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The use of radioisotope combined with isosulfan blue dye is not superior to radioisotope alone for the identification of sentinel lymph nodes in patients with breast cancer
The use of radioisotope combined with isosulfan blue dye is not superior to radioisotope alone for the identification of sentinel lymph nodes in patients with breast cancer Bines S, Kopkash K, Ali A, et al (Rush Univ School of Nursing, Chicago) Surgery 144:606-610, 2008
Background.—Isosulfan Blue dye (BD) allergic drug reactions (ADR) occur in up to 2% of patients undergoing SLN biopsy (SLNB). We sought to determine if BD enhances the performance of SLNB such that this risk is justified. Methods.—A retrospective review of 392 breast cancer patients undergoing SLNB between 8/99 and 8/04 was performed; 208 patients had radioisotope (ISO) alone, 167 had ISO + BD. Total SLN and positive SLN in each group were compared. We examined the ISO + BD group for concordance and the presence of blue only nodes. The effect of tumor location, injection site, angiolymphatic invasion, Her2/ neu expression, and the presence of a noninvasive component were studied. Chi-square, linear regression, Fisher t tests, and ANOVA were performed. Results.—SLN were identified in 94% of ISO and 96% of ISO + BD patients. The mean number SLN from the ISO group was 2.01, 1.93 for ISO + BD; 27% of ISO and 21% of ISO + BD patients had positive nodes. These differences were not significant. No difference for tumor location, injection site, angiolymphatic invasion, Her2/neu expression, or the presence of a noninvasive component was found. Conclusion.—The addition of BD to ISO in patients with invasive breast cancer does not significantly enhance the performance of SLNB.
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In this study, Bines and colleagues revisit the use of 1% isosulfan blue dye for SLNB in an effort to avoid the risk of anaphylaxis. We share the authors’ desire to minimize the risk of anaphylactic reactions and agree that it is an important consideration in choosing the appropriate mapping technique. The reported rate of anaphylaxis in this retrospective series of 392 breast cancer patients was 1.2%. However, in an earlier report of complications associated with SLNB from the prospective, multicenter American College of Surgeons Oncology Group Z0010 clinical trial of SLNB,1 anaphylaxis was reported in only 5 (0.1%) of 4975 patients. This low incidence in a very large study population may have been a more accurate reflection of the true incidence of anaphylaxis than was the 1.2% reported in the retrospective study by Bines and colleagues, in which only 167 patients received blue dye. This risk, however, may still be significant enough to warrant avoidance of the use of blue dye. Bines and colleagues concluded that SLNB can be accurately performed with radioisotope alone. There are two important factors in performing a successful SLNB: the SLN identification rate and the falsenegative (FN) rate. Although the authors demonstrated nearly equivalent rates of SLN identification between the group of patients mapped with radioisotope and blue dye and the group mapped with radioisotope alone, they did not address the FN rate of either mapping technique since completion axillary lymph node dissection (ALND) was not performed. Only successful SLN identification, but not the accuracy of the two mapping techniques, could be evaluated. However, we know from the broad body of literature on this subject that SLNB with single-agent
Breast Diseases: A Year BookÒ Quarterly Vol 20 No 1 2009
mapping can be accurately performed in experienced hands. Krag and colleagues2 performed a prospective, multicenter trial of SLNB by using radioisotope alone and validated the technique with completion ALND. Although these researchers showed a total FN rate of 11.4%, the rates varied widely among the individual surgeons in the study, from 0% to 28%. These surgeons had had a total of only 5 ‘‘training procedures’’ before accruing patients to the trial. Perhaps with more experience, the FN rates would have been lower. Many surgeons routinely perform SLNB with blue dye alone. In 1994, while SLNB was being developed, initial reports from the John Wayne Cancer Institute yielded an SLN identification rate of only 66% and an FN rate of 4.3% with blue dye alone.3 Three years later, with more experience, the institute reported an SLN identification rate of 94% and an FN rate of 0%, confirmed by completion ALND.4 Most studies have demonstrated that dual-agent mapping achieves better SLN identification and FN rates than does single-agent mapping, especially in inexperienced hands. However, in the only prospective randomized trial comparing blue dye alone with combined radioisotope and blue dye, Morrow and colleagues5 showed no difference in SLN identification between the two groups. In addition, the number of cases performed by an individual surgeon was a significant predictor of successful SLN identification. Surgeon experience has been shown to significantly affect SLN identification and FN rates.6 We feel that the combined technique should be used while surgeons are learning the SLNB procedure. However, in experienced hands, single-agent mapping for SLNB can be reliable, and the use of
a second agent may not significantly enhance performance. Finally, anaphylaxis from isosulfan blue dye is a rare event. In a comprehensive literature review on lymphatic mapping and SLNB, the incidence of allergic reactions to blue dye ranged from 0% to 2%, but no deaths resulting from blue dye anaphylaxis were reported.7 As in any procedure, one must consider the risks and benefits. While the use of blue dye does carry a small but serious risk, the surgeon must decide whether abandoning its use in SLNB is appropriate in his or her hands. A. P. Chung, MD A. E. Giuliano, MD
How Many Sentinel Lymph Nodes are Enough During Sentinel Lymph Node Dissection for Breast Cancer? Yi M, Meric-Bernstam F, Ross MI, et al (Univ of Texas M. D. Anderson Cancer Ctr, Houston) Cancer 113:30-37, 2008
Background.—It remains unclear how many sentinel lymph nodes (SLNs) must be removed to accurately predict lymph node status during SLN dissection in breast cancer. The objective of this study was to determine how many SLNs need to be removed for accurate lymph node staging and which patient and tumor characteristics influence this number. Methods.—The authors reviewed data for all patients in their prospective database with clinical tumor, lymph node, metastasis (TNM) T1 through T3, N0, M0 breast cancer who under-
References 1. Wilke L, McCall L, Posther K, et al. Surgical complications associated with sentinel lymph node biopsy: results from a prospective international cooperative group trial. Ann Surg Oncol. 2005;13:491-500. 2. Krag D, Weaver D, Ashikaga T, et al. The sentinel node in breast cancer: a multicenter validation study. N Engl J Med. 1998;339:941-946. 3. Giuliano A, Kirgan D, Guenther J, et al. Lymphatic mapping and sentinel lymphadenectomy for breast cancer. Ann Surg. 1994;220:391-401. 4. Giuliano A, Jones R, Brennan M, Statman R. Sentinel lymphadenectomy in breast cancer. J Clin Oncol. 1997;15:2345-2350.
went lymphatic mapping at their institution during the years 1994 through 2006. There were 777 patients who had at least 1 SLN that was positive for cancer. Simple and multiple quantile regression analyses were used to determine which patient and tumor characteristics were associated with the number of positive SLNs. The baseline number of SLNs that needed to be dissected for detection of 99% of positive SLNs in the total group of patients also was determined. Results.—The mean number of SLNs removed in the 777 lymph node-positive patients was 2.9 (range, 1-13 SLNs). Greater than 99% of positive SLNs were identified in the first 5 lymph nodes removed. On univariate analysis, tumor histology, patient race, tumor location, and tumor size significantly affected the number of SLNs that needed to be removed to identify 99% of all positive SLNs. On multivariate analysis, mixed ductal and lobular
5. Morrow M, Rademaker A, Bethke K, et al. Learning sentinel node biopsy: results of a prospective randomized trial of two techniques. Surgery. 1999; 126:714-720. 6. McMasters K, Wong S, Chao C, et al. Defining the optimal surgeon experience for breast cancer sentinel lymph node biopsy: a model for implementation of new surgical techniques. Ann Surg. 2001;234: 292-300. 7. Newman L. Lymphatic mapping and sentinel lymph node biopsy in breast cancer patients: a comprehensive review of variations in performance and technique. J Am Coll Surg. 2004; 199:804-816.
histology, Caucasian race, inner quadrant tumor location, and T1 tumor classification significantly increased the number of SLNs that needed to be removed to achieve 99% recovery of all positive SLNs. Conclusions.—In general, the removal of a maximum of 5 SLNs at surgery allowed for the recovery of >99% of positive SLNs in patients with breast cancer. The current findings indicated that tumor histology, patient race, and tumor size and location may influence this number. SLN biopsy was a major advance in the surgical management of patients with breast cancer, allowing surgeons to avoid the morbidity of axillary node dissection in nodenegative patients. Recently, there has been increasing interest in limiting the number of SLNs removed. In this article, Yi and colleagues found that 99% of all positive SLNs can be found
Breast Diseases: A Year BookÒ Quarterly Vol 20 No 1 2009
75
Background.—Isosulfan Blue dye (BD) allergic drug reactions (ADR) occur in up to 2% of patients undergoing SLN biopsy (SLNB). We sought to determine if BD enhances the performance of SLNB such that this risk is justified. Methods.—A retrospective review of 392 breast cancer patients undergoing SLNB between 8/99 and 8/04 was performed; 208 patients had radioisotope (ISO) alone, 167 had ISO + BD. Total SLN and positive SLN in each group were compared. We examined the ISO + BD group for concordance and the presence of blue only nodes. The effect of tumor location, injection site, angiolymphatic invasion, Her2/ neu expression, and the presence of a noninvasive component were studied. Chi-square, linear regression, Fisher t tests, and ANOVA were performed. Results.—SLN were identified in 94% of ISO and 96% of ISO + BD patients. The mean number SLN from the ISO group was 2.01, 1.93 for ISO + BD; 27% of ISO and 21% of ISO + BD patients had positive nodes. These differences were not significant. No difference for tumor location, injection site, angiolymphatic invasion, Her2/neu expression, or the presence of a noninvasive component was found. Conclusion.—The addition of BD to ISO in patients with invasive breast cancer does not significantly enhance the performance of SLNB.
74
In this study, Bines and colleagues revisit the use of 1% isosulfan blue dye for SLNB in an effort to avoid the risk of anaphylaxis. We share the authors’ desire to minimize the risk of anaphylactic reactions and agree that it is an important consideration in choosing the appropriate mapping technique. The reported rate of anaphylaxis in this retrospective series of 392 breast cancer patients was 1.2%. However, in an earlier report of complications associated with SLNB from the prospective, multicenter American College of Surgeons Oncology Group Z0010 clinical trial of SLNB,1 anaphylaxis was reported in only 5 (0.1%) of 4975 patients. This low incidence in a very large study population may have been a more accurate reflection of the true incidence of anaphylaxis than was the 1.2% reported in the retrospective study by Bines and colleagues, in which only 167 patients received blue dye. This risk, however, may still be significant enough to warrant avoidance of the use of blue dye. Bines and colleagues concluded that SLNB can be accurately performed with radioisotope alone. There are two important factors in performing a successful SLNB: the SLN identification rate and the falsenegative (FN) rate. Although the authors demonstrated nearly equivalent rates of SLN identification between the group of patients mapped with radioisotope and blue dye and the group mapped with radioisotope alone, they did not address the FN rate of either mapping technique since completion axillary lymph node dissection (ALND) was not performed. Only successful SLN identification, but not the accuracy of the two mapping techniques, could be evaluated. However, we know from the broad body of literature on this subject that SLNB with single-agent
Breast Diseases: A Year BookÒ Quarterly Vol 20 No 1 2009
mapping can be accurately performed in experienced hands. Krag and colleagues2 performed a prospective, multicenter trial of SLNB by using radioisotope alone and validated the technique with completion ALND. Although these researchers showed a total FN rate of 11.4%, the rates varied widely among the individual surgeons in the study, from 0% to 28%. These surgeons had had a total of only 5 ‘‘training procedures’’ before accruing patients to the trial. Perhaps with more experience, the FN rates would have been lower. Many surgeons routinely perform SLNB with blue dye alone. In 1994, while SLNB was being developed, initial reports from the John Wayne Cancer Institute yielded an SLN identification rate of only 66% and an FN rate of 4.3% with blue dye alone.3 Three years later, with more experience, the institute reported an SLN identification rate of 94% and an FN rate of 0%, confirmed by completion ALND.4 Most studies have demonstrated that dual-agent mapping achieves better SLN identification and FN rates than does single-agent mapping, especially in inexperienced hands. However, in the only prospective randomized trial comparing blue dye alone with combined radioisotope and blue dye, Morrow and colleagues5 showed no difference in SLN identification between the two groups. In addition, the number of cases performed by an individual surgeon was a significant predictor of successful SLN identification. Surgeon experience has been shown to significantly affect SLN identification and FN rates.6 We feel that the combined technique should be used while surgeons are learning the SLNB procedure. However, in experienced hands, single-agent mapping for SLNB can be reliable, and the use of
a second agent may not significantly enhance performance. Finally, anaphylaxis from isosulfan blue dye is a rare event. In a comprehensive literature review on lymphatic mapping and SLNB, the incidence of allergic reactions to blue dye ranged from 0% to 2%, but no deaths resulting from blue dye anaphylaxis were reported.7 As in any procedure, one must consider the risks and benefits. While the use of blue dye does carry a small but serious risk, the surgeon must decide whether abandoning its use in SLNB is appropriate in his or her hands. A. P. Chung, MD A. E. Giuliano, MD
How Many Sentinel Lymph Nodes are Enough During Sentinel Lymph Node Dissection for Breast Cancer? Yi M, Meric-Bernstam F, Ross MI, et al (Univ of Texas M. D. Anderson Cancer Ctr, Houston) Cancer 113:30-37, 2008
Background.—It remains unclear how many sentinel lymph nodes (SLNs) must be removed to accurately predict lymph node status during SLN dissection in breast cancer. The objective of this study was to determine how many SLNs need to be removed for accurate lymph node staging and which patient and tumor characteristics influence this number. Methods.—The authors reviewed data for all patients in their prospective database with clinical tumor, lymph node, metastasis (TNM) T1 through T3, N0, M0 breast cancer who under-
References 1. Wilke L, McCall L, Posther K, et al. Surgical complications associated with sentinel lymph node biopsy: results from a prospective international cooperative group trial. Ann Surg Oncol. 2005;13:491-500. 2. Krag D, Weaver D, Ashikaga T, et al. The sentinel node in breast cancer: a multicenter validation study. N Engl J Med. 1998;339:941-946. 3. Giuliano A, Kirgan D, Guenther J, et al. Lymphatic mapping and sentinel lymphadenectomy for breast cancer. Ann Surg. 1994;220:391-401. 4. Giuliano A, Jones R, Brennan M, Statman R. Sentinel lymphadenectomy in breast cancer. J Clin Oncol. 1997;15:2345-2350.
went lymphatic mapping at their institution during the years 1994 through 2006. There were 777 patients who had at least 1 SLN that was positive for cancer. Simple and multiple quantile regression analyses were used to determine which patient and tumor characteristics were associated with the number of positive SLNs. The baseline number of SLNs that needed to be dissected for detection of 99% of positive SLNs in the total group of patients also was determined. Results.—The mean number of SLNs removed in the 777 lymph node-positive patients was 2.9 (range, 1-13 SLNs). Greater than 99% of positive SLNs were identified in the first 5 lymph nodes removed. On univariate analysis, tumor histology, patient race, tumor location, and tumor size significantly affected the number of SLNs that needed to be removed to identify 99% of all positive SLNs. On multivariate analysis, mixed ductal and lobular
5. Morrow M, Rademaker A, Bethke K, et al. Learning sentinel node biopsy: results of a prospective randomized trial of two techniques. Surgery. 1999; 126:714-720. 6. McMasters K, Wong S, Chao C, et al. Defining the optimal surgeon experience for breast cancer sentinel lymph node biopsy: a model for implementation of new surgical techniques. Ann Surg. 2001;234: 292-300. 7. Newman L. Lymphatic mapping and sentinel lymph node biopsy in breast cancer patients: a comprehensive review of variations in performance and technique. J Am Coll Surg. 2004; 199:804-816.
histology, Caucasian race, inner quadrant tumor location, and T1 tumor classification significantly increased the number of SLNs that needed to be removed to achieve 99% recovery of all positive SLNs. Conclusions.—In general, the removal of a maximum of 5 SLNs at surgery allowed for the recovery of >99% of positive SLNs in patients with breast cancer. The current findings indicated that tumor histology, patient race, and tumor size and location may influence this number. SLN biopsy was a major advance in the surgical management of patients with breast cancer, allowing surgeons to avoid the morbidity of axillary node dissection in nodenegative patients. Recently, there has been increasing interest in limiting the number of SLNs removed. In this article, Yi and colleagues found that 99% of all positive SLNs can be found
Breast Diseases: A Year BookÒ Quarterly Vol 20 No 1 2009
75