No survival benefit for patients with melanoma undergoing sentinel lymph node biopsy: critical appraisal of the Multicenter Selective Lymphadenectomy Trial-I final report

Sladden, Michael J; Zagarella, Samuel; Popescu, C; Bigby, Michael

doi:10.1111/bjd.13675

Cited by 48 publications

(31 citation statements)

References 14 publications

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“…27 In addition, sentinel lymph node biopsy (SLNB) is a controversial issue in melanoma as randomized trial data show modest benefit at the expense of complications in one-third of patients. 28 Clearly, the decision to proceed with intensive therapy in patients with thin melanoma is not trivial, and how best to identify patients most likely to benefit from intensive therapy remains a clinical dilemma.…”

Section: Discussionmentioning

confidence: 99%

Using global gene expression to discriminate thin melanomas with poor outcomes

Hothem

Bayci

Thibodeau

et al. 2016

Molecular & Cellular Oncology

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Most melanomas present as thin lesions (1.0 mm) with a good prognosis; however, a small percentage of patients with thin lesions experience recurrence or metastasis. The aim of our study was to identify a distinct pattern of gene expression within thin melanomas known to have eventually metastasized to regional lymph nodes or distant sites compared with those that followed the typical course with good response to wide local excision alone. Patients who were disease-free for a minimum of 10 y served as controls (n D 10) to the experimental group who developed metastasis (n D 9). Laser capture microdissection was used to specifically isolate cancer cells from formalin-fixed paraffin-embedded tissue with subsequent gene expression analysis on Affymetrix Human Transcriptome Array 2.0 Arrays. Although gene expression differences were observed between the patients with thin melanoma with poor clinical outcome and those with good clinical outcome, neither the number of genes nor the magnitude of the fold difference was very substantial or significant. Cluster analysis with this subset of genes could definitively separate a subset of the poor responders from the good responders, but there remained a mixed group of tumors that could not be predicted from gene expression alone. Pathway analysis identified cellular processes that were regulated based on the response, including categories commonly associated with melanoma progression. Ultimately, we concluded that there were very few differences between these groups. Future research will be required and investigation of the mutational landscape may be another strategy to uncover genomic changes that drive recurrence and metastasis in thin melanoma.

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Section: Discussionmentioning

confidence: 99%

Using global gene expression to discriminate thin melanomas with poor outcomes

Hothem

Bayci

Thibodeau

et al. 2016

Molecular & Cellular Oncology

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“…While SNB is now widely accepted as a useful staging tool in the management of cutaneous melanoma, there continues to be a debate regarding its impact on patient outcomes (6-8). …”

Section: Introductionmentioning

confidence: 99%

Impact of Completion Lymph Node Dissection on Patients with Positive Sentinel Lymph Node Biopsy in Melanoma

Lee

Lau

Huynh

et al. 2016

Journal of the American College of Surgeons

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Background The need for complete lymph node dissection (CLND) in patients with positive sentinel lymph node biopsy (SNB) is an important unanswered clinical question. Study Design Patients diagnosed with positive SNB at a melanoma referral center from 1991 to 2013 were studied. Outcomes of patients who underwent CLND were compared to those who did not undergo immediate CLND (observation group, OBS). Results There were 471 patients who had positive SNB; 375 (79.6%) in the CLND group and 96 (20.4%) in the OBS group. The groups were similar except that the CLND group was younger and had more sentinel nodes removed. Five-year nodal recurrence free survival was significantly better in the CLND group compared to the OBS group (93.1% vs 84.4%, p= 0.005). However, the 5- (66.4% vs 55.2%) and 10- year (59.5% vs 45.0%) distant metastasis free survival was not significantly different (p= 0.061). The CLND group's melanoma specific survival (MSS) was superior to the OBS group; 5 year MSS was (73.7 vs 65.5%) and10 year MSS- (66.8 vs 48.3%, p=0.015). On multivariate analysis, CLND was associated with improved MSS (HR 0.60, 95% CI 0.40-0.89, p= 0.011) and lower nodal recurrence (HR 0.46, 95% CI 0.24-0.86, p=0.016). Increased Breslow thickness, older age, ulceration, and trunk melanoma were all associated with worse outcomes. On subgroup analysis, following factors were associated with better outcomes from CLND- male gender, non-ulcerated primary, intermediate thickness, Clark level IV or lower extremity tumors. Conclusions Treatment of positive SNB with CLND was associated with improved MSS and nodal recurrence rate. Follow up beyond 5 years was needed to see a significant difference in MSS.

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“…SLN biopsy is currently proposed for melanoma patients with high‐risk, locally invasive tumours as it offers added prognostic information. However, this additional procedure is best performed by experienced surgeons in advanced or tertiary settings, where there are added costs, a low but measurable incidence of lymphoedema, and there is ongoing debate about its influence on melanoma survival . By using a nomogram score which incorporates the prognostic powers of multiple previously established protein markers from the primary melanoma, added to existing clinicopathological factors, we here report survival prediction in a cohort of high‐risk melanoma patients without reference to SLN status.…”

Section: Discussionmentioning

confidence: 99%

Molecular markers to complement sentinel node status in predicting survival in patients with high-risk locally invasive melanoma

et al. 2016

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Sentinel lymph node status is a major prognostic marker in locally invasive cutaneous melanoma. However, this procedure is not always feasible, requires advanced logistics and carries rare but significant morbidity. Previous studies have linked markers of tumour biology to patient survival. In this study, we aimed to combine the predictive value of established biomarkers in addition to clinical parameters as indicators of survival in addition to or instead of sentinel node biopsy in a cohort of high-risk melanoma patients. Patients with locally invasive melanomas undergoing sentinel lymph node biopsy were ascertained and prospectively followed. Information on mortality was validated through the National Death Index. Immunohistochemistry was used to analyse proteins previously reported to be associated with melanoma survival, namely Ki67, p16 and CD163. Evaluation and multivariate analyses according to REMARK criteria were used to generate models to predict disease-free and melanomaspecific survival. A total of 189 patients with available archival material of their primary tumour were analysed. Our study sample was representative of the entire cohort (N 5 559). Average Breslow thickness was 2.5 mm. Thirty-two (17%) patients in the study sample died from melanoma during the follow-up period. A prognostic score was developed and was strongly predictive of survival, independent of sentinel node status. The score allowed classification of risk of melanoma death in sentinel nodenegative patients. Combining clinicopathological factors and established biomarkers allows prediction of outcome in locally invasive melanoma and might be implemented in addition to or in cases when sentinel node biopsy cannot be performed.Cutaneous melanoma is the deadliest form of skin malignancy with an incidence that is still rising in many age groups. 1,2 The large majority (>80%) of melanomas are currently diagnosed at a stage of local disease. Overall survival for these patients is good, especially for those with thin (<1 mm) melanomas. 3 However, for thicker lesions, or those with ulceration and detectable mitoses, there is a broad range of possible outcomes, with 10-year survival ranging from 86% for American Joint Committee on Cancer (AJCC) stage IB to 39% for AJCC stage IIC. 3 While the current staging for cutaneous melanoma, incorporating Breslow thickness, ulceration and mitotic index, predicts broad probabilities of disease progression for patients with locally invasive disease, 3 there remains a significant level of variability in terms of prognosis amongst patients diagnosed within the same stage.Sentinel lymph node (SLN) biopsy was introduced as an additional recommended staging procedure to address this issue for patients with tumours >1 mm in thickness and clinically

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No survival benefit for patients with melanoma undergoing sentinel lymph node biopsy: critical appraisal of the Multicenter Selective Lymphadenectomy Trial-I final report

Cited by 48 publications

References 14 publications

Using global gene expression to discriminate thin melanomas with poor outcomes

Using global gene expression to discriminate thin melanomas with poor outcomes

Impact of Completion Lymph Node Dissection on Patients with Positive Sentinel Lymph Node Biopsy in Melanoma

Molecular markers to complement sentinel node status in predicting survival in patients with high-risk locally invasive melanoma

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