Head and Neck Melanoma:Head and Neck Melanoma:Management of Neck Nodes Management of Neck Nodes

GBMC Head and Neck Grand RoundsGBMC Head and Neck Grand RoundsThe Milton J. Dance, Jr. Head & Neck CenterThe Milton J. Dance, Jr. Head & Neck Center

Simon Best, M.D.Simon Best, M.D.Babar Sultan, M.D.Babar Sultan, M.D.

October 3, 2008October 3, 2008

GBMC Grand Rounds:GBMC Grand Rounds:Case PresentationCase PresentationCase PresentationCase Presentation

Babar Sultan MDBabar Sultan MD10/3/0810/3/08

RMRM

nn 74 yo M, several months prior to 11/07 noted 74 yo M, several months prior to 11/07 noted lesion on top of scalp. Patient has had many lesion on top of scalp. Patient has had many basal cell carcinomas in past including left ear. basal cell carcinomas in past including left ear. Lesion not dark in color.Lesion not dark in color.Lesion not dark in color.Lesion not dark in color.

nn Biopsy by dermatologist: nodular malignant Biopsy by dermatologist: nodular malignant melanoma: 1.4 mm depth, no ulceration, Clark melanoma: 1.4 mm depth, no ulceration, Clark Level IV Level IV

RMRM

nn PMH: h/o Basal Cell, hypercholesterolemiaPMH: h/o Basal Cell, hypercholesterolemiann PSH: hernia repair, right knee replacement, PSH: hernia repair, right knee replacement,

hemorrhoidectomy, detached retina repairhemorrhoidectomy, detached retina repairnn SH: Quit smoking forty years ago (15 pack year), SH: Quit smoking forty years ago (15 pack year), nn SH: Quit smoking forty years ago (15 pack year), SH: Quit smoking forty years ago (15 pack year),

mod user of alcohol, no h/o radiation exposuremod user of alcohol, no h/o radiation exposurenn FH: No h/o melanoma, Father died of colonFH: No h/o melanoma, Father died of colon

cancer, mother of natural causes, Brother has cancer, mother of natural causes, Brother has pancreatic cancer pancreatic cancer

RMRM

nn PE: Vertex of scalp, 1.9 PE: Vertex of scalp, 1.9 cm transverse scar. cm transverse scar. Palpation, U/S: No neck Palpation, U/S: No neck lymphadenopathylymphadenopathy

RMRM

nn Underwent PET/CT scan: small focus of uptake Underwent PET/CT scan: small focus of uptake along the site of biopsy, no distant metastasis along the site of biopsy, no distant metastasis

nn 11/15/07: WLE, STSG, excision sentinel node 11/15/07: WLE, STSG, excision sentinel node in postauricular regionin postauricular regionin postauricular regionin postauricular region

nn Node: metastatic malignant melanomaNode: metastatic malignant melanomann 2/08: Left neck dissection Levels 2, 3, 5, 2/08: Left neck dissection Levels 2, 3, 5,

occipital exploration, partial lower occipital exploration, partial lower parotidectomy: All nodes negativeparotidectomy: All nodes negative

RMRM

nn 8/08: Patient returned for clinic visit8/08: Patient returned for clinic visit--Dermatologist biopsied lesion anterior and to Dermatologist biopsied lesion anterior and to right of his melanoma site on scalp: malignant right of his melanoma site on scalp: malignant melanoma: 2.2 mm deepmelanoma: 2.2 mm deepmelanoma: 2.2 mm deepmelanoma: 2.2 mm deep

nn On PE: dermal thickening and nodularity seen On PE: dermal thickening and nodularity seen near skin graft sitenear skin graft site

nn Biopsy: malignant melanomaBiopsy: malignant melanoma

RMRM

RMRM

nn Repeat PET/CT: Multiple pulmonary metastasis Repeat PET/CT: Multiple pulmonary metastasis as well as retroperitoneal lymph nodeas well as retroperitoneal lymph node

nn Consult Medical OncologyConsult Medical Oncology

PET/CT from 10/07 showing only the PET/CT from 10/07 showing only the single scalp lesionsingle scalp lesion

Axial PET/CT Images from 2008 showing Axial PET/CT Images from 2008 showing new scalp lesionsnew scalp lesions

Axial PET/CT images 2008 showing new lung Axial PET/CT images 2008 showing new lung metastasesmetastases

Axial PET/CT Images showing Axial PET/CT Images showing subcutaneous metastasis overlying the right subcutaneous metastasis overlying the right

back musculatureback musculature

Head and Neck Melanoma:Head and Neck Melanoma:Management of Neck Nodes Management of Neck Nodes

GBMC Head and Neck Grand RoundsGBMC Head and Neck Grand Rounds

Simon BestSimon BestOctober 3, 2008October 3, 2008

OutlineOutline

nn Review of clinical melanomaReview of clinical melanomann StagingStagingnn Excision MarginsExcision Margins

Role of Sentinel Node BiopsyRole of Sentinel Node Biopsynn Role of Sentinel Node BiopsyRole of Sentinel Node Biopsynn Role of Neck DissectionRole of Neck Dissectionnn Is H+N melanoma a separate entity?Is H+N melanoma a separate entity?

Clinical PresentationClinical Presentation

nn Malignancy of melanocytes, located predominatly in the Malignancy of melanocytes, located predominatly in the skin, but also found in eyes, ears, GI tract, skin, but also found in eyes, ears, GI tract, leptomeninges, oral and genital mucosa.leptomeninges, oral and genital mucosa.

nn 4% of skin cancers 4% of skin cancers –– 74% of skin cancer deaths74% of skin cancer deathsnn 4% of skin cancers 4% of skin cancers –– 74% of skin cancer deaths74% of skin cancer deaths

nn Incidence: tripled in Caucasian population past 20 Incidence: tripled in Caucasian population past 20 years, now sixth most common cancer. years, now sixth most common cancer. nn Lifetime incidence is 1 in 60 for CaucasiansLifetime incidence is 1 in 60 for Caucasiansnn Highest incidence in Australia and New Zealand.Highest incidence in Australia and New Zealand.

Clinical Presentation cont.Clinical Presentation cont.nn Clinical:Clinical: New or changing mole New or changing mole

or blemish.or blemish. Bleeding, itching, Bleeding, itching, ulcerationulceration

nn The “ABCDE” criteriaThe “ABCDE” criteriann AsymmetryAsymmetrynn Border irregularityBorder irregularitynn Color variegationColor variegationnn Diameter (> 6mm)Diameter (> 6mm)nn EvolvingEvolving

Risk FactorsRisk Factorsnn Etiology Etiology -- sites of sites of

intermittent, intense sun intermittent, intense sun exposure exposure nn FairFair--complexioncomplexionnn Residence near equatorResidence near equatornn Blistering sunburns in Blistering sunburns in nn Blistering sunburns in Blistering sunburns in

childhood and adolescencechildhood and adolescence

nn Age Age -- median age is 53median age is 53nn Most common cancer in Most common cancer in

women age 25women age 25--29, second only 29, second only to breast cancer in women age to breast cancer in women age 3030--3434

Race and MelanomaRace and MelanomaDisease effects primarily Caucasians- African Americans incidence 1/20th

- Hispanic incidence 1/6th

StagingStagingnn AJCC revised staging system from 2002AJCC revised staging system from 2002

nn Uses Breslow depth instead of Clark’s Level Uses Breslow depth instead of Clark’s Level except for IA and IBexcept for IA and IB

nn Ulceration is a significantly negative predictorUlceration is a significantly negative predictor

nn Staging validated in 17,000 patient studyStaging validated in 17,000 patient study

nn See HandoutSee Handout

Validated Survival CurveValidated Survival Curve

Surgical MarginsSurgical Margins

nn Melanoma in situ Melanoma in situ –– 5mm5mmnn <1.0 mm <1.0 mm –– 1 cm1 cmnn 11--2 mm 2 mm –– 1 cm1 cm

1 1 –– 4 mm 4 mm –– 2 cm2 cmnn 1 1 –– 4 mm 4 mm –– 2 cm2 cmnn >4 mm >4 mm –– 2 cm2 cm

Surgical MarginsSurgical Margins

nn Intergroup Melanoma Surgical Trial (Balch et al)Intergroup Melanoma Surgical Trial (Balch et al)nn Began in 1983Began in 1983nn Goal to examine optimal surgical margins for melanoma 1Goal to examine optimal surgical margins for melanoma 1--4 4

mm thick.mm thick.nn Trunk + extremity randomized to 2 or 4 cm margins.Trunk + extremity randomized to 2 or 4 cm margins.nn H+N given 2 cm margins.H+N given 2 cm margins.nn H+N given 2 cm margins.H+N given 2 cm margins.

nn No difference in local recurrence between 2 or 4 cm marginsNo difference in local recurrence between 2 or 4 cm marginsnn Local Recurrence by site:Local Recurrence by site:

nn H+N H+N –– 9.4%9.4%nn Proximal extremity Proximal extremity –– 1.1%1.1%nn Trunk Trunk -- 3.1%3.1%nn Distal extremity Distal extremity -- 5.3%5.3%

nn 5 year survival only 9% if local recurrence compared to 86% 5 year survival only 9% if local recurrence compared to 86% if no evidence of local diseaseif no evidence of local disease

Surgical Decision MakingSurgical Decision Making

nn Intermediate thickness melanoma have known rate of Intermediate thickness melanoma have known rate of lymph node recurrence / involvement (15lymph node recurrence / involvement (15--20%)20%)

nn Should all patients have comprehensive node Should all patients have comprehensive node dissections?dissections?

nn Should all patients be observed for clinical evidence of Should all patients be observed for clinical evidence of nn Should all patients be observed for clinical evidence of Should all patients be observed for clinical evidence of nodal involvement?nodal involvement?

nn Can sentinel node biopsy improve outcomes vs. either Can sentinel node biopsy improve outcomes vs. either of these two options?of these two options?nn If node is positive, what surgical procedure should be If node is positive, what surgical procedure should be

performed?performed?

Elective Lymph Node DissectionElective Lymph Node Dissection

nn Comprehensive dissection of lymph nodes Comprehensive dissection of lymph nodes assumed to drain primary tumorassumed to drain primary tumornn Advantages:Advantages:

nn Poor outcomes when clinical nodes are detectedPoor outcomes when clinical nodes are detectednn Poor outcomes when clinical nodes are detectedPoor outcomes when clinical nodes are detected

nn Disadvantages: Disadvantages: nn Unpredictable nature of drainage patternsUnpredictable nature of drainage patternsnn 8080--85% of patients undergo unnecessary surgery85% of patients undergo unnecessary surgery

EvidenceEvidence

nn Intergroup Melanoma Trial (Balch)Intergroup Melanoma Trial (Balch)nn Randomized trial, 10 year followup Randomized trial, 10 year followup –– Elective lymph node Elective lymph node

dissection vs. ‘Watch and wait’dissection vs. ‘Watch and wait’nn Combined analysis with of H+N with truncal melanoma Combined analysis with of H+N with truncal melanoma –– no no

survival difference between groupssurvival difference between groupssurvival difference between groupssurvival difference between groups

nn 3 of 10 cohort studies show survival benefit for ELND 3 of 10 cohort studies show survival benefit for ELND vs WWvs WWnn Lower depth cutLower depth cut--off 1.0off 1.0--1.5mm, upper limit 3.01.5mm, upper limit 3.0--4.0mm4.0mm

Watch and WaitWatch and Wait

nn Standard practice for thin melanoma (<1 mm)Standard practice for thin melanoma (<1 mm)nn Requires rigorous followupRequires rigorous followupnn Ultrasound is used for more sensitive detection Ultrasound is used for more sensitive detection

of nodesof nodesof nodesof nodesnn Small subgroup will have surgery earlier than Small subgroup will have surgery earlier than

detected by other methodsdetected by other methodsnn Survival advantage not clearSurvival advantage not clear

Sentinel Lymph NodeSentinel Lymph Node

nn Receives lymph directly from primary Receives lymph directly from primary melanoma, if free of disease, other nodes in melanoma, if free of disease, other nodes in basin will also be free of diseasebasin will also be free of diseasenn 10% rule 10% rule –– used to determine sentinel node’s’used to determine sentinel node’s’nn 10% rule 10% rule –– used to determine sentinel node’s’used to determine sentinel node’s’

nn Duel tracer results in higher identification ratesDuel tracer results in higher identification ratesnn Temporal variation in lymphatic flowTemporal variation in lymphatic flow

nn Most important prognostic indictor for longMost important prognostic indictor for long--term survivalterm survival

EvidenceEvidence

nn Multicenter Selective Lymphadenectomy Trial Multicenter Selective Lymphadenectomy Trial (MSLT)(MSLT)nn 1347 patients1347 patients randomized to sentinel node biopsy or randomized to sentinel node biopsy or

observation observation –– if node positive then complete if node positive then complete observation observation –– if node positive then complete if node positive then complete lymphadentectomy lymphadentectomy

nn Melanoma between 1.2 to 3.5 mm Melanoma between 1.2 to 3.5 mm nn Vital blue dye, radiocolloid Vital blue dye, radiocolloid

nn Disease free survival improved, but this is inherent in Disease free survival improved, but this is inherent in the study design, because of expected relapse in watch the study design, because of expected relapse in watch and wait groupand wait groupnn 78/500 (15.6%) patients in observation group had node 78/500 (15.6%) patients in observation group had node

relapserelapsenn 122/764 (16.0%) of sentinel nodes were positive 122/764 (16.0%) of sentinel nodes were positive

nn False negative rate 26/764 (3.6%)False negative rate 26/764 (3.6%)

nn Subgroup Analysis: 12% absolute risk reduction in Subgroup Analysis: 12% absolute risk reduction in melanomamelanoma--specific mortality comparing sentinelspecific mortality comparing sentinel--node node positive patients (including false negatives) vs. node positive patients (including false negatives) vs. node positive in observation grouppositive in observation groupnn 66% vs 54% 66% vs 54%

Management After Positive Sentinel Management After Positive Sentinel NodeNode

nn Multicenter Selective Lymphadenectomy TrialMulticenter Selective Lymphadenectomy Trial--22nn Ongoing and recruiting studyOngoing and recruiting studynn Randomizing patients with positive sentinelRandomizing patients with positive sentinel--node to node to

observation or completion lymphadenectomyobservation or completion lymphadenectomy

nn Positive nodes found in about 15% of patients Positive nodes found in about 15% of patients (range from 9% to 42%), even less clear if (range from 9% to 42%), even less clear if micromicro--metastases found have clinical metastases found have clinical significancesignificance

Sunbelt Melanoma TrialSunbelt Melanoma Trial

nn 79 center trial, goal of 3600 patients79 center trial, goal of 3600 patientsnn Dual goalsDual goals

nn Evaluate prognostic / surgical significance of Evaluate prognostic / surgical significance of micromets detected by PCR in sentinel lymph nodesmicromets detected by PCR in sentinel lymph nodesmicromets detected by PCR in sentinel lymph nodesmicromets detected by PCR in sentinel lymph nodes

nn Evaluate value of systemic Interferon treatment for Evaluate value of systemic Interferon treatment for localized melanomalocalized melanoma

Sunbelt Melanoma TrialSunbelt Melanoma Trial

Results of SunbeltResults of Sunbelt

nn Not yet published, presented at ASCONot yet published, presented at ASCOnn 64 month followup64 month followupnn No difference in DFS or OS in either Protocol A or No difference in DFS or OS in either Protocol A or

Protocol BProtocol B

nn Conclusions: Conclusions: nn Interferon does not improve survival in nonInterferon does not improve survival in non--disseminated disseminated

melanomamelanomann Interventions for nodes positive by RTInterventions for nodes positive by RT--PCR offers no PCR offers no

survival benefit over observation either by lymphadenectomy survival benefit over observation either by lymphadenectomy nor lymphadenectomy + Interferonnor lymphadenectomy + Interferon

Is H+N Melanoma a Separate Is H+N Melanoma a Separate Entity?Entity?

nn Unique sun exposureUnique sun exposurenn Rich and complex lymphatic drainageRich and complex lymphatic drainage

nn Anatomic predictions of nodal drainage basins is Anatomic predictions of nodal drainage basins is poorpoorpoorpoor

nn Most studies confirm increased likelihood of Most studies confirm increased likelihood of recurrence and diminished overall survivalrecurrence and diminished overall survival

nn Can evidence from larger clinical trials be Can evidence from larger clinical trials be applied to H+N melanoma?applied to H+N melanoma?

John Wayne Cancer CenterJohn Wayne Cancer Center

nn 773 patients with tumor negative sentinel lymph 773 patients with tumor negative sentinel lymph nodenodenn 8.9% developed recurrence8.9% developed recurrence

nn Multivariate analysisMultivariate analysisnn Multivariate analysisMultivariate analysisnn Tumor thickness, ulcerationTumor thickness, ulcerationnn Location on H+NLocation on H+Nnn All significant for decreased DFSAll significant for decreased DFS

Sunbelt Melanoma TrialSunbelt Melanoma Trialnn Higher number of SLN per nodal basin Higher number of SLN per nodal basin

nn 2.8, 2.7, 2.1 for H+N, trunk, extremity2.8, 2.7, 2.1 for H+N, trunk, extremity

nn Higher false negative ratesHigher false negative ratesnn 1.5% vs. 0.5% (p<0.05)1.5% vs. 0.5% (p<0.05)1.5% vs. 0.5% (p<0.05)1.5% vs. 0.5% (p<0.05)

nn Fewer histologically positive nodes despite similar Fewer histologically positive nodes despite similar Breslow thickness and presence of ulcerationBreslow thickness and presence of ulcerationnn 15% vs 23.4% and 19.5% (p<0.001)15% vs 23.4% and 19.5% (p<0.001)

nn Nodes less likely to contain blue dyeNodes less likely to contain blue dye

Population DatabasesPopulation Databases

nn SEER: 5 and 10 year survival worse for SEER: 5 and 10 year survival worse for scalp/neck compared to extremity, trunk, facescalp/neck compared to extremity, trunk, facenn 51,704 non51,704 non--Hispanic white adultsHispanic white adults

nn German Database: No difference in overall German Database: No difference in overall survival for H+N vs other sitessurvival for H+N vs other sitesnn 5702 patients5702 patients

ConclusionsConclusionsnn No evidence to support comprehensive lymph node dissection No evidence to support comprehensive lymph node dissection

in all patientsin all patients

nn Sentinel lymph node biopsy and subsequent lymph node Sentinel lymph node biopsy and subsequent lymph node dissection may improve outcomes in those with positive nodes, dissection may improve outcomes in those with positive nodes, but not in all patientsbut not in all patients

Aggressive treatment of micromets does not result in superior Aggressive treatment of micromets does not result in superior nn Aggressive treatment of micromets does not result in superior Aggressive treatment of micromets does not result in superior survival outcomessurvival outcomes

nn Sentinel node biopsy is technically and anatomically more Sentinel node biopsy is technically and anatomically more challenging in H+N melanomachallenging in H+N melanoma

nn Population studies may indicate that H+N melanoma is a Population studies may indicate that H+N melanoma is a distinct entity with worse outcomesdistinct entity with worse outcomes