Role of Sentinel Lymph Node biopsy in head and neck cancer

Role of Sentinel Lymph Node biopsy in head and neck cancer David Timme, MD Division of Otolaryngology, Southern Illinois University

TOPICS • 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

Case Presentation • 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

Lymphatic Drainage Pathways1 • 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

Lymphatic Drainage Pathways • 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

Lymphatic Drainage Pathways 5

Lymphatic Drainage Pathways • More than one primary drainage location may be present • Head and neck melanoma has more primary nodal sites than other organ sites 6

Lymphatic Drainage Pathways • 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

Lymphatic Drainage Pathways • 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

Basis of Sentinel Lymph Node8 • “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

The Challenge Nodal Basin • Ideal Model:9 Tumor Sentinel Node

The Challenge • Reality: Sentinel Node? Sentinel Node? Tumor Sentinel Node? Sentinel Node?

The Challenge • Reality: UNPREDICTABLE Sentinel Node? Sentinel Node? Tumor Sentinel Node? Sentinel Node?

The Challenge Analogy: UNPREDICTABLE

History of Neck Dissection1 • 19th 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

History of Neck Dissection • 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

Neck Dissection Balance • 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

Role for Sentinel Lymph Node Biopsy • 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”

Challenges for SLN in the Head • High density of lymph nodes • Close proximity to primary tumor • Complex lymphatic pathways • Optimization of localization and imaging essential for success

Techniques of Sentinel Lymph Node Localization • Dye • Pre-operative dynamic scintigraphy • Planar imaging • SPECT/CT • Intraoperative static scintigraphy

Technique – Dye 9 • Injection of Isosulfan blue dye submucously around tumor • Nodes stained blue in 15-45 min after injection • Exposure of nodal basin • Removal of stained node

Dye Limitations • 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 fluorescence10 • Similar limitations as with blue dye

Dye • 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 dye25 • 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

Radiolabeled Tracer11 • 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

Lymphoscintigraphy • 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

Lymphoscintigraphy

SPECT/CT scintigraphy12 • 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

SPECT/CT13 • 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

SPECT/CT

Intraoperative static lymphoscintigraphy • 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

Safety14 • 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

Risks • 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

Morbidity15 • 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

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

How Many Nodes • 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

Non-localization16 • 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

Non-localization • “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

Non-Localization • 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

Effect of Prior Treatment on Location17 • Chemoradiation may alter drainage pathways • 13 patients with pre-therapy SPECT/CT • Adjuvant chemoradiation • Pre-operative SPECT/CT • Intraoperativegammaprobe guided neck dissection

Effect of Treatment on Location • 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

Histopathologic Evaluation • 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

Histopathlogic Evaluation14 • Nodes in formalin • Routine H&E staining • If negative, then serial sectioning 150μm • Reevaluation with H&E staining • If negative, immunocytochemistry with pancytokeratin antibody

Histopathologic Evaluation • Recording of status • Macrometastases • Micrometastases • Isolated Tumor Cells

Role of Sentinel Lymph Node biopsy in head and neck cancer