Management of Head and Neck Cutaneous Squamous Cell Carcinoma Resident: Eugene Son, MD Faculty Mentor: Susan D. McCammon , MD. FACS The University of Texas Medical Branch Department of Otolaryngology Grand Rounds Presentation May 29, 2014 Series Editor: Francis B. Quinn, Jr., MD, FACS – Archivist: Melinda Stoner Quinn, MSICS
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Management of Head and Neck Cutaneous Squamous Cell Carcinoma
Resident: Eugene Son, MD
Faculty Mentor: Susan D. McCammon, MD. FACS
The University of Texas Medical Branch
Department of Otolaryngology
Grand Rounds Presentation
May 29, 2014
Series Editor: Francis B. Quinn, Jr., MD, FACS – Archivist: Melinda Stoner Quinn, MSICS
Source: Pathak I, et al. Do nodal metastases from cutaneous melanoma of the head and neck follow a clinically predictable pattern? Head & Neck 2001:785-790.
Source: Vauterin TJ, et al. Patterns of lymph node spread of cutaneous squamous cell carcinoma of the head and neck. Head & Neck 2005: 785-91.
• UVC does not reach earth’s surface• UVB causes cancer – does not go past derma-epidermal junction• UVA causes cancer, aging – longer wavelength allows deeper penetration to dermis.
Sunscreen
Source: Environmental Protection Agency. The Burning Facts. Sept 2006.
Medical Therapy
• 5-fluorouracil (5-FU)
• Imiquimod
• COX inhibitors
• Oral isotretinoin
• Topical retinoids
Source: Nouri K. Mohs Micrographic Surgery. New York: Springer, 2012.
Photodynamic Therapy (PDT)
• Photosensitizing drug + oxygen + light• Photosensitizer accumulates in tumor cells then exposed to light
• ROS results in necrosis and apoptosis, vascular compromise and inflammatory damage
• Photosensitizers• Given IV, po, or topical
• Porfimer Sodium
• 5-Aminolevulinic acid (5-ALA)• Combines forms protophyrin
• Methyl aminolevulinic acid (MAL)• More lipophilic for better penetration
Based on the AJCC Cancer Staging Manual 6th Ed, stage the following patient: 50 yo M with 1 cm in diameter lesion on right cheek. Biopsy shows SCC with poor differentiation and perinerual invasion. There is a 2.5 cm lymph node in left level II. No evidence of metastasis.
a) T1N1M0
b) T2N1M0
c) T1N2M0
d) T2N2M0
Old Staging
American Joint Committee on Cancer (AJCC), Cancer Staging Manual tumor, node, metastasis (TNM) system. 6th Ed. 2002.
• T0, Tis• T1 - 2 cm or less
• T2 – more than 2 cm, less than 5 cm
• T3 – more than 5 cm
• T4 – invades deep extradermal structures• Cartilage, muscle, bone
• N0 or N1
• M0 or M1
AJCC Cancer Staging Manual 6th Edition. New York: Springer, 2002.
Question
Based on the AJCC Cancer Staging Manual 7th Ed, stage the following patient: 50 yo M with 1 cm in diameter lesion on right cheek. Biopsy shows SCC with poor differentiation and perinerual invasion. There is a 2.5 cm lymph node in left level II. No evidence of metastasis.
a) T1N1M0
b) T2N1M0
c) T1N2M0
d) T2N2M0
Current Staging
American Joint Committee on Cancer (AJCC), Cancer Staging Manual tumor, node, metastasis (TNM) system. 7th Ed. 2010.
• T stage based on high-risk features• Depth/Invasion
• 2 mm or greater thickness, Clark level 4 or greater, PNI
• Anatomic location• Ear, non-hair-bearing lip
• Differentiation• Poorly or un- differentiated
• N and M stage same as UADT SCC staging.
AJCC Cancer Staging Manual 7th Edition. New York: Springer, 2010.
Source: Weber RS, Moore BA. Cutaneous Malignancy of the Head and Neck: A Multidisciplinary Approach. San Diego: Plural Publishing, 2011.
Clark and Breslow Levels
Source: Cummings, CW. Otolaryngology, Head and Neck Surgery. Ed. 5. Mosby, 2010.
Staging made easy…
• Stage 0 – CIS
• Stage 1 – T1
• Stage 2 – T2
• Stage 3 – T3 or N1
• Stage 4 – T4 or N2 or M1
Tumor (T)
• Horizontal size not used anymore.
• Brantsch et al landmark study with 615 pts. • 14/90 pts (16%) with >6 mm thick tumors had LN mets.
• 0 pts with <2 mm thick tumors had LN mets.
• Kraus et al • 1/3 of pts (33%) with SCC have >4 mm thickness but they account for >80% of
lesions with LN mets.
• Breuninger et al study with 500 pts.• 0% pts with <2 mm had LN mets
• 20% pts with >5 mm had LN mets.
Brantsch KD, et al. Analysis of risk factors determining prognosis of cutaneous squamous-cell carcinoma: a prospective study. Lancet Oncol 2008;9:713-20.Kraus DH, et al. Regional lymph node metastasis from cutaneous squamous cell carcinoma. Arch Otolaryngol Head and Neck Surg 1998;124:582-7.
Tumor (T)
• Australian study• 46% of pts with nodal mets had moderately or poorly differentiated tumors
• 12% of pts with nodal mets had well-differentiated tumors
• Goepfert reported tumors with PNI had 47% local recurrence rate and 34.8% metastasis rate.
• Other factors not accounted for:• Recurrent lesions
• 32% and 45% of recurrent lip and ear SCC had LN mets.
• Immunosuppression
Weber RS, Moore BA. Cutaneous Malignancy of the Head and Neck: A Multidisciplinary Approach. San Diego: Plural Publishing, 2011.
Nodal Metastasis
• Low risk SCC has 3-5% LN mets.
• Tertiary H&N cancer centers have 10-15% LN mets.
• Parotid most frequent site for mets
• 70-80% will have both parotid and cervical LN mets vs. 20-30% with only cervical LN mets.
• Over 70% of mets occur within 1 yr of treatment of primary lesion.
Nodal Metastasis
• Prior editions of AJCC consisted of Nx, N0, N1
• O’Brien et al came up with parotid+neck staging in 2002.
Source: O’Brien CJ, et al. Significance of clinical stage, extent of surgery, and pathologic findings in metastatic cutaneous squamous carcinoma of the parotid gland. Head Neck 2002:417-22.
Prognosis
• Majority cured with single modality.
• ~10% develop local recurrence.
• ~5% develop nodal mets.
• Southwell et al. study with 49 pts with metastatic SCC.• 9 had significant immunosuppression
• Recurrence rate of 56%
• 0% survival at 2 yrs vs. 87% survival in immunocompetent
Southwell KE, et al. Effects of immunocompromised on metastatic cutaneous squamous cell carcinoma in the parotid and neck. Head Neck 2006:244-8.
Westmead Hospital Group
• Study with 4-factor prognostic scoring system• ITEM (weight of Y/N):
• Immunosuppression (1.8/0)
• Treatment – multimodal (-1.8) vs single (0)
• ECS (4.8/0)
• +Margins (1/0)
• Ranges: 2.6 or less, greater than 2.6 to 3, greater than 3• 5 yr survival: 6%, 24%, 56%
• These factors most important in metastatic cutaneous SCC prognosis.
Southwell KE, et al. Effects of immunocompromised on metastatic cutaneous squamous cell carcinoma in the parotid and neck. Head Neck 2006:244-8.
Treatment
Treatment
• Surgical management
• Management of locoregional metastasis
• Other modalities• Radiation therapy
• Chemotherapy
• Topical medical treatment
• Photodynamic therapy
• Current research
Surgical ManagementStandard surgical excision
Moh’s micrographic surgery
Surgical Excision
• Wide local excision (WLE)• Cure rate 90-95%
• Margins• 4 mm will give > 95% cure rate for low risk lesions.
• NCCN guideline recommends 4-6 mm surgical margin.
• Recurrent lesions, >2 cm in size, rapid growth, near eyes or lips, poor differentiation, desmoplastic and spindle cell subtypes of SCC, invasion into subcutaneous tissue, PNI, lymphovascular invasion
• Face, scalp, anterior to half of EAC• Superficial parotidectomy + Levels II through IV
• Posterior to half of EAC• Levels II through V
• Lips, midface• Levels I through III
• Consider bilateral in midline lesions
Sentinel Lymph Node Biopsy (SLNB)
• Advantages• Minimally invasive• Cost-effective• Avoid morbidity with neck dissection
• Disadvantage• False negative
• More accepted in melanoma.
• Studies have shown high negative predictive value but limited to small sample size and short follow-up.
SLNB
• Systematic review of cSCCHN SLNB in Nov 2013.• 73 pts from 11 pubs with median 21.5 mo f/up
• At least 1 SLN identified in 100%• 13.5% (n=10) had +SLN
• 4.8% (n=3) failed regionally after –SLN.
• Pooled data:• 77% sensitivity
• 100% specificity
• 95.2% NPV
Ahmed MM, et al. Utility of head and neck cutaneous squamous cell carcinoma sentinel node biopsy: A systemic review. Otolaryngol – Head & Neck Surg 2013;150(2):180-7.
Parotid Gland Metastasis
• Superficial parotidectomy alone recommended for parotid nodal disease or parotid capsule invasion with intact facial nerve.
• No evidence suggests total parotidectomy (vs. superficial) improves locoregional control.
• Superficial parotidectomy with adjuvant XRT is adequate for mets to parotid with microscopic residual disease involving facial nerve and normal facial function.
• Weakness of facial nerve or temporal bone invasion requires radical parotidectomy with sacrifice of involved branches and likely temporal bone resection.
Prognostic Indicators
• Chart review of pts with cSCCHN s/p parotidectomy (2003-12), 2014.• 218 pts identified
• 49% had new primary lesion• 51% had recurrence• 91% had concurrent neck dissection
• Parotid and cervical LN status• 52% had +parotid LN• 28% had +cervical LN• 18% had both positive• 44% had both negative• 33% had only +parotid LN• 5% had only +cervical LN
• Overall survival• 2- and 5-yr survival was 0.71 and 0.58• Overall 5-yr survival lower for recurrent (0.49) vs new primary (0.69)• Overall 5-yr survival lower with cervical LN status: 0.47 vs. 0.62• No overall survival difference by: parotid involvement, margin status, PNI, FN sacrifice, type of
parotidectomy, +/- adjuvant radiation therapy
Sweeny L, et al. Head and neck cutaneous squamous cell carcinoma requiring parotidectomy: prognostic indicators and treatment selection. Otolaryngology-Head & Neck Surg 2014;150(4):610-7.
N+ Neck
• If clinically or radiographically evident nodal disease.
• At least the upper neck should be addressed if parotidectomy performed.
Anatomic Considerations
• Forehead and scalp• Frontozygomatic area can have supraorbital nerve or frontal nerve branch
involvement• Consider involvement of frontal sinus. • Neurosurgeon needed for calvarium, dura involvement.
• Periorbital• No consensus on margin but recommend 5 mm by large Australian series.• Lid margin needs full thickness excision.• Medial canthus lesions may involve lacrimal system which then would need
removal of drainage system• Orbital exenteration• Ophthalmologist needed
Auricular and Periauricular
• 10-16% with LN mets (vs. 0.5-5% all cSCCHN)• Consider involvement of TMJ, EAC, temporal bone• Auriculectomy
• When most of auricle involved.
• Lateral temporal bone resection• Bony canal involvement
• Weak FN or macroscopic involvement• Radical parotidectomy
• SCC of external ear with neck disease• 2 and 5 yr survival was 65% and 46%• 2 or more nodes dropped survival from 57% to 14%.
• ECS in 93% of these pts.
Reconstruction
• “Reconstructive ladder”
• Delay until margins are confirmed to be negative.
Image Source: Nouri K. Mohs Micrographic Surgery. New York: Springer, 2012.
• Surgery usually preferred method for primary lesion• Avoid in younger pts.
• Unacceptable long term cosmetic result
• More relevant to older pts.• Limited life expectancy
• Higher risk of perioperative complication.
• Regional LN mets• RT alone only in:
• Tumor extent makes unresectable
• Poor medical condition
Adjuvant Radiation Therapy
• Indications:• > 4 cm or recurrent tumors, aggressive histology, PNI, close or positive margins,
multiple positive nodes, ECS.
• Improves local control, disease-specific survival, overall survival in cases of PNI• Evidence for pathological PNI vs. clinically-evident/radiographic PNI• Australian study by Jackson et al. on SCC+BCC:
• Path PNI – 90% local control at 5 yrs• Clinical or radiographic PNI – 57% local control at 5 yrs
• General recommendation• Above indications for P+ and/or N+.• In P+ and N0, irradiate entire ipsilateral neck for high risk of subclinical disease.
Jackson JE, et al. Radiotherapy for perineural invasion in cutaneous head and neck carcinomas: toward a risk-adapted treatment approach. Head Neck 2009:604-10.
MDA Practice for Locoregional LN
• Cervical LN• 1 node without ECS
• Primary surgery alone, no XRT
• 2+ nodes or ECS• Postop XRT
• Parotid LN• Parotid node
• Parotidectomy + adjuvant XRT
• Parotid node fixed with possible unresectability• High dose pre-op XRT (6000-7000 cGy)
Weber RS, Moore BA. Cutaneous Malignancy of the Head and Neck: A Multidisciplinary Approach. San Diego: Plural Publishing, 2011.
XRT Techniques
• Primary Lesion• Orthovoltage RT
• Early SCC • Advantages: maximum dose at skin, bolus not required, smaller fields can be used, shielding
of eyes easier, less expensive• Disadvantages: higher dose to deeper tissue/bone/cartilage
• Electron beam• Scalp to reduce underlying brain dose
• High energy XR or photon• Advanced SCC with deep invasion
• Covers deep extent. Bolus used.
• IMRT• May also be used for primary lesion to reduce dose to surrounding structures
• Parotid and Neck – en face mixed beam of x-rays and high-energy electrons.
• Promising data with cisplatin, carboplatin, cetuximab.• Most data extrapolated from mucosal SCC of UADT.
• Retrospective cohort with pts with stage III/IV SCC with high risk features of 2+ LN, +margins, or ECS. • N – 61, 27 had adjuvant XRT vs. 34 had adjuvant XRT+chemo• Median recurrence-free survivals 15.4 and 40.3 mo• No difference in overall survival
Tanvetyanon T, et al. Postoperative concurrent chemotherapy and radiotherapy for high-risk cutaneous squamous cell carcinoma of the head and neck. Head Neck 2014; epub ahead of print.
Targeted Therapy
• EGFR inhibition• Rationale
• Ligand and receptor expression correlate with outcome• EGFR accelerates oncogenic signaling• Highly overexpressed in SCC
• Cetuximab used in mucosal H&N SCC.• EGFR Tyrosine kinase inhibitor
• Gefitinib• Erlotinib
• mTOR inhibiton• Sirolimus• Everolimus
Targeted Therapy
MDA prospective phase II study (Lewis et al.)
• Gefitinib as neoadjuvant chemotherapy for aggressive cSCCHN• 22 evaluated for response to therapy
• CR in 18.2%• No cancer found in n=3 in resulting surgical excision
• PR in 27.3%
• Overall 45.5% response rate
• Toxicity also evaluated• 13/22 had grade 2 toxicities
• 4/13 also had grade 3 toxicities
Lewis CM, et al. A phase II study of gefitinib for aggressive cutaneous squamous cell carcinoma of the head and neck. Clin Cancer Res 2012;18:1435-46.
Targeted Therapy
Sirolimus as a de novo therapy in OTR.
• 1st prospective randomized trial of sirolimus in renal transplant pts. • Sirolimus group (16)
• 1 new skin cancer
• Control group (17)• 8 new NMSC
• Benefits:• Delayed development of premalignancies
• Induced regression of pre-existing lesions
• Decelerate incidence of new skin cancers
Follow-up
• Local disease• q3-6 mo for 2 yr
• q6-12 mo for 3 yr
• q12 mo for life
• Regional disease• q1-3 mo for 1 yr
• q2-4 mo for 1 yr
• q4-6 mo for 3 yr
• q6-12 for life
Conclusion
• As the incidence of cSCCHN is rising, the responsibility is with the physician to help prevent and cure this treatable disease.
• Primary surgical excision usually provides cure as a single modality.
• The physician must be cognizant of features of aggressive cSCCHNwhich can metastasize locoregionally.• Addressing the lymph node basins while considering other modalities
including XRT and chemotherapy must be taken into account to prolong a disease free life of the patient.
• SLNB has promising data but more research needs to be done before it becomes standard of care.
Bibliography
Ahmed MM, et al. Utility of head and neck cutaneous squamous cell carcinoma sentinel node biopsy: A systemic review. Otolaryngol – Head & Neck Surg 2013;150(2):180-7.
AJCC Cancer Staging Manual 6th Edition. New York: Springer, 2002.
AJCC Cancer Staging Manual 7th Edition. New York: Springer, 2010.
Brantsch KD, et al. Analysis of risk factors determining prognosis of cutaneous squamous-cell carcinoma: a prospective study. Lancet Oncol 2008;9:713-20.
Byers R, et al. Squamous carcinoma of the external ear. Amer J Surg 1983;146:447-50.
Cummings, CW. Otolaryngology, Head and Neck Surgery. Ed. 5. Mosby, 2010.
Environmental Protection Agency. The Burning Facts. Sept 2006.
Kraus DH, et al. Regional lymph node metastasis from cutaneous squamous cell carcinoma. Arch Otolaryngol Head and Neck Surg 1998;124:582-7.
Jackson JE, et al. Radiotherapy for perineural invasion in cutaneous head and neck carcinomas: toward a risk-adapted treatment approach. Head Neck 2009:604-10.
Lardaro T, et al. Improvements in the staging of cutaneous squamous-cell carcinoma in the 7th edition of the AJCC Cancer Staging Manual. Ann Surg Oncol 2010;17:1979-80.
Leblanc KG, et al. The role of sirolimus in the prevention of cutaneous squamous cell carcinoma in organ transplant recipients. Amer Soc Derm Surg 2011;37:744-9.
Lewis CM, et al. A phase II study of gefitinib for aggressive cutaneous squamous cell carcinoma of the head and neck. Clin Cancer Res 2012;18:1435-46.
Nouri K. Mohs Micrographic Surgery. New York: Springer, 2012.
O’Brien CJ, et al. Incidence of cervical node involvement in metastatic cutaneous malignancy involving the parotid gland. Head Neck 2001:744-8.
O’Brien CJ, et al. Significance of clinical stage, extent of surgery, and pathologic findings in metastatic cutaneous squamous carcinoma of the parotid gland. Head Neck 2002:417-22.
Oddone N, et al. Metastatic cutaneous squamous cell carcinoma of the head and neck. Cancer 2009:1883-91.
Pathak I, et al. Do nodal metastases from cutaneous melanoma of the head and neck follow a clinically predictable pattern? Head & Neck 2001:785-790.
Southwell KE, et al. Effects of immunocompromised on metastatic cutaneous squamous cell carcinoma in the parotid and neck. Head Neck 2006:244-8.
Sweeny L, et al. Head and neck cutaneous squamous cell carcinoma requiring parotidectomy: prognostic indicators and treatment selection. Otolaryngology-Head & Neck Surg 2014;150(4):610-7.
Tanvetyanon T, et al. Postoperative concurrent chemotherapy and radiotherapy for high-risk cutaneous squamous cell carcinoma of the head and neck. Head Neck 2014; epub ahead of print.
Vauterin TJ, et al. Patterns of lymph node spread of cutaneous squamous cell carcinoma of the head and neck. Head & Neck 2005: 785-91.
Weber RS, Moore BA. Cutaneous Malignancy of the Head and Neck: A Multidisciplinary Approach. San Diego: Plural Publishing, 2011.