SKIN CANCER AFTER HSCT

Transcription

1 SKIN CANCER AFTER HSCT David Rice, PhD, MSN, RN, NP, NEA-BC Director, Education, Evidence-based Practice and Research City of Hope National Medical Center HOW THE EXPERTS TREAT HEMATOLOGIC MALIGNANCIES LAS VEGAS, NV MARCH 2019

2 Disclosures David Rice has no disclosures This presentation is compiled by Badri Modi, MD, Assistant Clinical Professor, Division of Dermatology, City of Hope National Medical Center

3 Objectives Review literature Secondary skin cancers after solid organ transplantation Secondary skin cancers after hematopoietic cell transplantation Provide screening recommendations, based on current literature

4 Development of Secondary Malignancies Advances in solid organ and hematopoietic cell transplantation (HCT) have led to substantial improvements in long-term survival for recipients. Challenge in the post-transplant setting is increased risk of secondary malignancies Secondary malignancies Post-transplant lymphoproliferative diseases Leukemia Myelodysplasia Solid cancers Secondary solid tumor malignancies can occur and can continue to rise in incidence over time Studies with follow-up to 20 years have not shown a plateau in their occurrence 1-3

5 Solid Organ Transplants non-melanoma Skin Cancers Squamous cell (SCC) and basal cell carcinomas (BCC) > 90 percent of all skin cancers in transplant recipients 4-7 SCC is the most common Occurring 65 to 250 times as frequently as in the general population Incidence of BCC increases 10-fold in transplant recipients. Mean interval between transplantation and diagnosis of a tumor 8 years for those who received transplants at 40 years of age 3 years for those who received transplants after the age of 60 Incidence increases with the duration of immunosuppressive therapy Affects 50% of white transplant recipients CD4 counts significantly lower in transplant recipients with cutaneous carcinomas than in those without such lesions

6 Solid Organ Transplants-SCC SCC more aggressive in transplant recipients than in non-immunosuppressed persons Grow rapidly Recur locally in 13.4% during the first 6 months after excision Metastasize in 5-8 %, usually in 2 nd year after excision Unfavorable prognosis associated with: Presence of multiple tumors 6,10,11 Cephalic location (head) Older age 10 High exposure to sun Fair skin 14 Rejection episodes in the first year after transplantation 15 possibly because they require higher levels of immunosuppressive treatment N Engl J Med 2003;348:

7 Metastatic Disease Squamous Cell Carcinoma Metastasis occurs in 5-8 %, usually in 2 nd year after excision Most medical centers have only limited experience with metastatic skin cancer in organ transplant recipients Transplant Skin Cancer Collaborative formed (international group) Aimed at elucidating the clinical course, treatment, and final outcome in these patients Metastasis from skin cancer in organ transplant recipients most commonly consisted of SCC in regional nodal basins Predominantly treated with a combination of surgery and radiation By one year after metastasis cumulative incidence of relapse was 29% The 3-year disease specific survival was 56% Patients whose initial metastases were distant or systemic had a significantly poorer disease specific survival than those whose initial metastases were in transit or regional

8 Solid Organ Transplant - Melanoma Risk increased as compared with the general population 1.6 to 3.4 in Europe 6,16,17 2 to 4 in Australia 6,16 Accounts for 6.2% of posttransplantation skin cancers in adults and for 15% in children 18 Occurs mainly in Fair complexion, light hair and eyes Tendency to freckle Nevi in large numbers (especially children) 18,19 Mean interval between transplantation and diagnosis is 5 years 6,17

9 Skin Cancer in Hematopoietic Cell Transplantation (HCT) Cutaneous malignant neoplasms most common types of second malignant neoplasms reported 20 Up to 58.5% of the total tumors observed SCC, BCC, and melanoma were the most common cutaneous malignant neoplasms reported less common types included myxofibrosarcoma, Kaposi sarcoma, and malignant fibrous histiocytoma.

10 Skin Cancer in HCT Age-standardized incidence rates of melanoma in men and women were 3.3 and 2.8, respectively, per person years worldwide in 2012 Age-standardized incidence rates of other skin cancers have not been reported Incidence rates of skin cancers after HCT 105 per person years for BCC 76 for SCC for melanoma The risk of developing melanoma was also increased after HCT with reducedintensity conditioning (RIC) regimens Chronic GVHD (cgvhd), younger age at HCT and myeloablative TBI (that is, single doses 10 Gy or fractionated doses 13 Gy) consistently reported risk factors for secondary skin cancer JAMA Dermatol. 2015;151(7):

11 Skin Cancer in HCT Median interval to diagnosis from the time of HCT 7.3 to 9.4 years for BCC 2.1 to 7.0 years for SCC 1 to 4 years for melanoma Compared with solid organ transplant, HCT recipients have 3-fold higher risk of melanoma The risk of BCC after allogeneic HSCT was seen in patients conditioned with total-body irradiation (HR, 3.9 [95%CI, ]). Risk of BCC was similar for allogeneic HSCT recipients and solid organ transplant Increased risk of SCC, but not as high as for solid organ transplant JAMA Dermatol. 2015;151(7):

12 HCT Risk Factors For SCC Primary diagnosis of leukemia or severe aplastic anemia Younger age at transplantation Chronic GVHD Immunosuppression for greater than 24months Immunosuppressive regimens containing azathioprine For BCC A primary diagnosis of leukemia, lymphoma Younger age at transplantation Total Body Irradiation For melanoma Chronic GVHD T-cell depletion Female sex Total Body Irradiation JAMA Dermatol. 2015;151(7):

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14 de Masson, A., Bouaziz, J-D., & Socie, G. (2019) Who needs a skin exam? Skin cancer in allogeneic hematopoietic stem cell transplant recipients in the contemporary era. Journal of Investigative Dermatology. 139:

15 Increased Risk of SCC in GVHD patients A case control study of 183 patients with post-transplantation solid cancers (58 SCCs, 125 non-sccs) and 501 matched control patients within a cohort of 24,011 patients who underwent HCT at 215 centers worldwide Chronic GVHD and its therapy were strongly related to the risk for SCC No increase in risk was found for non-sccs Major risk factors for the development of SCC were long duration of chronic GVHD therapy use of azathioprine, particularly when combined with cyclosporine and steroids severe cgvhd Given that most patients who received prolonged immunosuppressive therapy and those with severe cgvhd were also treated with azathioprine, the independent effects of these factors could not be evaluated Results also suggest that clinical screening for SCC is appropriate among patients exposed to persistent chronic GVHD, prolonged immunosuppressive therapy, or both Curtis RE, Metayer C, Rizzo JD, Socie G, Sobocinski KA, Flowers ME et al. Impact of chronic GVHD therapy on the development of squamous-cell cancers after hematopoietic stem-cell transplantation: an international case-control study. Blood 2005; 105:

16 At City of Hope 10yrs post transplant Developed SCC High risk for local recurrence / metastasis tumor diameter > 2cm the reported risk of death due to SCC for patients with primary tumors > 2cm is almost 20x higher than those with smaller skin tumors

17 Melanoma s/p HCT

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19 Merkel cell carcinoma after HCT

20 Inamoto, Y., Shah, N.N., Savani, B.N. et al. (2015) Secondary solid cancer screening following hematopoietic cell transplantation. Bone Marrow Transplant. 50(8):

21 Cancer Screening Recommendations for City of Hope HCT recipients should be advised of the risks of secondary cancers annually and encouraged to undergo recommended screening based on their predisposition The preventive management of these patients requires a close collaboration between the dermatologist and transplant team A pre-transplantation screening that includes a history of previous skin cancer to determine the appropriate follow-up frequency or the wait time before proceeding to transplantation Patient education concerning sun protection and skin selfexamination Post-transplantation surveillance

22 Future research Incidence of skin cancer in transplant database in collaboration with Saro Armenian Prospective data collection regarding skin cancer incidence made possible by day 100 screenings and regular follow up with City of Hope Dermatology