Prognostic Value of Sentinel Lymph Node Biopsy Compared with that of Breslow Thickness: Implications for Informed Consent in Patients with Invasive Melanoma
“…They found that survival percentage by Breslow thickness falls between the SLNB− and SLNB+ subsets. The prognostic value gained by SLNB in these studies was not useful …”
Section: Sentinel Lymph Node Biopsy and Prognostic Datamentioning
confidence: 76%
“…Freeman et al . performed a meta‐analysis and compared overall 5‐year survival with and without sentinel lymph node stratification.…”
Section: Sentinel Lymph Node Biopsy and Prognostic Datamentioning
However, critical appraisal of MSLT-I data does not support the claims of the final report. On the contrary, MSLT-I failed to demonstrate that there is a significant treatment-related difference in the 10-year melanoma-specific survival rate in the overall study population. Furthermore, there was no improvement in overall or melanoma-specific survival of the intermediate-thickness group (1·2-3·5 mm). Completion lymphadenectomy can result in complications in about a third of patients, with a rate of clinically significant lymphoedema following axillary or groin dissection of 5-10%. Unnecessary lymphadenectomy can therefore have a major effect on patient quality of life. The evidence provided by Morton et al. does not support the claim that sentinel lymph node biopsy followed by lymphadenectomy in patients with positive sentinel nodes should be the standard of care in patients with melanoma. Readers are encouraged to check with registration sites to make sure declared primary outcomes are fairly reported. Post-hoc analyses are at best exploratory and cannot be used to form the principal conclusions of a trial.
“…They found that survival percentage by Breslow thickness falls between the SLNB− and SLNB+ subsets. The prognostic value gained by SLNB in these studies was not useful …”
Section: Sentinel Lymph Node Biopsy and Prognostic Datamentioning
confidence: 76%
“…Freeman et al . performed a meta‐analysis and compared overall 5‐year survival with and without sentinel lymph node stratification.…”
Section: Sentinel Lymph Node Biopsy and Prognostic Datamentioning
However, critical appraisal of MSLT-I data does not support the claims of the final report. On the contrary, MSLT-I failed to demonstrate that there is a significant treatment-related difference in the 10-year melanoma-specific survival rate in the overall study population. Furthermore, there was no improvement in overall or melanoma-specific survival of the intermediate-thickness group (1·2-3·5 mm). Completion lymphadenectomy can result in complications in about a third of patients, with a rate of clinically significant lymphoedema following axillary or groin dissection of 5-10%. Unnecessary lymphadenectomy can therefore have a major effect on patient quality of life. The evidence provided by Morton et al. does not support the claim that sentinel lymph node biopsy followed by lymphadenectomy in patients with positive sentinel nodes should be the standard of care in patients with melanoma. Readers are encouraged to check with registration sites to make sure declared primary outcomes are fairly reported. Post-hoc analyses are at best exploratory and cannot be used to form the principal conclusions of a trial.
“…Patients with documented clinical follow-up had allowed correlation analyses of the clinical evolution with the immunocyte infiltration of the SLN or the primary tumor. A recent meta-analysis indicated that primary tumor depth influences the impact of SLN status on OS and represent a better prognostic factor than SLN status [ 28 ]. In individuals with thin melanoma (<1 mm), SLN - status conferred no survival advantage, while for intermediate depths, most studies reported worse survival in SLN + melanoma patients, although the difference was not statistically significant.…”
Melanomas are aggressive skin tumors characterized by high metastatic potential. Our previous results indicate that Natural Killer (NK) cells may control growth of melanoma. The main defect of blood NK cells was a decreased expression of activating NCR1/NKp46 receptor and a positive correlation of NKp46 expression with disease outcome in stage IV melanoma patients was found. In addition, in stage III melanoma patients, we identified a new subset of mature NK cells in macro-metastatic Lymph nodes (LN). In the present studies, we evaluated the numbers of NK cells infiltrating primary cutaneous melanoma and analyzed immune cell subsets in a series of sentinel lymph nodes (SLN). First, we show that NKp46+ NK cells infiltrate primary cutaneous melanoma. Their numbers were related to age of patients and not to Breslow thickness. Then, a series of patients with tumor-negative or -positive sentinel lymph nodes matched for Breslow thickness of the cutaneous melanoma was constituted. We investigated the distribution of macrophages (CD68), endothelial cells, NK cells, granzyme B positive (GrzB+) cells and CD8+ T cells in the SLN. Negative SLN (SLN-) were characterized by frequent adipose involution and follicular hyperplasia compared to positive SLN (SLN+). High densities of macrophages and endothelial cells (CD34), prominent in SLN+, infiltrate SLN and may reflect a tumor favorable microenvironment. Few but similar numbers of NK and GrzB+ cells were found in SLN- and SLN+: NK cells and GrzB+ cells were not correlated. Numerous CD8+ T cells infiltrated SLN with a trend for higher numbers in SLN-. Moreover, CD8+ T cells and GrzB+ cells correlated in SLN- not in SLN+. We also observed that the numbers of CD8+ T cells negatively correlated with endothelial cells in SLN-. The numbers of NK, GrzB+ or CD8+ T cells had no significant impact on overall survival. However, we found that the 5 year-relapse rate was higher in SLN with higher numbers of NK cells.
“…Though SLNB identifies patients with microscopic nodal disease, improves regional disease control, 7 and may facilitate the escalation of treatment, it is still controversial whether there is any therapeutic benefit of the procedure, especially in terms of survival. 8-10 In fact, the only randomized-controlled trial (RCT) to evaluate the question of a survival benefit demonstrated no difference in disease-specific survival (DSS) for those treated with SLNB for intermediate-thickness melanoma. 11,12 A criticism of the trial has been that it was under-powered to detect a small but clinically significant survival effect.…”
Importance
Sentinel lymph node biopsy (SLNB) provides prognostic information for melanoma; however, a survival benefit has not been demonstrated.
Objective
To assess the association of SLNB with survival for head and neck melanoma (HNM).
Design
Propensity score-matched retrospective cohort study using the Surveillance Epidemiology and End Results (SEER) database to compare patients with HNM initially treated with SLNB versus nodal observation.
Setting
United States population
Patients
Melanoma arising in head and neck subsites meeting current recommendations for SLNB, treated during the years 2004-2011 with either a) SLNB +/− neck dissection, or b) no SLNB or neck dissection. Intervention: SLNB +/− neck dissection
Main Outcome
Disease-specific survival (DSS) estimates based on the Kaplan-Meier method, and Cox proportional-hazards modeling to compare survival outcomes between matched-pair cohorts
Results
7266 HNM patients meeting study criteria were identified from the SEER database. Matching of treatment cohorts was performed utilizing propensity scores modeled on 10 covariates known to be associated with SLNB treatment or melanoma survival. Cohorts were stratified by tumor thickness (thin: >0.75-1mm Breslow depth, intermediate: >1-4mm, and thick: >4mm) and exactly-matched within five age categories. In the intermediate-thickness cohort, 2808 HNM patients were matched and balanced by propensity score for SLNB treatment; the 5-year DSS estimate for those treated by SLNB was 89% vs. 88% for nodal observation (log-rank p=0.30). The hazard ratio for melanoma-specific death was 0.87 for those undergoing SLNB (95% CI 0.66-1.14, p=0.31). In each of the other cohorts analyzed, including the thin, thick, and overall cohorts, no significant difference in DSS was demonstrated.
Conclusions
This SEER cohort analysis demonstrates no significant association between SLNB and improved disease survival for patients with HNM.
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