanoma or metastatic melanoma with BRAF V600E or V600K mutations, manufacturer GlaxoSmithKline announced on Jan. 9.

An FDA-approved test is used to detect the mutations, according to the company statement.

Trametinib, marketed as Mekinist, and dabrafenib, marketed as Tafinlar, were each approved in May 2013 as separate treatments for metastatic or unresectable melanomas that express the mutations – along with a companion test to detect the mutations. Both are kinase inhibitors.

The GSK statement noted that the accelerated approval of the combination therapy is based on the response rate and median duration of response results in a phase I/II study of 108 patients, which compared the combination (150 mg of dabrafenib twice a day and 2 mg of trametinib once a day) to treatment with dabrafenib alone. The overall response rates, as assessed by the investigators, were 76% among those on the combination and 54% for those on dabrafenib alone. The median duration of response was 10.5 months among those on the combination, vs. 5.6 months among those on dabrafenib alone.

The most common adverse events associated with the combination treatment included fever in 71% of patients, chills in 58%, fatigue in 52%, rash in 45%, nausea in 44%, vomiting in 40%, and diarrhea in 36%. Renal failure, pyrexia, back pain, and hemorrhage were among the most common grade-3 or -4 adverse events among those on the combination.

Serious adverse effects associated with treatment, including some potentially fatal effects, are new primary cutaneous skin cancers, tumor promotion in wild-type BRAF melanoma, and hemorrhagic events, according to GSK.

The FDA approval occurred through an accelerated process based on clinical evidence that the treatment has an effect on a surrogate endpoint that is reasonably likely to predict a clinical benefit to patients. As a condition of accelerated approval, manufacturers are required to provide more clinical data confirming benefit, and if the follow-up studies fail to confirm benefit, the FDA can withdraw approval.

Full approval is dependent on the results of an ongoing phase III study, GSK said.

The updated trametinib label states that "improvement in disease-related symptoms or overall survival has not been demonstrated" for the combination treatment.

The prescribing information for Mekinist is available at http://us.gsk.com/products/assets/us_mekinist.pdf. The prescribing information for Tafinlar (which does not yet include the updated information on the combination therapy approval) is available at http://us.gsk.com/products/assets/us_tafinlar.pdf.

[email protected]

A combination of two targeted, orally administered drug therapies – trametinib and dabrafenib – has been approved by the Food and Drug Administration for treating patients with unresectable melanoma or metastatic melanoma with BRAF V600E or V600K mutations, manufacturer GlaxoSmithKline announced on Jan. 9.

An FDA-approved test is used to detect the mutations, according to the company statement.

Trametinib, marketed as Mekinist, and dabrafenib, marketed as Tafinlar, were each approved in May 2013 as separate treatments for metastatic or unresectable melanomas that express the mutations – along with a companion test to detect the mutations. Both are kinase inhibitors.

The GSK statement noted that the accelerated approval of the combination therapy is based on the response rate and median duration of response results in a phase I/II study of 108 patients, which compared the combination (150 mg of dabrafenib twice a day and 2 mg of trametinib once a day) to treatment with dabrafenib alone. The overall response rates, as assessed by the investigators, were 76% among those on the combination and 54% for those on dabrafenib alone. The median duration of response was 10.5 months among those on the combination, vs. 5.6 months among those on dabrafenib alone.

The most common adverse events associated with the combination treatment included fever in 71% of patients, chills in 58%, fatigue in 52%, rash in 45%, nausea in 44%, vomiting in 40%, and diarrhea in 36%. Renal failure, pyrexia, back pain, and hemorrhage were among the most common grade-3 or -4 adverse events among those on the combination.

Serious adverse effects associated with treatment, including some potentially fatal effects, are new primary cutaneous skin cancers, tumor promotion in wild-type BRAF melanoma, and hemorrhagic events, according to GSK.

The FDA approval occurred through an accelerated process based on clinical evidence that the treatment has an effect on a surrogate endpoint that is reasonably likely to predict a clinical benefit to patients. As a condition of accelerated approval, manufacturers are required to provide more clinical data confirming benefit, and if the follow-up studies fail to confirm benefit, the FDA can withdraw approval.

Full approval is dependent on the results of an ongoing phase III study, GSK said.

The updated trametinib label states that "improvement in disease-related symptoms or overall survival has not been demonstrated" for the combination treatment.

The prescribing information for Mekinist is available at http://us.gsk.com/products/assets/us_mekinist.pdf. The prescribing information for Tafinlar (which does not yet include the updated information on the combination therapy approval) is available at http://us.gsk.com/products/assets/us_tafinlar.pdf.

[email protected]

A combination of two targeted, orally administered drug therapies – trametinib and dabrafenib – has been approved by the Food and Drug Administration for treating patients with unresectable melanoma or metastatic melanoma with BRAF V600E or V600K mutations, manufacturer GlaxoSmithKline announced on Jan. 9.

An FDA-approved test is used to detect the mutations, according to the company statement.

Trametinib, marketed as Mekinist, and dabrafenib, marketed as Tafinlar, were each approved in May 2013 as separate treatments for metastatic or unresectable melanomas that express the mutations – along with a companion test to detect the mutations. Both are kinase inhibitors.

The GSK statement noted that the accelerated approval of the combination therapy is based on the response rate and median duration of response results in a phase I/II study of 108 patients, which compared the combination (150 mg of dabrafenib twice a day and 2 mg of trametinib once a day) to treatment with dabrafenib alone. The overall response rates, as assessed by the investigators, were 76% among those on the combination and 54% for those on dabrafenib alone. The median duration of response was 10.5 months among those on the combination, vs. 5.6 months among those on dabrafenib alone.

The most common adverse events associated with the combination treatment included fever in 71% of patients, chills in 58%, fatigue in 52%, rash in 45%, nausea in 44%, vomiting in 40%, and diarrhea in 36%. Renal failure, pyrexia, back pain, and hemorrhage were among the most common grade-3 or -4 adverse events among those on the combination.

Serious adverse effects associated with treatment, including some potentially fatal effects, are new primary cutaneous skin cancers, tumor promotion in wild-type BRAF melanoma, and hemorrhagic events, according to GSK.

The FDA approval occurred through an accelerated process based on clinical evidence that the treatment has an effect on a surrogate endpoint that is reasonably likely to predict a clinical benefit to patients. As a condition of accelerated approval, manufacturers are required to provide more clinical data confirming benefit, and if the follow-up studies fail to confirm benefit, the FDA can withdraw approval.

Full approval is dependent on the results of an ongoing phase III study, GSK said.

The updated trametinib label states that "improvement in disease-related symptoms or overall survival has not been demonstrated" for the combination treatment.

The prescribing information for Mekinist is available at http://us.gsk.com/products/assets/us_mekinist.pdf. The prescribing information for Tafinlar (which does not yet include the updated information on the combination therapy approval) is available at http://us.gsk.com/products/assets/us_tafinlar.pdf.

[email protected]

SAN ANTONIO – Surgical removal of the primary tumor and affected lymph nodes afforded no overall survival benefit in women who had metastatic breast cancer at initial presentation, according to a pair of randomized trials presented at the San Antonio Breast Cancer Symposium.

In a first trial, conducted among 350 women in India who had responded to initial chemotherapy, about 20% of the women were still alive at 5 years regardless of whether they had surgery or just received more systemic therapy, first author Dr. Rajendra Badwe, director of the Tata Memorial Hospital in Mumbai, India, reported in a session and at a press briefing.

Superior locoregional control conferred by surgery was canceled out by a higher risk of progression in distant sites, lending support to more than 20-year-old preclinical data by Dr. Bernard Fisher and his colleagues suggesting that an intact primary suppresses growth of distant metastases (Cancer Res. 1989;49:1996-2001).

"Locoregional treatment of the primary tumor in women presenting with metastatic breast cancer did not result in any overall survival benefit and hence should not be offered as a routine practice," Dr. Badwe commented.

"The biological fallout of this study is that surgical removal of the primary tumor in these women appears to confer a growth advantage on distant metastases. ... This is the first time that we have evidence in human studies that locoregional treatment has a great kinetic effect on distant metastases," he added.

In a second trial, conducted among 293 women in Turkey with untreated de novo metastatic breast cancer, median estimated survival was statistically indistinguishable, at about 3.5 years, regardless of whether women had up-front surgery or simply systemic therapy, first author Dr. Atilla Soran reported in a session on behalf of the Turkish Federation of Societies for Breast Diseases.

Subgroup analyses suggested that surgery conferred a survival advantage among women with solitary bone metastases but a survival disadvantage among women with multiple liver or lung metastases.

The rate of locoregional progression was one-fifth as high with surgery as with systemic therapy.

"There was no statistically significant difference in overall survival at early follow-up, but we need longer follow-up," Dr. Soran commented. "There were potentially important subgroup differences."

The two trials have implications – both for other ongoing trials and for patient care – according to invited discussant Dr. Seema A. Khan, a professor of surgery and Bluhm Family Professor of Cancer Research at Northwestern University, Chicago, and a physician at the university’s Lynn Sage Breast Center.

"A large benefit of primary site local therapy seems unlikely based on the data we saw today," she maintained. "The assumptions we have used in our ongoing trial designs will need to be reassessed. Preplanned pooled analyses may yield sufficient power to detect smaller differences."

As for patient care, "it is pretty clear that at this point in time, we have to make sure that our patients understand that there is really no proven survival advantage to primary site local therapy," Dr. Khan said. "So I don’t think this treatment should be offered to patients with asymptomatic tumors unless they are participating in a clinical trial. There may be a local control advantage; we need to see more data on that."

Indian trial

Participants in the Indian trial, conducted between 2005 and 2013, were women with de novo metastatic breast cancer who had had a complete or partial response to anthracycline chemotherapy alone or with a taxane.

They were randomized evenly to receive locoregional therapy (lumpectomy or mastectomy with axillary lymph node dissection, plus radiation therapy to the chest wall or breast and lymph nodes) or no locoregional therapy as a control. Both groups received hormonal therapy if indicated.

In the control group, about 10% of women underwent a palliative mastectomy because of impending fungation or pain in the breast, as permitted by study protocol, according to Dr. Badwe.

The patients thus received contemporary therapy, he said, except that the 16% with HER2-positive disease did not receive the targeted agent trastuzumab (Herceptin).

Results showed that median overall survival was about 18 months, and the 5-year rate was 19.2% with locoregional therapy and 20.5% without it, a nonsignificant difference. "Uniformly, there was no difference at all in any subsets," Dr. Badwe reported.

The study had a one-sided superiority design, he noted. "We wouldn’t have been able to see a 2.5- or 3-month difference, or a 4% detriment" in overall survival.

The surgery group had a lower risk of local progression-free survival events (hazard ratio, 0.16; P = .00), but a higher risk of distant progression-free survival events (HR, 1.42; P = .01).

Several theories might explain why removal of the primary would accelerate growth of metastases, according to Dr. Badwe.

"The first and the foremost is that the act of surgery itself might elaborate some growth factors which might allow metastatic disease to grow. The second possibility, which was suggested by Dr. Fisher (Cancer Res. 1989;49:1996-2001) is that the primary tumor, which predates the onset of distant metastases, elaborates some inhibitory factors, and they are not there once the primary tumor is removed, bestowing autonomy of growth on the distant metastases," he explained. "And the third possibility is the act of surgery might induce some more metastatic processes by dissemination and create new disease."

Session attendee Dr. Steven Vogl, an oncologist in the Bronx, N.Y., said, "The ascertainment of disease progression requires disease that you can follow. A woman with bone-only metastases with her cancer in place, you can tell when her cancer is getting worse because the primary site or the axillary nodes are getting bigger. It’s much more difficult if you’ve taken those off and irradiated the chest wall. Have you looked at your data to see if that’s what was going on, why you had more distant metastases, because they couldn’t progress locally? This is a medical trial explanation that contradicts Fisher’s biologic hypothesis."

"There was a fixed time duration at which systemic investigations were performed to assess whether the distant metastases progressed," Dr. Badwe replied. If anything, the patients who did not have surgery had more assessments of their distant metastases, he said.

Dr. Tari A. King, a session attendee from the Memorial Sloan-Kettering Cancer Center, New York, noted that a lack of HER2 therapy in the trial may have had a large effect.

"We do have prospective registry data here [abstract 18-09, presented in a poster session] from a trial that we completed in the United States sponsored by the Translational Breast Cancer Research Consortium, and the patients in our study, whether they received surgery or not, their 2-year overall survival is far superior to what you’ve just showed us," she commented. "So I’m not sure that we can really apply your data to the modern targeted therapy regimens that we see in the United States."

Turkish trial

The Turkish trial, known as the MF07-01 trial, was conduced between 2008 and 2012 among treatment-naïve patients.

They were randomized evenly to receive either systemic therapy alone or surgery for the primary tumor (with or without axillary dissection) followed by radiation therapy if indicated, plus systemic therapy.

All patients received hormonal therapy as needed, and those with HER2-positive disease received trastuzumab.

With a median follow-up of 18 months, the median overall survival was 46 months with initial surgery and 42 months with initial systemic therapy, a nonsignificant difference, reported Dr. Soran, who disclosed no relevant conflicts of interest.

In unplanned subgroup analyses, the findings were similar for most subgroups of patients. However, surgery yielded superior survival in patients with solitary bone metastases (not reached vs. 42 months, P = .02) and inferior survival in patients having multiple liver or pulmonary metastases (16 months vs. not reached, P = .02).

The rate of locoregional progression was much lower with initial surgery than with initial systemic therapy (0.7% vs. 3.6%).

Dr. Soran emphasized that the trial’s planned median follow-up is 36 months, so the presented results are only preliminary. Quality of life and morbidity analyses are ongoing.

Dr. Badwe and Dr. Soran disclosed no relevant conflicts of interest.

SAN ANTONIO – Surgical removal of the primary tumor and affected lymph nodes afforded no overall survival benefit in women who had metastatic breast cancer at initial presentation, according to a pair of randomized trials presented at the San Antonio Breast Cancer Symposium.

In a first trial, conducted among 350 women in India who had responded to initial chemotherapy, about 20% of the women were still alive at 5 years regardless of whether they had surgery or just received more systemic therapy, first author Dr. Rajendra Badwe, director of the Tata Memorial Hospital in Mumbai, India, reported in a session and at a press briefing.

Superior locoregional control conferred by surgery was canceled out by a higher risk of progression in distant sites, lending support to more than 20-year-old preclinical data by Dr. Bernard Fisher and his colleagues suggesting that an intact primary suppresses growth of distant metastases (Cancer Res. 1989;49:1996-2001).

"Locoregional treatment of the primary tumor in women presenting with metastatic breast cancer did not result in any overall survival benefit and hence should not be offered as a routine practice," Dr. Badwe commented.

"The biological fallout of this study is that surgical removal of the primary tumor in these women appears to confer a growth advantage on distant metastases. ... This is the first time that we have evidence in human studies that locoregional treatment has a great kinetic effect on distant metastases," he added.

In a second trial, conducted among 293 women in Turkey with untreated de novo metastatic breast cancer, median estimated survival was statistically indistinguishable, at about 3.5 years, regardless of whether women had up-front surgery or simply systemic therapy, first author Dr. Atilla Soran reported in a session on behalf of the Turkish Federation of Societies for Breast Diseases.

Subgroup analyses suggested that surgery conferred a survival advantage among women with solitary bone metastases but a survival disadvantage among women with multiple liver or lung metastases.

The rate of locoregional progression was one-fifth as high with surgery as with systemic therapy.

"There was no statistically significant difference in overall survival at early follow-up, but we need longer follow-up," Dr. Soran commented. "There were potentially important subgroup differences."

The two trials have implications – both for other ongoing trials and for patient care – according to invited discussant Dr. Seema A. Khan, a professor of surgery and Bluhm Family Professor of Cancer Research at Northwestern University, Chicago, and a physician at the university’s Lynn Sage Breast Center.

"A large benefit of primary site local therapy seems unlikely based on the data we saw today," she maintained. "The assumptions we have used in our ongoing trial designs will need to be reassessed. Preplanned pooled analyses may yield sufficient power to detect smaller differences."

As for patient care, "it is pretty clear that at this point in time, we have to make sure that our patients understand that there is really no proven survival advantage to primary site local therapy," Dr. Khan said. "So I don’t think this treatment should be offered to patients with asymptomatic tumors unless they are participating in a clinical trial. There may be a local control advantage; we need to see more data on that."

Indian trial

Participants in the Indian trial, conducted between 2005 and 2013, were women with de novo metastatic breast cancer who had had a complete or partial response to anthracycline chemotherapy alone or with a taxane.

They were randomized evenly to receive locoregional therapy (lumpectomy or mastectomy with axillary lymph node dissection, plus radiation therapy to the chest wall or breast and lymph nodes) or no locoregional therapy as a control. Both groups received hormonal therapy if indicated.

In the control group, about 10% of women underwent a palliative mastectomy because of impending fungation or pain in the breast, as permitted by study protocol, according to Dr. Badwe.

The patients thus received contemporary therapy, he said, except that the 16% with HER2-positive disease did not receive the targeted agent trastuzumab (Herceptin).

Results showed that median overall survival was about 18 months, and the 5-year rate was 19.2% with locoregional therapy and 20.5% without it, a nonsignificant difference. "Uniformly, there was no difference at all in any subsets," Dr. Badwe reported.

The study had a one-sided superiority design, he noted. "We wouldn’t have been able to see a 2.5- or 3-month difference, or a 4% detriment" in overall survival.

The surgery group had a lower risk of local progression-free survival events (hazard ratio, 0.16; P = .00), but a higher risk of distant progression-free survival events (HR, 1.42; P = .01).

Several theories might explain why removal of the primary would accelerate growth of metastases, according to Dr. Badwe.

"The first and the foremost is that the act of surgery itself might elaborate some growth factors which might allow metastatic disease to grow. The second possibility, which was suggested by Dr. Fisher (Cancer Res. 1989;49:1996-2001) is that the primary tumor, which predates the onset of distant metastases, elaborates some inhibitory factors, and they are not there once the primary tumor is removed, bestowing autonomy of growth on the distant metastases," he explained. "And the third possibility is the act of surgery might induce some more metastatic processes by dissemination and create new disease."

Session attendee Dr. Steven Vogl, an oncologist in the Bronx, N.Y., said, "The ascertainment of disease progression requires disease that you can follow. A woman with bone-only metastases with her cancer in place, you can tell when her cancer is getting worse because the primary site or the axillary nodes are getting bigger. It’s much more difficult if you’ve taken those off and irradiated the chest wall. Have you looked at your data to see if that’s what was going on, why you had more distant metastases, because they couldn’t progress locally? This is a medical trial explanation that contradicts Fisher’s biologic hypothesis."

"There was a fixed time duration at which systemic investigations were performed to assess whether the distant metastases progressed," Dr. Badwe replied. If anything, the patients who did not have surgery had more assessments of their distant metastases, he said.

Dr. Tari A. King, a session attendee from the Memorial Sloan-Kettering Cancer Center, New York, noted that a lack of HER2 therapy in the trial may have had a large effect.

"We do have prospective registry data here [abstract 18-09, presented in a poster session] from a trial that we completed in the United States sponsored by the Translational Breast Cancer Research Consortium, and the patients in our study, whether they received surgery or not, their 2-year overall survival is far superior to what you’ve just showed us," she commented. "So I’m not sure that we can really apply your data to the modern targeted therapy regimens that we see in the United States."

Turkish trial

The Turkish trial, known as the MF07-01 trial, was conduced between 2008 and 2012 among treatment-naïve patients.

They were randomized evenly to receive either systemic therapy alone or surgery for the primary tumor (with or without axillary dissection) followed by radiation therapy if indicated, plus systemic therapy.

All patients received hormonal therapy as needed, and those with HER2-positive disease received trastuzumab.

With a median follow-up of 18 months, the median overall survival was 46 months with initial surgery and 42 months with initial systemic therapy, a nonsignificant difference, reported Dr. Soran, who disclosed no relevant conflicts of interest.

In unplanned subgroup analyses, the findings were similar for most subgroups of patients. However, surgery yielded superior survival in patients with solitary bone metastases (not reached vs. 42 months, P = .02) and inferior survival in patients having multiple liver or pulmonary metastases (16 months vs. not reached, P = .02).

The rate of locoregional progression was much lower with initial surgery than with initial systemic therapy (0.7% vs. 3.6%).

Dr. Soran emphasized that the trial’s planned median follow-up is 36 months, so the presented results are only preliminary. Quality of life and morbidity analyses are ongoing.

Dr. Badwe and Dr. Soran disclosed no relevant conflicts of interest.

SAN ANTONIO – Surgical removal of the primary tumor and affected lymph nodes afforded no overall survival benefit in women who had metastatic breast cancer at initial presentation, according to a pair of randomized trials presented at the San Antonio Breast Cancer Symposium.

In a first trial, conducted among 350 women in India who had responded to initial chemotherapy, about 20% of the women were still alive at 5 years regardless of whether they had surgery or just received more systemic therapy, first author Dr. Rajendra Badwe, director of the Tata Memorial Hospital in Mumbai, India, reported in a session and at a press briefing.

Superior locoregional control conferred by surgery was canceled out by a higher risk of progression in distant sites, lending support to more than 20-year-old preclinical data by Dr. Bernard Fisher and his colleagues suggesting that an intact primary suppresses growth of distant metastases (Cancer Res. 1989;49:1996-2001).

"Locoregional treatment of the primary tumor in women presenting with metastatic breast cancer did not result in any overall survival benefit and hence should not be offered as a routine practice," Dr. Badwe commented.

"The biological fallout of this study is that surgical removal of the primary tumor in these women appears to confer a growth advantage on distant metastases. ... This is the first time that we have evidence in human studies that locoregional treatment has a great kinetic effect on distant metastases," he added.

In a second trial, conducted among 293 women in Turkey with untreated de novo metastatic breast cancer, median estimated survival was statistically indistinguishable, at about 3.5 years, regardless of whether women had up-front surgery or simply systemic therapy, first author Dr. Atilla Soran reported in a session on behalf of the Turkish Federation of Societies for Breast Diseases.

Subgroup analyses suggested that surgery conferred a survival advantage among women with solitary bone metastases but a survival disadvantage among women with multiple liver or lung metastases.

The rate of locoregional progression was one-fifth as high with surgery as with systemic therapy.

"There was no statistically significant difference in overall survival at early follow-up, but we need longer follow-up," Dr. Soran commented. "There were potentially important subgroup differences."

The two trials have implications – both for other ongoing trials and for patient care – according to invited discussant Dr. Seema A. Khan, a professor of surgery and Bluhm Family Professor of Cancer Research at Northwestern University, Chicago, and a physician at the university’s Lynn Sage Breast Center.

"A large benefit of primary site local therapy seems unlikely based on the data we saw today," she maintained. "The assumptions we have used in our ongoing trial designs will need to be reassessed. Preplanned pooled analyses may yield sufficient power to detect smaller differences."

As for patient care, "it is pretty clear that at this point in time, we have to make sure that our patients understand that there is really no proven survival advantage to primary site local therapy," Dr. Khan said. "So I don’t think this treatment should be offered to patients with asymptomatic tumors unless they are participating in a clinical trial. There may be a local control advantage; we need to see more data on that."

Indian trial

Participants in the Indian trial, conducted between 2005 and 2013, were women with de novo metastatic breast cancer who had had a complete or partial response to anthracycline chemotherapy alone or with a taxane.

They were randomized evenly to receive locoregional therapy (lumpectomy or mastectomy with axillary lymph node dissection, plus radiation therapy to the chest wall or breast and lymph nodes) or no locoregional therapy as a control. Both groups received hormonal therapy if indicated.

In the control group, about 10% of women underwent a palliative mastectomy because of impending fungation or pain in the breast, as permitted by study protocol, according to Dr. Badwe.

The patients thus received contemporary therapy, he said, except that the 16% with HER2-positive disease did not receive the targeted agent trastuzumab (Herceptin).

Results showed that median overall survival was about 18 months, and the 5-year rate was 19.2% with locoregional therapy and 20.5% without it, a nonsignificant difference. "Uniformly, there was no difference at all in any subsets," Dr. Badwe reported.

The study had a one-sided superiority design, he noted. "We wouldn’t have been able to see a 2.5- or 3-month difference, or a 4% detriment" in overall survival.

The surgery group had a lower risk of local progression-free survival events (hazard ratio, 0.16; P = .00), but a higher risk of distant progression-free survival events (HR, 1.42; P = .01).

Several theories might explain why removal of the primary would accelerate growth of metastases, according to Dr. Badwe.

"The first and the foremost is that the act of surgery itself might elaborate some growth factors which might allow metastatic disease to grow. The second possibility, which was suggested by Dr. Fisher (Cancer Res. 1989;49:1996-2001) is that the primary tumor, which predates the onset of distant metastases, elaborates some inhibitory factors, and they are not there once the primary tumor is removed, bestowing autonomy of growth on the distant metastases," he explained. "And the third possibility is the act of surgery might induce some more metastatic processes by dissemination and create new disease."

Session attendee Dr. Steven Vogl, an oncologist in the Bronx, N.Y., said, "The ascertainment of disease progression requires disease that you can follow. A woman with bone-only metastases with her cancer in place, you can tell when her cancer is getting worse because the primary site or the axillary nodes are getting bigger. It’s much more difficult if you’ve taken those off and irradiated the chest wall. Have you looked at your data to see if that’s what was going on, why you had more distant metastases, because they couldn’t progress locally? This is a medical trial explanation that contradicts Fisher’s biologic hypothesis."

"There was a fixed time duration at which systemic investigations were performed to assess whether the distant metastases progressed," Dr. Badwe replied. If anything, the patients who did not have surgery had more assessments of their distant metastases, he said.

Dr. Tari A. King, a session attendee from the Memorial Sloan-Kettering Cancer Center, New York, noted that a lack of HER2 therapy in the trial may have had a large effect.

"We do have prospective registry data here [abstract 18-09, presented in a poster session] from a trial that we completed in the United States sponsored by the Translational Breast Cancer Research Consortium, and the patients in our study, whether they received surgery or not, their 2-year overall survival is far superior to what you’ve just showed us," she commented. "So I’m not sure that we can really apply your data to the modern targeted therapy regimens that we see in the United States."

Turkish trial

The Turkish trial, known as the MF07-01 trial, was conduced between 2008 and 2012 among treatment-naïve patients.

They were randomized evenly to receive either systemic therapy alone or surgery for the primary tumor (with or without axillary dissection) followed by radiation therapy if indicated, plus systemic therapy.

All patients received hormonal therapy as needed, and those with HER2-positive disease received trastuzumab.

With a median follow-up of 18 months, the median overall survival was 46 months with initial surgery and 42 months with initial systemic therapy, a nonsignificant difference, reported Dr. Soran, who disclosed no relevant conflicts of interest.

In unplanned subgroup analyses, the findings were similar for most subgroups of patients. However, surgery yielded superior survival in patients with solitary bone metastases (not reached vs. 42 months, P = .02) and inferior survival in patients having multiple liver or pulmonary metastases (16 months vs. not reached, P = .02).

The rate of locoregional progression was much lower with initial surgery than with initial systemic therapy (0.7% vs. 3.6%).

Dr. Soran emphasized that the trial’s planned median follow-up is 36 months, so the presented results are only preliminary. Quality of life and morbidity analyses are ongoing.

Dr. Badwe and Dr. Soran disclosed no relevant conflicts of interest.

SAN ANTONIO – Perineural injection of bupivacaine and dexamethasone was a simple and effective treatment for chronic neuropathic pain following mastectomy, based on results of a pilot study.

The effectiveness of this novel therapy strongly suggests the source of this common pain syndrome is damage to the T4 and T5 sensory nerves during surgery, rather than damage to the intercostobrachial nerve, as traditionally thought, according to Dr. Cathy J. Tang of the University of California, San Francisco.

The T4 and T5 sensory nerves come off the chest wall and enter the breast accompanied by a blood vessel. When these nerves are cut and cauterized during mastectomy, the resultant nerve damage can manifest as neuroma formation and neuropathic pain along the two dermatomes, she said at the San Antonio Breast Cancer Symposium.

Chronic postmastectomy breast pain is commonly referred to as postmastectomy pain syndrome. Published estimates of its incidence after mastectomy range from 20% to 68%. The pain can start in the immediate postoperative period, or onset can be delayed up to 6 months or more post mastectomy. The pain is typically experienced as a shooting or burning pain, with point tenderness. It persists well after the expected healing period.

The intervention involves identifying a patient’s points of maximum pain or tenderness, usually located laterally along the midaxillary line or at the inframammary fold directly below the nipple. These points are injected at the level of the chest wall. Each injection consists of 2 mL of an equal ratio of 0.5% bupivacaine plus 4 mg/mL of dexamethasone followed by a minute or two of massage to enhance infiltration of the area.

Dr. Tang reported on 19 patients who developed postmastectomy pain syndrome after either partial mastectomy, total mastectomy with immediate reconstruction, or lateral core biopsy in one case. A total of 29 points of maximum tenderness were identified and treated. All patients had pain relief within minutes, with point pain scores on a 0-10 scale falling from 8-9 to 0-1. Long-term pain relief was experienced after 17 of the 29 initial injections (59%) in 11 patients. Pain was resolved at another nine sites after a second injection. A third injection at one recalcitrant site led to long-term pain relief. Thus, perineural injections alleviated pain at 27 of 29 treated sites, or 93%, at a mean of 10.7 months of follow-up.

In light of how simple and safe this treatment is, Dr. Tang urged routine inquiry about postmastectomy neuropathic pain. Patients with postmastectomy pain often report an inability to lie on the affected side or to wear a bra.

The study also indicates the importance of careful dissection of the T4 and T5 sensory nerves during mastectomy in order to minimize the risk of postoperative neuroma formation.

Dr. Tang reported having no financial conflicts regarding this unfunded study.

[email protected]

SAN ANTONIO – Perineural injection of bupivacaine and dexamethasone was a simple and effective treatment for chronic neuropathic pain following mastectomy, based on results of a pilot study.

The effectiveness of this novel therapy strongly suggests the source of this common pain syndrome is damage to the T4 and T5 sensory nerves during surgery, rather than damage to the intercostobrachial nerve, as traditionally thought, according to Dr. Cathy J. Tang of the University of California, San Francisco.

The T4 and T5 sensory nerves come off the chest wall and enter the breast accompanied by a blood vessel. When these nerves are cut and cauterized during mastectomy, the resultant nerve damage can manifest as neuroma formation and neuropathic pain along the two dermatomes, she said at the San Antonio Breast Cancer Symposium.

Chronic postmastectomy breast pain is commonly referred to as postmastectomy pain syndrome. Published estimates of its incidence after mastectomy range from 20% to 68%. The pain can start in the immediate postoperative period, or onset can be delayed up to 6 months or more post mastectomy. The pain is typically experienced as a shooting or burning pain, with point tenderness. It persists well after the expected healing period.

The intervention involves identifying a patient’s points of maximum pain or tenderness, usually located laterally along the midaxillary line or at the inframammary fold directly below the nipple. These points are injected at the level of the chest wall. Each injection consists of 2 mL of an equal ratio of 0.5% bupivacaine plus 4 mg/mL of dexamethasone followed by a minute or two of massage to enhance infiltration of the area.

Dr. Tang reported on 19 patients who developed postmastectomy pain syndrome after either partial mastectomy, total mastectomy with immediate reconstruction, or lateral core biopsy in one case. A total of 29 points of maximum tenderness were identified and treated. All patients had pain relief within minutes, with point pain scores on a 0-10 scale falling from 8-9 to 0-1. Long-term pain relief was experienced after 17 of the 29 initial injections (59%) in 11 patients. Pain was resolved at another nine sites after a second injection. A third injection at one recalcitrant site led to long-term pain relief. Thus, perineural injections alleviated pain at 27 of 29 treated sites, or 93%, at a mean of 10.7 months of follow-up.

In light of how simple and safe this treatment is, Dr. Tang urged routine inquiry about postmastectomy neuropathic pain. Patients with postmastectomy pain often report an inability to lie on the affected side or to wear a bra.

The study also indicates the importance of careful dissection of the T4 and T5 sensory nerves during mastectomy in order to minimize the risk of postoperative neuroma formation.

Dr. Tang reported having no financial conflicts regarding this unfunded study.

[email protected]

SAN ANTONIO – Perineural injection of bupivacaine and dexamethasone was a simple and effective treatment for chronic neuropathic pain following mastectomy, based on results of a pilot study.

The effectiveness of this novel therapy strongly suggests the source of this common pain syndrome is damage to the T4 and T5 sensory nerves during surgery, rather than damage to the intercostobrachial nerve, as traditionally thought, according to Dr. Cathy J. Tang of the University of California, San Francisco.

The T4 and T5 sensory nerves come off the chest wall and enter the breast accompanied by a blood vessel. When these nerves are cut and cauterized during mastectomy, the resultant nerve damage can manifest as neuroma formation and neuropathic pain along the two dermatomes, she said at the San Antonio Breast Cancer Symposium.

Chronic postmastectomy breast pain is commonly referred to as postmastectomy pain syndrome. Published estimates of its incidence after mastectomy range from 20% to 68%. The pain can start in the immediate postoperative period, or onset can be delayed up to 6 months or more post mastectomy. The pain is typically experienced as a shooting or burning pain, with point tenderness. It persists well after the expected healing period.

The intervention involves identifying a patient’s points of maximum pain or tenderness, usually located laterally along the midaxillary line or at the inframammary fold directly below the nipple. These points are injected at the level of the chest wall. Each injection consists of 2 mL of an equal ratio of 0.5% bupivacaine plus 4 mg/mL of dexamethasone followed by a minute or two of massage to enhance infiltration of the area.

Dr. Tang reported on 19 patients who developed postmastectomy pain syndrome after either partial mastectomy, total mastectomy with immediate reconstruction, or lateral core biopsy in one case. A total of 29 points of maximum tenderness were identified and treated. All patients had pain relief within minutes, with point pain scores on a 0-10 scale falling from 8-9 to 0-1. Long-term pain relief was experienced after 17 of the 29 initial injections (59%) in 11 patients. Pain was resolved at another nine sites after a second injection. A third injection at one recalcitrant site led to long-term pain relief. Thus, perineural injections alleviated pain at 27 of 29 treated sites, or 93%, at a mean of 10.7 months of follow-up.

In light of how simple and safe this treatment is, Dr. Tang urged routine inquiry about postmastectomy neuropathic pain. Patients with postmastectomy pain often report an inability to lie on the affected side or to wear a bra.

The study also indicates the importance of careful dissection of the T4 and T5 sensory nerves during mastectomy in order to minimize the risk of postoperative neuroma formation.

Dr. Tang reported having no financial conflicts regarding this unfunded study.

[email protected]

SAN ANTONIO – MRI screening of women who were at average risk of breast cancer and had a negative screening mammogram resulted in the diagnosis of 11 cases of cancer per 1,000 women screened, Dr. Simone Schrading said at the San Antonio Breast Cancer Symposium.

"The additional cancer detection rate is high, even in heavily prescreened women. In experienced hands, the positive predictive value of MRI screening in this average-risk cohort was comparable to that seen in mammographic screening programs or in MRI high-risk screening cohorts," said Dr. Schrading, of the University of Aachen, Germany.

While MRI is well established as a screening method for women at high familial risk of breast cancer, there have been no data to support its use in average-risk women.

Courtesy ©SABCS/Todd Buchanan2012

Dr. Schrading reported on a prospective, single-center study evaluating the additional cancer yield and accuracy of breast MRI screening in 1,725 women at average risk for breast cancer. All had normal clinical breast examinations and digital screening mammograms. In addition, 89% of the women had undergone high-frequency breast ultrasound screening, which was normal in all cases. None of the subjects had a personal or family history of breast or ovarian cancer, and none had been diagnosed with breast proliferative changes or atypia. Their mean age was 55 years (range, 42-71 years).

MRI screening detected breast cancers in 18 of these patients, for a detection rate of 11 per 1,000 screened. Seven malignancies were ductal carcinoma in situ, and the other 11 were invasive breast cancer. The mean size of the invasive cancers was 11 mm. Five of the 7 ductal carcinomas in situ and 6 of 11 invasive cancers were high-grade cancers. On the other hand, the stage distribution of the invasive cancers was favorable: All were staged as pN0, M0.

Nearly 91% of screening MRIs were negative as defined by a BIRADS 1 or 2 rating. Another 5.9% were rated BIRADS 3; follow-up MRIs in this group of patients showed no breast cancers. Suspicious lesions – that is, BIRADS 4 or 5 – were noted in 54 patients, or 3.2% of the study group, and they were evaluated by MRI-guided biopsy. The lesions proved benign in 28 of 54 cases, high risk in 8, and malignant in 18.

Thus, the positive predictive value of breast MRI screening in this average-risk, extensively prescreened population was 33% if only BIRADS 4 and 5 cancers were defined as true positives, and 48% if BIRADS 4 and 5 high-risk lesions were also counted.

The age distribution of the patients with MRI-detected breast cancers was similar to that of the total study population. Mammographic breast density did not predict the likelihood of identifying breast cancer by MRI.

Dr. Laura J. Esserman rose from the audience to question the cost-benefit ratio of introducing MRI screening for the vast population of average-risk women.

The aggregate cost of breast cancer screening in the United States is already at least $8 billion annually. Utilizing MRI to screen average-risk women would push that figure up by an order of magnitude, observed Dr. Esserman, professor of surgery and of radiology and director of the Carol Franc Buck Breast Care Center at the University of California, San Francisco.

"MRI screening is still very expensive, it’s true," Dr. Schrading replied. "The main reason for the high cost of MRI is the long acquisition time and the long reading time. The long acquisition time is because the MRI protocols we have today are designed for diagnostic purposes, not for the purpose of screening. Our goal is to use a screening protocol for MRI, where the acquisition time is only 3 minutes and the reading time is less than 30 seconds. This might be a way to reduce the cost of MRI," she said.

The study was conducted free of commercial support. Dr. Schrading declared having no financial conflicts of interest.

[email protected]

SAN ANTONIO – MRI screening of women who were at average risk of breast cancer and had a negative screening mammogram resulted in the diagnosis of 11 cases of cancer per 1,000 women screened, Dr. Simone Schrading said at the San Antonio Breast Cancer Symposium.

"The additional cancer detection rate is high, even in heavily prescreened women. In experienced hands, the positive predictive value of MRI screening in this average-risk cohort was comparable to that seen in mammographic screening programs or in MRI high-risk screening cohorts," said Dr. Schrading, of the University of Aachen, Germany.

While MRI is well established as a screening method for women at high familial risk of breast cancer, there have been no data to support its use in average-risk women.

Courtesy ©SABCS/Todd Buchanan2012

Dr. Schrading reported on a prospective, single-center study evaluating the additional cancer yield and accuracy of breast MRI screening in 1,725 women at average risk for breast cancer. All had normal clinical breast examinations and digital screening mammograms. In addition, 89% of the women had undergone high-frequency breast ultrasound screening, which was normal in all cases. None of the subjects had a personal or family history of breast or ovarian cancer, and none had been diagnosed with breast proliferative changes or atypia. Their mean age was 55 years (range, 42-71 years).

MRI screening detected breast cancers in 18 of these patients, for a detection rate of 11 per 1,000 screened. Seven malignancies were ductal carcinoma in situ, and the other 11 were invasive breast cancer. The mean size of the invasive cancers was 11 mm. Five of the 7 ductal carcinomas in situ and 6 of 11 invasive cancers were high-grade cancers. On the other hand, the stage distribution of the invasive cancers was favorable: All were staged as pN0, M0.

Nearly 91% of screening MRIs were negative as defined by a BIRADS 1 or 2 rating. Another 5.9% were rated BIRADS 3; follow-up MRIs in this group of patients showed no breast cancers. Suspicious lesions – that is, BIRADS 4 or 5 – were noted in 54 patients, or 3.2% of the study group, and they were evaluated by MRI-guided biopsy. The lesions proved benign in 28 of 54 cases, high risk in 8, and malignant in 18.

Thus, the positive predictive value of breast MRI screening in this average-risk, extensively prescreened population was 33% if only BIRADS 4 and 5 cancers were defined as true positives, and 48% if BIRADS 4 and 5 high-risk lesions were also counted.

The age distribution of the patients with MRI-detected breast cancers was similar to that of the total study population. Mammographic breast density did not predict the likelihood of identifying breast cancer by MRI.

Dr. Laura J. Esserman rose from the audience to question the cost-benefit ratio of introducing MRI screening for the vast population of average-risk women.

The aggregate cost of breast cancer screening in the United States is already at least $8 billion annually. Utilizing MRI to screen average-risk women would push that figure up by an order of magnitude, observed Dr. Esserman, professor of surgery and of radiology and director of the Carol Franc Buck Breast Care Center at the University of California, San Francisco.

"MRI screening is still very expensive, it’s true," Dr. Schrading replied. "The main reason for the high cost of MRI is the long acquisition time and the long reading time. The long acquisition time is because the MRI protocols we have today are designed for diagnostic purposes, not for the purpose of screening. Our goal is to use a screening protocol for MRI, where the acquisition time is only 3 minutes and the reading time is less than 30 seconds. This might be a way to reduce the cost of MRI," she said.

The study was conducted free of commercial support. Dr. Schrading declared having no financial conflicts of interest.

[email protected]

SAN ANTONIO – MRI screening of women who were at average risk of breast cancer and had a negative screening mammogram resulted in the diagnosis of 11 cases of cancer per 1,000 women screened, Dr. Simone Schrading said at the San Antonio Breast Cancer Symposium.

"The additional cancer detection rate is high, even in heavily prescreened women. In experienced hands, the positive predictive value of MRI screening in this average-risk cohort was comparable to that seen in mammographic screening programs or in MRI high-risk screening cohorts," said Dr. Schrading, of the University of Aachen, Germany.

While MRI is well established as a screening method for women at high familial risk of breast cancer, there have been no data to support its use in average-risk women.

Courtesy ©SABCS/Todd Buchanan2012

Dr. Schrading reported on a prospective, single-center study evaluating the additional cancer yield and accuracy of breast MRI screening in 1,725 women at average risk for breast cancer. All had normal clinical breast examinations and digital screening mammograms. In addition, 89% of the women had undergone high-frequency breast ultrasound screening, which was normal in all cases. None of the subjects had a personal or family history of breast or ovarian cancer, and none had been diagnosed with breast proliferative changes or atypia. Their mean age was 55 years (range, 42-71 years).

MRI screening detected breast cancers in 18 of these patients, for a detection rate of 11 per 1,000 screened. Seven malignancies were ductal carcinoma in situ, and the other 11 were invasive breast cancer. The mean size of the invasive cancers was 11 mm. Five of the 7 ductal carcinomas in situ and 6 of 11 invasive cancers were high-grade cancers. On the other hand, the stage distribution of the invasive cancers was favorable: All were staged as pN0, M0.

Nearly 91% of screening MRIs were negative as defined by a BIRADS 1 or 2 rating. Another 5.9% were rated BIRADS 3; follow-up MRIs in this group of patients showed no breast cancers. Suspicious lesions – that is, BIRADS 4 or 5 – were noted in 54 patients, or 3.2% of the study group, and they were evaluated by MRI-guided biopsy. The lesions proved benign in 28 of 54 cases, high risk in 8, and malignant in 18.

Thus, the positive predictive value of breast MRI screening in this average-risk, extensively prescreened population was 33% if only BIRADS 4 and 5 cancers were defined as true positives, and 48% if BIRADS 4 and 5 high-risk lesions were also counted.

The age distribution of the patients with MRI-detected breast cancers was similar to that of the total study population. Mammographic breast density did not predict the likelihood of identifying breast cancer by MRI.

Dr. Laura J. Esserman rose from the audience to question the cost-benefit ratio of introducing MRI screening for the vast population of average-risk women.

The aggregate cost of breast cancer screening in the United States is already at least $8 billion annually. Utilizing MRI to screen average-risk women would push that figure up by an order of magnitude, observed Dr. Esserman, professor of surgery and of radiology and director of the Carol Franc Buck Breast Care Center at the University of California, San Francisco.

"MRI screening is still very expensive, it’s true," Dr. Schrading replied. "The main reason for the high cost of MRI is the long acquisition time and the long reading time. The long acquisition time is because the MRI protocols we have today are designed for diagnostic purposes, not for the purpose of screening. Our goal is to use a screening protocol for MRI, where the acquisition time is only 3 minutes and the reading time is less than 30 seconds. This might be a way to reduce the cost of MRI," she said.

The study was conducted free of commercial support. Dr. Schrading declared having no financial conflicts of interest.

[email protected]

Live from the 2013 San Antonio Breast Cancer Symposium, our onsite reporters checked in with meeting attendees to find out the "most interesting thing" they had learned so far. From identifying predictive signatures via genomic data to treating postmenopausal women with bisphosphonates, passing oncologists shared their favorite, potentially practice-changing highlights.

Live from the 2013 San Antonio Breast Cancer Symposium, our onsite reporters checked in with meeting attendees to find out the "most interesting thing" they had learned so far. From identifying predictive signatures via genomic data to treating postmenopausal women with bisphosphonates, passing oncologists shared their favorite, potentially practice-changing highlights.

Live from the 2013 San Antonio Breast Cancer Symposium, our onsite reporters checked in with meeting attendees to find out the "most interesting thing" they had learned so far. From identifying predictive signatures via genomic data to treating postmenopausal women with bisphosphonates, passing oncologists shared their favorite, potentially practice-changing highlights.

In an interview with Frontline Medical News, New York oncologist and San Antonio Breast Cancer Symposium star gadfly Dr. Steven Vogl gives his quick take on several of the studies making news at this year's meeting.

In an interview with Frontline Medical News, New York oncologist and San Antonio Breast Cancer Symposium star gadfly Dr. Steven Vogl gives his quick take on several of the studies making news at this year's meeting.

In an interview with Frontline Medical News, New York oncologist and San Antonio Breast Cancer Symposium star gadfly Dr. Steven Vogl gives his quick take on several of the studies making news at this year's meeting.