15 september 2021: lees ook dit artikel: https://kanker-actueel.nl/op-biopsie-gebaseerde-behandelingen-verlengt-de-ziektevrije-overleving-voor-patienten-met-een-melanoom-overall-overleving-tussen-biopt-en-standaard-lymfklieren-weghalen-geeft-geen-verschil.html

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*
Author information ► Copyright and License information ► Disclaimer
Go to:

Abstract

Go to:

Objective

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

Go to:

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.

Go to:

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.

Go to:

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).

Go to:

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.10–12

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.

References:

  1. International Agency for Research on Cancer. Malignant melanoma of the skin. http://eco.iarc.fr/eucan/Cancer.aspx?Cancer=20#block-table-a. [Site Accessed 19 March 2017]..
  3. Balch, C.M., Gershenwalk, J.E., Soong, S.J. et al, Final version of 2009 AJCC melanoma staging and classification. J Clin Oncol. 2009;27:6199–6206.
  4. Moody, J.A., Ali, R.F., Carbone, A.C., Singh, S., Hardwicke, J.T. Complications of sentinel lymph node biopsy for melanoma–a systematic review of the literature. Eur J Surg Onc. 2017;43:270–277.
  5. Morton, D.L., Thompson, J.F., Cochran, A.J. et al, Final trial report of sentinel-node biopsy versus nodal observation in melanoma. N Engl J Med. 2014;370:599–609.
  6. Cochran, A.J., Balda, B.R., Starz, H. et al, The Augsburg consensus. Techniques of lymphatic mapping, sentinel lymphadenectomy, and completion lymphadenectomy in cutaneous malignancies. Cancer. 2000;89:236–241.
  7. Pasquali, S., Spillane, A.J., de Wilt, J.H. et al, Surgeons' opinions on lymphadenectomy in melanoma patients with positive sentinel nodes: a worldwide web-based survey. Ann Surg Oncol. 2012;19:4322–4329.
  8. Bilimoria, K.Y., Balch, C.M., Bentrem, D.J. et al, Complete lymph node dissection for sentinel node-positive melanoma: assessment of practice patterns in the United States. Ann Surg Oncol. 2008;15:1566–1576.
  9. Hughes, T.M.D., A'Hern, R.P.A., Thomas, J.M. Prognosis and surgical management of patients with palpable inguinal lymph node metastases from melanoma. Br J Surg. 2000;87:892–901.
  10. Egberts, F., Hartje, C., Schafmayer, C. et al, Risk evaluation in cutaneous melanoma patients undergoing lymph node dissection: impact of POSSUM. Ann R Coll Surg Engl. 2011;93:514–522.
  11. Poos, H.P., Kruijff, S., Bastiaannet, E., van Ginkel, R.J., Hoekstra, H.J. Therapeutic groin dissection for melanoma: risk factors for short term morbidity. Eur J Surg Oncol. 2009;35:877–883.
  12. Namm, J.P., Chang, A.E., Cimmino, V.M., Rees, R.S., Johnson, T.M., Sabel, M.S. Is a level III dissection necessary for a positive sentinel lymph node in melanoma?. J Surg Oncol. 2012;105:225–228.
  13. Ul-Mulk, J., Hölmich, L.R. Lymph node dissection in patients with malignant melanoma is associated with high risk of morbidity. Dan Med J. 2012;59:A4441.
  14. Moher, D., Liberati, A., Tetzlaff, J., Altman, D.G. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Int J Surg. 2010;8:336–341.
  15. Slim, K., Nini, E., Forestier, D., Kwiatkowski, F., Panis, Y., Chipponi, J. Methodological index for non-randomised studies (MINORS): development and validation of a new instrument. ANZ J Surg. 2003;73:712–716.
  16. Detsky, A.S., Naylor, C.D., O'Rourke, K., McGeer, A.J., L'Abbé, K.A. Incorporating variations in the quality of individual randomized trials into meta-analysis. J Clin Epidemiol. 1992;45:255–265.
  17. Bhandari, M., Richards, R.R., Sprague, S., Schemitsch, E.H. The quality of reporting of randomized trials in the journal of bone and joint surgery from 1988 through 2000. J Bone Jt Surg Am. 2002;84A:388–396.
  18. Hardwicke, J.T., Bechar, J.A., Hodson, J., Osmani, O., Park, A.J. Fistula after single-stage primary hypospadias repair – a systematic review of the literature. J Plast Reconstr Aesthet Surg. 2015;68:1647–1655.
  19. Cochrane, W.G. The combination of estimates from different experiments. Biometrics. 1954;:101–129.
  20. DerSimonian, R., Laird, N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7:177–188.
  21. Freeman, M.F., Tukey, J.W. Transformations related to the angular and the square root. Ann Math Stat. 1950;21:607–611.
  22. Ahmed, A., Sadadcharam, G., Huisma, F. et al, Postoperative complications following nodal dissection and their association with melanoma recurrence. ISRN Surg. 2013;2013: 382138.
  23. Allan, C.P., Hayes, A.J., Thomas, J.M. Ilioinguinal lymph node dissection for palpable metastatic melanoma to the groin. ANZ J Surg. 2008;78:982–986.
  24. Bertheuil, N., Sulpice, L., Levi Sandri, G.B., Lavoué, V., Watier, E., Meunier, B. Inguinal lymphadenectomy for stage III melanoma: a comparative study of two surgical approaches at the onset of lymphoedema. Eur J Surg Oncol. 2015;41:215–219.
  25. Faries, M.B., Thompson, J.F., Cochran, A. et al, The impact on morbidity and length of stay of early versus delayed complete lymphadenectomy in melanoma: results of the Multicenter Selective Lymphadenectomy Trial (I). Ann Surg Oncol. 2010;17:3324–3329.
  26. Guggenheim, M.M., Hug, U., Jung, F.J. et al, Morbidity and recurrence after completion lymph node dissection following sentinel lymph node biopsy in cutaneous malignant melanoma. Ann Surg. 2008;247:687–693.
  27. Kretschmer, L., Thoms, K.M., Peeters, S., Haenssle, H., Bertsch, H.P., Emmert, S. Postoperative morbidity of lymph node excision for cutaneous melanoma-sentinel lymphonodectomy versus complete regional lymph node dissection. Melanoma Res. 2008;18:16–21.
  28. Leiter, U., Stadler, R., Mauch, C. et al, Complete lymph node dissection versus no dissection in patients with sentinel lymph node biopsy positive melanoma (DeCOG-SLT): a multicentre, randomised, phase 3 trial. Lancet Oncol. 2016;17:757–767.
  29. Sabel, M.S., Griffith, K.A., Arora, A. et al, Inguinal node dissection for melanoma in the era of sentinel lymph node biopsy. Surgery. 2007;141:728–735.
  30. Stoffels, I., Dissemond, J., Schulz, A., Hillen, U., Schadendorf, D., Klode, J. Reliability and cost-effectiveness of complete lymph node dissection under tumescent local anaesthesia vs. general anaesthesia: a retrospective analysis in patients with malignant melanoma AJCC stage III. J Eur Acad Dermatol Venereol. 2012;26:200–206.
  31. Theodore, J.E., Frankel, A.J., Thomas, J.M. et al, Assessment of morbidity following regional nodal dissection in the axilla and groin for metastatic melanoma. ANZ J Surg. 2017;87:44–48.
  32. van Akkooi, A.C., Bouwhuis, M.G., van Geel, A.N. et al, Morbidity and prognosis after therapeutic lymph node dissections for malignant melanoma. Eur J Surg Oncol. 2007;33:102–108.
  33. Wevers, K.P., Poos, H.P., van Ginkel, R.J., van Etten, B., Hoekstra, H.J. Early mobilization after ilio-inguinal lymph node dissection for melanoma does not increase the wound complication rate. Eur J Surg Oncol. 2013;39:185–190.
  34. Wrightson, W.R., Wong, S.L., Edwards, M.J. et al, Complications associated with sentinel lymph node biopsy for melanoma. Ann Surg Oncol. 2003;10:676–680.
  35. Morton, D.L., Wen, D.R., Wong, J.H. et al, Technical details of intraoperative lymphatic mapping for early stage melanoma. Arch Surg. 1992;127:392–399.
  36. Pasquali, S., Mocellin, S., Campana, L.G. et al, Early (sentinel lymph node biopsy-guided) versus delayed lymphadenectomy in melanoma patients with lymph node metastases: personal experience and literature meta-analysis. Cancer. 2010;116:1201–1209.
  37. Oude Ophuis, C.M., van Akkooi, A.C., Rutkowski, P. et al, Timing of completion lymphadenectomy after positive sentinel node biopsy in patients with melanoma. Br J Surg. 2017 Feb 20;
    DOI: https://doi.org/10.1002/bjs.10475
    ([Epub ahead of print]).
  38. Burke, E.E., Portschy, P.R., Tuttle, T.M., Kuntz, K.M. Completion lymph node dissection or observation for melanoma sentinel lymph node metastases: a decision analysis. Ann Surg Oncol. 2016;23:2772–2778.
Crown Copyright © 2017 Published by Elsevier Ltd. All rights reserved.

schildwachtkliermethode, sentinelmethode, melanomen, VUmc, meta-analyse, reviewstudie


Plaats een reactie ...

Reageer op "Schildwachtkliermethode - sentinelmethode bij melanomen voorlopig niet zinvol. Blijkt uit review van gerandomiseerde studies"


Gerelateerde artikelen
 

Gerelateerde artikelen

AI scanner ziet direct of >> Op biopsie gebaseerde behandelingen >> Schildwachtkliermethode - >> Diagnose: Melafind, een apparaat >> Diagnose melanomen: Kans op >> Diagnose melanomen: Vroegtijdig >>