Factors Associated with False-Negative Sentinel Lymph Node Biopsy in Melanoma Patients
ABSTRACT Some melanoma patients who undergo sentinel lymph node (SLN) biopsy will have false-negative (FN) results. We sought to determine the factors and outcomes associated with FN SLN biopsy.
Analysis was performed of a prospective multi-institutional study that included patients with melanoma of thickness > 1.0 mm who underwent SLN biopsy. FN results were defined as the proportion of node-positive patients who had a tumor-negative sentinel node biopsy. Kaplan-Meier survival analysis and univariate and multivariate analyses were performed.
This analysis included 2,451 patients with median follow-up of 61 months. FN, true-positive (TP), and true-negative (TN) SLN results were found in 59 (10.8%), 486 (19.8%), and 1,906 (77.8%) patients, respectively. On univariate analysis comparing the FN with TP groups, respectively, the following factors were significantly different: age (52.6 vs. 47.6 years, p = 0.004), thickness (mean 2.1 vs. 3.1 mm, p = 0.003), lymphovascular invasion (LVI; 3.7 vs. 13.7%, p = 0.037), and local/in-transit recurrence (LITR; 32.2 vs. 12.4%, p < 0.0001); these factors remained significant on multivariate analysis. Overall 5-year survival was greater in the TN group (86.7%) compared with the TP (62.3%) and FN (51.3%) groups (p < 0.0001); however, there was no significant difference in overall survival comparing the TP and FN groups (p = 0.32).
This is the largest study to evaluate FN SLN results in melanoma, with a FN rate of 10.8%. FN results are associated with greater patient age, lower mean thickness, less frequent LVI, and greater risk of LITR. However, survival of patients with FN SLN is not statistically worse than that of patients with TP SLN.
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ABSTRACT: Metastases rather than primary tumors are responsible for killing most cancer patients. Cancer cells often invade regional lymph nodes (LN) before colonizing other parts of the body. However, due to the low sensitivity and specificity of current imaging methods to detect localized nodal spread, an invasive surgical procedure - sentinel lymph node biopsy - is generally employed to identify metastatic cancer cells. Here we introduce a new approach for more sensitive in vivo detection of lymph node micrometastases, based on the use of ultrasound-guided spectroscopic photoacoustic (sPA) imaging of molecularly-activated plasmonic nanosensors (MAPS). Using a metastatic murine model of oral squamous cell carcinoma, we showed that MAPS targeted to the EGFR shifted their optical absorption spectrum to the red-near-infrared region after specific interactions with nodal metastatic cells, enabling their non-invasive detection by sPA. Notably, LN metastases as small as 50 µm were detected at centimeter-depth range with high sensitivity and specificity. Large sPA signals appeared in metastatic LN within 30 minutes of MAPS injection, in support of the clinical utility of this method. Our findings offer a rapid and effective tool to non-invasively identify micrometastases as an alternate to sentinal node biopsy analysis.Cancer Research 08/2014; 74(19). DOI:10.1158/0008-5472.CAN-14-0796 · 9.28 Impact Factor
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ABSTRACT: Background Tumors drive blood vessel growth to obtain oxygen and nutrients to support tumor expansion, and they also can induce lymphatic vessel growth to facilitate fluid drainage and metastasis. These processes have generally been studied separately, so that it is not known how peritumoral blood and lymphatic vessels grow relative to each other. Methods The murine B16-F10 melanoma and chemically-induced squamous cell carcinoma models were employed to analyze large red-colored vessels growing between flank tumors and draining lymph nodes. Immunostaining and microscopy in combination with dye injection studies were used to characterize these vessels. Results Each peritumoral red-colored vessel was found to consist of a triad of collecting lymphatic vessel, vein, and artery, that were all enlarged. Peritumoral veins and arteries were both functional, as detected by intravenous dye injection. The enlarged lymphatic vessels were functional in most mice by subcutaneous dye injection assay, however tumor growth sometimes blocked lymph drainage to regional lymph nodes. Large red-colored vessels also grew between benign papillomas or invasive squamous cell carcinomas and regional lymph nodes in chemical carcinogen-treated mice. Immunostaining of the red-colored vessels again identified the clustered growth of enlarged collecting lymphatics, veins, and arteries in the vicinity of these spontaneously arising tumors. Conclusions Implanted and spontaneously arising tumors induce coordinate growth of blood and lymphatic vessel triads. Many of these vessel triads are enlarged over several cm distance between the tumor and regional lymph nodes. Lymphatic drainage was sometimes blocked in mice before lymph node metastasis was detected, suggesting that an unknown mechanism alters lymph drainage patterns before tumors reach draining lymph nodes.BMC Cancer 05/2014; 14(1):354. DOI:10.1186/1471-2407-14-354 · 3.32 Impact Factor
Nuclear Medicine Communications 10/2014; 35(10):989-94. DOI:10.1097/MNM.0000000000000171 · 1.37 Impact Factor