Surgical Oncology

CHICAGO  – Radiation therapy dramatically improves local control in ductal carcinoma in situ, even in cases having favorable features, investigators reported.

The randomized Radiation Therapy Oncology Group (RTOG) 9804 trial was conducted among 585 women who had "good-risk" ductal carcinoma in situ (DCIS), meaning small, asymptomatic tumors of low grade and with adequate resection margins after lumpectomy.

The main results showed that women had a significant 86% relative reduction in the risk of local failure if they received radiation therapy instead of observation. But the absolute 5-year rate of local failure was only about 3%, even without this intervention.

"We were able, using standard pathology methods and our Web-based RTOG pathology tool, to define good-risk or low-risk DCIS patients who had an extremely low event rate even with observation," said lead investigator Dr. Beryl McCormick at the annual meeting of the American Society of Clinical Oncology.

Nonetheless, "for this good-risk disease, the addition of radiation significantly reduced the risk of local failure. Clearly, we are expecting to follow this group out longer," added Dr. McCormick, a radiation oncologist and chief of the external beam radiotherapy service at Memorial Sloan-Kettering Cancer Center in New York.

"The study was a positive study," commented discussant Dr. Eun-Sil Shelley Hwang of Duke University Medical Center in Durham, N.C. "The reasons for that are debatable. On this analysis, there was a lower recurrence rate in the excision-only group than had been predicted, but what drove the positive findings was the much lower rate in the radiation therapy group."

Dr. Hwang speculated that the use of tamoxifen by about two-thirds of women may have contributed to the low rate of local recurrence seen even in the absence of radiation therapy.

"Further follow-up is required, because many of these patients [had] a short follow-up that may explain why we saw such low recurrence risks in this study," she proposed.

Women with DCIS who were above age 26 were eligible for RTOG 9804 if they had no symptoms (their tumors had been found mammographically or incidentally), had only low or intermediate tumor grade, had a tumor size of 2.5 cm or less, and had a resection margin width of at least 3 mm.

The 585 study participants were randomly assigned in balanced fashion to observation or radiation therapy, each with or without tamoxifen. (Overall, 62% received the drug.) Radiation therapy began within 12 weeks of final surgery, and consisted of 42.5-50.4 Gy, with no boost.

The main trial results showed that the actuarial 5-year rate of local failure (invasive or noninvasive) in the treated breast was 3.2% in the observation group and 0.4% in the radiation therapy group, corresponding to an 86% reduction in risk (hazard ratio, 0.14; P = .002), Dr. McCormick reported.

In the radiation therapy group, there were no local failures in the same quadrant as the original tumor; in contrast, in the observation group, two-thirds of the failures were in the same quadrant.

The two groups were statistically indistinguishable with respect to the rate of contralateral breast events, disease-free survival, and overall survival.

The rate of acute grade 3 or worse nonhematologic toxicities was similar in the observation group and radiation therapy group (4.0% vs. 4.2%, respectively), although lower-grade toxicities were more common in the latter. The rate of late grade 3 or worse radiation therapy toxicity was 0.7% in the group given this therapy.

Dr. McCormick disclosed no relevant conflicts of interest. Dr. Hwang disclosed that she is a consultant to Genomic Health and receives research funding from Merck and Novartis.

CHICAGO  – Radiation therapy dramatically improves local control in ductal carcinoma in situ, even in cases having favorable features, investigators reported.

The randomized Radiation Therapy Oncology Group (RTOG) 9804 trial was conducted among 585 women who had "good-risk" ductal carcinoma in situ (DCIS), meaning small, asymptomatic tumors of low grade and with adequate resection margins after lumpectomy.

The main results showed that women had a significant 86% relative reduction in the risk of local failure if they received radiation therapy instead of observation. But the absolute 5-year rate of local failure was only about 3%, even without this intervention.

"We were able, using standard pathology methods and our Web-based RTOG pathology tool, to define good-risk or low-risk DCIS patients who had an extremely low event rate even with observation," said lead investigator Dr. Beryl McCormick at the annual meeting of the American Society of Clinical Oncology.

Nonetheless, "for this good-risk disease, the addition of radiation significantly reduced the risk of local failure. Clearly, we are expecting to follow this group out longer," added Dr. McCormick, a radiation oncologist and chief of the external beam radiotherapy service at Memorial Sloan-Kettering Cancer Center in New York.

"The study was a positive study," commented discussant Dr. Eun-Sil Shelley Hwang of Duke University Medical Center in Durham, N.C. "The reasons for that are debatable. On this analysis, there was a lower recurrence rate in the excision-only group than had been predicted, but what drove the positive findings was the much lower rate in the radiation therapy group."

Dr. Hwang speculated that the use of tamoxifen by about two-thirds of women may have contributed to the low rate of local recurrence seen even in the absence of radiation therapy.

"Further follow-up is required, because many of these patients [had] a short follow-up that may explain why we saw such low recurrence risks in this study," she proposed.

Women with DCIS who were above age 26 were eligible for RTOG 9804 if they had no symptoms (their tumors had been found mammographically or incidentally), had only low or intermediate tumor grade, had a tumor size of 2.5 cm or less, and had a resection margin width of at least 3 mm.

The 585 study participants were randomly assigned in balanced fashion to observation or radiation therapy, each with or without tamoxifen. (Overall, 62% received the drug.) Radiation therapy began within 12 weeks of final surgery, and consisted of 42.5-50.4 Gy, with no boost.

The main trial results showed that the actuarial 5-year rate of local failure (invasive or noninvasive) in the treated breast was 3.2% in the observation group and 0.4% in the radiation therapy group, corresponding to an 86% reduction in risk (hazard ratio, 0.14; P = .002), Dr. McCormick reported.

In the radiation therapy group, there were no local failures in the same quadrant as the original tumor; in contrast, in the observation group, two-thirds of the failures were in the same quadrant.

The two groups were statistically indistinguishable with respect to the rate of contralateral breast events, disease-free survival, and overall survival.

The rate of acute grade 3 or worse nonhematologic toxicities was similar in the observation group and radiation therapy group (4.0% vs. 4.2%, respectively), although lower-grade toxicities were more common in the latter. The rate of late grade 3 or worse radiation therapy toxicity was 0.7% in the group given this therapy.

Dr. McCormick disclosed no relevant conflicts of interest. Dr. Hwang disclosed that she is a consultant to Genomic Health and receives research funding from Merck and Novartis.

CHICAGO  – Radiation therapy dramatically improves local control in ductal carcinoma in situ, even in cases having favorable features, investigators reported.

The randomized Radiation Therapy Oncology Group (RTOG) 9804 trial was conducted among 585 women who had "good-risk" ductal carcinoma in situ (DCIS), meaning small, asymptomatic tumors of low grade and with adequate resection margins after lumpectomy.

The main results showed that women had a significant 86% relative reduction in the risk of local failure if they received radiation therapy instead of observation. But the absolute 5-year rate of local failure was only about 3%, even without this intervention.

"We were able, using standard pathology methods and our Web-based RTOG pathology tool, to define good-risk or low-risk DCIS patients who had an extremely low event rate even with observation," said lead investigator Dr. Beryl McCormick at the annual meeting of the American Society of Clinical Oncology.

Nonetheless, "for this good-risk disease, the addition of radiation significantly reduced the risk of local failure. Clearly, we are expecting to follow this group out longer," added Dr. McCormick, a radiation oncologist and chief of the external beam radiotherapy service at Memorial Sloan-Kettering Cancer Center in New York.

"The study was a positive study," commented discussant Dr. Eun-Sil Shelley Hwang of Duke University Medical Center in Durham, N.C. "The reasons for that are debatable. On this analysis, there was a lower recurrence rate in the excision-only group than had been predicted, but what drove the positive findings was the much lower rate in the radiation therapy group."

Dr. Hwang speculated that the use of tamoxifen by about two-thirds of women may have contributed to the low rate of local recurrence seen even in the absence of radiation therapy.

"Further follow-up is required, because many of these patients [had] a short follow-up that may explain why we saw such low recurrence risks in this study," she proposed.

Women with DCIS who were above age 26 were eligible for RTOG 9804 if they had no symptoms (their tumors had been found mammographically or incidentally), had only low or intermediate tumor grade, had a tumor size of 2.5 cm or less, and had a resection margin width of at least 3 mm.

The 585 study participants were randomly assigned in balanced fashion to observation or radiation therapy, each with or without tamoxifen. (Overall, 62% received the drug.) Radiation therapy began within 12 weeks of final surgery, and consisted of 42.5-50.4 Gy, with no boost.

The main trial results showed that the actuarial 5-year rate of local failure (invasive or noninvasive) in the treated breast was 3.2% in the observation group and 0.4% in the radiation therapy group, corresponding to an 86% reduction in risk (hazard ratio, 0.14; P = .002), Dr. McCormick reported.

In the radiation therapy group, there were no local failures in the same quadrant as the original tumor; in contrast, in the observation group, two-thirds of the failures were in the same quadrant.

The two groups were statistically indistinguishable with respect to the rate of contralateral breast events, disease-free survival, and overall survival.

The rate of acute grade 3 or worse nonhematologic toxicities was similar in the observation group and radiation therapy group (4.0% vs. 4.2%, respectively), although lower-grade toxicities were more common in the latter. The rate of late grade 3 or worse radiation therapy toxicity was 0.7% in the group given this therapy.

Dr. McCormick disclosed no relevant conflicts of interest. Dr. Hwang disclosed that she is a consultant to Genomic Health and receives research funding from Merck and Novartis.

CHICAGO – The new DCIS score, an offshoot of the Oncotype DX recurrence score, independently predicts the risk of ipsilateral recurrence or invasive disease in patients with ductal carcinoma in situ, according to a subgroup analysis from the prospective validation study.

The score correlated only moderately, poorly, or not at all with measures such as menopausal status and histologic grade among 327 patients with ductal carcinoma in situ (DCIS) treated with wide local excision and without radiation therapy, investigators reported.

And even after such measures were taken into account, each 50-point increase in the 100-point score was significantly associated with more than a doubling of the 10-year risk of recurrence or invasive disease in the same breast.

"The DCIS score provides independent information on ipsilateral breast risk beyond clinical and pathologic variables," lead author Dr. Sunil S. Badve said at the annual meeting of the American Society of Clinical Oncology.

"One can use the DCIS score to select patients with ... a clinically good prognosis who may have a higher DCIS score and may have a slightly [greater] risk than one would have estimated by traditional criteria," added Dr. Badve, a professor in the department of pathology and laboratory medicine and the department of internal medicine, and director of the Translational Genomics Core at Indiana University, Indianapolis.

"So particularly for the subset with a clinically good prognosis, we may be able to dissect which patients really might have a better prognosis and which patients may need to be more cautious."

Discussant Dr. Eun-Sil Shelley Hwang of Duke University Medical Center in Durham, N.C., called particular attention to the weak association between nuclear grade and DCIS Score.

"This is a very important point to make and a response to the criticism that’s often heard that the DCIS score or the Oncotype score may just be a surrogate – and a very expensive one – for proliferative index or Ki-67," she commented.

Next-generation sequencing and advances in epigenomics, proteomics, and molecular characterization of stroma are likely to make it possible to further risk-stratify DCIS in the future, according to Dr. Hwang.

"But none of this is important unless we can implement it into treatment of patients. So how this is implemented in our everyday practice will be very important to analyze – whether it impacts decision making, and whether it gives patients satisfaction with the decisions they make will also be very important to look at," she added.

"Finally, in this increasingly resource-constrained environment, cost-effectiveness issues will also be very important to analyze as we go forward," she noted.

Study analyses were based on a subset of women from the E5194 trial, a prospective study to validate the DCIS score, which contains 12 of the 21 genes included in the Oncotype DX recurrence score used in estrogen receptor–positive early-stage breast cancer.

All of the women had DCIS treated with wide local excision. They had a median age of 61 years and a median tumor size of 7 mm. Twenty-nine percent received tamoxifen. The median duration of follow-up was 8.8 years.

Results showed that the DCIS score was only moderately correlated with histologic grade (r = 0.41-0.46) and with the percentage of cells showing comedo necrosis (r = 0.49), and was poorly correlated with tumor size (r = 0.18), Dr. Badve reported. And there was no correlation with age, menopausal status, DCIS histologic pattern, or margin status.

In a multivariate analysis, each 50-point increase in DCIS score was associated with more than a doubling of the risk of a recurrence of DCIS or the occurrence of invasive disease in the ipsilateral breast (hazard ratio, 2.41; P = .02).

In addition, tumor size was an independent positive predictor of risk (HR for each 5-mm increase, 1.52; P = .01), and postmenopausal status was an independent negative predictor (HR, 0.49; P = .02).

Dr. Badve disclosed that he is a consultant to Genomic Health, which makes the assay. Dr. Hwang disclosed that she is a consultant to Genomic Health and receives research funding from Merck and Novartis.

CHICAGO – The new DCIS score, an offshoot of the Oncotype DX recurrence score, independently predicts the risk of ipsilateral recurrence or invasive disease in patients with ductal carcinoma in situ, according to a subgroup analysis from the prospective validation study.

The score correlated only moderately, poorly, or not at all with measures such as menopausal status and histologic grade among 327 patients with ductal carcinoma in situ (DCIS) treated with wide local excision and without radiation therapy, investigators reported.

And even after such measures were taken into account, each 50-point increase in the 100-point score was significantly associated with more than a doubling of the 10-year risk of recurrence or invasive disease in the same breast.

"The DCIS score provides independent information on ipsilateral breast risk beyond clinical and pathologic variables," lead author Dr. Sunil S. Badve said at the annual meeting of the American Society of Clinical Oncology.

"One can use the DCIS score to select patients with ... a clinically good prognosis who may have a higher DCIS score and may have a slightly [greater] risk than one would have estimated by traditional criteria," added Dr. Badve, a professor in the department of pathology and laboratory medicine and the department of internal medicine, and director of the Translational Genomics Core at Indiana University, Indianapolis.

"So particularly for the subset with a clinically good prognosis, we may be able to dissect which patients really might have a better prognosis and which patients may need to be more cautious."

Discussant Dr. Eun-Sil Shelley Hwang of Duke University Medical Center in Durham, N.C., called particular attention to the weak association between nuclear grade and DCIS Score.

"This is a very important point to make and a response to the criticism that’s often heard that the DCIS score or the Oncotype score may just be a surrogate – and a very expensive one – for proliferative index or Ki-67," she commented.

Next-generation sequencing and advances in epigenomics, proteomics, and molecular characterization of stroma are likely to make it possible to further risk-stratify DCIS in the future, according to Dr. Hwang.

"But none of this is important unless we can implement it into treatment of patients. So how this is implemented in our everyday practice will be very important to analyze – whether it impacts decision making, and whether it gives patients satisfaction with the decisions they make will also be very important to look at," she added.

"Finally, in this increasingly resource-constrained environment, cost-effectiveness issues will also be very important to analyze as we go forward," she noted.

Study analyses were based on a subset of women from the E5194 trial, a prospective study to validate the DCIS score, which contains 12 of the 21 genes included in the Oncotype DX recurrence score used in estrogen receptor–positive early-stage breast cancer.

All of the women had DCIS treated with wide local excision. They had a median age of 61 years and a median tumor size of 7 mm. Twenty-nine percent received tamoxifen. The median duration of follow-up was 8.8 years.

Results showed that the DCIS score was only moderately correlated with histologic grade (r = 0.41-0.46) and with the percentage of cells showing comedo necrosis (r = 0.49), and was poorly correlated with tumor size (r = 0.18), Dr. Badve reported. And there was no correlation with age, menopausal status, DCIS histologic pattern, or margin status.

In a multivariate analysis, each 50-point increase in DCIS score was associated with more than a doubling of the risk of a recurrence of DCIS or the occurrence of invasive disease in the ipsilateral breast (hazard ratio, 2.41; P = .02).

In addition, tumor size was an independent positive predictor of risk (HR for each 5-mm increase, 1.52; P = .01), and postmenopausal status was an independent negative predictor (HR, 0.49; P = .02).

Dr. Badve disclosed that he is a consultant to Genomic Health, which makes the assay. Dr. Hwang disclosed that she is a consultant to Genomic Health and receives research funding from Merck and Novartis.

CHICAGO – The new DCIS score, an offshoot of the Oncotype DX recurrence score, independently predicts the risk of ipsilateral recurrence or invasive disease in patients with ductal carcinoma in situ, according to a subgroup analysis from the prospective validation study.

The score correlated only moderately, poorly, or not at all with measures such as menopausal status and histologic grade among 327 patients with ductal carcinoma in situ (DCIS) treated with wide local excision and without radiation therapy, investigators reported.

And even after such measures were taken into account, each 50-point increase in the 100-point score was significantly associated with more than a doubling of the 10-year risk of recurrence or invasive disease in the same breast.

"The DCIS score provides independent information on ipsilateral breast risk beyond clinical and pathologic variables," lead author Dr. Sunil S. Badve said at the annual meeting of the American Society of Clinical Oncology.

"One can use the DCIS score to select patients with ... a clinically good prognosis who may have a higher DCIS score and may have a slightly [greater] risk than one would have estimated by traditional criteria," added Dr. Badve, a professor in the department of pathology and laboratory medicine and the department of internal medicine, and director of the Translational Genomics Core at Indiana University, Indianapolis.

"So particularly for the subset with a clinically good prognosis, we may be able to dissect which patients really might have a better prognosis and which patients may need to be more cautious."

Discussant Dr. Eun-Sil Shelley Hwang of Duke University Medical Center in Durham, N.C., called particular attention to the weak association between nuclear grade and DCIS Score.

"This is a very important point to make and a response to the criticism that’s often heard that the DCIS score or the Oncotype score may just be a surrogate – and a very expensive one – for proliferative index or Ki-67," she commented.

Next-generation sequencing and advances in epigenomics, proteomics, and molecular characterization of stroma are likely to make it possible to further risk-stratify DCIS in the future, according to Dr. Hwang.

"But none of this is important unless we can implement it into treatment of patients. So how this is implemented in our everyday practice will be very important to analyze – whether it impacts decision making, and whether it gives patients satisfaction with the decisions they make will also be very important to look at," she added.

"Finally, in this increasingly resource-constrained environment, cost-effectiveness issues will also be very important to analyze as we go forward," she noted.

Study analyses were based on a subset of women from the E5194 trial, a prospective study to validate the DCIS score, which contains 12 of the 21 genes included in the Oncotype DX recurrence score used in estrogen receptor–positive early-stage breast cancer.

All of the women had DCIS treated with wide local excision. They had a median age of 61 years and a median tumor size of 7 mm. Twenty-nine percent received tamoxifen. The median duration of follow-up was 8.8 years.

Results showed that the DCIS score was only moderately correlated with histologic grade (r = 0.41-0.46) and with the percentage of cells showing comedo necrosis (r = 0.49), and was poorly correlated with tumor size (r = 0.18), Dr. Badve reported. And there was no correlation with age, menopausal status, DCIS histologic pattern, or margin status.

In a multivariate analysis, each 50-point increase in DCIS score was associated with more than a doubling of the risk of a recurrence of DCIS or the occurrence of invasive disease in the ipsilateral breast (hazard ratio, 2.41; P = .02).

In addition, tumor size was an independent positive predictor of risk (HR for each 5-mm increase, 1.52; P = .01), and postmenopausal status was an independent negative predictor (HR, 0.49; P = .02).

Dr. Badve disclosed that he is a consultant to Genomic Health, which makes the assay. Dr. Hwang disclosed that she is a consultant to Genomic Health and receives research funding from Merck and Novartis.

SAN FRANCISCO – Regional recurrence is rare in breast cancer patients with a negative sentinel lymph node biopsy and does not appear to be associated with reduced overall survival, based on the latest results of a clinical trial including more than 5,500 patients.

"Regional recurrences were very low and remained so over the follow-up period," Dr. Kelly K. Hunt said at the annual meeting of the American Surgical Association. The 3-year cumulative incidence rate for regional recurrence was 0.003, and the rate at 5 years was 0.005. In comparison, the 3-year and 5-year rates for local recurrence were 0.013 and 0.024, respectively; the 3-year and 5-year rates for distant recurrence were 0.017 and 0.028, respectively.

Sentinel lymph node (SLN) dissection has been shown to improve staging, compared with axillary lymph node dissection (ALND) alone, and reduced morbidity and improved quality of life have been associated with SLN dissection. Thus, SLN dissection has replaced ALND in clinical practice for staging of regional lymph nodes in women with clinically node-negative, early-stage breast cancer. However, studies have shown false-negative rates ranging from 5% to 17%, noted Dr. Hunt of the department of surgical oncology at the MD Anderson Cancer Center in Houston.

She and her fellow researchers analyzed data from the American College of Surgeons Oncology Group (ACOSOG) Z0010 trial, a prospective multicenter trial designed to evaluate the prognostic implications of SLN and bone marrow micrometastases in women with early-stage breast cancer.

Eligible patients had biopsy-proven T1 or T2 breast cancer with clinically negative lymph nodes and were candidates for lumpectomy and whole breast irradiation. A total of 5,539 patients were enrolled from 126 participating sites. A total of 5,200 patients were fully evaluable, and a sentinel node was identified in 5,119.

Of those, 3,904 patients had negative lymph nodes based on standard H&E staining. Of the patients with negative SLNs on H&E staining, there were 3,326 who had sufficient samples for immunohistochemical staining for cytokeratin. Ten percent of these patients had positive nodes on immunohistochemistry (IHC).

In outcomes published last year, women with H&E positive sentinel nodes had decreased survival compared with those with H&E negative sentinel nodes (JAMA 2011;306:385-93 [doi:10.1001/jama.2011.1034]).

Patients were largely postmenopausal women with ductal breast cancers. They had mostly T1 tumors, many of which were hormone receptor–positive, low to intermediate grade. The majority of patients (98%) had breast-conserving surgery, and 68% patients received hormonal therapy as part of adjuvant treatment. Most patients (92%) finished adjuvant radiation, and almost half (44%) also received systemic chemotherapy. The median follow-up was 8.4 years. There were 127 local failures, 20 regional recurrences, and 134 distant recurrences. There were 317 deaths.

"Within this small group of locoregional recurrences, we did look at the differences in the patients who had IHC-positive vs. IHC-negative sentinel nodes and we did not see any difference between those two groups," Dr. Hunt said. As a result, they combined the two groups for subsequent analyses. "We did not see a difference in recurrence rates based on IHC status, despite the fact that we would suspect that some of these patients have residual disease in the axilla based on published false-negative rates from multicenter trials."

They also examined clinical factors, pathologic factors, and treatment factors that may have affected local and regional recurrences on univariable and multivariable analyses. In both models, younger age and negative hormone receptor status predicted both a greater rate of local failures and locoregional recurrences. With respect to distant recurrence, the important factors were increasing tumor size, the presence of lymphovascular invasion, and higher tumor grade.

Older age, larger tumor size, higher tumor grade, and the presence of a local recurrence predicted reduced overall survival. The hazard rate for local recurrence alone on multivariable analysis was 6.73 (P less than .0001).

"This study reassures anyone practicing in this field ... that those early clinical judgments we all made that drove early adoption of sentinel lymph node axillary staging and early, occasionally angst-ridden decisions to forgo axillary dissection in patients with early-stage breast cancer and minimal axillary nodal disease ... that those choices were correct," said invited discussant Dr. Barbara L. Bass, the John F. and Carolyn Bookout Distinguished Endowed Chair in the department of surgery at the Methodist Hospital in Houston and a professor of surgery at Cornell University in New York.

The regional recurrence rates are particularly interesting, she noted. "It practically makes you think that the axilla – our current bedrock for decision making and staging – is in fact a hostile soil for tumor cells, compared to the breast and distant sites." She asked why the axilla was practically immune from recurrence. "Clearly, those lymph nodes in that space were still there, but tumor does not go or grow there."

Dr. Hunt said earlier studies have suggested that some nodal disease is not clinically relevant and requires no treatment. However, with SLN surgery, "the more that we look, the more we find these micrometastases, and the bias is to treat them."

With improved adjuvant therapy, "we are eradicating disease with those treatments. We know that from neoadjuvant trials as well," Dr. Hunt added. In trials at MD Anderson, after chemotherapy 25% of patients who had fine-needle biopsy at initial diagnosis have complete eradication of disease in the nodes, she said.

"Now that we understand more about the subtypes, we see that in HER-2 positive disease, we’re eradicating about 75% of the disease in regional nodes with targeted therapies." Systemic therapy has gotten better, but it also appears that there are metastases that are not clinically or biologically relevant.

Because the first site of failure is generally the only site recorded, the researchers also performed a competing risk regression model to account for patients with local, regional, and distant recurrences. Evaluating competing risks demonstrated that hormone receptor–negative disease and lack of systemic chemotherapy are associated with increased risk of local recurrence. Older age, higher tumor size, greater tumor grade, and local recurrence predicted decreased survival.

Dr. Bass observed that currently, staging is based largely on the features of the primary tumor – gene assessments, tumor markers, and so on. In light of this, she wondered how long will it will be necessary to surgically stage the clinically negative axilla in patients with early-stage disease who are treated with breast-conserving therapy.

"Do the results of this trial mean that it might be possible to forgo sentinel lymph node staging of the axilla in some patients?" she asked.

That question remains to be answered, according to Dr. Hunt. Planning is underway for a trial in early-stage breast cancer to compare SLN surgery with no treatment of the axilla. "This is based on the fact that we know that different biologic subtypes have very different local and regional recurrence patterns." So, for example, in women with HER-2 positive or triple-negative disease, the systemic treatment regimen is clear with or without nodal involvement.

The researchers reported that they have no relevant conflicts of interest.

The complete manuscript of this presentation is anticipated to be published in the Annals of Surgery pending editorial review.

SAN FRANCISCO – Regional recurrence is rare in breast cancer patients with a negative sentinel lymph node biopsy and does not appear to be associated with reduced overall survival, based on the latest results of a clinical trial including more than 5,500 patients.

"Regional recurrences were very low and remained so over the follow-up period," Dr. Kelly K. Hunt said at the annual meeting of the American Surgical Association. The 3-year cumulative incidence rate for regional recurrence was 0.003, and the rate at 5 years was 0.005. In comparison, the 3-year and 5-year rates for local recurrence were 0.013 and 0.024, respectively; the 3-year and 5-year rates for distant recurrence were 0.017 and 0.028, respectively.

Sentinel lymph node (SLN) dissection has been shown to improve staging, compared with axillary lymph node dissection (ALND) alone, and reduced morbidity and improved quality of life have been associated with SLN dissection. Thus, SLN dissection has replaced ALND in clinical practice for staging of regional lymph nodes in women with clinically node-negative, early-stage breast cancer. However, studies have shown false-negative rates ranging from 5% to 17%, noted Dr. Hunt of the department of surgical oncology at the MD Anderson Cancer Center in Houston.

She and her fellow researchers analyzed data from the American College of Surgeons Oncology Group (ACOSOG) Z0010 trial, a prospective multicenter trial designed to evaluate the prognostic implications of SLN and bone marrow micrometastases in women with early-stage breast cancer.

Eligible patients had biopsy-proven T1 or T2 breast cancer with clinically negative lymph nodes and were candidates for lumpectomy and whole breast irradiation. A total of 5,539 patients were enrolled from 126 participating sites. A total of 5,200 patients were fully evaluable, and a sentinel node was identified in 5,119.

Of those, 3,904 patients had negative lymph nodes based on standard H&E staining. Of the patients with negative SLNs on H&E staining, there were 3,326 who had sufficient samples for immunohistochemical staining for cytokeratin. Ten percent of these patients had positive nodes on immunohistochemistry (IHC).

In outcomes published last year, women with H&E positive sentinel nodes had decreased survival compared with those with H&E negative sentinel nodes (JAMA 2011;306:385-93 [doi:10.1001/jama.2011.1034]).

Patients were largely postmenopausal women with ductal breast cancers. They had mostly T1 tumors, many of which were hormone receptor–positive, low to intermediate grade. The majority of patients (98%) had breast-conserving surgery, and 68% patients received hormonal therapy as part of adjuvant treatment. Most patients (92%) finished adjuvant radiation, and almost half (44%) also received systemic chemotherapy. The median follow-up was 8.4 years. There were 127 local failures, 20 regional recurrences, and 134 distant recurrences. There were 317 deaths.

"Within this small group of locoregional recurrences, we did look at the differences in the patients who had IHC-positive vs. IHC-negative sentinel nodes and we did not see any difference between those two groups," Dr. Hunt said. As a result, they combined the two groups for subsequent analyses. "We did not see a difference in recurrence rates based on IHC status, despite the fact that we would suspect that some of these patients have residual disease in the axilla based on published false-negative rates from multicenter trials."

They also examined clinical factors, pathologic factors, and treatment factors that may have affected local and regional recurrences on univariable and multivariable analyses. In both models, younger age and negative hormone receptor status predicted both a greater rate of local failures and locoregional recurrences. With respect to distant recurrence, the important factors were increasing tumor size, the presence of lymphovascular invasion, and higher tumor grade.

Older age, larger tumor size, higher tumor grade, and the presence of a local recurrence predicted reduced overall survival. The hazard rate for local recurrence alone on multivariable analysis was 6.73 (P less than .0001).

"This study reassures anyone practicing in this field ... that those early clinical judgments we all made that drove early adoption of sentinel lymph node axillary staging and early, occasionally angst-ridden decisions to forgo axillary dissection in patients with early-stage breast cancer and minimal axillary nodal disease ... that those choices were correct," said invited discussant Dr. Barbara L. Bass, the John F. and Carolyn Bookout Distinguished Endowed Chair in the department of surgery at the Methodist Hospital in Houston and a professor of surgery at Cornell University in New York.

The regional recurrence rates are particularly interesting, she noted. "It practically makes you think that the axilla – our current bedrock for decision making and staging – is in fact a hostile soil for tumor cells, compared to the breast and distant sites." She asked why the axilla was practically immune from recurrence. "Clearly, those lymph nodes in that space were still there, but tumor does not go or grow there."

Dr. Hunt said earlier studies have suggested that some nodal disease is not clinically relevant and requires no treatment. However, with SLN surgery, "the more that we look, the more we find these micrometastases, and the bias is to treat them."

With improved adjuvant therapy, "we are eradicating disease with those treatments. We know that from neoadjuvant trials as well," Dr. Hunt added. In trials at MD Anderson, after chemotherapy 25% of patients who had fine-needle biopsy at initial diagnosis have complete eradication of disease in the nodes, she said.

"Now that we understand more about the subtypes, we see that in HER-2 positive disease, we’re eradicating about 75% of the disease in regional nodes with targeted therapies." Systemic therapy has gotten better, but it also appears that there are metastases that are not clinically or biologically relevant.

Because the first site of failure is generally the only site recorded, the researchers also performed a competing risk regression model to account for patients with local, regional, and distant recurrences. Evaluating competing risks demonstrated that hormone receptor–negative disease and lack of systemic chemotherapy are associated with increased risk of local recurrence. Older age, higher tumor size, greater tumor grade, and local recurrence predicted decreased survival.

Dr. Bass observed that currently, staging is based largely on the features of the primary tumor – gene assessments, tumor markers, and so on. In light of this, she wondered how long will it will be necessary to surgically stage the clinically negative axilla in patients with early-stage disease who are treated with breast-conserving therapy.

"Do the results of this trial mean that it might be possible to forgo sentinel lymph node staging of the axilla in some patients?" she asked.

That question remains to be answered, according to Dr. Hunt. Planning is underway for a trial in early-stage breast cancer to compare SLN surgery with no treatment of the axilla. "This is based on the fact that we know that different biologic subtypes have very different local and regional recurrence patterns." So, for example, in women with HER-2 positive or triple-negative disease, the systemic treatment regimen is clear with or without nodal involvement.

The researchers reported that they have no relevant conflicts of interest.

The complete manuscript of this presentation is anticipated to be published in the Annals of Surgery pending editorial review.

SAN FRANCISCO – Regional recurrence is rare in breast cancer patients with a negative sentinel lymph node biopsy and does not appear to be associated with reduced overall survival, based on the latest results of a clinical trial including more than 5,500 patients.

"Regional recurrences were very low and remained so over the follow-up period," Dr. Kelly K. Hunt said at the annual meeting of the American Surgical Association. The 3-year cumulative incidence rate for regional recurrence was 0.003, and the rate at 5 years was 0.005. In comparison, the 3-year and 5-year rates for local recurrence were 0.013 and 0.024, respectively; the 3-year and 5-year rates for distant recurrence were 0.017 and 0.028, respectively.

Sentinel lymph node (SLN) dissection has been shown to improve staging, compared with axillary lymph node dissection (ALND) alone, and reduced morbidity and improved quality of life have been associated with SLN dissection. Thus, SLN dissection has replaced ALND in clinical practice for staging of regional lymph nodes in women with clinically node-negative, early-stage breast cancer. However, studies have shown false-negative rates ranging from 5% to 17%, noted Dr. Hunt of the department of surgical oncology at the MD Anderson Cancer Center in Houston.

She and her fellow researchers analyzed data from the American College of Surgeons Oncology Group (ACOSOG) Z0010 trial, a prospective multicenter trial designed to evaluate the prognostic implications of SLN and bone marrow micrometastases in women with early-stage breast cancer.

Eligible patients had biopsy-proven T1 or T2 breast cancer with clinically negative lymph nodes and were candidates for lumpectomy and whole breast irradiation. A total of 5,539 patients were enrolled from 126 participating sites. A total of 5,200 patients were fully evaluable, and a sentinel node was identified in 5,119.

Of those, 3,904 patients had negative lymph nodes based on standard H&E staining. Of the patients with negative SLNs on H&E staining, there were 3,326 who had sufficient samples for immunohistochemical staining for cytokeratin. Ten percent of these patients had positive nodes on immunohistochemistry (IHC).

In outcomes published last year, women with H&E positive sentinel nodes had decreased survival compared with those with H&E negative sentinel nodes (JAMA 2011;306:385-93 [doi:10.1001/jama.2011.1034]).

Patients were largely postmenopausal women with ductal breast cancers. They had mostly T1 tumors, many of which were hormone receptor–positive, low to intermediate grade. The majority of patients (98%) had breast-conserving surgery, and 68% patients received hormonal therapy as part of adjuvant treatment. Most patients (92%) finished adjuvant radiation, and almost half (44%) also received systemic chemotherapy. The median follow-up was 8.4 years. There were 127 local failures, 20 regional recurrences, and 134 distant recurrences. There were 317 deaths.

"Within this small group of locoregional recurrences, we did look at the differences in the patients who had IHC-positive vs. IHC-negative sentinel nodes and we did not see any difference between those two groups," Dr. Hunt said. As a result, they combined the two groups for subsequent analyses. "We did not see a difference in recurrence rates based on IHC status, despite the fact that we would suspect that some of these patients have residual disease in the axilla based on published false-negative rates from multicenter trials."

They also examined clinical factors, pathologic factors, and treatment factors that may have affected local and regional recurrences on univariable and multivariable analyses. In both models, younger age and negative hormone receptor status predicted both a greater rate of local failures and locoregional recurrences. With respect to distant recurrence, the important factors were increasing tumor size, the presence of lymphovascular invasion, and higher tumor grade.

Older age, larger tumor size, higher tumor grade, and the presence of a local recurrence predicted reduced overall survival. The hazard rate for local recurrence alone on multivariable analysis was 6.73 (P less than .0001).

"This study reassures anyone practicing in this field ... that those early clinical judgments we all made that drove early adoption of sentinel lymph node axillary staging and early, occasionally angst-ridden decisions to forgo axillary dissection in patients with early-stage breast cancer and minimal axillary nodal disease ... that those choices were correct," said invited discussant Dr. Barbara L. Bass, the John F. and Carolyn Bookout Distinguished Endowed Chair in the department of surgery at the Methodist Hospital in Houston and a professor of surgery at Cornell University in New York.

The regional recurrence rates are particularly interesting, she noted. "It practically makes you think that the axilla – our current bedrock for decision making and staging – is in fact a hostile soil for tumor cells, compared to the breast and distant sites." She asked why the axilla was practically immune from recurrence. "Clearly, those lymph nodes in that space were still there, but tumor does not go or grow there."

Dr. Hunt said earlier studies have suggested that some nodal disease is not clinically relevant and requires no treatment. However, with SLN surgery, "the more that we look, the more we find these micrometastases, and the bias is to treat them."

With improved adjuvant therapy, "we are eradicating disease with those treatments. We know that from neoadjuvant trials as well," Dr. Hunt added. In trials at MD Anderson, after chemotherapy 25% of patients who had fine-needle biopsy at initial diagnosis have complete eradication of disease in the nodes, she said.

"Now that we understand more about the subtypes, we see that in HER-2 positive disease, we’re eradicating about 75% of the disease in regional nodes with targeted therapies." Systemic therapy has gotten better, but it also appears that there are metastases that are not clinically or biologically relevant.

Because the first site of failure is generally the only site recorded, the researchers also performed a competing risk regression model to account for patients with local, regional, and distant recurrences. Evaluating competing risks demonstrated that hormone receptor–negative disease and lack of systemic chemotherapy are associated with increased risk of local recurrence. Older age, higher tumor size, greater tumor grade, and local recurrence predicted decreased survival.

Dr. Bass observed that currently, staging is based largely on the features of the primary tumor – gene assessments, tumor markers, and so on. In light of this, she wondered how long will it will be necessary to surgically stage the clinically negative axilla in patients with early-stage disease who are treated with breast-conserving therapy.

"Do the results of this trial mean that it might be possible to forgo sentinel lymph node staging of the axilla in some patients?" she asked.

That question remains to be answered, according to Dr. Hunt. Planning is underway for a trial in early-stage breast cancer to compare SLN surgery with no treatment of the axilla. "This is based on the fact that we know that different biologic subtypes have very different local and regional recurrence patterns." So, for example, in women with HER-2 positive or triple-negative disease, the systemic treatment regimen is clear with or without nodal involvement.

The researchers reported that they have no relevant conflicts of interest.

The complete manuscript of this presentation is anticipated to be published in the Annals of Surgery pending editorial review.

SAN DIEGO – Patients who underwent laparoscopic resection of gastric submucosal neoplasms had shorter operative times, less blood loss, lower postoperative morbidity, and shorter hospital lengths of stay compared with those who underwent open resection, according to results from a single-center study.

"Numerous reports not only have assessed the feasibility, but confirmed the long-term oncologic efficacy of laparoscopic resection for gastrointestinal stromal tumors [GISTs]," Dr. Sabha Ganai said at the annual Digestive Disease Week.

"However, in 2004, the European Society of Medical Oncology published a consensus report suggesting that laparoscopic surgery may result in a higher risk of tumor rupture and peritoneal seeding, and suggested that laparoscopic resection may be acceptable in cases of small intramural tumors – those 2 cm or smaller," she added (Ann. Oncol. 2005;16:566-78).

Dr. Ganai, a fellow in surgical oncology and clinical medical ethics at the University of Chicago, noted that concerns exist "regarding the ability to generalize laparoscopic techniques to the spectra of gastric submucosal neoplasms, specifically related to tumor size and location, particularly the GE junction/cardia, the antrum/pylorus, and posteriorly based lesions."

To evaluate patient selection for a minimally invasive approach to resection, Dr. Ganai and her associates compared laparoscopic and open techniques used in the resection of gastric submucosal neoplasms. "We hypothesized that there are predictors of unsuccessful laparoscopic resection, with failures defined by conversions, complications, and recurrences," she said.

The retrospective study involved 106 patients with gastric submucosal neoplasms who underwent operative management at the university from October 2002 to March 2012. There were 79 patients in the laparoscopic group and 27 in the open group. The mean age was 63 years, the mean body mass index was 29 kg/m², and 57% were male.

There was less preoperative use of ultrasound in the open group vs. the laparoscopic group (67% vs. 87%, respectively), and greater pretreatment lesion size (9.5 cm vs. 3.9 cm). In addition, the open group had a 6-month greater interval from diagnosis to surgery (10.1 months vs. 4.4 months), and more neoadjuvant imatinib was used in the open group (26% vs. 5%).

Most tumors (76%) were GISTs; the rest were leiomyomas (9%), schwannomas (6%), carcinoids (3%), and other types (6%).

There were no significant differences between the groups in terms of tumor location; most were found in the greater curvature (41% open vs. 32% laparoscopic). "There were slightly more posterior lesions in the open group, but this was not statistically significant," she said. "On presentation, patients in the open group had a significantly greater presentation with abdominal pain, while those in the laparoscopic group were more likely to present with GI bleed."

Most patients underwent sleeve or wedge resection, with 11% of patients undergoing transgastric wedge resections. A higher proportion of the open group required a gastroenteric anastomosis (37% vs. 6%) and a multivisceral resection (41% vs. 1%). Overall, operative time was significantly greater in the open group (a mean of 230 minutes vs. 132 minutes), as was the amount of estimated blood loss (a mean of 364 mL vs. 35 mL).

Most GISTs in the laparoscopic group (64%) ranged in size from 2 cm to 5 cm, while the majority in the open group (58%) were greater than 5 cm. In addition, the open group had a higher mitotic index (44% vs. 20%).

Postoperatively, hospital length of stay was significantly shorter in the laparoscopic group (a mean of 3.3 days) than in the open group (a mean of 8.4 days). The laparoscopic group also had significantly fewer surgical site infections (1% vs. 22%), anastomotic leaks (0% vs. 7%), and postoperative arrhythmias (0% vs. 15%).

Overall complications, evaluated on the basis of the Accordion Severity Grading System of surgical complications, were less severe in the laparoscopic group. "However, there was one perioperative death in the laparoscopic group related to a massive myocardial infarction, as well as two reoperations, one related to a port site hernia and one related to a gastric outlet obstruction in an antral lesion," Dr. Ganai said.

On multivariate analysis, conversion was predicted by tumor size greater than 8 cm (odds ratio, 18.48), while recurrence was predicted by having a mitotic rate of greater than 5 mitoses per 50 high-power fields (OR, 4.68). Laparoscopic resection resulted in better perioperative outcomes, with less morbidity, shorter operative times, less blood loss, and shorter lengths of stay (P less than .05). No significant difference was seen in survival; 90% and 81% of patients were alive 3 years after laparoscopic and open resection, respectively (hazard ratio, 0.4; P = .13). "Tumor biology and imatinib may play a greater role in oncologic outcome than technical considerations," Dr. Ganai suggested.

She acknowledged certain limitations of the study, including its retrospective design, the potential for selection bias, and limited follow-up, "especially in the lower-risk tumors."

Dr. Ganai said that she had no relevant financial conflicts to disclose.

SAN DIEGO – Patients who underwent laparoscopic resection of gastric submucosal neoplasms had shorter operative times, less blood loss, lower postoperative morbidity, and shorter hospital lengths of stay compared with those who underwent open resection, according to results from a single-center study.

"Numerous reports not only have assessed the feasibility, but confirmed the long-term oncologic efficacy of laparoscopic resection for gastrointestinal stromal tumors [GISTs]," Dr. Sabha Ganai said at the annual Digestive Disease Week.

"However, in 2004, the European Society of Medical Oncology published a consensus report suggesting that laparoscopic surgery may result in a higher risk of tumor rupture and peritoneal seeding, and suggested that laparoscopic resection may be acceptable in cases of small intramural tumors – those 2 cm or smaller," she added (Ann. Oncol. 2005;16:566-78).

Dr. Ganai, a fellow in surgical oncology and clinical medical ethics at the University of Chicago, noted that concerns exist "regarding the ability to generalize laparoscopic techniques to the spectra of gastric submucosal neoplasms, specifically related to tumor size and location, particularly the GE junction/cardia, the antrum/pylorus, and posteriorly based lesions."

To evaluate patient selection for a minimally invasive approach to resection, Dr. Ganai and her associates compared laparoscopic and open techniques used in the resection of gastric submucosal neoplasms. "We hypothesized that there are predictors of unsuccessful laparoscopic resection, with failures defined by conversions, complications, and recurrences," she said.

The retrospective study involved 106 patients with gastric submucosal neoplasms who underwent operative management at the university from October 2002 to March 2012. There were 79 patients in the laparoscopic group and 27 in the open group. The mean age was 63 years, the mean body mass index was 29 kg/m², and 57% were male.

There was less preoperative use of ultrasound in the open group vs. the laparoscopic group (67% vs. 87%, respectively), and greater pretreatment lesion size (9.5 cm vs. 3.9 cm). In addition, the open group had a 6-month greater interval from diagnosis to surgery (10.1 months vs. 4.4 months), and more neoadjuvant imatinib was used in the open group (26% vs. 5%).

Most tumors (76%) were GISTs; the rest were leiomyomas (9%), schwannomas (6%), carcinoids (3%), and other types (6%).

There were no significant differences between the groups in terms of tumor location; most were found in the greater curvature (41% open vs. 32% laparoscopic). "There were slightly more posterior lesions in the open group, but this was not statistically significant," she said. "On presentation, patients in the open group had a significantly greater presentation with abdominal pain, while those in the laparoscopic group were more likely to present with GI bleed."

Most patients underwent sleeve or wedge resection, with 11% of patients undergoing transgastric wedge resections. A higher proportion of the open group required a gastroenteric anastomosis (37% vs. 6%) and a multivisceral resection (41% vs. 1%). Overall, operative time was significantly greater in the open group (a mean of 230 minutes vs. 132 minutes), as was the amount of estimated blood loss (a mean of 364 mL vs. 35 mL).

Most GISTs in the laparoscopic group (64%) ranged in size from 2 cm to 5 cm, while the majority in the open group (58%) were greater than 5 cm. In addition, the open group had a higher mitotic index (44% vs. 20%).

Postoperatively, hospital length of stay was significantly shorter in the laparoscopic group (a mean of 3.3 days) than in the open group (a mean of 8.4 days). The laparoscopic group also had significantly fewer surgical site infections (1% vs. 22%), anastomotic leaks (0% vs. 7%), and postoperative arrhythmias (0% vs. 15%).

Overall complications, evaluated on the basis of the Accordion Severity Grading System of surgical complications, were less severe in the laparoscopic group. "However, there was one perioperative death in the laparoscopic group related to a massive myocardial infarction, as well as two reoperations, one related to a port site hernia and one related to a gastric outlet obstruction in an antral lesion," Dr. Ganai said.

On multivariate analysis, conversion was predicted by tumor size greater than 8 cm (odds ratio, 18.48), while recurrence was predicted by having a mitotic rate of greater than 5 mitoses per 50 high-power fields (OR, 4.68). Laparoscopic resection resulted in better perioperative outcomes, with less morbidity, shorter operative times, less blood loss, and shorter lengths of stay (P less than .05). No significant difference was seen in survival; 90% and 81% of patients were alive 3 years after laparoscopic and open resection, respectively (hazard ratio, 0.4; P = .13). "Tumor biology and imatinib may play a greater role in oncologic outcome than technical considerations," Dr. Ganai suggested.

She acknowledged certain limitations of the study, including its retrospective design, the potential for selection bias, and limited follow-up, "especially in the lower-risk tumors."

Dr. Ganai said that she had no relevant financial conflicts to disclose.

SAN DIEGO – Patients who underwent laparoscopic resection of gastric submucosal neoplasms had shorter operative times, less blood loss, lower postoperative morbidity, and shorter hospital lengths of stay compared with those who underwent open resection, according to results from a single-center study.

"Numerous reports not only have assessed the feasibility, but confirmed the long-term oncologic efficacy of laparoscopic resection for gastrointestinal stromal tumors [GISTs]," Dr. Sabha Ganai said at the annual Digestive Disease Week.

"However, in 2004, the European Society of Medical Oncology published a consensus report suggesting that laparoscopic surgery may result in a higher risk of tumor rupture and peritoneal seeding, and suggested that laparoscopic resection may be acceptable in cases of small intramural tumors – those 2 cm or smaller," she added (Ann. Oncol. 2005;16:566-78).

Dr. Ganai, a fellow in surgical oncology and clinical medical ethics at the University of Chicago, noted that concerns exist "regarding the ability to generalize laparoscopic techniques to the spectra of gastric submucosal neoplasms, specifically related to tumor size and location, particularly the GE junction/cardia, the antrum/pylorus, and posteriorly based lesions."

To evaluate patient selection for a minimally invasive approach to resection, Dr. Ganai and her associates compared laparoscopic and open techniques used in the resection of gastric submucosal neoplasms. "We hypothesized that there are predictors of unsuccessful laparoscopic resection, with failures defined by conversions, complications, and recurrences," she said.

The retrospective study involved 106 patients with gastric submucosal neoplasms who underwent operative management at the university from October 2002 to March 2012. There were 79 patients in the laparoscopic group and 27 in the open group. The mean age was 63 years, the mean body mass index was 29 kg/m², and 57% were male.

There was less preoperative use of ultrasound in the open group vs. the laparoscopic group (67% vs. 87%, respectively), and greater pretreatment lesion size (9.5 cm vs. 3.9 cm). In addition, the open group had a 6-month greater interval from diagnosis to surgery (10.1 months vs. 4.4 months), and more neoadjuvant imatinib was used in the open group (26% vs. 5%).

Most tumors (76%) were GISTs; the rest were leiomyomas (9%), schwannomas (6%), carcinoids (3%), and other types (6%).

There were no significant differences between the groups in terms of tumor location; most were found in the greater curvature (41% open vs. 32% laparoscopic). "There were slightly more posterior lesions in the open group, but this was not statistically significant," she said. "On presentation, patients in the open group had a significantly greater presentation with abdominal pain, while those in the laparoscopic group were more likely to present with GI bleed."

Most patients underwent sleeve or wedge resection, with 11% of patients undergoing transgastric wedge resections. A higher proportion of the open group required a gastroenteric anastomosis (37% vs. 6%) and a multivisceral resection (41% vs. 1%). Overall, operative time was significantly greater in the open group (a mean of 230 minutes vs. 132 minutes), as was the amount of estimated blood loss (a mean of 364 mL vs. 35 mL).

Most GISTs in the laparoscopic group (64%) ranged in size from 2 cm to 5 cm, while the majority in the open group (58%) were greater than 5 cm. In addition, the open group had a higher mitotic index (44% vs. 20%).

Postoperatively, hospital length of stay was significantly shorter in the laparoscopic group (a mean of 3.3 days) than in the open group (a mean of 8.4 days). The laparoscopic group also had significantly fewer surgical site infections (1% vs. 22%), anastomotic leaks (0% vs. 7%), and postoperative arrhythmias (0% vs. 15%).

Overall complications, evaluated on the basis of the Accordion Severity Grading System of surgical complications, were less severe in the laparoscopic group. "However, there was one perioperative death in the laparoscopic group related to a massive myocardial infarction, as well as two reoperations, one related to a port site hernia and one related to a gastric outlet obstruction in an antral lesion," Dr. Ganai said.

On multivariate analysis, conversion was predicted by tumor size greater than 8 cm (odds ratio, 18.48), while recurrence was predicted by having a mitotic rate of greater than 5 mitoses per 50 high-power fields (OR, 4.68). Laparoscopic resection resulted in better perioperative outcomes, with less morbidity, shorter operative times, less blood loss, and shorter lengths of stay (P less than .05). No significant difference was seen in survival; 90% and 81% of patients were alive 3 years after laparoscopic and open resection, respectively (hazard ratio, 0.4; P = .13). "Tumor biology and imatinib may play a greater role in oncologic outcome than technical considerations," Dr. Ganai suggested.

She acknowledged certain limitations of the study, including its retrospective design, the potential for selection bias, and limited follow-up, "especially in the lower-risk tumors."

Dr. Ganai said that she had no relevant financial conflicts to disclose.

Radiofrequency ablation could become an option for some patients facing adjuvant radiation after breast-conserving surgery for invasive breast cancer, the results of a phase II trial suggest.

Excision followed by radiofrequency ablation (eRFA) was at least as effective as radiation therapy following lumpectomy in preventing local tumor recurrence in the single-arm study of 73 patients who underwent breast conserving surgery, according to investigators. Only one patient had an in-site recurrence while three had recurrences, they reported at the annual meeting of the American Society of Breast Surgeons.

"For selected breast cancer patients undergoing breast-conservation therapy, eRFA is an attractive alternative to breast irradiation," said Dr. Misti Wilson at a press briefing.

The intraoperative procedure of excision followed by radiofrequency ablation employs heat to create an additional tumor-free zone, approximating the zone treated by brachytherapy, around the lumpectomy cavity. Its benefits include reduced likelihood of the need for re-excision and for additional radiation; lower cost, compared with radiation; and good to excellent cosmetic results, said Dr. Wilson, a breast surgical oncology fellow at the University of Arkansas in Little Rock.

The study enrolled 73 patients with tumors of less than 3 cm. Median follow-up was 55 months. All underwent standard lumpectomy followed by radiofrequency ablation, in which the RFA probe was deployed 1 cm circumferentially into the walls of the lumpectomy cavity and maintained at 100 degrees C for 15 minutes.

None of the patients received subsequent radiation or chemotherapy. Only those with grossly positive margins or residual calcifications on postoperative mammography were re-resected.

Among 19 patients who had inadequate margins, RFA spared 16 (84%) from additional surgery. Only three patients (4%) had to return to the operating room for resection because of grossly positive margins. There was just one in-site recurrence out of 73 patients, and 3 had recurrences elsewhere, Dr. Wilson reported.

Of 40 patients who scored their cosmesis, 18 (45%) reported excellent cosmetic results, 18 (45%) reported good results, and 4 (10%) reported fair cosmetic results.

"These findings show that this is a safe procedure, patients can have less repeat surgery, they have good cosmetic outcomes, and RFA may replace radiation therapy in patients with small tumors and are node negative," Dr. Wilson said in an interview.

The cost of eRFA is around $2,000 dollars. In contrast, standard whole breast radiation costs approximately $11,000, and partial breast around $18,000 depending upon site and location, she said.

The ABLATE trial is investigating eRFA in a larger patient population. To date, the trial includes five centers (Columbia University, N.Y; University of Kansas, Lawrence; Comprehensive Breast Care of San Diego, University of Arizona, Tucson; and Rockefeller Cancer Institute in Little Rock) and is actively recruiting and training additional sites.

Early results were presented in a poster by the primary investigator of both studies, Dr. V. Suzanne Klimberg, professor of surgery and pathology and director of the breast program at the University of Arkansas.

Of 55 patients (mean age 65 years) with ductal carcinoma in situ or invasive breast cancer with average tumor size 0.9 cm who underwent eRFA, 20 had positive margins: 14 had close margins (less than 2 mm), 2 had focally positive margins, and 4 had grossly positive margins. Of those, 15 were spared re-excision. Morbidity at 30 days was 7.2% and there were no deaths.

The University of Arkansas sponsored the study in collaboration with AngioDynamics, maker of the RFA delivery system.Dr. Wilson stated that she has no disclosures. Dr. Klimberg received research grants from AngioDynamics and retailers Fashion Footwear Association of New York and QVC.

Radiofrequency ablation could become an option for some patients facing adjuvant radiation after breast-conserving surgery for invasive breast cancer, the results of a phase II trial suggest.

Excision followed by radiofrequency ablation (eRFA) was at least as effective as radiation therapy following lumpectomy in preventing local tumor recurrence in the single-arm study of 73 patients who underwent breast conserving surgery, according to investigators. Only one patient had an in-site recurrence while three had recurrences, they reported at the annual meeting of the American Society of Breast Surgeons.

"For selected breast cancer patients undergoing breast-conservation therapy, eRFA is an attractive alternative to breast irradiation," said Dr. Misti Wilson at a press briefing.

The intraoperative procedure of excision followed by radiofrequency ablation employs heat to create an additional tumor-free zone, approximating the zone treated by brachytherapy, around the lumpectomy cavity. Its benefits include reduced likelihood of the need for re-excision and for additional radiation; lower cost, compared with radiation; and good to excellent cosmetic results, said Dr. Wilson, a breast surgical oncology fellow at the University of Arkansas in Little Rock.

The study enrolled 73 patients with tumors of less than 3 cm. Median follow-up was 55 months. All underwent standard lumpectomy followed by radiofrequency ablation, in which the RFA probe was deployed 1 cm circumferentially into the walls of the lumpectomy cavity and maintained at 100 degrees C for 15 minutes.

None of the patients received subsequent radiation or chemotherapy. Only those with grossly positive margins or residual calcifications on postoperative mammography were re-resected.

Among 19 patients who had inadequate margins, RFA spared 16 (84%) from additional surgery. Only three patients (4%) had to return to the operating room for resection because of grossly positive margins. There was just one in-site recurrence out of 73 patients, and 3 had recurrences elsewhere, Dr. Wilson reported.

Of 40 patients who scored their cosmesis, 18 (45%) reported excellent cosmetic results, 18 (45%) reported good results, and 4 (10%) reported fair cosmetic results.

"These findings show that this is a safe procedure, patients can have less repeat surgery, they have good cosmetic outcomes, and RFA may replace radiation therapy in patients with small tumors and are node negative," Dr. Wilson said in an interview.

The cost of eRFA is around $2,000 dollars. In contrast, standard whole breast radiation costs approximately $11,000, and partial breast around $18,000 depending upon site and location, she said.

The ABLATE trial is investigating eRFA in a larger patient population. To date, the trial includes five centers (Columbia University, N.Y; University of Kansas, Lawrence; Comprehensive Breast Care of San Diego, University of Arizona, Tucson; and Rockefeller Cancer Institute in Little Rock) and is actively recruiting and training additional sites.

Early results were presented in a poster by the primary investigator of both studies, Dr. V. Suzanne Klimberg, professor of surgery and pathology and director of the breast program at the University of Arkansas.

Of 55 patients (mean age 65 years) with ductal carcinoma in situ or invasive breast cancer with average tumor size 0.9 cm who underwent eRFA, 20 had positive margins: 14 had close margins (less than 2 mm), 2 had focally positive margins, and 4 had grossly positive margins. Of those, 15 were spared re-excision. Morbidity at 30 days was 7.2% and there were no deaths.

The University of Arkansas sponsored the study in collaboration with AngioDynamics, maker of the RFA delivery system.Dr. Wilson stated that she has no disclosures. Dr. Klimberg received research grants from AngioDynamics and retailers Fashion Footwear Association of New York and QVC.

Radiofrequency ablation could become an option for some patients facing adjuvant radiation after breast-conserving surgery for invasive breast cancer, the results of a phase II trial suggest.

Excision followed by radiofrequency ablation (eRFA) was at least as effective as radiation therapy following lumpectomy in preventing local tumor recurrence in the single-arm study of 73 patients who underwent breast conserving surgery, according to investigators. Only one patient had an in-site recurrence while three had recurrences, they reported at the annual meeting of the American Society of Breast Surgeons.

"For selected breast cancer patients undergoing breast-conservation therapy, eRFA is an attractive alternative to breast irradiation," said Dr. Misti Wilson at a press briefing.

The intraoperative procedure of excision followed by radiofrequency ablation employs heat to create an additional tumor-free zone, approximating the zone treated by brachytherapy, around the lumpectomy cavity. Its benefits include reduced likelihood of the need for re-excision and for additional radiation; lower cost, compared with radiation; and good to excellent cosmetic results, said Dr. Wilson, a breast surgical oncology fellow at the University of Arkansas in Little Rock.

The study enrolled 73 patients with tumors of less than 3 cm. Median follow-up was 55 months. All underwent standard lumpectomy followed by radiofrequency ablation, in which the RFA probe was deployed 1 cm circumferentially into the walls of the lumpectomy cavity and maintained at 100 degrees C for 15 minutes.

None of the patients received subsequent radiation or chemotherapy. Only those with grossly positive margins or residual calcifications on postoperative mammography were re-resected.

Among 19 patients who had inadequate margins, RFA spared 16 (84%) from additional surgery. Only three patients (4%) had to return to the operating room for resection because of grossly positive margins. There was just one in-site recurrence out of 73 patients, and 3 had recurrences elsewhere, Dr. Wilson reported.

Of 40 patients who scored their cosmesis, 18 (45%) reported excellent cosmetic results, 18 (45%) reported good results, and 4 (10%) reported fair cosmetic results.

"These findings show that this is a safe procedure, patients can have less repeat surgery, they have good cosmetic outcomes, and RFA may replace radiation therapy in patients with small tumors and are node negative," Dr. Wilson said in an interview.

The cost of eRFA is around $2,000 dollars. In contrast, standard whole breast radiation costs approximately $11,000, and partial breast around $18,000 depending upon site and location, she said.

The ABLATE trial is investigating eRFA in a larger patient population. To date, the trial includes five centers (Columbia University, N.Y; University of Kansas, Lawrence; Comprehensive Breast Care of San Diego, University of Arizona, Tucson; and Rockefeller Cancer Institute in Little Rock) and is actively recruiting and training additional sites.

Early results were presented in a poster by the primary investigator of both studies, Dr. V. Suzanne Klimberg, professor of surgery and pathology and director of the breast program at the University of Arkansas.

Of 55 patients (mean age 65 years) with ductal carcinoma in situ or invasive breast cancer with average tumor size 0.9 cm who underwent eRFA, 20 had positive margins: 14 had close margins (less than 2 mm), 2 had focally positive margins, and 4 had grossly positive margins. Of those, 15 were spared re-excision. Morbidity at 30 days was 7.2% and there were no deaths.

The University of Arkansas sponsored the study in collaboration with AngioDynamics, maker of the RFA delivery system.Dr. Wilson stated that she has no disclosures. Dr. Klimberg received research grants from AngioDynamics and retailers Fashion Footwear Association of New York and QVC.

ORLANDO – Surgery for ductal carcinoma in situ, with or without adjuvant therapy, saves lives, asserted a breast cancer surgeon at a symposium sponsored by the Society of Surgical Oncology.

Following a surgical biopsy alone, about half of all cases of low-grade ductal carcinoma in situ (DCIS) will progress to invasive cancer within an average of 10-15 years, said Dr. Kimberly J. Van Zee, a surgical oncologist at Memorial Sloan-Kettering Cancer Center in New York.

Additionally, without intervention, low-grade DCIS will result in death from ipsilateral invasive recurrence of breast cancer in about 18% of patients, Dr. Van Zee said.

"With treatment of DCIS, whether it’s breast conservation or mastectomy, with or without radiation, breast cancer–specific survival is over 95%," she noted.

The incidence of DCIS has increased steadily since 1975, when the rate was slightly more than 5 in 100,000 women. In 2009, the rate had reached approximately 36 in 100,000, according to Surveillance, Epidemiology, and End Results (SEER) data. The increase is probably a result of the growing adoption of screening mammography over the same period, Dr. Van Zee commented.

Treatment trends for DCIS showed a gradual but steady decline in mastectomy – from 70% in 1983 to about 28% in 1999 – and a corresponding increase in breast-conserving treatment, which increased from about 25% to 68% over the same period.

Beginning around 2005, however, there was evidence that the trend was reversing, with upticks in both mastectomy for unilateral breast cancer (J. Clin. Oncol. 2010;28:3437-41) and contralateral prophylactic mastectomy, both among women with invasive cancers and DCIS (Ann. Surg. Oncol. 2010;17:2554-62). The trends paralleled the rise in screening mammography in the United States and elsewhere in the world.

The gradual but steady decline in breast cancer deaths that began in the early 1990s appears to be attributable to a combination of increased screening mammography and improvements in adjuvant therapy, Dr. Van Zee noted, citing a 2005 study (N. Engl. J. Med. 2005;353:1784-92).

"They dissected all the various effects of treatment, incidence of screening-detected diseases, etc., and all their analyses concluded that about half of the reduction in death rate was due to screening and the other half was due to adjuvant therapy. So I think this is good circumstantial evidence that screening, with its resultant increased incidence in DCIS and the resulting increased treatment of DCIS, does result in a lower death rate from breast cancer," she said.

Further evidence comes from studies in which pathologists reviewed thousands of slides of biopsy-acquired breast tissue originally reported as benign. In each study (Cancer 1980;46[4 Suppl]:919-25; Cancer 2005;103:2481-84), the investigator identified about 30 samples with evidence of low-grade, relatively low-volume DCIS that was not recognized or treated. After 20-30 years of follow-up, half of the women had developed a clinically apparent ipsilateral breast cancer recurrence. The majority of tumors were invasive. In the second study, the authors noted that 5 of the 28 women (18%) with previously undetected DCIS died of breast cancer.

Evidence from a meta-analysis (Cancer 1999;85:616-28) suggests that the risk for invasive recurrence following a mastectomy for DCIS is 1.1%, and that the risk for breast cancer death is less than 1.1%.

The risk for distant recurrence and/or death from breast-conserving surgery with or without adjuvant radiotherapy in prospective randomized trials of radiotherapy for DCIS was less than 5%. Among patients with invasive local failure in those trials, however, 18%-25% developed metastatic disease, indicating the importance of avoiding local recurrence.

Mastectomy and breast-conserving surgery combined with radiotherapy and/or endocrine therapy all provide excellent disease-specific and overall survival results, Dr. Van Zee said.

"The goal should be avoiding local recurrence and, in particular, invasive recurrence, minimizing morbidity, and perhaps individualizing the treatment to the disease. One could consider age, comorbidities, [and] life expectancy, and weigh those against the morbidity of the treatment and the risk of local recurrence," she said.

Dr. Van Zee reported no relevant financial disclosures.

ORLANDO – Surgery for ductal carcinoma in situ, with or without adjuvant therapy, saves lives, asserted a breast cancer surgeon at a symposium sponsored by the Society of Surgical Oncology.

Following a surgical biopsy alone, about half of all cases of low-grade ductal carcinoma in situ (DCIS) will progress to invasive cancer within an average of 10-15 years, said Dr. Kimberly J. Van Zee, a surgical oncologist at Memorial Sloan-Kettering Cancer Center in New York.

Additionally, without intervention, low-grade DCIS will result in death from ipsilateral invasive recurrence of breast cancer in about 18% of patients, Dr. Van Zee said.

"With treatment of DCIS, whether it’s breast conservation or mastectomy, with or without radiation, breast cancer–specific survival is over 95%," she noted.

The incidence of DCIS has increased steadily since 1975, when the rate was slightly more than 5 in 100,000 women. In 2009, the rate had reached approximately 36 in 100,000, according to Surveillance, Epidemiology, and End Results (SEER) data. The increase is probably a result of the growing adoption of screening mammography over the same period, Dr. Van Zee commented.

Treatment trends for DCIS showed a gradual but steady decline in mastectomy – from 70% in 1983 to about 28% in 1999 – and a corresponding increase in breast-conserving treatment, which increased from about 25% to 68% over the same period.

Beginning around 2005, however, there was evidence that the trend was reversing, with upticks in both mastectomy for unilateral breast cancer (J. Clin. Oncol. 2010;28:3437-41) and contralateral prophylactic mastectomy, both among women with invasive cancers and DCIS (Ann. Surg. Oncol. 2010;17:2554-62). The trends paralleled the rise in screening mammography in the United States and elsewhere in the world.

The gradual but steady decline in breast cancer deaths that began in the early 1990s appears to be attributable to a combination of increased screening mammography and improvements in adjuvant therapy, Dr. Van Zee noted, citing a 2005 study (N. Engl. J. Med. 2005;353:1784-92).

"They dissected all the various effects of treatment, incidence of screening-detected diseases, etc., and all their analyses concluded that about half of the reduction in death rate was due to screening and the other half was due to adjuvant therapy. So I think this is good circumstantial evidence that screening, with its resultant increased incidence in DCIS and the resulting increased treatment of DCIS, does result in a lower death rate from breast cancer," she said.

Further evidence comes from studies in which pathologists reviewed thousands of slides of biopsy-acquired breast tissue originally reported as benign. In each study (Cancer 1980;46[4 Suppl]:919-25; Cancer 2005;103:2481-84), the investigator identified about 30 samples with evidence of low-grade, relatively low-volume DCIS that was not recognized or treated. After 20-30 years of follow-up, half of the women had developed a clinically apparent ipsilateral breast cancer recurrence. The majority of tumors were invasive. In the second study, the authors noted that 5 of the 28 women (18%) with previously undetected DCIS died of breast cancer.

Evidence from a meta-analysis (Cancer 1999;85:616-28) suggests that the risk for invasive recurrence following a mastectomy for DCIS is 1.1%, and that the risk for breast cancer death is less than 1.1%.

The risk for distant recurrence and/or death from breast-conserving surgery with or without adjuvant radiotherapy in prospective randomized trials of radiotherapy for DCIS was less than 5%. Among patients with invasive local failure in those trials, however, 18%-25% developed metastatic disease, indicating the importance of avoiding local recurrence.

Mastectomy and breast-conserving surgery combined with radiotherapy and/or endocrine therapy all provide excellent disease-specific and overall survival results, Dr. Van Zee said.

"The goal should be avoiding local recurrence and, in particular, invasive recurrence, minimizing morbidity, and perhaps individualizing the treatment to the disease. One could consider age, comorbidities, [and] life expectancy, and weigh those against the morbidity of the treatment and the risk of local recurrence," she said.

Dr. Van Zee reported no relevant financial disclosures.

ORLANDO – Surgery for ductal carcinoma in situ, with or without adjuvant therapy, saves lives, asserted a breast cancer surgeon at a symposium sponsored by the Society of Surgical Oncology.

Following a surgical biopsy alone, about half of all cases of low-grade ductal carcinoma in situ (DCIS) will progress to invasive cancer within an average of 10-15 years, said Dr. Kimberly J. Van Zee, a surgical oncologist at Memorial Sloan-Kettering Cancer Center in New York.

Additionally, without intervention, low-grade DCIS will result in death from ipsilateral invasive recurrence of breast cancer in about 18% of patients, Dr. Van Zee said.

"With treatment of DCIS, whether it’s breast conservation or mastectomy, with or without radiation, breast cancer–specific survival is over 95%," she noted.

The incidence of DCIS has increased steadily since 1975, when the rate was slightly more than 5 in 100,000 women. In 2009, the rate had reached approximately 36 in 100,000, according to Surveillance, Epidemiology, and End Results (SEER) data. The increase is probably a result of the growing adoption of screening mammography over the same period, Dr. Van Zee commented.

Treatment trends for DCIS showed a gradual but steady decline in mastectomy – from 70% in 1983 to about 28% in 1999 – and a corresponding increase in breast-conserving treatment, which increased from about 25% to 68% over the same period.

Beginning around 2005, however, there was evidence that the trend was reversing, with upticks in both mastectomy for unilateral breast cancer (J. Clin. Oncol. 2010;28:3437-41) and contralateral prophylactic mastectomy, both among women with invasive cancers and DCIS (Ann. Surg. Oncol. 2010;17:2554-62). The trends paralleled the rise in screening mammography in the United States and elsewhere in the world.

The gradual but steady decline in breast cancer deaths that began in the early 1990s appears to be attributable to a combination of increased screening mammography and improvements in adjuvant therapy, Dr. Van Zee noted, citing a 2005 study (N. Engl. J. Med. 2005;353:1784-92).

"They dissected all the various effects of treatment, incidence of screening-detected diseases, etc., and all their analyses concluded that about half of the reduction in death rate was due to screening and the other half was due to adjuvant therapy. So I think this is good circumstantial evidence that screening, with its resultant increased incidence in DCIS and the resulting increased treatment of DCIS, does result in a lower death rate from breast cancer," she said.

Further evidence comes from studies in which pathologists reviewed thousands of slides of biopsy-acquired breast tissue originally reported as benign. In each study (Cancer 1980;46[4 Suppl]:919-25; Cancer 2005;103:2481-84), the investigator identified about 30 samples with evidence of low-grade, relatively low-volume DCIS that was not recognized or treated. After 20-30 years of follow-up, half of the women had developed a clinically apparent ipsilateral breast cancer recurrence. The majority of tumors were invasive. In the second study, the authors noted that 5 of the 28 women (18%) with previously undetected DCIS died of breast cancer.

Evidence from a meta-analysis (Cancer 1999;85:616-28) suggests that the risk for invasive recurrence following a mastectomy for DCIS is 1.1%, and that the risk for breast cancer death is less than 1.1%.

The risk for distant recurrence and/or death from breast-conserving surgery with or without adjuvant radiotherapy in prospective randomized trials of radiotherapy for DCIS was less than 5%. Among patients with invasive local failure in those trials, however, 18%-25% developed metastatic disease, indicating the importance of avoiding local recurrence.

Mastectomy and breast-conserving surgery combined with radiotherapy and/or endocrine therapy all provide excellent disease-specific and overall survival results, Dr. Van Zee said.

"The goal should be avoiding local recurrence and, in particular, invasive recurrence, minimizing morbidity, and perhaps individualizing the treatment to the disease. One could consider age, comorbidities, [and] life expectancy, and weigh those against the morbidity of the treatment and the risk of local recurrence," she said.

Dr. Van Zee reported no relevant financial disclosures.

ORLANDO – Gastrointestinal stromal tumors of the duodenum can be managed safely with surgery, yielding good overall survival, an investigator reported at a symposium sponsored by the Society of Surgical Oncology.

In addition to surgery for duodenal gastrointestinal stromal tumors (GISTs), adjuvant treatment with imatinib (Gleevec) may reduce the risk of recurrence, and neoadjuvant imatinib may improve surgical outcomes, said Dr. Chiara Colombo, from the sarcoma service of the Fondazione Istituto Nazionale dei Tumori in Milan.

"Imatinib in the neoadjuvant setting might facilitate the surgical resection and possibly help preserve the biliary and pancreatic anatomy," she said.

Only about 5% of GISTs originate in the duodenum, but tumors occurring in this section of the small intestine are anatomically challenging and there is considerable debate about the most appropriate surgical and therapeutic approaches, she added.

To gain a better understanding of the problem, Dr. Colombo and colleagues at her center, as well as the University of Mannheim (Germany), Massachusetts General Hospital in Boston, and the Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology in Gliwice (Poland), pooled data on patients with a primary duodenal GIST treated from February 2000 through August 2011 at their institutions.

There were a total of 39 men and 45 women, median age 58 years, treated with either pancreaticoduodenectomy (28 patients, 33%) or limited resection (56 patients, 67%). In all, 11 patients received preoperative imatinib for a median of 8 months, and 23 received it after surgery for a median of 17 months.

Surgical complication rates were higher among patients who underwent pancreaticoduodenectomy, compared with patients who had limited resection. The complications occurred in 5 patients who underwent limited resection (9%) and 10 who underwent pancreaticoduodenectomy (36%) and included evisceration/wound dehiscence (2 and 1, respectively), infections (1 in each group), gastric obstruction/delayed emptying (0 and 2), and pancreatic/biliary leakage (2 and 6 patients).

Among all patients, overall survival was 98% at 3 years and 89% at 5 years; the median follow-up was 42 months. Overall survival of patients at low or intermediate risk for recurrence was similar whether they received imatinib or did not. Among high-risk patients, however, imatinib was associated with significantly better 5-year overall survival, and the survival curves began to converge after imatinib was withdrawn, Dr. Colombo said.

She noted that the results echo those of a recent phase III study of adjuvant imatinib in patients with operable GISTs (ASCO 2011 Abstract LBA1).

In the intention-to-treat population of the randomized trial, the hazard ratio for overall survival for 36 months vs. 12 months of adjuvant imatinib was 0.45 (P = .019). The longer treatment schedule was also associated with better recurrence-free survival (hazard ratio 0.46, P less than .0001).

In the neoadjuvant setting, imatinib was associated with tumor regression, allowing for safer resection than might otherwise be possible, Dr. Colombo commented. This analysis on tumor regression was based on the combined clinical experience at all the centers.

The study was supported by the participating institutions. Dr. Colombo reported no relevant financial disclosures.

ORLANDO – Gastrointestinal stromal tumors of the duodenum can be managed safely with surgery, yielding good overall survival, an investigator reported at a symposium sponsored by the Society of Surgical Oncology.

In addition to surgery for duodenal gastrointestinal stromal tumors (GISTs), adjuvant treatment with imatinib (Gleevec) may reduce the risk of recurrence, and neoadjuvant imatinib may improve surgical outcomes, said Dr. Chiara Colombo, from the sarcoma service of the Fondazione Istituto Nazionale dei Tumori in Milan.

"Imatinib in the neoadjuvant setting might facilitate the surgical resection and possibly help preserve the biliary and pancreatic anatomy," she said.

Only about 5% of GISTs originate in the duodenum, but tumors occurring in this section of the small intestine are anatomically challenging and there is considerable debate about the most appropriate surgical and therapeutic approaches, she added.

To gain a better understanding of the problem, Dr. Colombo and colleagues at her center, as well as the University of Mannheim (Germany), Massachusetts General Hospital in Boston, and the Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology in Gliwice (Poland), pooled data on patients with a primary duodenal GIST treated from February 2000 through August 2011 at their institutions.

There were a total of 39 men and 45 women, median age 58 years, treated with either pancreaticoduodenectomy (28 patients, 33%) or limited resection (56 patients, 67%). In all, 11 patients received preoperative imatinib for a median of 8 months, and 23 received it after surgery for a median of 17 months.

Surgical complication rates were higher among patients who underwent pancreaticoduodenectomy, compared with patients who had limited resection. The complications occurred in 5 patients who underwent limited resection (9%) and 10 who underwent pancreaticoduodenectomy (36%) and included evisceration/wound dehiscence (2 and 1, respectively), infections (1 in each group), gastric obstruction/delayed emptying (0 and 2), and pancreatic/biliary leakage (2 and 6 patients).

Among all patients, overall survival was 98% at 3 years and 89% at 5 years; the median follow-up was 42 months. Overall survival of patients at low or intermediate risk for recurrence was similar whether they received imatinib or did not. Among high-risk patients, however, imatinib was associated with significantly better 5-year overall survival, and the survival curves began to converge after imatinib was withdrawn, Dr. Colombo said.

She noted that the results echo those of a recent phase III study of adjuvant imatinib in patients with operable GISTs (ASCO 2011 Abstract LBA1).

In the intention-to-treat population of the randomized trial, the hazard ratio for overall survival for 36 months vs. 12 months of adjuvant imatinib was 0.45 (P = .019). The longer treatment schedule was also associated with better recurrence-free survival (hazard ratio 0.46, P less than .0001).

In the neoadjuvant setting, imatinib was associated with tumor regression, allowing for safer resection than might otherwise be possible, Dr. Colombo commented. This analysis on tumor regression was based on the combined clinical experience at all the centers.

The study was supported by the participating institutions. Dr. Colombo reported no relevant financial disclosures.

ORLANDO – Gastrointestinal stromal tumors of the duodenum can be managed safely with surgery, yielding good overall survival, an investigator reported at a symposium sponsored by the Society of Surgical Oncology.

In addition to surgery for duodenal gastrointestinal stromal tumors (GISTs), adjuvant treatment with imatinib (Gleevec) may reduce the risk of recurrence, and neoadjuvant imatinib may improve surgical outcomes, said Dr. Chiara Colombo, from the sarcoma service of the Fondazione Istituto Nazionale dei Tumori in Milan.

"Imatinib in the neoadjuvant setting might facilitate the surgical resection and possibly help preserve the biliary and pancreatic anatomy," she said.

Only about 5% of GISTs originate in the duodenum, but tumors occurring in this section of the small intestine are anatomically challenging and there is considerable debate about the most appropriate surgical and therapeutic approaches, she added.

To gain a better understanding of the problem, Dr. Colombo and colleagues at her center, as well as the University of Mannheim (Germany), Massachusetts General Hospital in Boston, and the Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology in Gliwice (Poland), pooled data on patients with a primary duodenal GIST treated from February 2000 through August 2011 at their institutions.

There were a total of 39 men and 45 women, median age 58 years, treated with either pancreaticoduodenectomy (28 patients, 33%) or limited resection (56 patients, 67%). In all, 11 patients received preoperative imatinib for a median of 8 months, and 23 received it after surgery for a median of 17 months.

Surgical complication rates were higher among patients who underwent pancreaticoduodenectomy, compared with patients who had limited resection. The complications occurred in 5 patients who underwent limited resection (9%) and 10 who underwent pancreaticoduodenectomy (36%) and included evisceration/wound dehiscence (2 and 1, respectively), infections (1 in each group), gastric obstruction/delayed emptying (0 and 2), and pancreatic/biliary leakage (2 and 6 patients).

Among all patients, overall survival was 98% at 3 years and 89% at 5 years; the median follow-up was 42 months. Overall survival of patients at low or intermediate risk for recurrence was similar whether they received imatinib or did not. Among high-risk patients, however, imatinib was associated with significantly better 5-year overall survival, and the survival curves began to converge after imatinib was withdrawn, Dr. Colombo said.

She noted that the results echo those of a recent phase III study of adjuvant imatinib in patients with operable GISTs (ASCO 2011 Abstract LBA1).

In the intention-to-treat population of the randomized trial, the hazard ratio for overall survival for 36 months vs. 12 months of adjuvant imatinib was 0.45 (P = .019). The longer treatment schedule was also associated with better recurrence-free survival (hazard ratio 0.46, P less than .0001).

In the neoadjuvant setting, imatinib was associated with tumor regression, allowing for safer resection than might otherwise be possible, Dr. Colombo commented. This analysis on tumor regression was based on the combined clinical experience at all the centers.

The study was supported by the participating institutions. Dr. Colombo reported no relevant financial disclosures.

A retrospective study of nearly 93,000 older women with invasive breast cancer suggests that brachytherapy after lumpectomy leads to more complications and more subsequent mastectomies than does postoperative whole-breast radiation.

The mastectomy rate 5 years later was about twice as high in women treated with brachytherapy – cumulative incidence 3.95% vs. 2.18% with whole-breast radiation (WBI) – and the difference persisted after a multivariate adjustment, with a hazard ratio of 2.19, according to a report published May 1, 2012 in JAMA.

Moreover, short-term and long-term complications, including breast pain, were significantly more common in women who had radiation delivered by brachytherapy. Overall survival was not significantly different, however, at about 87% in both groups studied.

What this means is that for every 56 women treated with brachytherapy, 1 woman was harmed with an unnecessary mastectomy (absolute excess risk, 1.77%), wrote Dr. Grace L. Smith of the University of Texas M.D. Anderson Cancer Center in Houston and her coauthors. At 1 year, 1 woman suffered an unnecessary postoperative complication for every 9 women treated with brachytherapy (absolute excess risk, 10.64%), and by 5 years, 1 woman for every 16 was harmed by an unnecessary postoperative radiation complication (absolute excess risk, 6.16%).

"Potential public health implications of these findings are substantial, given the high incidence of breast cancer, along with the recent rapid increase in breast brachytherapy use. Although these results await validation in the prospective setting, they also prompt caution over widespread application of breast brachytherapy outside the study setting," the authors concluded (JAMA 2012;307:1827-37).

An earlier version of the study stirred controversy when principal investigator Dr. Benjamin D. Smith, also of M.D. Anderson, presented it at the San Antonio Breast Cancer Symposium in December 2011. Three professional societies – the American Society for Radiation Oncology (ASTRO), American Society of Breast Surgeons, and American Brachytherapy Society – issued rebuttals soon after.

Among the objections raised were the retrospective nature of the study, limitations inherent in studies based on Medicare claims data, and the fact that the data did not take into account improvements in brachytherapy technology since the study years of 2000-2007. Definitive results from ongoing randomized trials comparing the safety and efficacy of brachytherapy and standard WBI are still years off, critics said, citing the ongoing phase III National Surgical Adjuvant Breast and Bowel Project (NSABP) B-39/Radiation Therapy Oncology Group (RTOG) 0413 trial.

For the current study, the investigators identified 92,735 women aged 67 years or older who had incident invasive breast cancer diagnosed between 2003 and 2007 and were followed through 2008. After lumpectomy, a large majority of the women studied, 85,783 (92.5%), underwent WBI, while 6,952 (7.5%) were treated with brachytherapy.

At 1 year, infectious skin or soft tissue infections were significantly more frequent with brachytherapy (16.20% vs. 10.33% with WBI), as were noninfectious postoperative complications (16.25% vs. 9.0%).

By 5 years, the cumulative incidence of breast pain reached 14.55% with brachytherapy, compared with 11.92% with WBI. Fat necrosis (8.26% vs. 4.05%) and rib fracture (4.53% vs. 3.62%) also occurred at higher rates in the brachytherapy group.

Dr. Smith was supported by a Multidisciplinary Postdoctoral Award from the Department of Defense. Coauthors Dr. Benjamin D. Smith and Dr. Sharon H. Giordano were supported by a grant from the Cancer Prevention and Research Institute of Texas. Dr. Ya-Chen Tina Shih was supported by grants from the Agency for Healthcare Research and Quality, the National Cancer Institute, and the University of Chicago Cancer Research Foundation Women’s Board. This study also was supported in part by grants from the National Cancer Institute and by a philanthropic gift from Ann and Clarence Cazalot.

A retrospective study of nearly 93,000 older women with invasive breast cancer suggests that brachytherapy after lumpectomy leads to more complications and more subsequent mastectomies than does postoperative whole-breast radiation.

The mastectomy rate 5 years later was about twice as high in women treated with brachytherapy – cumulative incidence 3.95% vs. 2.18% with whole-breast radiation (WBI) – and the difference persisted after a multivariate adjustment, with a hazard ratio of 2.19, according to a report published May 1, 2012 in JAMA.

Moreover, short-term and long-term complications, including breast pain, were significantly more common in women who had radiation delivered by brachytherapy. Overall survival was not significantly different, however, at about 87% in both groups studied.

What this means is that for every 56 women treated with brachytherapy, 1 woman was harmed with an unnecessary mastectomy (absolute excess risk, 1.77%), wrote Dr. Grace L. Smith of the University of Texas M.D. Anderson Cancer Center in Houston and her coauthors. At 1 year, 1 woman suffered an unnecessary postoperative complication for every 9 women treated with brachytherapy (absolute excess risk, 10.64%), and by 5 years, 1 woman for every 16 was harmed by an unnecessary postoperative radiation complication (absolute excess risk, 6.16%).

"Potential public health implications of these findings are substantial, given the high incidence of breast cancer, along with the recent rapid increase in breast brachytherapy use. Although these results await validation in the prospective setting, they also prompt caution over widespread application of breast brachytherapy outside the study setting," the authors concluded (JAMA 2012;307:1827-37).

An earlier version of the study stirred controversy when principal investigator Dr. Benjamin D. Smith, also of M.D. Anderson, presented it at the San Antonio Breast Cancer Symposium in December 2011. Three professional societies – the American Society for Radiation Oncology (ASTRO), American Society of Breast Surgeons, and American Brachytherapy Society – issued rebuttals soon after.

Among the objections raised were the retrospective nature of the study, limitations inherent in studies based on Medicare claims data, and the fact that the data did not take into account improvements in brachytherapy technology since the study years of 2000-2007. Definitive results from ongoing randomized trials comparing the safety and efficacy of brachytherapy and standard WBI are still years off, critics said, citing the ongoing phase III National Surgical Adjuvant Breast and Bowel Project (NSABP) B-39/Radiation Therapy Oncology Group (RTOG) 0413 trial.

For the current study, the investigators identified 92,735 women aged 67 years or older who had incident invasive breast cancer diagnosed between 2003 and 2007 and were followed through 2008. After lumpectomy, a large majority of the women studied, 85,783 (92.5%), underwent WBI, while 6,952 (7.5%) were treated with brachytherapy.

At 1 year, infectious skin or soft tissue infections were significantly more frequent with brachytherapy (16.20% vs. 10.33% with WBI), as were noninfectious postoperative complications (16.25% vs. 9.0%).

By 5 years, the cumulative incidence of breast pain reached 14.55% with brachytherapy, compared with 11.92% with WBI. Fat necrosis (8.26% vs. 4.05%) and rib fracture (4.53% vs. 3.62%) also occurred at higher rates in the brachytherapy group.

Dr. Smith was supported by a Multidisciplinary Postdoctoral Award from the Department of Defense. Coauthors Dr. Benjamin D. Smith and Dr. Sharon H. Giordano were supported by a grant from the Cancer Prevention and Research Institute of Texas. Dr. Ya-Chen Tina Shih was supported by grants from the Agency for Healthcare Research and Quality, the National Cancer Institute, and the University of Chicago Cancer Research Foundation Women’s Board. This study also was supported in part by grants from the National Cancer Institute and by a philanthropic gift from Ann and Clarence Cazalot.

A retrospective study of nearly 93,000 older women with invasive breast cancer suggests that brachytherapy after lumpectomy leads to more complications and more subsequent mastectomies than does postoperative whole-breast radiation.

The mastectomy rate 5 years later was about twice as high in women treated with brachytherapy – cumulative incidence 3.95% vs. 2.18% with whole-breast radiation (WBI) – and the difference persisted after a multivariate adjustment, with a hazard ratio of 2.19, according to a report published May 1, 2012 in JAMA.

Moreover, short-term and long-term complications, including breast pain, were significantly more common in women who had radiation delivered by brachytherapy. Overall survival was not significantly different, however, at about 87% in both groups studied.

What this means is that for every 56 women treated with brachytherapy, 1 woman was harmed with an unnecessary mastectomy (absolute excess risk, 1.77%), wrote Dr. Grace L. Smith of the University of Texas M.D. Anderson Cancer Center in Houston and her coauthors. At 1 year, 1 woman suffered an unnecessary postoperative complication for every 9 women treated with brachytherapy (absolute excess risk, 10.64%), and by 5 years, 1 woman for every 16 was harmed by an unnecessary postoperative radiation complication (absolute excess risk, 6.16%).

"Potential public health implications of these findings are substantial, given the high incidence of breast cancer, along with the recent rapid increase in breast brachytherapy use. Although these results await validation in the prospective setting, they also prompt caution over widespread application of breast brachytherapy outside the study setting," the authors concluded (JAMA 2012;307:1827-37).

An earlier version of the study stirred controversy when principal investigator Dr. Benjamin D. Smith, also of M.D. Anderson, presented it at the San Antonio Breast Cancer Symposium in December 2011. Three professional societies – the American Society for Radiation Oncology (ASTRO), American Society of Breast Surgeons, and American Brachytherapy Society – issued rebuttals soon after.

Among the objections raised were the retrospective nature of the study, limitations inherent in studies based on Medicare claims data, and the fact that the data did not take into account improvements in brachytherapy technology since the study years of 2000-2007. Definitive results from ongoing randomized trials comparing the safety and efficacy of brachytherapy and standard WBI are still years off, critics said, citing the ongoing phase III National Surgical Adjuvant Breast and Bowel Project (NSABP) B-39/Radiation Therapy Oncology Group (RTOG) 0413 trial.

For the current study, the investigators identified 92,735 women aged 67 years or older who had incident invasive breast cancer diagnosed between 2003 and 2007 and were followed through 2008. After lumpectomy, a large majority of the women studied, 85,783 (92.5%), underwent WBI, while 6,952 (7.5%) were treated with brachytherapy.

At 1 year, infectious skin or soft tissue infections were significantly more frequent with brachytherapy (16.20% vs. 10.33% with WBI), as were noninfectious postoperative complications (16.25% vs. 9.0%).

By 5 years, the cumulative incidence of breast pain reached 14.55% with brachytherapy, compared with 11.92% with WBI. Fat necrosis (8.26% vs. 4.05%) and rib fracture (4.53% vs. 3.62%) also occurred at higher rates in the brachytherapy group.

Dr. Smith was supported by a Multidisciplinary Postdoctoral Award from the Department of Defense. Coauthors Dr. Benjamin D. Smith and Dr. Sharon H. Giordano were supported by a grant from the Cancer Prevention and Research Institute of Texas. Dr. Ya-Chen Tina Shih was supported by grants from the Agency for Healthcare Research and Quality, the National Cancer Institute, and the University of Chicago Cancer Research Foundation Women’s Board. This study also was supported in part by grants from the National Cancer Institute and by a philanthropic gift from Ann and Clarence Cazalot.