1. SENTINEL LYMPH NODE BIOPSY FOR MELANOMA AMERICAN SOCIETY OF CLINICAL ONCOLOGY AND SOCIETY OF SURGICAL ONCOLOGY JOINT CLINICAL PRACTICE GUIDELINE

2. www.asco.org/guidelines/snbmelanomawww.asco.org/guidelines/snbmelanoma ©American Society of Clinical Oncology 2011. All rights reserved. Introduction Population: patients with newly diagnosed melanoma Metastases to regional lymph nodes most important prognostic factor in early-stage melanoma –Occur in 20% of patients with intermediate-thickness tumors (1-4 mm Breslow thickness) Sentinel lymph node (SLN) biopsy is accurate in staging regional nodes and has low morbidity Previous studies – Multicenter Selective Lymphadenectomy Trial I (MLST I) and Sunbelt Melanoma Trial –SLN biopsy vs. nodal observation – no difference in melanoma- specific survival (MLST I) –Positive SLN followed by complete lymph node dissection (CLND) – benefit in melanoma-specific survival, prolonged disease-free survival, decreased risk of recurrence

3. www.asco.org/guidelines/snbmelanomawww.asco.org/guidelines/snbmelanoma ©American Society of Clinical Oncology 2011. All rights reserved. Abbreviations SLN: sentinel lymph node CLND: complete lymph node dissection PSM: proportion of patients successfully mapped PVP: predictive value positive PVN: predictive value negative PTPN: post-test probability negative (1-PVN) FNR: false-negative rate (false negative/[true positive + false negative])

4. www.asco.org/guidelines/snbmelanomawww.asco.org/guidelines/snbmelanoma ©American Society of Clinical Oncology 2011. All rights reserved. Guideline Methodology: Systematic Review ASCO and Society of Surgical Oncology (SSO) convened an Expert Panel to review relevant medical literature Systematic review –Date parameters: January 1990-August 2011 –Databases searched: MEDLINE EMBASE –ASCO and SSO Annual Meeting proceedings 2006-2011 searched Meta-analysis completed (Valsecchi et al, JCO, 2011)

5. www.asco.org/guidelines/snbmelanomawww.asco.org/guidelines/snbmelanoma ©American Society of Clinical Oncology 2011. All rights reserved. Limitations of the literature Only one randomized clinical trial that addresses whether patients with melanoma managed using SLN biopsy have better clinical outcomes than those managed any other way –Multicenter Lymphadenectomy Trial I (MLST I) Systematic review, by necessity, included observational studies –Cohort studies (SLN biopsy with or without CLND) Significant variability across studies (e.g., in techniques used)

6. www.asco.org/guidelines/snbmelanomawww.asco.org/guidelines/snbmelanoma ©American Society of Clinical Oncology 2011. All rights reserved. Clinical Questions 1.What are the indications for sentinel lymph node biopsy? 2.What is the role of completion lymph node dissection?

7. www.asco.org/guidelines/snbmelanomawww.asco.org/guidelines/snbmelanoma ©American Society of Clinical Oncology 2011. All rights reserved. Recommendation 1 What are the indications for sentinel lymph node biopsy? Intermediate-thickness melanomas. SLN biopsy is recommended to patients with intermediate-thickness cutaneous melanomas (1 to 4 mm Breslow thickness) of any anatomic site. Routine use of SLN biopsy in this population provides accurate staging, with high estimates for PSM, and acceptable estimates for FNR, PTPN, and PVP. (continued on next slide)

8. www.asco.org/guidelines/snbmelanomawww.asco.org/guidelines/snbmelanoma ©American Society of Clinical Oncology 2011. All rights reserved. Recommendation 1, cont’d Thick melanomas. While there are few studies focusing specifically on patients with thick melanomas (T4; > 4 mm Breslow thickness), the use of SLN biopsy in this population may be recommended for staging purposes and to facilitate regional disease control. Thin melanoma. There is insufficient evidence to support routine SLN biopsy for patients with thin melanoma (T1; < 1 mm Breslow thickness), although it may be considered in selected cases with high risk features, when the benefits of pathologic staging may outweigh the potential risks of the procedure. Such risk factors may include ulceration or mitotic rate ≥ 1/mm 2, especially in the subgroup of patients with Breslow thickness 0.75 mm to 0.99 mm.

9. www.asco.org/guidelines/snbmelanomawww.asco.org/guidelines/snbmelanoma ©American Society of Clinical Oncology 2011. All rights reserved. Recommendation 2 What is the role of completion lymph node dissection? Recommendation CLND is recommended for all patients with a positive SLN biopsy. CLND achieves regional disease control, although whether or not CLND following a positive SLN biopsy improves survival is the subject of the ongoing Multicenter Selective Lymphadenectomy Trial II (MSLT II).

10. www.asco.org/guidelines/snbmelanomawww.asco.org/guidelines/snbmelanoma ©American Society of Clinical Oncology 2011. All rights reserved. PATIENT AND CLINICIAN COMMUNICATION Patient counseling is essential for informed decision-making Key question: What additional information necessary to guide a choice of treatment will SLN biopsy likely provide? Conduct an open dialogue that: –Discusses scientific evidence (in lay terms) –Weighs individual risks with potential harms and benefits –Considers patient values and preferences Consider Using ASCO Treatment Plan Template on asco.org. {http://www.asco.org/ASCOv2/Practice+%26+Guidelines/Quality+Care/Quality+Meas urement+%26+Improvement/Chemotherapy+Treatment+Plan+and+Summary/Cancer +Treatment+Plan+and+Summary+Resources}asco.orghttp://www.asco.org/ASCOv2/Practice+%26+Guidelines/Quality+Care/Quality+Meas urement+%26+Improvement/Chemotherapy+Treatment+Plan+and+Summary/Cancer +Treatment+Plan+and+Summary+Resources

11. www.asco.org/guidelines/snbmelanomawww.asco.org/guidelines/snbmelanoma ©American Society of Clinical Oncology 2011. All rights reserved. Future Directions Determining precise criteria for patient selection for SLN biopsy. Determining whether early identification of metastases in the SLN improves survival or is just “lead time bias.” Identifying criteria for individualized risks best inform appropriate risk stratification for patients at high risk for relapse, and those for whom CLND and/or adjuvant therapy are suitable. Establishing the role of prognostic markers from primary melanoma and SLN for appropriate risk stratification. Development of prediction-based models to aid in individualized decision-making.

12. www.asco.org/guidelines/snbmelanomawww.asco.org/guidelines/snbmelanoma ©American Society of Clinical Oncology 2011. All rights reserved. The Bottom Line Intervention SLN biopsy for patients with newly diagnosed melanoma Target Audience Surgical Oncologists, Medical Oncologists, Dermatologists, Primary Care Physicians, Pathologists, Nuclear Medicine Specialists Key Recommendations Intermediate-thickness melanomas: SLN biopsy is recommended to patients with cutaneous melanomas with 1 to 4 mm Breslow thickness of any anatomic site. Thick melanomas: SLN biopsy may be recommended for staging purposes and to facilitate regional disease control for patients with melanomas that are T4 or > 4 mm Breslow thickness. Thin melanomas: There is insufficient evidence to support SLN biopsy for patients with melanomas that are T1 or < 1mm Breslow thickness, although it may be considered in selected high-risk cases. Completion lymph node dissection is recommended for all patients with a positive SLN biopsy. Methods An Expert Panel was convened to develop guideline recommendations based on their review of evidence from a systematic review of the medical literature.

13. www.asco.org/guidelines/snbmelanomawww.asco.org/guidelines/snbmelanoma ©American Society of Clinical Oncology 2011. All rights reserved. Guideline Methodology: Panel Members Panel MembersAffiliation/Institution Sandra L. Wong, MD, Co-ChairUniversity of Michigan Gary H. Lyman, MD, MPH, Co-Chair Duke University Sanjiv S. Agarwala, MDSt. Luke’s Cancer Center Timothy J. Akhurst, MDPeter MacCallum Cancer Institute Charles M. Balch, MDUniversity of Texas Southwestern Alistair Cochran, MD UCLA Center for Health Services Janice N. Cormier, MD, MPH University of Texas MD Anderson Cancer Center Mark Gorman National Coalition for Cancer Survivorship Theodore Y. Kim, DO, MS Skagit Valley Regional Cancer Center

14. www.asco.org/guidelines/snbmelanomawww.asco.org/guidelines/snbmelanoma ©American Society of Clinical Oncology 2011. All rights reserved. Guideline Methodology: Panel Members, cont’d Panel MembersAffiliation/Institution Kelly McMasters, MD, PhD University of Louisville R. Dirk Noyes, MD Huntsman Cancer Institute Lynn Mara Schuchter, MD University of Pennsylvania Matias E. Valsecchi, MD Thomas Jefferson University Donald L. Weaver, MD University of Vermont College of Medicine

15. www.asco.org/guidelines/snbmelanomawww.asco.org/guidelines/snbmelanoma ©American Society of Clinical Oncology 2011. All rights reserved. Additional ASCO Resources The Executive Summary of the full Guideline includes the clinical questions, recommendations, a brief summary of the literature, and discussions. (JCO and the Annals of Surgical Oncology jointly published this.) The full Guideline (which includes a comprehensive discussion of the literature, a description of the methodology, and a complete reference list), along with a Data Supplement, an Appendix, and clinical tools and resources, can be found at http://www.asco.org/guidelines/snbmelanoma or online at the SSO website http://www.asco.org/guidelines/snbmelanoma SSO Meta-analysis and systematic review was published (Valsecchi ME, Silbermins D, de Rosa N, et al: Lymphatic mapping and sentinel lymph node biopsy in patients with melanoma: a meta-analysis. J Clin Oncol 29:1479-87, 2011) A patient guide is available at http://www.cancer.net http://www.cancer.net

16. www.asco.org/guidelines/snbmelanomawww.asco.org/guidelines/snbmelanoma ©American Society of Clinical Oncology 2011. All rights reserved. ASCO Guidelines This resource is a practice tool for physicians based on an ASCO® practice guideline. The practice guideline and this presentation are not intended to substitute for the independent professional judgment of the treating physician. Practice guidelines do not account for individual variation among patients and may not reflect the most recent evidence. This presentation does not recommend any particular product or course of medical treatment. Use of the practice guideline and this resource is voluntary. The full practice guideline and additional information are available at http://www.asco.org/guidelines/snbmelanoma. Copyright © 2012 by American Society of Clinical Oncology®. All rights reserved.