HEAD AND NECK MELANOMA & SENTINEL NODE BIOPSY. September 11, 2013 Jason A. Showmaker MD Robert P. Zitsch III, MD, FACS

Transcription

1 HEAD AND NECK MELANOMA & SENTINEL NODE BIOPSY September 11, 2013 Jason A. Showmaker MD Robert P. Zitsch III, MD, FACS

2 OBJECTIVES TNM Staging Prognostication Management of Regional Lymphatics Therapeutic Neck Dissection Elective Neck Dissection Lymphoscintigraphy and Sentinel Node Biopsy

3 TNM STAGING FOR MELANOMA T Tumor thickness Presence or absence of ulceration Mitotic rate N Number of nodes Micro vs Macrometastases Satellite lesions and in-transit metastases M Distant metastases LDH Level Balch CM, Gershenwald JE, Soong SJ, et al. Final version of 2009 AJCC melanoma staging and classification. J Clin Oncol 2009; 27:6199.

4 TNM STAGING FOR MELANOMA Tumor thickness (Breslow Depth) Increasing tumor thickness correlated with worse prognosis Measure from the thickest part of the lesion (WLE) T1: < or = 1.0mm (10-yr survival 89%) T2: mm T3: mm T4: >4.0 mm (10-yr survival 54%) Green AC, Baade P, Coory M, et al. Population-based 20-year survival among people diagnosed with thin melanomas in Queensland, Australia. J Clin Oncol 2012; 30:1462.

5 TNM STAGING FOR MELANOMA Thin Melanomas (<1.0 mm) Population study of 26,000 patients < or =1.00 mm thick Signficant at > 0.75 Breslow Depth (mm) 20-yr survival (%) < Green AC, Baade P, Coory M, et al. Population-based 20-year survival among people diagnosed with thin melanomas in Queensland, Australia. J Clin Oncol 2012; 30:1462.

6 TNM STAGING FOR MELANOMA Ulceration denoted a if absent or b if present Presence of ulceration correlates to worse prognosis in a comparable thickness lesion without ulceration Measurement of tumor thickness - base of the ulceration Mitotic Rate increased rates correlates to significantly worse prognosis 2 nd most important prognostic indicator in localized melanoma Hot spot <1 mitosis/mm 2 (10-yr survival rate 93%) >20 mitoses/mm2 (10-yr survival rate 48%) Thompson JF, Soong SJ, Balch CM, et al. Prognostic significance of mitotic rate in localized primary cutaneous melanoma: an analysis of patients in the multi-institutional American Joint Committee on Cancer melanoma staging database. J Clin Oncol 2011; 29:2199.

7 TNM STAGING FOR MELANOMA T Tumor thickness Presence or absence of ulceration Mitotic rate N Number of nodes Micro vs Macrometastases M Distant metastases LDH Level

8 TNM STAGING FOR MELANOMA Node Classification NX nodes not assessable (eg: previously removed) N0- no regional lymphatic metastases N1 1 node involvement N1a micrometastasis N1b macrometastasis N2 two-three nodes involved N2a micro N2b at least one node with macro N2c no lymph nodes involved but in-transit or satellite metastases present N3 four or more nodes, or matted nodes, or intransit/satellites with one node +

9 TNM STAGING FOR MELANOMA Node Classification NX nodes not assessable (eg: previously removed) N0- no regional lymphatic metastases N1 1 node involvement N1a micrometastasis N1b macrometastasis N2 two-three nodes involved N2a micro N2b at least one node with macro N2c no lymph nodes involved but in-transit or satellite metastases present N3 four or more nodes, or matted nodes, or intransit/satellites with one node +

10 TNM STAGING FOR MELANOMA Node Classification All patients with nodal involvement but without distant metastases are stage III regardless of degree of nodal involvement.

11 TNM STAGING FOR MELANOMA Micrometastases If nodal disease micro only then most important prognostic factor is the number of nodes involved. Number of nodes 5 yr survival rate (%) Balch CM, Gershenwald JE, Soong SJ, et al. Multivariate analysis of prognostic factors among 2,313 patients with stage III melanoma: comparison of nodal micrometastases versus macrometastases. J Clin Oncol 2010; 28:2452.

12 TNM STAGING FOR MELANOMA Macrometastases If nodal disease macro then most important prognostic factor is the number of nodes involved. Number of nodes 5 yr survival rate (%) Balch CM, Gershenwald JE, Soong SJ, et al. Multivariate analysis of prognostic factors among 2,313 patients with stage III melanoma: comparison of nodal micrometastases versus macrometastases. J Clin Oncol 2010; 28:2452.

13 TNM STAGING FOR MELANOMA Satellite Lesions and In-transit metastases Considered intralymphatic in TNM staging Convey similar negative prognostic implications Satellite discrete nests of melanoma separated from the tumor by normal subcutaneous tissue or reticular dermis. (in 33% if <3mm) In-transit skin or subcutaneous mets >2cm from primary León P, Daly JM, Synnestvedt M, et al. The prognostic implications of microscopic satellites in patients with clinical stage I melanoma. Arch Surg 1991; 126:1461.

14 TNM STAGING FOR MELANOMA Smaller than Micro? Sunbelt Melanoma Trial 1446 patients w/histo neg SLN RT-PCR allows detection of tumor-specific genetic material Identification of melanoma genetic material in 43% SLN RT-PCR positivity not associated with increased risk of recurrence (11% vs 10%). Scoggins CR, Ross MI, Reintgen DS, et al. Prospective multi-institutional study of reverse transcriptase polymerase chain reaction for molecular staging of melanoma. J Clin Oncol 2006; 24:2849.

15 TNM STAGING FOR MELANOMA T Tumor thickness Presence or absence of ulceration Mitotic rate N Number of nodes Micro vs Macrometastases M Distant metastases LDH Level

16 TNM STAGING FOR MELANOMA M M1a distant skin, subcutaneous or lymph nodes M1b lung M1c other visceral organ, or any metastasis with increased serum LDH Serum LDH 1 yr survival (%) 2 yr survival (%) Normal Elevated 32 18

17 TNM STAGING FOR MELANOMA Stage I pts with low-risk primary melanomas (T1a-T2a) without regional or distant mets Stage II pt with higher risk primaries (T2b-T4b) but no regional or distant mets Stage III Lymph node involvement present, satellite lesions or intransit mets Stage IV Distant metastases

18 TNM STAGING FOR MELANOMA Unknown Primary Isolated metastases to lypm hodes, skin, or subcutaneous tissue are Stage III Other sites of metastases from unknown primary Stage IV

19 ONLINE PROGNOSIS TOOL

20 OBJECTIVES TNM Staging Prognostication Management of Regional Lymphatics Therapeutic Neck Dissection Elective Neck Dissection Lymphoscintigraphy and Sentinel Node Biopsy

21 THERAPEUTIC NECK DISSECTION Treatment of choice for pathologically proven regional disease. Most common nodal metastases are to cervical or parotid/facial nodes. Site of primary Imaginary line drawn in coronal plane through EAC Anterior superficial parotidectomy and MRND Posterior posterolateral neck dissection Inferior eg Chin or neck need MRND, no parotidectomy

22 ELECTIVE NECK DISSECTION Historically controversial 16% chance of distant mets in absence of regional disease Only 10-20% of patients with melanoma have occult nodal metastasis. 80% of patients, therefore do not and would not benefit from elective neck dissection. Elective lymph node dissection does not provide a survival benefit over observation, replaced by sentinel node biopsy

23 SENTINEL NODE BIOPSY Minimally invasive, cost-effective, and efficacious for screening for nodal disease.

24 LYMPHOSCINTIGRAPHY Visualized study of the pattern of lymphatic drainage from a specific site Appreciation of lymphatic descriptions by scholars such as Hippocrates ( BC), Aristotle ( BC), and others

25 In the 19 th century Marie Sappey, a professor of anatomy in Paris, performed detailed studies of human lymphatic anatomy with injections of mercury into cannulated lymphatic vessels in cadavers. Lymphatic drainage from the skin of the trunk and limbs was thought to always go to the nearest axilla or groin nodal area. Lines of demarcation between these drainage fields have been referred to as Sappey s Lines.

26 1863 Virschow considered to have first described the concept of sentinel -type nodal drainage 1923 Braithwaite first to use the term sentinel in English literature 1960 Gould described drainage to a sentinel node at junction of anterior and posterior facial veins from parotid tumors 1966 Sayegh described sentinel node drainage from the testis 1977 Cabanas described sentinel node drainage from testis, penis, rectum, breast, and skin

27 MODERN LYMPHOSCINTIGRAPHY 1992 Morton reported use of injected blue dyes to help identify sentinel nodes in patients with cutaneous melanomas Alex and Krag described the use of radionuclides, nuclear imaging, and use of the handheld gamma probe to identify sentinel lymph nodes. Morton DL, Wen DR, Wong JH, et al. Technical details of intraoperative lymphatic mapping for early stage melanoma. Arch Surg 1992; 127:392. Krag DN, Meijer SJ, Weaver DL, et al. Minimal-access surgery for staging of malignant melanoma. Arch Surg 1995; 130:654.

28 TWO PREMISES OF THE SENTINEL NODE CONCEPT #1 Lymphatic flow from a primary tumor passes first to the sentinel node and then sequentially through a lymphatic chain. #2 Lymphatic metastasis from the primary tumor should develop first in the sentinel node.

29 TECHNIQUE Lymphoscintiraphy is currently performed after interstitial injection of either an inert colloid material tagged with a radionuclide (usually Technitium) 2-4 hours prior to surgery and/or a blue colored dye (usually isosulfan blue) injected intraoperatively.

30 RADIONUCLIDE AGENTS Au-198 colloid first agent widely used; now replaced Tc-99m antimony trisulfide colloid predominant agent in Australia Tc-99m nanocolloid predominant agent in Europe Tc-99m sulfur colloid predominant agent in North America Eshima D, Fauconnier T, Eshima L, Thornback JR. Radiopharmaceuticals for lymphoscintigraphy: including dosimetry and radiation considerations. Semin Nucl Med Jan;30(1):25-32.

31 The behavior of the injected colloid depends greatly on its particle size(s). Particles less than a few nanometers are most likely exchanged through the blood capillaries. Particles with diameters up to a few tens of nanometers will be absorbed into the lymph capillaries. Particles with diameters of hundreds of nanometers will remain trapped in the interstitial space for a longer time. While very small particles may be able to pass directly through the lymphatic capillary walls, most must undergo phagocytosis by macrophages that then pass into the lymphatic system.

32 The ideal radiopharmaceutical should pass quickly from the injection site into the lymphatic vessels and into the sentinel node. The material should remain trapped within the sentinel node for an acceptable period of time before being passed on to the more distal nodes of that particular drainage tract. The radionuclide should have a relatively short half-life so that toxicity is minimized.

33 We presently use Tc-99m sulfur colloid. The majority of the injected material is removed from the patient with the excision of the primary tumor and resection margin. Roughly 5-10% of the material may be removed with retrieval of the sentinel lymph node(s). Tc-99m has a half-life of approximately 6 hours.

34 Injections are done typically in 4 quadrants about the lesion or excision biopsy site 2-4 hours before surgery. Dynamic images are taken with attempt to identify course of collecting vessels An image is taken as the material reaches the node field (commonly min) Delayed scans are done with attempt to discern all draining pathways and sentinel nodes A skin mark may be placed over localized nodes, with consideration for the plane(s) used for this analysis

35 BLUE DYE 1% Isosulfan Blue is the dye most commonly used today Lymphatic channels and nodes will appear blue, which can help greatly in their identification at surgery There are a few isolated reports of patients who have experienced an anaphylactic response associated with use of Isosulfan Blue (<1% incidence)

36 Photo by Greg Renner MD

37 Photo by Greg Renner MD

38 SURGICAL TECHNIQUE Intradermal injection of radiotracer 2-4 hours before surgery Lymphoscintigraphy to visualize drainage and direct patient positioning Once induced, 1mL of isosulfan blue dye injected intradermally around lesion Wide local excision of primary Shine through Johnson, T. M., & Bradford, C. R. (n.d.). The Management of Head and Neck Melanoma and Advanced Cutaneous Malignancies. Cummings Otolaryngology Head and Neck Surgery (Fifth Edit., pp ). Copyright 2010

39 SURGICAL TECHNIQUE Hand held gamma probe used to identify and excise sentinel nodes Complete when counts per minute decreased to 10% of the hottest node (lower false neg rate) Nodes excised go for permanent (frozens carry 5-10% false neg rate) (Morton 2005) If positive nodes on permanent then return to OR within 2 weeks for completion Johnson, T. M., & Bradford, C. R. (n.d.). The Management of Head and Neck Melanoma and Advanced Cutaneous Malignancies. Cummings Otolaryngology Head and Neck Surgery (Fifth Edit., pp ). Copyright 2010 Morton DL, Cochran AJ, Thompson JF, et al: Sentinel node biopsy for early-stage melanoma accuracy and morbidity in MSLT-I, an international multicenter trial. Ann Surg 2005; 230:453..

40 PATHOLOGY PROCESSING Permanent sections gold standard SLND specimens can be evaluated more carefully than a full neck Avg tumor burden in nodes is 4.7mm3 (Wagner) and was only visualized on 73% with routine H&E (Joseph 1998) 21% of positive nodes in one study were clear on routine H&E (Karimipour DJ 2004) Special techniques required Serial sectioning 5um thick Immunohistochemistry for S-100, Melan-A, and HMB-45. (97, 96, 75% senstive respectively) (Karimipour DJ 2004) Karimipour DJ, Lowe L, Su L, et al: Standard immunostains for melanoma in sentinel lymph node specimens: which ones are most useful?. J Am Acad Dermatol 2004; 50:759. Wagner JD, Davidson D, Coleman III JJ, et al: Lymph node tumor volumes in patients undergoing sentinel lymph node biopsy for cutaneous melanoma. Ann Surg Oncol 1999; 6:398. Joseph E, Brobeil A, Glass F, et al: Results of complete lymph node dissection in 83 melanoma patients with positive sentinel nodes. Ann Surg Oncol 1998; 5:119

41 CONSIDERATIONS TO TECHNIQUE Close relationship with nuclear medicine Plan incisions to allow for standard completion incisions should they be required

42 SURGICAL PROFICIENCY Multicenter Selective Lymphadenectomy Trial 1 Thirty case learning curve anticipated First twenty five cases associated with node basin recurrence rate of 10.3% After second twenty five case recurrence dropped to 5.2% 55 case learning curve required to achieve 95% accuracy

43 SLN BIOPSY WHO NEEDS IT? Indications Breslow <1mm with adverse features (ulceration, high mitoses, lymphvasc invasion) Breslow 1-4mm Consider with Breslow >4mm for prognostication, risk of distant mets 65-70% Breslow <1mm without adverse features NOT INDICATED as risk of nodal mets <10%