Iatrogenic Immunosuppression and Cutaneous Malignancy

Transcription

1 Iatrogenic Immunosuppression and Cutaneous Malignancy Jerry D. Brewer, MD, MS, FAAD Professor of Dermatology Chair Division of Dermatologic Surgery Department of Dermatology Mayo Clinic / Mayo Clinic College of Medicine AAD March 6, MFMER 2015 MFMER slide-1 slide-1

2 Disclosures None 2011 MFMER 2015 MFMER slide-2 slide-2

3 The Dermatology Foundation has supported & advanced my career MFMER slide-3

4 Objectives Iatrogenic Immunosuppression and Malignancy Introduction Pathogenesis Epidemiology Outcomes Risk Factors Conclusions 2015 MFMER slide-4

5 I have seen bad outcomes in iatrogenically immunosuppressed patients with skin cancer in my practice 1. Frequently 2. Fairly regularly 3. Rarely 4. Never 2011 MFMER slide MFMER slide-5

6 Introduction 2015 MFMER slide-6

7 Skin Cancer Most common human malignancy Over 5 million NMSC per year in US Increased incidence and risk in immunosuppressed Solid organ transplantation NHL/CLL Rogers HW, Weinstock MA, Feldman SR, Coldiron BM. Incidence estimate of nonmelanoma skin cancer (keratinocyte carcinomas) in the US population, JAMA Dermatol 2015; 151(10): MFMER slide-7

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9 Original Biopsy 2015 MFMER slide-9

10 Organ Transplantation 2015 MFMER slide-10

11 Organ Transplantation Final defect size 8.1x5.5cm 2015 MFMER slide-11

12 US Organ Transplants in 2015 Total 30,973 Heart Renal Liver Kidney-Pancreas Lung Pancreas Intestine Heart-Lung > 250,000 Recipients Alive 2015 MFMER slide-12

13 Transplants per year 2015 MFMER slide-13

14 What would increase the number of transplant patients? Increasing the rate of donation Iran has legalized the sale of human organs Social acceptance of deceased and living donation Opt-out rather than opt-in policies Spain and Ireland Much higher donation rates 2015 MFMER slide-14

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18 Pathogenesis 2015 MFMER slide-18

19 Skin Cancer in Immunosuppressed Patients Multiple theories Decreased immune surveillance Direct carcinogenesis from medications Increased infections Human papilloma virus Merkel Cell Polyomavirus 2015 MFMER slide-19

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21 Epidemiology 2015 MFMER slide-21

22 Risk for developing skin cancer in transplant recipients Basal Cell Carcinoma --10X Squamous Cell Carcinoma X Merkel Cell Carcinoma -- 20X Kaposi s Sarcoma -- 84X Melanoma X 2015 MFMER slide-22

23 Characteristics of Skin Cancer in OTRs Age Duration of immunosuppression Intensity of immunosuppression Ultraviolet exposure HPV infection Type I-III skin CD4 lymphocytopenia Older = more Longer = more Stronger = more More = more Present = more Present = more Lower = more 2015 MFMER slide-23

24 73 year old outdoorsman s/p cardiac transplant MFMER slide-24

25 Outcomes 2015 MFMER slide-25

26 BCC and SCC 2015 MFMER slide-26

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28 Case SCC young in years, old in experience 2015 MFMER slide-28

29 History Pleasant 30 year old female History of ulcerative colitis Developed pulmonary fibrosis Due to UC treatment regimen 2015 MFMER slide-29

30 History Pulmonary fibrosis Progressed to bronchiolitis obliterans Bilateral living related lobar transplant 10/15/99 Bronchiolitis obliterans progressed First transplant failed Double lung transplant 2/ MFMER slide-30

31 Non-melanoma skin cancer Every visit At least biopsies Most superficially invasive SCC Around HAK s Around AKs Deep aggressive SCC requiring Mohs every 8-12 weeks 2015 MFMER slide-31

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39 Tumor Burden 2015 MFMER slide-39

40 Outcome Capecitabine stopped Antibody mediated rejection of lungs Bowel perforation following surveillance colonoscopy Recurrence of Aspergillus pneumonia Tumor rebound Recurrent aggressive SCC left neck/scalp Pulmonary nocardia infection Pulmonary mycobacterium avium complex infection 2015 MFMER slide-40

41 Outcome Cholangiocarcinoma Metastases Lung, bone, and multiple soft tissues Deceased Aug 15, MFMER slide-41

42 Lessons Learned The higher level of immunosuppression The bigger the cutaneous challenge! Age sometimes not a factor Aggressive treatment promptly is key! Systemic treatment options sometimes helpful Very humbling! 2015 MFMER slide-42

43 Incidence of and Risk Factors for Skin Cancer following Cardiac Transplantation Brewer JD, Colegio O, Phillips PK, Roenigk RK, Jacobs MA, Van de Beek D, Dierkhising RA, Kremers WK, McGregor C, Otley CC. Incidence of and Risk Factors for Skin Cancer after Cardiac Transplantation. Arch Dermatol. 2009;145(12): MFMER slide-43

44 Mortality Years post transplantation Cumulative incidence of death 5 yrs 18.4% (95% CI 13.6%-23.0%) 10 yrs 37.9% (95% CI 30.5%-44.5%) 15 yrs 63.5% (95% CI 51.5%-72.5%) 18 yrs 78.7% (95% CI 57.7%-89.3%) * The majority of death was due to heart failure 2015 MFMER slide-44

45 Mortality Mortality due to skin cancer Only 1 person died due to skin cancer Melanoma 8.6 years post transplantation 2015 MFMER slide-45

46 Melanoma 2015 MFMER slide-46

47 Melanoma in OTRs MM prior to transplant 62 cases of MM in 60 patients MM after transplant 703 cases of MM in 633 patients Brewer JD, Christenson LJ, Weaver AL, Dapprich DC, Weenig RH, Lim KK, Walsh JS, Otley CC, Cherikh W, Buell JF, Woodle SE, Arpey C, Patton PR. Malignant Melanoma in Solid Organ Transplant Recipients: collection of database cases and comparison with SEER data for outcome analysis. Arch Dermatol 2011; 147(7): MFMER slide-47

48 Overall Survival 3 year Overall Survival Breslow Depth (mm) MM post OTR SEER Data p value < % 96.7% < % 93.3% < % 87.4% <0.001 > % 76.2% Brewer JD, Christenson LJ, Weaver AL, Dapprich DC, Weenig RH, Lim KK, Walsh JS, Otley CC, Cherikh W, Buell JF, Woodle SE, Arpey C, Patton PR. Malignant Melanoma in Solid Organ Transplant Recipients: collection of database cases and comparison with SEER data for outcome analysis. Arch Dermatol 2011; 147(7): MFMER slide-48

49 MM Specific Survival 3 year MM Specific Survival (95% CI) Breslow Depth (mm) MM post OTR SEER Data p value < % 98.8% % 96.6% % 91.0% > % 81.0% 0.31 Brewer JD, Christenson LJ, Weaver AL, Dapprich DC, Weenig RH, Lim KK, Walsh JS, Otley CC, Cherikh W, Buell JF, Woodle SE, Arpey C, Patton PR. Malignant Melanoma in Solid Organ Transplant Recipients: collection of database cases and comparison with SEER data for outcome analysis. Arch Dermatol 2011; 147(7): MFMER slide-49

50 MM prior to Transplantation 60 patients with MM prior to Transplant 2 metastases 1 to LN s (1 month post MM diagnosis) 1 to lungs (14.8 years post MM diagnosis) No recurrences Brewer JD, Christenson LJ, Weaver AL, Dapprich DC, Weenig RH, Lim KK, Walsh JS, Otley CC, Cherikh W, Buell JF, Woodle SE, Arpey C, Patton PR. Malignant Melanoma in Solid Organ Transplant Recipients: collection of database cases and comparison with SEER data for outcome analysis. Arch Dermatol 2011; 147(7): MFMER slide-50

51 Conclusions MM in OTRs Overall survival is worse in OTRs with MM regardless of Breslow thickness MM cause specific survival appears to be worse in thicker MMs Recurrence of MM is no higher in OTRs with a prior history of MM 2015 MFMER slide-51

52 Risk Factors 2015 MFMER slide-52

53 Common Risk Factors for Skin Cancer in Transplant Patients Increasing incidence with increasing age Hereditary Fair Skin, blond or red hair SUN EXPOSURE Blue, green or gray eyes Celtic background History of previous NMSC HPV Sun exposure 2015 MFMER slide-53

54 Kim NN, Boone SL, Ortiz S, Mallett K, Stapleton J, Turrisi R et al. Squamous cell carcinoma in solid organ transplant recipients: influences on perception of risk and optimal time to provide education. Arch Dermatol 2009;145: MFMER slide-54

55 Dermatologic Surgery Volume 40, Issue 2, pages , 19 DEC 2013 DOI: /dsu MFMER slide-55

56 The Empty Vessel Concept Does Knowledge Equal Behavior? 2011 MFMER slide MFMER slide-56

57 Conclusions 2015 MFMER slide-57

58 How to Unlock the Puzzle?... Immune system Behavioral factors Other things that affects carcinogenesis 2015 MFMER slide-58

59 Summary What We Don t Know Immunosuppressed patients with skin cancer What is the underlying association Does education and prevention effect outcomes What predicts bad behavior 2015 MFMER slide-59

60 Future Direction and Research Pathogenic mechanisms Genetic associations Optimal management Formal recommendations needed Adjuvant therapy for high risk tumors Educational strategies Effects on outcome 2015 MFMER slide-60

61 What Physicians Need to Know about Skin Cancer in Immunosuppressed Patients Skin cancer can ruin a life Skin cancer can take a life Prevention must come early EARLY = CURE Less immunosuppression = less cancer Dermatologic surgeons and dermatologists should want to work with other specialties Expert help is available ( MFMER slide-61

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