Omgo E. Nieweg

Completion Dissection or Observation for Sentinel-Node Metastasis in Melanoma

BACKGROUND Sentinel‐lymph‐node biopsy is associated with increased melanoma‐specific survival (i.e., survival until death from melanoma) among patients with node‐positive intermediate‐thickness melanomas (1.2 to 3.5 mm). The value of completion lymph‐node dissection for patients with sentinel‐node metastases is not clear. METHODS In an international trial, we randomly assigned patients with sentinel‐node metastases detected by means of standard pathological assessment or a multimarker molecular assay to immediate completion lymph‐node dissection (dissection group) or nodal observation with ultrasonography (observation group). The primary end point was melanoma‐specific survival. Secondary end points included disease‐free survival and the cumulative rate of nonsentinel‐node metastasis. RESULTS Immediate completion lymph‐node dissection was not associated with increased melanoma‐specific survival among 1934 patients with data that could be evaluated in an intention‐to‐treat analysis or among 1755 patients in the per‐protocol analysis. In the per‐protocol analysis, the mean (±SE) 3‐year rate of melanoma‐specific survival was similar in the dissection group and the observation group (86±1.3% and 86±1.2%, respectively; P=0.42 by the log‐rank test) at a median follow‐up of 43 months. The rate of disease‐free survival was slightly higher in the dissection group than in the observation group (68±1.7% and 63±1.7%, respectively; P=0.05 by the log‐rank test) at 3 years, based on an increased rate of disease control in the regional nodes at 3 years (92±1.0% vs. 77±1.5%; P<0.001 by the log‐rank test); these results must be interpreted with caution. Nonsentinel‐node metastases, identified in 11.5% of the patients in the dissection group, were a strong, independent prognostic factor for recurrence (hazard ratio, 1.78; P=0.005). Lymphedema was observed in 24.1% of the patients in the dissection group and in 6.3% of those in the observation group. CONCLUSIONS Immediate completion lymph‐node dissection increased the rate of regional disease control and provided prognostic information but did not increase melanoma‐specific survival among patients with melanoma and sentinel‐node metastases. (Funded by the National Cancer Institute and others; MSLT‐II ClinicalTrials.gov number, NCT00297895.)

EANM practice guidelines for lymphoscintigraphy and sentinel lymph node biopsy in melanoma

PurposeSentinel lymph node biopsy is an essential staging tool in patients with clinically localized melanoma. The harvesting of a sentinel lymph node entails a sequence of procedures with participation of specialists in nuclear medicine, radiology, surgery and pathology. The aim of this document is to provide guidelines for nuclear medicine physicians performing lymphoscintigraphy for sentinel lymph node detection in patients with melanoma.MethodsThese practice guidelines were written and have been approved by the European Association of Nuclear Medicine (EANM) to promote high-quality lymphoscintigraphy. The final result has been discussed by distinguished experts from the EANM Oncology Committee, national nuclear medicine societies, the European Society of Surgical Oncology (ESSO) and the European Association for Research and Treatment of Cancer (EORTC) melanoma group. The document has been endorsed by the Society of Nuclear Medicine and Molecular Imaging (SNMMI).ConclusionThe present practice guidelines will help nuclear medicine practitioners play their essential role in providing high-quality lymphatic mapping for the care of melanoma patients.

The history of sentinel lymph node biopsy.

The sentinel node biopsy technique, developed by Drs Donald Morton and Alistair Cochran and reported in 1992, undoubtedly constitutes the most important recent development in surgical oncology. This article describes the evolution of the procedure and its contribution to the evolution of modern multidisciplinary cancer care and discusses its present role in the management of patients with melanoma, breast cancer, and a wide range of other malignancies.

The history of sentinel node biopsy in head and neck cancer: From visualization of lymphatic vessels to sentinel nodes

The aim of this report is to describe the history of sentinel node biopsy in head and neck cancer. Sentinel node biopsy is a minimally invasive technique to select patients for treatment of metastatic lymph nodes in the neck. Although this procedure has only recently been accepted for early oral cancer, the first studies on visualization of the cervical lymphatic vessels were reported in the 1960s. In the 1980s mapping of lymphatic drainage from specific head and neck sites was introduced. Sentinel node biopsy was further developed in the 1990s and after validation in this century the procedure is routinely performed in early oral cancer in several head and neck centers. New techniques may improve the accuracy of sentinel node biopsy further, particularly in difficult subsites like the floor of mouth.

Detailed Pathological Examination of Completion Node Dissection Specimens and Outcome in Melanoma Patients with Minimal (<0.1 mm) Sentinel Lymph Node Metastases

AbstractBackgroundnNonsentinel lymph nodes (NSLNs) are rarely involved in patients with minimal volume melanoma metastases in sentinel lymph nodes (SLNs). Therefore, it has been suggested that completion lymph node dissection (CLND) is not required. However, the lack of routine immunohistochemical staining and multiple sectioning may have led to failure to identify additional positive nodes. The present study sought to more reliably determine the tumor status of NSLNs in patients with minimally involved SLNs and their clinical outcome.MethodsA total of 21 tumor-negative CLND specimens from 20 patients with SLN metastases of <0.1xa0mm in diameter treated between 1991 and 2013 were examined with a more detailed pathologic protocol (five new sections stained with/for H&E, S-100, HMB45, Melan-A, and H&E). Clinical follow-up data were also obtained.ResultsOf the 343 examined NSLNs, 1 was found to harbor a 0.18-mm subcapsular sinus metastasis. No metastases were identified in the other NSLNs. Median follow-up was 48xa0months (range 17–130xa0months). Six patients (30xa0%) developed a recurrence. At the end of follow-up, 15 patients (75xa0%) were alive without sign of melanoma recurrence and 5 patients (25xa0%) had died of melanoma. Estimated 5-year melanoma-specific survival was 64xa0%. The patient with the additional positive NSLN remains without recurrence after 130xa0months follow-up.ConclusionsnAlthough the risk of additional nodal involvement is low, detailed pathologic examination may identify NSLN metastases not identified using routine protocols. Therefore, nodal clearance appears to be the safest option for these patients, pending the results of prospective trials.

Impact of Time Between Diagnosis and SLNB on Outcomes in Cutaneous Melanoma

BACKGROUNDnHypothetically, delay between melanoma diagnosis and SLNB could affect outcomes, either adversely by allowing growth and dissemination of metastases, or beneficially by allowing development of an anti-melanoma immune response. Available data are conflicting about the effect of SLNB delay on patient survival. Our objective was to determine whether delay between initial diagnosis and SLNB affects outcomes in patients with cutaneous melanoma.nnnSTUDY DESIGNnWe performed query and analysis of a large prospectively maintained database of patients with primary cutaneous melanomas undergoing SLNB. An independent dataset from MSLT-1 (Multicenter Selective Lymphadenectomy Trial-1) was used for validation. Primary outcomes included disease-free survival and melanoma-specific survival.nnnRESULTSnEarly and delayed SLNB were defined as less than 30 and 30 or more days from initial diagnosis, respectively. There were 2,483 patients that met inclusion criteria. Positive sentinel lymph nodes were identified in 17.4% (nxa0= 432). Among all patients, 42% had SLNB 30 or more days after diagnosis and 37% of positive sentinel lymph nodes were at 30 or more days. No differences in sex, anatomic site, or histopathologic features were identified between the 2 groups. There was no difference in melanoma-specific survival or disease-free survival between those undergoing early or delayed SLNB. Examination of MSLT-1 trial data similarly demonstrated no difference in survival outcomes.nnnCONCLUSIONSnThis, the largest study on this subject to date, found no adverse impact on long-term clinical outcomes of patients due to delay of SLNB beyond 30 days. The MSLT-1 data confirm this result. Patients can be reassured that if the operation is performed 30 or more days after diagnosis, it will not cause harm.

Outcome of Melanoma Patients Who Did Not Proceed to Sentinel Node Biopsy After Preoperative Lymphoscintigraphy

BackgroundAt our institution, a planned sentinel node biopsy (SNB) procedure is occasionally canceled after preoperative lymphoscintigraphy. This study reports the frequency of this, the reasons, and the management and outcomes of these patients.MethodsAll patients with clinically localized cutaneous melanoma treated at Melanoma Institute Australia between 2000 and 2009 whose planned SNB procedure was not undertaken after lymphoscintigraphy were included in this retrospective study.ResultsOf the 3148 patients in whom the procedure had been planned, 203 patients (6.4xa0%) did not have a SNB. The main reason for not proceeding with SNB (in 84xa0% of cases) was the lymphoscintigraphic demonstration of multiple drainage fields and/or multiple sentinel nodes (SNs). Patients who did not proceed to SNB were significantly older than those who did, more often had melanomas of the head or neck, and had more SNs and more nodal drainage fields. Of the 203 patients, 181 (89xa0%) were followed with high-resolution ultrasound of their SNs, which identified 33xa0% of the nodal recurrences before they were clinically apparent. Patients whose SNB was canceled had significantly worse recurrence-free survival and regional node disease-free survival, but melanoma-specific survival was similar. Compared to SN-positive patients, node-positive patients without SNB had significantly more involved nodes when a delayed lymphadenectomy was performed, but melanoma-specific survival was not significantly different after a median follow-up of 42xa0months.ConclusionsLymphoscintigraphy with ultrasound follow-up of previously identified SNs is an acceptable management strategy for patients in whom a SNB procedure is likely to be challenging.

Sentinel node biopsy is now part of routine staging in patients with clinically localized melanoma

Twenty per cent of the patients who present with a primary melanoma that has a Breslow thickness exceeding 1 mm have occult metastases in their regional lymph nodes. Without treatment, these later become evident as palpable nodes, but studies of elective (prophylactic) lymph node dissection have not shown an overall improvement in survival. Nevertheless in these studies, a survival benefit of approximately 20% was noted in the subgroup of patients who actually did have lymph node metastases. This survival advantage was greatest among individuals with melanomas of intermediate thickness, presumably because they have a high risk of lymph node involvement, while the risk of synchronous and usually fatal blood-borne metastases to visceral organs is still modest. In order to exploit this potential survival gain while not exposing patients without metastases to the morbidity of a regional node dissection, a diagnostic technique was required to detect such metastases at the time of the treatment of the primary tumour. The sentinel node biopsy (SNB) supplies this want. A multicentre randomized trial of this procedure was initiated in 1994. Patients with a melanoma at least 1 mm Breslow thickness or with Clark level IV invasion were randomized to wide excision plus SNB, with subsequent completion node dissection if metastases were identified, or to wide excision only, with node dissection if metastases later became evident. Three Australian centres contributed to this Multicenter Selective Lymphadenectomy Trial (MSLT-I) and many colleagues referred patients for participation. The final results of this, the largest and longest running surgical melanoma trial ever undertaken, have now been published.

The impact of smoking on sentinel node metastasis of primary cutaneous melanoma

BackgroundAlthough a well-established causative relationship exists between smoking and several epithelial cancers, the association of smoking with metastatic progression in melanoma is not well studied. We hypothesized that smokers would be at increased risk for melanoma metastasis as assessed by sentinel lymph node (SLN) biopsy.MethodsData from the first international Multicenter Selective Lymphadenectomy Trial (MSLT-I) and the screening-phase of the second trial (MSLT-II) were analyzed to determine the association of smoking with clinicopathologic variables and SLN metastasis.ResultsCurrent smoking was strongly associated with SLN metastasis (pxa0=xa00.004), even after adjusting for other predictors of metastasis. Among 4231 patients (1025 in MSLT-I and 3206 in MSLT-II), current or former smoking was also independently associated with ulceration (pxa0<xa00.001 and pxa0<xa00.001, respectively). Compared with current smoking, never smoking was independently associated with decreased Breslow thickness in multivariate analysis (pxa0=xa00.002) and with a 0.25xa0mm predicted decrease in thickness.ConclusionThe direct correlation between current smoking and SLN metastasis of primary cutaneous melanoma was independent of its correlation with tumor thickness and ulceration. Smoking cessation should be strongly encouraged among patients with or at risk for melanoma.

A pilot study of SPECT/CT-based mixed-reality navigation towards the sentinel node in patients with melanoma or Merkel cell carcinoma of a lower extremity.

ObjectiveTo explore the feasibility of an intraoperative navigation technology based on preoperatively acquired single photon emission computed tomography combined with computed tomography (SPECT/CT) images during sentinel node (SN) biopsy in patients with melanoma or Merkel cell carcinoma. Materials and methodsPatients with a melanoma (n=4) or Merkel cell carcinoma (n=1) of a lower extremity scheduled for wide re-excision of the primary lesion site and SN biopsy were studied. Following a 99mTc-nanocolloid injection and lymphoscintigraphy, SPECT/CT images were acquired with a reference target (ReTp) fixed on the leg or the iliac spine. Intraoperatively, a sterile ReTp was placed at the same site to enable SPECT/CT-based mixed-reality navigation of a gamma ray detection probe also containing a reference target (ReTgp).The accuracy of the navigation procedure was determined in the coronal plane (x, y-axis) by measuring the discrepancy between standard gamma probe-based SN localization and mixed-reality-based navigation to the SN. To determine the depth accuracy (z-axis), the depth estimation provided by the navigation system was compared to the skin surface-to-node distance measured in the computed tomography component of the SPECT/CT images. ResultsIn four of five patients, it was possible to navigate towards the preoperatively defined SN. The average navigational error was 8.0u2009mm in the sagittal direction and 8.5u2009mm in the coronal direction. Intraoperative sterile ReTp positioning and tissue movement during surgery exerted a distinct influence on the accuracy of navigation. ConclusionIntraoperative navigation during melanoma or Merkel cell carcinoma surgery is feasible and can provide the surgeon with an interactive 3D roadmap towards the SN or SNs in the groin. However, further technical optimization of the modality is required before this technology can become routine practice.