Conventional means of SLN mapping using blue dye and radioactive have been attempted in NSCLC but have remained unreliable secondary to physical properties of both the tracer and the lung. The initial attempt at SLN biopsy in lung cancer was performed in 1999 by Little et al.9 Thirty-six patients underwent intraoperative injection of blue dye with a SLN identified in only 47% of patients. Low success rates were attributed to the learning curve associated with the injection technique in presence of anthracotic nodes. The authors acknowledged an unacceptably low rate of SLN identification, but advocated for the addition of radiolabeled tracers to improve sensitivity and specificity. Unfortunately, however, this combination proved unsuccessful.
Intraoperative radioactive tracers were first used for SLN mapping in lung cancer by Liptay et al. in 2000.10 Intraoperative injection of technetium 99 resulted in successful radioisotope migration in 81% of patients and SLN identification in almost 87%. Roughly a quarter of the SLNs identified were located in the mediastinum representing skip metastasis. Furthermore, SLN analysis on previously deemed negative nodes detected occult micrometastatic disease in 24% of these patients. The SLN was the only metastatic node in just over a third of patients. As a result of this initial Phase I study, a multicenter Phase II trial under the direction of Cancer and Leukemia Group B (CALGB) research cooperative focused on intraoperative injection of technetium 99 in patients with suspected stage I NSCLC. Unfortunately, accrual was less than 50% and of those enrolled, only 51% of patients had an SLN identified. Poor accrual and the low success rate was attributed to logistical issues of organizing nuclear medicine, surgery, and pathology for intraoperative injection and analysis, and cumbersome regulations for radioactivity handling in addition to a difficult learning curve of the injection technique.11 Less than optimal results obtained with either blue dye or radioisotopes led to different variations of the technique in an effort to increase the sensitivity and specificity of SLN identification in lung cancer. Owing to the fact that lymphatic vessels may be disrupted during intraoperative incision and dissection, Nomori et al. hypothesized that preoperative CT-guided injection and intraoperative injection via a transbronchial approach may improve results, but findings were similar to the initial studies by Liptay et al.12 with successful SLN identification reported in only 81% of patients. Shine-through effect, residual radioactivity, and possible decreased lymphatic density or impaired lymphatic flow in COPD patients were also thought to contribute to these less than optimal results. Even more worrisome, however, was the increased morbidity noted with this technique. The preoperative injection was associated with complications of bleeding, pneumothorax, and potential tumor seeding along the injection track. These studies demonstrate that SLN mapping with single-agent blue dye or radioisotope is not optimal, but that a combined approach may be warranted.
Two separate groups attempted combining both blue dye and radioisotopes to aid in the detection of SLN in patients with lung cancer. Schmidt et al. used intraoperative injection of both blue dye and Tm-99, achieving a SLN identification rate of 81%.13 Tiffet et al. was the second group to evaluate intraoperative injection of both markers, but again demonstrated suboptimal results, identifying the SLN in only 13 of 24 patients (54%).14 The technical difficulties associated with each of these approaches included visualization of blue dye within anthracotic nodes, intrathoracic use of the Geiger counter to identify radioisotopes, and anatomical differences in patients, all of which were thought to contribute to the low accuracy in SLN identification. In addition to these technical issues, potential risks of radioactivity to the surgeon, operating room personnel, patient, and pathologist raise legitimate concerns that hampered adoption of this technique.
The search for a better technique has led surgical groups to innovate by exploring nonradioactive agents that not only promise more reliable and accurate SLN identification but also the potential for therapeutic intraoperative targeting of nodal metastases (Table 168-1).
Table 168-1Early Results of Sentinel Node Mapping in Lung Cancer ||Download (.pdf) Table 168-1Early Results of Sentinel Node Mapping in Lung Cancer
|GROUP ||YEAR ||TECHNIQUE ||SUCCESS RATE (%) |
|Little et al.9 ||1999 ||Blue dye ||47 |
|Liptay et al.10 ||2000 ||Radioisotope ||81 |
|Liptay et al.11 ||2009 ||Multicenter radioisotope trial ||51 |
|Nomori et al.12 ||2007 ||Preoperative radioisotope ||81 |
|Schmidt et al.13 ||2002 ||Intraoperative blue dye/radioisotope ||81 |
|Tiffet et al.14 ||2005 ||Intraoperative blue dye/radioisotope ||54 |