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Current management of patients with melanoma who are found to be sentinel node-positive.

ABSTRACT: BACKGROUND:The results of the DeCOG-SLT and MSLT-II studies, published in 2016 and mid-2017, indicated no survival benefit from completion lymph node dissection (CLND) in melanoma patients with positive sentinel nodes (SNs). Subsequently, several studies have been published reporting a benefit of adjuvant systemic therapy in patients with stage III melanoma. The current study assessed how these findings influenced management of SN-positive patients in a dedicated melanoma treatment centre. METHODS:SN-positive patients treated at Melanoma Institute Australia between July 2017 and December 2018 were prospectively identified. Surgeons completed a questionnaire documenting the management of each patient. Information on patients, primary tumours, SNs, further treatment and follow-up was collected from patient files, the institutional research database and pathology reports. RESULTS:During the 18-month study period, 483 patients underwent SN biopsy. A positive SN was found in 61 (13%). Two patients (3%) requested CLND because of anxiety about observation in view of unfavourable primary tumour and SN characteristics. The other 59 patients (97%) were followed with a four-monthly ultrasound examination of the relevant lymph node field(s). Two of them (3%) developed an isolated nodal recurrence after 4 and 11?months of follow-up. Fifty-seven patients (93%) were seen following the publication of the first two adjuvant systemic therapy studies in November 2017; 46 (81%) were referred to a medical oncologist to discuss adjuvant systemic therapy, which 32 (70%) chose to receive. CONCLUSION:At Melanoma Institute Australia most patients with an involved SN are now managed without CLND. The majority are referred to a medical oncologist and receive adjuvant systemic therapy.

SUBMITTER: Nijhuis AAG

PROVIDER: S-EPMC7216885 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Current management of patients with melanoma who are found to be sentinel node-positive.

Nijhuis Amanda A G AAG Spillane Andrew J AJ Stretch Jonathan R JR Saw Robyn P M RPM Menzies Alexander M AM Uren Roger F RF Thompson John F JF Nieweg Omgo E OE

ANZ journal of surgery 20191030 4

<h4>Background</h4>The results of the DeCOG-SLT and MSLT-II studies, published in 2016 and mid-2017, indicated no survival benefit from completion lymph node dissection (CLND) in melanoma patients with positive sentinel nodes (SNs). Subsequently, several studies have been published reporting a benefit of adjuvant systemic therapy in patients with stage III melanoma. The current study assessed how these findings influenced management of SN-positive patients in a dedicated melanoma treatment centr ...[more]

PMID: 31667924

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Project description:BackgroundMelanoma clinical trials demonstrated that completion lymph node dissection is low value for most sentinel lymph node-positive patients. Contemporaneous trials of adjuvant systemic immunotherapy and BRAF/MEK targeted therapy showed improved recurrence-free survival in high-risk sentinel lymph node-positive patients. To better understand how oncologic evidence is incorporated into practice (implementation), we evaluated factors associated with discontinuation of completion lymph node dissection and adoption of systemic treatment at United States Commission on Cancer-accredited centers.MethodsIn a retrospective cohort study of adults with sentinel lymph node-positive melanoma treated from 2012 to 2017 using the National Cancer Database, we evaluated use of completion lymph node dissection and adjuvant systemic treatment using mixed-effects logistic regression, reporting results as odds ratios with 95% confidence intervals.ResultsAmong 10,240 sentinel lymph node-positive melanoma patients, performance of completion lymph node dissection declined from 60% to 27%. Adjuvant systemic treatment increased from 29% to 43% (37% in stage IIIA patients, 46% in IIIB-C). Completion lymph node dissection was less common with lower extremity tumors (odds ratio = 0.53, 95% confidence interval = 0.44-0.64) and more common with multiple positive sentinel lymph nodes (odds ratio = 2.36, 95% confidence interval = 2.08-2.67), treatment at a high- or moderate-volume center (odds ratiohigh = 1.49, 95% confidence interval = 1.05-2.12; odds ratiomoderate = 1.32, 95% confidence interval = 1.05-1.64), and receipt of systemic therapy (odds ratio = 1.44, 95% confidence interval = 1.27-1.63). The increased likelihood of completion lymph node dissection in patients receiving adjuvant systemic treatment persisted in the most recent study years and in patients with a single positive sentinel lymph node.ConclusionAt a population level, completion lymph node dissection declined and adjuvant systemic treatment increased, reflecting evidence-responsive care. Variation in persistent use of completion lymph node dissection and in provision of adjuvant treatment for lower risk patients highlights residual gaps in both evidence and implementation.

Project description:Sentinel lymph node, the first node draining the primary tumor, is a key component of tumor microenvironment promoting immune tolerance. In melanoma, sentinel node is one of the most important prognostic factors and the most frequent site of regional metastasis. To unravel the immunomodulatory pathways that are triggered by melanoma cells in the draining node that allow tumor spreading, transcriptional profiles associated to disease progression were analyzed in archival sentinel node biopsies (SNB). Gene expression profiles of melanoma-positive and negative SNB selected to maximize the differences in terms of disease stage and course, revealed subgroups correlating with regional node involvement and disease progression within positive biopsies. Transcriptional profiles revealed that genes showing differential expression between tumor-positive SNB with/without disease progression were mainly related to inflammatory response and that were mostly down regulated in patients with poor prognosis. TNFRSF8 encoding CD30 showing up regulation in SNB from patients with progressing disease displayed higher expression by immunohistochemical staining compared to SNB from non progressing patients. Subpopulations of CD30 positive CD4/CD8 double negative and CD4 Foxp3/PD-1 CD147 positive T cells were identified by flow cytometry analysis in metastatic nodes, suggesting a potential role of regulatory and tolerogenic T cells in melanoma progression. Cutaneous melanoma patients undergoing SNB biopsy in 2001-2004 with available 5–year follow-up clinical data were selected. Data relative to 752 cases was extracted, 80% (n= 603) with a negative SNB and 20% (n=149) with SNB positivity for melanoma metastases. The latter underwent regional lymphadenectomy by CLND and 30% (n=44) resulted positive for melanoma metastases at non-sentinel regional lymph nodes while 70% (n=105) resulted negative. Analysis of follow-up data showed that disease recurrence at 5 yrs occurred in 9% SNB negative patients, 14% of the patients with positive SNB resulting negative at CLND, and in 57% of the patients with positive SNB resulting positive at CLND, consistent to the range of previously reported rates (Santinami M 2009, Balch CM 2009). In order to exploit gene expression profiles to unravel molecular modifications occurring in SNB from patients with progressing disease we selected two groups of cases representing the extremes of the survey, i.e. patients positive at CLND (stage IIIB-C) recurring within 5 years follow-up (SNB-PP), and patients negative at CLND (stage IIIA-B) and non-relapsing at 5 years (SNB-PN). In addition, a group of negative SNB patients without disease recurrence at 5 years was selected and analysed for comparison as tumor negative SNB (SNB-N).

Project description:Sentinel lymph node, the first node draining the primary tumor, is a key component of tumor microenvironment promoting immune tolerance. In melanoma, sentinel node is one of the most important prognostic factors and the most frequent site of regional metastasis. To unravel the immunomodulatory pathways that are triggered by melanoma cells in the draining node that allow tumor spreading, transcriptional profiles associated to disease progression were analyzed in archival sentinel node biopsies (SNB). Gene expression profiles of melanoma-positive and negative SNB selected to maximize the differences in terms of disease stage and course, revealed subgroups correlating with regional node involvement and disease progression within positive biopsies. Transcriptional profiles revealed that genes showing differential expression between tumor-positive SNB with/without disease progression were mainly related to inflammatory response and that were mostly down regulated in patients with poor prognosis. TNFRSF8 encoding CD30 showing up regulation in SNB from patients with progressing disease displayed higher expression by immunohistochemical staining compared to SNB from non progressing patients. Subpopulations of CD30 positive CD4/CD8 double negative and CD4 Foxp3/PD-1 CD147 positive T cells were identified by flow cytometry analysis in metastatic nodes, suggesting a potential role of regulatory and tolerogenic T cells in melanoma progression. Cutaneous melanoma patients undergoing SNB biopsy in 2001-2004 with available 5M-bM-^@M-^Syear follow-up clinical data were selected. Data relative to 752 cases was extracted, 80% (n= 603) with a negative SNB and 20% (n=149) with SNB positivity for melanoma metastases. The latter underwent regional lymphadenectomy by CLND and 30% (n=44) resulted positive for melanoma metastases at non-sentinel regional lymph nodes while 70% (n=105) resulted negative. Analysis of follow-up data showed that disease recurrence at 5 yrs occurred in 9% SNB negative patients, 14% of the patients with positive SNB resulting negative at CLND, and in 57% of the patients with positive SNB resulting positive at CLND, consistent to the range of previously reported rates (Santinami M 2009, Balch CM 2009). In order to exploit gene expression profiles to unravel molecular modifications occurring in SNB from patients with progressing disease we selected two groups of cases representing the extremes of the survey, i.e. patients positive at CLND (stage IIIB-C) recurring within 5 years follow-up (SNB-PP), and patients negative at CLND (stage IIIA-B) and non-relapsing at 5 years (SNB-PN). In addition, a group of negative SNB patients without disease recurrence at 5 years was selected and analysed for comparison as tumor negative SNB (SNB-N).

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Current management of patients with melanoma who are found to be sentinel node-positive.

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Current management of patients with melanoma who are found to be sentinel node-positive.

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