Topics for Discussion What is a sentinel lymph node (SLN)? Utility - PowerPoint PPT Presentation

5/17/2013 Topics for Discussion What is a sentinel lymph node (SLN)? Utility of sentinel lymph biopsies: therapeutic or staging? Thin Melanoma and Sentinel Node Dissection Groin Mapping Superficial/Deep Current Treatment of Timing of Sentinel Node Procedure Cutaneous Melanoma What should you do with a positive sentinel lymph node (+) SLN? Carlos Corvera, M.D. Associate Professor of Surgery UC San Francisco Malignant Melanoma Surgical Treatment • Brief review of surgical treatment – Primary lesion • Lymph Regional nodes: – Regional LNs – Direct relationship b/w primary tumor thickness, and LN mets – Clinically (-) / normal LN’s controversial topic – LN’s mets are a poor prognostic sign. • Microscopic invasion is an important predictor • Management: AJCC clinical stage III of outcome – FNA , or open bx to confirm metastatic melanoma • Two systems: – If (+), --->a complete regional lymph node dissection – Clark’s levels-depth of invasion – Breslow’s thickness • Prognosis: (depends on # of + LN’s found) but • Breslow’s is approx. 20%-50% – More reproducible/ less subjective – Tumor thickness conveys more prognostic information 1

5/17/2013 Clinically Normal Lymph Sentinel Lymph Node Nodes Biopsy • Thin (<1mm) Melanoma: – in situ , 0.5 cm margin is enough Elective Lymph Node Dissection (ELND) standard of – low rate of LN involvement (<5%) care prior to 1990’s – Wide excision of primary with at least 1-cm margin • Intermediate (1-4mm) -assoc. 20-25% occult LN metastasis Randomized trials failed to show survival benefit – 2cm excision margin, procedure considered outpt. with ELND • Trials: elective vs therapeutic LN dissection – No survival difference. Standard of care drifted towards observation of – These results argue against elective regional nodal basins • Thick (>4mm) – Increased risk of regional metastasis – Increased incidence occult systemic at Dx. – Exc. With 2 cm margin Therapy vs Staging Background Management of early stage Melanoma- controversy. Hypothesis: 1977 Cabanas Lymphatic mapping for penile cancer Primary--->Reg. LN’s----->Distant sites Delayed LND vs. Elective LND 1992 Morton fine-tuned and developed SLN SLN approach: Morton et al. 1992 technique with accurate staging and decreased morbidity 223 pts. ID’ed SLN in 194 pts(82%) A complete LND was performed in all cases *only 2/194 (1%) were mets found in non-SLN’s Continued controversy of “standard of care” 2

5/17/2013 Lymphatic Mapping and Sentinel Therapy vs Staging Lymphadenectomy in Melanoma Morton’s results indicate that the SLN histology is representative of the remaining nodal basin. Therefore, nodal staging could be completed by SLN bx alone. Currently, identification of SLN ~98% Lymphatic Mapping Lymphatic Mapping Lymphatic Mapping Lymphatic Mapping Lymphatic Mapping Pre-op lymphoscintigraphy Inject 0.5-0.8 mCi Image documents drainage patterns 3

5/17/2013 Locating the Sentinel Node Sentinel Node Recording Ex-vivo Count 4

5/17/2013 Recording Background Wide Local Excision of Primary Lesion Staging? Sentinel Lymph Node Status Gershenwald et al. Reto, study 612 pts. Compared with (+)SLN, Stage I and II. 1991-1995 a (-)SLN was associated Reviewed effects on tumor thickness, with 58.6% and 38. 5% ulceration, Clark level , location, and SLN increase in DFS and DSS status on dz-free survival 580 pts (95%) successful SLN bx. The presence of positive SLN positive=85 pts (15%) SLN is the most SLN negative=495pts (85%) important predictor of recurrence and survival. SLN status was the most significant prognostic factor with respect to dz-free and dz-specific survival Gershenwald et al., Jounal of Clinical Oncology, Vol 17, No.3 (March), 1999: pp 976-983 5

5/17/2013 Therapeutic? MSLT-I Multicenter Selective Lymphadenectomy Trial Essner et. al. - matched paired analysis Intermediate 534 pts. LM, SL, SCLND vs ELND thickness N=1269 Equivalent 5yr. Rates of dz-free survival and overall survival No signif. Difference in recurrence WE +Immediate WE + Observation SLNB 40% 60% Conclusion: Sentinel Node is Node negative therapeutically equivalent to ELND Regional recurrence Node positive Observation CLND Observe CLND MSLT-I MSLT-I 16% of pts undergoing SLN had positive node Median follow-up 5 yrs 3.4% of SLN “negative” pts recurred in nodal basin No overall survival benefit 15.6% in Observation arm had nodal relapse Disease-free survival better in SLN group 78.3% vs. 73.1% (p=0.009) 19.4% total in SLN group vs 15.6% observation Among patients with nodal metastasis* Removing unnecessary microscopic disease w/SLN SLN with CLND 72.3% 5yr overall survival Observation with CLND at time of clinical disease 52.4% 5yr overall survival 6

5/17/2013 Case #1 Thin Melanoma Long-term follow-up of patients with lesions < 1.0mm 39 yo male Most do well with wide excision alone 3-4 % will have recurrence Lower extremity melanoma 0.8mm What factors may predict for SLN positivity Clark level IV Breslow depth Clark level No ulceration Ulceration Mitotic rate >0 Age Male gender Wide excision alone? SLN? Primary tumor site Presence of regression JWCI Experience Results 1732 pts Univariate analysis Multivariate analysis Breslow depth < 1.0mm Sex p< 0.001 Sex (male nearly 4x higher risk) Breslow thickness p< 0.001 Wide excision alone (1cm margin) Clark level p< 0.001 Breslow thickness Age (< 50, >50) p=0.08 Age (grouped <30, 30-39, 40- Prognostic variables 49, 50-59, 60-69, >70) Breslow depth Risk decreased as age Clark level Breslow thickness increased Ulceration <0.25mm = 0% Primary tumor site 0.26-0.50mm = 1.1% Nomogram developed based Age 0.51-0.75mm = 4.3% on age, thickness, sex Sex 0.76-0.99mm = 8.5% Risk varies from 0.1% to 17.4% Morton et al., Arch Surg, 2010 Morton et al., Arch Surg, 2010 7

5/17/2013 High Risk Features Reliability of Lymphatic Mapping After Wide Local Excision of Cutaneous Melanoma, Ariyan et al ., Ann Surg Oncol , 2007 Ulceration Lymphoscintigraphy and Sentinel Node Biopsy Acurately Stage Increased mitotic rate Melanoma in Patients Presenting After Wide Local Excision, Evans et al ., Ann Surg Oncol , 2003 Angiolymphatic invasion Previous Wide Local Excision of Primary Melanoma Is Not Contraindicated for Sentinel Node Biopsy of the Trunk and Patients with thin Melanoma with these high risk Extremity, McCready et al ., J Surg Onc , 2003 features should undergo WLE + SLN Bx Single channel draining 2 nodes- Case #1 Superficial and deep? 39 yo male Lower extremity melanoma 0.8mm Clark level IV No ulceration Wide excision alone? SLN? Nomogram predicts 14% 8

5/17/2013 superficial node Deep node below inguinal ligament pelvis Indications for Pelvic SLN/ Sentinel Node Dissection Complete Dissection Superficial node only Deep SLNB if separate lymphatic channel Pelvic dissection if superficial SLN positive? 4 or more positive inguinal nodes identified Superficial node and Deep node Gross inguinal disease identified during groin dissection Pelvic nodal metastases identified clinically or If Superficial node positive? radiographically Extent of completion dissection? Lymphoscintigraphic drainage into pelvis that was not biopsied during original SLN (case specific) 9

5/17/2013 Case #2 Case #2 Lymphatic Mapping by SPEC Lymphatic Mapping by SPEC Lymphatic Mapping by SPEC Lymphatic Mapping by SPEC 71 yo male with melanoma of Right arm 8.3 mm Breslow Depth Clark level IV No ulceration Mitotic rate = 0 Clinically node negative Is there a benefit to SLNB in patients with Case #2 T4 melanoma? Sabel et al., Cancer 2009 Single institution review Wide Local Excision & Wide Local Excision & SLNBx Wide Local Excision & Wide Local Excision & SLNBx SLNBx SLNBx 227 pts with T4 melanoma underwent SLNB 107 (47%) positive Angiolymphatic invasion and ulceration strongest predictors of nodal involvement Median f/u 43 months 10

5/17/2013 SLNB and T4 Melanoma SLNB and T4 Melanoma Localregional recurrence rate (LRR) overall 22% Patients T4 melanoma, SLN-, no ulceration* SLN- LLR = 11% DDFS = 95% SLN+ LLR = 34% OS= 90% Distant disease-free survival (DDFS) at 5 years Patients T4 SLN-, WITH ULCERATION SLN- DDFS = 85.3% SLN+ DDFS = 47.8% HR = 5.78 for DDFS Overall survival (OS) SLN- OS = 80% * Most did not receive adjuvant Interferon SLN+ OS = 47% T4 and Beyond ! CONCLUSIONS Clinically node negative T4 pts should be offered SLNB SLN status is the most significant prognostic sign among these patients T4 patients with negative SLN in the absence of ulceration have an excellent prognosis and should not be considered candidates for adjuvant Interferon 11

5/17/2013 Recurrent Disease Postoperative 8 Weeks 18 months PREOPERATIVE STAGING Advanced Scalp Melanoma Large Nodal Metastasis Case Presentation 62 Year-old man Guard at our Cancer Center. Noticed enlarging ulcerating mass on the top of his head. MRI PET 12

5/17/2013 PREOPERATIVE MR IMAGING OPERATIVE PLANNING OPERATIVE PLANNING Operation 13

5/17/2013 In-transit Metastases Laser Treatment Unfavorable outcomes 5 year survival rates ~ 25-30 % Treatments: • Excision to clear margin when possible • Alternative: Isolated Limb Perfusion • Laser Treatment • Amputation (rare) Recurrent Refractory Advanced In-transit Melanoma Melanoma 14