Clinical Considerations on Sentinel Node Biopsy in Melanoma from an Italian Multicentric Study on 1,313 Patients (SOLISM–IMI)

Annals of Surgical Oncology (Impact Factor: 3.93). 07/2009; 16(7):2018-2027. DOI: 10.1245/s10434-008-0273-8


Although widely used for the management of patients with cutaneous melanoma, the sentinel lymph node (SLN) biopsy (SNB) procedure raises several issues. This study was designed to investigate: the predictive factors of SLN status, the false-negative (FN) rate, and patients’ prognosis after SNB.
Patients and Methods
This is an observational, prospective study conducted on a large series of consecutive patients (n = 1,313) enrolled by 23 Italian centers from 2000 through 2002. A commonly shared protocol was adopted for the SNB surgical procedure and the SLN pathological examination.
The SLN positive and false-negative (FN) rates were 16.9% and 14.4%, respectively (median follow-up, 4.5 years). At multivariable logistic regression analysis, the frequency of positive SLN increased with increasing Breslow thickness (p < 0.0001) and decreased in patients with melanoma regression (p = 0.024). At the multivariable Cox regression analysis, SLN status was the most important prognostic factor (hazards ratio (HR) = 3.08) for overall survival; the other statistically significant factors were sex, age, Breslow thickness, and Clark’s level. Considering SLN and NSLN status, including FN cases, we identified four groups of patients with different prognoses. The 5-year overall survival of patients with positive SLNs was 71.3% in those with negative nonsentinel lymph nodes (NSLNs) and 50.4% if NSLNs were positive.
Regression in the primary melanoma seems to be a protective factor from metastasis in the SLN. When correctly calculated, the SNB FN rate is 15–20%. Furthermore, the SNB is important to more precisely assess the prognosis of patients with melanoma.

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Available from: Giuseppe Trifiro, May 26, 2015
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    • "Our identification of altered lymphatic drainage is relevant for lymphography mapping of the sentinel tumor-draining LN in human cancer patients, for pathology analysis to diagnose whether the tumor has metastasized [52,53]. The accuracy of sentinel LN identification has been improved [54,55], however the difficulties in correctly identifying the tumor-draining LN could be caused by blocked lymphatic drainage as experimentally demonstrated here. "
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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.
    Full-text · Article · May 2014 · BMC Cancer
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    • "All patients in this study with SLN micrometastasis lacked regression or an associated nevus. This is consistent with contemporary studies demonstrating that regression is not a predictor of a positive SLNB in thin melanomas [35–37]. Previously, the presence of regression was considered to be a risk factor for SLN metastasis; however, based on currently available data, standard clinical practice does not generally incorporate regression as a criterion for SLNB in patients with thin melanomas [8, 37–39]. "
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    ABSTRACT: Context: The 7th (2009) edition of the AJCC melanoma staging system incorporates tumor (Breslow) thickness, MR, and ulceration in stratifying T1 primary melanomas. Compared to the prior 6th (2001) edition, MR has replaced CL for thin melanomas. Objective: We sought to identify and report differences of the classification of thin melanomas as well as outcome of SLNB in patients according to the 6th and 7th editions at our institution. Results: 106 patients were identified with thin melanomas verified by wide excision. 31 of 106 thin melanomas were reclassified according to the 7th edition of the AJCC. Of those 31, 15 CL II/III patients (6th edition T1a) were reclassified as T1b based on the presence of mitoses while 16 CL IV patients (6th edition T1b) were categorized as T1a based on the absence of mitoses. 26/31 reclassified patients underwent SLNB, and all were negative. Patients with thin melanoma and a +SLNB (N = 3) were all classified as T1b according to both staging systems. Conclusions: In our experience, 29% of thin melanomas were reclassified according to the 7th edition with similar proportions of patients re-distributed as T1a (14%) and T1b (15%). Cases with +SLN corresponded with T1b lesions in both 6th and 7th editions.
    Full-text · Article · Dec 2013
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    • "Negative SLN biopsy findings are well known prognostic factors. Other ways, the positivity to a SLN biopsy lead the patient to a completion lymph node dissection (CLND) and approximately the 35%–50% of SLN positive patients die within 5 years [13-15]. Morton et al. demonstrated a highly significant survival benefit in SLN-positive patients who had received CLND (5-year survival rate 72%) compared to SLN-positive patients who had received delayed ELND (Elective LND) after clinical detection of lymph node metastasis (5-year survival rate 52%) [16]. "
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    ABSTRACT: Complete lymph node dissection (CLND) is the gold standard treatment for patients with a positive sentinel lymph node (SLN) biopsy. Considering the morbidity associated with CLND it is important to identify histological features of the primary tumor and/or of SLN metastasis that could help to spare from CLND a subset of patients who have a very low risk of non-SLN metastasis. The objective of this study is to identify patients with a very low risk to develop non-SLNs recurrences and to limit unnecessary CLND. A retrospective long-term study of 80 melanoma patients with positive SLN, undergone CLND, was assessed to define the risk of additional metastasis in the regional nodal basin, on the basis of intranodal distribution of metastatic cells, using the micro-morphometric analysis (Starz classification). This study demonstrates that among the demographic and pathologic features of primary melanoma and of SLN only the Starz classification shows prognostic significance for non-SLN status (p<0.0001). This parameter was also significantly associated with disease-free survival rate (p<0.0013). The Starz classification can help to identify, among SLN positive patients, those who can have a real benefit from CLND. From the clinical point of view this easy and reliable method could lead to a significant reduction of unnecessary CLND in association with a substantial decrease in morbidity. The study results indicate that most of S1 subgroup patients might be safely spared from completion lymphatic node dissection. Furthermore, our experience demonstrated that Starz classification of SLN is a safe predictive index for patient stratification and treatment planning.
    Full-text · Article · Aug 2013 · Journal of Experimental & Clinical Cancer Research
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