Practical Tips for Caring for Melanoma Patients

Practical Tips for Caring for Melanoma Patients Caroline C. Kim, MD, Director Assistant Professor, Department of Dermatology Harvard Medical School Director, Pigmented Lesion Clinic Associate Director, Cutaneous Oncology Program Beth Israel Deaconess Medical Center, Boston, MA Managing Patients with Melanoma and Other Melanocytic Neoplasms Symposium S027 American Academy of Dermatology Annual Meeting, February 17, 2018 1:00pm, San Diego, CA

Disclosures No relevant conflicts of interest Relationships Hoffmann-La Roche, Ltd. Investigator

Role of Dermatologist in Care of Melanoma Patients Before diagnosis 1. Education/Prevention 2. Skin cancer screening, biopsy/diagnosis, wide excisions of thin melanomas After diagnosis 1. Referring for SLNBx/oncology 2. Education/prevention 3. Screening, biopsy/diagnosis, treatment of additional primary melanoma 3. Screening, biopsy/diagnosis, treatment of metastasis/disease progression 4. Coordination with other disciplines for patient care and systemic treatments

Clinical Pearls Look for signatures and the ugly duckling!

Clinical Pearls Look for signatures and the ugly duckling! Look at the edge of difficult lesions and beware of inflammation

Clinical Pearls Look for signatures and the ugly duckling! Look at the edge of difficult lesions and beware of inflammation Your biopsy and closure matters

Biopsy Variable types of biopsies performed my.webmd.com

2011: American Academy Dermatology and NCCN Guidelines FROM THE ACADEMY Guidelines of care for the management of primary cutaneous melanoma Work Group: Christopher K. Bichakjian, MD, a Allan C. Halpern, MD (Co-chair), b Timothy M. Johnson, MD (Co-chair), a Table IV. Recommendations Antoinette Foote Hood, MD, c for biopsy James M. Grichnik, MD, PhD, d Susan M. Swetter, MD, e,f Hensin Tsao, MD, PhD, g Preferred Victoria Holloway biopsy technique Barbosa, is MD, narrow h Tsu-Yi excisional Chuang, biopsy MD, MPH, that i,j Madeleine Duvic, MD, k Vincent C. Ho, MD, l encompasses Arthur J. Sober, entire MD, breadth g Karl R. ofbeutner, lesion with MD, clinically PhD, m,n Reva Bhushan, PhD, o negative margins and Wendy to depth Smith sufficient Begolka, toms ensure o that Ann Arbor, Michigan; Newlesion York, is New notyork; transected, Norfolk, which Virginia; may be Miami, accomplished Florida; Palo by Alto, Los Angeles, Palm Springs, San Francisco, elliptical and Fairfield, or punch California; excisionboston, with sutures, Massachusetts; or shave Chicago and Schaumburg, Illinois; removal Houston, totexas; depth and belowvancouver, anticipated British planecolumbia, of lesion. Canada Partial sampling (incisional biopsy) is acceptable in select clinical circumstances such as facial or acral location, low clinical suspicion or uncertainty of diagnosis, or very large lesion. Repeat biopsy is recommended if initial biopsy specimen is inadequate for diagnosis or microstaging of primary lesion. NCCN Practice Guidelines in Oncology v.2.2009 Melanoma

High suspicion for melanoma: narrow excisional biopsy preferred 1-3 mm margins

Partial/incisional biopsy: Facial or acral areas Very large lesions Low suspicion Be aware of limitations of partial / incisional biopsy

Think about your biopsy www.topnews.in Degree of suspicion for melanoma Possible need for wide local excision and sentinel lymph node biopsy

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Clinical Pearls Look for signatures and the ugly duckling! Look at the edge of difficult lesions and beware of inflammation Your biopsy and closure matters Talk to your pathologist for difficult lesions

Talk to your pathologist about difficult lesions *MELTUMP (Melanocytic Tumor of Uncertain Malignant Potential): ask for breslow depth *Regression: ask for assessment of depth

Clinical Pearls Look for signatures and the ugly duckling! Look at the edge of difficult lesions and beware of inflammation Your biopsy and closure matters Talk to your pathologist for difficult lesions * MELTUMP, regression Keep up with guidelines: SLNBx and management

What melanomas are you referring for a SLNBx currently? 1. I don t refer for SLNBx for my melanoma patients 2. Melanomas >=0.8 mm and thinner tumors with ulceration 3. Melanomas >=0.8 mm and those thinner with ulceration and mitoses 4. Melanomas >=1.0 mm and those thinner with ulceration and mitoses 5. None of the above, I use a different algorithm

2009 AJCC Melanoma TNM Classification 7 th edition Classification Thickness (mm) Ulceration Status/Mitoses T Tis NA NA T1 <=1.00 a: Without ulceration <=1.00 b: With ulceration or mitoses >=1/ mm 2 *T1B tumors T2 1.01-2.0 a: Without ulceration have ~ 5-10% risk of b: With ulceration occult T3 2.01-4.00 a: Without ulceration metastases in SLN b: With ulceration T4 > 4.00 a: Without ulceration b: With ulceration

2017 AJCC Melanoma TNM Classification 8 th edition Classification Thickness (mm) Ulceration Status T Tis NA NA T1 <0.8 a: Without ulceration <0.8 mm 0.8-1.0 b: With ulceration b: With or without ulceration T2 >1.0-2.0 a: Without ulceration b: With ulceration T3 >2.0-4.00 a: Without ulceration *T1B tumors have ~ 5-10% risk of occult metastases in SLN b: With ulceration T4 > 4.00 a: Without ulceration b: With ulceration

Guidelines for consideration of SLNBx AJCC 2017: --Melanomas >= 0.8 mm thick --Melanomas <0.8 mm with ulceration NCCN: -- Melanomas >=0.8 mm -- Melanomas <0.8 mm with ulceration -- Melanomas <0.8 mm with high-risk features such as mitotic rate >2 mits/mm2, lymphovascular invasion AJCC 8 th edition NCCN melanoma guidelines 2.2018

Follow-up for melanoma patients Education and total body skin examination including lymph node examination Frequency of follow-up depends on risk of recurrence --NCCN: Early stages (IA-IIA): every 6-12 mo for 5 years Later stages (stage IIB-IV): every 3-6 mo for 2 years then every 6-12 mo for 3 years MMIS/ melanoma patient: at least annually for life Consideration of total body photography if appropriate

Clinical Pearls Look for signatures and the ugly duckling! Look at the edge of difficult lesions and beware of inflammation Your biopsy and closure matters Talk to your pathologist for difficult lesions * MELTUMP, regression Keep up with guidelines: SLNBx and management Second primary melanomas may not look like the first

Second primary melanomas Incidence: Range reported in literature: 1.3%-20.4% of all melanoma patients; Relative risk of 2 nd primary melanoma: ~9 fold increased risk compared to population Risk factors: may include: older age, male, fair skinned, fair/blond hair, head/neck primaries, lower-staged disease (Jones et al.) Bradford PT et al. Increased risk of second primary cancers after diagnosis of melanoma. Arch Dermatol. 2010 Mar; 146(3): 265-272. Jones M.S. et al. Second Primary Melanoma: Risk Factors, Histopathologic Features, Survival, and Implications for Follow-Up. Am Surg 2016 Oct; 82(10): 1009-1013.

Second primary melanomas Incidence: Range reported in literature: 1.3%-20.4% of all melanoma patients; Relative risk of 2 nd primary melanoma: ~9 fold increased risk compare to population Risk factors: may include: older age, male, fair skinned, fair/blond hair, head/neck primaries, lower-staged disease (Jones et al.) Second primary melanomas likely thinner than 1 st melanoma Prognosis: may be better than those with one melanoma (Jones et al.) Jones M.S. et al. Second Primary Melanoma: Risk Factors, Histopathologic Features, Survival, and Implications for Follow-Up. Am Surg 2016 Oct; 82(10): 1009-1013.

2 nd primary melanomas: MMIS patients need to be followed Pomerantz H et al. Risk of subsequent melanoma after melanoma in situ and invasive melanoma: a population-based 1973-2011. J Am Acad Dermatol 2015 May: 72(5): 794-800. Cohort study: Patients identified as having melanoma in situ or invasive melanoma as their first cancer in the Surveillance, Epidemiology, and End Results (SEER) program between 1973-2011 Melanoma in situ cohort more likely: -- to develop a 2 nd melanoma at any stage after 2 years than invasive melanoma cohort (p<0.001) --to develop subsequent invasive melanoma after 10 years than invasive melanoma cohort (P=0.003) --to develop subsequent melanoma in situ at all time points (p < 0.001)

Second primary melanomas Vernali et al. Association of incident amelanotic melanoma with phenotypic characteristics, MC1R status and prior amelanotic melanoma. JAMA Dermatology (published online July 26, 2017). The Genes, Environment, and Melanoma (GEM) study: international cohort of patients from population-based and hospital-based registries (1998-2003). 527 patients with multiple primary melanomas 24 patients with amelanotic melanoma: 20.8% had prior amelanotic melanoma 503 patients with pigmented melanoma: 5.4% had prior amelanotic melanoma Patients with amelanotic melanoma more likely to have a prior amelanotic melanoma (OR 4.62; 95% CI, 1.25-14.13, p=0.01) However: Second primary melanomas may not look like the first melanoma! Educate patients: continue looking for any ugly ducklings

Clinical Pearls Look for signatures and the ugly duckling! Look at the edge of difficult lesions and beware of inflammation Your biopsy and closure matters Talk to your pathologist for difficult lesions * regression Keep up with guidelines: SLNBx and management Second primary melanomas may not look like the first Melanoma recurrences and metastases can be any color

In transit metastases Management depends on clinical scenario: One or few: --if feasible, excisional biopsy with clear margins --coordinate with oncologist/surgeon: restaging scans, treatment discusssions Multiple or unresectable: --coordinate with oncologist/surgeon: restaging scans, treatment discussions: Intralesional therapy (i.e. T-VEC), systemic therapy (immunomodulating agents, targeted inhibitors, clinical trials), other (BCG, imiquimod, XRT, limb perfusion) NCCN Guidelines 2.2018

Suspicious subcutaneous nodules or lymphadenopathy Coordinate with oncologist/surgeon Fine needle aspiration or core biopsy, other biopsy type, imaging may be needed

Clinical Pearls Look for signatures and the ugly duckling! Look at the edge of difficult lesions and beware of inflammation Your biopsy and closure matters Talk to your pathologist for difficult lesions * MELTUMP, regression Keep up with guidelines: SLNBx and management Second primary melanomas may not look like the first Melanoma recurrences and metastases can be any color Management principles for in transit metastases/nodal disease

Summary Dermatologists play an important role in patient care both before and after a melanoma diagnosis Clinical pearls: Look for signatures and the ugly duckling! Look at the edge of difficult lesions and beware of inflammation Your biopsy and closure matters Talk to your pathologist for difficult lesions * MELTUMP, regression Keep up with guidelines: SLNBx and management Second primary melanomas may not look like the first Melanoma recurrences and metastases can be any color Management principles for in transit metastases/nodal

Thank you! Caroline C. Kim, MD, Director Assistant Professor, Department of Dermatology Harvard Medical School Director, Pigmented Lesion Clinic Associate Director, Cutaneous Oncology Program Beth Israel Deaconess Medical Center, Boston, MA ckim3@bidmc.harvard.edu Managing Patients with Melanoma and Other Melanocytic Neoplasms Symposium S027 American Academy of Dermatology Annual Meeting, February 17, 2018 1:00pm, San Diego, CA