The indocyanine green method is equivalent to the 99mTc-labeled radiotracer method for identifying the sentinel node in breast cancer: A concordance and validation study
Introduction
Sentinel node biopsy (SNB) is the standard procedure for axillary staging in breast cancer. Randomized controlled trials have shown that five-year overall survival in patients with a negative SN who do not undergo axillary dissection is indistinguishable for that in comparable patients who do undergo axillary dissection, making it possible to avoid axillary dissection in a considerable fraction of patients, for whom the adverse sequelae of axillary dissection are avoided and quality of life is improved.1, 2, 3
Colloid labeled with technetium 99m (99mTc) is widely used to identify and localize the sentinel node (SN), either alone or in combination with blue dye.4 A method employing 99mTc bound to human albumin was developed at the European Institute of Oncology, Milan, where it has been in use for over 15 years, with over 22,000 SNBs performed.5 This method detects the sentinel node in a high (95–99%) proportion of cases.6 However radioisotopes are not available to all treatment centers, and their use requires licensing and a nuclear medicine department; furthermore the time window between radiotracer injection and surgery is limited.
A growing body of evidence supports the feasibility and efficacy of using the fluorescent dye indocyanine green (ICG) to identify the SN.7, 8, 9, 10 The method involves injection of ICG subdermally close to the tumor or in the peri-areolar region, and following its progress through the lymphatic ducts to the sentinel node (SN) using an excitation illumination system in combination with a high sensitivity camera, which detects the emitted fluorescence. The method is additionally characterized by very low complication and adverse event rates,11 however it has not been formally and prospectively compared with the gold-standard radiotracer method in terms of SN detection rate.
The aim of the present study was assess the concordance between the ICG method and the 99mTc-labeled radiotracer method, to determine whether ICG can be effectively used alone to identify the SN.
Section snippets
Materials and methods
Between June 2011 and January 2013, 134 patients with early breast cancer, confirmed by core or fine needle biopsy, and a clinically negative axilla, were enrolled in the present single-center study, approved by the Ethical Committee of the European Institute of Oncology, Milan, and registered as Eudract No. 2010-021815-18. Patients gave written informed consent to treatment with ICG for to SNB prior to enrollment. Those with cancer >3 cm, clinically positive lymph nodes, previous surgery for
Results
Patient and tumor characteristics are shown in Table 1. One hundred thirty-four patients provided a total of 246 SNs detected by one or both methods. 1, 2 and 3 SNs, respectively, were detected, excised and examined in 70 (52.2%), 39 (29.1%) and 17 (12.7%) patients; 4–10 SNs were detected and examined in the remaining 8 patients. Tc detected 231 of the 246 (93.9%) SNs found; ICG detected 245 (99.6%) of total SNs found (Table 2). The two methods were concordant for 230 of the 246 SNs (93.5%)
Discussion
This was a prospective study to compare the promising ICG method with the gold standard radiotracer method for finding and removing axillary SNs in early breast cancer. The comparison was designed to assess whether the ICG method can be used as a reliable alternative to the radiotracer method. We found that the ICG method detected 99.6% of all SNs found, while the Tc method detected 93.9% of all SNs. Furthermore only 1 SN (0.4% of total) was found by the Tc method and not the ICG method.
Conclusions
The ICG method has previously been shown to be surgically simple procedure that identifies axillary SNs in breast cancer patients, without the use or radiopharmaceutical. The present study has validated the ICG method by demonstrating that it is statistically non-inferior to the gold-standard method that used Tc-labeled albumin, allowing us to conclude that the ICG method can be used as a reliable and safe alternative to the radiotracer method. This finding is potentially of major importance in
Conflict of interest statement
We certify that there is no conflict of interest with any financial organization regarding the material discussed in the manuscript.
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