Precision Surgery for Melanoma

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1 Precision Surgery for Melanoma Giorgos C. Karakousis, M.D. Assistant Professor of Surgery Perelman School of Medicine at the University of Pennsylvania

2 Background 87,110 cases of melanoma estimated in 2017* 15% 85% Localized Nonlocalized Management of localized melanoma typically involves wide excision ± sentinel lymph node (SLN) biopsy Surveillance and Epidemiology and End Results Program (SEER)

3 Clinical Stage Localized Melanoma Melanoma with Regional Spread Melanoma with Distant Spread I and II III IV

4 EARLY STAGE DISEASE (CLINICAL STAGE I, II)

5 Diagnosing melanoma Evolving lesion

6 Acral lentiginous melanoma

7 After localized melanoma is diagnosed Referral for surgical evaluation Evaluation includes a thorough history and physical Satellitosis In-transit disease Swollen lymph nodes The type and extent of surgery will be determined by pathologic characteristics of the primary tumor and physical exam findings

8 Pathologic characteristics of primary tumor Thickness Ulceration Satellitosis Lymphovascular invasion Mitotic Index Perineural invasion Tumor infiltrating lymphocytes Regression Clark Level *Clark level should not be confused with stage of melanoma

9 Margins of Wide Excision Tumor Thickness Recommended Clinical Margins In situ 5 mm-1.0 cm (1/5-2/5 inch) 1.0 mm (T1) 1 cm (2/5 inch) mm (T2) 1-2 cm mm (T3) 2 cm (4/5 inch) > 4 mm (T4) 2 cm (4/5 inch) NCCN guidelines

10 Wide Excision Primary closure Skin graft

11 Wide Excision Keystone flap closure Abraham et al Clinics in Plastic Surgery 44 (2) 2017

12 Sentinel Lymph Node (SLN) Biopsy What is it? How is it done? For whom is it recommended?

13 Sentinel Lymph Node (SLN) Biopsy SLN Biopsy is a staging procedure that allows for the detection of microscopic spread of a melanoma at its earliest stages using dyes that get taken up by the lymphatics and travel to and get taken up by lymph nodes, mimicking the path of tumor spread. The procedure in essence gives a roadmap of likely areas of tumor spread.

14 SLN Biopsy Why do it? Primary reason: Prognosis (Gives us more information about the tumor) Who should get the procedure? Melanoma >1.00 mm Selectively for melanomas 1.00 mm mm with adverse features (mitogenic, ulceration)

15 Surgery for Regional Spread of Disease STAGE III DISEASE

16 What next if the SLN has cancerous cells? Standard approach after positive SLN is found is to remove the remainder of lymph nodes in the lymph node basin since the likelihood of a finding additional cancerous nodes is about 15-20% While completion lymphadenectomy has been the standard approach for patients with + SLN, a randomized trial has just been completed to determine the benefit of this approach Lymph nodes Lymph nodes Completion LN dissection Ultrasound

17 In-transit disease In-transit disease is when there are metastatic melanoma deposits beyond 2 cm from the primary melanoma but not in the immediate draining regional nodal basin Patient with in transit melanoma of the right thigh Courtesy of Dr. D.L. Fraker

18 Isolated limb perfusion (ILP) ILP is a technique that involves surgical isolation of the blood vessels to the arm or leg with in-transit melanoma for the administration of chemotherapy at doses much higher than could be given to the whole body. Courtesy of Dr. D.L. Fraker

19 Isolated limb infusion ILI is a technique is a less invasive method for administering regional therapy by a percutaneous approach not requiring a surgical incision. ILI New approaches to combining regional and systemic therapies are being investigated Beasley et al. J Am Coll Surgeons2009; 208 (5):

20 Surgery for Distant Spread of Disease STAGE IV DISEASE

21 Surgery for Distant Spread of Disease Liver Lung Small bowel

22 Surgery for Distant Spread of Disease Recovery time from these surgeries depends upon the surgery performed Role and timing of surgery in patients with advanced disease in the context of systemic therapies (targeted or immune therapies, chemotherapy)

23 Surgery for Distant Spread of Disease Decision for surgery takes into account the history and burden and sites of disease as well consideration for possible systemic or whole body therapy options Multidisciplinary approach

24 New Effective Drugs for Melanoma Immune checkpoint inhibitors Targeted therapies Alcala, Flaherty et al Clinical Cancer Research 2012

25 Precision Surgery

26 New emerging technologies in SLN biopsy Newer dyes (indocyanine green, Lymphoseek) Hybrid SPECT/CT for 3-D nuclear imaging localization of sentinel nodes More sensitive probes Dynamic (intra-operative) lymphoscintigraphy machines Olmos et al.

27 Imaging to find early responses to treatment PET/CT Research

28 Precision Surgery Center Making tumors glow to more easily identify them at time of surgery Dr. Sunil Singhal (Thoracic Surgery) Dr. Tom Guzzo (Urology) Dr. John Lee (Neurosurgery)

29 Developing more specific dyes to find melanoma cells

30 Photoacoustic imaging 2X 40X

31 What it s all about Surgery safer More precise Sparing normal tissue Easier recovery

32 Thank you for your attention

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