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David Timme, MD Division of Otolaryngology, Southern Illinois University.

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Presentation on theme: "David Timme, MD Division of Otolaryngology, Southern Illinois University."— Presentation transcript:

1 David Timme, MD Division of Otolaryngology, Southern Illinois University

2  Case Presentation  Lymphatic Drainage  History of neck dissection  Techniques of Sentinel Node Biopsy  Limitations  Histologic Evaluation  Role in Head/Neck Cancer  Directions for the Future

3  53 yo male with history of oral tongue cancer  Treated R partial glossectomy, b/l selective neck dissections (1-3)  Recurrence of tumor at primary site  Radiographic, clinical N0 neck  HANOT recommendation for wide local excision of site of recurrence  How to address elective neck dissection in previously dissected neck

4  Case Presentation  Lymphatic Drainage  History of neck dissection  Techniques of Sentinel Node Biopsy  Limitations  Histologic Evaluation  Role in Head/Neck Cancer  Directions for the Future

5  1622 Aselli observed draining lymphatics in dogs  1787 Cruikshank “The Anatomy of the Absorbing Vessels of the Human Body”  1932 Rouviere classification of cervical lymph nodes according to location  Memorial New York – described 7 levels

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7  Nodal basins at risk according to location 4  Oral cavity/Oropharynx I-III  Laryngeal/Hypopharyngeal II-IV  Posterior scalp/suboccipital II-V  Thyroid II-IV, VI  Common patterns reflected in NCCN clinical guidelines

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9  More than one primary drainage location may be present  Head and neck melanoma has more primary nodal sites than other organ sites 6

10  Superficial Drainage Patterns (Cadaveric Study) 7  Typically follow venous routes  Alternate patterns from one side to another  Lymphaticovenous shunt present  Anterior neck lymphatics above platysma, upward to mandible

11  Certain tumors may have skip metastases  First drainage node may differ from expected location  Tumor size can alter lymphatic drainage  Previous resection, lymphadenectomy, or radiation can all cause changes in drainage patterns  Current standard of care is based upon probabilities

12  “First draining lymph node to receive lymphatic drainage from a primary tumor of a specific site”  Concept that a tumor will have preferred nodal drainage basin, with a primary node  Seaman/Powers 1955 first echelon node, nodal basin with radioactive colloid gold  Gould 1960 labeled first-echelon node the “sentinel node”  Cabanas 1977 identified specific groin node in primary penile cancer  Morton 1992 demonstrated intraoperative mapping in humans with melanoma using dye

13  Ideal Model: 9 Tumor Sentinel Node Nodal Basin

14  Reality: Tumor Sentinel Node?

15  Reality: UNPREDICTABLE Tumor Sentinel Node?

16 Analogy: UNPREDICTABLE

17  Case Presentation  Lymphatic Drainage  History of neck dissection  Techniques of Sentinel Node Biopsy  Limitations  Histologic Evaluation  Role in Head/Neck Cancer  Directions for the Future

18  19 th Century occasional resection of grossly involved lymph nodes  1885 Butlin – elective removal of nodes in tongue cancer  1900 MacKenzie “extirpation of larynx with..lymphatics and glands… diseased or not”  1888 Jawdynski described radical en bloc neck dissection

19  1905 Crile 121 operations with illustrations of block resections of cervical lymph nodes  Introduction of radical neck dissection  Hayes Martin 1951 – removal of CN XI, IJ, SCM should be standard  Functional, or “modified radical neck dissection” emerged in the 1950s  1960 Ballantyne pioneered modified approach  Continued work to determine optimal level of appropriate dissection needed

20  Need to remove gross disease  Prophylaxis against future development of metastases  Improve clinical outcomes  Lessen undue morbidity  shoulder dysfunction, facial edema, carotid blowout  Improve Clinical Outcomes

21  Potentially lessen morbidity of large surgical resection  Guide treatment approaches (further neck dissection, radiation therapy, etc)  Further research of drainage patterns  Prognosis  Detect earlier stage “micrometastases”

22  High density of lymph nodes  Close proximity to primary tumor  Complex lymphatic pathways  Optimization of localization and imaging essential for success

23  Case Presentation  Lymphatic Drainage  History of neck dissection  Techniques of Sentinel Node Biopsy  Limitations  Histologic Evaluation  Role in Head/Neck Cancer  Directions for the Future

24  Dye  Pre-operative dynamic scintigraphy  Planar imaging  SPECT/CT  Intraoperative static scintigraphy

25  Injection of Isosulfan blue dye submucously around tumor  Nodes stained blue in min after injection  Exposure of nodal basin  Removal of stained node

26  Invasiveness of broad exposure  Dye spillage around tumor – obscure margins  0.7-2% risk anaphylaxis  Skin tattooing  Washout with delay  Bredell reported on indocyanin green fluorescence 10  Similar limitations as with blue dye

27  Is Dye Necessary?  Clinical Guidelines suggest use of dye may be optional  Some advocate for triple technique  Shoaib – more nodes identified with scintigraphy/dye combo compared to blue dye 25  5/13 with dye  12/13 with radioactive tracer  Shoaib – 2 tumor positive nodes identified with blue dye alone in series of 40 patients (combo approach) 26

28  Scintigraphy relies upon radioactive tracer  Ideal particle size 5-10nm – smaller particles may be taken into vascular system  Gold, iodine, Technetium have been used  99mTc attached to sulfur colloid or human albumin most commonly used tracer  Investigation into other agents  Lymphoseek – dextran based product, avg. size 5nm  Half life 6 hours  Radioactivity detected 3-6 hours after injection  Ideally surgery same day as injection

29  Radiolabeled colloid injection around tumor periphery  Gamma camera to visualize dynamic real-time flow to sentinel nodes  Static images in A-P/lateral views obtained  Marking site of localized “hot spot”on the skin  Need to keep patient in static positioning until marking

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31  Use of CT scanners as opposed to planar imaging  Combination with single photon emission CT (SPECT)  Better resolution of nodes adjacent to primary tumor where “shine through” obscures  Better definition of nodes relative to anatomical landmarks  Improved attenuation and scatter of gamma rays improves localization

32  9 studies looking at SPECT/CT in OSCC  7 compared against planar lymphoscintigraphy  All identified at least one additional lymph node  Largest studies, 34, 40 patients. Additional lymph nodes identified in 37%, 47% of patients  Occult metastases identified in additionally imaged nodes  Has not entered into official guidelines

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34  Use of handheld gamma probe to identify node  Nodes with peak reading removed  Any adjacent nodes with >10% activity also removed  Confirmation of excised nodes for positive activity  Remaining bed should have less than 10% activity  SLN ranked according to activity uptake ex- vivo

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36  Case Presentation  Lymphatic Drainage  History of neck dissection  Techniques of Sentinel Node Biopsy  Limitations  Histologic Evaluation  Role in Head/Neck Cancer  Directions for the Future

37  Pelvic lymphoscintigraphy contraindicated for pregnant women; no proscriptions for head/neck  Low dose for the staff  Fewer than 100 SLNB during gestation below radiation exposure limits  Breastfeeding should suspend feeding 24 hr following injection  May do lower dose same-day surgery protocol

38  Similar to neck dissection  Injury to facial nerve, spinal accessory nerve  Injury to vascular structures (Operative exposure is more limited)  Completion neck dissection is conducted in recently operated field

39  QOL may be higher in Sentinel Node Biopsy compared to selective neck dissection  Improved swallowing  Better pain, tactile sensation  Better scar appearance  Improved shoulder constant score  Trend towards less edema

40  Remove tumor before or after SLN removal?  Guidelines advocate either  Removal of tumor can lessen shine-through  If dye used, increased time for washout

41  How many nodes to remove?  Removal of strongest signal alone would miss some positive nodes  39% of tumor positive nodes were not strongest radioactivity  Advocate around 3 nodes removed  Rarely more than 5 SLN  Advocate removal of any suspicious nodes as well

42  5-10%  Predictive factors (review of 121 patients, 12 unsuccessful)  Location, floor of mouth/anterior tongue  T stage (higher stage more unsuccesful)  Pre-operative lymphoscintigraphy negative

43  “Shine through” from primary tumor can obscure identification  Tumor filling a node, distorting architecture, could redirect lymphatic flow  Suspicious nodes should be removed for that reason  Tumor size can directly compress draining lymphatics

44  Technical Incompetence  Two groups of surgeons, less than 10 prior experiences and more experienced group  More successful SLN identification in experienced group  Familiarity with techniques and principles  Inherent difficulties in the head/neck

45  Chemoradiation may alter drainage pathways  13 patients with pre-therapy SPECT/CT  Adjuvant chemoradiation  Pre-operative SPECT/CT  Intraoperative gammaprobe guided neck dissection

46  6/13 identical SLN  4/13 more SLN  3/13 less SLN  Post-treatment tumor changes may alter how injection is administered, although attempted to control

47  Case Presentation  Lymphatic Drainage  History of neck dissection  Techniques of Sentinel Node Biopsy  Limitations  Histologic Evaluation  Role in Head/Neck Cancer  Directions for the Future

48  Protocols for SLN evaluation differ from routine node  Routine lymph node  Longitudinal sectioning  H&E staining  May miss up to 21% of diseased nodes  Large volume of nodes sampled precludes detailed examination at this point

49  Nodes in formalin  Routine H&E staining  If negative, then serial sectioning 150 μm  Reevaluation with H&E staining  If negative, immunocytochemistry with pancytokeratin antibody

50  Recording of status  Macrometastases  Micrometastases  Isolated Tumor Cells

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52  Case Presentation  Lymphatic Drainage  History of neck dissection  Techniques  Limitations  Histologic Evaluation  Role in Head/Neck Cancers  Directions for the Future

53  Established roles in cutaneous melanoma  Merkel Cell Carcinoma  Investigational  Squamous Cell Carcinoma  Oral Cavity/Oropharynx  Other subsites  Thyroid Carcinoma

54  No NCCN guidelines regarding SLN for mucosal melanoma  Guidelines exist for primary cutaneous melanoma  Higher chance of + SLN in thicker tumors  3-7% chance in tumors <1mm thick  Higher survival rates for early dissection after +SLNB compared to delayed dissection  Early stage lesions have not shown survival benefit with addition of SLN at this point

55  Presence of any nodal disease classifies at least stage III  N1 and N2 disease can be further subclassified into a and b according to micro or macrometastases  Current guidelines stratify to clinical trial or completion lymphadenectomy pending SLN status

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57  Staging reflects micrometastases  Stage IIIa or IIIb depending on micro or macrometastases  Evaluation should include IHC for CK-20, and pancytokeratin

58  Joint Clinical Practice Guidelines  European Sentinel Node Biopsy Committee  European Assocation of Nuclear Medicine Oncology Committee  Annals of Surgical Oncology, 2009  Oral/Oropharyngeal Squamous Cell Carcinoma  T1/T2 disease

59  N0 neck  Stage ipsilateral neck in unilateral primary tumor  Assess bilateral neck in primary tumor near or crossing midline  Assess contralateral neck in primary tumors near midline with ipsilateral N+ neck to determine need for b/l neck dissection  Fit enough to undergo neck dissection  Prior radiation/surgical neck treatment “routinely excluded”

60  134 patients  79 SLNB alone  55 SLN assisted neck dissection  Triple method of SLN identification  T1/T2 oral cavity cancers  93% success of identification of SLN  FOM location lowest rates of identification

61  N0 necks upstaged 34% of the time  No difference in percent from SLN alone or END assisted  5 year follow-up  SNB-END: 22/53 upstaged (one node in neck specimen, not SLN)  Sensitivity 96%  NPV 97%  SND alone: 20/72 upstaged  Overall sensitivity 91%, NPV 95%  False negative SND alone:5  4/5 FOM

62  Need more validation with larger trials  Lending support to using SNB as a staging tool  Not recommended for FOM primary  No significant survival differences between groups

63  35 patients (50 necks)  SNB biopsy with gamma probe  Lip, Oral Cavity, Larynx, Oropharynx  SLN followed by END  41 necks SLN negative  5% positive neck nodes  9 necks SLN positive  H&E negative necks  2 nodes SSS/IHC positive  NPV 95%

64  Stoeckli cohort of 79 patients  T1/T2 oral cavity/oropharynx  Validation phase (28) and observational phase (51)  Pre-operative scintigraphy, SPECT/CT, gamma probe  Intraoperative frozen section, followed by SSS/IHC  28 had SNB in conjunction with END  100% NPV  51 had SNB, and END based on results  19 patients then had completion ND  2 (6%) patients with neg SLN had neck recurrence  83% NPV frozen; 94% NPV overall

65  Significant differences for disease specific survival, and neck control rate between SN(+) and SN(-)  10% of SLN (-) developed neck recurrence

66  Multi-institution 140 patient T1-2 Oral Cavity  Primary tumor resection, SLN biopsy, followed by completion ND  SLN and largest node of each level evaluated by SSS/IHC  28% had neck positive disease  21/41 positive nodes were the SLN

67  False negative rate 9.8%  10% tongue  25% FOM  0% other sites  For more experienced surgeons, and smaller lesions, 0%  96% NPV overall

68  103 patients T1-2 oral/oropharyngeal SCC  IA cisplatin chemotherapy  9 had SLN+, therapeutic neck dissection  Observation time 6.7 years  No false negative recurrences in ipsilateral neck SN +SN – 5 year overall38%85% Disease Free47%74% Locoregional recurrence22%11%

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70  29 patients T1-T3 N0 neck (clinical and CT)  SLND followed by b/l SND (I-VI)  5 subsites (submucosa, four quadrants and center) endoscopically  99mTc-albumin nanocolloid  Laser transoral tumor resection  1-2 hours later hand held gamma probe  Skin overlying peak radioactivity marked

71  Mean sentinel lymph nodes harvested: 3  22/95 SLN were positive  58 neck dissections, 1 positive node, SLN was also positive  Positive nodes identified in levels 2&3  Positive node from dissection pre-laryngeal

72  Sensitivity 100%  Negative Predictive Value 100%  5 year disease free survival 75%

73  SLN addresses some of the challenges of complex head/neck lymphatic drainage  SLN biopsy a new technique in the development of neck dissection  Expect refinements and improvement in technique, potential locations  As surgeons develop more experience, can have even better success  NPV of a negative node has good correlation with a negative neck dissection  Anticipate a broader role in future staging  Will await future NCCN guidelines to become standard of care

74  Absence of studies in previously operated neck  Our example patient a good example of potential new role for SLN  2 level V nodes removed, neg with SSS  Large long term studies with comparison to gold- standard ND  As evidence accumulates, potential entry into NCCN guidelines for SCCA  Prognosis of micrometastases compared to macrometastases altering survival?  Early knowledge(frozen section) vs. definitive knowledge, (SSS/IHC/PCR)?

75  1. Ferlito, A., et al Neck Dissection: Then and now. Auris, Nasis, Larynx, 33:  2. Myers, et al. Cancer of the neck 4E, Fig 18-1, p In Thomas, YW.  3. Robbins, et al Archives of Otolaryngology,134:  5. Thomas, YW Pathways for Cervical Metastases in Malignant Neoplasms of the Head and Neck Region. Clinical Anatomy, 25:  6. Reynolds, et al Head & Neck. New York Head and Neck Society  7. Pan, WR Lymphatic Drainage of the Superficial Tissues of the Head and Neck: Anatomical Study and Clinical Implications. Plastic and Reconstructive Surgery, 121:  8. El-Sayed, IH Sentinel Lymph Node Biopsy in Head and Neck Cancer. Otolaryngol Clin N Am. 38:  9. Kuriakose, MA Sentinel node biopsy in head and neck squamous cell carcinoma. Curr Opin Otol Head and Neck Surg. 17:  10. Bredell, MG Sentinel lymph node mapping by indocyanin gree fluorescence imaging in oropharyngeal cancer-preliminary experience. Head & Neck Oncol. 2: 31

76  11. Coughlin, A Oral Cavity Squamous Cell Carcinoma and the Clinically N0 Neck: The Past, Present, and Future of Sentinel Lymph Node Biopsy. Curr Oncol Rep. 12:  12. Vermeeren, L SPECT/CT for sentinel lymph node mapping in head and neck melanoma. Head&Neck. 33:1-6.  13. Stephan, HK SPECT/CT for Lymphatic Mapping of Sentinel Nodes in Early Squamous Cell Carcinoma of the Oral Cavity and Oropharynx.  14. Alkureishi, LWT Joint Practice Guidelines for Radionuclide Lymphoscintigraphy for Sentinel Node Localization in Oral/Oropharyngeal Squamous Cell Carcinoma. Ann Surg Oncol. 16:  15. Schiefke, F Function, postoperative morbidity, and quality of life after cervical sentinel node biopsy and after selective neck dissection. Head Neck 24:  16. Hornstra, MT Predictive Factors for Failure to Identify Sentinel Nodes in Head and Neck Squamous Cell Carcinoma. Head & Neck  17. Validity of Sentinel Lymph Node Detection Following Adjuvant Radiochemotherapy in Head and Neck Squamous Cell Carcinoma. Wagner, A., et al Technology in Cancer Research and Treatment, 6,  18. NCCN Guidelines Version Melanoma.  19. NCCN Guidelines Version Merkel Cell Carcinoma  20. Alkureishi, LWT Sentinel Node Biopsy in Head and Neck Squamous Cell Cancer: 5-Year Follow-up of a European Multicenter Trial. Ann Surg Oncol. 17:

77  21. Chones, CT Predictive Value of sentinel node biopsy in head and neck cancer. Acta Oto-Laryngologica. 128:  22. Stoeckli, SJ Sentinel Node Biopsy for Oral and Oropharyngeal Squamous Cell Carcinoma of the Head and Neck. Laryngoscope. 117:  23. Broglie, MA Long Term Experience in Sentinel Node Biopsy for Early Oral and Oropharyngeal Squamous Cell Carcinoma. Ann Surg Oncol  24. Civantos, FJ Sentinel Lymph Node Biopsy Accurately Stages the Regional Lymph Nodes for T1-T2Oral Squamous Cell Carcinomas: Results of a Prospective Multi- Institutional Trial. Journ Clinical Oncology: 29:  25. Shaib T, et al A suggested method for sentinel node biopsy in squamous cell carcinoma of the head and neck. Head Neck. 21:  26. Shoaib T The accuracy of head and neck carcinoma sentinel lymph node biopsy in the clinically N0 neck. Cancer 91:  27. Kovacs, AF Postive Sentinel Lymph Nodes are a Negative Prognostic Factor for Sruvival in T1-2 Oral/Oropharyngeal Cancer- A Long-Term Study of 103 patients. Annal Surg. Oncology. 16:  28. Lawson, G Reliability of Sentinel Node Technique in the Treatment of N0 Supraglottic Laryngeal Cancer. Laryngoscope, 120:

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