Anja Ulmer1, Klaus Dietz2, Melanie Werner-Klein3, Hans-Martin Häfner4, Claudia Schulz5, Philipp Renner6, Florian Weber7, Helmut Breuninger8, Martin Röcken9, Claus Garbe10, Gerhard Fierlbeck11, Christoph A Klein12. 1. Department of Dermatology, University of Tübingen, 72076 Tübingen, Germany. Electronic address: Anja.Ulmer@med.uni-tuebingen.de. 2. Department of Medical Biometry (Emeritus), University of Tübingen, Silcherstr. 5, 72076 Tübingen, Germany. Electronic address: klaus.dietz@uni-tuebingen.de. 3. Regensburg Center for Interventional Immunology (RCI) and University Medical Center of Regensburg, Franz-Josef Strauß Allee 11, 93053 Regensburg, Germany. Electronic address: melanie.werner-klein@ukr.de. 4. Department of Dermatology, University of Tübingen, 72076 Tübingen, Germany. Electronic address: hans-martin.haefner@med.uni-tuebingen.de. 5. Department of Dermatology, University of Tübingen, 72076 Tübingen, Germany. Electronic address: claudia.schulz@med.uni-tuebingen.de. 6. Department of Surgery, University Medical Center of Regensburg, Franz-Josef Strauß Allee 11, 93053 Regensburg, Germany. Electronic address: philipp.renner@ukr.de. 7. Institute of Pathology, University of Regensburg, Franz-Josef Strauß Allee 11, 93053 Regensburg, Germany. Electronic address: Florian.Weber@klinik.uni-regensburg.de. 8. Department of Dermatology, University of Tübingen, 72076 Tübingen, Germany. Electronic address: helmut.breuninger@med.uni-tuebingen.de. 9. Department of Dermatology, University of Tübingen, 72076 Tübingen, Germany. Electronic address: Martin.Roecken@med.uni-tuebingen.de. 10. Department of Dermatology, University of Tübingen, 72076 Tübingen, Germany. Electronic address: claus.garbe@med.uni-tuebingen.de. 11. Department of Dermatology, University of Tübingen, 72076 Tübingen, Germany. Electronic address: gerhard.fierlbeck@med.uni-tuebingen.de. 12. Experimental Medicine and Therapy Research, University of Regensburg, Franz-Josef Strauß Allee 11, 93053 Regensburg, Germany; Fraunhofer Institute of Toxicology and Experimental Medicine Regensburg ITEM-R, Division Personalized Tumour Therapy, Am Biopark 9, Regensburg, 93053, Germany. Electronic address: christoph.klein@ukr.de.
Abstract
INTRODUCTION: Complete lymph node dissection (CLND) after a positive sentinel node (SN) biopsy provides important prognostic information in melanoma patients but has been questioned for therapeutic use recently. We explored whether quantification of the tumour spread to SNs may replace histopathology of non-sentinel nodes (NSNs) for staging purposes. PATIENTS AND METHODS: We quantified melanoma spread in SNs and NSNs in 128 patients undergoing CLND for a positive SN. In addition to routine histopathology, one-half of each of all 1496 SNs and NSNs was disaggregated into a single cell suspension and stained immunocytochemically to determine the number of melanoma cells per 106 lymph node cells, i.e. the disseminated cancer cell density (DCCD). RESULTS: We uncovered melanoma spread to NSNs in the majority of patients; however, the tumour load and the proportion of positive nodes were significantly lower in NSNs than in SNs. The relation between SN and NSN spread could be described by a mathematical function with DCCDNSN = DCCDSNc/101-c (c = 0.69; 95% confidence interval [CI]: 0.62-0.76). At a median follow-up of 67 months, multivariable Cox regression analyses revealed that DCCDSN (p = 0.02; HR 1.34, 95% CI: 1.05-1.71) and the total number of pathologically positive nodes (p = 0.02; HR 1.53, 95% CI: 1.07-2.22) were significant risk factors after controlling for age, gender, thickness of melanoma and ulceration status. A prognostic model based on DCCDSN and melanoma thickness predicted outcome as accurately as a model including pathological information of both SNs and NSNs. CONCLUSION: The assessment of DCCDSN renders CLND for staging purposes unnecessary.
INTRODUCTION: Complete lymph node dissection (CLND) after a positive sentinel node (SN) biopsy provides important prognostic information in melanomapatients but has been questioned for therapeutic use recently. We explored whether quantification of the tumour spread to SNs may replace histopathology of non-sentinel nodes (NSNs) for staging purposes. PATIENTS AND METHODS: We quantified melanoma spread in SNs and NSNs in 128 patients undergoing CLND for a positive SN. In addition to routine histopathology, one-half of each of all 1496 SNs and NSNs was disaggregated into a single cell suspension and stained immunocytochemically to determine the number of melanoma cells per 106 lymph node cells, i.e. the disseminated cancer cell density (DCCD). RESULTS: We uncovered melanoma spread to NSNs in the majority of patients; however, the tumour load and the proportion of positive nodes were significantly lower in NSNs than in SNs. The relation between SN and NSN spread could be described by a mathematical function with DCCDNSN = DCCDSNc/101-c (c = 0.69; 95% confidence interval [CI]: 0.62-0.76). At a median follow-up of 67 months, multivariable Cox regression analyses revealed that DCCDSN (p = 0.02; HR 1.34, 95% CI: 1.05-1.71) and the total number of pathologically positive nodes (p = 0.02; HR 1.53, 95% CI: 1.07-2.22) were significant risk factors after controlling for age, gender, thickness of melanoma and ulceration status. A prognostic model based on DCCDSN and melanoma thickness predicted outcome as accurately as a model including pathological information of both SNs and NSNs. CONCLUSION: The assessment of DCCDSN renders CLND for staging purposes unnecessary.
Authors: Michael B Atkins; Clara Curiel-Lewandrowski; David E Fisher; Susan M Swetter; Hensin Tsao; Julio A Aguirre-Ghiso; Maria S Soengas; Ashani T Weeraratna; Keith T Flaherty; Meenhard Herlyn; Jeffrey A Sosman; Hussein A Tawbi; Anna C Pavlick; Pamela B Cassidy; Sunandana Chandra; Paul B Chapman; Adil Daud; Zeynep Eroglu; Laura K Ferris; Bernard A Fox; Jeffrey E Gershenwald; Geoffrey T Gibney; Douglas Grossman; Brent A Hanks; Douglas Hanniford; Eva Hernando; Joanne M Jeter; Douglas B Johnson; Samir N Khleif; John M Kirkwood; Sancy A Leachman; Darren Mays; Kelly C Nelson; Vernon K Sondak; Ryan J Sullivan; Glenn Merlino Journal: Clin Cancer Res Date: 2021-01-07 Impact factor: 13.801