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Highlights in Melanoma Research and Treatment

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Dana-Farber dermatologist Jennifer Lin, MD, discusses the latest research and treatment for melanoma.

This presentation was originally given as part of Dana-Farber's Tuesday Talks speaker series. In this talk, Lin provides an overview of melanoma, including recent research, progress and future goals.

Published in: Health & Medicine
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Highlights in Melanoma Research and Treatment

  1. 1. Approaching Melanoma in 2012: Highlights of the Progress and the Work Ahead Jennifer Y Lin, MD Melanoma Program, Dana-Farber/Brigham & Women’s Cancer Center Department of Dermatology, Brigham & Women’s Hospital
  2. 2. Disclosure of RelevantRelationships with Industry I do not have any relevant Relationships with industry.
  3. 3. Melanoma Program atDFCI/BWH CancerCenter Pigmented Lesion Clinic at BWH and Multidisciplinary Melanoma Clinic at DFCI Collaboration with pathologists, medical oncologists, surgical oncologists, radiation oncologists Weekly tumor board to discuss cases Monthly lectures to discuss the latest advances in the clinical and research aspects of melanoma
  4. 4. Goals1. What are my risks of developing melanoma?2. How can I decrease my risk?3. What are my options if I have been diagnosed with melanoma?4. What is in the horizon for melanoma?
  5. 5. Erdmann F etal. Int JCancer.2012.
  6. 6. 5th most common 7th most common• 76,250 new cases every year• 9,180 men and women will die from melanoma www.cancer.gov.
  7. 7. Increasing incidence of melanomaamong young adults (ages 18-39) 1970- 2009 4x 8x
  8. 8. Death from melanoma in older men isdisproportionately high J Amer Acad Dermatol. 2007 vol. 57 (4) pp. 555-72.
  9. 9. Detection of thin melanomas has improvedJID. (2010) 130, 793–797
  10. 10. Genetic Environmental•skin color •ultraviolet radiation•family history of • sunburnsmelanoma • # of moles•prior history of •immunosuppressionmelanoma •lack of access•atypical nevi •lack of education
  11. 11. Genetic Environmental•skin color •ultraviolet radiation•family history of • sunburnsmelanoma • # of moles•prior history of •immunosuppressionmelanoma •lack of access•atypical nevi •lack of education
  12. 12. Genetic Environmental•skin color •ultraviolet radiation•family history of • sunburnsmelanoma • # of moles•prior history of •immunosuppressionmelanoma •lack of access•atypical nevi •lack of education
  13. 13. Fitzpatrick’s Skin PhototypeFacultative pigmentation Constituitive pigmentation tan burn 1 2 3 4 5 6 library.thinkquest. org
  14. 14. Skin PhototypeLoss of function MC1R polymorphisms red hair fair skin light eyes freckling1 2 3 4 5 6 library.thinkquest. org
  15. 15. Genetic Environmental•skin color •ultraviolet radiation•family history of • sunburnsmelanoma • # of moles•prior history of •immunosuppressionmelanoma •lack of access•atypical nevi •lack of education
  16. 16. Genetic • full body skin•skin color exams•family history ofmelanoma • monthly self•prior history of checksmelanoma•atypical nevi
  17. 17. Benign acquired nevi • small, round, symmetric • can also be pink! and raised • acquired from childhood through adulthood • related to sun exposure Miller A and Mihm, M. NEJM, 2006.
  18. 18. Atypical nevi • diagnosis based on clinical and pathologic features • some evidence to suggest it could be a precursor lesion, but we lack diagnostic tools • Dysplastic Nevus Syndrome - Familial atypical multiple mole melanoma (FAMMM) Syndrome, B-K mole syndrome Miller A and Mihm, M. NEJM, 2006.
  19. 19. Atypical nevus (AN) and risk for melanoma • 1 AN 2.3x • <3-5 AN 4x • >5-10 AN 10x
  20. 20. ABCD’s A B C DAsymmetry Border Colors Diameter > Irregularity ¼ inch http://visualsonline.cancer.gov/about.cfm
  21. 21. E is for Evolution• Lesions that are changing – multiple colors – increasing in size – itching or pain – unlike any of your other moles
  22. 22. Genetic Environmental•skin color •ultraviolet radiation•family history of • sunburnsmelanoma • # of moles•prior history of •immunosuppressionmelanoma •lack of access•atypical nevi •lack of education
  23. 23. EnvironmentalGenetic •ultraviolet•skin color radiation•family history of • sunburnsmelanoma • # of moles•prior history of •immunosuppressionmelanoma •lack of access•atypical nevi •lack of education
  24. 24. UVR is a small component of solar radiationat the Earth’s surface SOLAR RADIATION = Visible light + Infrared + Ultraviolet light 10% (UVA, UVB) 40% 50% UVC UVB (5%) UVA (95%)
  25. 25. UVR – depth of penetration Depth of penetration increases with wavelength until about 1100 nm
  26. 26. Tanning isaddictive…J Am Acad Derm. 51(1): 45-51, 2004.
  27. 27. Tanning booths • 12X more UVA than sun, small amounts of UVB • Earlier exposure (high school vs. post college) associated with increased risk of skin cancer
  28. 28. Does sunscreen work?Does it decrease risk of skin cancer?
  29. 29. • 1,621 patients applied sunscreen daily for years• 14 year follow-up• 50% decrease in all melanoma, 73% decrease in invasive melanoma J Clin Onc. 29 (3): 257-263, 2011.
  30. 30. Sun Protection Factor (SPF) • SPF 15 = 15 times the UVB dose required to achieve MED • Practically this translates to amount of time: • If a patient’s skin normally takes 10 minutes to burn, the use of an SPF 15 sunscreen will now take him/her 150 minutes to burn. • Primarily a measure of UVB protection
  31. 31. Sunscreen (chemical) ActiveIngredients weak, stable Mexoryl HelioplexJ Am Acad Dermatol stable2005;52:93 7-58
  32. 32. Sunscreen (physical) ActiveIngredients • Titanium oxide • Zinc oxide stable
  33. 33. FDA guidelines
  34. 34. Fitzpatrick’s Skin PhototypeFacultative pigmentation Constituitive pigmentation tan burn 1 2 3 4 5 6 library.thinkquest. org
  35. 35. Acral Lentiginous Melanoma• 70% of melanomas in darkly complected people, 45% of Asians• Still more common in light-complected• Hutchinson sign: extension of pigment into proximal or lateral nail fold
  36. 36. Melanoma incidence rates byethnicity/raceIncidence rates by Male (per 100,000 Female (per 100,000race/ethnicity men) women)All races 23.6 14.9White 27.2 14.9Black 1.1 0.9Asian/Pacific Islander 1.7 1.3American Indian/Alaska 4.1 2.0nativeHispanic 4.5 4.6 Seer data 2000-2004 from 17 SEER geographic areas.
  37. 37. Melanoma death rates byethnicity/raceDeath rates by Male (per 100,000 Female (per 100,000race/ethnicity men) women)All races 3.9 /23.6 1.7White 4.3 /27.2 2Black 0.5 /1.1 0.4Asian/Pacific Islander 0.4 /1.7 0.3American 1.3 0.7Indian/Alaska nativeHispanic 0.9 0.6 Seer data 2000-2004 from 17 SEER geographic areas.
  38. 38. Diagnosing melanoma • Biopsy is performed removing entire lesion • Histopathology is read by dermatopathologist • Thickness • +/- ulceration • Number of mitoses
  39. 39. Breslow thickness– the most important prognostic factor
  40. 40. Pigmented lesion - improved software Improved clinical - non-invasive imaging detection Improved biologic -histologic markersmarkers to determine -blood markers biologic risk
  41. 41. EnvironmentalGenetic •ultraviolet•skin color radiation•family history of • sunburnsmelanoma • # of moles•prior history ofmelanoma •immunosuppression•atypical nevi •lack of access •lack of education
  42. 42. Sun-exposed melanomas associatedwith increased number of genomicmutations Sun exposure
  43. 43. Pigmented lesion - improved software Improved clinical - non-invasive imaging detection Improved biologic -histologic markersmarkers to determine -blood markers biologic risk
  44. 44. • Stay out of sun (10 AM to 4 PM)• Wear sun protective clothing• Reapply sunscreen• Replenish your vitamin D
  45. 45. EnvironmentalGenetic •ultraviolet radiation•skin color • sunburns•family history ofmelanoma • # of moles•prior history of •immunosuppressio nmelanoma•atypical nevi •lack of access •lack of education
  46. 46. Immunosurveillance for skincancer • Increased risk in the setting of immunosuppression • 65-250x more SCC • 10X more BCC • 8X more melanoma Rangwala S and Tsai KY. BJD. 165 (5): 953-65. Nov 2011.
  47. 47. Clinicalpresentation •55 yo WM •3 year h/o previously biopsied “freckle” on nasal tip
  48. 48. Pathology•LENTIGO MALIGNA, PRESENT AT MARGIN
  49. 49. Treatment options • Narrow margin excision • Radiotherapy • Topical immunomodulators
  50. 50. Imiquimod
  51. 51. 4 wks 10 wks BIW x 2 wks QD x 6 wks BID x 3 wks 5x/wk x 2 wks 24 wks 17 wks 13 wks QD x 4 wks QD x 4 wks none x 2 wksPhotographs courtesy of Andrew Werchniak, MD
  52. 52. Resultsand follow-up•Clinical resolution of disease•Close follow-up q 3-6 monthsfor years •Wood’s lamp •Dermoscopy •RCM •Surveillance biopsies
  53. 53. In-transit metastases QD x 2 wks QD x 4 wks
  54. 54. Clinicalpresentation• 47 yo bus driver• 6 month history of enlarging “callus”• In-transit metastases• Palpable inguinal LN• Restaging PET/CT: bilateral inguinal LAD & liver metastases
  55. 55. Stage IV Melanoma
  56. 56. Clinical trials
  57. 57. BRAF-V600E inhibitor
  58. 58. Rapid, dramatic tumor shrinkageobserved
  59. 59. Antibody to CTLA-4
  60. 60. Ipilimumab: CTLA-4 blockade T-cell activation T-cell inhibition T-cell potentiationT cell T cell T cell CTLA4 CTLA4 TCR X CTLA4 TCR TCR CD28 CD28 Antibody CD28 MHC B7 binds MHC B7 CD28 B7 MHC CTLA-4APC APC APC Courtesy of Steve Hodi MD
  61. 61. Kaplan-Meier analysis of survival 1.0 lpi + gp100 0.9 lpi alone 0.8 gp100 aloneOverall survival (%) 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0.0 1 2 3 4 Time (years)Hodi et al, NEJM 2010.
  62. 62. Summary• Melanoma continues to increase in incidence. Protecting against ultraviolet radiation exposure is the current best preventative strategy.• We aggressively screen high risk patients for melanoma and educate on sun protection, skin cancer screenings.• We continue to look for improved detection techniques and biomarkers to detect melanoma at its early, curable stage• We are interested in boosting the immune system in patients who are already at higher risk of developing melanoma
  63. 63. Future directions • Determine the immune response that is capable of clearing early melanoma and improve our body’s natural immunosurveillance • Discover biomarkers in precursor melanoma lesions to predict biologic potential and risk
  64. 64. Acknowledgements Jeffrey Feingold
  65. 65. Thank you!
  66. 66. Q&A• Do you see more melanoma in the Sun Belt?• If you have a skin legion, how do you know if it is precancerous? And if you wanted it removed to be safe, will insurance companies cover it? 80
  67. 67. Q&A• Is any sun exposure okay? 81
  68. 68. Q&A• Is it true that women get more melanoma on their legs and men get more melanoma on their body (trunk)?• How do you know how fast a melanoma will grow? 82
  69. 69. Q&A• What percent of melanomas go on to become advanced cancers (Stage IV)? 83
  70. 70. Q&A• Does clothing provide sun protection?• And what about special SPF clothing? 84
  71. 71. Q&A• How do you know what level of SPF to buy? 85
  72. 72. Q&A• What role does Vitamin D play in health?• And if we can’t be in the sun, should we take a Vitamin D supplement? 86
  73. 73. For more information…Watch our YouTube video on preventing and identifyingmelanoma here:•http://www.youtube.com/watch?v=OXt-yXFq39wVisit the DFCI Melanoma Treatment Center website:•http://www.dana-farber.org/Adult-Care/Treatment-and-Support/Melanoma.aspx

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