Top

Published in:

01-08-2010 | Melanomas

Sentinel Node Positive Melanoma Patients: Prediction and Prognostic Significance of Nonsentinel Node Metastases and Development of a Survival Tree Model

Authors: Martin Wiener, MBChB, Katharine M. Acland, MRCP, Helen M. Shaw, PhD, Seng-Jaw Soong, PhD, Hui-Yi Lin, PhD, Dung-Tsa Chen, PhD, Richard A. Scolyer, MD, Julie B. Winstanley, PhD, CStat, John F. Thompson, MD

Published in: Annals of Surgical Oncology | Issue 8/2010

Abstract

Background

Completion lymph node dissection (CLND) following positive sentinel node biopsy (SNB) for melanoma detects additional nonsentinel node (NSN) metastases in approximately 20% of cases. This study aimed to establish whether NSN status can be predicted, to determine its effect on survival, and to develop survival tree models for the sentinel node (SN) positive population.

Materials and Methods

Sydney Melanoma Unit (SMU) patients with at least 1 positive SN, meeting inclusion criteria and treated between October 1992 and June 2005, were identified from the Unit database. Survival characteristics, potential predictors of survival, and NSN status were assessed using the Kaplan–Meier method, Cox regression model, and logistic regression analyses, respectively. Classification tree analysis was performed to identify groups with distinctly different survival characteristics.

Results

A total of 323 SN-positive melanoma patients met the inclusion criteria. On multivariate analysis, age, gender, primary tumor thickness, mitotic rate, number of positive NSNs, or total number of positive nodes were statistically significant predictors of survival. NSN metastasis, found at CLND in 19% of patients, was only predicted to a statistically significant degree by ulceration. Multivariate analyses demonstrated that survival was more closely related to number of positive NSNs than total number of positive nodes. Classification tree analysis revealed 4 prognostically distinct survival groups.

Conclusions

Patients with NSN metastases could not be reliably identified prior to CLND. Prognosis following CLND was more closely related to number of positive NSNs than total number of positive nodes. Classification tree analysis defined distinctly different survival groups more accurately than use of single-factor analysis.

Clark WH, Jr., From L, Bernardino EA, Mihm MC. The histogenesis and biologic behavior of primary human malignant melanomas of the skin. Cancer Res. 1969;29:705–27.PubMed

Breslow A. Thickness, cross-sectional areas and depth of invasion in the prognosis of cutaneous melanoma. Ann Surg. 1970;172:902–8.CrossRefPubMed

Balch CM, Soong SJ, Gershenwald JE, Thompson JF, Reintgen DS, Cascinelli N, et al. Prognostic factors analysis of 17,600 melanoma patients: validation of the American Joint Committee on Cancer melanoma staging system. J Clin Oncol. 2001;19:3622–34.PubMed

Azzola MF, Shaw HM, Thompson JF, Soong SJ, Scolyer RA, Watson GF, et al. Tumor mitotic rate is a more powerful prognostic indicator than ulceration in patients with primary cutaneous melanoma: an analysis of 3661 patients from a single center. Cancer. 2003;97:1488–98.CrossRefPubMed

Scoggins CR, Ross MI, Reintgen DS, Noyes RD, Goydos JS, Beitsch PD, et al. Gender-related differences in outcome for melanoma patients. Ann Surg. 2006;243:693–8; discussion 698–700.CrossRefPubMed

McMasters KM, Wong SL, Edwards MJ, Ross MI, Chao C, Noyes RD, et al. Factors that predict the presence of sentinel lymph node metastasis in patients with melanoma. Surgery. 2001;130:151–6.CrossRefPubMed

Kruper LL, Spitz FR, Czerniecki BJ, Fraker DL, Blackwood-Chirchir A, Ming ME, et al. Predicting sentinel node status in AJCC stage I/II primary cutaneous melanoma. Cancer. 2006;107:2436–45.CrossRefPubMed

Paek SC, Griffith KA, Johnson TM, Sondak VK, Wong SL, Chang AE, et al. The impact of factors beyond Breslow depth on predicting sentinel lymph node positivity in melanoma. Cancer. 2007;109:100–8.CrossRefPubMed

Gershenwald JE, Thompson W, Mansfield PF, Lee JE, Colome MI, Tseng CH, et al. Multi-institutional melanoma lymphatic mapping experience; the prognostic value of sentinel lymph node status in 612 stage I or II melanoma patients. J Clin Oncol. 1999;17:976–83.PubMed

10.

Morton DL, Thompson JF, Cochran AJ, Mozzillo N, Elashoff R, Essner R, et al. Sentinel-node biopsy or nodal observation in melanoma. N Engl J Med. 2006;355:1307–17.CrossRefPubMed

11.

Wagner JD, Gordon MS, Chuang TY, Coleman JJ 3rd, Hayes JT, Jung SH, et al. Predicting sentinel and residual lymph node basin disease after sentinel lymph node biopsy for melanoma. Cancer. 2000;89:453–62.CrossRefPubMed

12.

McMasters KM, Wong SL, Edwards MJ, Chao C, Ross MI, Noyes RD, et al. Frequency of nonsentinel lymph node metastasis in melanoma. Ann Surg Oncol. 2002;9:137–41.CrossRefPubMed

13.

Salti GI, Das Gupta TK. Predicting residual lymph node basin disease in melanoma patients with sentinel lymph node metastases. Am J Surg. 2003;186:98–101.CrossRefPubMed

14.

Reeves ME, Delgado R, Busam KJ, Brady MS, Coit DG. Prediction of nonsentinel lymph node status in melanoma. Ann Surg Oncol. 2003;10:27–31.CrossRefPubMed

15.

Cochran AJ, Wen DR, Huang RR, Wang HJ, Elashoff R, Morton DL. Prediction of metastatic melanoma in nonsentinel nodes and clinical outcome based on the primary melanoma and the sentinel node. Mod Pathol. 2004;17:747–55.CrossRefPubMed

16.

Lee JH, Essner R, Torisu-Itakura H, Wanek L, Wang H, Morton DL. Factors predictive of tumor-positive nonsentinel lymph nodes after tumor-positive sentinel lymph node dissection for melanoma. J Clin Oncol. 2004;22:3677–84.CrossRefPubMed

17.

Scolyer RA, Li LX, McCarthy SW, Shaw HM, Stretch JR, Sharma R, et al. Micromorphometric features of positive sentinel lymph nodes predict involvement of nonsentinel nodes in patients with melanoma. Am J Clin Pathol. 2004;122:532–9.CrossRefPubMed

18.

Starz H, Siedlecki K, Balda BR. Sentinel lymphonodectomy and s-classification: a successful strategy for better prediction and improvement of outcome of melanoma. Ann Surg Oncol. 2004;11:162S–8S.PubMed

19.

Dewar DJ, Newell B, Green MA, Topping AP, Powell BW, Cook MG. The microanatomic location of metastatic melanoma in sentinel lymph nodes predicts nonsentinel lymph node involvement. J Clin Oncol. 2004;22:3345–9.CrossRefPubMed

20.

Fink AM, Weihsengruber F, Spangl B, Feichtinger H, Lilgenau N, Rappersberger K, et al. S-classification of sentinel lymph node biopsy predicts the results of complete regional lymph node dissection. Melanoma Res. 2005;15:267–71.CrossRefPubMed

21.

Sabel MS, Griffith K, Sondak VK, Lowe L, Schwartz JL, Cimmino VM, et al. Predictors of nonsentinel lymph node positivity in patients with a positive sentinel node for melanoma. J Am Coll Surg. 2005;201:37–47.CrossRefPubMed

22.

Vuylsteke RJ, Borgstein PJ, van Leeuwen PA, Gietema HA, Molenkamp BG, Statius Muller MG, et al. Sentinel lymph node tumor load: an independent predictor of additional lymph node involvement and survival in melanoma. Ann Surg Oncol. 2005;12:440–8.CrossRefPubMed

23.

Pearlman NW, McCarter MD, Frank M, Hurtubis C, Merkow RP, Franklin WA, et al. Size of sentinel node metastases predicts other nodal disease and survival in malignant melanoma. Am J Surg. 2006;192:878–81.CrossRefPubMed

24.

Cascinelli N, Bombardieri E, Bufalino R, Camerini T, Carbone A, Clemente C, et al. Sentinel and nonsentinel node status in stage IB and II melanoma patients: two-step prognostic indicators of survival. J Clin Oncol. 2006;24:4464–71.CrossRefPubMed

25.

van Akkooi AC, de Wilt JH, Verhoef C, Schmitz PI, van Geel AN, Eggermont AM, et al. Clinical relevance of melanoma micrometastases (<0.1 mm) in sentinel nodes: are these nodes to be considered negative? Ann Oncol. 2006;17:1578–85.CrossRefPubMed

26.

Debarbieux S, Duru G, Dalle S, Beatrix O, Balme B, Thomas L. Sentinel lymph node biopsy in melanoma: a micromorphometric study relating to prognosis and completion lymph node dissection. Br J Dermatol. 2007;157:58–67.CrossRefPubMed

27.

Page AJ, Carlson GW, Delman KA, Murray D, Hestley A, Cohen C. Prediction of nonsentinel lymph node involvement in patients with a positive sentinel lymph node in malignant melanoma. Am Surg. 2007;73:674–8; discussion 678–9.PubMed

28.

Roka F, Mastan P, Binder M, Okamoto I, Mittlboeck M, Horvat R, et al. Prediction of non-sentinel node status and outcome in sentinel node-positive melanoma patients. Eur J Surg Oncol. 2008;34:82–8.PubMed

29.

Rossi CR, De Salvo GL, Bonandini E, Mocellin S, Foletto M, Pasquali S, et al. Factors predictive of nonsentinel lymph node involvement and clinical outcome in melanoma patients with metastatic sentinel lymph node. Ann Surg Oncol. 2008;15:1202–10.CrossRefPubMed

30.

Satzger I, Volker B, Meier A, Kapp A, Gutzmer R. Criteria in sentinel lymph nodes of melanoma patients that predict involvement of nonsentinel lymph nodes. Ann Surg Oncol. 2008;15:1723–32.CrossRefPubMed

31.

Gershenwald JE, Andtbacka RH, Prieto VG, Johnson MM, Diwan AH, Lee JE, et al. Microscopic tumor burden in sentinel lymph nodes predicts synchronous nonsentinel lymph node involvement in patients with melanoma. J Clin Oncol. 2008;26:4296–303.CrossRefPubMed

32.

Wrightson WR, Wong SL, Edwards MJ, Chao C, Reintgen DS, Ross MI, et al. Complications associated with sentinel lymph node biopsy for melanoma. Ann Surg Oncol. 2003;10:676–80.CrossRefPubMed

33.

Morton DL, Cochran AJ, Thompson JF, Elashoff R, Essner R, Glass EC, et al. Sentinel node biopsy for early-stage melanoma: accuracy and morbidity in MSLT-I, an international multicenter trial. Ann Surg. 2005;242:302–11; discussion 311–3.PubMed

34.

de Vries M, Vonkeman WG, van Ginkel RJ, Hoekstra HJ. Morbidity after inguinal sentinel lymph node biopsy and completion lymph node dissection in patients with cutaneous melanoma. Eur J Surg Oncol. 2006;32:785–9.CrossRefPubMed

35.

Morton DL. Sentinel node mapping and an International Sentinel Node Society: current issues and future directions. Ann Surg Oncol. 2004;11:137S–43S.PubMed

36.

Thompson JF, Uren RF. Teaching points on lymphatic mapping for melanoma from the Sydney Melanoma Unit. Semin Oncol. 2004;31:349–56.CrossRefPubMed

37.

Li LX, Scolyer RA, Ka VS, McKinnon JG, Shaw HM, McCarthy SW, et al. Pathologic review of negative sentinel lymph nodes in melanoma patients with regional recurrence: a clinicopathologic study of 1152 patients undergoing sentinel lymph node biopsy. Am J Surg Pathol. 2003;27:1197–202.CrossRefPubMed

38.

Scolyer RA, Li LX, McCarthy SW, Shaw HM, Stretch JR, Sharma R, et al. Immunohistochemical stains fail to increase the detection rate of micrometastatic melanoma in completion regional lymph node dissection specimens. Melanoma Res. 2004;14:263–8.CrossRefPubMed

39.

Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc. 1958;53:457–81.CrossRef

40.

Cox DR. Regression models and life tables (with discussion). J R Stat Soc. 1972;34:187–220.

41.

LeBlanc M, Crowley J. Relative risk trees for censored survival data. Biometrics. 1992;48:411–25.CrossRefPubMed

42.

Tsai CA, Chen DT, Chen JJ, Balch CM, Thompson JF, Soong SJ. An integrated tree-based classification approach to prognostic grouping with application to localized melanoma patients. J Biopharm Stat. 2007;17:445–60.CrossRefPubMed

43.

Jakub JW, Huebner M, Shivers S, Nobo C, Puleo C, Harmsen WS, et al. The number of lymph nodes involved with metastatic disease does not affect outcome in melanoma patients as long as all disease is confined to the sentinel lymph node. Ann Surg Oncol. 2009;16:2245–51.CrossRefPubMed

44.

Ariyan CE, Brady MS, Busam KJ, Coit DG 2008 Positive non-sentinel lymph node predicts mortality in cutaneous melanoma patients. Ann Surg Oncol. 2008;15(S2):10.

45.

Wong SL, Morton DL, Thompson JF, Gershenwald JE, Leong SP, Reintgen DS, et al. Melanoma patients with positive sentinel nodes who did not undergo completion lymphadenectomy: a multi-institutional study. Ann Surg Oncol. 2006;13:809–16.CrossRefPubMed

46.

Govindarajan A, Ghazarian DM, McCready DR, Leong WL. Histological features of melanoma sentinel lymph node metastases associated with status of the completion lymphadenectomy and rate of subsequent relapse. Ann Surg Oncol. 2007;14:906–12.CrossRefPubMed

47.

Huang X, Soong S, McCarthy WH, Urist MM, Balch CM. Classification of localized melanoma by the exponential survival trees method. Cancer. 1997;79:1122–8.CrossRefPubMed

Title: Sentinel Node Positive Melanoma Patients: Prediction and Prognostic Significance of Nonsentinel Node Metastases and Development of a Survival Tree Model
Authors: Martin Wiener, MBChB
Katharine M. Acland, MRCP
Helen M. Shaw, PhD
Seng-Jaw Soong, PhD
Hui-Yi Lin, PhD
Dung-Tsa Chen, PhD
Richard A. Scolyer, MD
Julie B. Winstanley, PhD, CStat
John F. Thompson, MD
Publication date: 01-08-2010
Publisher: Springer-Verlag
Published in: Annals of Surgical Oncology / Issue 8/2010
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI: https://doi.org/10.1245/s10434-010-1049-5

At a glance: The STEP trials

Springer Medicine

Sentinel Node Positive Melanoma Patients: Prediction and Prognostic Significance of Nonsentinel Node Metastases and Development of a Survival Tree Model

Abstract

Background

Materials and Methods

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Materials and Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 8/2010

Prognostic Significance of Perineural Invasion in Patients with Gastric Cancer Who Underwent Curative Resection

Biobanking of Human Pancreas Cancer Tissue: Impact of Ex-Vivo Procurement Times on RNA Quality

Loss of SFRP1 Expression is Associated with Aberrant β-Catenin Distribution and Tumor Progression in Mucoepidermoid Carcinoma of Salivary Glands

Soft Tissue Sarcoma of Extremities: The Prognostic Significance of Adequate Surgical Margins in Primary Operation and Reoperation After Recurrence

Risk of Varices Bleeding after Spleen-Preserving Distal Pancreatectomy with Excision of Splenic Artery and Vein

Impact of Diabetes Mellitus on the Prognosis of Patients with Oral Squamous Cell Carcinoma: A Retrospective Cohort Study