Sentinel Lymph Node Biopsy for Head and Neck Cutaneous Melanoma

Transcription

1 Sentinel Lymph Node Biopsy for Head and Neck Cutaneous Melanoma S. Ross Patton, MD - PGY III Faculty Mentor: Susan McCammon, MD The University of Texas Medical Branch (UTMB Health) Department of Otolaryngology Grand Rounds Presentation November 28, 2012

2 Pre-Test 1. Which of the following is not a stain used to identify melanoma? hematoxylin and eosin a. Mart-1 b. HMB-45 c. S-100 d. Silver stain 2. In the absence of spread beyond the primary site of a melanoma, when is it appropriate to use SLNB? a. less than 1mm tumor thickness b. 1-4mm tumor thickness c. Greater than 4mm tumor thickness d. All of the above thickness can justify SLNB 3. What percentage of patients with a primary melanoma of the head/neck and no evidence of regional/distant spread will have occult regional metastases?? a. 5% b. 10% c. 20% d. 30%

3 Melanoma

4 Primary Classification TX Primary tumor cannot be assessed (e.g., curettaged or severely regressed melanoma). T0 Tis T1 T2 T3 T4 No evidence of primary tumor. Melanoma in situ. Melanomas 1.0 mm in thickness. Melanomas mm. Melanomas mm. Melanomas >4.0 mm. Note: a and b subcategories of T are assigned based on ulceration and number of mitoses per mm 2 as shown below: T classification Thickness (mm) Ulceration Status/Mitoses T1 1.0 a: w/o ulceration and mitosis <1/mm 2. T a: w/o ulceration. b: with ulceration or mitoses 1/mm 2. b: with ulceration. T a: w/o ulceration. b: with ulceration. T4 >4.0 a: w/o ulceration. b: with ulceration.

5 Nodal Classification NX N0 Patients in whom the regional nodes cannot be assessed (e.g., previously removed for another reason). No regional metastases detected. N1 3 Regional metastases based upon the number of metastatic nodes and presence or absence of intralymphatic metastases (in transit or satellite metastases). Note: N1 3 and a c subcategories assigned as shown below: N Classification No. of Metastatic Nodes Nodal Metastatic Mass N1 1 a: micrometastasis. b b: macrometastasis. c N2 2 3 a: micrometastasis. b N3 4 metastatic nodes, or matted nodes, or in transit met(s)/satellite(s) with metastatic node(s). b: macrometastasis. c c: in transit met(s)/satellites(s) without metastatic nodes.

6 Melanoma Staging Stage T N M Clinical Staging b 0 Tis N0 M0 IA T1a N0 M0 IB T1b N0 M0 T2a N0 M0 IIA T2b N0 M0 T3a N0 M0 IIB T3b N0 M0 T4a N0 M0 IIC T4b N0 M0 III Any T N1 M0 IV Any T Any N M1

7 Historical Treatment of N0 Melanoma

8 Watch and Wait Elective Lymph Node Dissection VS

9 ELND and Mortality WHO Trial- Veronesi et al Mayo Clinic- Sim et. al 1977 H&N Loree/Spiro pts Obrien pt series Kane pt series

10 Intergroup Melanoma Surgical Trial Balch 1996/2000

11 Why does ELND not decrease mortality in Head and Neck? Unpredictable Lymphatic Spread of melanoma Shah 1989 skip mets Leong 364

12 Obrien Classification O Brien CJ, Uren RF, Thompson JF, et al. Prediction of potential metastatic sites in cutaneous head and neck melanoma using lymphoscintigraphy. Am J Surg. 1995;170: % discordance with lymphoscintigraphy O Brien CJ, Uren RF, Thompson JF, et al. Prediction of potential metastatic sites in cutaneous head and neck melanoma using lymphoscintigraphy. Am J Surg. 1995;170:

13 Bilateral Nodal Drainage in H&N Carlson et al. Management of Malignant Melanoma of the Head and Neck Using Dynamic Lymphoscintigraphy and Gamma Probe Guided Sentinel Lymph Node Biopsy Arch Otolaryngol Head Neck Surg. 2000;126(3): %- Morton 1993

14 SLNB Technique Described- 1990/1992 Donald Morton

15 Competing Theories of Melanoma Metastasis Morton DL. Overview and update of the phase III Multicenter Selective Lymphadenectomy Trials (MSLT-I and MSLT II) in Melanoma. Clin Exp Metastasis (2012) 29:

16 Multi-Disciplinary Sentinel Lymph Node Biopsy Team cientist_sticker

17 Lymphoscintigraphy Stack BC. A technique for lymphoscintigraphy and sentinel node dissection for melanomas of the head and neck. Facial Plast Surg Clin N Am 11 (2003) Carlson et al. Management of Malignant Melanoma of the Head and Neck Using Dynamic Lymphoscintigraphy and Gamma Probe Guided Sentinel Lymph Node Biopsy Arch Otolaryngol Head Neck Surg. 2000;126(3):

18 SPECT CT

19 Gershenwald JE. Ross MI. Sentinel- Lymph-Node Biopsy for Cutaneous Melanoma. n engl j med 364;18 Stack BC. A technique for lymphoscintigraphy and sentinel node dissection for melanomas of the head and neck. Facial Plast Surg Clin N Am 11 (2003) 61 67

20 Blue Dye Boland GM. Gershenwald JE. Sentinel Lymph Node Biopsy in Melanoma The Cancer Journal. 2012:18,

21 Gamma Probe -- 10% rule

22 Stack BC. A technique for lymphoscintigraphy and sentinel node dissection for melanomas of the head and neck. Facial Plast Surg Clin N Am 11 (2003) 61 67

23 H&E Melanoma Stains S-100 HMB-45 E&hl=en&safe=active&tbo=d&tbm=isch&tbnid=3qch r2vuau2uqm:&imgrefurl=http e:malignant_melanoma_hmb45.jpg MART-1 **Permanent Section

24 Landmark SLNB Studies MSLT I (Morton) Sunbelt trial (McMasters) - analyzed by Chao for H&N SLN Working Group (Leong) Erman/Bradford et al 2012

25 MSLT-1 -Morton DL. Overview and update of the phase III Multicenter Selective Lymphadenectomy Trials (MSLT-I and MSLT II) in Melanoma. Clin Exp Metastasis (2012) 29:

26

27 SLNB Morbidity/Complications vs ELND MSLT-I (Morton 2005)

28 SLNB Morbidity/Complications Sunbelt Complication rate -4.5% in SLNB vs 23.2% for LND -1 transient facial nerve palsy, 2 spinal accessory nerve injuries during neck dissection

29 Early vs delayed LND- MSLT-1 4 th Interim analysis- Morton pts had early nodal dissection, 143 underwent delayed LND - lymphedema higher in delayed LND (20.4% vs 12.4% P=0.04) Neck - immediate: 18 - delayed: hospital stay vs 9.9 (P=0.02) Increased tumor burden?

30 Prognostic Information Gained by SLNB Most important independent predictor of recurrence and disease-free survival - Leong SLNWG more predictive than Breslow depth and ulceration *Confirmed by Erman/Michigan study Accurately reflects status of the nodal basin - Morton 1992: 0.06% non-sln positivity rate when SLN negative

31 Head and Neck Accuracy/False Negative Rate Chao et al 2003 H&N Analysis - SLN identification rate: 97% in h&n 100% in trunk/extremity Sunbelt trial (McMasters) - Higher false negative rate (same basin recurrence) - 1.9% in h&n - 0.5% in trunk/extremity - Lower incidence of detecting SLN metastasis - h&n: 15% 20%/23% t/e P=0.01

32 MSLT overall 95.3% success rate of identifying SLN - 85% success rate in the neck Carlson h&n patients - equivalent nodal recurrence between positive and negative SLNB s

33 SLNB for H&N melanoma is less reliable and more technically challenging than for melanomas in other locations

34 SLNB more difficult/less accurate in H&N? Faster washout - 59% h&n nodes stain blue - 68% & 74% trunk/ext (P<0.001) Smaller lymph nodes Shine through Complicated/delicate anatomy - (25% parotid SLN) In-transit mets Higher in H&N?

35 Accuracy/False Negative Rate Leong 362- chart of papers describing successful H&N melanoma SLNB techniques

36 Head &Neck Accuracy/False Negative Rate N=353 H&N melanoma patients 99.7% SLN identification rate H&N SLNB negative predictive value= 95.8% - False negative rate 14.8% Miller et al 2010-Oregon: 98.1% -153 pt study (32% false neg rate) Audrey Erman et al Controversy in Calculating false negative rate - false neg: false neg/false neg + true pos - false omission: false neg/false neg + true neg

37 Accuracy/False Negative Rate Controversy in Calculating false negative rate - false neg: false neg/false neg + true pos - false omission: false neg/false neg + true neg Michigan false ommision rate: 4.2% - MSLT: 3.4% SLN positivity rate: 19.7% - Sunbelt trunk/ext: 21.4% Audrey Erman et al

38 Accuracy/False Negative Rate Audrey Erman et al Comparable to trunk/extremity SLNB

39 Who should perform H&N SLNB? H&N Surgeons vs Surg Onc - surgical familiarity Learning curve - 30 cases- Morton - 60 cases- Erman Multidisciplinary Team- high volume center - nuclear medicine - melanoma pathologists

40 Parotid Nodes Formal parotidectomy vs excisional lymph node biopsy Loree 2006: 28 patient case series of H&N melanoma patients with SLN located in the parotiddid not perform formal parotidectomy - 96% success rate of identifying the SLN - no permanent facial nerve injuries - no increased risk of facial nerve injury on completion parotidectomy if parotid SLN was positive McKean cadaveric study performed - >92% of parotid nodes were lateral to facial nerve or in the tail Loree et al 2006

41 SLNB and Survival MSLT- 3 rd interim analysis statistically significant increase in disease-free survival - fewer positive nodes if recurrence occurred (1.9 vs 3.2) - no statistically significant difference in OVERALL survival **Final analysis pending

42 Who should receive SLNB? - NCCN recommendation is for patients with stage Ib or stage II (no evidence of spread outside the primary lesion - correlates to patients with primary melanomas less than 1 mm thick ulcerated histology or high mitosis rate - OR any patient with - much thinner melanomas have a lower propensity for spread and SLNB may be unnecessary - exception- there may be a role for SLNB for thin melanomas that have histologic features that have been associated with early nodal spread and poor outcomes: e.g. ulcerated histology - often patients are referred to head/neck surgeons after shave biopsy performed by dermatologists- if the deep margin of the shave is positive, the true depth of invasion cannot be known - thick melanomas: >4mm have been shown to be associated with early distant metastasis. A SLNB and subsequent regional LND would not address distant mets and would not improve survival (Morton 2003)

43 Future Areas of Research/Controversy MSLT-II RT-PCR - (molecular staging) - can detect 1 melanoma cell in 1 million normal cells (mrna) - plasma test for melanoma? Who should perform SLNB?

44 Summary/Conclusions - Elective Lymph node dissection in melanoma is not indicated - Sentinel lymph node biopsy is an accurate and relatively safe procedure (low-morbidity) for staging - accuracy/false negative rate for SLNB for the head/neck region specifically is currently being debated- (complex regional lymphatic drainage) - Who should perform SLNB in H&N is being debated - SLNB has not been shown to increase overall survival in melanoma in a randomized control trial, although it has been shown to increase disease-free survival - there continues to be ongoing research and debate in this area - 5th/final analysis from MSLT I - MSLT II trial - RT-PCR

45 Post-Test 1. Which of the following is not a stain used to identify melanoma? hematoxylin and eosin a. Mart-1 b. HMB-45 c. S-100 d. Silver stain 2. In the absence of spread beyond the primary site of a melanoma, when is it appropriate to use SLNB? a. less than 1mm tumor thickness b. 1-4mm tumor thickness c. Greater than 4mm tumor thickness d. All of the above thickness can justify SLNB 3. What percentage of patients with a primary melanoma of the head/neck and no evidence of regional/distant spread will have occult regional metastases?? a. 5% b. 10% c. 20% d. 30%

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47 Leong SP, Accortt NA, Essner R, et al. Impact of sentinel node status and other risk factors on the clinical outcome of head and neck melanoma patients. Arch Otolaryngol Head Neck Surg. 2006;132: Loree TR. Spiro RH. Cutaneous Melanoma of the Head and Neck. THE AMERICAN JOURNAL OF SURGERY. 1989, Loree TR. Tomljanovich PI. Cheney RT. Hicks WL. Rigual Nestor. Intraparotid Sentinel Lymph Node Biopsy for Head and Neck Melanoma. Laryngoscope 116: August McKean ME, McGregor IA. The distribution of lymph nodes in and around the parotid gland: an anatomical study. Br J Plast Surg 1985;38:1 5. McMasters KM et. al. Lessons learned from the Sunbelt Melanoma Trial. Journal of Surgical Oncology 2004;86: Miller MW et al. False Negative Sentinel Lymph Node Biopsy in Head and Neck Melanoma. Otolaryngology Head and Neck Surgery (4) Morton DL. Current management of malignant melanoma. Ann Surg. 1990;212: Morton D, Wen D, Wong J, et al.: Technical details of intraoperative lymphatic mapping for early stage melanoma. Arch Surg 1992;127: Morton DL, Wen DR, Foshag LJ, et al.: Intraoperative lymphatic mapping and selective cervical lymphadenectomy for early-stage melanomas of the head and neck. J Clin Oncol 1993;11: Morton DL, et al.: Sentinel-node biopsy or nodal observation in melanoma. N Engl J Med 2006;355: Morton DL. Overview and update of the phase III Multicenter Selective Lymphadenectomy Trials (MSLT-I and MSLT II) in Melanoma. Clin Exp Metastasis (2012) 29: O Brien CJ, Uren RF, Thompson JF, et al. Prediction of potential metastatic sites in cutaneous head and neck melanoma using lymphoscintigraphy. Am J Surg. 1995;170: O Brien CJ, Coates AS, Petersen-Schaefer K, et al. Experience with 998 cutaneous melanomas of the head and neck over 30 years. Am J Surg. 1991;162: Rigel DS: Epidemiology of melanoma. Semin Cutan Med Surg 2010;29: Russell-Jones R. When Will Selective Lymphadenectomy Become Standard of Care in Melanoma? Int J Clin Pract, July 2012, 66, 7, Shah JP, Kraus DH, Dubner S, et al. Patterns of regional lymph node metastases from cutaneous melanomas of the head and neck. Am J Surg. 1991;162:

48 Sim FH, Taylor WF, Ivins JC, et al.: A prospective randomized study of the efficacy of routine elective lymphadenectomy in management of malignant melanoma. Preliminary results. Cancer 1978;41: Stack BC. A technique for lymphoscintigraphy and sentinel node dissection for melanomas of the head and neck. Facial Plast Surg Clin N Am 11 (2003) Tanis PJ, Nieweg OE, van den Brekel MW, et al. Dilemma of clinically node-negative head and neck melanoma: outcome of watch and wait policy, elective lymph node dissection, and sentinel node biopsy a systematic review. Head Neck. 2008;30: Leong ST. Role of Selective Sentinel Lymph Node Dissection in Head and Neck Melanoma. J. Surg. Oncol. 2011;104: Veronesi U, Adamus J, Bandiera DC, et al.: Delayed regional lymph node dissection in stage I melanoma of the skin of the lower extremities. Cancer 1982;49: Wen D. Cochran AJ. Huang RR. Itakura E. Binder S. Clinically Relevant Information from Sentinel Lymph Node Biopsies of Melanoma Patients. Journal of Surgical Oncology 2011;104: