Cutaneous melanoma sentinel node biopsy: Target patient population, technique, and management of positive results

Diagnostic Value of HMB-45 and Anti-Melan A Staining of Sentinel Lymph Nodes with Isolated Positive Cells

Book review

For primary melanoma, there is a delay between the initial skin biopsy and sentinel lymph node dissection, which may cause anxiety for the patient. The consequences of this delay on disease progression are unknown. The goal of this study was to determine whether delay time for sentinel node dissection from the initial cutaneous melanoma biopsy affects patient outcomes. A retrospective analysis of 492 patients with melanoma who underwent a sentinel node dissection between 1993 and 1999 was carried out. The endpoints assessed were sentinel node tumor status, recurrence, and mortality. Time to sentinel node dissection was compared between patients with positive and negative sentinel nodes. Long-term survival and recurrence were evaluated in relation to the time between the cutaneous biopsy and the sentinel node dissection (delay time), comparing less than 40 days with at least 40 days. In total, 15.9% of patients had positive sentinel nodes. The median follow-up was 11.7 years. Positive sentinel node patients had a median delay of 35 days between the primary melanoma biopsy and the sentinel node dissection compared with 41 days for negative sentinel node patients (P=0.5). Kaplan-Meier survival curves showed that a delay time of less than 40 days versus at least 40 days was not related to recurrence of melanoma (log-rank P=0.13) or overall survival (log-rank P=0.14). On multivariate analysis of age, thickness, ulceration, and sentinel node status, there was no difference in disease-free survival (P=0.58) or overall survival (P=0.53) between the less than 40 days and the at least 40 days groups. A modest delay in sentinel node dissection from the initial melanoma biopsy does not adversely affect sentinel node status, recurrence, nor survival.

Nonclinical Toxicology in Support of Licensure of Gene Therapies

Sentinel lymph node biopsy (SLNB) is useful for staging of patients with melanoma. Although SLNB is mostly performed under general anesthesia (GA), tumescence local anesthesia (TLA) can also be used. However, less data are available regarding feasibility of SLNB under TLA. Here we present a post-operative follow-up of 150 patients. We prospectively analyzed data from 150 patients with primary cutaneous malignant melanoma. We assessed pain, post-operative complications and patients' satisfaction after SLNB under TLA. 32% of the patients reported post-operative pain within the first 48h after SLNB. Seroma was the most frequent complication, as 29 seromas after SLNB were observed. Wound infection was observed in 3.3% of the patients. 98.7% of the patients were satisfied with SLNB under TLA. SLNB under TLA is a safe and feasible option and should be considered for patients with melanoma. Especially with multimorbid or elderly patients, the risks of GA can be avoided.

PRM204 - Telephone Versus face-to-face Interviews for Patient-Reported Outcome Instrument Development

Reducing the Gastrointestinal Risks of Low-Dose Aspirin

Recommendations for the Analysis of ALK Gene Rearrangements in Non–Small-Cell Lung Cancer: A Consensus of the Italian Association of Medical Oncology and the Italian Society of Pathology and Cytopathology

To simulate the effects of previous wide cutaneous melanoma excision in sentinel lymph node (SLN) biopsy feasibility through a change in the radiotracer injection site. Thirty-three patients with cutaneous melanoma underwent two preoperatory lymphoscintigraphic studies. In the first, the radiopharmaceutical was injected intradermally 0.3 cm away from the lesion/scar. Dynamic images were acquired to find the SLN. On the following day, the procedure was repeated with the radiopharmaceutical injected 1 cm farther from the previous injection sites. The number of lymph nodes and sites of drainage were compared with the findings of the first study. All the patients underwent SLN biopsy using a gamma probe and patent blue. Seventy-five SLNs were identified with radiopharmaceutical injected at 0.3 cm from the lesion versus 82 SLNs when injected at 1.3 cm. All lymph nodes visualized with close injection were identified with the farther injection. Twenty-seven (81%) patients presented the same number and location of SLNs. Six (19%) patients presented more SLNs with the expanded technique, three patients in the same basin and three in a new lymph node station. All metastatic SLNs were harvested by the two injection techniques. The value of the SLN biopsy in patients with cutaneous melanoma is maintained even after the primary lesion has been removed with a margin of up to 1 cm. Some patients might show an increased number of SLNs and some might show drainage to additional lymph node stations.

Synchronous bilateral axillary sentinel lymph node metastases in a patient with truncal melanoma

Lymphatic mapping and sentinel lymph node (SLN) biopsy are widely used as a staging technique for patients with cutaneous malignant melanoma who are at risk for metastases. SLN status has been shown to be a strong predictor of prognosis, and a variety of techniques have been used to identify minimal metastatic disease in SLNs. However, there is no validated consensus method for the optimal histologic analysis of SLNs harvested from melanoma patients. This study was conducted: 1) to assess the yield of metastatic melanoma detected in SLNs deemed negative by initial routine pathologic analysis (RPA) by subjecting them (after review of the original slides) to enhanced pathologic analysis (EPA) that included complete step-sectioning and immunohistochemistry (IHC); 2) to characterize the distribution of metastatic melanoma deposits within the SLNs; 3) to determine a preferred method of pathologic analysis applicable to daily practice; and 4) to attempt to assess the clinical significance of disease detected by EPA. A total of 105 SLNs were harvested from 49 patients who underwent successful SLN biopsy procedures during the period of study. Ten SLNs from 10 patients were positive on initial RPA and were not analyzed further. Ninety-five SLNs from the remaining 39 patients were reviewed and processed with additional hematoxylin and eosin, S-100 protein, and HMB-45 stains at 50-microm intervals for 20 levels or until the SLN tissue was exhausted. A single pathologist reviewed all sections without knowledge of the results of the other stains. Overall, metastatic melanoma was discovered in SLNs from 20 of the 39 patients: SLNs from 6 patients were found to have melanoma on review of the original hematoxylin and eosin slides, and SLNs from 14 patients were positive only after EPA. Twenty-one individual positive SLNs from these 14 patients were detected by EPA; of these, 10 positive SLNs were identified solely by IHC, representing 12% of the patient cohort and 10% of all SLNs studied by EPA. Detection rates were significantly associated with the staining method and the number of levels performed (P < 0.01). S-100 protein staining resulted in the highest yield of SLN positivity (86%), followed by HMB-45 (81%) and hematoxylin and eosin (52%). No single method detected all of the micrometastases. A detailed topographic mapping of metastatic deposits in SLNs was carried out. When using all three staining techniques, all 20 levels were required to identify 100% of the micrometastases; 95% of positive SLNs were identified with 17 levels, 90% with 15 levels, 75% with 10 levels, and 42% with 3 levels. Projected rates of detection for various different sectioning strategies were determined, with alteration of either the number of levels examined, the interval between the levels, or both. Detection of SLN positivity can be increased to 71% by performing three levels at 250-mum intervals, each level being composed of a set of three sections stained with hematoxylin and eosin, S-100 protein, and HMB-45, respectively. Therefore, this is the methodology we propose for the study of SLNs in melanoma patients. After a median follow-up of 87 months (range, 9-134 months), patients with EPA-detected disease and those with negative SLNs by EPA demonstrated improved recurrence-free and disease-specific survival compared with patients with RPA-detected disease in SLNs. Sampling error introduced by variations in pathologic processing should be addressed by standardization of pathologic methods, and the clinical significance of minimal SLN disease should be addressed in prospective studies of homogeneously staged patients.

Background Lymphatic mapping and sentinel lymph node biopsy (SLNB) has been developed as a minimally invasive technique to determine the pathologic status of regional lymph nodes in patients without clinically palpable disease and incorporated in the latest version of the American Joint Committee on Cancer (AJCC) staging system for cutaneous melanoma. Objective To analyze the results of SLNB and the prognostic value of the micrometastases and the pattern of early recurrences in patients according to sentinel lymph node (SLN) status. Method Patients with cutaneous melanoma in stages I and II (AJCC 2002) who underwent lymphatic mapping and SLNB from 1997 to 2003 were included in a prospective database for analysis. Results The rate of identification of the SLN was 100%. Micrometastases to SLN were found in 20.8% of patients. The rate of SLN micrometastases increased according to Breslow thickness and clinical stage. Breslow thickness of 0.99 mm was the optimal cutpoint for predicting the SLNB result. Twenty-four patients (12.3%) developed a locoregional or distant recurrence at a median follow-up of 31 months. Recurrences were more frequent in patients with a positive SLN. Among patients who had a recurrence, those with a positive SLN were more likely to have distant metastases than those with negative SLN. Nodal recurrences were more frequent in patients with a negative SLN compared with those with a positive SLN. Conclusions The status of the SLN provides accurate staging for identifying patients who may benefit from further therapy and is the most important prognostic factor of relapse-free survival.

Lymphatic mapping and sentinel lymph node biopsy (SLNB) has been developed as a minimally invasive technique to determine the pathologic status of regional lymph nodes in patients without clinically palpable disease and incorporated in the latest version of the American Joint Committee on Cancer (AJCC) staging system for cutaneous melanoma. To analyze the results of SLNB and the prognostic value of the micrometastases and the pattern of early recurrences in patients according to sentinel lymph node (SLN) status. Patients with cutaneous melanoma in stages I and II (AJCC 2002) who underwent lymphatic mapping and SLNB from 1997 to 2003 were included in a prospective database for analysis. The rate of identification of the SLN was 100%. Micrometastases to SLN were found in 20.8% of patients. The rate of SLN micrometastases increased according to Breslow thickness and clinical stage. Breslow thickness of 0.99 mm was the optimal cutpoint for predicting the SLNB result. Twenty-four patients (12.3%) developed a locoregional or distant recurrence at a median follow-up of 31 months. Recurrences were more frequent in patients with a positive SLN. Among patients who had a recurrence, those with a positive SLN were more likely to have distant metastases than those with negative SLN. Nodal recurrences were more frequent in patients with a negative SLN compared with those with a positive SLN. The status of the SLN provides accurate staging for identifying patients who may benefit from further therapy and is the most important prognostic factor of relapse-free survival.

How many lymph nodes are enough during sentinel lymphadenectomy for primary melanoma?

Therapy of metastatic renal cell carcinoma (mRCC) involves the use of a number of alternative targeted drugs that demonstrate high clinical efficacy, but at the same time, require substantial costs of the health care system. Purpose of the study: cost-effectiveness assessment for axitinib and everolimus as a second-line target therapy in patients with mRCC. Materials and methods: The assessment was carried out by minimizing costs and budgetary impact from the standpoint of the health care system based on the results of meta-analyzes of randomized clinical trials (RCTs). The time horizont of study was 1 year. Results: in accordance with the results of meta-analyzes of RCTs, axitinib and everolimus provide improved patient prognosis compared with sorafenib and do not significantly differ in terms of overall survival (HR = 1,3 [0,46–3,67]) and progression-free survival (HR = 1,09 [0,7–1,68]). At the same time, the manufacturer’s maximum price for everolimus and the manufacturer’s recommended price for inclusion in the list of vital and essential drugs for axitinib – the use of the latter will reduce the cost of treatment for the patient by 451,516 rubles. (20,2%) per year. Also, the treatment with axitinib was characterized by the best safety indicators (OR = 0,14 [0,05–0,38]), allowing to reduce the associated costs of the health care system for stopping adverse events. The results of the analysis of the impact on the budget demonstrated the possibility of achieving savings in the resources of the health care system with the inclusion of аxitinib in the restrictive lists of drugs, demonstrating savings of 640,51–778,82 million rubles (11,5–14,0%) based on the target patient population – 2,659 people per year. The results of the sensitivity analysis showed the sustainability of the obtained results of the minimization of costs and the budget impact of the fluctuation of the drugs cost evaluated and the volume of the target population of patients, as well as indicators of PFS. Findings: Considering the results obtained, we can conclude about the clinical and economic advantage of axitinib in comparison with the everolimus and recommend it for inclusion in the list of vital and essential drugs.