17 augustus 2018: lees ook dit artikel: 

https://kanker-actueel.nl/chirurgie-pdt-foto-dynamische-therapie-met-bremachlorin-geeft-veel-betere-overall-overleving-op-5-jaar-dan-alleen-chirurgie-van-melanomen-vanuit-moedervlekken-ontstaan.html

17 augsutus 2018: Met dank aan arts-bioloog drs. Valstar die mij op deze studies wees. Bron: The Lancet

De schildwachtkliermethode zoals die ook bij melanomen wordt gebruikt en zoals het VUmc dit al enkele jaren hanteert blijkt dus niet zo goed te werken als eerder gedacht en vertelt. (zie ook in gerelateerde artikelen). De informatie van het VUmc is inmiddels verwijderd van de website van het VUmc maar het gaat om deze studie: Molecular Upstaging Based on Paraffin-embedded Sentinel Lymph Nodes. Ten-Year Follow-up Confirms Prognostic Utility in Melanoma Patients

Uit twee recente studies waaronder deze studie: Complete lymph node dissection versus no dissection in patients with sentinel lymph node biopsy positive melanoma (DeCOG-SLT): a multicentre, randomised, phase 3 trial blijkt er geen verschil in overall overleving te zijn tussen volledige lymfklierdissectie of een wait-and-see beleid.

Conclusie: Hoewel we niet het vereiste aantal gebeurtenissen bereikten, wat leidde tot een niet volledig onderbouwd onderzoek, toonden onze resultaten geen verschil in overleving bij patiënten die werden behandeld met volledige lymfeklierdissectie in vergelijking met alleen observatie. Dientengevolge dient volledige lymfklierdissectie niet te worden aanbevolen bij patiënten met melanoom met lymfekliermicrouitzaaiingen van ten minste een diameter van 1 mm of kleiner.

Ook uit een reviewstudie van 18 gerandomiseerde studies: Moody JA et al; Eur J Surg Oncol 2017 sep;43(9):1760-1767; PMID 28756017 kwam geen duidelijk statistisch significant verschil naar voren tussen operren op basis van positieve biopsie of opereren op basis van tastbare vergrote schildwachtlymfklier.

Hier wat arts-bioloog Engelbert Valstar mij over de twee studies stuurde.

Sentinelmethode - schildwachtkliermethode bij melanoom voorlopig niet zinvol

Leiter et al (1) zagen in een gerandomiseerd onderzoek van ongeveer 240 versus 240 patienten die allen met de sentinelmethode positieve lymfeklieren (Metastasen kleiner dan 1 mm) geen verschil tussen alle klieren verwijderen dan wel afwachten en later gericht handelen. Geen verschil wil zeggen geen verschil in overleving. Op zoek gaan naar lymfkliermeta’s terwijl je niks voelt heeft dus bij het maligne melanoom geen zin.

In geval van palpabele lymfkliermetastasen was er in een meta-analyse van 18 onderzoeken geen significant verschil in lokale complicaties tussen alleen de voelbare lymfklier verwijderen dan wel alle lymfeklieren op dezelfde plaats te verwijderen inclusief de vergrote klier, al was de tendens dat de beperktere operatie minder complicaties gaf (2). Feit is dat het  kennelijk geen routine is om bij een vergrote lymfklier ze allemaal maar weg te halen.

1)Leiter U et al; Lancet Oncol 2016 jun;17(6):757-767; PMID 27161539.

2)Moody JA et al; Eur J Surg Oncol 2017 sep;43(9):1760-1767; PMID 28756017

Hier de twee abstracten van genoemde studies:

Although we did not achieve the required number of events, leading to the trial being underpowered, our results showed no difference in survival in patients treated with complete lymph node dissection compared with observation only. Consequently, complete lymph node dissection should not be recommended in patients with melanoma with lymph node micrometastases of at least a diameter of 1 mm or smaller.

Complete lymph node dissection versus no dissection in patients with sentinel lymph node biopsy positive melanoma (DeCOG-SLT): a multicentre, randomised, phase 3 trial

for the

Published:May 05, 2016DOI:https://doi.org/10.1016/S1470-2045(16)00141-8

Summary

Background

Complete lymph node dissection is recommended in patients with positive sentinel lymph node biopsy results. To date, the effect of complete lymph node dissection on prognosis is controversial. In the DeCOG-SLT trial, we assessed whether complete lymph node dissection resulted in increased survival compared with observation.

Methods

In this multicentre, randomised, phase 3 trial, we enrolled patients with cutaneous melanoma of the torso, arms, or legs from 41 German skin cancer centres. Patients with positive sentinel lymph node biopsy results were eligible. Patients were randomly assigned (1:1) to undergo complete lymph node dissection or observation with permuted blocks of variable size and stratified by primary tumour thickness, ulceration of primary tumour, and intended adjuvant interferon therapy. Treatment assignment was not masked. The primary endpoint was distant metastasis-free survival and analysed by intention to treat. All patients in the intention-to-treat population of the complete lymph node dissection group were included in the safety analysis. This trial is registered with ClinicalTrials.gov, number NCT02434107. Follow-up is ongoing, but the trial no longer recruiting patients.

Findings

Between Jan 1, 2006, and Dec 1, 2014, 5547 patients were screened with sentinel lymph node biopsy and 1269 (23%) patients were positive for micrometastasis. Of these, 483 (39%) agreed to randomisation into the clinical trial; due to difficulties enrolling and a low event rate the trial closed early on Dec 1, 2014. 241 patients were randomly assigned to the observation group and 242 to the complete lymph node dissection group. Ten patients did not meet the inclusion criteria, so 233 patients were analysed in the observation group and 240 patients were analysed in the complete lymph node dissection group, as the intention-to-treat population. 311 (66%) patients (158 in the observation group and 153 in the dissection group) had sentinel lymph node metastases of 1 mm or less. Median follow-up was 35 months (IQR 20–54). Distant metastasis-free survival at 3 years was 77·0% (90% CI 71·9–82·1; 55 events) in the observation group and 74·9% (69·5–80·3; 54 events) in the complete lymph node dissection group. In the complete lymph node dissection group, grade 3 and 4 events occurred in 15 patients (6%) and 19 patients (8%) patients, respectively. Adverse events included lymph oedema (grade 3 in seven patients, grade 4 in 13 patients), lymph fistula (grade 3 in one patient, grade 4 in two patients), seroma (grade 3 in three patients, no grade 4), infection (grade 3 in three patients, no grade 4), and delayed wound healing (grade 3 in one patient, grade 4 in four patients); no serious adverse events were reported.

Interpretation

Although we did not achieve the required number of events, leading to the trial being underpowered, our results showed no difference in survival in patients treated with complete lymph node dissection compared with observation only. Consequently, complete lymph node dissection should not be recommended in patients with melanoma with lymph node micrometastases of at least a diameter of 1 mm or smaller.

This study provides information about the incidence of complications after Completion lymph node dissection (CLND) and lymphadenectomy for palpable disease (therapeutic lymph node dissection; TLND). It can be used to counsel patients about the procedures and it sets a benchmark against which surgeons can audit their practice.

Ann Surg. Author manuscript; available in PMC 2011 Mar 1.
Published in final edited form as:
PMCID: PMC3046555
NIHMSID: NIHMS269737
PMID: 21135695

Molecular Upstaging Based on Paraffin-embedded Sentinel Lymph Nodes

Ten-Year Follow-up Confirms Prognostic Utility in Melanoma Patients
Michael B. Nicholl, MD,* David Elashoff, PhD, Hiroya Takeuchi, MD, PhD,* Donald L. Morton, MD, and Dave S. B. Hoon, PhD, MSc*

Abstract

Objective

To determine the long-term clinical significance of molecular upstaging in histopathology-negative, paraffin-embedded (PE) sentinel lymph nodes (SLNs) from melanoma patients.

Background

Histopathologic evaluation can miss clinically relevant melanoma micrometastases in SLNs. This longitudinal correlative study is the first 10-year prognostic evaluation of a multimarker quantitative real-time reverse transcriptase–polymerase chain reaction (qRT) assay for PE melanoma-draining SLNs.

Methods

The SLN sections (n = 214) were assessed by qRT assay for 4 established messenger RNA biomarkers: MART-1, MAGE-A3, GalNAc-T, and PAX3.

Results

The qRT assay upstaged 48 of 161 histopathology-negative (hematoxylin-eosin and immunohistochemistry) SLN specimens. At a median follow-up of 11.3 years for the entire cohort, estimated rates of 10-year overall survival (OS) and melanoma-specific survival (MSS) were 82% and 94%, respectively, for histopathology-negative/qRT-negative patients; 56% and 61%, respectively, for histopathology-positive patients; and 52% and 60%, respectively, for histopathology-negative/qRT-positive patients (P < 0.001 for OS, P < 0.001 for MSS). In a multivariate analysis of known melanoma prognostic factors, qRT positivity was significant (P < 0.05) for disease-free survival (hazard ratio , 4.3; 95% confidence interval (CI), 2.3–7.8), distant disease-free survival (HR, 6.6; 95% CI, 2.9–14.6), MSS (HR, 6.2; 95% CI, 2.6–14.4), and OS (HR, 2.8; 95% CI, 1.6–4.9).

Conclusion

The multimarker qRT assay has prognostic significance for molecular upstaging of PE melanoma-draining SLNs. Molecular upstaging of histopathology-negative SLNs confers a prognosis similar to that associated with SLN micrometastasis, and the number of positive qRT biomarkers is correlated to disease outcome.

The undisputed prognostic significance of lymph node involvement in melanoma1,2 led to the development of sentinel lymphadenectomy (SLND), pioneered by our group.3 This minimally invasive technique selectively samples the first nodes on the most likely path of lymphatic spread from a primary cutaneous melanoma.4,5 Excised sentinel lymph nodes (SLNs) are subjected to pathologic ultrastaging, during which multiple fine sections of each SLN are examined by both hematoxylin and eosin (H&E) and melanoma-specific immunohistochemistry (IHC).4 The SLND is generally considered the standard of care for the staging of clinically localized melanoma,6,7 and management based on SLND can affect clinical outcome.8

However, current histopathologic analysis of the SLN has limitations. The IHC staining of serial sections from the SLN can detect metastases missed by standard H&E staining of bivalved sections, but it still has a 15% to 25% rate of false negatives because of sampling error.9 Moreover, melanoma will recur in up to 30% of patients who have no histopathologic evidence of tumor in the SLN specimen.1012

For the last decade, our group has been developing and improving quantitative molecular techniques to complement and supplement histopathologic assessment of the SLN. In 2004, we reported that the detection of tumor-related messenger RNA (mRNA) by quantitative real-time reverse transcriptase–polymerase chain reaction (qRT) assay of paraffin-embedded (PE) SLNs can identify clinically relevant metastases that are missed by histopathology.13 In the present study, we report 10-year follow-up data and further analysis for the same cohort, with particular attention to patients with histopathology-negative SLNs. This is the first longitudinal study of survival based on qRT detection of PE SLN metastasis, and the first long-term data to confirm the prognostic significance of histopathology-negative, qRT-positive SLNs in patients with clinically localized melanoma.

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