Effective Low-dose Escalation of Indocyanine Green for Near-infrared Fluorescent Sentinel Lymph Node Mapping in Melanoma

Background

Regional lymph node metastasis is the strongest prognostic factor in patients with melanoma. Published reports that used lymphoscintigraphy with radioactive colloids and blue dye demonstrated accurate sentinel lymph node (SLN) identification in inguinal nodes and axillary nodes, but decreased accuracy in cervical, popliteal, epitrochlear, and parascapular nodes. Near-infrared imaging (NIR) may utilize indocyanine green (ICG) to improve SLN identification. The safety, feasibility and optimal dose of albumin-bound ICG (ICG:HSA) was assessed by NIR to improve SLN mapping in patients with melanoma.

Methods

Twenty-five consecutive patients with biopsy-proven melanoma underwent standard SLN mapping with preoperatively administered technetium-99 m nanocolloid (Tc-99 m). Intraoperative NIR fluorescence imaging was performed after injection of 1.0 ml of 100, 250 or 500 μM of ICG:HSA in four quadrants around the primary lesion.

Results

NIR fluorescent imaging demonstrated accuracy of 98 % when compared with radioactive colloid. A total of 65 lymph nodes were identified (65 with Tc-99 m, 64 with ICG:HSA). Overall, successful mapping that used either technique was 96 % as one patient failed to map with either modality. As the dose of ICG was increased, the signal-to-background ratio increased from a median of 3.1 to 8.4 to 10.9 over the range of 100, 250, and 500 μM, respectively.

Conclusions

SLN mapping with ICG:HSA is feasible and accurate in melanoma. ICG has the added advantage of a low cost and an intraoperative technique that does not alter the surgical field, thus allowing for easy identification of SLNs.     

A Comparison of Indocyanine Green Fluorescence Imaging Plus Blue Dye and Blue Dye Alone for Sentinel Node Navigation Surgery in Breast Cancer Patients

Purpose

To evaluate two methods of sentinel node navigation surgery (SNNS) using blue dye with and without indocyanine green (ICG) fluorescence imaging (FI) to determine the usefulness of combined ICG and blue dye.

Methods

Between 2005 and 2010, a total of 501 patients underwent SNNS in our hospital. Detection of sentinel lymph node (SLN) was performed with sulfan blue (SB) alone until 2008 and with a combination of SB and ICG-FI since 2009. ICG 5?mg and SB 15?mg were injected in the subareolar region, and FI was obtained by a fluorescence imaging device.

Results

We attempted to identify SLNs in 393 patients by SB alone and in 108 patients by a combination of SB and FI. The mean number of SLNs detected was 1.6 (0?C5) for SB alone and 2.2 (1?C6) for the combination method. The SLN identification rate was 95.7?% for SB alone and 100?% for the combination method so that the combination was significantly superior to SB in terms of the identification rate (p?=?0.0037). In patients who received the combination method, detection of SLN was made through only SB in 1 patient, only ICG in 8 patients, and both in 99 patients. Lymph node metastasis was found in 56 patients with SB alone and in 16 patients with the combination method. Recurrence of an axillary node was observed in 3 patients (0.8?%) with SB alone and in no patients with the combination method.

Conclusions

ICG-FI is a useful method and is especially recommended in cases where no radiotracers are available.     

Randomized Comparison of Near-infrared Fluorescence Imaging Using Indocyanine Green and 99m Technetium With or Without Patent Blue for the Sentinel Lymph Node Procedure in Breast Cancer Patients

Background

Near-infrared (NIR) fluorescence imaging using indocyanine green (ICG) has the potential to improve sentinel lymph node (SLN) mapping of breast cancer. We performed a randomized clinical trial to assess the value of blue dyes when used in combination with NIR fluorescence. We also preliminarily examined the possibility of performing SLN mapping without radiotracers.

Methods

Clinical trial subjects were 24 consecutive breast cancer patients scheduled to undergo SLN biopsy. All patients received standard of care using 99^m technetium-nanocolloid and received 1.6?mL of 500???M ICG injected periareolarly. Patients were randomly assigned to undergo SLN biopsy with or without patent blue. To assess the need for radiocolloids to localize the SLN or SLNs, the surgeon did not use the handheld gamma probe during the first 15 min after the axillary skin incision.

Results

SLN mapping was successful in 23 of the 24 patients. No significant difference was found in signal-to-background ratio between the groups with and without patent blue (8.3?±?3.8 vs. 10.3?±?5.7, respectively, P?=?0.32). In both groups, 100?% of SLNs were radioactive and fluorescent, and in the patent blue group, only 84?% of SLNs were stained blue. In 25?% of patients, the use of the gamma probe was necessary to localize the SLN within the first 15 min.

Conclusions

This study shows that there is no benefit of using patent blue for SLN mapping in breast cancer patients when using NIR fluorescence and 99^m technetium-nanocolloid. NIR fluorescence imaging outperformed patent blue in all patients.     

Outcome of sentinel lymph node biopsy in breast cancer using dye alone: a single center review with a median follow-up of 5 years

Purpose

Various techniques are used for sentinel lymph node biopsy (SLNB) in breast cancer. While subareolar injection with dye alone is a relatively easy method, few studies have reported the outcome with a follow-up period. This study presents our results of SLNB using dye alone.

Methods

Between November 2002 and December 2010, 701 patients with breast cancer underwent SLNB using subareolar injection of indocyanine green or indigo carmine. Sentinel lymph node (SLN)-negative patients were followed without axillary lymph node dissection (ALND).

Results

SLNs were detected in 654 of 701 patients (93.3 %), and the rate increased to 98.1 % over the course of the study. The mean number of SLNs removed was 1.5. There was no significant difference in the detection rate between two dyes. No adverse events resulted from the injection of dyes. Of the 654 patients, 136 (20.8 %) had SLN metastasis. Five hundred patients were followed without ALND. Thirty-six patients experienced disease relapse during a median follow-up of 60 months. Thirteen patients (2.6 %) had regional lymph node relapse, and eight of them could undergo salvage lymph node dissection. The 5-year disease-free and overall survival rates were 92.4 and 96.1 %, respectively.

Conclusion

SLNB using subareolar injection with dye alone was safe and feasible even after a long follow-up.     

Indocyanine green fluorescence method for sentinel lymph node biopsy in breast cancer

Background/ObjectiveBreast biopsy and analysis of sentinel lymph nodes (SLNs) accurately predict tumor status in the affected basin and help in avoiding unnecessary axillary lymph node dissection, which is associated with remarkable morbidity risk. Blue dye and radioisotope are the most widely used mapping agents, but non-radioactive tracers of comparable accuracy warrant further investigation. This study aimed to investigate utilization of indocyanine green (ICG) fluorescence in sentinel node localization compared with blue dye and to assess the incremental value of ICG.MethodsA total of 39 consecutive patients underwent sentinel lymph node biopsy (SLNB) (40 cases: 38 unilateral and 1 bilateral) with combined blue dye and ICG for localization. The obtained fluorescence images of the lymphatic system were investigated.ResultsAll 84 lymph nodes removed in 40 procedures were identified by ICG, but only 37 were identified by blue dye. The ICG method identified an average of 2.1 SLNs in 39 of 40 cases with a detection rate of 97.5%, but only 0.93 SLN per case with blue dye. Subcutaneous lymphatic channel patterns were also detected by fluorescent imaging in 37 procedures, which all revealed lymphatic drainage toward the axilla except in one case with internal mammary pathway.ConclusionThis study demonstrated the accuracy and safety of ICG for SLNB and its superiority to blue dye method in SLN localization. Therefore, ICG fluorescence method is safe and effective addition in breast clinical settings, wherein blue dye alone is used.     

Axillary Reverse Mapping: A Prospective Study in Women with Clinically Node Negative and Node Positive Breast Cancer

Background

The primary aim of axillary reverse mapping (ARM) is to prevent lymphedema by preserving arm versus breast axillary lymphatics. Concerns regarding feasibility and oncologic safety have limited the adoption of the technique. This prospective study was undertaken to investigate ARM in clinically node negative and node positive breast cancer patients.

Methods

A total of 184 patients underwent 212 ARM procedures: 155 sentinel lymph node biopsies (SLNB) without axillary lymph node dissection (ALND) (group 1) and 57 ALNDs with/without SLNB (group 2). ARM lymphatics were not preserved if they were a SLN, directly entered a SLN, or were within ALND boundaries during ALND.

Results

SLN with radioisotope alone was successful in 92 % of procedures (181 of 197). ARM identification was 47 % (73 of 155) in group 1. Criteria were met in 30 % (47 of 155) for preservation, and 25 % (38 of 155) were preserved. Of those who met preservation criteria, 81 % (38 of 47) were preserved. In group 2, ARM identification was 72 % (41 of 57); 7 met criteria for preservation and were preserved. Of the ARM nodes, 10 % (22 of 212) were SLNs (crossover). ARM nodes contained metastatic disease in one crossover and two nonsentinel ARM nodes in clinically node positive patients with N2/N3 disease.

Conclusions

ARM is a feasible technique for identification and preservation of axillary arm lymphatics with an acceptable incidence of SLN crossover. A larger sample size is needed to determine if ARM can reduce the incidence of lymphedema in patients undergoing SLNB alone and to confirm the absence of ARM metastases in clinically node negative patients undergoing ALND.     

Toward Optimization of Imaging System and Lymphatic Tracer for Near-Infrared Fluorescent Sentinel Lymph Node Mapping in Breast Cancer

Background

Near-infrared (NIR) fluorescent sentinel lymph node (SLN) mapping in breast cancer requires optimized imaging systems and lymphatic tracers.

Materials and Methods

A small, portable version of the FLARE imaging system, termed Mini-FLARE, was developed for capturing color video and two semi-independent channels of NIR fluorescence (700 and 800 nm) in real time. Initial optimization of lymphatic tracer dose was performed using 35-kg Yorkshire pigs and a 6-patient pilot clinical trial. More refined optimization was performed in 24 consecutive breast cancer patients. All patients received the standard of care using ^99mTechnetium-nanocolloid and patent blue. In addition, 1.6 ml of indocyanine green adsorbed to human serum albumin (ICG:HSA) was injected directly after patent blue at the same location. Patients were allocated to 1 of 8 escalating ICG:HSA concentration groups from 50 to 1000 μM.

Results

The Mini-FLARE system was positioned easily in the operating room and could be used up to 13 in. from the patient. Mini-FLARE enabled visualization of lymphatic channels and SLNs in all patients. A total of 35 SLNs (mean = 1.45, range 1–3) were detected: 35 radioactive (100%), 30 blue (86%), and 35 NIR fluorescent (100%). Contrast agent quenching at the injection site and dilution within lymphatic channels were major contributors to signal strength of the SLN. Optimal injection dose of ICG:HSA ranged between 400 and 800 μM. No adverse reactions were observed.

Conclusions

We describe the clinical translation of a new NIR fluorescence imaging system and define the optimal ICG:HSA dose range for SLN mapping in breast cancer.     

Combined Analysis of Phase III Trials Evaluating [99mTc]Tilmanocept and Vital Blue Dye for Identification of Sentinel Lymph Nodes in Clinically Node-Negative Cutaneous Melanoma

Background

[^99mTc]Tilmanocept is a CD206 receptor-targeted radiopharmaceutical designed for sentinel lymph node (SLN) identification. Two nearly identical nonrandomized phase III trials compared [^99mTc]tilmanocept to vital blue dye.

Methods

Patients received [^99mTc]tilmanocept and blue dye. SLNs identified intraoperatively as radioactive and/or blue were excised and histologically examined. The primary end point, concordance, was the proportion of blue nodes detected by [^99mTc]tilmanocept; 90 % concordance was the prespecified minimum concordance level. Reverse concordance, the proportion of radioactive nodes detected by blue dye, was also calculated. The prospective statistical plan combined the data from both trials.

Results

Fifteen centers contributed 154 melanoma patients who were injected with both agents and were intraoperatively evaluated. Intraoperatively, 232 of 235 blue nodes were detected by [^99mTc]tilmanocept, for 98.7 % concordance (p < 0.001). [^99mTc]Tilmanocept detected 364 nodes, for 63.7 % reverse concordance (232 of 364 nodes). [^99mTc]Tilmanocept detected at least one node in more patients (n = 150) than blue dye (n = 138, p = 0.002). In 135 of 138 patients with at least one blue node, all blue nodes were radioactive. Melanoma was identified in the SLNs of 22.1 % of patients; all 45 melanoma-positive SLNs were detected by [^99mTc]tilmanocept, whereas blue dye detected only 36 (80 %) of 45 (p = 0.004). No positive SLNs were detected exclusively by blue dye. Four of 34 node-positive patients were identified only by [^99mTc]tilmanocept, so 4 (2.6 %) of 154 patients were correctly staged only by [^99mTc]tilmanocept. No serious adverse events were attributed to [^99mTc]tilmanocept.

Conclusions

[^99mTc]Tilmanocept met the prespecified concordance primary end point, identifying 98.7 % of blue nodes. It identified more SLNs in more patients, and identified more melanoma-containing nodes than blue dye.     

Axillary Ultrasonography in Breast Cancer Patients Helps in Identifying Patients Preoperatively with Limited Disease of the Axilla

Background

The sentinel lymph node biopsy (SLNB) procedure is the method of choice for the identification and monitoring of regional lymph node metastases in patients with breast cancer. In the case of a positive sentinel lymph node (SLN), additional lymph node dissection is still warranted for regional control, although 40–65 % have no additional axillary disease. Recent studies show that after breast-conserving surgery, SLNB, and adjuvant systemic therapy, there is no significant difference between recurrence-free period and overall survival if there are ≤2 positive axillary nodes. The purpose of this study was preoperative identification of patients with limited axillary disease (≤2 macrometastases) by using ultrasonography.

Methods

Data from 1,103 consecutive primary breast cancer patients with tumors smaller than 50 mm, no palpable adenopathy, and a maximum of 2 SLNs with macrometastases were collected. The variable of interest was US of the axilla.

Results

Of the 1,103 patients included, 1,060 remained after exclusion criteria. Of these, 102 (9.6 %) had more than 2 positive axillary nodes on ALND. Selected by unsuspected US, the chance of having >2 positive lymph nodes (LNs) is substantially lower (4.2 %). This is significant on univariate and multivariate analysis. After excluding the patients with extracapsular extension of the SLN, the chance of having >2 positive LNs is only 2.6 %. For pT1–2, this is 2.2 %.

Conclusions

The risk of more than 2 positive axillary nodes is relatively small in patients with cT1–2 breast cancer. US of the axilla helps in further identifying patients with a minimal risk of additional axillary disease, putting ALND up for discussion.     

Impact of the American College of Surgeons Oncology Group (ACOSOG) Z0011 trial on Clinical Management of the Axilla in Older Breast Cancer Patients: A SEER-Medicare Analysis

Background

American College of Surgeons Oncology Group (ACOSOG) Z0011 demonstrated that eligible breast cancer patients with positive sentinel lymph nodes (SLN) could be spared an axillary lymph node dissection (ALND) without sacrificing survival or local control. Although heralded as a “practice-changing trial,” some argue that the stringent inclusion criteria limit the trial’s clinical significance. The objective was to assess the potential impact of ACOSOG Z0011 on axillary surgical management of Medicare patients and examine current practice patterns.

Methods

Medicare beneficiaries aged ≥66 years with nonmetastatic invasive breast cancer diagnosed from 2001 to 2007 were identified from the Surveillance, Epidemiology and End Results-Medicare database (n = 59,431). Eligibility for ACOSOG Z0011 was determined: SLN mapping, tumor <5 cm, no neoadjuvant treatment, breast conservation; number of positive nodes was determined. Actual surgical axillary management for eligible patients was assessed.

Results

Twelve percent (6,942/59,431) underwent SLN mapping and were node positive. Overall, 2,637 patients (4.4 % (2,637/59,431) of the total cohort, but 38 % (2,637/6,942) of patients with SLN mapping and positive nodes) met inclusion criteria for ACOSOG Z0011, had 1 or 2 positive lymph nodes, and could have been spared an ALND. Of these 2,637 patients, 46 % received a completion ALND and 54 % received only SLN biopsy.

Conclusions

Widespread implementation of ACOSOG Z0011 trial results could potentially spare 38 % of older breast cancer patients who undergo SLN mapping with positive lymph nodes an ALND. However, 54 % of these patients are already managed with SLN biopsy alone, lessening the impact of this trial on clinical practice in older breast cancer patients.     

Sentinel Lymph Node Biopsy Using Intraoperative Indocyanine Green Fluorescence Imaging Navigated with Preoperative CT Lymphography for Superficial Esophageal Cancer

Background

The sentinel lymph node (SLN) concept has been gaining attention for gastrointestinal neoplasms but remains controversial for esophageal cancer. This study evaluated the feasibility of SLN identification using intraoperative indocyanine green (ICG) fluorescence imaging (IGFI) navigated by preoperative computed tomographic lymphography (CTLG) to treat superficial esophageal cancer.

Methods

Subjects comprised 20 patients clinically diagnosed with superficial esophageal cancer. Five minutes after endoscopic submucosal injection of iopamidol around the primary lesion using a four-quadrant injection pattern with a 23-gauge endoscopic injection sclerotherapy needle, three-dimensional multidetector computed tomography was performed to identify SLNs and lymphatic routes. ICG solution was injected intraoperatively around the tumor. Fluorescence imaging was obtained by infrared ray electronic endoscopy. Thoracoscope-assisted standard radical esophagectomy with lymphadenectomy was performed to confirm fluorescent lymph nodes detected by CTLG.

Results

Lymphatic vessels and SLNs were identified preoperatively using CTLG in all cases. Intraoperative detection rates were 100% using CTLG and 95% using IGFI. Lymph node metastases were found in four cases, including one false-negative case with SLNs occupied by bulky metastatic tumor that were not enhanced with both methods. The other 19 cases, including three cases of metastatic lymph nodes, were accurately identified by both procedures.

Conclusions

Preoperative CTLG visualized the correct number and site of SLNs in surrounding anatomy during routine computed tomography to evaluate distant metastases. Referring to CTLG, SLNs were identified using IGFI, resulting in successful SLN navigation and saving time and cost. This method appears clinically applicable as a less-invasive method for treating superficial esophageal cancer.     

Thoracoscopic Color and Fluorescence Imaging System for Sentinel Lymph Node Mapping in Porcine Lung Using Indocyanine Green-Neomannosyl Human Serum Albumin: Intraoperative Image-Guided Sentinel Nodes Navigation

Purpose

This study was performed to validate a newly developed sentinel lymph node (SLN) targeting tracer, indocyanine green-neomannosyl human serum albumin (ICG:MSA), and a thoracoscopic version of the intraoperative color and fluorescence imaging system (ICFIS) for lung cancer SLN mapping.

Methods

ICG alone or ICG:MSA (5 μg/kg) was injected into the rat thigh, and the results were compared. The fluorescence signal-to-background ratios of SLNs were recorded and evaluated over a 2-h period by using ICFIS. Additionally, a SLN biopsy was performed via video-assisted thoracoscopic surgery with the use of ICG:MSA in porcine lung by using thoracoscopic ICFIS.

Results

The newly developed ICG:MSA showed a significantly improved signal-to-background ratio compared with ICG alone throughout the trials. All SLNs were identified in both rats (ten SLNs in ten rat thighs) and pigs (ten SLNs in ten porcine lungs) under in vivo conditions. All SLNs were dissected successfully by using video-assisted thoracoscopic surgery with the help of thoracoscopic ICFIS.

Discussion

ICG:MSA accumulates in the SLN by uptake and retention through the mannose-specific receptors on macrophages. Thoracoscopic ICFIS successfully assisted SLN mapping despite low near-infrared light transmission in the commercial thoracoscope. On the basis of the results of the thoracoscopic SLN mapping, we anticipate that ICG:MSA and thoracoscopic ICFIS can be translated to clinical trials in the near future.     

Comparative Evaluation of [99mTc]Tilmanocept for Sentinel Lymph Node Mapping in Breast Cancer Patients: Results of Two Phase 3 Trials

Background

Sentinel lymph node (SLN) surgery is used worldwide for staging breast cancer patients and helps limit axillary lymph node dissection. [^99mTc]Tilmanocept is a novel receptor-targeted radiopharmaceutical evaluated in 2 open-label, nonrandomized, within-patient, phase 3 trials designed to assess the lymphatic mapping performance.

Methods

A total of 13 centers contributed 148 patients with breast cancer. Each patient received [^99mTc]tilmanocept and vital blue dye (VBD). Lymph nodes identified intraoperatively as radioactive and/or blue stained were excised and histologically examined. The primary endpoint, concordance (lower boundary set point at 90 %), was the proportion of nodes detected by VBD and [^99mTc]tilmanocept.

Results

A total of 13 centers contributed 148 patients who were injected with both agents. Intraoperatively, 207 of 209 nodes detected by VBD were also detected by [^99mTc]tilmanocept for a concordance rate of 99.04 % (p < 0.0001). [^99mTc]tilmanocept detected a total of 320 nodes, of which 207 (64.7 %) were detected by VBD. [^99mTc]Tilmanocept detected at least 1 SLN in more patients (146) than did VBD (131, p < 0.0001). In 129 of 131 patients with ≥1 blue node, all blue nodes were radioactive. Of 33 pathology-positive nodes (18.2 % patient pathology rate), [^99mTc]tilmanocept detected 31 of 33, whereas VBD detected only 25 of 33 (p = 0.0312). No pathology-positive SLNs were detected exclusively by VBD. No serious adverse events were attributed to [^99mTc]tilmanocept.

Conclusion

[^99mTc]Tilmanocept demonstrated success in detecting a SLN while meeting the primary endpoint. Interestingly, [^99mTc]tilmanocept was additionally noted to identify more SLNs in more patients. This localization represented a higher number of metastatic breast cancer lymph nodes than that of VBD.     

Reoperative sentinel lymph node biopsy: a new option for patients with primary or locally recurrent breast carcinoma

BACKGROUND: Sentinel lymph node (SLN) biopsy is a new standard of care for axillary node staging in patients with primary operable breast cancer. An increasing proportion of these patients undergo breast-conserving surgery, and 10% to 15% will develop local relapse requiring reoperation. Although previous breast or axillary surgery is often considered a contraindication to SLN biopsy, few data support this position. We report our experience with SLN biopsy in the reoperative setting. STUDY DESIGN: We examined the 3,490 consecutive SLN biopsy procedures for breast cancer performed at our institution between September 1996 and July 2001; 32 (1%) of these followed previous axillary surgery: 22 (69%) for breast recurrence after SLN biopsy or axillary lymph node dissection (ALND); 7 (22%) after a recent, failed SLN biopsy or inadequate ALND; and 3 (9%) after earlier axillary surgery for an unrelated condition. RESULTS: SLNs were identified in 24 of 32 (75%) cases and were positive in 3 of 24 (13%). Reoperative SLN biopsy was more successful when less than 10 versus 10 or more nodes had been removed previously (87% versus 44%). Both blue dye and isotope identified the SLN in 16 of 24 successful procedures (67%). Additional, nonsentinel nodes (mean, eight nodes) were removed in 17 of 24 patients (71%) and were negative in all cases. At a median followup of 13 months, no axillary recurrences have occurred. CONCLUSIONS: Reoperative SLN biopsy after earlier SLN biopsy or ALND is feasible in selected breast cancer patients and is more likely to succeed when fewer than 10 nodes were removed during the earlier procedure. Further study is required to better define the subset of patients in whom reoperative SLN biopsy can replace ALND.     

The Extent of Extracapsular Extension May Influence the Need for Axillary Lymph Node Dissection in Patients with T1–T2 Breast Cancer

Background

Whether extracapsular extension (ECE) of tumor in the sentinel lymph node (SLN) is an indication for axillary lymph node dissection (ALND) in patients managed by American College of Surgeons Oncology Group Z0011 criteria is controversial. Here we examine the correlation between ECE in the SLN and disease burden in the axilla.

Methods

Patients meeting Z0011 clinicopathologic criteria (pT1–2, cN0 with <3 positive SLNs) were selected from a prospectively maintained database (2006–2013). Chart review documented the presence and extent of ECE. Neoadjuvant chemotherapy patients were excluded. Comparisons were made by presence and extent (≤2 vs. >2 mm) of ECE.

Results

Of 11,730 patients, 778 were pT1–2, cN0 with <3 positive SLNs without ECE, and 331 (2.8 %) had ECE. Of these, 180 had ≤2 mm and 151 had >2 mm of ECE. Patients with ECE were older (57 vs. 54 years; p = 0.001) and had larger (2.0 vs. 1.7 cm; p < 0.0001), multifocal (p = 0.006), hormone receptor–positive tumors (p = 0.0164) with lymphovascular invasion (p < 0.0001). Presence and extent of ECE were associated with greater axillary disease burden; 20 and 3 % of patients with and without ECE, respectively, had ≥4 additional positive nodes at completion ALND (p < 0.0001), and 33 % of patients with >2 mm ECE had ≥4 additional positive nodes at completion ALND, compared with 9 % in the <2 mm group (p < 0.0001). On multivariate analysis, >2 mm of ECE was the strongest predictor of ≥4 positive nodes at completion ALND (odds ratio 14.2).

Conclusions

Presence and extent of ECE were significantly correlated with nodal tumor burden at completion ALND, thus suggesting that >2 mm of ECE may be an indication for ALND or radiotherapy when applying Z0011 criteria to patients with metastases in <3 SLNs. ECE reporting should be standardized to facilitate future studies.     

Selective Sentinel Lymph Node Dissection for Melanoma: Importance of Harvesting Nodes with Lower Radioactive Counts without the Need for Blue Dye

Background

Determining how many sentinel lymph nodes (SLNs) should be removed for melanoma is important. The purpose of this study is to determine the frequency at which nodes that are less radioactive than the “hottest” node (which is negative) are positive for melanoma, how low of a radioactivity should warrant harvest, and if isosulfan blue is necessary.

Methods

We reviewed 1,152 melanoma patients who underwent lymphoscintigraphy with technetium, with or without blue dye, and SLN dissection from 1996 to 2008. SLNs with radioactivity ≥10% of the “hottest” SLN, all blue nodes, and all suspicious nodes were removed and analyzed. The miss rate was calculated as the proportion of node positive cases in which the “hottest” SLN was negative.

Results

SLNs were identified in 1,520 nodal basins in 1,152 patients. SLN micrometastases were detected in 218 basins (14%) in 204 patients (18%). In 16% of SLN-positive patients (33/204 patients), the positive SLN was found to have a lower radioactive count than the “hottest” SLN, which was negative. In 21 of these cases, the positive SLNs had radioactivity ≤50% of the “hottest” SLN. The 10% rule significantly reduced the miss rate to 2.5% compared with removal of only the “hottest” SLN (miss rate = 16%). Also, blue dye did not significantly decrease the miss rate compared with radiocolloid alone using the 10% rule.

Conclusions

To decrease the miss rate, all SLNs with ≥10% of the ex vivo radioactivity of the “hottest” SLN should be removed and blue dye is not essential.     

Predictors of Completion Axillary Lymph Node Dissection in Patients With Immunohistochemical Metastases to the Sentinel Lymph Node in Breast Cancer

Background

Axillary lymph node dissection (ALND) in patients with immunohistochemistry (IHC)-determined metastases to the sentinel lymph node (SLN) is controversial. The goal of this study was to examine factors associated with ALND in IHC-only patients.

Methods

Retrospective review of an institutional SLN database from July 1997 to July 2003 was performed. We compared sociodemographic, pathologic, and therapeutic variables between IHC-only patients who had SLN biopsy alone and those that had ALND.

Results

Our study group consisted of 171 patients with IHC-only metastases to the SLN. Young age, estrogen receptor negative status, high Memorial Sloan-Kettering Cancer Center nomogram score, and chemotherapy were associated with ALND. Among patients who had ALND (n = 95), 18% had a positive non-SLN. Rates of systemic therapy were similar between those with and without positive non-SLNs at ALND. No axillary recurrences were observed in this series with a median follow-up of 6.4 years. The percentage of patients who were recurrence-free after 5 years was 97% (95% confidence interval, 92.1–98.6).

Conclusions

On the basis of our findings and the lack of prospective randomized data, the practice of selectively limiting ALND to IHC-only patients thought to be at high risk and to patients for whom the identification of additional positive nodes may change systemic therapy recommendations seems to be a safe and reasonable approach.     

Multidisciplinary Management of the Axilla in Patients with cT1-T2 N0 Breast Cancer Undergoing Primary Mastectomy: Results from a Prospective Single-Institution Series

Background

The after mapping of the axilla: radiotherapy or surgery (AMAROS) trial concluded that for patients with cT1-2 N0 breast cancer and one or two positive sentinel lymph nodes (SLNs), axillary radiotherapy (AxRT) provides equivalent locoregional control and a lower incidence of lymphedema compared with axillary lymph node dissection (ALND). The study prospectively assessed how often ALND could be replaced by AxRT in a consecutive cohort of patients undergoing mastectomy for cT1-2 N0 breast cancer.

Methods

In November 2015, our multidisciplinary group agreed to omit routine intraoperative SLN evaluation for cT1-2 N0 patients undergoing upfront mastectomy and potentially eligible for postmastectomy radiation therapy (PMRT), including those 60 years of age or younger and those older than 60 years with high-risk features. Patients with one or two positive SLNs on final pathology were reviewed to determine whether PMRT including the full axilla was an appropriate alternative to ALND.

Results

From November 2015 to December 2016, 154 patients met the study criteria, and 114 (74%) formed the final study cohort. Intraoperative SLN evaluation was omitted for 76 patients (67%). Of these patients, 20 (26%) had one or two positive SLNs, and 14 of these patients received PMRT?+?AxRT as an alternative to ALND. Three patients returned for ALND, and three patients were observed. On univariate analysis, tumor size, LVI, number of positive lymph nodes, and receipt of chemotherapy were associated with receipt of PMRT.

Conclusions

For the majority of patients with one or two positive SLNs, ALND was avoided in favor of PMRT?+?AxRT. With appropriate multidisciplinary strategies, intraoperative evaluation of the SLN and immediate ALND can be avoided for patients meeting the AMAROS criteria and eligible for PMRT.

     

Reoperative Sentinel Lymph Node Biopsy: A New Frontier in the Management of Ipsilateral Breast Tumor Recurrence

Background

Breast conservation therapy (BCT) with sentinel lymph node (SLN) biopsy is a well-established standard of care for primary operable breast cancer; 5–10% of BCT patients will develop local recurrence (LR). The question then arises: How best to manage the axilla in the setting of LR after previous BCT and SLN biopsy or axillary dissection (ALND)?

Methods

Between 9/96 and 12/04, 117 reoperative SLN were performed for LR after BCT and either SLN biopsy or ALND more than 6 months previously. Because of wide variation in the number of nodes removed at the initial procedure, validation by backup ALND was not feasible in all cases.

Results

Reoperative SLN was successful in 64/117 (55%) patients. SLNs were identified by isotope and dye in 28/64 (44%); isotope only in 29/64 (45%); dye only in 4/64 (6%); 3/64 (5%) unknown. Positive reoperative SLN were found in 10/64 (16%) successful cases. Among 54/64 (84%) patients with negative reoperative SLNs, 23 (43%) had additional non-SLN removed concurrently: these were negative in 21/23 cases (91%). In 2/23 (9%), reoperative SLN were falsely negative: one with a positive intramammary node, and the other with a positive non-SLN palpated at surgery. Success of reoperative SLN was inversely related to number of nodes removed previously, and was more likely to be successful after a previous SLN biopsy than a previous ALND (74% vs. 38%, P = 0.0002). Non-axillary drainage was identified by lymphoscintigraphy significantly more often in reoperative SLN than in primary SLN biopsy (30% vs. 6%, P < 0.0001). There were no local or axillary recurrences at a mean follow up of 2.2 years; 6 patients developed systemic recurrence.

Conclusions

Reoperative SLN biopsy is feasible in the setting of LR after previous BCT/axillary surgery and deserves further study in this increasingly common clinical scenario. The added benefit of lymphoscintigraphy in identifying sites of non-axillary drainage may be greater in the setting of reoperative SLN than for the initial SLN procedure.

     

Prospective Study Evaluating Oncological Safety of Axillary Reverse Mapping

Background

Axillary reverse mapping (ARM) is a new technique developed with the aim of reducing lymphedema rates by preserving lymphatic drainage of the upper limbs during sentinel lymph node biopsy and axillary lymph node dissection (ALND). However, it is unclear whether preservation of these lymph nodes affects oncological risk. The present study evaluated the presence of metastases in ARM nodes.

Methods

A total of 45 patients underwent ARM during ALND. Blue dye was used for ARM nodes localization. All axillary lymph nodes, including ARM nodes, were removed and sent separately for pathological evaluation of metastases.

Results

ARM identification was achieved in 40/45 patients (88.9 %). The average number of removed ARM nodes was 1.9. ARM nodes metastasis occurred in 10 of 40 patients (25 %). Patients with an axilla extensively affected by cancer had an elevated risk of metastasis to the arm’s lymph nodes (p < 0.001).

Conclusions

The rate of arm lymph nodes compromised by metastases calls into question the viability of the ARM technique. Larger studies may point to particular patient profiles for which ARM can be safely use.